Aims. The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. Methods. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis. Results. This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128). Conclusion. In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results. Cite this article: Bone Jt Open 2024;5(3):210–217

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

Aims. The Birmingham Hip Resurfacing (BHR) was introduced in 1997 to address the needs of young active patients using a historically proven large-diameter metal-on-metal (MoM) bearing. A single designer surgeon’s consecutive series of 130 patients (144 hips) was previously reported at five and ten years, reporting three and ten failures, respectively. The aim of this study was to extend the follow-up of this original cohort at 25 years. Methods. The study extends the reporting on the first consecutive 144 resurfacing procedures in 130 patients for all indications. All operations were undertaken between August 1997 and May 1998. The mean age at operation was 52.1 years (SD 9.93; 17 to 76), and included 37 female patients (28.5%). Failure was defined as revision of either component for any reason. Kaplan-Meier survival analysis was performed. Routine follow-up with serum metal ion levels, radiographs, and Oxford Hip Scores (OHSs) was undertaken. Results. Overall implant survival was 83.50% (95% confidence interval (CI) 0.79 to 0.90) at 25 years, and the number at risk was 79. Survival in male patients at 25 years was 89.5% (95% CI 0.83 to 0.96) compared to 66.9% for female patients (95% CI 0.51 to 0.83). Ten additional failures occurred in the period of ten to 25 years. These involved an adverse reaction to metal debris in four patients, a periprosthetic femoral neck fracture affecting five patients, and aseptic loosening in one patient. The median chromium levels were 49.50 nmol/l (interquartile range (IQR) 34 to 70), and the median cobalt serum levels were 42 nmol/l (IQR 24.50 to 71.25). The median OHS at last follow-up was 35 (IQR 10 to 48). During the 25-year study period, 29 patients died. Patient survival at 25 years was 75.10% (95% CI 0.67 to 0.83). Conclusion. This study demonstrates that MoM hip resurfacing using the BHR provides a durable alternative to total hip arthroplasty (THA), particularly in younger male patients with osteoarthritis wishing to maintain a high level of function. These results compare favourably to the best results for THAs. Cite this article: Bone Joint J 2024;106-B(6):540–547

Aims. The number of revision total ankle arthroplasties (TAAs) which are undertaken is increasing. Few studies have reported the survival after this procedure. The primary aim of this study was to analyze the survival of revision ankle arthroplasties using large datasets. Secondary aims were to summarize the demographics of the patients, the indications for revision TAA, further operations, and predictors of survival. Methods. The study combined data from the National Joint Registry and NHS Digital to report the survival of revision TAA. We have previously reported the failure rates and risk factors for failure after TAA, and the outcome of fusion after a failed TAA, using the same methodology. Survival was assessed using life tables and Kaplan Meier graphs. Cox proportional hazards regression models were fitted to compare failure rates. Results. A total of 228 patients underwent revision TAA. The mean follow-up was 2.6 years (SD 2.0). The mean time between the initial procedure and revision was 2.3 years (SD 1.8). The most commonly used implant was the Inbone which was used in 81 patients. A total of 29 (12.7%) failed; nine (3.9%) patients underwent a further revision, 19 (8.3%) underwent a fusion, and one (0.4%) had an amputation. The rate of survival was 95.4% (95% confidence interval (CI) 91.6 to 97.5) at one year, 87.7% (95% CI 81.9 to 91.7; n = 124) at three years and 77.5% (95% CI 66.9 to 85.0; n = 57) at five years. Revision-specific implants had a better survival than when primary implants were used at revision. A total of 50 patients (21.9%) had further surgery; 19 (8.3%) underwent reoperation in the first 12 months. Cox regression models were prepared. In crude analysis the only significant risk factors for failure were the use of cement (hazard ratio (HR) 3.02 (95% CI 1.13 to 8.09)) and the time since the primary procedure (HR 0.67 (95% CI 0.47 to 0.97)). No risk factors for failure were identified in multivariable Cox regression modelling. Conclusion. Revision TAAs have good medium term survival and low rates of further surgery. New modular revision implants appear to have improved the survival compared with the use of traditional primary implants at revision. Cite this article: Bone Joint J 2023;105-B(11):1184–1188

Aims. Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results. The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion. Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents. Cite this article: Bone Joint J 2023;105-B(11):1216–1225

Aims. This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. Methods. This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results. The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion. State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E. Cite this article: Bone Joint J 2024;106-B(2):203–211

Aims. Implant failure has become more common as the number of primary total ankle arthroplasties (TAAs) performed has increased. Although revision arthroplasty has gained attention for functional preservation, the long-term results remain unclear. This study aimed to assess the long-term outcomes of revision TAA using a mobile-bearing prosthesis in a considerably large cohort; the risk factors for failure were also determined. Methods. This single-centre retrospective cohort study included 116 patients (117 ankles) who underwent revision TAA for failed primary TAA between July 2000 and March 2010. Survival analysis and risk factor assessment were performed, and clinical performance and patient satisfaction were evaluated preoperatively and at last follow-up. Results. The mean duration from initial revision TAA to last follow-up was 15.0 years (SD 3.0; 11.2 to 20.5). The cumulative survival rates of the revised ankles were 81% (95% confidence interval (CI) 74% to 88%), 74% (65% to 82%), and 70% (61% to 79%) at five, ten, and 15 years, respectively. Comorbidities prior to primary TAA, aseptic loosening, instability, or grafting of cysts were found to be the most common risk factors for secondary revision. The median value for preoperative pain, as assessed using the visual analogue scale, declined from 6 (interquartile range (IQR) 5 to 8) to 2 (IQR 0 to 5) (p < 0.001) and the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from 43 (SD 17) preoperatively to 70 (SD 20) (p < 0.001) at last follow-up. Conclusion. Revision TAA offers acceptable survival rates after 15 years; it therefore offers a valuable option for treatment of implant failure in carefully selected cases. Although patient-reported outcomes improve substantially, the degree of improvement reported following primary TAA is not achieved. Cite this article: Bone Joint J 2024;106-B(1):46–52

Aims. The aim of this study was to report the long-term follow-up of cemented short Exeter femoral components when used in primary total hip arthroplasty (THA). Methods. We included all primary 394 THAs with a cemented short Exeter femoral component (≤ 125 mm) used in our tertiary referral centre between October 1993 and December 2021. A total of 83 patients (21%) were male. The median age of the patients at the time of surgery was 42 years (interquartile range (IQR) 30 to 55). The main indication for THA was a childhood hip disease (202; 51%). The median follow-up was 6.7 years (IQR 3.1 to 11.0). Kaplan-Meier survival analyses were performed to determine the rates of survival with femoral revision for any indication, for septic loosening, for fracture of the femoral component and for aseptic loosening as endpoints. The indications for revision were evaluated. Fractures of the femoral component were described in detail. Results. The 20-year rate of survival was 85.4% (95% confidence interval (CI) 73.9 to 92.0) with revision for any indication, 96.2% (95% CI 90.5 to 98.5) with revision for septic loosening and 92.7% (95% CI 78.5 to 97.6) with revision for fracture of the femoral component. No femoral components were revised for aseptic loosening. There were 21 revisions of the femoral component; most (seven) as part of a two-stage management of infection. Fracture of the femoral component occurred in four THAs (1.0%) at 6.6, 11.6, 16.5, and 18.2 years of follow-up, respectively. Three of these were transverse fractures and occurred at the level of the lesser trochanter. In one THA, there was a fracture of the neck of the component. Conclusion. THAs using cemented short Exeter femoral components showed acceptable rates of survival of the femoral component at long-term follow-up, in this young cohort of patients. Although fracture is a rare complication of these components, surgeons should be aware of their incidence and possible risk factors. Cite this article: Bone Joint J 2024;106-B(3 Supple A):137–142

Aims. The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry. Methods. All TEAs recorded in the Dutch national registry between 2014 and 2020 were included. The Kaplan-Meier method was used for survival analysis, and a logistic regression model was used to assess the factors associated with revision. Results. A total of 514 TEAs were included, of which 35 were revised. The five-year implant survival was 91%. Male sex, a higher BMI, and previous surgery to the same elbow showed a statistically significant association with revision (p < 0.036). Of the 35 revised implants, ten (29%) underwent a second revision. Conclusion. This study reports a five-year implant survival of TEA of 91%. Patient factors associated with revision are defined and can be used to optimize informed consent and shared decision-making. There was a high rate of secondary revisions. Cite this article: Bone Jt Open 2023;4(2):110–119

Aims. The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this. Methods. This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression. Results. A total of 164 patients were included with a median survival time of 1.6 years (interquartile range 0.5 to 3.1) after surgery. On multivariable analysis, a higher American Society of Anesthesiologists grade (p < 0.001), a high white cell count (p = 0.002), hyponatraemia (p = 0.001), a preoperative resting heart rate of > 100 bpm (p = 0.052), and the type of primary cancer (p = 0.026) remained significant predictors of reduced survival time. The predictive model developed showed good discrimination and calibration to predict both six- and 12-month survival in patients with metastatic bone disease. Conclusion. In addition to surgical and oncological factors, the level of comorbidity and physiological state of the patient has a significant impact on survival in patients with metastatic bone disease. These factors should be considered when assessing the appropriateness of surgical intervention. This is the first study to examine other patient factors alongside surgical and oncological data to identify a relationship between these and survival. Cite this article: Bone Joint J 2021;103-B(11):1725–1730

Aims. Our primary aim was to assess reoperation-free survival at one year after the index injury in patients aged ≥ 75 years treated with internal fixation (IF) or arthroplasty for undisplaced femoral neck fractures (uFNFs). Secondary outcomes were reoperations and mortality analyzed separately. Methods. We retrieved data on all patients aged ≥ 75 years with an uFNF registered in the Swedish Fracture Register from 2011 to 2018. The database was linked to the Swedish Arthroplasty Register and the National Patient Register to obtain information on comorbidity, mortality, and reoperations. Our primary outcome, reoperation, or death at one year was analyzed using restricted mean survival time, which gives the mean time to either event for each group separately. Results. Overall, 3,909 patients presenting with uFNFs were included. Of these patients, 3,604 were treated with IF and 305 with primary arthroplasty. There were no relevant differences in age, sex, or comorbidities between groups. In the IF group 58% received cannulated screws and 39% hook pins. In the arthroplasty group 81% were treated with hemiarthroplasty and 19% with total hip arthroplasty. At one year, 32% were dead or had been reoperated in both groups. The reoperation-free survival time over one year of follow-up was 288 days (95% confidence interval (CI) 284 to 292) in the IF group and 279 days (95% CI 264 to 295) in the arthroplasty group, with p = 0.305 for the difference. Mortality was 26% in the IF group and 31% in the arthroplasty group at one year. Reoperation rates were 7.1% in the IF group and 2.3% in the arthroplasty group. Conclusion. In older patients with a uFNF, reoperation-free survival at one year seems similar, regardless of whether IF or arthroplasty is the primary surgery. However, this comparison depends on the choice of follow-up time in that reoperations were more common after IF. In contrast, we found more early deaths after arthroplasty. Our study calls for a randomized trial comparing these two methods. Cite this article: Bone Jt Open 2024;5(2):86–92

Aims. The aim of this study was to investigate the distribution of phenotypes in Asian patients with end-stage osteoarthritis (OA) and assess whether the phenotype affected the clinical outcome and survival of mechanically aligned total knee arthroplasty (TKA). We also compared the survival of the group in which the phenotype unintentionally remained unchanged with those in which it was corrected to neutral. Methods. The study involved 945 TKAs, which were performed in 641 patients with primary OA, between January 2000 and January 2009. These were classified into 12 phenotypes based on the combined assessment of four categories of the arithmetic hip-knee-ankle angle and three categories of actual joint line obliquity. The rates of survival were analyzed using Kaplan-Meier methods and the log-rank test. The Hospital for Special Surgery score and survival of each phenotype were compared with those of the reference phenotype with neutral alignment and a parallel joint line. We also compared long-term survival between the unchanged phenotype group and the corrected to neutral alignment-parallel joint line group in patients with Type IV-b (mild to moderate varus alignment-parallel joint line) phenotype. Results. The most common phenotype was Type I-b (mild to moderate varus alignment-medial joint line; 27.1% (n = 256)), followed by Type IV-b (23.2%; n = 219). There was no significant difference in the clinical outcomes and long-term survival between the groups. In Type IV-b phenotypes, the neutrally corrected group showed higher 15-year survival compared with the unchanged-phenotype group (94.9% (95% confidence interval (CI) 92.0 to 97.8) vs 74.2% (95% CI 98.0 to 100); p = 0.020). Conclusion. Constitutional varus was confirmed in more than half of these patients. Mechanically aligned TKA can achieve consistent clinical outcomes and long-term survival, regardless of the patient’s phenotype. The neutrally corrected group had better long-term survival compared with the unchanged phenotype group. Cite this article: Bone Joint J 2024;106-B(5):460–467

Aims. Several different designs of hemiarthroplasty are used to treat intracapsular fractures of the proximal femur, with large variations in costs. No clinical benefit of modular over monoblock designs has been reported in the literature. Long-term data are lacking. The aim of this study was to report the ten-year implant survival of commonly used designs of hemiarthroplasty. Methods. Patients recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) between 1 September 1999 and 31 December 2020 who underwent hemiarthroplasty for the treatment of a hip fracture with the following implants were included: a cemented monoblock Exeter Trauma Stem (ETS), cemented Exeter V40 with a bipolar head, a monoblock Thompsons prosthesis (Cobalt/Chromium or Titanium), and an Exeter V40 with a Unitrax head. Overall and age-defined cumulative revision rates were compared over the ten years following surgery. Results. A total of 41,949 hemiarthroplasties were included. Exeter V40 with a Unitrax head was the most commonly used (n = 20,707, 49.4%). The overall rate of revision was small. A total of 28,201 patients (67.2%) were aged > 80 years. There were no significant differences in revision rates across all designs of hemiarthroplasty in patients of this age at any time. The revision rates for all designs were < 3.5%, three years postoperatively. At subsequent times the ETS and Exeter V40 with a bipolar head performed well in all age groups. The unadjusted ten-year mortality rate for the whole cohort was 82.2%. Conclusion. There was no difference in implant survival between all the designs of hemiarthroplasty in the first three years following surgery, supporting the selection of a cost-effective design of hemiarthroplasty for most patients with an intracapsular fracture of the hip, as determined by local availability and costs. Beyond this, the ETS and Exeter bipolar designs performed well in all age groups. Cite this article: Bone Joint J 2023;105-B(8):864–871

Aims. The aim of this study was to assess the clinical and radiological outcomes of an antiprotrusio acetabular cage (APC) when used in the surgical treatment of periacetabular bone metastases. Methods. This retrospective cohort study using a prospectively collected database involved 56 patients who underwent acetabular reconstruction for periacetabular bone metastases or haematological malignancy using a single APC between January 2009 and 2020. The mean follow-up was 20 months (1 to 143). The primary outcome measure was implant survival. Postoperative radiographs were analyzed for loosening and failure. Patient and implant survival were assessed using a competing risk analysis. Secondary parameters included primary malignancy, oncological treatment, surgical factors, length of stay in hospital, and postoperative complications. Results. A total of 33 patients (59%) died during the study period at a mean of 15 months postoperatively (1 to 63). No patient had radiological evidence of loosening or failure. Acetabular component survival was 100%. Three patients (5.4%) had further surgery; one (1.8%) underwent revision of the femoral component for dislocation, one required debridement with implant retention for periprosthetic joint infection, and one required closed reduction for dislocation. Using death as a competing risk, at 100 months, the probability of revision was 0.036 and the risk of death was 0.84. Conclusion. With appropriate patient selection, the antiprotrusio cage offers good implant survival, with a reasonable perioperative complication rate in this high-risk group of patients when managing metastatic disease or haematological malignancy around the acetabulum. Cite this article: Bone Joint J 2022;104-B(4):504–509

Aims. To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis. Methods. Empty adenovirus (EP) and a HDAC4 overexpression adenovirus were transfected into cultured human chondrocytes. The cell survival rate was examined by real-time cell analysis (RTCA) and EdU and flow cytometry assays. Cell biofunction was detected by Western blotting. The expression profiles of messenger RNAs (mRNAs) in the EP and HDAC4 transfection groups were assessed using whole-transcriptome sequencing (RNA-seq). Volcano plot, Gene Ontology, and pathway analyses were performed to identify differentially expressed genes (DEGs). For verification of the results, the A289E/S246/467/632 A sites of HDAC4 were mutated to enhance the function of HDAC4 by increasing HDAC4 expression in the nucleus. RNA-seq was performed to identify the molecular mechanism of HDAC4 in chondrocytes. Finally, the top ten DEGs associated with ribosomes were verified by quantitative polymerase chain reaction (QPCR) in chondrocytes, and the top gene was verified both in vitro and in vivo. Results. HDAC4 markedly improved the survival rate and biofunction of chondrocytes. RNA-seq analysis of the EP and HDAC4 groups showed that HDAC4 induced 2,668 significant gene expression changes in chondrocytes (1,483 genes upregulated and 1,185 genes downregulated, p < 0.05), and ribosomes exhibited especially large increases. The results were confirmed by RNA-seq of the EP versus mutated HDAC4 groups and the validations in vitro and in vivo. Conclusion. The enhanced ribosome pathway plays a key role in the mechanism by which HDAC4 improves the survival rate and biofunction of chondrocytes. Cite this article: Bone Joint Res 2023;12(7):433–446

Aims. The aim of this study to compare 30-day survival and recovery of mobility between patients mobilized early (on the day of, or day after surgery for a hip fracture) and patients mobilized late (two days or more after surgery), and to determine whether the presence of dementia influences the association between the timing of mobilization, 30-day survival, and recovery. Methods. Analysis of the National Hip Fracture Database and hospital records for 126,897 patients aged ≥ 60 years who underwent surgery for a hip fracture in England and Wales between 2014 and 2016. Using logistic regression, we adjusted for covariates with a propensity score to estimate the association between the timing of mobilization, survival, and recovery of walking ability. Results. A total of 99,667 patients (79%) mobilized early. Among those mobilized early compared to those mobilized late, the weighted odds ratio of survival was 1.92 (95% confidence interval (CI) 1.80 to 2.05), of recovering outdoor ambulation was 1.25 (95% CI 1.03 to 1.51), and of recovering indoor ambulation was 1.53 (95% CI 1.32 to 1.78) by 30 days. The weighted probabilities of survival at 30 days post-admission were 95.9% (95% CI 95.7% to 96.0%) for those who mobilized early and 92.4% (95% CI 92.0% to 92.8%) for those who mobilized late. The weighted probabilities of regaining the ability to walk outdoors were 9.7% (95% CI 9.2% to 10.2%) and indoors 81.2% (95% CI 80.0% to 82.4%), for those who mobilized early, and 7.9% (95% CI 6.6% to 9.2%) and 73.8% (95% CI 71.3% to 76.2%), respectively, for those who mobilized late. Patients with dementia were less likely to mobilize early despite observed associations with survival and ambulation recovery for those with and without dementia. Conclusion. Early mobilization is associated with survival and recovery for patients (with and without dementia) after hip fracture. Early mobilization should be incorporated as a measured indicator of quality. Reasons for failure to mobilize early should also be recorded to inform quality improvement initiatives. Cite this article: Bone Joint J 2021;103-B(7):1317–1324

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

Aims. Surgical intervention in patients with bone metastases from breast cancer is dependent on the estimated survival of the patient. The purpose of this paper was to identify factors that would predict survival so that specific decisions could be made in terms of surgical (or non-surgical) management. . Methods. The records of 113 consecutive patients (112 women) with metastatic breast cancer were analysed for clinical, radiological, serological and surgical outcomes. Their median age was 61 years (interquartile range 29 to 90) and the median duration of follow-up was 1.6 years (standard deviation (. sd. ) 1.9, 95% confidence interval (CI) 0 to 5.9). The cumulative one- and five-year rates of survival were 68% and 16% (95% Cl 60 to 77 and 95% CI 10 to 26, respectively). . Results. Linear discriminant analysis identified a ‘quadruple A’ predictor of survival by reclassifying the sum of the albumin, adjusted calcium, alkaline phosphatase and age covariates each multiplied by a determined factor. The accuracy of this ‘quadruple A’ predictor was 90% with a sensitivity of 100% and a specificity of 88%. A receiver operating characteristic (ROC) curve revealed an area under the curve of 79%. Survival analysis for this ‘quadruple A’ predictor (<  = one or > one year survival) was statistically significant using the log rank test (p = 0.0004) and Cox proportional hazard (p = 0.001). Multivariate analysis showed the 'quadruple A' predictor to be the only independent predictor of survival (p = 0.01). . Discussion. The 'quadruple A' predictor, together with other positive predictors of survival, can be used by oncologists, orthopaedic and breast surgeons to estimate survival and therefore guide management. Cite this article: Bone Joint J 2016;98-B:266–70

Aims. Meniscal allograft transplantation (MAT) for patients with symptomatic meniscal loss has demonstrated good clinical results and survivorship. Factors that affect both functional outcome and survivorship have been reported in the literature. These are typically single-centre case series with relatively small numbers and conflicting results. Our aim was to describe an international, two-centre case series, and identify factors that affect both functional outcome and survival. Methods. We report factors that affect outcome on 526 patients undergoing MAT across two sites (one in the UK and one in Italy). Outcomes of interest were the Knee injury and Osteoarthritis Outcome Score four (KOOS4) at two years and failure rates. We performed multiple regression analysis to examine for factors affecting KOOS, and Cox proportional hazards models for survivorship. Results. Our results indicate that baseline KOOS4 score affects functional outcome at two years, but no other included factors were significantly related to functional outcome. The only factor that affected failure rate was the presence of cartilage lesions down to bone on both the femur and tibia, decreasing the five-year survivorship from 95% (95% confidence interval (CI) 91 to 99) to 84% (95% CI 74 to 94). Conclusion. To our knowledge, this is the largest international cohort reporting on MAT. Our results indicate that factors such as age, BMI, and cartilage lesions down to bone on both the femur and tibia of the affected compartment should not present barriers to offering MAT. Baseline KOOS4 score and the presence of bone-on-bone arthritis can be used to help counsel patients regarding the expected risks and rewards of surgery. Cite this article: Bone Joint J 2022;104-B(6):657–662

Aims. Urgent referral to a specialist centre for patients with a soft-tissue sarcoma (STS) has been recommended by the National Institute for Health and Care Excellence (NICE) in the UK since 2006. However, the impact of this recommendation on the prognosis for these patients remains unclear. We aimed to determine the impact of the NICE guidelines on the disease-specific survival (DSS) of patients with an STS. Methods. A total of 2,427 patients with an STS referred to a supraregional centre in the ten-year periods before (n = 1,386) and after (n = 1,041) the issue of the NICE guidelines were evaluated. Results. The mean size of the tumour was significantly smaller at the time of diagnosis (10.3 cm (SD 6.5) vs 9.1 cm (SD 6.2); p < 0.001) and the number of patients who had undergone an inadvertent excision significantly decreased (28% (n = 389) vs 20% (n = 204); p < 0.001) following the introduction of the NICE guidelines. The five-year DSS was 63% in the pre-NICE and 71% in post-NICE groups (p < 0.001). The improved survival was more significant for those with a high-grade tumour (pre-NICE, 48%; post-NICE, 68%; p < 0.001). In those with a high-grade tumour, the mean size of the tumour (11.6 cm (SD 6.2) vs 9.6 cm (SD 5.8); p < 0.001) and the number of patients with metastasis at the time of diagnosis (15% (n = 124 vs 10% (n = 80); p = 0.007) significantly decreased in the post-NICE group. Conclusion. An improvement in survival was seen after the introduction of the NICE guidelines, especially in patients with a high-grade STS. More patients were referred at an earlier stage, indicating a clearer pathway after the issue of national policy for the management of STSs in the UK. Cite this article: Bone Joint J 2021;103-B(3):569–577