Aims. Despite numerous studies focusing on periprosthetic joint infections (PJIs), there are no robust data on the risk factors and timing of metachronous infections. Metachronous PJIs are PJIs that can arise in the same or other artificial joints after a period of time, in patients who have previously had PJI. Methods. Between January 2010 and December 2018, 661 patients with multiple joint prostheses in situ were treated for PJI at our institution. Of these, 73 patients (11%) developed a metachronous PJI (periprosthetic infection in patients who have previously had PJI in another joint, after a lag period) after a mean time interval of 49.5 months (SD 30.24; 7 to 82.9). To identify patient-related risk factors for a metachronous PJI, the following parameters were analyzed: sex; age; BMI; and pre-existing comorbidity. Metachronous infections were divided into three groups: Group 1, metachronous infections in ipsilateral joints; Group 2, metachronous infections of the contralateral lower limb; and Group 3, metachronous infections of the lower and upper limb. Results. We identified a total of 73 metachronous PJIs: 32 PJIs in Group 1, 38 in Group 2, and one in Group 3. The rate of metachronous infection was 11% (73 out 661 cases) at a mean of four years following first infection. Diabetes mellitus incidence was found significantly more frequently in the metachronous infection group than in non-metachronous infection group. The rate of infection in Group 1 (21.1%) was significantly higher (p = 0.049) compared to Groups 2 (6.2%) and 3 (3%). The time interval of metachronous infection development was shorter in adjacent joint infections. Concordance between the bacterium of the first PJI and that of the metachronous PJI in Group 1 (21/34) was significantly higher than Group 2 (13/38; p = 0.001). Conclusion. The findings of this study suggest that metachronous PJI occurs in more than one in ten patients with an index PJI. Female patients, diabetic patients, and patients with a polymicrobial index PJI are at significantly higher risk for developing a metachronous PJI. Furthermore, metachronous PJIs are significantly more likely to occur in an adjacent joint (e.g. ipsilateral hip and knee) as opposed to a more remote site (i.e. contralateral or upper vs lower limb). Additionally, adjacent joint PJIs occur significantly earlier and are more likely to be caused by the same bacteria as the index PJI. Cite this article: Bone Joint J 2023;105-B(3):294–300

Aims. The primary aim was to assess whether preoperative health-related quality of life (HRQoL) was associated with postoperative mortality following total hip arthroplasty (THA) and knee arthroplasty (KA). Secondary aims were to assess whether patient demographics/comorbidities and/or joint-specific function were associated with postoperative mortality. Methods. Patients undergoing THA (n = 717) and KA (n = 742) during a one-year period were identified retrospectively from an arthroplasty register. Patient demographics, comorbidities, Oxford score, and EuroQol five-dimension (EQ-5D) were recorded preoperatively. Patients were followed up for a minimum of seven years and their mortality status was obtained. Cox regression analysis was used to adjust for confounding. Results. During the study period, 111 patients (15.5%) undergoing THA and 135 patients (18.2%) undergoing KA had died at a mean follow-up of 7.5 years (7 to 8). When adjusting for confounding, the preoperative EQ-5D was associated with postoperative mortality, and for each 0.1 difference in the utility there was an associated change in mortality risk of 6.7% (p = 0.048) after THA, and 6.8% (p = 0.047) after KA. Comorbidities of connective tissue disease (p ≤ 0.026) and diabetes (p ≤ 0.028) were associated with mortality after THA, whereas MI (p ≤ 0.041), diabetes (p ≤ 0.009), and pain in other joints (p ≤ 0.050) were associated with mortality following KA. The preoperative Oxford score was associated with mortality, and for each one-point change in the score there was an associated change in mortality risk of 2.7% (p = 0.025) after THA and 4.3% (p = 0.003) after KA. Conclusion. Worse preoperative HRQoL and joint specific function were associated with an increased risk of postoperative mortality. Both HRQoL and joint-specific function decline with longer waiting times to surgery for THA and KA and therefore may result in an increased postoperative mortality risk than would have been expected if surgery had been undertaken earlier. Cite this article: Bone Jt Open 2022;3(12):933–940

Aims. The aim of this study was to determine the prevalence and impact of tourniquet use in patients undergoing limb salvage surgery with endoprosthetic reconstruction for a tumour around the knee. Methods. We retrieved data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial; specifically, differences in baseline characteristics, surgical details, and postoperative functional outcomes between patients who had undergone surgery under tourniquet and those who had not. A linear regression model was created to evaluate the impact of tourniquet use on postoperative Toronto Extremity Salvage Scores (TESSs) while controlling for confounding variables. A negative-binomial regression model was constructed to explore predictors of postoperative length of stay (LOS). Results. Of the 604 patients enrolled in the PARITY trial, 421 had tumours around the knee joint, of whom 225 (53%) underwent surgery under tourniquet. The tourniquet group was younger (p = 0.014), more likely to undergo surgery for a tumour of the tibia, and had shorter operating times by a mean of 50 minutes (95% confidence interval 30 to 72; p < 0.001). The adjusted linear regression model found that the use of a tourniquet, a shorter operating time, and a higher baseline TESS independently predicted better function at both three- and six-month follow-up. The negative-binomial regression model showed that tourniquet use, shorter operating time, younger age, and intraoperative tranexamic acid administration independently predicted a shorter LOS in hospital. Conclusion. The results of this study show that in patients undergoing resection of a tumour around the knee and endoprosthetic reconstruction, the use of an intraoperative tourniquet is associated with a shorter operating time, a reduced length of stay in hospital, and a better early functional outcome. Cite this article: Bone Joint J 2022;104-B(10):1168–1173

Aims. Debridement, antibiotics, and implant retention (DAIR) is a widely accepted form of surgical treatment for patients with an early periprosthetic joint infection (PJI) after primary arthroplasty. The outcome of DAIR after revision arthroplasty, however, has not been reported. The aim of this study was to report the success rate of DAIR after revision arthroplasty with a follow-up of two years. Methods. This retrospective study, conducted at the Sint Maartenskliniek, Nijmegen, the Netherlands, included 88 patients who underwent DAIR within 90 days of revision total hip or total knee arthroplasty between 2012 and 2019. Details of the surgical procedures and PJI were collected. Univariate analysis and a subgroup analysis of the culture-positive group were performed. Kaplan-Meier survivorship curves were constructed. Results. The overall success rate of DAIR, with respect to the retention of components and the cure of infection, was 68% after two years. DAIR performed with an interval of > 30 days after the index revision procedure (odds ratio (OR) 0.24 (95% confidence interval (CI) 0.08 to 0.72); p = 0.008), a repeated DAIR within 90 days (OR 0.37 (95% CI 0.14 to 0.97); p = 0.040), and the use of an immunosuppressive agent (OR 0.13 (95% CI 0.02 to 0.67); p = 0.012) were associated with a significantly reduced success rate. In the culture-positive group, a mismatch between the antibiotic treatment and the susceptibility of the organism was associated with a significantly lower success rate (OR 0.13 (95% CI 0.03 to 0.62); p = 0.007). Conclusion. DAIR is an acceptable form of surgical treatment for patients with a suspected early PJI after revision arthroplasty of the hip or knee. DAIRs performed after a prolonged interval, multiple DAIRs, and antibiotic mismatches were significantly associated with an increased risk of failure. Optimization of the host immune response and the prevention of antibiotic mismatch are modifiable factors that may improve the outcome. The high rate of mismatches was an important finding, underlining the need for a review of the local microbiological data, which might improve the outcome. Cite this article: Bone Joint J 2022;104-B(4):464–471

Aims. To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods. Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10. 6. ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results. In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion. ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786

Aims. The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Aims. Hip fracture commonly affects the frailest patients, of whom many are care-dependent, with a disproportionate risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England. Methods. We conducted a cohort study of patients with hip fracture recorded in the National Hip Fracture Database between 1 February 2019 and 31 October 2020 in England. Data were linked to Hospital Episode Statistics to quantify patient characteristics and comorbidities, Office for National Statistics mortality data, and Public Health England’s SARS-CoV-2 testing results. Multivariable Cox regression examined determinants of 90-day mortality. Excess mortality attributable to COVID-19 was quantified using Quasi-Poisson models. Results. Analysis of 102,900 hip fractures (42,630 occurring during the pandemic) revealed that among those with COVID-19 infection at presentation (n = 1,120) there was a doubling of 90-day mortality; hazard ratio (HR) 2.09 (95% confidence interval (CI) 1.89 to 2.31), while the HR for infections arising between eight and 30 days after presentation (n = 1,644) the figure was greater at 2.51 (95% CI 2.31 to 2.73). Malnutrition (1.45 (95% CI 1.19 to 1.77)) and nonoperative treatment (2.94 (95% CI 2.18 to 3.95)) were the only modifiable risk factors for death in COVID-19-positive patients. Patients who had tested positive for COVID-19 more than two weeks prior to hip fracture initially had better survival compared to those who contracted COVID-19 around the time of their hip fracture; however, survival rapidly declined and by 365 days the combination of hip fracture and COVID-19 infection was associated with a 50% mortality rate. Between 1 January and 30 June 2020, 1,273 (99.7% CI 1,077 to 1,465) excess deaths occurred within 90 days of hip fracture, representing an excess mortality of 23% (99.7% CI 20% to 26%), with most deaths occurring within 30 days. Conclusion. COVID-19 infection more than doubles the rate of early hip fracture mortality. Those contracting infection between 8 and 30 days after initial presentation are at even higher mortality risk, signalling the potential for targeted interventions during this period to improve survival. Cite this article: Bone Joint J 2022;104-B(10):1156–1167

Aims. This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results. A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion. ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689

Aims. There has been an increasing use of early operative fixation for scaphoid fractures, despite uncertain evidence. We conducted a meta-analysis to evaluate up-to-date evidence from randomized controlled trials (RCTs), comparing the effectiveness of the operative and nonoperative treatment of undisplaced and minimally displaced (≤ 2 mm displacement) scaphoid fractures. Methods. A systematic review of seven databases was performed from the dates of their inception until the end of March 2021 to identify eligible RCTs. Reference lists of the included studies were screened. No language restrictions were applied. The primary outcome was the patient-reported outcome measure of wrist function at 12 months after injury. A meta-analysis was performed for function, pain, range of motion, grip strength, and union. Complications were reported narratively. Results. Seven RCTs were included. There was no significant difference in function between the groups at 12 months (Hedges’ g 0.15 (95% confidence interval -0.02 to 0.32); p = 0.082). The complication rate was higher in the operative group and involved more serious complications. Conclusion. We found no difference in functional outcome at 12 months for fractures of the waist of the scaphoid with ≤ 2 mm displacement treated operatively or nonoperatively. The complication rate was higher with operative treatment. Cite this article: Bone Joint J 2022;104-B(8):953–962

Aims. The primary aim of this study was to assess whether patients waiting six months or more for a total hip (THA) or knee (KA) arthroplasty had a deterioration in their health-related quality of life (HRQoL). Secondary aims were to assess changes in frailty and the number of patients living in a state considered to be worse than death (WTD), and factors associated with changes in HRQoL and frailty. Methods. This cross-sectional study included 326 patients, 150 males (46.0%) and 176 females (54.0%), with a mean age of 68.6 years (SD 9.8) who were randomly selected from waiting lists at four centres and had been waiting for six months or more (median 13 months, interquartile range 10 to 21) for a primary THA (n = 161) or KA (n = 165). The EuroQol five-dimension questionnaire (EQ-5D) and visual analogue scores (EQ-VAS), Rockwood Clinical Frailty Scale (CFS), and 36-Item Short Form Survey subjective change in HRQoL were assessed at the time and recalled for six months earlier. A state that was WTD was defined as an EQ-5D of less than zero. Results. There were significant deteriorations in the EQ-5D (mean 0.175, 95% confidence interval (CI) 0.145 to 0.204; p < 0.001), EQ-VAS (mean 8.6, 95% CI 7.0 to 10.4; < 0.001), and CFS (from 3 “managing well” to 4 “vulnerable”; p < 0.001), and a significant increase in the number of those in a state that was WTD (n = 48; p < 0.001) during the previous six months for the whole cohort. A total of 110 patients (33.7%) stated that their health was much worse and 107 (32.8%) felt it was somewhat worse compared with six months previously. A significantly greater EQ-5D (-0.14, 95% CI 0.08 to 0.28; p = 0.038) and a state that was not WTD (-0.14, 95% CI 0.01 to 0.26; p = 0.031) were associated with a deterioration in the EQ-5D. THA (0.21, 95% CI 0.07 to 0.34; p = 0.002) or a lower (better) CFS (0.14, 95% CI 0.07 to 0.20; p < 0.001) were independently significantly associated with a deterioration in the CFS. Conclusion. Patients waiting more than six months for THA or KA had a significant deterioration in their HRQoL and increased frailty, with two-thirds of patients feeling that their health had worsened. Cite this article: Bone Joint J 2022;104-B(11):1215–1224

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714

Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients. Cite this article: Bone Joint J 2022;104-B(8):915–921

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. Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. Methods. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Results. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. Conclusion. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two ‘at risk’ alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making. Cite this article: Bone Jt Open 2023;4(3):182–187

Aims. We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism. Methods. Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature. Results. We identified three PMOP-related subtypes and four core modules. The muscle system process, muscle contraction, and actin filament-based movement were more active in the hub genes. We obtained five feature genes related to PMOP. Our analysis verified that the gene signature had good predictive power and applicability. The outcomes of the GSE56815 cohort were found to be consistent with the results of the earlier studies. qRT-PCR results showed that RAB2A and FYCO1 were amplified in clinical samples. Conclusion. The PMOP-related gene signature we developed and verified can accurately predict the risk of PMOP in patients. These results can elucidate the molecular mechanism of RAB2A and FYCO1 underlying PMOP, and yield new and improved treatment strategies, ultimately helping PMOP monitoring. Cite this article: Bone Joint Res 2022;11(8):548–560

Aims. Large-diameter metal-on-metal (MoM) total hip arthroplasty (THA) has demonstrated unexpected high failure rates and pseudotumour formation. The purpose of this prospective cohort study is to report ten-year results in order to establish revision rate, prevalence of pseudotumour formation, and relation with whole blood cobalt levels. Methods. All patients were recalled according to the guidelines of the Dutch Orthopaedic Association. They underwent clinical and radiographical assessments (radiograph and CT scan) of the hip prosthesis and whole blood cobalt ion measurements. Overall, 94 patients (95 hips) fulfilled our requirements for a minimum ten-year follow-up. Results. Mean follow-up was 10.9 years (10 to 12), with a cumulative survival rate of 82.4%. Reason for revision was predominantly pseudotumour formation (68%), apart from loosening, pain, infection, and osteolysis. The prevalence of pseudotumour formation around the prostheses was 41%, while our previous report of this cohort (with a mean follow-up of 3.6 years) revealed a 39% prevalence. The ten-year revision-free survival with pseudotumour was 66.7% and without pseudotumour 92.4% (p < 0.05). There was poor discriminatory ability for cobalt for pseudotumour formation. Conclusion. This prospective study reports a minimum ten-year follow-up of large-head MoM THA. Revision rates are high, with the main reason being the sequelae of pseudotumour formation, which were rarely observed after five years of implantation. Blood ion measurements show limited discriminatory capacity in diagnosing pseudotumour formation. Our results evidence that an early comprehensive follow-up strategy is essential for MoM THA to promptly identify and manage early complications and revise on time. After ten years follow-up, we do not recommend continuing routine CT scanning or whole cobalt blood measurements, but instead enrolling these patients in routine follow-up protocols for THA. Cite this article: Bone Jt Open 2022;3(1):61–67

Aims. Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. Methods. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). Results. At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). Conclusion. We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion. Cite this article: Bone Joint J 2022;104-B(9):1095–1100

Aims. The Open-Fracture Patient Evaluation Nationwide (OPEN) study was performed to provide clarity in open fracture management previously skewed by small, specialist centre studies and large, unfocused registry investigations. We report the current management metrics of open fractures across the UK. Method. Patients admitted to hospital with an open fracture (excluding phalanges or isolated hand injuries) between 1 June 2021 and 30 September 2021 were included. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture software. All domains of the British Orthopaedic Association Standard for Open Fracture Management were recorded. Results. Across 51 centres, 1,175 patients were analyzed. Antibiotics were given to 754 (69.0%) in the emergency department, 240 (22.0%) pre-hospital, and 99 (9.1%) as inpatients. Wounds were photographed in 848 (72.7%) cases. Median time to first surgery was 16 hrs 14 mins (interquartile range (IQR) 8 hrs 29 mins to 23 hrs 19 mins). Complex injuries were operated on sooner (median 12 hrs 51 mins (IQR 4 hrs 36 mins to 21 hrs 14 mins)). Of initial procedures, 1,053 (90.3%) occurred between 8am and 8pm. A consultant orthopaedic surgeon was present at 1,039 (89.2%) first procedures. In orthoplastic centres, a consultant plastic surgeon was present at 465 (45.1%) first procedures. Overall, 706 (60.8%) patients required a single operation. At primary debridement, 798 (65.0%) fractures were definitively fixed, while 734 (59.8%) fractures had fixation and coverage in one operation through direct closure or soft-tissue coverage. Negative pressure wound therapy was used in 235 (67.7%) staged procedures. Following wound closure or soft-tissue cover, 509 (47.0%) patients received antibiotics for a median of three days (IQR 1 to 7). Conclusion. OPEN provides an insight into care across the UK and different levels of hospital for open fractures. Patients are predominantly operated on promptly, in working hours, and at specialist centres. Areas for improvement include combined patient review and follow-up, scheduled operating, earlier definitive soft-tissue cover, and more robust antibiotic husbandry. Cite this article: Bone Joint J 2022;104-B(9):1073–1080

Aims. The aims of this network meta-analysis (NMA) were to examine nonunion rates and functional outcomes following various operative and nonoperative treatments for displaced mid-shaft clavicle fractures. Methods. Initial search strategy incorporated MEDLINE, PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials (RCTs). Four treatment arms were created: nonoperative (NO); intramedullary nailing (IMN); reconstruction plating (RP); and compression/pre-contoured plating (CP). A Bayesian NMA was conducted to compare all treatment options for outcomes of nonunion, malunion, and function using the Disabilities of the Arm Shoulder and Hand (DASH) and Constant-Murley Shoulder Outcome scores. Results. In all, 19 RCTs consisting of 1,783 clavicle fractures were included in the NMA. All surgical options demonstrated a significantly lower odds ratio (OR) of nonunion in comparison to nonoperative management: CP versus NO (OR 0.08; 95% confidence interval (CI) 0.04 to 0.17); IMN versus NO (OR 0.07; 95% CI 0.02 to 0.19); RP versus NO (OR 0.07; 95% CI: 0.01 to 0.24). Compression plating was the only treatment to demonstrate significantly lower DASH scores relative to NO at six weeks (mean difference -10.97; 95% CI -20.69 to 1.47). Conclusion. Surgical fixation demonstrated a lower risk of nonunion compared to nonoperative management. Compression plating resulted in significantly less disability early after surgery compared to nonoperative management. These results demonstrate possible early improved functional outcomes with compression plating compared to nonoperative treatment. Surgical fixation of mid-shaft clavicle fractures with compression plating may result in quicker return to activity by rendering patients less disabled early after surgery. Cite this article: Bone Jt Open 2021;2(8):646–654