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RMD Open Feb 2022The aim of this work was to summarise the literature evaluating the impact of biopsy procedures, tissue handling, tissue quality and disease-specific aspects including...
Impact of synovial biopsy procedures and disease-specific aspects on synovial tissue outcome: a systematic literature review informing the EULAR points to consider for the minimal reporting requirements in synovial tissue research in rheumatology.
BACKGROUND
The aim of this work was to summarise the literature evaluating the impact of biopsy procedures, tissue handling, tissue quality and disease-specific aspects including joint biopsied and disease stage, on synovial tissue outcome.
METHODS
Two reviewers independently identified eligible studies according to the Patients, Intervention, Comparator and Outcome framework obtained for five research questions formulated during the first EULAR task force meeting to produce points to consider (PtC) for minimal reporting requirements in synovial tissue studies. The databases explored were Medline, Embase, CENTRAL and Cinhal. The risk of bias of each study was evaluated using an adapted version of the Joanna Briggs Institute checklist for analytical cross-sectional studies.
RESULTS
Of the 7654 records yielded, 75 full texts were assessed, leading to the inclusion of 26 manuscripts in the systematic literature review (SLR). Two papers assessed the impact of biopsy procedures on the quality and quantity of tissue retrieved alongside patient tolerability; six papers focused on synovial tissue variability. Four papers studied the impact of sample handling or randomisation and 14 assessed the impact of disease stage and state, namely early or established active rheumatoid arthritis and remission on histopathological and transcriptomic results.
CONCLUSIONS
This SLR informs the EULAR PtC for minimal reporting requirements in synovial tissue research in rheumatology. Characteristics related to the study design, population, sample handling, randomisation and analysis can affect the final synovial tissue outcome in the studies reviewed. Thus, accurate reporting of these factors is required in order to ensure the scientific validity of manuscripts describing synovial tissue outcomes.
Topics: Arthritis, Rheumatoid; Biopsy; Cross-Sectional Studies; Humans; Rheumatology; Synovial Membrane
PubMed: 35177556
DOI: 10.1136/rmdopen-2021-002116 -
Journal of Orthopaedic Surgery and... Oct 2021Periprosthetic joint infection is a grievous complication after arthroplasty that greatly affects the quality of life of patients. Rapid establishment of infection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periprosthetic joint infection is a grievous complication after arthroplasty that greatly affects the quality of life of patients. Rapid establishment of infection diagnosis is essential, but great challenges still exist.
METHODS
We conducted research in the PubMed, Embase, and Cochrane databases to evaluate the diagnostic accuracy of D-lactate for PJI. Data extraction and quality assessment were completed independently by two reviewers. The pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), summarized receiver operating characteristic curve (sROC), and area under the sROC curve (AUC) were constructed using the bivariate meta-analysis framework.
RESULTS
Five eligible studies were included in the quantitative analysis. The pooled sensitivity and specificity of D-lactate for the diagnosis of PJI were 0.82 (95% CI 0.70-0.89) and 0.76 (95% CI 0.69-0.82), respectively. The value of the pooled diagnostic odds ratio (DOR) of D-lactate for PJI was 14.18 (95% CI 6.17-32.58), and the area under the curve (AUC) was 0.84 (95% CI 0.80-0.87).
CONCLUSIONS
According to the results of our meta-analysis, D-lactate is a valuable synovial fluid marker for recognizing PJI, with high sensitivity and specificity.
Topics: Arthritis, Infectious; Biomarkers; Humans; Lactic Acid; Prosthesis-Related Infections; Quality of Life; Synovial Fluid
PubMed: 34656157
DOI: 10.1186/s13018-021-02778-8 -
Cells Apr 2021Intra-articular fractures are a major cause of post-traumatic osteoarthritis (PTOA). Despite adequate surgical treatment, the long-term risk for PTOA is high. Previous...
Intra-articular fractures are a major cause of post-traumatic osteoarthritis (PTOA). Despite adequate surgical treatment, the long-term risk for PTOA is high. Previous studies reported that joint injuries initiate an inflammatory cascade characterized by an elevation of synovial pro-inflammatory cytokines, which can lead to cartilage degradation and PTOA development. This review summarizes the literature on the post-injury regulation of pro-inflammatory cytokines and the markers of cartilage destruction in patients suffering from intra-articular fractures. We searched Medline, Embase, and Cochrane databases (1960-February 2020) and included studies that were performed on human participants, and we included control groups. Two investigators assessed the quality of the included studies using Covidence and the Newcastle-Ottawa Scale. Based on the surveyed literature, several synovial pro-inflammatory cytokines, including interleukins (IL)-1β, IL-2, IL-6, IL-8, IL-12p70, interferon-y, and tumor necrosis factor-α, were significantly elevated in patients suffering from intra-articular fractures compared to the control groups. A simultaneous elevation of anti-inflammatory cytokines such as IL-10 and IL-1RA was also observed. In contrast, IL-13, CTX-II, and aggrecan concentrations did not differ significantly between the compared cohorts. Overall, intra-articular fractures are associated with an increase in inflammation-related synovial cytokines. However, more standardized studies which focus on the ratio of pro- and anti-inflammatory cytokines at different time points are needed.
Topics: Case-Control Studies; Cytokines; Humans; Inflammation Mediators; Intra-Articular Fractures; Joints; Synovial Fluid
PubMed: 33919965
DOI: 10.3390/cells10040902 -
Arthritis Research & Therapy Apr 2021Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among... (Review)
Review
OBJECTIVE
Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among inflammatory cells involved, macrophages play a crucial role and are mediated by the local microenvironment to exhibit different phenotypes and polarization states. Therefore, we conducted a systematic review to uncover the phenotypic alterations of macrophages during OA and summarized the potential therapeutic interventions via modulating macrophages.
METHODS
A systematic review of multiple databases (PubMed, Web of Science, ScienceDirect, Medline) was performed up to February 29, 2020. Included articles were discussed and evaluated by two independent reviewers. Relevant information was analyzed with a standardized and well-designed template.
RESULTS
A total of 28 studies were included. Results were subcategorized into two sections depending on sources from human tissue/cell-based studies (12 studies) and animal experiments (16 studies). The overall observation indicated that M1 macrophages elevated in both synovium and circulation during OA development, along with lower numbers of M2 macrophages. The detailed alterations of macrophages in both synovium and circulation were listed and analyzed. Furthermore, interventions against OA via regulating macrophages in animal models were highlighted.
CONCLUSION
This study emphasized the importance of the phenotypic alterations of macrophages in OA development. The classical phenotypic subcategory of M1 and M2 macrophages was questionable due to controversial and conflicting results. Therefore, further efforts are needed to categorize macrophages in an exhaustive manner and to use advanced technologies to identify the individual roles of each subtype of macrophages in OA.
Topics: Animals; Humans; Inflammation; Macrophages; Osteoarthritis; Phenotype; Synovial Membrane
PubMed: 33838669
DOI: 10.1186/s13075-021-02457-3 -
Arthritis Research & Therapy Feb 2021Bisphosphonates have been proposed as possible disease-modifying drugs in osteoarthritis. However, the evidence of their efficacy is poor and their outcomes presented a... (Review)
Review
Bisphosphonates have been proposed as possible disease-modifying drugs in osteoarthritis. However, the evidence of their efficacy is poor and their outcomes presented a great heterogeneity. Therefore, the aim of this study is to systematically review the main effects of bisphosphonate use on synovial joint tissues and biochemical markers in preclinical studies over the past two decades (2000-2020). Three databases (Pubmed, Scopus, and Web of Science) were searched, and after screening, twenty-six studies with five different types of bisphosphonates were included in the review. The animal model selected, the type of bisphosphonate used, the therapy duration, and the main effects of individual drugs on synovial tissues were evaluated. Additionally, the quality and risk of bias assessments were performed using the Animals in Research Reporting In Vivo Experiments guidelines and the Systematic Review Centre for Laboratory animal Experimentation tool. Studies showed high variability in experimental designs. Consequently, the comparison of the findings in order to draw specific conclusions about the effectiveness of the drugs is complicated. However, the results of this systematic review suggested that bisphosphonates seemed to reduce the osteoarthritic changes in a dose-dependent manner showing better chondroprotective effects at high doses. Besides, a time-dependent efficacy was also detected in terms of cartilage status. One can conclude that the disease stage of the time-point of treatment initiation may constitute a key factor in the antiresorptive drug efficacy. Generally, we noted that bisphosphonate administration seemed to show positive subchondral bone conservation and fewer biomarker alterations. However, they did not appear to suppress the osteophyte development and their chondroprotective effect is highly variable among the studies. Bisphosphonates appeared to show a positive anti-inflammatory effect on the synovial membrane. However, only a few included publications were focused on their investigation. Regarding the therapy duration, there is a significant lack of evidence on evaluating their effectiveness in preclinical long-term studies and further experimental studies may be needed to examine the pharmacological response in these circumstances. This systematic review might help to clarify the efficacy of bisphosphonates and their function as disease-modifying treatments in osteoarthritis.
Topics: Animals; Bone Density Conservation Agents; Diphosphonates; Osteoarthritis; Osteophyte; Pharmaceutical Preparations
PubMed: 33618776
DOI: 10.1186/s13075-021-02446-6 -
Osteoarthritis and Cartilage May 2021To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals... (Comparative Study)
Comparative Study Meta-Analysis
The diagnostic value of conventional radiography and musculoskeletal ultrasonography in calcium pyrophosphate deposition disease: a systematic literature review and meta-analysis.
OBJECTIVE
To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals deposition disease (CPPD).
DESIGN
A systematic search of electronic databases (PubMed, Embase, and Cochrane), conference abstracts and reference lists was undertaken. Studies which evaluated the accuracy of CR and/or US in the diagnosis of CPPD, using synovial fluid analysis (SFA), histology or classification criteria as reference tests were included. Subgroup analyses by anatomic site and by reference test were performed.
RESULTS
Twenty-six studies were included. Using SFA/histology as reference test, CR and US showed an excellent (CR AUC = 0.889, 95%CI = 0.811-0.967) and an outstanding (US AUC = 0.954, 95%CI = 0.907-1.0) diagnostic accuracy (p < 0.01), respectively. Furthermore, US showed a higher sensitivity (0.85, 95%CI = 0.79-0.90 vs 0.47, 95%CI = 0.40-0.55) and only a little lower specificity (0.87, 95%CI = 0.83-0.91 vs 0.95, 95%CI = 0.92-0.97) than CR. A considerable heterogeneity between the studies was found, with adopted reference test being the main source of heterogeneity. In fact, subgroup analysis showed a significant change in the diagnostic accuracy of CR, but not of US, using Ryan and McCarty criteria or SFA/histology as reference test (CR: AUC = 0.956, 95%CI = 0.925-1.0 vs AUC = 0.889, 95%CI = 0.828-0.950, respectively, p < 0.01) (US: AUC = 0.922, 95%CI = 0.842-1.0 vs AUC = 0.957, 95%CI = 0.865-1.0, respectively, p = 0.08) CONCLUSIONS: Although US is more sensitive and a little less specific than CR for identifying CPP crystals, both these two techniques showed a great diagnostic accuracy and should be regarded as complementary to each other in the diagnostic work-up of patients with CPPD.
Topics: Calcium Pyrophosphate; Chondrocalcinosis; Fascia; Humans; Joints; Ligaments, Articular; Muscle, Skeletal; Radiography; Sensitivity and Specificity; Synovial Fluid; Tendons; Ultrasonography
PubMed: 33577959
DOI: 10.1016/j.joca.2021.01.007 -
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 -
Journal of Orthopaedic Surgery (Hong... 2020Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is its difficulty in diagnosis. This systematic review and meta-analysis aimed to compare the diagnostic accuracy of -defensin, D-dimer, and interleukin-6 (IL-6) in clinical practice.
METHOD
Online databases were systematically searched until June 18th, 2020 with keywords and medical sub-headings terms. Studies mentioned the sensitivity and specificity of biological markers in detecting PJI were included in our study. The sensitivity, specificity, and diagnostic odds ratios (DORs) were obtained after integration.
RESULTS
A total of 34 studies with 1036 patients diagnosing as PJI were included for comparing -defensin, D-dimer, and IL-6. The sensitivity and specificity of -defensin for PJI were 0.88 and 0.96, and the DOR was 189 (95% CI 72-496), respectively. The sensitivity and specificity of D-dimer (0.82 and 0.72) and IL-6 (0.80 and 0.89) were lower than -defensin.
CONCLUSION
The detection of -defensin is a promising biomarker for diagnosing PJI. The optional cut-off needs to be curtained when using other biomarkers.
Topics: Biomarkers; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Prosthesis-Related Infections; Synovial Fluid; alpha-Defensins
PubMed: 33225796
DOI: 10.1177/2309499020971861 -
Cartilage Dec 2021The aim of this systematic review was to analyze the evidence about the efficacy of the several synovial fluid (SF) biomarkers proposed for knee osteoarthritis (OA),...
OBJECTIVE
The aim of this systematic review was to analyze the evidence about the efficacy of the several synovial fluid (SF) biomarkers proposed for knee osteoarthritis (OA), categorizing them by both molecular characteristics and clinical use according to the BIPEDs criteria, to provide a comprehensive and structured overview of the current literature.
DESIGN
A systematic review was performed in May 2020 on PubMed, Cochrane Library, and Embase databases about SF biomarkers in patients with knee OA. The search was limited to articles in the last 20 years on human studies, involving patients with knee OA, reporting SF biomarkers. The evidence for each selected SF biomarker was quantified according to the 6 categories of BIPEDs classification.
RESULTS
A total of 159 articles were included in the qualitative data synthesis and 201 different SF biomarkers were identified. Among these, several were investigated multiple times in different articles, for a total of 373 analyses. The studies included 13,557 patients with knee OA. The most promising SF biomarkers were C4S, IL-6, IL-8, Leptin, MMP-1/3, TIMP-1, TNF-α, and VEGF. The "burden of disease" and "diagnostic" categories were the most represented with 132 and 106 different biomarkers, respectively.
CONCLUSIONS
The systematic review identified numerous SF biomarkers. However, despite the high number of studies on the plethora of identified molecules, the evidence about the efficacy of each biomarker is supported by limited and often conflicting findings. Further research efforts are needed to improve the understanding of SF biomarkers for a better management of patients with knee OA.
Topics: Biomarkers; Cytokines; Humans; Inflammation; Knee Injuries; Osteoarthritis, Knee; Synovial Fluid
PubMed: 32713185
DOI: 10.1177/1947603520942941 -
Cartilage Dec 2021Biomarkers in osteoarthritis (OA) could serve as objective clinical indicators for various disease parameters, and act as surrogate endpoints in clinical trials for...
OBJECTIVE
Biomarkers in osteoarthritis (OA) could serve as objective clinical indicators for various disease parameters, and act as surrogate endpoints in clinical trials for disease-modifying drugs. The aim of this systematic review was to produce a comprehensive list of candidate molecular biomarkers for knee OA after the 2013 ESCEO review and discern whether any have been studied in sufficient detail for use in clinical settings.
DESIGN
MEDLINE and Embase databases were searched between August 2013 and May 2018 using the keywords "knee osteoarthritis," "osteoarthritis," and "biomarker." Studies were screened by title, abstract, and full text. Human studies on knee OA that were published in the English language were included. Excluded were studies on genetic/imaging/cellular markers, studies on participants with secondary OA, and publications that were review/abstract-only. Study quality and bias were assessed. Statistically significant data regarding the relationship between a biomarker and a disease parameter were extracted.
RESULTS
A total of 80 studies were included in the final review and 89 statistically significant individual molecular biomarkers were identified. C-telopeptide of type II collagen (CTXII) was shown to predict progression of knee OA in urine and serum in multiple studies. Synovial fluid vascular endothelial growth factor concentration was reported by 2 studies to be predictive of knee OA progression.
CONCLUSION
Despite the clear need for biomarkers of OA, the lack of coordination in current research has led to incompatible results. As such, there is yet to be a suitable biomarker to be used in a clinical setting.
Topics: Biomarkers; Collagen Type I; Collagen Type II; Genetic Markers; Humans; Osteoarthritis, Knee; Peptides; Synovial Fluid; Vascular Endothelial Growth Factor A
PubMed: 32680434
DOI: 10.1177/1947603520941239