Pain is the primary reason patients with knee osteoarthritis (OA) seek surgical intervention when pharmacological treatments lose efficacy. The pain arises from complex mechanisms involving peripheral and central sensitization and inflammatory processes. Emerging research links altered metabolites and lipids, such as lysophosphatidylcholine 16:0 and polyunsaturated fatty acids, to OA pathophysiology and pain modulation. Metabolomic studies in serum and synovial fluid have revealed potential biomarkers and novel therapeutic targets related to pain severity. This study aims to identify metabolic signatures in serum and cerebrospinal fluid (CSF) from knee OA patients, explore systemic and central metabolic interactions, and examine associations with symptom severity. The study included 36 knee OA patients, 38 healthy controls (HC) for serum analysis, and a separate non-healthy CSF control group of 39 individuals with non-inflammatory neurological symptoms (NINS). Samples were subjected to two targeted metabolomics methods using liquid chromatography high resolution mass spectrometry. Participants completed detailed questionnaires assessing pain intensity, fatigue, sleep disturbances, depression, anxiety, and functional disability. HC exhibited higher levels of 11 amino acids (including branched-chain amino acids, histidine, and tryptophan), five bile acids, and four lipids in serum. Conversely, OA patients showed elevated uracil concentrations. Notably, bile acids, glycocholic acid, and glycochenodeoxycholic acid were positively correlated with pain and symptom severity, despite being reduced in OA patients. Lower levels of alanine, isoleucine, and short-chain acylcarnitines (CARs 3:0, 4:0, and 5:0) were associated with higher fatigue ratings. Nucleotides and their derivatives correlated with knee pain intensity, pressure pain sensitivity, and fatigue. In CSF, OA patients generally had increased metabolite levels compared to NINS controls, such as 3-hydroxyphenylacetic acid, histamine, indole, and glutarylcarnitine. Histamine and 3-hydroxyphenylacetic acid were also significantly associated with pain intensity, sleep disturbance, and pressure pain sensitivity. Furthermore, numerous CSF metabolites showed moderate to high correlations with serum levels. This study reveals serum and CSF metabolic changes in knee OA patients linked to symptoms like pain and fatigue. It highlights complex systemic and central metabolism interactions and identifies potential biomarkers for personalized OA treatment, advancing clinical understanding.

Indigofera truxillensis Kunth is traditionally used in Brazilian folk medicine as an oral infusion of the aerial parts, taken as one cup several times daily for at least one week, to relieve inflammatory pain and gastrointestinal complaints. To chemically characterize and evaluate the anti-arthritic and analgesic properties of the methanolic extract (MEIT) and indigo obtained from the aerial parts of I. truxillensis. The chemical analysis of MEIT and the identification of indigo were performed by electrospray ionization tandem mass spectrometry and nuclear magnetic resonance. Anti-inflammatory and anti-hyperalgesic activities were assessed in mice using carrageenan-induced pleurisy and paw inflammation, complete Freund's adjuvant (CFA), and zymosan-induced articular inflammation models. Cytotoxicity and phagocytic activity were evaluated in vitro using leukocyte viability (MTT) and neutrophil phagocytosis assays. MEIT and indigo significantly inhibited leukocyte recruitment in carrageenan-induced pleurisy. In the carrageenan paw model, both reduced mechanical hyperalgesia, cold sensitivity, and edema. In CFA-induced inflammation, MEIT and indigo decreased mechanical hyperalgesia, cold response, myeloperoxidase activity, and protein exudation. In the zymosan-induced arthritis model, both treatments reduced knee edema, mechanical hyperalgesia, leukocyte migration, protein extravasation, and nitric oxide levels in synovial fluid. MEIT and indigo did not exhibit cytotoxicity in vitro; MEIT reduced neutrophil phagocytosis at specific concentrations, whereas indigo did not alter phagocytic activity. MEIT and indigo exhibit significant anti-inflammatory, anti-hyperalgesic, and anti-arthritic activities, supporting the traditional use of I. truxillensis for painful and inflammatory conditions and identifying indigo as a key bioactive constituent.

Sakuranetin ameliorates joint inflammation and bone erosion in rheumatoid arthritis by suppressing NLRP3 inflammasome-mediated inflammatory signaling.

To assess the effectiveness of cord blood nucleated cell extract (CBNCE) in rheumatoid arthritis (RA) and explore the mechanism preliminarily. CBNCE injection was prepared by adding HClO4 and KOH to cord blood. The efficacy of CBNCE was assessed through a lymphocyte proliferation assay. Subsequently, the CIA model was utilized as the RA model, with rats being randomly assigned to a normal group, model group, CBNCE group (1mL/d), and HSS group (hydrocortisone sodium succinate, 0.2mL/d). Following a 7-day period of immune system enhancement, continuous medication was administered for the subsequent 21days. Foot swelling tests, HE staining, flow cytometry, ELISA, WB, and immunofluorescence were conducted. The average inhibitory rate of CBNCE on lymphocyte proliferation was 83.51%. Compared with the model group, rats in the CBNCE group showed a decrease of inflammatory cell infiltration in ankle tissue. The left hindfoot volume (days 5, 9, 10, and 12-21), Th17 percentage and Th17/Treg ratio in peripheral blood, and the levels of IL-1, IL-6, IL-8, and IL-17 in ankle effusion, as well as the MMP-3 protein expression in synovial tissue were significantly decreased (P < 0.05). There were significant (P < 0.05) increases in the fluorescence intensity of Aggrecan and Collagen type I, as well as in the amounts of IL-4 and IL-10. CBNCE modulates the Th17/Treg balance by decreasing the Th17 cells, suppressing the secretion of IL-1, IL-6, IL-8, and IL-17, enhancing the secretion of IL-4 and IL-10, and further inhibiting the expression of MMP-3 protein, thereby increasing the level of Aggrecan and Collagen type I. Ultimately, CBNCE alleviates RA. Key Points • Our study was the first to explore the effect and mechanism of cord blood nucleated cell extract in the treatment of rheumatoid arthritis. • This study offers a theoretical foundation and introduces a novel concept for utilizing cord blood in the treatment of rheumatoid arthritis.

CUL4A promotes glycolytic metabolism of fibroblast-like synoviocytes by targeting FGF2 in rheumatoid arthritis.

Osteoarthritis is the most common degenerative joint disease worldwide, yet no intra-articular disease-modifying osteoarthritis drugs (DMOADs) have succeeded in clinical trials due to poor therapeutic outcomes and limited cartilage targeting. Positively charged nanosized carriers have been shown to penetrate the dense, negatively charged cartilage. Here, we synthesized a cationic avidin-biotin-PEG 2 -kartogenin (Av-bKGN) nanocarrier in a rapid, scalable manner. Over 80 % of Av-bKGN remained stable after 24 hours in PBS and simulated synovial fluid, whereas a new kartogenin derivative was predominantly generated in esterase-rich media. Av-bKGN suppressed inflammatory mediators (NO 2 - , IL-6) in human chondrocytes and macrophages, and its nanosize (8.7 ± 0.26 nm) and positive charge (+18.3 ± 0.75 mV) enhanced cartilage uptake by 4.3- and 11.4-fold, respectively, and cartilage retention by 2-fold over 10 days in PBS and simulated synovial fluid compared to its neutral counterpart, neutravidin. A custom diffusion chamber showed Av-bKGN diffuses tenfold slower than neutravidin, driven by electrostatic binding to cartilage glycosaminoglycans (GAGs). Combining avidin’s delivery platform with bKGN’s DMOAD activity reduced GAG loss in in vitro IL-1a-stimulated OA model. A single Av-bKGN dose provided protection equivalent to multiple free-drug doses (25 % reduced GAG loss), with repeated Av-bKGN doses achieved 1.7-fold greater chondroprotection. These findings highlight electrostatic interaction-driven uptake and retention of Av-bKGN as a promising strategy for targeted cartilage therapy.

Assessment of a beta-metastable titanium alloy for orthopedic use: Corrosion in biomimetic synovial fluid and biocompatibility

Canine osteoarthritis (OA) is a major contributor to chronic pain, mobility loss, and premature euthanasia. Although multimodal care is standard, many dogs experience incomplete relief, adverse events, or limited access to care. Radiosynoviorthesis (RSO) is a targeted IA therapy that delivers localized radiation to inflamed synovial tissue, reducing synovial effusion and alleviating joint pain. While various RSO agents have been used for over 70 years in human medicine to manage inflammatory joint disease, tin-117m (Sn-117m) is the first RSO agent adapted for veterinary use and approved for the treatment of canine OA. Sn-117m is a radionuclide emitting low-energy conversion electrons with minimal tissue penetration and, unlike systemic radiotherapeutics, Sn-117m remains confined within the joint capsule and does not form radioactive metabolites. This containment minimizes environmental contamination and limits caregiver exposure. This narrative review synthesized current evidence on the clinical use of Sn-117m RSO in dogs, addressing therapeutic efficacy and effectiveness, safety, and caregiver radiation exposure. Sn-117m offers a minimally invasive alternative to fill this treatment gap. Following a single injection for OA, prospective clinical trials report sustained improvements in objective gait analysis and caregiver-reported pain scores with benefits lasting up to 12 months. Modeled and measured radiation exposures for caregivers remain below US Nuclear Regulatory Commission limits, allowing outpatient use without isolation. This review evaluated existing data, highlighted regulatory and implementation considerations, and identified areas of potential further research. Long-term outcome tracking and expanded joint-specific data could help refine the use of RSO in human and veterinary medicine.

Abstract Background Osteoarticular tuberculosis (TB) is a rare but serious manifestation of extrapulmonary TB. Despite improvements in imaging and microbiological diagnostics, bone TB remains challenging to identify because its clinical presentation is often nonspecific. While the spine and knee are the most frequently affected sites, involvement of less typical skeletal locations can occur, further complicating timely diagnosis. Methods We retrospectively reviewed all cases of bone TB diagnosed at the ‘Malattie Infettive e Ortopedia Settica’ Department—ATS Liguria, Savona area, from 2022 to 2025. Diagnostic confirmation relied on imaging, histopathology, culture, and polymerase chain reaction (PCR) testing for Mycobacterium tuberculosis. Results Eight patients (6 males, 2 females; mean age 50 years) were identified. Three were Italian, and five were foreign-born. Two patients had vertebral TB: an 80-year-old Ukrainian woman and a 25-year-old Gambian man. Both developed paraparesis requiring surgical stabilization; intraoperative cultures confirmed the diagnosis. Two patients (aged 19 and 23) presented with chronic knee arthritis. Initial arthrocentesis cultures and PCR were negative. Diagnosis was achieved through surgical biopsy; in one case, culture remained negative, but histopathology revealed necrotizing granulomas with Langhans giant cells, and PCR on the histological piece identified M. tuberculosis. A 75-year-old Italian woman with diabetes developed a tuberculous prosthetic joint infection, confirmed by synovial fluid culture. An 86-year-old Italian man with squamous cell carcinoma had mandibular TB diagnosed by bone biopsy, along with concurrent pulmonary TB. A 74-year-old Italian man presented with wrist pain and a draining fistula; bone culture was positive for M. tuberculosis. A 14-year-old boy had ankle inflammation and cervical lymphadenopathy; bone biopsy confirmed TB. All patients tested positive on the QuantiFERON-TB Gold assay. Only one had pulmonary involvement, and one had lymph node disease. All isolates were susceptible to first-line drugs. Treatment typically lasted 12 months, although one patient discontinued therapy after eight months due to hepatotoxicity. Conclusions Bone TB should be considered in cases of chronic osteoarticular infection, even in non-endemic settings and when atypical anatomical sites are involved. Diagnostic accuracy improves when culture, histopathology, and molecular testing are combined. Early recognition and multidisciplinary management are essential to optimize outcomes.

Background: Gout and chronic lymphocytic leukemia (CLL) represent distinct hematologic and rheumatologic pathologies; however, their concurrent presentation presents significant diagnostic and therapeutic challenges. Tumor lysis syndrome and chemotherapy-induced hyperuricemia are recognized complications of hematologic malignancies, yet the manifestation of acute gouty arthritis with crystallographic confirmation in CLL patients remains an underreported clinical scenario requiring careful diagnostic stratification. Case presentation: We present a 69-year-old male farmer with newly diagnosed CLL (stage C, Binet classification) admitted for acute left knee arthritis with effusion, left ankle arthritis, and concurrent community-acquired pneumonia (CAP). Clinical examination revealed articular inflammation characterized by pain, swelling, erythema, warmth, and significant joint effusion with documented flexion limitation and positive bulging sign. Musculoskeletal ultrasound demonstrated double contour sign, synovial hypertrophy, and effusion measuring 5.8 cm in the suprapatellar recess with monosodium urate (MSU) crystal deposition confirmed by polarized light microscopy of synovial fluid (5,350 cells/mm³, 40% polymorphonuclear neutrophils, 60% mononuclear cells, positive MSU crystals). Serum uric acid was elevated at 10.6 mg/dL. The patient was successfully managed with colchicine, methylprednisolone, arthrocentesis, and supportive care while maintaining CLL treatment preparedness. Conclusion: This case illustrates the importance of confirmatory synovial fluid analysis and ultrasound imaging in the diagnosis of acute gout in the context of hematologic malignancy. Optimal management requires careful coordination between rheumatology and hematology-oncology services to prevent therapeutic complications and ensure safe chemotherapy initiation in CLL patients with concurrent acute gouty arthritis and hyperuricemia.

To describe the case presentation, treatment, and outcome of horses treated with Toll-like receptor 3 (TLR-3)-activated allogeneic umbilical cord blood-derived mesenchymal stromal cells (CB-MSCs). 3 horses presenting with chronic or antimicrobial-resistant (AMR) septic synovitis. All horses presented with clinical signs associated with septic synovitis including marked grade 4/5 lameness, joint effusion, heat/swelling of the limb, and synovial fluid parameters consistent with sepsis. Case 1 presented 3 weeks following the onset of clinical signs. Cases 2 and 3 developed infections 4 and 5 weeks after elective arthroscopy and third phalanx fracture fixation, respectively. In cases 2 and 3, culture and sensitivity identified AMR bacteria. All cases had ultrasonographic and radiographic evidence of septic synovitis in addition to osteitis (n = 2) and presumptive septic tendinitis (1). All cases were treated with systemic and regional antimicrobials and synovial lavage. In 2 cases, TLR-3-activated CB-MSCs were used following a lack of response to conventional treatments and in the third case because of infection chronicity and the presence of septic tendinitis. Twenty million TLR-3-activated CB-MSCs were administered by regional limb perfusion or direct IA injection as dictated by the horse's clinical presentation. In all cases, the septic synovitis was resolved following combination treatment. Because of the increasing emergence of AMR infections in both veterinary species and humans, the advancement of alternative and synergistic therapeutics is imperative. This case series highlights the use of TLR-3-activated CB-MSCs as an adjunctive treatment in cases of synovial sepsis involving chronic or AMR infections.

The aurosome, a concept introduced half a century ago, refers to intracellular vesicles that contain gold-based materials. The widespread clinical use of gold salts for the treatment of rheumatoid arthritis, together with advances in ultramicrotomy and biological transmission electron microscopy (TEM) in the 1970s, stimulated investigations into the deposition of gold salts in synovial tissues. These studies revealed a distinctive intracellular biotransformation process in which gold salts were converted within lysosomes into flower-like nanostructures composed of assembled nanofibers; these lysosomes were consequently termed aurosomes. However, research on aurosomes remained largely dormant for nearly four decades as more effective therapeutics replaced gold salts in clinical practice. In recent years, aurosomes have re-emerged following discoveries that ultrasmall (< 3nm) engineered gold nanoparticles (AuNPs) undergo intracellular biotransformation similar to that of gold salts. These findings highlight the profound alterations in nanoparticle physicochemical properties induced by interactions with the complex intracellular environment. Moreover, fundamental studies on the biotransformation of ultrasmall AuNPs have advanced our understanding of their in vivo fate and expanded their potential biomedical applications. In this review, we revisit the historical development of aurosomes, summarize current research on aurosomes derived from ultrasmall AuNPs, and offer perspectives on future directions in this field.

Closed-loop temporomandibular joint arthrocentesis: pilot of a technique for effective synovial fluid collection.

Rotator cuff tears are one of the most common shoulder disorders and can lead to pain, weakness, and limited mobility. Although the clinical condition has been widely studied, its molecular mechanisms are still not fully understood. In this exploratory study, we analyzed the proteomic profile of synovial fluid in patients with full-thickness rotator cuff tears and compared the results to those from a control group. Proteomic analysis was performed on synovial fluid samples from seven patients with full-thickness tears and three patients with partial-thickness tears, who served as the control group. Label-free quantification using the MaxQuant platform identified 284 proteins at 1% FDR. Among them, CLEC3B (tetranectin) showed the most significant difference, with a fold change of 40.35 and a p-value of 2.6 × 10⁻³. Tetranectin exhibited a large effect size (Hedges' g = 2.53), suggesting that it could be a potential candidate protein associated with full-thickness rotator cuff tear severity. Gene ontology enrichment analysis revealed biological processes related to extracellular matrix remodeling, fibrinolysis, and inflammation. Given its known roles in extracellular matrix remodeling, tetranectin was identified as a potential candidate protein associated with full-thickness rotator cuff tear, providing insight into pathological processes such as tendon degeneration and fatty infiltration.

Laser powder bed fusion (LPBF) enables the fabrication of complex CoCrMo alloy implants but introduces detrimental residual stresses that compromise their structural integrity and tribological performance. While heat treatment (HT) is a common stress‐relief strategy, its specific impact on the bio‐tribological behavior under physiologically relevant conditions remains unclear. Hence, this study elucidates the effect of HT (550°C, 675°C, 800°C, and 1100°C) on the microstructural evolution, stress relief, and bio‐tribological properties of LPBF‐fabricated CoCrMo. The microstructural analysis confirmed progressive stress relaxation, with recrystallization and extensive M 23 C 6 carbide/Cr 2 O 3 oxide formation dominating at 1100°C. The 1100°C HT reduced the main body (plates) wear by 25% and 50% under dry conditions and synovial fluid lubrication, respectively. The counter‐body (balls) wear was reduced by 40 and 60%, respectively, demonstrating a synergistic protective effect crucial for the longevity of biomedical implant systems. Raman spectroscopy revealed that the superior performance at 1100°C is governed by the formation of a multifunctional tribo‐layer, comprising lubricious Co 3 O 4 , graphitic carbon (dry) and a stable oxide‐phosphate film (lubricated). Our findings demonstrate that HT at 1100°C provides an optimal combination of complete stress relief, extreme hardness, and protective surface chemistry, establishing it as an excellent approach to enhance the longevity and reliability of biomedical implants.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and progressive joint destruction. Ginkgetin (GK), a biflavonoid derived from Ginkgo biloba, exhibits strong anti-inflammatory and antioxidant properties. However, its therapeutic potential and underlying molecular mechanisms in RA remain insufficiently understood. An integrative strategy combining network pharmacology, transcriptomic profiling, molecular docking, and in vitro experiments was applied to elucidate the mechanisms of GK against RA. Differentially expressed genes (DEGs) were identified from four GEO datasets of RA synovial tissues, and overlapping targets between GK and RA were screened. Gene Ontology (GO), KEGG pathway enrichment, and protein-protein interaction (PPI) analyses were conducted to identify key pathways and hub genes. Molecular docking and single-cell transcriptomic analyses were performed to predict binding interactions and cellular localization. Finally, MH7A synovial fibroblasts were used to validate GK's effects on inflammation, proliferation, migration, and apoptosis. Thirty-two potential therapeutic targets of GK in RA were identified, among which six hub genes (CXCR4, HIF1A, STAT1, VEGFA, CDK1, and CCNB1) were highlighted. Enrichment analyses indicated that these targets were primarily involved in the HIF-1, VEGF, and cell cycle signaling pathways. Molecular docking demonstrated strong binding affinities between GK and key proteins. In vitro, GK inhibited LPS-induced proliferation and migration of MH7A cells, reduced IL-6 and IL-1β expression, and promoted apoptosis. qRT-PCR analysis confirmed that GK downregulated all six hub genes, indicating its multi-target regulatory activity on hypoxia, angiogenesis, and inflammatory signaling. GK exerts anti-inflammatory, anti-proliferative, and pro-apoptotic effects in RA synovial fibroblasts by modulating multiple signaling pathways, particularly the HIF-1α/VEGFA, STAT1, and CXCR4 axes. These findings provide mechanistic insight into GK's pharmacological actions and support its potential as a novel multi-target therapeutic candidate for RA. Key Points •Network pharmacology identified six hub genes (CXCR4, HIF1A, STAT1, VEGFA, CDK1, CCNB1) linking Ginkgetin (GK) to rheumatoid arthritis pathology. •Molecular docking confirmed strong binding affinities of GK with key targets, supporting its multitarget pharmacological potential. •GK inhibits proliferation and migration, suppresses inflammatory cytokines, and promotes apoptosis in LPS-stimulated MH7A synovial fibroblasts. •These findings provide mechanistic evidence supporting GK as a promising multi-target candidate for rheumatoid arthritis therapy.

The infrapatellar fat pad (IFP) is a rich source of mesenchymal stem cells (MSCs) with dual contributions from adipose and synovial tissues. The heterogeneity of IFP-derived MSCs and the lack of standardized isolation protocols, however, hinder consistent therapeutic outcomes. This study aimed to optimize collagenase-based isolation protocols for IFP-MSCs, with a focus on the effects of enzyme concentration and treatment duration on tissue digestion, cell origin, viability, and functional properties. IFP tissues harvested from patients undergoing knee arthroscopy were enzymatically digested using various collagenase concentrations (0.1-2%) and incubation times (2-48h). Histological, immunohistochemical, flow cytometric, and functional assays were performed to evaluate tissue degradation, surface marker expression, colony-forming ability, and trilineage differentiation. Milder digestion conditions (2h, 0.2-0.4% collagenase) preferentially extracted synovial membrane MSCs (CD55+ cells) and supported higher CFUs and chondrogenic/osteogenic differentiation. In contrast, prolonged digestion (48h) led to increased cell yields and adipogenic differentiation, but reduced cell viability and percentage of synovial marker expression. In conclusion, enzymatic digestion parameters critically influence the cellular composition and regenerative potential of IFP-MSCs. Optimizing collagenase treatment conditions allows for a more selective, lineage-based MSC harvest, offering a practical strategy for tailored regenerative utilization of IFP-MSCs.

Cold temperatures have been recognized as a possible catalyst for gouty arthritis exacerbations in individuals with hyperuricemia. The mechanisms underlying cold-induced gout are, however, minimally recognized. The article examines the pathophysiological connection between hyperuricemia and cold-induced gout flare triggers, emphasizing the molecular and physiological mechanisms involved. Genetic predisposition significantly influences an individual's risk of developing hyperuricemia and subsequent gout, underscoring the relevance of genetic variables in disease susceptibility. The diagnosis of gout depends on a combination of laboratory testing, such as blood uric acid levels, synovial fluid examination for urate crystals, and imaging to evaluate joint damage. Cold exposure is a significant environmental element that promotes the crystallization of monosodium urate in synovial fluid, initiating an inflammatory response. Activating the NLR family pyrin domain-containing 3 (NLRP3) inflammasome triggers the production of pro-inflammatory cytokines, consequently contributing to the pathophysiology of gout flares. The NLRP3 inflammatory system gets activated, leading to the secretion of pro-inflammatory cytokines. Low temperatures additionally impair blood circulation and the efficacy of immune cells, hence exacerbating inflammation. This review highlights the recent findings on epidemiology, pathophysiology, and diagnostic techniques of gouty arthritis, providing insights into prospective preventive strategies, therapies for those affected, and offering hope for the future. Overall, it provides an overview of the mechanisms behind cold-induced gout flares.

To establish whether tourniquet type and number influence synovial fluid amikacin concentrations of the tarsocrural joint (TCJ) or metatarsophalangeal joint (MTPJ) after standing saphenous IV regional limb perfusion (IVRLP) with 2 g of amikacin. 8 healthy adult horses underwent 4 saphenous IVRLP protocols with amikacin, differing in tourniquet type (pneumatic vs wide rubber) and number (1 placed mid-gaskin vs 1 placed mid-gaskin and 1 mid-metatarsus) in a randomized, crossover design. Amikacin concentrations were measured in serum and synovial fluid of the TCJ and MTPJ at 15 and 30 minutes after perfusate administration. A linear mixed-effects model was used to compare amikacin concentrations between protocols and within joints. Mean synovial fluid amikacin concentrations were not different between the single-tourniquet protocols but were higher with the dual pneumatic protocol compared to the dual wide rubber protocol. Mean synovial fluid amikacin concentrations were not different between single and dual pneumatic protocols. Mean TCJ synovial fluid amikacin concentrations were higher with the single wide rubber protocol compared to the dual wide rubber protocol, but those in the MTPJ were not different. Pneumatic tourniquets resulted in lower serum amikacin concentrations compared to wide rubber tourniquets. Single-tourniquet protocols yield synovial fluid amikacin concentrations in the TCJ and MTPJ similar to or higher than those of dual-tourniquet protocols, and wide rubber tourniquets result in more systemic leakage of amikacin compared to pneumatic tourniquets during saphenous IVRLP. A single mid-gaskin pneumatic tourniquet should be considered over multiple tourniquets of either type when saphenous IVRLP is performed in standing, sedated horses.

Macrophages play a pivotal role in the progression of synovitis and joint destruction in rheumatoid arthritis (RA). MS4A4A, a transmembrane protein, has been linked to RA disease activity, but its role in synovitis remains unclear. The present cross-sectional study analyzed MS4A4A and CX3CR1 expression on monocytes and macrophages from peripheral blood and synovial tissue from 15 RA and 14 osteoarthritis (OA) patients. MS4A4A+ cells were increased in RA compared to OA across all monocyte subsets (p < 0.001). In the synovium, MS4A4A was selectively elevated on infiltrating (CD206−MerTK−) macrophages in RA (p = 0.008), but not on resident macrophages. In RA, MS4A4A+ non-classical monocytes correlated with MS4A4A+ infiltrating macrophages (r = 0.44, p = 0.016), and these infiltrating macrophages correlated with the Clinical Disease Activity Index (CDAI) (r = 0.58, p = 0.024). Across all subsets, MS4A4A+ monocytes expressed higher CX3CR1 than MS4A4A− monocytes (p < 0.001); only MS4A4A+CX3CR1+ non-classical monocytes correlated with MS4A4A+ infiltrating macrophages (r = 0.57, p = 0.026). MS4A4A may therefore link systemic monocyte upregulation to local infiltrating macrophage accumulation and disease activity. Given MS4A4A’s reported role in promoting M2 macrophage polarization, its selective upregulation on infiltrating macrophages may indicate a plastic macrophage population and a potential biomarker for predicting therapeutic response in RA.