An update on the study of synovial fluid in the geriatric patient.

BACKGROUND: The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. OBJECTIVE: To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. MATERIALS AND METHODS: A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. RESULTS: The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults' SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). CONCLUSIONS: The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis.

OBJECTIVES: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. METHODS: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). RESULTS: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89-98; I2=23%) and 88% (95% CI, 83-92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92-0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. CONCLUSIONS: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.

Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study.

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Calcium ions have a detrimental impact on the boundary lubrication property of hyaluronic acid and lubricin (PRG-4) both alone and in combination.

Cartilage demineralisation in Osteoarthritis (OA) patients can elevate calcium ion levels in synovial fluid, as evidenced by the prevalence of precipitated calcium phosphate crystals in OA synovial fluid. Although it has been reported that there is a potential connection between elevated concentrations of calcium ions and a deterioration in the lubrication and wear resistance of cartilage tissues, the mechanism behind the strong link between calcium ion concentration and decreased lubrication performance is unclear. In this work, the AFM friction, imaging, and normal force distance measurements were used to investigate the lubrication performances of hyaluronic acid (HA), Lubricin (LUB), and HA-LUB complex in the presence of calcium ions (5 mM, 15 mM, and 30 mM), to understand the possible mechanism behind the change of lubrication property. The results of AFM friction measurements suggest that introducing calcium ions to the environment effectively eliminated the lubrication ability of HA and HA-LUB, especially with relatively low loading applied. The AFM images indicate that it is unlikely that structural or morphological changes in the surface-bound layer upon calcium ions addition are primarily responsible for the friction results demonstrated. Further, the poor correlation between the effect of calcium ions on the adhesion forces and its impact on friction suggests that the decrease in the lubricating ability of both layers is likely a result of changes in the hydration of the HA-LUB surface bound layers than changes in intermolecular or intramolecular binding. This work provides the first experimental evidence lending towards the relationship between bone demineralisation and articular cartilage degradation at the onset of OA and the mechanism through which elevated calcium levels in the synovial fluid act on joint lubrication.

Neutrophil-Lymphocyte Ratio and Lymphocyte-Monocyte Ratio correlate with Chronic Prosthetic Joint Infection but are not useful markers for diagnosis.

PURPOSE: To investigate reported correlations between Neutrophil-to-Lymphocyte (NLR) and Lymphocyte-to-Monocyte (LMR) ratios and their value in diagnosis of chronic prosthetic joint infection (PJI) in a large cohort of patients from a single specialist hospital. METHODS: Diagnostic aspirations of 362 patients under investigation for PJI were identified. Of the included patients 185 patients received a final diagnosis of PJI and 177 were classed as aseptic. Established criteria (ICM 2018) were employed to define PJI. Included in the analysis are differential white cell counts, C-Reactive Protein (CRP), Synovial Leukocyte Count, Synovial Alpha-defensin ELISA and Synovial Leukocyte esterase activity. Receiver-operator characteristic (ROC) curves were calculated for each of the available diagnostic tests together with the corresponding area under the curve values (AUC). Youden's index was utilized to identify the optimal diagnostic threshold point for the NLR and LMR. Other diagnostic tests were evaluated as per the threshold values previously defined in the literature and specified in the ICM criteria. RESULTS: Using Youden's Index to identify the optimal NLR cut-off within our cohort we established a value of 2.93. This yielded a sensitivity of 0.60 and specificity of 0.64. The area under the curve (AUC) of a receiving operator characteristics (ROC) curve was 0.625. Regarding the LMR the results demonstrate similar findings; a positive correlation with a diagnosis of infection but poor sensitivity and specificity. The AUC for LMR was 0.633 and was not superior to NLR (P = 0.753). CONCLUSIONS: There is a significant correlation between higher Neutrophil-Lymphocyte and Lymphocyte-Monocyte ratios, and a diagnosis of PJI. The sensitivity and specificity of this calculation is poor and the does not add value to the diagnostic algorithm for PJI. LEVEL OF EVIDENCE: Level III Retrospective Cohort analysis.

Knee Osteotomy Decreases Joint Inflammation Based on Synovial Histology and Synovial Fluid Analysis.

PURPOSE: To examine the biological changes in the joints of patients with knee osteoarthritis (OA) before and after around-knee osteotomy (AKO), focusing on synovial fluid (SF) and synovial pathological changes. METHODS: Patients who underwent AKO for medial compartment knee OA between 2019 and 2021 were examined. SF and synovium were obtained at the time of AKO and plate removal after bone union (mean, 16.8 months [range: 11-38 months] postoperatively). SF volume and interleukin (IL)-6 concentrations in SF were assayed using enzyme-linked immunosorbent assay. Synovitis was assessed histologically using a semiquantitative scoring system. Macrophage infiltration was assessed by immunohistochemistry using a semiquantitative score for F4/80 expression. The M1/M2 ratio was calculated using percentage of cells positive for CD80 and CD163. The expression of proinflammatory cytokines was assessed by the percentage of IL-1ß- and IL-6-positive cells. The number of vascular endothelial growth factor-positive luminal structures was counted to assess angiogenesis. The change in each parameter was compared before and after AKO using the Wilcoxon matched-pairs signed-rank test. RESULTS: Twenty-four knees of 21 patients were included. SF volume and IL-6 concentration significantly decreased postoperatively (12.6 ± 2.1 mL vs 4.2 ± 0.6 mL; P < .0001 and 50.5 ± 8.6 pg/mL vs 20.7 ± 3.8 pg/mL; P = .0001, respectively). A significant reduction in synovitis score (P = .0001), macrophage infiltration (P < .0003), M1/M2 ratio (P < .0007), angiogenesis (P < .0001), and the percentage of IL-1ß- and IL-6-positive cells in the intima (P < .008 and P < .002, respectively) was found after AKO. CONCLUSIONS: SF volume and IL-6 concentrations in the SF decreased and inflammatory synovium pathology improved after AKO. In addition to biomechanical changes, the biological environment of the joint can be improved after AKO. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Two-dimensional liquid chromatography measurement of meropenem concentration in synovial fluid of patients with periprosthetic joint infection.

Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery. One potential treatment approach for PJI could be the combination of one-stage revision and intra-articular infusion of antibiotics. Meropenem is one of the commonly used intra-articular antibiotics in our institution. Determining the concentration of meropenem in the joint cavity could be crucial for optimizing its local application, effectively eradicating biofilm infection, and improving PJI treatment outcomes. In this study, we developed a simple, precise, and accurate method of two-dimensional liquid chromatography (2D-LC) for determining the concentration of meropenem in human synovial fluid. The method was then validated based on the guidelines of the Food and Drug Administration and the Chinese Pharmacopoeia. Meropenem showed good linearity in the range of 0.31-25.01 µg/mL (r ≥ .999). Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, and stability validation results were all within the acceptance range. This method has been successfully applied to the determination of synovial fluid samples from PJI patients, providing a useful detection method for meropenem therapeutic drug monitoring (TDM) in PJI patients.

Morphine concentrations in distal thoracic limb synovial fluid following intravenous regional limb perfusion in horses.

Twelve adult horses were randomly assigned to 2 groups in a prospective experimental trial. A pneumatic tourniquet (425 mmHg) was placed, under sedation, proximal to the carpus on one randomly chosen thoracic limb. A cephalic vein catheter was placed distal to the tourniquet to establish an intravenous regional limb perfusion technique (IVRLP) with morphine (0.1 mg/kg) diluted with saline 0.9% to 0.1 mL/kg, and the tourniquet left in place for 30 minutes. Horses were euthanized at 1 h (Group I) or 6 h (Group II) following the IVRLP and synovial fluid from the radiocarpal, intercarpal, metacarpophalangeal, distal interphalangeal, and digital flexor tendon sheath was obtained from the injected and contralateral (control) limb immediately after. Morphine concentrations were determined using liquid chromatography-mass spectrometry. An unpaired t-test was used to compare morphine concentrations from both groups (P < 0.05). Synovial morphine concentrations were detected in the injected limb in all horses in Group I, except in one horse in the radiocarpal joint, and detected in 5 of 6 horses in Group II. Mean synovial concentrations ranged between 301.8 ± 192.3 and 608 ± 446.6 ng/mL in Group I and between 27.0 ± 17.7 and 136.8 ± 103.6 ng/mL in Group II and were significantly higher in Group I between paired anatomical sites of both groups for the radiocarpal and distal interphalangeal joints, and the digital flexor tendon sheath. In conclusion, concentrations of morphine after IVRLP can be detected in synovial fluid distal to the tourniquet at 1 and 6 hours in horses.

Douze chevaux adultes ont été assignés au hasard à deux groupes dans un essai expérimental prospectif. Un garrot pneumatique (425 mmHg) a été placé, sous sédation, à proximité du carpe sur un membre thoracique choisi au hasard. Un cathéter de la veine céphalique a été placé en aval du garrot pour établir une technique de perfusion intraveineuse régionale des membres (IVRLP) avec de la morphine (0,1 mg/kg) diluée avec une solution saline de 0,9 % à 0,1 mL/kg, et le garrot a été laissé en place pendant 30 minutes. Les chevaux ont été euthanasiés 1 h (groupe I) ou 6 h (groupe II) après l'IVRLP et le liquide articulaire de la gaine radiocarpienne, intercarpienne, métacarpo-phalangienne, interphalangienne distale et du tendon fléchisseur digital a été obtenu à partir du membre injecté et controlatéral (témoin) juste après. Les concentrations de morphine ont été déterminées par chromatographie liquide-spectrométrie de masse. Un test de t non apparié a été utilisé pour comparer les concentrations de morphine des deux groupes (P < 0,05). Des concentrations de morphine synoviale ont été détectées dans le membre injecté chez tous les chevaux du groupe I, sauf chez un cheval dans l'articulation radiocarpienne et détectées chez 5 des 6 chevaux du groupe II. Les concentrations synoviales moyennes variaient entre 301,8 ± 192,3 et 608 ± 446,6 ng/mL dans le groupe I et entre 27,0 ± 17,7 et 136,8 ± 103,6 ng/mL dans le groupe II et étaient significativement plus élevées dans le groupe I entre les sites anatomiques appariés des deux groupes pour le radiocarpien et les articulations interphalangiennes distales, et la gaine du tendon fléchisseur numérique. En conclusion, les concentrations de morphine après IVRLP peuvent être détectées dans le liquide synovial en aval du garrot à 1 et 6 heures chez les chevaux.(Traduit par Docteur Serge Messier).

The Diagnostic Utility of Fast Tests for Detecting C-Reactive Protein in Synovial Fluid in Periprosthetic Joint Infections.

BACKGROUND: Despite the fact that many synovial fluid biomarkers have found application in the routine diagnosis of periprosthetic joint infection (PJI), this process still remains a challenge for orthopaedic surgeons. To simplify this process, fast point-of-care (POC) tests can be used during ambulatory visits and in operating room conditions. However, before such tests can be routinely used in clinical practice, they require validation. The purpose of the present study was to evaluate the diagnostic accuracy of different fast POC tests for detecting C-reactive protein (CRP) in synovial fluid for the diagnosis of PJI. METHODS: Synovial fluid samples were collected from 120 consecutive patients who underwent revision total joint arthroplasty (TJA). The patients were divided into 2 groups. The first group included 76 patients who underwent revision for reasons other than infection (the aseptic revision TJA [arTJA] group), and the second group included 44 patients who underwent revision because of periprosthetic joint infection (PJI). The diagnosis of infection was made according to the International Consensus Meeting (ICM) 2018 criteria. All patients were operatively treated at a single orthopaedic center from January 2022 to February 2023. Four fast CRP tests with different cutoff values (1 and 3 mg/L, ≥8 mg/L, ≥10 mg/L [cassette], ≥10 mg/L [strip]) were used off-label for synovial fluid testing. Tests were performed on the same synovial fluid samples, and the results of these tests were compared with those obtained with the laboratory method. RESULTS: The cassette test with a minimum cutoff value of ≥8 mg/L demonstrated the best accuracy for the diagnosis of chronic PJI, with a sensitivity and specificity of 90.9% and 90.8%, respectively. For the cassette test with a cutoff value of >3 mg/L, the sensitivity and specificity were 68.2% and 77.6%, respectively. For the tests with a minimum cutoff value of ≥10 mg/L, the sensitivity and specificity were 77.3% and 94.7%, respectively, for the cassette test and 77.3% and 96.1%, respectively, for the strip test. The laboratory method with the statistically calculated threshold (2.7 mg/L) revealed the highest AUC (area under the receiver operating characteristic curve) value (0.95), with 90.9% sensitivity and 94.7% specificity. CONCLUSIONS: The cassette POC test with the minimum cutoff value of ≥8 mg/L had very good accuracy for the diagnosis of chronic PJI. This test had comparable sensitivity and slightly lower specificity in comparison with the laboratory method with the calculated threshold of 2.7 mg/L. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Leukocyte esterase and alpha-defensin in periprosthetic joint infection: predictive quality and correlation in a prospective study.

PURPOSE: Periprosthetic joint infection (PJI) is a rare but serious complication of total joint arthroplasty (TJA). An accurate diagnosis of PJI preoperatively does not exist. Alpha-defensin (AD) is a proven and common indicator. The diagnostic marker of leukocyte esterase (LE) promises some advantages: feasibility, availability, and fast result reporting. The aim of this study was the evaluation of the predictive quality and correlation between both diagnostic tools in the diagnosis of PJI. METHODS: A prospective study was conducted between April 2018 and August 2022. All patients with suspicion of PJI on hip and knee joint were included and underwent a routine and standardized joint punction. For laboratory diagnostics of AD, the synovial liquid was analyzed by ELISA. The sample was additionally applied to a LE test strip (Combur 10 Test, Roche Diagnostics, Mannheim, Germany). RESULTS: A total of 249 patients were examined (mean age 67.12 ± 11.89; gender distribution man/woman 139 (55.8%)/110(44.2%), hip/knee 71(28.5%)/178 (71.5%). According to EBJIS criteria, PJI was diagnosed in 54 (21.7%) patients. AD showed excellent results with an AUC of 0.930 (sensitivity/specificity 0.870/0.990). LE yielded very good results with an AUC of 0.820 (sensitivity/specificity 0.722/0.918). Both parameters showed a strong positive correlation. CONCLUSION: LE is a rapidly available alternative in PJI diagnostics. The simultaneous determination of both markers may enhance diagnostic reliability. A routine usage may shorten the time from diagnosis to treatment of PJI.

Longitudinal evaluation of fentanyl concentrations in equine plasma and synovial fluid following application of transdermal fentanyl patches over one carpal joint.

OBJECTIVE: To determine if transdermally delivered fentanyl can achieve greater concentrations of fentanyl in synovial fluid when applied over a synovial structure. STUDY DESIGN: Randomized, experimental study. ANIMALS: Six healthy adult horses. METHODS: Each horse had two 100 µg/h fentanyl matrix patches applied on the dorsal aspect of one, randomly assigned, carpometacarpal joint (CMCJ) for 48 h. Whole blood and bilateral synovial samples from the intercarpal joint were obtained at 0, 2, 6, 12, 24, 36 and 48 h. Fentanyl concentrations were measured with liquid chromatography-mass spectrometry. RESULTS: All subjects achieved detectable concentrations of fentanyl in both plasma and synovial fluid. Time to peak synovial and plasma concentration was 12 h. At 6 h, the synovial concentration in the untreated carpus (0.104 ng/mL ± 0.106) was lower than plasma fentanyl concentrations 0.31 ± 0.27 (p = .036). At 12 h, both treated (0.55 ng/mL ± 0.3) and untreated (0.53 ng/mL ± 0.28) synovial fluid fentanyl concentrations were lower than plasma (0.87 ng/mL ± 0.48) concentrations (p < .001 and p = .001, respectively). Synovial concentrations of fentanyl did not differ between treated and untreated joints (p > 0.608 for all time points). CONCLUSION: Application of fentanyl matrix patches directly over the CMCJ did not result in increased fentanyl concentrations in the synovial fluid of the treated intercarpal joint in normal horses. CLINICAL SIGNIFICANCE: There is likely no analgesic advantage to placing fentanyl patches directly over the affected joint, as it did not result in increased synovial concentrations at the tested site.

Arthrocentesis and soft tissue aspiration and injection.

Accessing a joint with a needle (arthrocentesis) to extract synovial fluid is a skill intrinsic to the rheumatologist's praxis. Joint aspirations are essential for diagnosing or excluding septic joints, are the gold standard for diagnosing acute crystal arthritis, and can provide valuable information about the nature of other forms of arthritis. In appropriate settings, injecting medications into joints can provide rapid, temporary, or even prolonged relief of pain and swelling and can provide a window of relief until other treatment modalities (anti-inflammatories, immunomodulators, and physical therapy) can enforce durable responses. Soft tissue aspirations (e.g., of bursae) and soft tissue injections (of bursae, tendons, trigger points, and areas of nerve compression) can provide similar relief, earning the practitioner the gratitude of the patient. Here, we provide a primary on joint and soft tissue aspiration and injection, including indications for and against procedures, preparing for procedures, and approaches to specific musculoskeletal structures.

Synovial fluid analysis: Relevance for daily clinical practice.

Synovial fluid analysis can provide a prompt and definite diagnosis of crystal-induced arthritis, the most common acute inflammatory arthritis and a cause of chronic arthritis that may mimic rheumatoid, psoriatic, or peripheral spondyloarthritis. In many patients the diagnosis of gout or calcium pyrophosphate arthritis cannot be made with certainty without synovial fluid analysis. Additional information from fluid analysis can assist the clinician in honing the differential diagnosis of non-crystalline arthritis.

Synovial Calprotectin for Diagnosing Periprosthetic Joint Infection in Loose Hip and Knee Arthroplasties: A Prospective Cohort Study.

BACKGROUND/AIM: Synovial calprotectin has been demonstrated as a promising biomarker for periprosthetic joint infections (PJI) in painful total hip (THA) and knee arthroplasties (TKA). However, its diagnostic utility has not been evaluated explicitly in cases with marked loosening or migration of the implant. Concerns have already been raised in cases with metallosis and severe periprosthetic osteolysis because wear-induced inflammation may yield false positive results. The purpose of this study was to evaluate calprotectin for the diagnosis of PJI in cases that preoperatively demonstrate moderate to severe periprosthetic osteolysis or implant migration as signs for implant loosening in THA and TKA. PATIENTS AND METHODS: Thirty-three patients were included in this prospective study between February of 2019 and November of 2021. The extent of osteolysis was classified according to Engh et al., Paprosky et al., and the modern Knee Society Radiographic Evaluation and Scoring System. Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin using a lateral-flow-assay were tested against the European Bone and Joint Infection Society (EBJIS) definition for PJI. Statistic quality criteria were calculated and compared using a binary classification test. RESULTS: Ten patients were classified as confirmed infections according to the EBJIS definition (7 THA and 5 TKA). The calprotectin assay yielded a sensitivity of 0.60, a specificity of 0.61, a positive predictive value of 0.40, and a negative predictive value of 0.78. The calprotectin assay resulted in nine false positive and four false negative cases. No correlation between the extent of osteolysis and false classification by means of the calprotectin assay was observed. CONCLUSION: The diagnostic accuracy of synovial calprotectin is impaired if moderate to severe signs of implant loosening are present. If PJI is unlikely, the calprotectin LFT can be applied as a further exclusion tool as the negative predictive value remains relatively high.

It can be unnecessary to combine common synovial fluid analysis and alpha-defensin tests for periprosthetic joint infection diagnosis.

BACKGROUND: Periprosthetic joint infection is a serious complication after total joint arthroplasty. Despite that alpha-defensin was used as diagnostic test in the 2018 ICM (international consensus meeting) criteria, its position in the PJI diagnostic pipeline was controversial. Therefore, we performed a retrospective pilot study to identify whether synovial fluid alpha-defensin test was necessary when corresponding synovial fluid analysis (WBC count, PMN% and LE tests) was performed. METHODS: Between May 2015 and October 2018, a total of 90 suspected PJI patients who underwent revisions after TJA were included in this study. Based on the 2018 ICM criteria, the interobserver agreements between preoperative diagnostic results and postoperative diagnostic results and the interobserver reliability between preoperative diagnostic results and postoperative diagnostic results with or without synovial fluid alpha-defensin tests were calculated. After that, the ROC analysis, and the direct cost-effectiveness of adding alpha-defensin was performed. RESULTS: There were 48,16 and 26 patients in the PJI group, inconclusive group and non-PJI group, respectively. Adding the alpha-defensin tests into 2018 ICM criteria can't change the preoperative diagnostic results, postoperative diagnostic results, and the concordance between preoperative and postoperative diagnostic results. Moreover, the Risk-benefit Ratio is over 90 per changed decision and the direct cost-effectiveness of alpha-defensin was more than $8370($93*90) per case. CONCLUSIONS: Alpha-defensin assay exhibit high sensitivity and specificity for PJI detection as a standalone test based on the 2018 ICM criteria. However, the additional order of Alpha-defensin can't offer additional evidence for PJI diagnosis when corresponding synovial fluid analysis was performed (synovial fluid WBC count, PMN% and LE strip tests). EVIDENCE LEVEL: Level II, Diagnostic study.

Expression and diagnostic significance of integrin beta-2 in synovial fluid of patients with osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is characterized by synovial cartilage degeneration and is the leading cause of disability and pain worldwide. This study sought to investigate the expression of integrin beta-2 (ITGB2) in synovial fluid of OA patients and its clinical significance. METHODS: A total of 110 OA patients were enrolled, who were classified into grade I (N = 35), II (N = 42), and III (N = 33) according to the Kellgren-Lawrence classification, with 110 healthy subjects as controls, and their clinical data were compared. ITGB2 level was detected by RT-qPCR. The receiver operating characteristic curve was used to analyze the predictive value of ITGB2 on OA occurrence. The correlation between ITGB2 and bone metabolism indexes procollagen type I N-terminal peptide (PINP), bone glaprotein (BGP), bone alkaline phosphatase (BALP), and ß-collagen I telopeptide (ß-CTX) was analyzed by the Pearson method. Logistic regression model was performed to analyze the influencing factors of OA. RESULTS: The content of red blood cells, white blood cells, PINP, BGP, and BALP was lowered in OA patients, while ß-CTX was elevated. ITGB2 was highly-expressed in OA patients, negatively-correlated with PINP, BGP, and BALP, but positively-correlated with ß-CTX. ITGB2 level increased with the elevation of OA grade. The ITGB2 level >1.375 had certain diagnostic values for OA. ITGB2 level is related to OA severity and may be a biomarker for OA classification. ITGB2 was an independent risk factor for OA. CONCLUSION: High expression of ITGB2 in synovial fluid can assist OA diagnosis and may be a biomarker for OA grade.

Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection-A Systematic Review and Meta-Analysis of Their Diagnostic Accuracy According to Different Definitions.

BACKGROUND: Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate their performance according to different PJI definitions. METHODS: A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin. RESULTS: Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values. CONCLUSION: All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.

Automatic Detection of Two Synovial Fluid Periprosthetic Joint Infection Biomarkers on an Integrated Microfluidic System.

Post-arthroplasty periprosthetic joint infection (PJI) is a serious ailment that can be difficult to diagnose. Herein, we developed a novel integrated microfluidic system (IMS) capable of detecting two common PJI biomarkers, alpha defensin human neutrophil peptide 1 (HNP-1) and C-reactive protein (CRP), from synovial fluid (SF). A magnetic bead-based one-aptamer-one-antibody assay was carried out automatically within 45 min on a single chip for simultaneous detection of both biomarkers at concentration ranges of 0.01-50 (HNP-1) and 1-100 (CRP) mg/L. It is the first report for utilizing these two biomarkers as targets to establish the new one-aptamer-one-antibody assay to detect PJI on-chip, and the aptamers demonstrated high specificity to their SF targets. As 20 clinical samples were correctly diagnosed with our IMS (verified by a common gold standard kit), it could serve as a promising tool for PJI diagnostics.

Increased n-6 Polyunsaturated Fatty Acids Indicate Pro- and Anti-Inflammatory Lipid Modifications in Synovial Membranes with Rheumatoid Arthritis.

Emerging evidence suggests that fatty acids (FAs) and their lipid mediator derivatives can induce both beneficial and detrimental effects on inflammatory processes and joint degradation in osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA). The present study characterized the detailed FA signatures of synovial membranes collected during knee replacement surgery of age- and gender-matched OA and RA patients (n = 8/diagnosis). The FA composition of total lipids was determined by gas chromatography and analyzed with univariate and multivariate methods supplemented with hierarchical clustering (HC), random forest (RF)-based classification of FA signatures, and FA metabolism pathway analysis. RA synovium lipids were characterized by reduced proportions of shorter-chain saturated FAs (SFAs) and elevated percentages of longer-chain SFAs and monounsaturated FAs, alkenyl chains, and C20 n-6 polyunsaturated FAs compared to OA synovium lipids. In HC, FAs and FA-derived variables clustered into distinct groups, which preserved the discriminatory power of the individual variables in predicting the RA and OA inflammatory states. In RF classification, SFAs and 20:3n-6 were among the most important FAs distinguishing RA and OA. Pathway analysis suggested that elongation reactions of particular long-chain FAs would have increased relevance in RA. The present study was able to determine the individual FAs, FA groups, and pathways that distinguished the more inflammatory RA from OA. The findings suggest modifications of FA elongation and metabolism of 20:4n-6, glycerophospholipids, sphingolipids, and plasmalogens in the chronically inflamed RA synovium. These FA alterations could have implications in lipid mediator synthesis and potential as novel diagnostic and therapeutic tools.