Association of prior fluoroquinolone treatment with survival outcomes of immune checkpoint inhibitors in Asia.

WHAT IS KNOWN AND OBJECTIVE: Gut microbiota plays an important role in shaping immune responses. Several studies have reported that antibiotics may alter gut microbiota diversity and compromise the therapeutic response to immune checkpoint inhibitors (ICIs). Nevertheless, the impact of a specific class of antibiotics on ICIs therapy is still not known. The aim of this study was to analyse the influence of antibiotics on the clinical outcomes of non-small cell lung cancer (NSCLC) patients treated with ICIs and to compare the effects of fluoroquinolones vs. other broad-spectrum antibiotics. METHODS: This retrospective cohort study (n = 340) analysed data from Chang Gung Research Database, which comprises work from seven medical institutions in Taiwan. Patients with NSCLC who received ICIs between January 2016 and March 2019 were evaluated. The data of patients who received antibiotics (ie fluoroquinolone) within 30 days prior to ICIs therapy were analysed. Overall survival (OS) was the goal of our study and was calculated from the time the ICIs therapy start. Survival analysis was estimated using the Kaplan-Meier and Cox statistics. RESULTS: A total of 340 patients were identified for analysis. Of the 340 patients, only over one third (38%) of patients received antibiotics 30 days prior to ICI therapy. These patients exhibited a shorter OS compared with those not receiving antibiotics (median OS, 266 days vs. 455 days; hazard ratio (HR), 2.9; 95% confidence interval (CI), 1.1-8.1, p = 0.003). In this study, 127 out of 128 patients who were exposed to antibiotics had received at least one broad-spectrum antibiotic. We observed patients who had received fluoroquinolone had a shorter OS compared with those receiving other broad-spectrum antibiotics (median OS, 121 days vs. 370 days; HR, 1.582; 95% CI 1.007-2.841; p = 0.047). WHAT IS NEW AND CONCLUSION: Antibiotic treatment, especially fluoroquinolone, prior to ICIs therapy was associated with poorer clinical efficacy in NSCLC patients. Antibiotics should not be withheld when there is a clear need for them despite the possibility of interfering with the microbiome, which may, in turn, adversely affect the ICI's effectiveness. However, one should consider avoiding the use of fluoroquinolones antibiotics.

A structure-free digital microfluidic platform for detection of influenza a virus by using magnetic beads and electromagnetic forces.

H1N1, a subtype of influenza A virus, has emerged as a global threat in the past decades. Due to its highly infectious nature, an accurate and rapid detection assay is urgently required. Therefore, this study presents a new type of digital microfluidic platform for H1N1 virus detection by utilizing a one-aptamer/two-antibodies assay on magnetic beads. The droplets containing magnetic beads were driven by electromagnetic forces on a structure-free, super-hydrophobic surface to automate the entire assay within 40 min. With different levels of hydrophobic modification, the droplets could be easily controlled and positioned without any assisted microstructure. The tunable electromagnetic forces could be adjusted for three kinds of operating modes for the manipulations of beads and droplets, including movement of droplets containing magnetic beads, mixing of two droplets and beads extraction out of droplets. When compared with previous studies, the manipulations of droplets and magnetic particles in this study are more flexible as they can be easily adjusted by fine-tuning the magnetic flux density. Furthermore, the magnetic beads also served as three-dimensional substrates for the new enzyme-linked immunosorbent assay (ELISA)-like assay. The magnetic beads were conjugated with aptamers, which have high specificity towards H1N1 viruses such that they could be specifically captured and detected. The horseradish peroxidase-conjugated secondary antibody was then used to activate tyramide-tetramethylrhodamine (TTMR) such that fluorescent signals could be amplified. With this approach, the limit of detection was experimentally found to be 0.032 hemagglutination units/reaction, which is sensitive enough for clinical diagnostics. This kind of digital microfluidic platform with the ELISA-like assay could effectively reduce the consumption of samples and reagents such that the volume of all droplets including the H1N1 sample, antibodies, TTMR and wash buffers was only 20 µL. This is the first time that a digital microfluidic platform was demonstrated such that the entire diagnostic process for influenza A H1N1 viruses could be performed by using electromagnetic forces, which could be promising for rapid and accurate diagnosis of influenza.