Etiology of Severe Community-Acquired Pneumonia in Adults Based on Metagenomic Next-Generation Sequencing: A Prospective Multicenter Study

2020 ◽  
Author(s):  
Xiaodong Wu ◽  
Yuanyuan Li ◽  
Ming Zhang ◽  
Xue Dong ◽  
Miaomiao Li ◽  
...  
Author(s):  
Ting Sun ◽  
Xiaojing Wu ◽  
Ying Cai ◽  
Tianshu Zhai ◽  
Linna Huang ◽  
...  

BackgroundMetagenomic next-generation sequencing (mNGS) is a promising technique for pathogens diagnosis. However, application of mNGS in immunocompromised adults with severe community-acquired pneumonia (SCAP) is relatively limited.MethodsWe retrospectively reviewed 23 immunocompromised and 21 immunocompetent SCAP patients with mNGS detection from April 2019 to December 2019. The performances of pathogenic diagnosis and subsequently antibiotic adjustment in immunocompromised SCAP patients were compared to immunocompetent SCAP patients. The defined by days of therapy (DOT) method was used for estimate daily antibiotic use.ResultsThere was a significant difference in the diagnostic positivity rate between mNGS and conventional test in both groups (P<0.001). Compared to immunocompetent patients, more mixed pathogens in immunocompromised patients were found (P=0.023). Before the availability of mNGS, the DOTs in immunocompromise patients were higher than immunocompetent patients (3.0 [3.0, 4.0] vs. 3.0 [2.0, 3.0], P=0.013). Compared to immunocompetent patients, immunocompromised patients had fewer full pathogen covered empirical antibiotic therapy (14.7% vs. 57.1%, P=0.022), more adjustments of antibiotic treatment (87.0%) vs. 57.1%, P=0.027). More than a half (13 of 23) SCAP patients in immunosuppressed group had reduced or downgraded antibiotic adjustments based on the results.ConclusionsmNGS may be a useful technique for detecting mixed pathogens and personalized antibiotic treatment in immunocompromised SCAP patients.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 51-51
Author(s):  
Rongbo Lin ◽  
Shen Zhao ◽  
Lisheng Cai ◽  
Shaoqin Chen ◽  
Jinhuo Lai ◽  
...  

51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.


2020 ◽  
Author(s):  
Shanshan Su ◽  
Jiahao Zeng ◽  
Yunlei Li ◽  
Pengcheng Lin ◽  
Junjie Chen ◽  
...  

Abstract Background Legionella and Chlamydia psittaci cause atypical community-acquired pneumonia, which mimic each other. Our aim was to compare the clinical characteristics of Legionella pneumonia (LP) and psittacosis and assess whether metagenomic next-generation sequencing (mNGS) is an effective method for early diagnosis. Methods We conducted a retrospective study and compared seventeen patients with Chlamydia psittaci pneumonia and nine patients with LP, diagnosed by mNGS. This study was carried out in the First Affiliated Hospital of Wenzhou Medical University, China, from July 2018 to May 2020. mNGS was carried out from bronchial alveolar lavage fluid (BALF) and/or lung tissues. Results 76.5% of psittacosis cases and 0% of legionellosis cases had an avian exposure history (p < 0.001). Compared with LP patients, psittacosis patients had significantly higher hemoglobin (118.9 ± 20.2 vs. 93.2 ± 23.2 g/L, p = 0.007), serum sodium (138.9 ± 5.4 vs. 133.9 ± 6.5 mmol/L, p = 0.047), and higher proportion of elevated aspartate aminotransferase levels (88.2 vs. 44.4%, p = 0.028). Other clinical parameters were similar in psittacosis and LP patients: normal or slightly elevated leucocytes (10.5 vs. 9.5 × 109/L, p > 0.05), neutrophils (9.4 vs. 8.3 × 109/L, p > 0.05), and procalcitonin (0.8 vs 5.1 ng/mL, p > 0.05); highly increased C-reactive protein levels (205.1 vs. 234.9 mg/L, p > 0.05); and decreased lymphocytes (0.7 vs. 0.6 × 109/L, p > 0.05). Extra-pulmonary manifestations and mortality (11.8% in psittacosis vs. 22.2% in LP group, p = 0.591) were also similar in both the groups. mNGS detected Chlamydia psittaci in 17/17 BALF samples, and Legionella in 8/8 BALF samples and 1/1 lung tissue sample. Conclusions Apart from sharing many features with legionellosis, psittacosis is a vital differential diagnosis for LP, especially in patients with avian exposure history. mNGS is a sensitive and promising method for early diagnosis of both psittacosis and LP.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21742-e21742
Author(s):  
Huafei Chen ◽  
Wen xian Wang ◽  
Chunwei Xu ◽  
You-cai Zhu ◽  
Wu Zhuang ◽  
...  

e21742 Background: Currently, with the advances in detection techniques, such as next generation sequencing (NGS), more and more rare or atypical TP53 fusions had been identified. Such as TP53-PSMD14, the importance of EGFR signaling in the pathogenesis of lung cancer and the efficacy of EGFR-TKI treatment had been demonstrated. The aim of this study was to evaluate the prevalence of TP53 fusions in Chinese NSCLC populations, which had not been reported earlier, and to describe targeting potential in Chinese NSCLC populations. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. A total of 2743 patients with NSCLC were screened by using next-generation sequencing (NGS)-based 381 genes panel assay for detecting TP53 fusions. Results: Of this entire cohort, just four (0.15%) patients were identified with a TP53 fusion, including DNAH2-TP53 (1), TP53-MPDU1 (1), TP53-FXR2 (1), TP53-VEZF1 (1). Of the TP53 fusion NSCLC patients, 50.00% were detected in female patients. Biopsies were obtained from primary lung tumor (25.00%) and metastatic sites (75.00%). Overall TMB in the TP53 fusion was high, which had more than 20 mut/Mb. Of the TP53 fusion NSCLC, two cases (50.00%) featured EGFR SV alterations. Conclusions: The frequency of TP53 fusions in Chinese populations with NSCLC is extremely rare (0.17%). TP53 fusions may reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions or exon 21 L858R.


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