Synovial fluid NMR-based metabolomics in septic and aseptic revision total knee arthroplasty: Implications on diagnosis and treatment.

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.

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

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

Effects of intra-articular administration of hyaluronic acid or platelet-rich plasma as a complementary treatment to arthroscopy in horses with osteochondritis dissecans.

Although arthroscopy is the treatment of choice for horses with osteochondritis dissecans (OCD), it is not yet known whether intra-articular therapies in the postoperative period can bring any benefit to the recovery of these animals. This study evaluated the effects of the intra-articular application of platelet-rich plasma (PRP), hyaluronic acid (HA) or lactated Ringer's solution (LR) in horses with OCD undergoing arthroscopy. Eighteen male and female Brazilian Sport horses aged between 2 and 6 years were evaluated. All animals presented OCD fragments in the middle crest of the tibia. Ten days after surgery, animals were randomly distributed into three groups and received intra-articular application of PRP (n = 6), HA (n = 6), or LR (control group, n = 6). Clinical, radiographic, ultrasound and synovial fluid evaluations were performed on the day of surgery and after 10, 30 and 60 days. An increase in the thickness of the joint capsule was observed 30 days after surgery in the three groups evaluated. In the control group, there was significant improvement in the flexion test 30 and 60 days after surgery, and in the PRP group, there was worsening of this parameter in the same evaluations. In the control group, there was a reduction in the degree of synovial effusion, and in the PRP and HA groups, there was increased effusion. There was a significant increase in the number of leukocytes in the HA group. Intra-articular use of PRP or HA ten days after arthroscopy did not promote positive effects on the recovery of horses with OCD.

Estudio de los pacientes con monoartritis aguda en un hospital de tercer nivel / Acute monoarthritis in a third level hospital

Resumen Introducción: La monoartritis aguda (MA) represen ta una causa relevante de morbilidad que requiere de atención médica oportuna: El estudio del líquido sino vial constituye un elemento clave para su diagnóstico. El objetivo del estudio fue determinar la frecuencia y características clínicas-analíticas de los episodios de MA y bursitis agudas valoradas en un hospital durante un período de 6 años. Métodos: Estudio analítico retrospectivo de corte transversal en un hospital de Córdoba, Argentina. Se identificaron todos los episodios de monoartritis y bur sitis agudas que ocurrieron en pacientes de ≥18 años entre 2012 y 2017. Se excluyeron los cuadros de MA en embarazadas y las monoartritis crónicas. Resultados: Se incluyeron 180 episodios de MA y 12 de bursitis aguda. Entre las MA, 120 (66.7%) ocurrieron en hombres, la edad promedio fue 62.1±16.9 años. La principal causa de MA fue séptica, identificándose 70 (36%) casos, seguida la secundaria a microcristales con 54 episodios (28%) que correspondieron 27 (14%) a MA por gota y 27 (14%) a MA por depósitos de pirofosfato de calcio dihidratado (CPPD). Se identificaron cristales de urato monosódico en 26 (14.3%) pacientes, CPPD en 28 (15.6%) y de colesterol en 1 (0.6%). Discusión: La principal causa de MA fue séptica, seguida de la secundaria a microcristales (gota y secun daria a CPPD). La principal articulación afectada fue la rodilla, seguida del hombro. El análisis del líquido sino vial fue un elemento clave a la hora de poder realizar el diagnóstico diferencial entre las distintas causas de monoartritis aguda y bursitis.

Abstract Introduction: Acute monoarthritis (AM) represents a relevant cause of morbidity that requires prompt medical care. The study of synovial fluid becomes re levant to allow a rapid diagnostic approach. The main objective of the study was to determine the frequency and clinical-analytical characteristics of episodes of AM and acute bursitis evaluated in a hospital during a period of 6 years. Methods: Cross-sectional retrospective analytical study in a hospital at Córdoba, Argentina. All episodes of acute monoarthritis and bursitis that occurred in patients aged 18 years or older between 2012 and 2017 were included. AM in pregnant women and chronic monoarthritis were excluded. Results: One hundred and eighty episodes of AM and 12 of acute bursitis were included. Among the AM, 120 (66.7%) occurred in male patients and the average age was 62.1±16.9 years. The main cause of AM was septic, identifying 70 (36%) cases, followed by microcrystalline AM identify 54 (28%) cases, which corresponded to gout and calcium pyrophosphate dihydrate (CPPD) with 27 (14%) cases each one. Monosodium urate crystals were identified in 26 (14.3%) patients, CPPD in 28 (15.6%) and cholesterol in 1 (0.6%). Discussion: The main cause of AM was septic arthri tis, followed by microcrystalline AM (gout and secondary to CPPD). The main affected joint was the knee, followed by the shoulder. Synovial fluid analysis was a key ele ment when making the differential diagnosis between the different causes of acute monoarthritis and bursitis.

[Acute monoarthritis in a third level hospital]. / Estudio de los pacientes con monoartritis aguda en un hospital de tercer nivel.

INTRODUCTION: Acute monoarthritis (AM) represents a relevant cause of morbidity that requires prompt medical care. The study of synovial fluid becomes relevant to allow a rapid diagnostic approach. The main objective of the study was to determine the frequency and clinical-analytical characteristics of episodes of AM and acute bursitis evaluated in a hospital during a period of 6 years. METHODS: Cross-sectional retrospective analytical study in a hospital at Córdoba, Argentina. All episodes of acute monoarthritis and bursitis that occurred in patients aged 18 years or older between 2012 and 2017 were included. AM in pregnant women and chronic monoarthritis were excluded. RESULTS: One hundred and eighty episodes of AM and 12 of acute bursitis were included. Among the AM, 120 (66.7%) occurred in male patients and the average age was 62.1±16.9 years. The main cause of AM was septic, identifying 70 (36%) cases, followed by microcrystalline AM identify 54 (28%) cases, which corresponded to gout and calcium pyrophosphate dihydrate (CPPD) with 27 (14%) cases each one. Monosodium urate crystals were identified in 26 (14.3%) patients, CPPD in 28 (15.6%) and cholesterol in 1 (0.6%). DISCUSSION: The main cause of AM was septic arthritis, followed by microcrystalline AM (gout and secondary to CPPD). The main affected joint was the knee, followed by the shoulder. Synovial fluid analysis was a key element when making the differential diagnosis between the different causes of acute monoarthritis and bursitis.

Introducción: La monoartritis aguda (MA) representa una causa relevante de morbilidad que requiere de atención médica oportuna: El estudio del líquido sinovial constituye un elemento clave para su diagnóstico. El objetivo del estudio fue determinar la frecuencia y características clínicas-analíticas de los episodios de MA y bursitis agudas valoradas en un hospital durante un período de 6 años. Métodos: Estudio analítico retrospectivo de corte transversal en un hospital de Córdoba, Argentina. Se identificaron todos los episodios de monoartritis y bursitis agudas que ocurrieron en pacientes de =18 años entre 2012 y 2017. Se excluyeron los cuadros de MA en embarazadas y las monoartritis crónicas. Resultados: Se incluyeron 180 episodios de MA y 12 de bursitis aguda. Entre las MA, 120 (66.7%) ocurrieron en hombres, la edad promedio fue 62.1±16.9 años. La principal causa de MA fue séptica, identificándose 70 (36%) casos, seguida la secundaria a microcristales con 54 episodios (28%) que correspondieron 27 (14%) a MA por gota y 27 (14%) a MA por depósitos de pirofosfato de calcio dihidratado (CPPD). Se identificaron cristales de urato monosódico en 26 (14.3%) pacientes, CPPD en 28 (15.6%) y de colesterol en 1 (0.6%). Discusión: La principal causa de MA fue séptica, seguida de la secundaria a microcristales (gota y secundaria a CPPD). La principal articulación afectada fue la rodilla, seguida del hombro. El análisis del líquido sinovial fue un elemento clave a la hora de poder realizar el diagnóstico diferencial entre las distintas causas de monoartritis aguda y bursitis.

Articular mobilization promotes improvement in functional and inflammatory parameters in a gouty arthritis model

ABSTRACT Objective Gouty arthritis is characterized by painful inflammation due to the deposition of monosodium urate crystals in joint tissues. Despite available treatments, many patients experience ineffective management and adverse effects. This study evaluated a manual therapy protocol involving passive joint mobilization at the peak of inflammation in a gouty arthritis model using functional and inflammatory parameters. Methods Twenty male Wistar rats, 12 weeks old, were divided into two groups (n=10 each): Gouty Arthritis and Control Groups, which were further subdivided into treated and untreated groups (n=5 each). The Gouty Arthritis Group received intraarticular knee injection of 50µL of monosodium urate crystals, while the Control Group received 50µL of phosphate buffered saline. The treatment involved a 9-minutes session of grade III joint mobilization (according to Maitland). Nociception, grip strength, and edema were evaluated before induction (EV0), 7 hours after assessment (EV1), immediately after treatment (EV2), and 1 hour after treatment (EV3). The animals were euthanized, and synovial fluid was collected to analyze leukocyte migration. Results The model mimicked the signs of the Gouty Arthritis Group, with a decrease in the threshold of nociception and strength and an increase in edema and leukocyte count. The mobilization protocol significantly increased the nociceptive threshold and grip strength and reduced edema; however, it did not reverse the increase in leukocyte count. Conclusion Our results suggest that mobilization promotes analgesia and may modulate the inflammatory process owing to reduced edema and subtle attenuation of cell migration, which contributes to strength gain.

Gonococcal arthritis in a healthy adult. Is it that possible?

A case report is presented of a 50-year-old woman who was seen in Accident and Emergency because of pain in the lumbar area. She was subsequently diagnosed with septic arthritis of the left hip due to being Neisseria gonorrhoeae positive for beta-lactamase. She responded to treatment with ceftriaxone, but later required a total hip replacement.

Presentamos el caso de una mujer de 50 arios, sin antecedentes de importancia, a quien se le diagnosticó inicialmente lumbago e infección de vías urinarias. Por persistencia del dolor y limitación de la movilidad en la cadera izquierda se inicia el estudio de artritis séptica, que fue provocada por Neisseria gonorrhoeae betalactamasa positiva, sensible a tratamiento con ceftriaxona, con posterior deterioro articular, el cual requirió reemplazo total de cadera.

Cell-free Deoxyribonucleic Acid: A Potential Biomarker of Chronic Periprosthetic Knee Joint Infection.

BACKGROUND: The correct diagnosis of a chronic periprosthetic joint infection (PJI) is a major challenge in clinical practice, with the "gold standard" for diagnosis yet to be established. Synovial fluid analysis has been proven to be a useful tool for that purpose. Cell-free DNA (cf-DNA) levels have been shown to be increased in several conditions such as cancer, trauma, and sepsis. Therefore, this study was designed to evaluate the potential of synovial fluid cf-DNA quantification for the diagnosis of chronic periprosthetic infections following total knee arthroplasty. METHODS: A prospective study with patients undergoing total knee arthroplasty revision surgery for any indication was performed. PJI diagnosis was defined according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. The study cohort consisted of 26 patients classified as infected and 40 as noninfected. Synovial fluid cf-DNA direct quantification by fluorescent staining was made. Sensitivity, specificity, and receiver operating characteristic curve were calculated. RESULTS: The cf-DNA levels were significantly higher in patients who had PJIs (122.5 ± 57.2 versus 4.6 ± 2.8 ng/µL, P < .0001). With a cutoff of 15 ng/µL, the area under the receiver operating characteristic, sensitivity, and specificity of cf-DNA were 0.978, 96.2%, and 100%, respectively. CONCLUSION: The present study has shown that cf-DNA is increased in synovial fluid of patients who have chronic PJIs. It is a promising biomarker for knee PJI diagnosis and further studies are needed to confirm its utility.

BMP-4, TGF-ß and Smad3 as Modulators of Synovial Fluid Cells Viability.

Objective Our goal was to evaluate the modulation of the synovial fluid cells (SFC) from patients with and without osteoarthritis (OA) by bone morphogenetic protein 4 (BMP-4), Smad-3 and transforming growth factor beta (TGF-ß). Methods Synovial fluid was collected from patients submitted to knee arthroscopy or replacement and were centrifuged to isolate cells from the fluid. Cells were cultured for 21 days and characterized as mesenchymal stem cells (MSCs) according to the criteria of the International Society of Cell Therapy. Then, we performed an [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (MTT) assay after exposing cells with and without OA to TGF-ß, Smad3 and BMP-4 pathway inhibitors and to different concentrations of BMP4. Results Exposure to the TGF-ß, Smad3 and BMP-4 inhibitors modifies the mitochondrial activity of the SFCs. The activity of the SFCs is modified by influences of increasing concentrations of BMP4, but there is no difference in cellular activity between patients with and without OA. Conclusion TGF-ß, Smad3 and BMP-4 modulate the activity of SFCs from patients with and without knee OA.

Glucose and leukocyte esterase levels are possible biomarkers for bacterial septic arthritis.

OBJECTIVE: The objective of the study was to determine the added value of synovial fluid (SF) glucose levels and other biochemical parameters as possible biomarkers of bacterial septic arthritis (SA). MATERIALS AND METHODS: We prospectively examined adult patients with SA. As a control group, adults with uninfected joints were enrolled. SF samples were obtained, and microbiological analyses were made. SF glucose levels, pH, and leukocyte esterase were measured using a glucometer and colorimetric test strips. Blood samples were collected from both groups to determine glucose levels. RESULTS: We included eight subjects with knee ligaments lesions, six with meniscus lesions, and five with osteoarthritis as the control group, as well as 20 patients with SA. SF culture was positive in 60%. SF glucose levels from patients were lower than the controls (p = 0.0018) with the lowest concentration in patients with a positive culture (p = 0.0004). Blood and SF glucose concentration from the positive culture patients were compared (p < 0.0001). Leukocyte esterase presented the highest values in patients with a positive culture (p < 0.0001) and a more acidic pH was found compared to the control group (p < 0.0001). CONCLUSION: These biochemical parameters might be a quick and inexpensive added value for distinguishing between infective and non-infective joint disease.

OBJETIVO: Evaluar el valor añadido de los niveles de glucosa en el líquido sinovial (LS) y otros parámetros bioquímicos en el diagnostico de artritis séptica (AS). MATERIAL Y MÉTODOS: Análisis prospectivo de pacientes adultos con AS. Pacientes con articulaciones no infectadas fueron incluidos como grupo control. Se tomaron muestras de LS y sangre para la realización de análisis microbiológicos y bioquímicos en los pacientes y controles. RESULTADOS: Incluimos 8 sujetos con lesión ligamentosa de rodilla, 6 con lesiones meniscales y 5 con osteoartritis como grupo control, así como 20 pacientes con AS. El cultivo de LS fue positivo en 60%. Los niveles de glucosa en LS de pacientes con AS fueron más bajos que los controles (P = 0.0018) con la concentración más baja en pacientes con cultivo positivo (p = 0.0004). La relación de glucosa en sangre y LS de pacientes con cultivo positivo se vio afectada (p < 0.0001). La esterasa leucocitaria presentó valores más altos en pacientes con cultivo positivo (p < 0.0001); se encontró un pH más ácido en comparación con el grupo control (p < 0.0001). CONCLUSIÓN: Estos parámetros bioquímicos podrían ser un valor agregado útil, rápido y económico para distinguir entre enfermedad articular infecciosa y no infecciosa.

Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA. METHODS: HLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry. RESULTS: We identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γ expression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN-γ-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity. CONCLUSIONS: We significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.

BMP-4, TGF-β and Smad3 as Modulators of Synovial Fluid Cells Viability / BMP-4, TGF-β e Smad3 como moduladores da viabilidade das células do líquido sinovial

Abstract Objective Our goal was to evaluate the modulation of the synovial fluid cells (SFC) from patients with and without osteoarthritis (OA) by bone morphogenetic protein 4 (BMP-4), Smad-3 and transforming growth factor beta (TGF-β). Methods Synovial fluid was collected from patients submitted to knee arthroscopy or replacement and were centrifuged to isolate cells from the fluid. Cells were cultured for 21 days and characterized as mesenchymal stem cells (MSCs) according to the criteria of the International Society of Cell Therapy. Then, we performed an [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (MTT) assay after exposing cells with and without OA to TGF-β, Smad3 and BMP-4 pathway inhibitors and to different concentrations of BMP4. Results Exposure to the TGF-β, Smad3 and BMP-4 inhibitors modifies the mitochondrial activity of the SFCs. The activity of the SFCs is modified by influences of increasing concentrations of BMP4, but there is no difference in cellular activity between patients with and without OA. Conclusion TGF-β, Smad3 and BMP-4 modulate the activity of SFCs from patients with and without knee OA.

Resumo Objetivo Nosso objetivo foi avaliar a modulação das células do líquido sinovial (SFCs, na sigla em inglês) de pacientes com e sem osteoartrite (OA) por proteína morfogenética óssea 4 (BMP-4), Smad3 e transformador do fator de crescimento β (TGF-β). Métodos O do líquido sinovial foi coletado de pacientes submetidos a artroscopia ou artroplastia do joelho, e centrifugados para isolar as células do liquido sinovial. As células foram cultivadas por 21 dias e caracterizadas como células-tronco mesenquimais (MSCs, na sigla em inglês) de acordo com os critérios da International Society of Cell Therapy. Em seguida, realizamos um ensaio de brometo de 3-4,5-dimetil-tiazol-2-il-2,5difeniltetrazólio (MTT) depois de expor células com e sem OA para TGF-β, inibidores de via Smad3 e BMP-4 e para diferentes concentrações de BMP-4. Resultados A exposição aos inibidores TGF-β, Smad3 e BMP-4 modifica a atividade mitocondrial das SFCs. A atividade das SFCs é modificada por influências sobre o aumento das concentrações de BMP-4, mas não há diferença na atividade celular entre pacientes com e sem OA. Conclusão TGF-β, Smad3 e BMP-4 modulam a atividade das SFCs de pacientes com e sem OA do joelho.

Biomarcadores inflamatorios en líquido sinovial de trastornos intraarticulares de la articulación temporomandibular. Revisión sistemática / Inflammatory biomarkers in synovial fluid of intra-articular disorders of the temporomandibular joint. Systematic review

RESUMEN Objetivo: Determinar los biomarcadores inflamatorios del líquido sinovial (LS) de pacientes adultos con trastornos intraarticulares (TI) de la articulación temporomandibular (ATM) y su capacidad diagnóstica. Métodos: Se realizó búsqueda electrónica/manual de artículos (2010-2019) en paralelo por dos investigadores. La calidad de los estudios, se determinó por medio de CONSORT y STROBE y el sesgo según criterios Cochrane RoB 2 en ensayos clínicos aleatorizados y Escala Newcastle-Ottawa en estudios observacionales. Se estudiaron pacientes con TI de la ATM y determinación de biomarcadores del LS. Resultados: De 264 artículos encontrados, 6 cumplieron los criterios inclusión-exclusión, incluyendo 262 pacientes, [OA=153, 93 con desplazamientos discales (DD) y 16 con OA+DD]. Todas las muestras fueron obtenidas por artrocentesis y detectadas por ELISA. Se determinaron 19 biomarcadores en pacientes con OA; 9 en DD y 2 en diagnosticados con OA+DD. El incremento de biomarcadores en el LS de la ATM se asocia con TI. Conclusión: Los biomarcadores detectados con mayor frecuencia en LS de pacientes con TI de ATM fueron IL-1β, IL-6 y TNF-α y en segunda frecuencia TGF-β1, MMP-3 e IFN-γ. Dada la inconsistencia de los protocolos utilizados la evidencia fue débil, imposibilitando asociar biomarcadores con diagnóstico de TI determinado, ni efectuar análisis estadístico.

ABSTRACT: Objective: To determine the evidence of inflammatory biomarkers present in the synovial fluid (SF) of adult patients with intra-articular disorders (ID) of the temporomandibular joint (TMJ) and their diagnostic ability. Methods: Electronic/manual search of articles (2010-2019) was performed. Data were extracted in duplicate. The quality of the studies was determined by CONSORT, STROBE and risk of bias was determined by Cochrane RoB 2 and Newcastle-Ottawa Scale. The populations studied were patients with TMJ ID and with studies of SF biomarkers. Results: Out of 264 articles found, 6 met the inclusion-exclusion criteria, including 262 patients, 93 with disc displacements (DD) and 16 with OA+DD. All samples were obtained by arthrocentesis and detected by ELISA. Nineteen biomarkers were evaluated in patients with OA, 9 in patients with DD and 2 in those diagnosed with OA+DD. Increased inflammatory biomarkers in the SF of TMJ are associated with ID. Conclusion: The most frequent biomarkers detected in SF of patients with TMJ ID were IL-1β, IL-6 and TNF-α and in second frequency TGF-β1, MMP-3 and IFN-γ. Given the inconsistency of the protocols used, the evidence was weak, making it impossible to associate biomarkers with a given IT diagnosis, or to perform statistical analysis.

Primary meningococcal septic arthritis associated with joint calcium oxalate crystals: A case report and review of the literature.

Primary meningococcal septic arthritis (PMSA) is an extremely rare local infection by Neisseria meningitidis in the absence of meningitis or meningococcaemia syndrome. A 30-year-old healthy, immunocompetent man presented with arthralgia, fever, chest rash, and significant swelling of the right knee. On admission, a disseminated maculopapular and purpuric rash, oligoarthritis, neutrophilia, and elevated acute phase reactants were documented. Following arthrocentesis of the right knee, isolation of N. meningitidis and the presence of calcium oxalate crystals in the synovial fluid were reported. The diagnosis of PMSA was made. Histological analysis of the skin lesion showed leucocytoclastic vasculitis. He was treated with intravenous ceftriaxone plus open surgical drainage and ambulatory cefixime with adequate response. After 1 month, he presented resolution of the pathological process. We performed an extensive review of the literature, finding that the key elements supporting the diagnosis of PMSA are prodromal upper respiratory tract symptoms and skin involvement prior to or synchronous with the arthritis. Also, the most frequently involved joint is the knee. This report is the first case of a patient presenting with PMSA associated with calcium oxalate crystals in the synovial fluid. Herein, we discuss the most frequent clinical manifestations, the unusual histological features, the recommended treatment, and the reported prognosis of this rare entity.

Commercial Synovial Antibody Testing is No Better Than Traditional Culture in Identification of Pathogen(s) Causing Periprosthetic Joint Infection.

BACKGROUND: Identification of infective organism causing periprosthetic joint infections (PJIs) is crucial to tailor the best combination of surgical and antimicrobial treatment. Traditional culture, with all its limitations, has been utilized for this purpose. A synovial fluid antibody assay against some common pathogens has been introduced by a commercial entity recently. This study aimed to determine if the antibody testing could be used as a proxy to traditional culture, and whether it provided additional information, in the setting of PJI. METHODS: A retrospective study was conducted of patients who underwent revision total hip and knee arthroplasty between January 2019 and 2020. Aspirated synovial fluid was sent for analyses including the commercial antibody testing. All patients had samples harvested for culture per standard of care. Results of the antibody testing and culture, in terms of concordance, were compared. Receiver operating characteristic curve and Youden's criterion were used to compare the 2 methods. RESULTS: A total of 419 patients were included. Using the International Consensus Meeting criteria as reference standard for PJI, antibody testing had a sensitivity and specificity of 40.5% and 93.4%, respectively. There were 59.5% false negative results with antibody testing compared with 50% for culture. Of the 12 patients who had positive results in both tests, 5 (41.7%) had discordant pathogens identified in each test. CONCLUSION: Synovial fluid antibody testing does not provide clinical benefit when compared to traditional cultures for PJI diagnosis. The antibody testing had a low sensitivity and a high rate of discordance with culture, when both tests were positive.

Artritis séptica. Revisión descriptiva / Septic Arthritis. Descriptive Review / Artrite séptica. Revisão descritiva

Introducción: La artritis séptica es considerada una emergencia en ortopedia. Se define como el proceso inflamatorio desproporcionado, desencadenado por la colonización de algún microorganismo en el espacio articular que con los cambios fisiopatológicos ocasionados degradan el cartílago y aumentan la morbimortalidad, la prolongación de la estancia hospitalaria, las secuelas irreversibles, así como los costos para el sistema de salud. Por tal razón, es vital que el médico general, quien tiene el primer contacto con el paciente, sea capaz de reconocer las manifesta-ciones, e instaure un tratamiento para evitar complicaciones y secuelas del paciente. Objetivo: Identificar los aspectos importantes de la artritis séptica y proporcionar al lector información relevante de forma práctica y concreta para su actuar médico diario. Método: Búsqueda de artículos originales en bases de datos, empleando términos MeSH y DeCS, consulta de textos guía, en el periodo 2010-2022. Resultados: Con mayor frecuencia se ven afectados pacientes en extremos de edad, como los mayores de 60 años y los menores de 20 años, y la rodilla es la principal articulación afectada. La fiebre no es un criterio necesario para el diagnóstico de artritis séptica y el principal factor de riesgo es la enfermedad articular previa. Conclusiones: El análisis del líquido sinovial y la tinción de Gram, junto con el cultivo, permiten hacer el diagnóstico. El tratamiento antibiótico empírico es guiado por los factores de riesgo del paciente y, posteriormente, por los resultados del cultivo

Introduction: Septic arthritis is considered an emergency in orthopedics, it is defined as the dispro-portionate inflammatory process triggered by the colonization of some microorganism in the joint space, causing pathophysiological changes that degrade the cartilage causing increased morbidity and mortality, prolongation of hospital stay, irreversible sequelae, as well as increased costs for the health system, for this reason it is of vital importance that the general practitioner who has the first contact with the patient can recognize the manifestations, and establish treatment to avoid compli-cations and sequelae of the patient.Objective: To identify the important aspects of septic arthritis and provide the reader with relevant information in a practical and concrete way for his daily medical practice.Method: We searched for original articles in databases using MeSH and DeCS terms, consulting guide texts, with a search period from 2010 to 2022. Results: Patients in extremes of age are more frequently affected, such as patients older than 60 years and younger than 20 years, being the knee the main affected joint. Fever is not a necessary criterion for the diagnosis of septic arthritis and the main risk factor is previous joint disease. Conclusions: Synovial fluid analysis and Gram stain together with culture allow making diagnosis. Empirical antibiotic treatment is guided by the patient's risk factors, then by the culture results.

Introdução: a artrite séptica é considerada uma emergência na ortopedia. É definida como um processo inflamatório desproporcional, desencadeado pela colonização de um microrganismo no espaço arti-cular que, com as mudanças fisiopatológicas causadas, degrada a cartilagem e aumenta a morbidade e a mortalidade, a permanência hospitalar prolongada, sequelas irreversíveis, assim como os custos para o sistema de saúde. Por esta razão, é vital que o clínico geral, que tem o primeiro contato com o paciente, seja capaz de reconhecer as manifestações, e instituir tratamento para evitar complicações e sequelas para o paciente. Objetivo: Identificar os aspetos importantes da artrite séptica e fornecer ao leitor informações relevan-tes de uma forma prática e concreta para a prática médica diária. Método: Pesquisa de artigos originais em bancos de dados, usando termos MeSH e DeCS, consulta de textos guias, no período de 2010-2022. Resultados: Os mais frequentemente afetados são os pacientes em extremos de idade, como aqueles com mais de 60 anos e menos de 20 anos, e o joelho é a principal articulação afetada. A febre não é um critério necessário para o diagnóstico de artrite séptica e o principal fator de risco é a doença articular prévia. Conclusões: A análise do líquido sinovial e a coloração de Gram, junto com a cultura em meios espe-cíficos, permitem que o diagnóstico seja feito. O tratamento antibiótico empírico é orientado pelos fatores de risco do paciente e, posteriormente, pelos resultados da cultura

Lubricación in vitro en prótesis articulares / In Vitro Lubrication In Joint Prostheses

Entender el desgaste prematuro en reemplazos articulares debido a una lubricación deficiente, que puede resultar en valores de fricción altos, es un tema amplio e intrincado de abordar. Además, si el lubricante es el fluido sinovial, los mecanismos de lubricación que ocurren son aún más complejos de develar. En este artículo se revisa el estado de conocimiento actual de la lubricación sinovial, así como las características reológicas del fluido lubricante. Asimismo, se mencionan algunas técnicas experimentales y métodos numéricos con los que se ha estudiado el problema de la lubricación. En algunas simulaciones numéricas de la lubricación en reemplazos articulares no se considera el efecto del esfuerzo cortante del líquido sinovial ya que se asume que tiene un comportamiento newtoniano, sin embargo, otras investigaciones han demostrado que al asumir un comportamiento no newtoniano el proceso de lubricación se afecta significativamente. Con todo esto, incorporar todos los factores que pueden afectar la lubricación en reemplazos articulares, en simulaciones numéricas hasta la fecha es un reto. A través de diversas investigaciones se buscan nuevos materiales, diseños y técnicas de análisis que permitan incrementar la vida útil de los implantes para así reducir las cirugías de revisión(AU)

derstanding premature wear in joint replacements due to poor lubrication, which can result in high friction values, is a broad and intricate topic to address. In addition, if the lubricant is the synovial fluid, the lubrication mechanisms that occur are even more complex to unveil. This article reviews the current state of knowledge on synovial lubrication, as well as the rheological characteristics of the lubricating fluid. It is also made a mention of some experimental techniques and numerical methods with which the problem of lubrication has been studied. In some numerical simulations of lubrication in joint replacements the effect of the shear stress of the synovial fluid is not considered since it is assumed to have a Newtonian behavior; however, other research has shown that by assuming a non-Newtonian behavior the lubrication process is significantly affected. With all this, incorporating all the factors that can affect lubrication in joint replacements, in numerical simulations to date is a challenge. Through various investigations, new materials, designs and analysis techniques are sought to increase the useful life of implants in order to reduce revision surgeries(AU)

Ankle Osteoarthritis.

Osteoarthritis (OA) is characterized by a chronic, progressive and irreversible degradation of the joint surface associated with joint inflammation. The main etiology of ankle OA is post-traumatic and its prevalence is higher among young and obese people. Despite advances in the treatment of fractures around the ankle, the overall risk of developing post-traumatic ankle OA after 20 years is almost 40%, especially in Weber type B and C bimalleolar fractures and in fractures involving the posterior tibial border. In talus fractures, this prevalence approaches 100%, depending on the severity of the lesion and the time of follow-up. In this context, the current understanding of the molecular signaling pathways involved in senescence and chondrocyte apoptosis is fundamental. The treatment of ankle OA is staged and guided by the classification systems and local and patient conditions. The main problems are the limited ability to regenerate articular cartilage, low blood supply, and a shortage of progenitor stem cells. The present update summarizes recent scientific evidence of post-traumatic ankle OA with a major focus on changes of the synovia, cartilage and synovial fluid; as well as the epidemiology, pathophysiology, clinical implications, treatment options and potential targets for therapeutic agents.

Ankle Osteoarthritis / Osteoartrite do tornozelo

Abstract Osteoarthritis (OA) is characterized by a chronic, progressive and irreversible degradation of the joint surface associated with joint inflammation. The main etiology of ankle OA is post-traumatic and its prevalence is higher among young and obese people. Despite advances in the treatment of fractures around the ankle, the overall risk of developing posttraumatic ankle OA after 20 years is almost 40%, especially in Weber type B and C bimalleolar fractures and in fractures involving the posterior tibial border. In talus fractures, this prevalence approaches 100%, depending on the severity of the lesion and the time of follow-up. In this context, the current understanding of the molecular signaling pathways involved in senescence and chondrocyte apoptosis is fundamental. The treatment of ankle OA is staged and guided by the classification systems and local and patient conditions. The main problems are the limited ability to regenerate articular cartilage, low blood supply, and a shortage of progenitor stem cells. The present update summarizes recent scientific evidence of post-traumatic ankle OA with a major focus on changes of the synovia, cartilage and synovial fluid; as well as the epidemiology, pathophysiology, clinical implications, treatment options and potential targets for therapeutic agents.

Resumo A osteoartrite (OA) é caracterizada por uma degradação crônica, progressiva e irreversível da superfície articular, associada a inflamação articular. A principal etiologia da OA do tornozelo é pós-traumática e sua prevalência é maior entre os jovens e obesos. Apesar dos avanços no tratamento das fraturas ao redor do tornozelo, o risco geral de desenvolver OA pós-traumática do tornozelo após 20 anos do trauma é de quase 40%; especialmente nas fraturas bimaleolares de Weber tipo B e C e fraturas envolvendo a borda tibial posterior. Nas fraturas do tálus, essa prevalência se aproxima de 100%, dependendo da gravidade da lesão e do tempo de seguimento. Nesse cenário, é fundamental a compreensão atual das vias de sinalização moleculares envolvidas na senescência e apoptose dos condrócitos. O tratamento da OA do tornozelo é estagiado e guiado pelos sistemas de classificação, condições locais e do paciente. Os principais problemas são a limitada capacidade de regeneração da cartilagem articular, o baixo suprimento de sangue e a escassez de células-tronco progenitoras. A presente atualização resume evidências científicas básicas recentes da OA póstraumática do tornozelo, com foco principal nas alterações metabólicas da sinóvia, da cartilagem e do líquido sinovial. Epidemiologia, fisiopatologia, implicações clínicas, e opções de tratamento são também discutidas.

Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation.

Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administration. Doxycycline concentration was measured by competitive enzyme immunoassay. Serum concentrations versus time data were fitted simultaneously using the stochastic approximation expectation-maximization algorithm for nonlinear mixed effects. A one-compartment model with linear elimination and first-order absorption after intragastric administration, best described the available pharmacokinetic data. Final parameter estimates indicate that DXC has a high volume of distribution (108 L/kg) as well as high absorption (10.3 h-1) in donkeys. However, results suggest that oral DXC at 10 mg/kg q12 h in donkeys would not result in a therapeutic concentration in serum, urine, synovial fluid or endometrium by comparison to the minimum inhibitory concentration of common equine pathogens. Further studies are recommended to identify appropriate dosage and dosing intervals of oral DXC in donkeys.