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1.
J Therm Biol ; 123: 103915, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38981303

ABSTRACT

The liveliness of a human potentially depends on his/her smooth movability. To accomplish the work of daily life, the joints of the body need to be healthy. However, the occurrence of Rheumatoid arthritis and Osteoarthritis has a significant prevalence towards the immovability of humankind. Rheumatoid arthritis (RA) and Osteoarthritis (OA) mostly affect the joints of the hand and knee which result in lifelong pain, inability to climb, walk, etc. In the early stages, these diseases attack the synovial membrane and synovial fluid, and further it destroys the soft tissues and bone structure. By early diagnosis, we can start the treatment in the early stage which may cure these diseases with such extreme consequences. As per clinical studies of previous literature, it is observed that synovial fluid imbalance appears in the early stage of such diseases and Hyaluronic Acid (HA) concentration also decreases for that. Therefore, estimation of HA is a significant key to arthritis disease classification and grading. In this paper, we proposed a hybrid framework for classification of arthritic knee joints based on the analysis of the discontinuous appearances of the HA concentration using infrared imaging technology. To meet up the specific necessities, firstly we have proposed a modified K-Means clustering algorithm for extraction of the region of interest (ROI) i.e., the knee joint surface. Secondly, a mathematical formulation is proposed to calculate the concentration of HA from the segmented ROIs. This experimental process was implemented on the publicly available IR (Infrared) Knee Joint Dataset and for further evaluation of the novelty of mathematical formulation, we have extended the proposed work to the classification of healthy and arthritis affected knee joints depending on significant discriminative characteristics of the HA concentration with respect to the existing significant imaging features. Experimental results and analysis demonstrates that concentration of HA has the dominant potential for classifying healthy and arthritic knee joints using infrared holistic images. Our experimental analysis reveals that estimation and combination of the HA concentration features with conventional handcrafted and deep features increases the classification performance with an average accuracy of 91% and 97.22% respectively as compared to the each individual feature sets.

3.
Microorganisms ; 12(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38930616

ABSTRACT

Prosthetic joint infection (PJI) is one of the most serious complications of joint replacement surgery among orthopedic surgeries and occurs in 1 to 2% of primary surgeries. Additionally, the cause of PJIs is mostly bacteria from the Staphylococcus species, accounting for more than 98%, while fungi cause PJIs in only 1 to 2% of cases and can be difficult to manage. The current gold-standard microbiological method of culturing synovial fluid is time-consuming and produces false-negative and -positive results. This study aimed to identify a novel, accurate, and convenient molecular diagnostic method. The DreamDX primer-hydrolysis probe set was designed for the pan-bacterial and pan-fungal detection of DNA from pathogens that cause PJIs. The sensitivity and specificity of DreamDX primer-hydrolysis probes were 88.89% (95% CI, 56.50-99.43%) and 97.62% (95% CI, 87.68-99.88%), respectively, compared with the microbiological method of culturing synovial fluid, and receiver operating characteristic (ROC) area under the curve (AUC) was 0.9974 (*** p < 0.0001). It could be concluded that the DreamDX primer-hydrolysis probes have outstanding potential as a molecular diagnostic method for identifying the causative agents of PJIs, and that host inflammatory markers are useful as adjuvants in the diagnosis of PJIs.

4.
J Forensic Sci ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38876480

ABSTRACT

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.

5.
J Orthop Res ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38725379

ABSTRACT

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.

6.
J Orthop Traumatol ; 25(1): 26, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38761247

ABSTRACT

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


Subject(s)
Anti-Bacterial Agents , Prosthesis-Related Infections , Reoperation , Humans , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/surgery , Anti-Bacterial Agents/therapeutic use , Arthroplasty, Replacement/adverse effects , Arthroplasty, Replacement/methods , C-Reactive Protein , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Blood Sedimentation , Synovial Fluid/microbiology
7.
Knee Surg Relat Res ; 36(1): 19, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773579

ABSTRACT

BACKGROUND: This study aimed to identify plasma and urinary cytokines as potential biomarkers for severe knee osteoarthritis (OA). It also investigated associations between these cytokines and cartilage markers, as well as their connections with synovial fluid (SF) markers. METHODS: Samples of plasma, urine, and SF were obtained from patients (n = 40) undergoing total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) due to severe knee OA. Control samples of plasma and urine were collected from non-OA individuals (n = 15). We used a Luminex immunoassay for the simultaneous measurement of 19 cytokines, MMP-1, and MMP-3 levels. COMP, CTX-II, and hyaluronan (HA) levels were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Receiver operating characteristic (ROC) curves were utilized to analyze each biomarker's performance. Correlations among these biomarkers were evaluated via Spearman's correlation. RESULTS: The levels of plasma (p)CCL11, pCXCL16, pIL-8, pIL-15, pHA, urinary (u)CCL2, uCCL11, uCCL19, uCXCL16, uIL-1ß, uIL-6, uIL-8, uIL-12p70, uIL-15, uIL-33, uMMP-3, uHA, uCTX-II, and uCOMP were significantly elevated in individuals with severe knee OA. Notably, specific correlations were observed between the plasma/urine biomarkers and SF biomarkers: pCCL11 with sfHA (r = 0.56) and sfTNF-α (r = 0.58), pIL-15 with sfCCL19 (r = 0.43) and sfCCL20 (r = 0.44), and uCCL19 with sfCCL11 (r = 0.45) and sfIL-33 (r = 0.51). Positive correlations were also observed between uCCL11 and its corresponding sfCCL11(r = 0.49), as well as between sfCCL11 and other cytokines, namely sfCCL4, sfCCL19, sfCCL20, sfIL-33, and sfTNF-α (r = 0.46-0.63). CONCLUSION: This study provides an extensive profile of systemic inflammatory mediators in plasma of knee OA and identified four inflammatory markers (pCCL11, pIL-15, uCCL11, and uCCL19) reflecting joint inflammation.

8.
J Arthroplasty ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38797446

ABSTRACT

BACKGROUND: Debridement, antibiotics, and implant retention (DAIR) are the mainstays surgical treatment for acute periprosthetic joint infection (PJI). However, reoperation following DAIR is common and the risk factors for DAIR failure remain unclear. This study aimed to assess the perioperative characteristics of patients who failed initial DAIR treatment. METHODS: A retrospective review was conducted on 83 patients who underwent DAIR for acute PJI within 3 months following index surgery from 2011 to 2022, with a minimum one-year follow-up. Surgical outcomes were categorized using the Musculoskeletal Infection Society outcome reporting tool (Tiers 1 to 4). Patient demographics, laboratory data, and perioperative outcomes were compared between patients who had failed (Tiers 3 and 4) (n = 32) and successful (Tiers 1 and 2) (n = 51) DAIR treatment. Logistic regression was also performed. RESULTS: After logistic regression, Charlson Comorbidity Index (odds ratio [OR]: 1.57; P = .003), preoperative C-reactive protein (OR: 1.06; P = .014), synovial white blood cell (OR: 1.14; P = .008), and polymorphonuclear cell (PMN%) counts (OR: 1.05; P = .015) were independently associated with failed DAIR. Compared with total hip arthroplasty, total knee arthroplasty patients (OR: 6.08; P = .001) were at increased risk of DAIR failure. The type of organism and time from primary surgery were not correlated with DAIR failure. CONCLUSIONS: Patients who had failed initial DAIR tended to have significantly higher Charlson Comorbidity Index, C-reactive protein, synovial white blood cell, and PMN%. The total knee arthroplasty DAIRs were more likely to fail than the total hip arthroplasty DAIRs. These characteristics should be considered when planning acute PJI management, as certain patients may be at higher risk for DAIR failure and may benefit from other surgical treatments. LEVEL OF EVIDENCE: III.

9.
Cartilage ; : 19476035241247659, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726690

ABSTRACT

OBJECTIVE: Hyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthritis by affecting inflammation and cartilage degradation. It remains unknown whether HA and EVs display joint-specific alterations in arthritic SFs. DESIGN: We investigated the numbers and characteristics of HA-particles and large EVs in SF from knees and shoulders of 8 OA and 8 RA patients and 8 trauma controls, and in plasma from 10 healthy controls and 11 knee OA patients. The plasma and SF HA concentrations were determined with a sandwich-type enzyme-linked sorbent assay, and EVs and HA-particles were characterized from plasma and unprocessed and centrifuged SFs with confocal microscopy. The data were compared according to diagnosis, location, and preanalytical processing. RESULTS: The main findings were: (1) OA and RA SFs can be distinguished from trauma joints based on the distinctive profiles of HA-particles and large EVs, (2) there are differences in the SF HA and EV characteristics between shoulder and knee joints that could reflect their dissimilar mobility, weight-bearing, and shock absorption properties, (3) EV counts in SF and plasma can positively associate with pain parameters independent of age and body adiposity, and (4) low-speed centrifugation causes alterations in the features of HA-particles and EVs, complicating their examination in the original state. CONCLUSIONS: Arthritis and anatomical location can affect the characteristics of HA-particles and large EVs that may have potential as biomarkers and effectors in joint degradation and pain.

10.
Int J STD AIDS ; : 9564624241254877, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748748

ABSTRACT

In recent years, there has been an increase in Neisseria gonorrhoeae infections in Europe and Spain. Disseminated gonococcal infection is an uncommon clinical presentation that includes gonococcal arthritis. Improved antibiotic treatment has reduced the incidence of gonococcal arthritis. However, the increase in gonococcal infections may have increased the frequency of this clinical entity in recent times. We report five cases of gonococcal arthritis in patients in a tertiary-care hospital in the northern area of Madrid (Spain) from October 2022 to October 2023. Major cases occurred in male patients with unprotected sex and polyarticular symptoms requiring hospital admission and treatment with ceftriaxone and cefixime. The use of molecular techniques has allowed the detection of a greater number of culture-negative cases of gonococcal arthritis, as well as the detection of mutations associated with resistance to fluoroquinolone for switching to oral treatment.

11.
Mol Cell Proteomics ; 23(6): 100785, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750696

ABSTRACT

The molecular mechanisms that drive the onset and development of osteoarthritis (OA) remain largely unknown. In this exploratory study, we used a proteomic platform (SOMAscan assay) to measure the relative abundance of more than 6000 proteins in synovial fluid (SF) from knees of human donors with healthy or mildly degenerated tissues, and knees with late-stage OA from patients undergoing knee replacement surgery. Using a linear mixed effects model, we estimated the differential abundance of 6251 proteins between the three groups. We found 583 proteins upregulated in the late-stage OA, including MMP1, collagenase 3 and interleukin-6. Further, we selected 760 proteins (800 aptamers) based on absolute fold changes between the healthy and mild degeneration groups. To those, we applied Gaussian Graphical Models (GGMs) to analyze the conditional dependence of proteins and to identify key proteins and subnetworks involved in early OA pathogenesis. After regularization and stability selection, we identified 102 proteins involved in GGM networks. Notably, network complexity was lost in the protein graph for mild degeneration when compared to controls, suggesting a disruption in the regular protein interplay. Furthermore, among our main findings were several downregulated (in mild degeneration versus healthy) proteins with unique interactions in the healthy group, one of which, SLCO5A1, has not previously been associated with OA. Our results suggest that this protein is important for healthy joint function. Further, our data suggests that SF proteomics, combined with GGMs, can reveal novel insights into the molecular pathogenesis and identification of biomarker candidates for early-stage OA.


Subject(s)
Protein Interaction Maps , Proteomics , Synovial Fluid , Humans , Synovial Fluid/metabolism , Proteomics/methods , Female , Male , Aged , Middle Aged , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , Osteoarthritis/metabolism , Osteoarthritis/pathology , Interleukin-6/metabolism , Proteome/metabolism , Matrix Metalloproteinase 1/metabolism
12.
Scand J Clin Lab Invest ; 84(3): 211-217, 2024 May.
Article in English | MEDLINE | ID: mdl-38767606

ABSTRACT

PsoP27 is an antigen expressed in psoriatic lesions. It plays an inflammatory role in psoriasis. This study objective was to characterize antibodies (Abs) against PsoP27 in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Levels of Abs against native and citrullinated PsoP27 in PsA and RA patients' synovial fluid (SF) and sera were determined by ELISA. SF of osteoarthritis (OA) patients and sera of healthy donors were used as controls. Levels of Abs against PsoP27 were correlated with disease activity scores. Abs against native and citrullinated PsoP27 levels in SF of PsA (n = 48; 0.38 ± 0.03 and 0.44 ± 0.04, respectively) and RA (n = 22; 0.57 ± 0.1 and 0.62 ± 0.09, respectively) were significantly higher than in OA patients (n = 23; 0.14 ± 0.01 and 0.15 ± 0.01, respectively) (p < .0001). For both Abs, there were no significant differences between their level in PsA and RA patients. There was no difference in the level of Abs against citrullinated PsoP27 in SF of seronegative versus seropositive RA patients. Levels of Abs against both native and citrullinated PsoP27 in the SF and level of systemic C-reactive protein in PsA correlated positively, while in RA there were no significant correlations with disease activity scores. No differences in level of Abs against PsoP27 were found in the sera of all three study groups. Abs against native and citrullinated PsoP27 are present in PsA and RA SF but not in those of OA patients, suggesting a potential role of those Abs in inflammatory joint diseases.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Autoantibodies , Synovial Fluid , Humans , Arthritis, Psoriatic/immunology , Arthritis, Psoriatic/blood , Arthritis, Psoriatic/metabolism , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Synovial Fluid/immunology , Synovial Fluid/metabolism , Autoantibodies/blood , Autoantibodies/immunology , Male , Middle Aged , Female , Adult , Aged , Case-Control Studies , Osteoarthritis/immunology , Osteoarthritis/blood , Enzyme-Linked Immunosorbent Assay
13.
Antibiotics (Basel) ; 13(4)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38667022

ABSTRACT

Implant loosening is a severe complication after total joint replacement. Here, differential diagnosis between septic and aseptic cases is crucial for further surgical treatment, but low-grade periprosthetic joint infections (PJIs) in particular remain a challenge. In this study, we analyzed the synovial fluid proteome of 21 patients undergoing revision surgery for septic (eight cases) or aseptic (thirteen cases) implant failure using LC-MS/MS to identify potential new biomarkers as future diagnostic tools. Staphylococci were found in four cases, Streptococci in two cases, Serratia marcescens and Cutibacterium acnes in one case. Proteomic analysis of the synovial fluid resulted in the identification of 515 different proteins based on at least two peptides. A statistical comparison revealed 37 differentially abundant proteins (p < 0.05), of which 17 proteins (46%) showed a higher abundance in the septic group. The proteins with the highest fold change included the known marker proteins c-reactive protein (7.57-fold) and the calprotectin components protein S100-A8 (4.41-fold) and protein S100-A9 (3.1-fold). However, the protein with the highest fold change was leucine-rich alpha-2-glycoprotein 1 (LRG1) (9.07-fold), a currently discussed new biomarker for inflammatory diseases. Elevated LRG1 levels could facilitate the diagnosis of PJI in the future, but their significance needs to be further investigated.

14.
Animals (Basel) ; 14(7)2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38612225

ABSTRACT

Osteoarthritis is a leading cause of lameness and joint disease in horses. A simple, economical, and accurate diagnostic test is required for routine screening for OA. This study aimed to evaluate infrared (IR)-based synovial fluid biomarker profiling to detect early changes associated with a traumatically induced model of equine carpal osteoarthritis (OA). Unilateral carpal OA was induced arthroscopically in 9 of 17 healthy thoroughbred fillies; the remainder served as Sham-operated controls. The median age of both groups was 2 years. Synovial fluid (SF) was obtained before surgical induction of OA (Day 0) and weekly until Day 63. IR absorbance spectra were acquired from dried SF films. Following spectral pre-processing, predictive models using random forests were used to differentiate OA, Sham, and Control samples. The accuracy for distinguishing between OA and any other joint group was 80%. The classification accuracy by sampling day was 87%. For paired classification tasks, the accuracies by joint were 75% for OA vs. OA Control and 70% for OA vs. Sham. The accuracy for separating horses by group (OA vs. Sham) was 68%. In conclusion, SF IR spectroscopy accurately discriminates traumatically induced OA joints from controls.

15.
Reumatol Clin (Engl Ed) ; 20(4): 193-198, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38644030

ABSTRACT

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.


Subject(s)
Synovial Fluid , Humans , Synovial Fluid/chemistry , Aged , Male , Female , Retrospective Studies , Middle Aged , Gout/epidemiology , Aged, 80 and over , Arthritis, Rheumatoid , Mexico/epidemiology , Leukocyte Count , Age Factors
16.
Immunol Lett ; 267: 106859, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38670465

ABSTRACT

The synovial fluid (SF) microenvironment in rheumatoid arthritis (RA) may alter the stability and function of Tregs. In the present study, we assessed cytokine levels and percentage of Tregs, Tregs expressing CXCR3 (Th1-like Treg), CCR6 (Th17-like Treg) in RA peripheral blood (PB) and RA-SF using fluorescence cytometry. Effect of autologous SF on plasticity and function of RA-PB Tregs (pTregs; CD4+CD25hiCD127Lo/-) and induced vimentin-pulsed Tregs (iTregsVIM) was assessed in vitro. Cytokines and percentage of Th1-like and Th17-like Tregs were higher in RA-PB than OA-PB; higher in RA-SF than osteoarthritis (OA)-SF. Compared to OA-SF exposed OA-pTregs, RA-SF exposed RA-pTregs showed higher percentage of Th1-like (11% vs 20%) and Th17-like (16% vs 36%) Tregs; higher T-bet (p = 0.0001), RORγ (p = 0.0001) and lower FOXP3 (p = 0.0001) gene expression; and diminished percentage suppression of autologous T effector cells (36% vs 74%). RA-SF exposed iTregsVIM showed increased percentage of Th1-like and Th17-like Tregs compared to iTregsVIM exposed to AB serum (8% vs 0.1%; 21% vs 0.1%). IL-2, Tocilizumab and 5-azacytidine reduced the conversion of iTregsVIM (8% vs 2.4%; 21% vs 6.9%), when used in combination. To conclude, microenvironment in the RA synovial fluid is possibly responsible for conversion of pTregs into Th-like Tregs and their functional loss. A blockade of cytokine receptors and methyl transferases could inhibit Tregs conversion, providing clinical relevance for future Tregs targeting therapies.


Subject(s)
Arthritis, Rheumatoid , Cell Plasticity , Cytokines , Synovial Fluid , T-Lymphocytes, Regulatory , Humans , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Synovial Fluid/immunology , Synovial Fluid/metabolism , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/therapy , Male , Female , Middle Aged , Cytokines/metabolism , Cell Plasticity/immunology , Aged , Th17 Cells/immunology , Th17 Cells/metabolism , Cells, Cultured , Adult , Osteoarthritis/immunology , Osteoarthritis/metabolism , Osteoarthritis/therapy , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
17.
Cureus ; 16(3): e55641, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38586694

ABSTRACT

Introduction Synovial fluid (SF) cultures can yield false-positive or negative results when diagnosing periprosthetic joint infection (PJI). False-positives may arise during sample collection or from laboratory contamination. Understanding false-positive SF culture rates is crucial for interpreting PJI laboratory data, yet clinical laboratories rarely report these rates. This study aimed to define the false-positive SF culture rate at a major specialized clinical laboratory. Methods This study retrospectively analyzed prospectively collected data at a single clinical laboratory that receives SF for clinical testing for PJI. A total of 180,317 periprosthetic SF samples from the hip, knee, and shoulder were identified from January 2016 to December 2023, which met the inclusion criteria for this study. Samples were classified by both a modified 2018 International Consensus Meeting (ICM) score and an inflammation score that combined the SF-C-reactive protein, alpha-defensin, SF-white blood cell count, and SF-polymorphonuclear% into one standardized metric. Logistic regression was utilized to evaluate the impact of various collection-based characteristics on culture positivity, including inflammation biomarkers, the source joint, quality control metrics, and days of specimen transport to the laboratory. SF culture false-positivity was calculated based on the ICM category of "not-infected" or low inflammation score. Results Overall, 13.3% (23,974/180,317) of the samples were associated with a positive culture result: 12.5% for knee samples, 20.3% for hip samples, and 14.7% for shoulder samples. The false-positive SF culture rate among 131,949 samples classified as "not-infected" by the modified 2018 ICM definition was 0.47% (95%CI: 0.43 to 0.51%). Stratification by joint revealed a false-positive rate of 0.34% (95%CI: 0.31 to 0.38%) for knee samples, 1.24% (95%CI: 1.05 to 1.45%) for hip samples, and 3.02% (95%CI: 2.40 to 3.80%) for shoulder samples, with p < 0.0001 for all comparisons. The false-positive SF culture rate among 90,156 samples, representing half of all samples with the lowest standardized inflammation scores, was 0.47% (95%CI: 0.43 to 0.52%). Stratification by joint revealed a false-positive rate of 0.33% (95%CI: 0.29 to 0.37%) for knee samples, 1.45% (95%CI: 1.19 to 1.77%) for hip samples, and 3.09% (95%CI: 2.41 to 3.95%) for shoulder samples, with p<0.0001 for all comparisons. Multivariate logistic regression demonstrated the joint source (hip, shoulder) and poor sample quality as collection-based factors associated with a false-positive culture. Evaluation of a cohort of samples selected to minimize collection-based causes of false-positive culture demonstrated a false-positive rate of 0.30%, representing the ceiling limit for laboratory-based SF culture false-positivity. Conclusions This study utilizes two methods to estimate the false-positive SF culture rate at a single specialized clinical laboratory, demonstrating an overall false-positive rate of approximately 0.5%. Stratification of samples by source joint demonstrated that periprosthetic SF from the shoulder and hip have a substantially higher false-positive culture rate than that of the knee. The lowest false-positive SF culture rate (0.30%) was observed among samples from the knee-passing quality control. Culture positivity due to contamination at this specific laboratory is less than 0.30% because all specimens undergo identical processing.

18.
Article in English | MEDLINE | ID: mdl-38608288

ABSTRACT

Osteoarthritis (OA), primarily characterized by the deterioration of articular cartilage, is a highly prevalent joint-disabling disease. The pathological onset and progression of OA are closely related to cartilage lubrication dysfunction and synovial inflammation. Synergistic options targeted at restorative lubrication and anti-inflammation are expected to be the most attractive candidates to treat OA and perhaps help prevent it. Herein, a bioinspired lubricant (HA/PA@Lipo) was fabricated by combining anionic hyaluronan-graft-poly(2-acrylamide-2-methylpropanesulfonic acid sodium salt) (HA/PA) with cationic liposomes (Lipo) via electrostatic interaction. HA/PA@Lipo mimicked the lubrication complex located on the outer cartilage surface and was endowed cartilage with excellent cartilage-lubricating performances. After the antioxidant gallic acid (GA) was loaded for dual functionality, HA/PA@Lipo-GA was prepared with added anti-inflammatory properties. HA/PA@Lipo-GA showed favorable biocompatibility with C28/I2 cells, inhibited the production of reactive oxygen, and regulated the expression levels of anabolic genes and proteins. The therapeutic effects of HA/PA@Lipo-GA were evaluated using a sodium iodoacetate-induced OA rat model, and the preventive effects of HA/PA@Lipo-GA were estimated in vivo. The results suggested the robust potential of HA/PA@Lipo-GA with dual functions as a candidate option for OA treatment and prevention.

19.
Vet Res Commun ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662317

ABSTRACT

Differences between serum C-reactive protein (SCRP) and synovial fluid C-reactive protein (SFCRP) concentrations in healthy animals may be influenced by the sex of the individual and associated with various factors. The objective of this study was to evaluate the disparities in SCRP and SFCRP concentrations between females and males, as well as within each sex. Sixty healthy dogs (N = 60), comprising both sexes, were enrolled in the study. Peripheral blood and knee synovial fluid samples were collected for SCRP and SFCRP analysis, respectively. Serum C-reactive protein (SCRP) and SFCRP concentrations were measured, with mean of 9.61 ± 4.96 mg/L for SCRP and 1.28 ± 3.05 mg/L for SFCRP. Notably, SFCRP concentrations were consistently lower than SCRP concentrations in both sexes. Statistically significant differences were observed between sexes for both SCRP (P = 0.021) and SFCRP (P = 0.007). Further analysis within females revealed statistically significant differences between SCRP and SFCRP concentrations (P = 0.002), whereas in males, such differences were not significant (P = 0.175). Additionally, weak correlations were found between SCRP and SFCRP concentrations for both sexes (females r = 0.07; males r = 0.29). Joint capsule thickness was assessed using ultrasonography, revealing thicker joint capsules in males. A robust positive association was noted between joint capsule thickness and the SFCRP concentration in both sexes. These findings offer valuable insights into the dynamics of CRP in the context of joint health in male and female patients, elucidating the underlying pathological mechanisms of joint disease and inflammation. Overall, this underscores the importance of considering sex-specific factors in the assessment and management of joint health, as well as in the design and interpretation of studies involving SFCRP concentrations.

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