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The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 458 - 464
1 Apr 2017
Abrahams JM Kim YS Callary SA De Ieso C Costi K Howie DW Solomon LB

Aims. This study aimed to determine the diagnostic performance of radiographic criteria to detect aseptic acetabular loosening after revision total hip arthroplasty (THA). Secondary aims were to determine the predictive values of different thresholds of migration and to determine the predictive values of radiolucency criteria. Patients and Methods. Acetabular component migration to re-revision was measured retrospectively using Ein-Bild-Rontgen-Analyse (EBRA-Cup) and manual measurements (Sutherland method) in two groups: Group A, 52 components (48 patients) found not loose at re-revision and Group B, 42 components (36 patients) found loose at re-revision between 1980 and 2015. The presence and extent of radiolucent lines was also assessed. Results. Using EBRA, both proximal translation and sagittal rotation were excellent diagnostic tests for detecting aseptic loosening. The area under the receiver operating characteristic (ROC) curves was 0.94 and 0.93, respectively. The thresholds of 2.5 mm proximal translation or 2° sagittal rotation (EBRA) in combination with radiolucency criteria had a sensitivity of 93% and specificity of 88% to detect aseptic loosening. The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of radiolucency criteria were 41%, 100%, 100% and 68% respectively. Manual measurements of both proximal translation and sagittal rotation were very good diagnostic tests. The area under the ROC curve was 0.86 and 0.92 respectively. However, manual measurements had a decreased specificity compared with EBRA. Radiolucency criteria had a poor sensitivity and NPV of 41% and 68% respectively. Conclusion. This study shows that EBRA and manual migration measurements can be used as accurate diagnostic tools to detect aseptic loosening of cementless acetabular components used at revision THA. Radiolucency criteria should not be used in isolation to exclude loosening of cementless acetabular components used at revision THA given their poor sensitivity and NPV. Cite this article: Bone Joint J 2017;99-B:458–64


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 68 - 68
24 Nov 2023
Luger M Windhager R Sigmund I
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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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 9 - 9
1 Oct 2022
Klim S Madl T Habisch H Amerstorfer F Stradner M Hauer G Leithner A Glehr M
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Aim. The aim of this study was to investigate the metabolomic profile of synovial fluid in periprosthetic joint infection (PJI) cases regarding a possible diagnostic approach. Also, further information about the metabolic composition of synovial fluid in PJI may point to future diagnostic and therapeutic approaches. Method. Patients with a clinical suspicion of a prosthesis infection who underwent a joint puncture in our outpatient department or ward were included. After sample preparation, the nuclear magnetic resonance (NMR) experiments were performed at 310 K on an AVANCE™ NeoBruker Ultrashield 600 MHz spectrometer. Bruker Topspin version 4.0.2 was used for NMR data acquisition. The spectra for all samples were automatically processed (exponential line broadening of 0.3 Hz), phased, and referenced using TSP at 0.0 ppm. In total, 37 metabolites were analysed using a volume of 200 µl per synovial sample. The PJI and aseptic cases were assigned according to the EBJIS criteria. Results. In total, 76 samples were included in the final analysis with 48 PJI cases and 28 aseptic cases. Five measured metabolites have shown an area under the curve (AUC) over 0.8, with Taurine (AUC 0.8558, p<0.0001) and Glutamine (AUC 0.8333, p<0.0001) showing the best diagnostic performance. When combining two metabolites, the AUC indicated even higher diagnostic performance: Glucose/Glycogen (AUC 0.9073, p<0.0001), Taurine/Mannose (AUC 0.9073, p<0.0001), Mannose/Glycogen (AUC 0.8992, p<0.0001) and Taurine/Glucose (AUC 0.8956, p<0.0001). Conclusions. While NMR as a method in PJI diagnostics is currently not broadly available for daily clinical work, our results indicate that certain synovial metabolites and their combinations can be used for PJI diagnosis


Bone & Joint 360
Vol. 13, Issue 3 | Pages 28 - 31
3 Jun 2024

The June 2024 Wrist & Hand Roundup. 360. looks at: One-year outcomes of the anatomical front and back reconstruction for scapholunate dissociation; Limited intercarpal fusion versus proximal row carpectomy in the treatment of SLAC or SNAC wrist: results after 3.5 years; Prognostic factors for clinical outcomes after arthroscopic treatment of traumatic central tears of the triangular fibrocartilage complex; The rate of nonunion in the MRI-detected occult scaphoid fracture: a multicentre cohort study; Does correction of carpal malalignment influence the union rate of scaphoid nonunion surgery?; Provision of a home-based video-assisted therapy programme in thumb carpometacarpal arthroplasty; Is replantation associated with better hand function after traumatic hand amputation than after revision amputation?; Diagnostic performance of artificial intelligence for detection of scaphoid and distal radius fractures: a systematic review


Bone & Joint Open
Vol. 2, Issue 10 | Pages 879 - 885
20 Oct 2021
Oliveira e Carmo L van den Merkhof A Olczak J Gordon M Jutte PC Jaarsma RL IJpma FFA Doornberg JN Prijs J

Aims. The number of convolutional neural networks (CNN) available for fracture detection and classification is rapidly increasing. External validation of a CNN on a temporally separate (separated by time) or geographically separate (separated by location) dataset is crucial to assess generalizability of the CNN before application to clinical practice in other institutions. We aimed to answer the following questions: are current CNNs for fracture recognition externally valid?; which methods are applied for external validation (EV)?; and, what are reported performances of the EV sets compared to the internal validation (IV) sets of these CNNs?. Methods. The PubMed and Embase databases were systematically searched from January 2010 to October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The type of EV, characteristics of the external dataset, and diagnostic performance characteristics on the IV and EV datasets were collected and compared. Quality assessment was conducted using a seven-item checklist based on a modified Methodologic Index for NOn-Randomized Studies instrument (MINORS). Results. Out of 1,349 studies, 36 reported development of a CNN for fracture detection and/or classification. Of these, only four (11%) reported a form of EV. One study used temporal EV, one conducted both temporal and geographical EV, and two used geographical EV. When comparing the CNN’s performance on the IV set versus the EV set, the following were found: AUCs of 0.967 (IV) versus 0.975 (EV), 0.976 (IV) versus 0.985 to 0.992 (EV), 0.93 to 0.96 (IV) versus 0.80 to 0.89 (EV), and F1-scores of 0.856 to 0.863 (IV) versus 0.757 to 0.840 (EV). Conclusion. The number of externally validated CNNs in orthopaedic trauma for fracture recognition is still scarce. This greatly limits the potential for transfer of these CNNs from the developing institute to another hospital to achieve similar diagnostic performance. We recommend the use of geographical EV and statements such as the Consolidated Standards of Reporting Trials–Artificial Intelligence (CONSORT-AI), the Standard Protocol Items: Recommendations for Interventional Trials–Artificial Intelligence (SPIRIT-AI) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis–Machine Learning (TRIPOD-ML) to critically appraise performance of CNNs and improve methodological rigor, quality of future models, and facilitate eventual implementation in clinical practice. Cite this article: Bone Jt Open 2021;2(10):879–885


Bone & Joint Research
Vol. 13, Issue 8 | Pages 372 - 382
1 Aug 2024
Luger M Böhler C Puchner SE Apprich S Staats K Windhager R Sigmund IK

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 76 - 76
1 Dec 2018
Bosch P van den Kieboom J Plate J IJpma F Houwert M Huisman A Hietbrink F Leenen L Govaert G
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Aim. Diagnosing fracture related infections (FRI) based on clinical symptoms alone can be challenging and additional diagnostic tools such as serum inflammatory markers are often utilized. The aims of this study were 1) to determine the individual diagnostic performance of three commonly used serum inflammatory markers: C-Reactive Protein (CRP), Leukocyte Count (LC) and Erythrocyte Sedimentation Rate (ESR), and 2) to determine the diagnostic performance of a combination of these markers and their value additionally to clinical predictors for FRI. Method. This cohort study included patients who presented with a suspected FRI at two level I academic trauma centers between February 1. st. 2009 and December 31. st. 2017. The parameters CRP, LC and ESR, were obtained from hospital records when FRI was suspected. The gold standard for diagnosing or ruling out FRI was defined as: positive microbiology results of surgically obtained tissue samples, or absence of FRI at a clinical follow-up of at least six months. Separate markers were analysed using hospital thresholds, to determine current diagnostic performance, and continuously, to determine maximum possible diagnostic performance. Multivariable logistic regression analyses were performed to obtain the discriminative performance (Area Under the Receiver Operating Characteristic, AUROC) of (1) the combined inflammatory markers, and (2) the value of these markers additional to clinical parameters. Results. A total of 168 patients met the inclusion criteria and were included for analysis. CRP had a 38% sensitivity, 34% specificity, 42% positive predictive value (PPV) and 78% negative predictive value (NPV). For LC this was 39%, 74%, 46% and 67% and for ESR 62%, 64%, 45% and 76% respectively. The diagnostic accuracy was 52%, 61% and 80% respectively. The AUROC was 0.64 for CRP, 0.60 for LC and 0.58 for ESR. The AUROC of the combined inflammatory markers was 0.63. Serum inflammatory markers combined with clinical parameters resulted in AUROC of 0.66 as opposed to 0.62 for clinical parameters alone. Conclusions. The added diagnostic value of CRP, LC and ESR for diagnosing FRI is limited. Clinicians should be aware of this finding in the diagnostic work-up of suspected FRI


Aims. Monocyte-lymphocyte ratio (MLR) or neutrophil-lymphocyte ratio (NLR) are useful for diagnosing periprosthetic joint infection (PJI), but their diagnostic values are unclear for screening fixation-related infection (FRI) in patients for whom conversion total hip arthroplasty (THA) is planned after failed internal fixation for femoral neck fracture. Methods. We retrospectively included 340 patients who underwent conversion THA after internal fixation for femoral neck fracture from January 2008 to September 2020. Those patients constituted two groups: noninfected patients and patients diagnosed with FRI according to the 2013 International Consensus Meeting Criteria. Receiver operating characteristic (ROC) curves were used to determine maximum sensitivity and specificity of these two preoperative ratios. The diagnostic performance of the two ratios combined with preoperative CRP or ESR was also evaluated. Results. The numbers of patients with and without FRI were 19 (5.6%) and 321 (94.4%), respectively. Areas under the ROC curve for diagnosing FRI were 0.763 for MLR, 0.686 for NLR, 0.905 for CRP, and 0.769 for ESR. Based on the Youden index, the optimal predictive cutoffs were 0.25 for MLR and 2.38 for NLR. Sensitivity and specificity were 78.9% and 71.0% for MLR, and 78.9% and 56.4% for NLR, respectively. The combination of CRP with MLR showed a sensitivity of 84.2% and specificity of 94.6%, while the corresponding values for the combination of CRP with NLR were 89.5% and 91.5%, respectively. Conclusion. The presence of preoperative FRI among patients undergoing conversion THA after internal fixation for femoral neck fracture should be determined. The combination of preoperative CRP with NLR is sensitive tool for screening FRI in those patients. Cite this article: Bone Joint J 2021;103-B(9):1534–1540


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 97 - 102
1 Jan 2022
Hijikata Y Kamitani T Nakahara M Kumamoto S Sakai T Itaya T Yamazaki H Ogawa Y Kusumegi A Inoue T Yoshida T Furue N Fukuhara S Yamamoto Y

Aims. To develop and internally validate a preoperative clinical prediction model for acute adjacent vertebral fracture (AVF) after vertebral augmentation to support preoperative decision-making, named the after vertebral augmentation (AVA) score. Methods. In this prognostic study, a multicentre, retrospective single-level vertebral augmentation cohort of 377 patients from six Japanese hospitals was used to derive an AVF prediction model. Backward stepwise selection (p < 0.05) was used to select preoperative clinical and imaging predictors for acute AVF after vertebral augmentation for up to one month, from 14 predictors. We assigned a score to each selected variable based on the regression coefficient and developed the AVA scoring system. We evaluated sensitivity and specificity for each cut-off, area under the curve (AUC), and calibration as diagnostic performance. Internal validation was conducted using bootstrapping to correct the optimism. Results. Of the 377 patients used for model derivation, 58 (15%) had an acute AVF postoperatively. The following preoperative measures on multivariable analysis were summarized in the five-point AVA score: intravertebral instability (≥ 5 mm), focal kyphosis (≥ 10°), duration of symptoms (≥ 30 days), intravertebral cleft, and previous history of vertebral fracture. Internal validation showed a mean optimism of 0.019 with a corrected AUC of 0.77. A cut-off of ≤ one point was chosen to classify a low risk of AVF, for which only four of 137 patients (3%) had AVF with 92.5% sensitivity and 45.6% specificity. A cut-off of ≥ four points was chosen to classify a high risk of AVF, for which 22 of 38 (58%) had AVF with 41.5% sensitivity and 94.5% specificity. Conclusion. In this study, the AVA score was found to be a simple preoperative method for the identification of patients at low and high risk of postoperative acute AVF. This model could be applied to individual patients and could aid in the decision-making before vertebral augmentation. Cite this article: Bone Joint J 2022;104-B(1):97–102


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 874 - 880
1 Jul 2020
Langerhuizen DWG Bergsma M Selles CA Jaarsma RL Goslings JC Schep NWL Doornberg JN

Aims. The aim of this study was to investigate whether intraoperative 3D fluoroscopic imaging outperforms dorsal tangential views in the detection of dorsal cortex screw penetration after volar plating of an intra-articular distal radial fracture, as identified on postoperative CT imaging. Methods. A total of 165 prospectively enrolled patients who underwent volar plating for an intra-articular distal radial fracture were retrospectively evaluated to study three intraoperative imaging protocols: 1) standard 2D fluoroscopic imaging with anteroposterior (AP) and elevated lateral images (n = 55); 2) 2D fluoroscopic imaging with AP, lateral, and dorsal tangential views images (n = 50); and 3) 3D fluoroscopy (n = 60). Multiplanar reconstructions of postoperative CT scans served as the reference standard. Results. In order to detect dorsal screw penetration, the sensitivity of dorsal tangential views was 39% with a negative predictive value (NPV) of 91% and an accuracy of 91%; compared with a sensitivity of 25% for 3D fluoroscopy with a NPV of 93% and an accuracy of 93%. On the postoperative CT scans, we found penetrating screws in: 1) 40% of patients in the 2D fluoroscopy group; 2) in 32% of those in the 2D fluoroscopy group with AP, lateral, and dorsal tangential views; and 3) in 25% of patients in the 3D fluoroscopy group. In all three groups, the second compartment was prone to penetration, while the postoperative incidence decreased when more advanced imaging was used. There were no penetrating screws in the third compartment (extensor pollicis longus groove) in the 3D fluoroscopy groups, and one in the dorsal tangential views group. Conclusion. Advanced intraoperative imaging helps to identify screws which have penetrated the dorsal compartments of the wrist. However, based on diagnostic performance characteristics, one cannot conclude that 3D fluoroscopy outperforms dorsal tangential views when used for this purpose. Dorsal tangential views are sufficiently accurate to detect dorsal screw penetration, and arguably more efficacious than 3D fluoroscopy. Cite this article: Bone Joint J 2020;102-B(7):874–880


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 1 - 1
1 Oct 2022
Simon S Frank BJH Aichmair A Dominkus M Mitterer JA Hartmann S Kasparek M Hofstätter J
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Purpose. Unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic revision-total-knee-arthroplasties (rTKA) are common, and the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, an identification of an underlying pathogen was not possible, so called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate alpha defensin (AD) levels in these patient populations. Methods. In this retrospective analysis of our prospectively maintained biobank, we evaluated synovial AD levels from 143 rTKAs. The 2018-Musculoskeletal Infection Society score (MSIS) was used to define our study groups. Overall, 20 rTKA with UPIC with a minimum of one positive intraoperative culture with MSIS 2-≥6 and 14 UNIC samples with MSIS≥6 were compared to 34 septic culture-positive samples (MSIS ≥6) and 75 aseptic culture-negative (MSIS 0–1) rTKAs. Moreover, we compared the performance of both AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) to test the presence of AD in native and centrifuged synovial fluid. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were considered. Results. AD was detected in 31/34 (91.2%) samples from the infected-group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly (p<0.001) associated with culture positive and infection related histopathological results. Moreover, we found significantly (p=0.001) more high-virulent microorganisms 19/34 (55.9%) in the infected-group compared to the UPIC-group (0/20). Samples from the infected group with high virulent microorganisms 17/19 (89.5%) showed a positive AD. The presence of methicillin resistant Staphylococcus epidermis (MRSE) led to increased AD (p=0.003) levels when compared to those determined in samples positive for methicillin susceptible S. epidermdis (MSSE). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. Conclusion. AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnostic of UPIC and UNIC associated to rTKAs. AD levels produced by patients with PJIs caused by high-virulent microorganisms and MRSE are significantly higher compared to those in patients with PJIs caused by either low-virulent or antibiotic susceptible microorganisms. Centrifugation of synovial fluid had no influence in the outcome of ADLF quantification. Keywords: Alpha-defensin, UPIC, UNIC, revision-knee-arthroplasty


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 55 - 55
1 Dec 2019
Klim S Glehr G Amerstorfer F Leitner L Krassnig R Leithner A Bernhardt G Glehr M
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Aim. In the diagnosis of prosthetic joint infection (PJI), many biomarkers have shown a sound performance in terms of accuracy, sensitivity and specificity. In this study we aimed to test the frequently used serum biomarkers C-reactive Protein (CRP), Fibrinogen, Leukocytes, Interleukin-6 (IL-6), Interferon alpha (IF-alpha) and Procalcitonin (PCT) regarding these qualities. Following that, the optimal multi-biomarker combination was calculated to further improve the diagnostic performance. Method. 124 knee or hip revision arthroplasty procedures were prospectively investigated focusing on preoperative serum blood levels of CRP, Fibrinogen, Leukocytes, IL-6, IF-alpha and PCT. The presence of PJI was determined by a blinded researcher. Logistic regression with lasso-regularization was used for the biomarkers and all their ratios. Following cross-validation on a training sample set to get optimal performance estimates, we performed the final model on a test set (25% of all samples). Results. Out of all evaluated biomarkers, CRP (AUC 0.91, p-value 0.03) and Fibrinogen (AUC 0.93, p-value 0.02) had the best performances. The optimal combination when testing multiple biomarkers in 32 cross-validation runs was calculated including Fibrinogen, CRP, the ratio of Fibrinogen to CRP and the ratio of serum Thrombocytes to CRP (AUC 0.92, accuracy 0.77, specificity 0.92, sensitivity 0.68, cut-off 0.63, p-value 0.04). Conclusions. It was not possible to increase the diagnostic performance by combining multiple biomarkers using sophisticated statistical methods. The calculated Multi-biomarker models did not improve the AUC, accuracy, sensitivity and specificity when compared to single biomarkers


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 84 - 84
1 Dec 2018
Lemans J Hobbelink M IJpma F van den Kieboom J Bosch P Leenen L Kruyt M Plate J Glaudemans A Govaert G
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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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_14 | Pages 20 - 20
1 Dec 2022
Gallazzi E Famiglini L La Maida GA Giorgi PD Misaggi B Cabitza F
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Introduction:. Most of the published papers on AI based diagnosis have focused on the algorithm's diagnostic performance in a ‘binary’ setting (i.e. disease vs no disease). However, no study evaluated the actual value for the clinicians of an AI based approach in diagnostic. Detection of Traumatic thoracolumbar (TL) fractures is challenging on planar radiographs, resulting in significant rates of missed diagnoses (30-60%), thus constituting a field in which a performance improvement is needed. Aim of this study is therefore to evaluate the value provided by AI generated saliency maps (SM), i.e. the maps that highlight the AI identified region of interests. Methods:. An AI model aimed at identifying TL fractures on plain radiographs was trained and tested on 567 single vertebrae images. Three expert spine surgeons established the Ground Truth (GT) using CT and MRI to confirm the presence of the fracture. From the test set, 12 cases (6 with a GT of fracture and 6 with a GT of no fracture, associated with varying levels of algorithm confidence) were selected and the corresponding SMs were generated and shown to 7 independent evaluators with different grade of experience; the evaluators were requested to: (1) identify the presence or absence of a fracture before and after the saliency map was shown; (2) grade, with a score from 1 (low) to 6 (high) the pertinency (correlation between the map and the human diagnosis), and the utility (the perceived utility in confirming or not the initial diagnosis) of the SM. Furthermore, the usefulness of the SM was evaluated through the rate of correct change in diagnosis after the maps had been shown. Finally, the obtained scores were correlated with the algorithm confidence for the specific case. Results:. Of the selected maps, 8 had an agreement between the AI diagnosis and the GT, while in 4 the diagnosis was discordant (67% accuracy). The pertinency of the map was found higher when the AI diagnosis was the same as the GT and the human diagnosis (respectively p-value = .021 and <.000). A positive and significant correlation between the AI confidence score and the perceived utility (Spearman: 27%, p-value=.0-27) was found. Furthermore, evaluator with experience < 5 year found the maps more useful than the experts (z-score=2.004; p-value=.0455). Among the 84 evaluation we found 12 diagnostic errors in respect to the GT, 6 (50%) of which were reverted after the saliency map evaluation (z statistic = 1.25 and p-value = .21). Discussion:. The perceived utility of AI generated SM correlate with the model confidence in the diagnosis. This highlights the fact that to be considered helpful, the AI must provide not only the diagnosis but also the case specific confidence. Furthermore, the perceived utility was higher among less experienced users, but overall, the SM were useful in improving the human diagnostic accuracy. Therefore, in this setting, the AI enhanced approach provides value in improving the human performance


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 51 - 51
1 Dec 2019
Karbysheva S Yermak K Trampuz A
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Aim. To evaluate the analytical performance of synovial fluid D-lactate test for the diagnosis of PJI. Method. Consecutive patients undergoing diagnostic joint aspiration of prosthetic joint were prospectively included. PJI was diagnosed according to the proposed European Bone and Joint Infection Society (EBJIS) definition criteria. Synovial fluid was collected for culture, D-lactate measurement (by spectrophotometry, λ = 570 nm) and leukocyte count and differential (by flow cytometry). The receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of D-lactate and leukocyte count. Results. Diagnostic joint aspiration was performed in 224 patients with prosthetic joints. PJI was diagnosed in 87 patients (39%). The optimal D-lactate cut-off value for diagnosing PJI was 1.2 mmol/l. The sensitivity of synovial fluid D-lactate was 97.7%, specificity 83.9%, whereas the sensitivity of synovial fluid leukocyte count was 87.5% with specificity 95.7%. Concentration of SF D-lactate was significantly higher in patients with PJI compared to aseptic loosening of prosthesis (median (range)) 2.33 (0.99–3.36) vs 0.77 (0.01–2.4), p<0.0001. We found positive correlation between D-lactate and erythrocytes in synovial fluid sample in the aseptic group (ρ = 0.339, p< 0.01). Conclusions. The synovial fluid D-lactate showed a good diagnostic performance for the diagnosis of PJI, which was comparable to the synovial fluid leukocyte count. Currently available (UV)-based method for detection of D-lactate showed low specificity (84%) due to influence of hemoglobin with the similar absorbance wavelengths (λ = 540 nm). More specific high-performance methods such as electro-chemical sensing system or lateral flow immunochromatographic assays should be implemented


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 6 | Pages 781 - 785
1 Jun 2005
Temmerman OPP Raijmakers PGHM Berkhof J Hoekstra OS Teule GJJ Heyligers IC

In this meta-analysis we included 32 English-language articles published between January 1975 and June 2004 on the diagnostic performance of plain radiography, subtraction arthrography, nuclear arthrography and bone scintigraphy in detecting aseptic loosening of the femoral component, using criteria based on the Cochrane systematic review of screening and diagnostic tests. The mean sensitivity and specificity were, respectively, 82% (95% confidence interval (CI) 76 to 87) and 81% (95% CI 73 to 87) for plain radiography and 85% (95% CI 75 to 91) and 83% (95% CI 75 to 89) for nuclear arthrography. Pooled sensitivity and specificity were, respectively, 86% (95% CI 74 to 93) and 85% (95% CI 77 to 91) for subtraction arthrography and 85% (95% CI 79 to 89) and 72% (95% CI 64 to 79) for bone scintigraphy. Although the diagnostic performance of the imaging techniques was not significantly different, plain radiography and bone scintigraphy are preferred for the assessment of a femoral component because of their efficacy and lower risk of patient morbidity


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 47 - 47
1 Dec 2021
Lüthje FL Skovgaard K Jensen HE Heegaard P Gottlieb H Kirketerp-M⊘ller K Blirup SA Jensen LK
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Aim. The liver is the major source of acute phase proteins (APPs) and serum concentrations of several APPs are widely used as markers of inflammation and infection. The aim of the present study was to explore if a local extra hepatic osseous acute phase response occurs during osteomyelitis. Method. The systemic (liver tissue and serum) and local (bone tissue) expression of several APPs during osteomyelitis was investigated with qPCR and ELISA in a porcine model of implant associated osteomyelitis (IAO) at 5, 10 and 15 days after inoculation with S. aureus or saline, respectively. Additionally, samples were also collected from normal heathy pigs and pigs with spontaneous, chronic, haematogenous osteomyelitis. Afterwards, immunohistochemistry towards different upregulated APPs was performed on the porcine osteomyelitis lesions and on bone biopsies from human patients with chronic osteomyelitis. Results. All infected porcine bone lesions (apart from Day 5 in the IAO model) were made up by necrosis, pus, and various degree of fibrotic encapsulation. A local, highly significant upregulation of Serum Amyloid A (SAA, up to 4000-fold upregulation), Complement component C3 (C3), and Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4) were present in infected pigs compared to sterile controls. For the experimental IAO animals, the upregulation of C3 and ITIH4 increased over time, i.e., the highest expression was seen on day 15 after bacterial inoculation. In the liver, only C-reactive protein (CRP) and ITIH4 (not SAA or C3) were slightly upregulated in infected pigs. Serum concentrations of CRP, SAA and haptoglobin were only upregulated at day 5 in IAO infected animals. Immunohistochemically, comparable numbers of APP positive cells (leucocytes and bone cells) were found in human and porcine bone samples with chronic osteomyelitis. Conclusions. This is to our knowledge the first description of local APP up-regulation during chronic bone infection. Only small changes in the expression of APPs were found in the liver and serum samples. Thus, the presence of an osseous upregulation of APPs appears to be part of a predominantly local response that will be difficult to measure systemically. The importance of a local immune response in bone infections seems logical as the blood supply is severely impaired during osteomyelitis. There is a real need for supportive diagnostic bone infection criteria which should be based on a comprehensive understanding of the local inflammatory response. As seen from the present study, staining for SAA or C3 could potentially improve the diagnostic performance of histopathology


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 32 - 32
1 Dec 2021
Mihalic R Zdovc J Brumat P Trebse R
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Aim. The cut-off values for synovial fluid leukocyte count and neutrophils differential (%PMN) for differentiating aseptic from septic failure in total knee arthroplasties were already defined in the past. Our goal was to determine the cut-off values for synovial fluid leukocyte count and %PMN in failed total hip arthroplasties (THA). Method. Patients undergoing revision THA were prospectively included. In perioperative assessment phase, synovial fluid leukocyte count and %PMN were determined. During the surgery, at least 4 intraoperative samples for microbiological and one for histopathological analysis were obtained. Infection was defined as presence of sinus tract, inflammation in histopathological samples, and ≥2 tissue and/or synovial fluid samples growing the same microorganism. Exclusion criteria were systemic inflammatory diseases, revision surgery performed less than 3 months from index surgery and insufficient tissue sampling. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance and Youden's J statistic was computed to identify optimal cut-off values. Results. During the study period (between June 2006 and June 2011) 227 revision THAs were performed by the senior author. 31 patients were excluded. 196 patients (mean age, 69 years; 68% females) with THA failure were included. Aseptic failure was diagnosed in 150 patients (76,5%) and THA infection was diagnosed in 46 patients (23,5%). Synovial fluid leukocyte counts were significantly higher in the infected group (median, 5.50×10. 6. leukocytes/ml range, 0.05 to 143.9×10. 6. leukocytes/mL) than in the aseptic group (median, 0.23×10. 6. cells/ml; range, 0 to 21.3×10. 6. leukocytes/ml, P<0,0001). The %PMN was also significantly higher in the infected group (median, 83%; range, 6% to 97%) than in the aseptic group (median, 27,5%; range, 0% to 94%, P<0,0001). A synovial fluid leukocyte count of > 1.54×10. 6. leukocytes/ml, had a sensitivity of 63%, specificity of 95%, positive and negative predictive values of 78% and 89%, respectively. A synovial fluid %PMN of > 64%, had a sensitivity of 65%, specificity of 93%, positive and negative predictive values of 73% and 90%, respectively. Conclusion. The synovial fluid leukocyte count of > 1.54×10. 6. leukocytes/ml and %PMN of > 64% are useful and reliable tests for excluding THA infection, having a negative predictive value of around 90%. This tests and calculated cut-off values are highly recommended in the diagnostic process of failed THAs


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 33 - 33
1 Dec 2021
Logoluso N Balato G Pellegrini AV De Vecchi E Romanò CL Drago L Lenzi M Ascione T
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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


Bone & Joint Research
Vol. 7, Issue 1 | Pages 79 - 84
1 Jan 2018
Tsang STJ McHugh MP Guerendiain D Gwynne PJ Boyd J Simpson AHRW Walsh TS Laurenson IF Templeton KE

Objectives. Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. Methods. Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. Results. The prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = 0.005), failing to identify its presence in approximately one-third of patients undergoing joint arthroplasty surgery. Conclusion. Modelling these results to national surveillance data, it was estimated that approximately 5000 to 8000 S. aureus surgical site infections could be prevented, and approximately $140 million to $950 million (approximately £110 million to £760 million) saved in treatment costs annually in the United States and United Kingdom combined, by using alternative diagnostic methods to direct culture in preoperative S. aureus screening and eradication programmes. Cite this article: S. T. J. Tsang, M. P. McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh, I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed. Bone Joint Res 2018;7:79–84. DOI: 10.1302/2046-3758.71.BJR-2017-0175.R1