METHODS: In this study, bidirectional Mendelian randomization (MR) analysis, which includes MR-Egger, weighted median, weighted mode, and inverse variance weighted (IVW) approaches, was utilized to evaluate the bidirectional causal relationship between peripheral immune cell counts and the risk of PCa.
RESULTS: The primary analysis using the IVW method suggests a potential causal association between basophil counts and the risk of prostate cancer (PCa), with an odds ratio (OR) of 1.111 and a 95% confidence interval (CI) of 1.011-1.222 (P = 0.028). Conversely, non-causal associations have been observed between other peripheral immune cell types, such as white blood cells, neutrophils, lymphocytes, eosinophils, or monocytes, and the incidence of PCa (P values > 0.05). Furthermore, although reverse analysis indicated a causal link between PCa and the counts of leukocytes and neutrophils (OR = 1.013; 95% CI = 1.002-1.225; P = 0.018 and OR = 1.013; 95% CI = 1.002-1.025; P = 0.019), no causal association was detected between PCa and basophil count (P value > 0.050).
CONCLUSION: This study suggests a potential bidirectional link between peripheral immune cells and prostate cancer, but inconsistencies in Mendelian Randomization methods mean these findings are preliminary and require further investigation.
RESULTS: We found that cumulative food intake was not changed in the group with 12 h daily fasting, but significantly decreased in the 16 and 20 h fasting groups. The composition of gut microbiota was altered by all these types of intermittent fasting. At genus level, 16 h fasting led to increased level of Akkermansia and decreased level of Alistipes, but these effects disappeared after the cessation of fasting. No taxonomic differences were identified in the other two groups.
CONCLUSIONS: These data indicated that intermittent fasting shapes gut microbiota in healthy mice, and the length of daily fasting interval may influence the outcome of intermittent fasting.
METHODS: A partitioned survival model was established using the TreeAge 2019 software to evaluate the cost-effectiveness. The model includes three states, namely progression-free survival, progressive disease, and death. Clinical data were derived from three randomized controlled studies involving patients with advanced HCC who received the following treatment: sorafenib and lenvatinib (NCT01761266); atezolizumab in combination with bevacizumab (NCT03434379); and sintilimab in combination with bevacizumab (NCT03794440). Cost and clinical preference data were obtained from the literature and interviews with clinicians.
RESULTS: All compared with sorafenib therapy, lenvatinib had an incremental cost-effectiveness ratio (ICER) of US$188,625.25 per quality-adjusted life year (QALY) gained; sintilimab plus bevacizumab had an ICER of US$75,150.32 per QALY gained; and atezolizumab plus bevacizumab had an ICER of US$144,513.71 per QALY gained. The probabilistic sensitivity analysis indicated that treatment with sorafenib achieved a 100% probability of cost-effectiveness at a threshold of US$36,600/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the medical insurance reimbursement ratio and drug prices.
CONCLUSIONS: In this economic evaluation, therapy with lenvatinib, sintilimab plus bevacizumab, and atezolizumab plus bevacizumab generated incremental QALYs compared with sorafenib; however, these regimens were not cost-effective at a willingness-to-pay threshold of US$36,600 per QALY. Therefore, some patients may achieve preferred economic outcomes from these three therapies by tailoring the regimen based on individual patient factors.