Aims. The escalating demand for medical resources to address spinal diseases as society ages is an issue that requires careful evaluation. However, few studies have examined trends in spinal surgery, especially unscheduled hospitalizations or surgeries performed after hours, through large databases. Our study aimed to determine national trends in the number of spine surgeries in Japan. We also aimed to identify trends in after-hours surgeries and unscheduled hospitalizations and their impact on complications and costs. Methods. We retrospectively investigated data extracted from the Diagnosis Procedure Combination database, a representative inpatient database in Japan. The data from April 2010 to March 2020 were used for this study. We included all patients who had undergone any combination of laminectomy, laminoplasty, discectomy, and/or spinal arthrodesis. Results. This investigation included 739,474 spinal surgeries and 739,215 hospitalizations in Japan. There was an average annual increase of 4.6% in the number of spinal surgeries. Scheduled hospitalizations increased by 3.7% per year while unscheduled hospitalizations increased by 11.8% per year. In-hours surgeries increased by 4.5% per year while after-hours surgeries increased by 9.9% per year. Complication rates and costs increased for both after-hours surgery and unscheduled hospitalizations, in comparison to their respective counterparts of in-hours surgery and scheduled hospitalizations. Conclusion. This study provides important insights for those interested in improving spine care in an ageing society. The swift surge in after-hours spinal surgeries and unscheduled hospitalizations highlights that the medical needs of an increasing number of patients due to an ageing society are outpacing the capacity of existing medical resources. Cite this article: Bone Jt Open 2024;5(8):662–670

Aims. Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123

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

Aims. The aim of this study was to characterize the influence of social deprivation on the rate of complications, readmissions, and revisions following primary total shoulder arthroplasty (TSA), using the Social Deprivation Index (SDI). The SDI is a composite measurement, in percentages, of seven demographic characteristics: living in poverty, with < 12 years of education, single-parent households, living in rented or overcrowded housing, households without a car, and unemployed adults aged < 65 years. Methods. Patients aged ≥ 40 years, who underwent primary TSA between 2011 and 2017, were identified using International Classification of Diseases (ICD)-9 Clinical Modification and ICD-10 procedure codes for TSA in the New York Statewide Planning and Research Cooperative System database. Readmission, reoperation, and other complications were analyzed using multivariable Cox proportional hazards regression controlling for SDI, age, ethnicity, insurance status, and Charlson Comorbidity Index. Results. A total of 17,698 patients with a mean age of 69 years (SD 9.6), of whom 57.7% were female, underwent TSA during this time and 4,020 (22.7%) had at least one complication. A total of 8,113 patients (45.8%) had at least one comorbidity, and the median SDI in those who developed complications 12 months postoperatively was significantly greater than in those without a complication (33 vs 38; p < 0.001). Patients from areas with higher deprivation had increased one-, three-, and 12-month rates of readmission, dislocation, humeral fracture, urinary tract infection, deep vein thrombosis, and wound complications, as well as a higher three-month rate of pulmonary embolism (all p < 0.05). Conclusion. Beyond medical complications, we found that patients with increased social deprivation had higher rates of humeral fracture and dislocation following primary TSA. The large sample size of this study, and the outcomes that were measured, add to the literature greatly in comparison with other large database studies involving TSA. These findings allow orthopaedic surgeons practising in under-served or low-volume areas to identify patients who may be at greater risk of developing complications. Cite this article: Bone Joint J 2024;106-B(2):174–181

Aims. This study aimed to evaluate the relationship between hip shape and mid-term function in Perthes’ disease. It also explored whether the modified three-group Stulberg classification can offer similar prognostic information to the five-group system. Methods. A total of 136 individuals aged 12 years or older who had Perthes’ disease in childhood completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility score (function), Nonarthritic Hip Score (NAHS) (function), EuroQol five-dimension five-level questionnaire (EQ-5D-5L) score (quality of life), and the numeric rating scale for pain (NRS). The Stulberg class of the participants’ hip radiographs were evaluated by three fellowship-trained paediatric orthopaedic surgeons. Hip shape and Stulberg class were compared to PROM scores. Results. A spherical hip was associated with the highest function and quality of life, and lowest pain. Conversely, aspherical hips exhibited the lowest functional scores and highest pain. The association between worsening Stulberg class (i.e. greater deviation from sphericity) and worse outcome persisted after adjustment for age and sex in relation to PROMIS (predicted mean difference -1.77 (95% confidence interval (CI) -2.70 to -0.83)), NAHS (-5.68 (95% CI -8.45 to -2.90)), and NRS (0.61 (95% CI 0.14 to 1.08)), but not EQ-5D-5L (-0.03 (95% CI -0.72 to 0.11)). Conclusion. Patient-reported outcomes identify lower function, quality of life, and higher pain in aspherical hips. The magnitude of symptoms deteriorated with time. Hip sphericity (i.e. the modified three-group classification of spherical, oval, and aspherical) appeared to offer similar levels of detail to the five-group Stulberg classification. Cite this article: Bone Joint J 2023;105-B(6):711–716

Aims. Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery. Methods. Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites. Results. We initially identified 4,402 clinical trials, 27 of which were eligible for inclusion and analysis, including nine shoulder surgery trials, eight knee surgery trials, two ankle surgery trials, two hand surgery trials, and six peripheral nerve graft trials. Nine of the trials were completed. We identified only one product that will be commercially available for use in knee surgery with significant mechanical load resistance. Peracetic acid and gamma irradiation were frequently used for sterilization. Conclusion. Despite the demand for decellularized tissue, few decellularized tissue products are currently commercially available, particularly for the knee joint. To be viable in orthopaedic surgery, decellularized tissue must exhibit biocompatibility and mechanical strength, and these requirements are challenging for the clinical application of decellularized tissue. However, the variety of available decellularized products has recently increased. Therefore, decellularized grafts may become a promising option in orthopaedic surgery. Cite this article: Bone Joint Res 2023;12(3):179–188

Aims. Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease. Methods. A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed. Results. A total of 161 studies were included, which covered capsule, ligaments, meniscus, skeletal muscle, synovium, and tendon in both humans and animals, and fat pad and intervertebral disc in humans only. These studies covered a wide variety of ECM features, including individual ECM components (i.e. collagens, proteoglycans, and glycoproteins), ECM architecture (i.e. collagen fibre organization and diameter), and viscoelastic properties (i.e. elastic and compressive modulus). Some ECM changes, notably calcification and the loss of collagen fibre organization, have been extensively studied across osteoarthritic tissues. However, most ECM features were only studied by one or a few papers in each tissue. When comparisons were possible, the results from animal experiments largely concurred with those from human studies, although some findings were contradictory. Conclusion. Changes in ECM composition and architecture occur throughout non-cartilage soft tissues in the osteoarthritic joint, but most of these remain poorly defined due to the low number of studies and lack of healthy comparator groups. Cite this article: Bone Joint Res 2024;13(12):703–715

Aims. Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and avascular necrosis of the humeral head. To address these challenges, various augmentation techniques to increase medial column support have been developed. There are currently no recent studies that definitively establish the superiority of augmented fixation over non-augmented implants in the surgical treatment of proximal humeral fractures. The aim of this systematic review and meta-analysis was to compare the outcomes of patients who underwent locking-plate fixation with cement augmentation or bone-graft augmentation versus those who underwent locking-plate fixation without augmentation for proximal humeral fractures. Methods. The search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Articles involving patients with complex proximal humeral fractures treated using open reduction with locking-plate fixation, with or without augmentation, were considered. A meta-analysis of comparative studies comparing locking-plate fixation with cement augmentation or with bone-graft augmentation versus locking-plate fixation without augmentation was performed. Results. A total of 19 studies were included in the qualitative synthesis, and six comparative studies were included in the meta-analysis. Overall, 120 patients received locking-plate fixation with bone-graft augmentation, 179 patients received locking-plate fixation with cement augmentation, and 336 patients received locking-plate fixation without augmentation. No statistically relevant differences between the augmented and non-augmented cohorts were found in terms of the Disabilities of the Arm, Shoulder and Hand questionnaire score and Constant-Murley Score. The cement-augmented group had a significantly lower rate of complications compared to the non-augmented group. Conclusion. While locking-plate fixation with cement augmentation appears to produce a lower complication rate compared to locking-plate fixation alone, functional outcomes seem comparable between augmented and non-augmented techniques. Cite this article: Bone Joint J 2024;106-B(7):646–655

Aims. After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Methods. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed. Results. Coexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation. Conclusion. Through SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine. Cite this article: Bone Joint Res 2023;12(1):46–57

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

Aims. The present study seeks to investigate the correlation of pubofemoral distances (PFD) to α angles, and hip displaceability status, defined as femoral head coverage (FHC) or FHC during manual provocation of the newborn hip < 50%. Methods. We retrospectively included all newborns referred for ultrasound screening at our institution based on primary risk factor, clinical, and PFD screening. α angles, PFD, FHC, and FHC at follow-up ultrasound for referred newborns were measured and compared using scatter plots, linear regression, paired t-test, and box-plots. Results. We included 2,735 newborns, of whom 754 received a follow-up hip ultrasound within six weeks of age. After exclusion, 1,500 hips were included for analysis. Sex distribution was 372 male and 380 female, and the mean age at examination was 36.6 days (4 to 87). We found a negative linear correlation of PFD to α angles (p < 0.001), FHC (p < 0.001), and FHC during provocation (p < 0.001) with a 1 mm increase in PFD corresponding to a -2.1° (95% confidence interval (CI) -2.3 to -1.9) change in α angle and a -3.4% (95% CI -3.7 to -3.0) change in FHC and a -6.0% (-6.6 to -5.5) change in FHC during provocation. The PFD was significantly higher with increasing Graf types and in displaceable hips (p < 0.001). Conclusion. PFD is strongly correlated to both α angles and hip displaceability, as measured by FHC and FHC during provocation, in ultrasound of newborn hips. The PFD increases as the hips become more dysplastic and/or displaceable. Cite this article: Bone Jt Open 2023;5(1):3–8

Aims. A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients. Methods. Episodes of knee or hip PJI (defined by the European Bone and Joint Infection Society criteria) treated at our institution between January 2015 and October 2020 were included in a retrospective PJI cohort. Episodes with a follow-up of > one year were stratified by route of infection into haematogenous and non-haematogenous PJI. Probability of failure-free survival was estimated using the Kaplan-Meier method, and compared between groups using log-rank test. Univariate and multivariate analysis was applied to assess risk factors for failure. Results. A total of 305 PJI episodes (174 hips, 131 knees) were allocated to the haematogenous (n = 146) or the non-haematogenous group (n = 159). Among monomicrobial infections, Staphylococcus aureus was the dominant pathogen in haematogenous PJI (76/140, 54%) and coagulase-negative staphylococci in non-haematogenous PJI (57/133, 43%). In both groups, multi-stage exchange (n = 55 (38%) in haematogenous and n = 73 (46%) in non-haematogenous PJI) and prosthesis retention (n = 70 (48%) in haematogenous and n = 48 (30%) in non-haematogenous PJI) were the most common surgical strategies. Median duration of antimicrobial treatment was 13.5 weeks (range, 0.5 to 218 weeks) and similar in both groups. After six years of follow-up, the probability of failure-free survival was significantly lower in haematogenous compared to non-haematogenous PJI (55% vs 74%; p = 0.021). Infection-related mortality was significantly higher in haematogenous than non-haematogenous PJI (7% vs 0% episodes; p = 0.001). Pathogenesis of failure was similar in both groups. Retention of the prosthesis was the only independent risk factor for failure in multivariate analysis in both groups. Conclusion. Treatment failure was significantly higher in haematogenous compared to non-haematogenous PJI. Retention of the prosthesis was the only independent risk factor for failure in both groups. Cite this article: Bone Joint J 2023;105-B(12):1294–1302

Aims. Wrist arthroscopy is a standard procedure in hand surgery for diagnosis and treatment of wrist injuries. Even though not generally recommended for similar procedures, general administration of perioperative antibiotic prophylaxis (PAP) is still widely used in wrist arthroscopy. Methods. A clinical ambispective dual-centre study was performed to determine whether PAP reduces postoperative infection rates after soft tissue-only wrist arthroscopies. Retrospective and prospective data was collected at two hospitals with departments specialized in hand surgery. During the study period, 464 wrist arthroscopies were performed, of these 178 soft-tissue-only interventions met the study criteria and were included. Signs of postoperative infection and possible adverse drug effects (ADEs) of PAP were monitored. Additionally, risk factors for surgical site infection (SSIs), such as diabetes mellitus and BMI, were obtained. Results. The overall infection rate of SSI was zero. Neither in the PAP group (n = 69) nor in the control group (n = 109) were signs of postoperative infection observed. Observed symptoms of ADEs were three-times higher in the PAP group when compared to the control-group (16.3 vs 5.5%; p = 0.043). No major ADEs were observed, but one in ten patients in the PAP group reported mild to severe intestinal or hypersensitivity symptoms. Conclusion. We demonstrate that the number needed to treat (NNT) with PAP to prevent one postoperative infection in soft-tissue arthroscopies of the wrist is > 109. Conversely, symptoms of ADEs were reported by one out of ten patients given PAP. Considering the high NNT to prevent postoperative infection and the large number of ADEs caused by PAP, we recommend not to use PAP routinely in soft-tissue arthroscopies of the wrist. Subsequent large-scale studies should be conducted to substantiate these results. Cite this article: Bone Jt Open 2023;4(4):219–225

Aims. Reverse total shoulder arthroplasty (rTSA) can be used in complex cases when the glenoid requires reconstruction. In this study, a baseplate with composite bone autograft and a central trabecular titanium peg was implanted, and its migration was assessed for two years postoperatively using radiostereometric analysis (RSA). Methods. A total of 14 patients who underwent a rTSA with an autograft consented to participate. Of these, 11 had a primary rTSA using humeral head autograft and three had a revision rTSA with autograft harvested from the iliac crest. The mean age of the patients was 66 years (39 to 81). Tantalum beads were implanted in the scapula around the glenoid. RSA imaging (stereographic radiographs) was undertaken immediately postoperatively and at three, six, 12, and 24 months. Analysis was completed using model-based RSA software. Outcomes were collected preoperatively and at two years postoperatively, including the Oxford Shoulder Score, the American Shoulder and Elbow Score, and a visual analogue score for pain. A Constant score was also obtained for the assessment of strength and range of motion. Results. RSA analysis showed a small increase in all translation and rotational values up to six months postoperatively, consistent with settling of the implant. The mean values plateaued by 12 months, with no evidence of further migration. In four patients, there was significant variation outside the mean, which corresponded to postoperative complications. There was a significant improvement in the clinical and patient-reported outcomes from the preoperative values to those at two years postoperatively (p < 0.001). Conclusion. These findings show, using RSA, that a glenoid baseplate composite of a trabecular titanium peg with autograft stabilizes within the glenoid about 12 months after surgery, and reinforce findings from a previous study of this implant/graft with CT scans at two years postoperatively, indicating that this type of structural composite results in sound early fixation. Cite this article: Bone Joint J 2023;105-B(8):912–919

Aims. The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs. Methods. Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm’s method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman’s rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)). Results. We identified a negative correlation between PTA and anterior viable areas (rho −0.477; p = 0.001), and no correlation between PTA and necrotic (rho 0.229; p = 0.067) or posterior viable areas (rho 0.204; p = 0.132). Conclusion. Our results suggest that residual posterior tilt after FNF could affect the anteroposterior localization of necrosis. Cite this article: Bone Jt Open 2024;5(5):394–400

Aims. This study aimed to investigate the risk of postoperative complications in COVID-19-positive patients undergoing common orthopaedic procedures. Methods. Using the National Surgical Quality Improvement Programme (NSQIP) database, patients who underwent common orthopaedic surgery procedures from 1 January to 31 December 2021 were extracted. Patient preoperative COVID-19 status, demographics, comorbidities, type of surgery, and postoperative complications were analyzed. Propensity score matching was conducted between COVID-19-positive and -negative patients. Multivariable regression was then performed to identify both patient and provider risk factors independently associated with the occurrence of 30-day postoperative adverse events. Results. Of 194,121 included patients, 740 (0.38%) were identified to be COVID-19-positive. Comparison of comorbidities demonstrated that COVID-19-positive patients had higher rates of diabetes, heart failure, and pulmonary disease. After propensity matching and controlling for all preoperative variables, multivariable analysis found that COVID-19-positive patients were at increased risk of several postoperative complications, including: any adverse event, major adverse event, minor adverse event, death, venous thromboembolism, and pneumonia. COVID-19-positive patients undergoing hip/knee arthroplasty and trauma surgery were at increased risk of 30-day adverse events. Conclusion. COVID-19-positive patients undergoing orthopaedic surgery had increased odds of many 30-day postoperative complications, with hip/knee arthroplasty and trauma surgery being the most high-risk procedures. These data reinforce prior literature demonstrating increased risk of venous thromboembolic events in the acute postoperative period. Clinicians caring for patients undergoing orthopaedic procedures should be mindful of these increased risks, and attempt to improve patient care during the ongoing global pandemic. Cite this article: Bone Jt Open 2023;4(9):704–712

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. Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods. Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results. Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion. HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466

Aims. 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. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225

Aims. A review of the literature on elbow replacement found no consistency in the clinical outcome measures which are used to assess the effectiveness of interventions. The aim of this study was to define core outcome domains for elbow replacement. Methods. A real-time Delphi survey was conducted over four weeks using outcomes from a scoping review of 362 studies on elbow replacement published between January 1990 and February 2021. A total of 583 outcome descriptors were rationalized to 139 unique outcomes. The survey consisted of 139 outcomes divided into 18 domains. The readability and clarity of the survey was determined by an advisory group including a patient representative. Participants were able to view aggregated responses from other participants in real time and to revisit their responses as many times as they wished during the study period. Participants were able to propose additional items for inclusion. A Patient and Public Inclusion and Engagement (PPIE) panel considered the consensus findings. Results. A total of 45 respondents completed the survey. Nine core mandatory domains were identified: ‘return to work or normal daily role’; delivery of care was measured in the domains ‘patient satisfaction with the outcome of surgery’ and ‘would the patient have the same operation again’; ‘pain’; ‘revision’; ‘elbow function’; ‘independence in activities of daily living’; ‘health-related quality of life’; and ‘adverse events’. ‘Elbow range of motion’ was identified as important by consensus but was felt to be less relevant by the PPIE panel. The PPIE panel unanimously stated that pain should be used as the primary outcome domain. Conclusion. This study defined core domains for the clinical outcomes of elbow replacement obtained by consensus from patients, carers, and healthcare professionals. Pain may be used as the primary outcome in future studies, where appropriate. Further work is required to define the instruments that should be used. Cite this article: Bone Joint J 2024;106-B(11):xxx–xxx