临床药师参与1例糖尿病酮症酸中毒患者抗感染治疗分析

临床药师参与1例糖尿病酮症酸中毒尿路感染合并血流感染,后因长期使用抗菌药物导致艰难梭菌相关腹泻患者的治疗。临床药师通过日常药学查房、药学会诊,根据患者病情、病原学检测结果,查阅国内外指南并与临床医师讨论后,考虑患者为导管相关耐碳青霉烯类肺炎克雷伯菌血流感染,拔除股静脉导管,给予替加环素100mg,q12h联合亚胺培南西司他丁1g,q8h抗感染治疗。后期会诊针对抗菌药物导致艰难梭菌相关腹泻,药师建议患者口服万古霉素125mg,q6h,医师采纳意见。患者治疗效果较好,未出现不良反应,最终好转出院。临床药师在抗感染药学实践中发挥了积极有效作用,体现了临床药师多学科协助诊疗的职业价值。

Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability

Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.

Clinical value of next-generation sequencing in guiding decisions regarding endocrine therapy for advanced HR-positive/HER-2-negative breast cancer

Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer patients.Methods: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation.Conclusions: The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing(NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.

Focus on anticancer therapy-induced cardiotoxicity from the perspective of oncologists

To the Editor:Cancer and cardiovascular(CV)disease are associated with the largest morbidity and mortality in the world,and they are related to each other through some common risk factors.