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The Bone & Joint Journal
Vol. 103-B, Issue 12 | Pages 1745 - 1753
1 Dec 2021
Walinga AB Stornebrink T Langerhuizen DWG Struijs PAA Kerkhoffs GMMJ Janssen SJ

Aims. This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint?. Methods. We performed a search of PubMed, Embase, and Cochrane libraries for relevant studies published between January 1980 and April 2020. Of 3,209 identified studies, we included 27 after full screening. Sensitivity, specificity, area under the curve, and Youden index of diagnostic tests were extracted from included studies. We grouped test characteristics per diagnostic modality. We extracted the definitions used to establish a definitive diagnosis of bacterial arthritis of a native joint per study. Results. Overall, 28 unique diagnostic tests for diagnosing bacterial arthritis of a native joint were identified. The following five tests were deemed most useful: serum ESR (sensitivity: 34% to 100%, specificity: 23% to 93%), serum CRP (sensitivity: 58% to 100%, specificity: 0% to 96%), serum procalcitonin (sensitivity: 0% to 100%, specificity: 68% to 100%), the proportion of synovial polymorphonuclear cells (sensitivity: 42% to 100%, specificity: 54% to 94%), and the gram stain of synovial fluid (sensitivity: 27% to 81%, specificity: 99% to 100%). Conclusion. Diagnostic methods with relatively high sensitivities, such as serum CRP, ESR, and synovial polymorphonuclear cells, are useful for screening. Diagnostic methods with a relatively high specificity, such as serum procalcitonin and synovial fluid gram stain, are useful for establishing a diagnosis of bacterial arthritis. This review helps to interpret the value of various diagnostic tests for diagnosing bacterial arthritis of a native joint in clinical practice. Cite this article: Bone Joint J 2021;103-B(12):1745–1753


Bone & Joint Research
Vol. 12, Issue 9 | Pages 559 - 570
14 Sep 2023
Wang Y Li G Ji B Xu B Zhang X Maimaitiyiming A Cao L

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 431 - 438
15 Mar 2023
Vendeuvre T Tabard-Fougère A Armand S Dayer R

Aims. This study aimed to evaluate rasterstereography of the spine as a diagnostic test for adolescent idiopathic soliosis (AIS), and to compare its results with those obtained using a scoliometer. Methods. Adolescents suspected of AIS and scheduled for radiographs were included. Rasterstereographic scoliosis angle (SA), maximal vertebral surface rotation (ROT), and angle of trunk rotation (ATR) with a scoliometer were evaluated. The area under the curve (AUC) from receiver operating characteristic (ROC) plots were used to describe the discriminative ability of the SA, ROT, and ATR for scoliosis, defined as a Cobb angle > 10°. Test characteristics (sensitivity and specificity) were reported for the best threshold identified using the Youden method. AUC of SA, ATR, and ROT were compared using the bootstrap test for two correlated ROC curves method. Results. Of 212 patients studied, 146 (69%) had an AIS. The AUC was 0.74 for scoliosis angle (threshold 12.5°, sensitivity 75%, specificity 65%), 0.65 for maximal vertebral surface rotation (threshold 7.5°, sensitivity 63%, specificity 64%), and 0.82 for angle of trunk rotation (threshold 5.5°, sensitivity 65%, specificity 80%). The AUC of ROT was significantly lower than that of ATR (p < 0.001) and SA (p < 0.001). The AUCs of ATR and SA were not significantly different (p = 0.115). Conclusion. The rasterstereographic scoliosis angle has better diagnostic characteristics than the angle of trunk rotation evaluated with a scoliometer, with similar AUCs and a higher sensitivity. Cite this article: Bone Joint J 2023;105-B(4):431–438


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 5 | Pages 734 - 736
1 Sep 1993
Otremski I Newman R Kahn P Stadler J Kariv N Skornik Y Goldman G

This new blood test for infection is based on the phenomenon of leukergy in which white cells agglomerate in the peripheral blood of patients with inflammatory diseases. It was used in 26 patients with proven bone or joint infection and was positive in 25. The leukergy test was more accurate than the ESR, white cell count or blood culture. The percentage of cells agglomerated correlated with the clinical severity of the infection and the test detected reactivation of the septic process better than the other haematological tests. It is a rapid and inexpensive method which is useful in the diagnosis and management of bone and joint infections.


Bone & Joint Open
Vol. 2, Issue 10 | Pages 796 - 805
1 Oct 2021
Plumarom Y Wilkinson BG Willey MC An Q Marsh L Karam MD

Aims

The modified Radiological Union Scale for Tibia (mRUST) fractures score was developed in order to assess progress to union and define a numerical assessment of fracture healing of metadiaphyseal fractures. This score has been shown to be valuable in predicting radiological union; however, there is no information on the sensitivity, specificity, and accuracy of this index for various cut-off scores. The aim of this study is to evaluate sensitivity, specificity, accuracy, and cut-off points of the mRUST score for the diagnosis of metadiaphyseal fractures healing.

Methods

A cohort of 146 distal femur fractures were retrospectively identified at our institution. After excluding AO/OTA type B fractures, nonunions, follow-up less than 12 weeks, and patients aged less than 16 years, 104 sets of radiographs were included for analysis. Anteroposterior and lateral femur radiographs at six weeks, 12 weeks, 24 weeks, and final follow-up were separately scored by three surgeons using the mRUST score. The sensitivity and specificity of mean mRUST score were calculated using clinical and further radiological findings as a gold standard for ultimate fracture healing. A receiver operating characteristic curve was also performed to determine the cut-off points at each time point.



The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 21 - 28
1 Jan 2023
Ndlovu S Naqshband M Masunda S Ndlovu K Chettiar K Anugraha A

Aims. Clinical management of open fractures is challenging and frequently requires complex reconstruction procedures. The Gustilo-Anderson classification lacks uniform interpretation, has poor interobserver reliability, and fails to account for injuries to musculotendinous units and bone. The Ganga Hospital Open Injury Severity Score (GHOISS) was designed to address these concerns. The major aim of this review was to ascertain the evidence available on accuracy of the GHOISS in predicting successful limb salvage in patients with mangled limbs. Methods. We searched electronic data bases including PubMed, CENTRAL, EMBASE, CINAHL, Scopus, and Web of Science to identify studies that employed the GHOISS risk tool in managing complex limb injuries published from April 2006, when the score was introduced, until April 2021. Primary outcome was the measured sensitivity and specificity of the GHOISS risk tool for predicting amputation at a specified threshold score. Secondary outcomes included length of stay, need for plastic surgery, deep infection rate, time to fracture union, and functional outcome measures. Diagnostic test accuracy meta-analysis was performed using a random effects bivariate binomial model. Results. We identified 1,304 records, of which six prospective cohort studies and two retrospective cohort studies evaluating a total of 788 patients were deemed eligible for inclusion. A diagnostic test meta-analysis conducted on five cohort studies, with 474 participants, showed that GHOISS at a threshold score of 14 has a pooled sensitivity of 93.4% (95% confidence interval (CI) 78.4 to 98.2) and a specificity of 95% (95% CI 88.7 to 97.9) for predicting primary or secondary amputations in people with complex lower limb injuries. Conclusion. GHOISS is highly accurate in predicting success of limb salvage, and can inform management and predict secondary outcomes. However, there is a need for high-quality multicentre trials to confirm these findings and investigate the effectiveness of the score in children, and in predicting secondary amputations. Cite this article: Bone Joint J 2023;105-B(1):21–28


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 158 - 165
1 Feb 2023
Sigmund IK Yeghiazaryan L Luger M Windhager R Sulzbacher I McNally MA

Aims. The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI). Methods. In this retrospective diagnostic study, patients undergoing revision surgery after total hip or knee arthroplasty (n = 119) between January 2015 and July 2018 were included. Multiple specimens of the periprosthetic membrane and pseudocapsule were obtained for histopathological analysis at revision arthroplasty. Based on the Infectious Diseases Society of America (IDSA) 2013 criteria, the International Consensus Meeting (ICM) 2018 criteria, and the European Bone and Joint Infection Society (EBJIS) 2021 criteria, PJI was defined. Using a mixed effects logistic regression model, the sensitivity and specificity of the histological diagnosis were calculated. The optimal number of periprosthetic tissue specimens for histopathological analysis was determined by applying the Youden index. Results. Based on the EBJIS criteria (excluding histology), 46 (39%) patients were classified as infected. Four to six specimens showed the highest Youden index (four specimens: 0.631; five: 0.634; six: 0.632). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of five tissue specimens were 76.5% (95% confidence interval (CI) 67.6 to 81.4), 86.8% (95% CI 81.3 to 93.5), 66.0% (95% CI 53.2 to 78.7), and 84.3% (95% CI 79.4 to 89.3), respectively. The area under the curve (AUC) was calculated with 0.81 (as a function of the number of tissue specimens). Applying the ICM and IDSA criteria (excluding histology), 40 (34%) and 32 (27%) patients were categorized as septic. Three to five specimens had the highest Youden index (ICM 3: 0.648; 4: 0.651; 5: 0.649) (IDSA 3: 0.627; 4: 0.629; 5: 0.625). Conclusion. Three to six tissue specimens of the periprosthetic membrane and pseudocapsule should be collected at revision arthroplasty and analyzed by a pathologist experienced and skilled in interpreting periprosthetic tissue. Cite this article: Bone Joint J 2023;105-B(2):158–165


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 18 - 25
1 Jan 2021
McNally M Sousa R Wouthuyzen-Bakker M Chen AF Soriano A Vogely HC Clauss M Higuera CA Trebše R

Aims. The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. Methods. This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. Results. This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI. Conclusion. The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18–25


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


Bone & Joint Open
Vol. 1, Issue 12 | Pages 737 - 742
1 Dec 2020
Mihalič R Zdovc J Brumat P Trebše R

Aims. Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Methods. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. Results. In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. Conclusions. Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI. Level of Evidence: Therapeutic Level II. Cite this article: Bone Jt Open 2020;1-12:737–742


Bone & Joint Research
Vol. 10, Issue 8 | Pages 536 - 547
2 Aug 2021
Sigmund IK McNally MA Luger M Böhler C Windhager R Sulzbacher I

Aims. Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. Methods. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared. Results. Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001). Conclusion. With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: Bone Joint Res 2021;10(8):536–547


The Bone & Joint Journal
Vol. 99-B, Issue 1 | Pages 66 - 72
1 Jan 2017
Sigmund IK Holinka J Gamper J Staats K Böhler C Kubista B Windhager R

Aims. The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, α-defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of α-defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. Patients and Methods. We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of α-defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. Results. The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p-values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). Conclusion. With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI. Cite this article: Bone Joint J 2017;99-B:66–72


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 904 - 911
1 Jul 2020
Sigmund IK Dudareva M Watts D Morgenstern M Athanasou NA McNally MA

Aims. The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. Methods. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results. Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10. 9. /l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion. The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 26 - 31
4 Jan 2021
Kildow BJ Ryan SP Danilkowicz R Lazarides AL Penrose C Bolognesi MP Jiranek W Seyler TM

Aims. Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI. Methods. In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31


Bone & Joint Research
Vol. 10, Issue 1 | Pages 85 - 95
27 Jan 2021
Akhbari P Jaggard MK Boulangé CL Vaghela U Graça G Bhattacharya R Lindon JC Williams HRT Gupte CM

Aims. The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. Methods. In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. Results. A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). Conclusion. Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85–95


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 6 | Pages 713 - 719
1 Jun 2011
Duckworth AD Ring D McQueen MM

A suspected fracture of the scaphoid remains difficult to manage despite advances in knowledge and imaging methods. Immobilisation and restriction of activities in a young and active patient must be balanced against the risks of nonunion associated with an undiagnosed and undertreated fracture of the scaphoid. The assessment of diagnostic tests for a suspected fracture of the scaphoid must take into account two important factors. First, the prevalence of true fractures among suspected fractures is low, which greatly reduces the probability that a positive test will correspond with a true fracture, as false positives are nearly as common as true positives. This situation is accounted for by Bayesian statistics. Secondly, there is no agreed reference standard for a true fracture, which necessitates the need for an alternative method of calculating diagnostic performance characteristics, based upon a statistical method which identifies clinical factors tending to associate (latent classes) in patients with a high probability of fracture. The most successful diagnostic test to date is MRI, but in low-prevalence situations the positive predictive value of MRI is only 88%, and new data have documented the potential for false positive scans. The best strategy for improving the diagnosis of true fractures among suspected fractures of the scaphoid may well be to develop a clinical prediction rule incorporating a set of demographic and clinical factors which together increase the pre-test probability of a fracture of the scaphoid, in addition to developing increasingly sophisticated radiological tests


Bone & Joint Research
Vol. 9, Issue 5 | Pages 202 - 210
1 May 2020
Trotter AJ Dean R Whitehouse CE Mikalsen J Hill C Brunton-Sim R Kay GL Shakokani M Durst AZE Wain J McNamara I O’Grady J

Aims. This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods. A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results. According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion. This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required. Cite this article:Bone Joint Res. 2020;9(5):202–210


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 40 - 48
1 Jan 2016
Matharu GS Mansour R Dada O Ostlere S Pandit HG Murray DW

Aims. The aims of this study were to compare the diagnostic test characteristics of ultrasound alone, metal artefact reduction sequence MRI (MARS-MRI) alone, and ultrasound combined with MARS-MRI for identifying intra-operative pseudotumours in metal-on-metal hip resurfacing (MoMHR) patients undergoing revision surgery. . Methods. This retrospective diagnostic accuracy study involved 39 patients (40 MoMHRs). The time between imaging modalities was a mean of 14.6 days (0 to 90), with imaging performed at a mean of 5.3 months (0.06 to 12) before revision. The prevalence of intra-operative pseudotumours was 82.5% (n = 33). Results. Agreement with the intra-operative findings was 82.5% (n = 33) for ultrasound alone, 87.5% (n = 35) for MARS-MRI alone, and 92.5% (n = 37) for ultrasound and MARS-MRI combined. The diagnostic characteristics for ultrasound alone and MARS-MRI alone reached similar sensitivities (90.9% vs 93.9%) and positive predictive values (PPVs; 88.2% vs 91.2%), but higher specificities (57.1% vs 42.9%) and negative predictive values (NPVs; 66.7% vs 50.0%) were achieved with MARS-MRI. Ultrasound and MARS-MRI combined produced 100% sensitivity and 100% NPV, whilst maintaining both specificity (57.1%) and PPV (91.7%). For the identification of a pseudotumour, which was confirmed at revision surgery, agreement was substantial for ultrasound and MARS-MRI combined (κ = 0.69), moderate for MARS-MRI alone (κ = 0.54), and fair for ultrasound alone (κ = 0.36). Discussion. These findings suggest that ultrasound and/or MARS-MRI have a role when assessing patients with a MoMHR, with the choice dependent on local financial constraints and the availability of ultrasound expertise. However in patients with a MoMHR who require revision, combined imaging was most effective. Take home message: Combined imaging with ultrasound and MARS-MRI always identified intra-operative pseudotumours if present. Furthermore, if neither imaging modality showed a pseudotumour, one was not found intra-operatively. Cite this article: Bone Joint J 2016;98-B:40–8


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 119 - 124
1 Jan 2018
Broderick C Hopkins S Mack DJF Aston W Pollock R Skinner JA Warren S

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