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%

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

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

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

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. 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%)

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.