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Introduction: This study tried to ascertain (1) the accuracy of synovial fluid white blood cell count and polymorphonucleate percentage in the diagnosis of periprosthetic hip and knee infections, (2) which test yielded superior test performance, and (3) the influence on diagnostic accuracy of study characteristics such as patient number, study design, study level, anatomic site, and threshold value.Methods: A systematic search was conducted including papers assessing more effective cutoffs for synovial fluid tests, having comparative design, evaluating an exclusive cohort of hip or knee prostheses, including a clear definition of infected cases, and reporting sufficient data for the calculation of true-positive, false-positive, false-negative, and true-negative.Results: A total of 375 articles were collected and, given the inclusion criteria, ten manuscripts were included. These studies assessed 1155 hip prostheses (276 infected cases) and 1235 knee prostheses (401 infected cases). The specificity of synovial fluid white blood cell count was significantly increased by using the threshold value ≥ 3000 cell/μL (p = 0.006); the sensitivity of polymorphonucleate percentage was significantly higher in detecting knee infections (p = 0.034).Discussion: Both tests had a high specificity and sensitivity in detecting periprosthetic joint infections, and no clear superiority of one over the other existed. Furthermore, cutoff and anatomic site significantly influenced synovial fluid white blood cell count and polymorphonucleate percentage, respectively.Conclusion: Synovial fluid analysis is adequate in differentiating patients with periprosthetic hip and knee infections. Our data confirms international guidelines suggesting the use of 3000 cell/μL as cutoff threshold for synovial fluid white blood cell count. Since an anatomic site effect has been demonstrated, the goal of future studies will be to identify different cutoffs for hip and knee prostheses. [ABSTRACT FROM AUTHOR]

Purpose: Septic arthritis presents with good joint function, but sometimes leads to poor outcomes. Concurrent systemic sepsis has been regarded as the poor outcome, and the exact cause remains unclear. This paper was performed to identify factors associated with concurrent systemic sepsis and to research results to predict poor outcomes in patients with septic arthritis.Methods: Laboratory and medical data were reviewed for 137 adults with acute septic arthritis who underwent open or arthroscopic surgical debridement at our institution between January 2005 and December 2014. The patients were divided according to whether they had septic arthritis alone (Group A) or in combination with systemic sepsis (Group B). Systemic sepsis was defined as two more systemic inflammatory signs in response to an infectious process. Patient characteristics, laboratory findings, synovial fluid findings and cultures, and surgical results were compared between two groups.Results: Of the 137 patients, 41 (29.9%) had initial systemic sepsis at the diagnosis of septic arthritis. Independent t test revealed that duration of prodromal symptom (p = 0.012), serum neutrophil percent (p = 0.008), C-reactive protein (p = 0.001), Charlson comorbidity index (p = 0.001), positive culture in synovial fluid (p = 0.001), and methicillin-sensitive Staphylococcus aureus (MSSA) isolate in synovial fluid (p = 0.001) had significant correlations with the group B. Repeated debridement was performed for those who had recurrence of infection, and this procedure was more often in group B (23 versus 21 joints, 23.9 versus 51.2%, p = 0.012). Progression of arthritis occurred more often in group B (16 versus 17 joints, 16.7 versus 41.5%, p = 0.001).Conclusion: Septic arthritis combined with systemic sepsis was related to duration of prodromal symptom, serum neutrophil percent, C-reactive protein, Charlson comorbidity index, positive culture in synovial fluid, and a MSSA isolate in synovial fluid. Concurrent systemic sepsis led to poor outcomes in patients with septic arthritis in terms of recurrence of infection and progression of arthritis.Level Of Evidence: III Case control study. [ABSTRACT FROM AUTHOR]

Purpose: The diagnostic criteria of prosthetic joint infection (PJI) recommended by the most commonly used diagnostic algorithms can be obscured or distorted by other inflammatory processes or aseptic pathology. Furthermore, the most reliable diagnostic criteria are garnered during revision surgery. A robust, reliable addition to the preoperative diagnostic cascade is warranted. Calprotectin has been shown to be an excellent diagnostic marker for PJI. In this study, we aimed to evaluate a lateral flow test (LFT) in the challenging patient cohort of a national referral centre for revision arthroplasty. Methods: Beginning in March 2019, we prospectively included patients scheduled for arthroplasty exchange of a total hip (THA) or knee arthroplasty (TKA). Synovial fluid samples were collected intra-operatively. We used the International Consensus Meeting of 2018 (ICM) score as the gold standard. We then compared the pre-operative ICM score with the LFT result to calculate its diagnostic accuracy as a standalone pre-operative marker and in combination with the ICM score as part of an expanded diagnostic workup. Results: A total of 137 patients with a mean age of 67 (± 13) years with 53 THA and 84 TKA were included. Ninety-nine patients (72.8%) were not infected, 34 (25.0) were infected, and four (2.9%) had an inconclusive final score and could not be classified after surgery. The calprotectin LFT had a sensitivity (95% confidence interval) of 0.94 (0.80–0.99) and a specificity of 0.87 (0.79–0.93). The area under the receiver operating characteristic curve (AUC) for the calprotectin LFT was 0.94 (0.89–0.99). In nine cases with an inconclusive pre-operative ICM score, the calprotectin LFT would have led to the correct diagnosis of PJI. Conclusions: The synovial fluid calprotectin LFT shows excellent diagnostic metrics both as a rule-in and a rule-out test, even in a challenging patient cohort with cases of severe osteolysis, wear disease, numerous preceding surgeries, and poor soft tissue conditions, which can impair the common diagnostic criteria. As it is available pre-operatively, this test might prove to be a very useful addition to the diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of periprosthetic joint infection (PJI) after total joint replacement remains challenging. Synovial biomarkers are recommended as the major diagnostic criteria for PJI. The purpose of this study was to test the accuracy of the alpha-defensin test and compare it with that of the leukocyte esterase (LE) test for the diagnosis of PJI. Methods: We obtained 130 hip or knee aspirates from May 2015 to September 2018. PJI was defined according to the European Bone and Joint Infection Society (EBJIS) criteria. Synovial fluid samples were tested with the alpha-defensin ELISA and a LE strip. For the LE strip test, besides using the traditional threshold 500 (equal to ++), we are also using an improved one, with 500 (equal to ++) serving as the threshold for the tests before centrifugation and both 250 and 500 indicating positive results after centrifugation. The receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value, negative predictive value, and Cohen's Kappa value were calculated for the LE and alpha-defensin tests. Results: The area under the curve (AUC) of alpha-defensin, LE strip test with traditional, and improved interpretation strategy were 0.875, 0.854, and 0.877, respectively. The Cohen's Kappa value for the alpha-defensin tests was 0.826 with the traditional LE interpretation strategy and 0.875 with the improved strategy. Conclusion: The present study shows that the use of the LE strip to test synovial fluid yielded an accuracy similar to that of the alpha-defensin immunoassay for the diagnosis of PJI; this finding supports the 2018 ICM PJI definition, which considers positive alpha-defensin and LE test results to be equivalent. [ABSTRACT FROM AUTHOR]

Aims: Recently, the determination of biochemical markers has been intensely explored to better understand the mechanisms underlying knee OA. In this study, we aimed to explore the expression pattern of five biochemical markers in patients with knee OA. Methods: After IRB approval and signed informed consent, 26 patients were enrolled. Serum and synovial samples were collected prior to knee arthroscopy. Pre-operative assessment included diagnosis, Lysholm, Tegner Activity Scale, IKDC score, and radiographic Kellgren and Lawrence classification. ELISA of CTX-I, CTX-II, NTX-I, MMP3, and MMP13 were measured in serum and synovial fluid samples. Results: Twenty-six patients were included, with a mean age of 42 ± 15 years old. Mean results and standard deviation of the biomarkers in serum were as follows: CTX-I 5.8 ± 5.5 ng/mL, CTX-II 3.8 ± 1.7 ng/mL, NTX-I 52 ± 71 (nM BCE), MMP3 1.18 ± 0.6 ng/mL, and MMP13 1243.6 ± 1422 pg/mL; synovial fluid results were as follows: CTX-I 0.74 ± 0.5 ng/mL, CTX-II 5.1 ± 2.5 ng/mL, NTX-I 254 ± 85 (nM BCE), MMP3 0.4 ± 0.4 ng/mL, and MMP13 797 ± 1391 pg/mL. We observed a differential pattern of expression in serum NTX-I in patients with chronic meniscus injuries when compared with ACL injuries or cartilage lesions. Conclusions: In conclusion, the clinical criteria of early OA are useful to categorize patients with knee conditions. The biochemical markers explored did not yield a differential pattern that can be associated with this classification. Serum NTX-I could be a useful marker of chronic meniscal lesion in future longitudinal studies, after adjusting for age and sex. [ABSTRACT FROM AUTHOR]

Purpose: Besides other diagnostic test methods, established serum inflammatory markers such as serum C-reactive protein or leukocyte count are widely used preoperatively to aid in diagnosing periprosthetic joint infections (PJI). Although low accuracies were reported, these parameters are easily accessible and routinely available. Novel biomarkers with promising results in diagnosing PJI (platelet count to mean platelet volume ratio) or other infectious conditions (percentage of neutrophils, neutrophils to lymphocytes ratio) were described. The purpose of this study was to investigate the diagnostic value of established and novel serum inflammatory biomarkers for the diagnosis of PJI so as to compare the results to find the serum inflammatory marker with the best performance. Methods: In 177 patients with a previous total hip (n = 91) or knee (n = 86) arthroplasty and indicated revision surgery, the diagnostic value of the routinely available serum inflammatory markers C-reactive protein (CRP), white blood cell count (WBC), percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), fibrinogen and platelet count to mean platelet volume ratio (PC/mPV) were examined retrospectively via receiver operating characteristic curve analysis (AUC). The curves were compared using the z-test. Results: Sensitivities of serum CRP, WBC, %N, NLR, fibrinogen and PC/mPV were calculated with 68%, 36%, 66%, 63%, 69% and 43%, respectively. Specificities were 87%, 89%, 67%, 73%, 89% and 81%, respectively. Serum CRP (0.78) and fibrinogen (0.79) showed significantly better AUCs compared with serum WBC (0.63), %N (0.67), NLR (0.68) and PC/mPV (0.62) (p < 0.0001). Patients with PJI caused by a low-virulent microorganism (median CRP: 17.6 mg/L) obtained lower CRP levels compared with infections caused by high-virulent microorganisms (median CRP: 49.2 mg/L; p = 0.044). The combination of CRP and fibrinogen showed a better sensitivity (77%) with similar specificity (83%) than one method alone but not at a significant level (CRP (p = 0.200); fibrinogen (p = 0.437)). Conclusion: Serum CRP and fibrinogen showed the best accuracies among these widely available serum inflammatory parameters. However, due to the insufficient performance, these biomarkers can only be recommended as suggestive criteria in diagnosing PJI. The preoperative workup should always be complemented by more specific tests such as synovial fluid analysis. [ABSTRACT FROM AUTHOR]

Background: Total joint arthroplasty (TJA) is considered one of the most successful surgical procedures ever developed. It can successfully provide pain relief, restore joint function, and improve mobility and quality of life. Prosthetic joint infection (PJI) presents with a wide variety and severity of signs and symptoms. It remains a major threat to the outcome of TJA procedures and usually necessitates surgical intervention and prolonged courses of antibiotics. Inappropriate treatment of an unrecognized PJI usually ends with unacceptable and sometimes catastrophic results.the Aim: The understanding and evaluation of diagnostic investigations are extremely important to properly diagnose PJI, including frequently unrecognized low-grade infections, and to provide healthcare professionals with needed information for the care of patients affected by this condition. This article aims to review most of the methods available in PJI diagnostics, to emphasize the strengths and the weaknesses of each of them, and to provide a guideline on how to select the surgical treatment strategy based on the level of diagnostic certainty during the evaluation period. To safely accomplish this, it is crucial to be aware of the limitations of each diagnostic modality.the Focus: The emphasis will be on the use and interpretation of the core criteria for PJI diagnosis, including the pathognomonic sinus tract communicating with the implant, purulent synovial fluid, inflammation in the periprosthetic tissue, cell count with differential, microbial growth in the synovial fluid culture, tissue sample cultures, and sonication samples. [ABSTRACT FROM AUTHOR]

Purpose: Periprosthetic joint infection (PJI) is a catastrophic complication after total joint arthroplasty (TJA). Treatment of PJI is challenging, especially when causative microorganism is not identified. The purpose of this systematic review was to guide diagnostic approach and treatment of culture-negative (CN) PJI.Methods: A systematic review was undertaken on clinical studies from MEDLINE, EMBASE, Cochrane Library, and Scopus databases. Basic science studies, letters, studies written in languages other than English, case reports, and review articles were excluded.Results: Proportion of CN PJI ranged from 5 to 42% of PJIs. Risk factors for culture negativity included prior use of antibiotic before culture test, inappropriate culture tools, insufficient culture period, and post-operative wound drainage. Specific diagnostic protocols including repeating sampling, longer incubation period, culture in blood culture bottles, sonication of implants, polymerase chain reaction in synovial fluid, and next-generation sequencing are recommended to identify undetected microorganisms. Vancomycin and cephalosporins are the most commonly used antibiotics. Two-stage revision arthroplasty showed success rate of 70-100%.Conclusions: A comprehensive review was performed to provide an up-to-date, evidence-based guide to the management of CN PJI. [ABSTRACT FROM AUTHOR]

Purpose: Septic arthritis caused by Mycoplasma is rare. The diagnosis and effective treatment of mycoplasmal septic arthritis remains a serious problem for clinicians. The aim of this systematic review was to document the available evidence on the diagnosis and treatment methods for mycoplasmal septic arthritis and to provide guidance for clinicians.Methods: The PubMed, EMBASE, and Cochrane Library databases were searched in December 2018.The searches were limited to the English language. Article screening and data extraction and compilation were conducted by two independent reviewers. All the included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS) tool.Results: There was a total of 33 articles including 34 cases of mycoplasmal septic arthritis and eight of them were periprosthetic joint infection (PJI). Twenty-four patients (70.6%) were immunocompromised, and the synovial fluid white blood cell (WBC) count was significantly lower in the immunocompromised group than in the immunocompetent group (48,527 × 106/L vs. 100,640 × 106/L; P = 0.009). The traditional culture method took longer, and the positivity rate was lower than that of nucleic acid testing (50% vs. 100%; P = 0.016). Only 19.2% (5/26) of patients treated with empiric antibiotics were relieved of symptoms, while 82.4% (28/34) of patients achieved satisfactory results after being treated with antibiotics against Mycoplasma.Conclusion: The possibility of mycoplasmal septic arthritis should be considered if patients with joint infections have a history of immunocompromised, repeated negative cultures, and poor empiric antibiotic treatment results. The rational use of nucleic acid testing technologies can help in the clinical diagnosis and treatment of mycoplasmal septic arthritis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the pre-operative performance of an automated multiplex PCR (mPCR) system in patients with suspected periprosthetic joint infection (PJI).Methods: Under sterile conditions, synovial fluid samples from patients with a suspected PJI were collected pre-operatively. One hundred eighty microliter of the aspirate was used for analysis in the mPCR. The remaining joint fluid was sent for microbiological analysis. PJI was diagnosed by using the Musculoskeletal Infection Society (MSIS) criteria. Total percentage agreement and Cohen's kappa coefficient were calculated to measure overall agreement.Results: Overall, 90 patients with a suspected PJI were included. Using MSIS criteria, 38 (42%) patients were classified as septic. Total percent agreement between mPCR and synovial fluid culture was 86% with a Cohen's kappa of 0.68. The mPCR and synovial fluid culture showed sensitivities of 71% and 84%, respectively. Combined evaluation provided an even higher sensitivity of 92%. While Cutibacterium spp. were detected five times by mPCR, it could only be cultured once. A higher detection rate of CoNS by mPCR (n = 7) compared to conventional culture (n = 5) was also demonstrated. In comparison to synovial fluid culture, the mPCR missed Staphylococcus aureus five times.Conclusion: With a moderate agreement between synovial fluid mPCR and culture, the mPCR system could be a useful adjunct in diagnosing a PJI pre-operatively. Due to faster availability of results and a higher detection rate of low-virulent microorganisms, it can complement conventional culture. [ABSTRACT FROM AUTHOR]

Background: Histopathological tissue analysis is a key parameter within the diagnostic algorithm for suspected periprosthetic joint infections (PJIs), conventionally acquired in open surgery. In 2014, Hügle and co-workers introduced novel retrograde forceps for retrograde synovial biopsy with simultaneous fluid aspiration of the knee joint. We hypothesised that tissue samples acquired by retrograde synovial biopsy are equal to intra-operatively acquired deep representative tissue samples regarding bacterial detection and differentiation of periprosthetic infectious membranes.Method: Thirty patients (male n = 15, 50%; female n = 15, 50%) with 30 suspected PJIs in painful total hip arthroplasties (THAs) were included in this prospective, controlled, non-blinded trial. The results were compared with intra-operatively obtained representative deep tissue samples.Results: In summary, 27 out of 30 patients were diagnosed correctly as infected (17/17) or non-infected (10/13). The sensitivity to predict a PJI using the Retroforce® sampling forceps in addition to standard diagnostics was 85%, the specificity 100%.Conclusions: Retrograde synovial biopsy is a new and rapid diagnostic procedure under local anaesthesia in patients with painful THAs with similar histological results compared to deep tissue sampling. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic tissue cultures, sonication and synovial fluid cultures remain the gold standard for prosthetic joint infection (PJI) diagnosis. However, some 15-20% culture-negative PJI are still reported. Therefore, there is the need for other diagnostic criteria. One point of concern relative to the different definitions of PJI is as to the inclusion of the c-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as diagnostic criteria for PJI despite them being non-specific inflammatory blood tests.Purpose: The purpose of the present study was to determine the relevance of CRP and the ESR in the diagnosis of PJI.Methods: All PJI with positive cultures over a two-year period in two hospitals were reviewed. The main variables of the present study were the type of prosthesis and the CRP level. More information was recorded in those patients with normal CRP: radiographs, physical examination records and the ESR.Results: Seventy-three patients were included in study. Pre-operative CRP levels were normal (lower than 0.8 mg/dl) in 23 patients, representing 32% of all PJI with positive cultures. Low virulence micro-organisms, 12 coagulase-negative staphylococci and four P. acnes, grew in most of them. They represented 70% of all PJI with normal CRP levels. In addition, 17 patients (23% of all PJI with positive cultures) had a normal ESR, a normal physical examination (they only presented with pain) and no clear loosening was observed in the radiographs.Conclusions: Per the American Association of Orthopaedic Surgeons (AAOS) guidelines or the Musculoskeletal Infection Society (MSIS), 23% of the patients in the present study with PJI would never have been identified. Blood inflammatory markers such as the CRP level and ESR may not be accurate as diagnostic tools in PJI, particularly to identify low-grade and chronic PJI. [ABSTRACT FROM AUTHOR]

Purpose: Diagnosing periprosthetic infection remains a challenge. Multiplex-PCR and biomarkers such as alpha-defensin are potentially useful and fast methods for detecting periprosthetic infection. This study compared these new methods with clinical assessment, conventional microbiological methods and histo-pathological examination.Methods: Twenty-eight consecutive patients with 30 joints and a mean age of 67.7 years (range 39 to 88) with removal of total hip arthroplasty (THA) or total knee replacement (TKR) were included in this study. Patients were classified according to the modified Musculoskeletal Infection Society score (MSIS) for infected joints. Punction fluid and tissue specimens were taken for conventional microbiological examination, alphadefensin test was performed, a synovial membrane specimen was used for multiplex-PCR and histopathological examination was carried out.Results: The alpha-defensin test and multiplex-PCR showed a sensitivity of 76.9 vs. 30.8% and a specificity of 82.4 vs. 100%, respectively. We found a significant difference between the positive and negative results (p = 0.0023). The conventional microbiological methods were not significantly different from the alpha-defensin test (p = 0.244) with a sensitivity of 84.6% and a specificity of 100% but did differ significantly from the multiplex PCR (p = 0.0030). There was a significant difference between modified MSIS classification and multiplex PCR (p = 0.0007).Conclusions: Neither alpha-defensin test nor multiplex-PCR could detect periprosthetic infection immediately and reliably. Multiplex-PCR was suitable for detecting the non-infected but not the truly infected. Alpha-defensin test was helpful but showed no satisfactory results. Conventional microbiological methods remain the most reliable for periprosthetic infection diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Periprosthetic joint infection (PJI) continues to be a significant complication after total joint arthroplasty. Diagnosis of PJI can be challenging and elusive in the absence of a gold standard. This purpose of this article is to review the current evidence on the utility of serum and synovial fluid biomarkers to help aid in the diagnosis of PJI with focusing on synovial fluid alpha-defensin.Methods: Articles and data for this review were identified by searches of PubMed and Ovid MEDLINE up to June 1, 2016. In addition, we manually reviewed the bibliographies of the retrieved articles for additional citations for references from relevant articles on the diagnosis of PJI.Results: Serum biomarkers can be elevated in various inflammatory conditions. Synovial fluid biomarkers are more accurate for the diagnosis of PJI compared to serum biomarkers. Based on current available data, alpha-defensin is the most promising synovial fluid biomarker for the diagnosis of PJI and is commercially available.Conclusions: Synovial fluid alpha-defensin could enhance our ability to identify PJI and incorporate into the diagnostic algorithm in the future. Large-scale studies are needed to provide more data for its significance for the diagnosis of PJI. [ABSTRACT FROM AUTHOR]

Objective: There is still a lack of reliable data on cytokine concentrations in the ankle and their value for prognosis. Methods: In a prospective clinical trial, lavage fluids were collected from 49 patients with an arthroscopy of the ankle. The fluids were investigated by ELISA for cytokine levels. Clinical scores (FFI, AOFAS) were evaluated both pre-operatively and then again 12 months after surgery ( n = 43, 88%). Radiological changes were noted with the Kellgren-Lawrence-Score (KLS) and the Ankle Osteoarthritis Scoring System (AOSS). Based on the difference between the pre- and postoperative clinical scores, two groups were defined according to whether they had benefited from the surgical therapy (Δ score ≥ 10) or not (Δ score < 10). Results: The average clinical scores had improved to a statistically significant extent in the one-year follow-up ( p < 0.01). BMP-2 ( p = 0.02), IGF-1 ( p = 0.04), BMP-7 ( p = 0.01) and aggrecan ( p = 0.04) showed significant correlations with pre-operative clinical and radiological scores ( p = 0.02, p = 0.01, p = 0.01, p = 0.01). Furthermore, BMP-2 ( p = 0.01), IGF-1/TPC ( p = 0.03) and aggrecan ( p = 0.01) correlated with scores after one year ( p = 0.02, p = 0.01). High aggrecan concentrations were associated with a low clinical and a high radiological score at both time points, both indicating progress of cartilage degeneration in contrast to BMP-2 or IGF-1. Furthermore, MMP-13 concentrations were significantly higher in the non-benefit group ( p = 0.02). Conclusion: BMP-2, IGF-1, aggrecan and MMP-13 seem to be involved in the degenerative process of cartilage in the ankle joint. Additionally, high synovial MMP-13 concentrations indicate a worse clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine calcitonin gene-related peptide (CGRP) concentrations in serum and synovial fluid of patients with primary knee osteoarthritis (OA) and healthy controls and to explore their relationship with clinical and radiographic severity of OA. Methods: Sixty-five patients with primary knee OA and 21 healthy controls were recruited. CGRP concentrations in the serum and synovial fluid were measured using enzyme-linked immunosorbent assays. The radiographic severity of OA was evaluated using the Kellgren and Lawrence (KL) classification. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess pain, stiffness and physical function. Results: Serum and synovial fluid CGRP concentrations tended to be higher with the increase in KL grades ( r = 0.565 and r = 0.441, P < 0.001, respectively), and were significantly positively correlated with KL grades, total WOMAC score and each subscale (pain, stiffness and physical function). Conclusions: The result demonstrated that CGRP in serum and synovial fluid was related to progressive joint damage in knee OA. CGRP can be selected as a biomarker for monitoring disease severity and could be a predictive role on prognosis and progression of knee OA. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to investigate whether serum and synovial-fluid (SF) concentrations of interleukin-6 (IL-6), leptin, adiponectin, resistin or visfatin are associated with joint pain in hip and knee in end-stage osteoarthritis (OA). Methods: A cross-sectional study assessing patients with hip and knee OA undergoing total joint arthroplasty between January and December 2010 was conducted at a large university hospital. Serum and SF cytokine and adipokine concentrations were determined in samples obtained on the day of surgery. The main outcome was pain severity measured pre-operatively using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) pain scores. Results: A total of 206 patients were involved (112 with hip and 94 with knee OA). Median age was 72 years [interquartile range (IQR) 66-79], 59 % were women. All adipokine levels were significantly higher in the SF of hip joints than in that of knee joints, except for leptin, which tended to be higher in the knee. In both hip and knee OA, median serum concentrations of leptin, adiponectin, resistin and visfatin exceeded those in SF, whereas for IL-6, median concentrations were much higher in SF than in serum. In hip OA, worse pain was significantly associated with high SF concentrations of IL-6, visfatin and leptin; in knee OA, it was associated with high SF leptin and low SF adiponectin concentrations and a low adiponectin-leptin ratio. Conclusion: Our findings support a connection between intra-articular concentrations of several adipokines and severity of preoperative OA pain. However, the specific adipokines differed by joints: in hip OA, pain was associated with IL-6 and visfatin and in knee OA with adiponectin; leptin played a role in both hip and knee OA. [ABSTRACT FROM AUTHOR]

Purpose: Periprosthetic joint infections remain a major challenge for the surgeon in modern arthroplasty. The decision on how to handle a case is often difficult due to the variety of clinical presentations. The aim of this study was to establish the leucocyte esterase test as an intra-operative rapid diagnostic tool in an unclear infected or aseptic situation. Methods: In the setting of 364 endoprosthetic joint procedures on knee, hip and shoulder, we aspirated synovial fluid before performing capsulotomy. We performed a leucocyte esterase test. The results were correlated with the pre-operative synovial fluid aspirations, the laboratory blood sample parameters (C-reactive protein, white blood cells) and the intra-operative histopathological and microbiological findings. Results: The leucocyte esterase test has a sensitivity of 100 % and a specificity of 96.5 %. The positive predictive value was 82 % and the negative predictive value was 100 %. Correlation with conventional methods such as serum C-reactive protein and serum white blood cells is given. The histopathological evaluation confirmed the microbiological results in all but three cases. Conclusions: Based on our results and the current literature, we recommend the leucocyte esterase test as a useful tool in the diagnosis of periprosthetic joint infection. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare angiogenic cytokine levels in knee osteoarthritis (OA) patients and healthy controls and to investigate the relationships between angiogenic cytokines and the OA severity. Methods: Thirty-one knee OA patients and 15 healthy controls were recruited. Nine angiogenic cytokines (angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin (IL)-8, leptin, platelet-derived growth factor-BB (PDGF-BB), platelet endothelial cell adhesion molecule (PECAM)-1, and vascular endothelial growth factor (VEGF)) in plasma and synovial fluid were measured using a multiplex immunoassay. Results: PECAM-1, HGF, VEGF, angiopoietin-2, follistatin, G-CSF, and IL-8 concentrations in plasma were significantly higher in OA patients than those in controls. Plasma angiopoietin-2 was significantly greater in advanced OA than in early OA. Synovial fluid VEGF was positively correlated with the severity ( r = 0.367, P = 0.04). Plasma follistatin was significantly lower in advanced knee OA than in early OA and was negatively correlated with the severity ( r = −0.374, P < 0.05). Conclusions: Angiogenic cytokine concentrations in plasma can distinguish between controls and OA patients. Local and circulating levels of angiogenic cytokines could give an insight into the pathophysiology of OA. Follistatin, angiopoietin-2, and VEGF may have potential as biochemical markers for the assessment of OA severity. [ABSTRACT FROM AUTHOR]

Purpose: Recent evidence suggests that angiogenesis and inflammation contribute to the development and progression of osteoarthritis (OA). The purpose of this study was to investigate vascular endothelial growth factor (VEGF) levels in plasma and synovial fluid of patients with knee OA and to determine the relationship of VEGF levels with disease severity in knee OA. Methods: A total of 100 subjects were enrolled in this study (80 knee OA patients and 20 healthy controls). Plasma and synovial fluid VEGF levels were analysed using enzyme-linked immunosorbent assay. VEGF expressions in synovial membrane and articular cartilage samples were assessed using immunohistochemistry. Results: VEGF level in synovial fluid of knee OA patients was tenfold higher than that in paired plasma ( P < 0.001). Both plasma and synovial fluid VEGF exhibited a positive correlation with radiographic severity ( r = 0.454 and r = 0.727, P < 0.001, respectively). VEGF expression was highly detectable in synovial lining cells and articular chondrocytes of knee OA patients. Conclusions: VEGF levels in both plasma and synovial fluid were positively correlated with the severity of knee OA. Therefore, VEGF may be useful for monitoring OA severity and could play a substantial role in the development and progression of knee OA. [ABSTRACT FROM AUTHOR]

Purpose: Hip prostheses with metal-on-metal (MoM) coupling can release cobalt-chromium particles and ions. The aim of this work is to verify the correlation between particles in the synovial fluid and circulating ions. Methods: Forty patients were enrolled; particles from synovial fluid were analysed by SEM-EDX (Scanning Electron Microscopy-Energy Dispersion X-rays analysis) and levels of circulating Co and Cr were assayed by ICP-MS (inductively-coupled plasma mass spectrometry). Results: In 16 cases we did not find any particles in the synovial fluid and the Co level in whole blood was 0.05-4.42 ppb; in seven with few particles the blood level was 2.2-15.6 ppb; in six cases with several particles the level was 5.0-54.3 ppb; finally, in 11 cases we isolated not only Co-Cr particles, but also Cr particles with low or absent Co and in these patients the circulating level of Co was 23.8-109.6 ppb. Co in serum and Cr level both whole blood and serum have shown a similar trend to Co; the correlation between all these values and the corresponding particles is statistically significant in all cases. Conclusion: Co and Cr both in serum and whole blood represents a systemic representation of the particle release at local level and can therefore be used to confirm a diagnosis and monitor the wear process of MoM articular prostheses. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess osteoclastogenic potential of peripheral blood mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in different forms of arthritis and to correlate it with inflammatory mediators within intra-articular and circulatory compartments. Methods: Paired PBMC and SFMC samples of patients with rheumatoid arthritis (RA; n = 10) and psoriatic arthritis (PsA; n = 10), and PBMC of healthy controls were cultured to assess osteoclastogenic potential by the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor activator of nuclear factor-κΒ ( RANK), cFMS, and TRAP). Osteoclastogenesis was correlated with the arthritis-related inflammatory indicators in serum and synovial fluid (SF). Results: Number of OCs differentiated from PBMC was significantly higher in RA and PsA compared with control, with RA having more OCs compared with PsA. There was no difference in SFMC OC number between arthritic patients, but RANK expression in OCs differentiated from SFMC was higher in PsA compared with RA. SF of PsA patients more potently induced OC differentiation from control CD3CD19CD56CD11bCD115 PBMC compared with RA, paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC gene expression of interleukin-18 and Fas-ligand were observed. Conclusion: Osteoclastogenic potential is systemically enhanced in patients with RA, paralleled by disordered systemic and local expression of proinflammatory mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our study reveals arthritis-specific mediators associated with the form of arthritis, indicating clinical relevance for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a proteomic analysis of synovial fluid (SF) to identify differentially expressed proteins and analyse their correlation with osteoarthritis (OA) severity. Our primary purpose was to gain insight into the pathogenesis of OA. Methods: SF samples were acquired from 12 knee OA patients and 12 non-OA controls (ten had a meniscus injury, two had a discoid meniscus and all exhibited intact articular cartilage) and sequentially subjected to two-dimensional electrophoresis (2-DE). The radiographic grading of knee OA was performed using the Kellgren-Lawrence criteria. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Proteins of interest identified from SF were detected using an enzyme-linked immunosorbent assay (ELISA). Results: A total of 31 protein spots showed significant differences ( p < 0.05) between the sample groups; 25 of the 31 spots (80.6 %) were identified as proteins of interest. Among them 20 corresponded to up-regulation and five to down-regulation in OA samples. HLA-DR was one of the proteins up-regulated, which was confirmed by ELISA. Conclusions: These observations have implications in delineating the protein expression underlying the pathogenesis of OA and facilitate further elucidation of molecular mechanisms involved in disease progression. Substantial alterations of the protein profile in SF may be associated with OA severity. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this prospective study was to evaluate the diagnostic efficacy of sonicate fluid cultures (SFC) and the histological analysis of the periprosthetic membrane (PM) for the detection of periprosthetic joint infection (PJI). Methods: The histological samples were evaluated according to the consensus classification of PM as defined by Morawietz and Krenn. All explanted endoprosthesis were subject to sonication. Additionally, a synovial aspiration and microbiological culture of tissue samples were performed for each patient. Twenty three of the 59 patients had an established PJI. Results: Sonication achieved the highest sensitivity out of all diagnostic methods with 91 % and a specificity of 81 %. The PM achieved a sensitivity of 87 % and a specificity of 100 %. In three cases of PJI a pathogen was isolated solely by sonication while all other microbiological methods were negative. In seven cases there was a positive bacterial culture through sonication with negative histology. Conclusions: Our results show a high correlation between the microbiological and histological results. In our patient group sonication achieved the highest sensitivity out of all diagnostic methods and was more sensitive than conventional microbiological methods. [ABSTRACT FROM AUTHOR]

Purpose: Two of the most common joint diseases are rheumatoid arthritis (RA) and osteoarthritis (OA). Cartilage degradation and erosions are important pathogenetic mechanisms in both joint diseases and have presently gained increasing interest. The aim of the present study was to investigate the effects of the synovial fluid environment of OA patients in comparison with synovial fluids of RA patients on human chondrocytes in vitro. Methods: Primary human chondrocytes were incubated in synovial fluids gained from patients with OA or RA. The detection of vital cell numbers was determined by histology and by using the Casy Cell Counter System. Cytokine and chemokine secretion was determined by a multiplex suspension array. Results: Microscopic analysis showed altered cell morphology and cell shrinkage following incubation with synovial fluid of RA patients. Detection of vital cells showed a highly significant decrease of vital chondrocyte when treated with RA synovial fluids in comparison with OA synovial fluids. An active secretion of cytokines such as vascular endothelial growth factor (VEGF) of chondrocytes treated with OA synovial fluids was observed. Conclusions: Significantly increased levels of various cytokines in synovial fluids of RA, and surprisingly of OA, patients were shown. Activation of pro-inflammatory cytokines of human chondrocytes by synovial fluids of OA patient supports a pro-inflammatory process in the pathogenesis of OA. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the management and fate of acutely inflamed joints with a negative synovial fluid culture. Methods: Between January and December 2009, all the patients who presented to our institution with an acutely inflamed joint and were subjected to microbiological assessment of their synovial fluid, were included in the study. Patients with a positive synovial fluid culture, a prosthetic joint replacement in situ and where an aspirate was obtained for a rheumatological diagnosis were excluded. This cohort was then divided into two groups depending on whether a diagnosis could be established through the course of their treatment. Group I included patients in whom a diagnosis could be established and group II included patients in whom a diagnosis could not be established. A thorough review of the patients' medical records and the hospital database was performed. Following this, a database consisting of the patient demographics, clinical features, investigations, treatment and outcome was created. Results: A total of 144 patients met the inclusion criteria (group I: 95, group II: 49). The most commonly affected joint in both the groups was the knee. The average time to presentation was shorter in group II. Clinical findings at presentation were comparable in both groups. However, inflammatory markers were more likely to be raised in group II in comparison with group I. Eighty-two percent of group II required antibiotic treatment compared with 15% of group I. The mean duration of antibiotic treatment in group I was ten days and in group II was 26 days. Mean hospital stay differed significantly between the two groups, with group II being more than twice as long as compared with group I ( p = 0.001). The rate of mortality was also higher in group II (8.2%, p = 0.03). Conclusion: Our study shows that patients presenting with an acutely inflamed joint and a negative synovial fluid culture in whom a diagnosis cannot be established during their hospital stay have a longer hospital stay and an increased rate of mortality as compared with patients in whom a diagnosis can be established. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to evaluate the utility of Newman's classification in predicting outcomes in patients presenting with crystal arthritis. Methods: Between January and December 2009, all patients who presented to our institution with acute crystal arthritis and were investigated with microbiological assessment of their synovial fluid were included in the study. Patients were divided into two groups depending on the fulfilment of Newman's criteria for culture-negative septic arthritis. Group 1 included patients that fulfilled Newman's B criteria. Group 2 included patients that fulfilled Newman's C criteria. A database looking at the demographics, mode of presentation, investigations, treatment and outcomes was then established and the results compared between the two groups. Results: A total of 58 patients were identified (group 1: n = 13; group 2: n = 45). The average age was 71 years (range 33-96). The joint most commonly involved was the knee followed by the wrist. Clinical findings at presentation were comparable in both groups; however, WBC and C-reactive protein (CRP) were more likely to be raised in group 1. Although most patients in group 1 were treated with antibiotics (62%) there was still a higher rate of morbidity, greater use of supportive therapy and a longer hospital stay (22.3 days, SD 17.4) in comparison with group 2, where most patients were treated by observation only (76%, mean hospital stay 3.5 days, SD ± 4.4). The difference in length of hospital stay was statistically significant ( p < 0.0001). Conclusions: Newman's criteria are a good indicator for prognosis in patients with crystal arthritis. However, the presence of crystals in an acutely inflamed joint does not exclude the need for supportive therapy and long hospital stay even in the absence of positive synovial fluid culture. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate plasma and synovial fluid basic fibroblast growth factor (bFGF) levels in patients with primary knee osteoarthritis (OA) and to evaluate the correlation between bFGF levels and disease severity. Methods: Thirty-five patients with knee OA and 15 healthy individuals were recruited into this study. Knee OA grading was performed according to the Kellgren-Lawrence classification. bFGF concentrations in both plasma and synovial fluid were determined using enzyme-linked immunosorbent assay. Results: Plasma and synovial fluid bFGF levels in knee OA patients were significantly higher than in controls ( P < 0.001). Moreover, plasma and synovial fluid bFGF concentrations were positively correlated with radiographic severity ( r = 0.535, P < 0.001 and r = 0.570, P < 0.001, respectively). Further analysis revealed that there was a positive correlation between plasma and synovial fluid bFGF levels ( r = 0.674, P < 0.001). Conclusions: Plasma and synovial fluid bFGF levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. These findings indicate that bFGF levels may be a monitor of disease severity and could play an essential part in the pathophysiology of degenerative process in OA. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to use matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in osteoarthritis research. Our aim was to find differentially expressed disease-related and condition-specific peptide in synovial fluid in the knee joint of patients suffering from osteoarthritis (OA), and to develop and validate the peptide classification model for OA diagnosis. Methods: Based on the American College of Rheumatology criteria, 30 OA cases and ten healthy donors were enrolled and underwent analysis. Magnetic beads-based weak cation exchange chromatography (MB-WCX) was performed for sample processing, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was conducted for peptide profile. ClinProt software 2.2 was used for data analysis and a genetic algorithm was created for class prediction. Results: Two peptide peaks were found which may be characterised as the potential diagnostic markers for OA. Two other significantly different peptide peaks were found in OA patients at a medium stage compared to the early and late stages. A genetic algorithm (GA) was used to establish differential diagnosis models of OA. As a result, the algorithm models marked 100% of OA, and of 97.92% of medium-stage OA. Conclusion: This study demonstrated that use of proteomics methods to identify potential biomarkers of OA is possible, and the identified potential biomarkers may be potential markers for diagnosis and monitoring the progression of OA. [ABSTRACT FROM AUTHOR]

Apelin is a recently discovered hormone secreted by adipocytes. The aim of this study, therefore, was to evaluate the distribution of apelin in paired serum and synovial fluid (SF) of osteoarthritis (OA) patients, as compared to that in healthy controls, and to characterise the expression profile of apelin and its cognate receptor APJ in human chondrocytes. Apelin levels in serum and SF were analysed by enzyme-linked immunosorbent assay (ELISA). Expression of apelin and APJ in human chondrocytes was determined by real-time quantitative polymerase chain reaction (PCR). Apelin was found to be present in OA SF, and concentrations were positively correlated with the severity of OA. OA serum exhibited significantly elevated levels of apelin (2.18 ± 0.22 ng/ml) as compared to normal serum (1.31 ± 0.12 ng/ml) ( p < 0.05), and serum apelin levels exceeded those in paired SF ( p < 0.001). The apelin and APJ transcripts were identified in chondrocytes, and levels were significantly higher in OA cartilage than in healthy donors. These findings suggest that apelin may contribute to the onset and/or progression of OA, and may provide new insights into the pathophysiology of OA. [ABSTRACT FROM AUTHOR]