Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: a meta-analysis and validation study.

BACKGROUND: The prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups. METHODS: We performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540). RESULTS: Pretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66-2.31) and DFS (HR = 1.90, 95%CI = 1.41-2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses. CONCLUSIONS: Meta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics.

Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality.

Astrocytes play a key role in brain homeostasis, protecting neurons against neurotoxic stimuli such as oxidative stress. Therefore, the neuroprotective therapeutics that enhance astrocytic functionality has been regarded as a promising strategy to reduce brain damage. We previously reported that ciclopirox, a well-known antifungal N-hydroxypyridone compound, protects astrocytes from oxidative stress by enhancing mitochondrial function. Using the N-hydroxypyridone scaffold, we have synthesized a series of cytoprotective derivatives. Mitochondrial activity assay showed that N-hydroxypyridone derivatives with biphenyl group have comparable to better protective effects than ciclopirox in astrocytes exposed to H2O2. N-hydroxypyridone derivatives, especially 11g, inhibited H2O2-induced deterioration of mitochondrial membrane potential and oxygen consumption rate, and significantly improved cell viability of astrocytes. The results indicate that the N-hydroxypyridone motif can provide a novel cytoprotective scaffold for astrocytes via enhancing mitochondrial functionality.