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Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 85 - 85
1 Dec 2015
Gamba C Diez J Prieto D Fabrego A Verdie L Perez F Canovas C
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Successfully treatment of acute shoulder arthroplasty infections strongly depends on the timing of treatment. The objective of this study is to determine the normalization curve of C-reactive protein (CRP) after shoulder arthroplasty. Prospective study including 63 patients undergoing shoulder arthroplasty (46 reverse shoulder arthroplasty (RSA) and 17 total shoulder (TSA)). Mean age 74.1 years old. 25 cuff deficient shoulders, 14 acute fractures, 19 primary gleno-humeral arthritis and 5 fracture sequel were included. Blood samples to determine CRP were obtained before surgery the day of surgery, 24 and 48 hours after surgery and then 6, 8 and 14 days after surgery (data of blood samples was determined based on a previous limited study). Co-morbidities that could interfere CRP were also recorded. Normal value of CRP before surgery (mean 1.28) slightly increases 24 hours after surgery (mean 3.92), reach maximum value at 48 hours after surgery (mean 6.91) and then slowly decreases to normalize at 14 days (6th day mean 3.80, 8th day 2.33 and 14th day 1.08). Normalization curve is not affected by age, diagnosis or type of arthroplasty. CRP after shoulder arthroplasty reaches maximum value at 48h and then slowly decreases to become normal at 14 days. Any deviation from this normalization curve may help in diagnosis and early treatment of acute shoulder arthroplasty infections


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 206 - 206
1 Sep 2012
Cashman J MacKenzie J Parvizi J
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Background. The diagnosis of Periprosthetic Joint Infection (PJI) is a considerable challenge in total joint arthroplasty. The mainstay for diagnosis of PJI is a combination of serological markers, including C-reactive protein (CRP), along with joint aspirate for white cell count, differential and culture. The aim of this study was to examine the use of synovial fluid CRP in the diagnosis of PJI. Material & Methods. Synovial fluid samples were collected prospectively from patients undergoing primary and revision knee arthroplasty. Samples were assessed for CRP, cell count and differential. Three groups were analyzed; those undergoing primary knee arthroplasty, aseptic knee arthroplasties and infected arthroplasties. Demographic data, along with associated medical co-morbidities, were collected,. Statistical analysis was performed. Synovial fluid CRP was correlated with serum CRP values. Sensitivity and specificity were calculated. Results. 50 synovial fluid samples were collected from 50 patients. Synovial fluid CRP was 0.3 +/− 0.4 in native knees, 0.2 +/− 0.5 in aseptic knee arthroplasties, 4.3+/−4.1 in patients with infected knee arthroplasties. Synovial fluid CRP was significantly higher in septic total knee arthroplasties by comparison to both aseptic total knees (p< 0.001) and native knees (p=0.006). The specificity was 100% and the sensitivity was 89% at a CRP of 1. Conclusion. While this is preliminary data, synovial fluid CRP was found to be significantly elevated in patients with infected total knee arthroplasties. This test is easily performed under routine hospital laboratory conditions without specific, expensive assays. We believe synovial CRP assay holds great promise as a new, potentially low-cost, diagnostic marker for PJI


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 127 - 127
1 Jul 2020
Shefelbine L Bouchard M Bompadre V
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C-reactive protein (CRP) level is used at our tertiary paediatric hospital in the diagnosis, management, and discharge evaluation of paediatric septic arthritis patients. The purpose of this study was to evaluate the efficacy of a discharge criterion of CRP less than 2 mg/dL for patients with septic arthritis in preventing reoperation and readmission. We also aimed to identify other risk factors of treatment failure. Patients diagnosed with septic arthritis between January 1, 2007 and December 31, 2017 were reviewed retrospectively. The diagnosis of septic arthritis was made based on clinical presentation, laboratory results and the finding of purulent material on joint aspiration or the isolation of a bacterial pathogen from joint fluid or tissue. Bivariate tests of associations between patient or infection factors and readmission and reoperation were performed. Quantitative variables were analyzed using Mann-Whitney tests and categorical variables were analyzed using Chi-square tests. One hundred eighty-three children were included in the study. Seven (3.8%) were readmitted after hospital discharge for further management, including additional advanced imaging, and IV antibiotics. Six (85.7%) of the readmitted patients underwent reoperation. Mean CRP values on presentation were similar between the two groups: 8.26 mg/dL (± 7.87) in the single-admission group and 7.94 mg/dL (± 11.26) in the readmission group (p = 0.430). Mean CRP on discharge for single-admission patients was 1.71 mg/dL (± 1.07), while it was 1.96 mg/dL (± 1.19) for the readmission group (p = 0.664), with a range of < 0 .8 to 6.5 mg/dL and a median of 1.5 mg/dL for the two groups combined. A total of 48 children (25.9%) had CRP values greater than the recommended 2 mg/dL at discharge, though only three of these patients (6.2%) were later readmitted. The only common variable in the readmitted children was either a negative culture result at time of discharge or atypical causative bacteria. CRP values are useful in monitoring treatment efficacy but not as reliable as a discharge criterion to prevent readmission or reoperation in children with septic arthritis. We recommend determining discharge readiness on the basis of clinical improvement and downtrending CRP values. There was a higher risk of readmission in children with an atypical causative bacteria and when culture results were negative at discharge. Close monitoring of these patients after discharge is suggested to identify signs of persistent infection


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 53 - 53
1 Dec 2019
Stone W Gray CF Parvataneni HK Al-Rashid M Vlasak RG Prieto H
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Aim. Diagnosing periprosthetic joint infection after total joint arthroplasty is often challenging. The alpha defensin test has been recently reported as a promising diagnostic test for periprosthetic joint infection. The goal of this study was to determine the diagnostic accuracy of alpha defensin testing. Method. One hundred and eighty-three synovial alpha defensin and synovial fluid C-reactive protein (CRP) tests performed in 183 patients undergoing evaluation for periprosthetic joint infection were reviewed. Results were compared with the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection. Results. Alpha defensin tests were performed prior to surgical treatment for infection, and 37 of these patients who had these tests were diagnosed by MSIS criteria as having infections. Among this group, the alpha defensin test had a sensitivity of 81.1% (95% confidence interval [CI], 64.8% to 92.0%) and a specificity of 95.9% (95% CI, 91.3% to 98.5%). There were 6 false-positive results, 4 of which were associated with metallosis. There were 7 false negatives, all of which were associated with either draining sinuses (n = 3) or low-virulence organisms (n = 4). A combined analysis of alpha defensin and synovial fluid CRP tests was performed in which a positive result was represented by a positive alpha defensin test and a positive synovial fluid CRP test (n = 28). Among this group, the sensitivity was calculated to be 73.0% (95% CI, 55.9% to 86.2%) and the specificity was calculated to be 99.3% (95% CI, 96.2% to 99.9%). An additional combined analysis was performed where a positive result was represented by a positive alpha defensin test or positive synovial fluid CRP test (n = 64). Among this group, the sensitivity was calculated tobe91.9%(95%CI, 78.1%to98.3%) andthe specificitywas calculated tobe79.5%(95%CI, 72.0%to85.7%). Conclusions. Alpha defensin in combination with synovial fluid CRP demonstrates very high sensitivity for diagnosing periprosthetic joint infection, but may yield false-positive results in the presence of metallosis or false-negative results in the presence of low-virulence organisms. When both alpha defensin and synovial fluid CRP tests are positive, there is a very high specificity for diagnosing periprosthetic joint infection


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 104 - 104
1 Dec 2015
De Vecchi E Villa F Agrappi S Toscano M Drago L
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Culture examination is still considered the gold standard for diagnosis of bone and joint infections, including prosthetic ones, even if in up to 20–30% of cases, particularly prosthetic joint infections, it fails to yield microbial growth. To overcome this limitation, determination of markers of inflammation and or infection directly in joint fluid has been proposed. Aim of this study was to evaluate the applicability of measurement of lecukocyte esterase (LE), C-reactive protein (CRP) and glucose in synovial fluid for diagnosis of bone and joint infections. Synovial fluids from 80 patients were aseptically collected and sent to laboratory for microbiological cultures. After centrifugation at 3000 rpm for 10 minutes, pellet was used for cultures, while the surnatant was used for determination of LE, CRP and glucose. LE and glucose were evaluated by means of enzymatic colorimetric strips developed for urinanalysis. One drop of synovial fluid was placed on the LE and on the glucose pads and the results were read after about 120 seconds. A LE test graded + or ++, and a glucose test equal to trace or negative were considered suggestive for infection. CRP was measured by an automated turbidimetric method. On the basis of clinical findings, microbiological, haematological and histological analyses patients were retrospectively divided into 2 groups. Group 1 comprised 19 infected patients (12 males, 7 females age: 70.6 ± 10.3 yrs, range: 47 – 88 yrs) while Group 2 included 61 aseptic patients (32 males and 29 females, age: 61.5 ± 16.3 yrs, range: 15 – 84). Sensitivity of the three tests was 89.5%. 84% and 73,7% for LE, CRP and glucose, respectively. Specificity was 98.4%, 88.5% and 70% for LE, CRP and glucose, respectively. Positive and negative predictive values were 94.4% and 96.8% for LE, 69.6% and 94.6% for CRP and 77.8% and 89.6% for glucose test. When LE was combined with CRP, sensitivity increased to 94.7%, while no differences were observed for LE combined with glucose. Leukocyte esterase has proven to be a rapid, simple and inexpensive test to rule in or out bone and joint infections. Combination of its measurement with that of CRP increased sensitivity. In conclusion, the combination of leukocyte esterase and CRP may represent a simple and useful tool for diagnosis of bone and joint infections


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_4 | Pages 148 - 148
1 Apr 2019
Londhe S Shah R
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INTRODUCTION

This study is to determine the response of CRP after TKR surgery, both unilateral and simultaneous bilateral TKR. According to the previously published literature from North America and Europe CRP value peaks on the 1st and 2nd post-operative day and then gradually comes down to normal by 6–8 weeks post-operatively.

AIM

To determine the trend of CRP in Indian patients undergoing TKR, both unilateral and simultaneous bilateral TKR. To see whether it follows the trend in North American and European population and to determine whether there is a difference in the CPR pattern in unilateral versus simultaneous bilateral TKR patients.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 54 - 54
1 Dec 2019
Ribau A Carvalho AD Barbosa TA Abreu M Soares DE Sousa R
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Aim

C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR) are non-specific markers with variable reported accuracy in the diagnosis of prosthetic joint infection(PJI). They are often used as a part of the initial diagnostics as they are widely available and inexpensive. Given its high false-negative rate, CRP is an insufficient screening tool for PJI especially in low virulence microorganisms. Nevertheless, many advocate ESR offers no added advantage and is useless in this setting. Our goal is to determine if the combined measurement of ESR and CRP offers increased sensitivity for the preliminary screening of PJI over isolated CRP measurement.

Method

We retrospectively evaluated every single- or first-stage for presumed aseptic or known infected revision total hip/knee arthroplasty procedures between 2013–2018. Cases without preoperative CRP and ESR measurement as well those without synovial fluid for differential leukocyte count and/or no multiple cultures including sonication of removed implant obtained during surgery were excluded. Diagnostic accuracy was compared against two different PJI definitions: 2013 International Consensus Meeting and ProImplant Foundation definitions.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_8 | Pages 145 - 145
1 May 2016
Lee B Kim T
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Objectives

C-reactive protein(CRP) Used as screening test for acute periprosthetic joint infection has high sensitivity and low specificity. So there are many reasons except acute infection after total knee arthroplasty to elevate CRP level but it is unclear what reasons exactly were concerned. We therefore performed this study to determine the Causes of elevated CRP level in the early-postoperative period after primary total knee arthroplasty.

Methods

Between 2005 and 2013, 502 patients undergone primary total knee arthroplasty were included. We excluded patients performed total knee arthroplasty with inflammatory arthritis and revision total knee arthroplasty, We measured the serial CRP levels in the all cases and then found cases with CRP level show elevation-depression-elevation pattern(bimodal graph) or >23.5mg/dl. We analyzed causes of elevated CRP level of that


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 73 - 73
23 Feb 2023
Hunter S Baker J
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Acute Haematogenous Osteomyelitis (AHO) remains a cause of severe illness among children. Contemporary research aims to identify predictors of acute and chronic complications. Trends in C-reactive protein (CRP) following treatment initiation may predict disease course. We have sought to identify factors associated with acute and chronic complications in the New Zealand population. A retrospective review of all patients <16 years with presumed AHO presenting to a tertiary referral centre between 2008–2018 was performed. Multivariate was analysis used to identify factors associated with an acute or chronic complication. An “acute” complication was defined as need for two or more surgical procedures, hospital stay longer than 14-days, or recurrence despite IV antibiotics. A “chronic” complication was defined as growth or limb length discrepancy, avascular necrosis, chronic osteomyelitis, pathological fracture, frozen joint or dislocation. 151 cases met inclusion criteria. The median age was 8 years (69.5% male). Within this cohort, 53 (34%) experienced an acute complication and 18 (12%) a chronic complication. Regression analysis showed that contiguous disease, delayed presentation, and failure to reduce CRP by 50% at day 4/5 predicted an acutely complicated disease course. Chronic complication was predicted by need for surgical management and failed CRP reduction by 50% at day 4/5. We conclude that CRP trends over 96 hours following commencement of treatment differentiate patients with AHO likely to experience severe disease


Shoulder septic arthritis is uncommon and frequently misdiagnosed, resulting in severe consequences. This study evaluated the demographics, bacteriological profile, antibiotic susceptibility, treatment regimens, and clinical outcomes. This is a 10-year retrospective observational analysis of 30 patients (20 males and 10 females) who were treated for septic arthritis of the shoulder. The data collecting process utilised clinical records, laboratory archives, and x-ray archives. We gathered demographic information, pre- and post-intervention clinical data, serum biochemical markers, and the results of imaging examinations. All patients had a surgical arthrotomy and joint debridement in the operating room, and specimens were taken for culture and sensitivity testing. The specimens were cultivated for at least seventy-two hours. Shoulder joint ranges of motion, comorbidities, and the presence of osteomyelitis were assessed clinically to determine the outcome. All statistical analyses were conducted using the STATA 17 statistical software. Analysis of correlation between categorical variables was performed using the chi-squared test. The majority of the study patients were black Africans (97%). The age range of the group was from 8 days to 17 years. At presentation, 33% of patients had a low-grade fever, whereas the majority (60%) had normal body temperature. The average length of symptoms was 3.9 days (ranged from 1 day to 15 days), and the majority of patients had an increased white cell count (83%) and C-reactive protein (98%). There was accumulation of fluid in the joint of all individuals who received shoulder ultrasound imaging. We noted a significant incidence of gram-positive cocci, which were mostly susceptible to first-line antibiotics. Shoulder stiffness affected 63% of patients and chronic osteomyelitis affected 50% of individuals. Neither the severity nor the duration of the symptoms was related to an increased risk of osteomyelitis. The results of this study revealed that the clinical characteristics and bacterial profile of septic arthritis of the shoulder conform to typical patterns. The likelihood of osteomyelitis and an unfavourable prognosis is considerable


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_11 | Pages 30 - 30
1 Nov 2022
Barakat A Ahmed A Ahmed S White H Mangwani J
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Abstract. Background. Distinction between foot and ankle wound healing complications as opposed to infection is crucial for appropriate allocation of antibiotic therapy. Our aim was to evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. Methods. Data were reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals – United Kingdom between July 2014 and February 2020 (68 months). All diabetic patients were excluded. For the infected non-diabetic included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0–10 mg/L and WCC 4.0–11.0 ×109 /L were considered normal. Results. 25 patients met our inclusion criteria. Infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with foot osteomyelitis (OM), 11 (44%) with ankle OM, 5 (20%) with ankle septic arthritis, and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metalwork. CRP sensitivity was 84%, while WCC sensitivity was only 28%. Conclusion. CRP had good sensitivity, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of a clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 52 - 52
22 Nov 2024
Schulze M Nonhoff M Hasselmann J Fobker M Gosheger G Moriarty F Zeiter S Tapia-Dean J Kuntze A Puetzler J
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Aim. The utilization of silver as an anti-infective agent is a subject of debate within the scientific community, with recurring discussions surrounding its biocompatibility. Presently, galvanic silver coating finds widespread clinical application in mitigating infection risks associated with large joint arthroplasties. While some instances have linked this coating to sporadic cases of localized argyria, these occurrences have not exhibited systematic or functional limitations. To address concerns regarding biocompatibility, a novel approach has been devised for anti-infective implant coatings: encapsulating silver nitrate within a biopolymer reservoir for non-articulating surfaces. This poly-L-lactic acid layer releases silver ions gradually, thereby circumventing biocompatibility concerns. Method. Female C57BL/6 mice were utilized as an experimental model, with 6x2 mm Ti6Al4V discs, coated with or without the biopolymer-protected silver coating, implanted subcutaneously on both sides of the vertebrae. Daily blood samples were collected, and serum was analyzed for C-reactive protein (CRP) and silver concentration. After three days, histopathological analyses were conducted on the surrounding soft tissue pouch. Results. Maximum CRP levels in the silver group (4.80 mg/L; Median: 3.29 mg/L; IQR: 2.38 to 3.73) did not significantly differ from the control group (4.58 mg/L; Median: 2.93 mg/L; IQR: 1.91 to 3.78) over the study period. Silver levels in serum 24 hours post-implantation were 64 µg/L (IQR: 35 to 78) and decreased subsequently over three days to 23 µg/L (IQR: 13 to 28). Histopathological examinations revealed a similarly strong expression of inflammation signs in tissue samples from the two groups. Conclusions. Despite evidence of local inflammation indicated by CRP and histopathological analysis, no significant difference was observed between the coated and uncoated groups. This suggests that any inflammation may be attributed to the implantation procedure rather than silver influence. Furthermore, silver levels remained below the toxic limit, indicating the efficacy of the biopolymer-protected reservoir in aiding biocompatibility. This study underlines the potential of biopolymer-protected silver reservoirs in enhancing the safety profile of anti-infective silver implant coatings, warranting further investigation into their clinical application


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. 105-B, Issue SUPP_17 | Pages 15 - 15
24 Nov 2023
Trenkwalder K Erichsen S Weisemann F Augat P Militz M Hackl S
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Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 81 - 81
24 Nov 2023
Weisemann F Siverino C Trenkwalder K Heider A Moriarty F Hackl S
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Aim. Differentiation of infected (INF) nonunion from aseptic (AS) nonunion is crucial for the choice of intra- and postoperative treatment. Preoperative diagnosis of infected nonunion is challenging, especially in case of low-grade infection lacking clinical signs of infection. Standard blood markers such as C-reactive protein or leucocyte count do not aid in preoperative diagnosis. Proteomic profiling has shown promising results for differentiation of numerous chronic disease states, and in this study was applied to preoperative blood samples of patients with nonunion in an attempt to identify potential biomarkers. Method. This prospective multicenter study enrolled patients undergoing revision surgery of femur or tibia nonunion. Patients with implant removal after regular fracture healing (HEAL) were included as a control-group. Preoperative blood samples, intraoperative tissue samples, sonication of osteosynthesis material and 1-year-follow-up questionnaire were taken. Nonunion patients were grouped into INF or AS after assessing bacterial culture and histopathology of retrieved samples. Diagnosis of infection followed the fracture related infection consensus group criteria, with additional consideration of healing one year after revision surgery. Targeted proteomics was used to investigate a predefined panel of 45 cytokines in preoperative blood samples. Statistical differences were calculated with Kruskal Wallis and Dunn's post hoc test. Cytokines with less than 80% of samples being above the lower limit of detection range (LLDR) were excluded for this study. Results. We recruited 62 AS, 43 INF and 32 HEAL patients. Patients in the two nonunion groups (INF and AS) did not differ concerning smoking, diabetes or initial open or closed fracture. Thirty-two cytokines were above LLDR in >80% of patients. INF patients showed a significant difference in expression of 8 cytokines compared to AS, with greatest differences observed for Macrophage Colony Stimulating Factor 1 (MCSF-1) and Hepatocyte Growth Factor (HGF) (p<0.01). In comparing AS with HEAL patients, 9 cytokines displayed significant differences, including interleukin (IL)-6, Vascular Endothelial Growth Factor A (VEGFA), Matrix Metalloproteinase 1 (MMP-1). Comparison of INF with HEAL patients revealed significantly different expression of 20 cytokines, including. IL-6, IL-18, VEGFA or MMP-1. Conclusions. Our study revealed differences in plasma cytokine profile of blood samples from INF and AS patients. Although no single biomarker is sufficient to differentiate these patients preoperatively in isolation, future multivariant analysis of this cytokine data in combination with clinical characteristics may provide valuable diagnostic insights. Funded by German Social Accident Insurance (FF-FR 0276) and AO Trauma (AR2021_04)


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_4 | Pages 7 - 7
3 Mar 2023
Hughes I May J Carpenter C
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Introduction. Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition characterised by bony pain and swelling which may be initially mistaken for bacterial osteomyelitis. The episodic course of the disease may confound the diagnosis and potentially be mistaken for a partial response to antimicrobial therapy. It is an orphan disease and consequently results in many unclear aspects of diagnosis, treatment and follow up for patients. The aim of this study is to evaluate a national tertiary centre's experience with the clinical condition and present one of the largest cohorts to date, emphasizing the vast array of clinical spectrum, course and response to treatment. Methods. We retrospectively evaluated all children identified with CRMO from the period 2000–2022 within Wales. Demographic data and clinical parameters were selectively identified through the utilisation of a national clinical platform (Welsh Clinical Portal). The diagnosis was based on clinical findings, radiological images, histopathological and microbiological studies. Results. A total of 21 patients were identified as suitable for inclusion. The mean age of diagnosis was 9.4 ±2 years. The age range of children being diagnosed was 6–14 years. Of the 21 patients, only 2 reported feeling unwell prior to their first presentation with generalized coryzal illness reported. The most common presenting site for CRMO was knee (33%) followed by back pain (28%). 19% of the included cases at initial presentation had localised warmth and had nocturnal pain. 4 of the patients went on to have dermatological conditions of which psoriasis was the most common (14%). Bilateral symptoms developed in 38% of the included patients. Biochemical investigations revealed only 19% of patients had a raised C-reactive protein level and erythrocyte sedimentation rate whilst 9/21 patients went on to have a bone biopsy to aid diagnosis. 100% of patients had MRI whilst whole body MRI was utilised in 8/21 patients. NSAID's were utilised for 81%, Pamidronate for 33% and methotrexate for 14%. Biologics were utilised for a further 24% of the total population in failed medical therapy. Surgical intervention was utilised for a single individual in this cohort of patients in the form of posterior spinal stabilisation. The most common referring speciality for these patients was Rheumatology (71%) followed by Orthopaedics (33%). Discussion. CRMO represents a challenging diagnosis to make with such varied clinical and biochemical presentations for this condition. The absence of diagnostic Radiological features on X-ray could argue over early MRI imaging. The utilisation of whole body-MRI can now identify multifocal disease burden which may facilitate a timely diagnosis and ensure that effective medical treatment is started promptly without delay. This study is the largest cohort of CRMO patients conducted in this country. Future work will serve to build upon a framework and national referral pathway so that these patients can be seen by the appropriate specialist in a timely manner


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 83 - 83
1 Oct 2022
Browning S Manning L Metcalf S Paterson DL Robinson O Clark B Davis JS
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Aim. Culture negative (CN) prosthetic joint infections (PJI) account for approximately 10% of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJI within a large prospective cohort study, and to compare their characteristics and outcomes with culture positive cases. Methods. The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, binational, multicentre observational cohort study conducted at 27 hospitals between July 2014 and December 2017. We compared baseline characteristics and outcomes of all patients with culture negative (CN) prosthetic joint infection (PJI) from the PIANO cohort with culture positive (CP) cases. “Treatment success” was defined as absence of clinical or microbiological signs of infection, no need for ongoing antibiotics, and no need for revision or resection arthroplasty since the end of the initial treatment. We also describe PJI diagnostic criteria in the CN cohort and apply internationally recognised PJI diagnostic guidelines. Results. Of the 650 patients eligible for inclusion, 55 (8.5%) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female [32 (58.2%) vs 245 (41.2%); p=0.02], involve the shoulder joint [5 (9.1%) vs. 16 (2.7%); p=0.03] and have a lower mean C-reactive protein (142 mg/L vs. 187 mg/L; p=0.02). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (aOR 3.78; 95%CI 1.65 – 8.67). Of the 55 CN cases meeting Infectious Diseases Society of America (IDSA) diagnostic criteria, 45 (82%) met European Bone and Joint Infection Society (EBJIS) criteria (probable or definite) and 39 (71%) met the 2013 Musculoskeletal Infection Society (MSIS) criteria. Conclusions. Culture negativity is an independent predictor of treatment success in PJI. It is unclear whether this is because some of them are not actually infections, or for other reasons such as lower bacterial load or earlier effective antibiotic treatment. Diagnostic criteria for PJI vary substantially in their sensitivity, with MSIS criteria being the least sensitive. Acknowledgements. This work is being presented on behalf of the broader PIANO investigators and the Australasian Society for Infectious Diseases Clinical Research Network. The PIANO study received seed funding from Heraeus Medical and the John Hunter Hospital Charitable Trust Fund


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. 98-B, Issue SUPP_23 | Pages 86 - 86
1 Dec 2016
Serrano P Silva MS Dias J Oliveira JC Oliveira A Sousa R
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Aim. Our goal is to increase diagnostic accuracy of synovial fluid testing in differentiating prosthetic joint infection(PJI) by more exhaustively studying simple and inexpensive biomarkers. For that purpose, we sought to determine: 1) if synovial fluid C-reactive protein(CRP), alpha-2-macrogloblulin(A2M), procalcitonin and adenosine deaminase(ADA) concentrations are different between infected and aseptic cases; 2) performance and optimal cutoff values of each marker; 3) whether any such test may help improve diagnostic performance of traditional leukocyte count. Method. Between January/2013 and December/2015 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples as well as the implant for sonication were gathered for microbiological study. Definitive diagnosis was classified as infection or aseptic on the basis of the recent International Consensus Meeting definition of PJI. Using receiver operating characteristic curves, we determined cutoff values as well as sensitivity and specificity for each marker. Results. Fifty-five out of 143 revision arthroplasties fully respected the inclusion criteria. Two supposedly aseptic cases were ultimately classified as infected resulting in 32 aseptic and 23 infected cases available for analysis. Total leukocyte count, proportion of PMN, C-reactive protein, ADA and alpha-2-macroglobulin but not procalcitonin were significantly different between both groups. Cutoff values for optimal performance in the diagnosis of infection were: total leukocyte count >1,463 cells/μL; proportion of PMN >81%; CRP >6.7mg/L and ADA >61U/L. Conclusions. Synovial fluid leukocyte count offers great negative predictive value and interpreting it together with other more specific markers such as C-reactive protein and ADA is helpful in improving its positive predictive value. These simple and inexpensive markers may reduce the number of equivocal synovial fluid results requiring more expensive investigation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 24 - 24
1 Dec 2021
Diniz SE Ribau A Vinha A Guerra D Soares DE Oliveira JC Abreu M Sousa R
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Aim. Our goal is to assess diagnostic accuracy of synovial fluid testing in diagnosing prosthetic joint infection (PJI) as defined by the European Bone and Joint Infection Society (EBJIS). In addition to differential leukocyte count, simples and inexpensive biomarkers such as synovial fluid C-reactive protein (CRP), adenosine deaminase (ADA) and alpha-2-macrogloblulin(A2M) were also investigated and its possible role in increasing accuracy assessed. Method. Between January/2013 and December/2019 total hip or knee arthroplasty revision cases (regardless of preoperative diagnosis) were prospectively included provided enough synovial fluid for biomarker analysis was collected and at least four tissue samples, as well as the implant for sonication, were gathered for microbiological study. Definitive diagnosis was classified according to the new EBJIS PJI definition. Using receiver operating characteristic curves, we determined cutoff values as well as diagnostic accuracy for each marker. Results. Out of 364 revision arthroplasties performed, 102 fully respected inclusion criteria. There were 58 unlikely, 8 likely and 36 confirmed infections. Synovial fluid total leukocyte count, proportion of polymorphonuclear neutrophils (PMN), CRP, ADA and A2M were significantly different between groups. Area under the curve was 0.94 for total leucocyte count, 0.91 for proportion of PMN, 0.90 for CRP, 0.82 for ADA and 0.76 for A2M. Sensitivity, specificity, and predictive values for statistically optimal but also selected rule-in and rule-out cutoffs values are shown in Table 1. Interpreting a raised level of CRP(>2.7mg/L) or ADA(>60U/L) together with high leukocyte count (>1470 cells/μL) or proportion of PMN (>62.5%) significantly increases specificity and positive predictive value for affirming PJI. Conclusions. Differential leukocyte count cutoffs proposed by the EBJIS PJI definition are shown to perform well in ruling out (<1,500 cells/μL) and ruling in (>3,000 cells/μL) PJI. Adding simple and inexpensive biomarkers such synovial CRP or ADA is helpful in interpreting inconclusive results. For any tables or figures, please contact the authors directly