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The Cochrane Database of Systematic... Mar 2021Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a... (Meta-Analysis)
Meta-Analysis
Prognostic value of test(s) for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide.
BACKGROUND
Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O-methylguanine-DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide.
OBJECTIVES
To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide.
SEARCH METHODS
We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014.
SELECTION CRITERIA
Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan-Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis.
DATA COLLECTION AND ANALYSIS
Two review authors independently undertook all steps of the identification and data extraction process for multiple-method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'-cytosine-phosphate-guanine-3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta-analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals.
MAIN RESULTS
We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status.
AUTHORS' CONCLUSIONS
PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies making such comparisons.
Topics: Adult; Antineoplastic Agents, Alkylating; Bias; Brain Neoplasms; Cohort Studies; CpG Islands; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Promoter Regions, Genetic; Temozolomide; Tumor Suppressor Proteins
PubMed: 33710615
DOI: 10.1002/14651858.CD013316.pub2 -
Chemical Society Reviews Mar 2021The novel human infectious coronaviruses (CoVs) responsible for severe respiratory syndromes have raised concerns owing to the global public health emergencies they have...
The novel human infectious coronaviruses (CoVs) responsible for severe respiratory syndromes have raised concerns owing to the global public health emergencies they have caused repeatedly over the past two decades. However, the ongoing coronavirus disease 2019 (COVID-19) pandemic induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has received unprecedented attention internationally. Monitoring pathogenic CoVs in environmental compartments has been proposed as a promising strategy in preventing the environmental spread and tracing of infectious diseases, but a lack of reliable and efficient detection techniques is still a significant challenge. Moreover, the lack of information regarding the monitoring methodology may pose a barrier to primary researchers. Here, we provide a systematic introduction focused on the detection of CoVs in various environmental matrices, comprehensively involving methods and techniques of sampling, pretreatment, and analysis. Furthermore, the review addresses the challenges and potential improvements in virus detection techniques for environmental surveillance.
Topics: Aerosols; COVID-19; COVID-19 Testing; Environmental Monitoring; Fomites; High-Throughput Nucleotide Sequencing; Humans; Immunoassay; Pandemics; Quality Control; SARS-CoV-2; Sewage; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Wastewater
PubMed: 33710177
DOI: 10.1039/d0cs00595a -
Water Research Apr 2021The emergence of next generation sequencing (NGS) is revolutionizing the potential to address complex microbiological challenges in the water industry. NGS technologies... (Review)
Review
The emergence of next generation sequencing (NGS) is revolutionizing the potential to address complex microbiological challenges in the water industry. NGS technologies can provide holistic insight into microbial communities and their functional capacities in water and wastewater systems, thus eliminating the need to develop a new assay for each target organism or gene. However, several barriers have hampered wide-scale adoption of NGS by the water industry, including cost, need for specialized expertise and equipment, challenges with data analysis and interpretation, lack of standardized methods, and the rapid pace of development of new technologies. In this critical review, we provide an overview of the current state of the science of NGS technologies as they apply to water, wastewater, and recycled water. In addition, a systematic literature review was conducted in which we identified over 600 peer-reviewed journal articles on this topic and summarized their contributions to six key areas relevant to the water and wastewater fields: taxonomic classification and pathogen detection, functional and catabolic gene characterization, antimicrobial resistance (AMR) profiling, bacterial toxicity characterization, Cyanobacteria and harmful algal bloom identification, and virus characterization. For each application, we have presented key trends, noteworthy advancements, and proposed future directions. Finally, key needs to advance NGS technologies for broader application in water and wastewater fields are assessed.
Topics: Cyanobacteria; Harmful Algal Bloom; High-Throughput Nucleotide Sequencing; Wastewater; Water
PubMed: 33610927
DOI: 10.1016/j.watres.2021.116907 -
Reviews in Medical Virology Sep 2021Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental... (Meta-Analysis)
Meta-Analysis Review
Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental evidence. Recent studies have investigated the association between all viruses (the 'virome') and IA/T1D using metagenomic next-generation sequencing (mNGS). Current associations between the early life virome and the development of IA/T1D were analysed in a systematic review and meta-analysis of human observational studies from Medline and EMBASE (published 2000-June 2020), without language restriction. Inclusion criteria were as follows: cohort and case-control studies examining the virome using mNGS in clinical specimens of children ≤18 years who developed IA/T1D. The National Health and Medical Research Council level of evidence scale and Newcastle-Ottawa scale were used for study appraisal. Meta-analysis for exposure to specific viruses was performed using random-effects models, and the strength of association was measured using odds ratios (ORs) and 95% confidence intervals (CIs). Eligible studies (one case-control, nine nested case-control) included 1,425 participants (695 cases, 730 controls) and examined IA (n = 1,023) or T1D (n = 402). Meta-analysis identified small but significant associations between IA and number of stool samples positive for all enteroviruses (OR 1.14, 95% CI 1.00-1.29, p = 0.05; heterogeneity χ = 1.51, p = 0.68, I = 0%), consecutive positivity for enteroviruses (1.55, 1.09-2.20, p = 0.01; χ = 0.19, p = 0.91, I = 0%) and number of stool samples positive specifically for enterovirus B (1.20, 1.01-1.42, p = 0.04; χ = 0.03, p = 0.86, I = 0%). Virome analyses to date have demonstrated associations between enteroviruses and IA that may be clinically significant. However, larger prospective mNGS studies with more frequent sampling and follow-up from pregnancy are required to further elucidate associations between early virus exposure and IA/T1D.
Topics: Autoimmunity; Child; Diabetes Mellitus, Type 1; High-Throughput Nucleotide Sequencing; Humans; Infant; Prospective Studies; Virome
PubMed: 33378601
DOI: 10.1002/rmv.2209 -
Journal of Child Neurology Apr 2021Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal...
OBJECTIVE
Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal dominant sleep-related hypermotor epilepsy patients are medically intractable. In preclinical models, pathogenic nAChR variants cause a gain of function mutation with sensitivity to acetylcholine antagonists and agonists. Nicotine modifies the activity of nAChRs and can be used as targeted therapy.
METHODS
We reviewed next-generation sequencing epilepsy panels from a single laboratory (GeneDx) from patients at Children's Medical Center Dallas between 2011 and 2015 and identified patients with nAChR variants. Retrospective review of records included variant details, medical history, neuroimaging findings, and treatment history.
RESULTS
Twenty-one patients were identified. Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction.
CONCLUSIONS
Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. We propose consideration of transdermal nicotine treatment in intractable epilepsy with known nAChR variants as an experimental therapy. Further clinical trials are needed to fully define therapeutic effects.
Topics: Administration, Cutaneous; Adolescent; Adult; Child; Epilepsy; Ganglionic Stimulants; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Male; Nicotine; Receptors, Nicotinic; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 33284031
DOI: 10.1177/0883073820974851 -
PloS One 2020Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die. The current study aimed to assess the accuracy of metagenomic next generation sequencing (mNGS) for TBM, and to identify a new test for the early diagnosis of TBM.
METHODS
We searched for articles published in Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data up to June 30, 2020 for studies that assessed the efficacy of mNGS for the diagnosis of TBM. Then, the accuracy between mNGS and a composite reference standard (CRS) in these articles was compared using the meta-analysis approach.
RESULTS
Four independent studies with 342 samples comparing mNGS and a CRS were included in this study. The sensitivity of mNGS for TBM diagnosis ranged from 27% to 84%. The combined sensitivity of mNGS was 61%, and the I2 value was 92%. Moreover, the specificity of mNGS for TBM diagnosis ranged from 96% to 100%. The combined specificity of mNGS was 98%, and the I2 value was 74%. The heterogeneity between studies in terms of sensitivity and specificity was significant. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for TBM was 0.98.
CONCLUSIONS
The sensitivity of mNGS for TBM diagnosis was moderate. Furthermore, the specificity was extremely high, and the AUC of the SROC indicated a very good diagnostic efficacy. mNGS could be used as an early diagnostic method for TBM, however, the results should be treated with caution for the heterogeneity between studies was extremely significant.
SYSTEMATIC REVIEW REGISTRATION
INPLASY202070100.
Topics: China; Early Diagnosis; High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Mycobacterium tuberculosis; ROC Curve; Reference Standards; Sensitivity and Specificity; Tuberculosis, Meningeal
PubMed: 33259541
DOI: 10.1371/journal.pone.0243161 -
Gynecologic Oncology Feb 2021Ovarian cancer is often diagnosed in an advanced stage and is associated with a high mortality rate. It is assumed that early detection of ovarian cancer could improve...
Ovarian cancer is often diagnosed in an advanced stage and is associated with a high mortality rate. It is assumed that early detection of ovarian cancer could improve patient outcomes. Unfortunately, effective screening methods for early diagnosis of ovarian cancer are still lacking. Extracellular RNAs circulating in human biofluids can reliably be measured and are emerging as potential biomarkers in cancer. In this systematic review, we present 75 RNA biomarkers detectable in human biofluids that have been studied for early diagnosis of ovarian cancer. The majority of these markers are microRNAs identified using RT-qPCR or microarrays in blood-based fluids. A handful of studies used RNA-sequencing and explored alternative fluids, such as urine and ascites. Candidate RNA biomarkers that were more abundant in biofluids of ovarian cancer patients compared to controls in at least two independent studies include miR-21, the miR-200 family, miR-205, miR-10a and miR-346. Amongst the markers confirmed to be lower in at least two studies are miR-122, miR-193a, miR-223, miR-126 and miR-106b. While these biomarkers show promising diagnostic potential, further validation is required before implementation in routine clinical care. Challenges related to biomarker validation and reflections on future perspectives to accelerate progress in this field are discussed.
Topics: Ascitic Fluid; Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; Early Detection of Cancer; Female; Humans; Liquid Biopsy; MicroRNAs; Ovarian Neoplasms; RNA-Seq
PubMed: 33257015
DOI: 10.1016/j.ygyno.2020.11.018 -
Epilepsia Jan 2021Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic review of the success rate (diagnostic yield) of clinical sequencing through next-generation sequencing (NGS) across NDDs. We compare the genetic testing yield across NDD subtypes and sequencing technology.
METHODS
We performed a systematic review of the PubMed literature until May 2020. We included clinical sequencing studies that utilized NGS in individuals with epilepsy, autism spectrum disorder (ASD), or intellectual disability (ID). Data were extracted, reviewed, and categorized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators performed clinical evaluation and grouping following the International League Against Epilepsy (ILAE) guidelines. Pooled rates of the diagnostic yield and 95% confidence intervals were estimated with a random-effects model.
RESULTS
We identified 103 studies (epilepsy, N = 72; ASD, N = 14; ID, N = 21) across 32,331 individuals. Targeted gene panel sequencing was used in 73, and exome sequencing in 36 cohorts. Given highly selected patient cohorts, the diagnostic yield was 17.1% for ASD, 24% for epilepsy, and 28.2% for ID (23.7% overall). The highest diagnostic yield for epilepsy subtypes was observed in individuals with ID (27.9%) and early onset seizures (36.8%). The diagnostic yield for exome sequencing was higher than for panel sequencing, even though not statistically significant (27.2% vs 22.6%, P = .071). We observed that clinical sequencing studies are performed predominantly in countries with a high Inequality-adjusted Human Development Index (IHDI) (countries with sequencing studies: IHDI median = 0.84, interquartile range [IQR] = 0.09 vs countries without sequencing studies: IHDI median = 0.56, IQR = 0.3). No studies from Africa, India, or Latin America were identified, indicating potential barriers to genetic testing.
SIGNIFICANCE
This meta-analysis and systematic review provides a comprehensive overview of clinical sequencing studies of NDDs and will help guide policymaking and steer decision-making in patient management.
Topics: Age of Onset; Autism Spectrum Disorder; Epilepsy; High-Throughput Nucleotide Sequencing; Humans; Intellectual Disability; Sequence Analysis, DNA; Exome Sequencing
PubMed: 33200402
DOI: 10.1111/epi.16755 -
Orphanet Journal of Rare Diseases Oct 2020Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue... (Review)
Review
BACKGROUND
Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue diagnosis, either histopathology or enzyme assay, are invasive. Meanwhile, GSDs are diseases with significant genetic heterogeneity, and gene-sequencing methods can be more useful. This systematic review aims to review the literature to assess the value of massively parallel sequencing in the diagnosis of GSDs on patients with previously undiagnosed hepatic involvement.
METHODS
Relevant studies identified in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science Core Collection databases up to July 2019 with no time and language restrictions. Publications were included in the review if they analyzed GSDs with hepatic involvement (GSD I, GSD III, GSD IV, GSD VI, GSD IX), using targeted gene sequencing (TGS) or exome sequencing (ES).
RESULTS
Eleven studies were included in this systematic review. ES demonstrated a 93% diagnostic yield. These methods correctly distinguished all types of pathogenic variants. The diagnostic yield of the TGS method was around 79.7%.
CONCLUSIONS
According to our results, TGS analysis can be considered as the first-line diagnostic method with valuable results and ES can be used to diagnose complex cases of GSD with liver involvement. Overall, these molecular methods are considered as accurate diagnostic tools, which expedite correct diagnosis and treatment with significant cost-effectiveness by reducing unnecessary and inaccurate tests.
PROSPERO REGISTRATION
CRD42020139931. Registered 8 January 2020.
Topics: Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Glycogen Storage Disease Type VI; High-Throughput Nucleotide Sequencing; Humans
PubMed: 33054851
DOI: 10.1186/s13023-020-01573-8 -
Oral and Maxillofacial Surgery Dec 2020Dysbiosis has been identified in oral squamous cell carcinoma (OSCC). The aim of this study was to carry out a systematic review of an electronic research that was...
PURPOSE
Dysbiosis has been identified in oral squamous cell carcinoma (OSCC). The aim of this study was to carry out a systematic review of an electronic research that was carried out on articles published between January 2008 and September 2018.
METHODS
Eight studies were selected after applying the inclusion and exclusion criteria.
RESULTS
All articles targeted the hypervariable regions of the 16S rRNA gene. At the phylum level, it was found reduction of Bacteroidetes (2/8 studies) and increase of Firmicutes (2/8 studies). At the genus level, Rothia increased (1/8 studies) and decreased (2/8 studies) in tumor samples, and Streptococcus also was found increased (3/8 studies) and reduced (3/8 studies). Fusobacterium only increased in OSCC samples (3/8 studies). At species level, an increase in F. nucleatum subsp. polymorphum was more associated to OSCC (2/8 studies) than with controls, as was P. aeruginosa (3/8 studies).
CONCLUSION
In summary, the results corroborated dysbiosis in OSCC patients, with enrichment of microbial taxa that are associated with inflammation and production of acetaldehyde. However, variations of study design and sample size were observed among the studies, as well as a shortage of more detailed analyses of possible correlations between risk habits and OSCC. This lack of more detailed analysis may be the cause of the inconsistencies in regard of the alterations reported for certain genera and species. In conclusion, there is an association between OSCC and oral microbiota dysbiosis, but its role in oral carcinogenesis needs to be clarified in more detail.
Topics: Carcinoma, Squamous Cell; High-Throughput Nucleotide Sequencing; Humans; Microbiota; Mouth Neoplasms; RNA, Ribosomal, 16S
PubMed: 32621033
DOI: 10.1007/s10006-020-00873-4