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Osteoarthritis and Cartilage Oct 2013In 2010, in Osteoarthritis and Cartilage, we published a comprehensive systematic review applying the consensus BIPED criteria (Burden of Disease, Investigative,... (Review)
Review
In 2010, in Osteoarthritis and Cartilage, we published a comprehensive systematic review applying the consensus BIPED criteria (Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic) criteria on serum and urinary biochemical markers for knee and hip osteoarthritis (OA) using publications that were available at that time. It appeared that none of the biochemical markers at that time were sufficiently discriminating to allow diagnosis and prognosis of OA in individual or limited numbers of patients, nor performed so consistently that they could function as primary outcome parameters in clinical trials. Also at present, almost 3 years later, this ultimate goal has not been reached (yet). Frankly, it might be questioned whether we are making the most adequate steps ahead and maybe we have to take a step back to reconsider our approaches. Some reflections are made and discussed: A critical review of molecular metabolism in OA and validation of currently investigated marker molecules in this may be vital and may lead to new and better markers. Creating cohorts in which synovial fluid (SF) is obtained in a systematic way, together with serum and urine, may also bring the field a further step ahead. Thirdly, better understanding of different phenotypes (subtypes) of OA may facilitate identification and validation of biochemical markers. Finally, the systems biology approach as discussed in the last years OA in review on biomarkers, although very complex, might provide steps forward. Looking ahead, we are optimistic but realistic in our expectations, we believe that the field can be brought forward by critically and cautiously reconsidering our approaches, and making changes forward, one step at a time.
Topics: Biomarkers; Diagnostic Techniques and Procedures; Genetic Markers; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Prognosis; Specimen Handling; Synovial Fluid
PubMed: 23954702
DOI: 10.1016/j.joca.2013.08.012 -
Osteoarthritis and Cartilage May 2010Molecules that are released into biological fluids during matrix metabolism of articular cartilage, subchondral bone, and synovial tissue could serve as biochemical... (Review)
Review
CONTEXT
Molecules that are released into biological fluids during matrix metabolism of articular cartilage, subchondral bone, and synovial tissue could serve as biochemical markers of the process of osteoarthritis (OA). Unfortunately, actual breakthroughs in the biochemical OA marker field are limited so far.
OBJECTIVE
By reviewing the status of commercially available biochemical OA markers according to the "Burden of disease, Investigative, Prognostic, Efficacy of intervention, and Diagnostic" ("BIPED") classification, future use of this "BIPED" classification is encouraged and more efficient biochemical OA marker research stimulated.
DATA SOURCES
Three electronic databases [PubMed, Scopus, EMBASE (1997-May 2009)] were searched for publications on blood and urinary biochemical markers in human primary knee and hip-OA.
STUDY SELECTION
Stepwise selection of original English publications describing human studies on blood or urinary biochemical markers in primary knee or hip-OA was performed. Selected articles were fully read to determine whether biochemical markers were investigated on performance within any of the "BIPED" categories. Eighty-four relevant publications were identified.
DATA EXTRACTION
Data from relevant publications were tabulated according to the "BIPED" classification. Individual analyses within a publication were summarized in general "BIPED" scores.
DATA SYNTHESIS
An uneven distribution of scores on biochemical marker performance and heterogeneity among the publications complicated direct comparison of individual biochemical markers. Comparison of categories of biochemical markers was therefore performed instead. In general, biochemical markers of cartilage degradation were investigated most extensively and performed well in comparison with other categories of biochemical markers. Biochemical markers of bone metabolism performed less adequately. Biochemical markers of synovial tissue metabolism were not investigated extensively, but performed quite well.
CONCLUSIONS
Specific biochemical markers and categories of biochemical markers as well as their nature, origin and metabolism, need further investigation. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers.
Topics: Biomarkers; Bone and Bones; Cartilage, Articular; Cost of Illness; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Prognosis; Synovial Membrane
PubMed: 20175979
DOI: 10.1016/j.joca.2010.01.012 -
Journal of Orthopaedic Surgery and... Dec 2019Synovial fluid proteins had been applied as diagnostic biomarkers for periprosthetic joint infection (PJI) in recent research papers. Thus, this meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Synovial fluid proteins had been applied as diagnostic biomarkers for periprosthetic joint infection (PJI) in recent research papers. Thus, this meta-analysis aimed to estimate the diagnostic efficiency of synovial fluid α-defensin and leukocyte esterase (LE) for PJI.
METHODS
We conducted our systematic review by searching the keywords in online databases such as PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to October 2018. Inclusion criteria were as follows: patients who have undergone knee, hip, or shoulder joint replacements; α-defensin or leukocyte esterase (LE strip) of synovial fluid was detected as the biomarker for PJI diagnosis; and Musculoskeletal Infection Society (MSIS) or utilizing a combination of clinical data was considered as the gold standard. Diagnostic parameters including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary of receiver operating characteristics curve (AUSROC) were calculated for the included studies to evaluate the synovial fluid α-defensin and LE for PJI diagnosis.
RESULTS
After full-text review, 28 studies were qualified for this systematic review, 16 studies used α-defensin and the other 12 were conducted using LE strip. The pooled sensitivity, specificity, and DOR of LE strip were 87% (95% CI 84-90%), 96% (95% CI 95-97%), and 170.09 (95% CI 97.63-296.32), respectively, while the pooled sensitivity, specificity, and DOR of α-defensin were 87% (95% CI 83-90%), 97% (95% CI 96-98%), and 158.18 (95% CI 74.26-336.91), respectively. The AUSROC for LE strip and α-defensin were 0.9818 and 0.9685, respectively.
CONCLUSION
Both LE strip and α-defensin of synovial fluid provide rapid and convenient diagnosis for PJI. Sensitivity of α-defensin and LE strip are the same, while both these two methods have high specificity in clinical practice.
Topics: Carboxylic Ester Hydrolases; Hip Prosthesis; Humans; Knee Prosthesis; Prosthesis-Related Infections; Reproducibility of Results; Shoulder Prosthesis; Synovial Fluid; alpha-Defensins
PubMed: 31856885
DOI: 10.1186/s13018-019-1395-3 -
Evidence Report/technology Assessment Sep 2007Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the... (Review)
Review
OBJECTIVES
Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement.
DATA SOURCES
We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings.
REVIEW METHODS
The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies.
RESULTS
Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement.
CONCLUSIONS
Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.
Topics: Aged; Arthroscopy; Chondroitin; Debridement; Drug Therapy, Combination; Female; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Knee; Male; Middle Aged; Osteoarthritis, Knee; Pain; Synovial Fluid; Therapeutic Irrigation; Treatment Outcome
PubMed: 18088162
DOI: No ID Found -
Osteoarthritis and Cartilage Dec 2012Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune... (Review)
Review
OBJECTIVE
Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their cytokines in synovial tissues (STs) of OA patients.
DESIGN
Broad literature search in different databases was performed which resulted in 100 articles.
RESULTS
Of 100 articles 33 solely investigated inflammation in OA ST with or without comparison with normal samples; the remaining primarily focussed on rheumatoid arthritis (RA) ST. Studies investigating different severity stages or cellular source of cytokines were sparse. OA ST displayed mild/moderate grade inflammation when investigated by means of haematoxylin and eosin (H&E) staining. Most frequently found cells types were macrophages, T cells and mast cells (MCs). Overall the number of cells was lower than in RA, although the number of MCs was as high as or sometimes even higher than in RA ST. Cytokines related to T cell or macrophage function were found in OA ST. Their expression was overall higher than in normal ST, but lower than in RA ST. Their cellular source remains largely unknown in OA ST.
CONCLUSION
Inflammation is common in OA ST and characterized by immune cell infiltration and cytokine secretion. This inflammation seems quantitatively and qualitatively different from inflammation in RA. Further research is needed to clarify the role of inflammation, immune cells and their cytokines in the pathogenesis of OA.
Topics: Cytokines; Humans; Immunity, Cellular; Mast Cells; Osteoarthritis; Synovial Membrane; T-Lymphocytes
PubMed: 22960092
DOI: 10.1016/j.joca.2012.08.027 -
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 -
Acta Orthopaedica Et Traumatologica... Dec 2016The aim of this systematic review was to assess the efficacy of Saline load tests (SLTs) to evaluate extension of periarticular wounds into capsule in emergent settings. (Review)
Review
INTRODUCTION
The aim of this systematic review was to assess the efficacy of Saline load tests (SLTs) to evaluate extension of periarticular wounds into capsule in emergent settings.
METHODS
We systematically reviewed the literature to evaluate the accuracy of the SLT in diagnosing penetrating joint injuries in the elbow, wrist, shoulder, knee, or ankle.
RESULTS
The SLT values to determine knee arthrotomies vary from 73.8 mL to 194 mL with sensitivities ranging between 91% and 99% depending on the size of the laceration. A SLT of 30 mL in the ankle yields sensitivities ranging from 95% to 99% in assessing joint penetration. A SLT of 45 mL in the elbow yields a sensitivity of 95% in assessing joint penetration. The addition of methylene blue does not change the sensitivity of the SLT.
CONCLUSION
Several studies have demonstrated the utility of the SLT as a diagnostic modality for penetrating joint injuries. However, the literature analyzed in this study was inconclusive and more studies are required to make definitive recommendations. In addition, more studies will be needed on joints other than the knee, pediatric patients, and the use of methylene blue dye in conjunction with SLT.
LEVEL OF EVIDENCE
Level II, Diagnostic study.
Topics: Arthroscopy; Humans; Injections, Intra-Articular; Joints; Range of Motion, Articular; Sodium Chloride; Tomography, X-Ray Computed; Wounds, Penetrating
PubMed: 27979366
DOI: 10.1016/j.aott.2016.01.004 -
Evidence-based Complementary and... 2020The study aimed to explore the efficacy and safety of Kunxian Capsule (KXC) in the treatment of rheumatoid arthritis (RA). The randomized controlled trials (RCTs)...
The study aimed to explore the efficacy and safety of Kunxian Capsule (KXC) in the treatment of rheumatoid arthritis (RA). The randomized controlled trials (RCTs) comparing the effects of KXC in patients with RA were included in this study. Weighted mean differences (MDs) were calculated for net changes by employing Review Manager meta-analysis software. Nine RCTs were included in the systematic review with a total of 747 patients. The overall effects showed that KXC alone or combined with disease-modifying antirheumatic and drugs decreased tender joint counts (=0.02, MD = -1.07, 95% CI: -1.95 to -0.18), shortened duration of morning stiffness ( < 0.0001, MD = -9.01, 95% CI: -13.08 to -4.93), lowered erythrocyte sedimentation rate ( < 0.00001, MD = -5.27, 95% CI: -6.78 to -3.77), and reduced C-reactive protein ( < 0.0001, MD = -5.04, 95% CI: -7.28 to -2.80). The most common adverse events were gastrointestinal disturbances and abnormal liver function. These results suggest that KXC is likely to be a more effective and safe candidate for treating RA compared with conventional therapies.
PubMed: 32849899
DOI: 10.1155/2020/4178140 -
The Journal of Rheumatology Sep 2017Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to... (Review)
Review
OBJECTIVE
Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to reliably identify synovitis, bone marrow edema, bone erosion, and joint space narrowing (JSN)/cartilage loss. Understanding the exact relationship between each MRI feature and local synovial pathobiology is critical to dissect disease pathogenesis as well as develop future predictive models.
METHODS
A systematic review was performed of the current published literature examining the relationship between MRI abnormalities and synovial pathobiology in patients with RA.
RESULTS
Eighteen studies were identified; most focused on validation of MRI as a tool to detect and quantify synovitis, with a significant relationship demonstrated. Additionally, from the limited data available, a critical role seems likely for synovial pathways, at least in driving joint damage. However, there was a lack of data examining the relationship between synovial pathobiology and bone marrow abnormalities and JSN.
CONCLUSION
Although understanding the interrelationship of these disease biomarkers offers the potential to enhance the predictive validity of modern imaging with concomitant synovial pathobiological analysis, further studies integrating MRI with synovial tissue analysis in well-controlled cohorts at distinct disease stages before and after therapeutic intervention are required to achieve this.
Topics: Arthritis, Rheumatoid; Humans; Magnetic Resonance Imaging; Synovial Membrane; Synovitis
PubMed: 28711880
DOI: 10.3899/jrheum.161314 -
Arthritis Care & Research Aug 2018Shoulder symptoms are common, and imaging is being increasingly used to help with management. However, the relationship between imaging and symptoms remains unclear....
OBJECTIVE
Shoulder symptoms are common, and imaging is being increasingly used to help with management. However, the relationship between imaging and symptoms remains unclear. This review aims to understand the relationship between imaging-detected pathologies, symptoms, and their persistence.
METHODS
A systematic review using Medline, EMBASE, Cochrane, and grey literature was conducted to April 2017. The cross-sectional and longitudinal relationships between imaging-detected abnormalities and symptoms were analyzed and associations qualitatively characterized by a best-evidence synthesis based on study design, covariate adjustment, and the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Modalities included ultrasound, magnetic resonance imaging (MRI), radiographs, positron emission tomography (PET), bone scintigraphy, and computed tomography.
RESULTS
A total of 6,569 abstracts was screened and 56 articles were included. In total, 50 studies did not adjust for covariates and 36 analyzed individual pathologies only. The majority of studies showed conflicting results. There was no significant association between most imaging features and symptoms among high-quality, cross-sectional studies. There was low-quality evidence that enhancement of the joint capsule on MRI and increased uptake on PET were associated with symptoms in adhesive capsulitis. Based on high-quality longitudinal studies, enlarging rotator cuff tears were associated with an increased incidence of symptoms.
CONCLUSION
There were conflicting results on the association of imaging features with shoulder symptoms and their persistence. The existing evidence was very low in quality, based on the GRADE methodology. Further high-quality studies are required to understand the relationship between imaging and shoulder symptoms and to determine the appropriate role of imaging in care pathways.
Topics: Age Factors; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Multimodal Imaging; Positron-Emission Tomography; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Factors; Shoulder Joint; Shoulder Pain; Time Factors; Tomography, X-Ray Computed; Ultrasonography, Doppler
PubMed: 29513925
DOI: 10.1002/acr.23554