Aim. Haematogenous prosthetic joint infections account for 20-35% of total prosthetic infections. Debridement, antibiotics and implant retention (DAIR) is a well-accepted treatment for these infections and probably the most desired by surgeons, since it tries to maintain a functional and stable implant. However, the risk of DAIR failure is not negligible and some risk factors have been described, and also, different scores, such as CRIME80. Nonetheless, less is known about the impact of positive blood cultures may have on DAIR treatment. The aim of our study is to analyze whether the presence of a positive culture is a risk factor for DAIR failure. Method. A retrospective cohort study of 50 late acute haematogenous TKA infections was performed from 2015 to 2023. DAIR failure was defined as the need of a subsequent intervention either a new DAIR or a revision surgery. So, patients were divided into two groups depending on the surgical outcome: successful (SG) vs failure (FG). Demographic variables including age, gender, affected side and body mass index were collected. Patient's comorbidities were also collected including chronic obstructive pulmonary disease (COPD), diabetes, rheumatoid arthritis (RA), cirrhosis and chronic renal failure, etc. Other variables, such as ones included in CRIME80 (C-reactive protein (CRP) >150mg/dl and polyethylene exchange), were also collected. Results. 30 patients had a successful DAIR outcome (60%). Age and sex do not act as risk factors [OR 0.7 (0.2-2.6) and OR 0.4 (0.1-1.3)]. Neither do COPD [OR 3.3 (0.5-2.0), p=0.2]; RA [OR 0.8 (0.2-3.1), p=0.7]; CRP value [3.2 (0.9-11.2), p=0.06]; and polyethylene exchange [OR 0.4 (0.1-2.5), p= 0.3]. Thirty-five blood cultures (70%) were obtained before surgery (20 SG and 15 FG). Nine of the obtained blood cultures were positive (25.7%), being 7 from FG (46.7%) [OR 7.6 (1.3-4.8), p=0.02]. A logistic regression was performed where positive blood cultures were the only significant variable to predict DAIR failure (OR 12, 95% CI 1.1−18, p=0.049), after adjusting for all CRIME80 variables. Skin and soft tissue origin was described in 5 of the nine positive blood cultures (55.6%). Cardiovascular system was the second most common spread (22.2%), and then followed by urogenital and digestive tract. The most common microorganism in FG was Staphylococcus aureus (57.1%) [OR 6.4 (0.2-18.0), p=0.2]. Conclusions. Positive blood cultures may be another risk factor for DAIR failure. This can be important in diagnosis and it may be taken into account in antibiotic and surgical treatment strategies

Aim. Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections. Considernig that each gram of fosfomycin contains 330 mg of sodium, electrolytic imbalance due to sodium overload could pose safety issues, especially in the cardiopatic patients and/or in the frail elderly. The aim of this study was to compare the efficacy of using reduced vs. standard daily dose fosfomycin in combination with daptomycin in a cohort of patients with osteoarticular infections. Method. This analysis included adult patients with osteoarticular infections admitted to the Infectious Diseases Unit of our University hospital in the period Nov 2022 – Feb 2024 and who were treated with daptomycin (8-10 mg/kg/daily) plus 24h-continuous infusion (CI) fosfomycin at the standard-dose of 16 g daily (standard-dose group) or at the reduced-dose of 8-12 g daily (reduced-dose group). All the patients underwent therapeutic drug monitoring (TDM) of fosfomycin for granting a pharmacodynamic target attainment of 24h-area under the concentration-time curve over minimum inhibitory concentration (AUC24h/MIC) >95 against Staphylococcus aureus with an MIC value up to 32 mg/L and of 70%t>MIC. Estimated glomerular filtration rate (eGFR) was assessed at each TDM session. Patient clinical outcome was assessed. Results. The standard- and the reduced-dose groups included 43 (29 males, 67.4%) and 21 (11 males, 52.4%) patients, respectively. No differences in median age (54 vs. 63 years, p=36), weight (80 vs. 76 kg, p=0.13) and type of diagnosis [prosthetic joint infections (16 vs. 29, p=0.38), osteomyelitis (2 vs. 9, p=0.72), septic arthritis (3 vs. 3, p=0.39) and spondilodiscitis (0 vs. 2, p=1.0)] were observed between the two groups. Median eGFR was similar in the standard vs. the reduced-dose group (109 vs. 98 mL/min/1.73m2, p=0.004). In the reduced-dose group, CI fosfomycin was administerd at 8 and 12 g/daily in 12 and 9 patients, respectively. There was no difference between the standard- and reduced-dose groups in attainment of the pharmacodynamic targets of AUC24h/MIC>95 (41/43 vs. 20/21, p=1.0), of 70%t>MIC (43/43 vs. 21/21 p=1.0) and of clinical cure (39/43 vs. 19/21, p=1.0). Conclusions. Combination therapy of 8-10 mg/kg/daily daptomycin plus 8-12 g/daily CI fosfomycin may be as effective as that of 8-10 mg/kg/daily daptomycin plus 16 g/daily CI fosfomycin. The fosfomycin reduced-dose strategy allows to decrease the daily sodium load by 25-50% compared to the standard dose, thus reducing the risk of cardiac adverse events. TDM may be a valuable strategy for individualizing fosfomycin dose in patients with osteoarticular infections

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. The aim of this study was to develop an in-house multiplex PCR real-time assay on the LightCycler 480 system (Roche, Basel, Switzerland) with the aim of rapid detection of common pathogens in prosthetic joint infections (PJI), followed by validation on clinical samples (sonication fluid and tissue biopsies) routinely collected for PJI diagnosis. Methods. Using the PrimerQuest and CLC WorkBench tool, we designed six primer sets with specific fluorescently labelled TaqMan probes for the nuc gene in different Staphylococcus species (S. aureus, S. epidermidis, S. capitis, S. lugdunensis, S. hominis, S. haemolyticus). In addition, primers previously developed by Renz et al. (2022) for C. acnes were integrated into our assay with internal control of isolation, leading to the development of specific mPCR assay with seven included targets. Analytical sensitivity and specificity were evaluated using reference bacterial strains. To determine the assay's limit of detection (LOD), we conducted serial dilutions of eluates containing known concentrations of bacterial DNA copies/µl. The overall LOD in spiked clinical samples, including sample preparation and DNA isolation on MagnaPure24, was measured through 10-fold serial dilutions (from 10. 9. to 10. -1. CFU/ml) including additional dilutions of 5000, 500, 50 and 5 CFU/ml. Results. The results with LOD in serial dilutions of eluates and spiked clinical samples, together with analytical sensitivity and specificity, are shown in Table 1. Conclusion. The mPCR assay showed excellent analytical sensitivity and specificity, but with considerably lower LOD after sample preparation and further DNA isolation in spiked clinical samples. Although still promising in diagnostics of acute infections, the use of mPCR could be challenging in chronic, low-grade infections with lower microbial burden. Nevertheless, PCR offers significant advantages in terms of speed and can shorten the time to result, especially for C. acnes infections. Additionally, it represents a promising complementary approach in patients with suspected PJI on antibiotic therapy with negative culture results. 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. To evaluate the bacterial counts of sonicatied implants in patients with osteoarticular infections. Various studies have demostrated the usefulness of sonication of retrieved implants in order to provide an accurate microbiological diagnosis. Although cutoff values for original sonicate counts have been established, the use of centrifugation may influence these values. Method. A retrospective, single-center study, including sonication fluid samples from implants removed between January 2011 and October 2023, was performed. Patients were diagnosed with implant-associated infection based on the criteria available at the time of diagnosis. Osteoarticular implants were sonicated following the protocol described by Esteban et al. Sonicated fluid was centrifuged for 20 minutes at 3000 x g, and the sediment was resuspended in 5 mL of phosphate buffer solution. Ten µl of the sample were streaked onto each medium for quantitative culture. Bacterial counts exceeding 100,000 CFU/mL were considered as 100,000 CFU/mL for statistical analysis. Results. The study included 457 sonication fluid samples. Of these, 316 samples were from patients with prosthetic joint infection (PJI), with 26.3 % diagnosed with acute PJI and 73.7 % with chronic PJI. Additionally, 141 samples were from patients with osteosynthesis infection. The median CFU/ml in the sonication fluid was 40,000 CFU/mL (IQR 1,000 CFU/mL-100,000 CFU/mL). No statistically significant difference was observed between the different types of implants (prosthesis vs. osteosynthesis, p=0.218). A trend of higher counts was noted for acute PJI compared to chronic PJI (р=0.052). Most infections were monomicrobial, but 16.2% were polymicrobial. Statistically significant higher bacterial counts were observed in polymicrobial infections compared to monomicrobial infections (р<0.005). Among monomicrobial infections, no differences were found between Gram-negative and Gram-positive microorganisms (р=0.416). No differences were also found between joints (knee vs. hip) (p=0.353). Conclusions. Significant variability was observed in the number of colonies detected in all samples, regardless of the type of implant, the number of microorganisms or the species identified. Higher counts were detected in polymicrobial infections, and a trend was also noted for higher counts in acute infections

Background. Two-stage revision arthroplasty is the standard treatment for chronic hip and knee periprosthetic joint infections (PJI). Accurate diagnosis of persistent infections at 2nd stage using established biomarkers and diagnostic criteria is of paramount importance. This study aimed to evaluate the diagnostic value of synovial calprotectin and alpha-defensin, and compare established diagnostic criteria from the International Consensus Meeting (ICM 2018) and the European Bone and Joint Infection Society (EBJIS 2021) to determine persistent PJI at the 2nd stage of a two-stage revision arthroplasty. Methods. We retrospectively analyzed 97 patients who underwent 100 two-stage revisions (hip: 39, knee: 61). Synovial fluid samples were assessed for calprotectin and alpha-defensin levels. ICM 2018 and EBJIS 2021 were applied to all patients undergoing 2nd stage revision. Receiver operating characteristic (ROC) curves and Youden Index were utilized to determine optimal cut-off values, and correlations between biomarkers were evaluated. The microbiological spectrum was analyzed at 2nd stage and re-revision surgery. Results. Calprotectin levels showed a sensitivity of 66.7%, specificity of 32.9%, and accuracy of 38.0% in predicting septic failure. Alpha-defensin showed sensitivity of 28.6%, specificity of 87.8%, and accuracy of 79.2%. Significant correlations included: calprotectin with PMN% (r = 0.471, p = 0.05) and alpha-defensin with WBC (r = 0.830, p < 0.01) in the successful cohort. For septic re-revisions, calprotectin and alpha-defensin were highly correlated (r = 0.969, p < 0.01). ICM correctly diagnosed persistent PJI in 26.7%, while EBJIS diagnosed 24.2%. The microbial spectrum shifted from gram-positive to gram-negative bacteria between reimplantation and re-revision surgeries. Conclusion. Synovial calprotectin and alpha-defensin demonstrated limited accuracy in ruling out persistent PJI at reimplantation. The low sensitivity of current diagnostic criteria, combined with the observed shift in microbial spectrum, underscores the challenges in diagnosing persistent PJI during 2nd stage of a two-stage revisions arthroplasty

Aims

Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH.

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

Aim. Diagnosing low-grade periprosthetic joint infections (PJI) can be very challenging due to low-virulent microorganisms capable of forming biofilm. Clinical signs can be subtle and may be similar to those of aseptic failure. To minimize morbidity and mortality and to preserve quality of life, accurate diagnosis is essential. The aim of this study was to assess the performance of various diagnostic tests in diagnosing low-grade PJI. Methods. Patients undergoing revision surgery after total hip and knee arthroplasty were included in this retrospective cohort study. A standardized diagnostic workup was performed using the components of the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI. For statistical analyses, the respective test was excluded from the infection definition to eliminate incorporation bias. Receiver-operating-characteristic curves were used to calculate the diagnostic performance of each test, and their area-under-the-curves (AUC) were compared using the z-test. Results. 422 patients undergoing revision surgery after total hip and knee arthroplasty were included in this study. 208 cases (49.3%) were diagnosed as septic. Of those, 60 infections (28.8%) were defined as low-grade PJI (symptoms >4 weeks and caused by low-virulent microorganisms (e. g. coagulase-negative staphylococci, Cutibacterium spp., enterococci and Actinomyces)). Performances of the different test methods are listed in Table 1. Synovial fluid (SF) - WBC (white blood cell count) >3000G/L (0.902), SF - %PMN (percentage of polymorphonuclear neutrophils) > 65% (0.959), histology (0.948), and frozen section (0.925) showed the best AUCs. Conclusion. The confirmatory criteria according to the EBJIS definition showed almost ideal performances in ruling-in PJI (>99% specificity). Histology and synovial fluid cell count (SF-WBC and SF-%PMN) showed excellent accuracies for diagnosing low-grade PJI. However, a reduced immune reaction in these cases may necessitate lower cut-off values. Intraoperative frozen section may be valuable in cases with inconclusive preoperative diagnosis. For any tables or figures, please contact the authors directly

Aim. Periprosthetic joint infection (PJI) is one of the most serious and frequent complications in prosthetic surgery. Despite significant improvements in the criteria for diagnosis of PJI, the diagnostic workflow remains complex and, sometimes, inconclusive. Host immune factors hold great potential as diagnostic biomarkers in bone and joint infections. We have recently reported that the synovial concentration of the humoral pattern recognition molecule long pentraxin 3 (PTX3) is a sensitive and specific marker of PJI in total hip and knee arthroplasty patients (THA and TKA) undergoing revision surgery [1]. However, the contribution to risk and diagnosis of PJI of the genetic variation in PTX3 and inflammatory genes that are known to affect its expression (IL-1b, IL-6, IL-10, and IL-17A) has not been addressed. Therefore, we assessed these relationships in a cohort of THA and TKA patients who underwent prosthesis revision by focusing on a panel of single nucleotide polymorphisms (SNPs) in the PTX3, IL-1β, IL-6, IL-10 and IL-17A genes. Method. A case-control retrospective study was conducted on an historic cohort of patients that received THA or TKA revision and were diagnosed with PJI (cases) or aseptic complications (controls) [1]. Samples of saliva were collected from 93 subjects and used for extraction of genomic DNA to perform genotyping of the PTX3, IL-1β, IL-6, IL-10 and IL-17A polymorphisms. Moreover, whenever available, samples of synovial fluid and plasma [1] were used to measure the concentration of the IL-1β, IL-10, and IL-6 proteins by immunoassay. Uni-and multivariate analyses were performed to evaluate the relationships between genetic, biochemical, and clinical variables. Results. The rs3024491 (IL-10) and rs2853550 (IL-1b) SNPs were found to be strongly associated with the risk of PJI. The synovial levels of PTX3, IL-1β, IL-10, and IL-6 were higher in cases than in controls, and a clear correlation emerged between the synovial concentration of PTX3 and IL-1b in cases only. Also, we identified a causal relationship between rs2853550, synovial concentration of IL-1b and that of PTX3 (that is induced by IL-1b). Conclusions. Our findings suggest that SNPs in the IL-10 and IL-1b genes could be used for early identification of THA and TKA patients with high risk of PJI. It is therefore conceivable that integrating genetic data into current diagnostic criteria would improve diagnosis of 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. Diagnosis of prosthetic joint infection are often complicated by the presence of biofilm, which hampers bacteria dislodging from the implants, thus affecting sensitivity of cultures. In the last 20 years several studies have evidenced the usefulness of implant sonication to improve microbial recovery from biofilm formed on inert substrates. More recently, treatment of prosthetic joints and tissues with Dithiothreitol, a sulphur compound already used in routine diagnostic workflow for fluidification of respiratory samples, has proved to be not inferior to sonication in microbiological diagnosis of prosthetic joint infections. This study aimed to evaluate if the combination of the two treatments could further improve microbial retrieval from biofilm in an in vitro model. Method. Three isolates of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Eschericha coli and Pseudomonas aeruginosa responsible of prosthetic joint infections were used. They were grown onto 3 titanium discs (20 mm diameter) and incubated in 3 sterile plastic containers with 15 mL of Triptyc Soy Broth. After overnight incubation, not adhered cells were removed and fresh broth was added to each sample. After 48 hours incubation, the exausted broth was removed and one sample was used for sonication, one for treatment with 0,1% (v:v) Dithiothreitol and one treated with Dithiothreitol followed by sonication. Treated fluids were plated on Muller Hinton Agar plates for colony count. One-way ANOVA analysis was performed to evidence statistical differences between treatments. Results. Similar colony counts were observed for the 3 treatments: 10.1± 0.77 log CFU/mL for Dithiothreitol, 10.0 ± 0.75 for sonication and 10.1 ±0.73 for dithiothreitol + sonication. No statistical differences between the 3 treatments were evidenced by ANOVA analysis. Conclusions. Results seems to confirm that treatment with dithiothreitol is equivalent to sonication in recovering bacteria from biofilm grown on inert surface. Combining dithiotreitol treatment with sonication does not significantly improve bacterial recovery in respect to each treatment alone

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. A substantial portion of periprosthetic joint infections (PJI) literature is comprised of observational studies. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines emphasize the importance of clearly defining variables and providing diagnostic criteria. Well-defined variables in these studies play a crucial role in ensuring data consistency, fostering comparability among studies, and laying a robust foundation for evidence-based decision-making. We aimed to determine the definition of these variables and determine the objectivity of the definitions. Method. We reviewed observational studies on hip or knee PJI that focused on variables and their association with treatment outcomes. The inclusion criteria comprised studies from Jan 2017 to Jan 2023. We focused on 13 variables that were possibly subjective. These were smoking, alcohol use, diabetes mellitus, hypertension, lung disease, rheumatoid arthritis, liver diseases, kidney diseases, cardiovascular diseases, malignancy, immunosuppression, use of antibiotics, and type of infection. The reviewers examined the text of the articles, along with any available online supplements or protocols, for definitions of the selected variables. We classified a definition as objective if there was the presence of time element, severity, staging, frequencies, laboratory cut-off, medication dependence, among others. Chart review was deemed subjective. Results. We included 75 studies in the analysis. The most common factors studied were diabetes mellitus (79%), cardiovascular disease, smoking history, and rheumatoid arthritis (47% each). The variables that were objectively defined most often were antibiotic use (100%) and type of infection (95%). Smoking history (16%) and alcohol use (20%) were the least frequently objectively defined variables. Further analysis revealed that a considerable number of studies incorporated variables into their primary analyses without clear definitions. For instance, out of the 59 studies where diabetes was considered a variable, 41 studies (70%) included diabetes in their main analyses as a factor for PJI treatment outcomes, despite only 34 studies having defined this variable. Moreover, of the 34 provided definitions of diabetes mellitus, only 12 provided objective criteria for diagnosis. The rest of the provided definitions relied on “chart review” without further specification. Table 1 outlines the proportion of studies with variables defined and included in their analysis. Conclusions. Study variables were not clearly defined in most of the observational studies raising concerns about the reproducibility and reliability of findings. Our study underscores the vital need for standardized variable definitions in PJI research. Professional societies may play a crucial role in setting standards for the definition of variables. For any tables or figures, please contact the authors directly

Aim. Predicting success of a Debridement, Antibiotics and Implant Retention (DAIR) procedure for Periprosthetic Joint Infection (PJI) remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimise factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection. Method. A retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their hip or knee arthroplasty. Diagnosis of PJI was confirmed using the Musculoskeletal Infection Society (MSIS) 2013 and the European Bone and Joint Infection Society (EBJIS) 2021 classification systems. DAIR surgery was grouped into “successful” or “unsuccessful” outcomes as per the MSIS working group outcome-reporting tool. Results. Sixty-Four consecutive patients with an acute PJI underwent a DAIR procedure between 2009 and 2020. Treatment was successful in 44 (69%). The chance of a successful DAIR was significantly greater if performed within one week of symptom onset compared to greater than one week duration (adjusted odds ratio (OR 0.11; p=0.027; 95% CI [0.02- 0.78]). The chances of a successful DAIR was not influenced by whether the surgeon was an arthroplasty or non-arthroplasty surgeon (OR 0.28; p=0.13; 95% CI [0.05- 1.48]). Isolated Streptococcus infection had a success rate of 100%; followed by Coagulasenegative Staphylococci 71% and Methicillin-susceptible Staphylococcus Aureus 65%. Polymicrobial infection had the worst outcome with a success rate of 47%. Conclusions. In our experience DAIR surgery performed within one week of symptom onset, significantly increased chances of successful infection eradication. Collaborative work is required to ensure arthroplasty patients access prompt appropriate surgical decision-making, remove barriers to early assessment and minimise delays to surgery

Aim. This study seeks to outline the clinical, laboratory, and imaging features of patients with pyogenic spondylitis. It aims to define a novel imaging sign that could indicate the severity of suppurative spondylitis, aiding in its early diagnosis and treatment. Method. This retrospective study included 137 patients from 2013 to 2023. Through the analysis and summary of imaging characteristics among all patients, we identified a distinct MRI sign known as ‘the Disc Penetration sign’ (DP). This sign is defined as an image finding on sagittal MRI depicting the anterior and posterior penetration of an abscess through the intervertebral disc space, affecting both the anterior margin of the vertebrae and the structures within the spinal canal. Observational parameters included WBC, ESR, CRP, hemoglobin, and albumin levels. Documentation of the study included location and segment of the lesion, presence or absence of spinal cord compression, and paravertebral abscesses. Results. 56 patients presented with the Disc Penetration sign(DP) and 81 did not. In both groups, there were no significant differences in gender ratio or age (P > 0.05). However, significant differences were observed in the presence of comorbid diabetes and chronic kidney disease (p < 0.05). The DP group had a significantly greater ESR level (74.30±33.79 mm/h vs. 51.46±30.46 mm/h, P < 0.001) and CRP level (47.28 mg/L vs. 26.18 mg/L, P = 0.003). Additionally, the DP group had a significantly lower Hb (100.66±19.82 g/L vs. 116.99±19.99g/L,P < 0.001) and the serum albumin level (28.81±6.59 g/L vs. 34.09±6.17 g/L,P < 0.001). Imaging results showed no significant differences in affected spinal segments or parts (p>0.05). Patients in the DP group showed a higher likelihood of developing paravertebral abscesses compared to those in the non-DP group (n = 54 [96.4%] vs. n = 33 [40.7%], P < 0.001), and also exhibited a higher incidence of spinal cord compression(n = 32 [57.1%] vs. n = 17 [21.0%], P < 0.001). Conclusions. The study suggests that the Disc Penetration sign in pyogenic spondylitis patients correlates with more severe inflammation and higher incidence of paraspinal abscess, pointing to worse stability of the spine, longer bone restructuring time, and potentially poorer prognosis. These findings enable clinicians to rapidly assess the severity of the disease and prognosticate outcomes more effectively We emphasize the need for early, pathogen-specific diagnosis and treatment, particularly considering surgical intervention for patients demonstrating substantial paraspinal abscesses or spinal instability

Aim. Evaluate if Neutrophil Extracellular Traps related biomarkers (citrullinated histone H3 [H3Cit], cellfree DNA [cfDNA], and myeloperoxidase) are increased in synovial fluid of patients with PJI and investigate the diagnostic accuracy of NET formation biomarkers for PJI. Method. Patients who underwent hip or knee revision total joint arthroplasty were categorised into two groups according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. Sixteen patients were classified as infected and 16 as non-infected. cf-DNA, myeloperoxidase and H3Cit were measured in synovial fluid collected during surgery. Sensitivity, specificity, and receiver operating characteristic (ROC) curve were calculated. Results. Patients with PJI presented significantly higher levels of synovial fluid cf-DNA (105.5 ng/ml ± 58.3 vs 1.9 ± 1.2, p>0.0001), myeloperoxidase (1575 pg/ml ± 826 vs 50.16 ± 100, p<0.0001) and citrullinated histone H3 (1.688 ± 1.214 vs 13.88 ± 24.4, p < 0.0001). In the ROC curve analyses, the area under the curve for cf-DNA, myeloperoxidase and H3cit were 1 [0.89 – 1], 0.98 [0.86 – 1], and 0.94 [0.8 – 0.99], respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 93,7% for myeloperoxidase, and 87,5% for H3cit. The sensitivity for cf-DNA and myeloperoxidase was 100%, and 87,5 % for H3cit. Conclusions. Our results show that neutrophils within periprosthetic microenvironment release NETs as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for the identification of new biomarkers and for a better use of the available ones. Furthermore, novel studies are needed to define whether and how NET-related biomarkers can be useful for the diagnosis of PJI

Aim

To date, no ultimate diagnostic gold standard for prosthetic joint infections (PJI) has been established. In recent years, next generation sequencing (NGS) has emerged as a promising new tool, especially in culture-negative samples. In this prospective study, we performed metagenomic analysis using 16S rRNA V3-V4 amplicon NGS in samples from patients with suspected PJI.

Aim. Megaprosthesis have become a standard option in limb preserving surgery after bone resection in musculoskeletal tumors. Recently they have also been used in complex revision arthroplasty in cases with massive bone loss. The aim of this study was to analyze the incidence of periprosthetic joint infection (PJI) both in primary oncology cases and aseptic revision cases and analyze which are the significant risk factors for PJI with a special interest on the use of prophylactic antibiotic loaded calcium sulfate beads. Method. All patients undergoing surgery with the use of megaprosthesis in our institution between January/2012 and December/2022 were retrospectively reviewed. Data was collected from electronic medical records. We identified 108 procedures involving megaprosthesis in 90 patients with an average follow-up of 37 months. Indications were 79 primary musculoskeletal tumors and 29 aseptic complex revision arthroplasty. Results. Table 1 shows relevant clinical information. No significant risk factor was found either in uni or multivariate analysis. PJI rate was 15% (12/79) for primary musculoskeletal surgery and 31% (9/29) for complex revision surgery. The use of antibiotic loaded calcium sulfate beads did not show an advantage – 22% (9/41) with vs. 18% (12/67) without. Conclusions. In this relatively small series it was not possible to show a significal association between PJI and certain known risk factors such as gender, ASA score, site of surgery (knee) and revision surgery. The use of antibiotic loaded calcium sulfate beads as prophylaxis was not beneficial in reducing PJI rates in our cohort. We acknowledge the limitations of our study: a small sample group, in a single institution with heterogeneity in terms of diagnosis and surgical site. We recognize the need for a multicentric study with a larger cohort to validate these findings. For any tables or figures, please contact the authors directly