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      The Utility of Metagenomic Next-Generation Sequencing (mNGS) in the Management of Patients With Bronchiectasis: A Single-Center Retrospective Study of 93 Cases

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          Abstract

          Background

          Bronchiectasis is a chronic inflammatory respiratory disease mainly caused by pathogenic infections. However, standard methods of pathogen detection show prolonged cycle durations and unsatisfactory sensitivity and detection rates. Macrogenomic next-generation sequencing (mNGS) emerges as a promising technique for swift, effective, and unbiased pathogen detection and subsequent data interpretation.

          Methods

          Here, a retrospective analysis of 93 patients with suspected bronchiectasis was performed to assess the clinical applicability of mNGS. Bronchoalveolar alveolar lavage fluid (BALF) samples were collected from these subjects, followed by standard assays and mNGS separately. The turnaround time, detection rate, and pathogen identification using mNGS were compared with those of standard methods.

          Results

          mNGS identified a greater number of bacteria (72 vs 16), fungi (26 vs 19), and viruses (14 vs 0) than standard methods. Specifically, the commonly identified bacteria were Haemophilus, Mycobacterium intracellulare, Pseudomonas, and Streptococcus pneumoniae, while the most detected fungi were Aspergillus and the most prevalent viruses were human herpesviruses. Of note, 29 out of 30 patients (96.67%) who received optimized treatment strategies based on mNGS results experienced recovery.

          Conclusions

          Collectively, these findings suggest that mNGS has the potential to improve the diagnosis and treatment of bronchiectasis patients by enabling rapid and precise pathogen detection, which can lead to timely and effective treatment strategies.

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          Most cited references29

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          Validation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection.

          - Metagenomic sequencing can be used for detection of any pathogens using unbiased, shotgun next-generation sequencing (NGS), without the need for sequence-specific amplification. Proof-of-concept has been demonstrated in infectious disease outbreaks of unknown causes and in patients with suspected infections but negative results for conventional tests. Metagenomic NGS tests hold great promise to improve infectious disease diagnostics, especially in immunocompromised and critically ill patients.
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            Next-generation sequencing diagnostics of bacteremia in septic patients

            Background Bloodstream infections remain one of the major challenges in intensive care units, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However a prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identification of bacteria. Methods Here we describe the establishment of a complete diagnostic workflow for the identification of infectious microorganisms from seven septic patients based on unbiased sequence analyses of free circulating DNA from plasma by next-generation sequencing. Results We found significant levels of DNA fragments derived from pathogenic bacteria in samples from septic patients. Quantitative evaluation of normalized read counts and introduction of a sepsis indicating quantifier (SIQ) score allowed for an unambiguous identification of Gram-positive as well as Gram-negative bacteria that exactly matched with blood cultures from corresponding patient samples. In addition, we also identified species from samples where blood cultures were negative. Reads of non-human origin also comprised fragments derived from antimicrobial resistance genes, showing that, in principle, prediction of specific types of resistance might be possible. Conclusions The complete workflow from sample preparation to species identification report could be accomplished in roughly 30 h, thus making this approach a promising diagnostic platform for critically ill patients suffering from bloodstream infections. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0326-8) contains supplementary material, which is available to authorized users.
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              Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity

              Bronchiectasis is a condition characterized by pathological dilation of the airways. More specifically, the radiographic demonstration of airways enlargement is the common feature of a heterogeneous set of conditions and clinical presentations. There are no approved therapies for the condition other than for bronchiectasis caused by cystic fibrosis. The heterogeneity of bronchiectasis is the major challenge in clinical practice and the major reason for difficulty in achieving endpoints in clinical trials. Recent observations have improved our knowledge regarding bronchiectasis such that it may be more effective to describe patients according to a heterogeneous group of endotypes, defined by a distinct functional or pathobiological mechanism, or clinical phenotypes, defined by relevant and common features of disease. In doing so, we may finally develop more specific therapies needed to effectively treat our patients. Here we describe some of the recent advances in endotyping, genetics and disease heterogeneity of bronchiectasis including observations related to the microbiome.
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                Author and article information

                Contributors
                Journal
                Open Forum Infect Dis
                Open Forum Infect Dis
                ofid
                Open Forum Infectious Diseases
                Oxford University Press (US )
                2328-8957
                August 2023
                10 August 2023
                10 August 2023
                : 10
                : 8
                : ofad425
                Affiliations
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Biological Medicine Research and Development Center, Yangtze Delta of Zhejiang , Hangzhou, Zhejiang, China
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Biological Medicine Research and Development Center, Yangtze Delta of Zhejiang , Hangzhou, Zhejiang, China
                Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer , Jiaxing, Zhejiang, China
                Author notes

                Hui Zhang and Dongfeng Shen equal contribution.

                Potential conflicts of interest. All authors: no reported conflicts.

                Correspondence: Xiaolong Ma, BS, Department of Respiratory Medicine, The First Hospital of Jiaxing (the Affiliated Hospital of Jiaxing University), The Key Laboratory of Precision Therapy for Lung Cancer, No. 1882 Zhonghuan South Road, Chengnan Street, Nanhu District, Jiaxing City, Zhejiang Province, China. E-mail: maxiaolong068210@ 123456163.com
                Author information
                https://orcid.org/0009-0005-9516-9523
                Article
                ofad425
                10.1093/ofid/ofad425
                10470666
                37663088
                dc72dbe1-6084-4541-be2b-212d1d02a48f
                © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 21 April 2023
                : 03 August 2023
                : 09 August 2023
                : 31 August 2023
                Page count
                Pages: 8
                Funding
                Funded by: Zhejiang Medical and Health Science and Technology;
                Award ID: 2022KY373
                Funded by: Key Construction Disciplines of Provincial and Municipal Co-construction of Zhejiang;
                Award ID: 2023-SSGJ-002
                Categories
                Major Article
                AcademicSubjects/MED00290

                bronchiectasis,bronchoalveolar alveolar lavage fluid,macrogenomic next-generation sequencing,pathogens

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