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The clinical value and usage of inflammatory and nutritional markers in survival prediction for gastric cancer patients with neoadjuvant chemotherapy and D2 lymphadenectomy.
Li, Z, Li, S, Ying, X, Zhang, L, Shan, F, Jia, Y, Ji, J
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2020;(3):540-549
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Abstract
BACKGROUND The clinical values of inflammatory and nutritional markers remained unclear for gastric cancer with neoadjuvant chemotherapy (NACT). METHODS The inflammatory, nutritional markers and their changes were analyzed for locally advanced gastric cancer with NACT. The predictive value was evaluated by the Cox proportional hazards regressions under three hypothesized scenarios. The nomograms including independent prognostic factors were plotted for survival prediction. RESULTS A total of 225 patients were included in the study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index, and hemoglobin (Hgb) were significantly reduced, and the body mass index was significantly increased after NACT (all P < 0.05). The pre-NACT NLR [hazard ratio (HR) = 1.176, P = 0.059] showed a trend to correlate with the overall survival (OS) when only pre-NACT markers available; The post-NACT Hgb (HR = 0.982, P = 0.015) was the independent prognostic factor when only post-NACT markers available; The post-NACT Hgb (HR = 0.984, P = 0.025) and the change value of LMR (HR = 1.183, P = 0.036) were the independent prognostic factors when both pre- and post-NACT markers available. The nomogram had a similar Harrell's C-statistic compared to ypTNM stage (0.719 vs. 0.706). CONCLUSION For locally advanced gastric cancer, the NACT could significantly decrease some inflammatory markers. The pre-NACT NLR, the post-NACT Hgb and the change value of LMR had some values in survival prediction combined with age, sex, tumor location and the clinical stages under different clinical scenarios. The elevated initial NLR, the preoperative anemia and the greater change value of LMR implied a poor prognosis.
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Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.
Jevnikar, Z, Östling, J, Ax, E, Calvén, J, Thörn, K, Israelsson, E, Öberg, L, Singhania, A, Lau, LCK, Wilson, SJ, et al
The Journal of allergy and clinical immunology. 2019;(2):577-590
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Abstract
BACKGROUND Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. OBJECTIVE We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. METHODS An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. RESULTS Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β. CONCLUSIONS Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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Effects of binge alcohol consumption on sleep and inflammation in healthy volunteers.
Wilkinson, AN, Afshar, M, Ali, O, Bhatti, W, Hasday, JD, Netzer, G, Verceles, AC
The Journal of international medical research. 2018;(9):3938-3947
Abstract
Objective Alcohol is a hypnotic that modifies immune function, specifically the cytokines interferon gamma (IFN-γ) and interleukin 2 (IL-2). We evaluated the association between unscheduled napping and acute alcohol-induced augmentation of IFN-γ and IL-2 expression. Methods In this prospective, observational pilot study, volunteers completed questionnaires on sleep quality, alcohol use, and hangover characteristics. Actigraph recordings began three nights before and continued for four nights after study initiation. Napping was recorded by actigraphy and self-reporting. A weight-based dose of 100-proof vodka was consumed, and the blood alcohol content (BAC) and phytohemagglutinin-M stimulated cytokine level were measured before and 20 minutes, 2 hours, and 5 hours after binge consumption. Results Ten healthy volunteers participated (mean age, 34.4 ± 2.3 years; mean body mass index, 23.9 ± 4.6 kg/m2; 60% female). The mean 20-minute BAC was 137.7 ± 40.7 mg/dL. Seven participants took an unscheduled nap. The ex vivo IFN-γ and IL-2 levels significantly increased at all time points after binge consumption in the nappers, but not in the non-nappers. Conclusion Augmented IFN-γ and IL-2 levels are associated with unscheduled napping after binge alcohol consumption. Further studies are needed to clarify the associations among alcohol consumption, sleep disruption, and inflammatory mediators.