Anti-Human EGFR monoclonal antibody, Alexa Fluor 555

An increasing number of studies outline renal function as an important risk marker for mortality in acute heart failure (AHF). However, routine estimation of glomerular filtration rate (eGFR) based on serum creatinine is imprecise. This study aims to compare the prognostic impact of CKD-EPI creatinine based equation (eGFRcr), cystatin C based equation (eGFRcyst), and creatinine-cystatin C equation (eGFRcrcyst) for the mortality stratification in AHF. A total of 354 Patients with AHF were prospectively included between January 2012 and June 2016. Creatinine and cystatin C were measured using the same blood sample tube on admission. We quantified eGFR by the eGFRcr, eGFRcyst, and eGFRcrcyst equations. The continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were calculated to compare the discriminative prognostic value of different CKD-EPI formula. After a median follow-up of 35 months, 161 patients (45.5%) died. Reduced eGFRcyst and eGFRcrcyst remained significant association with death after adjustment. eGFRcyst showed the best area under the curve value (0.706) for the prediction of all-cause mortality. Considering mortality reclassification, both eGFRcyst (IDI = 7.3%, P < .001; cNRI = 19.6%, P = .012) and eGFRcrcyst (IDI = 4.3%, P < .001; cNRI = 8.7%, P = .138) showed its tendency in improving risk prediction compared to eGFRcr. Compared to eGFRcrcyst showed, eGFRcyst further improved mortality stratification (IDI = 3%, P = .049; cNRI = 11.1%, P = .036). In patients with AHF, our study demonstrates the eGFR calculated by CKD-EPI cystatin C-based equation improved the risk stratification of mortality over both creatinine-based and creatinine/cystatin C-based equations.

The WJOG8815L phase II clinical study involves patients with non-small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third-generation EGFR-TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR-TKI-sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing-and T790M-EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation-positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression-free survival were observed between the sensitizing EGFR MF-high and sensitizing EGFR MF-low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).