Aims. To examine whether natural language processing (NLP) using a clinically based large language model (LLM) could be used to predict patient selection for total hip or total knee arthroplasty (THA/TKA) from routinely available free-text radiology reports. Methods. Data pre-processing and analyses were conducted according to the Artificial intelligence to Revolutionize the patient Care pathway in Hip and knEe aRthroplastY (ARCHERY) project protocol. This included use of de-identified Scottish regional clinical data of patients referred for consideration of THA/TKA, held in a secure data environment designed for artificial intelligence (AI) inference. Only preoperative radiology reports were included. NLP algorithms were based on the freely available GatorTron model, a LLM trained on over 82 billion words of de-identified clinical text. Two inference tasks were performed: assessment after model-fine tuning (50 Epochs and three cycles of k-fold cross validation), and external validation. Results. For THA, there were 5,558 patient radiology reports included, of which 4,137 were used for model training and testing, and 1,421 for external validation. Following training, model performance demonstrated average (mean across three folds) accuracy, F1 score, and area under the receiver operating curve (AUROC) values of 0.850 (95% confidence interval (CI) 0.833 to 0.867), 0.813 (95% CI 0.785 to 0.841), and 0.847 (95% CI 0.822 to 0.872), respectively. For TKA, 7,457 patient radiology reports were included, with 3,478 used for model training and testing, and 3,152 for external validation. Performance metrics included accuracy, F1 score, and AUROC values of 0.757 (95% CI 0.702 to 0.811), 0.543 (95% CI 0.479 to 0.607), and 0.717 (95% CI 0.657 to 0.778) respectively. There was a notable deterioration in performance on external validation in both cohorts. Conclusion. The use of routinely available preoperative radiology reports provides promising potential to help screen suitable candidates for THA, but not for TKA. The external validation results demonstrate the importance of further model testing and training when confronted with new clinical cohorts. Cite this article: Bone Joint J 2024;106-B(7):688–695

Aims. Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results. A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion. Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614

Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493

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. Methods. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures. Results. Out of 1,160 studies initially identified, 39 were included. Most studies (85%) were published between 2020 and 2024, with 82% using publicly available datasets, primarily the Osteoarthritis Initiative. ML methods were predominantly supervised, with significant variability in the definitions of OA progression: most studies focused on structural changes (59%), while fewer addressed pain progression or both. Deep learning was used in 44% of studies, while automated ML was used in 5%. There was a lack of standardization in evaluation metrics and limited external validation. Interpretability was explored in 54% of studies, primarily using SHapley Additive exPlanations. Conclusion. Our systematic review demonstrates the feasibility of ML models in predicting OA progression, but also uncovers critical limitations that currently restrict their clinical applicability. Future priorities should include diversifying data sources, standardizing outcome measures, enforcing rigorous validation, and integrating more sophisticated algorithms. This paradigm shift from predictive modelling to actionable clinical tools has the potential to transform patient care and disease management in orthopaedic practice. Cite this article: Bone Joint J 2024;106-B(11):1216–1222

Aims. Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. Methods. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). Results. A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Conclusion. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection. Cite this article: Bone Joint J 2024;106-B(9):907–915

Aims. In-hospital length of stay (LOS) and discharge dispositions following arthroplasty could act as surrogate measures for improvement in patient pathways, and have major cost saving implications for healthcare providers. With the ever-growing adoption of robotic technology in arthroplasty, it is imperative to evaluate its impact on LOS. The objectives of this study were to compare LOS and discharge dispositions following robotic arm-assisted total knee arthroplasty (RO TKA) and unicompartmental arthroplasty (RO UKA) versus conventional technique (CO TKA and UKA). Methods. This large-scale, single-institution study included patients of any age undergoing primary TKA (n = 1,375) or UKA (n = 337) for any cause between May 2019 and January 2023. Data extracted included patient demographics, LOS, need for post anaesthesia care unit (PACU) admission, anaesthesia type, readmission within 30 days, and discharge dispositions. Univariate and multivariate logistic regression models were also employed to identify factors and patient characteristics related to delayed discharge. Results. The median LOS in the RO TKA group was 76 hours (interquartile range (IQR) 54 to 104) versus 82.5 (IQR 58 to 127) in the CO TKA group (p < 0.001) and 54 hours (IQR 34 to 77) in the RO UKA versus 58 (IQR 35 to 81) in the CO UKA (p = 0.031). Discharge dispositions were comparable between the two groups. A higher percentage of patients undergoing CO TKA required PACU admission (8% vs 5.2%; p = 0.040). Conclusion. Our study showed that robotic arm assistance was associated with a shorter LOS in patients undergoing primary UKA and TKA, and no difference in the discharge destinations. Our results suggest that robotic arm assistance could be advantageous in partly addressing the upsurge of knee arthroplasty procedures and the concomitant healthcare burden; however, this needs to be corroborated by long-term cost-effectiveness analyses and data from randomized controlled studies. Cite this article: Bone Jt Open 2023;4(10):791–800

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review

Aims. To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Methods. Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways. Results. Arthritic mice improved their physical fitness by 42.5% after PE intervention; it induced the differential expression of 2,554 genes. The bioinformatic analysis showed that the downregulated genes (n = 1,371) were significantly associated with cellular processes that mediate the inflammation, including Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT), Notch, and cytokine receptor interaction signalling pathways. Moreover, the protein interaction network showed that the downregulated inflammatory mediators interleukin (IL) 4, IL5, IL2 receptor alpha (IL2rα), IL2 receptor beta (IL2rβ), chemokine ligand (CXCL) 9, and CXCL12 were interacting in several pathways associated with the pathogenesis of arthritis. The upregulated genes (n = 1,183) were associated with processes involved in the remodelling of the extracellular matrix and bone mineralization, as well as with the processes of aerobic metabolism. At the histological level, PE attenuated joint inflammatory infiltrate and cartilage erosion. Conclusion. Physical exercise influences parameters intimately linked to inflammatory arthropathies. Research on the effect of PE on the pathogenesis process of arthritis is still necessary for animal and human models. Cite this article:Bone Joint Res. 2020;9(1):36–48

Aims. The aim of this meta-analysis was to determine the pooled incidence of postoperative urinary retention (POUR) following total hip and knee arthroplasty (total joint replacement (TJR)) and to evaluate the risk factors and complications associated with POUR. Methods. Two authors conducted searches in PubMed, Embase, Web of Science, and Scopus on TJR and urinary retention. Eligible studies that reported the rate of POUR and associated risk factors for patients undergoing TJR were included in the analysis. Patient demographic details, medical comorbidities, and postoperative outcomes and complications were separately analyzed. The effect estimates for continuous and categorical data were reported as standardized mean differences (SMDs) and odds ratios (ORs) with 95% CIs, respectively. Results. A total of 31 studies were included in the systematic review. Of these, 29 studies entered our meta-analysis, which included 3,273 patients diagnosed with POUR and 11,583 patients without POUR following TJR. The pooled incidence of POUR was 28.06%. Demographic risk factors included male sex (OR 1.81, 95% CI 1.26 to 2.59), increasing age (SMD 0.16, 95% CI 0.04 to 0.27), and American Society of Anesthesiologists grade 3 to 4 (OR 1.39, 95% CI 1.10 to 1.77). Patients with a history of benign prostatic hyperplasia (OR 1.99, 95% CI 1.41 to 2.83) and retention (OR 3.10, 95% CI 1.58 to 6.06) were more likely to develop POUR. Surgery-related risk factors included spinal anaesthesia (OR 1.44, 95% CI 1.19 to 1.74) and postoperative epidural analgesia (OR 2.82, 95% CI 1.65 to 4.82). Total hip arthroplasty was associated with higher odds of POUR compared to total knee arthroplasty (OR 1.10, 95% CI 1.02 to 1.20). Postoperatively, POUR was associated with a longer length of stay (SMD 0.21, 95% CI 0.02 to 0.39). Conclusion. Our meta-analysis demonstrated key risk variables for POUR following TJR, which may assist in identifying at-risk patients and direct patient-centered pathways to minimize this postoperative complication. Cite this article: Bone Jt Open 2024;5(7):601–611

Aims. Understanding of open fracture management is skewed due to reliance on small-number lower limb, specialist unit reports and large, unfocused registry data collections. To address this, we carried out the Open Fracture Patient Evaluation Nationwide (OPEN) study, and report the demographic details and the initial steps of care for patients admitted with open fractures in the UK. Methods. Any patient admitted to hospital with an open fracture between 1 June 2021 and 30 September 2021 was included, excluding phalanges and isolated hand injuries. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture. Demographic details, injury, fracture classification, and patient dispersal were detailed. Results. In total, 1,175 patients (median age 47 years (interquartile range (IQR) 29 to 65), 61.0% male (n = 717)) were admitted across 51 sites. A total of 546 patients (47.1%) were employed, 5.4% (n = 63) were diabetic, and 28.8% (n = 335) were smokers. In total, 29.0% of patients (n = 341) had more than one injury and 4.8% (n = 56) had two or more open fractures, while 51.3% of fractures (n = 637) occurred in the lower leg. Fractures sustained in vehicle incidents and collisions are common (38.8%; n = 455) and typically seen in younger patients. A simple fall (35.0%; n = 410) is common in older people. Overall, 69.8% (n = 786) of patients were admitted directly to an orthoplastic centre, 23.0% (n = 259) were transferred to an orthoplastic centre after initial management elsewhere, and 7.2% were managed outwith specialist units (n = 81). Conclusion. This study describes the epidemiology of open fractures in the UK. For a decade, orthopaedic surgeons have been practicing in a guideline-driven, network system without understanding the patient features, injury characteristics, or dispersal processes of the wider population. This work will inform care pathways as the UK looks to the future of trauma networks and guidelines, and how to optimize care for patients with open fractures. Cite this article: Bone Jt Open 2022;3(10):746–752

Aims. Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study. Methods. In vitro cultured human normal chondrocyte C28/I2 was exposed to interleukin (IL)-1β to mimic the microenvironment of OA. The expression of circSCAPER, microRNA (miR)-140-3p, and enhancer of zeste homolog 2 (EZH2) was detected using quantitative real-time polymerase chain reaction and Western blot assays. The extracellular matrix (ECM) degradation, proliferation, and apoptosis of chondrocytes were determined using Western blot, cell counting kit-8, and flow cytometry assays. Targeted relationships were predicted by bioinformatic analysis and verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein were detected using Western blot assays. Results. CircSCAPER was highly expressed in OA cartilage tissues and IL-1β-induced chondrocytes. Knockdown of circSCAPER reduced IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes. Mechanistically, circSCAPER directly bound to miR-140-3p, and miR-140-3p inhibition reversed the effects of circSCAPER knockdown on IL-1β-induced chondrocytes. miR-140-3p was verified to target EZH2, and overexpression of miR-140-3p protected chondrocytes against IL-1β-induced dysfunction via targeting EZH2. Additionally, we confirmed that circSCAPER could regulate EZH2 through sponging miR-140-3p, and the circSCAPER/miR-140-3p/EZH2 axis could activate the PI3K/AKT pathway. Conclusion. CircSCAPER promoted IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes via regulating miR-140-3p/EZH2 axis, which gained a new insight into the pathogenesis of OA. Cite this article: Bone Joint Res 2022;11(2):61–72

Aims. Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. Methods. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. Results. Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. Conclusion. This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening. Cite this article: Bone Joint Res 2020;9(8):501–514

Aims. Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results. Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion. Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688

Aims. The primary aim of this prospective, multicentre study is to describe the rates of returning to golf following hip, knee, ankle, and shoulder arthroplasty in an active golfing population. Secondary aims will include determining the timing of return to golf, changes in ability, handicap, and mobility, and assessing joint-specific and health-related outcomes following surgery. Methods. This is a multicentre, prospective, longitudinal study between the Hospital for Special Surgery, (New York City, New York, USA) and Edinburgh Orthopaedics, Royal Infirmary of Edinburgh, (Edinburgh, UK). Both centres are high-volume arthroplasty centres, specializing in upper and lower limb arthroplasty. Patients undergoing hip, knee, ankle, or shoulder arthroplasty at either centre, and who report being golfers prior to arthroplasty, will be included. Patient-reported outcome measures will be obtained at six weeks, three months, six months, and 12 months. A two-year period of recruitment will be undertaken of arthroplasty patients at both sites. Conclusion. The results of this prospective study will provide clinicians with accurate data to deliver to patients with regard to the likelihood of return to golf and timing of when they can expect to return to golf following their hip, knee, ankle, or shoulder arthroplasty, as well as their joint-specific functional outcomes. This will help patients to manage their postoperative expectations and plan their postoperative recovery pathway. Cite this article: Bone Jt Open 2023;4(7):490–495

Aims. In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism. Methods. SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated. Results. Interleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs. Conclusion. HDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis. Cite this article: Bone Joint Res 2022;11(1):40–48

Aims. With resumption of elective spine surgery services in the UK following the first wave of the COVID-19 pandemic, we conducted a multicentre British Association of Spine Surgeons (BASS) collaborative study to examine the complications and deaths due to COVID-19 at the recovery phase of the pandemic. The aim was to analyze the safety of elective spinal surgery during the pandemic. Methods. A prospective observational study was conducted from eight spinal centres for the first month of operating following restoration of elective spine surgery in each individual unit. Primary outcome measure was the 30-day postoperative COVID-19 infection rate. Secondary outcomes analyzed were the 30-day mortality rate, surgical adverse events, medical complications, and length of inpatient stay. Results. In all, 257 patients (128 males) with a median age of 54 years (2 to 88) formed the study cohort. The mean number of procedures performed from each unit was 32 (16 to 101), with 118 procedures (46%) done as category three prioritization level. The majority of patients (87%) were low-medium “risk stratification” category and the mean length of hospital stay was 5.2 days. None of the patients were diagnosed with COVID-19 infection, nor was there any mortality related to COVID-19 during the 30-day follow-up period, with 25 patients (10%) having been tested for symptoms. Overall, 32 patients (12%) developed a total of 34 complications, with the majority (19/34) being grade 1 to 2 Clavien-Dindo classification of surgical complications. No patient required postoperative care in an intensive care setting for any unexpected complication. Conclusion. This study shows that safe and effective planned spinal surgical services can be restored avoiding viral transmission, with diligent adherence to national guidelines and COVID-19-secure pathways tailored according to the resources of the individual spinal units. Cite this article: Bone Jt Open 2021;2(12):1096–1101

Aims. The aim of this study is to assess the impact of a pilot enhanced recovery after surgery (ERAS) programme on length of stay (LOS) and post-discharge resource usage via service evaluation and cost analysis. Methods. Between May and December 2019, 100 patients requiring hip or knee arthroplasty were enrolled with the intention that each would have a preadmission discharge plan, a preoperative education class with nominated helper, a day of surgery admission and mobilization, a day one discharge, and access to a 24/7 dedicated helpline. Each was matched with a patient under the pre-existing pathway from the previous year. Results. Mean LOS for ERAS patients was 1.59 days (95% confidence interval (CI) 1.14 to 2.04), significantly less than that of the matched cohort (3.01 days; 95% CI 2.56 to 3.46). There were no significant differences in readmission rates for ERAS patients at both 30 and 90 days (six vs four readmissions at 30 days, and nine vs four at 90 days). Despite matching, there were significantly more American Society of Anesthesiologists (ASA) grade 3 patients in the ERAS cohort. There was a mean cost saving of £757.26 (95% CI £-1,200.96 to £-313.56) per patient. This is despite small increases in postoperative resource usage in the ERAS patients. Conclusion. ERAS represents a safe and effective means of reducing LOS in primary joint arthroplasty patients. Implementation of ERAS principles has potential financial savings and could increase patient throughput without compromising care. In elective care, a preadmission discharge plan is key. Cite this article: Bone Jt Open 2021;2(11):966–973

Aims. The Uppföljningsprogram för cerebral pares (CPUP) Hip Score distinguishes between children with cerebral palsy (CP) at different levels of risk for displacement of the hip. The score was constructed using data from Swedish children with CP, but has not been confirmed in any other population. The aim of this study was to determine the calibration and discriminatory accuracy of this score in children with CP in Scotland. Methods. This was a total population-based study of children registered with the Cerebral Palsy Integrated Pathway Scotland. Displacement of the hip was defined as a migration percentage (MP) of > 40%. Inclusion criteria were children in Gross Motor Function Classification System (GMFCS) levels III to V. The calibration slope was estimated and Kaplan-Meier curves produced for five strata of CPUP scores to compare the observed with the predicted risk of displacement of the hip at five years. For discriminatory accuracy, the time-dependent area under the receiver operating characteristic curve (AUC) was estimated. In order to analyze differences in the performance of the score between cohorts, score weights, and subsequently the AUC, were re-estimated using the variables of the original score: the child’s age at the first examination, GMFCS level, head shaft angle, and MP of the worst hip in a logistic regression with imputation of outcomes for those with incomplete follow-up. Results. The discriminatory accuracy of the score in the new population of 367 children was high (AUC 0.78 (95% confidence interval (CI) 0.71 to 0.86)). The calibration of the score was insufficient (slope 0.48 (95% CI 0.31 to 0.65)), and the absolute risks of displacement of the hip in this population were overestimated. The AUC increased with re-estimated weights (0.85 (95% CI 0.79 to 0.91)). Conclusion. The CPUP Hip Score had a high ability to discriminate between children at different levels of risk for displacement of the hip. The score overestimated the absolute risks of displacement in this population, which may have resulted from differences in the way children were initially registered in the two programmes. The results are promising, but the score weights may need re-estimation before its clinical application in Scotland. Cite this article: Bone Joint J 2022;104-B(5):640–644

Aims. This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results. We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion. The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article:Bone Joint Res. 2020;9(3):90–98

Introduction. Virtual fracture clinics (VFCs) are being increasingly used to offer safe and efficient orthopaedic review without the requirement for face-to-face contact. With the onset of the COVID-19 pandemic, we sought to develop an online referral pathway that would allow us to provide definitive orthopaedic management plans and reduce face-to-face contact at the fracture clinics. Methods. All patients presenting to the emergency department from 21March 2020 with a musculoskeletal injury or potential musculoskeletal infection deemed to require orthopaedic input were discussed using a secure messaging app. A definitive management plan was communicated by an on-call senior orthopaedic decision-maker. We analyzed the time to decision, if further information was needed, and the referral outcome. An analysis of the orthopaedic referrals for the same period in 2019 was also performed as a comparison. Results. During the study period, 295 patients with mean age of 7.93 years (standard error (SE) 0.24) were reviewed. Of these, 25 (9.8%) were admitted, 17 (5.8%) were advised to return for planned surgical intervention, 105 (35.6%) were referred to a face-to-face fracture clinic, 137 (46.4%) were discharged with no follow-up, and seven (2.4%) were referred to other services. The mean time to decision was 20.14 minutes (SE 1.73). There was a significant difference in the time to decision between patients referred to fracture clinic and patients discharged (mean 25.25 minutes (SE 3.18) vs mean 2.63 (SE 1.42); p < 0.005). There were a total of 295 referrals to the fracture clinic for the same period in 2019 with a further 44 emergency admissions. There was a statistically significant difference in the weekly referrals after being triaged by the VFC (mean 59 (SE 5.15) vs mean 21 (SE 2.17); p < 0.001). Conclusion. The use of an electronic referral pathway to deliver a point of care virtual fracture clinic allowed for efficient use of scarce resources and definitive management plan delivery in a safe manner. Cite this article: Bone Joint Open 2020;1-6:293–301