Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study.

BACKGROUND: Central nervous system tuberculosis (CNS TB) is a severe Mycobacterium tuberculosis (MTB) infection. It is unclear whether a patient's immune status alters the clinical manifestations and treatment outcomes of CNS TB. METHODS: Between January 2007-December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID). RESULTS: Of 310 subjects, 160 (51.6%) were in the ID group-132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status -HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups. CONCLUSIONS: TBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients.

Gastrointestinal microbiota profile and clinical correlations in advanced EGFR-WT and EGFR-mutant non-small cell lung cancer.

INTRODUCTION: Difference in clinical responses to cancer therapy in each patient is from several factors. Gastrointestinal microbiota is one of the reasons. However, this correlation remains unknown. This study aims to explore correlation between gastrointestinal microbiota profile and clinical outcomes in Thai advanced non-small cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) status. METHODS: We enrolled 13 patients with advanced EGFR-wild-type (WT) NSCLC who received chemotherapy and 15 patients with EGFR-mutant NSCLC who received EGFR tyrosine kinase inhibitors. We collected fecal samples at baseline and first disease evaluation and performed 16S rRNA gene sequencing by NGS to assess microbiota profile. The correlations between gastrointestinal microbiota and clinical variables were studied. RESULTS: The clinical characteristics were balanced between the cohorts, excluding significantly higher albumin levels in the EGFR-mutant group. Albumin was the only significant clinical factor affecting the treatment response in multivariate analysis (ORR 15.6%, P = 0.03). Proteobacteria counts were higher in the EGFR-WT group, whereas Bacteroidetes and Firmicutes counts were higher in the EGFR-mutant group. The alpha diversity of the gastrointestinal microbiome was significantly higher in the EGFR-mutant group (Shannon index: 3.82 vs. 3.25, P = 0.022). Following treatment, Proteobacteria counts were lower and Bacteroidetes and Firmicutes counts were higher in both cohorts; the changes were more prominent in the EGFR-WT cohort. No significant correlation between microbiota profile and treatment response were demonstrated in our study. However, beta diversity was significantly different according to severity of adverse events. Enrichment of Clostridia and Bacteroidia was associated with higher adverse event risk in the EGFR-WT cohort. CONCLUSIONS: Proteobacteria was dominant in Thai lung cancer patients both EGFR-WT and EGFR-mutant, and this phylum maybe associate with lung cancer carcinogenesis. Chemotherapy altered the gastrointestinal microbiota, whereas EGFR-TKIs had less effects. Our findings highlight the potential predictive utility of the gastrointestinal microbiota for lung cancer carcinogenesis. Studies with larger cohorts and comparison with the healthy Thai population are ongoing to validate this pilot study.