The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence.

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat P. aeruginosa infections. In this study, 25 P. aeruginosa isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients. Pacbio and Illumina sequencing were used to analyse the in vivo evolutionary trajectories of these isolates. Our analysis showed that positive selection dominantly shaped P. aeruginosa genomes during VAP infections and led to three convergent evolution events, including loss-of-function mutations of lasR and mpl, and a pyoverdine-deficient phenotype. Specifically, lasR encodes one of the major transcriptional regulators in quorum sensing, whereas mpl encodes an enzyme responsible for recycling cell wall peptidoglycan. We also found that P. aeruginosa isolated at late stages of VAP infections produce less elastase and are less virulent in vivo than their earlier isolated counterparts, suggesting the short-term in vivo evolution of P. aeruginosa leads to attenuated virulence.

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis.

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5%) received S-1-based therapy and 470 (51.5%) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.96, P = 0.015, and HR 0.69, 95% CI 0.60-0.80, P = 0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95% CI 1.34-2.06, P = 0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P = 0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.

Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children.

UNLABELLED: The efficacy of probiotics supplementation in children undergoing Helicobacter pylori (H. pylori) eradication therapy remains controversial. This study aimed to meta-analyze whether probiotics supplementation in triple therapy could improve H. pylori eradication rates and reduce therapy-related side effects in children. Electronic databases PubMed and Embase were searched to identify all randomized controlled trials in pediatric patients comparing probiotics supplementation with placebo or no extra intervention in H. pylori eradication therapy. Two authors independently extracted the data. Results were expressed as odds ratios (ORs) and accompanying 95 % confidence intervals (CIs). Stata version 12.0 was used to perform all statistical analyses. Seven studies consisting of 508 pediatric patients were included in our study. The pooled ORs (studies n = 7) of eradication rates by intention-to-treat and per-protocol analysis in the probiotics group versus the control group were 1.96 (95 % CI 1.28-3.02) and 2.25 (95 % CI 1.41-3.57), respectively. The pooled OR (studies n = 5) of incidence of total side effects was 0.32 (95 % CI 0.13-0.79), with significant heterogeneity observed (I (2) = 71.9 %). CONCLUSION: Probiotics supplementation in triple therapy for H. pylori infection may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea, in children.