Aims. Biopsy of the periprosthetic tissue is an important diagnostic tool for prosthetic joint infection (PJI) as it enables the detection of the responsible microorganism with its sensitivity to antibiotics. We aimed to investigate how often the bacteria identified in the tissue analysis differed between samples obtained from preoperative biopsy and intraoperative revision surgery in cases of late PJI; and whether there was a therapeutic consequence. Methods. A total of 508 patients who required revision surgery of total hip arthroplasty (THA) (n = 231) or total knee arthroplasty (TKA) (n = 277) because of component loosening underwent biopsy before revision surgery. The tissue samples collected at biopsy and during revision surgery were analyzed according to the criteria of the Musculoskeletal Infection Society (MSIS). Results. In total, 178 (113 THA, 65 TKA) were classified as infected. The biopsy procedure had a sensitivity of 93.8%, a specificity of 97.3%, a positive predictive value (PPV) of 94.9%, a negative predictive value (NPV) of 96.7%, and an accuracy of 96.1%. Of the 178 infected patients, 26 showed a difference in the detected bacteria from the biopsy and the revision surgery (14.6%). This difference required a change to antibiotic therapy in only two cases (1.1%). Conclusion. Biopsy is a useful tool to diagnose PJI, but there may be a difference in the detected bacteria between the biopsy and revision surgery. However, this did not affect the choice of antibiotic therapy in most cases, rendering the clinical relevance of this phenomenon as low. Cite this article: Bone Joint J 2020;102-B(3):329–335

Aims. The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD). Patients and Methods. Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF). Results. Of the 29 pyogenic SD patients, 17 had positive microbiology and 21 positive histology (i.e. one or more NPs per HPF on average). All non-SD patients showed less than one NP per HPF. The presence of one or more NPs per HPF had a diagnostic sensitivity of 72.4%, specificity 100%, accuracy 100%, positive predictive value (PPV) 81.0%, and negative predictive value (NPV) 61.9%. Sensitivity, specificity, and accuracy were greater using the criterion of positive histology and/or microbiology than positive histology or microbiology alone. Granulomas were identified histologically in seven mycobacterial SD patients, and positive microbiology was detected in four. Conclusion. The diagnosis of pyogenic SD was more often confirmed by positive histology (one or more NPs per HPF on average) than by microbiology, although diagnostic sensitivity was greater when both histology and microbiology were positive. Cite this article: Bone Joint J 2019;101-B:246–252

Aims. A pragmatic multicentre randomized controlled trial, UK FROzen Shoulder Trial (UK FROST), was conducted in the UK NHS comparing the cost-effectiveness of commonly used treatments for adults with primary frozen shoulder in secondary care. Methods. A cost utility analysis from the NHS perspective was performed. Differences between manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR), and early structured physiotherapy plus steroid injection (ESP) in costs (2018 GBP price base) and quality adjusted life years (QALYs) at one year were used to estimate the cost-effectiveness of the treatments using regression methods. Results. ACR was £1,734 more costly than ESP ((95% confidence intervals (CIs) £1,529 to £1,938)) and £1,457 more costly than MUA (95% CI £1,283 to £1,632). MUA was £276 (95% CI £66 to £487) more expensive than ESP. Overall, ACR had worse QALYs compared with MUA (-0.0293; 95% CI -0.0616 to 0.0030) and MUA had better QALYs compared with ESP (0.0396; 95% CI -0.0008 to 0.0800). At a £20,000 per QALY willingness-to-pay threshold, MUA had the highest probability of being cost-effective (0.8632) then ESP (0.1366) and ACR (0.0002). The results were robust to sensitivity analyses. Conclusion. While ESP was less costly, MUA was the most cost-effective option. ACR was not cost-effective. Cite this article: Bone Jt Open 2021;2(8):685–695

Aims. The purpose of this study was to validate our hypothesis that centrifugation may eliminate false-positive leucocyte esterase (LE) strip test results caused by autoimmune diseases in the diagnosis of knee infection. Methods. Between January 2016 and May 2019, 83 cases, including 33 cases of septic arthritis and 50 cases of aseptic arthritis, were enrolled in this study. To further validate our hypothesis, another 34 cases of inflammatory arthritis from the Department of Rheumatology of our institution were also included. After aspiration, one drop of synovial fluid was applied to LE strips before and after centrifugation. The results were recorded after approximately three minutes according to the different colour grades on the colour chart. The differences of LE results between each cohort were analyzed. Results. Before centrifugation, 46% (23/50) of the LE strip tests in the aseptic arthritis group were false-positives. Most of the false-positive results were due to inflammatory arthritis; after centrifugation, 78.3% (18/23) of the tests yielded negative results. Similar results were observed in cases from the Department of Rheumatology. The sensitivity of the centrifuged LE strip test was 0.818 (0.639 to 0.924), which is still an acceptable level compared with the uncentrifuged results, which yielded a sensitivity of 0.909 (0.745 to 0.976). However, the specificity was increased from 0.540 (0.395 to 0.679) to 0.900 (0.774 to 0.963) after centrifugation. Conclusion. Although inflammatory arthritis can yield a false-positive LE strip test result in the diagnosis of knee infection, centrifugation may eliminate these false-positive results. Cite this article: Bone Joint Res. 2020;9(5):236–241

Aims. This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods. A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results. According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion. This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required. Cite this article:Bone Joint Res. 2020;9(5):202–210

Aims. Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients. Methods. A retrospective cohort study was undertaken using autonomous CTFEA performed on existing abdominal or pelvic CT data comparing two groups of T2DM patients: a study group of 27 patients who had sustained a hip fracture within the year following the CT scan and a control group of 24 patients who did not have a hip fracture within one year. The main outcome of the CTFEA is a novel measure of hip bone strength termed the Hip Strength Score (HSS). Results. The HSS was significantly lower in the study group (1.76 (SD 0.46)) than in the control group (2.31 (SD 0.74); p = 0.002). A multivariate model showed the odds of having a hip fracture were 17 times greater in patients who had an HSS ≤ 2.2. The CTFEA has a sensitivity of 89%, a specificity of 76%, and an area under the curve of 0.90. Conclusion. This preliminary study demonstrates the feasibility of using a CTFEA-based bone strength parameter to assess hip fracture risk in a population of T2DM patients. Cite this article: Bone Joint J 2021;103-B(9):1497–1504

Aims. The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods. Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results. Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion. The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977

Aims. The aim of this study was to estimate the cost-effectiveness of negative-pressure wound therapy (NPWT) in comparison with standard wound management after initial surgical wound debridement in adults with severe open fractures of the lower limb. Patients and Methods. An economic evaluation was conducted from the perspective of the United Kingdom NHS and Personal Social Services, based on evidence from the 460 participants in the Wound Management of Open Lower Limb Fractures (WOLLF) trial. Economic outcomes were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Bivariate regression of costs (given in £, 2014 to 2015 prices) and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained associated with NPWT dressings. Sensitivity and subgroup analyses were undertaken to assess the impacts of uncertainty and heterogeneity, respectively, surrounding aspects of the economic evaluation. Results. The base case analysis produced an incremental cost-effectiveness ratio of £267 910 per QALY gained, reflecting higher costs on average (£678; 95% confidence interval (CI) -£1082 to £2438) and only marginally higher QALYS (0.002; 95% CI -0.054 to 0.059) in the NPWT group. The probability that NPWT is cost-effective in this patient population did not exceed 27% regardless of the value of the cost-effectiveness threshold. This result remained robust to several sensitivity and subgroup analyses. Conclusion. This trial-based economic evaluation suggests that NPWT is unlikely to be a cost-effective strategy for improving outcomes in adult patients with severe open fractures of the lower limb. Cite this article: Bone Joint J 2019;101-B:1392–1401

Aims. The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI). Materials and Methods. Studies using alpha-defensin or Synovasure (Zimmer Biomet, Warsaw, Indiana) to diagnose PJI were identified from systematic searches of electronic databases. The quality of the studies was evaluated using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) tool. Meta-analysis was completed using a bivariate model. Results. A total of 11 eligible studies were included. The median QUADAS score was 13 (interquartile range 13 to 13) out of 14. Significant conflicts of interest were identified in five studies. The pooled sensitivity for the laboratory alpha-defensin test was 0.95 (95% confidence interval (CI) 0.91 to 0.98) and the pooled specificity was 0.97 (95% CI 0.95 to 0.98) for four studies with a threshold level of 5.2 mgl. -1. The pooled sensitivity for the lateral flow cassette test was 0.85 (95% CI 0.74 to 0.92) and the pooled specificity was 0.90 (95% CI 0.91 to 0.98). There was a statistically significant difference in sensitivity (p = 0.019), but not specificity (p = 0.47). Conclusion. Laboratory-based alpha-defensin testing remains a promising tool for diagnosing PJI. The lateral flow cassette has a significantly lower performance and pooled results are comparable to the leucocyte esterase test. Further studies are required before the widespread adoption of the lateral flow cassette alpha-defensin test. Cite this article: Bone Joint J 2018;100-B:703–11

Aims. The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development. Methods. Diabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot. Results. The established diabetic mice were more sensitive to ovariectomy (OVX)-induced osteoporosis, and DMF treatment inhibited the sensitivity. OVX-treated diabetic mice exhibited higher TRAP5b and c-terminal telopeptides of type 1 (CTX1) levels, and DMF treatment inhibited the enhancement. DMF reduced RAW 264.7 cell viability. Glucose treatment enhanced the levels of TRAP5b, cathepsin K, Atp6v0d2, and H. +. -ATPase, ROS, while DMF reversed this phenotype. The glucose-increased protein levels were inhibited by DMF in cells treated with RANKL. The expression levels of antioxidant enzymes Gclc, Gclm, Ho-1, and Nqo1 were upregulated by DMF. DMF attenuated high glucose-caused osteoclast differentiation by targeting mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signalling in BMMs. Conclusion. DMF inhibits high glucose-induced osteoporosis by targeting MAPK and NF-κB signalling. Cite this article: Bone Joint Res 2022;11(4):200–209

Aims. Abnormal femoral torsion (FT) is increasingly recognized as an additional cause for femoroacetabular impingement (FAI). It is unknown if in-toeing of the foot is a specific diagnostic sign for increased FT in patients with symptomatic FAI. The aims of this study were to determine: 1) the prevalence and diagnostic accuracy of in-toeing to detect increased FT; 2) if foot progression angle (FPA) and tibial torsion (TT) are different among patients with abnormal FT; and 3) if FPA correlates with FT. Patients and Methods. A retrospective, institutional review board (IRB)-approved, controlled study of 85 symptomatic patients (148 hips) with FAI or hip dysplasia was performed in the gait laboratory. All patients had a measurement of FT (pelvic CT scan), TT (CT scan), and FPA (optical motion capture system). We allocated all patients to three groups with decreased FT (< 10°, 37 hips), increased FT (> 25°, 61 hips), and normal FT (10° to 25°, 50 hips). Cluster analysis was performed. Results. We found a specificity of 99%, positive predictive value (PPV) of 93%, and sensitivity of 23% for in-toeing (FPA < 0°) to detect increased FT > 25°. Most of the hips with normal or decreased FT had no in-toeing (false-positive rate of 1%). Patients with increased FT had significantly (p < 0.001) more in-toeing than patients with decreased FT. The majority of the patients (77%) with increased FT walk with a normal foot position. The correlation between FPA and FT was significant (r = 0.404, p < 0.001). Five cluster groups were identified. Conclusion. In-toeing has a high specificity and high PPV to detect increased FT, but increased FT can be missed because of the low sensitivity and high false-negative rate. These results can be used for diagnosis of abnormal FT in patients with FAI or hip dysplasia undergoing hip arthroscopy or femoral derotation osteotomy. However, most of the patients with increased FT walk with a normal foot position. This can lead to underestimation or misdiagnosis of abnormal FT. We recommend measuring FT with CT/MRI scans in all patients with FAI. Cite this article: Bone Joint J 2019;101-B:1218–1229

Aims. The aims of this study were to evaluate wear on the surface of cobalt-chromium (CoCr) femoral components used in total knee arthroplasty (TKA) and compare the wear of these components with that of ceramic femoral components. Methods. Optical profilometry was used to evaluate surface roughness and to examine the features created by the wear process in a knee wear simulator. We developed a method of measuring surface changes on five CoCr femoral components and quantifying the loss of material from the articular surface during the wear process. We also examined the articular surface of three ceramic femoral components from a previous test for evidence of surface damage, and compared it with that of CoCr components. Results. We found that the surface roughness of CoCr components rapidly increased during the first 1,000 wear cycles, then reached a steady state, but material loss from the surface continued at a rate of 1,778,000 μm. 3. per million cycles as carbides were removed from its matrix. These carbides formed third-body wear particles, leading to the formation of new scratches even as older scratches were worn away. In contrast, no scratching, loss of material, or other surface damage, when evaluated with one nanometer resolution, was found on the surface of the ceramic components after a 15 M wear cycle test. Conclusion. This study showed wear and loss of CoCr material from scratching and microabrasive wear in TKA. The material loss from the surface continued in a linear relationship with increasing cycles. We also found the absence of scratching and roughening of ceramic femoral components in simulated wear, suggesting an advantage in wear rate and avoiding metal sensitivity. This may have implications in the management of persistent pain after TKA. Cite this article: Bone Joint J 2021;103-B(6 Supple A):94–101

Aims. Adverse local tissue reactions associated with abnormal wear considerably slowed down the general use of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), now limited to a few specialized centres. In this study, we provide the clinical results of 400 consecutive MoM HRAs implanted more than 20 years ago in one such centre. Methods. A total of 355 patients (400 hips) were treated with Conserve Plus HRA between November 1996 and November 2000. There were 96 female (27%) and 259 male patients (73%). Their mean age was 48.2 years (SD 10.9). The University of California, Los Angeles (UCLA) hip scores and 12-item Short Form Survey (SF-12) quality of life scores were reported. Survivorship was assessed using Kaplan-Meier analyses. Results. The mean follow-up was 16.5 years (0.1 to 24.0), including 34 patients (37 hips) who died. The mean UCLA hip scores were 9.3 (2 to 10), 9.1 (3 to 10), 9.0 (3 to 10), and 6.9 (2 to 10) for pain, walking, function, and activity, respectively. The mean SF-12 scores were 48.4 (16.0 to 62.1) for the physical component and 48.5 (10.5 to 66.5) for the mental component, and did not differ from those of the general population of the USA. A total of 60 hips in 55 patients were revised. Using revision for any indication as the endpoint, the Kaplan-Meier survivorship was 83.5% at 20 years. A diagnosis of developmental dysplasia (hazard ratio (HR) 2.199 (95% confidence interval (CI) 1.140 to 4.239); p = 0.019) and a low BMI (HR 0.931 (95% CI 0.873 to 0.994); p = 0.032) were risk factors for revision. Female sex was a risk factor only because of hip dysplasia and small component size. There were no cases of metal sensitivity associated with revision surgery. Radiological analysis showed persistent fixation in all but one hip. Conclusion. The 83.5% 20-year survivorship of this initial series surpasses that of total hip arthroplasties in use 20 years ago in these young patients, suggesting satisfactory lifelong durability of the device for almost all of the remaining patients. Cite this article: Bone Joint J 2021;103-B(7 Supple B):25–32

Aims. The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. Methods. In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. Results. A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). Conclusion. Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85–95

Aims. This study of patients with osteoarthritis (OA) of the hip aimed to: 1) characterize the contribution of the hip, spinopelvic complex, and lumbar spine when moving from the standing to the sitting position; 2) assess whether abnormal spinopelvic mobility is associated with worse symptoms; and 3) identify whether spinopelvic mobility can be predicted from static anatomical radiological parameters. Patients and Methods. A total of 122 patients with end-stage OA of the hip awaiting total hip arthroplasty (THA) were prospectively studied. Patient-reported outcome measures (PROMs; Oxford Hip Score, Oswestry Disability Index, and Veterans RAND 12-Item Health Survey Score) and clinical data were collected. Sagittal spinopelvic mobility was calculated as the change from the standing to sitting position using the lumbar lordosis angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic-femoral angle (PFA), and acetabular anteinclination (AI) from lateral radiographs. The interaction of the different parameters was assessed. PROMs were compared between patients with normal spinopelvic mobility (10° ≤ ∆PT ≤ 30°) or abnormal spinopelvic mobility (stiff: ∆PT < ± 10°; hypermobile: ∆PT > ± 30°). Multiple regression and receiver operating characteristic (ROC) curve analyses were used to test for possible predictors of spinopelvic mobility. Results. Standing to sitting, the hip flexed by a mean of 57° (. sd. 17°), the pelvis tilted backwards by a mean of 20° (. sd. 12°), and the lumbar spine flexed by a mean of 20° (. sd. 14°); strong correlations were detected. There was no difference in PROMs between patients in the different spinopelvic mobility groups. Maximum hip flexion, standing PT, and standing AI were independent predictors of spinopelvic mobility (R. 2. = 0.42). The combined thresholds for standing was PT ≥ 13° and hip flexion ≥ 88° in the clinical examination, and had 90% sensitivity and 63% specificity of predicting spinopelvic stiffness, while SS ≥ 42° had 84% sensitivity and 67% specificity of predicting spinopelvic hypermobility. Conclusion. The hip, on average, accounts for three-quarters of the standing-to-sitting movement, but there is great variation. Abnormal spinopelvic mobility cannot be screened with PROMs. However, clinical and standing radiological features can predict spinopelvic mobility with good enough accuracy, allowing them to be used as reliable screening tools. Cite this article: Bone Joint J 2019;101-B:902–909

Objectives. The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). Methods. The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus. Results. The 16s rDNA test proved to be very robust and was able to provide a result in 97% of all samples within 25 minutes. The 16s rDNA test was able to diagnose PJI with a sensitivity of 87.5% and 82%, and a specificity of 100% and 89%, in the proof-of-principle and validation cohorts, respectively. The microbiological culture of synovial fluid achieved a sensitivity of 80% and a specificity of 93% in the validation cohort. Conclusion. The 16s rDNA test offers reliable intraoperative detection of all bacterial species within 25 minutes with a sensitivity and specificity comparable with those of conventional microbiological culture of synovial fluid for the detection of PJI. The 16s rDNA test performance is independent of possible blood contamination, culture time and bacterial species. Cite this article: V. Janz, J. Schoon, C. Morgenstern, B. Preininger, S. Reinke, G. Duda, A. Breitbach, C. F. Perka, S. Geissler. Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study. Bone Joint Res 2018;7:12–19. DOI: 10.1302/2046-3758.71.BJR-2017-0103.R2

Aims. To determine whether half-threaded screw holes in a new titanium locking plate design can substantially decrease the notch effects of the threads and increase the plate fatigue life. Methods. Three types (I to III) of titanium locking plates were fabricated to simulate plates used in the femur, tibia, and forearm. Two copies of each were fabricated using full- and half-threaded screw holes (called A and B, respectively). The mechanical strengths of the plates were evaluated according to the American Society for Testing and Materials (ASTM) F382-14, and the screw stability was assessed by measuring the screw removal torque and bending strength. Results. The B plates had fatigue lives 11- to 16-times higher than those of the A plates. Before cyclic loading, the screw removal torques were all higher than the insertion torques. However, after cyclic loading, the removal torques were similar to or slightly lower than the insertion torques (0% to 17.3%), although those of the B plates were higher than those of the A plates for all except the type III plates (101%, 109.8%, and 93.8% for types I, II, and III, respectively). The bending strengths of the screws were not significantly different between the A and B plates for any of the types. Conclusion. Removing half of the threads from the screw holes markedly increased the fatigue life of the locking plates while preserving the tightness of the screw heads and the bending strength of the locking screws. However, future work is necessary to determine the relationship between the notch sensitivity properties and titanium plate design. Cite this article: Bone Joint Res 2020;9(10):645–652

Aims. The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Methods. Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA. Results. PLS-DA produced a streamlined biomarker model with excellent sensitivity (95%), specificity (98.4%), and reliability (97.4%). The eight-biomarker model produced a fingerprint for esOA comprising type IIA procollagen N-terminal propeptide (PIIANP), tissue inhibitor of metalloproteinase (TIMP)-1, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), monocyte chemoattractant protein (MCP)-1, interferon-γ-inducible protein-10 (IP-10), and transforming growth factor (TGF)-β3. Receiver operating characteristic (ROC) analysis demonstrated excellent discriminatory accuracy: area under the curve (AUC) being 0.970 for esOA, 0.957 for knee injury, and 1 for inflammatory arthritis. All ten validation test patients were classified correctly as esOA (accuracy 100%; reliability 100%) by the biomarker model. Conclusion. SF analysis coupled with machine learning produced a partially validated biomarker model with cohort-specific fingerprints that accurately and reliably discriminated esOA from knee injury and inflammatory arthritis with almost 100% efficacy. The presented findings and approach represent a new biomarker concept and potential diagnostic tool to stage disease in therapy trials and monitor the efficacy of such interventions. Cite this article: Bone Joint Res 2020;9(9):623–632

Aims. To evaluate if union of clavicle fractures can be predicted at six weeks post-injury by the presence of bridging callus on ultrasound. Methods. Adult patients managed nonoperatively with a displaced mid-shaft clavicle were recruited prospectively. Ultrasound evaluation of the fracture was undertaken to determine if sonographic bridging callus was present. Clinical risk factors at six weeks were used to stratify patients at high risk of nonunion with a combination of Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) ≥ 40, fracture movement on examination, or absence of callus on radiograph. Results. A total of 112 patients completed follow-up at six months with a nonunion incidence of 16.7% (n = 18/112). Sonographic bridging callus was detected in 62.5% (n = 70/112) of the cohort at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n = 69/70). If absent, nonunion developed in 40.5% of cases (n = 17/42). The sensitivity to predict union with sonographic bridging callus at six weeks was 73.4% and the specificity was 94.4%. Regression analysis found that failure to detect sonographic bridging callus at six weeks was associated with older age, female sex, simple fracture pattern, smoking, and greater fracture displacement (Nagelkerke R. 2. = 0.48). Of the cohort, 30.4% (n = 34/112) had absent sonographic bridging callus in addition to one or more of the clinical risk factors at six weeks that predispose to nonunion. If one was present the nonunion rate was 35%, 60% with two, and 100% when combined with all three. Conclusion. Ultrasound combined with clinical risk factors can accurately predict fracture healing at six weeks following a displaced midshaft clavicle fracture. Cite this article: Bone Joint Res 2021;10(2):113–121

Aims. To estimate the measurement properties for the Oxford Knee Score (OKS) in patients undergoing revision knee arthroplasty (responsiveness, minimal detectable change (MDC-90), minimal important change (MIC), minimal important difference (MID), internal consistency, construct validity, and interpretability). Methods. Secondary data analysis was performed for 10,727 patients undergoing revision knee arthroplasty between 2013 to 2019 using a UK national patient-reported outcome measure (PROM) dataset. Outcome data were collected before revision and at six months postoperatively, using the OKS and EuroQol five-dimension score (EQ-5D). Measurement properties were assessed according to COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) guidelines. Results. A total of 9,219 patients had complete outcome data. Mean preoperative OKS was 16.7 points (SD 8.1), mean postoperative OKS 29.1 (SD 11.4), and mean change in OKS + 12.5 (SD 10.7). Median preoperative EQ-5D index was 0.260 (interquartile range (IQR) 0.055 to 0.691), median postoperative EQ-5D index 0.691 (IQR 0.516 to 0.796), and median change in EQ-5D index + 0.240 (IQR 0.000 to 0.567). Internal consistency was good with Cronbach’s α 0.88 (baseline) and 0.94 (post-revision). Construct validity found a high correlation of OKS total score with EQ-5D index (r = 0.76 (baseline), r = 0.83 (post-revision), p < 0.001). The OKS was responsive with standardized effect size (SES) 1.54 (95% confidence interval (CI) 1.51 to 1.57), compared to SES 0.83 (0.81 to 0.86) for the EQ-5D index. The MIC for the OKS was 7.5 points (95% CI 5.5 to 8.5) based on the optimal cut-off with specificity 0.72, sensitivity 0.60, and area under the curve 0.66. The MID for the OKS was 5.2 points. The MDC-90 was 3.9 points. The OKS did not demonstrate significant floor or ceiling effects. Conclusion. This study found that the OKS was a useful and valid instrument for assessment of outcome following revision knee arthroplasty. The OKS was responsive to change and demonstrated good measurement properties. Cite this article: Bone Joint J 2021;103-B(4):627–634