Aims. Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays. Patients and Methods. This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records. Results. A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). ‘Typical’ symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days versus 36 days, p = 0.016). Conclusion. Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article: Bone Joint J 2018;100-B:119–24

Aims. This study aimed to assess the performance of an automated multiplex polymerase chain reaction (mPCR) technique for rapid diagnosis of native joint septic arthritis. Patients and Methods. Consecutive patients with suspected septic arthritis undergoing aseptic diagnostic joint aspiration were included. The aspirate was used for analysis by mPCR and conventional microbiological analysis. A joint was classed as septic according to modified Newman criteria. Based on receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) values of the mPCR and the synovial fluid culture were compared using the z-test. A total of 72 out of 76 consecutive patients (33 women, 39 men; mean age 64 years (22 to 92)) with suspected septic arthritis were included in this study. Results. Of 72 patients, 42 (58%) were deemed to have septic joints. The sensitivity of mPCR and synovial fluid culture was 38% and 29%, respectively. No significant differences were found between the AUCs of both techniques (p = 0.138). A strong concordance of 89% (Cohen’s kappa: 0.65) was shown. The mPCR failed to detect Staphylococcus aureus (n = 1) and Streptococcus pneumoniae (n = 1; no primer included in the mPCR), whereas the synovial fluid culture missed six microorganisms (positive mPCR: S. aureus (n = 2), Cutibacterium acnes (n = 3), coagulase-negative staphylococci (n = 2)). Conclusion. The automated mPCR showed at least a similar performance to the synovial fluid culture (the current benchmark) in diagnosing septic arthritis, having the great advantage of a shorter turnaround time (within five hours). Cite this article: Bone Joint J 2019;101-B:288–296

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

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

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

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. Periprosthetic joint infection (PJI) is one of the most frequent and devastating complications of total knee arthroplasty (TKA). Accurate diagnosis and proper treatment are essential to prevent functional loss and progression to systemic infection. However, the correct diagnosis of PJI is still a challenge since there is no accurate diagnostic method and the existing diagnostic criteria are based on serological, histological and microbiological tests that are imprecise and time-consuming. Recently, it was demonstrated that cell-free DNA is increased in the synovial fluid of patients with PJI. Therefore, this study aims to evaluate a new point-of-care methodology for quantifying free DNA in synovial fluid. Method. A prospective study was carried out with patients undergoing TKA revision surgery, from whom it was possible to collect synovial fluid (SF) during the surgical procedure. Cell-free DNA quantification was performed directly from the SF, using a portable fluorimeter. Sensitivity, specificity and receiver operating characteristic (ROC) curve were calculated. Results. Fifty-four patients were included in the study, of which 25 were diagnosed with PJI. Cell-free DNA levels measured immediately after collection were increased in the synovial fluid of patients with PJI (26.3 ± 14.8) in comparison with the uninfected group (4.6 ng/ml ± 3.8, p< 0.0001). The area under the receiver operating characteristic curve (AUC ROC) was 0.981 (95% CI 0.914 to 0.999). Conclusions. From the results presented, we can conclude that the quantification of free DNA with a portable fluorimeter proved to be a test with high sensitivity and specificity for the diagnosis of PJI

Aim. Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. Diagnosing PJI can be challenging as preoperative screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique to improve microbiological PJI diagnosis. This study aims to determine the clinical relevance of routinely using sonication for all septic and aseptic revisions. Method. All patients who underwent (partial) hip or knee revision arthroplasty for all causes between 2012 and 2021 at our institution were retrospectively reviewed. Based on the European Bone and Joint Society PJI criteria, we categorized them into three groups: infection confirmed, infection likely, and infection unlikely. We analyzed the clinical, laboratory, and radiological screening that could confirm or refute suspicion of PJI. We analyzed microbiology cultures and the most frequently detected microorganisms. Sensitivity and specificity were calculated for synovial fluid cultures (preoperative), tissue cultures, and sonication fluid cultures. We determined the clinical relevance of sonication as the percentage of patients for whom sonication confirmed (microbiological) PJI diagnosis. Results. 429 patients who underwent (partial) revision of hip (246 patients) or knee (183 patients) arthroplasty were included. Sensitivity and specificity were 69% and 99% for preoperative synovial fluid cultures, 76% and 92% for intraoperative tissue cultures, and 80% and 89% for sonication fluid cultures, respectively. Sonication fluid cultures improved tissue culture sensitivity and specificity to 83% and 99%, respectively. In 12 (11%) out of 110 PJIs, sonication fluid cultures were decisive for confirming the causative pathogen. This was applicable to acute and chronic infections. In 29 (9%) out of 319 aseptic cases, a negative sonication fluid culture could confirm contamination of tissue cultures. Conclusions. Routine sonication fluid cultures enhanced the sensitivity and specificity of PJI diagnostics. In 11% of PJI cases, causative pathogens were confirmed by sonication fluid culture results. Routine sonication may be helpful in confirming contamination of synovial fluid cultures and tissue cultures. Routine sonication fluid culture should be performed in all revision arthroplasties

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

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. Prosthetic joint infection (PJI) is assessed using clinical history and examination, imaging studies and laboratory investigations which inform diagnostic tools such as that proposed by the European Bone and Joint Infection Society to determine the probability of infection. Infection is often confirmed by microbiology culture and histology from intraoperative samples, but ideally a diagnosis of infection is made preoperatively to guide management decisions. At our institution, a tertiary referral centre for PJI, ultrasound (US)-guided synovial biopsy is routinely used as an adjunct to preoperative joint aspiration. Our aim was to evaluate the sensitivity and specificity of microbiology and histology results from US-guided synovial biopsy samples when compared to intraoperative samples. Method. In this retrospective study we analysed all prosthetic hip and knee US-guided biopsies performed at our institution over a 5 year period between 2018 and 2022. Microbiology and histology results from preoperative biopsy samples were individually compared to microbiology and histology findings from intraoperative samples. Results. 381 biopsies were performed; 281 knee, 100 hip. US-guided biopsy results showed strong positive predictive values (PPVs) in hip biopsies (microbiology PPV (79.3%), histology PPV (85.7%)) and knee biopsies (microbiology PPV (77%), histology PPV (85%)). Biopsies showed low sensitivity in predicting intraoperative findings (hip microbiology sensitivity (62%), hip histology sensitivity (31%), knee microbiology sensitivity (70%), knee histology sensitivity (21%). Biopsies showed high specificity for knee (microbiology specificity (89%), histology specificity (97%)) and hip (microbiology specificity (73%), histology specificity (91%)). Conclusions. This study demonstrates that US-guided biopsy is a valuable diagnostic aid for PJI with high specificities and PPVs. Furthermore US-biopsy is valuable when there is limited fluid for aspiration

Aim. Evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties. Method. The synovial fluids from 21 patients scheduled for revision total knee arthroplasty (11 with the diagnosis of PJI and 10 with aseptic failures) were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyses were used to identify metabolites that were differentially abundant between those groups. Results. A total of 28 metabolites were identified and five of them found to be differentially abundant between infected and non-infected synovial fluids. Lactate, acetate and 3-hydroxybutyrate were found to be in a higher concentration, and glucose and creatine were found reduced in the synovial fluid from PJI patients. Conclusions. Synovial fluid from patients with PJI exhibit a distinct metabolic profile, possibly reflecting metabolic adaptation that occurs in the infected periprosthetic microenvironment. Further research and studies are warranted to gain a broader insight into the metabolic pathways engaged by both pathogen and immune cells in the context of a PJI

Aim. Accurate diagnosis is key in correctly managing prosthetic joint infection(PJI). Shoulder PJI definition and diagnosis is challenging. Current PJI definitions, based overwhelmingly in hip/knee research, may not accurately diagnose shoulder PJI. Our aim is to compare the preoperative performance of two PJI definitions comparing it to definitive postoperative classification. Method. This is a retrospective study of patients who have undergone total shoulder revision surgery for infection between 2005 and 2022. Cases were classified using two different PJI definitions: a)the European Bone and Joint Infection Society (EBJIS) and; 2)the 2018 International Consensus Meeting(ICM) PJI specific shoulder definition. Preoperative classification was based on clinical features, inflammatory markers and synovial fluid leukocyte count and definitive classification also considered microbiology and histology results. Results. Preoperative and definitive PJI classification status of the 21 patients included were evaluated and is summarized in table 1. The shoulder specific 2018 ICM definition showed the highest agreement between preoperative and definitive classification (76.2%, k=0.153, p=0.006) compared to EBJIS (52.4%, k=0.205, p=0.006). In all cases, the classification was changed because of positive intraoperative microbiology (at least two identical isolates). Microbiology findings showed coagulase negative staphylococci, Staphyloccocus aureus and Cutibacterium acnes to be the most frequent. Four patients had polymicrobial infections. Conclusions. Both the EBJIS 2021 and 2018 ICM definitions have low accuracy in predicting shoulder PJI preoperatively. Clearly further studies with larger cohorts are in dire need focusing specifically on shoulder revision arthroplasty to improve on existing definitions. Caution is advised while extrapolating of criteria/thresholds recommended for hip/knee joints. For any tables or figures, please contact the authors directly

Aim. Periprosthetic joint infection (PJI) is one of the main reasons for revision surgery after primary unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or total hip arthroplasty (THA). Currently the MSIS and EBJIS criteria sets are considered to be the gold standards in determining PJI. These criteria sets are complex and contain tests that are time-consuming and many are rather costly. Therefore, further research is indicated to find a simpler but equally reliable diagnostic test. In this study we evaluated the additional value of calprotectine measurement in synovial fluid in patients undergoing hip and knee (revision) arthroplasty following routine work-up. Method. In a retrospective cohort study, we analyzed 182 synovial fluid samples from 143 patients with suspected PJI after UKA, TKA, THA or revision arthroplasty. Twenty-six of those cases were classified as PJI according to the MSIS and EBJIS criteria. Subsequently, synovial calprotectin was determined, using a lateral flow assay and two cut-off thresholds of ≥14 mg/L and ≥50 mg/L. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of synovial calprotectin was determined. Results. When applying the MSIS and EBJIS criteria and a calprotectin level ≥14 mg/L, synovial calprotectin revealed an area under the curve of 0.96 (95% CI 0.90-1.00), with 92.3% sensitivity and 100% specificity. The PPV and NPV were 100% and 92.9% respectively. When applying the MSIS and EBJIS criteria and a calprotectin level ≥ 50 mg/L, synovial calprotectin revealed an area under the curve of 0.94 (95% CI 0.87-1.00), with 88.5% sensitivity and 100% specificity. The PPV and NPV were 100% and 89.7% respectively. Conclusions. The value of calprotectin in synovial fluid gives valuable information with a single test result, resulting in high predictive value in the diagnosis of PJI after hip or knee arthroplasty and should seriously be considered as part of PJI diagnostics in an outpatient clinical setting. The high specificity can help rule in patients that are suspected of PJI. Therefor this test can be helpful in a preop diagnostic work-up to avoid unnecessary revisions in patients with well-placed and well-fixed arthroplasties with a suspected PJI. These conclusions are independent of which criteria set was used as a gold standard

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

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