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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 -
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 -
Children (Basel, Switzerland) Jan 2023: Some variants in () and () genes can be associated with oral diseases. Herein, we designed a systematic review and meta-analysis to evaluate the association of (, ,... (Review)
Review
Evaluation of Beta-Defensin 1 and Mannose-Binding Lectin 2 Polymorphisms in Children with Dental Caries Compared to Caries-Free Controls: A Systematic Review and Meta-Analysis.
: Some variants in () and () genes can be associated with oral diseases. Herein, we designed a systematic review and meta-analysis to evaluate the association of (, , and ) and ( and ) polymorphisms with the susceptibility to dental caries (DC) in children. : A systematic literature search was conducted in the PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases until 3 December 2022, without any restrictions. The odds ratio (OR), along with a 95% confidence interval (CI) of the effect sizes, are reported. Analyses including a subgroup analysis, a sensitivity analysis, and funnel plot analyses were conducted. : A total of 416 records were identified among the databases, and nine articles were entered into the meta-analysis. A significant relationship was found between the T allele of polymorphism and DC susceptibility, and the T allele was related to an elevated risk of DC in children (OR = 1.225; 95%CI: 1.022, 1.469; = 0.028; I = 0%). No other polymorphisms were associated with DC. All articles were of moderate quality. Egger's test in homozygous and dominant models demonstrated a significant publication bias for the association of polymorphism with DC risk. : The results demonstrated that the T allele of polymorphism had an elevated risk for DC in children. However, there were only few studies that evaluated this association.
PubMed: 36832361
DOI: 10.3390/children10020232 -
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 -
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 -
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 -
The Bone & Joint Journal Jun 2018The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems... (Review)
Review Meta-Analysis
AIMS
The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI).
MATERIALS AND METHODS
Studies using alpha-defensin or Synovasure (Zimmer Biomet, Warsaw, Indiana) to diagnose PJI were identified from systematic searches of electronic databases. The quality of the studies was evaluated using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) tool. Meta-analysis was completed using a bivariate model.
RESULTS
A total of 11 eligible studies were included. The median QUADAS score was 13 (interquartile range 13 to 13) out of 14. Significant conflicts of interest were identified in five studies. The pooled sensitivity for the laboratory alpha-defensin test was 0.95 (95% confidence interval (CI) 0.91 to 0.98) and the pooled specificity was 0.97 (95% CI 0.95 to 0.98) for four studies with a threshold level of 5.2 mgl The pooled sensitivity for the lateral flow cassette test was 0.85 (95% CI 0.74 to 0.92) and the pooled specificity was 0.90 (95% CI 0.91 to 0.98). There was a statistically significant difference in sensitivity (p = 0.019), but not specificity (p = 0.47).
CONCLUSION
Laboratory-based alpha-defensin testing remains a promising tool for diagnosing PJI. The lateral flow cassette has a significantly lower performance and pooled results are comparable to the leucocyte esterase test. Further studies are required before the widespread adoption of the lateral flow cassette alpha-defensin test. Cite this article: Bone Joint J 2018;100-B:703-11.
Topics: Arthroplasty; Biomarkers; Enzyme-Linked Immunosorbent Assay; Humans; Predictive Value of Tests; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid; alpha-Defensins
PubMed: 29855233
DOI: 10.1302/0301-620X.100B6.BJJ-2017-1563.R1 -
BMC Medicine Oct 2022Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.
METHODS
We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.
RESULTS
We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.
CONCLUSIONS
Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
Topics: Elafin; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins; Immunologic Factors; Interferons; Interleukin 1 Receptor Antagonist Protein; Interleukin-16; Interleukin-1alpha; Interleukin-6; Interleukins; Lactoferrin; Menstrual Cycle; Muramidase; Progesterone; beta-Defensins
PubMed: 36195867
DOI: 10.1186/s12916-022-02532-9 -
Orthopaedic Surgery Nov 2022The current diagnostic criteria for periprosthetic joint infection (PJI) are diverse and controversial, leading to delayed diagnosis. This study aimed to evaluate and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The current diagnostic criteria for periprosthetic joint infection (PJI) are diverse and controversial, leading to delayed diagnosis. This study aimed to evaluate and unify their diagnostic accuracy and the threshold selection of serum and synovial routine tests for PJI at an early stage.
METHODS
We searched the MEDLINE and Embase databases for retrospective or prospective studies which reported preoperative-available assays (serum, synovial, or culture tests) for the diagnosis of chronic PJI among inflammatory arthritis (IA) or non-IA populations from January 1, 2000 to June 30, 2022. Threshold effective analysis was performed on synovial polymorphonuclear neutrophils (PMN%), synovial white blood cell (WBC), serum C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to find the relevant cut-offs.
RESULTS
Two hundred and sixteen studies and information from 45,316 individuals were included in the final analysis. Synovial laboratory-based α-defensin and calprotectin had the best comprehensive sensitivity (0.91 [0.86-0.94], 0.95 [0.88-0.98]) and specificity (0.96 [0.94-0.97], 0.95 [0.89-0.98]) values. According to the threshold effect analysis, the recommended cut-offs are 70% (sensitivity 0.89 [0.85-0.92], specificity 0.90 [0.87-0.93]), 4100/μL (sensitivity 0.90 [0.87-0.93], specificity 0.97 [0.93-0.98]), 13.5 mg/L (sensitivity 0.84 [0.78-0.89], specificity 0.83 [0.73-0.89]), and 30 mm/h (sensitivity 0.79 [0.74-0.83], specificity 0.78 [0.72-0.83]) for synovial PMN%, synovial WBC, serum CRP, and ESR, respectively, and tests seem to be more reliable among non-IA patients.
CONCLUSIONS
The laboratory-based synovial α-defensin and synovial calprotectin are the two best independent preoperative diagnostic tests for PJI. A cut off of 70% for synovial PMN% and tighter cut-offs for synovial WBC and serum CRP could have a better diagnostic accuracy for non-IA patients with chronic PJI.
Topics: Humans; alpha-Defensins; Arthritis, Infectious; Arthroplasty, Replacement, Hip; C-Reactive Protein; Diagnostic Tests, Routine; Leukocyte L1 Antigen Complex; Prospective Studies; Prosthesis-Related Infections; Retrospective Studies; Synovial Fluid
PubMed: 36181336
DOI: 10.1111/os.13500 -
Journal of Orthopaedic Surgery (Hong... 2020Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is its difficulty in diagnosis. This systematic review and meta-analysis aimed to compare the diagnostic accuracy of -defensin, D-dimer, and interleukin-6 (IL-6) in clinical practice.
METHOD
Online databases were systematically searched until June 18th, 2020 with keywords and medical sub-headings terms. Studies mentioned the sensitivity and specificity of biological markers in detecting PJI were included in our study. The sensitivity, specificity, and diagnostic odds ratios (DORs) were obtained after integration.
RESULTS
A total of 34 studies with 1036 patients diagnosing as PJI were included for comparing -defensin, D-dimer, and IL-6. The sensitivity and specificity of -defensin for PJI were 0.88 and 0.96, and the DOR was 189 (95% CI 72-496), respectively. The sensitivity and specificity of D-dimer (0.82 and 0.72) and IL-6 (0.80 and 0.89) were lower than -defensin.
CONCLUSION
The detection of -defensin is a promising biomarker for diagnosing PJI. The optional cut-off needs to be curtained when using other biomarkers.
Topics: Biomarkers; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Prosthesis-Related Infections; Synovial Fluid; alpha-Defensins
PubMed: 33225796
DOI: 10.1177/2309499020971861