Aims. This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Methods. Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model. Results. We discovered for the first time that MCL was substantially enriched in the synovial fluid of OA patients and promoted the release of inflammatory cytokines from FLSs through MCL phagocytosis. Through LC‒MS, ANT3 was identified and determined to be significantly upregulated in MCL and OA-FLSs, corresponding to impaired mitochondrial function and cell viability in OA-FLSs. Mitochondrial homeostasis was restored by ANT3 suppression, thereby alleviating synovial inflammation. Furthermore, elevated ANT3 levels inhibited ERK phosphorylation. Specifically, silencing ANT3 prevented inhibition of ERK phosphorylation and significantly reduced the elevation of reactive oxygen species (ROS) and JC1 membrane potential in MCL-induced synovial inflammation. Conclusion. This study revealed the important roles of MCL and ANT3 in FLS mitochondria. Silencing ANT3 rescued ERK phosphorylation, thereby restoring mitochondrial homeostasis in FLSs and alleviating synovitis and OA development, offering a potential target for treating synovitis and preventing early-stage OA. Cite this article: Bone Joint Res 2023;12(4):274–284

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

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. Clinical management of open fractures is challenging and frequently requires complex reconstruction procedures. The Gustilo-Anderson classification lacks uniform interpretation, has poor interobserver reliability, and fails to account for injuries to musculotendinous units and bone. The Ganga Hospital Open Injury Severity Score (GHOISS) was designed to address these concerns. The major aim of this review was to ascertain the evidence available on accuracy of the GHOISS in predicting successful limb salvage in patients with mangled limbs. Methods. We searched electronic data bases including PubMed, CENTRAL, EMBASE, CINAHL, Scopus, and Web of Science to identify studies that employed the GHOISS risk tool in managing complex limb injuries published from April 2006, when the score was introduced, until April 2021. Primary outcome was the measured sensitivity and specificity of the GHOISS risk tool for predicting amputation at a specified threshold score. Secondary outcomes included length of stay, need for plastic surgery, deep infection rate, time to fracture union, and functional outcome measures. Diagnostic test accuracy meta-analysis was performed using a random effects bivariate binomial model. Results. We identified 1,304 records, of which six prospective cohort studies and two retrospective cohort studies evaluating a total of 788 patients were deemed eligible for inclusion. A diagnostic test meta-analysis conducted on five cohort studies, with 474 participants, showed that GHOISS at a threshold score of 14 has a pooled sensitivity of 93.4% (95% confidence interval (CI) 78.4 to 98.2) and a specificity of 95% (95% CI 88.7 to 97.9) for predicting primary or secondary amputations in people with complex lower limb injuries. Conclusion. GHOISS is highly accurate in predicting success of limb salvage, and can inform management and predict secondary outcomes. However, there is a need for high-quality multicentre trials to confirm these findings and investigate the effectiveness of the score in children, and in predicting secondary amputations. Cite this article: Bone Joint J 2023;105-B(1):21–28

Aims. Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty – the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most. Methods. We used causal forest analysis to compare subgroup- and individual-level treatment effects between cemented and modern uncemented hemiarthroplasty in patients aged > 60 years with an intracapsular fracture of the hip, using data from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized clinical trial. EuroQol five-dimension index scores were used to measure health-related quality of life at one, four, and 12 months postoperatively. Results. Our analysis revealed a complex landscape of responses to the use of a cemented hemiarthroplasty in the 12 months after surgery. There was heterogeneity of effects with regard to baseline characteristics, including age, pre-injury health status, and lifestyle factors such as alcohol consumption. This heterogeneity was greater at the one-month mark than at subsequent follow-up timepoints, with particular regard to subgroups based on age. However, for all subgroups, the effect estimates for quality of life lay within the confidence intervals derived from the analysis of all patients. Conclusion. The use of a cemented hemiarthroplasty is expected to increase health-related quality of life compared with modern uncemented hemiarthroplasty for all subgroups of patients aged > 60 years with a displaced intracapsular fracture of the hip. Cite this article: Bone Joint J 2024;106-B(7):656–661

Aims. Osteochondral lesions of the talus (OLT) are a common cause of disability and chronic ankle pain. Many operative treatment strategies have been introduced; however, they have their own disadvantages. Recently lesion repair using autologous cartilage chip has emerged therefore we investigated the efficacy of particulated autologous cartilage transplantation (PACT) in OLT. Methods. We retrospectively analyzed 32 consecutive symptomatic patients with OLT who underwent PACT with minimum one-year follow-up. Standard preoperative radiography and MRI were performed for all patients. Follow-up second-look arthroscopy or MRI was performed with patient consent approximately one-year postoperatively. Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score and International Cartilage Repair Society (ICRS) grades were used to evaluate the quality of the regenerated cartilage. Clinical outcomes were assessed using the pain visual analogue scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Scale (FAOS). Results. All patients had ICRS grade IV cartilage lesions, except for one (ICRS grade III). The paired MOCART scores significantly improved from 42.5 (SD 1.53) to 63.5 (SD 22.60) (p = 0.025) in ten patients. Seven patients agreed to undergo second-look arthroscopy; 5 patients had grade I (normal) ICRS scores and two patients had grade II (nearly normal) ICRS scores. VAS, FFI, and all subscales of FAOS were significantly improved postoperatively (p ≤ 0.003). Conclusion. PACT significantly improved the clinical, radiological, and morphological outcomes of OLT. We consider this to be a safe and effective surgical method based on the short-term clinical results of this study. Cite this article: Bone Jt Open 2023;4(12):942–947

Aims. Paediatric fractures are highly prevalent and are most often treated with plaster. The application and removal of plaster is often an anxiety-inducing experience for children. Decreasing the anxiety level may improve the patients’ satisfaction and the quality of healthcare. Virtual reality (VR) has proven to effectively distract children and reduce their anxiety in other clinical settings, and it seems to have a similar effect during plaster treatment. This study aims to further investigate the effect of VR on the anxiety level of children with fractures who undergo plaster removal or replacement in the plaster room. Methods. A randomized controlled trial was conducted. A total of 255 patients were included, aged five to 17 years, who needed plaster treatment for a fracture of the upper or lower limb. Randomization was stratified for age (five to 11 and 12 to 17 years). The intervention group was distracted with VR goggles and headphones during the plaster treatment, whereas the control group received standard care. As the primary outcome, the post-procedural level of anxiety was measured with the Child Fear Scale (CFS). Secondary outcomes included the children’s anxiety reduction (difference between CFS after and CFS before plaster procedure), numerical rating scale (NRS) pain, NRS satisfaction of the children and accompanying parents/guardians, and the children’s heart rates during the procedure. An independent-samples t-test and Mann-Whitney U test (depending on the data distribution) were used to analyze the data. Results. The post-procedural CFS was significantly lower (p < 0.001) in the intervention group (proportion of children with no anxiety = 78.6%) than in the control group (56.8%). The anxiety reduction, NRS pain and satisfaction scores, and heart rates showed no significant differences between the control group and the intervention group. Subanalyses showed an increased effect of VR on anxiety levels in young patients, females, upper limb fractures, and those who had had previous plaster treatment. Conclusion. VR effectively reduces the anxiety levels of children in the plaster room, especially in young girls. No statistically significant effects were seen regarding pain, heart rate, or satisfaction scores. Cite this article: Bone Joint J 2024;106-B(7):728–734

Aims. There is no level I evidence dealing with the optimal period of immobilization for patients with a displaced distal radial fracture following closed reduction. A shorter period might lead to a better functional outcome due to less stiffness and pain. The aim of this study was to investigate whether this period could be safely reduced from six to four weeks. Methods. This multicentre randomized controlled trial (RCT) included adult patients with a displaced distal radial fracture, who were randomized to be treated with immobilization in a cast for four or six weeks following closed reduction. The primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) score after follow-up at one year. Secondary outcomes were the abbreviated version of the Disability of Arm, Shoulder and Hand (QuickDASH) score after one year, the functional outcome at six weeks, 12 weeks, and six months, range of motion (ROM), the level of pain after removal of the cast, and complications. Results. A total of 100 patients (15 male, 85 female) were randomized, with 49 being treated with four weeks of immobilization in a cast. A total of 93 completed follow-up. The mean PRWE score after one year was 6.9 (SD 8.3) in the four-week group compared with 11.6 (SD 14.3) in the six-week group. However, this difference of -4.7 (95% confidence interval -9.29 to 0.14) was not clinically relevant as the minimal clinically important difference of 11.5 was not reached. There was no significant difference in the ROM, radiological outcome, level of pain, or complications. Conclusion. In adult patients with a displaced and adequately reduced distal radial fracture, immobilization in a cast for four weeks is safe, and the results are similar to those after a period of immobilization of six weeks. Cite this article: Bone Joint J 2023;105-B(9):993–999

Aims. Multiligament knee injuries (MLKI) are devastating injuries that can result in significant morbidity and time away from sport. There remains considerable variation in strategies employed for investigation, indications for operative intervention, outcome reporting, and rehabilitation following these injuries. At present no study has yet provided a comprehensive overview evaluating the extent, range, and overall summary of the published literature pertaining to MLKI. Our aim is to perform a methodologically rigorous scoping review, mapping the literature evaluating the diagnosis and management of MLKI. Methods. This scoping review will address three aims: firstly, to map the current extent and nature of evidence for diagnosis and management of MLKI; secondly, to summarize and disseminate existing research findings to practitioners; and thirdly, to highlight gaps in current literature. A three-step search strategy as described by accepted methodology will be employed to identify peer-reviewed literature including reviews, technical notes, opinion pieces, and original research. An initial limited search will be performed to determine suitable search terms, followed by an expanded search of four electronic databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Web of Science). Two reviewers will independently screen identified studies for final inclusion. Dissemination. We will map key concepts and evidence, and disseminate existing research findings to the wider orthopaedic and sports medicine community, through both peer-reviewed and non-peer-reviewed literature, and conference and in-person communications. We will highlight gaps in the current literature and determine future priorities for further research. Cite this article: Bone Jt Open 2022;3(11):894–897

Aims. The aim of this study was to investigate the association between additional rehabilitation at the weekend, and in-hospital mortality and complications in patients with hip fracture who underwent surgery. Methods. A retrospective cohort study was conducted in Japan using a nationwide multicentre database from April 2010 to March 2018, including 572,181 patients who had received hip fracture surgery. Propensity score matching was performed to compare patients who received additional weekend rehabilitation at the weekend in addition to rehabilitation on weekdays after the surgery (plus-weekends group), as well as those who did not receive additional rehabilitation at the weekend but did receive weekday rehabilitation (weekdays-only group). After the propensity score matching of 259,168 cases, in-hospital mortality as the primary outcome and systemic and surgical complications as the secondary outcomes were compared between the two groups. Results. The plus-weekends group was significantly associated with lower in-hospital mortality rates compared with the weekdays-only group (hazard ratio 0.86; 95% confidence interval 0.8 to 0.92; p < 0.001). Systemic complications such as acute coronary syndrome, heart failure, renal failure, and sepsis were significantly lower in the plus-weekends group, whereas urinary tract infection (UTI) and surgical complications such as surgical site infection and haematoma were significantly higher in the plus-weekends group. Conclusion. Additional weekend rehabilitation was significantly associated with lower in-hospital mortality, as well as acute coronary syndrome, heart failure, renal failure, and sepsis, but was also significantly associated with a higher risk of UTI and surgical complications. This result can facilitate the effective use of the limited rehabilitation resources at the weekend and improve the clinical awareness of specific complications. To establish more robust causal associations between additional rehabilitation over the weekend and clinical outcomes, further prospective studies or randomized controlled trials with larger sample sizes are warranted. Cite this article: Bone Joint J 2023;105-B(8):872–879

Aims. The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours. Methods. We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital. Results. In all, 17 patients with locally aggressive bone tumours (Enneking stage IIB) located in the femoral shaft underwent JSLSS and reconstruction with 3D-printed modular prostheses between January 2020 and June 2022. The median surgical time was 153 minutes (interquartile range (IQR) 117 to 248), and the median estimated blood loss was 200ml (IQR 125 to 400). Osteosarcoma was the most common pathological type (n = 12; 70.6%). The mean osteotomy length was 197.53 mm (SD 12.34), and the median follow-up was 25 months (IQR 19 to 38). Two patients experienced local recurrence and three developed distant metastases. Postoperative complications included wound infection in one patient and screw loosening in another, both of which were treated successfully with revision surgery. The median Musculoskeletal Tumor Society score at the final follow-up was 28 (IQR 27 to 28). Conclusion. The 3D-printed modular prosthesis is a reliable and feasible reconstruction option for patients with malignant femoral diaphyseal tumours. It helps to improve the limb salvage rate, restore limb function, and achieve better short-term effectiveness. Cite this article: Bone Jt Open 2024;5(4):317–323

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. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351

Aims. The Exeter V40 femoral stem is the most implanted stem in the National Joint Registry (NJR) for primary total hip arthroplasty (THA). In 2004, the 44/00/125 stem was released for use in ‘cement-in-cement’ revision cases. It has, however, been used ‘off-label’ as a primary stem when patient anatomy requires a smaller stem with a 44 mm offset. We aimed to investigate survival of this implant in comparison to others in the range when used in primary THAs recorded in the NJR. Methods. We analyzed 328,737 primary THAs using the Exeter V40 stem, comprising 34.3% of the 958,869 from the start of the NJR to December 2018. Our exposure was the stem, and the outcome was all-cause construct revision. We stratified analyses into four groups: constructs using the 44/00/125 stem, those using the 44/0/150 stem, those including a 35.5/125 stem, and constructs using any other Exeter V40 stem. Results. In all 328,737 THAs using an Exeter V40 stem, the revision estimate was 2.8% (95% confidence interval (CI) 2.7 to 2.8). The 44/00/125 stem was implanted in 2,158 primary THAs, and the ten-year revision estimate was 4.9% (95% CI 3.6 to 6.8). Controlling for age, sex, year of operation, indication, and American Society of Anesthesiologists grade demonstrated an increased overall hazard of revision for constructs using the 44/00/125 stem compared to constructs using other Exeter V40 femoral stems (hazard ratio 1.8 (95% CI 1.4 to 2.3)). Conclusion. Although the revision estimate is within the National Institute for Health and Care Excellence ten-year benchmark, survivorship of constructs using the 44/00/125 stem appears to be lower than the rest of the range. Adjusted analyses will not take into account ‘confounding by indication’, e.g. patients with complex anatomy who may have a higher risk of revision. Surgeons and patients should be reassured but be aware of the observed increased revision estimate, and only use this stem when other implants are not suitable. Cite this article: Bone Joint J 2023;105-B(5):504–510

Aims. The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD. Methods. A comprehensive literature search was conducted to identify eligible studies reporting postoperative outcomes in IBD patients undergoing joint arthroplasty. The primary outcomes included postoperative complications, while the secondary outcomes included unplanned readmission, length of stay (LOS), joint reoperation/implant revision, and cost of care. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model when heterogeneity was substantial. Results. Eight retrospective studies involving 29,738 patients with IBD were included. Compared with non-IBD controls, patients with IBD were significantly more likely to have overall complications (OR 2.11 (95% CI 1.67 to 2.66), p < 0.001), medical complications (OR 2.15 (95% CI 1.73 to 2.68), p < 0.001), surgical complications (OR 1.43 (95% CI 1.21 to 1.70), p < 0.001), and 90-day readmissions (OR 1.42 (95% CI 1.23 to 1.65), p < 0.001). The presence of IBD was positively associated with the development of venous thromboembolism (OR 1.60 (95% CI 1.30 to 1.97), p < 0.001) and postoperative infection (OR 1.95 (95% CI 1.51 to 2.51), p < 0.001). In addition, patients with IBD tended to experience longer LOS and higher costs of care. Conclusion. The findings suggest that IBD is associated with an increased risk of postoperative complications and readmission after joint arthroplasty, resulting in longer hospital stay and greater financial burden. Surgeons should inform their patients of the possibility of adverse outcomes prior to surgery and make appropriate risk adjustments to minimize potential complications. Cite this article: Bone Joint Res 2023;12(6):362–371

Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion. DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD. Cite this article: Bone Joint Res 2024;13(5):247–260

Aims. A significant reduction in wear at five and ten years was previously reported when comparing Durasul highly cross-linked polyethylene with nitrogen-sterilized Sulene polyethylene in total hip arthroplasty (THA). We investigated whether the improvement observed at the earlier follow-up continued, resulting in decreased osteolysis and revision surgery rates over the second decade. Methods. Between January 1999 and December 2001, 90 patients underwent surgery using the same acetabular and femoral components with a 28 mm metallic femoral head and either a Durasul or Sulene liner. A total of 66 hips of this prospective randomized study were available for a minimum follow-up of 20 years. The linear femoral head penetration rate was measured at six weeks, one year, and annually thereafter, using the Dorr method on digitized radiographs with a software package. Results. In the Durasul group, no patients underwent revision due to loosening or showed radiological evidence of osteolysis. In the Sulene group, four patients (four hips) were revised due to femoral component loosening. The 20-year cumulative failure incidence in the presence of the competing event of death for revision surgery was 4.5% (95% confidence interval (CI) 0.8 to 13.6) in the Durasul group, and 8.9% (95% CI 2.8 to 19.5) in the Sulene group. The mean wear one year after surgery was 0.09 mm (SD 0.007) in the Durasul group and 0.24 (SD 0.015) in the Sulene group (p < 0.001). From one to 20 years after surgery, the mean total penetration was 0.32 mm (SD 0.045) in the Durasul group and 1.07 mm (SD 0.13) in the Sulene group (p < 0.001). Mean femoral head penetration at 20 years was approximately 70.0% less in the Durasul group than the Sulene group. Conclusion. The significant reduction in femoral head penetration obtained with the Durasul compared with Sulene in uncemented THA resulted in lower osteolysis and revision rates after 20 years. Cite this article: Bone Joint J 2022;104-B(9):1032–1038

Aims. Periprosthetic femoral fracture (PPF) is a major complication following total hip arthroplasty (THA). Uncemented femoral components are widely preferred in primary THA, but are associated with higher PPF risk than cemented components. Collared components have reduced PPF rates following uncemented primary THA compared to collarless components, while maintaining similar prosthetic designs. The purpose of this study was to analyze PPF rate between collarless and collared component designs in a consecutive cohort of posterior approach THAs performed by two high-volume surgeons. Methods. This retrospective series included 1,888 uncemented primary THAs using the posterior approach performed by two surgeons (PKS, JMV) from January 2016 to December 2022. Both surgeons switched from collarless to collared components in mid-2020, which was the only change in surgical practice. Data related to component design, PPF rate, and requirement for revision surgery were collected. A total of 1,123 patients (59.5%) received a collarless femoral component and 765 (40.5%) received a collared component. PPFs were identified using medical records and radiological imaging. Fracture rates between collared and collarless components were analyzed. Power analysis confirmed 80% power of the sample to detect a significant difference in PPF rates, and a Fisher’s exact test was performed to determine an association between collared and collarless component use on PPF rates. Results. Overall, 17 PPFs occurred (0.9%). There were 16 fractures out of 1,123 collarless femoral components (1.42%) and one fracture out of 765 collared components (0.13%; p = 0.002). The majority of fractures (n = 14; 82.4%) occurred within 90 days of primary THA. There were ten reoperations for PPF with collarless components (0.89%) and one reoperation with a collared component (0.13%; p = 0.034). Conclusion. Collared femoral components were associated with significant decreases in PPF rate and reoperation rate for PPF compared to collarless components in uncemented primary THA. Future studies should investigate whether new-generation collared components reduce PPF rates with longer-term follow-up. Cite this article: Bone Joint J 2024;106-B(3 Supple A):115–120

Aims. Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods. A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion. This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties. Cite this article: Bone Joint J 2024;106-B(3 Supple A):51–58