Clinical Efficacy of Immune Checkpoint Inhibitors in Older Non-small-Cell Lung Cancer Patients: A Meta-Analysis.

Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape among non-small-cell lung cancer (NSCLC) patients. The efficacy of ICI therapy in older patients (≥65 years) is controversial and not fully clarified. We performed a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced or metastatic NSCLC based on age (<65 years vs. ≥65 years). Methods: A comprehensive literature search for eligible randomized control phase II/III trials that compared the efficacy of anti-PD-1/PD-L1 agents against chemotherapy in advanced or metastatic NSCLC patients. Pooled overall survival (OS) and progression-free survival (PFS) estimates were calculated based on random/fixed effects models according to the heterogeneity between the studies. Results: A total of 10 studies involving 8 randomized controlled trials (2 updates) were enrolled in this meta-analysis [2,662 young patients (<65 years) and 1,971 older patients (≥65 years)]. The efficacy of anti-PD-1/PD-L1 agents is comparable between young (<65 years) and older (≥65 years) patients for OS [HR 0.75 95% CI (0.64-0.88) vs. 0.76 95% CI (0.66-0.87)]. However, our pooled analysis was not sufficient to show a significant benefit in terms of PFS for anti-PD-1/PD-L1 agents [HR 0.87 95% CI (0.74-1.01), P = 0.06]. In addition, we failed to see a PFS superiority of anti-PD-1/PD-L1 agents against chemotherapy in two age subgroups [<65 years and ≥65 years, HR 0.85 95% CI (0.72-1.01), P = 0.07 and HR 0.87 95% CI (0.68-1.10), P = 0.25]. Conclusion: ICIs therapy presents comparable efficacy in older advanced or metastatic NSCLC patients with young patients.

Dark tea extracts: Chemical constituents and modulatory effect on gastrointestinal function.

Processing of dark tea varieties, such as Fu brick tea, Liupao tea, Qianliang tea, and Qing brick tea, includes solid-state fermentation involving microorganisms. In this study, we analyzed the major chemical constituents of dark tea extracts and evaluated their modulatory effect on the gastrointestinal function in normal mice, including the improvement of gastrointestinal transit and intestinal microbial, as well as the attenuation of intestinal microbial dysbiosis and intestinal pathological damage, and the adjustment of immune function in antibiotic-treated mice. Substantial differences in major chemical constituents, including total polyphenols, total organic acids, water extract content, 18 free amino acids, gallic acid, and six tea catechins, were observed among Fu brick tea, Qianliang tea, Qing brick tea, and Liupao tea extracts. Extracts from the four dark tea varieties significantly promoted gastrointestinal transit and colonization of beneficial Bifidobacterium and Lactobacillus, and inhibited the growth of harmful Escherichia coli and Enterococcus in normal mice. In addition, Qianliang tea, Qing brick tea, and Liupao tea extracts significantly accelerated the reversal of the ampicillin sodium-induced pathological damage in the ileum, intestinal bacterial dysbiosis (Bifidobacterium, Lactobacillus, E. coli, and Enterococcus), and low immunity.

Polymorphisms of VEGFA gene and susceptibility to hemorrhage risk of brain arteriovenous malformations in a Chinese population.

AIM: To evaluate the influence of the vascular endothelial growth factor A (VEGFA) polymorphisms on risk of presentation with intracerebral hemorrhage (ICH). METHODS: Nine selected VEGFA single-nucleotide polymorphisms (SNPs) were genotyped in 311 patients with brain arteriovenous malformations (BAVM) in a Chinese population. Associations between individual SNPs/haplotypes and the hemorrhage risk of BAVMs were evaluated using logistic regression analysis. RESULTS: In the single-locus analysis, rs1547651 was associated with increased risk of ICH (adjusted OR=2.11, 95% CI=1.01-4.42 compared with the AA genotype). In particular, an increased risk for ICH was associated with this variant in female patients (adjusted OR=3.21, and 95% CI=0.99-10.36). Haplotype-based analyses revealed that haplotype 'GC' in block 1 and haplotype 'ACC' in block 2 were associated with a 30%-38% reduction in the risk of ICH in patients with BAVMs compared to the most common haplotype (P(sim)=0.033 and P(sim)=0.005, respectively). The protective effect of haplotype 'ACC' in block 2 was more evident in male patients and subjects with BAVMs of a size ≥3 cm (adjusted OR=0.57, 95% CI=0.34-0.97 and adjusted OR=0.57, 95% CI=0.31-0.86, respectively). CONCLUSION: The results suggest that VEGFA gene variants may contribute to ICH risk of BAVM.

Survey of attitudes and behaviors of healthcare professionals on delirium in ICU.

OBJECTIVE: To assess the medical community's awareness and practice regarding delirium in the intensive care unit (ICU). METHODS: One hundred and ten predesigned questionnaires were distributed to ICU practitioners in the affiliated hospitals of Zhejiang University. RESULTS: A total of 105 valid questionnaires were collected. Totally, 55.3% of the clinicians considered that delirium was common in the ICU. Delirium was believed to be a significant or serious problem by 70.5% of respondents, and under-diagnosis was acknowledged by 56.2% of the respondents. The incidence of ICU delirium is even more under-estimated by the pediatric doctors compared with their counterparts in adult ICU (P less than 0.05). Primary disease of the brain (agreed by 82.1% of the respondents) was believed to be the most common risk factor for delirium. None of the ICU professionals screened delirium or used a specific tool for delirium assessment routinely. The vast majority (92.4%) of respondents had little knowledge on the diagnosis and the standard treatment of delirium. CONCLUSIONS: Although delirium is considered as a serious problem by a majority of the surveyed ICU professionals, it is still under-recognized in routine critical care practice. Data from this survey show a disconnection between the perceived significance of delirium and the current practices of monitoring and treatment in ICU in China.