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ABSTRACT Prosthetic implant‐associated inflammation and failure can be caused by bacterial infections and mechanical wear of the prosthesis. Currently, there is no diagnostic modality that allows simultaneous identification of both causes of implant failure. Here, we present a proof‐of‐principle study to assess whether Raman spectroscopy can be applied to diagnose implant failure. Synovial fluids from 10 patients with a clinical suspicion of implant‐related complications were previously collected and cultured to determine the presence of bacteria. The presence of microparticles in these synovial fluids was assessed by Raman spectroscopy and verified by scanning electron microscopy combined with energy‐dispersive X‐ray spectroscopy (SEM‐EDX). For control, the possibility to detect in vitro‐cultured Staphylococcus aureus by Raman spectroscopy was investigated. Raman spectroscopy revealed that all 10 synovial fluid samples contained microparticles: eight contained microplastics (polyethylene, polypropylene, and polystyrene), and nine contained titanium dioxide nanoparticles (anatase and rutile) as verified by SEM‐EDX. There was no clear difference in the microparticle content of synovial fluids with or without bacteria. Raman signals relating to individual bacteria and clusters of bacteria were detectable in in vitro cultures of S. aureus, but it was not possible to demonstrate the presence of bacteria in synovial fluids by Raman spectroscopy. Raman spectroscopy is a potential tool for characterizing microparticles in synovial fluids from patients with implant‐related complications. This is of clinical relevance as these microparticles can cause joint inflammation. The identification of bacteria by Raman spectroscopy is feasible, but further research is needed before clinical implementation. [ABSTRACT FROM AUTHOR]

The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose‐dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full‐length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose‐dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence To evaluate the infection rate following anterior cruciate ligament reconstruction (ACLR) using all‐soft tissue quadriceps tendon (ASTQT) autograft.All primary ASTQT autograft ACLRs within a single surgeon's prospectively collected database from 2011 to 2021 were retrospectively reviewed. No topical antibiotics were administered and no graft‐soaking with antibiotics was performed during the study period. Patients who underwent multiligament knee reconstruction or a cartilage restoration procedure were excluded. Patients who underwent a subsequent procedure, including irrigation and debridement (I&D) of the knee joint, were included. Case‐specific data, including fluid culture analysis, antibiotics (type, route of administration and duration), time to debridement and method of debridement, were collected. Descriptive statistics were utilized to analyze demographics, incidence and possible association between the need for I&D and concomitant meniscus surgery.Out of 1053 cases (mean age: 20.2 ± 6.3, 44.6% female), four patients (0.38%) (mean age: 18.5 ± 4.0, 25% female) underwent subsequent I&D (arthroscopic I&D only [n = 1], graft harvest site I&D only [n = 1], combined graft harvest site and arthroscopic I&D [n = 1] and tibia wound and arthroscopic I&D [n = 1]). There was no significant difference with regard to demographics. No joint fluid cultures returned positive; one wound culture returned positive for Methicillin‐susceptible Staphylococcus aureus from their graft harvest site. The time to I&D ranged from 18 to 23 days. Concomitant meniscectomy or meniscal repair was not associated with requiring surgical I&D. All patients who underwent I&D were prescribed antibiotics for a minimum of 10 days and a maximum of 31 days (mean: 16.25 days). Three patients (75%) who underwent I&D ultimately returned to sport. One patient was lost to follow‐up. ACL grafts were retained in all patients.The incidence of culture‐positive septic arthritis following ASTQT autograft ACLR is 0%, while the overall need for I&D of 0.38% is low and not related to concomitant meniscal procedures or patient‐specific factors.Level IV. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is widely recognized as the prevailing joint disease associated with aging. The ketogenic diet (KD) has been postulated to impede the advancement of various inflammatory ailments. β‐Hydroxybutyrate (βOHB), a prominent constituent of ketone bodies, has recently been proposed to possess crucial signaling capabilities. In this study, we propose to explore the role and mechanism of βOHB in OA. Tissue staining and inflammatory factor assay were employed to evaluate the impacts of KD and βOHB on OA rats. The oxidative stress conditions in chondrocytes were induced using tert‐butyl hydroperoxide (TBHP). The mechanisms were determined using the siRNA of hydroxycarboxylic acid receptor 2 (HCAR2), the antagonist of adenosine monophosphate‐activated protein kinase (AMPK), and the inhibitor of mitophagy. The administration of KD demonstrated a reduction in pathological damage to cartilage, as well as a decrease in plasma levels of inflammatory factors. Furthermore, it resulted in an increase in the concentration of βOHB in the blood and synovial fluid. In vitro experiments showed that βOHB facilitated mitophagy and adenosine triphosphate production. Besides, βOHB mitigated chondrocyte senescence, inflammatory factors secretion, extracellular matrix degradation, and apoptosis induced by TBHP. Subsequent investigations indicated that the protective effects of βOHB were no longer observed following the knockdown of HCAR2, the antagonist of AMPK, or the inhibitor of mitophagy. Moreover, in vivo studies suggested that βOHB played a protective role by targeting the HCAR2‐AMPK‐PINK1 axis. In conclusion, βOHB enhanced chondrocyte mitophagy through the HCAR2/AMPK/PINK1/Parkin pathway, offering a potential therapeutic approach for the treatment of OA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To clarify the anti-inflammatory effect of platelet lysate (PL) on equine persistent synovitis by using a model of synovitis induced by monoiodoacetic acid (MIA). METHODS: Nonseptic synovitis was induced by administering MIA into both antebrachiocarpal joints of 6 clinically healthy horses on day 0. On days 23, 30, and 37, carpal circumference measurement and synovial fluid collection for assays (leucocytes, LDH, tumor necrosis factor-a, and TGF-ß1) were performed, after which PL was injected into 1 antebrachiocarpal joint and saline into the contralateral joint. Synovium and synovial fluid were obtained on day 44 for histological analysis and quantification of inflammation-related genes (matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs 4, receptor activator of nuclear factor β ligand, and collagen type I a2 chain) and the abovementioned proteins. RESULTS: The LDH level on day 44 was significantly lower in the PL-injected joint than in the saline-treated one. However, no significant differences were found in the other indices quantified, including osteoclast counts on the synovium. CONCLUSIONS: Multiple IA administration of PL does not exert anti-inflammatory effects on the equine persistent synovitis induced by MIA. CLINICAL RELEVANCE: Intra-articular PL administration did not alter many inflammatory biomarkers, suggesting that PL does not have a direct anti-inflammatory effect. However, the reduction in synovial LDH levels suggests that PL promoted joint tissue repair and may consequently alleviate inflammation at the site of administration. [ABSTRACT FROM AUTHOR]

Modeling the lumbar facet capsular ligament's (FCL) mechanical behavior under various physiological motions has often been a challenge due to limited knowledge about the on-joint in situ ligament state arising from attachment to the bone or other internal loads. Building on prior work, this study presents an enhanced computational model of the lumbar facet capsular ligament by incorporating residual strain and joint pressurization strain, factors neglected in prior models. Further, the model can predict strain and stress distribution across the ligament under various spinal motions, highlighting the influence of the ligament's attachment to the bone, internal synovial fluid pressurization, and distribution of collagen fiber alignment on the overall mechanical response of the ligament. Joint space inflation was found to influence the total observed stress and strain fields, both at rest and during motion. A significant portion of the ligament was found to be in tension, even in the absence of external load. Additionally, the model's ability to account for residual strain offers a more realistic portrayal of the collagen fibers and elastin matrix's role in ligament mechanics. We conclude that (1) computational models of the lumbar facet capsular ligament should not assume that the ligament is unloaded when the joint is in its neutral position, and (2) the ligament is nearly always in tension, which may be important in terms of its long-term growth and remodeling. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7‐10) would result in an OA phenotype. We hypothesized that FN7‐10 stimulation of equine articular cells would result in an OA phenotype with gene and protein expression changes similar to those previously described for human chondrocytes stimulated with FN7‐10. Synovial fibroblasts and chondrocytes isolated from four horses were stimulated in monolayer culture for 6 or 18 h with 1 µM purified recombinant 42 kD FN7‐10 in serum‐free media. At the conclusion of stimulation, RNA was collected for targeted gene expression analysis and media for targeted protein production analysis. Consistent with our hypothesis, FN7‐10 stimulation resulted in significant alterations to many important genes that are involved in OA pathogenesis including increased expression of IL‐1β, IL‐4, IL‐6, CCL2/MCP‐1, CCL5/RANTES, CXCL6/GCP‐2, MMP‐1, MMP‐3, and MMP13. The results of this study suggest that the equine matrikine stimulation model of OA may prove useful for in vitro experiments leading up to preclinical trials. [ABSTRACT FROM AUTHOR]

Objective: Synovial fluid (SF)–derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population. Methods: In this study, we used single‐cell RNA sequencing paired with single‐cell T cell receptor (TCR) sequencing to directly compare memory T cells from paired samples of SF and ST from six patients with inflammatory arthritis to investigate their similarity in terms of TCR repertoire and T cell subset composition. Results: The TCR repertoires of SF and ST T cells were strikingly similar, particularly for CD8+ T cells. A median of 49% of the total CD8+ TCR repertoire in SF was shared with ST, compared with 20% shared with blood. Similarly, 47% of the ST CD8+ TCR repertoire was shared with SF compared to 25% with blood. Furthermore, once the effect of collagenase digestion on gene expression by ST T cells had been accounted for, the frequencies of specific CD8+ and CD4+ T cell subsets were, in general, similar in SF and ST and were distinct from blood. Conclusion: Our results suggest that T cells migrate and equilibrate between the SF and ST and maintain similar phenotypes in both sites. We conclude that SF is an appropriate proxy for investigating the T cell infiltrate in inflamed synovium, particularly in terms of investigating the TCR repertoire. [ABSTRACT FROM AUTHOR]

The incidence or prevalence of Lyme arthritis (LA) in Denmark is unknown and assumed very low. No published cases of polymerase chain reaction (PCR)-confirmed LA from Denmark exist. Clinically, LA does not differ from other rheumatic oligoarthritic disorders posing a differential diagnostic challenge. To review the incidence and prevalence of LA to our knowledge and to present a case series of PCR-confirmed LA cases from Denmark. We conducted a systematic literature review via MEDLINE and EMBASE to explore incidence and prevalence rates of LA. Additionally, we present six cases of patients diagnosed with LA in Denmark. Our literature review identified 23 studies reporting prevalence or incidence, yet only ten studies provided estimates ranging from 1.1 to 280/100.000 in the general population. Our case series identified six patients with LA from a localized region in Southern Denmark; all confirmed by Borrelia-specific real-time PCR from synovial fluid. The diagnostic delay was up to 38 months. All patients except one had a history of previous tick bites; none had erythema migrans lesions. All presented with recurrent arthritis in the knee joint, and two had arthritis in the wrist. The literature review showed an incidence of LA ranging from 1.1 to 15.8 per 100.000 in Europe. Our case series suggests a potentially higher prevalence of LA in Denmark than previously believed. Lack of tick exposure history, antibody assessments and test of Borrelia burgdorferi sensu lato DNA in synovial fluid might lead to misdiagnosed cases potentially explaining the assumed low incidence of LA in Denmark. [ABSTRACT FROM AUTHOR]

Objective: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia? Materials and methods: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis. Results: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17–33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76–0.97; circular ROI: ICC = 0.82, 95% CI 0.66–0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI − 0.06–0.94; circular RO: ICC = 0.99, 95% CI 0.98–0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms). Conclusion: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility. [ABSTRACT FROM AUTHOR]

Severe joint infections, such as septic arthritis, require rapid diagnostic testing of the synovial fluid aspirated from joints level so that a surgical team can be assembled quickly. We present a diffuse reflectance spectroscopy (DRS) system for noncontact determination of infection. Using a light‐tight syringe holder and fiber optic probe, diffusely reflected light from 475 to 655 nm was acquired from 18 patient samples through the wall of a syringe in a noncontact and sterile manner. We determined the reflectance ratios at two different wavelengths—R490/R600 and R580/R600 and found statistically significant differences (p < 0.05) in both ratios between the infected and noninfected groups. Critically, the R490/R600 and R580/R600 ratios were significantly correlated with clinical biomarkers—the white blood cell (WBC) and red blood cell (RBC) counts, respectively. This study demonstrates the potential of DRS as a rapid diagnostic tool for joint infections. [ABSTRACT FROM AUTHOR]

This study was designed as a randomized, placebo-controlled, double-blinded, cross-over trial performed to investigate the effects of a dietary supplement containing undenatured type II collagen (UCII®) and Boswellia Serrata on mobility, pain and joint metabolism in mild moderate osteoarthritis (OA) in dogs. A total of 60 dogs with mobility problems were evaluated and enrolled in the study. Seventeen of these dogs with mild/moderate OA were randomized to receive the product A (UCII® + Boswellia Serrata supplement–UCII®-BW) or product B (Placebo -PL), 1 chew per day for 8 weeks by oral route, and repeated in a crossover design after 4 weeks of washout period. All the subjects had veterinary evaluations during the trial and owners were requested to fill out a questionnaire on mobility impairment using the Liverpool Osteoarthritis in dogs scale (L.O.A.D.) at each time of the study. Objective tools were used to assess mobility, activity, and pain. Metabolomic analysis was performed on synovial fluid of most affected joint at the beginning and the end of the study. The results proved that UCII®+Boswellia serrata supplemented group over a period of eight weeks results in an improvement of mobility impairment, already at 4 weeks of administration, according to the owner´s evaluation. In contrast, its absence increased the risk of OA crisis and decreased the pain threshold on the most affected joint. Furthermore, the synovial fluid metabolic profile showed moderate differences between the beginning and the end of the supplementation period, with a particular influence associated to the time of UCII®-BW administration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is a glycosaminoglycan composed of D-glucuronic acid and N-acetylglucosamine with an up-to-several-million-Daltons chain-length responsible for the lubricating properties of the temporomandibular joint (TMJ) synovial fluid. Arthritis results in the predominance of HA degradation over synthesis leading to temporomandibular disorders (TMDs). TMD injection treatments are divided into HA supplementation and platelet-rich plasma (PRP) inflammation suppression. We questioned whether either approach lubricated the TMJ better and answered it in a two-arm equal-allocation trial with a non-concurrent active treatment control (two groups of 39 patients each). HA statistically significantly improved (p < 0.01) and PRP did not statistically significantly change (0.06 ≤ p ≤ 0.53) articular mobility compared to baselines in 128 TMJs. Statistically significant inter-group discrepancies were observed for abduction (MD = −4.05 mm; SE = 1.08; p = 0.00; d = −0.85) and protrusion (MD = −0.97 mm; SE = 0.43; p = 0.03; d = −0.51) but not for rightward (MD = −0.21; SE = 0.43; p = 0.63; d = −0.11) and leftward (MD = −0.30; SE = 0.42; p = 0.47; d = −0.16) movements. HA supplementation proved superior to PRP autografting in ad hoc TMJ lubrication and hence is more appropriate in hypomobile TMD cases of symptomatic treatment. [ABSTRACT FROM AUTHOR]

Placental‐derived allografts have been of interest as a potential nonsurgical treatment to reduce pain and improve function in knee osteoarthritis (OA). The purpose of this study was to evaluate the effect of single and repeat injection of amniotic suspension allograft (ASA) on pain, function, and cytokine levels using a destabilization of the medial meniscus (DMM) rat model of OA. Post‐DMM surgery, animals were treated with a single injection of either ASA, vehicle, or triamcinolone, or repeated injection of either ASA or vehicle. Behavioral testing including knee swelling, pain threshold, dynamic weight bearing (DWB), and gait analysis were evaluated during the in‐life phase. Postsacrifice, histopathology and serum and synovial fluid analyses were evaluated. Significant improvements in both DWB differentials and pain threshold were seen in response to repeated injection of ASA, while a single injection of ASA and triamcinolone resulted in significant improvements in pain threshold. Histopathology analysis found no significant differences regardless of treatment compared to vehicle, except for an increase in synovitis following repeated injection of ASA. A single injection of ASA and triamcinolone resulted in increased anti‐inflammatory cytokines; repeated ASA injection resulted in significant increases in several immune‐modulating factors relevant to OA. When comparing the impact of single and repeat ASA treatments on behavioral testing, repeated injection provided significant additional improvements in both pain and function. This study provides evidence demonstrating the impact of a second injection while also providing additional data for evaluating the use of ASA as a nonsurgical treatment for knee OA. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection (PJI) is one of the most challenging complications following total knee arthroplasty. Despite its importance, there is a paucity of reports in the literature regarding its pathogenesis. Recently, cellular metabolic reprogramming has been shown to play an important role in the progression and outcome of infectious diseases. Therefore, the aim of this study was to evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties. The synovial fluids from 21 patients scheduled for revision total knee arthroplasty (11 with the diagnosis of PJI and 10 with aseptic failures) were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyzes were used to identify metabolites that were differentially abundant between those groups. A total of 28 metabolites were identified and five of them found to be differentially abundant between infected and non‐infected synovial fluids. Lactate, acetate and 3‐hydroxybutyrate were found to be in a higher concentration, and glucose and creatine were found reduced in the synovial fluid from PJI patients. Synovial fluid from patients with PJI exhibit a distinct metabolic profile, possibly reflecting metabolic adaptation that occurs in the infected periprosthetic microenvironment. Further research and studies are warranted to gain a broader insight into the metabolic pathways engaged by both pathogen and immune cells in the context of a PJI. [ABSTRACT FROM AUTHOR]

Cationic contrast‐enhanced computed tomography (CECT) capitalizes on increased contrast agent affinity to the charged proteoglycans in articular cartilage matrix to provide quantitative assessment of proteoglycan content with enhanced images. While high resolution microCT has demonstrated success, we investigate cationic CECT use in longitudinal in vivo imaging at clinical resolution. We hypothesize that repeated administration of CA4+ will have no adverse side effects or complications, and that sequential in vivo imaging assessments will distinguish articular cartilage repair tissue from early degenerative and healthy cartilage in critically sized chondral defects. In an established equine translational preclinical model, lameness and synovial effusion scores are similar to controls after repeated injections of CA4+ (eight injections over 16 weeks) compared to controls. Synovial fluid total protein, leukocyte concentration, and sGAG and PGE2 concentrations and articular cartilage and synovial membrane scores are also equivalent to controls. Longitudinal in vivo cationic CECT attenuation in repair tissue is significantly lower than peripheral to (adjacent) and distantly from defects (remote sites) by 4 weeks (p < 0.001), and this difference persists until 16 weeks. At the 6‐ and 8‐week time points, the adjacent locations exhibit significantly lower cationic CECT attenuation compared with the remote sites, reflecting peri‐defect degeneration (p < 0.01). Cationic CECT attenuation at clinical resolution significantly correlates with cationic CECT (microCT) (r = 0.69, p < 0.0001), sGAG (r = 0.48, p < 0.0001), and ICRS II histology score (r = 0.63, p < 0.0001). In vivo cationic CECT imaging at clinical resolution distinguishes fibrous repair tissue from degenerative and healthy hyaline cartilage and correlates with molecular tissue properties of articular cartilage. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability—in particular, between genders. Recent research has increasingly focused on the role of adipokines—especially leptin, adiponectin, and resistin—in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin's role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease. [ABSTRACT FROM AUTHOR]

Objective: Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. Materials and Methods: We conducted the high‐resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. Results: FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the in vitro and in vivo results are consistent with protein changes detected in MS profile. Conclusion: This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets. [ABSTRACT FROM AUTHOR]

The toxicologist ascertains drug assumptions in case of paediatric intoxications and death for overdose. The analytical approach consists of initially screening and consequently confirming drug positivity. We developed a toxicological screening method and validated its use comparing the results with a LC–MS/MS analysis. The method identifies 751 drugs and metabolites (704 in positive and 47 in negative mode). Chromatographic separation was achieved eluting mobile phase A (10 mM ammonium formate) and B (0.05% formic acid in methanol) in gradient on Kinetex Phenyl-Hexyl (50 × 4.6 mm, 2.6 μm) with 0.7 mL/min flow rate for 11 min. Multiple Reaction Monitoring (MRM) was adopted as survey scan and, after an Information-Dependent Analysis (IDA) (threshold of 30,000 for positive and 1000 cps for negative mode), the Enhanced Product Ion (scan range: 50–700 amu) was triggered. The MS/MS spectrum generated was compared with one of the libraries for identification. Data processing was optimised through creation of rules. Sample preparation, mainly consisting of deproteinization and enzymatic hydrolysis, was set up for different matrices (blood, urine, vitreous humor, synovial fluid, cadaveric tissues and larvae). Cut-off for most analytes resulted in the lowest concentration tested. When the results from the screening and LC–MS/MS analysis were compared, an optimal percentage of agreement (100%) was assessed for all matrices. Method applicability was evaluated on real paediatric intoxications and forensic cases. In conclusion, we proposed a multi-targeted, fast, sensitive and specific MRM-IDA-EPI screening having an extensive use in different toxicological fields. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the microbial yield and factors predicting culture positivity for image-guided arthrocentesis of suspected septic sternoclavicular (SC) arthritis. Materials and methods: An electronic health record search identified image-guided SC joint aspirations for suspected septic arthritis. Data was extracted by retrospective chart review including patient demographics, procedure characteristics, pre-procedure lab testing, joint culture results, final SC joint diagnoses and any effect of positive synovial cultures on subsequent antibiotic therapy. Factors associated with positive joint fluid cultures were assessed using a Chi-squared test for categorical predictors and logistic regression for continuous predictors. Results: A total of 31 SC arthrocenteses met inclusion criteria with most (81%) performed using ultrasound guidance. Synovial fluid was successfully aspirated in 19/31 (61%) of cases, and in all other cases lavage fluid was successfully obtained. Synovial cultures were positive in 9/31 (29%) of cases. A final diagnosis of septic arthritis was assigned to 20/31 cases (65%) in which 9/20 (45%) had positive synovial cultures. There was no statistically significant association between synovial culture positivity and risk factors for septic arthritis, positive blood cultures, pre-aspiration antibiotics and whether synovial fluid or lavage fluid was cultured. Serum white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) demonstrated statistically significant positive correlation with positive synovial cultures. Conclusion: Arthrocentesis is effective for microbial speciation in SC septic arthritis, and diagnostic yield may be increased with lavage when encountering a dry tap. Normal serum WBC and ESR values indicate an extremely low likelihood of positive synovial cultures. [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]

Background: Anterior cruciate ligament (ACL) injury is frequently associated with injuries to other parts of the knee, including the menisci and articular cartilage. After ACL injury and reconstruction, there may be progressive chondral degradation. Biomarkers in blood, urine, and synovial fluid can be measured after ACL injury and reconstruction and have been proposed as a means of measuring the associated cellular changes occurring in the knee. Purpose: To systematically review the literature regarding biomarkers in urine, serum, or synovial fluid that have been associated with an outcome measure after ACL reconstruction. Study Design: Systematic review; Level of evidence, 3. Methods: This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The MEDLINE, Embase, CINAHL, and Web of Science databases were searched to identify studies published before September 2023 that reported on patients undergoing ACL reconstruction where a biomarker was measured and related to an outcome variable. Of 9360 results, 16 studies comprising 492 patients were included. Findings were reported as descriptive summaries synthesizing the available literature. Results: A total of 45 unique biomarkers or biomarker ratios were investigated (12 serum, 3 urine, and 38 synovial fluid; 8 biomarkers were measured from >1 source). Nineteen different outcome measures were identified, including the International Knee Documentation Committee Subjective Knee Form, Knee injury and Osteoarthritis Outcome Score, numeric pain scores, radiological outcomes (magnetic resonance imaging and radiography), rates of arthrofibrosis and cyclops lesions, and gait biomechanics. Across the included studies, 17 biomarkers were found to have a statistically significant association (P <.05) with an outcome variable. Serum interleukin 6 (s-IL-6), serum and synovial fluid matrix metalloproteinase-3 (s-MMP-3 and sf-MMP-3), urinary and synovial fluid C-terminal telopeptide of type 2 collagen (u-CTX-II and sf-CTX-II), and serum collagen type 2 cleavage product (s-C2C) showed promise in predicting outcomes after ACL reconstruction, specifically regarding patient-reported outcome measures (s-IL-6 and u-CTX-II), gait biomechanical parameters (s-IL-6, sf-MMP-3, s-MMP-3, and s-C2C), pain (s-IL-6 and u-CTX-II), and radiological osteoarthritis (ratio of u-CTX-II to serum procollagen 2 C-propeptide). Conclusion: The results highlight several biomarkers that have been associated with clinically important postoperative outcome measures and may warrant further research to understand if they can provide meaningful information in the clinical environment. [ABSTRACT FROM AUTHOR]

In this study, we investigated joint effusion in patients with temporomandibular disorders (TMDs) with disc displacement. The magnetic resonance (MR) images of 97 temporomandibular joints (TMJs) were evaluated, and the appearance of joint effusion was investigated. Myofascial pain and TMJ pain were considered in addition to the duration from manifestation. Disc displacement with and without reduction, as well as the region and the area of joint effusion, were investigated using the MR images. Fisher's test was used for the analyses. Joint effusion was recognized in 70 TMJs, including 55 in the superior articular cavity, 1 in the inferior articular cavity, and 14 in both the superior and inferior articular cavities. The appearance of joint effusion did not differ with the existence of myofascial pain or TMJ pain. The region of joint effusion did not differ between disc displacement with and without reduction. A larger area of joint effusion was recognized in disc displacement without reduction (p < 0.05). The results showed that the amount of synovial fluid in the joint effusion did not change with the existence of myofascial pain or TMJ pain. Joint effusion commonly appeared in disc displacement without reduction. [ABSTRACT FROM AUTHOR]

Research progress from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) pilot award program was presented and discussed at the GRAPPA 2023 annual meeting. Topics included identification of protein biomarkers associated with enthesitis in psoriatic arthritis (PsA), the role of HLA-B27 on gut microbial dysbiosis in PsA, single-cell profiling of synovial fluid vs psoriatic skin lesions in PsA, and the role of mechanotransduction in hyperactivation of transforming growth factor-β via αVβ6 integrin in psoriatic epidermis. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aims to evaluate the impact of the PCR multiplex panel (BioFire JI®) on the diagnosis and management of pediatric osteoarticular infections. Methods: This retrospective study analyzed data from pediatric patients diagnosed with osteoarticular infections between January 2023 and April 2024. The effectiveness of the PCR multiplex panel in identifying pathogens was compared with traditional culture methods. Results: In total, 50 patients were identified (66.6% male, 74% under 3 years of age). They were diagnosed as follows: septic arthritis in 46%, osteomyelitis in 26%, and septic osteoarthritis in 22%. An identifiable agent was isolated by conventional culture in 22 cases (44%). Kingella kingae was the predominant pathogen identified, accounting for 50% of cases (11/22), followed by Staphylococcus aureus (9/22). The BioFire JI® Panel PCR demonstrated a sensitivity of 93%, with a specificity of 63% when evaluated against synovial fluid culture as the reference standard. The panel identified seven additional pathogens not detected by conventional culture methods: 2/9 MSSA (22%), 1/1 S. pyogenes (100%), and 4/11 K. kingae (37%), increasing the yield by 14%. The rapid identification of pathogens facilitated timely and targeted therapeutic interventions. Conclusions: The PCR multiplex panel (BioFire JI®) improved the diagnosis of pediatric osteoarticular infections. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the incidence of septic arthritis across adult age groups in Västra Götaland Region (VGR) of Sweden, while also comparing disease characteristics among different age groups with hematogenous septic arthritis. Methods: Using ICD-10 codes for septic arthritis from 2016 to 2019, we identified 955 patients in VGR. We reviewed the medical records of 216 adult patients with hematogenous septic arthritis and compared data across age groups. Results: The overall incidence of septic arthritis in adults was 4 per 100,000 persons annually, rising to 14 per 100,000 in those ≥80 years. The median age of the 216 patients was 71. The comparison across age groups (18–64, 65–79, and ≥80) showed significantly longer hospital stays and higher mortality rate in the older groups. CRP levels were higher in the middle age group, SF-WBC counts were lower in the youngest age group, and synovial fluid crystals were more common in the oldest. No differences were found in joint involvement or the organisms isolated. Conclusion: The incidence of septic arthritis is 6.5 times higher in patients aged ≥ 80 compared to those under 65, highlighting the need to consider age-related differences in disease management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The lubrication process of natural joint cartilage involves a series of coordinated mechanisms, a key aspect of which is its ability to continuously extract lubricating components from synovial fluid to achieve sustained lubrication. Inspired by this natural phenomenon, this study reports a novel polyelectrolyte hydrogel, specifically integrating ε‐poly‐L‐lysine (ε‐PL), adeptly captures lipids from environment to achieve effective lubrication similar to human joints. The ε‐PL within the hydrogel facilitates the dynamic sequestration of lipids, fostering interfacial self‐assembly. This setup, enriched with highly hydrated lipid head groups, enhances boundary lubrication capabilities for extended performance. Through rigorous evaluation of friction coefficients and supramolecular interactions between the hydrogel and lipids, it identified hydrogen bonding, charge‐dipole, and hydrophobic interactions as key to this self‐assembly. The findings affirm the versatility of polyelectrolytes in synthesizing lubricating hydrogels, bridging the gap to the creation of biomimetic hydrogels that mimic natural lubrication with enhanced durability and efficiency. [ABSTRACT FROM AUTHOR]

ObjectivesMethodResultsConclusionThis study explores the early identification of rheumatoid arthritis (RA) patients at elevated risk of progression. Haem-oxygenase-1 (HO-1) is a marker of oxidative stress in inflammation. Here, we investigate HO-1 as a biomarker of oxidative stress and its association with clinical disease activity and radiographic progression in RA.Baseline HO-1 was measured sequentially in plasma samples from patients with early rheumatoid arthritis (eRA) (n = 80). Disease Activity Score based on 28-joint count–C-reactive protein, Clinical Disease Activity Index, and total Sharp score were used to evaluate the disease course serially over 2 years. Paired plasma and synovial fluid samples were examined for HO-1 in active established rheumatoid arthritis (esRA) (n = 20). Plasma from healthy control subjects was also included (n = 35).Plasma HO-1 levels were increased in eRA {1373 pg/mL [interquartile range (IQR) 1110–2050]} and esRA [2034 pg/mL (IQR 1630–2923)] compared with controls [1064 pg/mL (IQR 869.5–1378)]. HO-1 plasma levels decreased with treatment. Baseline HO-1 correlated with disease activity and radiographic progression. A strong, linear correlation was found between synovial and plasma HO-1 levels (r = 0.75, p < 0.001).In eRA, plasma levels of HO-1 were increased and correlated with disease and radiographic progression. A baseline measurement of plasma HO-1 levels demonstrated superior performance to currently used clinical and serological disease markers in the prediction of radiographic progression. Plasma HO-1 may function as a first-in-class biomarker of synovial oxidative stress in RA. [ABSTRACT FROM AUTHOR]

Background: To evaluate the diagnostic characteristics of tryptophanyl tRNA synthetase (WRS) for the diagnosis of septic arthritis of the knee joint and to determine whether it is a reliable and sensitive synovial biomarker for discriminating septic arthritis from other types of arthritis. Methods: Patients joint effusions for which septic arthritis was suspected were prospectively recruited between January 2019 and September 2020. A total of 9 patients had septic arthritis, 6 had acute gout attack, 1 had an acute flare of chronic rheumatic arthritis, and 46 had pseudogout or reactive arthropathy. Traditional inflammatory markers were measured, and their diagnostic abilities were compared. Neutrophil count, C-reactive protein (CRP) level, WRS, and human neutrophil α-defensin levels were assessed in the synovial fluids. Demographic parameters and biomarkers with a P < 0.05 in differentiating septic from nonseptic arthritis were included in a multivariable model. A multivariable logistic regression with a stepwise selection was performed to build the final combined model. Receiver operating characteristic curves were used to establish optimal thresholds for the diagnosis of septic arthritis of the knee joint, and the area under the curve was calculated to determine the overall accuracy of these tests compared with patients with nonseptic inflammatory arthritis. Results: Patients with septic arthritis were more likely to display higher serum WBC and CRP levels, synovial neutrophil counts, and levels of two synovial biomarkers, including WRS and α-defensin. WRS showed the highest specificity (87.5%) and sensitivity (83.3%) with α-defensin among the three synovial biomarkers. Conclusions: Synovial fluid WRS is a relevant biomarker in discriminating septic arthritis from other inflammatory arthritis and should be tested in an independent cohort. Level of evidence: prospective observational study, III. [ABSTRACT FROM AUTHOR]

Background: Reinfection rates after two-stage revision (TSR) for prosthetic joint infection (PJI) range from 7.9 to 14%. Many factors, including sinus tracts, are associated with reinfection after this procedure. This study aimed to delineate whether the presence of sinus tract could increase reinfection rate after TSR and to investigate other potential risk factors for reinfection after TSR. Methods: We conducted a case-control study by retrospectively reviewing patients who underwent TSR for prosthetic hip joint infection from 2002 to 2022. The case group included patients who developed reinfection after TSR, while the control group consisted of patients who did not experience reinfection. PJI and reinfection after TSR were defined based on Delphi-based international consensus criteria. Patient demographics, past medical history, clinical manifestations, laboratory results, interval between stages, microbiological culture results were collected. Univariate analyses were utilized to assess the effect of sinus tract on reinfection and to identify other risk factors for reinfection after TSR. Results: Six patients with reinfection after TSR were included as the case group and 32 patients without reinfection were in the control group. Significant difference was observed in percentage of patients with sinus tracts between the two groups (67% in the case group versus 19% in the control group, p = 0.031, OR = 8.7). Significant difference was also found in percentage of patients with positive cultures of synovial fluid and synovium harvested during the first-stage revision between the two groups (100% in the case group versus 50% in the control group, p = 0.030). Additionally, patients in the case group had a significantly higher C-reactive protein (CRP) level prior to the second stage revision than that of patients in the control group (8.80 mg/L versus 2.36 mg/L, p = 0.005), despite normal CRP levels in all patients. Conclusions: Our study revealed that the presence of sinus tracts could significantly increase risk of postoperative reinfection after TSR. Positive cultures during the first stage revision and elevated CRP level prior to the second stage revision could also increase the risk of reinfection after TSR. Further studies with a larger sample size are required. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Gout and calcium pyrophosphate crystal deposition disease (CPPD) are common forms of inflammatory arthritis whose prevalence has increased in recent years. Although the identification of monosodium urate crystals (MSU) and calcium pyrophosphate crystals (CPP) in synovial fluid (SF) by polarized light microscopy are the gold standard for diagnosing these diseases, SF analysis is not always available. An early diagnosis and specific treatment, especially in gout, allows avoiding irreversible structural damage, comorbidities, and a severe impact on the quality of life of patients. Musculoskeletal ultrasound (US) is a noninvasive tool that allows detecting aggregates of microcrystals at multiple anatomical sites and helps to establish a specific diagnosis. The objective of this review is to evaluate the applications of US in the diagnosis and clinical management of the main microcrystalline arthropathies. The US has helped improve our understanding of the natural history of the disease, due to its ability to visualize not only soft tissue inflammation and structural damage, but also the characteristics of MSU and CPP crystal deposition. The anatomical sites of crystal deposition are also a key factor for differential diagnosis in different microcrystalline diseases. The US allows establishing an early diagnosis, especially in asymptomatic hyperuricemia, to discriminate with other inflammatory diseases, to assess the extent of microcrystalline deposition and their sensitivity to change after treatment. Given its increasing availability in clinical practice and strong evidence, US is a bedside imaging technique helping clinicians to improve diagnosis and therapy monitoring in their daily practice. [ABSTRACT FROM AUTHOR]

Synovial fluid analysis is important in diagnosing prosthetic joint infection (PJI). The rate of culture-positive PJI in patients who have a dry tap of a total hip arthroplasty (THA) is not well described. We reviewed all image-guided THA aspirations, performed from 2014 to 2021 at a single academic institution. Aspirations were categorized as successful (≥ 0.5 mL) or unsuccessful (< 0.5 mL, "dry tap"). We analyzed culture data on all repeat aspirations and revision surgeries performed within 90 days of the initial dry tap. We reviewed 275 consecutive attempted THA aspirations of which 100 (36.4%) resulted in a dry tap. The dry tap cohort had a significantly higher percentage of fluoroscopic-guided aspirations (64%) and fewer ultrasound-guided aspirations (36%) compared to the successful aspiration cohort (48.9% fluoroscopic, 53.1% ultrasound, P =.0061). Of the 100 patients who have dry taps, 48 underwent revision surgery within 90 days of the initial dry tap, and 15 resulted in 2 or more positive cultures. The rate of PJI defined by MusculoSkeletal Infection Society major criteria in the dry tap cohort was 16.0%. Attempted aspiration of a THA resulted in a dry tap 36.4% of the time. Of those patients who had a dry tap, 16.0% were subsequently found to have PJI based on MusculoSkeletal Infection Society major criteria. Therefore, a "dry tap" does not exclude the diagnosis of infection and should not be considered reassuring for the absence of PJI. [ABSTRACT FROM AUTHOR]

Introduction: Information about analyte stability is of crucial importance. The aims of this study were to determine the short- and long-term stability of synovial fluid calprotectin at various temperature conditions (4-8 °C for 7 days, - 20 °C and - 80 °C for 6 weeks). Materials and methods: Eleven samples from patients were included in this study. The samples were promptly transported at room temperature (RT) to the laboratory immediately after arthrocentesis. Upon arrival, the samples were transferred into plastic tubes without additives and pretreated with hyaluronidase solution. After centrifugation at 1500xg for 10 minutes at RT, the baseline calprotectin concentrations were determined. Seven aliquots were stored in LoBind tubes (Eppendorf) at 4-8 °C and the calprotectin was measured every day. Six additional aliquots were stored at temperatures - 20 °C and - 80 °C and the concentration of calprotectin was measured weekly. Analysis was done using Buhlmann fCAL turbo reagent on analyzer Siemens Atellica Solution (Siemens Healthcare, Erlangen, Germany). Data were analyzed by Microsoft Excel and MedCalc statistical software. The percentage difference (PD%) was calculated. The maximum permissible difference (MPD) was 9.1% for PD%. Results: The PD% with the corresponding 95% confidence intervals were inside the predefined MPD. The instability equations and correlation coefficient for storage temperatures were PD% = 0.1644 x time (day), r = 0.06, P = 0.614 for 4-8°C, PD% = 0.5190 x time (week), r = - 0.22, P = 0.080 for - 20°C, and PD% = 0.1316 x time (week), r = 0.08, P = 0.545 for - 80°C. Conclusions: The calprotectin in the synovial fluid is stable when stored long-term for 6 weeks at - 20 °C or at - 80 °C or short-term (7 days) at 4-8 °C. [ABSTRACT FROM AUTHOR]

Phospholipids (PLs), essential components of cell membranes, play significant roles in maintaining the structural integrity and functionality of joint tissues. One of the main components of synovial joint fluid (SJF) is PLs. Structures such as PLs that are found in low amounts in biological fluids may need to be selectively enriched to be analyzed. Monodisperse-mesoporous SiO2 microspheres were synthesized by a multi-step hydrolysis condensation method for the selective enrichment and separation of PLs in the SJF. The microspheres were characterized by SEM, XPS, XRD, and BET analyses. SiO2 microspheres had a 161.5 m2/g surface area, 1.1 cm3/g pore volume, and 6.7 nm pore diameter, which were efficient in the enrichment of PLs in the SJF. The extracted PLs with sorbents were analyzed using Q-TOF LC/MS in a gradient elution mode with a C18 column [2.1 × 100 mm, 2.5 μM, Xbridge Waters (Milford, MA, USA)]. An untargeted lipidomic approach was performed, and the phospholipid enrichment was successfully carried out using the proposed solid-phase extraction (SPE) protocol. Recovery of the SPE extraction of PLs using sorbents was compared to the classical liquid–liquid extraction (LLE) procedure for lipid extraction. The results showed that monodisperse-mesoporous SiO2 microspheres were eligible for selective enrichment of PLs in SJF samples. These microspheres can be used to identify PLs changes in articular joint cartilage (AJC) in physiological and pathological conditions including osteoarthritis (OA) research. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, leading to pain and functional impairment. A key contributor to OA progression is the decline in cartilage lubrication. In physiological conditions, synovial fluid (SF) macromolecules like hyaluronic acid (HA), phospholipids, and lubricin play a crucial role in the boundary lubrication of articular cartilage. In early OA, cartilage damage triggers inflammation, altering SF composition and compromising the lubrication layer. This increases friction between mating interfaces, worsening cartilage degradation and local inflammation. Therefore, early-stage restoration of lubrication (by injecting in the joint different classes of compounds and formulations) could alleviate, and potentially reverse, OA progression. In the light of this, a broad variety of lubricants have been investigated for their ability to reduce friction in OA joints and promote cartilage repair in clinical and preclinical studies. This review examines recent advancements in lubricant-based therapy for OA, focusing on natural, bioinspired, and alternative products. Starting from the currently applied therapy, mainly based on natural lubricants as HA, we will present their modified versions, either in hydrogel form or with specific biomimetic moieties with the aim of reducing their clearance from the joint and of enhancing their lubricating properties. Finally, the most advanced and recent formulation, represented by alternative strategies, will be proposed. Particular emphasis will be placed on those ones involving new types of hydrogels, microparticles, nanoparticles, and liposomes, which are currently under investigation in preclinical studies. The potential application of particles and liposomes could foster the transition from natural lubricants to Drug Delivery Systems (DDSs) with lubricant features; transition which could provide more complete OA treatments, by simultaneously providing lubrication replacement and sustained release of different payloads and active agents directly at the joint level. Within each category, we will examine relevant preclinical studies, highlighting challenges and future prospects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Graphic type differentiation of cell count data of synovial aspirates is a new method for the diagnosis of early and late periprosthetic joint infection. OBJECTIVE: 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). METHODS: 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. RESULTS: 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/ μ L (median) and for the LMNE-type III (combined type of infection and abrasion) 3570/ μ L (median). CONCLUSION: 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. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine the effect of varying ozone doses on proinflammatory cytokine levels in the synovial fluid collected from individuals with knee osteoarthritis. Patients and methods: The controlled clinical trial was conducted with 82 patients (61 females, 21 males; mean age: 63.1±10.0 years; range, 40 to 73 years) between 21 April 2023 and 20 May 2023. Synovial fluid samples were collected from the patients under ultrasound guidance and divided into three tubes, one of which was not injected with ozone, and the other two were injected with 10 and 30 gamma (γ) ozone, respectively. The total antioxidant status, total oxidant status, oxidative stress index, interleukin (IL)-1 beta (β), IL-6, and tumor necrosis factor-alpha (TNF-α) in the joint fluids were measured. Results: The oxidative stress index and IL-1 β, IL-6, and TNF-α levels in the synovial fluid were lower at 10 and 30 γ compared to 0 and 10 γ, respectively. In vitro ozone injection at 30 gamma was more effective in reducing proinflammatory cytokines in the synovial fluid than that at 10 and 0 γ. Ozone injection into the pathological joint fluid was more effective in terms of total antioxidant status at 10 and 30 γ compared to 0 and 10 γ, respectively. No significant difference in total oxidant status was observed between the groups. Conclusion: This study showed that in vitro ozone injection at 30 γ was more effective in reducing proinflammatory cytokines in the synovial fluid and in improving total antioxidant status than that at 10 and 0 γ. The results showed the potential significance of the ozone injection dosage in treating knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) in horses often affects the metacarpal/metatarsophalangeal (MCP/MTP) joints and its detection in the early stages is crucial for effective management. I t was hypothesized that the extent of cartilage damage positively correlates with synovial membrane (SM) and synovial fluid (SF) pathological findings in the MCP/MTP joints of Serbian mountain horses that transported heavy loads but did not show signs of lameness. The study was conducted on 32 MCP/MTP joints of eight horses between seven to 12 years of age. Horse limbs were transferred from the abattoir to the necropsy room and SF was sampled. Its appearance, total nucleated cell count (TNCC), mononuclear cell count (MNC), total proteins (TP), and haptoglobin (Hp) were determined. Samples of SM were collected from the dorsal palmar/plantar pouch for histology. A macroscopic examination of gross condylar pathology of the third metacarpal/metatarsal bone was performed with Indian Ink staining. Scoring was done based on Osteoarthritis Research Society International recommendations. SF was clear, pale yellow, and mostly fairly viscous. Half of the samples had TNCC above, and all had TP within the reference range. Hp values were below the reference range and were omitted from further analyses. TNCC correlated with MNC (ρs=0.81, P<0.001), microscopic (ρs=0.62, P=0.003) and macroscopic scores (ρs=0.47, P=0.008). In addition, MNC correlated with macroscopic scores (ρs=0.40, P=0.03). All pathological findings were mild and their correlation indicated that these processes are interrelated and that could be ascribed to early OA. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is the main component of the temporomandibular joint (TMJ) synovial fluid. Arthritis in temporomandibular disorders (TMDs) disrupts HA metabolism, resulting in shorter polymeric chain predominance and increased friction. Intra-articular injections of HA supplement the larger molecules of this glycosaminoglycan, and the platelet-rich plasma (PRP) delivered in this way releases growth factors, suppressing inflammation. This PRISMA-compliant PROSPERO-registered (CRD42024564382) systematic review aimed to assess the validity of mixing HA with PRP in the injectable treatment of TMJ disorders. We searched the medical literature for eligible randomized clinical trials using BASE, Google Scholar, PubMed and Scopus engines on 9 May 2024, with no time frame limit. Selected reports were assessed for risk of bias using the Cochrane RoB2 tool. Numerical data were collected on articular pain and mandibular mobility. We provided mean differences from baseline and between study and control groups at each observation point. The efficacy of TMD treatment with HA/PRP versus HA or PRP alone was assessed meta-analytically. Of 171 identified records, we selected 6 studies. In the 6-month follow-up, the mean advantage of PRP supplementation with HA was 2.52 (SE = 2.44; d = 0.83) mm and the benefit of adding PRP to HA was 1.47 (SE = 2.68; d = 0.34) mm in mandibular abduction. The pain-improvement scores were −1.33 (SE = 1.02; d = −1.05) and −1.18 (SE = 0.92; d = 0.80), respectively. Presumably, the HA/PRP range of therapeutic efficiency includes cases non-respondent to HA or PRP alone. [ABSTRACT FROM AUTHOR]

Articular cartilage receives nutrients and oxygen from the synovial fluid to maintain homeostasis. However, compared to tissues with abundant blood flow, articular cartilage is exposed to a hypoxic environment (i.e., physioxia) and has an enhanced hypoxic stress response. Hypoxia-inducible factors (HIFs) play a pivotal role in this physioxic environment. In normoxic conditions, HIFs are downregulated, whereas in physioxic conditions, they are upregulated. The HIF-α family comprises three members: HIF-1α, HIF-2α, and HIF-3α. Each member has a distinct function in articular cartilage. In osteoarthritis, which is primarily caused by degeneration of articular cartilage, HIF-1α is upregulated in chondrocytes and is believed to protect articular cartilage by acting anabolically on it. Conversely, in contrast to HIF-1α, HIF-2α exerts a catabolic influence on articular cartilage. It may therefore be possible to develop a new treatment for OA by controlling the expression of HIF-1α and HIF-2α with drugs or by altering the oxygen environment in the joints. [ABSTRACT FROM AUTHOR]

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system's cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis. [ABSTRACT FROM AUTHOR]

Background/Objectives: To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). Methods: A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. Results: The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R2 = 0.642; p = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R2 = 0.827; p = 0.001) and relative CPM (R2 = 0.882; p < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R2 = 0.728; p = 0.02). Conclusions: This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives: The pathophysiology of osteoarthritis is mainly unknown. Matrix Gla protein (MGP) and Gla-rich protein (GRP) are both vitamin-K-dependent mineralization inhibitors. In this study, we aimed to compare the levels of MGP and GRP in the synovial fluid of osteoarthritic (OA) and non-osteoarthritic (non-OA) knee joints. Materials and Methods: Two groups were formed, with one consisting of patients with OA and the other non-OA, serving as a control group. The non-OA group included individuals who had arthroscopic surgery for non-cartilage-related issues. In the OA group, all participants had undergone total knee arthroplasty because of grade 4 primary degenerative osteoarthritis. During the operation, at least 1 mL of knee synovial fluid was collected. The GRP and MGP levels in the synovial fluid were measured using an ELISA kit. Results: The mean age in the OA group (62.03 ± 11.53 years) was significantly higher than that in the non-OA group (47.70 ± 14.49 years; p = 0.0001). GRP levels were significantly higher in the OA group (419.61 ± 70.14 ng/mL) compared to the non-OA group (382.18 ± 62.34 ng/mL; p = 0.037). MGP levels were significantly higher in the OA group (67.76 ± 11.36 ng/mL) compared to the non-OA group (53.49 ± 18.28 ng/mL; p = 0.001). Calcium levels (Ca++) were also significantly higher in the OA group (12.89 ± 3.43 mg/dL) compared to the non-OA group (9.51 ± 2.15 mg/dL; p = 0.0001). There was a significantly positive correlation between MGP levels and age (p = 0.011, R = +0.335). Linear regression analysis was performed to determine the effect of age on MGP levels (p = 0.011, R-Square = 0.112). The dependent variable in this analysis was MGP (ng/mL), and age was the predictor. Conclusions: In conclusion, both GRP and MGP are potentially usable biomarkers in osteoarthritis. However, GRP seems to be more valuable because it is not associated with age. In the future, both proteins could provide important contributions to the diagnosis and treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

OBJECTIVE To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation. ANIMALS 4 healthy horses without evidence of forelimb lameness. METHODS A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 μg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points. RESULTS Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point. CLINICAL RELEVANCE Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intraarticular medications for treatment of equine joint disease. [ABSTRACT FROM AUTHOR]

To date, synovial fluid has not been the subject of targeted analysis as a possible substrate to search for the presence of diatoms in the forensic context of drowning. However, its unique characteristics of production and isolation from the external environment could make it suitable for this purpose, similar to what has already been demonstrated in the literature for vitreous humor. By considering this, synovial fluid was analyzed in a specific case that came to our attention, where the coexisting signs of polytrauma and drowning were documented during autopsy, demonstrating a period of vitality during immersion. After a thin smear of the supernatant was obtained from the centrifugation of the synovial fluid sample, diatoms were successfully detected, consistent with those found in other organs and the water of the canal. The detection of diatoms in the synovial fluid was an objective finding, but its generalizability is limited because this was a pilot application. However, in cases where death by drowning is suspected and the body has multiple areas breached by trauma, the technique of analyzing diatoms in the synovial fluid could have great potential. Therefore, it is appropriate to further explore this technique in order to obtain more forensic evidence in such a setting. [ABSTRACT FROM AUTHOR]

Purpose: Searching for quick determinable biomarkers with high sensitivity and specificity is necessary to improve and optimise the early diagnosis of periprosthetic elbow infection (PEI). Therefore, this study's objective was to evaluate the diagnostic value of synovial fluid interleukin-6 (IL-6) levels for diagnosing PEI in total elbow arthroplasty. Method: Twelve prospective enrolled patients underwent total elbow arthroplasty revision surgery, during which synovial fluid was obtained. Between the initial implantation and the revision procedure were 33.5 ± 41 months (range, 2–144 months). Synovial fluid was collected for immediate IL-6 analysis parallel to the revision surgery. Furthermore, microbiological samples were obtained and analysed. Two groups were defined based on the microbiological results: non-infection and infection group. The ability of synovial fluid IL-6 analysis to predict infection status was explored using receiver operating characteristic curves and further statistical analysis. Results: Synovial fluid IL-6 analysis had a good diagnostic accuracy of 83% for PEI with an area under the curve of 0,79 and an ideal cutoff value (determined using Youden's criterion) of 15244 pg/mL. Discussion: This is the first study to clinically evaluate IL-6 as a diagnostical marker for periprosthetic joint infection (PJI) in total elbow arthroplasty. Our results suggest a good accuracy and high sensitivity for IL-6 to identify a PEI. The analysis of IL-6 can improve surgical decision-making regarding managing total elbow arthroplasty in terms of one- or two-staged revision. Conclusion: IL-6 can play an important role in the perioperative differentiation of infected and non-infected situations. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis. RA is routinely treated by various systemic drugs; on the other hand, administration of intra-articular corticosteroids or different types of synovectomies can be used in case of systemic medication's failure. Chemical, radio isotopic, and surgical synovectomies are being used as therapeutic options for chronic synovitis to improve joint function. Chemical synovectomy is not well tolerated, and the long-term response is relatively low. Surgical synovectomy has a better success rate, but it recommends higher expenses. In radiation synovectomy, radioactive labeled particles are applied directly in the articular cavity, followed by homogeneous distribution in joint. Next, the radioactive particles are transported in the depth of synovia and phagocytized by inflammatory cells. Finally, the radiation leads to fibrosis and sclerosis of formerly inflamed synovial membrane; thus, it stops the inflammation and reduces the symptoms. It has a success rate of 40–100% and its effect can be similar to surgical synovectomy. Materials and methods: Thirty-one patients with resistant monoarthritis of the knee were enrolled in this study. One millicurie of phosphorus-32 was injected into patients' knee via US guide. Saline was injected afterwards to prevent leakage. Direct pressure was performed after removing the needle and the knee was flexed slowly to ensure homogenous distribution and fixed with a splint for 1 to 2 weeks. Patients were followed up after 2 weeks, 1 month, 2 months, and 6 months. The following variables were assessed by the treating rheumatologist: patients' pain, joint tenderness, effusion, and ROM. At the time of injection and after the first week, patients were investigated for any complication including infection, necrosis, pain, and swelling. The effect of clinical characteristics and demographic data on existing complications and the changes of pain, joint tenderness, effusion, and ROM was assessed. Results: Thirty-one patients with the mean age of 54.5 ± 12.2 years and the mean disease duration of 12 ± 6.5 years were enrolled in this study. Mean DAS-28 ESR score for our patients was 4 ± 0.7. The pain, effusion, and reduced ROM were decreased significantly after all follow-up intervals. Knee tenderness was not affected in the first 2 weeks, but it was reduced significantly after 1, 2, and 6 months. No serious complications like infection and necrosis were reported through our study. 51.6% and 54.8% of our patients reported pain and swelling in the administration site. Furthermore, 19.4% and 16.1% of patients reported deterioration of pain and effusion in the first week of injection. Conclusion: In our study, we demonstrated that pain, tenderness, effusion, and ROM are improved after radiation synovectomy with phosphorus-32. We also showed that there was no serious adverse effect like infection and necrosis. However, more than half of our patients experienced pain and swelling of injection site at the time of administration. Key points • We demonstrated the efficacy of radiation synovectomy as a medication for monoarthritis. • The results of our study can lead to a bigger clinical trial to assess the benefits and adverse effects of radiation synovectomy in comparison to treatment with local or systemic corticosteroids. [ABSTRACT FROM AUTHOR]

Obesity has a pivotal and multifaceted role in pain associated with osteoarthritis (OA), extending beyond the mechanistic influence of BMI. It exerts its effects both directly and indirectly through various modifiable risk factors associated with OA-related pain. Adipose tissue dysfunction is highly involved in OA-related pain through local and systemic inflammation, immune dysfunction, and the production of pro-inflammatory cytokines and adipokines. Adipose tissue dysfunction is intricately connected with metabolic syndrome, which independently exerts specific effects on OA-related pain, distinct from its association with BMI. The interplay among obesity, adipose tissue dysfunction and metabolic syndrome influences OA-related pain through diverse pain mechanisms, including nociceptive pain, peripheral sensitization and central sensitization. These complex interactions contribute to the heightened pain experience observed in individuals with OA and obesity. In addition, pain management strategies are less efficient in individuals with obesity. Importantly, therapeutic interventions targeting obesity and metabolic syndrome hold promise in managing OA-related pain. A deeper understanding of the intricate relationship between obesity, metabolic syndrome and OA-related pain is crucial and could have important implications for improving pain management and developing innovative therapeutic options in OA. In this Review, the authors explore the complex interactions between osteoarthritis-related pain and obesity, adipose tissue dysfunction and metabolic syndrome, and discuss how knowledge of these relationships could help improve pain management and identify new therapeutic options. Key points: Obesity serves as an important risk factor for pain in osteoarthritis (OA) and is associated with all modifiable risk factors related to OA-related pain. Adipose tissue dysfunction has a specific role in OA-related pain independently of BMI. Serum and synovial fluid levels of leptin are closely associated with OA-related pain after adjustment for BMI, whereas the role of adiponectin in OA pain is controversial. Metabolic syndrome is associated with OA-related pain independently of BMI. Obesity modulates nociceptive, neuropathic-like and nociplastic pain through neuromodulators and both peripheral and central sensitization. Therapeutics used in the treatment of obesity and metabolic syndrome could also hold promise for the management of OA-related pain, particularly GLP1R agonists. [ABSTRACT FROM AUTHOR]