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

Background. Establishing the diagnosis in a child presenting with an atraumatic limp can be difficult. Clinical prediction algorithms have been devised to distinguish septic arthritis (SA) from transient synovitis (TS). Within Europe measurement of the Erythrocyte Sedimentation Rate (ESR) has largely been replaced with assessment of C-Reactive Protein (CRP) as an acute phase protein. We produce a prediction algorithm to determine the significance of CRP in distinguishing between TS and SA. Method. All children with a presentation of ‘atraumatic limp’ and a proven effusion on hip ultrasound between 2004 and 2009 were included. Patient demographics, details of the clinical presentation and laboratory investigations were documented to identify a response to each of the four variables (Weight bearing status, WCC >12,000 cells/m3, CRP >20mg/L and Temperature >38.5°C). SA was defined based upon culture and microscopy of the operative findings. Results. 311 hips were included within the study. Of these 282 were considered to have transient synovitis. 29 patients met criteria to be classified as SA based upon laboratory assessment of the synovial fluid. The introduction of CRP eliminated the need for a four variable model as the use of two variables (CRP and weight bearing status) had similar efficacy. Treating individuals who were non-weight-bearing and a CRP >20mg/L as SA correctly classified 94.8% individuals, with a sensitivity of 75.9%, specificity of 96.8%, positive predictive value of 71.0%, and negative predictive value of 97.5%. CRP was a significant independent predictor of septic arthritis. Conclusions. CRP was a strong independent risk factor of septic arthritis, and its inclusion within a regression model simplifies the diagnostic algorithm. Nevertheless, this and other models are generally more reliable in excluding SA, than confirming SA, and therefore a clinician's acumen remains important in identifying SA in those individuals with a single abnormal variable

Background:. Until recently, there has been no consensus of the best approach to dIfferentiating aseptic from septic loosening in joint replacement patients. The recent AAOS Clinical Practice Guideline Summary that was published in 2010, tasks orthopedic surgeons with the strong recommendation of obtaining ESR and CRP for all patients needing hip and knee arthroplasty revision surgery and aspirating the joint based upon these results. The purpose of this study is to determine from our patients whether this guideline has been helpful and cost effective in determining periprosthetic joint infections. Methods:. We retrospectively reviewed charts of 50 consecutive patients who underwent revision total hip or knee arthroplasty. Each patient received an ESR and CRP level prior to operation and patients with known periprosthetic joint infections were excluded from the study. As guidelines recommend, aspiration with cultures and cell count were obtained on all knees with either elevated ESR or CRP and all hips with both ESR and CRP elevated. We then determined how many patients needing revision arthroplasty of the hip or knee benefited from ESR, CRP, and aspiration by finding subclinical periprosthetic infection and changing the intraoperative treatment. Hospital charge data was used to report cost of this protocol. Results. Sixty-four percent (32/50) patients had elevated ESR and/or CRP. Eighteen patients (12 hips; 7 knees) required joint aspirations per the guidelines. None of the aspirations were positive for bacterial growth. The total hospital charges for aspiration and cultures in this patient population were $81, 712.44. No sub clinical infection was identified. Conclusion:. Although guidelines may more readily diagnose every case of subclinical joint infection, we must continue to evaluate the cost of this type protocol in a busy revision practice

Background. Osteomyelitis can be difficult to diagnose. Unlike septic arthritis no defined diagnostic criteria exist as a guide. Inflammatory markers are frequently utilized at initial presentation, (in addition to white cell count). Methods. All radiologically confirmed cases of long bone osteomyelitis without septic arthritis, joint effusion or abscess, in paediatric patients, presenting to one hospital over an eighteen-month period were included. These patients were compared with all culture positive septic arthrides presenting to the same hospital within the same time period. Inflammatory markers taken on the day of admission were studied. Results. Thirty-seven patients with long bone osteomyelitis and thirteen with culture positive septic arthritis were identified. The two groups were comparable with regards to age and gender. At presentation 65% of the osteomyelitis patients had an ESR less than 40mm/hour, 48% below 20mm/hour and 19% within the normal range. 23% of the septic arthritis patients had an ESR below 40mm/hour, and none had an ESR below 20mm/hour or in the normal range. The CRP was in the normal range in 46% of the osteomyelitis patients and none of the septic arthritis patients. The average ESR and CRP in the osteomyelitis patients were 47mm/hour and 35mg/L respectively, while in the septic arthritis group these were 72mm/hour, (P< 0.021), and 107mg/L, (P< 0.028). Conclusions. The initial rise in inflammatory markers due to long bone osteomyelitis is significantly less than that in septic arthritis. A proportion of patients presenting with osteomyelitis have normal inflammatory markers at presentation. A high index of suspicion is required in diagnosing osteomyelitis, and inflammatory markers, while a useful adjunct to monitoring treatment, may offer false reassurance regarding the initial diagnosis

Aim. The diagnosis of periprosthetic joint infection (PJI) remains a clinical dilemma, since presentations of PJI usually greatly overlap with aseptic failure (AF). The aim of this study is to evaluate the values of plasma fibrinogen, individually or in combination with CRP, ESR and WBC, for distinguishing PJI from AF. Method. We retrospectively enrolled 357 cases who underwent revision hip or knee arthroplasties in the Third Affiliated Hospital of Southern Medical University, Sun Yat-sen Memorial Hospital and the First Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2021, including 197 AF, 116 PJI and 44 reimplantation. The diagnostic capacity of preoperative fibrinogen, CRP, ESR and WBC as well as their combinations for differentiating PJI from AF were assessed by ROC curves. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated according to the optimal cutoff value based on the Youden index. All biomarkers were further investigated for their potential ability to predict optimal timing of reimplantation as well as their diagnostic capacity in the subgroups of the knee and hip PJI. Furthermore, the correlations among fibrinogen, CRP and ESR in the patients with PJI and AF were analyzed to further evaluate the potential capacity of fibrinogen in the diagnosis of PJI. Results. The levels of fibrinogen, CRP, ESR and WBC were significantly higher in PJI group than in AF group. ROC analyses showed that the AUCs of fibrinogen, CRP, ESR and WBC were 0.879, 0.903, 0.879 and 0.685, respectively. The optimal threshold of fibrinogen is 4.04 g/L (74.1% sensitivity, 85.6% specificity, 76.1% PPV, 85.0% NPV and 81.8% accuracy). Combining fibrinogen with CRP and/or ESR (AUC: 0.903∼0.914) yielded almost equivalent diagnostic efficiency compared with the combination of CRP and ESR (AUC: 0.910). Besides, fibrinogen yielded AUCs of 0.869 (cutoff: 3.44 g/L) and 0.887 (cutoff: 4.12 g/L) in the hip and knee subgroups, with higher specificity and PPV of 93.1% and 96.1% in the knee PJI. Intriguingly, as for the cases with CRP < 10mg/L and ESR ≧ 30 mm/h, the specificity and NPV of fibrinogen for diagnosing PJI were 92.2% and 83.9%. Conclusions. Plasma fibrinogen is considered as a potential first-line screening marker for PJI detection and timing of reimplantation. As for the patients with an increased ESR but normal CRP, a low fibrinogen level (below 4.04 g/L) is more likely to rule out PJI

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

Background. The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice and the analysis of synovial fluid (SF) is a useful diagnostic tool. Recently, two synovial biomarkers (leukocyte esterase (LE) strip test, alpha-defensin (AD)) have been introduced into the MSIS (MusculoSkeletal Infection Society) algorithm for the diagnosis of PJI. AD, although promising with high sensitivity and specificity, remains expensive. Calprotectin is another protein released upon activation of articular neutrophils. The determination of calprotectin and joint CRP is feasible in a routine laboratory practice with low cost. Purpose. Our objective was to evaluate different synovial biomarkers (calprotectin, LE, CRP) for the diagnosis of PJI. Methods. In this monocentric study, we collected SF from hip, knee, ankle and shoulder joints of 42 patients who underwent revision or puncture for diagnostic purposes. Exclusion criteria included a joint surgery in the previous 3 months and a diagnosis of a systemic inflammatory disease. PJI was diagnosed in a multidisciplinary consultation meeting (RCP) of the Reference Centers for Osteoarticular Infections of the Great West (CRIOGO). SF was analysed for LE, CRP and calprotectin. The cut-off values used were 50 mg/L for calprotectin, 8.8 mg/L for CRP and 125 WBC/µL for LE. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for these different synovial markers. Results. Of the 42 patients included, 28 were considered as infected and 14 uninfected. The statistical parameters are presented in Table 1. Conclusion. The present study shows that the synovial calprotectin assay has an excellent sensitivity and a 100% NPV for the diagnosis of PJI, suggesting that a result < 50 mg/L could exclude PJI. This promising study suggests that calprotectin should be included with synovial CRP in a new decision algorithm for the diagnosis of PJI. For any tables or figures, please contact the authors directly

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

Aim. Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. Method. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria. Results. The sensitivities of serum CRP (cut-off: ≥10mg/L), WBC (≥10×10^9 cells/L), %N (≥69.3%), NLR(≥ 3.82), fibrinogen (≥ 457 mg/dL), and PC/mPV (≥ 29.4) were calculated with 68% (95% CI: 57–78), 36% (26 – 47), 66% (54 – 76), 63% (51 – 73), 69% (57 – 78), and 43% (32 – 54), respectively. Specificities were 87% (79 – 93), 89% (81 – 94), 67% (57 76), 73% (63 – 81), 89% (80 – 93), and 81% (72 – 88), respectively. Serum CRP and fibrinogen showed better performances than the other evaluated serum parameters (p<0.0001). The median serum CRP (17.6 mg/L) in patients with PJI caused by a low virulence microorganism was lower compared with infections caused by high virulence organisms (49.2 mg/L; p=0.044). Synovial fluid leucocyte count and histology showed better accuracies than serum CRP, serum WBC, %N, NLR, serum fibrinogen, and PC/mPV (p<0.0001). Conclusions. Although serum CRP and fibrinogen showed the best performances among the evaluated serum inflammatory markers, their results should be interpreted with caution in clinical practice. Serum parameters may remain normal in chronic infections or may be elevated in patients with other inflammatory conditions. In addition, they also correlated poorly with synovial fluid leukocyte count and histology. Therefore, serum parameters are still insufficient to confirm or exclude a periprosthetic joint infection. Hence, they can only be recommended as suggestive criteria in diagnosing PJI

Aim. The diagnosis of septic arthritis mostly relies on clinical examination, several blood parameters including white blood cell count, C-reactive protein, sedimentation, and the analysis of the joint aspiration. However, the diagnosis can be difficult when the symptoms are vague and the information obtained from laboratory might be insufficient for definitive diagnosis. This study aimed to evaluate several ratios obtained from routine blood tests for a possible use in the diagnosis of septic arthritis. Method. The adult patients who were operated in our clinic due to septic arthritis between 2014–2020 were identified and retrospectively evaluated. The patients with any blood disorders or missing file information were excluded. A total of 36 patients were found to be eligible for inclusion. The control group included 40 patients without any sign of infection who underwent total knee arthroplasty due to knee osteoarthritis. Preoperative blood tests of each patients were examined. In addition to CRP and sedimentation values, neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet count-mean platelet volume were calculated and receiving operating characteristics (ROC) curve analysis was made to determine the sensitivity, specificity and area under curve (AUC) values of these parameters. Results. The distribution of affected joint in septic arthritis group was as follow; 22 knees, 6 hips, 4 shoulders, 2 elbows, 1 wrist and 1 ankle. The cultures of joint aspiration yielded positive result in 19 patients while the cultures were negative in 17 patients. All of the analyzed parameters were significantly different between the groups (p<0.001). ROC curve analysis results are given in detail, in Table 1 and Figure 1. The AUC value was 97.3 when only CRP and sedimentation values were used but increased to 98.6 when neutrophile/ lymphocyte ratio was added and increased to 100 when all analyzed parameters were included. Conclusions. The analyzed parameters were found to increase the overall sensitivity and specificity when used together with acute phase reactants. However, when evaluated separately, CRP and sedimentation were still found as the most valuable parameters in the diagnosis of septic arthritis. In the diagnosis of septic arthritis, 35 mm/hr cut-off value for sedimentation and 10 mg/L cut-off value for CRP were found more sensitive and specific compared to standard laboratory cut-off values of 20 mm/hr and 5 mg/L. For any tables or figures, please contact the authors directly

Abstract. Aim. To study and compare the rise of Inflammatory markers post TKR operated by Medial parapatellar approach with tourniquet (MP) and by Subvastus approach used without tourniquet. (SV). Materials and Methods. 100 patients were operated for a TKR by two experienced Arthroplasty surgeons utilising either the MP approach or the SV approach. (50 knees each). The groups were well matched as regards age, degree of deformity, obesity, pre-op knee scores and co-morbidities. The patients were managed peri-operatively in an identical manner .5 inflammatory markers viz: IL-6, AST, LDH, CRP and ESR were measured pre-operatively and at 12, 24,48 and 72 hours postoperatively. Additionally, the patients' VAS score at these intervals and Morbidity Index was determined. Results. All the 5 inflammatory markers increased post surgery in both groups. However, the rise of 4 out of the 5 inflammatory markers i(IL-6, AST, CRP, ESR) in the MP group was statistically significantly higher than in the SV group. The LDH values were similar in the two groups. The VAS scores were better in the SV group and the Morbidity Index showed a higher degree of morbidity in the MP group. Discussion. Surgical technique and approach can influence the rise of Inflammatory markers post TKR. Conclusion. The Subvastus tourniquetless approach reliably produces a lesser degree of rise in inflammatory markers post TKR than the medial parapatellar approach used with tourniquet. The subvastus approach should be utilised more to improve the immediate post-operative results following a TKR

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

Aim. Prosthetic joint infection (PJI) presents the second most common complication of total joint arthroplasty (TJA). Accumulating evidence suggests that up to 20% of aseptic failures are low-grade PJI. However, there is still no single test to reliably diagnose all PJI. In his thesis, Mazzucco emphasized the viscosity differences between normal, osteoarthritic, and rheumatic synovial fluid. Similarly, a recent study by Fu et al. reported significantly lower viscosity in patients with PJI compared to the aseptic failure cohort. The primary aim of our study was to determine whether synovial fluid viscosity is a more reliable diagnostic criterion for PJI compared to the synovial fluid cell count with differential and serum C-reactive protein (CRP) levels. Method. We prospectively analyzed the viscosity of synovial fluid samples obtained during TJA of hip and knee joint revision procedures. We sampled 2.5–5 mL of synovial fluid for viscosity measurement. The samples were centrifuged (4 min at 7000 rpm) and the resulting supernatant was immediately transferred into the Ostwald viscometer. Viscosity was derived from the time required for a given volume of synovial fluid to pass the viscometer at 20 °C. The synovial fluid samples were also analysed for their cell count with differential and serum CRP was measured. The definite diagnosis of PJI was established on basis of EBJIS criteria. For the viscosity, the threshold for detecting PJI was set at 65 seconds. Results. Between December 2020 and March 2021, we analyzed 12 knee and 11 hip TJA revision samples. These included 14 septic and 9 aseptic synovial fluid samples. The average viscometer time in the PJI group was 31s (range 20–48s) compared to 247s (range 68–616s) in the group of aseptic revision procedures. The specificity and sensitivity of our viscosity measurements were 100%. The sensitivity and specificity of cell count was 100% and 85.7%, for the synovial fluid differential they were 100% and 85.7%, and for the CRP they were 88.9% and 71.4%, respectively. Conclusions. Our study is the first to report a significant difference in synovial fluid viscosity between the PJI and the aseptic cohort. It points towards the diagnostic superiority of viscosity measurements over conventional synovial fluid cell count, synovial fluid differential, and serum CRP levels. Albeit currently limited by small sample size, the study remains ongoing

Aim. D-dimer is a widely available serum test that detects fibrinolytic activities that occur during infection. Prior studies have explored its utility for diagnosis of chronic periprosthetic joint infections (PJI), but not explored its prognostic value for prediction of subsequent treatment failure. The purpose of this study was to: (1) assess the ability of serum D-dimer and other standard-of-care serum biomarkers to predict failure following reimplantation, and (2) establish a new cutoff value for serum D-dimer for prognostic use prior to reimplantation. Method. This prospective study enrolled 92 patients undergoing reimplantation between April 2015 and March 2019 who had previously undergone total hip/knee resection arthroplasty with placement of an antibiotic spacer for treatment of chronic PJI. Serum D-dimer level, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured preoperatively for all patients. Failure following implantation was defined per the Delphi consensus criteria. Optimal cutoffs for D-dimer, ESR, and CRP were calculated based on ROC curves and compared in their association with failure following reimplantation criteria at minimum 1-year follow-up. Results. 15/92(16.3%) patients failed reimplantation surgery at mean follow up of 2.9 years (range 1.0–4.8). Optimal thresholds for D-Dimer, ESR and CRP were determined to be 1300ng/mL, 30mm/hr, and 1mg/L, respectively. The failure rate in patient with positive D-dimer was significantly higher at 32.0% (8/25) compared to those with negative D-dimer 10.6% (7/66); p=0.024. In comparison, 17.8% (8/45) of patients with ESR above threshold failed, compared to 13.89% (5/41) below (p=0.555) and 16.0% (4/25) of patients with CRP above threshold failed, compared to 16.1% (10/62) below (p=1.000). Conclusions. Patients with elevated D-Dimer appear to be at higher risk of failure after reimplantation surgery. This serum marker may be used to generate an additional data point in patients undergoing reimplantation surgery, especially in circumstances when optimal timing of reimplantation cannot be determined based on clinical circumstances

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 1. st. and 2. nd. 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. MATERIAL & METHODS. Twenty six patients were included in this study. 13 patients each had unilateral TKR and simultaneous bilateral TKR. All the patients were operated by a single surgeon and assistant. Patients who had Rheumatoid arthritis and post operative adverse events like urinary tract infection were excluded from this study. All 26 patients were female patients and the mean age in the unilateral group was 67 years and in the simultaneous bilateral TKR group was 73 years. CRP levels were measured pre- operatively on 2. nd. day and 8 weeks. TKR was performed in a standard fashion. Both the groups received standard pre and post operative antibiotic prophylaxis. All patients received a posterior stabilized knee implant (Maxx Freedom Knee). RESULTS. In both the groups CRP level shot up on the 2. nd. post-operative day. Although the rise in CRP level was significantly higher in the simultaneous bilateral TKR group as against the unilateral TKR group. This difference was statistically significant. The CRP level came back to normal in about 39% of unilateral TKR patients at 8 weeks post operatively, while in majority (12 out of 13) of bilateral simultaneous TKR patient it was still elevated at 8 weeks post-op and had not come to normal. DISCUSSION. Macrophages are the important in the development of acute phase response namely CRP. The macrophages are present in the bone and bone marrow and less often in the skeletal muscle. The bone and bone marrow injury happening while performing TKR is responsible for elevation of CRP. Various North-American and European studies have shown that the CRP level increases significantly on the 1. st. postoperative day and the decreases from a peak on the 2. nd. postoperative day, attaining normal value at 6 to 8 weeks after operation. The result of our study are in variance to this published literature. Nearly 39% of our unilateral TKR patients and majority all of our simultaneous bilateral TKR patients did not achieve a normal CRP at 8 weeks after operation. These findings are significant as CRP is often used as a very sensitive indicator of post operative joint infection. Hence we conclude that the Indian TKR patients take longer time for the CRP values to become normal and the published literature regarding the normal levels of CRP in Unilateral TKR should not be extrapolated to simultaneous bilateral TKR group

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. Results. A total of 398 revision were performed during the study period. After excluding 293 cases with insufficient information, a total of 105 patients were studied. Naturally, CRP and ESR mean values were significantly higher among PJI cases compared to aseptic cases. When compared against 2013 International Consensus Meeting definition, CPR has a sensibility 86.5% (45/52) that increases to 94.2% (49/52) with the combined measurement (ESR and CRP). The sensitivity also increased when compared against the ProImplant Foundation definition (72.6% (45/62) vs 85.5% (53/62)). Conclusions. After the inciting insult, CRP raises and drops rapidly and ESR response is slower but also much more enduring. One can only hypothesize that chronic PJI runs perhaps a fluctuating inflammatory course that can sometimes be more accurately picked up by ESR and not CRP measurement. Our results seem to corroborate that ESR measurement is a valid adjunct to isolated CRP measurement in the initial screening of PJI in painful total joint arthroplasties

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

Background. Preoperative diagnosis of fracture related infections can be challenging, especially when confirmatory criteria such as sinus tract and purulent discharge are absent. Although serum parameters, such as CRP and white blood cell count (WBC), showed poor accuracy in the literature, they are still often used in clinical practice. The European Bone and Joint Infection Society (EBJIS) defined evidence-based criteria for fracture related infection. Elevated serum inflammatory markers were regarded as suggestive criteria only, as the literature was of limited quality. This study assessed the diagnostic value of the serum parameters CRP, WBC and differential cell count in the diagnosis of fracture related infections defined by the EBJIS-criteria for fracture related infections. Methods. In this retrospective cohort study, 94 patients who underwent surgical treatment for suspected infected non unions after failed fracture fixation were included. Preoperatively, blood samples including serum inflammatory markers were taken. For this study, cut-offs of 5 mg/L for CRP, 10×10⁁9 cells/L for WBC, and >70% for the percentage of neutrophils were regarded as positive for infection. All patients had intraoperative samples taken for microbiology and histology. Analysis of diagnostic accuracy was based on the receiver-operating characteristic (ROC). Results. Based on the EBJIS criteria, 40 patients (43%) were diagnosed with a fracture related infection. 11/94 (12%) patients had an elevated serum WBC count, 13/94 (14%) an increased percentage of neutrophils, and 43/82 (52%) an elevated serum CRP. The mean values of CRP concentration, WBC count, and percentage of neutrophils in the infection group were 7.9 mg/L (IQR:6.4 – 9.7), 18.3 G/l (IQR: 3.9 – 24.9), and 63% (IQR: 58 – 67%), respectively. The sensitivity, specificity, and area under the curve of serum WBC count were 20% (95% CI: 10 −35%), 94.4% (84 −99%), and 0.57 (0.50 – 0.64), respectively; of percentage of neutrophils 12.5% (5 – 27%), 85.2% (73 −93%), and 0.49 (0.42 – 0.56); and of serum CRP 67.6% (51 – 90%), 60.0% (45 – 73%), and 0.64 (0.53 – 0.74), respectively. A statistically significant difference between the AUCs of all three serum parameters and AUC of tissue culture as well as AUC of histology was shown (p <0.0001). A simple decision tree approach using only low WBC and CRP may allow identification of aseptic cases. Conclusion. Based on the standardized and evidence-based EBJIS criteria, the three inflammatory serum markers showed an insufficient accuracy for the diagnosis of fracture related infections. They also correlate poorly with culture or histological diagnosis. Therefore, they should not be used alone as a confirmatory test

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

Aim. Bone and joint infections (BJI) need frequently prolonged antibiotic treatment at high dosage for a total of 6 or 12 weeks depending the type of infection. Impact of such prolonged antibiotic exposure on the gut microbiota has never been assessed. Method. We performed a national multicentric prospective study of patients with BJI to monitor the gut microbiota dynamic all along antimicrobial treatment. Clinical data and stool collection were performed at the baseline visit (B) within 24h before starting antibiotics, at the end of the treatment (EOT) and 2 weeks after antibiotic withdrawal during a follow-up visit (FU). Microbiota composition was determined by shotgun metagenomic sequencing. Biological markers of gut permeability and inflammation were monitored at each time point. Results. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI and 21 prosthetic joint infections (PJI). At EOT there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI but not in patients with osteosynthesis-related BJI (p<0.05, Wilcoxon test). At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. Principal Component Analysis (PCoA) of the Bray Curtis distance, showed a significant change of the gut microbiota at the end of treatment compared to baseline (p<0.01, PERMANOVA) that only partially recover at FU. The taxonomic analysis showed that microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks to patients treated for 12 weeks. No particular antibiotic (especially fluoroquinolones) was associated with a lower Shannon index or distinct dynamic of recovery at the end of treatment. PCoA analysis of the Bray Curtis distance shows that patients with elevated plasma level of CRP (≥5mg/L) at EOT had a distinct gut microbial composition compared to others. Conclusions. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery 2 weeks after antibiotic withdrawal, independently on the duration of the therapy and on the type of the antibiotic used. Elevated CRP at EOT might reflect persistent alteration of the gut microbiota. Assessment of long-term impact after the end of treatment is on-going