Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib.

BACKGROUND: Concurrent programmed death-ligand-1 (PD-(L)1) plus osimertinib is associated with severe immune related adverse events (irAE) in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Now that PD-(L)1 inhibitors are routinely used as adjuvant and first-line treatments, sequential PD-(L)1 inhibition followed by osimertinib use may become more frequent and have unforeseen serious toxicity. METHODS: We identified patients with EGFR-mutant NSCLC who were treated with PD-(L)1 blockade and EGFR- tyrosine kinase inhibitors (TKIs), irrespective of drug or sequence of administration (total n = 126). Patient records were reviewed to identify severe (NCI-CTCAE v5.0 grades 3-4) toxicity. RESULTS: Fifteen percent [6 of 41, 95% confidence interval (CI) 7% to 29%] of all patients treated with sequential PD-(L)1 blockade followed later by osimertinib developed a severe irAE. Severe irAEs were most common among those who began osimertinib within 3 months of prior PD-(L)1 blockade (5 of 21, 24%, 95% CI 10% to 45%), as compared with >3-12 months (1 of 8, 13%, 95% CI 0% to 50%), >12 months (0 of 12, 0%, 95% CI 0% to 28%). By contrast, no severe irAEs were identified among patients treated with osimertinib followed by PD-(L)1 (0 of 29, 95% CI 0% to 14%) or PD-(L)1 followed by other EGFR-TKIs (afatinib or erlotinib, 0 of 27, 95% CI 0% to 15%). IrAEs occurred at a median onset of 20 days after osimertinib (range 14-167 days). All patients with irAEs required steroids and most required hospitalization. CONCLUSION: PD-(L)1 blockade followed by osimertinib is associated with severe irAE and is most frequent among patients who recently received PD-(L)1 blockade. No irAEs were observed when osimertinib preceded PD-(L)1 blockade or when PD-(L)1 was followed by other EGFR-TKIs. This association appears to be specific to osimertinib, as no severe irAEs occurred with administration of other EGFR-TKIs.

Magnetic Nanoparticles: Properties, Synthesis and Biomedical Applications.

Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine.

Antimicrobial potential of bacteriocin producing Lysinibacillus jx416856 against foodborne bacterial and fungal pathogens, isolated from fruits and vegetable waste.

In this study, antimicrobial potential, some probiotics properties and bacteriocin nature of Lysinibacillus, isolated from fruits and vegetable waste were evaluated. For this, 125 Lactobacillus isolates were tested against foodborne bacterial and fungal pathogens. Among these, an isolated Bacillus spp. showed significant aggregation-co-aggregation probiotics properties and potentially inhibits the foodborne gram positive microbial pathogens such as Staphylococcus aureus, (22 mm ZOI), Staphylococcus epedermidis and Bacillus cereus (18 mm). Phenotypically and molecularly it was identified as Lysinibacillus (NCBI accession no. JX416856) and it was found closest to Lysinibacillus fusiformis, Lysinibacillus sphaericus and Lysinibacillus xylanilyticus. Physico-biochemically, it was found to be negative for amylase, protease, gelatinase, nitrate reductase and urease while positive for catalase. The diagnostic fatty acid was 22;2 (3.51). The growth conditions and bacteriocin activity were found to be optimum with MRS media at pH 7-10, Temperature 35-40 °C and salt tolerance at 1-3%. Eventually its production was optimized with MRS broth at pH 7.6, 37 °C, for 36 h in shaking conditions at the rate of 100 rpm. Active bacteriocin was isolated at 60% ammonium sulfate precipitation. The molecular weight of given bacteriocin was found to be nearly 25-35 kDa by SDS-PAGE. Based on physico- biochemical properties, the isolated bacteriocin was to be categories in class II bacteriocin. The bacteriocin was found to be stable in the range of 4-80 °C temperature, 6-10 pH and even in the presence of surfactant (such as SDS and Tween 80). However, proteases like pepsin and trypsin were found to degrade the bacteriocin. Collectively, the broad spectrum inhibitory potential and physical stability offered the antimicrobial potential to Lysinibacillus, and its relevant bacteriocin might be used as an alternative food preservative or therapeutic agent to control spoilage of different food products.