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BMC Infectious Diseases Jan 2024Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns,... (Meta-Analysis)
Meta-Analysis
Diagnostic performance of metagenomic next-generation sequencing for the detection of pathogens in cerebrospinal fluid in pediatric patients with central nervous system infection: a systematic review and meta-analysis.
BACKGROUND
Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI.
METHODS
Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd's ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance.
RESULTS
A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I = 66.77%, p < 0.001), and the combined specificity was 0.89 (95% CI: 0.80 to 0.95, I = 83.37%, p < 0.001). The AUC of sROC was 0.85 (95% CI, 0.81 to 0.87). The quality level of evidence elevated by the GRADE score system was low.
CONCLUSIONS
Current evidence shows that mNGS presents a good diagnostic performance in pediatric CNSI. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.
Topics: Humans; Child; ROC Curve; Central Nervous System Infections; High-Throughput Nucleotide Sequencing
PubMed: 38238719
DOI: 10.1186/s12879-024-09010-y -
Transfusion Medicine Reviews Jan 2024Molecular analysis of blood groups is important in transfusion medicine, allowing the prediction of red blood cell (RBC) antigens. Many blood banks use single nucleotide... (Meta-Analysis)
Meta-Analysis
Molecular analysis of blood groups is important in transfusion medicine, allowing the prediction of red blood cell (RBC) antigens. Many blood banks use single nucleotide variant (SNV) based methods for blood group analysis. While this is a well-established approach, it is limited to the polymorphisms included in genotyping panels. Thus, variants that alter antigenic expression may be ignored, resulting in incorrect prediction of phenotypes. The popularization of next-generation sequencing (NGS) has led to its application in transfusion medicine, including for RBC antigens determination. The present review/meta-analysis aimed to evaluate the applicability of the NGS for the prediction of RBC antigens. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were selected based on predefined criteria and evaluated using Strengthening the Reporting of Observational studies in Epidemiology guidelines. The characteristics and results of the studies were extracted and meta-analysis was performed to verify the agreement between results from standard molecular methods and NGS. Kell (rs8176058), Duffy (rs2814778, rs12078), or Kidd (rs1085396) alleles were selected as a model for comparisons. Additionally, results are presented for other blood group systems. Of the 864 eligible studies identified, 10 met the inclusion criteria and were selected for meta-analysis. The pooled concordance proportion for NGS compared to other methods ranged from 0.982 to 0.994. The sequencing depth coverage was identified as crucial parameters for the reliability of the results. Some studies reported difficulty in analyzing more complex systems, such as Rh and MNS, requiring the adoption of specific strategies. NGS is a technology capable of predicting blood group phenotypes and has many strengths such as the possibility of simultaneously analyzing hundred individuals and gene regions, and the ability to provide comprehensive genetic analysis, which is useful in the description of new alleles and a better understanding of the genetic basis of blood groups. The implementation of NGS in the routine of blood banks depends on several factors such as cost reduction, the availability of widely validated panels, the establishment of clear quality parameters and access to bioinformatics analysis tools that are easy to access and operate.
Topics: Humans; Transfusion Medicine; High-Throughput Nucleotide Sequencing; Reproducibility of Results; Blood Group Antigens; Erythrocytes
PubMed: 37914611
DOI: 10.1016/j.tmrv.2023.150776 -
Frontiers in Immunology 2023The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to comprehensively evaluate its diagnostic accuracy for the early diagnosis of TBM.
METHODS
English (PubMed, Medline, Web of Science, Cochrane Library, and Embase) and Chinese (CNKI, Wanfang, and CBM) databases were searched for relevant studies assessing the diagnostic accuracy of mNGS for TBM. Review Manager was used to evaluate the quality of the included studies, and Stata was used to perform the statistical analysis.
RESULTS
Of 495 relevant articles retrieved, eight studies involving 693 participants (348 with and 345 without TBM) met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver-operating characteristic curve of mNGS for diagnosing TBM were 62% (95% confidence interval [CI]: 0.46-0.76), 99% (95% CI: 0.94-1.00), 139.08 (95% CI: 8.54-2266), 0.38 (95% CI: 0.25-0.58), 364.89 (95% CI: 18.39-7239), and 0.97 (95% CI: 0.95-0.98), respectively.
CONCLUSIONS
mNGS showed good specificity but moderate sensitivity; therefore, a more sensitive test should be developed to assist in the diagnosis of TBM.
Topics: Humans; Tuberculosis, Meningeal; Sensitivity and Specificity; ROC Curve; High-Throughput Nucleotide Sequencing; Databases, Factual
PubMed: 37822937
DOI: 10.3389/fimmu.2023.1223675 -
Journal of Orthopaedic Surgery and... Aug 2023Accurate diagnosis of prosthetic joint infection (PJI) enables early and effective treatment. However, there is currently no gold standard test for microbial detection... (Meta-Analysis)
Meta-Analysis
Comparison of microbial detection rates in microbial culture methods versus next-generation sequencing in patients with prosthetic joint infection: a systematic review and meta-analysis.
BACKGROUND
Accurate diagnosis of prosthetic joint infection (PJI) enables early and effective treatment. However, there is currently no gold standard test for microbial detection of PJI and traditional synovial fluid culture is relatively insensitive. Recently, it has been reported that sonicating fluid culture and next-generation sequencing (NGS) improve microbial detection rates. Hence, we performed a systematic review and meta-analysis to compare microbial detection rates in microbial culture methods with and without sonication versus NGS.
METHODS
We systematically searched EMBASE, PubMed, Scopus, CINAHL, and Ichushi databases and other sources (previous reviews) until August 2022. We evaluated the detection rates of pathogens in NGS and microbial cultures using samples of synovial or sonicated fluid.
RESULTS
Of the 170 citations identified for screening, nine studies were included. Pooled analysis indicated that NGS had the highest detection rate among the microbial detection methods (NGS vs. sonicated, odds ratios [OR] 5.09, 95% confidential interval [CI] 1.67-15.50; NGS vs. synovial, OR 4.52, 95% CI 2.86-7.16). Sonicated fluid culture showed a higher detection rate than synovial fluid culture (OR 2.11, 95% CI 1.23-3.62).
CONCLUSION
NGS might be useful as a screening tool for culture-negative patients. In clinical settings, sonicated fluid culture is a practical method for diagnosing PJI.
Topics: Humans; High-Throughput Nucleotide Sequencing; Arthritis, Infectious; Databases, Factual; Odds Ratio; Sonication
PubMed: 37587529
DOI: 10.1186/s13018-023-03973-5 -
European Journal of Medical Research Jul 2023RNA sequencing has emerged as the standard method for transcriptome profiling of several human diseases. We performed a systematic review detailing the state of RNA-seq...
RNA sequencing has emerged as the standard method for transcriptome profiling of several human diseases. We performed a systematic review detailing the state of RNA-seq analyses in Africa from its inception till February 2022. Our goal was to provide an update on the state of RNA-seq analyses in Africa, including research gaps, funding information, participants information, authorship and collaborations. Following the PRISMA guidelines, we performed an exhaustive literature search for RNA-seq studies conducted in Africa, using PubMed, Scopus and Academic Search Complete (EBSCOhost). The output was exported to Endnote X9 for analyses. The initial literature search yielded 10,369 articles spread across PubMed (4916), Scopus (4847) and EBSCOhost (580). By applying our exclusion criteria, 28 full-text articles remained and were thoroughly analyzed. Overall, 17 human diseases were studied, including cancers (10/28), infectious disease (4/28), parasitic disease (4/28), autoimmune disorders (2/28) and neglected tropical diseases (2/28). Majority of the articles were published in PLoS Pathogens, BioMed Central and Nature. The National Institutes of Health (42.4%), the Bill & Melinda Gates Foundation (7.5%) and the Wellcome Trust (7.5%) were the top funders of the research studies. Eleven African countries contributed to the participant group, with 57% located in Eastern Africa, 23.1% from Western and 16.7% from Southern Africa. The extremely low number of RNA-seq research studies in Africa is worrying and calls for an immediate investment in research by the African governments. The funding agencies and institutional review boards should also ensure that African collaborators are treated equitably in the course of the research projects.
Topics: United States; Humans; RNA-Seq; Africa; Gene Expression Profiling; Autoimmune Diseases; Evidence Gaps
PubMed: 37480073
DOI: 10.1186/s40001-023-01206-3 -
Frontiers in Cellular and Infection... 2023Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia.
METHODS
We systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU.
RESULTS
Totally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [ = 6.81, 95% (4.59, 10.11, < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [ = 0.35, 95% (0.23, 0.55), < 0.001, = 0%] and 43.43%(109/251) [ = 0.34, 95% (0.21, 0.54), < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% (- 3.56, - 1.96), P < 0.001] and the length of stay in ICU [ = -4.11, 95% (- 5.35, - 2.87), < 0.001].
CONCLUSION
The pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.
Topics: Humans; High-Throughput Nucleotide Sequencing; Hospitals; Metagenome; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 37091676
DOI: 10.3389/fcimb.2023.1106859 -
Frontiers in Pediatrics 2023Pediatric and neonatal sepsis is one of the main causes of mortality and morbidity in these age groups. Accurate and early etiological identification is essential for... (Review)
Review
INTRODUCTION
Pediatric and neonatal sepsis is one of the main causes of mortality and morbidity in these age groups. Accurate and early etiological identification is essential for guiding antibiotic treatment, improving survival, and reducing complications and sequelae. Currently, the identification is based on culture-dependent methods, which has many limitations for its use in clinical practice, and obtaining its results is delayed. Next-generation sequencing enables rapid, accurate, and unbiased identification of multiple microorganisms in biological samples at the same time. The objective of this study was to characterize the etiology of neonatal and pediatric sepsis by metagenomic techniques.
METHODS
A systematic review of the literature was carried out using the PRISMA-2020 guide. Observational, descriptive, and case report studies on pediatric patients were included, with a diagnostic evaluation by clinical criteria of sepsis based on the systemic inflammatory response, in sterile and non-sterile biofluid samples. The risk of bias assessment of the observational studies was carried out with the STROBE-metagenomics instrument and the CARE checklist for case reports.
RESULTS AND DISCUSSION
Five studies with a total of 462 patients were included. Due to the data obtained from the studies, it was not possible to perform a quantitative synthesis (meta-analysis). Based on the data from the included studies, the result identified that mNGS improves the etiological identification in neonatal and pediatric sepsis, especially in the context of negative cultures and in the identification of unusual microorganisms (bacteria that are difficult to grow in culture, viruses, fungi, and parasites). The number of investigations is currently limited, and the studies are at high risk of bias. Further research using this technology would have the potential to improve the rational use of antibiotics.
PubMed: 37063664
DOI: 10.3389/fped.2023.1011723 -
Radiology and Oncology Mar 2023Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12 December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria.
RESULTS
Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, , , and , emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes (OR = 1.58, CI [1.51, 1.66] p < 0.00001) (OR = 1.36, CI [1.12, 1.65], p < 0.002), and (OR = 1.02, CI [1.00, 1.04], p < 0.001).
CONCLUSIONS
According to obtained data, we noticed that the gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested , and genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; High-Throughput Nucleotide Sequencing; Transcription Factors, TFIII
PubMed: 36942904
DOI: 10.2478/raon-2023-0013 -
Clinical Genetics May 2023In recent years, massively parallel sequencing or next generation sequencing (NGS) has considerably changed both the research and diagnostic fields, and rapid... (Review)
Review
In recent years, massively parallel sequencing or next generation sequencing (NGS) has considerably changed both the research and diagnostic fields, and rapid developments have led to the combination of NGS techniques in clinical practice, ease of analysis, and detection of genetic mutations. This article aimed at reviewing the economic evaluation studies of the NGS techniques in the diagnosis of genetic diseases. In this systematic review, scientific databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus, and CEA registry) were searched from 2005 to 2022 to identify the related literature on the economic evaluation of NGS techniques in the diagnosis of genetic diseases. Full-text reviews and data extraction were all performed by two independent researchers. The quality of all the articles included in this study was evaluated using the Checklist of Quality of Health Economic Studies (QHES). Out of 20 521 screened abstracts, 36 studies met the inclusion criteria. The mean score of the QHES checklist for the studies was 0.78 (high quality). Seventeen studies were conducted based on modeling. Cost-effectiveness analysis, cost-utility analysis, and cost-minimization analysis were done in 26 studies, 13 studies, and 1 study, respectively. Based on the available evidence and findings, exome sequencing, which is one of the NGS techniques, could have the potential to be used as a cost-effective genomic test to diagnose children with suspected genetic diseases. The results of the present study support the cost-effectiveness of exome sequencing in diagnosing suspected genetic disorders. However, the use of exome sequencing as a first- or second-line diagnostic test is still controversial. Most studies have been conducted in high-income countries, and research on the cost-effectiveness of NGS methods is recommended in low- and middle-income countries.
Topics: Child; Humans; Cost-Benefit Analysis; Mutation; Cost-Effectiveness Analysis; High-Throughput Nucleotide Sequencing
PubMed: 36808726
DOI: 10.1111/cge.14313 -
Zhonghua Jie He He Hu Xi Za Zhi =... Apr 2023Metagenomic next-generation sequencing (mNGS) enables sensitive and unbiased detection of all potential pathogens in lower respiratory tract infection(LRTI). But the...
Metagenomic next-generation sequencing (mNGS) enables sensitive and unbiased detection of all potential pathogens in lower respiratory tract infection(LRTI). But the lack of consensus and uniformity of applicable clinical scenarios and interpretation of results for mNGS largely limit its utilization. To solve these issues, an expert panel including pulmonary physicians, intensivists and microbiologists is organized by Chinese Thoracic Society. The panel conducted a systematic review of progress and challenges regarding the application of mNGS on etiological diagnosis of LRTI. The panel formulated 17 specific recommendations spanning questions of suitable clinical situations, sample quality control, process of reports interpretation and subsequent medical decisions. Hopefully, this consensus can provide practical guidelines for clinicians and promote the rational application of mNGS in LRTI.
Topics: Humans; Critical Pathways; Consensus; China; High-Throughput Nucleotide Sequencing; Respiratory Tract Infections; Sensitivity and Specificity
PubMed: 36787941
DOI: 10.3760/cma.j.cn112147-20220701-00553