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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 61 - 61
1 Dec 2018
Loppini M Traverso F Ferrari MC Avigni R Leone R Bottazzi B Mantovani A Grappiolo G
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Aim. Diagnosis of periprosthetic joint infection (PJI) is challenging given the limitations of available diagnostic tests. Recently, several studies have shown a role of the long pentraxin PTX3 as a biomarker in inflammatory diseases and infections. This single-center prospective diagnostic study evaluated the diagnostic ability of synovial fluid and serum PTX3 for the infection of total hip arthroplasty (THA) and total knee arthroplasty (TKA). Method. Consecutive patients undergoing revision surgery for painful THA or TKA were enrolled. Patients with antibiotic therapy suspended for less than 2 weeks prior to surgery and patients eligible for metal-on-metal implant revision or spacer removal and prosthesis re-implantation were excluded. Quantitative assessment of synovial fluid and serum PTX3 was performed with ELISA method. Musculoskeletal Infection Society (MSIS) criteria were used as reference standard for diagnosis of PJI. Continuous data values were compared for statistical significance with univariate unpaired, 2-tailed Student's t-tests. Receiver operating characteristic (ROC) curve analyses was performed to assess the ability of serum and synovial fluid PTX3 concentration to determine the presence of PJI. Youden's J statistic was used to determine optimum threshold values for the diagnosis of infection. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative (LR-) likelihood ratio, area under the ROC curve (AUC) were calculated. Results. One-hundred fifteen patients (M:F=49:66) with a mean age of 62 years (40–79) underwent revision of THA (n=99) or TKA (n=16). According with MSIS criteria, 18 cases were categorized as septic and 97 as aseptic revisions. The average synovial fluid concentration of PTX3 was significantly higher in patients with PJI compared to patients undergoing aseptic revision (24,3 ng/dL vs 3,64 ng/dL; P=0.002). There was no significant difference in terms of serum concentration of PTX3 between the two groups. Synovial fluid PTX3 demonstrated an AUC of 0.96 (95%IC 0.89–0.98) with Se 94%, Sp 90%, PPV 67%, NPV 100%, LR+ 9.4 and LR- 0.06 for a threshold value of 4.5 ng/dL. Serum PTX3 demonstrated an AUC of 0.70 (95%IC 0.51–0.87) with Se 72%, Sp 67%, PPV 30%, NPV 93%, LR+ 2.2 and LR- 0.42 for a threshold value of 4.5 ng/dL. Conclusions. In patients undergoing revision surgery for painful THA or TKA, synovial PTX3 demonstrated a strong diagnostic ability for PJI. Synovial PTX3 could represent a more useful biomarker for detection of PJI compared with serum PTX3


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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 86 - 86
1 Jul 2020
Innmann MM Grammatopoulos G Beaulé P Merle C Gotterbarm T
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Spinopelvic mobility describes the change in lumbar lordosis and pelvic tilt from standing to sitting position. For 1° of posterior pelvic tilt, functional cup anteversion increases by 0.75° after total hip arthroplasty (THA). Thus, spinopelvic mobility is of high clinical relevance regarding the risk of implant impingement and dislocation.

Our study aimed to 1) determine the proportion of OA-patients with stiff, normal or hypermobile spino-pelvic mobility and 2) to identify clinical or static standing radiographic parameters predicting spinopelvic mobility.

This prospective diagnostic cohort study followed 122 consecutive patients with end-stage osteoarthritis awaiting THA. Preoperatively, the Oxford Hip Score, Oswestry Disability Index and Schober's test were assessed in a standardized clinical examination. Lateral view radiographs were taken of the lumbar spine, pelvis and proximal femur using EOS© in standing position and with femurs parallel to the floor in order to achieve a 90°-seated position. Radiographic measurements were performed for the lumbar lordosis angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI) and pelvic-femoral-angle (PFA). The difference in PT between standing and seated allowed for patient classification based on spino-pelvic mobility into stiff (±30°).

From the standing to the sitting position, the pelvis tilted backwards by a mean of 19.6° (SD 11.6) and the hip was flexed by a mean of 57° (SD 17). Change in pelvic tilt correlated inversely with change in hip flexion.

Spinopelvic mobility is highly variable in patients awaiting THA and we could not identify any clinical or static standing radiographic parameter predicting the change in pelvic tilt from standing to sitting position. In order to identify patients with stiff or hypermobile spinopelvic mobility, we recommend performing lateral view radiographs of the lumbar spine, pelvis and proximal femur in all patients awaiting THA. Thereafter, implants and combined cup inclination/anteversion can be individually chosen to minimize the risk of dislocation.

No predictors could be identified. We recommend performing sitting and standing lateral view radiographs of the lumbar spine and pelvis to determine spinopelvic mobility in patients awaiting THA.


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. 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


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 36 - 36
7 Nov 2023
Waters R Held M Dunn R Laubscher M Adikary N Coussens A
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Specific and rapid detection methods for spinal tuberculosis, with sufficient sensitivity in HIV-1 co-infected individuals, are needed, to ensure early initiation of appropriate treatment to prevent physical disability and neurological fallout. In addition, understanding the systemic and local pathophysiology of spinal tuberculosis, and its interaction with HIV-1 infection, is crucial to guide future therapeutic interventions. We prospectively enrolled adult patients presenting with signs and symptoms of suspected spinal tuberculosis, at Groote Schuur Hospital, between November 2020 and December 2021. TB diagnostic testing was performed on open and CT-guided spinal biopsies using Xpert MTB/RIF Ultra compared to gold standards TB culture and histology. A highly sensitive droplet digital PCR assay for detecting and quantifying Mycobacterium tuberculosis complex (MTBC) and HIV-1 DNA was tested. Plasma inflammatory proteins were measured to assess systemic inflammation. Xpert Ultra had a high sensitivity of 94.7% and specificity of 100% for STB against TB culture and histology in both open and CT-guided biopsy samples. The ddPCR assay confirmed TB detection in 94% of patients with positive Xpert Ultra results. Four patients with negative TB diagnostic results had MTBC DNA detected by ddPCR. HIV-1 DNA was detected in the spinal tissues from all HIV-1-infected patients. MTBC DNA levels were significantly higher in HIV-1-co-infected spinal tissue samples (p< 0.01). We identified four biomarkers significantly associated with higher bacterial burden at the disease site (p< 0.01). Xpert Ultra and MTBC ddPCR improve the detection of STB. DdPCR can be utilized as an additional, highly sensitive tool for detecting and quantifying Mtb, in pathological samples that may be paucibacillary. These findings provide novel diagnostic and pathophysiologic insight into STB, in the context of HIV-1 infection, and provide rationale to include these tests in hospital and research settings for patients from communities burdened by TB and HIV-1


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 79 - 79
22 Nov 2024
Luger M Böhler C Staats K Windhager R Sigmund IK
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Aim. Diagnosing low-grade periprosthetic joint infections (PJI) can be very challenging due to low-virulent microorganisms capable of forming biofilm. Clinical signs can be subtle and may be similar to those of aseptic failure. To minimize morbidity and mortality and to preserve quality of life, accurate diagnosis is essential. The aim of this study was to assess the performance of various diagnostic tests in diagnosing low-grade PJI. Methods. Patients undergoing revision surgery after total hip and knee arthroplasty were included in this retrospective cohort study. A standardized diagnostic workup was performed using the components of the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI. For statistical analyses, the respective test was excluded from the infection definition to eliminate incorporation bias. Receiver-operating-characteristic curves were used to calculate the diagnostic performance of each test, and their area-under-the-curves (AUC) were compared using the z-test. Results. 422 patients undergoing revision surgery after total hip and knee arthroplasty were included in this study. 208 cases (49.3%) were diagnosed as septic. Of those, 60 infections (28.8%) were defined as low-grade PJI (symptoms >4 weeks and caused by low-virulent microorganisms (e. g. coagulase-negative staphylococci, Cutibacterium spp., enterococci and Actinomyces)). Performances of the different test methods are listed in Table 1. Synovial fluid (SF) - WBC (white blood cell count) >3000G/L (0.902), SF - %PMN (percentage of polymorphonuclear neutrophils) > 65% (0.959), histology (0.948), and frozen section (0.925) showed the best AUCs. Conclusion. The confirmatory criteria according to the EBJIS definition showed almost ideal performances in ruling-in PJI (>99% specificity). Histology and synovial fluid cell count (SF-WBC and SF-%PMN) showed excellent accuracies for diagnosing low-grade PJI. However, a reduced immune reaction in these cases may necessitate lower cut-off values. Intraoperative frozen section may be valuable in cases with inconclusive preoperative diagnosis. For any tables or figures, please contact the authors directly


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 43 - 43
22 Nov 2024
Bekkers W Zwart V Swietoslawki A Oost IK Nijs A Emmen J Van Geenen R
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Aim. Periprosthetic joint infection (PJI) is one of the main reasons for revision surgery after primary unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or total hip arthroplasty (THA). Currently the MSIS and EBJIS criteria sets are considered to be the gold standards in determining PJI. These criteria sets are complex and contain tests that are time-consuming and many are rather costly. Therefore, further research is indicated to find a simpler but equally reliable diagnostic test. In this study we evaluated the additional value of calprotectine measurement in synovial fluid in patients undergoing hip and knee (revision) arthroplasty following routine work-up. Method. In a retrospective cohort study, we analyzed 182 synovial fluid samples from 143 patients with suspected PJI after UKA, TKA, THA or revision arthroplasty. Twenty-six of those cases were classified as PJI according to the MSIS and EBJIS criteria. Subsequently, synovial calprotectin was determined, using a lateral flow assay and two cut-off thresholds of ≥14 mg/L and ≥50 mg/L. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of synovial calprotectin was determined. Results. When applying the MSIS and EBJIS criteria and a calprotectin level ≥14 mg/L, synovial calprotectin revealed an area under the curve of 0.96 (95% CI 0.90-1.00), with 92.3% sensitivity and 100% specificity. The PPV and NPV were 100% and 92.9% respectively. When applying the MSIS and EBJIS criteria and a calprotectin level ≥ 50 mg/L, synovial calprotectin revealed an area under the curve of 0.94 (95% CI 0.87-1.00), with 88.5% sensitivity and 100% specificity. The PPV and NPV were 100% and 89.7% respectively. Conclusions. The value of calprotectin in synovial fluid gives valuable information with a single test result, resulting in high predictive value in the diagnosis of PJI after hip or knee arthroplasty and should seriously be considered as part of PJI diagnostics in an outpatient clinical setting. The high specificity can help rule in patients that are suspected of PJI. Therefor this test can be helpful in a preop diagnostic work-up to avoid unnecessary revisions in patients with well-placed and well-fixed arthroplasties with a suspected PJI. These conclusions are independent of which criteria set was used as a gold standard


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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 34 - 34
1 Dec 2022
Lapner P Pollock J Hodgdon T Sheikh A Shamloo A Fernandez AA McIlquham K Desjardins M Drosdowech D Nam D Rouleau D
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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


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


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 76 - 76
1 Dec 2017
Renz N Mudrovcic S Perka C Trampuz A
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Aim. To assess the clinical characteristics, diagnostic tests and treatment strategies in orthopedic implant-associated infections (OIAI) caused by Cutibacterium spp. Method. We retrospectively included consecutive patients with OIAI caused by Cutibacterium spp. treated at our institution from January 2012 to January 2017. OIAI was diagnosed when: (i) macroscopic purulence, sinus tract or exposed implant was present; (ii) acute inflammation in peri-implant-tissue was documented; (iii) Cutibacterium spp. grew in joint aspirate, ≥2 intraoperative peri-implant tissue samples or in sonication fluid of the removed implant (>50 CFU/ml). Results. Of 67 patients with Cutibacterium OIAI, 42 (63%) had an infected joint prosthesis (21 hip, 12 shoulder, 9 knee) and 25 (37%) an infected fixation device (10 spinal hardware, 11 osteosynthesis, 2 anchorages after rotator cuff reparation, 2 cruciate ligament grafts). 53 (84%) presented with a delayed (3–24 months) or late (>24months) infection. 62 infections were caused by C. acnes and 5 by C. avidum, all being susceptible to levofloxacin and rifampin. Among non-culture-based diagnostic tests, tissue histology had the highest sensitivity (68%), followed by increased synovial fluid leukocyte count/differential (59%). Of culture-based tests, sonication fluid culture showed the highest sensitivity (83%), followed by tissue culture (71%) and synovial fluid culture (61%). Culture positivity rates of synovial fluid, peri-implant tissue and sonication fluid were 20%, 41% and 40%, respectively, after 7 days of incubation and 58%, 74% and 78%, respectively, after 14 days. Most patients were treated with one-stage (24%) or two-stage (55%) implant exchange of the implant. The majority of patients received oral levofloxacin and rifampin for 6–12 weeks. Conclusions. Cutibacterium spp. affected various types of orthopaedic implants in different anatomic locations (lower and upper limbs and spine). Conventional diagnostic tests showed limited sensitivity of Cutibacterium OIAI and can be easily missed when cultures are incubated less than 10–14 days. All Cutibacterium isolates were susceptible to levofloxacin and rifampin


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


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 16 - 16
1 Dec 2017
Loppini M Traverso F Ferrari MC Avigni R Leone R Bottazzi B Mantovani A Grappiolo G
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Aim. Diagnosis of periprosthetic joint infection (PJI) is still challenging due to limitations of available diagnostic tests. Many efforts are ongoing to find out novel methods for PJI diagnosis. Recently, several studies have shown a role of the long pentraxin PTX3 as a biomarker in inflammatory diseases and infections. This pilot diagnostic study evaluated the diagnostic ability of synovial fluid and serum PTX3 for the infection of total hip arthroplasty (THA) and total knee arthroplasty (TKA). Method. Consecutive patients undergoing revision surgery for painful THA or TKA were enrolled. Patients with antibiotic therapy suspended for less than 2 weeks prior to surgery and patients eligible for spacer removal and prosthesis re-implantation were excluded. Quantitative assessment of synovial fluid and serum PTX3 was performed with ELISA method. Musculoskeletal Infection Society (MSIS) criteria were used as reference standard for diagnosis of PJI. Continuous data values were compared for statistical significance with univariate unpaired, 2-tailed Student's t-tests. Receiver operating characteristic (ROC) curve analyses was performed to assess the ability of serum and synovial fluid PTX3 concentration to determine the presence of PJI. Youden's J statistic was used to determine optimum threshold values for the diagnosis of infection. Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative (LR-) likelihood ratio, area under the ROC curve (AUC) were calculated. Results. Sixty-two patients (M:F=28:34) with a mean age of 64 years (40–78) underwent revision of THA (n=52) or TKA (n=10). According with MSIS criteria, 10 cases were categorized as septic and 52 as aseptic revisions. The average synovial fluid concentration of PTX3 was significantly higher in patients with PJI compared to patients undergoing aseptic revision (23,56 ng/mL vs 3,71 ng/mL; P=0.0074). There was no significant difference in terms of serum concentration of PTX3 between the two groups. Synovial fluid PTX3 demonstrated an AUC of 0.93 (95%IC 0.86–0.97) with Se 100%, Sp 85%, PPV 55%, NPV 100%, LR+ 6.6 and LR- <0.01 for a threshold value of 3 ng/mL. Serum PTX3 demonstrated an AUC of 0.59 (95%IC 0.38–0.8) with Se 78%, Sp 50%, PPV 25%, NPV 90%, LR+ 1.56 and LR- 0.44 for a threshold value of 3 ng/mL. Conclusions. Synovial PTX3 demonstrated a strong diagnostic ability for PJI. PTX3 could represent a useful biomarker for detection of PJI in patients undergoing revision surgery for painful THA or TKA. Larger diagnostic studies are required to confirm these preliminary data


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_6 | Pages 95 - 95
1 Mar 2017
White P Carli A Meftah M Alexiades M Windsor R Ranawat A
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Introduction. Several studies have shown that functional outcomes are similar regardless of being discharged directly to home or to a rehabilitation center after total knee arthroplasty (TKA). Therefore, we sought to determine if there is a difference in patient care or patient satisfaction for patients discharged to in-patient rehabilitation or home-based rehabilitation. Materials and Methods. Between February and May of 2015, one hundred and seventy one consecutive patients were prospective identified after undergoing TKA by one of three surgeons. At an average of six-weeks post TKA, all patients were asked a patient administered questionnaire to determine if diagnostic testing (ultrasounds, or x-rays) or blood transfusions were performed during the first-six weeks at either home (n=86) or a rehab (n=85) facility. Results. Patients discharged to in-patient rehabilitation were found to be significantly older and sicker than patients discharged to home-based rehabilitation. Overall a greater number of diagnostic tests were performed on patient discharged to in-patient rehabilitation (23.5%) compared to patients discharged to home-based rehabilitation (8.1%) (p=0.032). Statistical analysis revealed discharge location, rather than age or health status, as the sole independent risk factor for a diagnostic testing being performed. The incidence of radiographs taken prior to the six week postoperative appointment was greater for patients discharged to rehab (10.6%) compared to those discharged home (1.1%) (p=0.008). There was no difference in the frequency of patients feeling like they received adequate physical therapy, adequate care or overall satisfaction. Twenty-nine (34.1%) patients were discharged under the care of the visiting nurse service after leaving the rehabilitation facility. Conclusions. Patients discharged to a rehabilitation facility underwent more testing than patients discharged directly to home. There was no difference in the patient satisfaction or their perception of their overall care. Over a third of patients who go to Rehab are subsequently discharged home under the care of the visiting nurse service. For any figures or tables, please contact authors directly (see Info & Metrics tab above).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 50 - 50
1 Dec 2021
Gelderman S Faber C Ploegmakers J Jutte P Kampinga G Glaudemans A Wouthuyzen-Bakker M
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Aim. Low-grade infections are difficult to diagnose. As the presence of a chronic infection requires extensive surgical debridement and antibiotic treatment, it is important to diagnose a SII prior to surgery, especially when the hardware is revised. We investigated whether serum inflammatory markers or nuclear imaging can accurately diagnose a chronic spinal instrumentation infection (SII) prior to surgery. Method. All patients who underwent revision spinal surgery after a scoliosis correction between 2017 and 2019 were retrospectively evaluated. The diagnostic accuracy of serum C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR), . 18. F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) and Technetium-99m-methylene diphosphonate (99mTc-MDP) 3-phase bone scintigraphy (TPBS) to diagnose infection were studied. Patients with an acute infection or inadequate culture sampling were excluded. SII was diagnosed if ≥ 2 of the same microorganism(s) were isolated from intra-operative tissue cultures. Results. 31 patients were included. The indication for hardware extraction was pseudoarthrosis in the majority of patients (n = 15). 22 patients (71%) were diagnosed with SII. In all infected cases, Cutibacterium acnes was isolated, including 5 cases with a polymicrobial infection. Sensitivity, specificity, PPV and NPV was: 4.5%, 100%, 100% and 30.0% for CRP >10.0 mg/L, 5.5%, 100%, 100% and 29% for ESR > 30 mm/h; 56%, 80%, 83% and 50% for FDG-PET/CT and 50%, 100%, 100% and 20% for TPBS, respectively. Conclusions. The prevalence of SII in patients undergoing revision spinal surgery is high, with Cutibacterium acnes as the main pathogen. No diagnostic tests could be identified that could accurately diagnose or exclude SII prior to surgery. Future studies should aim to find more sensitive diagnostic modalities to detect low-grade inflammation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_14 | Pages 27 - 27
1 Nov 2021
Gehrke T Althaus L Linke P Salber J Krenn V Citak M
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Arthrofibrosis is a relatively frequent complication after total knee arthroplasty. Although stiffness after total hip arthroplasty (THA), because of formation of heterotopic ossification or other causes, is not uncommon, to the authors’ best knowledge, arthrofibrosis after THA has not been described. The aim of this study is to describe the arthrofibrosis of the hip after primary total hip arthroplasty using an established clinical and histological classification of arthrofibrosis. We retrospectively examined all patients who were histologically confirmed to have arthrofibrosis after primary THA during revision surgery by examination of tissue samples in our clinic. Arthrofibrosis was diagnosed according to the histopathological SLIM-consensus classification, which defines seven different SLIM types of the periimplant synovial membrane. The SLIM type V determines the diagnosis of endoprosthesis-associated arthrofibrosis. The study population consists of 66 patients who were revised due to arthrofibrosis after primary THA. All patients had a limitation in range of motion prior to revision with a mean flexion of 90° (range from 40 to 125), mean internal rotation of 10° (range from 0 to 40) and mean external rotation of 20° (range from 0 to 50). All patients had histological SLIM type V arthrofibrosis, corresponding to endoprosthesis-associated arthrofibrosis. Histological examination revealed that seven patients (10.6%) had particle-induced and 59 patients (89.4%) had non-particle-induced arthrofibrosis. This is the first decription of endoprosthetic-associated arthrofibrosis after primary THA on the basis of a well-established histological classification. Our study results could enable new therapeutic and diagnostic opportunities in patients with such an arthrofibrosis. Surgeons should keep arthrofibrosis as a possible cause for stiffness and pain after primary total hip arthroplasty in mind. Level of evidence Diagnostic study, Level of Evidence IV. Thorsten Gehrke and Lara Althaus contributed equally to the writing of this manuscript


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


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_2 | Pages 3 - 3
1 Mar 2022
Guta D Santini A Fountain J Scott S Rourke H Davidson J Folb J
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Aims. The International Consensus Meeting on Musculoskeletal Infection (ICM, Philadelphia 2018) recommended histology as one of the diagnostic tests although this is not routinely used in a number of UK hospitals. This study aims to explore the role of histology in the diagnosis of infection and whether it is of practical use in those cases where the microbiology samples are either diagnostically unclear or do not correspond to the pre-operative diagnosis or the clinical picture. Patients and Methods. We identified 85 patients who underwent revision knee arthroplasty for either septic or aseptic loosening and for whom both microbiology and histology samples were taken. The procedures were performed by the senior experienced surgeons specialised in revision knee arthroplasty in two centres from Liverpool. Each patient had a minimum of five tissue samples taken, using separate knife and forceps and each sample was divided in half and sent for microbiology and histology in different containers. Fifty-four patients (63.5%) underwent a single-staged revision; ten patients (11.8%) underwent the 1. st. stage of a two staged revision; eleven patients (12.9%) underwent the 2. nd. stage of a two staged revision; one patient (1.2%) underwent an additional revision stage; three patients (3.5%) were treated with a DAIR; three patients (3.5%) had a 2-in-1 revision; two patients (2.4%) had a debridement and polyethylene exchange; and one patient (1.2%) had an arthroscopy biopsy of knee replacement. The cost to process five microbiology samples for each patient was £122.45 on average and for the five histology samples was £130. Results. In 63.5% (n=54) the histology and microbiology confirmed an aseptic joint as suspected beforehand. In 8.2% (n=7) the histology result was the same as the microbiology result confirming infection as suspected beforehand. In 15.3% (n=13) where asepsis was suspected beforehand, one of the five microbiology samples unexpectedly grew an organism but all the histological samples showed no evidence of infection. In these cases, the histology result supported the diagnosis of the likelihood of a contaminant. In 5.9% (n=5) we found differences in the microbiology and histology in one sample and in 7.1% (n=6) the histology was different to the microbiology in more than one sample. Conclusions. In cases where the diagnosis of sepsis within a knee replacement is not in doubt due to pre-operative microbiology, we found no benefit in additional histology sampling. In 28.3% of the cases, the histology was of use in the diagnosis of infection in complex cases and a useful tool in the decision process for further management. In over half of the cases where the revision was for aseptic loosening, the histology result did not alter the management but 28.3% of cases that were thought to be aseptic, microbiology revealed at least one positive sample hence the histology was of use in making a final diagnosis, be that of infection, contamination or to rule out infection. Whilst histology is of use in the latter groups but not the aseptic group, these outcomes are not predictable until after the post-operative period hence histology is required in all these cases. Overall, the histology is a cheap test which is of benefit in the diagnosis of complex peri-prosthetic joint infection in one–third of cases and we support the ICM recommendation


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_1 | Pages 20 - 20
1 Jan 2018
Renz N Mudrovcic S Trampuz A Perka C
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Cutibacterium species (formerly Propionibacterium species) are increasingly recognized as causative pathogens of low-grade periprosthetic joint infections (PJI). The clinical manifestation of infections caused by this low virulent microorganism is nonspecific and the interpretation remains challenging. In this prospective cohort study from 01/2012 to 07/2017 we analyzed the clinical and diagnostic characteristics of microbiologically proven hip PJI caused by Cutibacterium species. PJI was defined by growth of Cutibacteria in ≥2 periprosthetic tissue samples or in sonication fluid of the removed implant (>50 CFU/ml) at revision surgery. If Cutibacteria grew only in synovial fluid at least one other positive microbiological specimen or non-microbiological criterion was required. We included 26 patients suffering from Cutibacterium hip PJI, among them 19 were males (73%). The majority of PJI (24, 92%) presented delayed (3–24 months) or late (>24 months) after implantation. Sinus tract was present in 4 patients (16%) and radiological implant loosening in 16 patients (62%). Among non-microbiological diagnostic tests, increased synovial fluid leukocyte count showed the highest sensitivity (82%), followed by tissue histology (71%) and serum C-reactive protein (58%). After 7 days of incubation Cutibacterium grew in synovial fluid, periprosthetic tissue and sonication fluid culture in 20%, 42% and 32%, respectively, and in 43%, 76% and 83%, respectively, after 14 days of incubation. We conclude that Cutibacterium PJI was diagnosed late in the disease course and presented with subtle clinical signs. Prolonged culture incubation and implant sonication improved the poor performance of conventional microbiological tests. Due to lack of reliable diagnostic tests, Cutibacterium remains difficult to detect making the diagnosis challenging