Induction immune-checkpoint inhibitors for resectable oncogene-mutant NSCLC: A multicenter pooled analysis.

Despite limited efficacy of immunotherapy for advanced non-small-cell lung cancer (NSCLC) with driver mutations, whether neoadjuvant immunotherapy could be clinically valuable in those patients warrants further investigation. We utilized 40 oncogene-mutant NSCLC treated with induction immunotherapy from a large consecutive multicenter cohort. Overall response rate was 62.5% while 2 patients had disease progression. Of 39 patients that received surgery, R0 resection rate was 97.4%. The major pathological response (MPR) rate was 37.5% and the pathological complete response (pCR) rate was 12.5%. Pre-treatment PD-L1 expression was not a predictive biomarker in these patients. Median disease-free survival for all oncogenic mutation and EGFR mutation was 28.5 months. Indirect comparison through integrating CTONG1103 cohort showed neoadjuvant immunotherapy plus chemotherapy yielded the most superior efficacy among erlotinib and chemotherapy for resectable EGFR-mutant NSCLC. No MPR patients were identified with neoadjuvant immunotherapy plus chemotherapy for uncommon EGFR insertion or point mutations. Our results indicated the potential clinical feasibility of neoadjuvant immunotherapy for resectable localized oncogene-mutant NSCLC especially for EGFR-mutant NSCLC.

Clinical metagenomic sequencing for rapid diagnosis of pneumonia and meningitis caused by Chlamydia psittaci.

BACKGROUND: Chlamydia psittaci (C. psittaci) is a gram-negative intracellular parasitic pathogenic bacterium that can infect avian and mammalian hosts, including humans. The detection of C. psittaci infections typically relies on traditional antigen-based immunoassays or serological testing that often lack sensitivity and/or specificity. Metagenomic next generation sequencing (mNGS) is an emerging tool for diagnosis. AIM: To demonstrate that mNGS represents a valuable tool for rapid, sensitive, and accurate pathogen detection including C. psittaci infections. METHODS: Four cases of psittacosis pneumonia and one case of pediatric psittacosis meningitis were diagnosed between December 2019 and May 2020 using mNGS at Changzhou Second People's Hospital affiliated to Nanjing Medical University. Patients' clinical characteristics, manifestations, and treatment histories were retrospectively evaluated. RESULTS: All five patients had a history of exposure to wild (psittacine or other birds) or domesticated birds (chickens). All patients had a high fever (> 39℃) and three of them (60%) experienced organ insufficiency during the disease. The laboratory data showed normal to slightly increased leucocyte and neutrophil counts, and elevated procalcitonin levels in all five cases, and very high C-reactive protein levels in psittacosis pneumonia patients. mNGS identified a potential pathogen, C. psittaci, in patients' bronchoalveolar lavage fluid or cerebrospinal fluid. Computed tomography revealed lung air-space consolidation, pleural thickening, and effusion fluid buildup in psittacosis pneumonia cases, and an arachnoid cyst in the right temporal lobe of the pediatric psittacosis meningitis patient. All patients experienced complete recovery following the administration of targeted anti-chlamydia therapy. CONCLUSION: This study not only demonstrated that mNGS represents a valuable tool for rapid, sensitive, and accurate pathogen detection, but also raised public health concerns over C. psittaci infections.

Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA.

Background: Malignant lymphomas are a group of distinct lymphoid neoplasms, exhibiting marked diversity in biological behaviors and clinical outcomes. Liquid biopsy, such as circulating cell-free DNA (cfDNA), has recently been attempted to be used for mutation profiling of lymphomas using next-generation sequencing (NGS). However, only limited data about cfDNA are restricted in Hodgkin's lymphoma and B cell lymphoma, and there is no report in the T cell lymphoma so far. Patient and Methods: Medical records of a total of 50 lymphoma patients were retrospectively reviewed, and cfDNA samples were analyzed by capture-based NGS targeting 390 lymphoma- and cancer- relevant genes. We sought to explore the clinical utility of cfDNA in establishing the mutation profiles of different lymphoma subtypes and analyze the correlation between cfDNA concentration and other clinical indices such as serum LDH and IPI. Results: Somatic alterations were identified in cfDNA samples with a median of 64 variants per sample. The concentration of cfDNA in the plasma was found to be significantly correlated with the clinical indices in diffuse large B cell lymphoma (DLBCL). The genetic heterogeneity of different lymphoma subtypes was clearly observed in cfDNAs from germinal center B-cell (GCB) DLBCL, non-GCB DLBCL and natural killer/T-cell lymphoma (NKTCL), confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas. Conclusion: Our findings demonstrate that NGS-based cfDNA mutation profiling reveals genetic heterogeneity across lymphoma subtypes, with potential implications for the discovery of therapeutic targets, the exploration of genome evolution and the development of risk-adapted treatment.