Synovial Aspiration Research Articles

Novel Method for Routine Ultrasound-Guided Serum Collection for Biomarker Analysis Around the Knee Joint

Background Biomarkers are essential tools in modern medicine, allowing stratification and monitoring of clinical care and treatment response. While systemic blood biomarkers, typically collected from the antecubital vein (AV), are widely used, their sensitivity for joint-specific pathologies such as osteoarthritis (OA) may be limited due to systemic dilution. At present, no serum biomarker reliably reflects the microenvironment of an affected joint in clinical practice. Although synovial fluid (SF) assessment can provide insights into localised pathology and are clinically used for diagnosis in crystal arthropathies and joint infections, their collection is invasive, painful, and carries risks, including infection, making repeated sampling impractical, limiting utility for monitoring treatment responses. This study introduces a novel ultrasound-guided venous sampling technique targeting the saphenous vein (SV) proximal to the knee joint as a less invasive alternative to SF aspiration, hypothesising that it may better reflect the joint-specific microenvironment. Methods A standardised gel model was used to train medically qualified researchers in ultrasound-guided venepuncture of vescles around 2-15 mm in diameter. Subsequently, 32 participants consented to blood sampling from the SV above the knee, with a proximally applied tourniquet to dilate vein diameter for easier venepuncture collection. Results The technique achieved serum collection in over 80% of consented individuals with minimal adverse effects (including n=2 minor bruising and n=1 transient nerve irritation). Key procedural insights included optimal site selection, appropriate pressure application, and effective tourniquet use. Discussion This method demonstrates feasibility, acceptability, and the potential for more localised sample collection, advancing biomarker research. Further validation, including paired SF comparisons, is required to confirm diagnostic utility and develop therapeutic strategies for joint-specific conditions.

Concomitant Streptococcus Suis Septic Arthritis and Gouty Arthritis: A Case Report

Septic arthritis, when occurring together with crystal-induced arthritis such as gout, can make the diagnosis more difficult and increase the risk of complications compared with septic arthritis without concomitant gout. Streptococcus suis, a common pathogen in swine, can be transmitted from animals to humans. Human infections are rare. Patients often have a history of contact with or consumption of undercooked pork. Most patients present with meningitis, septicemia, endocarditis, and septic arthritis. A 71-year-old man presented with bilateral knee pain, swelling, and fever. Synovial fluid aspiration from the knee revealed intracellular urate crystals and Streptococcus suis on the culture. He was diagnosed with septic arthritis due to Streptococcus suis with concomitant gouty arthritis. The patient was treated with intravenous ceftriaxone and bilateral knee arthrotomy. After clinical improvement, he was switched to oral amoxicillin and completed a total of 4 months of antibiotics. At the 1-year follow-up, his function was near pre-infection levels. This is the first reported case of septic arthritis due to Streptococcus suis, an uncommon pathogen, in a patient with gouty arthritis. Concurrent septic arthritis and gouty arthritis can make the diagnosis more difficult. A high index of suspicion for septic arthritis with gouty arthritis is important for the accurate diagnosis and appropriate treatment in order to minimize complications.

Risk of orthopaedic implant infection during bacteraemia.

Orthopaedic implant material can get infected via haematogenous spread from a distant source at any point after implantation. The sources of haematogenous orthopaedic implant infections have been studied only for prosthetic joints. The most common source of infection has varied, but it can be, for example from the skin and soft tissues, cardiovascular system and dental infections. The risk for developing a periprosthetic joint infection (PJI) during bacteraemia is dependent on the pathogen: it is highest for Staphylococcus aureus and beta-haemolytic streptococci, but low for gram-negative bacteria. The risk for developing a (PJI) during Staphylococcus aureus bacteraemia (SAB) has varied between 12 and 41%; the risk for developing an infection in any orthopaedic implant in the extremities during SAB is probably almost the same as for prosthetic joints, but data are very limited. The risk of developing an infection in spinal implants during bacteraemia is not known, as it has not been studied. Especially in the case of SAB, infected orthopaedic implants are usually symptomatic, so asymptomatic implants do not routinely require further diagnostic work-up, such as synovial fluid aspiration.

Analysis of Synovial Fluid Aspirations in Aseptic Loosening and Instability After Total Knee Arthroplasty.

Aseptic total knee arthroplasty (TKA) complications can be challenging to diagnose. Many studies have defined periprosthetic joint infection (PJI) using synovial aspirations, but few studies have described aspiration characteristics in aseptic TKA problems. The aim of this study was to determine the synovial fluid characteristics of patients who had TKA failure caused by two common aseptic diagnoses: aseptic loosening and instability. We sought to compare the characteristics between these groups in addition to the failure caused by PJI. A retrospective study was performed in which consecutive patients who had a preoperative knee aspiration and underwent TKA revision for one of three diagnoses (PJI, aseptic loosening, or instability) were evaluated. Clinical notes were used to obtain demographics, comorbidity data, aspiration cell count, and differential to compare among the groups. There were 399 patients included: 240 PJI, 103 aseptic loosening, and 56 instability. There were significant differences between mean white blood cell (WBC) count and polymorphonuclear, lymphocyte, and monocyte percentages between all groups. Findings consistent with a diagnosis of aseptic loosening included a mean WBC count of 1,021.9 cells/μL with 29.7% polymorphonuclear leukocyte (PMNs), 32.7% lymphocytes, and 44.6% monocytes, and relatively elevated PMN/lymphocyte (2.1) and PMN/monocyte (3.5) ratios. Findings consistent with a diagnosis of instability included a mean WBC count of 1,261.2 cells/μL with 23.5% PMNs, 35.6% lymphocytes, and 50.0% monocytes, and a relatively lower PMN/lymphocyte (1.1) and PMN/monocyte (1.5) ratios compared to aseptic loosening. In both aseptic loosening and instability, there were significantly more lymphocytes and monocytes than in PJI. In addition, instability cases had a higher mean red blood cell (RBC) count of 405,996.9 cells/μL (P = 0.012). Differentiating between instability and aseptic loosening in TKA remains a diagnostic challenge. This study provides insight into the cellular pathophysiology of aseptic TKA complications and can be used to aid in clarifying the diagnosis of aseptic loosening versus instability.

Synovial Fluid White Blood Cell Count as a Potential Biomarker for the Clinical Severity of Knee Osteoarthritis: A Prospective Study

Knee osteoarthritis is categorized classically as a non-inflammatory arthropathy. However, there has been increasing evidence regarding the supplementary role of inflammation in the pathogenesis and disease progression of knee osteoarthritis. This study aims to identify a potential correlation between synovial fluid white blood cell (SF WBC) count and the severity of knee osteoarthritis clinical presentation. 200 knees (200 patients) were assessed through SF aspiration and cytology analysis for WBC count. All patients have filled out the Knee Injury and Osteoarthritis Outcome Score for clinical correlation. For the 200 knees, there was a statistically significant positive correlation between the severity of osteoarthritis clinical presentation as expressed by the Knee Injury and Osteoarthritis Outcomes Score (KOOS) and the synovial white blood cell count among the studied cases (p-value < 0.001). There was no statistically significant correlation found between the patient's age, sex, or side and KOOS or SF white cell count. The clinical severity of knee osteoarthritis is directly correlated with increased SF white cell count, and hence, SF WBCs may play a role in identifying and grading osteoarthritis clinical severity. This may raise the interest in identifying the role of using specific disease-modifying drugs that deal with the WBC function in cases of osteoarthritis along with other modalities.

Changes and associations between synovial fluid and magnetic resonance imaging markers of osteoarthritis after high tibial osteotomy

BackgroundMechanobiological mechanisms of osteoarthritis (OA) are unclear. Our objectives were to explore: 1) changes in knee joint physiology using a large panel of synovial fluid biomarkers from before to one year after high tibial osteotomy (HTO) surgery, and 2) the association of changes in the synovial fluid biomarkers with the changes in MRI measures of knee effusion-synovitis and articular cartilage composition.MethodsTwenty-six patients with symptomatic knee OA and varus alignment underwent synovial fluid aspirations and 3 T MRI before and one year after medial opening wedge HTO. Cytokine and growth factor levels in synovial fluid were measured with multiplex assays. Ontology and pathway enrichment was assessed using data protein sets with gene set enrichment analysis (GSEA), and analyzed using linear mixed effects models. MRIs were analyzed for effusion-synovitis and T2 cartilage relaxation time using manual segmentations. Changes in biomarker concentrations were correlated to changes in MRI effusion-synovitis volume and articular cartilage T2 relaxation times.ResultsDecreased enrichment in Toll-like receptor and TNF-α signalling was detected one year after HTO. The leading contributors to this reduction included IL-6, TNF-α and IL-1β, whereas the highest contributors to positive enrichment were EGF, PDGF-BB and FGF-2. Effusion-synovitis volume decreased (mean [95%CI]) one year after HTO (-2811.58 [-5094.40, -528.76mm3]). Effusion-synovitis volume was moderately correlated (r [95% CI]) with decreased MMP-1 (0.44 [0.05; 0.71]), IL-7 (0.41 [0.00; 0.69]) and IL-1β (0.59 [0.25; 0.80]) and increased MIP-1β (0.47 [0.10; 0.73]). Medial tibiofemoral articular cartilage T2 relaxation time decreased (mean [95% CI]) one year after HTO (-0.33 [-2.69; 2.05]ms). Decreased T2 relaxation time was moderately correlated to decreased Flt-3L (0.61 [0.28; 0.81]), IL-10 (0.47 [0.09; 0.73]), IP-10 (0.42; 0.03–0.70) and increased MMP-9 (-0.41 [-0.7; -0.03]) and IL-18 (-0.48 [-0.73; -0.10]).ConclusionsDecreased aberrant knee mechanical loading in patients with OA is associated with decreased biological and imaging measures of inflammation (measured in synovial fluid and on MRI) and increased anabolic processes. These exploratory findings suggest that improvement in knee loading can produce long-term (one year) improvement in joint physiology.

Diagnostic accuracy of preoperative percutaneous synovial biopsy and aspirate compared with open biopsy for prosthetic shoulder infections

BackgroundShoulder arthroplasty revision is associated with a high prevalence of prosthetic infection, and diagnosis remains difficult. The primary aim of the study was to determine the diagnostic accuracy of percutaneous synovial biopsy (PSB) and joint aspiration compared with open culture results in detecting infection in revision shoulder arthroplasty. The second aim was to determine whether biopsy location within the shoulder was associated with culture status. MethodsThis was a multicenter prospective cohort study involving four sites and 69 patients undergoing revision shoulder arthroplasty. The cohort was 57% female with a mean age of 64 years. Preoperative fluoroscopic-guided PSB’s and aspirates were carried out by a musculoskeletal radiologist prior to revision shoulder arthroplasty. The original prostheses consisted of hemiarthroplasties, total shoulder arthroplasties (TSA), resurfacing TSA, reverse shoulder arthroplasties (RSA), and antibiotic spacers. Six synovial tissue biopsies from separate regions in the shoulder were obtained both preoperatively and intra-operatively. The shoulder joint was aspirated, and synovial fluid collected, if available. Infection was considered positive in the setting of two or more matching positive cultures. The PSB cultures were considered “true positive” if the PSB cultures matched the open biopsy cultures. ResultsNineteen percent had positive infection based on PSB and 23% had confirmed culture positive infections based on intra-operative biopsy. The diagnostic accuracy of PSB compared with open biopsy was as follows: sensitivity 0.37 (95% CI 0.13-0.61), specificity 0.81 (95% CI 0.7-0.91), positive predictive value 0.37 (95% CI 0.13 – 0.61), negative predictive value 0.81 (95% CI 0.70-0.91), positive likelihood ratio 1.98 and negative likelihood ratio 0.77. Of the 71 patients, aspiration yielded synovial fluid in 33 patients. Preoperative aspirates detected no infections confirmed positive by open biopsy and correctly identified 81% of absent infections. The diagnostic accuracy of aspirates compared with open biopsy was as follows: sensitivity 0%, specificity 0.81 (95% CI 0.66-0.96), positive predictive value 0%, negative predictive value 0.78 (95% CI 0.63-0.93). Biopsy location within the shoulder was not associated with infection status. DiscussionPreoperative aspiration detected none of the infections proven positive via open biopsy. Although PSB was superior to synovial fluid aspirate, poor likelihood ratios suggests that PSB is not useful as an isolated test in the preoperative workup of the potentially infected patient.Biopsy location was not associated with culture status suggesting that the capsule is uniformly infected, and the location of tissue biopsies does not appear to matter.

Synovial fluid D-lactate- a pathogen-specific biomarker for septic arthritis: a prospective multicenter study.

The performance of synovial fluid biomarker D-lactate to diagnose septic arthritis (SA) and differentiate it from crystal-induced arthritis (CA), other non-infectious rheumatic joint diseases (RD) and osteoarthrosis (OA) was evaluated. Consecutive adult patients undergoing synovial fluid aspiration due to joint pain were prospectively included in different German and Swiss centers. Synovial fluid was collected for culture, leukocyte count and differentiation, detection of crystals, and D-lactate concentration. Youden's J statistic was used to determine optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. In total 231 patients were included. Thirty-nine patients had SA and 192 aseptic arthritis (56 patients with OA, 68 with CA, and 68 with RD). The median concentration of synovial fluid D-lactate was significantly higher in patients with SA than in those with OA, CA, and RD (p<0.0001, p<0.0001 and p<0.0001, respectively). The optimal cut-off of synovial fluid D-lactate to diagnose SA was 0.033 mmol/L with a sensitivity of 92.3 % and specificity of 85.4 % independent of previous antimicrobial treatment. Sensitivity and specificity of synovial fluid leukocyte count at a cut-off of 20,000 cells/µL was 81.1 % and 80.8 %, respectively. Synovial fluid D-lactate showed a high performance for diagnosing SA which was superior to synovial fluid leukocyte count. Given its high sensitivity and specificity, it serves as both an effective screening tool for SA and a differentiator between SA and RD, especially CA.

Graphic type differentiation of cell count data for diagnosis of early and late periprosthetic joint infection: A new method.

Graphic type differentiation of cell count data of synovial aspirates is a new method for the diagnosis of early and late periprosthetic joint infection. The aim of the study was to analyse if the same 6 LMNE-types can be differentiated in the new Yumizen H500 cell counter as it was the case for the old cell counter ABX Pentra XL 80 of previous publications, to verify if the erythrocyte and thrombocyte curves of the new device give additional information and to calculate the difference of cell count in LMNE-type I and III (with abrasion) in the cell counter and in the manual counting chamber (Neubauer improved). 450 aspirates of 152 total hip arthroplasties and 298 knee arthroplasties obtained for the diagnosis of periprosthetic joint infection were analysed with the Yumizen H500. All LMNE-matrices of the 450 aspirates could assigned to one of the six LMNE-types. There were 76 LMNE-type I, 72 LMNE-type II, 14 LMNE-type III, 241 LMNE-type IV, 36 LMNE-type V and 12 LMNE-type VI. The erythrocyte and thrombocyte distribution curves were very helpful for differentiation of hematoma and infection. The cell count in the manual counting procedure was lower than in the cell counter: for the LMNE-type I (abrasion type) the median of the difference was 925/μL (median) and for the LMNE-type III (combined type of infection and abrasion) 3570/μL (median). The described graphic type differentiation is a new and helpful method for differentiation of hematoma and early PJI as well as abrasion and late PJI.

The impact of extended preoperative examination on the treatment tactics choice before the second stage of revision hip arthroplasty

Background. Reinfection and recurrence of periprosthetic infection rates during the second stage of revision hip arthroplasty (RHA) remain quite high. Performing preoperative diagnostic aspiration in patients with the installed hip spacer is a controversial issue. Aims of the study: 1) to compare the diagnostic accuracy, specificity and sensitivity of the used infection markers as a part of preoperative diagnostic protocols in order to exclude reinfection in patients with installed hip spacer before the second stage of RHA; 2) to analyze and compare the microbiological spectrum obtained at the stages of RHA. Methods. Diagnostic accuracy parameters of the used infection markers were assessed in order to exclude reinfection/recurrence in 107 patients with installed hip spacer. All patients were divided into two groups. In Group 1 (prospective), blood tests as well as diagnostic aspiration of synovial fluid were performed within the extended diagnostic protocol. In Group 2 (retrospective), the examination was performed according to the screening preoperative diagnostic protocol including blood tests. The used reference range of inflammatory biomarkers was based on the “small criteria” of ICM 2018. According to the results of the intraoperative microbiological examination of peri-implant tissue samples at the first and second stages of RHA, the analysis of detected microflora was conducted in order to assess probable reinfection/recurrence. Results. According to the results of the intraoperative microbiologic examination during the second stage of RHA, reinfection was detected in 40% of cases: in Group 1 — 9 cases, in Group 2 — 31 case. Synovial fluid was obtained from 85% of cases when preoperative diagnostic aspiration was performed. Synovial fluid could not be obtained in 15% cases (dry joint). Conclusion. Performing preoperative diagnostic aspiration before the second stage of RHA in patients with the installed spacer allowed choosing correct treatment tactics in 9% of cases. The parameters of diagnostic accuracy accounted for 82,6%. In the structure of detected pathogens in case of recurrence and reinfection, the representatives of Gram-positive coagulase-negative flora were the most frequent.

Poster 229: Intra-articular VEGF and MMP-1 Are the Primary Drivers of Worse Baseline KOOS Symptoms and Quality of Life Subscores at Time of Knee Chondroplasty

Objectives: Biomarkers are a topic of interest in orthopaedics in the setting of osteoarthritis and patients undergoing knee arthroscopy for any reason. However, in patients undergoing knee arthroscopy for chondral defects, the influence of cytokines on patient pain and function is not fully understood. The purpose of this study is to investigate the concentrations of synovial inflammatory cytokines in patients undergoing arthroscopic chondroplasty for chondral defects in the knee and correlate those cytokine levels with baseline patient reported outcome measures (PROs) and defect characteristics. We hypothesized that the synovial cytokine environment will correlate with patient symptoms more so than baseline defect characteristics. Methods: Sixty patients 18-50 years old undergoing arthroscopic chondroplasty for knee cartilage defects were enrolled. Patients were assigned preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee International Knee Documentation Committee (IKDC) Subjective Knee Forms. Preoperative magnetic resonance images were used to calculate AMADEUS (Area Measurement And Depth Underlying Structure) scores. All patients received a successful synovial fluid aspiration just prior to initiation the arthroscopic procedure. The number of defects, total defect area, and ICRS grades were recorded based on intraoperative assessment. Patients with concomitant procedures beyond partial meniscectomy were excluded. Multiplex ELISA analyzed aspirations for: PDGF-BB, CCL-5/RANTES, MMP-3, MMP-1, EGF, VEGF, IL-1a, FGF-2, CCL-2, BMP-2, and aggrecan. Univariate correlation testing was used to assess significance between cartilage defect characteristics, PROs, and cytokine concentrations (Figure 1). The Akaike Information Criterion (AIC) was utilized to select the best-fit multivariate regression model using the 4 most significant independent variables for each cytokine (Figure 2). AIC best-fit modeling was repeated for each PRO that had at least two significant cytokine associations on univariate testing (Figure 3). Significance was set at P&lt;0.05. Results: MMP-1 had a positive correlation with number of defects treated ( P=0.016) and negative correlation with KOOS quality of life (QOL) subscores ( P=0.035; R2 =0.173). VEGF was positively correlated with defects treated ( P=0.005) and negatively correlated with KOOS Symptoms scores ( P=0.035; R2 =0.225). The treatment of multiple defects was an independent predictor of elevated IL-1a ( P=0.002, R2 =0.202). CCL-2 was positively correlated with multiple defects ( P=0.012) and negatively with KOOS QOL ( P=0.016, R2 =0.173). Female sex was correlated with higher concentrations of MMP-3 ( P=0.007, R2 =0.144), FGF ( P=0.012, R2 =0.178), and BMP-2 ( P=0.008; R2 = 0.169). BMP-2 was negatively correlated with KOOS Symptom ( P=0.019). The primary driver of preoperative KOOS Symptoms scores on multivariate analysis was VEGF ( P=0.023, R2 =0.120), influencing patient symptoms beyond defect characteristics. Similarly, KOOS QOL was independently correlated with MMP-1 concentration ( P= 0.045, R2 =0.079), more so than ICRS grade (Figure 3). Conclusions: Multivariate regression analysis revealed that elevated MMP-1 was the primary driver of worse preoperative KOOS QOL scores, more so than defect characteristics such as the number of lesions treated. Similarly, worse preoperative KOOS Symptoms scores were more strongly correlated with elevated VEGF concentrations rather than defect ICRS grades. Our study demonstrated that synovial fluid cytokines appear to be the primary drivers of patients’ subjective assessments of their pain and function preoperatively.

The predictive value and reliability of ultrasound-guided synovial aspiration and biopsies for diagnosing periprosthetic shoulder infections.

Preoperative diagnosis of periprosthetic shoulder infections (PSI) is difficult. Infections are mostly caused by low virulence bacteria and patients do not show typical signs of infection. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination with multiplex polymerase chain reaction (mPCR), serum markers, and/or synovial markers for the preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. A prospective explorative diagnostic cohort study was performed including 55 patients undergoing revision shoulder replacement surgery. A shoulder puncture was performed preoperatively before incision to collect synovial fluid for mPCR analysis and for measurement of interleukin-6, calprotectin, white blood cell count (WBC), and polymorphonuclear cells. Also prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two for mPCR analysis. A blood sample was obtained to determine serum C-reactive protein, WBC, and erythrocyte sedimentation rate. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; the primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, blood and synovial markers, mPCR, and combinations thereof. Routine tissue cultures were positive for infection in 24 patients. Cultures from ultrasound-guided biopsies diagnosed infection in 7 of these patients, yielding a sensitivity, specificity, PPV, NPV, and accuracy of 29.2%, 93.5%, 77.8%, 63.0%, and 65.6%, respectively. The best diagnostic value was found for the combination of ultrasound-guided biopsies for culture, synovial WBC, and calprotectin with a sensitivity of 69.2%, specificity of 80.0%, PPV of 69.2%, and NPV of 80.0%. Ultrasound-guided biopsies for cultures alone and in combination with mPCR, and/or blood and/or synovial markers are not reliable enough to use in clinical practice for the preoperative diagnosis of PSI. Diagnostic study level II.

Functional infrared thermography imaging can be used to assess the effectiveness of Maxicam Gel® in pre-emptively treating transient synovitis and lameness in horses.

Diagnosing and treating lameness in horses is essential to improving their welfare. In equine orthopedic practice, infrared thermography (IRT) can indirectly detect soreness. Non-steroidal anti-inflammatory drugs can treat painful and inflammatory processes in horses. Using IRT, the efficacy of meloxicam (Maxicam Gel®) was evaluated in pre-treating transient synovitis in horses induced by a middle carpal joint injection of lipopolysaccharides (LPS) from E. coli 055:B5 at a dose of 10 endotoxin units. In a cross-over design, six healthy horses were randomly assigned to receive either 0.6 mg/kg of oral Maxicam Gel® (MAXVO) or a mock administration (control group, C) following a two-week washout period. IRT of the middle carpal joint, visual lameness assessment and joint circumference were recorded over time. Clinical and hematological evaluations were performed. Synovial fluid aspirates were analyzed for total nucleated cell count, total protein, and prostaglandin E2. A mixed effects analysis of variance was performed for repeated measures over time, followed by Tukey's test. A multinomial logistic regression was conducted to determine whether there is a relationship between a thermography temperature change and the lameness score. There were no changes in joint circumference. The MAXVO group showed a lower rectal temperature 4 h after synovitis induction. The C group presented an increase in neutrophils and a decrease in total hemoglobin and hematocrit 8 h after induction. No changes were observed in the synovial fluid between groups. The horses that received meloxicam did not show clinically significant lameness at any time, while the C group showed an increase in lameness 2, 4, and 8 h after synovitis induction. IRT indicated that the skin surface temperature of the middle carpal joint was lower in horses who received meloxicam, suggesting a reduction in the inflammatory process induced by LPS. It was observed that the maximum temperature peaks in the dorsopalmar and lateropalmar positions can be utilized to predict the severity of lameness, particularly when the temperature rises above 34°C. Horses pre-treated with meloxicam showed either reduced or no indication of mild to moderate pain and presented a lowehr thermographic temperature, which indicates the effectiveness of Maxicam Gel® as an anti-inflammatory.

OA13 Alkaptonuria: a big mimic

Abstract Background/Aims Alkaptonuria is a rare metabolic disorder, often misdiagnosed as spondyloarthritis or degenerative musculoskeletal disease. The population most affected are young males in their 30s with characteristic arthritis involving the spine and large joints. The patient may notice their urine turning dark on standing and pigmentation over the skin and connective tissues (ochronosis); however, these subtle features may sometimes go unnoticed. Methods A 38-year-old-male with long standing back pain presented with right knee swelling. With a diagnosis of spondyloarthritis, he was previously treated with DMARDS but did not have any relief. There was a history of urine turning dark on standing. On examination, there was subtle hyperpigmentation over left ear concha and a spot on the sclera. An x-ray of the thoracic spine showed flattening and calcification of intervertebral disc spaces at multiple levels. Aspiration of synovial fluid showed suspended fragments of articular cartilage. His inflammatory markers were negative. We performed gas chromatography mass spectrometry which showed elevated excretion of homogentisic acid (HGA). A homozygous pathogenic variant in the homogentisate 1,2-dioxygenase gene associated with alkaptonuria was reported on whole genome sequencing. Results Ochronotic arthropathy is defined as progressive degenerative joint disease mainly affecting the spine and large joints. Most patients require at least one joint replacement by age 55. Small joints of hands and feet and sacroiliac joints are usually spared. Arthroscopy of the joint may reveal dark brown to black pigmented cartilage defects. The synovium may show fragments of pigmented cartilage suspended in the fluid (ground pepper sign). Plain spine radiographs may show flattening and calcifications of the intervertebral discs with a characteristic vacuum phenomenon (radiolucent gas collection). Periarticular structures like tendons and ligaments are also affected, leading to rupture in around 20-30% of patients. Alkaptonuria is also associated with decreased bone mineral density and subsequent risk for fragility fracture. Conclusion Alkaptonuria often mimics ankylosing spondylitis. A triad of ochronosis, dark urine and ochronotic arthropathy is the key to diagnosis. Definitive diagnosis is through biochemical or genetic testing. Nitisinone has proved to be effective but shows significant side effects. Management mainly involves physiotherapy and palliative care. Disclosure M. Shah: None. S. Upadhyaya: None.

Intra-articular VEGF and MMP-1 are the Primary Drivers of Worse Baseline KOOS Symptoms and Quality of Life Subscores at Time of Knee Chondroplasty

Objectives: Biomarkers are a topic of interest in orthopaedics in the setting of osteoarthritis and patients undergoing knee arthroscopy for any reason. However, in patients undergoing knee arthroscopy for chondral defects, the influence of cytokines on patient pain and function is not fully understood. The purpose of this study is to investigate the concentrations of synovial inflammatory cytokines in patients undergoing arthroscopic chondroplasty for chondral defects in the knee and correlate those cytokine levels with baseline patient reported outcome measures (PRO’s) and defect characteristics. We hypothesized that the synovial cytokine environment will correlate with patient symptoms more so than baseline defect characteristics. Methods: Sixty patients 18-50 years old undergoing arthroscopic chondroplasty for knee cartilage defects were enrolled. Patients were assigned preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee International Knee Documentation Committee (IKDC) Subjective Knee Forms. Preoperative magnetic resonance images were used to calculate AMADEUS (Area Measurement And Depth Underlying Structure) scores.1 All patients received a successful synovial fluid aspiration just prior to initiation the arthroscopic procedure. The number of defects, total defect area, and ICRS grades were recorded based on intraoperative assessment. Patients with concomitant procedures beyond partial meniscectomy were excluded. Multiplex ELISA analyzed aspirations for: PDGF-BB, CCL-5/RANTES, MMP-3, MMP-1, EGF, VEGF, IL-1a, FGF-2, CCL-2, BMP-2, and aggrecan. Univariate correlation testing was used to assess significance between cartilage defect characteristics, PROs, and cytokine concentrations (Figure 1). The Akaike Information Criterion (AIC) was utilized to select the best-fit multivariate regression model using the 4 most significant independent variables for each cytokine (Figure 2). AIC best-fit modeling was repeated for each PRO that had at least two significant cytokine associations on univariate testing (Figure 3). Significance was set at P&lt;0.05. Results: MMP-1 had a positive correlation with number of defects treated (P=0.016) and negative correlation with KOOS quality of life (QOL) subscores (P=0.035; R2 =0.173). VEGF was positively correlated with defects treated (P=0.005) and negatively correlated with KOOS Symptoms scores (P=0.035; R2 =0.225). The treatment of multiple defects was an independent predictor of elevated IL-1a (P=0.002, R2 =0.202). CCL-2 was positively correlated with multiple defects (P=0.012) and negatively with KOOS QOL (P=0.016, R2 =0.173). Female sex was correlated with higher concentrations of MMP-3 (P=0.007, R2 =0.144), FGF (P=0.012, R2 =0.178), and BMP-2 (P=0.008; R2 = 0.169). BMP-2 was negatively correlated with KOOS Symptom (P=0.019). The primary driver of preoperative KOOS Symptoms scores on multivariate analysis was VEGF (P=0.023, R2 =0.120), influencing patient symptoms beyond defect characteristics. Similarly, KOOS QOL was independently correlated with MMP-1 concentration (P= 0.045, R2 =0.079), more so than ICRS grade (Figure 3). Conclusions: Multivariate regression analysis revealed that elevated MMP-1 was the primary driver of worse preoperative KOOS QOL scores, more so than defect characteristics such as the number of lesions treated. Similarly, worse preoperative KOOS Symptoms scores were more strongly correlated with elevated VEGF concentrations rather than defect ICRS grades. Our study demonstrated that synovial fluid cytokines appear to be the primary drivers of patients’ subjective assessments of their pain and function preoperatively.

Common inflammatory markers in the screening of knee arthroprosthesis infections

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;br /&amp;gt;&amp;lt;/strong&amp;gt; To evaluate the sensitivity and specificity of serum C-reactive protein (CRP) in early and late total knee arthroplasty (TKA)&amp;lt;br /&amp;gt;infections.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;br /&amp;gt;&amp;lt;/strong&amp;gt; Blood tests to determine CRP levels (cut-off 10 mg/L) were conducted before surgery, at 1st day, 7th day and 15th day after surgery and at 1, 3, 6,12, 24 and 36 months. Patients had routine follow-up visits and radiological evaluations at 14 days and at 1, 3, 6, 12, 24 and 36 months. Infections were recorded and classified according to Widmer classification. The &amp;amp;chi;2 test or Fisher (in subgroups smaller than 10 patients) exact test was used to compare categorical variables. The statistical significance was set at p &amp;amp;lt; 0.05.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;br /&amp;gt;&amp;lt;/strong&amp;gt; A total of 19 infections were diagnosed during the followup. According to Widmer, five were classified as early post-operative and 14 as late chronic. All patients with early infections had suspected symptoms such as fever, swelling and pain. During the first month, 59 patients who had high CRP level but negative microbiological culture were considered as false positive representing a CRP sensitivity of 80% and a specificity of 67.6%. Fourteen patients had late chronic infection.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;br /&amp;gt;&amp;lt;/strong&amp;gt; This study suggests that a synovial fluid aspiration should be performed in patients with persistent inflammation&amp;lt;br /&amp;gt;symptoms with or without radiographic signs of loosening. Moreover, it recommends the use of different serum and synovial tests for periprosthetic joint infection (PJI) diagnosis.&amp;lt;/p&amp;gt;

Administering Antibiotics for Less Than Four Weeks Increases the Risk of Relapse in Culture-Positive Septic Arthritis of Native Joints.

(1) Objectives: This study investigated the optimal duration of antibiotic therapy and determined the risk factors associated with relapse in patients with culture-proven septic arthritis of native joints. (2) Methods: A retrospective review was conducted on patients aged ≥18 years diagnosed with native joint septic arthritis, with bacteria isolated from joints and/or blood. The exclusion criteria were prosthetic joint infections and cases with no identified microorganisms. The outcomes were assessed in the remission and relapse groups. (3) Results: Among 479 patients with native joint septic arthritis, 137 met the inclusion criteria, with a median follow-up duration of 2.7 years. The relapse rate was 9.5%, which mainly occurred within 30 days after antibiotic treatment completion. Compared with the remission group, the relapse group showed a significantly higher proportion of cases that received antibiotic therapy for ≤ 4 weeks (4.8% vs. 46.2%, p < 0.001), synovial fluid white blood cell (WBC) counts ≥150 × 103/mm3 (25.3% vs. 60.0%, p = 0.030), acute kidney injury (19.2% vs. 50%, p = 0.024), and extended-spectrum beta-lactamases-producing Enterobacteriaceae (0.8 vs. 15.4%, p = 0.024). Independent risk factors for relapse were determined as antibiotic therapy duration of ≤ 4 weeks (odds ratio (OR), 25.47; 95% confidence interval (CI), 1.57-412.33; p = 0.023) and synovial fluid WBC counts ≥150 × 103/mm3 (OR, 17.46; 95% CI, 1.74-175.62; p = 0.015). (4) Conclusions: Patients with native joint septic arthritis require vigilant monitoring for relapse, particularly when treated with antibiotic regimens administered for less than four weeks or when synovial aspirates exhibit elevated WBC counts at diagnosis.

What Is the Most Reliable Concordance Rate of Preoperative Synovial Fluid Aspiration and Intraoperative Biopsy to Detect Periprosthetic Joint Infection in Knee, Hip and Shoulder Arthroplasty?

The accuracy of preoperative synovial fluid microbe detection in periprosthetic joint infection (PJI) is widely reported. However, the reliability of this diagnostic modality amongst the different joints is not yet described. We aimed to compare the concordance rate between preoperative synovial fluid and intraoperative tissue cultures in shoulder, knee and hip PJIs. A total of 150 patients who met the 2018 International Consensus Meeting criteria for shoulder, hip and knee PJI were retrospectively reviewed. This cohort was divided into three groups based on the involved joint (should, hip or knee), with 50 patients in each group. Cultures were collected and held for culture for 14 days. The overall concordance rate was 56.7%. Concordance rates between preoperative and intraoperative cultures were 60%, 56% and 54% for the knee, shoulder and hip joints, respectively. The analysis of high- or low-virulence and difficult- or not-difficult-to-treat germs did not reveal any significant differences between preoperative and intraoperative cultures in any of the groups. However, even considering the higher concordance in knee PJI, the overall discordance between preoperative and intraoperative cultures should prompt surgeons not to rely solely on preoperative synovial fluid culture data in determining appropriate treatment and antibiotics.

Umbilical Cord Stem Cell Lysate: A New Biologic Injectate for the Putative Treatment of Acute Temporomandibular Joint Inflammation.

To compare in vivo, the acute anti-inflammatory effects of a lysate derived from human umbilical perivascular mesenchymal cells with the cells themselves in both an established hind-paw model of carrageenan-induced inflammation and also in the inflamed temporomandibular joint. Human umbilical cord perivascular cells were harvested and cultured in xeno- and serum-free conditions to P3. In addition, P3 cells were used to prepare a proprietary 0.22 micron filtered lysate. First, CD1 immunocompetent mice underwent unilateral hind-paw injections of carrageenan for induction of inflammation, followed immediately by treatment with saline (negative control), 1% cell lysate, or viable cells. The contralateral paw remained un-injected with carrageenan. Paw circumference was measured prior to injections and 48 hr later and myeloperoxidase and TNF-alpha concentrations were measured post-sacrifice in excised tissue. Second, immunocompetent Male Wistar rats underwent unilateral intra-articular temporomandibular (TMJ) injections from the same treatment groups and were sacrificed at 4 and 48 hr post-injection. The contralateral TMJ remained un-injected with carrageenan. Articular tissue and synovial aspirates, from the treated TMJ were obtained for histologic and leukocyte infiltration analyses. The lysate and cell-treated hind-paw demonstrated reduced tissue edema, and significantly lower concentrations of myeloperoxidase and TNF-alpha at 48 hr compared to untreated controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium compared to controls and histologic evidence, in the peri-articular tissue, of reduced inflammation. In this preliminary study, both the human umbilical perivascular cells and a highly diluted lysate produced therefrom were anti-inflammatory.

Evidence of Bacterial Metabolism in Synovial Fluid of Patients With Graft Failure After Anterior Cruciate Ligament Reconstruction: A Microbiological Comparison of Primary Anterior Cruciate Ligament and Hamstring Tendon Autograft Ruptures

To investigate whether the bacterial presence in a primary ruptured native anterior cruciate ligament (ACL) differs from that in a ruptured hamstrings ACL autograft and whether low-grade infections cumulatively can be detected in the case of graft failure. In a retrospective case-control study with prospectively collected data, synovial fluid aspirates and tissue samples of failed ACL grafts were examined for evidence of bacterial colonization and compared to samples of the native ACL in primary ACL reconstruction (ACLR) using microbiological culture, 16S rRNA-PCR and histopathological examination. Furthermore, synovial fluid aspiration was investigated for possible future biomarkers for a low-grade infection. A total of 112 consecutive patients undergoing primary ACLR without history of previous surgeries to the affected knee (n= 59) and revision ACLR after reconstruction with a hamstring tendon autograft (n= 53) were recruited from one center. No patient had a history or showed clinical signs of infection. A total of 389 samples were analyzed by culture. Bacteria were detected in 9.4% of patients with a graft rupture (n= 5/53) compared to 3.4% of patients with a primary ACL rupture (n= 2/59) showing no statistical difference (P= .192). One patient with a "true" low-grade infection was found in our study population, resulting in a prevalence of 1.9% (1/53) in the graft group. The percentage of polymorphonuclear leukocytes (PMN%) as a highly sensitive marker for joint infections was significantly higher in aspirated synovial fluid of graft ruptures (27% ± 3% vs 20% ± 4%; P= .032), as well as glucose levels were significantly lower (83 mg/dL ± 2 mg/dL vs 88 mg/dL ± 2 mg/dL; P= .042). Synovial fluid obtained before revision ACLR showed a higher percentage of polymorphonuclear leukocytes and lower glucose levels compared with primary ACLR, suggesting bacterial metabolism and demonstrating that the intra-articular milieu changes significantly after ACLR. Tissue samples of ACL grafts revealed a low-grade infection in one case, although overall cultivable bacterial presence did not differ significantly when compared to samples of a native ACL. Level III, retrospective case-control study.