A case of hemorrhagic fever with renal syndrome and abnormal serum levels of ferritin, vitamin B12, and folic acid.

INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) is a globally prevalent infectious disease caused by the hantavirus in rodents. CASE STUDY: This report describes a case of a 36-year-old male presenting with elevated ferritin, vitamin B12, and folic acid deficiency during the early onset phase of HFRS. Despite normal renal function at admission, the patient exhibited persistent fever and thrombocytopenia, leading to a potential misdiagnosis of an atypical HFRS presentation. Abnormal serum levels of ferritin, vitamin B12, and folic acid served as early indicators of renal dysfunction in patients with HRFS. The patient's condition improved rapidly with a combination of vitamin B6, methyl cobalamin, and folic acid, as evidenced by a subsequent decrease in the ferritin levels, from 3000 to 600 ng/mL, on days 4 and 24, respectively, and an increase in the vitamin B12 and folic acid levels to 200 pg/mL and 36.7 ng/mL, separately. CONCLUSIONS: These findings suggest that ferritin, vitamin B12, and folic acid have the potential to serve as biomarkers for HFRS and play a predictive role in the diagnosis and treatment of the disease.

Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study.

BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.

A complex association between DNA methylation and gene expression in human placenta at first and third trimesters.

The human placenta is a maternal-fetal organ essential for normal fetal development and maternal health. During pregnancy, the placenta undergoes many structural and functional changes in response to fetal needs and environmental exposures. Previous studies have demonstrated widespread epigenetic and gene expression changes from early to late pregnancy. However, on the global level, how DNA methylation changes impact on gene expression in human placenta is not yet well understood. We performed DNA methylome analysis by reduced representation bisulfite sequencing (RRBS) and gene expression analysis by RNA-Seq for both first and third trimester human placenta tissues. From first to third trimester, 199 promoters (corresponding to 189 genes) and 2,297 gene bodies were differentially methylated, with a clear dominance of hypermethylation (96.8% and 93.0% for promoters and gene bodies, respectively). A total of 2,447 genes were differentially expressed, of which 77.2% were down-regulated. Gene ontology analysis using differentially expressed genes were enriched for cell cycle and immune response functions. The correlation between DNA methylation and gene expression was non-linear and complex, depending on the genomic context (promoter or gene body) and gene expression levels. A wide range of DNA methylation and gene expression changes were observed at different gestational ages. The non-linear association between DNA methylation and gene expression indicates that epigenetic regulation of placenta development is more complex than previously envisioned.