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The paper proposes a method based on a combination of the provisions of the phonon theory of liquid, V–T formalism, and Frenkel's theory of determining the P–T parameters of a liquid system, to determine the pressure and temperature values at which the transition from a denser liquid fraction to a less dense one occurs. Its use makes it possible to analyze the motion of fluid components in joint complexes and to determine their lifetime. It is also shown that at short time intervals, regardless of the physical state of the system, the components of the liquid move as independent particles, and their motion can be represented within the framework of the vibrational-hopping diffusion model. In this paper, the developed methodology is used to study the structural and dynamic properties of argon near the triple point on the liquid–gas coexistence curve. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unexplained causes. Its pathological features include synovial tissue hyperplasia, inflammatory cell infiltration in joint cavity fluid, cartilage bone destruction, and joint deformation. C–C motif chemokine ligand 3 (CCL3) belongs to inflammatory cell chemokine. It is highly expressed in inflammatory immune cells. Increasingly, studies have shown that CCL3 can promote the migration of inflammatory factors to synovial tissue, the destruction of bone and joint, angiogenesis, and participate in the pathogenesis of RA. These symptoms indicate that the expression of CCL3 is highly correlated with RA disease. Therefore, this paper reviews the possible mechanism of CCL3 in the pathogenesis of RA, which may provide some new insights for the diagnosis and treatment of RA. [ABSTRACT FROM AUTHOR]

Fundamental knowledge about in vivo kinematics and contact conditions at the articulating interfaces of total knee replacements are essential for predicting and optimizing their behavior and durability. However, the prevailing motions and contact stresses in total knee replacements cannot be precisely determined using conventional in vivo measurement methods. In silico modeling, in turn, allows for a prediction of the loads, velocities, deformations, stress, and lubrication conditions across the scales during gait. Within the scope of this paper, we therefore combine musculoskeletal modeling with tribo-contact modeling. In the first step, we compute contact forces and sliding velocities by means of inverse dynamics approach and force-dependent kinematic solver based upon experimental gait data, revealing contact forces during healthy/physiological gait of young subjects. In a second step, the derived data are employed as input data for an elastohydrodynamic model based upon the finite element method full-system approach taking into account elastic deformation, the synovial fluid's hydrodynamics as well as mixed lubrication to predict and discuss the subject-specific pressure and lubrication conditions. [ABSTRACT FROM AUTHOR]

Viscosupplementation by intra-articular (i.a.) injection of the non-sulfated glycosaminoglycan (GAG) hyaluronic acid (HA) is a conservative therapy widely accepted in clinical practice for the management of osteoarthritis (OA) and joint diseases. The aim of viscosupplementation is to restore the rheological properties of the synovial fluid to relieve joint inflammation and pain and improve joint function through a chondroprotective effect. However, there is a range of hyaluronic acid products for OA that differ in preparation, molecular weight, rheological characteristics and concentration, and different i.a. formulations are more suited to particular patient populations and clinical situations, in part because of anatomical differences between joints. This paper focuses on innovative hybrid cooperative complexes of high and low molecular weight hyaluronic acid (HA-HL) and hyaluronic acid plus sodium chondroitin (HA-SC) that have been developed. Both products are formulated with pharmaceutical-grade, highly purified hyaluronic acid obtained with a multi-step biofermentation process, with properties that make them suitable across a range of degenerative joint diseases. They represent progress in building on the symptomatic and functional benefits of viscosupplementation in joint disease, with the additional beneficial effect of treating the patient with a high concentration of GAGs by a low number of injections. Here, we review the clinical evidence for the efficacy of a hybrid cooperative compound of HA-HL in various degenerative joint diseases, which suggests a synergistic effect of the different molecular weight hyaluronans that together more closely mimic the physiological composition of synovial fluid. Similarly, the evidence shows that HA-SC is safe, effective, and well tolerated in hip OA, with rapid and clinically significant improvements in pain symptoms and functionality. Such innovations in viscosupplementation expand the usefulness of the modality in the management of OA and other joint diseases, complemented by a lack of systemic or local side effects that allow the concurrent use of other drugs if needed. [ABSTRACT FROM AUTHOR]

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]

Rheumatoid arthritis (RA) is an autoimmune disorder that typically affects people between 23 and 60 years old causing chronic synovial inflammation, symmetrical polyarthritis, destruction of large and small joints, and chronic disability. Clinical diagnosis of RA is stablished by current ACR-EULAR criteria, and it is crucial for starting conventional therapy in order to minimize damage progression. The 2010 ACR-EULAR criteria include the presence of swollen joints, elevated levels of rheumatoid factor or anti-citrullinated protein antibodies (ACPA), elevated acute phase reactant, and duration of symptoms. In this paper, a computer-aided system for helping in the RA diagnosis, based on quantitative and easy-to-acquire variables, is presented. The participants in this study were all female, grouped into two classes: class I, patients diagnosed with RA (n = 100), and class II corresponding to controls without RA (n = 100). The novel approach is constituted by the acquisition of thermal and RGB images, recording their hand grip strength or gripping force. The weight, height, and age were also obtained from all participants. The color layout descriptors (CLD) were obtained from each image for having a compact representation. After, a wrapper forward selection method in a range of classification algorithms included in WEKA was performed. In the feature selection process, variables such as hand images, grip force, and age were found relevant, whereas weight and height did not provide important information to the classification. Our system obtains an AUC ROC curve greater than 0.94 for both thermal and RGB images using the RandomForest classifier. Thirty-eight subjects were considered for an external test in order to evaluate and validate the model implementation. In this test, an accuracy of 94.7% was obtained using RGB images; the confusion matrix revealed our system provides a correct diagnosis for all participants and failed in only two of them (5.3%). Graphical abstract. [ABSTRACT FROM AUTHOR]

Aim and objective: The concentration of lipoproteins and apolipoprotein are extremely low in the synovial fluid of any healthy person as compared to the concentrations in plasma. However, in the synovial fluid of any diseased patient the amount of cholesterol and lipids is sharply increased. The current review defines the role of various apolipoproteins and lipoproteins and their constituent subfractions in the synovial fluid embarking its principal role in rheumatoid arthritis. It also explains the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins in synovial fluid. Materials and methods: Various research and review articles highlighting the role of apolipoproteins and lipoproteins were procured from medical websites mainly Pubmed, Medline, Science Direct, etc., and studied for the writing of the review paper. Conclusion: Mainly apolipoproteins A-1, B and E are prominently increased in chronic inflammatory joint disorders. Several theories have been proposed to understand the source of increase of lipids and apolipoproteins in synovial fluid of the diseased patients compared to healthy individuals, yet the precise mechanism is still not lucid. Lipoproteins are believed to play both functional role and pathological role in the synovial fluid. The activated T-lymphocytes in patients of RA lead to activation of inflammatory cytokines such as tumor necrosis factor and interleukins which embark to be the principal mechanism for induction of the disease. It can be thus concluded that the apolipoproteins prevent the activation of monocytes by blocking their contact of activation and thus play critical role in management of RA by inhibiting the production of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Hip joint replacements represent the most effective way of treatment for patients suffering from joint diseases. Despite the rapid improvement of implant materials over the last few decades, limited longevity associated with wear-related complications persists as the main drawback. Therefore, improved tribological performance is required in order to extend the service life of replacements. The effect of surface texturing of ultra-high molecular weight polyethylene (UHMWPE) acetabular cup was investigated in the present study. Unique tilling method was utilized for manufacturing the dimples with controlled diameter and depths on the contact surface of the cup. The experiments with four commercial femoral components and two model lubricants were realized. The main attention was paid to a coefficient of friction considering the differences between the original and the dimpled cups. Results showed remarkable lowering of friction, in general. Focusing on the simulated human synovial fluid, friction was reduced by 40% (alumina ceramic), 38.8% (zirconia toughened ceramic), 25.5% (metal), and 9.9% (oxinium). In addition, the dimples helped to keep the friction stable without fluctuations. To conclude, the paper brings a new insight into frictional behaviour of the hip replacements during running-in phase which is essential for overall implant lifespan. It is believed that proper surface texturing may rapidly improve the life quality of millions of patients and may lead to considerable financial savings. [ABSTRACT FROM AUTHOR]

The analysis of synovial fluid is an important method in diagnosing and handling septic arthritis. To achieve a quick diagnosis could be a great advantage in the therapy. The differential scanning calorimetry (DSC) proved to be a useful technique in the differential diagnosis of tumors using blood plasma or sera. The aim of this paper is to show up some characteristic thermal parameters in the diagnosis of different grades of arthritis, which are in good agreement with the severity of disease checked by conventional X-ray supported grading. To follow the effect of different bacterial strains, the synovial fluids were inoculated by three types of bacterial strains (with 103–105 CFU mL−1 concentrations) at 37 °C and stored trough 24 h. After that, they were denatured in 20–90 °C temperature range with 0.3 K min−1 scanning rate. The change in the maximum denaturation temperature (Tm) and calorimetric enthalpy (∆H) monitored the severity of sepsis and depended on the type of bacteria. The proliferation characteristics of bacteria should be strain specific. The synovial fluid samples inoculated with the most frequently occurring bacteria were monitored in isotherm mode (isoperibol calorimeter) at 37 °C up to the end of the proliferation. The isoperibolic scans clearly demonstrated specific, concentration-dependent representative curves in case of each bacterium (duration of proliferation, maximum of proliferation rates, etc.). Therefore, thermal analysis of human synovial fluid samples by DSC or isoperibolic calorimetry could be a useful tool in the staging of osteoarthritis and the diagnostics of septic arthritis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is an autoimmune disease characterized by inflammation in the synovial fluid within the synovial joint connecting two contiguous bony surfaces. The inflammation diffuses into the cartilage adjacent to each of the bony surfaces, resulting in their gradual destruction. The interface between the cartilage and the synovial fluid is an evolving free boundary. In this paper we consider a two-phase free boundary problem based on a simplified model of rheumatoid arthritis. We prove global existence and uniqueness of a solution, and derive properties of the free boundary. In particular it is proved that the free boundary increases in time, and the cartilage shrinks to zero as t → ∞ , even under treatment by a drug. It is also shown in the reduced one-phased problem, with cartilage alone, that a larger prescribed inflammation function leads to a faster destruction of the cartilage. [ABSTRACT FROM AUTHOR]

Glucosamine (GlcN) is an amine sugar, in which a hydroxyl group of glucose is replaced with an amino group. It is an important part of the polysaccharides chitin and chitosan and is highly hydrophilic. It is also an important compound required for the formation of cartilage cells and represents one of the elementary units of the cartilage matrix and joint fluid. GlcN has been widely used in food, cosmetics, health care, and pharmaceutical industries. This paper fully addresses the categories and biomanufacturing methods of GlcN, including its production by fermentation with wild-type as well as engineered microorganisms and enzymatic catalysis with a series of chitinolytic enzymes. However, GlcN is usually produced from glucose by fermentation in a coupled manner with N-acetylglucosamine (GlcNAc). Enzymatic catalysis is thus a specific pathway for production of GlcN where chitin can be directly hydrolyzed to GlcN. In industry, GlcN produced with fungal mycelium as raw materials (plant GlcN) is thought as a high-end product because of vegetarian and non-transgenosis. In our opinion, more studies should be performed in order to develop a competitive enzymatic pathway using Aspergillus niger mycelium for the preparation of high-end GlcN. [ABSTRACT FROM AUTHOR]

The introduction of biologic disease modifying anti-rheumatic drugs (bMDARDs) have revolutionised the treatment of psoriatic arthritis (PsA). This combined with a ‘treat-to-target’ approach, means that achieving remission is increasingly possible. In patients with well-controlled PsA, there is little consensus on whether bDMARDs should be continued, tapered or discontinued altogether. Tapering or discontinuation of bDMARDs could offer significant financial savings and minimise patient burden and unwanted drug-related side effects. However, there is a risk of loss of remission. The primary focus of this paper is to review the current evidence on bDMARD tapering and discontinuation in PsA. We explore the criteria employed by studies to define patients eligible for bDMARD tapering or discontinuation and the process by which this occurs. We also review the outcomes of bDMARD tapering and discontinuation, the predictors, and the likelihood of restoring remission following relapse. To date, bDMARD tapering seems to be feasible and safe in patients with PsA who are in remission or with low disease activity. Lower disease activity prior to tapering seems to increase the likelihood of successful bDMARD tapering. In contrast, discontinuing bDMARDs appears to carry a substantial risk of loss of remission. Those with higher disease activity at time of tumour necrosis factor inhibitors discontinuation, current smokers, male sex, increased skin involvement, and synovial hypertrophy seen on ultrasound prior to discontinuation are at greater risk of losing remission post-bDMARD discontinuation. In those who lose remission, reinstating the standard dose of bDMARD appears to be effective in restoring remission. [ABSTRACT FROM AUTHOR]

The diagnosis of prosthetic joint infection (PJI) remains challenging, despite multiple available laboratory tests for both serum and synovial fluid analysis. The clinical symptoms of PJI are not always characteristic, particularly in the chronic phase, and there is often significant overlap in symptoms with non-infectious forms of arthroplasty failure. Further exacerbating this challenge is lack of a universally accepted definition for PJI, with publications from multiple professional societies citing different diagnostic criteria. While not included in many of the major societies' guidelines for diagnosis of PJI, diagnostic imaging can play an important role in the workup of suspected PJI. In this article, we will review an approach to diagnostic imaging modalities (radiography, ultrasound, CT, MRI) in the workup of suspected PJI, with special attention to the limitations and benefits of each modality. We will also discuss the role that image-guided interventions play in the workup of these patients, through ultrasound and fluoroscopically guided joint aspirations. While there is no standard imaging algorithm that can universally applied to all patients with suspected PJI, we will discuss a general approach to diagnostic imaging and image-guided intervention in this clinical scenario. [ABSTRACT FROM AUTHOR]

Subcutaneous nodular lesions in a patient with significantly elevated inflammatory markers always raise the possibility of infectious diagnoses such as atypical infection, pyogenic abscess, mycobacterial infection, and malignancy. Definitive diagnosis requires tissue biopsy and histopathologic examination. The atypical presentation of a foreign body granuloma with concurrent intraoperative findings supports the diagnosis of gouty arthritis. We report a case of a 67-year-old man who presented with an inflammatory nodular lesion on the left elbow that was initially suspected to have an infectious cause. Histopathologic examination of the nodular tissue later revealed that the patient had a foreign body granuloma due to urate crystal deposition. The atypical appearance of the gouty arthritis, the low serum urate level, the negative crystal identification in the synovial fluid, and the markedly elevated inflammatory markers, which did not respond to the previous antibiotic and steroid therapy, raised the suspicion of atypical infection in this case. [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]

Crystallization of monosodium urate monohydrate (MSU) leads to painful gouty arthritis. Despite extensive research it is still unknown how this pathological biomineralization occurs, which hampers its prevention. Here we show how inflammatory MSU crystals form after a non-inflammatory amorphous precursor (AMSU) that nucleates heterogeneously on collagen fibrils from damaged articular cartilage of gout patients. This non-classical crystallization route imprints a nanogranular structure to biogenic acicular MSU crystals, which have smaller unit cell volume, lower microstrain, and higher crystallinity than synthetic MSU. These distinctive biosignatures are consistent with the template-promoted crystallization of biotic MSU crystals after AMSU at low supersaturation, and their slow growth over long periods of time (possibly years) in hyperuricemic gout patients. Our results help to better understand gout pathophysiology, underline the role of cartilage damage in promoting MSU crystallization, and suggest that there is a time-window to treat potential gouty patients before a critical amount of MSU has slowly formed as to trigger a gout flare. A multi-analytical study of MSU crystals in synovial fluid of gouty patients discloses distinctive textural and ultrastructural features which are not present in abiotic MSU crystals, offering new clues to understand their pathological formation. [ABSTRACT FROM AUTHOR]

Background: Joint access is essential for arthrocentesis, or joint aspiration of fluids. Joint treatments that are not performed properly can result in avoidable patient issues such as damage to the muscles, tendons, and blood vessels surrounding the joint. The use of ultrasound has become the gold standard for this procedure and proven to be a support in the skill learning process. However, success with this equipment, particularly in small joints like the wrist, depends on a clinician's capacity to recognize the crucial landmarks that guide these procedures. Prior to executing on a real patient, task trainers have proven to be an effective way for doctors to practice and prepare for procedures. However, shortcomings of current solutions include high purchase costs, incompatibility with ultrasound imaging, and low reusability. In addition, since this is a procedure that is not performed frequently, there may not be space or resources available in healthcare facilities to accommodate one at the point of care. This study aimed to close the existing gap by developing a DIY ultrasound compatible task trainer for wrist joint access training. Results: We developed a novel ultrasound compatible wrist joint model that can be made from sustainable materials and reusable parts, thus reducing the costs for acquisition and environmental impact. Our model, which was produced utilizing small-batch production methods, is made up of 3D-printed bones enclosed in an ultrasound-compatible gelatin mixture. It can be easily remade after each practice session, removing needle tracks that are visible under ultrasound for conventional phantoms. The ultrasonic properties of this model were tested through pixel brightness analysis and visual inspection of simulated anatomical structures. Conclusion: Our results report the advantages and limitations of the proposed model regarding production, practice, and ultrasound compatibility. While future work entails the transfer to patients of the same skill, this reusable and replicable model has proven, when presented to experts, to be successful in representing the physical characteristics and ultrasound profile of significant anatomical structures. This novel DIY product could be an effective alternative to teach procedures in the context of resource-restrained clinical simulation centers. [ABSTRACT FROM AUTHOR]

Total joint arthroplasty is the recommended treatment for patients with end-stage osteoarthritis, as it reduces disability and pain and restores joint function. However, prosthetic joint infection is a serious complication of this procedure, with the two-stage exchange being the most common treatment method. While there is consensus on diagnosing prosthetic joint infection, there is a lack of agreement on the parameters that can guide the surgeon in performing definitive reimplantation in a two-stage procedure. One approach that has been suggested to improve the accuracy of microbiologic investigations before definitive reimplantation is to observe a holiday period from antibiotic therapy to improve the accuracy of cultures from periprosthetic tissues, but these cultures report some degree of aspecificity. Therefore, several pieces of evidence highlight that performing reimplantation using continuous antibiotic therapy should be considered a safe and effective approach, leading to higher cure rates and a shorter period of disability. Dosage of C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer are helpful in diagnosing prosthetic joint infection, but only D-dimer has shown sufficient accuracy in predicting the risk of infection recurrence after a two-stage procedure. Synovial fluid analysis before reimplantation has been shown to be the most accurate in predicting recurrence, and new cutoff values for leukocyte count and neutrophil percentage have shown a useful predictive rule to identify patients at risk of unfavourable outcome. A new scoring system based on a numerical score calculated from the beta coefficient derived through multivariate analysis of D-dimer levels, synovial fluid leukocytes and relative neutrophils percentage has demonstrated high accuracy when it comes to guiding the second step of two-stage procedure. In conclusion, reimplantation may be a suitable option for patients who are on continuous therapy without local symptoms, and with CRP and ERS within the normal range, with low synovial fluid leukocytes (< 952/mL) and a low relative neutrophil percentage (< 52%) and D-dimer below 1100 µg/mL. A numerical score derived from analysing these three parameters can serve as a valuable tool in determining the feasibility of reimplantation in these patients. [ABSTRACT FROM AUTHOR]

The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in tribology. In this study, to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid (SF), cartilage specimens were processed with four different treatments: gentle and severe washing with detergent, incubation in NaCl solution, and trypsin digestion to selectively remove certain constituents from the cartilage surface. Subsequently, the frictional characteristics were examined in phosphate-buffered saline (PBS) and SF against glass. Angularly reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage specimens. Meanwhile, the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion methods. The coefficient of friction (COF) of the prepared cartilage specimens was varied from 0.05 to over 0.3 in PBS. However, a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited variation. For the low COF group of specimens, all four treatments increased the COF in PBS to different extents, and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by treatments. This means that the intact cartilage surface had lubricating constituents to maintain low friction, and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage surface. The variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage surface. The lubricating effect of SF could be confirmed even after degenerative treatment. [ABSTRACT FROM AUTHOR]

This paper considers metal tribomaterial features for implants into the human body in the form of special products and methods for increasing life cycle. [ABSTRACT FROM AUTHOR]

The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes. We define the location of Axl/MerTK in rheumatoid synovium using immunohistochemistry/fluorescence and digital spatial profiling and show that Axl is preferentially expressed in the lining layer. Moreover, its ectodomain, released in the synovial fluid, is associated with synovial histopathology. We also show that Toll-like-receptor 4-stimulated synovial fibroblasts from patients with RA modulate MerTK shedding by macrophages. Lastly, Axl/MerTK synovial expression is influenced by disease stage and therapeutic intervention, notably by IL-6 inhibition. These findings suggest that Axl/MerTK are a dynamic axis modulated by synovial cellular features, disease stage and treatment. The TAM tyrosine kinases, Axl and MerTK, have been implicated in rheumatoid arthritis (RA). Here, using a synovial tissue bioresource of patients with RA, the authors describe how Axl and MerTK expression and function are linked to synovial histopathology, disease activity, and therapeutic intervention with IL-6 inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: The literature presents a wide range of success rates for a single surgical intervention of bacterial‐septic‐arthritis, and there is a lack of clear criteria for identifying treatment failure and making decisions about reintervention. This Delphi study aims to establish a consensus among an international panel of experts regarding the definition of treatment failure and the criteria for reintervention in case of bacterial arthritis. Methods: The conducting and reporting Delphi studies (CREDES) criteria were used. Data from a systematic review was provided as the basis for the study. A list of 100 potential experts were identified. The study was designed and conducted as follows: (I) identification and invitation of an expert panel, (II) informing the participating expert panel on the research question and subject, and (III) conducting two or three Delphi rounds to reach consensus on explicit research items. Potential criteria were rated on a five‐point Likert scale. Results: Sixty orthopaedic experts from nine countries participated in this Delphi study, with 55 completing all three rounds. The mean experience as an orthopaedic surgeon was 15 years (SD ± 9). Strong (96%) consensus was reached on the definition of treatment failure: the persistence of physical signs of arthritis (e.g., pain and swelling) and/or systemic inflammation (e.g., fever and no improvement in CRP) despite surgical and antibiotic treatment. Furthermore, consensus (>80%) was reached on six criteria influencing the decision for reintervention; pain (81%), sepsis (98%), fever (88%), serum CRP (93%), blood culture (82%), and synovial fluid culture (84%). Conclusion: The definition of treatment failure for bacterial arthritis after a single surgical intervention was established through a three‐round Delphi study. Additionally, consensus was reached on six criteria that are helpful for determining the need for reintervention. This definition and these criteria may help in the development of clinical guidelines, and will empower physicians to make more precise and consistent decisions regarding reintervention for patients, ultimately aiming to reduce over‐ and undertreatment and improve patient outcomes. Level of Evidence: Level V. [ABSTRACT FROM AUTHOR]

The role of bovine calf serum (BCS) related to the functional performance of synovial fluid on the tribological behavior of borides grown on cobalt–28chromium–6molybdenum (Co–28Cr–6Mo) alloy used in orthopedic prostheses is not known yet. Here, the borides were grown on Co–28Cr–6Mo surface for 5 and 7 hours at 975 °C using 90 wt pct boron carbide (B4C) and 10 wt pct sodium tetrafluoroborate (NaBF4) powders. The borides were characterized by X-ray diffractometer (XRD), nanoindentation, scanning electron microscope (SEM) and energy dispersive spectroscope (EDS). The tribological performance of the borides was evaluated using a ball-on-disk type tribometer in dry-sliding condition and different biological fluids (phosphate buffered saline (PBS) and BCS). The thickness, nanohardness and elastic modulus values of the borides composed of a bilayer Co2B and CoB phases were observed to be 33.3 to 40 µm, 22.34 to 24.30 GPa and 224.46 to 229.27 GPa, respectively. Following the boriding process, the volume loss of Co–28Cr–6Mo decreased from 0.275 to 0.122-0.142 mm3 owing to the high hardness and elastic modulus of the formed boride layers. The lubricating effect of PBS and BCS fluids has a great influence on the friction and wear performance of the boride layers. With the introduction of PBS lubricant into the tribosystem, the worn volume and COF of the borides significantly decreased from 0.122-0.142 to 0.014 mm3 and from 0.68-0.75 to 0.21-0.25, respectively. Plasma proteins present in BCS lubricant managed to reduce these values even further and showed a COF of 0.09 and the worn volume of 0.002 to 0.003 mm3. SEM and EDS analyses showed that the main failure mechanism of the borides was changed from oxidation-assisted delamination in dry-sliding condition to micro-scratches in BCS lubricant. The superior wear and friction performance of the borides (grown on Co–28Cr–6Mo) in BCS lubricant suggests its potential usage for orthopedic implant products although further in-vitro and in-vivo studies are needed to verify this potential. [ABSTRACT FROM AUTHOR]

The scientific article offers an analytical solution for the model of synovial fluid flow between the cartilage under the influence of load on the cartilage surface, inlet pressure and flux. The tangent hyperbolic fluid model is used in the analogy of spongy cartilage to discuss the rheology of synovial fluid in rectangular slit having permeable boundary. The transverse velocity on the surface of permeable cartilage is measured by the pressure difference, and axial velocity is assumed to be maximum at the centre of slit. The two-dimensional and two-directional flow is produced by the pressure gradient or pressure difference, which is modelled by the physical laws of mass and momentum with the nonhomogeneous boundary conditions in finite domain. The complex system of nonlinear equations is solved by the perturbation technique with the assumption that elastic forces are weaker than the viscous forces. The effect of filtration rate, power-law index, inlet pressure and Weissenberg number on flow properties are observed through graphs, and it is examined that when these emerging parameters rises, then the flow towards the cartilage surface begins to thin. As a result, the viscosity of the synovial fluid near the cartilage become weak but it is strong between the cartilage surfaces that is filled by the synovial fluid. Also, the filtration rate against pressure and permeability is also measured by the formulas calculated in this research and it is concluded that the high filtration rate requires the less pressure and high permeability on the boundary of the cartilage cavity. [ABSTRACT FROM AUTHOR]

For knee osteoarthritis and related conditions, analysis of biomarkers hold promise to improve early diagnosis and/or offer patient-specific treatment. To compare biomarker analyses, reliable, high-quality biopsies are needed. The aim of this work is to summarize the literature on the current best practices of biopsy of the synovium and synovial fluid arthrocentesis. Therefore, PubMed, Embase and Web of Science were systematically searched for articles that applied, demonstrated, or evaluated synovial biopsies or arthrocentesis. Expert recommendations and applications were summarized, and evidence for superiority of techniques was evaluated. Thirty-one studies were identified for inclusion. For arthrocentesis, the superolateral approach in a supine position, with a 0°-30° knee flexion was generally recommended. 18-gage needles, mechanical compression and ultrasound-guidance were found to give superior results. For blind and image-guided synovial biopsy techniques, superolateral and infrapatellar approaches were recommended. Single-handed tools were preconized, including Parker-Pearson needles and forceps. Sample quantity ranged approximately from 2 to 20. Suggestions were compiled for arthrocentesis regarding approach portal and patient position. Further evidence regarding needle size, ultrasound-guidance and mechanical compression were found. More comparative studies are needed before evidence-based protocols can be developed. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) involves several classes of pathogenic autoantibodies, some of which react with type-II collagen (COL2) in articular cartilage. We previously described a subset of COL2 antibodies targeting the F4 epitope (ERGLKGHRGFT) that could be regulatory. Here, using phage display, we developed recombinant antibodies against this epitope and examined the underlying mechanism of action. One of these antibodies, R69-4, protected against cartilage antibody- and collagen-induced arthritis in mice, but not autoimmune disease models independent of arthritogenic autoantibodies. R69-4 was further shown to cross-react with a large range of proteins within the inflamed synovial fluid, such as the complement protein C1q. Complexed R69-4 inhibited neutrophil FCGR3 signaling, thereby impairing downstream IL-1β secretion and neutrophil self-orchestrated recruitment. Likewise, human isotypes of R69-4 protected against arthritis with comparable efficiency. We conclude that R69-4 abrogates autoantibody-mediated arthritis mainly by hindering FCGR3 signaling, highlighting its potential clinical utility in acute RA. Rheumatoid arthritis (RA) involves several types of autoantibodies, which are usually considered pathogenic. In this study, the authors use phage display to develop antibodies targeting type-II collagen that are protective in multiple experimental models of RA. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate prolactin (PRL) levels in gingival crevicular fluid (GCF), synovial fluid, and serum in patients suffering from moderately active rheumatoid arthritis (RA) with and without periodontitis (P). Further, to evaluate the effect of non-surgical periodontal treatment on these levels compared to controls. Materials and methods: Eighty subjects were divided into 4 groups: group 1: 20 patients with RA + P, group 2: 20 periodontitis patients (systemically healthy), group 3: RA patients (periodontally healthy), and group 4: healthy controls. Patients with periodontitis received scaling and root planning (SRP). PRL was measured using enzyme‐linked immunosorbent assay. Results: At baseline, in GCF of RA + P group showed the highest mean PRL levels, followed by P group whereas groups 3 and 4 showed a statistically less values than the first 2 groups. Serum values showed non-significant difference between the first three groups, although higher than healthy controls. SRP reduced GCF and serum levels of PRL in both P groups as well as synovial fluid PRL in group 1. SRP caused no change in DAS scores while reduced ESR values were observed in group 1 after treatment. Conclusions: Local GCF and synovial levels of PRL seem to be linked to the disease process of both periodontitis and rheumatoid arthritis than serum levels. SRP reduced these local levels. Clinical relevance: In patients with RA and CP, local PRL seems to play a role in the association between the two conditions; further, periodontal treatment is essential to improve periodontal condition in RA patients. Trial registration: Clinicaltrials.gov. Identifier: NCT04279691. [ABSTRACT FROM AUTHOR]

This study was to explore the effects of dopamine melanin nanoparticles (D–M nanoparticles) and collagen matrix combined with platelet-rich plasma (PRP) on arthritis chondrocytes and oxygen free radicals. 230–250 g rats were randomly divided into three groups, group A was treated with PRP, group B was treated with PRP combined with a collagen matrix, and group C was treated with PRP combined with collagen matrix and D–M nanoparticles. Each group was established an osteoarthritis model. The rats were sacrificed after the 10th week to detect and observe the proliferation of chondrocytes, changes in cell morphology, survival, changes in cartilage-specific genes, and the degree of cartilage in the model animals. compared with group A, both group B and group C had obvious cartilage differentiation and the effect of group C was better than group B; the cell proliferation in group C was much better in the other two groups; and the expression of cartilage-specific matrix proteoglycans in group C was better in contrast to group B and group A. Such results indicated that PRP could more effectively promote cartilage cell regeneration and prevent cartilage differentiation based on nanoparticle administration. In the D–M nanoparticle group, the level of free radicals in the synovial fluid of rats was greatly reduced (P < 0.05) and showed a quantitative dependence, indicating that the injection of D–M nanoparticles in the joint cavity could effectively lower the level of free radicals in joint tissues. PRP combined with collagen matrix can effectively improve chondrocyte activity, promote extracellular matrix secretion, and induce cartilage formation. The dopamine D–M nanoparticles could effectively reduce the level of oxygen free radicals in the joint cavity. The above drugs had potential values in the clinical treatment of osteoarthritis. [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]

Introduction: Early diagnosis of periprosthetic hip and knee infection still represents a major challenge, as no single test can achieve ideal results. Currently, multiple preoperative indicators were performed to diagnose periprosthetic joint infection (PJI) to confirm or exclude infection in the early stage. However, the diagnostic value of biopsy-related tests in diagnosing periprosthetic hip and knee infection remains unclear. Materials and methods: Publications in PubMed, Embase, and the Web of Science databases were searched systematically until October 2020. Inclusion and exclusion criteria were used for screening biopsy-related studies of the diagnosis of periprosthetic hip and knee infection. Results: Three biopsy-related tests were identified in 14 articles and further analyzed in the present meta-analysis. The combined method had the highest value for the area under the curve (0.9805), followed by histology (0.9425) and microbiological tests (0.9292). In the subgroup, statistical differences were identified in sensitivity and specificity for PJI diagnosis between the synovial fluid culture and biopsy culture group, as well as in the biopsy-related combined method and serum C-reactive protein. Conclusions: Biopsy culture does not appear to be advantageous compared to synovial fluid culture in the preoperative diagnosis of periprosthetic hip and knee infection. In contrast, combined biopsy microbial culture with histology analysis shows great potential in improving the preoperative diagnosis of PJI. The standard procedure of biopsy needs to be further explored. Further research is required to verify our results. [ABSTRACT FROM AUTHOR]

Objective and design: The purpose of this study was to explore pathological processes during the first 4 weeks after anterior cruciate ligament reconstruction (ACLR). Subjects: Sixteen ACL-injured patients (8 females/8 males, mean age = 19.1, mean BMI = 28.6). Methods: Arthrocentesis was performed 1 and 4 weeks after ACLR. Proteins in the synovial fluid were identified using nanoLC–ESI-MS/MS. Differentially up- or down-regulated proteins were identified and quantified, and a pathway analysis was performed. All identified proteins were mapped into a protein–protein interaction (PPI) network, and networks of PPIs with a combined score > 0.9 were then visualized. Results: Seven pathways were upregulated after ACLR: PI3K-AKT signaling pathway, extracellular matrix (ECM)–receptor interaction, focal adhesion, protein digestion and absorption, ameobiasis, and platelet activation. Network analyses identified 8 proteins that were differentially upregulated with strong PPI interactions (periostin and 7 collagen-related proteins). Increases in periostin moderately correlated with increases in a synovial fluid biomarker of type II cartilage degradation (ρ = 0.51, p = 0.06). Conclusion: Pro-inflammatory pathways and periostin were upregulated after ACLR. Periostin demonstrated strong network connections with markers of collagen breakdown, and future work is needed to determine whether periostin may offer a biomarker of early cartilage degradation after ACLR and/or play an active role in early post-traumatic osteoarthritis (PTOA) progression. [ABSTRACT FROM AUTHOR]

Introduction: Different approaches have been proposed for bacterial identification in patients with a suspected periprosthetic joint infection (PJI). If a one-stage procedure is considered, a higher rate of preoperative bacterial identification can be achieved if biopsy is included in the diagnostic work-up. The performance of open biopsy (OB) in the context of PJI has not been clearly determined yet. The purpose of this study was to determine the value of an OB added to two consecutive culture-negative joint aspirations during PJI workup. Materials and methods: We retrospectively analyzed the OB data from a single institution. Patients under PJI work-up of the hip or knee with two culture-negative periprosthetic aspirations who underwent OB were included. Sensitivity and specificity were calculated using the musculoskeletal infection society (MSIS) criteria as gold standard. Patients undergoing urgent irrigation and debridement and patients with history of surgery to the affected joint in the prior 6 weeks were excluded. Results: 126 patients were included in this study. 62 (49.2%) patients had prior revisions, 48 of them due to PJI. The sensitivity and specificity of OB was 69.4% and 89.1%, respectively. The OB procedure led to the identification of the causative germ in 50 out of 126 (40%) cases so they could undergo one-stage (septic) exchange. Conclusion: The OB is a valuable resource if preoperative synovial fluid cultures are negative, a high suspicion of infection persists and a one-stage procedure is preferred. It intends bacteria identification and allows surgeons to evaluate prosthetic complications for further surgical procedures. [ABSTRACT FROM AUTHOR]

The joint pore pressure inside rock mass significantly affects groundwater bursting. To investigate the couple effect of joint pore pressure and joint orientations on rock strength, this study utilized the three-dimensional numerical modeling code of 3DEC to carry out the experiments of uniaxial and triaixal compression tests. Seven three-dimensional models with parallel oriented joints of 0°, 15°, 30°, 45°, 60°, 75°, 90° inclination angle were developed. The input parameters of rock, joints and fluid properties were calibrated based on the results of previous studies. The established models were tested in the uniaxial and triaxial compression tests under uncoupled mechanical state and coupled hydro-mechanical state with various joint pore pressures (0.5, 1.0, 2.0, 3.0 MPa). The results show that the strength varied with different joint orientations producing the classic "U"-shaped curve. However, when the joint pore pressure was involved, the strength changed to a "W"-shaped curve. Additionally, the effect of the joint pore pressure on rock strength depends on orientations. The strength was decreasing with the increase of joint pore pressure when the orientations are 0°, 15°, 30°, 75° and 90°; the strength was increasing with the increase of joint pore pressure when the orientation is 60°; the strength was increasing first and then decreasing when the orientation is 45°. The results indicate that the joint orientation plays more important role than joint pore pressure on the strength change, thus needs to be considered for studying groundwater bursting. [ABSTRACT FROM AUTHOR]

Total joint arthroplasty is a common surgical procedure resulting in improved quality of life; however, a leading cause of surgery failure is infection. Periprosthetic joint infections often involve biofilms, making treatment challenging. The metabolic state of pathogens in the joint space and mechanism of their tolerance to antibiotics and host defenses are not well understood. Thus, there is a critical need for increased understanding of the physiological state of pathogens in the joint space for development of improved treatment strategies toward better patient outcomes. Here, we present a quantitative, untargeted NMR-based metabolomics strategy for Pseudomonas aeruginosa suspended culture and biofilm phenotypes grown in bovine synovial fluid as a model system. Significant differences in metabolic pathways were found between the suspended culture and biofilm phenotypes including creatine, glutathione, alanine, and choline metabolism and the tricarboxylic acid cycle. We also identified 21 unique metabolites with the presence of P. aeruginosa in synovial fluid and one uniquely present with the biofilm phenotype in synovial fluid. If translatable in vivo, these unique metabolite and pathway differences have the potential for further development to serve as targets for P. aeruginosa and biofilm control in synovial fluid. [ABSTRACT FROM AUTHOR]

Research on biomarkers for the diagnosis and monitoring of psoriatic arthritis (PsA) is ongoing. The purpose of this study was to assess the potential of serum and synovial fluid matrix metalloproteinase-3 (MMP-3) and myeloperoxidase (MPO) as biomarkers for PsA and their relation to disease activity indices. This case–control study involved 156 psoriatic arthritis patients, 50 gonarthrosis patients, and 30 healthy controls. The target parameters were measured with the enzyme-linked immunosorbent assay (ELISA) kits. Serum MMP-3 and MPO levels were elevated in the PsA patients in comparison to the two control groups (p < 0.001) and distinguished PsA from GoA patients and healthy controls with 100% accuracy. Synovial MMP-3 discriminated PsA from GoA patients irrespective of the presence of crystals (AUC = 1.00). PsA patients with crystals in the synovial fluid had elevated synovial MPO (p < 0.001) and were distinguished from PsA patients without crystals with accuracy of 88.50% and from GoA patients with accuracy of 88.30%. Synovial fluid MPO was positively associated with the following indicators of disease activity: VAS (rs = 0.396); DAPSA (rs = 0.365); mCPDAI (rs = 0.323). Synovial MMP-3 showed a weaker positive association with DAPSA (rs = 0.202) and mCPDAI (rs = 0.223). Our results suggest that serum MMP-3 and MPO could serve as biomarkers for PsA. Synovial fluid MMP-3 showed a potential as a biomarker for PsA versus GoA. Synovial MPO could be utilized as a marker for the presence of crystals in PsA patients. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) involves peri-articular sarcopenia. The infrapatellar articularis genu (AG) links to the quadriceps femoris (QF) and can be sampled from discarded tissue during arthroplasty. We predict disuse-mediated changes in AG myofiber type ratio and atrophy similar to reports on the QF during OA. OA AGs (n = 40) were preserved and grouped by poor (≤ 85°; n = 11), fair (90°–110°; n = 19), and good (≥ 115°; n = 10) range of motion (ROM). Immunolabeling of slow and fast myosin heavy chains in AG sections allowed comparing distribution and cross-sectional area (CSA) of type-I (T1) and type-II (T2) myofibers between groups and associating to ROM. T1/T2 ratios in fair and poor ROM groups was consistent with those published in OA QF. Increasing mean ± SD T2 percentages from good (43.31 ± 11.76), to fair (50.96 ± 5.85), and poor (60.02 ± 8.29) ROM groups was significant between poor versus fair (p = 0.018) and good (p < 0.0001) in association with ROM deficits (r = − 0.729; p < 0.0001). T1 and T2 CSA decreased with worsening ROM, which associates with lower symptom scores (r = 0.3198; p = 0.0472). In-depth evaluation of the OA AG as a surrogate for the OA QF relative to serum and/or synovial fluid biomarkers of sarcopenia could refine diagnostics of peri-articular muscle health to guide individualized strength rehabilitation after surgery. [ABSTRACT FROM AUTHOR]

Synovial fluid was collected from 113 patients who had suffered tibial plateau (n = 48), tibial plafond (n = 29), or rotational ankle fractures (n = 36). Concentrations of IL-1β, IL-1RA, IL-6, IL-8, IL-10, and MMP-1, -3, and -13 were quantified using multiplex assays. A cluster analysis of synovial fluid biomarker concentrations was performed. Patient demographics, fracture type, Injury Severity Score (ISS), Charlson Comorbidity Index (CCI), and biomarker concentrations were compared between clusters. A subset of patients demonstrated a dysregulated inflammatory response after articular fracture including elevated pro-inflammatory cytokines and degradative enzymes previously linked to the development of post-traumatic osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Intra-articular blood causes irreversible joint damage, whilst clinical differentiation between haemorrhagic joint effusion and other effusions can be challenging. An accurate non-invasive method for the detection of joint bleeds is lacking. The aims of this phantom study were to investigate whether magnetic resonance imaging (MRI) T1 and T2 mapping allows for differentiation between simple and haemorrhagic joint effusion and to determine the lowest blood concentration that can be detected. Methods: Solutions of synovial fluid with blood concentrations ranging from 0 to 100% were scanned at 1.5, 3, and 7 T. T1 maps were generated with an inversion recovery technique and T2 maps from multi spin-echo sequences. In both cases, the scan acquisition times were below 5 min. Regions of interest were manually drawn by two observers in the obtained T1 and T2 maps for each sample. The lowest detectable blood concentration was determined for all field strengths. Results: At all field strengths, T1 and T2 relaxation times decreased with higher blood concentrations. The lowest detectable blood concentrations using T1 mapping were 10% at 1.5 T, 25% at 3 T, and 50% at 7 T. For T2 mapping, the detection limits were 50%, 5%, and 25%, respectively. Conclusions: T1 and T2 mapping can detect different blood concentrations in synovial fluid in vitro at clinical field strengths. Especially, T2 measurements at 3 T showed to be highly sensitive. Short acquisition times would make these methods suitable for clinical use and therefore might be promising tools for accurate discrimination between simple and haemorrhagic joint effusion in vivo. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) features of active sacroiliac joint inflammation include joint space fluid and enhancement, but it is unclear to what extent these are present in normal children. Objective: To describe normal MRI appearances of pediatric sacroiliac joint spaces in boys and girls of varying ages. Materials and methods: In this ethics-approved prospective study, 251 children (119 boys, 132 girls; mean age: 12.4 years, range: 6.1–18.0 years), had both oblique-coronal T1-weighted and short tau inversion recovery (STIR) sacroiliac joint MRI. Of these, 127 were imaged for other reasons and had asymptomatic sacroiliac joints ("normal cohort") while 124 had low back pain with no features of sacroiliitis on initial clinical MRI review ("low-back-pain cohort"). Post-gadolinium T1-weighted sequences were available in 16/127 normal and 124/124 low-back-pain subjects. Three experienced radiologists scored high signal in the sacroiliac joint space on STIR (score 0=absent; 1=high signal compared to normal bone marrow present anywhere in the joint but not as bright as fluid [compared to vessels, cerebrospinal fluid]; 2=definite fluid signal in part of the joint; 3=definite fluid signal, entire vertical height, majority of slices) and, when available, joint space post-contrast enhancement (0=no high signal/enhancement; 1=thin, symmetrical, mildly increased linear high signal present in the joint space; 2=focal, thick or intense enhancement). Associations between joint signal scores, age, gender and sacral apophyseal closure were analysed. Results: Increased signal on STIR (score 1–3) was present in 74.7% of pediatric sacroiliac joint spaces, as intense as fluid in 18.4%. There was no significant difference in proportion by gender, side or cohort, but girls showed peak signal earlier than boys (10 years old vs. 12 years old, respectively). On post-gadolinium T1-weighted sequences, a thin rim of increased signal was nearly universally seen in sacroiliac joint spaces without focal, intense or thick post-contrast enhancement. Conclusion: Sacroiliac joint spaces of most children demonstrate mildly increased signal on STIR, compared to normal bone marrow, and thin rim-like enhancement on post-contrast T1 images, likely related to cartilage. These findings should not be confused with sacroiliitis. [ABSTRACT FROM AUTHOR]

The rheological properties of synovial fluid and hyaluronate (HA) solutions have been studied using a variety of viscometers and rheometers. These devices measure the viscosity of the fluid's resistance to shearing forces, which is useful when studying the lubrication and frictional properties of movable joints. Less commonly used is a squeeze-film fluid test, mechanistically similar to when two joint surfaces squeeze interposed fluid. In our study, we used squeeze-film tests to determine the rheological response of normal bovine synovial fluid and 10 mg/ml HA-based solutions, Hyalgan/Hyalovet, commercially available 500–700 kDa HA viscosupplements, and a 1000 kDa sodium hyaluronate (NaHy) solution. We found similar rheological responses (fluid thickness, viscosity, viscosity–pressure relationship) for all three fluids, though synovial fluid's minimum squeeze-film thickness was slightly thicker. Squeeze-film loading speed did not affect these results. Different HA concentrations and molecular weights also did not have a significant or consistent effect on the squeeze-film responses. An unexpected result for the HA-solutions was a linear increase in minimum fluid-film thickness with increasing initial fluid-film thickness. This result was attributed to faster gelling of thicker HA-solutions, which formed at a lower squeeze-film strain and higher squeeze-film strain rate compared to thinner layers. Also included is a review of the literature on viscosity measurements of synovial fluid and HA solutions. [ABSTRACT FROM AUTHOR]

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program. In order to identify how the synovial microenvironment impinges on CD4+ T cells pathogenic functions in Rheumatoid Arthritis (RA), Amaral-Silva examined RA patient blood and synovial fluif and identified the presence of a TLR4+ follicular helper T (Tfh) cell-like population. They provided mechanistic insight into how TLR4+ T cells uniquely reconcile an ability to promote systemic antibody production with a local synovial driven-tissue damage program. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not been completely elucidated yet. Extracellular vesicles (EVs) are membrane-contained vesicles released by cells playing a role in cell-to-cell communication and they could be involved in different diseases. Evidence on the involvement of EVs in RA is currently inconclusive. Therefore, a systematic review on the role of EVs in RA was performed in order to explore this relationship. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research was conducted on PubMed, Scopus, and Embase up to March 5, 2020: 41 studies were analyzed out of 674 screened. The total plasmatic and synovial fluid (SF) EV number seems increased in RA as compared with healthy controls. Both RA plasma and SF contained EVs subpopulations of heterogenous origin, especially derived from platelets and immune system cells. No univocal evidence emerged on miRNA expression and EV content profile within RA patients. EVs showed to enhance pro-inflammatory pathways, such as cytokines and chemokine release and TNF blockade seemed to revert this effect. Our work highlights the requirement to standardize study methodologies in order to make results comparable and draw conclusions that remain, at present, unclear. [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]

Osteoarthritis (OA) is a multifactorial disease contributing to significant disability and economic burden in Western populations. The aetiology of OA remains poorly understood, but is thought to involve genetic, mechanical and environmental factors. Currently, the diagnosis of OA relies predominantly on clinical assessment and plain radiographic changes long after the disease has been initiated. Recent advances suggest that there are changes in joint fluid metabolites that are associated with OA development. If this is the case, biochemical and metabolic biomarkers of OA could help determine prognosis, monitor disease progression and identify potential therapeutic targets. Moreover, for focussed management and personalised medicine, novel biomarkers could sub-stratify patients into OA phenotypes, differentiating metabolic OA from post-traumatic, age-related and genetic OA. To date, OA biomarkers have concentrated on cytokine action and protein signalling with some progress. However, these remain to be adopted into routine clinical practice. In this review, we outline the emerging metabolic links to OA pathogenesis and how an elucidation of the metabolic changes in this condition may provide future, more descriptive biomarkers to differentiate OA subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosing a (low-grade) periprosthetic joint infection (PJI) after hip or knee arthroplasty remains a diagnostic challenge. The aim of this study was to evaluate the utility of using a novel multiplex protein microarray system for synovial biomarkers in determining PJI in patients undergoing revision knee or hip arthroplasty. Materials and methods: The individual synovial fluid levels of 12 cytokines (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, GM-CSF, TNF-α, and INF-γ) were analysed with a novel multiplex protein microarray system in 32 patients undergoing revision hip (n = 22) or knee (n = 10) arthroplasty. Cases were classified into septic and aseptic groups on basis of pre- and interoperative findings: [PJI (n = 14) vs. non-PJI (n = 18)]. Receiver operator characteristic (ROC) curves were calculated to assess the discriminatory strength of the individual parameters. A multiple regression model was used to determine the utility of using a combination of the tested cytokines to determine the infection status. Results: The levels of all of the evaluated cytokines were significantly elevated in the PJI-group. Best sensitivity and specificity were found for IL-6, followed by IL-1b, IL-10, and IL-17. The multiple regression models revealed a combination of IL-2, IL-4, IL-5, IL6, lL-12, and GM-CSF to be associated with the best sensitivity (100%) and specificity (88.9%) for a cut-off value of 0.41, with a likelihood ratio of 9.0. Conclusion: Analysis of individual synovial fluid cytokine levels showed both high sensitivity and high specificity in diagnosing PJI. A combined model using several cytokines showed even higher sensitivity and specificity in diagnosing PJI and could thus be a useful predictive tool to determine the probability of PJI in patients with a painful prosthesis. Level of Evidence: Diagnostic IV. [ABSTRACT FROM AUTHOR]

Galectin 1 (Gal1) is a lectin with a wide cellular expression that functions as a negative regulator of the immune system in several animal models of autoimmune diseases. Identification of patients with rheumatoid arthritis (RA) has improved during the last decade, although there is still a need for biomarkers allowing an early diagnosis. In this regard, it has been recently proposed that Gal1 serum levels are increased in patients with RA compared to the general population. However, this topic is controversial in the literature. In this work, we provide additional information about the potential usefulness of Gal1 serum levels as a biomarker for RA diagnosis. We studied Gal1 serum and synovial fluid levels and clinical parameters in samples from 62 patients with early arthritis belonging to the PEARL study. In addition, 24 healthy donors were studied. We found that both patients fulfilling RA criteria and patients with undifferentiated arthritis showed higher Gal1 levels than healthy donors. Similar findings were observed in synovial fluid, which showed even higher levels than serum. However, we did not find correlation between Gal1 levels and disease activity or disability. Therefore, our results suggest that Gal1 could be a diagnostic but not a severity biomarker. [ABSTRACT FROM AUTHOR]

Purpose: We endeavored to determine which characteristics of diabetic ulcers portend the strongest risk for osteomyelitis in patients whose initial T1-weighted imaging was normal. By determining which features have a greater risk for osteomyelitis, clinicians can treat patients more aggressively to reduce the sequela of inadequately treated osteomyelitis.Materials and Methods: We performed a retrospective analysis of MR imaging from 60 pedal ulcers with suspected osteomyelitis. Ulcer dimensions and depth were measured. Ratios of marrow ROI/joint fluid ROI on T2/STIR sequences were obtained. Progression to osteomyelitis on subsequent MRI was characterized by loss of normal marrow signal on T1-weighted images. Statistical analysis was performed with a two-sample t test and Cox proportional hazard model. A p value < 0.05 was used as the threshold for statistical significance.Results: Sixty MR exams were identified. Thirty-four progressed to osteomyelitis. Marrow ROI/joint fluid ratios averaged 65% in the osteomyelitis group, and 45% in the non-osteomyelitis group, p < 0.001. ROI ratios > 53% had a 6.5-fold increased risk of osteomyelitis, p < 0.001. Proximity to bone averaged 6 mm in the osteomyelitis group and 9 mm in the non-osteomyelitis group, p = 0.02. Ulcer size averaged 4 cm2 in the osteomyelitis group versus 2.4 cm2 in the non-osteomyelitis group, p = 0.07. Ulcers greater than 3 cm2 has a 2-fold increase in the risk of osteomyelitis, p = 0.04.Conclusion: Increasing bone marrow ROI signal/joint fluid ratios on T2/STIR images were the strongest risk factors for developing osteomyelitis, while ulcer size and depth are weaker predictors. [ABSTRACT FROM AUTHOR]