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Antimicrobial Agents and Chemotherapy Mar 2021The objectives of this study were to evaluate the population pharmacokinetics of prophylactic cefazolin (CFZ) from its serum and hip joint capsule concentrations in...
The objectives of this study were to evaluate the population pharmacokinetics of prophylactic cefazolin (CFZ) from its serum and hip joint capsule concentrations in patients undergoing total hip arthroplasty and to establish the pharmacodynamic target concentration exceeding the MIC for designing an effective dosing regimen for serum and the hip joint capsule. We analyzed 249 serum samples and 125 hip joint capsule samples from 125 individuals using a nonlinear mixed-effects model. The pharmacodynamic index target value obtained from our results indicates the probability of maintaining CFZ trough and hip joint capsule concentrations exceeding the MIC of 1 mg/liter to account for methicillin-susceptible (MSSA). We estimated the population pharmacokinetics using a two-compartment model. The estimated population pharmacokinetic parameters were as follows: clearance (CL) (liters/h) = 1.46 × (creatinine clearance [CL] [ml/min]/77), volume of distribution of the central compartment (V) (liters) = 7.5, central-hip joint capsule compartment clearance (Q) (liters/h) = 3.38, and volume of distribution in the hip joint capsule compartment (V) (liters) = 36.1. The probability of achieving concentrations exceeding the MIC for MSSA was approximately 100% for serum and 100% for the hip joint capsule at 3 h after the initial dose. Our findings suggest that population-based parameters are useful for evaluating CFZ pharmacokinetics and that individual dosages should be determined based on the dosage regimen that achieves and maintains adequate tissue CFZ concentration.
Topics: Anti-Bacterial Agents; Arthroplasty, Replacement, Hip; Cefazolin; Humans; Joint Capsule; Microbial Sensitivity Tests; Staphylococcus aureus
PubMed: 33526489
DOI: 10.1128/AAC.02114-20 -
Arthritis Research & Therapy Jul 2017A hallmark of osteoarthritis is increased proteolytic cleavage of aggrecan. Cross talk between cartilage and the synovium + joint capsule (SJC) can drive cartilage...
BACKGROUND
A hallmark of osteoarthritis is increased proteolytic cleavage of aggrecan. Cross talk between cartilage and the synovium + joint capsule (SJC) can drive cartilage degradation by activating proteases in both tissues. We investigated aggrecan proteolysis patterns in cartilage explants using a physiologically relevant explant model of joint injury combining cartilage mechanical compression and coincubation with SJC.
METHODS
Bovine cartilage explants were untreated; coincubated with SJC; or subjected to mechanical injury and coincubated with SJC, mechanical injury alone, or mechanical injury and incubated with tumor necrosis factor-α (TNF-α). To compare the patterns of aggrecan proteolysis between 6 h and 16 days, release of sulfated glycosaminoglycans and specific proteolytic aggrecan fragments into medium or remaining in cartilage explants was measured by dimethylmethylene blue and Western blot analysis.
RESULTS
Aggrecanase activity toward aggrecan was observed in all conditions, but it was directed toward the TEGE↓ARGS interglobular domain (IGD) site only when cartilage was coincubated with SJC or TNF-α. Matrix metalloproteinase (MMP) activity at the aggrecan IGD site (IPES↓FFGV) was not detected when cartilage was exposed to TNF-α (up to 6 days), but it was in all other conditions. Compared with when bovine cartilage was left untreated or subjected to mechanical injury alone, additional aggrecan fragment types were released into medium and proteolysis of aggrecan started at an earlier time when SJC was present.
CONCLUSIONS
Indicative of different proteolytic pathways for aggrecan degradation, the SJC increases both aggrecanase and MMP activity toward aggrecan, whereas TNF-α inhibits MMP activity against the IGD of aggrecan.
Topics: Animals; Cartilage, Articular; Cattle; Coculture Techniques; Endopeptidases; Joint Capsule; Matrix Metalloproteinases; Organ Culture Techniques; Osteoarthritis; Synovial Membrane
PubMed: 28679445
DOI: 10.1186/s13075-017-1318-9 -
Clinical Rheumatology Sep 2021Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not been completely elucidated yet. Extracellular vesicles (EVs) are membrane-contained vesicles released by cells playing a role in cell-to-cell communication and they could be involved in different diseases. Evidence on the involvement of EVs in RA is currently inconclusive. Therefore, a systematic review on the role of EVs in RA was performed in order to explore this relationship. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research was conducted on PubMed, Scopus, and Embase up to March 5, 2020: 41 studies were analyzed out of 674 screened. The total plasmatic and synovial fluid (SF) EV number seems increased in RA as compared with healthy controls. Both RA plasma and SF contained EVs subpopulations of heterogenous origin, especially derived from platelets and immune system cells. No univocal evidence emerged on miRNA expression and EV content profile within RA patients. EVs showed to enhance pro-inflammatory pathways, such as cytokines and chemokine release and TNF blockade seemed to revert this effect. Our work highlights the requirement to standardize study methodologies in order to make results comparable and draw conclusions that remain, at present, unclear.
Topics: Arthritis, Rheumatoid; Blood Platelets; Extracellular Vesicles; Humans; MicroRNAs; Synovial Fluid
PubMed: 33544235
DOI: 10.1007/s10067-021-05614-w -
AJR. American Journal of Roentgenology Mar 2022Synovitis, inflammation of the synovial membrane, is a common manifestation of osteoarthritis (OA) and is recognized to play a role in the complex pathophysiology of OA.... (Review)
Review
Synovitis, inflammation of the synovial membrane, is a common manifestation of osteoarthritis (OA) and is recognized to play a role in the complex pathophysiology of OA. Increased recognition of the importance of synovitis in the OA disease process and its potential as a target for treatment has increased the need for noninvasive detection and characterization of synovitis using medical imaging. Numerous imaging methods can assess synovitis involvement in OA with varying sensitivity, specificity, and complexity. This article reviews the role of contrast-enhanced MRI, conventional MRI, novel unenhanced MRI, gray-scale ultrasound (US), and power Doppler US in the assessment of synovitis in patients with OA. The role of imaging in disease evaluation and the challenges of conventional imaging methods are discussed. We also provide an overview of the potential utility of emerging techniques for imaging of early inflammation and molecular inflammatory markers of synovitis, including quantitative MRI, superb microvascular imaging, and PET. The development of therapeutic treatments targeting inflammatory features, particularly in early OA, would greatly increase the importance of these imaging methods for clinical decision-making and evaluation of therapeutic efficacy.
Topics: Diagnostic Imaging; Humans; Inflammation; Osteoarthritis; Synovial Membrane
PubMed: 34286595
DOI: 10.2214/AJR.21.26170 -
Scientific Reports Jul 2022B cells play a significant role in established Rheumatoid Arthritis (RA). However, it is unclear to what extent differentiated B cells are present in joint tissue...
B cells play a significant role in established Rheumatoid Arthritis (RA). However, it is unclear to what extent differentiated B cells are present in joint tissue already at the onset of disease. Here, we studied synovial biopsies (n = 8) captured from untreated patients at time of diagnosis. 3414 index-sorted B cells underwent RNA sequencing and paired tissue pieces were subjected to spatial transcriptomics (n = 4). We performed extensive bioinformatics analyses to dissect the local B cell composition. Select plasma cell immunoglobulin sequences were expressed as monoclonal antibodies and tested by ELISA. Memory and plasma cells were found irrespective of autoantibody status of the patients. Double negative memory B cells were prominent, but did not display a distinct transcriptional profile. The tissue architecture implicate both local B cell maturation via T cell help and plasma cell survival niches with a strong CXCL12-CXCR4 axis. The immunoglobulin sequence analyses revealed clonality between the memory B and plasma cell pools further supporting local maturation. One of the plasma cell-derived antibodies displayed citrulline autoreactivity, demonstrating local autoreactive plasma cell differentiation in joint biopsies captured from untreated early RA. Hence, plasma cell niches are not a consequence of chronic inflammation, but are already present at the time of diagnosis.
Topics: Arthritis, Rheumatoid; Autoantibodies; Cell Differentiation; Humans; Synovial Membrane; Transcriptome
PubMed: 35831338
DOI: 10.1038/s41598-022-15293-5 -
Frontiers in Immunology 2024
Topics: Arthritis, Rheumatoid; Humans; Fibroblasts; Synoviocytes; Immunomodulation; Animals; Synovial Membrane
PubMed: 38779670
DOI: 10.3389/fimmu.2024.1415672 -
Stem Cell Research & Therapy Sep 2023Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified...
BACKGROUND
Synovial fluid mesenchymal stem cells (SF-MSCs) originate in the synovium and contribute to the endogenous repair of damaged intra-articular tissues. Here, we clarified the relationship between their numbers and joint structural changes during osteoarthritis (OA) progression and investigated whether SF-MSCs had phenotypes favorable for tissue repair, even in an OA environment.
METHODS
Partial medial meniscectomy (pMx) and sham surgery were performed on both knees of rats. SF and knee joints were collected from intact rats and from rats at 2, 4, and 6 weeks after surgery. SF was cultured for 1 week to calculate the numbers of colony-forming cells and colony areas. Joint structural changes were evaluated histologically to investigate their correlation with the numbers and areas of colonies. RNA sequencing was performed for SF-MSCs from intact knees and knees 4 weeks after the pMx and sham surgery.
RESULTS
Colony-forming cell numbers and colony areas were greater in the pMx group than in the intact and sham groups and peaked at 2 and 4 weeks, respectively. Synovitis scores showed the strongest correlation with colony numbers (R = 0.583) and areas (R = 0.456). RNA sequencing revealed higher expression of genes related to extracellular matrix binding, TGF-β signaling, and superoxide dismutase activity in SF-MSCs in the pMx group than in the sham group.
CONCLUSION
The number of SF-MSCs was most closely correlated with the severity of synovitis in this rat OA model. Tissue-reparative gene expression patterns were observed in SF-MSCs from OA knees, but not from knees without intra-articular tissue damage.
Topics: Animals; Rats; Synovial Fluid; Synovitis; Mesenchymal Stem Cells; Osteoarthritis; Phenotype
PubMed: 37679780
DOI: 10.1186/s13287-023-03487-1 -
Orthopaedics & Traumatology, Surgery &... Dec 2019During the surgical treatment of terrible triad elbow injury (TTEI), the usefulness of re-attaching the anterior joint capsule when the coronoid tip is fractured remains...
BACKGROUND
During the surgical treatment of terrible triad elbow injury (TTEI), the usefulness of re-attaching the anterior joint capsule when the coronoid tip is fractured remains unclear. The primary objective of this study was to assess potential benefits during surgery for TTEI of re-attaching the joint capsule when the coronoid tip is fractured.
HYPOTHESIS
Re-attaching the anterior joint capsule in TTEI with a fractured coronoid tip improves clinical and radiological outcomes and decreases the complication and revision rates.
MATERIALS AND METHODS
This single-centre retrospective study included patients who underwent surgery at the acute phase of TTEI with a fractured coronoid tip. In all patients, a physical examination and elbow radiographs were performed at least 1year after surgery. A statistical analysis was done to compare the groups with vs. without re-attachment of the anterior capsule and coronoid tip.
RESULTS
The study included 30 patients, 16 females and 14 males, with a mean age of 51years (range: 21-84years). Among them, 11 did and 19 did not undergo re-attachment. The two groups were comparable regarding demographic features and follow-up duration. No significant differences were found at last follow-up for flexion-extension motion arc (p=0.75), pronation-supination motion arc (p=0.3051), or the Mayo Elbow Performance Score (p=0.19). Radiographic evidence of humero-radial osteoarthritis was significantly more common in the absence of re-attachment (p=0.04), whereas no differences were evidenced regarding humero-ulnar osteoarthritis (p=0.73), the occurrence of subluxation or dislocation (p=0.43), or loosening of the radial head implant (p=0.47). The complication and revision rates were similar in the two groups.
CONCLUSION
In our experience, re-attaching the anterior capsule during the surgical treatment of TTEI with a coronoid tip fracture did not improve the clinical or radiographic outcomes after a mean follow-up of 54months.
LEVEL OF EVIDENCE
IV, retrospective study.
Topics: Adult; Aged; Aged, 80 and over; Arm Injuries; Elbow Joint; Female; Follow-Up Studies; Fracture Fixation, Internal; Humans; Joint Capsule; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Ulna Fractures; Young Adult; Elbow Injuries
PubMed: 31732394
DOI: 10.1016/j.otsr.2019.09.024 -
Journal of Orthopaedic Surgery (Hong... 2020The purpose of this study was to investigate the relationship between the superior capsule tear patterns and synovitis with subacromial pathologies, such as bursal-sided...
PURPOSE
The purpose of this study was to investigate the relationship between the superior capsule tear patterns and synovitis with subacromial pathologies, such as bursal-sided rotator cuff tear and subacromial impingement syndrome.
METHODS
Fifty patients who underwent arthroscopic treatment for isolated bursal-sided tear were included in the study. Fifty more patients who underwent arthroscopic treatment for isolated Superior Labrum Anterior Posterior (SLAP) 2 lesion without pathology in the rotator cuff were included in the control group. Firstly, superior capsule tear and common synovitis on the rotator cable were assessed during glenohumeral joint examination. Coracoacromial Ligament (CAL) degeneration grading was performed according to the Royal Berkshire Hospital classification. Bursal-sided partial tear grading was done using Ellman classification. Whether or not there was a relationship between synovitis, classic capsule tear, plus reverse flap capsule tear, and partial bursal-sided tear existence.
RESULTS
There were 21 patients with reverse flap capsule tear in the study group and 3 patients in the control group. In addition, there were 13 patients with synovitis in the study group and 4 in the control group. Compared to the control group, there was also a significant positive correlation in the presence of both synovitis and reverse flap capsule tear with the presence of bursal-sided tear in the study group ( = 0.000). There was, however, no significant difference between the presence of classical capsule tear and the presence of bursal-sided tear ( = 0.485).
CONCLUSION
This study shows that the presence of reverse flap capsule tear and synovitis was associated with partial bursal-sided tears. Therefore, if the reverse flap capsule tear or synovitis is detected in the superior capsule, the rotator cuff should be evaluated in more detail during subacromial bursoscopy in order not to miss a bursal-sided partial cuff tear.
Topics: Adult; Arthroscopy; Female; Humans; Joint Capsule; Male; Middle Aged; Rotator Cuff; Rotator Cuff Injuries; Rupture; Shoulder Joint
PubMed: 31934819
DOI: 10.1177/2309499019895153 -
Frontiers in Immunology 2022Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and...
PURPOSE
Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and synovial microvascular pathology have not been established. Since complement causes vascular pathology in other diseases and since sex-differences exist in complement activation and in OA, we investigated sex differences in synovial fluid complement factors, synovial tissue vascular pathology, and associations between complement and synovial vascular pathology in patients with late-stage knee OA.
METHODS
Patients with symptomatic, late-stage radiographic knee OA undergoing total knee arthroplasty or high tibial osteotomy provided matched synovial fluid and tissue biopsies during surgery. Complement factors (C2, C5, adipsin, MBL, and CFI) and terminal complement complex (sC5b-C9) were measured in synovial fluid by multiplex or enzyme-linked immunosorbent assay, respectively. Features of synovial vascular pathology (vascularization, perivascular edema, and vasculopathy) were assessed by histopathology. Multivariate linear regression models were used to assess associations between synovial fluid complement factors and histopathological features of vascular pathology, with adjustment for age, sex, body mass index, and sex interaction. Sex-disaggregated comparisons were completed.
RESULTS
Synovial fluid biomarker and histopathology data were included from 97 patients. Most synovial fluid complement factors and synovial tissue histopathological features were similar between sexes. Synovial fluid C5 trended to lower levels in males (-20.93 ng/mL [95%CI -42.08, 0.23] 0.05). Median vasculopathy scores (0.42 [95%CI 0.07, 0.77] 0.02) were higher in males. In the full cohort, C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.010, -0.0001] 0.04) while accounting for sex*C5 interaction. In sex-disaggregated analyses, increased C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.009, -0.0001] 0.04) in male patients, but not in female patients. Males had higher sC5b-C9 compared to females. Additionally, males with high C5 had a higher synovial fluid concentration of sC5b-C9 compared to males with low C5. No differences were found in females.
CONCLUSION
Higher synovial fluid C5 levels were associated with increased complement activation and decreased synovial vascularization in males but not in females with OA. Future studies should test whether synovial fluid complement activation suppresses synovial angiogenesis and identify mechanisms accounting for C5-related sex-differences in synovial fluid complement activation in patients with knee OA.
Topics: Complement Activation; Female; Humans; Male; Osteoarthritis, Knee; Sex Characteristics; Synovial Fluid; Synovial Membrane
PubMed: 35686134
DOI: 10.3389/fimmu.2022.890094