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Reumatologia Clinica Mar 2024Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis.
METHODS
We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472).
RESULTS
Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89-98; I=23%) and 88% (95% CI, 83-92; I=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92-0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity.
CONCLUSIONS
Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.
Topics: Humans; Adenosine Deaminase; Synovial Fluid; Sensitivity and Specificity; Tuberculosis, Osteoarticular; Arthritis
PubMed: 38494302
DOI: 10.1016/j.reumae.2024.02.002 -
Molecular & Cellular Proteomics : MCP Aug 2023Osteoarthritis (OA) is the most prevalent rheumatic pathology. However, OA is not simply a process of wear and tear affecting articular cartilage but rather a disease of...
Osteoarthritis (OA) is the most prevalent rheumatic pathology. However, OA is not simply a process of wear and tear affecting articular cartilage but rather a disease of the entire joint. One of the most common locations of OA is the knee. Knee tissues have been studied using molecular strategies, generating a large amount of complex data. As one of the goals of the Rheumatic and Autoimmune Diseases initiative of the Human Proteome Project, we applied a text-mining strategy to publicly available literature to collect relevant information and generate a systematically organized overview of the proteins most closely related to the different knee components. To this end, the PubPular literature-mining software was employed to identify protein-topic relationships and extract the most frequently cited proteins associated with the different knee joint components and OA. The text-mining approach searched over eight million articles in PubMed up to November 2022. Proteins associated with the six most representative knee components (articular cartilage, subchondral bone, synovial membrane, synovial fluid, meniscus, and cruciate ligament) were retrieved and ranked by their relevance to the tissue and OA. Gene ontology analyses showed the biological functions of these proteins. This study provided a systematic and prioritized description of knee-component proteins most frequently cited as associated with OA. The study also explored the relationship of these proteins to OA and identified the processes most relevant to proper knee function and OA pathophysiology.
Topics: Humans; Cartilage, Articular; Knee Joint; Osteoarthritis, Knee
PubMed: 37356495
DOI: 10.1016/j.mcpro.2023.100606 -
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 -
International Journal of Molecular... Mar 2023The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs... (Meta-Analysis)
Meta-Analysis Review
The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.
Topics: Humans; Arthritis, Psoriatic; Tumor Necrosis Factor Inhibitors; Antirheumatic Agents; Adalimumab; Biomarkers
PubMed: 36902437
DOI: 10.3390/ijms24055006 -
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 -
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 -
Cartilage Jun 2023Traumatic knee injury results in a 4- to 10-fold increased risk of post-traumatic osteoarthritis (PTOA). Currently, there are no successful interventions for preventing...
BACKGROUND
Traumatic knee injury results in a 4- to 10-fold increased risk of post-traumatic osteoarthritis (PTOA). Currently, there are no successful interventions for preventing PTOA after knee injury. The aim of this study is to identify inflammatory proteins that are increased in serum and synovial fluid after acute knee injury, excluding intra-articular fractures.
METHODS
A literature search was done according to the PRISMA guidelines. Articles reporting about inflammatory proteins after knee injury, except fractures, up to December 8, 2021 were collected. Inclusion criteria were as follows: patients younger than 45 years, no radiographic signs of knee osteoarthritis at baseline, and inflammatory protein measurement within 1 year after trauma. Risk of bias was assessed of the included studies. The level of evidence was determined by the Strength of Recommendation Taxonomy.
RESULTS
Ten studies were included. All included studies used a healthy control group or the contralateral knee as healthy control. Strong evidence for interleukin 6 (IL-6) and limited evidence for CCL4 show elevated concentrations of these proteins in synovial fluid (SF) after acute knee injury; no upregulation in SF for IL-2, IL-10, CCL3, CCL5, CCL11, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was found. Limited evidence was found for no difference in serum concentration of IL-1β, IL-6, IL-10, CCL2, and tumor necrosis factor alpha (TNF-α) after knee injury.
CONCLUSION
Interleukin 6 and CCL4 are elevated in SF after acute knee injury. Included studies failed to demonstrate increased concentration of inflammatory proteins in SF samples taken 6 weeks after trauma. Future research should focus on SF inflammatory protein measurements taken less than 6 weeks after injury.
Topics: Humans; Synovial Fluid; Interleukin-6; Interleukin-10; Biomarkers; Osteoarthritis, Knee; Knee Injuries; Fractures, Bone
PubMed: 36661182
DOI: 10.1177/19476035221141417 -
Journal of Orthopaedic Surgery and... Dec 2022Early and accurate detection of periprosthetic joint infection (PJI) after hip and/or knee arthroplasty remains challenging. This systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early and accurate detection of periprosthetic joint infection (PJI) after hip and/or knee arthroplasty remains challenging. This systematic review and meta-analysis of diagnostic test accuracy studies aimed to evaluate the diagnostic accuracy of serum and synovial fluid interleukin (IL)-6 in detecting PJI.
METHODS
We searched 3 databases for studies through December 31, 2021, using medical sub-headings terms and keywords. Studies reported sensitivity and specificity of serum and synovial fluid IL-6 in detecting PJI were considered. We calculated the pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic curve (AUC) to evaluate the diagnostic accuracy of serum and synovial fluid IL-6.
RESULTS
Thirty studies were included. The pooled sensitivity, specificity, positive and negative likelihood ratio, DOR, and AUC of serum IL-6 in detecting PJI were 0.76 (0.69-0.81), 0.88 (0.82-0.92), 6.2 (4.3-9.0), 0.28 (0.22-0.35), 22 (14-36), and 0.88 (0.85-0.91), respectively. However, synovial fluid IL-6 achieved a pooled sensitivity of 0.87 (0.75-0.93), specificity of 0.90 (0.85-0.93), positive and negative likelihood ratio of 8.5 (5.3-13.6) and 0.15 (0.08-0.29), DOR of 57 (21-156), and AUC of 0.94 (0.92-0.96), which were higher than serum IL-6.
CONCLUSIONS
Synovial fluid IL-6 test may be a promising test for PJI after hip and/or knee arthroplasty. However, considering the limited volume of synovial fluid and invasive acquisition of synovial fluid IL-6, serum IL-6 test may be also considered.
Topics: Humans; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Diagnostic Tests, Routine; Interleukin-6; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid
PubMed: 36566223
DOI: 10.1186/s13018-022-03458-x -
Rheumatology (Oxford, England) May 2023Prompt diagnosis of septic arthritis (SA) in acute native hot joints is essential for avoiding unnecessary antibiotics and hospital admissions. We evaluated the utility... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Prompt diagnosis of septic arthritis (SA) in acute native hot joints is essential for avoiding unnecessary antibiotics and hospital admissions. We evaluated the utility of synovial fluid (SF) and serum tests in differentiating causes of acute hot joints.
METHODS
We performed a systematic literature review of diagnostic testing for acute hot joints. Articles were included if studying ≥1 serum or SF test(s) for an acute hot joint, compared with clinical assessment and SF microscopy and culture. English-language articles only were included, without date restriction. The following were recorded for each test, threshold and diagnosis: sensitivity, specificity, positive/negative predictive values and likelihood ratios. For directly comparable tests (i.e. identical fluid, test and threshold), bivariate random-effects meta-analysis was used to pool sensitivity, specificity, and areas under the curves.
RESULTS
A total of 8443 articles were identified, and 49 were ultimately included. Information on 28 distinct markers in SF and serum, differentiating septic from non-septic joints, was extracted. Most had been tested at multiple diagnostic thresholds, yielding a total of 27 serum markers and 156 SF markers. Due to heterogeneity of study design, outcomes and thresholds, meta-analysis was possible for only eight SF tests, all differentiating septic from non-septic joints. Of these, leucocyte esterase had the highest pooled sensitivity [0.94 (0.70, 0.99)] with good pooled specificity [0.74 (0.67, 0.81)].
CONCLUSION
Our review demonstrates many single tests, individually with diagnostic utility but suboptimal accuracy for exclusion of native joint infection. A combination of several tests with or without a stratification score is required for optimizing rapid assessment of the hot joint.
Topics: Humans; Sensitivity and Specificity; Arthritis, Infectious; Biomarkers; Predictive Value of Tests; Leukocyte Count; Synovial Fluid
PubMed: 36264140
DOI: 10.1093/rheumatology/keac606 -
Knee Surgery, Sports Traumatology,... Sep 2023The purpose of this meta-analysis was to compare the diagnostic parameters of synovial next-generation sequencing (NGS) and cultures in diagnosing periprosthetic joint... (Meta-Analysis)
Meta-Analysis Review
Higher sensitivity and accuracy of synovial next-generation sequencing in comparison to culture in diagnosing periprosthetic joint infection: a systematic review and meta-analysis.
PURPOSE
The purpose of this meta-analysis was to compare the diagnostic parameters of synovial next-generation sequencing (NGS) and cultures in diagnosing periprosthetic joint infections (PJI).
METHODS
PubMed, Web of Science, Cochrane, and Google Scholar were searched from inception until 8 Jan 2022 for literature investigating the role of NGS in comparison to culture in the diagnosis of PJI. The studies were included if they investigated the diagnostic value of culture and NGS in diagnosing PJIs against the Musculoskeletal Infection Society (MSIS) criteria. Diagnostic parameters, such as sensitivity, specificity, positive predictive value, negative predictive value, positive-likelihood ratio, negative-likelihood ratio, accuracy, and area under the curve (AUC), were calculated for the included studies to evaluate the performance of NGS in comparison to culture in PJI diagnosis.
RESULTS
The total number of the included patients was 341 from seven articles. The pooled sensitivity, specificity, and diagnostic odds ratio of NGS were 94% (95% CI 91-97%), 89% (95% CI 82-95%), and 138.5 (95% CI 49.1-390.5), respectively. NGS has positive- and negative-likelihood ratios of 7.9 (95% CI 3.99-15.6) and 0.1 (95% CI 0.0-0.1), respectively. On the other hand, the pooled sensitivity, specificity, and diagnostic odds ratio of culture were 70% (95% CI 61-79%), 94% (95% CI 88-98%), and 28.0 (95% CI 12.6-62.2), respectively. The SROC curve for NGS showed that the accuracy (AUC) was 91.9%, and that the positive and negative predictive values were 8.6 (95% CI 5.0-19.5) and 0.1 (95% CI 0.0-0.1), respectively. While, culture SROC curve demonstrated that the accuracy (AUC) was 80.5% and the positive- and negative-likelihood ratio were 12.1 (95% CI 4.5-49.6) and 0.3 (95% CI 0.2-0.4).
CONCLUSIONS
NGS has a potential role in diagnosing hip and knee PJIs due to its high sensitivity, specificity, and accuracy. However, the sensitivity and specificity reported by the studies varied according to the time of synovial sampling (preoperative, postoperative, or mixed).
Topics: Humans; Knee Prosthesis; Hip Prosthesis; Prosthesis-Related Infections; Arthroplasty, Replacement, Knee; Sensitivity and Specificity; Synovial Fluid; High-Throughput Nucleotide Sequencing; Biomarkers
PubMed: 36244018
DOI: 10.1007/s00167-022-07196-9