bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRE-TREATING PJI WITH SYSTEMIC ANTIBIOTICS DECREASES TISSUE AND IMPLANT BACTERIAL COUNTS: RESULTS FROM AN IN VIVO MODEL
Authors: Chao Christina , Khilnani Tyler , Jo Suenghwan , Yang Xu , Bostrom Mathias , Carli Alberto 
Published: November 2024

AimPeriprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction.MethodPJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test.ResultsVancRif, the combined treatment significantly reduced bacterial burden in the periprosthetic soft tissue, bone, and implant compared to control (p<0.001) and Vanc alone (p<0.001). While not significant, Vanc alone did reduce bacterial load as compared to control. The ipsilateral weight of the iliac lymph nodes was significantly reduced in Vanc and VancRif mice compared to controls (p<0.001), was well as in VancRif versus Vanc alone (p<0.001). Interestingly, SAA levels did not significantly differ among all groups. During tissue harvesting, minimal purulence was observed in antibiotic treatment groups, unlike controls.ConclusionsTreating active PJI with vancomycin alone decreases periprosthetic bacterial loads and reduces the local immunological response. This effect is significantly enhanced with the combined rifampin use. These findings could suggest that when culture positive PJI is diagnosed, pre-surgical treatment with antibiotics may decrease immunosuppression and soft tissue infiltration, leading to a better chance of infection cure with subsequent surgical debridement. Histological investigations and repeat experiments involving subsequent surgical treatment are underway.AcknowledgementsFunding comes from internal institutional grants.
THE VALUE OF SYNOVIAL CALPROTECTIN IN THE DIAGNOSIS OF PERIPROSTHETIC JOINT INFECTION AFTER HIP AND KNEE ARTHROPLASTY
Authors: Bekkers Wouter , Zwart Vivian , Swietoslawki Adam , Oost Iris Koenraadt-van , Nijs Anouk , Emmen Judith , Van Geenen Rutger 
Published: November 2024

AimPeriprosthetic 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.MethodIn 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.ResultsWhen 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.ConclusionsThe 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.
CAN THE USE OF A SYNTHETIC SYNOVIAL FLUID MEDIUM IN COMBINATION WITH ISOTHERMAL MICROCALORIMETRY IMPROVE ACCURACY AND REDUCE TIME TO DETECTION IN PERIPROSTHETIC JOINT INFECTIONS?
Authors: De Bleeckere Amber , Neyt Jeroen , Vandendriessche Stien , Boelens Jerina , Coenye Tom 
Published: November 2024

AimFast and accurate identification of pathogens causing periprosthetic joint infections (PJI) is essential to initiate effective antimicrobial treatment. Culture-based approaches frequently yield false negative results, despite clear signs of infection. This may be due to the use of general growth media, which do not mimic the conditions at site of infection. Possible alternative approaches include DNA-based techniques, the use of in vivo-like media and isothermal microcalorimetry (ITC). We developed a synthetic synovial fluid (SSF) medium that closely resembles the in vivo microenvironment and allows to grow and study PJI pathogens in physiologically relevant conditions. In this study we investigated whether the use of ITC in combination with the SSF medium can improve accuracy and time to detection in the context of PJI.MethodsIn this study, 120 synovial fluid samples were included, aspirated from patients with clinical signs of PJI. For these samples microbiology data (obtained in the clinical microbiology lab using standard procedures) and next generation sequencing (NGS) data, were available. The samples were incubated in the SSF medium at different oxygen levels (21% O2, 3% O2 and 0% O2) for 10 days. Every 24h, the presence of growth was checked. From positive samples, cultures were purified on Columbia blood agar and identified using MALDI-TOF. In parallel, heat produced by metabolically active microorganisms present in the samples was measured using ITC (calScreener, Symcel), (96h at 37°C, in SSF, BHI and thioglycolate). From the resulting thermograms the ‘time to activity’ could be derived. The accuracy and time to detection were compared between the different detection methods.ResultsSo far, seven samples were investigated. Using conventional culture-based techniques only 14.3% of the samples resulted in positive cultures, whereas NGS indicated the presence of microorganisms in 57.1% of the samples (with 3/7 samples being polymicrobial). Strikingly, 100% of the samples resulted in positive cultures after incubation in the SSF medium, with time to detection varying from 1 to 9 days. MALDI-TOF revealed all samples to be polymicrobial after cultivation in SSF, identifying organisms not detected by conventional techniques or NGS. For the samples investigated so far, signals obtained with ITC were low, probably reflecting the low microbial load in the first set of samples.ConclusionThese initial results highlight the potential of the SSF medium as an alternative culture medium to detect microorganisms in PJI context. Further studies with additional samples are ongoing; in addition, the microcalorimetry workflow is being optimized.
COMPARISON OF SYNOVIAL CALPROTECTIN AND ALPHA-DEFENSIN FOR THE DIAGNOSIS OF PERSISTENT PERIPROSTHETIC JOINT INFECTION AT THE SECOND STAGE OF A TWO-STAGE REVISION ARTHROPLASTY
Authors: Mitterer Jennyfer A , Hartmann Susana Gardete , Simon Sebastian , Sebastian Sujeesh , Chlud Leonie , Hofstaetter Jochen G 
Published: November 2024

BackgroundTwo-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.MethodsWe 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.ResultsCalprotectin 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.ConclusionSynovial 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.
NEUTROPHIL EXTRACELLULAR TRAP-RELATED BIOMARKERS ARE INCREASED IN SYNOVIAL FLUID OF PATIENTS WITH PERIPROSTHETIC JOINT INFECTION
Authors: Kimura Osamu , Mozella Alan , Cobra Hugo , Saraiva Augusto , Leal Ana Carolina 
Published: November 2024

AimEvaluate 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.MethodPatients 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.ResultsPatients 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.ConclusionsOur 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.
INTERNATIONAL PRACTICE VARIATION OF SUPPRESSIVE ANTIMICROBIAL TREATMENT FOR PERIPROSTHETIC JOINT INFECTION: A GLOBAL SURVEY STUDY
Authors: Hanssen Jaap , Gademan Maaike , Wouthuyzen-Bakker Marjan , Davis Joshua Saul , Dewar David , Manning Laurens , Campbell David , van Prehn Joffrey , Miller Andy , van der Wal Robert , van der Linden Enrike , Cortes-Penfield Nicolas , Soriano Alex , De Boer Mark G.J. , Scheper Henk 
Published: November 2024

AimSuppressive antimicrobial therapy (SAT) is used worldwide for patients with a prosthetic joint infection (PJI but clear definitions or guidelines regarding the indications, antimicrobial strategy or treatment duration are currently lacking in the literature. The aim of this study was to identify the global differences in the clinical practice of SAT for PJI.MethodAn online survey was designed to investigate the current opinion on indication and treatment goals, preferred antimicrobial drugs, dosing and treatment duration and follow-up of patients with PJI on suppression. The survey was distributed using e-mail lists of several international bone and joint infection societies and study groups. Recipients were asked to share the survey with colleagues who were not a member of one of the societies but who were involved in PJI care.ResultsThe questionnaire was fully completed by 330 physicians from 43 different countries on six continents (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 14%). Antimicrobial treatment for PJI was discussed in a multidisciplinary team in Europe (90%), Oceania (42%) and North America (12%). In six of eight (75%) different clinical scenarios, respondents from North America would most often place a patient on SAT. In seven of eight (88%) scenarios, SAT was started least often by European respondents. The presence of a fistula was considered a contra-indication for suppression by 74 respondents (22%). First choices of SAT for staphylococcal PJI were: oral cephalosporins (39%) and tetracyclines (31%) in North America; anti-staphylococcal penicillins (55%) and oral cephalosporins (24%) in Oceania; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe. For streptococcal PJI, most clinicians preferred penicillins (91% in Oceania, 67% in Europe, and 53% in North America). Preferred SAT for gram negative PJI was: fluoroquinolones and a penicillin/betalactamase inhibitor in North America (26% and 18%, respectively) and Oceania (23% and 27%, respectively); fluoroquinolones (31%) and Cotrimoxazole (28%) in Europe. The dosage of SAT was never lowered (n=126, 38%), standardly lowered for all antibiotics (n=79, 24%) or only lowered for specific antibiotics (n=125, 38%). SAT was prescribed for an indefinite duration (n=43, 13%), as fixed duration between six months and three years (n=104, 32%) or for an undetermined prespecified duration (n=154, 47%).ConclusionsSubstantial variation in the practice of SAT for PJI exists between physicians worldwide and throughout the different continents. This reflects the paucity of data regarding the indication and treatment of PJI with SAT.
ULTRATHIN SILVER-POLYSILOXANE-COATED PLATES FOR REVISION OF INFECTED FEMORAL NONUNION: FIRST RESULTS
Authors: Mueller Maximilian M. , Kowald Birgitt , Gerlach Ulf-Joachim , Grimme Cornelius , Schulz Arndt-Peter , Frosch Karl-Heinz , Schoop-Schmetgens Rita 
Published: November 2024

AimAim of this study was to establish the first clinical results after implantation of ultrathin silver-polysiloxane-coated1 plates in the treatment of infected non-union of the femoral shaft.MethodAs part of the REFECT study, a prospective, non-interventional analysis was conducted encompassing all patients who received internal stabilization with a silver-coated1 plate from 01/2023 to 09/2024 as part of the treatment for infected non-union of the femur. Standardized clinical follow-ups including PROMs (WOMAC-Index, LEF-S, EQ-5D, VAS) and X-rays were performed 3, 6, 12 (and 24) months postoperatively.For comparison, a retrospective analysis of 76 patients with infected femoral non-union, who had received a stabilization with an uncoated plate in the past 10 years, was performed.ResultsThe mean follow-up of the 8 included patients (mean bone defect: 3.6 cm) was 9 months (as of 04/24). Multiresistant bacteria were found in the intraoperative samples of 5 patients. The concentration of silver ions in blood serum reached a maximum of 0.014 mg/l in the laboratory controls. All patients showed a positive healing process with no sign of re-infection and no adverse procedure-associated events. Full weight bearing was achieved after an average of 4 months (n=6) with improved WOMAC-, LEF-S-, EQ-5D and VAS-score at 1-year FU. In the reference group (uncoated, mean FU: 3.5 years), there was a re-infection rate of 25 %, mostly in the first 2 years. Difficult-to-treat bacteria were detected in 22%, multiresistant Staph. epidermidis in 28% of cases.ConclusionsThe silver-coated1 implants showed good biocompatibility with no evidence of procedure-associated complications.The use of silver-coated1 implants could reduce the risk of re-infection.Further clinical data with longer follow-up are needed to assess the long-term value of the procedure.
EVALUATION OF A NEW POINT-OF-CARE APPROACH FOR SYNOVIAL FLUID CELL-FREE DNA QUANTIFICATION FOR PERIPROSTHETIC JOINT INFECTION DIAGNOSIS
Authors: Cobra Hugo , Mozella Alan , Leal Ana Carolina 
Published: November 2024

AimPeriprosthetic 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.MethodA 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.ResultsFifty-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).ConclusionsFrom 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.
16S RRNA V3-V4 AMPLICON NEXT-GENERATION SEQUENCING IN THE DIAGNOSIS OF PERIPROSTHETIC JOINT INFECTIONS
Authors: Erbeznik Anja , Šturm Andraž Celar , Smrdel Katja Strašek , Triglav Tina , Kocjancic Boštjan , Pompe Borut , Dolinar Drago , Mavcic Blaz , Mercun Aljaz , Kolar Matic , Avsec Klemen , Papst Lea , Vodicar Polona Maver 
Published: November 2024

AimTo 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.MethodsA total of 257 (187 culture-negative (CN) and 70 culture-positive (CP)) prospectively collected tissues and sonication fluid from 32 patients (56 revisions) were included. 16S rRNA V3-V4 amplicons were sequenced using Illumina's MiSeq (California, USA) followed by bioinformatic analysis using nf-core/ampliseq pipeline.ResultsWe successfully sequenced 255 samples and detected a total of 105 microorganisms. These were mainly environmental microorganisms present in a small number of reads (≤100), indicating possible contamination. Pseudomonas spp. (non-aeruginosa species) was detected most frequently in 73% (187/255) of samples. The test showed limitations in species classification and identified microorganisms mainly at genus level. Significant differences in the number of reads were observed when comparing CN (≤100) and CP (≥1000) samples. In two CP, no bacteria were identified with sequencing, which is probably due to low bacterial load (1 CFU. Haemophilus spp. was detected with a significant number of reads (≥10000) in five samples from a single patient, in whom infection was considered likely according to EBJIS criteria, changing it to confirmed infection. Staphylococcus spp. was identified with ≥10000 reads in two CNs from an individual who was receiving antibiotic treatment at the time, had clinical signs of infection, and had a confirmed infection with S. lugdunensis one month earlier. Cutibacterium spp. with 36% (93/257) and Staphylococcus spp. with 34% (87/257) were detected with a minimal number of reads (≤100) in several CN, indicating possible contamination with normal skin microbiota. In one patient, Facklamia spp., an opportunistic pathogen, was detected in two samples by sequencing, but not by culture.ConclusionsWe consider 16S rRNA V3-V4 amplicon sequencing to be a promising tool; however, further studies are needed to clarify uncertainties regarding the interpretation of the results in combination with other criteria. Using this method, we were able to successfully confirm infection in two patients whose microbiological results were initially negative, leading to a change from likely to confirmed infection in one case. The thresholds and interpretation of the results are currently unclear, therefore the method is being used experimentally rather than diagnostically at the time of writing.