Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study.

PURPOSE: Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy. METHODS: This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors. RESULTS: Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence. CONCLUSION: Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.

Concerted derivatization and concentration method with dispersive liquid-liquid microextraction for liquid chromatographic analysis of 5-hydroxyindoles in human serum.

We developed a concerted derivatization and concentration method based on dispersive liquid-liquid microextraction (DLLME) for the liquid chromatography (LC) determination of 5-hydroxyindoles (5-HIs; serotonin, 5-hydroxyindole-3-acetic acid, N-acetylserotonin, and 5-hydroxytryptohol). Concerted derivatization and concentration could be affected by adding a mixture of an ionic liquid (1-hexyl-3-methylimidazolium hexafluorophosphate, extraction solvent), methanol (disperser), and water containing fluorescence derivatization reagents [benzylamine and potassium hexacyanoferrate(III)] into the sample. The resulting sedimented phase was injected into a reversed-phase LC column using a mixture of acetonitrile and 250 mM acetate buffer (pH 4.3) as the mobile phase for gradient elution, and the derivatives obtained were fluorometrically detected at excitation and emission wavelengths of 345 nm and 452 nm, respectively. The derivatization (reagent concentrations and pH) and extraction (extraction and disperser solvent type) conditions were optimized simultaneously. The limits of detection of the 5-HIs were in the range of 0.08-0.33 nM. The method was validated for 10 and 50 pmol/mL human serum levels, and the recovery of 5-HIs was between 66% and 98%, within a relative standard deviation of 9.5%. The proposed method is well suited for the highly sensitive analysis of trace amounts of 5-HIs in human serum samples.