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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 -
The Journal of Bone and Joint Surgery.... Dec 2017The search for a single standard reference test for determining periprosthetic joint infection (PJI) through analysis of synovial fluid has yielded numerous biomarkers... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The search for a single standard reference test for determining periprosthetic joint infection (PJI) through analysis of synovial fluid has yielded numerous biomarkers as potential candidates. The purpose of the present systematic review and meta-analysis was to evaluate the diagnostic accuracy of synovial fluid biomarkers and to determine which test has the highest diagnostic odds ratio (DOR) for the diagnosis of PJI.
METHODS
An online literature search of the MEDLINE, Embase, and Cochrane databases identified 33 articles reporting a total of 13 major parameters for diagnosing PJI through analysis of synovial fluid. Each of the included articles was independently analyzed for risk of bias and for concerns regarding applicability utilizing the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool. The mada (meta-analysis of diagnostic accuracy) tool was used to generate forest plots for sensitivity, specificity, and the log of the DOR, as well as summary statistics.
RESULTS
In this analysis, 13 index tests (leukocyte count; measurement of the percentage of polymorphonucleocytes [PMN%] and the levels of C-reactive protein [CRP], α-defensin, leukocyte esterase [LE], interleukin [IL]-6, IL-8, IL-10, IL-1β, vascular endothelial growth factor [VEGF], and granulocyte-colony stimulating factor [G-CSF]; culture; and polymerase chain reaction [PCR] analysis) were evaluated on the basis of ≥2 articles. Of these tests, 8 (leukocyte count, PMN%, CRP, α-defensin, LE, IL-6, IL-8, and culture) were appropriate for pooled analysis. The overall sensitivity of these 8 markers was 0.85, and all but culture showed a sensitivity of ≥0.8. All markers showed a specificity of ≥0.9. Of the 8 tests, measurement of the α-defensin level showed the highest log DOR.
CONCLUSIONS
Synovial fluid leukocyte count, PMN%, CRP, α-defensin, LE, IL-6, and IL-8 all demonstrated high sensitivity for diagnosing PJI, with α-defensin being the best synovial marker based on the highest log DOR. However, other synovial fluid tests that demonstrate good diagnostic performance can also be used in combination for the diagnosis of PJI.
LEVEL OF EVIDENCE
Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Topics: Arthroplasty, Replacement; Biomarkers; C-Reactive Protein; Female; Humans; Male; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid; Vascular Endothelial Growth Factor A; alpha-Defensins
PubMed: 29257013
DOI: 10.2106/JBJS.17.00123 -
The Journal of the American Academy of... Nov 2017This study is a systematic review of all reported synovial fluid markers for the diagnosis of periprosthetic joint infection and a meta-analysis of the most frequently... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This study is a systematic review of all reported synovial fluid markers for the diagnosis of periprosthetic joint infection and a meta-analysis of the most frequently reported markers to identify those of greatest diagnostic utility.
METHODS
A search of six databases was conducted to identify all studies evaluating the utility of synovial fluid markers in the diagnosis of periprosthetic joint infection. Two observers assessed methodologic quality and extracted data independently. A meta-analysis of the most frequently reported markers was performed.
RESULTS
Twenty-three studies were included in the meta-analysis. The most common markers (and their respective area under the curve) were interleukin-17 (0.974), leukocyte esterase (0.968), α-defensin (0.958), interleukin-6 (0.956), interleukin-1β (0.948), and C-reactive protein (0.927). Among these markers, α-defensin had the highest diagnostic odds ratio but did not achieve statistically significant superiority.
CONCLUSION
The most frequently studied synovial fluid markers for the diagnosis of periprosthetic joint infection are C-reactive protein, leukocyte esterase, interleukin-6, interleukin-1β, α-defensin, and interleukin-17, all of which have high diagnostic utility.
LEVEL OF EVIDENCE
Level II.
Topics: Biomarkers; Humans; Joint Prosthesis; Odds Ratio; Prosthesis-Related Infections; ROC Curve; Synovial Fluid
PubMed: 29059113
DOI: 10.5435/JAAOS-D-16-00548 -
International Orthopaedics Dec 2017Alpha-defensin, a novel biomarker, has shown great potential for the accurate diagnosis of periprosthetic joint infection (PJI) in recent years: many published studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alpha-defensin, a novel biomarker, has shown great potential for the accurate diagnosis of periprosthetic joint infection (PJI) in recent years: many published studies have presented encouraging results. Nevertheless, the diagnostic accuracy of alpha-defensin is inconsistent across published studies. Moreover, the optimum value of the diagnostic threshold urgently needs to be ascertained. This meta-analysis sought to estimate the precision of alpha-defensin for the diagnosis of PJI and, where possible, to confirm the threshold.
METHOD
We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov for relevant literature on alpha-defensin in the diagnosis of PJI (searching publications from the inception of each database until February 2017, with no language restriction). Pooled sensitivity, specificity, diagnostic odds ratios, and likelihood ratios were the indexes used for assessment, with the use of a random-effects model.
RESULT
Eleven of the 426 studies that evaluated the diagnostic accuracy of alpha-defensin in periprosthetic joint infection (PJI) were included in this analysis. The pooled diagnostic sensitivity of alpha-defensin for PJI was 0.96 (95% confidence interval [CI], 0.87 to 0.99) and the specificity was 0.95 (95% CI, 0.91 to 0.97). Since there was substantial heterogeneity among studies, based on the inconsistency index (I), threshold, site of arthroplasty, study design and techniques for the alpha-defensin test, subgroup analyses were performed to estimate the impacts of these variables on heterogeneity.
CONCLUSION
In summary, this meta-analysis clearly lends support to the conclusion that alpha-defensin is a promising addition to the current methods for diagnosis of PJI.
Topics: Adult; Aged; Aged, 80 and over; Arthritis, Infectious; Biomarkers; Female; Humans; Male; Middle Aged; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid; alpha-Defensins
PubMed: 28963626
DOI: 10.1007/s00264-017-3647-3 -
American Journal of Orthopedics (Belle... 2017Prosthetic joint infection (PJI) may be underreported because of difficulty in making a diagnosis, especially in infections with low-virulence organisms. Reports of PJI... (Review)
Review
Prosthetic joint infection (PJI) may be underreported because of difficulty in making a diagnosis, especially in infections with low-virulence organisms. Reports of PJI cases misdiagnosed as aseptic loosening suggest that current screening and diagnostic tools are not sensitive enough to detect all infections and that PJI likely is underdiagnosed. We reviewed the literature on recently developed novel synovial biomarkers and polymerase chain reaction (PCR) technologies, of which several have proved promising as highly sensitive and specific tools for detecting PJI. We followed the recommendations of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Of 90 papers screened by title or abstract and then by full text, 15 met our inclusion criteria. Sensitivities reported in the included studies ranged from 63% to 100% for α-defensin, from 46.8% to 90.9% for interleukin 6, from 28.6% to 100% for leukocyte esterase, and from 67.10% to 95.7% for PCR. Specificities ranged from 95% to 100% for α-defensin, from 85.7% to 97.6% for interleukin 6, from 63.6% to 96.5% for leukocyte esterase, and from 12.3% to 97.8% for PCR. α-Defensin is a highly sensitive and specific screening tool that may help improve the accuracy of PJI detection, particularly in low-grade infections.
Topics: Biomarkers; Humans; Joint Prosthesis; Polymerase Chain Reaction; Prosthesis-Related Infections; Synovial Fluid; alpha-Defensins
PubMed: 28856346
DOI: No ID Found -
Surgical Infections 2017Total joint arthroplasty (TJA) has been one of the most beneficial interventions for treating patients suffering from joint disorders. However, peri-prosthetic joint... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Total joint arthroplasty (TJA) has been one of the most beneficial interventions for treating patients suffering from joint disorders. However, peri-prosthetic joint infection (PJI) is a serious complication that often accompanies TJA and the diagnosis of PJI is remains difficult. Questions remain regarding whether certain biomarkers can be valuable in the diagnosis of PJI.
PATIENTS AND METHODS
We conducted our systematic review by searching PubMed, Embase, Web of Science, the Cochrane Library, and Science Direct with the key words "periprosthetic joint infection," "synovial fluid," and "α-defensin." Studies that provided sufficient data to construct 2 × 2 contingency tables were chosen based on inclusion and exclusion criteria. The quality of included studies was assessed according to the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for the included studies. The summary receiver operating characteristic (SROC) curve and the area under the summary receiver operating characteristic (AUSROC) were used to evaluate the overall diagnostic performance.
RESULTS
Eight studies were included in this systematic review. Among them four articles were included in meta-analysis. A total of 421 participants were studied in the meta-analysis. The pooled sensitivity, specificity, and DOR were 0.98 (95% confidence interval [CI]: 0.94-1.00), 0.97 (95% CI: 0.95-0.99), and 1095.49 (95% CI: 283.68.58-4230.45), respectively. The AUSROC was 0.9949 (standard error [SE] 0.0095).
CONCLUSION
Synovial fluid α-defensin is a biomarker of high sensitivity and specificity for the diagnosis of PJI.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Humans; Middle Aged; Prosthesis-Related Infections; ROC Curve; Synovial Fluid; alpha-Defensins
PubMed: 28686144
DOI: 10.1089/sur.2017.006 -
Brazilian Oral Research Jun 2017Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions... (Review)
Review
Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.
Topics: DMF Index; Dental Caries; Dental Caries Susceptibility; Female; Genetic Association Studies; Genetic Markers; Humans; Male; Polymorphism, Genetic; Risk Factors; Salivary Proteins and Peptides
PubMed: 28591238
DOI: 10.1590/1807-3107BOR-2017.vol31.0041 -
Shock (Augusta, Ga.) Jun 2017Sepsis is a systemic host response to an infection leading to organ failure. This is associated with dynamic expression of endogenous host defense peptides.... (Review)
Review
BACKGROUND
Sepsis is a systemic host response to an infection leading to organ failure. This is associated with dynamic expression of endogenous host defense peptides. Dysregulation of these peptides is associated with septic morbidity and mortality.
METHODS
We performed a systematic search of articles indexed in PubMed, ISI Web of Knowledge, EmBase, and Scopus database from inception to October 2016. Both preclinical and clinical studies investigating the role of host defense peptides in pathogenesis and as biomarkers for sepsis were included.
RESULTS
Of the available literature, cathelicidin, defensin, and hepcidin are among the best-characterized peptides. These regulate immune response, and crosstalk with pyroptosis and coagulation cascades. The applicability of these peptides as septic biomarkers has been investigated in vitro and in vivo studies. However, numerous studies were based on endotoxemia without an infection, jeopardizing interpretation of the outcomes. Cathelicidin and defensin were frequently reported in adult sepsis while hepcidin in neonatal sepsis. The expression level of these peptides is significantly associated with septic condition. Most of the studies employed a cross-sectional design, precluding the establishment of a temporal relationship between candidate peptide biomarkers and sepsis.
CONCLUSIONS
Innate defense peptides have been insufficiently evaluated as either diagnostic or prognostic biomarkers. In the future, evaluation of host defense peptides as septic biomarkers may employ a longitudinal design and consider a panel of multiple peptides.
Topics: Antimicrobial Cationic Peptides; Cross-Sectional Studies; Defensins; Female; Hepcidins; Humans; Infant, Newborn; Male; Neonatal Sepsis; Cathelicidins
PubMed: 27941592
DOI: 10.1097/SHK.0000000000000815 -
Current Medicinal Chemistry 2017Crohn's disease (CD) and ulcerative colitis (UC) are classified under inflammatory bowel disease (IBD) which has been linked to a multifaceted etiology involving both... (Review)
Review
Crohn's disease (CD) and ulcerative colitis (UC) are classified under inflammatory bowel disease (IBD) which has been linked to a multifaceted etiology involving both environmental and genetic factors that intersect with the vitamin D pathway. Dysfunctions in innate immune defense mechanisms in the epithelial compartment of the intestine play a crucial role in the pathogenesis of IBD. Symptoms of IBD are caused by excessive immune responses to luminal bacteria, and vitamin D has been shown to play a role in intestinal defense by aiding in the suppression of microbial invasion into the epithelium. Vitamin D, as an immunomodulator, can modify the innate immune response of the body. Vitamin D attenuates the transcription of pro-inflammatory cytokines that are upregulated in the event of epithelial stress common in patients with IBD. Vitamin D deficiency was identified in 82% of IBD patients compared to the 31% national average and has been linked to defective epithelial processes at both genomic and proteomic levels. Mucosal damage and an impaired immune response are at the center of IBD, and vitamin D aids in sustaining the structural integrity of epithelial cells while enhancing innate immune responses in the mucosa. Here we provide a systematic review of the pathophysiological effects of cytokines in IBD in the presence of vitamin D deficiency. Also, analysis of the immunomodulatory effect of vitamin D in regulating immunopathogenic factors like chemokines, growth factors, and human defensins will enhance knowledge of the underlying molecular mechanisms of the therapeutic role of vitamin D in IBD and thus aid in the development of better patient management strategies.
Topics: Humans; Immunity; Inflammatory Bowel Diseases; Vitamin D
PubMed: 27784213
DOI: 10.2174/0929867323666161026124951 -
The Journal of Bone and Joint Surgery.... Jun 2016Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Synovial biomarkers have recently been adopted as diagnostic tools for periprosthetic joint infection (PJI), but their utility is uncertain. The purpose of this systematic review and meta-analysis was to synthesize the evidence on the accuracy of the alpha-defensin immunoassay and leukocyte esterase colorimetric strip test for the diagnosis of PJI compared with the Musculoskeletal Infection Society diagnostic criteria.
METHODS
We performed a systematic review to identify diagnostic technique studies evaluating the accuracy of alpha-defensin or leukocyte esterase in the diagnosis of PJI. MEDLINE and Embase on Ovid, ACM, ADS, arXiv, CERN DS (Conseil Européen pour la Recherche Nucléaire Document Server), CrossRef DOI (Digital Object Identifier), DBLP (Digital Bibliography & Library Project), Espacenet, Google Scholar, Gutenberg, HighWire, IEEE Xplore (Institute of Electrical and Electronics Engineers digital library), INSPIRE, JSTOR (Journal Storage), OAlster (Open Archives Initiative Protocol for Metadata Harvesting), Open Content, Pubget, PubMed, and Web of Science were searched for appropriate studies indexed from inception until May 30, 2015, along with unpublished or gray literature. The classification of studies and data extraction were performed independently by 2 reviewers. Data extraction permitted meta-analysis of sensitivity and specificity with construction of receiver operating characteristic curves for each test.
RESULTS
We included 11 eligible studies. The pooled diagnostic sensitivity and specificity of alpha-defensin (6 studies) for PJI were 1.00 (95% confidence interval [CI], 0.82 to 1.00) and 0.96 (95% CI, 0.89 to 0.99), respectively. The area under the curve (AUC) for alpha-defensin and PJI was 0.99 (95% CI, 0.98 to 1.00). The pooled diagnostic sensitivity and specificity of leukocyte esterase (5 studies) for PJI were 0.81 (95% CI, 0.49 to 0.95) and 0.97 (95% CI, 0.82 to 0.99), respectively. The AUC for leukocyte esterase and PJI was 0.97 (95% CI, 0.95 to 0.98). There was substantial heterogeneity among studies for both diagnostic tests.
CONCLUSIONS
The diagnostic accuracy for PJI was high for both tests. Given the limited number of studies and the large cost difference between the tests, more independent research on these tests is warranted.
LEVEL OF EVIDENCE
Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Topics: Biomarkers; Carboxylic Ester Hydrolases; Colorimetry; Humans; Predictive Value of Tests; Prosthesis-Related Infections; Sensitivity and Specificity; alpha-Defensins
PubMed: 27307359
DOI: 10.2106/JBJS.15.01142