目的应用蒙特卡洛模拟评价奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌和大肠埃希菌感染的疗效。方法结合药动学参数和药效学参数,以AUC/MIC为PK/PD模型进行蒙特卡洛模拟,得到6种给药方案对上述3种病原菌的达标概率(PTA)及累积...目的应用蒙特卡洛模拟评价奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌和大肠埃希菌感染的疗效。方法结合药动学参数和药效学参数,以AUC/MIC为PK/PD模型进行蒙特卡洛模拟,得到6种给药方案对上述3种病原菌的达标概率(PTA)及累积反应分数(CFR)。结果奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌(抑菌靶值下模拟),都能达到CFR>90%;对于金黄色葡萄球菌(杀菌靶值下模拟),仅600 mg po q24h和多剂量C组(负荷剂量450 mg po q12h,维持剂量450 mg poq24h)达到CFR>90%;但对大肠埃希菌,所有给药方案的CFR均不达标。结论奥马环素的说明书推荐给药方案(负荷剂量200 mg iv,维持剂量300 mg po q24h)对肺炎链球菌、金黄色葡萄球菌有较好的治疗效果;但对大肠埃希菌,6种给药方案均达不到预期疗效。展开更多
Background: Pancreatic cancer is one of the most lethal types of cancer, and immunotherapy has become a promising remedy with advancements in tumor immunology. However, predicting the clinical response to immunotherap...Background: Pancreatic cancer is one of the most lethal types of cancer, and immunotherapy has become a promising remedy with advancements in tumor immunology. However, predicting the clinical response to immunotherapy in pancreatic cancer remains a dilemma for clinicians. Methods: GEPIA database was used to analyze the differential expression of MMR and PD-L1 genes in 33 common cancer types including pancreatic cancer. The expression levels of MMR and PD-L1 genes were downloaded from the GEPIA and GEO databases to analyze the correlation between MMR genes and PD-L1, and the clinicopathological and survival information were downloaded from the TCGA databases to analyze the relationship between the expression of MMR, PD-L1 and clinicopathological characteristics, prognosis. Meanwhile, the tumor tissue samples of 41 patients with pancreatic cancer were collected, and the protein expression levels of MMR and PD-L1 were detected by immunohistochemical assay. Furthermore, we analyzed the correlation between MMR and PD-L1, and the correlation between the expression of MMR, PD-L1 and clinicopathological characteristics, prognosis of pancreatic cancer patients. Results: Bioinformatics analysis showed that MLH1, MLH3, MSH2, MSH3, and PMS2 were highly expressed in most cancer types including pancreatic cancer (P P = 0.012), clinical stage (I vs II: P = 0.016), MSH2 expression was related to clinical stage (P < 0.05), T stage (T3 vs T4: P = 0.039), and MSH3 expression was related to T stage (P < 0.05). Besides, both MSH2 expression (P P = 0.044) were significantly associated with prognosis. GEPIA data also showed that MSH2 expression was related to prognosis (P = 0.008). The correlation analysis revealed that the expressions MSH2, MLH1, PMS2 had strong correlations with PD-L1 both in GEPIA and GEO databases. Real-world data indicated that of the 41 pancreatic cancer patients, 5 cases had MLH1 deletion, 5 cases had MSH2 deletion, 4 cases had PMS2 deletion, and 12 cases had PD-L1 positive expression. Notably, PMS2 deletion was associated with PD-L1 positive expression (P = 0.035). In addition, MLH1 was related to clinical stage (P = 0.033), age (P = 0.048), and MSH2 was related to clinical stage (P = 0.033). However, MLH1 (P = 0.697), MSH2 (P = 0.956), PMS2 (P = 0.341), and PD-L1 (P = 0.734) appeared to have no impact on overall survival among patients with pancreatic cancer. Conclusion: Both bioinformatics and real-world data showed that there were correlation between PMS2 deletion and PD-L1 expression, and correlation between MLH1, MSH2 and clinical stage.展开更多
目的介绍美罗培南在危重症、脓毒症及脓毒症休克、肾功能不全、病态肥胖、烧伤等特殊机体状态下的PK/PD及给药方案研究进展,为其临床合理应用提供参考。方法查阅国内外相关文献,进行系统的文献整理和综合分析。结果患者特殊的病理生理状...目的介绍美罗培南在危重症、脓毒症及脓毒症休克、肾功能不全、病态肥胖、烧伤等特殊机体状态下的PK/PD及给药方案研究进展,为其临床合理应用提供参考。方法查阅国内外相关文献,进行系统的文献整理和综合分析。结果患者特殊的病理生理状态,可使美罗培南的PK和PD发生重要改变,其中最重要的改变是Vd和CL。多个研究报道,增大美罗培南给药剂量,延长输注时间,可提高目标获得概率(Probability of target attainment,PTA)或累积反应分数(Cumulative fraction of response,CFR),但对于敏感的致病菌常规给药方案仍可得到良好的治疗效果。药物对治疗靶部位的组织穿透力也是影响PD的重要指标。研究发现,美罗培南可以很好的渗透到脑脊液、腹腔、肺部、软组织、前列腺、胰腺等。结论临床医生在使用美罗培南前,应了解患者的病理生理状态,明确病原菌、感染部位,根据PK/PD制定合理的给药方案。展开更多
文摘目的应用蒙特卡洛模拟评价奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌和大肠埃希菌感染的疗效。方法结合药动学参数和药效学参数,以AUC/MIC为PK/PD模型进行蒙特卡洛模拟,得到6种给药方案对上述3种病原菌的达标概率(PTA)及累积反应分数(CFR)。结果奥马环素等6种给药方案对肺炎链球菌、金黄色葡萄球菌(抑菌靶值下模拟),都能达到CFR>90%;对于金黄色葡萄球菌(杀菌靶值下模拟),仅600 mg po q24h和多剂量C组(负荷剂量450 mg po q12h,维持剂量450 mg poq24h)达到CFR>90%;但对大肠埃希菌,所有给药方案的CFR均不达标。结论奥马环素的说明书推荐给药方案(负荷剂量200 mg iv,维持剂量300 mg po q24h)对肺炎链球菌、金黄色葡萄球菌有较好的治疗效果;但对大肠埃希菌,6种给药方案均达不到预期疗效。
文摘Background: Pancreatic cancer is one of the most lethal types of cancer, and immunotherapy has become a promising remedy with advancements in tumor immunology. However, predicting the clinical response to immunotherapy in pancreatic cancer remains a dilemma for clinicians. Methods: GEPIA database was used to analyze the differential expression of MMR and PD-L1 genes in 33 common cancer types including pancreatic cancer. The expression levels of MMR and PD-L1 genes were downloaded from the GEPIA and GEO databases to analyze the correlation between MMR genes and PD-L1, and the clinicopathological and survival information were downloaded from the TCGA databases to analyze the relationship between the expression of MMR, PD-L1 and clinicopathological characteristics, prognosis. Meanwhile, the tumor tissue samples of 41 patients with pancreatic cancer were collected, and the protein expression levels of MMR and PD-L1 were detected by immunohistochemical assay. Furthermore, we analyzed the correlation between MMR and PD-L1, and the correlation between the expression of MMR, PD-L1 and clinicopathological characteristics, prognosis of pancreatic cancer patients. Results: Bioinformatics analysis showed that MLH1, MLH3, MSH2, MSH3, and PMS2 were highly expressed in most cancer types including pancreatic cancer (P P = 0.012), clinical stage (I vs II: P = 0.016), MSH2 expression was related to clinical stage (P < 0.05), T stage (T3 vs T4: P = 0.039), and MSH3 expression was related to T stage (P < 0.05). Besides, both MSH2 expression (P P = 0.044) were significantly associated with prognosis. GEPIA data also showed that MSH2 expression was related to prognosis (P = 0.008). The correlation analysis revealed that the expressions MSH2, MLH1, PMS2 had strong correlations with PD-L1 both in GEPIA and GEO databases. Real-world data indicated that of the 41 pancreatic cancer patients, 5 cases had MLH1 deletion, 5 cases had MSH2 deletion, 4 cases had PMS2 deletion, and 12 cases had PD-L1 positive expression. Notably, PMS2 deletion was associated with PD-L1 positive expression (P = 0.035). In addition, MLH1 was related to clinical stage (P = 0.033), age (P = 0.048), and MSH2 was related to clinical stage (P = 0.033). However, MLH1 (P = 0.697), MSH2 (P = 0.956), PMS2 (P = 0.341), and PD-L1 (P = 0.734) appeared to have no impact on overall survival among patients with pancreatic cancer. Conclusion: Both bioinformatics and real-world data showed that there were correlation between PMS2 deletion and PD-L1 expression, and correlation between MLH1, MSH2 and clinical stage.
文摘目的介绍美罗培南在危重症、脓毒症及脓毒症休克、肾功能不全、病态肥胖、烧伤等特殊机体状态下的PK/PD及给药方案研究进展,为其临床合理应用提供参考。方法查阅国内外相关文献,进行系统的文献整理和综合分析。结果患者特殊的病理生理状态,可使美罗培南的PK和PD发生重要改变,其中最重要的改变是Vd和CL。多个研究报道,增大美罗培南给药剂量,延长输注时间,可提高目标获得概率(Probability of target attainment,PTA)或累积反应分数(Cumulative fraction of response,CFR),但对于敏感的致病菌常规给药方案仍可得到良好的治疗效果。药物对治疗靶部位的组织穿透力也是影响PD的重要指标。研究发现,美罗培南可以很好的渗透到脑脊液、腹腔、肺部、软组织、前列腺、胰腺等。结论临床医生在使用美罗培南前,应了解患者的病理生理状态,明确病原菌、感染部位,根据PK/PD制定合理的给药方案。
