Serum Uric Acid Levels in Neurodegenerative Disorders: A Cross-Sectional Study.

BACKGROUND: Excessive oxidative stress may contribute to neurodegeneration by leading to protein aggregation and mitochondrial dysfunction. Uric acid (UA) is an important endogenous antioxidant that protects against oxidative stress, yet its exact role in neurodegeneration remains unclear. OBJECTIVE: To explore the performance of serum UA in neurodegenerative disorders. METHODS: A total of 839 controls and 840 patients, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), motor neuron disease (MND), Creutzfeldt-Jakob disease (CJD), and mixed dementia (MixD) were enrolled. Fasting serum UA levels were measured in all participants and compared between patients and controls. Linear regression models were utilized to explore possible relationships of serum UA with cognition, disease duration, age, and age of onset. RESULTS: Compared to controls (355.48 ±â€Š85.38 µmol/L), serum UA was significantly lower in AD (291.29 ±â€Š83.49 µmol/L, p < 0.001), PD (286.95 ±â€Š81.78 µmol/L, p < 0.001), PSP (313.32 ±â€Š88.19 µmol/L, p < 0.001), FTD (313.89 ±â€Š71.18 µmol/L, p = 0.001), and DLB (279.23 ±â€Š65.51 µmol/L, p < 0.001), adjusting for confounding factors including age, gender, education, etc. In addition, serum UA was positively correlated with cognitive levels in all patients (Mini-Mental State Examination: r = 0.136, p = 0.001; and Montreal Cognitive Assessment Scale: r = 0.108, p = 0.009). CONCLUSION: Decreased levels of serum UA were correlated with AD, PD, PSP, FTD, and DLB, offering significant potential as a promisingly relevant, less-invasive marker of multiple neurodegenerative disorders.

Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30-90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13-3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81-4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5-1.7) and 8.8 months (95% CI: 8.5-9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

The incidence of gastrointestinal adverse events in patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors: a meta-analysis.

BACKGROUND: We conducted a meta-analysis to evaluates the incidence of the gastrointestinal (GI) adverse events with the use of PD-1 inhibitors among patients with advanced non-small cell lung cancer (NSCLC). METHODS: The PICOs (participants, intervention, comparison, and outcomes) elements were used for the selection of studies to meet the inclusion and exclusion criteria. Google Scholar, PubMed, Science Direct and proceedings of major oncology conferences were systematically searched from their inception to December 2020, to identify studies which reported the GI adverse events of PD-1 inhibitors among patients with NSCLC. Risks of bias were assessed by using a revised methodological index for nonrandomized studies (MINORS). Pooled incidences and weighted relative risk (RR) estimate for GI adverse events, the incidence of treatment discontinuation due to GI adverse events was also calculated. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. OpenMeta 10.10, Stata 11.0 and RevMan 5.3 software were used for data analysis. RESULTS: The research included 15 studies comprising of a total of 3,716 patients. The incidences of all-grade GI symptoms were: diarrhea 8.6% (95% CI: 6.6-10.6%), nausea 9.2% (95% CI: 7.3-11.0%), vomiting 3.2% (95% CI: 1.9-4.5%), constipation 2.8% (95% CI: 1.8-3.9%), colitis 0.7% (95% CI: 0.4-1.1%), stomatitis (95% CI: 1.0-2.7%), and decreased appetite 10.0% (95% CI: 8.3-11.7%). Therapy using PD-1 inhibitors was discontinued in 2.5% (95% CI: 0.0-5.1%) of patients with nausea, in 3.0% (95% CI: 0.7-5.3%) of those with diarrhea, and in 45.7% (95% CI: 20.6-70.7%) of patients with colitis. Compared with chemotherapy, the use of PD-1 inhibitors showed significant increase in the occurrence of grade 1-4 colitis (RR =3.90, 95% CI: 1.41-10.81, P=0.009) and grade 3-4 colitis (RR =3.76, 95% CI: 1.07-13.26, P=0.04). DISCUSSION: This meta-analysis provides a reliable estimate of the incidences of GI adverse events among NSCLC patients. Especially when colitis does occur, it often results in therapy discontinuation. Use of PD-1 inhibitors led to a higher incidence of colitis as compared to the use of chemotherapy.

Lack of association between ADRA2B-4825 gene insertion/deletion polymorphism and migraine in Chinese Han population.

OBJECTIVE: The present study aimed to estimate the association between susceptibility to migraine and the 12-nucleotide insertion/deletion (indel) polymorphism in promoter region of alpha(2B)-adrenergic receptor gene (ADRA2B). METHODS: A case-control study was carried out in Chinese Han population, including 368 cases of migraine and 517 controls. Genomic DNA was extracted from blood samples, and DNA fragments containing the site of polymorphism were amplified by PCR. Data were adjusted for sex, age, migraine history and family history, and analyzed using a logistic regression model. RESULTS: There was no association between indel polymorphism and migraine, at either the allele or the genotype level. CONCLUSION: These findings do not support a functional significance of ADRA2B indel polymorphism at position -4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.