Conclusions: IrAEs were associated with improved efficacy in advanced NSCLC patients when a landmark analysis was applied. Patients receiving corticosteroids had significantly poorer outcomes when they were used for cancer-related symptoms.

Background: Diarrheagenic Escherichia coli (DEC) strains are a major cause of diarrhea in children under 5 years of age worldwide. DEC pathogenicity relies on the interaction of bacteria with environmental factors, including the host's resident gut microbiota. Previous reports have shown changes in the gut microbiota's composition during episodes of diarrhea, which may increase the pathogenicity of DEC strains. More intense and detailed identification of microbiota strains specifically associated with DEC infections and disease is needed to pinpoint their role in DEC pathogenicity.Aim: To identify resident indicative bacterial taxa in DEC-positive diarrhea stool samples of Chilean children.Methods: We analyzed 63 diarrheal stool samples from children 1–5 years of age by FilmArray® GI in order to identify a potential pathogen and to group diarrhea episodes into those caused by DEC as sole pathogen (DEC group, 32 samples) and those caused by an enteric virus as sole pathogen (viral group, 31 samples). In addition, 30 stool samples from healthy children, negative for enteric pathogens, were evaluated (healthy group). The 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs) at 99% identity and their representatives were used to assign them to operational phylogenetic units (OPUs) using a phylogenetic inference approach.Results: Taxa assignment using the OPU approach resulted in a lower number of units but with higher accuracy compared to the OTU approach. Data analysis indicated an increase in sequences belonging to the phylum Proteobacteria in the DEC group compared to the viral and healthy groups. Samples displayed a statistically different community structure by sample grouping by redundancy analysis and ANOVA. Escherichia albertii (p = 0.001), Citrobacter werkmanii (p = 0.001), Yersinia enterocolitica, subsp. paleartica (p = 0.048), and Haemophilus sputorum (p = 0.028) were indicative species for the DEC group as compared to the viral and healthy groups.Conclusion: Gut microbiota in Chilean children with DEC-positive diarrhea differed from microbiota associated with enteric virus and healthy children. Indicative species found in this study may prove relevant in advancing our understanding of the relationship between resident gut microbiota and DEC leading to the occurrence of disease.

Introduction: Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation.Methods: We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and α1-antitrypsin by ELISA and we evaluated the expression of IL8 and IL1β genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs).Results: In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and α1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the IL8 and IL1β genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of Enterococcus, Streptococcus, Enterobacter, Lactococcus, and Propionibacterium.Conclusions: We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.