Aims. Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence. Methods. A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken. Results. Pooled analysis of four studies including 651 patients found the mean 25(OH)D level to be 50.7 nmol/l with a mean incidence of infection of 70%. There was a paucity of literature exploring prophylactic 25(OH)D supplementation on reducing orthopaedic infection, however, there was evidence of association between low 25(OH)D levels and increased incidence of orthopaedic infection. Conclusion. The results indicate a significant proportion of orthopaedic patients have low 25(OH]D levels, as well as an association between low 25(OH)D levels and orthopaedic infection, but more randomized controlled trials need to be conducted to establish the benefit of prophylactic supplementation and the optimum regimen by dose and time. Cite this article: Bone Jt Open 2021;2(9):721–727

Aims. Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy. Methods. The human osteoblast-like Saos-2 cells infected with S. aureus EDCC 5055 strain and treated with 8 µg/ml RMP underwent osteogenic stimulation for up to 21 days. Test groups were Saos-2 cells + S. aureus and Saos-2 cells + S. aureus + 8 µg/ml RMP, and control groups were uninfected untreated Saos-2 cells and uninfected Saos-2 cells + 8 µg/ml RMP. Results. The S. aureus-infected osteoblasts showed a significant number of intracellular bacteria colonies and an unusual higher metabolic activity (p < 0.005) compared to uninfected osteoblasts. Treatment with 8 µg/ml RMP significantly eradicated intracellular bacteria and the metabolic activity was comparable to uninfected groups. The RMP-treated infected osteoblasts revealed a significantly reduced amount of mineralized extracellular matrix (ECM) at seven days osteogenesis relative to uninfected untreated osteoblasts (p = 0.007). Prolonged osteogenesis and RMP treatment at 21 days significantly improved the ECM mineralization level. Ultrastructural images of the mineralized RMP-treated infected osteoblasts revealed viable osteoblasts and densely distributed calcium crystal deposits within the extracellular organic matrix. The expression levels of prominent bone formation genes were comparable to the RMP-treated uninfected osteoblasts. Conclusion. Intracellular S. aureus infection impaired osteoblast metabolism and function. However, treatment with low dosage of RMP eradicated the intracellular S. aureus, enabling extracellular organic matrix formation and mineralization of osteoblasts at later stage. Cite this article: Bone Joint Res 2022;11(5):327–341

Aims. Prior to the availability of vaccines, mortality for hip fracture patients with concomitant COVID-19 infection was three times higher than pre-pandemic rates. The primary aim of this study was to determine the 30-day mortality rate of hip fracture patients in the post-vaccine era. Methods. A multicentre observational study was carried out at 19 NHS Trusts in England. The study period for the data collection was 1 February 2021 until 28 February 2022, with mortality tracing until 28 March 2022. Data collection included demographic details, data points to calculate the Nottingham Hip Fracture Score, COVID-19 status, 30-day mortality, and vaccination status. Results. A total of 337 patients tested positive for COVID-19. The overall 30-day mortality in these patients was 7.7%: 5.5% in vaccinated patients and 21.7% in unvaccinated patients. There was no significant difference between post-vaccine mortality compared with pre-pandemic 2019 controls (7.7% vs 5.0%; p = 0.068). Independent risk factors for mortality included unvaccinated status, Abbreviated Mental Test Score ≤ 6, male sex, age > 80 years, and time to theatre > 36 hours, in decreasing order of effect size. Conclusion. The vaccination programme has reduced 30-day mortality rates in hip fracture patients with concomitant COVID-19 infection to a level similar to pre-pandemic. Mortality for unvaccinated patients remained high. Cite this article: Bone Joint J 2022;104-B(12):1362–1368

Aims. Factors associated with high mortality rates in geriatric hip fracture patients are frequently unmodifiable. Time to surgery, however, might be a modifiable factor of interest to optimize clinical outcomes after hip fracture surgery. This study aims to determine the influence of postponement of surgery due to non-medical reasons on clinical outcomes in acute hip fracture surgery. Methods. This observational cohort study enrolled consecutively admitted patients with a proximal femoral fracture, for which surgery was performed between 1 January 2018 and 11 January 2021 in two level II trauma teaching hospitals. Patients with medical indications to postpone surgery were excluded. A total of 1,803 patients were included, of whom 1,428 had surgery < 24 hours and 375 had surgery ≥ 24 hours after admission. Results. Prolonged total length of stay was found when surgery was performed ≥ 24 hours (median 6 days (interquartile range (IQR) 4 to 9) vs 7 days (IQR 5 to 10); p = 0.001) after admission. No differences in postoperative length of hospital stay nor in 30-day mortality rates were found. In subgroup analysis for time frames of 12 hours each, pressure sores and urinary tract infections were diagnosed more frequently when time to surgery increased. Conclusion. Longer time to surgery due to non-medical reasons was associated with a higher incidence of postoperative pressure sores and urinary tract infections when time to surgery was more than 48 hours after admission. No association was found between time to surgery and 30-day mortality rates or postoperative length of hospital stay. Cite this article: Bone Joint J 2022;104-B(12):1369–1378

Aims. Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods. Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay. Results. We found that treatment with DEL-1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL-1 treatment augmented LC3 conversion and p62 degradation as well as AMPK phosphorylation. Moreover, small interfering RNA for AMPK or 3-methyladenine (3-MA), an autophagy inhibitor, abolished the suppressive effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes. Similar to DEL-1, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, also attenuated palmitate-induced inflammation, ER stress, and apoptosis in tenocytes, which 3-MA reversed. Conclusion. These results revealed that DEL-1 suppresses inflammation and ER stress, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL-1 may directly contribute to improving tendinitis exacerbated by obesity and insulin resistance. Cite this article: Bone Joint Res 2022;11(12):854–861

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776

Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Aims. To establish the survivorship, function, and metal ion levels in an unselected series of metal-on-metal hip resurfacing arthroplasties (HRAs) performed by a non-designer surgeon. Methods. We reviewed 105 consecutive HRAs in 83 patients, performed by a single surgeon, at a mean follow-up of 14.9 years (9.3 to 19.1). The cohort included 45 male and 38 female patients, with a mean age of 49.5 years (SD 12.5). Results. At the time of review 13 patients with 15 hips had died from causes unrelated to the hip operation, and 14 hips had undergone revision surgery, giving an overall survival rate of rate of 86.7% (95% confidence interval (CI) 84.2 to 89.1). The survival rate in men was 97.7% (95% CI 96.3 to 98.9) and in women was 73.4% (95% CI 70.6 to 75.1). The median head size of the failed group was 42 mm (interquartile range (IQR) 42 to 44), and in the surviving group was 50 mm (IQR 46 to 50). In all, 13 of the 14 revised hips had a femoral component measuring ≤ 46 mm. The mean blood levels of cobalt and chromium ions were 26.6 nmol/l (SD 24.5) and 30.6 nmol/l (SD 15.3), respectively. No metal ion levels exceeded the safe limit. The mean Oxford Hip Score was 41.5 (SD 8.9) and Harris Hip Score was 89.9 (14.8). In the surviving group, four patients had radiolucent lines around the stem of the femoral component, and one had lysis around the acetabular component; eight hips demonstrated heterotopic ossification. Conclusion. Our results confirm the existing understanding that HRA provides good long-term survival and function in patients with adequate-sized femoral heads. This is evidenced by a 97.7% survival rate among men (larger heads) in our series at a mean follow-up of 14.9 years. Failure is closely related to head sizes ≤ 46 cm. Cite this article: Bone Jt Open 2022;3(1):68–76

Aims. The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA. Methods. A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity. Results. Overall, 25 patients met inclusion criteria. There were eight benign tumours, seven metastatic, seven primary sarcomas, one multiple myeloma, and two patients without a biopsy proven diagnosis. There was no priority level 0, two priority level I, six priority level II, and 17 priority level III cases. The mean duration of delay for priority level I was 114 days (84 to 143), priority level II was 88 days (63 to 133), and priority level III was 77 days (35 to 269). Prolonged pain/disability and delay in diagnosis, affecting 52% and 40%,respectively, represented the two most frequent morbidities. Local tumour progression and increased systemic disease affected 32% and 24% respectively. No patients tested positive for COVID-19. Conclusion. COVID-19 related delays in surgical management led to major morbidity in this studied orthopaedic oncologic patient population. By understanding these morbidities through clearer hindsight, a thoughtful approach can be developed to balance the risk of COVID-19 exposure versus delay in treatment, ensuring optimal care for orthopedic oncologic patients as the pandemic continues with intermittent calls for halting surgery. Cite this article: Bone Jt Open 2021;2(4):236–242

Data of high quality are critical for the meaningful interpretation of registry information. The National Joint Registry (NJR) was established in 2002 as the result of an unexpectedly high failure rate of a cemented total hip arthroplasty. The NJR began data collection in 2003. In this study we report on the outcomes following the establishment of a formal data quality (DQ) audit process within the NJR, within which each patient episode entry is validated against the hospital unit’s Patient Administration System and vice-versa. This process enables bidirectional validation of every NJR entry and retrospective correction of any errors in the dataset. In 2014/15 baseline average compliance was 92.6% and this increased year-on-year with repeated audit cycles to 96.0% in 2018/19, with 76.4% of units achieving > 95% compliance. Following the closure of the audit cycle, an overall compliance rate of 97.9% was achieved for the 2018/19 period. An automated system was initiated in 2018 to reduce administrative burden and to integrate the DQ process into standard workflows. Our processes and quality improvement results demonstrate that DQ may be implemented successfully at national level, while minimizing the burden on hospitals. Cite this article: Bone Jt Open 2022;3(9):716–725

Aims. The aim of this study was to assess factors associated with the estimated lifetime risk of revision surgery after primary knee arthroplasty (KA). Methods. All patients from the Scottish Arthroplasty Project dataset undergoing primary KA during the period 1 January 1998 to 31 December 2019 were included. The cumulative incidence function for revision and death was calculated up to 20 years. Adjusted analyses used cause-specific Cox regression modelling to determine the influence of patient factors. The lifetime risk was calculated as a percentage for patients aged between 45 and 99 years using multiple-decrement life table methodology. Results. The estimated lifetime risk of revision ranged between 32.7% (95% confidence interval (CI) 22.6 to 47.3) for patients aged 45 to 49 years and 0.6% (95% CI 0.1 to 4.5) for patients aged over 90 years. At 20 years, the overall cumulative incidence of revision (6.8% (95% CI 6.6 to 7.0)) was significantly less than that of death (66.3% (95% CI 65.4 to 67.1)). Adjusted analyses demonstrated converse effect of increasing age on risk of revision (hazard ratio (HR) 0.5 (95% CI 0.5 to 0.6)) and death (HR 3.6 (95% CI 3.4 to 3.7)). Male sex was associated with increased risks of revision (HR 1.1 (95% CI 1.1 to 1.2); p < 0.001) and death (HR 1.4 (95% CI 1.3 to 1.4); p < 0.001). Compared to patients undergoing primary KA for osteoarthritis, patients with inflammatory arthropathy had a higher risk of death (HR 1.7 (95% CI 1.7 to 1.8); p < 0.001), but were less likely to be revised (HR 0.9 (95% CI 0.7 to 1.0); p < 0.001). Patients with a greater number of comorbidities (HR 1.4 (95% CI 1.3 to 1.4)) and greater levels of socioeconomic deprivation (HR 1.4 (95% CI 1.4 to 1.5)) were at increased risk of death, but neither increased the risk of revision. Conclusion. The estimated lifetime risk of revision KA varied depending on patient sex, age, and underlying diagnosis. Patients aged between 45 and 49 years had a one in three risk of undergoing revision surgery within their lifetime, which decreased with age to one in 159 in those aged 90 years or more. Cite this article: Bone Joint J 2022;104-B(12):1313–1322

Aims. The follow-up interval of a study represents an important aspect that is frequently mentioned in the title of the manuscript. Authors arbitrarily define whether the follow-up of their study is short-, mid-, or long-term. There is no clear consensus in that regard and definitions show a large range of variation. It was therefore the aim of this study to systematically identify clinical research published in high-impact orthopaedic journals in the last five years and extract follow-up information to deduce corresponding evidence-based definitions of short-, mid-, and long-term follow-up. Methods. A systematic literature search was performed to identify papers published in the six highest ranked orthopaedic journals during the years 2015 to 2019. Follow-up intervals were analyzed. Each article was assigned to a corresponding subspecialty field: sports traumatology, knee arthroplasty and reconstruction, hip-preserving surgery, hip arthroplasty, shoulder and elbow arthroplasty, hand and wrist, foot and ankle, paediatric orthopaedics, orthopaedic trauma, spine, and tumour. Mean follow-up data were tabulated for the corresponding subspecialty fields. Comparison between means was conducted using analysis of variance. Results. Of 16,161 published articles, 590 met the inclusion criteria. Of these, 321 were of level IV evidence, 176 level III, 53 level II, and 40 level I. Considering all included articles, a long-term study published in the included high impact journals had a mean follow-up of 151.6 months, a mid-term study of 63.5 months, and a short-term study of 30.0 months. Conclusion. The results of this study provide evidence-based definitions for orthopaedic follow-up intervals that should provide a citable standard for the planning of clinical studies. A minimum mean follow-up of a short-term study should be 30 months (2.5 years), while a mid-term study should aim for a mean follow-up of 60 months (five years), and a long-term study should aim for a mean of 150 months (12.5 years). Level of Evidence: Level I. Cite this article: Bone Jt Open 2021;2(5):344–350

Aims. The main objective of this study is to analyze the penetration of bone cement in four different full cementation techniques of the tibial tray. Methods. In order to determine the best tibial tray cementation technique, we applied cement to 40 cryopreserved donor tibiae by four different techniques: 1) double-layer cementation of the tibial component and tibial bone with bone restrictor; 2) metallic cementation of the tibial component without bone restrictor; 3) bone cementation of the tibia with bone restrictor; and 4) superficial bone cementation of the tibia and metallic keel cementation of the tibial component without bone restrictor. We performed CT exams of all 40 subjects, and measured cement layer thickness at both levels of the resected surface of the epiphysis and the endomedular metaphyseal level. Results. At the epiphyseal level, Technique 2 gave the greatest depth compared to the other investigated techniques. At the endomedular metaphyseal level, Technique 1 showed greater cement penetration than the other techniques. Conclusion. The best metaphyseal cementation technique of the tibial component is bone cementation with cement restrictor. Additionally, if full tibial component cementation is to be done, the cement volume used should be about 40 g of cement, and not the usual 20 g. Cite this article: Bone Joint Res 2021;10(8):467–473

Aims. There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients. Methods. This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. Results. Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). Conclusion. Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III. Cite this article: Bone Jt Open 2022;3(4):284–290

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. The primary aim of this study was to determine the rates of return to work (RTW) and sport (RTS) following a humeral shaft fracture. The secondary aim was to identify factors independently associated with failure to RTW or RTS. Methods. From 2008 to 2017, all patients with a humeral diaphyseal fracture were retrospectively identified. Patient demographics and injury characteristics were recorded. Details of pre-injury employment, sporting participation, and levels of return post-injury were obtained via postal questionnaire. The University of California, Los Angeles (UCLA) Activity Scale was used to quantify physical activity among active patients. Regression was used to determine factors independently associated with failure to RTW or RTS. Results. The Work Group comprised 177 patients in employment prior to injury (mean age 47 years (17 to 78); 51% female (n = 90)). Mean follow-up was 5.8 years (1.3 to 11). Overall, 85% (n = 151) returned to work at a mean of 14 weeks post-injury (0 to 104), but only 60% (n = 106) returned full-time to their previous employment. Proximal-third fractures (adjusted odds ratio (aOR) 4.0 (95% confidence interval (CI) 1.2 to 14.2); p = 0.029) were independently associated with failure to RTW. The Sport Group comprised 182 patients involved in sport prior to injury (mean age 52 years (18 to 85); 57% female (n = 104)). Mean follow-up was 5.4 years (1.3 to 11). The mean UCLA score reduced from 6.9 (95% CI 6.6 to 7.2) before injury to 6.1 (95% CI 5.8 to 6.4) post-injury (p < 0.001). There were 89% (n = 162) who returned to sport: 8% (n = 14) within three months, 34% (n = 62) within six months, and 70% (n = 127) within one year. Age ≥ 60 years was independently associated with failure to RTS (aOR 3.0 (95% CI 1.1 to 8.2); p = 0.036). No other factors were independently associated with failure to RTW or RTS. Conclusion. Most patients successfully return to work and sport following a humeral shaft fracture, albeit at a lower level of physical activity. Patients aged ≥ 60 yrs and those with proximal-third diaphyseal fractures are at increased risk of failing to return to activity. Cite this article: Bone Jt Open 2022;3(3):236–244

Aims. Patients with A1 and A2 trochanteric hip fractures represent a substantial proportion of trauma caseload, and national guidelines recommend that sliding hip screws (SHS) should be used for these injuries. Despite this, intramedullary nails (IMNs) are routinely implanted in many hospitals, at extra cost and with unproven patient outcome benefit. We have used data from the National Hip Fracture Database (NHFD) to examine the use of SHS and IMN for A1 and A2 hip fractures at a national level, and to define the cost implications of management decisions that run counter to national guidelines. Methods. We used the NHFD to identify all operations for fixation of trochanteric fractures in England and Wales between 1 January 2021 and 31 December 2021. A uniform price band from each of three hip fracture implant manufacturers was used to set cost implications alongside variation in implant use. Results. We identified 18,156 A1 and A2 trochanteric hip fractures in 162 centres. Of these, 13,483 (74.3%) underwent SHS fixation, 2,352 (13.0%) were managed with short IMN, and 2,321 (12.8%) were managed with long IMN. Total cost of IMN added up to £1.89 million in 2021, and the clinical justification for this is unclear since rates of IMN use varied from 0% to 97% in different centres. Conclusion. Most trochanteric hip fractures are managed with SHS, in keeping with national guidelines. There is considerable variance between hospitals for implant choice, despite the lack of evidence for clinical benefit and cost-effectiveness of more expensive nailing systems. This suggests either a lack of awareness of national guidelines or a choice not to follow them. We encourage provider units to reassess their practice if outwith the national norm. Funding bodies should examine implant use closely in this population to prevent resource waste at a time of considerable health austerity. Cite this article: Bone Jt Open 2022;3(10):741–745

Aims. We introduced a self-care pathway for minimally displaced distal radius fractures, which involved the patient being discharged from a Virtual Fracture Clinic (VFC) without a physical review and being provided with written instructions on how to remove their own cast or splint at home, plus advice on exercises and return to function. Methods. All patients managed via this protocol between March and October 2020 were contacted by a medical secretary at a minimum of six months post-injury. The patients were asked to complete the Patient-Rated Wrist Evaluation (PRWE), a satisfaction questionnaire, advise if they had required surgery and/or contacted any health professional, and were also asked for any recommendations on how to improve the service. A review with a hand surgeon was organized if required, and a cost analysis was also conducted. Results. Overall 71/101 patients completed the telephone consultation; no patients required surgery, and the mean and median PRWE scores were 23.9/100 (SD 24.9) and 17.0/100 (interquartile range (IQR) 0 to 40), respectively. Mean patient satisfaction with treatment was 34.3/40 (SD 9.2), and 65 patients (92%) were satisfied or highly satisfied. In total there were 16 contact calls, 12 requests for a consultant review, no formal complaints, and 15 minor adjustment suggestions to improve patient experience. A relationship was found between intra-articular injuries and lower patient satisfaction scores (p = 0.025), however no relationship was found between PRWE scores and the nature of the fracture. Also, no relationship was found between the type of immobilization and the functional outcome or patient satisfaction. Cost analysis of the self-care pathway V traditional pathway showed a cost savings of over £13,500 per year with the new self-care model compared to the traditional model. Conclusion. Our study supports a VFC self-care pathway for patients with minimally displaced distal radius fractures. The pathway provides a good level of patient satisfaction and function. To improve the service, we will make minor amendments to our patient information sheet. Cite this article: Bone Jt Open 2022;3(9):726–732

Aims. The aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee periprosthetic joint infection (PJI). Methods. We conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane library from inception until May 2021. Random effects meta-analyses and meta-regression was used to estimate, on a study level, the success rate of DAIR related to component exchange. Risk of bias was appraised using the (AQUILA) checklist. Results. We included 65 studies comprising 6,630 patients. The pooled overall success after DAIR for PJI was 67% (95% confidence interval (CI) 63% to 70%). This was 70% (95% CI 65% to 75%) for DAIR for hip PJI and 63% (95% CI 58% to 69%) for knee PJI. In studies before 2004 (n = 27), our meta-regression analysis showed a 3.5% increase in success rates for each 10% increase in component exchange in DAIR for hip PJI and a 3.1% increase for each 10% increase in component exchange for knee PJI. When restricted to studies after 2004 (n = 37), this association changed: for DAIR for hip PJI a decrease in successful outcome by 0.5% for each 10% increase in component exchange and for DAIR for knee PJI this was a 0.01% increase in successful outcome for each 10% increase in component exchange. Conclusion. This systematic review and meta-regression found no benefit of modular component exchange on reduction of PJI failure. This limited effect should be weighed against the risks for the patient and cost on a case-by-case basis. The association between exchange of modular components and outcome changed before and after 2004. This suggests the effect seen after 2004 may reflect a more rigorous, evidence-based, approach to the infected implant compared to the years before. Level of Evidence: Level III. Cite this article: Bone Jt Open 2021;2(10):806–812

Aims. Dual mobility (DM) implants have been shown to reduce the dislocation rate after total hip arthroplasty (THA), but there remain concerns about the use of cobalt chrome liners inserted into titanium shells. The aim of this study was to assess the clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) at mid-term follow-up in young, active patients receiving a modular DM THA. Methods. This was a prospective study involving patients aged < 65 years, with a BMI of < 35 kg/m. 2. , and University of California, Los Angeles activity score of > 6 who underwent primary THA with a modular cobalt chrome acetabular liner, highly cross-linked polyethylene mobile bearing, and a cementless titanium femoral stem. Patient-reported outcome measures, whole blood metal ion levels (μg/l), and periprosthetic femoral BMD were measured at baseline and at one, two, and five years postoperatively. The results two years postoperatively for this cohort have been previously reported. Results. A total of 43 patients were enrolled. At minimum follow-up of five years, 23 (53.4%) returned for clinical and radiological review, 25 (58.1%) had metal ion analysis performed, 19 (44.2%) underwent dual energy x-ray absorptiometry scans, and 25 (58%) completed a pain-drawing questionnaire. The mean modified Harris Hip Scores improved significantly from 54.8 (SD 19) preoperatively to 93.08 (SD 10.5) five years postoperatively (p < 0.001). One patient was revised for aseptic acetabular loosening. The mean cobalt levels increased from 0.065 μg/l (SD 0.03) to 0.08 (SD 0.05) and the mean titanium levels increased from 0.35 (SD 0.13) to 0.78 (SD 0.29). The femoral BMD ratio decreased in Gruen Zone 1 (91.9%) at five years postoperatively compared with the baseline scores at six weeks potoperatively. The femoral BMD ratio was maintained in Gruen zones 2 to 7. Conclusion. The use of a modular DM component and a cementless, tapered femoral stem shows excellent mid-term survivorship with minimal concerns for corrosion and metal ion release in a cohort of young, active patients undergoing primary THA. Cite this article: Bone Joint J 2021;103-B(7 Supple B):73–77