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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 -
Archives of Orthopaedic and Trauma... Mar 2020Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the diagnostic accuracy of synovial fluid α-defensin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection.
MATERIALS AND METHODS
We searched (from inception to May 2018) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on α-defensin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed using the bivariate diagnostic random-effects model. The receiver-operating curve for each method was calculated.
RESULTS
We included 13 articles in our meta-analysis, including 1170 patients who underwent total hip and knee arthroplasties revision; 368 (31%) had a joint infection according to MSIS and MSIS-modified criteria. Considering the false-positive result rate of 8% and false-negative result rate of 3%, pooled sensitivity and specificity were 0.90 (95% CI 0.83-0.94) and 0.95 (0.92-0.96), respectively. The area under the curve (AUC) was 0.94 (0.92-0.94). No statistical differences in terms of sensitivity and specificity were found between the laboratory-based and qualitative test. The pooled sensitivity and specificity of the two alpha-defensin assessment methods were: laboratory-based test 0.97 (95% CI 0.93-0.99) and 0.96 (95% CI 0.94-0.98), respectively; qualitative test 0.83 (95% CI 0.73-0.91) and 0.94 (95% CI 0.89-0.97), respectively. The diagnostic odds ratio of the α-defensin laboratory based was superior to that of the qualitative test (1126.085, 95% CI 352.172-3600.702 versus 100.9, 95% CI 30.1-338.41; p < 0.001). The AUC for immunoassay and qualitative tests was 0.97 (0.95-0.99) and 0.91 (0.88-0.99), respectively.
CONCLUSION
Detection of α-defensin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two alpha-defensin assessment methods is comparable. The lateral flow assay is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.
Topics: Biomarkers; Hip Joint; Hip Prosthesis; Humans; Knee Joint; Knee Prosthesis; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid; alpha-Defensins
PubMed: 31300864
DOI: 10.1007/s00402-019-03232-5 -
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 -
Biomolecules Jul 2020The grass family (Poaceae) is one of the largest families of flowering plants, growing in all climatic zones of all continents, which includes species of exceptional... (Review)
Review
The grass family (Poaceae) is one of the largest families of flowering plants, growing in all climatic zones of all continents, which includes species of exceptional economic importance. The high adaptability of grasses to adverse environmental factors implies the existence of efficient resistance mechanisms that involve the production of antimicrobial peptides (AMPs). Of plant AMPs, defensins represent one of the largest and best-studied families. Although wheat and barley seed γ-thionins were the first defensins isolated from plants, the functional characterization of grass defensins is still in its infancy. In this review, we summarize the current knowledge of the characterized defensins from cultivated and selected wild-growing grasses. For each species, isolation of defensins or production by heterologous expression, peptide structure, biological activity, and structure-function relationship are described, along with the gene expression data. We also provide our results on in silico mining of defensin-like sequences in the genomes of all described grass species and discuss their potential functions. The data presented will form the basis for elucidation of the mode of action of grass defensins and high adaptability of grasses to environmental stress and will provide novel potent molecules for practical use in medicine and agriculture.
Topics: Defensins; Disease Resistance; Gene Expression Regulation, Plant; Models, Molecular; Plant Proteins; Poaceae; Protein Conformation; Structure-Activity Relationship
PubMed: 32664422
DOI: 10.3390/biom10071029 -
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 -
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 Arthroplasty Apr 2022Total knee arthroplasty (TKA) provides successful results in most patients. Periprosthetic joint infection (PJI) accounts for up to 25% of failed TKAs needing revision.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Total knee arthroplasty (TKA) provides successful results in most patients. Periprosthetic joint infection (PJI) accounts for up to 25% of failed TKAs needing revision. In clinical practice, consensus in diagnostic strategy for excluding or diagnosing PJI is still lacking. In this systematic review and meta-analysis, we aim to provide a simplified data-driven diagnostic strategy for aseptic knee and hip revision surgeons to rule out PJI in the outpatient clinic phase.
METHODS
A literature search in EMBASE, MEDLINE, PubMed, and Cochrane was conducted. Studies involving the diagnosis of PJI in patients with failed TKAs and total hip arthroplasties needing revision were identified. Only studies using the Musculoskeletal Infection Society criteria were included. Quality was assessed using MINORS criteria. Meta-analysis was performed for each diagnostic test identified in the included studies. Pooled estimates of diagnostic accuracy measures were calculated using a bivariate model and plotted in summary receiver-operator characteristic curves. Positive and negative predictive values were calculated in a hypothetical sample of patients with a given disease prevalence.
RESULTS
Twenty-four studies met the inclusion criteria, describing a total of 2974 patients. Quality scores ranged from 13 to 19. Meta-analysis could be performed on 7 unique diagnostic tests. Highest pooled sensitivity and specificity were demonstrated for α-defensin with values of 86% and 96.6%, respectively. α-defensin and white blood cell count in synovial fluid demonstrate highest negative predictive value values.
CONCLUSIONS
We recommend, in a clinical setting with low-intermediate prevalence of PJI, performing arthrocentesis and joint fluid analysis using α-defensin and/or white blood cell count before revision TKA and revision total hip arthroplasty surgery to rule out PJI.
Topics: Arthritis, Infectious; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Humans; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid; alpha-Defensins
PubMed: 34952165
DOI: 10.1016/j.arth.2021.12.020 -
The Journal of Arthroplasty Dec 2023Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic... (Meta-Analysis)
Meta-Analysis
Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection-A Systematic Review and Meta-Analysis of Their Diagnostic Accuracy According to Different Definitions.
BACKGROUND
Different synovial fluid biomarkers have emerged to improve periprosthetic joint infection (PJI) diagnosis. The goals of this paper were (i) to assess their diagnostic accuracy and (ii) to evaluate their performance according to different PJI definitions.
METHODS
A systematic review and meta-analysis was performed using studies that reported diagnostic accuracy of synovial fluid biomarkers using validated PJI definitions published from 2010 to March 2022. A database search was performed through PubMed, Ovid MEDLINE, Central, and Embase. The search identified 43 different biomarkers with four being the more commonly studied, with 75 papers overall: alpha-defensin; leukocyte esterase; synovial fluid C-reactive protein; and calprotectin.
RESULTS
Overall accuracy was higher for calprotectin, followed by alpha-defensin, leukocyte esterase, and synovial fluid C-reactive protein with sensitivities of 78 to 92% and specificities of 90 to 95%. Their diagnostic performance was different according to which definition was adopted as the reference. Specificity was consistently high across definitions for all four biomarkers. Sensitivity varied the most with lower values for the more sensitive European Bone and Joint Infection Society or Infectious Diseases Society of America definitions with higher values for the Musculoskeletal Infection Society definition. The International Consensus Meeting 2018 definition showed intermediate values.
CONCLUSION
All evaluated biomarkers had good specificity and sensitivity, making their use acceptable in the diagnosis of PJI. Biomarkers perform differently according to the selected PJI definitions.
Topics: Humans; C-Reactive Protein; Sensitivity and Specificity; Synovial Fluid; alpha-Defensins; Prosthesis-Related Infections; Biomarkers; Arthritis, Infectious; Leukocyte L1 Antigen Complex
PubMed: 37321521
DOI: 10.1016/j.arth.2023.06.017 -
Postepy Dermatologii I Alergologii Jun 2023Basal cell carcinoma (BCC) is the most common skin cancer in humans, occurring in more than 50% of Caucasians during their lifetime, with a frequency rate that is... (Review)
Review
INTRODUCTION
Basal cell carcinoma (BCC) is the most common skin cancer in humans, occurring in more than 50% of Caucasians during their lifetime, with a frequency rate that is continually increasing.
MATERIAL AND METHODS
We present a systematic review summarizing the role of transforming growth factor β (TGF-β), cathelicidin, and human β-defensins (HBDs) in the pathogenesis of BCC. The major online databases including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to extract studies regarding the levels of TGF-β, HBD, and cathelicidin in BCC.
RESULTS
A total of 14 studies met the inclusion criteria and were included in this systematic review. There were 6 studies that included initially established levels of TGF-β in BCCs. A total of 87 BCCs were analysed, and a common result was that the TGF-β levels increase in the BCCs compared to the control groups. Analogously, 2 studies contained numerical data on HBD levels but with a different in methodology. The level of cathelicidin was established in 108 BCCs and was significantly higher in the BCC group than in the control group.
CONCLUSIONS
The presented review shows evidence that proteins like TGF-β, HBD, and cathelicidin play a role in developing BCC. Protein levels or their expression are elevated in patients with BCC. Furthermore, a critical review of the literature was presented and discussed, highlighting its shortcomings.
PubMed: 37545828
DOI: 10.5114/ada.2023.124747 -
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