Suchergebnisse

Yi Jiang,1 Ning Zhang,1 Hailin Pang,1 Xiaobo Gao,2 Helong Zhang1,3 1Department of Oncology, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shan'xi, China; 2Department of Medicine, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shan'xi, China; 3Institute of Cancer, Air Force Military Medical University, Xi'an, Shan'xi, China Background: Given the increasing use of immune checkpoint inhibitors (ICIs), a concomitant rise in adverse events is inevitable. In a recent Phase III trial of ICIs versus placebo, we found the staggering difference of incidence of fatal adverse events (FAEs). Hence, we should determine the risk of FAEs in ICIs. Objective: To address the risks of FAEs associated with each ICI regimen, we performed a systematic review and meta-analysis of clinical trials with the Food and Drug Administration-approved ICI regimens in patients with advanced solid tumors. Methods: Literature searching was based on PubMed before April 15, 2018. The numbers of FAEs in both study group and placebo group were collected. We assessed the risk of fatal adverse reactions associated with ICIs on Pooled Peto OR and associated 95% CI. Results: Twelve trials were identified. OR value of FADs in all ICIs was 2.32 (95% CI: 1.33, 4.05; P=0.003). The incidence of FAE in ICI in all included studies were up to 3.2%. OR value of clinical trials of prostate cancer was 3.71 (95% CI: 1.12, 12.26; P=0.03). Among the ICI cohorts, the common FAEs were gastrointestinal toxicity (n=12, 25%), pulmonary toxicity (n=10, 20%), cardiac toxicity (n=5, 10%), and hepatic toxicity (n=5, 10%). Conclusion: The cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitors have a significantly higher risk of FAE (P=0.01), whereas programmed cell death protein 1 (PD-1) inhibitors were not. The most common CTLA-4-related FAE was gastrointestinal toxicity, and the most common PD-1-related FAE was pulmonary toxicity. Moreover, we have shown that ipilimumab has significant dose-dependent lethal toxicity. Keywords: treatment-related mortality, immune mediated death, immune mediated mortality

Abstract
Background
Insight into temporal–spatial variations of dissolved organic matter (DOM) fractions were undertaken to trace potential factors toward a further understanding aquatic environment in Lake Shahu, a brackish-water lake in northwest China, using synchronous fluorescence spectroscopy (SFS) combined with principal component analysis (PCA), second derivative and canonical correlation analysis (CCA).

Result
Five fluorescence peaks were extracted from SFS by PCA, including tyrosine-like fluorescence (TYLF), tryptophan-like fluorescence (TRLF), microbial humic-like fluorescence (MHLF), fulvic-like fluorescence (FLF), and humic-like fluorescence (HLF), whose relative contents were obtained by second derivative synchronous fluorescence spectroscopy. The increasing order of total fluorescence components contents was July (11,789.38 ± 12,752.61) < April (12,667.58 ± 15,246.91) < November (19,748.87 ± 17,192.13), which was attributed to tremendous enhancement in TYLF content from April (1615.56 ± 258.56) to November (5631.96 ± 634.82). The PLF (the sum of TYLF and TRLF) dominated the fluorescence components, whose proportion was 40.55, 37.09, or 46.91% in April, July, or November. DOM fractions in November were distinguished from April and July, which could be attributed to that water of the Yellow River was continuously loaded into the lake as water replenishment from April to September. From the replenishment period to non-replenishment, the contents of the five components gradually changed from low in the middle and high around the lake to high throughout entire lake. Based on the CCA results, the potential factors included TYLF, TRLF, MHLF, SD, and BOD5 in April, which were relative to organic matter pollution. The potential factors contained TYLF, TRLF, FLF, Chl-a, TP, CODCr, and DO in July, indicating the enrichment of TP lead algae and plants growth. The potential factors in November consisted of TYLF, TRLF, CODCr, SD, TN, and FLF, representing residue of the algae and plants have been deeply degraded.

Conclusion
The replenishment of water led to enrichment of TP, resulting in growth of algae and plants, and was the key factor of water quality fluctuations. This work provided a workflow from perspective of DOM to reveal causes of water quality fluctuations in a brackish-water lake and may be applied to other types of waterbodies.