Objectives. The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. Methods. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Results. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Conclusion. Our review helped to identify factors that can influence serum biomarkers’ level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: A. Saleh, J. George, M. Faour, A. K. Klika, C. A. Higuera. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018;7:85–93. DOI: 10.1302/2046-3758.71.BJR-2017-0323

Aims

The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition.

Obesity is associated with worse outcomes following total knee/hip arthroplasty (TKA/TKA). This study aimed to determine the feasibility of a dietitian-led low-inflammatory weight-loss program for people with obesity awaiting arthroplasty. Quasi-experimental pilot study enrolled people with obesity waitlisted for primary TKA/THA into ‘usual care’ (UC) or weight-loss (low-inflammatory diet) program (Diet). Recruitment occurred between July 2019 and February 2020 at Fairfield and Campbelltown Hospitals. Assessments at baseline, pre-surgery, time of surgery and 90-days following surgery included anthropometric measurements, patient-reported outcomes, serum biomarkers and 90-day postoperative complication rate. 97 people consented to the study (UC, n=47, mean age 67, BMI 37, TKA 79%; Diet, n=50, mean age 66, BMI 36, TKA 72%). Baseline characteristics indicated gross joint impairments and poor compliance with a low-inflammatory diet. Study feasibility criteria included recruitment rate (52%), proportion of diet patients that improved compliance to low-inflammatory diet by ≥10% (57%) and had ≥60% attendance of dietitian consultations (72%), proportion of patients who undertook serum biomarkers (55%). By presurgery assessments, the diet group had more patients who cancelled their surgery due to symptom improvement (4 vs 0), reduced waist-circumference measurements, increased compliance with the Low-Inflammatory diet and preservation of physical activity parameters. More usual care participants experienced at least one postoperative complication to 90-days (59% vs 47%) and were discharged to inpatient rehabilitation (21% vs 11%). There was no difference in weight change, physical function, and patient-reported outcome measures from pre-surgery to 90-days post-surgery, and length of hospital stay. Using pre-determined feasibility criteria, conducting a definitive trial is not feasible. However, intervention audit demonstrated high intervention fidelity. Pilot data suggest our program may promote weight loss but the clinical effects for most are modest. Further research utilising a stronger intervention may be required to assess the effectiveness of a pre-arthroplasty weight-loss intervention

Aim. We outline a treatment protocol for subjects with chronic periprosthetic joint infections (PJI) who elected not to have surgery. We developed a method of serial “fluid-depleting” aspirations with intra-articular gentamycin injections to affect the population of the biofilm community. We have experienced many treatment failures, as expected, but have also had a group of subjects who responded exceptionally well, requiring no surgical intervention. Our longest follow-up is 10 years. Method. From June 2009 to December 2018, 372 clinical cases of chronic PJI involving primary and revision TKA and THA were treated. Of these, 25 subjects were treated with an active suppression protocol, in lieu of surgery. The protocol entailed frequent aspirations and intra-articular antibiotic injections to quell the PJI inflammatory response. All aspirations were performed by the treating surgeon in the orthopaedic clinic without fluoroscopic guidance. Based on a subject's response to the protocol, he/she was identified as 1 of 3 classifications: 1) Ongoing Treatment – Biofilm Trained (OTBT), 2) Ongoing Treatment – Biofilm Untrained (OTBU), and 3) Treatment Failure (TF). OTBT subjects showed no clinical signs of infection. Serum biomarkers (CRP, ESR) remained consistently normal and subjects were not on oral suppressive antibiotics. Aspiration analysis and cultures remained negative. Maintenance treatment consisted of a fluid-depleting aspiration with an intra-articular gentamycin injection every 12–16 weeks. OTBU subjects showed improved clinical symptoms, lowered serum biomarkers, and lowered WBC counts, but still demonstrated objective signs of infection. TF subjects did not respond to the protocol and showed unchanged/worsening clinical symptoms. Results. Of the 25 subjects, 8 were THA's and 17 were TKA's. Of these cases, 21 (84%) were endoprosthetic replacements. 8 subjects (32%) were classified as OTBT, 6 (24%) as OTBU, and 11 (44%) as TF. All TF subjects were treated with a two-stage exchange protocol. Conclusions. This study is the first describing the potential of modifying bacterial biofilm in a chronic PJI. While our success rate was modest (32%), “Biofilm Trained” subjects demonstrated dramatic changes. Subjects led normal lives, only minimally disrupted by an aspiration and injection every 3–4 months. In the future, we are looking at different agents to modify the enveloping biofilm, including a pre-aspiration injection of EDTA to disrupt the biofilm surface, followed by injecting benevolent bacteria to transform the biofilm to a benevolent state. If able to achieve such a state in a consistent fashion, the impact on the patient and healthcare communities would be enormous

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

Aims. We wished to quantify the extent of soft-tissue damage sustained during minimally invasive total hip arthroplasty through the direct anterior (DA) and direct superior (DS) approaches. Materials and Methods. In eight cadavers, the DA approach was performed on one side, and the DS approach on the other, a single brand of uncemented hip prosthesis was implanted by two surgeons, considered expert in their surgical approaches. Subsequent reflection of the gluteus maximus allowed the extent of muscle and tendon damage to be measured and the percentage damage to each anatomical structure to be calculated. Results. The DA approach caused substantially greater damage to the gluteus minimus muscle and tendon when compared with the DS approach (t-test, p = 0.049 and 0.003, respectively). The tensor fascia lata and rectus femoris muscles were damaged only in the DA approach. There was no difference in the amount of damage to the gluteus medius muscle and tendon, piriformis tendon, obturator internus tendon, obturator externus tendon or quadratus femoris muscle between approaches. The posterior soft-tissue releases of the DA approach damaged the gluteus minimus muscle and tendon, piriformis tendon and obturator internus tendon. Conclusion. The DS approach caused less soft-tissue damage than the DA approach. However the clinical relevance is unknown. Further clinical outcome studies, radiographic evaluation of component position, gait analyses and serum biomarker levels are necessary to evaluate and corroborate the safety and efficacy of the DS approach. Cite this article: Bone Joint J 2016;98-B1036–42

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. 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

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Aims

The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model.

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The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

Aims

Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

Aim. Diagnosis of clavicle osteomyelitis (OM) is often difficult with delayed treatment due to the lower incidence of this disease. The present study aimed to summarize clinical experience with clinical features and treatment of clavicle OM. Method. We systematically searched the Pubmed database to identify studies regarding clinical characteristics and management of clavicle OM from 1980 to 2016, with publication language limited to English. Effective data were collected and pooled for analysis. Results. Altogether 69 reports comprising 188 cases were included for analysis. The average age of included patients was 24.95 years, 57.98% of whom were younger than 20 years. According to different etiologies, 86 cases (45.74%) were categorized as infectious OM with 102 cases (54.26%) as noninfectious. Of all the 102 noninfectious OM, 62.13% were diagnosed as chronic recurrent multifocal osteomyelitis (CRMO). The female-to-male ratio of infectious clavicle OM was 1.09, with 3.43 of noninfectious clavicle OM. The most common and earliest clinical symptom was pain, which occurred in 86.81% of the patients. Positive rate of serum erythrocyte sedimentation rate (ESR) was the highest among serum inflammatory biomarkers reported (92.47%). Staphylococcus aureus (46.94%) was the most frequently detected pathogen among patients with infectious clavicle OM. A total of 50 patients received surgical interventions finally (42.37 %). The most frequently used antibiotic was cephalosporin. Most cases achieved favorable outcomes (89.91%). Conclusions. Clavicle OM, classified as infectious and noninfectious, mostly occurred in the young people and females. The most frequently identified clinical symptom was pain. Despite different treatment strategies, most patients could achieve favorable outcomes

Aims

Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

Aims

It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs.

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.

Objectives

Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis.

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.

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.