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

Introduction. Lumbosacral transitional vertebrae (LSTV) are increasingly recognized as a common anatomical variant and is the most common congenital anomaly of the lumbosacral spine. Patients can have symptomatic LSTV, known as Bertolotti's Syndrome, where transitional anatomy can cause back, L5 distribution leg, hip, and groin pain. We propose an outline for diagnosis and treatment of Bertolotti's Syndrome. Methods. We retrospectively reviewed over 500 patients presenting to the primary author with low back, buttock, hip, groin and/or leg pain from April 2009 through April 2024. Patients with radiographic findings of an LSTV and clinical presentation underwent diagnostic injections to confirm diagnosis of Bertolotti's syndrome. Treatment was determined based on patient's LSTV classification. 157 patients with confirmed Bertolotti's syndrome underwent surgical treatment. Results. Over 500 patients presented with an appropriate clinical presentation and radiographic findings of an LSTV. Diagnostic injections were targeted into the transitional anatomy confirming the LSTV as the primary pain generator to make the diagnosis of Bertolotti's syndrome. The decision in the type of surgical intervention, resection or fusion, was made based on patient's LSTV anatomy. 157 patients with confirmed Bertolotti's Syndrome underwent surgical treatment (121 fusions (77%), 36 resections (23%)). The classification system and surgical outcomes, in part, have been previously published in World Neurosurgery. Conclusion. We have outlined the best practice of diagnosis and treatment selection for Bertolotti's syndrome. We have shown significant improvement in outcomes based on this method. We hope to aid in both patient education and provide an outline on how clinicians can become knowledgeable on Bertolotti's syndrome. Conflicts of interest. No conflicts of interest. Sources of funding. No funding obtained

Introduction. Fracture related infection (FRI) is a challenging complication to manage in an orthoplastic setting. Consensus guidelines have been created to standardise the diagnosis of FRI and comprise confirmatory and suggestive criteria. In this study, the aim is to assess the diagnostic criteria and management of FRI with a particular focus on soft tissue reconstruction. Materials & Methods. A retrospective study to identify the outcomes of FRI in the lower limb over a five year period at a Major Trauma Centre. Fracture specific information that was analysed includes: open versus closed, fractured bone(s) and site, initial fracture management, method of diagnosis and soft tissue management. Results. A total of 40 patients were identified, 80% of whom were male (n= 32). The mean age for FRI diagnosis was 54 years (range 18–83 years). In our patient cohort, 10% were immunosuppressed and another 12.5% had a formal diagnosis of Diabetes Mellitus. A diagnosis of acute FRI (i.e. < six weeks from time of injury) was made in 9 patients (22.5%). Chronic FRI was noted in 25 patients (62.5%). There was equal incidence of FRI in patients with closed fractures and open fractures (42.5%). Tibia and fibula fractures were most common (87.5%, n=35). Regardless of fractured bone(s), the more distal the fracture the higher the incidence of FRI (60% distal versus 12.5% proximal). Gram-positive cocci were the most commonly identified pathogens, identified in 25% of patients. Five patients underwent free flap reconstruction, two patients received pedicled muscle flaps and another two patients received split thickness skin grafts. Conclusions. The diagnosis of FRI can be confirmed through the presence of a combination of confirmatory and suggestive criteria. We advocate a staged approach in the management of FRI with radical wound excision and temporary coverage followed by definitive soft tissue reconstruction

Background. The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice and the analysis of synovial fluid (SF) is a useful diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase (LE) strip test, alpha-defensin (AD)) have been introduced into the MSIS (MusculoSkeletal Infection Society) algorithm for the diagnosis of PJI. AD, although promising with high sensitivity and specificity, remains expensive. Calprotectin is another protein released upon activation of articular neutrophils. The determination of calprotectin and joint CRP is feasible in a routine laboratory practice with low cost. Purpose. Our objective was to evaluate different synovial biomarkers (calprotectin, LE, CRP) for the diagnosis of PJI. Methods. In this monocentric study, we collected SF from hip, knee, ankle and shoulder joints of 42 patients who underwent revision or puncture for diagnostic purposes. Exclusion criteria included a joint surgery in the previous 3 months and a diagnosis of a systemic inflammatory disease. PJI was diagnosed in a multidisciplinary consultation meeting (RCP) of the Reference Centers for Osteoarticular Infections of the Great West (CRIOGO). SF was analysed for LE, CRP and calprotectin. The cut-off values used were 50 mg/L for calprotectin, 8.8 mg/L for CRP and 125 WBC/µL for LE. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for these different synovial markers. Results. Of the 42 patients included, 28 were considered as infected and 14 uninfected. The statistical parameters are presented in Table 1. Conclusion. The present study shows that the synovial calprotectin assay has an excellent sensitivity and a 100% NPV for the diagnosis of PJI, suggesting that a result < 50 mg/L could exclude PJI. This promising study suggests that calprotectin should be included with synovial CRP in a new decision algorithm for the diagnosis of PJI. For any tables or figures, please contact the authors directly

Aims. This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). Methods. In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. Results. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. Conclusion. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120

Introduction:. Most of the published papers on AI based diagnosis have focused on the algorithm's diagnostic performance in a ‘binary’ setting (i.e. disease vs no disease). However, no study evaluated the actual value for the clinicians of an AI based approach in diagnostic. Detection of Traumatic thoracolumbar (TL) fractures is challenging on planar radiographs, resulting in significant rates of missed diagnoses (30-60%), thus constituting a field in which a performance improvement is needed. Aim of this study is therefore to evaluate the value provided by AI generated saliency maps (SM), i.e. the maps that highlight the AI identified region of interests. Methods:. An AI model aimed at identifying TL fractures on plain radiographs was trained and tested on 567 single vertebrae images. Three expert spine surgeons established the Ground Truth (GT) using CT and MRI to confirm the presence of the fracture. From the test set, 12 cases (6 with a GT of fracture and 6 with a GT of no fracture, associated with varying levels of algorithm confidence) were selected and the corresponding SMs were generated and shown to 7 independent evaluators with different grade of experience; the evaluators were requested to: (1) identify the presence or absence of a fracture before and after the saliency map was shown; (2) grade, with a score from 1 (low) to 6 (high) the pertinency (correlation between the map and the human diagnosis), and the utility (the perceived utility in confirming or not the initial diagnosis) of the SM. Furthermore, the usefulness of the SM was evaluated through the rate of correct change in diagnosis after the maps had been shown. Finally, the obtained scores were correlated with the algorithm confidence for the specific case. Results:. Of the selected maps, 8 had an agreement between the AI diagnosis and the GT, while in 4 the diagnosis was discordant (67% accuracy). The pertinency of the map was found higher when the AI diagnosis was the same as the GT and the human diagnosis (respectively p-value = .021 and <.000). A positive and significant correlation between the AI confidence score and the perceived utility (Spearman: 27%, p-value=.0-27) was found. Furthermore, evaluator with experience < 5 year found the maps more useful than the experts (z-score=2.004; p-value=.0455). Among the 84 evaluation we found 12 diagnostic errors in respect to the GT, 6 (50%) of which were reverted after the saliency map evaluation (z statistic = 1.25 and p-value = .21). Discussion:. The perceived utility of AI generated SM correlate with the model confidence in the diagnosis. This highlights the fact that to be considered helpful, the AI must provide not only the diagnosis but also the case specific confidence. Furthermore, the perceived utility was higher among less experienced users, but overall, the SM were useful in improving the human diagnostic accuracy. Therefore, in this setting, the AI enhanced approach provides value in improving the human performance

Aim. Synovial fluid D-lactate may be useful for diagnosing septic arthritis (SA) as this biomarker is almost exclusively produced by bacteria. We evaluated the performance of synovial fluid D-lactate and determined its optimal cut-off value for diagnosing SA. Method. Consecutive patients with suspicion of septic arthritis were prospectively included. They underwent joint aspiration and synovial fluid was collected for culture, leukocyte count and D-lactate concentration (by spectrophotometry). Youden's J statistic was used for determining optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. Results. A total of 155 patients were included. Using institutional criteria, 21 patients (14%) were diagnosed with SA and 134 (86%) patients with aseptic arthropathy, out of which 43 (27%) had osteoarthrosis, 80 (52%) had rheumatic arthropathy and 11 (7%) reactive arthritis. The optimal cut-off of synovial fluid D-lactate to differentiate SA from aseptic cases was 0,035 mmol/l. Synovial fluid D-lactate had a sensitivity 90% (95% CI: 70–99%) and specificity 87% (95% CI: 80–92%) compared to leukocyte count with sensitivity 81% (95% CI: 60–95%) and specificity 83% (95% CI: 76–90%). Culture was positive in only 17 (80%) out of 21 patients with SA. Conclusions. The synovial fluid D-lactate showed high sensitivity and specificity for diagnosis of SA which was higher than the current gold standard of diagnosis (culture and leukocyte count). The high sensitivity makes this biomarker useful as a point-of-care screening test for SA

Aims. The International Consensus Meeting on Musculoskeletal Infection (ICM, Philadelphia 2018) recommended histology as one of the diagnostic tests although this is not routinely used in a number of UK hospitals. This study aims to explore the role of histology in the diagnosis of infection and whether it is of practical use in those cases where the microbiology samples are either diagnostically unclear or do not correspond to the pre-operative diagnosis or the clinical picture. Patients and Methods. We identified 85 patients who underwent revision knee arthroplasty for either septic or aseptic loosening and for whom both microbiology and histology samples were taken. The procedures were performed by the senior experienced surgeons specialised in revision knee arthroplasty in two centres from Liverpool. Each patient had a minimum of five tissue samples taken, using separate knife and forceps and each sample was divided in half and sent for microbiology and histology in different containers. Fifty-four patients (63.5%) underwent a single-staged revision; ten patients (11.8%) underwent the 1. st. stage of a two staged revision; eleven patients (12.9%) underwent the 2. nd. stage of a two staged revision; one patient (1.2%) underwent an additional revision stage; three patients (3.5%) were treated with a DAIR; three patients (3.5%) had a 2-in-1 revision; two patients (2.4%) had a debridement and polyethylene exchange; and one patient (1.2%) had an arthroscopy biopsy of knee replacement. The cost to process five microbiology samples for each patient was £122.45 on average and for the five histology samples was £130. Results. In 63.5% (n=54) the histology and microbiology confirmed an aseptic joint as suspected beforehand. In 8.2% (n=7) the histology result was the same as the microbiology result confirming infection as suspected beforehand. In 15.3% (n=13) where asepsis was suspected beforehand, one of the five microbiology samples unexpectedly grew an organism but all the histological samples showed no evidence of infection. In these cases, the histology result supported the diagnosis of the likelihood of a contaminant. In 5.9% (n=5) we found differences in the microbiology and histology in one sample and in 7.1% (n=6) the histology was different to the microbiology in more than one sample. Conclusions. In cases where the diagnosis of sepsis within a knee replacement is not in doubt due to pre-operative microbiology, we found no benefit in additional histology sampling. In 28.3% of the cases, the histology was of use in the diagnosis of infection in complex cases and a useful tool in the decision process for further management. In over half of the cases where the revision was for aseptic loosening, the histology result did not alter the management but 28.3% of cases that were thought to be aseptic, microbiology revealed at least one positive sample hence the histology was of use in making a final diagnosis, be that of infection, contamination or to rule out infection. Whilst histology is of use in the latter groups but not the aseptic group, these outcomes are not predictable until after the post-operative period hence histology is required in all these cases. Overall, the histology is a cheap test which is of benefit in the diagnosis of complex peri-prosthetic joint infection in one–third of cases and we support the ICM recommendation

Our understanding of pre-arthritic hip disease has evolved tremendously but challenges remain in categorizing diagnosis, which ultimately impacts choice of treatments and clinical outcomes. This study aims to report patient reported outcome measures (PROMs) comparing four different condition groups within hip preservation surgery by a group of fellowship-trained surgeons. From 2018 to 2021, 380 patients underwent hip preservation surgery at our center and were classified into five condition groups: dysplasia: 82 (21.6%), femoro-acetabular impingement (FAI): 173 (45.4%), isolated labral tear: 103 (27.1%), failed hip preservation: 20 (5.3%) and history of childhood disease/other: 2 (0.5%). International hip outcomes Tool 12 (IHOT-12), numeric pain score and patient-reported outcomes measurement information system (PROMIS) were collected pre-operatively and at 3 months and 1 year post-operatively, with 94% and 82% follow-up rate respectively. Arthroscopy (75.5%) was the most common procedure followed by peri-acetabular osteotomy (PAO) (22.4%) and surgical dislocation (2.1%). Re-operation rate were respectively 18.3% (15), 5.8% (10), 4.9% (5), 30% (6) and 0%. There were 36 re-operations in the cohort, 14 (39%) for unintended consequences of initial surgery, 10 (28%) for mal-correction leading to a repeat operation, 8 (22%) progression of arthritis, and 4 (11%) for incorrect initial diagnosis/intervention. Most common re-operations were hardware removal 31% (7 PAO, 3 surgical hip dislocation and 1 femoral de-rotational osteotomy), arthroscopy 31% (11) and arthroplasty 28% (10). All groups had significant improvements in their IHOT-12 as well as PROMIS physical and numerical pain scales, except those with failed hip preservation. Dysplasia group showed a slower recovery. Overall, this study demonstrated a clear relation between the condition groups, their respective intervention and the significant improvements in PROMs with isolated labral pathology being a valid diagnosis. Establishing tertiary referral centers for hip preservation and longer follow-up is needed to monitor the overall survivorship of these various procedures

Aims. Only a few studies have investigated the long-term health-related quality of life (HRQoL) in patients with an idiopathic scoliosis. The aim of this study was to investigate the overall HRQoL and employment status of patients with an idiopathic scoliosis 40 years after diagnosis, to compare it with that of the normal population, and to identify possible predictors for a better long-term HRQoL. Methods. We reviewed the full medical records and radiological reports of patients referred to our hospital with a scoliosis of childhood between April 1972 and April 1982. Of 129 eligible patients with a juvenile or adolescent idiopathic scoliosis, 91 took part in the study (71%). They were evaluated with full-spine radiographs and HRQoL questionnaires and compared with normative data. We compared the HRQoL between observation (n = 27), bracing (n = 46), and surgical treatment (n = 18), and between thoracic and thoracolumbar/lumbar (TL/L) curves. Results. The mean time to follow-up was 40.8 years (SD 2.6) and the mean age of patients was 54.0 years (SD 2.7). Of the 91 patients, 86 were female (95%) and 51 had a main thoracic curve (53%). We found a significantly lower HRQoL measured on all the Scoliosis Research Society 22r instrument (SRS-22r) subdomains (p < 0.001) with the exception of mental health, than in an age-matched normal population. Incapacity to work was more prevalent in scoliosis patients (21%) than in the normal population (11%). The median SRS-22r subscore was 4.0 (interquartile range (IQR) 3.3 to 4.4) for TL/L curves and 4.1 (IQR 3.8 to 4.4) for thoracic curves (p = 0.300). We found a significantly lower self-image score for braced (median 3.6 (IQR 3.0 to 4.0)) and surgically treated patients (median 3.6 (IQR 3.2 to 4.3)) than for those treated by observation (median 4.0 (IQR 4.1 to 4.8); p = 0.010), but no statistically significant differences were found for the remaining subdomains. Conclusion. In this long-term follow-up study, we found a significantly decreased HRQoL and capacity to work in patients with an idiopathic scoliosis 40 years after diagnosis. Cite this article: Bone Joint J 2023;105-B(2):166–171

Introduction. It is generally held that blood tests are not particularly helpful in establishing the diagnosis of bone tumours but may be useful in prognosis. We reviewed the results of blood tests taken at the time of diagnosis to establish the frequency of abnormalities in common blood tests and whether this was significant in staging or prognosis. Method. Blood test results on all newly diagnosed patients with bone tumours from 2005 – 2010 were exported and abnormalities identified. This was matched to diagnosis, clinical features and prognosis. Results. There were 541 patients included in the analysis of whom 221 had osteosarcoma, 167 chondrosarcoma, 87 Ewing's, and 66 other bone tumours. 340 were adults, 103 children (under 14) and 98 TYA. The most frequently abnormal blood test was a low haemoglobin (⋋13) in 56%, raised alkaline phosphatase in 40%, and raised ESR and CRP in 32%. Patients with metastases at diagnosis tended to have higher levels of ESR (p⋋0.0001) but there was no other significant difference overall. Older patients tended to have a greater number of abnormal results apart from the CRP which was highest in the TYA group. No single blood test was related to prognosis. Conclusion. Abnormal blood tests are common in patients at the time of diagnosis of bone tumours. None are either particularly diagnostic or prognostic

Aim. Diagnosing periprosthetic joint infections (PJI) can be very challenging, especially infections caused by low virulence microorganisms. No single test with a 100% accuracy is available yet. Hence, different infection definitions were introduced to improve the diagnostic confidence and quality of research articles. Due to constant developments in this field, infection definitions are adopted continuously. The aim of our study was to find the most sensitive currently available infection definition among three currently used criteria (International Consensus Meeting – criteria 2018 (ICM), Infectious Diseases Society of America - criteria 2013 (IDSA), and European Bone and Joint Infection Society – criteria 2021 (EBJIS)) for the diagnosis of PJI. Method. Between 2015 and 2020, patients with an indicated revision surgery due to septic or aseptic failure after a total hip or knee replacement were included in this retrospective analysis of prospectively collected data. A standardized diagnostic workup was done in all patients. The components of the IDSA-, ICM-, and EBJIS- criteria for the diagnosis of PJI were identified in each patient. Results. Overall, 206 patients (hip: n=104 (50%); knee: n=102 (50%)) with a median age of 74 years (IQR 65 – 80y) were included. 101 patients (49%) were diagnosed with PJI when using the EBJIS- criteria. Based on the IDSA- and ICM- criteria, 99 patients (48%, IDSA) and 86 patients (42%, ICM) were classified as septic. Based on all three criteria, 84 cases (41%) had an infection. 15 septic cases (n=15/206; 7%) were only identified by the IDSA- and EBJIS- criteria. In 2 patients (n=2/206, 1%), an infection was present based on only the ICM and EBJIS criteria. No case was classified as infected by one infection definition alone. A statistically significant higher number of inconclusive cases was observed when the ICM criteria (n=30/206; 15%) were used in comparison to the EBJIS criteria (likely infections: n=16/206; 8%) (Fisher's exact test, p=0.041). The EBJIS definition showed a better preoperative performance in comparison to the other two definitions (p<0.0001). Conclusions. The most sensitive infection definition seems to be the novel EBJIS– criteria covering all infections diagnosed by the IDSA- and ICM-criteria without detecting any further infection. In addition, less inconclusive (infection likely) cases were detected by the EBJIS-criteria in comparison with the ICM-criteria reducing the so called ‘grey zone’ significantly which is of utmost importance in clinical routine

In the last decades, the use of artificial intelligence (AI) has been increasingly investigated in intervertebral disc degeneration (IDD) and chronic low back pain (LBP) research. To date, several AI-based cutting-edge technologies, such as computer vision, computer-assisted diagnosis, decision support system and natural language processing have been utilized to optimize LBP prevention, diagnosis, and treatment. This talk will provide an outline on contemporary AI applications to IDD and LBP research, with a particular attention towards actual knowledge gaps and promising innovative tools

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570

Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for Macrophage Colony Stimulating Factor 1 (MCSF-1) and Hepatocyte Growth Factor (HGF) (p<0.01). In comparing AS with HEAL patients, 9 cytokines displayed significant differences, including interleukin (IL)-6, Vascular Endothelial Growth Factor A (VEGFA), Matrix Metalloproteinase 1 (MMP-1). Comparison of INF with HEAL patients revealed significantly different expression of 20 cytokines, including. IL-6, IL-18, VEGFA or MMP-1. Conclusions. Our study revealed differences in plasma cytokine profile of blood samples from INF and AS patients. Although no single biomarker is sufficient to differentiate these patients preoperatively in isolation, future multivariant analysis of this cytokine data in combination with clinical characteristics may provide valuable diagnostic insights. Funded by German Social Accident Insurance (FF-FR 0276) and AO Trauma (AR2021_04)

Aim. While 16S rRNA PCR - Sanger sequencing has paved the way for the diagnosis of culture-negative bacterial infections, it does not provide the composition of polymicrobial infections. We aimed to evaluate the performance of the Nanopore-based 16S rRNA metagenomic approach using partial-length amplification of the gene, and to explore its feasibility and suitability as a routine diagnostic tool for bone and joint infections (BJI) in a clinical laboratory. Method. Sixty-two clinical samples from patients with BJI were sequenced on MinION* using the in-house partial amplification of the 16S rRNA gene. BJI were defined based on the ICM Philly 2018 and EBJIS 2021 criteria. Among the 62 samples, 16 (26%) were culture-positive, including 6 polymicrobial infections, and 46 (74%) were culture-negative from mono- and polymicrobial infections based on Sanger-sequencing. Contamination, background noise definition, bacterial identification, and time-effectiveness issues were addressed. Results. Results were obtained within one day. Setting a threshold at 1% of total reads overcame the background noise issue and eased interpretation of clinical samples. The partial 16S rRNA metagenomics approach had a greater sensitivity compared both to the culture method and the Sanger sequencing. All the 16 culture-positive samples were confirmed with the metagenomic sequencing. Bacterial DNA was detected in 32 culture-negative samples (70%), with pathogens consistent with BJI. The 14 Nanopore negative samples included 7 negative results confirmed after implementation of other molecular techniques and 7 false-negative MinION results: 3 Kingella kingae infections detected after targeted-PCR only, 2 Staphylococcus aureus infections and 2 Pseudomonas aeruginosa infections sterile on agar plate media and detected only after implementation of blood culture media, advocating for the very low inoculum. Conclusions. The results discriminated polymicrobial samples, and gave accurate bacterial identifications compared to Sanger-based results. They confirmed that Nanopore technology is user-friendly as well as cost- and time-effective. They also indicated that 16S rRNA targeted metagenomics is a suitable approach to be implemented for routine diagnosis of culture-negative samples in clinical laboratories. * Oxford Nanopore Technologies

Aim. The analysis of synovial fluid has proved to be of crucial importance in the diagnostic process of prosthetic joint infections (PJI), suggesting the presence of an infection before the microbiological culture results. In this context, several studies illustrated the efficacy of synovial calprotectin in supporting the diagnosis of PJI [1, 2]. However, several testing methods have been explored to detect synovial calprotectin levels, emphasizing the need to use a standardized, rapid and rapid test. In this study, synovial calprotectin was analyzed by means of a commercial stool test [3] to explore whether the detected levels might predict PJIs and, therefore, being a promising tool for the fast and reliable diagnosis of this complication. Method. The synovial fluid of 55 patients underwent to revision of the prosthetic implant were analyzed. The measurement of calprotectin was carried out by of commercial stool test, following the protocol for liquid samples. Calprotectin levels were then compared to other synovial biomarkers of PJI such as leucocyte esterase and count and percentage of polymorphonuclear cells. Data analysis were performed using R software v4.1.1 (R Core Team) and package “pROC” [4]. Receiver operator characteristics curves were designed using culture test as gold standard to evaluate the area under curve (AUC) of each method (with DeLong method for confidence-interval calculation). Thresholds were calculated to maximize Youden's index; sensitivity and specificity were reported. One-to-one Pearson's correlations coefficient were calculated for each pair of methods. P value <0.05 were considered statistically significant. Results. Of the 55 synovial fluids analyzed, 13 patients were diagnosed with PJI and 42 with an aseptic failure of the implant. The specificity, sensitivity, and AUC of calprotectin resulted 0.90, 0.85, and 0.86 (95%CI: 0.72–0.99), respectively with a set threshold of 226.5 µg/g. The values of calprotectin had a moderate and statistically relevant correlation with the synovial leucocyte counts (r. s. = 0.54, p = 0.0003) and the percentage of polymorphonuclear cells (r. s. = 0.68, p = 0.0000). Conclusions. From this analysis, it can be concluded that synovial calprotectin is a valuable biomarker that correlates with other established indicator of local infection, delivering a rapid and reliable results and supporting the diagnostic process of PJI

Aims. Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI. Methods. In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31

Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results. Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion. Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320

Aims. The aim of this study was to assess the prognostic value of the modified three-group Stulberg classification, which is based on the sphericity of the femoral head, in patients with Perthes’ disease. Methods. A total of 88 patients were followed from the time of diagnosis until a mean follow-up of 21 years. Anteroposterior pelvic and frog-leg lateral radiographs were obtained at diagnosis and at follow-up of one, five, and 21 years. At the five- and 21-year follow-up, the femoral heads were classified using a modified three-group Stulberg classification (round, ovoid, or flat femoral head). Further radiological endpoints at long-term follow-up were osteoarthritis (OA) of the hip and the requirement for total hip arthroplasty (THA). Results. There were 71 males (81%) and 17 females. A total of 13 patients had bilateral Perthes’ disease; thus 101 hips were analyzed. At five-year follow-up, 37 hips were round, 38 ovoid, and 26 flat. At that time, 66 hips (65%) were healed and 91 (90%) were skeletally immature. At long-term follow-up, when the mean age of the patients was 28 years (24 to 34), 20 hips had an unsatisfactory outcome (seven had OA and 13 had required THA). There was a strongly significant association between the modified Stulberg classification applied atfive-year follow-up and an unsatisfactory outcome at long-term follow-up (p < 0.001). Between the five- and 21-year follow-up, 67 hips (76%) stayed in their respective modified Stulberg group, indicating a strongly significant association between the Stulberg classifications at these follow-ups (p < 0.001). Conclusion. The modified Stulberg classification is a strong predictor of long-term radiological outcome in patients with Perthes’ disease. It can be applied at the healing stage, which is usually reached five years after the diagnosis is made and before skeletal maturity. Cite this article: Bone Joint J 2021;103-B(12):1815–1820

Background. The identification of novel biomarker which is highly specific and sensitive for periprosthetic joint (PJI) have the potential to improve diagnostic accuracy and ultimately improve patient outcomes. Thus, the aim of this systemic review is to identify and evaluate novel biomarkers for the preoperative diagnostics of PJI. Methods. MEDLINE, EMBASE, PubMed and Cochrane Library databases identified from 1. st. of January 2018 to 30. th. of September. 2022. We used “periprosthetic joint infection” OR “prosthetic joint infection” OR “periprosthetic infection” as the diagnosis of interest and the target index applied AND “marker”. To focus on novel biomarkers already used biomarkers of the established PJI diagnostic criteria of MSIS, ICM and EBJIS were not included in the analysis. These three criteria were considered the reference standard during quality assessment. Results. A total of 19 studies were included. In these, fourteen different novel biomarkers were analyzed. Fifteen studies (79%) had prospective designs and the other four (22%) were retrospective studies. Six studies (33%) included only periprosthetic knee infections and thirteen (67%) included periprosthetic knee and hip infections. Proteins were analyzed in most cases (nine studies), followed by molecules (three studies), exosome (two studies) as well as DNA (two studies), interleukin (one study) and lysosome (one study). One novel and promising marker that had been frequently analyzed is calprotectin. Conclusion. No marker demonstrated higher sensitivity and specificity than already known parameters used for standardized treatment based on established PJI definitions. Further studies are needed to elucidate the benefit and usefulness of implementing new biomarkers in diagnostic PJI settings

Aim. Despite the availability of numerous tests, the diagnosis of periprosthetic infection (PJI) continues to be complex. Although several studies have suggested that coagulation-related markers, such as D-dimer and fibrinogen, may be promising tools in the diagnosis of prosthetic infections, their role is still controversial. The aim of this study is to evaluate the diagnostic accuracy of serum D-dimer and fibrinogen in patients with painful total knee replacement. Method. 83 patients with painful total knee replacement and suspected peri-prosthetic infection were included. All patients underwent pre-operative blood tests to evaluate inflammation indices (ESR and CRP) and serum D-Dimer and Fibrinogen levels. The diagnostic performance of the tests was assessed using the ICM definition as the gold standard. The diagnostic accuracy of the D-dimer and fibrinogen was measured by assessing sensitivity, specificity and by calculating the area under the ROC curve. Results. The definition of prosthetic infection based on the ICM criteria has made it possible to classify 40 peri-prosthetic infections and 43 aseptic failures. The mean value of fibrinogen, D-Dimer, VES and PCR observed in patients with prosthetic infection was significantly higher than in patients with aseptic failure [fibrinogen 468 mg / dl vs 331 mg / dl, p <0.001; D-Dimero 2177 ng/mL vs. 875 ng / mL, p <0.005], ESR 49 mm / hr vs 24 mm/h, p <0.001; PCR 25.5 mg /L vs 8.9 mg/L, p <0.001]. The optimal threshold value of the fibrinogen indicative of the presence of infection was 418 mg/dl, with a sensitivity of 72% and a specificity of 88%. The serum concentration of d-dimer greater than 945 ng / ml showed a sensitivity of 72.5% and a specificity of 76.7%. Conclusions. Although in this multicenter prospective study we found that serum D-dimer may have significantly higher statistical values in PJI than aseptic failures, its diagnostic power appears however limited when compared with other markers including plasma fibrinogen. Fibrinogen is regularly analyzed before surgery, the evaluation of this marker does not involve additional costs. The diagnostic accuracy appears to be similar to that of classic markers such as the level of PCR and VES. Plasma D-dimer may have a limited value in the diagnosis of PJI unlike plasma fibrinogen which has shown moderate sensitivity and excellent specificity. However, in our limited series of cases, both tests cannot be used alone in the diagnosis of infection but could contribute to the diagnosis if contextualized to ves and pcr

Aim. The diagnosis of septic arthritis mostly relies on clinical examination, several blood parameters including white blood cell count, C-reactive protein, sedimentation, and the analysis of the joint aspiration. However, the diagnosis can be difficult when the symptoms are vague and the information obtained from laboratory might be insufficient for definitive diagnosis. This study aimed to evaluate several ratios obtained from routine blood tests for a possible use in the diagnosis of septic arthritis. Method. The adult patients who were operated in our clinic due to septic arthritis between 2014–2020 were identified and retrospectively evaluated. The patients with any blood disorders or missing file information were excluded. A total of 36 patients were found to be eligible for inclusion. The control group included 40 patients without any sign of infection who underwent total knee arthroplasty due to knee osteoarthritis. Preoperative blood tests of each patients were examined. In addition to CRP and sedimentation values, neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet count-mean platelet volume were calculated and receiving operating characteristics (ROC) curve analysis was made to determine the sensitivity, specificity and area under curve (AUC) values of these parameters. Results. The distribution of affected joint in septic arthritis group was as follow; 22 knees, 6 hips, 4 shoulders, 2 elbows, 1 wrist and 1 ankle. The cultures of joint aspiration yielded positive result in 19 patients while the cultures were negative in 17 patients. All of the analyzed parameters were significantly different between the groups (p<0.001). ROC curve analysis results are given in detail, in Table 1 and Figure 1. The AUC value was 97.3 when only CRP and sedimentation values were used but increased to 98.6 when neutrophile/ lymphocyte ratio was added and increased to 100 when all analyzed parameters were included. Conclusions. The analyzed parameters were found to increase the overall sensitivity and specificity when used together with acute phase reactants. However, when evaluated separately, CRP and sedimentation were still found as the most valuable parameters in the diagnosis of septic arthritis. In the diagnosis of septic arthritis, 35 mm/hr cut-off value for sedimentation and 10 mg/L cut-off value for CRP were found more sensitive and specific compared to standard laboratory cut-off values of 20 mm/hr and 5 mg/L. For any tables or figures, please contact the authors directly

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

Aim. The aim of this study was to investigate the metabolomic profile of synovial fluid in periprosthetic joint infection (PJI) cases regarding a possible diagnostic approach. Also, further information about the metabolic composition of synovial fluid in PJI may point to future diagnostic and therapeutic approaches. Method. Patients with a clinical suspicion of a prosthesis infection who underwent a joint puncture in our outpatient department or ward were included. After sample preparation, the nuclear magnetic resonance (NMR) experiments were performed at 310 K on an AVANCE™ NeoBruker Ultrashield 600 MHz spectrometer. Bruker Topspin version 4.0.2 was used for NMR data acquisition. The spectra for all samples were automatically processed (exponential line broadening of 0.3 Hz), phased, and referenced using TSP at 0.0 ppm. In total, 37 metabolites were analysed using a volume of 200 µl per synovial sample. The PJI and aseptic cases were assigned according to the EBJIS criteria. Results. In total, 76 samples were included in the final analysis with 48 PJI cases and 28 aseptic cases. Five measured metabolites have shown an area under the curve (AUC) over 0.8, with Taurine (AUC 0.8558, p<0.0001) and Glutamine (AUC 0.8333, p<0.0001) showing the best diagnostic performance. When combining two metabolites, the AUC indicated even higher diagnostic performance: Glucose/Glycogen (AUC 0.9073, p<0.0001), Taurine/Mannose (AUC 0.9073, p<0.0001), Mannose/Glycogen (AUC 0.8992, p<0.0001) and Taurine/Glucose (AUC 0.8956, p<0.0001). Conclusions. While NMR as a method in PJI diagnostics is currently not broadly available for daily clinical work, our results indicate that certain synovial metabolites and their combinations can be used for PJI diagnosis

Abstract. Background. The influence of diagnosis on outcomes after reverse shoulder arthroplasty (RSA) is not completely understood. The purpose of this study was to compare clinical outcomes of different pathologies. Methods. A total of 78 RSAs were performed for the following diagnoses: (1) rotator cuff tear arthropathy(RCA), (2) massive cuff tear(MCT) with osteoarthritis(OA), (3) MCT without OA, (4) arthritis, (5) acute proximal humerus fracture. Mean follow up 36 months (upto 5 years) Range of motion, Oxford Shoulder Score were obtained preoperatively and postoperatively. Results. Mean OSS was 30. The RCA, MCT-with-OA, MCT-without-OA, and arthritis groups all exhibited significant improvements in all outcome scores and in all planes of motion. After adjustment for age and compared with RCA, those with OA had significantly better abduction (P < .05), and those with fractures had significantly worse patient satisfaction (P < .05). Among male patients, those with MCTs without OA had significantly worse satisfaction (P < .05). Conclusion. RSA reliably provides improvement regardless of preoperative diagnosis. Although subtle differences exist between male and female patients, improvements in clinical outcome scores were apparent after RSA

Aim. The diagnosis of periprosthetic joint infection (PJI) remains a clinical dilemma, since presentations of PJI usually greatly overlap with aseptic failure (AF). The aim of this study is to evaluate the values of plasma fibrinogen, individually or in combination with CRP, ESR and WBC, for distinguishing PJI from AF. Method. We retrospectively enrolled 357 cases who underwent revision hip or knee arthroplasties in the Third Affiliated Hospital of Southern Medical University, Sun Yat-sen Memorial Hospital and the First Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2021, including 197 AF, 116 PJI and 44 reimplantation. The diagnostic capacity of preoperative fibrinogen, CRP, ESR and WBC as well as their combinations for differentiating PJI from AF were assessed by ROC curves. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated according to the optimal cutoff value based on the Youden index. All biomarkers were further investigated for their potential ability to predict optimal timing of reimplantation as well as their diagnostic capacity in the subgroups of the knee and hip PJI. Furthermore, the correlations among fibrinogen, CRP and ESR in the patients with PJI and AF were analyzed to further evaluate the potential capacity of fibrinogen in the diagnosis of PJI. Results. The levels of fibrinogen, CRP, ESR and WBC were significantly higher in PJI group than in AF group. ROC analyses showed that the AUCs of fibrinogen, CRP, ESR and WBC were 0.879, 0.903, 0.879 and 0.685, respectively. The optimal threshold of fibrinogen is 4.04 g/L (74.1% sensitivity, 85.6% specificity, 76.1% PPV, 85.0% NPV and 81.8% accuracy). Combining fibrinogen with CRP and/or ESR (AUC: 0.903∼0.914) yielded almost equivalent diagnostic efficiency compared with the combination of CRP and ESR (AUC: 0.910). Besides, fibrinogen yielded AUCs of 0.869 (cutoff: 3.44 g/L) and 0.887 (cutoff: 4.12 g/L) in the hip and knee subgroups, with higher specificity and PPV of 93.1% and 96.1% in the knee PJI. Intriguingly, as for the cases with CRP < 10mg/L and ESR ≧ 30 mm/h, the specificity and NPV of fibrinogen for diagnosing PJI were 92.2% and 83.9%. Conclusions. Plasma fibrinogen is considered as a potential first-line screening marker for PJI detection and timing of reimplantation. As for the patients with an increased ESR but normal CRP, a low fibrinogen level (below 4.04 g/L) is more likely to rule out PJI

Introduction. Diagnosis of chronic osteomyelitis (COM) is based mainly on the correlation between history, clinical picture, lab analysis, bacteriological, pathological, and imaging studies. Bone biopsy for culture and sensitivity is the gold standard for the correct identification of the causative organism. The present prospective study aims to evaluate the accuracy of FDG PET-CT in the diagnosis of COM in comparison to the bacteriological, pathological findings. Materials and Methods. 18 patients (16 males/two females) underwent FDG-PET/CT scanning for clinically or radiologically suspected COM of the lower extremity. Fourteen patients had septic non-union, three patients with aseptic non-union, and one with chronic diffuse sclerosing OM of Garre. Seven patients had implants at site of examination at the time of the scan. Diagnosis of COM was confirmed by deep surgical cultures and pathological analysis (index debridement done by s single surgeon in one centre) following PET/CT scanning. FDG-PET uptake was measured by SUV max (the highest uptake of the radioisotope in the infection area). These findings were correlated to the microbiological and histopathological results. Results. Infection was clinically evident at a mean of 15 weeks (range, 2 to 60 weeks) after the date of injury. Patients had a mean of 2.3 (range 0 – 7) operations, before index debridement. The mean SUV max on the affected side was (9.55 ± 5.22), While mean SUV max on the contralateral healthy side was (1.82 ± 0.98). The pattern of FDG-uptake was diffuse in nine (50%), localised in seven (38.9%), and intramedullary in two (11.1%) patients respectively. The sensitivity, specificity, accuracy, PPV and NPV of PET SUV max were 100%, 66.7%, 94.44%, 93.75% and 100% respectively in the diagnosis of COM at a cut-off value of (4.46). The present study included 15 true positive, two true negative and one false-positive PET/CT results. Conclusions. 18F-FDG PET/CT is a highly sensitive and specific method for the evaluation of chronic osteomyelitis in patients with or without trauma. PET/CT provides anatomical localisation and characterisation of the infected area and has a crucial role in preoperative planning

Heterotopic ossification (HO) is a well-known complication of traumatic elbow injuries. The reported rates of post-traumatic HO formation vary from less than 5% with simple elbow dislocations, to greater than 50% in complex fracture-dislocations. Previous studies have identified fracture-dislocations, delayed surgical intervention, and terrible triad injuries as risk factors for HO formation. There is, however, a paucity of literature regarding the accuracy of diagnosing post-traumatic elbow HO. Therefore, the purpose of our study was to determine the inter-rater reliability of HO diagnosis using standard radiographs of the elbow at 52 weeks post-injury, as well as to report on the rate of mature compared with immature HO. We hypothesized inter-rater reliability would be poor among raters for HO formation. Prospectively collected data from a large clinical trial was reviewed by three independent reviewers (one senior orthopedic resident, one senior radiology resident, and one expert upper extremity orthopedic surgeon). Each reviewer examined anonymized 52-week post-injury radiographs of the elbow and recorded: 1. the presence or absence of HO, 2. the location of HO, 3. the size of the HO (in cm, if present), and 4. the maturity of the HO formation. Maturity was defined by consensus prior to image review and defined as an area of well-defined cortical and medullary bone outside the cortical borders of the humerus, ulna, or radius. Immature lesions were defined as an area of punctate calcification with an ill-defined cloud-like density outside the cortical borders of the humerus, ulna or radius. Data were collected using a standardized online data collection form (CognizantMD, Toronto, ON, CA). Inter-rater reliability was calculated using Fleiss’ Kappa statistic and a multivariate logistic regression analysis was performed to identify risk factors for HO formation in general, as well as mature HO at 52 weeks post injury. Statistical analysis was performed using RStudio (version1.4, RStudio, Boston, MA, USA). A total of 79 radiographs at the 52-week follow-up were reviewed (54% male, mean age 50, age SD 14, 52% operatively treated). Inter-rater reliability using Fleiss’ Kappa was k= 0.571 (p = 0.0004) indicating moderate inter-rater reliability among the three reviewers. The rate of immature HO at 52 weeks was 56%. The multivariate logistic regression analysis identified male sex as a significant risk factor for HO development (OR 5.29, 1.55-20.59 CI, p = 0.011), but not for HO maturity at 52 weeks. Age, time to surgery, and operative intervention were not found to be significant predictors for either HO formation or maturity of the lesion in this cohort. Our study demonstrates moderate inter-rater reliability in determining the presence of HO at 52 weeks post-elbow injury. There was a high rate (56%) of immature HO at 52-week follow-up. We also report the finding of male sex as a significant risk factor for post traumatic HO development. Future research directions could include investigation into possible male predominance for traumatic HO formation, as well as improving inter-rater reliability through developing a standardized and validated classification system for reporting the radiographic features of HO formation around the elbow

Aim. The clinical relevance of microbial DNA detected via next-generation sequencing (NGS) remains unknown. This multicenter study was conceived to: 1) identify species on NGS that may predict periprosthetic joint infection (PJI), then 2) build a predictive model for PJI in a developmental cohort, and 3) validate predictive utility of the model in a separate multi-institutional cohort. Method. Fifteen institutions prospectively collected samples from 194 revision TKA and 184 revision THA between 2017–2019. Synovial fluid, tissue and swabs were obtained intraoperatively and sent to MicrogenDx (Lubbock, TX) for NGS analysis. Reimplantations were excluded. Patients were classified per the 2018 ICM definition of PJI. DNA analysis of community similarities (ANCOM) was used to identify 17 bacterial species of 294 (W-value>50) for differentiating infected vs. noninfected cases. Logistic regression with LASSO selection and random-forest algorithms were then used to build a model for predicting PJI. ICM classification was the response variable (gold-standard) and species identified through ANCOM were predictors. Patients were randomly allocated 1:1 into training and validation sets. Using the training set, a model for PJI diagnosis was generated. The entire model-building procedure and validation was iterated 1000 times. Results. The model's assignment accuracy was 75.9%. There was high accuracy in true-negative and false-negative classification using this model, which has previously been a criticism of NGS. Specificity was 97.1%, PPV 75.0% and NPV 76.2%. On comparison of abundance between ICM-positive and ICM-negative patients, Staphylococcus aureus was the strongest contributor (F=0.99) to model predictive power. In contrast, Cutibacterium acnes was less predictive (F=0.309) and abundant across infected and noninfected revisions. Discussion. This is the first study to utilize predictive algorithms on a large multicenter dataset to transform analytic NGS data into a clinically relevant diagnostic model. Our collaborative findings suggest NGS may be an independent adjunct for PJI diagnosis, while also facilitating pathogen identification. Future work applying machine-learning will improve accuracy and utility of NGS

Aims. Besides conventional radiographs, the use of MRI, CT, and bone scintigraphy is frequent in the diagnosis of a fracture of the scaphoid. However, which techniques give the best results remain unknown. The investigation of a new imaging technique initially requires an analysis of its precision. The primary aim of this study was to investigate the interobserver agreement of high-resolution peripheral quantitative CT (HR-pQCT) in the diagnosis of a scaphoid fracture. A secondary aim was to investigate the interobserver agreement for the presence of other fractures and for the classification of scaphoid fracture. Methods. Two radiologists and two orthopaedic trauma surgeons evaluated HR-pQCT scans of 31 patients with a clinically-suspected scaphoid fracture. The observers were asked to determine the presence of a scaphoid or other fracture and to classify the scaphoid fracture based on the Herbert classification system. Fleiss kappa statistics were used to calculate the interobserver agreement for the diagnosis of a fracture. Intraclass correlation coefficients (ICCs) were used to assess the agreement for the classification of scaphoid fracture. Results. A total of nine (29%) scaphoid fractures and 12 (39%) other fractures were diagnosed in 20 patients (65%) using HR-pQCT across the four observers. The interobserver agreement was 91% for the identification of a scaphoid fracture (95% confidence interval (CI) 0.76 to 1.00) and 80% for other fractures (95% CI 0.72 to 0.87). The mean ICC for the classification of a scaphoid fracture in the seven patients diagnosed with scaphoid fracture by all four observers was 73% (95% CI 0.42 to 0.94). Conclusion. We conclude that the diagnosis of scaphoid and other fractures is reliable when using HR-pQCT in patients with a clinically-suspected fracture. Cite this article: Bone Joint J 2020;102-B(4):478–484

Aims. The diagnosis of developmental dysplasia of the hip (DDH) is challenging owing to extensive variation in paediatric pelvic anatomy. Artificial intelligence (AI) may represent an effective diagnostic tool for DDH. Here, we aimed to develop an anteroposterior pelvic radiograph deep learning system for diagnosing DDH in children and analyze the feasibility of its application. Methods. In total, 10,219 anteroposterior pelvic radiographs were retrospectively collected from April 2014 to December 2018. Clinicians labelled each radiograph using a uniform standard method. Radiographs were grouped according to age and into ‘dislocation’ (dislocation and subluxation) and ‘non-dislocation’ (normal cases and those with dysplasia of the acetabulum) groups based on clinical diagnosis. The deep learning system was trained and optimized using 9,081 radiographs; 1,138 test radiographs were then used to compare the diagnoses made by deep learning system and clinicians. The accuracy of the deep learning system was determined using a receiver operating characteristic curve, and the consistency of acetabular index measurements was evaluated using Bland-Altman plots. Results. In all, 1,138 patients (242 males; 896 females; mean age 1.5 years (SD 1.79; 0 to 10) were included in this study. The area under the receiver operating characteristic curve, sensitivity, and specificity of the deep learning system for diagnosing hip dislocation were 0.975, 276/289 (95.5%), and 1,978/1,987 (99.5%), respectively. Compared with clinical diagnoses, the Bland-Altman 95% limits of agreement for acetabular index, as determined by the deep learning system from the radiographs of non-dislocated and dislocated hips, were -3.27° - 2.94° and -7.36° - 5.36°, respectively (p < 0.001). Conclusion. The deep learning system was highly consistent, more convenient, and more effective for diagnosing DDH compared with clinician-led diagnoses. Deep learning systems should be considered for analysis of anteroposterior pelvic radiographs when diagnosing DDH. The deep learning system will improve the current artificially complicated screening referral process. Cite this article: Bone Joint J 2020;102-B(11):1574–1581

Aims. Perthes’ disease is a condition which leads to necrosis of the femoral head. It is most commonly reported in children aged four to nine years, with recent statistics suggesting it affects around five per 100,000 children in the UK. Current treatment for the condition aims to maintain the best possible environment for the disease process to run its natural course. Management typically includes physiotherapy with or without surgical intervention. Physiotherapy intervention often will include strengthening/stretching programmes, exercise/activity advice, and, in some centres, will include intervention, such as hydrotherapy. There is significant variation in care with no consensus on which treatment option is best. The importance of work in this area has been demonstrated by the British Society for Children’s Orthopaedic Surgery through the James Lind Alliance’s prioritization of work to determine/identify surgical versus non-surgical management of Perthes’ disease. It was identified as the fourth-highest priority for paediatric lower limb surgery research in 2018. Methods. Five UK NHS centres, including those from the NEWS (North, East, West and South Yorkshire) orthopaedic group, contributed to this case review, with each entre providing clinical data from a minimum of five children. Information regarding both orthopaedic and physiotherapeutic management over a two-year post-diagnosis period was reviewed. Results. Data were extracted from the clinical records of 32 children diagnosed with Perthes’ disease; seven boys and 25 girls. The mean age of the children at diagnosis was 6.16 years (standard deviation (SD) 3.001). In all, 26 children were referred for physiotherapy. In the two-year period following diagnosis, children were seen a median of 7.5 times (interquartile range (IQR) 4.25 to 11) by an orthopaedic surgeon, and a median of 9.5 times (IQR 8 to 18.25) by a physiotherapist. One centre had operated on all of their children, while another had operated on none. Overall, 17 (53%) of the children were managed conservatively in the two-year follow-up period, and 15 (47%) of the children underwent surgery in the two-year follow-up period. Conclusion. The results of this case review demonstrate a variation of care provided to children in the UK with Perthes’ disease. Further national and international understanding of current care is required to underpin the rationale for different treatment options in children with Perthes’ disease. Cite this article: Bone Joint Open 2020;1-11:691–695

Aims. As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients. Methods. In this prospective study, 177 specimens were collected from 59 revision arthroplasties, including periprosthetic tissues, synovial fluid, and prosthetic sonicate fluid. Each specimen was divided into two, one for mNGS and one for culture. The criteria of the Musculoskeletal Infection Society were used to define PJI (40 cases) and aseptic failure (19 cases). Results. The sensitivity and specificity of mNGS in the diagnosis of PJI were 95% and 94.7%, respectively, for all types of specimen. The sensitivity and specificity were 65% and 100%, respectively, for periprosthetic tissues, 87.5% and 94.7%, respectively, for synovial fluid, and 92.5% and 94.7%, respectively, for prosthetic sonicate fluid. The mNGS of prosthetic sonicate fluid outperformed that for other types of specimen in the rates of detection of pathogens (84.6%), sequencing reads (> ten-fold) and the rate of genome coverage (> five-fold). Conclusion. mNGS could serve as an accurate diagnostic tool in the detection of pathogens in patients with a PJI using three types of specimen. Due to its superior perfomance in identifying a pathogen, mNGS of prosthetic sonicate fluid provides the most value and may partly replace traditional tests such as bacteriological culture in these patients. Cite this article: Bone Joint J 2021;103-B(5):923–930

Aims. This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI. Methods. Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Results. A total of 93 patients were enrolled. There was no difference in demographic data between both groups. Synovial fluid IL-6, with a threshold of 1,855.36 pg/ml, demonstrated a mean sensitivity of 94.59% (95% confidence interval (CI) 81.8% to 99.3%) and a mean specificity of 92.86% (95% CI 82.7 to 98.0) for detecting chronic PJI. Then 6.7 pg/ml was determined to be the optimal threshold value of serum IL-6 for the diagnosis of chronic PJI, with a mean sensitivity of 97.30% (95% CI 85.8% to 99.9%) and a mean specificity of 76.79% (95% CI 63.6% to 87.0%). The combination of synovial IL-6 and serum IL-6 led to improved accuracy of 96.77% in diagnosing chronic PJI. Conclusion. The present study identified that a combination of IL-6 in serum and synovial IL-6 has the potential for further improvement of the diagnosis of PJI. Cite this article: Bone Joint Res 2020;9(9):587–592

Background. Septic arthritis diagnostic is an emergency which implies a treatment with antibiotics and hospitalization. The diagnosis is based on the cytobacteriological examination of the synovial fluid (SF), but direct bacteriological examination is insensitive, and the result of the culture is obtained only after several days. Therefore, there is still a need for a rapid, simple and reliable method for the positive diagnosis of septic arthritis. Such method must allow avoiding both unrecognized septic arthritis leading to major functional consequences, and overdiagnosis that will induce unnecessary expensive hospitalization and unjustified treatment. Mid-infrared (MIR) spectroscopy, that gives a metabolic profiling of biological fluids, has been proposed for early and fast diagnosis. Objectives. To confirm the MIR spectroscopy to discriminate SF samples from patients with septic arthritis from other causes of joint effusion. Methods. Synovial fluids from 402 patients referred for suspected arthropathies were prospectively collected in six hospitals and stored at °80°C. The infrared absorption spectrum was acquired for each of the frozen samples using a chalcogenide fiber biosensor. The most informative spectral variables were selected and then used to develop an algorithm. Then, the algorithm has been validated on independent synovial fluids collected straight after arthrocentesis from 86 patients. Results. The calibration (n=402) and validation (n=86) cohorts consists of synovial fluid samples from patients exhibiting various etiologies. These samples (n=488), by using SF bacteriological analysis and culture and 16S PCR analysis were classified as septic arthritis (n=43) or non-septic arthritis (n=443). On the calibration cohort, the performances of the algorithm show a sensitivity of 90%, a specificity of 90%, a NPV of 99% and a PPV of 41%, the area under the ROC curve (AUROC) was 0.95. On the validation cohort, the performances of the algorithm show a sensitivity of 92%, a specificity of 81%, a NPV of 98% and a PPV of 46%, the area under the ROC curve (AUROC) was 0.90. Conclusions. This study confirms the diagnostic performances of MIR spectroscopy for the discrimination between septic and non-septic synovial fluids. The high negative predictive value and the very short time (within ten minutes) required to obtain the result makes it possible to quickly rule out an infection diagnosis

Aim. The diagnosis of prosthetic joint infection (PJI) is challenging and relies on a combination of parameters. However, the currently recommended diagnostic algorithms have not been validated for patients with recent surgery, dislocation or other events associated with a local inflammatory response. As a result, these algorithms are not safely applicable offhand in such conditions. Calprotectin is a leukocyte protein that has been shown to be a reliable biomarker of PJI. The purpose of this study was to evaluate the use of calprotectin to rule out PJI within 3 months after surgery or dislocation. Method. We included patients who underwent arthroplasty revision surgery at our institution within 3 months after any event causing inflammation. Calprotectin was measured using a lateral-flow assay. European Bone and Joint Infection Society (EBJIS) criteria were used as gold standard. The diagnostic accuracy of calprotectin was calculated. Results. Twenty-two patients (14 females, 8 males) with a mean age of 65.1 ± 12.3 years with 13 total hip (THA) and 9 total knee arthroplasties (TKA) were included. There were 4 instances of possible early-onset acute infection, 4 dislocations, 2 patella tendon ruptures, 1 local tissue reaction to the sutures, 4 cases of early loosening, 2 component breakages and 1 avulsion of a polyethylene patella button. Using the EBJIS criteria, PJI was confirmed postoperatively in 12 cases. With a cut-off at 50mg/L, the calprotectin lateral flow test was positive in 10 cases. This results in a sensitivity of the calprotectin test of 0.75, a specificity of 0.9, positive and negative predictive values of 0.9 and 0.75, respectively, and a positive and negative likelihood ratio of 7.5 and 0.28, respectively. Conclusions. Aggravating the difficulties of ruling out PJI prior to revision surgery, local inflammation can be caused by some conditions in which the widely accepted PJI definition criteria cannot be applied. Nevertheless, an accurate diagnosis of PJI is just as crucial in these situations as it is in planned revision surgery. This study suggests that calprotectin is a promising diagnostic parameter for ruling out PJI in such cases. The calprotectin lateral-flow assay is readily applicable at the beginning of the procedure, yielding results that can assist in the decision whether to perform septic revision or aseptic partial or component exchange within 15 minutes, and with an overall accuracy of 81.8%

Aim. Culture-based conventional methods are still the gold standard to identify microorganisms in hip and knee PJIs diagnosis. However, such approach presents some limitations due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range polymerase chain reaction (PCR), are available for diagnostic use in a suspected PJI. However, limited data is available on their sensitivity and specificity. This study aimed to evaluate the performance of a rapid and simple Investigational Use Only (IUO) version of the BioFire® JI multiplex PCR panel when compared to traditional microbiological procedures. Method. Fifty-eight native synovial fluid samples were recovered from 49 patients (female n=26; male =23) who underwent one or multiple septic or aseptic revision arthroplasties of the hip (n=12) and knee (n=46). The JI panel methodology was used either on specimens freshly collected (n=6) or stored at −80°C in our Musculoskeletal Biobank (n=52). The JI panel performance was evaluated by comparison with culture reference methods. Patient's medical records were retrieved from our institutional arthroplasty registry as well as our prospectively maintained PJI infection database. Results. The JI panel identified additional microorganisms in 3/39 (7.7%) positive cases, and a different microorganism in 1/39 (2.6%) sample. Out of 9/58 (15.5%) culture negative samples, two (22%) were positively detected by the JI panel. In total 49/58 (84%) native synovial fluid specimens were positive by culture methods, versus 39/58 (81.2%) with the JI panel. Ten samples are currently under investigation for confirmatory results. Out of 39 positive detections with the JI panel, 35 (89.7%) were concordant with the identified microorganism (n=29 same species; n=6 same genus). The combined information from the JI panel results and clinical records revealed the existence of 6/58 (10.3%) PJIs’ cases which would have required a different antibiotic therapeutic approach. Conclusions. The work presented, provides additional value for the clinical use of the JI panel to the improvement of PJI management in terms of rapid and successful treatment decisions, patient outcome, and healthcare costs. This technique shows high sensitivity to detect PJIs specific microorganisms in both fresh as well frozen native synovial fluid samples, thus emphasizing its use for retrospective studies analysis

The number of shoulder arthroplasty procedures performed in the United States continues to rise. Currently, the number of procedures performed per year ranges from 55,000–80,000 and is expected to increase more than 300% in the coming years. Periprosthetic joint infection (PJI) is one of the most serious complications associated with arthroplasty surgery, leading to poor outcomes, increased cost, and technically difficult revision surgery. The incidence of infection following primary shoulder arthroplasty has been reported between 0.7% and 4%, representing 2.9–4.6% of all complications. Prosthetic shoulder joint infections are unlike prosthetic joint infections of the hip and knee. Shoulder PJIs are primarily indolent in nature and difficult to diagnose using traditional methods that have been shown to be accurate for periprosthetic infections of the hip and knee. The majority of infected revision shoulder arthroplasties are associated with growth of Propionibacterium acnes (P. Acnes). This slow-growing, anaerobic organism requires longer than normal incubation times for culture (7–21 days), and typically demonstrates a subtle, non-specific clinical presentation that can make the presence of infection difficult to identify. In the reported literature, P. Acnes accounts for about 70% of cases with positive cultures associated with revision for treatment of a painful shoulder arthroplasty and due to the bacteria's slow growing nature and virulence profile, the rate of infection following shoulder arthroplasty may often be underestimated. A more recent and promising tool for evaluation of periprosthetic infection has been analysis of synovial fluid. Synovial fluid biomarkers have been identified as part of the innate response to pathogens, and include pro-inflammatory cytokines and anti-microbial peptides, and marker levels have shown promise for improved diagnostic efficacy in hip and knee PJI. Currently, no highly predictive clinical test for diagnosis of PJI in the shoulder exists, however, several of these synovial biomarkers have recently been analyzed for their diagnostic capacity in the setting of periprosthetic shoulder infection. Synovial fluid cytokine analysis shows the potential to improve diagnosis of infection in revision shoulder arthroplasty. This information can help to guide decision-making in the management of PJI of the shoulder, including the decision to perform a single- vs. two-stage revision surgery, and the need for post-operative antibiotics following an unexpected positive culture result after revision surgery. However, there are still challenges to broader use of these synovial biomarkers. Synovial α-defensin (Synovsure, CD Diagnostic) is the only marker currently available as a commercial test, and no point-of-care test is currently available for any of the biomarkers to allow for intraoperative decision-making. While a preoperative synovial aspirate is possible to send for α-defensin analysis currently, with results back in approximately 24 hours, dry fluid aspirations are frequent in the shoulder because of the predominance of indolent pathogens and may limit utility of the test. In summary, indolent infection associated with P. acnes is a common cause for the painful total shoulder arthroplasty. Pre-operative diagnosis of infection is difficult as a result of the poor diagnostic accuracy of traditional methods of testing. Synovial biomarker testing may ultimately improve our ability to more accurately diagnosis and treat prosthetic shoulder joint infections

Background. Preoperative diagnosis of fracture related infections can be challenging, especially when confirmatory criteria such as sinus tract and purulent discharge are absent. Although serum parameters, such as CRP and white blood cell count (WBC), showed poor accuracy in the literature, they are still often used in clinical practice. The European Bone and Joint Infection Society (EBJIS) defined evidence-based criteria for fracture related infection. Elevated serum inflammatory markers were regarded as suggestive criteria only, as the literature was of limited quality. This study assessed the diagnostic value of the serum parameters CRP, WBC and differential cell count in the diagnosis of fracture related infections defined by the EBJIS-criteria for fracture related infections. Methods. In this retrospective cohort study, 94 patients who underwent surgical treatment for suspected infected non unions after failed fracture fixation were included. Preoperatively, blood samples including serum inflammatory markers were taken. For this study, cut-offs of 5 mg/L for CRP, 10×10⁁9 cells/L for WBC, and >70% for the percentage of neutrophils were regarded as positive for infection. All patients had intraoperative samples taken for microbiology and histology. Analysis of diagnostic accuracy was based on the receiver-operating characteristic (ROC). Results. Based on the EBJIS criteria, 40 patients (43%) were diagnosed with a fracture related infection. 11/94 (12%) patients had an elevated serum WBC count, 13/94 (14%) an increased percentage of neutrophils, and 43/82 (52%) an elevated serum CRP. The mean values of CRP concentration, WBC count, and percentage of neutrophils in the infection group were 7.9 mg/L (IQR:6.4 – 9.7), 18.3 G/l (IQR: 3.9 – 24.9), and 63% (IQR: 58 – 67%), respectively. The sensitivity, specificity, and area under the curve of serum WBC count were 20% (95% CI: 10 −35%), 94.4% (84 −99%), and 0.57 (0.50 – 0.64), respectively; of percentage of neutrophils 12.5% (5 – 27%), 85.2% (73 −93%), and 0.49 (0.42 – 0.56); and of serum CRP 67.6% (51 – 90%), 60.0% (45 – 73%), and 0.64 (0.53 – 0.74), respectively. A statistically significant difference between the AUCs of all three serum parameters and AUC of tissue culture as well as AUC of histology was shown (p <0.0001). A simple decision tree approach using only low WBC and CRP may allow identification of aseptic cases. Conclusion. Based on the standardized and evidence-based EBJIS criteria, the three inflammatory serum markers showed an insufficient accuracy for the diagnosis of fracture related infections. They also correlate poorly with culture or histological diagnosis. Therefore, they should not be used alone as a confirmatory test

Aim. While metagenomic (microbial DNA) sequencing technologies can detect the presence of microbes in a clinical sample, it is unknown whether this signal represents dead or live organisms. Metatranscriptomics (sequencing of RNA) offers the potential to detect transcriptionally “active” organisms within a microbial community, and map expressed genes to functional pathways of interest (e.g. antibiotic resistance). We used this approach to evaluate the utility of metatrancriptomics to diagnose PJI and predict antibiotic resistance. Method. In this prospective study, samples were collected from 20 patients undergoing revision TJA (10 aseptic and 10 infected) and 10 primary TJA. Synovial fluid and peripheral blood samples were obtained at the time of surgery, as well as negative field controls (skin swabs, air swabs, sterile water). All samples were shipped to the laboratory for metatranscriptomic analysis. Following microbial RNA extraction and host analyte subtraction, metatranscriptomic sequencing was performed. Bioinformatic analyses were implemented prior to mapping against curated microbial sequence databases– to generate taxonomic expression profiles. Principle Coordinates Analysis (PCoA) and Partial Least Squares-Discriminant Analysis were utilized to ordinate metatranscriptomic profiles, using the 2018 definition of PJI as the gold-standard. Results. After RNA metatranscriptomic analysis, blinded PCoA modeling revealed accurate and distinct clustering of samples into 3 separate cohorts (infected, aseptic, and primary joints) – based on their active transcriptomic profile, both in synovial fluid and blood (synovial anosim p=0.001; blood anosim p=0.034). Differential metatranscriptomic signatures for infected versus noninfected cohorts enabled us to train machine learning algorithms to 84.9% predictive accuracy for infection. Multiple antibiotic resistance genes were expressed, with high concordance to conventional antibiotic sensitivity data. Conclusions. Our findings highlight the potential of metatranscriptomics for infection diagnosis. To our knowledge, this is the first report of RNA sequencing in the orthopaedic literature. Further work in larger patient cohorts will better inform deep learning approaches to improve accuracy, predictive power, and clinical utility of this technology

The average wait for a MRI Scan of the knee for an elective knee complaint is 12–18 months. This has a vast impact on family economy and quality of life considering the affected patients are young. We retrospectively reviewed 85 knee arthroscopies performed by a single surgeon during a one year period. We correlated the arthroscopy findings with the provisional diagnosis made in the clinic. There were 49 males and 36 females. The average wait for surgery was 4.6 months.The diagnosis was correct in 49 (60%), correct with additional findings in 18 (20%) and incorrect in 18 (20%). In a district general hospital setting where acces to MR Scan is difficult with a long waiting time, physical examination is reliable and arthroscopy can be performed after informed consent

SUMMARY. A retrospective cohort study of 19 patients of EOS who underwent MCGR rod instrumentation with subsequent serial distractions, measured using ultrasonography. The degree of distraction achieved during each session were analyzed and subgroup analysis done. HYPOTHESIS. The degree of distraction/ distractibility of the MCGR rod is closely linked to the etiology of EOS. The degree of distraction achieved at each session progressively diminishes with successive distractions. STUDY DESIGN. Retrospective cohort study. INTRODUCTION. MCGR rods have gained popularity as an alternative to traditional growing rods for the treatment of Early-onset scoliosis (EOS), serially distracting with an aim to mimic the normal spinal growth, which can be achieved in an outpatient setting using external remote controller. The use of ultrasound as a tool to measure the degree of distraction achieved has been validated previously. However the association between the etiological diagnosis of EOS and the degree of distraction achieved has not been studied previously. METHODS. We performed a retrospective cohort study of 19 patients with EOS of varying etiologies who underwent MCGR rod instrumentation at our institution since 2016. Their hospital records were analyzed to assess the demographics, distraction interval and the degree of distraction achieved at each session. RESULTS. 19 patients (12 females and 7 males) were included in the study. The average age of the study population was 7 years (4–13 years). The average follow up was 2.1 years (1–4). The following were the etiological diagnoses: Idiopathic EOS(8), Neuromuscular scoliosis(5), Syndromic(5), Congenital(1). The average interval between each distraction was 109.8days (88.2–140.6). The overall mean distraction was 1.66mm (0.6–3.427). The mean distraction achieved for the concave rod was 1.69mm (0.6–3.03) as against 1.59mm (0.2–3.427) for the convex rod. The degree of distraction achieved per session was the greatest in patients with neuromuscular scoliosis 2.79mm (0.94–4.62), while it was the least in Congenital scoliosis 0.99mm (0.8–2.93). The degree of distraction in Syndromic and Idiopathic scoliosis groups were 2.19mm (0.1–4.2) and 1.50mm (0.2–4.45) respectively. The mean distraction achieved during the first session after MCGR instrumentation was 2.82mm (0.4–9.8) as against 1.98mm (0.1–4.2) and 1.18mm (0.2–2.3), achieved during the 5. th. and 10. th. distractions respectively. CONCLUSIONS. The average distraction of the MCGR rod achieved per session depends upon the etiological diagnosis of EOS. Neuromuscular curves are the most amenable to MCGR distractions, while the congenital curves are the least. The degree of distraction achieved progressively diminishes with each successive distractions. The distraction achieved slumps to 70% of the initial distraction by the 5. th. session and further declines to 41% of the initial distraction by the 10. th. session. TAKE HOME MESSAGE. The distractibility of the MCGR rod is closely linked to the etiology of EOS. MCGR rods are most effective in cases of neuromuscular scoliosis, while least effective in congenital scoliosis. The law of diminishing returns holds true even with MCGR rods

Aims

This study aimed to evaluate rasterstereography of the spine as a diagnostic test for adolescent idiopathic soliosis (AIS), and to compare its results with those obtained using a scoliometer.

Aim. To assess the analytical performance and to establish the cut-off of synovial fluid D-lactate concentration for the diagnosis of prosthetic joint infection (PJI) and septic arthritis (SA) using commercial kits provided by two manufacturers (A and B). Method. We prospectively included patients with native or prosthetic joints undergoing synovial fluid aspiration as routine diagnostic procedure. Among 224 patients with prosthetic joints, 137 patients had aseptic loosening (AL) and 87 were diagnosed with PJI. Among 71 patients with native joints, 39 were diagnosed with osteoarthrosis (OA) and 32 with SA. Results. Kits for the measurement D-lactate provided by the manufacturer A. Patients with prosthetic joints. The mean D-lactate concentration was significantly higher in patients with PJI than with AL (2.33 vs 0.77 mMol, respectively; p<0.0001). The optimal D-lactate cut off was 1.2 mmol/l (sensitivity = 97.7%, specificity = 83.9%, PPV = 79.4%, NPV = 98.3%; AUC = 0.99). Patients with native joints. We found significantly higher concentration of D-lactate in patients with SA compared to OA (2.27 vs 0.46 mMol, respectively; p<0.0001). The optimal D-lactate cut off was 1.2 mmol/l (sensitivity = 93.8%, specificity = 94.9%, PPV = 93.7%, NPV = 94.9%; AUC = 0.99). Kits for the measurement D-lactate provided by the manufacturer B. Patients with prosthetic joints. The difference between concentration of D-lactate in patients with PJI and AL was also significant (mean, 2.5 vs 0.04 mmol/L, respectively; p<0,0001). The optimal D-lactate cut off was 0.5 mmol/L (sensitivity = 94.7%, specificity = 92,0%, PPV = 85.7%, NPV = 97.1%; AUC = 0.99). Patients with native joints. Significantly higher concentration of D-lactate in patients with SA in comparison with OA (mean, 2.0 vs 0.28 mmol/L, respectively; p<0.0001). The optimal D-lactate cut off was 0.5 mmol/L (sensitivity = 100%, specificity = 92.0%, PPV = 81.8%, NPV = 100%; AUC = 0.99). Conclusions. The synovial fluid D-lactate test shows high analytical performance and diagnostic capabilities in the diagnosis of PJI and SA. The optimal cut-off for the diagnosis of infection differ between manufactures. Synovial fluid D-lactate is reliable bacterial-specific marker for diagnosis of PJI and SA

Aims. The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods. Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results. A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). Conclusion. Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345–51

While stable long-term clinical results have been achieved in total joint arthroplasty, periprosthetic joint infection (PJI) has been actualized as difficult issue in this decade. For accurate diagnosis, it is important to establish standard criteria such as MSIS criteria, and it is prevailing now. As an issue involving PJI, however, the existence of viable, but non-culturable (VNC) bacteria must be noticed. It is difficult to identify the VNC state infection, because microbiologic culture result shows negative and other markers tend to be negative. Here, molecular diagnosis based on polymerase chain reaction (PCR) has certain role as potential diagnostic tools for such VNC infection. We have applied a real-time PCR system for the diagnosis of PJI, which is able to detect methicillin-resistant Staphylococcus (MRS) and distinguish gram-positive from gram-negative bacteria. The prominent advantage is that PCR is the singular way to identify MRS in such culture negative cases. Recent development of full-automatic PCR system may improve the time efficiency for routine application. In this presentation, we will show the overall sensitivity and specificity of our PCR system for diagnosing PJI and discuss the current problem and future prospect

Aim. The aim was to investigate the value of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods. The clinical features, microbiology culture results and histological analysis in 156 surgically treated non-unions were used to stratify the likelihood of associated infection. There were 64 confirmed infected non-unions (≥1 confirmatory criteria; pus, sinus and bacterial growth in ≥2 samples), 66 aseptic non-unions (no confirmatory criteria) and 26 possibly infected (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorphs (NPs) counts per high power field (HPF) and compared to the established diagnosis. Results. Assuming a cut-off of >5NPs/HPF for positive histological diagnosis, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of any NPs/HPF (>0) for negative histological diagnosis there was a sensitivity of 98% and a specificity of 85% (accuracy 92%). Conclusion. Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of >5 NPs/HPF has a positive predictive value of 100%, while the complete absence of any NPs is almost always indicative of an aseptic non-union (negative predictive value: 98%)

There are many reasons why a total knee replacement (TKR) may fail and qualify for revision. Successful revision surgery depends as much on accurate assessment of the problem TKR as it does on revision implant design and surgical technique. Specific modes of failure require specific surgical solutions. Causes of failure are often presented as a list or catalogue, without a system or process for making a decision. In addition, strict definitions and consensus on modes of failure are lacking in published series and registry data. How we approach the problem TKR is an essential but neglected aspect of understanding knee replacement surgery. It must be carried out systematically, comprehensively and efficiently. Eight modes of failure are described: 1) sepsis; 2) extensor discontinuity; 3) stiffness; 4) tibial- femoral instability; 5) patellar tracking; 6) aseptic loosening and osteolysis; 7) periprosthetic fracture and 8) component breakage. A ninth ‘category’, unexplained pain is an indication for further investigation but not surgery.

Cite this article: Bone Joint J 2014;96-B(11 Suppl A):105–11.

Aims

We investigated the prevalence of late developmental dysplasia of the hip (DDH), abduction bracing treatment, and surgical procedures performed following the implementation of universal ultrasound screening versus selective ultrasound screening programmes.

Aims. This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods. The clinical features, microbiology culture results, and histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis. Results. Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%). Conclusion. Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966–72

Aims. Leucocyte esterase (LE) has been shown to be an accurate marker of prosthetic joint infection (PJI), and has been proposed as an alternative to frozen section (FS) histology for intraoperative diagnosis. In this study, the intraoperative assessment of LE was compared with FS histology for the diagnosis of prosthetic hip infection. Patients and Methods. A total of 119 patients undergoing revision total hip arthroplasty (THA) between June 2015 and December 2017 were included in the study. There were 56 men and 63 women with a mean age of 66.2 years (27 to 88). Synovial fluid was collected before arthrotomy for the assessment of LE using enzymatic colourimetric strips. Between five and six samples were stained with haematoxylin and eosin for FS histology, and considered suggestive of infection when at least five polymorphonuclear leucocytes were found in five high-power fields. Results. The sensitivity and specificity of the LE assay were 100% and 93.8%, respectively; the positive (PPV) and the negative (NPV) predictive values were 79.3% and 100%, respectively. The mean time between the collection of the sample and the result being known was 20.1 minutes (. sd. 4.4). The sensitivity and specificity of FS histology were 78.3% and 96.9%, respectively; the PPV and the NPV were 85.7% and 94.9%, respectively. The mean time between the collection of the sample and the result being known was 27.2 minutes (. sd. 6.9). Conclusion. The sensitivity of LE assay was higher, with similar specificity and diagnostic accuracy, compared with FS histology. The faster turnaround time, its ease of use, and low costs make LE assay a valuable alternative to FS histology. We now use it routinely for the intraoperative diagnosis of PJI. Cite this article: Bone Joint J 2019;101-B:372–377

Aims. Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples. Methods. Between July 2014 and October 2019, patients with suspected joint infection (JI) from whom synovial fluid (SF) was obtained preoperatively were enrolled. Preoperative aspirated SF was analyzed by conventional microbial culture and mNGS. In addition to samples taken for conventional microbial culture, some samples were taken for intraoperative culture to optimize the culture method according to the preoperative mNGS results. The demographic characteristics, medical history, laboratory examination, mNGS, and culture results of the patients were recorded, and the possibility of the optimized culture methods improving diagnostic efficiency was evaluated. Results. A total of 56 cases were included in this study. There were 35 cases of JI and 21 cases of non-joint infection (NJI). The sensitivity, specificity, and accuracy of intraoperative microbial culture after optimization of the culture method were 94.29%, 76.19%, and 87.5%, respectively, while those of the conventional microbial culture method were 60%, 80.95%, and 67.86%, respectively. Conclusion. Preoperative aspirated SF detected via mNGS can provide more aetiological information than preoperative culture, which can guide the optimization and improve the sensitivity of intraoperative culture. Cite this article: Bone Joint J 2021;103-B(1):39–45

The term mid-flexion instability has entered the orthopaedic literature as a concept, but has not been confirmed as a distinct clinical entity. The term is used freely, sometimes as a synonym for flexion instability. However, the terms need to be clearly separated. A cadaver study published in 1990 associated joint line elevation with decreased stability at many angles of flexion, but that model was not typical of clinical scenarios. The literature is considered and it is proposed that the more common entity of an uncorrected flexion contracture after a measured resection arthroplasty technique is more likely to produce clinical findings that suggest instability mid-flexion.

It is proposed that the clinical scenario encountered is generalised instability, with the appearance of stability in full extension from tight posterior structures.

This paper seeks to clarify whether mid-flexion instability exists as an entity distinct from other commonly recognised forms of instability.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):84–8.

Aim. We report on the performance of a simple algorithm using a combination of synovial fluid White blood cell count(WBC), C-reactive protein(CRP) and α-Defensin(AD) tests to aid in the diagnosis of prosthetic joint infections. Methods. Sixty-six synovial fluid samples were collected prospectively in patients with suspected PJI (hip and knee). All samples were tested by: WBC counts (read manually) and CRP test (Alere-Afinion™ validated in-house); and on 37 of these with AD test. Synovial fluid samples were collected in 5 ml ethylenediaminetetraacetic acid (EDTA) tubes. Samples that were very viscous were pre-processed by the addition of 100µl of hyaluronidase solution. Grossly blood stained and clotted samples were excluded. A clinical diagnosis of infection was based IDSA definitions. 1. Cut offs of >3000 × 10. 6. cells/L for total synovial WBC count and >12mg/L for CRP were used to define infection. 2,3. . Results. Of 66 samples tested, 20 samples were categorised as clinically infected. Combination of WBC count and CRP yielded a sensitivity of 95% (95% CI: 75.13% to 99.87%) and specificity of 100% (95% CI: 92.29% to 100.00%). Only one patient, who had a chronic infection with S.epidermidis and S.warneri, had a CRP and WBC count that was falsely negative (<5mg/L and 93 × 10. 6. cells/L respectively). AD test was used on 37 samples (of which 20 were infected). Sensitivity of this test alone was 85.71% (95% CI: 63.66% to 96.95%) and specificity 87.5% (95% CI: 61.65% to 98.45%). There were 2 falsely positive AD test results (one of whom had a metal on metal prosthesis) and 3 false negative results (2 E.coli infections and one patient with chronic infection with S.epidermidis and S.warneri). Conclusion. Use of a combination of synovial fluid WBC count and CRP (both of which can be performed using simple and inexpensive laboratory tests), has a sensitivity of 95% and 100% specificity in the diagnosis of PJI. AD test may be useful on some occasions when near patient testing result may affect patient management

Background. The anterior-posterior (AP) pelvis radiograph is crucial for diagnosis of neck of femur (NOF) fractures, especially as this is one of the commonest fractures in the elderly population. Anecdotally we found that initial AP pelvis radiographs for these suspected fractures did not always exhibit the bones sufficiently. Repeat radiographs were needed, leading to delays in diagnosis, treatment, and repeated radiation exposure. Missed diagnoses can have significant consequences for this patient group. We assessed how many initial AP pelvis radiographs taken for suspected NOF fracture fitted criteria for adequate diagnostic imaging. Methods. A retrospective study was carried out assessing the initial AP pelvis radiograph done for each patient presenting to our dedicated NOF unit with suspected NOF fracture for 1st June – 31st July 2014. European Guidelines for Diagnostic Imaging were used as the benchmark. Each radiograph was scored out of six, one for each criteria fulfilled. Guidelines deemed images scoring ≤3 as inadequate. Results. 76 images were assessed with mean patient age 85 years. 51.3% of images scored ≤3 and mean score was 3.59. The least-met criterion was “sharp reproduction of sacrum and vertebral foramina” (26.3%). Crucially only 52.6% achieved “visually sharp reproduction of spongiosa, trochanters and corticalis of both femurs”, important in diagnosis of NOF fractures. Conclusion. More than half initial AP pelvis radiographs taken for suspected NOF fracture were inadequate based on European Guidelines at a dedicated NOF unit. Part of the difficulty can be attributed to challenging patient demographics, however adequate initial radiographs should be aimed for, as repeat radiographs can lead to delays in diagnosis and treatment as well as repeated radiation exposure. Missed diagnoses can have significant consequences for this patient group; we particularly recommend care to be taken to sharply visualise the trochanters and proximal femora to avoid missing subtle fractures

Aims. The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP. Methods. PubMed, Embase, and the Cochrane Library were searched in February 2020 to identify articles reporting on the diagnostic value of D-dimer on PJI. Pooled analysis was conducted to investigate the diagnostic value of D-dimer, CRP, and ESR. Results. Six studies with 1,255 cases were included (374 PJI cases and 881 non-PJI cases). Overall D-dimer showed sensitivity of 0.80 (95% confidence interval (CI) 0.69 to 0.87) and specificity of 0.76 (95% CI 0.63 to 0.86). Sub-group analysis by excluding patients with thrombosis and hyper-coagulation disorders showed sensitivity of 0.82 (95% CI 0.70 to 0.90) and specificity of 0.80 (95% CI 0.70 to 0.88). Serum D-dimer showed sensitivity of 0.85 (95% CI 0.76 to 0.92), specificity of 0.83 (95% CI 0.74 to 0.90). Plasma D-dimer showed sensitivity of 0.67 (95% CI 0.60 to 0.73), specificity of 0.58 (95% CI 0.45 to 0.72). CRP showed sensitivity of 0.78 (95% CI 0.72 to 0.83), specificity of 0.81 (95% CI 0.72 to 0.87). ESR showed sensitivity of 0.68 (95% CI 0.63 to 0.73), specificity of 0.83 (95% CI 0.78 to 0.87). Conclusion. In patients without thrombosis or a hyper-coagulation disorder, D-dimer has a higher diagnostic value compared to CRP and ESR. In patients with the aforementioned conditions, D-dimer has higher sensitivity but lower specificity compared to ESR and CRP. We do not recommend the use of serum D-dimer in patients with thrombosis and hyper-coagulation disorders for diagnosing PJI. Serum D-dimer may perform better than plasma D-dimer. Further studies are needed to compare serum D-dimer and plasma D-dimer in arthroplasty patients. Cite this article: Bone Joint Res 2020;9(10):701–708

Aims. The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. Methods. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results. Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10. 9. /l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion. The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911

Aim. To evaluate the analytical performance of synovial fluid D-lactate test for the diagnosis of PJI. Method. Consecutive patients undergoing diagnostic joint aspiration of prosthetic joint were prospectively included. PJI was diagnosed according to the proposed European Bone and Joint Infection Society (EBJIS) definition criteria. Synovial fluid was collected for culture, D-lactate measurement (by spectrophotometry, λ = 570 nm) and leukocyte count and differential (by flow cytometry). The receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of D-lactate and leukocyte count. Results. Diagnostic joint aspiration was performed in 224 patients with prosthetic joints. PJI was diagnosed in 87 patients (39%). The optimal D-lactate cut-off value for diagnosing PJI was 1.2 mmol/l. The sensitivity of synovial fluid D-lactate was 97.7%, specificity 83.9%, whereas the sensitivity of synovial fluid leukocyte count was 87.5% with specificity 95.7%. Concentration of SF D-lactate was significantly higher in patients with PJI compared to aseptic loosening of prosthesis (median (range)) 2.33 (0.99–3.36) vs 0.77 (0.01–2.4), p<0.0001. We found positive correlation between D-lactate and erythrocytes in synovial fluid sample in the aseptic group (ρ = 0.339, p< 0.01). Conclusions. The synovial fluid D-lactate showed a good diagnostic performance for the diagnosis of PJI, which was comparable to the synovial fluid leukocyte count. Currently available (UV)-based method for detection of D-lactate showed low specificity (84%) due to influence of hemoglobin with the similar absorbance wavelengths (λ = 540 nm). More specific high-performance methods such as electro-chemical sensing system or lateral flow immunochromatographic assays should be implemented

The “Toddler Fracture” is an un-displaced oblique distal tibia fracture seen in children 9–36months of age presenting with refusal to walk, often after an unwitnessed or minor injury. Diagnosis is often made clinically, because initial x-rays are negative in up to 50% of patients, and then confirmed by the presence of periosteal reaction on follow up x-ray 7–10 days later. Point of Care Ultrasound (POCUS) has shown excellent ability to detect distal radius, clavicle and other extremity fractures and published case reports suggest that POCUS can also detect Toddler Fractures. The objective of this proof of concept study was to establish the feasibility and preliminary sensitivity and specificity of POCUS in the diagnosis of Toddler Fractures, and to characterize the POCUS findings in patients presenting with clinical Toddler Fractures. This was a prospective reviewer-blinded cross-sectional study of patients presenting to the emergency department of a paediatric tertiary care centre with presumed toddler fractures. All patients with suspected toddler fracture underwent lower limb x-ray. Those enrolled in the study also underwent POCUS of both lower extremities by a specialized provider. Treating clinicians were blinded to ultrasound results, and study sonographers were blinded to x-ray results. Study patients were then seen in paediatric orthopaedic follow up clinics 7–10 days later, and clinical assessment and follow up x-ray were performed as necessary to confirm diagnosis. Toddler Fracture was confirmed in 5 of 27 patients enrolled in the study. Preliminary results demonstrate that these POCUS findings were detected on the scan in all 5 confirmed toddler fractures. Three of these patients had an initial positive x-ray and 2 went on to have toddler fracture confirmed on follow up x-ray and orthopaedic assessment. POCUS findings consistent with a toddler fracture were found to be cortical disruption and periosteal hematoma. POCUS may be a useful adjunct to confirming a diagnosis of a toddler fracture when clinical suspicion is high and initial x-ray is negative. This pilot study provides positive impetus for further prospective study. The use of POCUS to confirm toddler fracture can decrease further radiation exposure to patients, allow early guidance to families on the management and expected recovery, and has potential to decrease burden on families and the healthcare system by potentially eliminating unnecessary follow-up appointments. Future study will help to better guide diagnostic and technical criteria, and provide guidance for appropriate medical education in this technique and interpretation

Aims. Microbiological culture is a key element in the diagnosis of periprosthetic joint infection (PJI). However, cultures of periprosthetic tissue do not have optimal sensitivity. One of the main reasons for this is that microorganisms are not released from the tissues, either due to biofilm formation or intracellular persistence. This study aimed to optimize tissue pretreatment methods in order to improve detection of microorganisms. Methods. From December 2017 to September 2019, patients undergoing revision arthroplasty in a single centre due to PJI and aseptic failure (AF) were included, with demographic data and laboratory test results recorded prospectively. Periprosthetic tissue samples were collected intraoperatively and assigned to tissue-mechanical homogenization (T-MH), tissue-manual milling (T-MM), tissue-dithiothreitol (T-DTT) treatment, tissue-sonication (T-S), and tissue-direct culture (T-D). The yield of the microbial cultures was then analyzed. Results. A total of 46 patients were enrolled, including 28 patients in the PJI group and 18 patients in the AF group. In the PJI group, 23 cases had positive culture results via T-MH, 22 cases via T-DTT, 20 cases via T-S, 15 cases via T-MM, and 13 cases via T-D. Three cases under ongoing antibiotic treatment remained culture-negative. Five tissue samples provided the optimal yield. Any ongoing antibiotic treatment had a relevant influence on culture sensitivity, except for T-DTT. Conclusion. T-MH had the highest sensitivity. Combining T-MH with T-DTT, which requires no special equipment, may effectively improve bacterial detection in PJI. A total of five periprosthetic tissue biopsies should be sampled in revision arthroplasty for optimal detection of PJI. Cite this article: Bone Joint Res 2021;10(2):96–104

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

Background. Currently, the gold standard for the microbiological diagnosis remains the culturing of preoperative aspirated joint fluid and intraoperative periprosthetic tissue samples, which give false negative results in about 7 % of cases. Lytic bacteriophages are viruses that specifically infect and lyse bacteria within their replication cycle. Aim. The aim of our study was to explore possibilities for the use of bacteriophage K for the detection of live Staphylococcus spp. bacteria in sonicate fluid of infected prosthetic joints, to possibly contribute to the development of a faster, more sensitive, specific and at the same time economical and handy method for the establishment of the right diagnosis. Material and methods. Sonicate fluid samples obtained from 104 patients with revision arthroplasty were analysed. After the optimisation two indirect phage-based methods were used: a) bioluminescence detection of bacterial intracellular ATP released by bacteriophage K mediated lysis and b) q-PCR with primers specific for bacteriophage K DNA. The results were compared with classical microbiological cultivation methods. Results. With both methods the analysis of sonicate fluid and the analysis of its over-night culture achieved 100 % specificity and predictive value, as there were no false positive results. The sensitivity of the methods was lower when analysing sonicate fluid samples directly, without cultivation. The sensitivity of qPCR detection was higher (81.25 %) compared to the sensitivity of ATP detection (62.5 %) in sonicate fluid directly as a result of 3 false negative results with the qPCR method compared to 6 false negatives with the ATP detection method. The sensitivity of the methods was significantly improved (to 94.12 %) with overnight cultivation of sonicate fluid samples prior to analysis, with no difference in detection between the methods. With both methods, with pre-cultivation of sonicate fluid samples, only one of the tested samples resulted in a false negative result. However, the same sample was negative even when tested with standard microbiological methods. In this patient, only the microbiological cultivation of the periprosthetic tissue sample was positive. The bioluminescence method took 3h with a limit of detection (LOD) in the bacterial concentration range of 10. 3. CFU/mL. The method with qPCR took 4h and had a LOD of 10. 2. CFU/mL. Conclusion. Detection of staphylococci within sonicate fluid with bacteriophage K based methods is a rapid, sensitive and specific approach

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

Objectives. The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial. Materials and Methods. The Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus. Results. Full or near consensus was reached in 20 of the 29 cases. The Fleiss kappa value was calculated as 0.44 (95% confidence interval (CI) 0.35 to 0.53), or moderate agreement. The greatest statistical agreement was observed in the outcome of no infection, 0.61 (95% CI 0.49 to 0.72, substantial agreement). Panelists reached a full consensus in 12 of 29 cases and near consensus in five of 29 cases when CDC criteria were used (superficial, deep or organ space). A stable maximum Fleiss kappa of 0.46 (95% CI 0.50 to 0.35) at CAC sizes greater than three members was obtained. Conclusions. There is substantial agreement among the members of the PARITY CAC regarding the presence or absence of surgical site infection. Agreement on the level of infection, however, is more challenging. Additional clinical information routinely collected by the prospective PARITY trial may improve the discriminatory capacity of the CAC in the parent study for the diagnosis of infection. Cite this article: J. Nuttall, N. Evaniew, P. Thornley, A. Griffin, B. Deheshi, T. O’Shea, J. Wunder, P. Ferguson, R. L. Randall, R. Turcotte, P. Schneider, P. McKay, M. Bhandari, M. Ghert. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res 2016;5:347–352. DOI: 10.1302/2046-3758.58.BJR-2016-0036.R1

Introduction

Treatment pathways of 5^th metatarsal fractures are commonly directed based on fracture classification, with Jones types for example, requiring closer observation and possibly more aggressive management.

Developmental dysplasia of the hip (DDH) should be diagnosed as early as possible to optimise treatment. The current United Kingdom recommendations for the selective screening of DDH include a clinical examination at birth and at six weeks. In Northern Ireland babies continue to have an assessment by a health visitor at four months of age. As we continue to see late presentations of DDH, beyond one year of age, we hypothesised that a proportion had missed an opportunity for earlier diagnosis. We expect those who presented to our service with Tonnis grade III or IV hips and decreased abduction would have had clinical signs at their earlier assessments. We performed a retrospective review of all patients born in Northern Ireland between 2008 and 2010 who were diagnosed with DDH after their first birthday. There were 75 856 live births during the study period of whom 645 children were treated for DDH (8.5 per 1000). The minimum follow-up of our cohort from birth, to detect late presentation, was four years and six months. Of these, 32 children (33 hips) were diagnosed after their first birthday (0.42 per 1000). With optimum application of our selective screening programme 21 (65.6%) of these children had the potential for an earlier diagnosis, which would have reduced the incidence of late diagnosis to 0.14 per 1000. As we saw a peak in diagnosis between three and five months our findings support the continuation of the four month health visitor check. Our study adds further information to the debate regarding selective versus universal screening. . Cite this article: Bone Joint J 2015;97-B:1572–6

Introduction. The intra-operative diagnosis of Prosthetic Joint Infection (PJI) is a dilemma requiring intra-operative sampling of suspicious tissues for frozen section, deep tissue culture and histopathology to secure a diagnosis. Alfa defensin-1 testing has been introduced as a quick and reliable test for confirming or ruling out PJI. This study aims to assess its intra-operative reliability compared to the standard tests. Methods. Twenty patients who underwent revision hip and knee arthroplasty surgery were included. Patients joint aspirate was tested intra-operatively with the Synovasure kit, which takes approximately ten minutes for a result. Our standard protocol of collecting 5 deep tissue samples for culture and one sample for histopathology was followed. Results for Alfa defensin-1 test were then compared with final culture and histopathology results in all these patients. Results. Our results show an excellent correlation with the final deep tissue cultures and histopathology outcomes. Literature reports frozen section to have low (58–73%) sensitivity but high (96%) specificity. Conclusions. Alfa defensin-1 test is easy, quick and efficient; results were available immediately intra-operatively. Cryosection is time consuming with samples shipped to the reference laboratory at times resulting in intra-operative delays. In our practice Alfa defensin-1 test certainly will replace frozen section for intra-operative testing

Recent evidence suggests that the microbial community, its spatial distribution and activity play an important role in the prolongation of treatment and healing of chronic infections. Standard bacterial cultures often underestimate the microbial diversity present in chronic infections. This lack of growth is often due to a combination of inadequate growth conditions, prior usage of antibiotics and presence of slow-growing, fastidious, anaerobic or unculturable bacteria living in biofilms. Thus, diagnosis of chronic infections is challenged by lack of appropriate sampling strategies and by limitations in microbiological testing methods. The purpose of this study was to improve sampling and diagnosis of prosthetic joint infections (PJI) and chronic wounds, especially considering the biofilm issue. Systematic sampling, sonication of prosthesis and extended culture were applied on patients with chronic wounds and patients with suspected PJIs. Optimized DNA extraction, quantitative PCR, cloning, next generation sequencing and PNA FISH were applied on the different types of specimens for optimized diagnosis. For further investigation of the microbial pathogenesis, in situ transcriptomics and metabolomics were applied. In both chronic wounds and PJIs, molecular techniques detected a larger diversity of microorganisms than culture methods in several patients. Especially in wounds, molecular methods identified more anaerobic pathogens than culture methods. A heterogeneous distribution of bacteria in various specimens from the same patient was evident for both patient groups. In chronic wounds, multiple biopsies from the same ulcer showed large differences in the abundance of S. aureus and P. aeruginosa at different locations. Transcriptomic and metabolomic analyses indicated the important virulence genes and nutrient acquisition mechanisms of Staphylococcus aureus in situ. As an example, diagnosis and treatment of a patient with a chronic biofilm prosthesis infection persisting for 7 years will be presented. Our studies show that diagnosis of chronic biofilm related infections required multiple specimen types, standardized sampling, extended culture and molecular analysis. Our results are useful for improvement of sampling, analysis and treatment in the clinic. It is our ambition to translate studies on bacterial activity into clinical practice in the future

Joint replacement is a life-enhancing, cost-effective surgical intervention widely used to treat disabling joint pain mainly caused by osteoarthritis. Hip and knee joint replacements are common, highly successful operations bringing many patients relief from pain, and improve mobility. Prosthetic joint infections (PJI) are often difficult to diagnose; diagnosis often relying on a combination of clinical findings, microbiological data and histological evaluation of periprosthetic tissue. The majority of recent studies demonstrate a higher sensitivity for the culture of sonication fluid (62–94%) than periprosthetic tissue (55–88%). The Royal Devon & Exeter NHS Foundation Trust provided a specialist multidisciplinary team. We evaluated the use of sonication for identifying pathogens during revision hip and knee replacement in our unit with the intention of applying for further grants to study this technology in more detail; it was a diagnostic feasibility study. The target recruitment was 50 patients; 25 consecutive patients undergoing revision hip arthroplasty for any reason, and 25 undergoing revision knee arthroplasty for any reason. The majority of patients were identified in outpatient clinics. Our results show that tissue culture remains more sensitive than sonication. The sensitivity for direct sonication was 75% compared with 80% for tissue culture; sensitivity of enriched sonication was 80 %, compared to the unit results for tissue culture of 83%. The combined sensitivity of tissue culture was better as a higher number of tissue specimens were obtained. The different methodology might explain reported differences between this and other studies; however, our study does not support the use of sonication as the only tool in the diagnosis of PJI

The true results of revision total knee arthroplasty (TKA) are not fully understood, for a variety of understandable reasons. But it is has been clear for decades that revision without a diagnosis is likely to fail. The evaluation of the problem TKA should be systematic (follow the same scheme every time) and comprehensive (all possibilities should be considered even if one diagnosis seems obvious). Evaluation begins, as with all of medicine with a list of possible causes: the mechanisms of failure. John Moreland was the first to describe a coherent system which needed only one simple addition to be complete: 1.) Prosthetic joint infection; 2.) Extensor disruption; 3.) Patella and malrotation; 4.) Loose; 5.) Component breakage; 6.) PP fracture; 7.) Poor motion; and 8.) Tibial femoral instability. Evaluation begins with the history, where 10 questions in particular are useful: 1.) What seems to be the problem? 2.) Was the “knee” ever successful after surgery? If there was never pain relief, is the current pain, the same or different? 3.) Standard pain quality questions - Location, duration, frequency, quality, exacerbating, ameliorating. 4.) Swelling? 5.) Stiffness? 6.) Giving way? 7.) Weakness? 8.) Things “just don't feel right”? 9.) Possible sepsis questions - Fever, chills, sources, primary TKA healing. 10.) Mood, social situation?. The physical exam should cover these ten points: 1.) Active extension; 2.) Rising from chair; 3.) Gait: hip, knee alignment, knee instability; 4.) Hip (internal rotation); 5.) Inspection; 6.) Tenderness; 7.) ROM; 8.) Stability (extension and 30–45 degrees flexion; 9.) Sitting on edge of exam table (knee at 90 degrees); and 10.) Step up on low stool (stair). Investigations include: 1.) ESR + CRP; 2.) CBC; 3.) HGB- anemia; 4.) Lymphocytes- nutrition; 5.) GGT- alcohol abuse; 6.) Albumen- nutrition; 7.) HbA1c- diabetic control. Imaging includes: 1.) Single leg weightbearing AP; 2.) Lateral; 3.) Merchant; 4.) Full length (hip-knee-ankle); 5.) AP pelvis; 6.) CT scan; and 7.) (Technitium bone scan)

Introduction. Rupture of the anterior cruciate ligament (ACL) is a common injury and often presents with a typical injury pattern. Historic literature has shown that the accuracy of diagnosis of ACL ruptures is poor at the initial medical consultation despite the history of injury strongly suggesting an ACL injury. The aims of this study were to determine: if the accuracy of diagnosis of ACL ruptures at initial presentation has improved over the last decade; grade of medical staff at initial and subsequent consultations; the mechanism of injury; and the subsequent delay in diagnosis and definitive treatment. Materials and Methods. One hundred and thirty two consecutive patients who underwent ACL reconstruction between January 2005 and January 2009 were analysed using prospective collected data. The mean age of the patients was 29 years (12-57). Sixteen patients were excluded due to chronic ACL injury (15). Results. One hundred and sixteen patients (117 ACL ruptures) were included in the analysis. A typical injury pattern was documented in 87 (75%) of cases. The most common sporting activities associated with an ACL injury were football (35.3%), skiing (21.6%), rugby (10.3%) and other (32.8%). The vast majority of patients (68.1%) sought medical attention within 1 week from time of injury. The diagnosis of an ACL rupture was made in 33 cases (28%) at the initial medical consultation. The diagnosis was made in 13 (11%) of cases with the use of MRI and 6 (5%) cases at arthroscopy. The most common diagnoses made in cases of failed ACL rupture diagnosis were medial meniscal tear (10.3%), medial collateral ligament injury (7.8%) and none (33.6%). The mean time to diagnosis was 21 weeks (0-192) and the mean time to ACL reconstruction was 44 weeks (1-240). Conclusions. Despite a typical mechanism of injury leading to ACL rupture the rate of initial diagnosis remains poor. This often leads to an unnecessary delay in diagnosis and subsequent treatment. Possible reasons for this are discussed

The diagnosis of prosthetic-joint infection (PJI) is challenging, as bacteria adhere on implant and form biofilm. Therefore, current diagnostic methods, such as preoperative culture of joint aspirate have limited sensitivity with false-negative results. Aim. To evaluate the performance of measurement synovial fluid (SF) D-lactate (as a pathogen-specific marker) for the diagnosis of PJI and estimate of treatment success. Method. 224 patients undergoing removal knee or hip prosthesis were included in the study between January 2015 and March 2017. 173 patients of this group had aseptic loosening of prosthesis and 87 were diagnosed with PJI. Prior to surgery, synovial fluid routine culture, D-lactate test, leukocyte count and neutrophils (%) were performed for each patient. In order to evaluate a treatment success, the measurement of SF D-lactate before second two-stage exchange procedure (after treatment) was implemented in 30 patients. Diagnosis of PJI was established according to modified Zimmerli criteria. Results. Of 87 patients with infection of prosthetic joints, 61 (70%) had positive synovial fluid cultures, including Staphylococcus spp. (70%), Streptococcus spp. (10%), Enterococcus spp. (6%), Anaerobes (6%), Enterobacteriacae (4%), P. aeruginosa (2%), C. parapsilosis (2%). There was no significant difference in SF D-lactate levels due to different bacterial strains. The optimal D-lactate cut off was 1,2 mmol/l (sensitivity = 98%, specificity = 84%, PPV = 79%, NPV = 98%, AUC 0,99). Concentration of SF D-lactate was significantly higher in patients with PJI compared to aseptic loosening of prosthesis (median (range)) 2.33 (0.99–3.36) vs 0.77 (0.01–2.4), p<0.0001.D-lactate has better sensitivity for diagnosis of PJI (98%), compared to leukocytes (80%) and neutrophils % (89%), p<0.0001). The concentration of D-lactate decreased below cut off within four weeks after revision surgery (after treatment) in all patients except of three, showing relapse of infection (p<0.0001). Conclusions. The measurement of synovial fluid D-lactate demonstrated high analytical performance in the diagnosis of PJI, it is a reliable pathogen specific marker. D-lactate has the best sensitivity as independent diagnostic method and could be implemented for the evaluation of treatment success

INTRODUCTION. Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. However, infection of these implants, called Periprosthetic Joint Infection (PJI), remains one of the biggest challenges facing orthopaedics today. PJI can lead to additional surgeries, revision, fusion and amputation. Diagnosis of PJI. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. These include the erythrocyte sedimentation rate (ESR), the serum C-reactive protein (CRP), the synovial fluid white blood cell count and the leukocyte differential. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The Synovasure® Test for Periprosthetic Joint Infection (PJI). The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. These biomarkers include inflammatory proteins, cytokines, and microbicidal peptides / proteins that are known to be involved in the host response to infection. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. DISCUSSION. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. CONCLUSIONS. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

In years past, the most common reason for revision following knee replacement was polyethylene wear. A more recent study indicates that polyethylene wear is relatively uncommon as a cause for total knee revision counting for only 10% or fewer of revisions. The most common reason for revision currently is aseptic loosening followed closely by instability and infection. The time to revision was surprisingly short. In a recent series only 30% of knees were greater than 5 years from surgery at the time of revision. The most common time interval was less than 2 years. This is likely because of the higher incidence of infection and instability that occurs most commonly at a relatively early time frame. Evaluation of a painful total knee should take into account these findings. All total knees that are painful within 5 years of surgery should be assumed to be infected until proven otherwise. Therefore, virtually all should be aspirated for cell count, differential, and culture. Alpha-defensin is also available in cases in which a patient may have been on antibiotics within a month or less, as well as cases in which diagnosis is a challenge for some reason. Instability can be diagnosed with physical exam focusing on mid-flexion instability which can be usually determined with the patient seated and the knee in mid-flexion, with the foot flat on the floor at which point sagittal plane laxity can be discerned. This is also frequently associated with symptoms of giving way and recurring effusions and difficulty descending stairs. A new phenomenon of tibial de-bonding has been described, which can be a challenge to diagnose. Radiographs can appear normal when loosening occurs between the implant and the cement mantle. This seems to be more common with the use of higher viscosity cement. Obviously this is technique dependent since good results have been reported with the use of high viscosity cement. Component malposition can cause stiffness and pain and relatively good results have been reported by component revision when malrotation has been confirmed with CT scan. When infection, instability and loosening are not present, extra-articular causes should be ruled out including lumbar spine, vascular compromise, complex regional pain syndromes and fibromyalgia, and peri-articular causes such as bursitis, tendonitis, tendon impingement among others. One of the most common causes of pain following total knee is unrealistic patient expectations. Performing total knee replacement in early stages of arthritis with only mild to moderate symptoms and radiographic changes has been associated with persistent pain and dissatisfaction. It may be prudent to obtain the immediate preoperative x-rays to determine if early intervention was undertaken and patients have otherwise normal appearing total knee x-rays and a negative work up. A recent study indicated that this was likely a cause or a major contributing factor to persistent pain following otherwise a well performed knee replacement. A national multicenter study of the appropriateness of indications for TKA also indicated that early intervention was a major cause of persistent pain, dissatisfaction, and failure to improve following total knee replacement

Introduction: Rupture of the anterior cruciate ligament (ACL) is a common injury and often presents with a typical injury pattern. Historic literature has shown that the accuracy of diagnosis of ACL ruptures is poor at the initial medical consultation despite the history of injury strongly suggesting an ACL injury. The aims of this study were to determine: if the accuracy of diagnosis of ACL ruptures at initial presentation has improved over the last decade; grade of medical staff at initial and subsequent consultations; the mechanism of injury; and the subsequent delay in diagnosis and definitive treatment. Materials and Methods: One hundred and thirty two consecutive patients who underwent ACL reconstruction between January 2005 and January 2009 were analysed using prospective collected data. The mean age of the patients was 29 years (12–57). Sixteen patients were excluded due to chronic ACL injury (15). Results: One hundred and sixteen patients (117 ACL ruptures) were included in the analysis. A typical injury pattern was documented in 87 (75%) of cases. The most common sporting activities associated with an ACL injury were football (35.3%), skiing (21.6%), rugby (10.3%) and other (32.8%). The vast majority of patients (68.1%) sought medical attention within 1 week from time of injury. The diagnosis of an ACL rupture was made in 33 cases (28%) at the initial medical consultation. The diagnosis was made in 13 (11%) of cases with the use of MRI and 6 (5%) cases at arthroscopy. The most common diagnoses made in cases of failed ACL rupture diagnosis were medial meniscal tear (10.3%), medial collateral ligament injury (7.8%) and none (33.6%). The mean time to diagnosis was 21 weeks (0–192) and the mean time to ACL reconstruction was 44 weeks (1–240). Conclusions: Despite a typical mechanism of injury leading to ACL rupture the rate of initial diagnosis remains poor. This often leads to an unnecessary delay in diagnosis and subsequent treatment. Possible reasons for this are discussed

Purpose. Ultrasound of the neonatal and infantile hip is a useful tool in diagnosis and treatment of the developmental dysplasia of the hip (DDH), especially given the fact that numerous cases of DDH do not present any findings in the clinical examination. Methods. Between January 2014 and May 2020, 10536 (5273 neonates and infants, 53% girls, 47% boys) consecutive neonatal and infantile hip joints were studied using the Graf Hip Ultrasound method. Results. 607 hips were diagnosed as abnormal. 523 (5%) hip joints were type IIA, 18 (0.17%) were type ΙΙΒ, 19 (0.18%) were type ΙΙC, 33 (0.31%) were type ΙΙΙ and 14 (0.13%) were type IV. 72% of patients were girls, 55% of patients were firstborns, 35,7% presented breech, 8,2% had a positive family history of DDH, 6% were part of a multiple pregnancy, while 27,2% had no predisposing factor for the disease. Type ΙΙΑ hips were treated with follow- up only and had all matured (turned to normal- type I hips) within a trimester. Type ΙΙΒ και ΙΙC hips were treated using an abductor harness and were normal (type I) within three months. 35.7% of type ΙΙΙ were treated with an abductor harness and 64.3% with hip spica. All type IV hips were treated with hip spica. The duration of therapy for type III and type IV hips was 3 months. Conclusion. The early use of a hip ultrasound provides us with the ability to diagnose and treat DDH efficiently, resulting in a normal hip joint within the first months of life

Objectives. Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). Methods. We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis. Results. The circulating exosome level of the ONFH group was significantly lower than that of control group. The area under the curve was 0.72, suggesting that the level of serum exosomes has moderate diagnostic accuracy for steroid-induced ONFH. Conclusion. Circulating exosome levels are valuable in the diagnosis of steroid-induced ONFH. Cite this article: H-Y. Zhu, Y-C. Gao, Y. Wang, C-Q. Zhang. Circulating exosome levels in the diagnosis of steroid-induced osteonecrosis of the femoral head. Bone Joint Res 2016;5:276–279. DOI: 10.1302/2046-3758.56.BJR-2015-0014.R1

The medical model of history, examination and investigation forms the bedrock of diagnosis and management of all patients. The essence is the recognition of patterns of symptoms and signs. In the modern era there are an increasing number of non-medical resources ranging from web-based information, computer diagnostic aids and non-specialist healthcare professionals to provide a diagnosis and commence management of a wide range of conditions, including knee problems. We analysed the quality and patterns of clinical presentation in order to answer the question how closely clinical symptoms and examination findings correlate to diagnosis based on MRI scan and/or arthroscopic findings. The analysis was a dataset of a consecutive series of patients, aged 18 to 45, with no past history of knee problems or end stage arthritis, presenting to a single specialist triage physiotherapist, working within an integrated knee service, who fully completed a standardised knee assessment proforma of presenting symptoms and signs at a large district general hospital. The study comprises 86 patients and 98 knees. We analysed this data based on diagnostic findings of MRI scan or arthroscopy to provide definitive intra-articular diagnosis. Based on standard textbook descriptions of common presentations, we went on to define the patients' presentation history and examination as typical or atypical, with typical meaning the symptoms and signs correlated with the diagnosis. The null hypothesis is that patients have a high chance of typical presentations for common knee conditions. In the 75% of patients with a significant intra-articular pathology we found the majority had chondral rather than meniscal tears 1.7 to 1. Forty four percent of patients had atypical symptoms and 71% had atypical clinical signs, 30% and only 26% of the cohort had both typical symptoms and signs together, reflecting a surprisingly low positive predictive probability of symptoms and signs in this group of patients, particularly those with chondral lesions which was 44%. In this cohort, 57% of the cohort has 3 or more multiple diagnoses. In the diagnostically normal group, 43% had symptoms and signs typical for a meniscal tear. We conclude that clinical symptoms and signs surprisingly inaccurate in guiding intra-articular pathology within the knee, even in a sub-set considered the easy and accurate to assess. The number of multiple diagnoses and the incidence of false positive results also means that simplistic interpretations of non-definitive diagnoses and linear causation of pain pathways should be treated cautiously

Diagnosis of chronic prosthetic joint infection (PJI) is often challenging. Painful prosthesis is frequently due to an infection but to diagnose it is somethimes difficult. All recent guidelines stress the central role of joint punction in diagnosis of PJI if the infection is not demonstrated. However which test on synovial fluid must be carried out is not so clearly defined. Total white blood cell count and differential leukocite count are usually considered useful in diagnosis but cut offs reported by different studies are quite different. Moreover this test needs a relatively large amount of fluid and blood contamination of it largely affects the result. What's more the synovial fluid WBC count may be unreliable in the setting of a metal-on-metal bearing or corrosion reaction. Routine cultures should be maintained between 5 and 14 days, their sensitivity appears low in chronic infection even if witholding antimicrobial therapy before the collection of the fluid can increase the likelihood of recovery an organism. Synovial leukocyte esterase can be performed as a rapid office or intraoperative point of care test using urinalysis strips. It is cheap and easy to perform, but the presence of blood in the sample can affect the result and it needs centrifugation. Recently a new test has been proposed to detect alfa-defensine in synovial fluid. It shows a high sensitivity and an exellent specificity. We performed 25 joint punctions on 25 patients with suspected PJI (enrollment is going on). Synovial fluid collected was tested for: leukocite esterase, WBC count and differential, colture in blood colture bottle for anerobe and aerobes (BacT/ALERT Biomerieux, inc) and detection of alfa-defensine level (Synovasure – Zimmer). In patients who underwent surgery at least 5 samples of periprotesic tissue were collected for microbiologic analysis and the removed implant was sonicated according with the methodic. Furthermore samples for frozen section were sent and a histologic examination was made according to the Moriewitz – Kerr classification. The MSIS criteria was utilized to classify the case as infected or not

Aim. Our goal is to assess diagnostic accuracy of synovial fluid testing in diagnosing prosthetic joint infection (PJI) as defined by the European Bone and Joint Infection Society (EBJIS). In addition to differential leukocyte count, simples and inexpensive biomarkers such as synovial fluid C-reactive protein (CRP), adenosine deaminase (ADA) and alpha-2-macrogloblulin(A2M) were also investigated and its possible role in increasing accuracy assessed. Method. Between January/2013 and December/2019 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples, as well as the implant for sonication, were gathered for microbiological study. Definitive diagnosis was classified according to the new EBJIS PJI definition. Using receiver operating characteristic curves, we determined cutoff values as well as diagnostic accuracy for each marker. Results. Out of 364 revision arthroplasties performed, 102 fully respected inclusion criteria. There were 58 unlikely, 8 likely and 36 confirmed infections. Synovial fluid total leukocyte count, proportion of polymorphonuclear neutrophils (PMN), CRP, ADA and A2M were significantly different between groups. Area under the curve was 0.94 for total leucocyte count, 0.91 for proportion of PMN, 0.90 for CRP, 0.82 for ADA and 0.76 for A2M. Sensitivity, specificity, and predictive values for statistically optimal but also selected rule-in and rule-out cutoffs values are shown in Table 1. Interpreting a raised level of CRP(>2.7mg/L) or ADA(>60U/L) together with high leukocyte count (>1470 cells/μL) or proportion of PMN (>62.5%) significantly increases specificity and positive predictive value for affirming PJI. Conclusions. Differential leukocyte count cutoffs proposed by the EBJIS PJI definition are shown to perform well in ruling out (<1,500 cells/μL) and ruling in (>3,000 cells/μL) PJI. Adding simple and inexpensive biomarkers such synovial CRP or ADA is helpful in interpreting inconclusive results. For any tables or figures, please contact the authors directly

Aim. Over the past three years, roughly 100,000 hip and knee replacements have been performed by the Brazilian Public Healthcare System. Prosthetic joint infection (PJI) is expected to range between 1% to 10% after primary and revisions joint arthroplasties, respectively. So far, there have been no published national PJI data which would be helpful at developing local preventive strategies and guide surgeons and clinicians. We aimed at describing the epidemiological, clinical and microbiological PJI results of a national and collaboration study among infectious diseases specialists and orthopaedic surgeons, including academic, public and private institutions. Method. We prospectively enrolled patients with PJI in a national cohort study among 12 hospitals from 6 different States to describe host, pathogens, diagnosis, surgery strategies adopted (according to the standard hospital-based guideline) and outcome after 1- and 2-years follow-up. PJI was defined using the IDSA criteria (Osmon D, et al. Clin Infect Dis. 2013). Patients were enrolled from July 2013 to December 2015. Results. Overall, 234 patients undergoing hip, knee and shoulder (n=3) arthroplasty were eligible; 35 were excluded: did not fulfil the inclusion criteria (n=14), withdrawal informed consent (n=11) and early lost to follow-up (n=10). A total of 199 were available for analysis. Twenty-two (11%) patients died during the follow-up, most of which (95%) occurred within 1 year of PJI diagnosis. In the one-year (12 patients lost to follow-up) and two-year (18 patients lost to follow-up) post-diagnosis analysis, overall treatment failure occurred in 13.3% (n=22/166), and 17% (n=25/147). Knee and hip rate failure in the 1- and 2-year follow up were 12.2% (n=9/74), 15.4% (n=14/91), and 16.2% (n=11/68), 18.2% (n=14/77), respectively. Debridement with implant retention (DAIR), one-stage exchange, two-stage exchange, and arthrodesis was performed in 44.7%, 25.4%, 22.3%, 7.6% respectively. Failure rates for DAIR, one-stage exchange, two-stage exchange, and arthrodesis after 1- and 2-year follow-up were 24.2% (n=16/66), 4.3% (n=2/46), 9.8% (4/41), 0% (n=0/15), and 28.6% (n=16/56), 4.8% (n=2/42), 15.8% (n=6/38), 0% (n=0/15), respectively. Microbial diagnosis yielded positive culture in 71.7%. Staphylococcus aureus (34%), coagulase-negative staphylococci (28%), Pseudomonas aeruginosa (17%) were more prevalent. Polymicrobial PJI were diagnosed in 32.8%. Conclusions. This is so far the largest Brazilian cohort of patients with PJI showing an overall 2-years failure-free survival rate of 83%, in which DAIR is the most frequent and less successful strategy, single-stage exchange seems to be a growing surgical option. Polymicrobial and non-fermenting Gram-negative bacilli and Enterobacteriacae is frequent

Aim. Pre-operative distinction between prosthetic joint infections (PJI) and non-infectious causes of joint failure is particularly challenging, especially in chronic situations. Guidelines propose different algorithms using numerous preoperative tests. We evaluated place of serology. Method. During a 9 month period, we included consecutive patients undergoing arthroplasty revision for a suspected chronic hip or knee infection. Serologies were sampled at the same day than the other blood tests. Results were compared with the final diagnosis, determined with peroperative bacteriological and histological results. Serology was performed using a multiplex antibody detection*. This multiplex antibody detection assay detects antibodies against Staphylococcus species, Propionibacterium acnes and Streptococcus agalactiae. Results. A total of 52 patients were enrolled. Median time from last arthroplasty was 30 months (extremes 8 months − 17 years). Median clinical signs duration was 6 months (extremes 1 – 40 months). Median CRP value was 6 mg/l (extremes 2 – 150) and sedimentation rate 12 mm (extremes 2 – 82). Diagnostic of PJI was finally retained for 17 patients and ruled out for 35. It was Staphylococcus aureus 3 times, coagulase negative staphylococci (CoNS) 5 times, P. acnes 4 times, candida sp. 2 times, Streptococcus agalactiae one time, Enterobacter cloacae one time and undetermined one time. Serology was concordant and accurate with the final diagnosis for 38 patients (27 sterile and 11 infected). For 7 of them, serology was the key parameter. In these cases, a CoNS or a P. acnes was isolated per-operatively on a single culture, out of 5 samples. Serology allowed confirming a contamination in 5 cases; and in 2 cases, even if not fulfilling the definition, it determined a PJI. In this study, serology had a global sensitivity of 65%, 77% specificity, 58% positive predictive value, and 82% negative predictive value. Serology reached 89% sensitivity with unchanged specificity in the subgroup of 11 patients with a CRP > 10 mg/l. Conclusions. We evaluated place of serology in the most complex cases of suspected chronic PJIs, with finally, only 33% cases with an infection. Modest results of serology can be explained because antigens included in the assay were not those expressed in sessile bacteria. And by persistence of a humoral response, witnesses of past infections, for patients who had past surgeries on the joint. However, simple and practical, when combined with all other parameters, serology could provide a valuable support in preoperative evaluation of chronic PJIs. * BJI InoplexTM

Aims. The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm. 3. and ≥ 65% for TKA and ≥ 3,000 cells/mm. 3. and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126

Aim. Unexpected positive infections are distinct entity in prosthetic revision surgery. The prevalence and characteristics of unexpected positive cultures in internal fixation are however less established. The aim of this study was to describe the prevalence and characteristics of unexpected diagnosis of infection in a prospective cohort of revision surgeries following internal fixation. Method. We reviewed the microbiological results following 356 surgeries that included partial or complete removal of internal fixation, performed in 328 patients (54% male, mean age 53 ± 17 years), in which infection was not initially suspected. This prospective study was performed in a large single center for musculoskeletal surgery from 2013–2017. The implants most commonly removed were plate and/or screws (281 cases, 78,9%), followed by intramedullary nails (64 cases, 18,0%). The main indications for surgery were nonunion (89 cases, 25%) and symptomatic hardware (70 cases, 19,7%). All removed implants were sonicated, and tissue cultures were obtained depending on the surgeon's criteria. Diagnosis of infection was established by the presence of 2 or more positive tissue cultures (1 with a highly virulent microorganism), or ≥ 50 colony-forming units found in the sonication fluid. Results. Infection was confirmed in 47 cases (13,2%); diagnosis was obtained with tissue cultures in 5 cases (1,4%), sonication in 14 cases (3,9%) and a combination of both sonication and tissue samples in 28 cases (7,9%). In another 24 cases (6,7%), ≥ 50 CFU of low-virulence microorganisms were isolated in the sonication fluid, but no tissue samples were available to confirm the diagnosis. Low-virulent microorganisms such as Propionibacterium acnes (22 cases / 46,8%) or coagulase-negative Staphycoccci (13 cases, 27,7%) were most commonly isolated. Sonication was key for the diagnosis of 61,7% of unexpected-positive surgeries. Nearly half of the patients received a new implant (internal fixation in 40,4%; arthroplasty in 6,4%), but only 34% of the patients were treated with antibiotics on discharge. Conclusions. Unexpected diagnosis of infection occurs in approximately 13,2% of revision surgeries following internal fixation, most commonly due to low-virulent microorganisms. Sonication was key for the diagnosis of the majority of these infections. The clinical relevance of these infections remains unclear, though the insertion of new implants raises concern. We recommend sonication of all internal fixation devices removed, especially if new implants are inserted in the revision surgery

Introduction. Accurate diagnosis of peri-prosthetic joint infection is critical to allow adequate treatment. Currently, the criteria of the Musculo-Skeletal Infection Society (MSIS) serve as a validated reference tool. More recently, these criteria have been modified for better accuracy. The goal of this study was to compare retrospectively the diagnostic accuracy of these two different tools in cases of known peri-prosthetic hip or knee infection or in aseptic cases and to analyze one additional criterion: presence of an early loosening (prior to 2 years after implantation). Material – Methods. All cases of hip or knee prosthesis exchange operated on at our department during the year 2017 have been selected. There were 130 cases in 127 patients: 67 men and 60 women, with a mean age of 69 years − 69 total hip (THA) and 61 total knee (TKA) arthroplasties. 74 cases were septic and 53 cases were aseptic. All criteria included in both classifications were collected: presence of a fistula, results of bacteriological samples, ESR and CRP levels, analysis of the joint fluid, histological analysis. Additionally, the presence of an early loosening was recorded. The diagnosis accuracy of the classical MSIS classification and of the 2018 modification were assessed and compared with a Chi-square test at a 0.05 level of significance. Results. The conventional MSIS classification correctly discriminated between infected and non-infected cases in 128/130 cases (98%). There were two failures by infected cases: one case was considered infected with no major criteria and only three minor criteria; one case was considered infected with no major criteria and only two minor criteria. There was no failure by non-infected cases. The new MSIS classification correctly discriminated between infected and non-infected cases in 129/130 cases (99%). There was one single failure by infected cases: one case was considered infected despite a score of 4 points. There was no significant difference between the diagnostic accuracy of both classifications. The presence of an early loosening had a high specificity (85%) but a low sensitivity (22%). Discussion. The conventional MSIS classification had a high diagnostic accuracy. The new MSIS classification offered only minor, non significant increase of this accuracy. As the new classification involves several additional biological assays, these results might question the cost-effectiveness of the new classification. The presence of an early loosening might be an interesting additional criterion at no additional cost

Aims. The aims of this study were to increase the diagnostic accuracy of the analysis of synovial fluid in the differentiation of prosthetic joint infection (PJI) by the addition of inexpensive biomarkers such as the levels of C-reactive protein (CRP), adenosine deaminase (ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Patients and Methods. Between January 2013 and December 2015, synovial fluid and removed implants were requested from 143 revision total joint arthroplasties. A total of 55 patients met inclusion criteria of the receipt of sufficient synovial fluid, tissue samples and removed implants for analysis. The diagnosis of PJI followed the definition from a recent International Consensus Meeting to create two groups of patients; septic and aseptic. Using receiver operating characteristic curves we determined the cutoff values and diagnostic accuracy for each marker. Results. There were 23 PJIs and 32 patients with aseptic loosening. The levels of total leucocyte count, proportion of polymorphonuclear leucocytes (PMNs), CRP, ADA and α2M in the synovial fluid were all significantly higher in those with a PJI than in those with aseptic loosening. The levels of procalcitonin were comparable in the two groups. Cutoff values for the optimal performance in the diagnosis of infection were: total leucocyte count > 1463 cells/μL (sensitivity (Sens) 100%, specificity (Spec) 71.9%, positive predictive value (PPV) 71.9%, negative predictive value (NPV) 100%); proportion of PMNs > 81% (Sens 78.3%, Spec 75.0%, PPV 69.2%, NPV 82.8%); CRP > 6.7mg/L (Sens 78.3%, Spec 93.8%, PPV 90.0%, NPV 85.7%); ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%) and α2M > 958 mg/L (Sens 47.8%, Spec 96.9%, PPV 91.7%, NPV 72.1%). The addition of a raised level of CRP or ADA to the total leukocyte count increased the specificity: total leukocyte count > 1463 cells/μL and CRP > 6.7mg/L (Sens 78.3%, Spec 100%, PPV 100%, NPV 86.5%) or with ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%). . Conclusion. The total leucocyte count in the synovial fluid offers great negative predictive value in the diagnosis of PJI and the addition of more specific markers such as CRP and ADA improves the positive predictive value. Thus the addition of simple and inexpensive markers to the measurement of the leucocyte count in the synovial fluid may reduce the number of equivocal results which demand more expensive investigation. Cite this article: Bone Joint J 2017;99-B:351–7

Specific and rapid detection methods for spinal tuberculosis, with sufficient sensitivity in HIV-1 co-infected individuals, are needed, to ensure early initiation of appropriate treatment to prevent physical disability and neurological fallout. In addition, understanding the systemic and local pathophysiology of spinal tuberculosis, and its interaction with HIV-1 infection, is crucial to guide future therapeutic interventions.

We prospectively enrolled adult patients presenting with signs and symptoms of suspected spinal tuberculosis, at Groote Schuur Hospital, between November 2020 and December 2021. TB diagnostic testing was performed on open and CT-guided spinal biopsies using Xpert MTB/RIF Ultra compared to gold standards TB culture and histology. A highly sensitive droplet digital PCR assay for detecting and quantifying Mycobacterium tuberculosis complex (MTBC) and HIV-1 DNA was tested. Plasma inflammatory proteins were measured to assess systemic inflammation.

Xpert Ultra had a high sensitivity of 94.7% and specificity of 100% for STB against TB culture and histology in both open and CT-guided biopsy samples. The ddPCR assay confirmed TB detection in 94% of patients with positive Xpert Ultra results. Four patients with negative TB diagnostic results had MTBC DNA detected by ddPCR. HIV-1 DNA was detected in the spinal tissues from all HIV-1-infected patients. MTBC DNA levels were significantly higher in HIV-1-co-infected spinal tissue samples (p< 0.01). We identified four biomarkers significantly associated with higher bacterial burden at the disease site (p< 0.01).

Xpert Ultra and MTBC ddPCR improve the detection of STB. DdPCR can be utilized as an additional, highly sensitive tool for detecting and quantifying Mtb, in pathological samples that may be paucibacillary. These findings provide novel diagnostic and pathophysiologic insight into STB, in the context of HIV-1 infection, and provide rationale to include these tests in hospital and research settings for patients from communities burdened by TB and HIV-1.

Aim. Metagenomic nanopore sequencing is demonstrating potential as a tool for diagnosis of infections directly from clinical samples. We have previously shown nanopore sequencing can be used to determine the causative bacterial species in prosthetic joint infections (PJI). However, to make predictions regarding antimicrobial resistance, human DNA contamination must be reduced so a greater proportion of sequence data corresponds to the microbial portion of the DNA extract. Here, we utilise selective DNA extraction from sonication fluid samples to begin to make predictions regarding antimicrobial resistance in PJI. Method. We investigated host cell DNA depletion with 5% saponin selective human cell lysis followed by nuclease digestion. Subsequently, bacterial cells were mechanically lysed before DNA extraction. Sequencing libraries from samples treated with and without saponin were prepared with a Rapid PCR Barcoding Kit. 1. and sequenced in multiplexes of 2–8 samples/flowcell on a GridION. Sequencing reads were analysed using the CRuMPIT pipeline and thresholds to indicate presence of a specific bacterial genus/species were investigated. Antimicrobial resistance determinants were detected using previously published sequences specifically for Staphylococcus aureus, as an example organism frequently causing PJI. Results. 247 DNA extracts from 115 sonication fluids plus controls were subjected to metagenomic sequencing, comprising extracts from 67 culture-positive (10 of which were culture-positive at <50 CFU/ml) and 48 culture-negative samples. 5% saponin depleted human DNA contamination, reducing the number of human sequenced bases to a median 12% from 98% in comparison to 5μm filtration without saponin. In 11 samples 5% saponin depleted human bases by <12% in comparison to 5μm filtration, which may be indicative of incomplete depletion. Bacteria observed in sonication fluid culture were identified to species-level in 49/65 (75%) cases, and to genus-level in 51/65 (78%). Specificity of sequencing was 103/114 (90%). Sequencing made a completely successful prediction of antimicrobial susceptibility in 8/19 S. aureus culture-positive samples treated with 5% saponin, and a partial prediction in 5/19 for the 8 antibiotics investigated. Without 5% saponin treatment sequencing could only detect a limited number of AMR determinants in 3/19 samples. Sequencing correctly predicted 13/15 (87%) resistant and 74/74 (100%) susceptible phenotypes where sufficient sequence data were available. Conclusions. Nanopore metagenomic sequencing can provide species identification in PJI. Additionally, depletion of human DNA improves depth of coverage and allows detection of antimicrobial resistance determinants, demonstrating as a proof of principle that nanopore sequencing could potentially provide a complete diagnostic tool in PJI. 1. Oxford Nanopore Technologies

Background. Online video is increasingly becoming a key source for people to satisfy their information needs. YouTube is one of the post popular websites used for information exchange, with more than one billion unique visitors every month. Questions/purposes. In an attempt to participate in personal health decisions related to hip arthritis, patients may access YouTube for further information. As YouTube is a non peer-reviewed platform and little is known about the quality of available videos. We therefore asked the following research questions: (1) What is the information quality of YouTube videos related to the diagnosis of hip arthritis and (2) what information for the treatment of hip arthritis can be found on YouTube?. Methods. YouTube search was performed on December 23, 2014 for videos related to the diagnosis and the treatment of hip arthritis. The following search terms were used: (1) hip arthritis, (2) hip arthritis symptoms, (3) hip arthritis diagnosis, (4) hip arthritis treatment and (5) hip replacement. After exclusion of videos that did not meet the inclusion criteria, 133 videos were analyzed. In order to qualitatively assess the YouTube video content for to the diagnosis and the treatment of hip arthritis, two new grading systems with a scale of 0 to 12 points were developed. Videos were grouped into poor quality (grade 0–3), moderate quality (grade 4–7) and excellent quality (grade 8–12), respectively. Videos were categorized into the following: educational-physician, educational- non physician, commercial, technique, personal testimony or other. Results. The vast majority of YouTube videos lack essential information for an appropriate diagnosis of hip arthritis. Eighty-four percent (n=112) were graded as being of poor quality, 14 percent (n=19) of moderate quality and only 2 percent (n=2) of excellent quality, respectively. The information quality of educational-physician videos for the diagnosis of hip arthritis was significantly higher (p < 0.001) than for educational-non physician videos. YouTube is a poor information source for the treatment of hip arthritis. In 86 percent (n=114), videos provided poor information quality. Eleven percent (n=15) of videos had a moderate quality and only 3 percent (n=4) an excellent quality, respectively. The quality of information for the treatment of hip arthritis was significantly higher (p = 0.005) than the quality of information for the diagnosis of hip arthritis. Conclusions. The present review of YouTube video material demonstrates that hip arthritis diagnosis and treatment information is overall insufficient. The exchange of video-based information is going to grow rapidly within the next years and videos going to become the primary source of information. The medical community should take chance of the opportunity the define gold standards for comprehensive and innovative evidence-based educational videos addressing the diagnosis and treatment of hip arthritis

Introduction:. The diagnosis of implant-associated infections is challenging, and the conventional culturing of periprosthetic tissue has been the gold standard for diagnosis of implant-associated infections. However, conventional diagnostic tests are inaccurate because the pathogenesis of implant-associated infection is related to microorganisms growing in biofilms. We compared culture of samples obtained by sonication of explanted implants to dislodge adherent bacteria from implants with conventional culture of periprosthetic tissue. The purpose of this study is to evaluate the results of sonication that is microbiological diagnostic method for implant-associated infections. Materials and Methods:. Between January 2013 and April 2013, a total of 19 consecutive patients underwent the removal of implants at our institution. There were 15 women and 4 men with a mean age of 71 years (32 to 90) at the time of the operation. Implants were removed because of aseptic loosening in 9 patients, infection in 6 patients, necrosis in 2 patients, dislocation in 1 patient and implant fracture in 1 patient. Removed implants, including 17 joint prostheses and 2 fracture fixation devices, were subjected to sonication in a BactoSonic (BANDELIN, Germany). Preoperative bacterial culture, intraoperative conventional culture of periprosthetic tissue, intraoperative culture of sonicate-fluid, and pathological examination were assessed. Results:. Of the 9 patients with aseptic loosening, 1 patient was positive for intraoperative conventional culture of periprosthetic tissue, and 2 patients were positive for intraoperative culture of sonicate-fluid. In the patient with negative culture of periprosthetic tissue and positive culture of sonicate-fluid, pathological findings indicated the presence of neutrophils in tissue specimen. Of the 6 patients with infection, 4 patients were positive for intraoperative conventional culture of periprosthetic tissue, and 3 patients were positive for intraoperative culture of sonicate-fluid. Of the 4 patients with necrosis, dislocation, and implant fracture, no patients were positive for intraoperative conventional culture of periprosthetic tissue or intraoperative culture of sonicate-fluid. Conclusion:. Culture of sonicate-fluid has been shown to improve the diagnosis of implant-associated infections. In the future, it may be common technique for diagnosis of implant-associated infections associated with biofilm, but this new technique needs further study

Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease. However, the Periprosthetic Joint Infection (PJI) remains one of the biggest challenges facing orthopaedics today. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. The most common symptom of PJI is pain. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

Aim: To determine the accuracy of clinical diagnosis in patients undergoing arthroscopic surgery of the knee. Methods: A retrospective analysis of patients who had undergone knee arthroscopy at the Norfolk and Norwich University Hospital was performed from a prospectively gathered database. Pre-operative diagnosis was compared with operative diagnosis to determine the accuracy, sensitivity and specificity of the clinical diagnosis. The data was then analysed to determine how many patients underwent a beneficial procedure, which was defined as “a procedure from which the patient is likely to have benefited, either as a result of confirming the diagnosis or therapeutic intervention”. Finally, the results were compared with those from studies where the accuracy of MRI was assessed, to determine whether MRI is a more accurate diagnostic modality than clinical examination. Results: The data of 698 patients was analysed. Of these 64% were male and 36% were female. The mean age at operation was 41 years (9 to 92). The overall accuracy, sensitivity and specificity of clinical diagnosis was 99%, 70% and 99% respectively. 90% of patients underwent a beneficial procedure, while 10% had a normal knee diagnosed at operation. Medial meniscal tear was the hardest pathology to diagnose, with accuracy, sensitivity and specificity rates of 82%, 92% and 79%. The results fell within the range of those found in studies, which examined the accuracy, sensitivity and specificity of MRI. Conclusion: Our results show that clinical examination remains an accurate method of diagnosing intra-articular pathologies of the knee. Medial meniscal tear appears to be the hardest pathology to diagnose, and was the only condition with an accuracy rate under the 90th percentile. This is probably because medial tibio-femoral articular dysfunction has similar clinical findings. MRI was found to be no more effective than clinical examination at diagnosing pathologies of the knee

Aim. Diagnosis of periprosthetic joint infection (PJI) is challenging given the limitations of available diagnostic tests. Recently, several studies have shown a role of the long pentraxin PTX3 as a biomarker in inflammatory diseases and infections. This single-center prospective diagnostic study evaluated the diagnostic ability of synovial fluid and serum PTX3 for the infection of total hip arthroplasty (THA) and total knee arthroplasty (TKA). Method. Consecutive patients undergoing revision surgery for painful THA or TKA were enrolled. Patients with antibiotic therapy suspended for less than 2 weeks prior to surgery and patients eligible for metal-on-metal implant revision or spacer removal and prosthesis re-implantation were excluded. Quantitative assessment of synovial fluid and serum PTX3 was performed with ELISA method. Musculoskeletal Infection Society (MSIS) criteria were used as reference standard for diagnosis of PJI. Continuous data values were compared for statistical significance with univariate unpaired, 2-tailed Student's t-tests. Receiver operating characteristic (ROC) curve analyses was performed to assess the ability of serum and synovial fluid PTX3 concentration to determine the presence of PJI. Youden's J statistic was used to determine optimum threshold values for the diagnosis of infection. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative (LR-) likelihood ratio, area under the ROC curve (AUC) were calculated. Results. One-hundred fifteen patients (M:F=49:66) with a mean age of 62 years (40–79) underwent revision of THA (n=99) or TKA (n=16). According with MSIS criteria, 18 cases were categorized as septic and 97 as aseptic revisions. The average synovial fluid concentration of PTX3 was significantly higher in patients with PJI compared to patients undergoing aseptic revision (24,3 ng/dL vs 3,64 ng/dL; P=0.002). There was no significant difference in terms of serum concentration of PTX3 between the two groups. Synovial fluid PTX3 demonstrated an AUC of 0.96 (95%IC 0.89–0.98) with Se 94%, Sp 90%, PPV 67%, NPV 100%, LR+ 9.4 and LR- 0.06 for a threshold value of 4.5 ng/dL. Serum PTX3 demonstrated an AUC of 0.70 (95%IC 0.51–0.87) with Se 72%, Sp 67%, PPV 30%, NPV 93%, LR+ 2.2 and LR- 0.42 for a threshold value of 4.5 ng/dL. Conclusions. In patients undergoing revision surgery for painful THA or TKA, synovial PTX3 demonstrated a strong diagnostic ability for PJI. Synovial PTX3 could represent a more useful biomarker for detection of PJI compared with serum PTX3

Introduction. Next generation sequencing (NGS) has been shown to facilitate detection of microbes in a clinical sample, particularly in the setting of culture-negative periprosthetic joint infection (PJI). However, it is unknown whether every microbial DNA signal detected by NGS is clinically relevant. This multi-institutional study was conceived to 1) identify species detected by NGS that may predict PJI, then 2) build a predictive model for PJI in a developmental cohort; and 3) validate the predictive utility of the model in a separate multi-institutional cohort. Methods. This multicenter investigation involving 15 academic institutions prospectively collected samples from 194 revision total knee arthroplasties (TKA) and 184 revision hip arthroplasties (THA) between 2017–2019. Patients undergoing reimplantation or spacer exchange procedures were excluded. Synovial fluid, deep tissue and swabs were obtained at the time of surgery and shipped to MicrogenDx (Lubbock, TX) for NGS analysis. Deep tissue specimens were also sent to the institutional labs for culture. All patients were classified per the 2018 Consensus definition of PJI. Microbial DNA analysis of community similarities (ANCOM) was used to identify 17 candidate bacterial species out of 294 (W-value >50) for differentiating infected vs. noninfected cases. Logistic Regression with LASSO model selection and random forest algorithms were then used to build a model for predicting PJI. For this analysis, ICM classification was the response variable (gold standard) and the species identified through ANCOM were the predictor variables. Recruited cases were randomly split in half, with one half designated as the training set, and the other half as the validation set. Using the training set, a model for PJI diagnosis was generated. The optimal resulting model was then tested for prediction ability with the validation set. The entire model-building procedure and validation was iterated 1000 times. From the model set, distributions of overall assignment rate, specificity, sensitivity, positive predictive value (PPV) and negative predicative value (NPV) were assessed. Results. The overall predictive accuracy achieved in the model was 75.9% (Figure 1). There was a high accuracy in true-negative and false-negative classification of patients using this predictive model (Figure 2), which has previously been a criticism of NGS interpretation and reporting. Specificity was 97.1%, PPV was 75.0%, and NPV was 76.2%. On comparison of the distribution of abundances between ICM-positive and ICM-negative patients, Staphylococcus aureus was the strongest contributor (F=0.99) to the predictive power of the model (Figure 3). In contrast, Cutibacterium acnes was less predictive (F=0.309) and noted to be abundant across both infected and noninfected revision TJA samples. Discussion. This study is the first to utilize predictive modeling algorithms on a large prospective multicenter database in order to transform analytic NGS data into a clinically relevant diagnostic signal. Our collaborative findings suggest the microbial DNA signal identified on NGS may be an independent useful adjunct for the diagnosis of PJI, as well as help identify causative organisms. Further work applying artificial intelligence tools will improve accuracy, predictive power and clinical utility of high-throughput sequencing technology. For figures, tables, or references, please contact authors directly

Aims. The purpose of this study was to validate the diagnosis of periprosthetic joint infection (PJI) in the Danish Hip Arthroplasty Register (DHR). Patients and Methods. We identified a cohort of patients from the DHR who had undergone primary total hip arthroplasty (THA) since 1 January 2005 and followed them until first-time revision, death, emigration or until 31 December 2012. Revision for PJI, as registered in the DHR, was validated against a benchmark which included information from microbiology databases, prescription registers, clinical biochemistry registers and clinical records. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for PJI in the DHR alone and in the DHR when combined with microbiology databases. Results. In total, 1382 of the 37 826 primary THAs in the DHR were registered as having been revised for any cause once 26 patients with errors in registration had been excluded: 232 of these were for PJI. For this group, the sensitivity was 67%, specificity 95%, PPV 77%, and NPV 92%. Combining the data from the DHR with those from microbiology databases increased the sensitivity to 90% and also improved specificity (100%), PPV (98%) and NPV (98%). Conclusion. Only two thirds of revisions for PJI were captured in the DHR and only 77% of the PJI reported to the DHR could be confirmed to be infected. . Take home message: combining the data from the DHR with those from microbiology databases substantially improved the validity of the diagnosis of PJI and should enable future register-based studies. Cite this article: Bone Joint J 2016;98-B:320–5

This is the first study in the Ponseti-era to compare severity and outcomes in cases of idiopathic congenital talipes equinovarus (CTEV) diagnosed antenatally versus those diagnosed at birth. Small pre-Ponseti studies showed antenatal diagnosis to be a predictor of severity and poor prognosis. Prospective data collection was used to compare indicators of severity and outcomes for idiopathic CTEV between these two groups. These include Pirani score, number of casts, follow-up Roye score and need for surgery. 68 children with 106 affected feet were included. Antenatal diagnosis (AD) was made in 45 children (71 feet), with birth diagnosis (BD) in 23 children (35 feet). Mean follow-up age was 4.8 years (AD = 4.9, BD = 4.7), male:female ratio 2:1 (AD=BD) with bilateral CTEV in 55% (AD = 58%, BD=52%). Mean initial Pirani scores were 5.25 in the AD group vs 4.86 in the BD group (p=0.06). Mean Roye score at follow-up was 1.39/4 in the AD group vs 1.26/4 in the BD group (p=0.33) with 33% vs 30% complaining of pain respectively (p=0.80). Surgery was needed in 11/71 (15.5%) in the AD group vs 1/35 (2.9%) in the BD group (p=0.06)). There is no significant difference in severity between antenatal and birth diagnoses of idiopathic CTEV and no difference in outcomes between these groups when treated with the Ponseti regime. Although small, our sample size is greater than the largest published comparable study

Introduction. Periprosthetic joint infection (PJI) is considered one of the most feared causes of implant failure, due to the difficulty in formulating a proper and timely diagnosis. In the diagnostic workup are often used test with a low specificity, such as the dosage of ESR and CRP, or sensitivity, such as cultures or the leukocyte count of the synovial fluid. Radiological investigations are expensive and unreliable to play a direct role in the diagnosis of PJI. The alpha-defensin is an antimicrobial peptide released by neutrophils in response to pathogens and it is an ideal biomarker for the diagnosis of PJI. It is now possible to verify the presence of alpha-defensin in periprosthetic synovial fluid with an ELISA (Synovasure® PJI, Zimmer) that provides results in 10 minutes, with a sensitivity of 97% and a specificity of 96%, without being affected by systemic inflammatory diseases or by the assumption of antibiotics. The purpose of this study is to assess the applicability and reliability of Synovasure® PJI, correlating its results with microbiological analyzes, laboratory tests and imaging studies of the patient. Materials and Methods. Patients recruited are those who have undergone a previous total hip or knee arthroplasty where there is suspicion of PJI. The test can be performed either during surgery or during the diagnostic iter, through the execution of an arthrocentesis. The synovial fluid is partly used for Synovasure® PJI and partly put in culture for microbiological analyzes. Once ready, culture results are compared with the results of the test to get a confirmation of its reliability or reference to identify the microorganism responsible for PJI. These data are then compared, with laboratory tests and radiological investigations performed by the patient. Results. Up to now we have full results in 10 patients (11 implants). In four cases, the test showed the presence of alpha-defensin in the synovial fluid, while in seven cases the test result were negative. In case of negative test culture of synovial fluid showed no growth of microorganisms that could indicate the presence of false negatives. All patients with positive test have arthrocentesis positive for pathogenic microorganisms. We are waiting for culture results of two other patients (one with positive test and one with negative test). In the next few months will be tested other patients with suspicion of PJI. Discussion. Timeliness and accuracy in the diagnosis are essential for the proper management of the patient with suspected PJI. Diagnostic tools currently available are often sensitive but not very specific or conversely, specific but insensitive. New synovial markers such as alpha-defensin and rapid ELISA tests for their dosage open new horizons in the diagnosis of periprosthetic infections. Conclusions. Synovasure® PJI is a practical and reliable tool in the diagnosis of periprosthetic joint infections. Thanks to the quick response and the ease of execution the test can be used both during the diagnostic iter and during the revision surgery helping the orthopedic to apply the most appropriate measures to each case

Literature debates whether fluid aspirates for suspected PJI should undergo prolonged incubation for cultures. We looked at sensitivity and specificity of 14-day cultures, compared to 7-days, for aspirates from prosthetic hips and knees. Design and methods. Conducted at a quaternary referral centre for PJIs from Jan 2017 to July 2019. Suspected PJIs who underwent aspiration, incubated 14 days and later surgical intervention with minimum three tissue samples were included. Results. 176 aspirates were included. This is an increased number compared to our historic figures (average 88 Vs 48 pts/yr). 47 patients had fluid and tissue positive (true positive), 20 fluid +ive but tissue -ive (false positive), 98 fluid and tissue -ive (true negative) and 15 fluid negative but tissue +ive (False negative). Thus, sensitivity 76%, specificity 83%, positive predictive value70% and negative predictive value 87%. Of 88 positive aspirates, only 75% were within 7-day cultures. Low virulence organisms as Propionibacterium acnes and coagulase negative staph were grown later. Of 48 with only one tissue sample positive, 38 were culture-negative on aspiration and 6 grew different organisms on aspirate and tissues. Also, as many were cultured later, it suggests contamination. Conclusion. Increased numbers reflect quaternary referral nature of institution and increasing PJI load. Modest drop in sensitivity and specificity of 14-day cultures compared to 7-day(84 and 85% respectively) is due to higher false negatives. Contamination contributes to false-ive as more tissue samples become positive (there were 1076 tissue samples due to multiple sampling Vs 176 aspirates). Higher tissue yield may also be because they are more representative. Effect of antibiotic use between samples cannot be determined. Organism profile suggest14-day culture produces more contaminant growth despite a well-equipped microbiology lab with laminar airflow for subcultures. Caution in interpreting 14-day results in diagnosis of PJI of Hip and Knee is advised

INTRODUCTION. Joint replacement is one of the most common orthopaedic procedures, with over 2 million surgeries performed each year across the globe. Loss of implant fixation, or aseptic loosening, is the leading cause of revision following primary joint replacement, accounting for ∼25% of all revision cases [1]. However, diagnosis of aseptic loosening and its underlying causes remain challenging due to the low sensitivity and specificity of plain radiographs. To address this, we propose a novel approach inspired by [2] involving the use of a self-sensing bone cement (by imparting strain-dependent electrical conductivity or piezoresistivity) combined with electrical impedance tomography (EIT). Piezoresistivity is imparted to cement via incorporation of micro/nanoscale conductive fillers. Therefore mechanical effects such as loosening and cracks will manifest as a conductivity change of the cement. This work explores if EIT is able to detect strains and cracks within the bone cement volume. METHODS. Experiments were designed to determine whether EIT combined with piezoresistive cement can be used to detect strains and cracks (Fig. 1). The setup consists of a tank filled with water, 16 electrodes, sample, a loading machine (MTS), and an EIT system. To develop the piezoresistive bone cement, microscale carbon fibers were used with varying CF/PMMA volumetric ratios (VR) from VR = 0.25% to 3.0%. Three conical samples were made to model a loading condition similar to knee implants (Fig. 1). The samples were compressed while the conductivity map of the tank was measured with the EIT system. RESULTS. Figure 2 shows the conductivity of the piezoresistive bone cement with respect to the CF/PMMA VR, the percolation happens at VR = 1.0% and the maximum gradient occurs at VR = 1.5%. Three conical samples were built and experimented to examine the hypothesis. The samples were loaded from F = 0 to F = 4000 N for the strain measurement and then loaded until the first crack initiates. Figure 3 (a) and (b) show the conductivity difference map measured by EIT for strain measurement and crack detection respectively. It can be seen in Fig. 3(a) that due to the shear stresses within the bone cement the conductivity of the sample decreases under compression. At the crack initiation the conductivity of the samples increases significantly (Fig. 3(b)). Figure 3(c) shows evolution of sample conductivity difference measured by EIT as a function of the applied load, VR = 1.5% shows the largest sensitivity. DISCUSSION. The results validate our hypothesis; both cracks and strains resulted in electrical conductivity changes measurable by EIT. While these initial results are encouraging, the approach must be validated via testing of surrogate and cadaver bones in an EIT phantom. If successful, this approach could for the first time provide means of in-vivo studying of aseptic loosening, leading to a paradigm shift in the understanding of this important clinical problem. For any figures or tables, please contact the authors directly