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Critical Reviews in Oncology/hematology Jan 2022This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Humans; Mutation; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins p21(ras)
PubMed: 34843928
DOI: 10.1016/j.critrevonc.2021.103548 -
The Cochrane Database of Systematic... Feb 2017Microbial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Microbial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.
OBJECTIVES
To assess the diagnostic accuracy of various molecular methods for the diagnosis of culture-positive bacterial and fungal sepsis in neonates and to explore heterogeneity among studies by analyzing subgroups classified by gestational age and type of sepsis onset and compare molecular tests with one another.
SEARCH METHODS
We performed the systematic review as recommended by the Cochrane Diagnostic Test Accuracy Working Group. On 19 January 2016, we searched electronic bibliographic databases (the Cochrane Library, PubMed (from 1966), Embase (from 1982), and CINAHL (from 1982)), conference proceedings of the Pediatric Academic Societies annual conference (from 1990), clinical trial registries (ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) registry, and World Health Organization (WHO) International Clinical Trials Platform (ICTRP) Search portal), and Science Citation Index. We contacted experts in the field for studies.
SELECTION CRITERIA
We included studies that were prospective or retrospective, cohort or cross-sectional design, which evaluated molecular assays (index test) in neonates with suspected sepsis (participants) in comparison with microbial cultures (reference standard).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the methodologic quality of the studies and extracted data. We performed meta-analyses using the bivariate and hierarchical summary receiver operating characteristic (HSROC) models and entered data into Review Manager 5.
MAIN RESULTS
Thirty-five studies were eligible for inclusion and the summary estimate of sensitivity was 0.90 (95% confidence interval (CI) 0.82 to 0.95) and of specificity was 0.93 (95% CI 0.89 to 0.96) (moderate quality evidence). We explored heterogeneity by subgroup analyses of type of test, gestational age, type of sepsis onset, and prevalence of sepsis and we did not find sufficient explanations for the heterogeneity (moderate to very low quality evidence). Sensitivity analyses by including studies that analyzed blood samples and by good methodology revealed similar results (moderate quality evidence).
AUTHORS' CONCLUSIONS
Molecular assays have the advantage of producing rapid results and may perform well as 'add-on' tests.
Topics: DNA, Bacterial; DNA, Fungal; Humans; Infant, Newborn; Infant, Premature; Polymerase Chain Reaction; Sepsis
PubMed: 28236648
DOI: 10.1002/14651858.CD011926.pub2 -
Acta Obstetricia Et Gynecologica... Sep 2021Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the...
INTRODUCTION
Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.
MATERIAL AND METHODS
The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.
RESULTS
A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.
CONCLUSIONS
Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.
Topics: DNA Damage; Ganciclovir; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Spermatozoa
PubMed: 33755191
DOI: 10.1111/aogs.14151 -
Frontiers in Allergy 2023Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and... (Review)
Review
BACKGROUND
Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research.
METHODS
A systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS.
RESULTS
The review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating and changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (), , and . In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, , aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription.
CONCLUSIONS
Epigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.
PubMed: 37284022
DOI: 10.3389/falgy.2023.1165271 -
Systematic Reviews Aug 2022The aims of this systematic review were to (1) identify primary- and model-based economic evaluations of cervical cancer screening methods and to (2) provide a...
OBJECTIVE
The aims of this systematic review were to (1) identify primary- and model-based economic evaluations of cervical cancer screening methods and to (2) provide a contextual summary of valuation outcomes associated with three types of cervical cancer screening tests: visual inspection with acetic acid, human papillomavirus deoxyribonucleic acid, and Papanicolaou smear.
INTRODUCTION
Cervical cancer screening is an important public health priority with the potential to improve the detection of precancerous lesions in high-risk females for early intervention and disease prevention. Test performance and cost-effectiveness differ based on the specific screening method used across different platforms. There is a need to appraise existing economic evaluations of cervical cancer screening methods.
METHODS
This review considered primary-based and model-based full economic evaluations of cervical cancer screening methods. The evaluation methods of interest included cost-effectiveness analysis, cost-utility analysis, cost-minimization analysis, cost-benefit analysis, and cost-consequence analysis. We searched Scopus, PubMed, National Health Economic Evaluation Database (NH EED), Cochrane, and the Health Economic Evaluation Database for full economic evaluations of cancer screening methods. No formal date restrictions were applied. Model-based and primary-based full economic evaluations were included. A critical appraisal of included studies was performed by the main investigator, while a second independent reviewer assessed critical appraisal findings for any inconsistencies. Data were extracted using a standardised data extraction tool for economic evaluations. The ultimate outcomes of costs, effectiveness, benefits, and utilities of cervical cancer screening modalities were extracted from included studies, analysed, and summarised.
RESULTS
From a total of 671 screened studies, 44 studies met the study inclusion criteria. Forty-three studies were cost-effectiveness analyses, one study reported both cost-utility and cost-effectiveness outcomes, and another study reported cost utilities of cervical cancer screening methods only. Human papillomavirus (HPV) DNA testing was reported as a dominant stand-alone screening test by 14 studies, while five studies reported visual inspection with acetic acid (VIA) as a dominant stand-alone screening test. Primary HPV screening strategies were dominant in 21 studies, while three studies reported cytology-based screening strategies as the dominant screening method.
CONCLUSIONS
Existing evidence indicates that HPV-based and VIA testing strategies are cost-effective, but this is dependent on setting. Our review suggests the limited cost-effectiveness of cytology-based testing, which may be due in part to the need for specific infrastructures and human resources.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020212454 .
Topics: Cost-Benefit Analysis; Early Detection of Cancer; Female; Humans; Mass Screening; Papillomavirus Infections; Uterine Cervical Neoplasms; Vaginal Smears
PubMed: 35945642
DOI: 10.1186/s13643-022-02017-z -
Reviews in Medical Virology Jan 2023Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic... (Meta-Analysis)
Meta-Analysis Review
Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03-1.32; HR: 1.05, 95% CI: 0.97-1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87-0.94; HR: 0.74, 95% CI: 0.71-0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.
Topics: Humans; Torque teno virus; Retrospective Studies; Prospective Studies; Organ Transplantation; Immunosuppression Therapy; Viral Load; DNA, Viral
PubMed: 36056751
DOI: 10.1002/rmv.2393 -
International Journal of Cardiology.... Aug 2023Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function. (Review)
Review
BACKGROUND
Tissue necrosis releases cell-free deoxyribonucleic acid (cfDNA), leading to rapid increases in plasma concentration with clearance independent of kidney function.
AIM
To explore the diagnostic role of cfDNA in acute myocardial infarction (AMI).
METHODS
This systematic review and -analysis included studies of cfDNA in patients with AMI and a comparator group without AMI. The quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool was used, with AMI determined from the criteria of the original study. Standardised mean differences (SMD) were obtained using a random-effects inverse variance model. Heterogeneity was reported as I. Pooled sensitivity and specificity were computed using a bivariate model. The area under the curve (AUC) was estimated from a hierarchical summary receiver operating characteristics curve.
RESULTS
Seventeen studies were identified involving 1804 patients (n = 819 in the AMI group, n = 985 in the comparator group). Circulating cfDNA concentrations were greater in the AMI group (SMD 3.47 (95%CI: 2.54-4.41, p < 0.001)). The studies were of variable methodological quality with substantial heterogeneity (I = 98%, p < 0.001), possibly due to the differences in cfDNA quantification methodologies (Chi 25.16, p < 0.001, I = 92%). Diagnostic accuracy was determined using six studies (n = 804), which yielded a sensitivity of 87% (95%CI: 72%-95%) and specificity of 96% (95%CI: 92%-98%). The AUC was 0.96 (95%CI: 0.93-0.98). Two studies reported a relationship between peak cfDNA and peak troponin. No studies reported data for patients with pre-existing kidney impairment.
CONCLUSION
Plasma cfDNA appears to be a reliable biomarker of myocardial injury. Inferences from existing results are limited owing to methodology heterogeneity.
PubMed: 37560328
DOI: 10.1016/j.ijcha.2023.101246 -
Clinical Epigenetics Apr 2019Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk. The aims of this systematic review were to identify and synthesise the evidence for an association between peripherally measured DNA methylation age and longevity, age-related disease, and mortality risk.
METHODS
A systematic search was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using relevant search terms, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsychINFO databases were searched to identify articles meeting the inclusion criteria. Studies were assessed for bias using Joanna Briggs Institute critical appraisal checklists. Data was extracted from studies measuring age acceleration as a predictor of age-related diseases, mortality or longevity, and the findings for similar outcomes compared. Using Review Manager 5.3 software, two meta-analyses (one per epigenetic clock) were conducted on studies measuring all-cause mortality.
RESULTS
Twenty-three relevant articles were identified, including a total of 41,607 participants. Four studies focused on ageing and longevity, 11 on age-related disease (cancer, cardiovascular disease, and dementia), and 11 on mortality. There was some, although inconsistent, evidence for an association between increased DNA methylation age and risk of disease. Meta-analyses indicated that each 5-year increase in DNA methylation age was associated an 8 to 15% increased risk of mortality.
CONCLUSION
Due to the small number of studies and heterogeneity in study design and outcomes, the association between DNA methylation age and age-related disease and longevity is inconclusive. Increased epigenetic age was associated with mortality risk, but positive publication bias needs to be considered. Further research is needed to determine the extent to which DNA methylation age can be used as a clinical biomarker.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; Humans; Mortality
PubMed: 30975202
DOI: 10.1186/s13148-019-0656-7 -
Fertility and Sterility Sep 2016Exposure to air pollution has been clearly associated with a range of adverse health effects, including reproductive toxicity, but its effects on male semen quality are... (Review)
Review
UNLABELLED
Exposure to air pollution has been clearly associated with a range of adverse health effects, including reproductive toxicity, but its effects on male semen quality are still unclear. We performed a systematic review (up to June 2016) to assess the impact of air pollutants on sperm quality. We included 17 semi-ecological, panel, and cohort studies, assessing outdoor air pollutants, such as PM2.5, PM10, NOx, SO2, and O3, and their effects on DNA fragmentation, sperm count, sperm motility, and sperm morphology. Thirteen studies assessed air pollution exposure measured environmentally, and six used biomarkers of air pollution exposure (two did both). We rated the studies using the Newcastle-Ottawa Scale and assessed with the exposure method. Taking into account these factors and the number of studies finding significant results (positive or negative), the evidence supporting an effect of air pollution on DNA fragmentation is weak but suggestive, on sperm motility is limited and probably inexistent, on lower sperm count is inconclusive, and on sperm morphology is very suggestive. Because of the diversity of air pollutants and sperm parameters, and the studies' designs, we were unable to perform a meta-analysis. In summary, most studies concluded that outdoor air pollution affects at least one of the four semen quality parameters included in the review. However, results lack consistency, and furthermore, studies were not comparable. Studies using standardized air pollution and semen measures are required to obtain more reliable conclusions.
PROSPERO REGISTRATION NUMBER
CRD42015007175.
Topics: Air Pollutants; Air Pollution; DNA Fragmentation; Endocrine Disruptors; Environmental Monitoring; Fertility; Humans; Infertility, Male; Male; Paternal Exposure; Reproduction; Risk Assessment; Risk Factors; Sperm Count; Sperm Motility; Spermatozoa
PubMed: 27565259
DOI: 10.1016/j.fertnstert.2016.08.022 -
Cancer Medicine Sep 2023Circulating tumor DNA (ctDNA) is an emerging biomarker for locally advanced rectal cancer (LARC), giving hope for stratified treatment. As the completed studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating tumor DNA (ctDNA) is an emerging biomarker for locally advanced rectal cancer (LARC), giving hope for stratified treatment. As the completed studies have small sample sizes and different experimental methods, systematic review and meta-analysis were performed to explore their role in predicting pathological complete response (pCR), tumor recurrence, and prognosis.
METHODS
PubMed, Embase, and the Web of Science were searched for potentially eligible studies published up to September 6, 2022. Pooled relative risk (RR) was calculated to predict pCR and tumor recurrence, and pooled hazard ratio (HR) was calculated to evaluate the prognosis of overall survival (OS), recurrence-free survival (RFS), and metastasis-free survival (MRS).
RESULTS
Twelve studies published between 2018 and 2022 included 931 patients, and 2544 serum samples were eventually included in the meta-analysis. The pooled revealed that ctDNA-negative patients were more likely to have a pCR (RR = 1.64, 95% confidence interval [CI]: 1.26-2.12). The pooled revealed that ctDNA-positive patients were at high risk of recurrence (RR = 3.37, 95% CI: 2.34-4.85) and had a poorer prognosis for OS (HR = 3.03, 95% CI: 1.86-4.95), RFS (HR = 7.08, 95% CI: 4.12-12.14), and MRS (HR = 2.77, 95% CI: 2.01-3.83).
CONCLUSION
ctDNA may be useful for stratifying treatment and assessing prognosis in patients with LARC, but its clinical application still needs to be confirmed in a prospective multicenter study with large samples.
Topics: Humans; Circulating Tumor DNA; Neoplasm Recurrence, Local; Prognosis; Proportional Hazards Models; Rectal Neoplasms; Multicenter Studies as Topic
PubMed: 37553845
DOI: 10.1002/cam4.6434