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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 -
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... Mar 2022Lipoma arborescens (LA) is a rare benign synovial tumour characterized by the proliferation of mature adipocytes within the synovial cells. Given its rarity, current... (Review)
Review
BACKGROUND
Lipoma arborescens (LA) is a rare benign synovial tumour characterized by the proliferation of mature adipocytes within the synovial cells. Given its rarity, current evidence is mainly based on case reports and case series, and no guidelines are available. The present study investigated the current surgical management and related outcomes of LA in the upper limb.
METHODS
This systematic review was conducted following the PRISMA guidelines. PubMed, Scopus, and Virtual Health Library were accessed in September 2021. Clinical studies evaluating patients with LA undergoing surgical treatment were considered eligible for this systematic review. Only studies which reported data on LA located in the upper limb with histopathological confirmation were considered. Articles that reported data from nonsurgical management were not considered.
RESULTS
A total of 21 studies reporting 22 lesions in 21 patients were assessed. The mean age of the patients was 48.48 years (range 22-77). Most studies evaluated the restoration of range of motion and symptom resolution for the functional outcome assessment. Open or arthroscopic excision and synovectomy were the most common surgical procedures for LA. The concomitant lesions were treated in a single-stage procedure. All patients had satisfactory outcomes after open or arthroscopic excision and synovectomy without recurrence at a mean follow-up of 21.14 months (range 2-60). One patient developed postoperative cellulitis (4.55%).
CONCLUSION
Open and arthroscopic excision combined with synovectomy should be considered the standard treatment option of upper limb LA. Concomitant pathologies can be addressed in a one-stage procedure. Although LA was recognized as a clinical entity decades ago, there is a lack of evidence based guidelines and long term outcome data are unavailable.
Topics: Adult; Aged; Arthroscopy; Humans; Knee Joint; Lipoma; Middle Aged; Soft Tissue Neoplasms; Synovectomy; Synovial Membrane; Treatment Outcome; Young Adult
PubMed: 35246183
DOI: 10.1186/s13018-022-02997-7 -
Seminars in Arthritis and Rheumatism Apr 2023Osteoarthritis (OA) is a joint disease that is clinically diagnosed using components of history, physical exam, and characteristic radiographic findings, such as joint... (Review)
Review
PURPOSE
Osteoarthritis (OA) is a joint disease that is clinically diagnosed using components of history, physical exam, and characteristic radiographic findings, such as joint space narrowing. Currently, there are no laboratory findings that are specific to a diagnosis of OA. The purpose of this systematic review is to evaluate the state of current studies of metabolomic biomarkers that can aid in the diagnosis and treatment of OA.
METHODS
Articles were gathered from PubMed and Web of Science using the search terms "osteoarthritis" and "biomarkers" and "metabolomics". Last search of databases took place December 3rd, 2022. Duplicates were manually screened, along with any other results that were not original journal articles. Only original reports involving populations with diagnosed primary or secondary OA (human participants) or surgically induced OA (animal participants) and a healthy control group for comparison were considered for inclusion. Metabolites and metabolic pathways reported in included articles were then manually extracted and evaluated for importance based on reported a priori p-values and/or area under the receiver-operator curve (AUC).
RESULTS
Of the 161 results that were returned in the database searches, 43 unique articles met the inclusion criteria. Articles were categorized based on body fluid analyzed: 6 studies on urine samples, 13 studies on plasma samples, 11 studies on synovial fluid (SF) samples, 11 studies on serum samples, 1 study on both synovial fluid and serum, and 1 study that involved both plasma and synovial fluid. To synthesize results, individual metabolites, as well as metabolic pathways that involve frequently reported metabolites, are presented for each study. Indications as to whether metabolite levels were increased or decreased are also included if this data was included in the original articles.
CONCLUSIONS
These studies clearly show that there are a wide range of metabolic pathways perturbed in OA. For this period, there was no consensus on a single metabolite, or panel of metabolites, that would be clinically useful in early diagnosis of OA or distinguishing OA from a healthy control. However, many common metabolic pathways were identified in the studies, including TCA cycle, fatty acid metabolism, amino acid metabolism (notably BCAA metabolism and tryptophan metabolism via kynurenine pathway), nucleotide metabolism, urea cycle, cartilage matrix components, and phospholipid metabolism. Future research is needed to define effective clinical biomarkers of osteoarthritis from metabolomic and other data.
Topics: Animals; Humans; Osteoarthritis; Metabolomics; Biomarkers; Synovial Fluid; Metabolic Networks and Pathways
PubMed: 36736024
DOI: 10.1016/j.semarthrit.2023.152163 -
The Bone & Joint Journal Jan 2018α-defensin is a biomarker which has been described as having a high degree of accuracy in the diagnosis of periprosthetic joint infection (PJI). Current meta-analyses... (Meta-Analysis)
Meta-Analysis Review
AIMS
α-defensin is a biomarker which has been described as having a high degree of accuracy in the diagnosis of periprosthetic joint infection (PJI). Current meta-analyses are based on the α-defensin laboratory-based immunoassay rather than the quick on-table lateral flow test kit. This study is the first meta-analysis to compare the accuracy of the α-defensin laboratory-based immunoassay and the lateral flow test kit for the diagnosis of PJI.
MATERIALS AND METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were all clinical studies where the diagnosis of PJI was uncertain. All studies selected used the Musculoskeletal Infection Society (MSIS) or modified MSIS criteria. Two independent reviewers reviewed the studies and extracted data. A meta-analysis of results was carried out: pooled sensitivity, specificity, positive and negative likelihood ratio, heterogeneity and areas under curves are reported.
RESULTS
Ten studies (759 patients) were included. Of these, seven studies (640 patients) evaluated the laboratory-based α-defensin immunoassay and three (119 patients) the lateral flow test. The pooled sensitivity and specificity of the qualitative α-defensin laboratory immunoassay was 0.953 (95% confidence interval (CI) 0.87 to 0.984) and 0.965 (95% CI 0.943 to 0.979) respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 34.86 (95% CI 19.34 to 62.85) and 0.02 (95% CI 0.00 to 0.11). The pooled sensitivity and specificity of the lateral flow test were 0.774 (95% CI 0.637 to 0.870) and 0.913 (95% CI 0.828 to 0.958), respectively. The pooled PLR and NLR were 8.675 (95% CI 4.229 to 17.794) and 0.248 (95% CI 0.147 to 0.418), respectively.
CONCLUSION
The pooled sensitivity and specificity of the lateral flow test were lower than those of the α-defensin laboratory-based immunoassay test. Hence, care must be taken with interpretation of the lateral flow test when relying on its results for the intra-operative diagnosis of PJI. Cite this article: 2018;100-B:66-72.
Topics: Biomarkers; Humans; Immunoassay; Joint Prosthesis; Prosthesis Failure; Prosthesis-Related Infections; Reagent Kits, Diagnostic; Reoperation; Sensitivity and Specificity; Synovial Fluid; alpha-Defensins
PubMed: 29305453
DOI: 10.1302/0301-620X.100B1.BJJ-2017-0630.R1 -
European Review For Medical and... Jun 2017Osteoarthritis (OA) is the most common joint disease, and in recent years has become a major public health problem. The hallmark of OA is cartilage destruction with... (Review)
Review
Osteoarthritis (OA) is the most common joint disease, and in recent years has become a major public health problem. The hallmark of OA is cartilage destruction with local commitment of subchondral bone and the synovial membrane. Hypoxia-inducible factors (HIFs) are transcriptional factors and key regulators of the cellular response to hypoxia. To date, three members of the human HIF-α protein family have been described: HIF-1α, HIF-2α, and HIF-3α. HIF-1α plays an essential role in the articular cartilage (a hypoxic tissue), as it has a protective effect in the maintenance of the articular cartilage matrix, HIF-2α has a harmful effect on the articular cartilage matrix, and HIF-3α acts as a negative regulator of HIF-1α and HIF-2α. Due to the recent growing interest in the role of HIFs in rheumatic diseases, we focused this review on the potential role of these key regulators in articular cartilage maintenance as the central axis in OA development.
Topics: Basic Helix-Loop-Helix Transcription Factors; Cartilage, Articular; Cell Hypoxia; Chondrocytes; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Osteoarthritis
PubMed: 28682438
DOI: No ID Found -
Osteoarthritis and Cartilage Aug 2022Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including... (Review)
Review
OBJECTIVE
Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions.
METHOD
PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and Quality Assessment of Diagnostic Accuracy Score 2 (QUADAS-2) analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared.
RESULTS
9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies.
CONCLUSION
This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context.
REGISTRATION NUMBER
PROSPERO CRD42022304298. Study protocol available on PROSPERO website.
Topics: Biomarkers; Cartilage, Articular; Humans; Knee Joint; Osteoarthritis; Osteoarthritis, Knee; Synovial Fluid
PubMed: 35618204
DOI: 10.1016/j.joca.2022.05.007 -
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 -
Knee Surgery, Sports Traumatology,... Aug 2023Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by... (Review)
Review
Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 2: bone marrow-derived cell-based injectable therapies.
PURPOSE
Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models.
METHODS
A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool.
RESULTS
Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%.
CONCLUSION
This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice.
LEVEL OF EVIDENCE
II.
Topics: Animals; Bone Marrow; Osteoarthritis; Synovial Membrane; Disease Models, Animal; Injections, Intra-Articular; Mesenchymal Stem Cell Transplantation; Osteoarthritis, Knee
PubMed: 36823238
DOI: 10.1007/s00167-023-07320-3 -
Musculoskeletal Surgery Jun 2024Pigmented Villonodular Synovitis (PVNS) is a proliferative disease arising from the synovial membrane, mainly affects large joints such as the knee (almost 80% of... (Review)
Review
PURPOSE
Pigmented Villonodular Synovitis (PVNS) is a proliferative disease arising from the synovial membrane, mainly affects large joints such as the knee (almost 80% of total). Prostheses implanted in PVNS osteoarthritis show a higher revision rate when compared to primary osteoarthritis, due to the recurrence of disease and the overall surgical complications. The purpose of this systematic review is to summarize and compare indications, clinical and functional outcomes, disease-related and surgical-related complications of total knee arthroplasty in PVNS osteoarthritis.
MATERIALS AND METHODS
A systematic review of the literature was performed with a primary search on Medline through PubMed. The PRISMA 2009 flowchart and checklist were used to edit the review. Screened studies had to provide preoperative diagnosis, previous treatments, main treatment, concomitant strategies, mean follow-up, outcomes and complications to be included in the review.
RESULTS
A total of 8 articles were finally included. Most of papers reported the use of non-constrained design implants, mainly posterior stabilized (PS) and in case of PVNS with extensive joint involvement implants with higher degree of constraint to obtain a fulfilling balancing. Recurrence of PVNS has been indicated as the major complication, followed by aseptic loosening of the implant and difficult post-operative course with an increased risk of stiffness.
CONCLUSION
Total knee arthroplasty represents a valid treatment for patients with PVNS end-stage osteoarthritis, with good clinical and functional results, even in longer follow-up. It would be advisable a multidisciplinary management and a meticulous rehabilitation and monitoring following the procedure, to reduce the emergence of recurrence and overall complications.
Topics: Humans; Synovitis, Pigmented Villonodular; Arthroplasty, Replacement, Knee; Osteoarthritis, Knee; Treatment Outcome; Knee Prosthesis; Postoperative Complications
PubMed: 37338752
DOI: 10.1007/s12306-023-00793-y