The diagnosis of infection following shoulder arthroplasty is notoriously difficult. The prevalence of prosthetic shoulder infection after arthroplasty ranges from 3.9 – 15.4% and the most common infective organism is Cutibacterium acnes. Current preoperative diagnostic tests fail to provide a reliable means of diagnosis including WBC, ESR, CRP and joint aspiration. Fluoroscopic-guided percutaneous synovial biopsy (PSB) has previously been reported in the context of a pilot study and demonstrated promising results. The purpose of this study was to determine the diagnostic accuracy of percutaneous synovial biopsy compared with open culture results (gold standard). This was a multicenter prospective cohort study involving four sites and 98 patients who underwent revision shoulder arthroplasty. The cohort was 60% female with a mean age was 65 years (range 36-83 years). Enrollment occurred between June 2014 and November 2021. Pre-operative fluoroscopy-guided synovial biopsies were carried out by musculoskeletal radiologists prior to revision surgery. A minimum of five synovial capsular tissue biopsies were obtained from five separate regions in the shoulder. Revision shoulder arthroplasty was performed by fellowship-trained shoulder surgeons. Intraoperative tissue samples were taken from five regions of the joint capsule during revision surgery. Of 98 patients who underwent revision surgery, 71 patients underwent both the synovial biopsy and open biopsy at time of revision surgery. Nineteen percent had positive infection based on PSB, and 22% had confirmed culture positive infections based on intra-operative tissue sampling. The diagnostic accuracy of PSB compared with open biopsy results were as follows: sensitivity 0.37 (95%CI 0.13-0.61), specificity 0.81 (95%CI 0.7-0.91), positive predictive value 0.37 (95%CI 0.13 – 0.61), negative predictive value 0.81 (95%CI 0.70-0.91), positive likelihood ratio 1.98 and negative likelihood ratio 0.77. A patient with a positive pre-operative PSB undergoing revision surgery had an 37% probability of having true positive infection. A patient with a negative pre-operative PSB has an 81% chance of being infection-free. PSB appears to be of value mainly in ruling out the presence of peri-prosthetic infection. However, poor likelihood ratios suggest that other ancillary tests are required in the pre-operative workup of the potentially infected patient

Aim. Diagnosing Fracture-Related Infections (FRI) is challenging. White blood cell (WBC) scintigraphy is considered the best nuclear imaging technique to diagnose FRI; a recent study by our group found a diagnostic accuracy of 92%. However, many centers use . 18. F-fluorodeoxyglucose positron emission tomography/computed tomography (. 18. F-FDG-PET/CT) which has several logistic advantages. Whether . 18. F-FDG-PET/CT has better diagnostic performance than white blood cell (WBC) scintigraphy is uncertain. Therefore, we aimed: 1) to determine the diagnostic performance of . 18. F-FDG-PET/CT for diagnosing FRI (defined as infection following an open fracture or fracture surgery) and 2) to determine cut-off values of standardized uptake values (SUV) that result in optimal diagnostic performance. Method. This retrospective cohort study included all consecutive patients who received . 18. F-FDG-PET/CT to diagnose FRI in two level 1 trauma centers. Baseline demographic- and surgical characteristics were retrospectively reviewed. The reference standard consisted of at least 2 representative microbiological culture results or the presence or absence of clinical confirmatory FRI signs in at least 6 months of clinical follow-up. A nuclear medicine specialist, blinded to the reference standard, re-reviewed all scans. Additionally, SUVs were measured using the “European Association of Nuclear Medicine Research Ltd. (EARL)” reconstructed . 18. F-FDG-PET/CT scans. Volume of interests were drawn around the suspected- and corresponding contralateral area to obtain the absolute values (SUVmax) and the ratio between suspected and contralateral area (SUVratio). Diagnostic accuracy of the re-reviewed scans was calculated (sensitivity and specificity). Additionally, diagnostic characteristics of the SUV measurements were plotted in the area under the receiver operating characteristics curve (AUROC). The sensitivity and specificity at the optimal threshold was deducted from the AUROC with the Q-point method. Results. 158 . 18. F-FDG-PET/CTs were included. Mean age was 46.2 years, 71.5% was male. Most cases (56.3%) were tibial shaft- or ankle fractures. Sixty patients (38.0%) had FRI. The sensitivity and specificity of the FDG-PET/CT scan was 70.0% (95% CI 56.8–81.2) and 79.6% (95% CI 70.3–87.1) respectively. Diagnostic accuracy was 76.0% (95% CI 68.5–82.4). AUROCs of SUVmax and SUVratio were 0.80 (95% CI 0.73–0.87) and 0.73 (95% CI 0.64–0.81), respectively. The optimal SUVmax threshold of 4.2 resulted in 80.0% sensitivity and 71.3% specificity, while an SUVratio of 2.9 resulted in 58.3% sensitivity and 80.9% specificity. Conclusions. The . 18. F-FDG-PET/CT has a sensitivity of 70.0%, specificity of 79.6% and a diagnostic accuracy of 76.0%. This makes . 18. F-FDG-PET/CT less accurate than WBC scintigraphy in diagnosing FRI, although adding SUV measurements may possibly increase its diagnostic accuracy

Background. The development of T-smart tomosynthesis has greatly improved the imaging quality of THA by reducing the peri-implant artifacts. In order to find out whether these improvements could lead to diagnostic advantages on stability of cementless THA arthroplasty components, we conducted a diagnostic research by comparing T-smart tomosynthesis, X-ray, and computed tomography. Methods. We retrospectively included 48 patients who undergone THA revisions in our center between Aug, 2013 and Mar, 2014. For patients with hybrid fixation as their primary prosthesis, the femoral or acetabular components with cement fixation were excluded. There were 41 cementless femoral stems and 35 cementless acetabular cups remained for evaluation. All patients took anterior-posterior and lateral view x-ray examination, anterior-posterior T-smart tomosynthesis scan, and computed tomography before revision surgery. As the gold standard, intraoperative pull-out tests and twisting tests were done for every patient to examine the stability of all implants. 7 orthopedic surgeons evaluated the preoperative images independently, who were divided into the senior group (3 doctors with 6∼13 years’ clinical experience) and the junior group (4 doctors with 2∼4 years’ clinical experience). The x-rays were evaluated first, followed by computed tomography 4 weeks later, and after another 4 weeks’ interval the T-smart tomosynthesis were assessed. All doctors used the same criteria for diagnosis. Diagnostic accuracy for each imaging examination was calculated by comparing with the results of intraoperative tests. The diagnostic accuracy, kappa values between 3 imaging techniques were calculated, and chi-square tests were conducted to examine the difference between the senior and junior groups for each technique. Results. The accuracy of T-smart tomosynthesis on stability diagnosis (loosening or stable) is 82.6% for femoral stem and 84.5% for acetabular cup. The accuracy of X-ray is 44.3% for stem and 67.3% for cup, and the accuracy of CT is 39.6% for stem and 74.6% for cup. The kappa values between the 3 techniques range from −0.053 to 0.22. For plain X-ray, The diagnostic accuracy of the senior group is significantly higher than that of the junior group (p<0.05), but no significance was found between the 2 groups for tomosynthesis and CT. Discussion. Our research indicates that, compared with x-ray and CT, the T-smart tomosynthesis technique can greatly improve the diagnostic accuracy on stability of cementless THA components, and significantly shorten the learning curve of inexperienced surgeons. With T-smart tomosynthesis, the peri-implant trabecular bone can be clearly imaged with least metal artifacts ever. T-smart tomosynthesis is an effective and promising imaging technique for diagnosing the stability of THA components

Aim. White blood cell (WBC) scintigraphy for diagnosing fracture-related infections (FRIs) has only been investigated in small patient series. Aims of this study were (1) to establish the accuracy of WBC scintigraphy for diagnosing FRIs, and (2) to investigate whether the duration of the time interval between surgery and WBC scintigraphy influences its accuracy. Method. 192 consecutive WBC scintigraphies with . 99m. Tc-HMPAO-labelled autologous leucocytes performed for suspected peripheral FRI were included. The goldstandard was based on the outcome of microbiological investigation in case of surgery, or - when these were not available - on clinical follow-up of at least six months. The discriminative ability of the imaging modalities was quantified by several measures of diagnostic accuracy. A multivariable logistic regression analysis was performed to identify predictive variables of a false-positive or false-negative WBC scintigraphy test result. Results. WBC scintigraphy had a sensitivity of 0.79, a specificity of 0.97, a positive predicting value of 0.91, a negative predicting value of 0.93 and a diagnostic accuracy of 0.92 for detecting an FRI in the peripheral skeleton. The duration of the interval between surgery and the WBC scintigraphy did not influence its diagnostic accuracy; neither did concomitant use of antibiotics or NSAIDs. There were 11 patients with a false-negative (FN) WBC scintigraphy, the majority of these patients (n = 9, 82%) suffered from an infected nonunion. Four patients had a false-positive (FP) WBC scintigraphy. Conclusions. WBC scintigraphy showed a high diagnostic accuracy (0.92) for detecting FRIs in the peripheral skeleton. Duration of the time interval between surgery for the initial injury and the WBC did not influence the results which indicate that WBC scintigraphy is accurate shortly after surgery

Aim. Prompt recognition and identification of the causative microorganism in acute septic arthritis of native and prosthetic joints is vital to increase the chances of successful treatment. The aim of this study was to independently assess the diagnostic accuracy of the multiplex BIOFIRE® Joint Infection (JI) Panel (investigational use only) in synovial fluid for rapid diagnosis. Method. Synovial fluid samples were prospectively collected at the University Medical Center Groningen from patients who had a clinical suspicion of a native septic arthritis, early acute (post-operative, within 3 months after arthroplasty) periprosthetic joint infection (PJI) or late acute (hematogenous) PJI. JI Panel results were compared to culture-based methods as reference standard. Results. A total of 45 samples were analyzed. The BIOFIRE JI Panel showed a high specificity (100%, 95% CI 73 – 100) and positive predictive value (100%, 95% CI 79 – 100) in all patient categories. Sensitivity and negative predictive value were 83% (95% CI 36 – 99) and 88% (95% CI 47 – 99) respectively for patients with a clinical suspicion of native septic arthritis (n=12), 77% (95% CI: 46 – 94) and 63% (95% CI: 26 – 90) for patients with a clinical suspicion of a late acute PJI (n=14), and 27% (95% CI 7 – 61) and 27% (95% CI: 7 – 61) for patients with a clinical suspicion of an early acute PJI (n=19). Conclusions. The results of this pilot study indicate a clear clinical benefit of the BIOFIRE JI Panel in patients with a suspected native septic arthritis and late acute (hematogenous) PJI, but a low clinical benefit in patients with an early acute (post-operative) PJI due to the absence of low-grade microorganisms in the panel

Aim. Fracture related infection (FRI) remains a challenging diagnosis in orthopedic and trauma surgery. In addition to clinical signs and imaging, serum inflammatory markers are often used to estimate the probability of FRI. To what extent serum inflammatory markers can be used to rule out and diagnose FRI remains unclear. The aim of this systematic review was to assess the diagnostic value of the serum inflammatory markers C-reactive protein (CRP), leukocyte count (LC) and erythrocyte sedimentation rate (ESR) in suspected fracture related infection. Method. PubMed, Embase and Cochrane databases were searched for all articles focusing on the diagnostic value of CRP, LC and ESR in FRI. Studies on other inflammatory markers or other types of orthopedic infection, such as periprosthetic and diabetic foot infections, were excluded. For each serum inflammatory marker, all reported sensitivity and specificity combinations were extracted and graphically visualized. Average estimates were obtained using bivariate mixed effects models. This study utilized the QUADAS-2 criteria and was reported following the PRISMA statement. Results. The search resulted in 8280 articles, of which seven were eligible for inclusion. One study was excluded after quality assessment. CRP was reported in all included studies, with sensitivity ranging from 60.0 to 100.0% and specificity from 34.3 to 85.7%. Five of these studies were pooled. The average pooled sensitivity and specificity of CRP were, respectively, 77.0% (95% CI 66.5–85.0%) and 67.9% (95% CI 38.7–87.6%). LC was reported in five studies. Sensitivity ranged from 22.9 to 72.6% and specificity from 73.5 to 85.7%. The results of four of these studies were pooled, resulting in a 51.7% (95% CI 27.2–75.5%) sensitivity and 67.1% (95% CI 19.3–50.2%) specificity. ESR was reported in five studies. Sensitivity and specificity ranged from 37.1 to 100.0% and 59.0 to 85.0% respectively. Three of these studies were pooled, showing a 45.1% (95% CI 37.8–52.6%) sensitivity and 79.3% (95% CI 71.7–85.2%) specificity of ESR. Four studies analyzed the combined value of inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. Conclusions. The serum inflammatory markers CRP, LC and ESR are insufficiently accurate to diagnose FRI. These markers cannot rule out the presence of FRI, but they may be used as a suggestive sign in the diagnosis of FRI

Aim. Our goal is to increase diagnostic accuracy of synovial fluid testing in differentiating prosthetic joint infection(PJI) by more exhaustively studying simple and inexpensive biomarkers. For that purpose, we sought to determine: 1) if synovial fluid C-reactive protein(CRP), alpha-2-macrogloblulin(A2M), procalcitonin and adenosine deaminase(ADA) concentrations are different between infected and aseptic cases; 2) performance and optimal cutoff values of each marker; 3) whether any such test may help improve diagnostic performance of traditional leukocyte count. Method. Between January/2013 and December/2015 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples as well as the implant for sonication were gathered for microbiological study. Definitive diagnosis was classified as infection or aseptic on the basis of the recent International Consensus Meeting definition of PJI. Using receiver operating characteristic curves, we determined cutoff values as well as sensitivity and specificity for each marker. Results. Fifty-five out of 143 revision arthroplasties fully respected the inclusion criteria. Two supposedly aseptic cases were ultimately classified as infected resulting in 32 aseptic and 23 infected cases available for analysis. Total leukocyte count, proportion of PMN, C-reactive protein, ADA and alpha-2-macroglobulin but not procalcitonin were significantly different between both groups. Cutoff values for optimal performance in the diagnosis of infection were: total leukocyte count >1,463 cells/μL; proportion of PMN >81%; CRP >6.7mg/L and ADA >61U/L. Conclusions. Synovial fluid leukocyte count offers great negative predictive value and interpreting it together with other more specific markers such as C-reactive protein and ADA is helpful in improving its positive predictive value. These simple and inexpensive markers may reduce the number of equivocal synovial fluid results requiring more expensive investigation

Classification systems for tibial plateau fractures suffer from poor interobserver agreement, and their value in preoperative assessment to guide surgical fixation strategies is limited. For tibial plateau fractures four major characteristics are identified: lateral split fragment, posteromedial fragment, anterior tubercle fragment, and central zone of comminution. These fracture characteristics support preoperative assessment of fractures and guide surgical decision-making as each specific component requires a respective fixation strategy. We aimed to evaluate the additional value of 3D-printed models for the identification of tibial plateau fracture characteristics in terms of the interobserver agreement on different fracture characteristics.

Preoperative images of 40 patients were randomly selected. Nine trauma surgeons, eight senior and eight junior registrars indicated the presence or absence of four fracture characteristics with and without 3D-printed models. The Fleiss kappa was used to determine interobserver agreement for fracture classification and for interpretation, the Landis and Koch criteria were used.

3D-printed models lead to a categorical improvement in interobserver agreement for three of four fracture characteristics: lateral split (Kconv = 0.445 versus K3Dprint = 0.620; P < 0.001), anterior tubercle fragment (Kconv = 0.288 versus K3Dprint = 0.449; P < 0.001) and zone of comminution (Kconv = 0.535 versus K3Dprint = 0.652; P < 0.001).

The overall interobserver agreement improved for three of four fracture characteristics after the addition of 3D printed models. For two fracture characteristics, lateral split and zone of comminution, a substantial interobserver agreement was achieved.

Fracture characteristics seem to be a more reliable way to assess tibial plateau fractures and one should consider including these in the preoperative assessment of tibial plateau fractures compared to the commonly used classification systems.

The use of peritumoral oedema on magnetic resonance (MR) imaging to predict soft tissue tumour grade is controversial. The clinical significance of oedema visualised on MR scans is poorly defined in the literature. We undertook this study to ascertain a diagnostic relationship between peritumoral oedema surrounding soft tissue sarcomas and the histological grade of the tumour. One hundred and ten consecutive soft tissue tumours were extracted from the New Zealand Bone and Soft Tissue Tumour Registry. Key inclusion criteria were tumours deep to fascia, measuring more than 5cm in any dimension. Both benign and malignant sarcomas were included. MR scans and histology were reviewed, separately and in random order by a single author. Histology was graded as benign, low or high grade (based on the American Joint Committee on Cancer grading system). Peritumoral oedema was defined as the increased signal intensity, on T2 or STIR images, immediately surrounding a discrete lesion. It was measured on two or more planes with the largest value used in diagnostic calculations. Oedema greater than or equal to 20mm was defined as a positive test result. Twenty five random scans were double read to ensure inter-observer reliability. Data was obtained for 83 tumours, 36 benign and 47 malignant (34 high grade and 13 low grade). The tumours in all groups were matched for size. The mean peritumoral oedema was 10.5mm for benign tumours, 20.6mm for low grade sarcomas (p<0.1), 28.1mm for high grade tumours (p<0.01) and 26.1mm if all malignant tumours were included as a single group (p<0.01). Using peritumoral oedema as a diagnostic test for tumour grade resulted in a specificity of 72%. The highest diagnostic ability was found when comparing benign to high grade tumours which yielded sensitivity of 59% and a positive likelihood ratio of 2.1. This data suggests a high false negative rate and that the test adds little to the diagnostic process. To our knowledge this is the first study which assesses the diagnostic accuracy of peritumoral oedema to predict the histological grade of soft tissue sarcomas. Our results show a statistically significant difference, in surrounding peritumoral oedema, exists when comparing benign to high grade sarcomas and to all malignant tumours. This relationship is not apparent for low grade tumours. As a diagnostic test, using only peritumoral oedema to predict histological grade is unreliable

Purpose

Many studies have found associations between laboratory biomarkers and periprosthetic joint infection (PJI), but it remains unclear whether these biomarkers are clinically useful in ruling out PJI. This meta-analysis compared the performance of interleukin-6 (IL-6) versus procalcitonin (PCT) for the diagnosis of PJI.

Ultrasound (US) imaging is recommended for early detection of Developmental Dysplasia of the Hip (DDH) to guide decisions about possible surgical treatment. However, a number of studies have raised concerns over the efficacy of US in early diagnosis. The main limitation of US-based diagnosis is sub-standard reliability of the primary dysplasia metric measurements: namely, the alpha and beta angles. In this study, we have proposed a novel and automatic method to extract dysplasia metrics from 2D US, which we hope will improve the overall reliability of US-based DDH measurements by removing error due to subjective measurements. We hypothesise that improvements in reliability of dysplasia metric measurements will reduce the chances of missed early-diagnosis, and therefore reduce the need for later complex surgical treatments.

We evaluated performance of the algorithm on 4 infants diagnosed with US scans for DDH. The typical runtime of our algorithm is less than 1 second for an US image. We found a 6° bias between manual and automatic measurements, with automatic measurements tending to be lower in value; the standard deviation in the discrepancy values was also relatively high at 7°. This suggests that there is considerable variability in the angle estimation process, which is typically done manually, which supports our contention that further work needs to be done to establish an accurate and repeatable measurement technique. Further, we found agreements in the Graf-classification types in six out of seven sessions. For the one patient where there was a discrepancy in classification, later US sessions suggest the manual technique possibly missed the opportunity for early detection, in contrast to the automatic method which classified the patient as having evidence of dysplasia. Thus, such an automatic method may improve the reliability of current US-based DDH diagnosis techniques. The primary limitation of this study is that we have done strictly an intra-image discrepancy analysis and have not compared the results with what could be considered a ‘gold standard’ reference. In future work, we plan to assess these indices on 3D images of the hip and assess the accuracy of proposed 2D and 3D-based automatic index calculation techniques against a 3D reference model.

Abstract. Introduction. A spotlight has been placed upon virtual assessment of patients during the coronavirus pandemic. This has been particularly prevalent in the assessment of acute knee injuries. In this study we aim to assess the accuracy of telephone triage, confirmed by Magnetic Resonance Imaging (MRI) in the diagnosis of acute knee injuries. Methods. Case records of patients triaged by telephone in the acute knee clinic at Leeds General Infirmary were analysed. Provisional diagnoses made following telephone triage were compared to radiological diagnoses made on subsequent MRI scans. Diagnostic accuracy was compared between those patients assessed virtually and those assessed in face-to-face clinics. Results. 1160 patients were referred to the acute knee injury clinic during the study period. 587 of these were triaged telephonically. MRI scans were requested for 107 (18%) virtually reviewed patients. Of these patients, 92 (79%) had an MRI scan requested after making a provisional diagnosis over the phone. Of the MRI requests made after virtual consultation, there was a 75% diagnostic accuracy of the pre-imaging diagnosis. Of the patients seen in face-to-face appointments, a diagnostic accuracy of 73% was observed. Conclusion. Virtual assessment can provide an efficient and cost-effective establishment of diagnosis of acute knee injuries whilst reducing hospital attendance. A combination of virtual and in-person clinics may allow quicker access to specialist opinion and therefore reduce patient waiting times

Aim. Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). Method. From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC). Results. A total of 275 patients with rTHA and rTKA were included, 144 joints (52.4%) were identified as septic. Decreased AGR and elevated CRP were strongly associated with PJI, optimal diagnostic thresholds were calculated with 1.253 and 9.4 mg/L, respectively. Sensitivities were 62.5% (95%-confidence interval: 54.3–70.0) and 73.6% (65.8–80.1), and specificities 84.7% (77.5–89.9) and 87.8% (80.9–92.4), respectively. CRP showed a significantly higher AUC than AGR (0.807 (0.761–0.853) and 0.736 (0.686–0.786); p<0.0001). Subgroup analysis of acute versus chronic infections yielded significantly higher diagnostic accuracies in acute PJI for both parameters (p<0.0001). Similar results were observed when focusing on the causative microorganism; a better diagnostic performance was observed in high-virulence PJI compared to low-virulence PJI (p≤0.005). Furthermore, higher AUCs were calculated in knee PJI compared with hip PJI, with a significant difference for AGR (p=0.043). Conclusions. Due to its limited diagnostic accuracy, serum AGR cannot be recommended as an additional marker for diagnosing PJI. Serum parameters are generally unspecific and can be influenced by comorbidities and other foci of infection. Additionally, parameters may remain within normal levels in low-grade PJI. Evaluating AGR, further possible pitfalls must be considered, for example an increased latency until bottom values are reached and the impact of malnutrition

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

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

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. 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

Abstract. Background. Distinction between foot and ankle wound healing complications as opposed to infection is crucial for appropriate allocation of antibiotic therapy. Our aim was to evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. Methods. Data were reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals – United Kingdom between July 2014 and February 2020 (68 months). All diabetic patients were excluded. For the infected non-diabetic included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0–10 mg/L and WCC 4.0–11.0 ×109 /L were considered normal. Results. 25 patients met our inclusion criteria. Infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with foot osteomyelitis (OM), 11 (44%) with ankle OM, 5 (20%) with ankle septic arthritis, and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metalwork. CRP sensitivity was 84%, while WCC sensitivity was only 28%. Conclusion. CRP had good sensitivity, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of a clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM

Aim. Diagnosing or excluding a chronic prosthetic joint infection (PJI) prior to revision surgery can be a clinical challenge. To enhance accuracy of diagnosis, several biomarkers were introduced in recent years, but most are either expensive or not available as a rapid test. We compared the diagnostic accuracy of leucocyte esterase (€0.20 per sample), calprotectin (€20 per sample) and alpha defensin (€200 per sample). Method. We prospectively evaluated PJI patients with chronic pain with or without prosthetic loosening between 2017 and 2018. Synovial fluid was collected prior to revision surgery. Leucocyte esterase was measured using a reagent strip (2+ considered as positive), and calprotectin and alpha defensin were measured using a lateral flow immunoassay. Intraoperative cultures (5 periprosthetic tissue samples, synovial fluid and sonication fluid) incubated for 9 days, were used as gold standard. At least two positive cultures of low-grade microorganisms with the same antibiogram were required to diagnose PJI. Results. A total of 19 patients were included (knee =11, hip =8). None of the patients were treated with antibiotics prior to revision surgery. A PJI was diagnosed in 8 patients (42.1%). The diagnostic accuracy of leucocyte esterase vs. calprotectin vs. alpha defensin was as follows; sensitivity 50.0% vs. 87.5% vs. 87.5%, specificity 81.8% vs. 90.9% vs. 100%, positive predictive value 60.0% vs. 87.5% vs. 100% and negative predictive value 75.0% vs. 90.9% vs. 91.6%, respectively. Both calprotectin and alpha defensin were false negative in one PJI caused by Cutibacterium acnes. The other two C. acnes PJIs were correctly diagnosed with both tests. Conclusions. Calprotectin is as accurate as alpha defensin in excluding a chronic PJI at 10% of the costs. Future studies with a large number of patients are necessary to analyze its diagnostic accuracy in very low-grade infections, in particularly caused by C. acnes