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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 -
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 -
Journal of Orthopaedics 2021The aim of this study was to systematically review the literature regarding accurate shoulder prosthetic joint infection (PJI) diagnosis.
INTRODUCTION
The aim of this study was to systematically review the literature regarding accurate shoulder prosthetic joint infection (PJI) diagnosis.
METHODS
Using PRISMA guidelines, we analyzed 25 studies reporting on 5535 patients and 646 infections.
RESULTS
cultures were positive in 60% of patients. Serum markers WBC, CRP, ESR, and IL-6 appear to lack diagnostic reliability. Synovial IL-6 and alpha-defensin may be more accurate in detecting infections.
CONCLUSION
Synovial IL-6 and alpha-defensin appear to have greater utility than serum markers. These may be incorporated into new criteria to accurately diagnose shoulder PJI.
LEVEL OF EVIDENCE
IV.
PubMed: 34305349
DOI: 10.1016/j.jor.2021.07.012 -
Clinical Orthopaedics and Related... Jun 2020Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication that causes severe morbidity and adds a major financial burden to the... (Meta-Analysis)
Meta-Analysis
Does the Alpha Defensin ELISA Test Perform Better Than the Alpha Defensin Lateral Flow Test for PJI Diagnosis? A Systematic Review and Meta-analysis of Prospective Studies.
BACKGROUND
Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication that causes severe morbidity and adds a major financial burden to the healthcare system. Although there is plenty of research on the alpha-defensin (AD) test, a meta-analysis consisting of only prospective studies investigating AD's diagnostic efficacy has not been performed. Additionally, some important subgroups such as THA and TKA have not been separately analyzed, particularly regarding two commonly used versions of the AD test, the laboratory-based (ELISA) and lateral-flow (LF).
QUESTIONS/PURPOSES
(1) Does the AD ELISA test perform better in the detection of PJI than the AD LF test, in terms of pooled sensitivity and specificity, when including prospective studies only? (2) Are there differences in sensitivity or specificity when using AD ELISA and AD LF tests for PJI diagnosis of THA or TKA PJI separately?
METHODS
Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we included prospective studies describing the use of either AD test in the workup of pain after total joint arthroplasty (primary or revision, but not after resection arthroplasty). Fifteen studies (AD ELISA: 4; AD LF: 11) were included, with 1592 procedures. Subgroup data on THA and TKA could be retrieved for 1163 procedures (ELISA THA: 123; LF THA: 257; ELISA TKA: 228; LF TKA: 555). Studies not describing THA or TKA, those not using Musculoskeletal Infection Society (MSIS) criteria as the standard for determining the presence or absence of PJI, those not clearly reporting data for the AD test for the total cohort, and those describing data published in another study were excluded. Studies were not excluded based on follow-up duration; the MSIS criteria could be used within a few weeks, when test results were available. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Study quality was generally good. The most frequent sources of bias were related to patient selection (such as unclear inclusion and exclusion criteria) and flow and timing (uncertainty in place and time of aspiration, for example). Heterogeneity was moderate to high; a bivariate random-effects model therefore was used. To answer both research questions, sensitivity and specificity were calculated for AD ELISA and LF test groups and THA and TKA subgroups, and were compared using z-test statistics and meta-regression analysis.
RESULTS
No differences were found between the AD ELISA and the AD LF for PJI diagnosis in the pooled cohorts (THA and TKA combined), in terms of sensitivity (90% versus 86%; p = 0.43) and specificity (97% versus 96%; p = 0.39). Differences in sensitivity for PJI diagnosis were found between the THA and TKA groups for the AD ELISA test (70% versus 94%; p = 0.008); pooled AD LF test sensitivity did not differ between THA and TKA (80% versus 87%; p = 0.20). No differences in specificity were found in either subgroup.
CONCLUSIONS
Both the AD ELISA and AD LF test can be used in clinical practice because both have high sensitivity and very high specificity for PJI diagnosis. The lower sensitivity found for diagnosis of PJI in THA for the AD ELISA test must be carefully interpreted because the pooled data were heterogenous and only two studies for this group were included. Future research should analyze TKAs and THAs separately to confirm or disprove this finding.
LEVEL OF EVIDENCE
Level II diagnostic study.
Topics: Arthroplasty, Replacement; Biomarkers; Enzyme-Linked Immunosorbent Assay; Humans; Joint Prosthesis; Point-of-Care Testing; Predictive Value of Tests; Prosthesis-Related Infections; Reproducibility of Results; alpha-Defensins
PubMed: 32324670
DOI: 10.1097/CORR.0000000000001225 -
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 -
JID Innovations : Skin Science From... Jul 2022As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous... (Review)
Review
As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.
PubMed: 35620703
DOI: 10.1016/j.xjidi.2022.100126 -
Nutrients Jan 2021Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs)....
Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are , respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms "vitamin D" and "" or "Respiratory Syncytial Virus" or "Influenza". A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Topics: Child; Child, Preschool; Cytokines; Humans; Immunity, Innate; Immunomodulation; Infant; Influenza A virus; Influenza, Human; Pneumonia, Pneumococcal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Vitamin D
PubMed: 33478006
DOI: 10.3390/nu13010276 -
Revista Medica Del Instituto Mexicano... Jul 2023Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic... (Review)
Review
Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic review, to identify SNPs recently associated with dental caries in pediatric populations. We included studies performed in humans up to 18 years of age that evaluated the relationship between SNPs and dental caries from 2017 to 2022. Articles that covered other study variables were excluded. PubMed, ScienceDirect and Web of Science were used to search for information and the included articles were evaluated with one of the Joanna Briggs Institute's tools. Twenty-five articles were selected, 60% of which were given high methodological quality. A total of 10,743 research subjects, ranging in age from 20 months to 17 years, participated in the study. The SNPs considered risk factors were identified in the genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 and MMP13; those considered protective factors were identified in the genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM and HLA-DRB1. This systematic review presents the genetic polymorphisms that are associated with the etiology of caries in children and adolescents, some of which act as risk factors and others as protective factors against the disease.
Topics: Adolescent; Humans; Child; Dental Caries; HLA-DRB1 Chains; Polymorphism, Single Nucleotide; Mannose-Binding Lectin; beta-Defensins; MicroRNAs
PubMed: 37540722
DOI: 10.5281/zenodo.8200501 -
Frontiers in Microbiology 2024The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic...
The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic surgeries carry a risk of infection, especially in patients with comorbidities. The rise of antibiotic resistance exacerbates this issue, necessitating alternatives like bioengineered antimicrobial peptides (AMPs), offering broad-spectrum activity and multiple action mechanisms. This review aimed to assess the prevalence of antimicrobial potential and the yield after purification among recombinant AMP families. The antimicrobial potential was evaluated using the Minimum Inhibitory Concentration (MIC) values against the most common bacteria involved in clinical infections. This systematic review adhered to PRISMA guidelines, focusing on studies of recombinant AMPs. The search strategy was run on PubMed, Scopus and Embase up to 30 March 2023. The Population, Exposure and Outcome model was used to extract the data from studies and ToxRTool for the risk of bias analysis. This review included studies providing peptide production yield data and MIC values against pathogenic bacteria. Non-English texts, reviews, conference abstracts, books, studies focusing solely on chemical synthesis, those reporting incomplete data sets, using non-standard MIC assessment methods, or presenting MIC values as ranges rather than precise concentrations, were excluded. From 370 publications, 34 studies on AMPs were analyzed. These covered 46 AMPs across 18 families, with Defensins and Hepcidins being most common. Yields varied from 0.5 to 2,700 mg/L. AMPs were tested against 23 bacterial genera, with MIC values ranging from 0.125 to >1,152 μg/mL. Arenicins showed the highest antimicrobial activity, particularly against common orthopedic infection pathogens. However, AMP production yields varied and some AMPs demonstrated limited effectiveness against certain bacterial strains. This systematic review emphasizes the critical role of bioengineered AMPs to cope infections and antibiotic resistance. It meticulously evaluates recombinant AMPs, focusing on their antimicrobial efficacy and production yields. The review highlights that, despite the variability in AMP yields and effectiveness, Arenicins and Defensins are promising candidates for future research and clinical applications in treating antibiotic-resistant orthopedic infections. This study contributes significantly to the understanding of AMPs in healthcare, underscoring their potential in addressing the growing challenge of antibiotic resistance. https://osf.io/2uq4c/.
PubMed: 38756724
DOI: 10.3389/fmicb.2024.1370826 -
BMC Medical Genetics Sep 2019Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role in the pathogenesis of rotator cuff disease. Several genes are responsible for rotator cuff disease. The aim of this study was to perform a systematic review on genetic association between rotator cuff disease and genes variations.
METHODS
A systematic review of the literature was performed, in accordance with the PRISMA guidelines. PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases were searched comprehensively using the keywords: "Rotator cuff", "Gene", "Genetic", "Predisposition", "Single-nucleotide polymorphism" and "Genome-wide association".
RESULTS
8 studies investigating genes variations associated with rotator cuff tears were included in this review. 6 studies were case-control studies on candidate genes and 2 studies were GWASs. A significant association between SNPs and rotator cuff disease was found for DEFB1, FGFR1, FGFR3, ESRRB, FGF10, MMP-1, TNC, FCRL3, SASH1, SAP30BP, rs71404070 located next to cadherin8. Contradictory results were reported for MMP-3.
CONCLUSION
Further investigations are warranted to identify complete genetic profiles of rotator cuff disease and to clarify the complex interaction between genes, encoded proteins and environment. This may lead to individualized strategies for prevention and treatment of rotator cuff disease.
LEVEL OF EVIDENCE
Level IV, Systematic Review.
Topics: Cadherins; Databases, Factual; Fibroblast Growth Factor 10; Genetic Variation; Genome-Wide Association Study; Humans; Matrix Metalloproteinase 1; Nuclear Proteins; Polymorphism, Single Nucleotide; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Estrogen; Receptors, Immunologic; Rotator Cuff; Rotator Cuff Injuries; Tenascin; Transcription Factors; Tumor Suppressor Proteins; beta-Defensins
PubMed: 31477042
DOI: 10.1186/s12881-019-0883-y