Personalized medicine最新文献

Aim: Prevalence of clinically actionable genetic variants of CYP2C19 is lacking in specific population subgroups. This study aims to assess the frequencies of CYP2C19*2, *3, and *17 in Asian, Native Hawaiian and Pacific Islander (NHPI) population subgroups compared with Europeans. Patients & methods: The study included repository DNA samples of 1064 women, 18 years or older, who self-reported as Filipino, Korean, Japanese, Native Hawaiian, Marshallese and Samoan. Results: The overall frequencies of CYP2C19*2 (25-36%) and CYP2C19*3 (2.5-10%) were significantly higher in all our subgroups than in Europeans (15 and 0.02%, respectively). The overall frequency of CYP2C19*17 was significantly lower in all our subgroups (1-6%) than in Europeans (21.7%). Conclusion: This is the first report on the frequencies of CYP2C19*2, *3, and *17 in women of Asian and NHPI descent with distinct population subgroup differences. Differential allele frequencies of CYP2C19 among population subgroups underscore the importance of increasing racial and ethnic diversity in pharmacogenetic research.

In recent years, major advances have been achieved in our understanding of non-small-cell lung cancer (NSCLC) with oncogenic driver alterations and in the specific treatment of these with tyrosine kinase inhibitors. Currently, state-of-the-art management of patients with NSCLC (particularly adenocarcinoma or non-adenocarcinoma but with mild tobacco exposure) consists of the determination of EGFR, ALK, ROS1 and BRAF status, as they have US FDA and EMA approved targeted therapies. The increase in molecular knowledge of NSCLC and the development of drugs against other targets has settled new therapeutic indications. In this review we have incorporated the development around MET, KRAS and NTRK in the diagnosis of NSCLC given the therapeutic potential that they represent, as well as the drugs approved for these indications.

Aim: To observe the difference in the risk of polymyxin B (PMB)-induced acute kidney injury (AKI) with or without dose adjustment based on the patients renal function. Materials & methods: This retrospective cohort analysis was carried out in 115 patients treated with PMB from November 2018 to October 2019. Results: No significant difference in the incidence of AKI as well as secondary outcomes was observed between these two groups (47.5 vs 37.14%; p = 0.304). Conclusion: Dosing adjustment based on renal function does not significantly lower the risk of PMB-induced AKI. A non adjusted dosing strategy for PMB is recommended in patients exhibiting various levels of renal impairment.

Aim: Commercial plan coverage policies for multigene panel tests may vary and could result in geographic variation in coverage due to the fragmented nature of the commercial insurance market. This study aimed to characterize the alignment of multigene panel tests coverage policies to that of clinical guidelines, overall and by state. Materials & methods: We reviewed NCCN Guidelines^® for four tumors. Public coverage policies were identified via web search. Payer policies included those with the largest or second largest number of commercial lives in each state. Policies were classified as 'more restrictive' or 'consistent' with the guidelines. Results: Of 38 plans/policies reviewed, 71% were classified as 'more restrictive' than the guidelines, with variation in the number of commercial lives by state. Among these, 52% restricted on panel size and 63% restricted in all or select tumors. Conclusion: Most coverage policies were more restrictive. Clinical guideline clarity and state policies may improve alignment to guidelines and geographic variations.

Aim: The authors aimed to investigate whether polymorphisms of PON-1 were associated with the susceptibility to and severity of ischemic stroke (IS). Methods: In this study, 302 IS patients and 303 healthy controls were enrolled. Polymorphisms rs854560 and rs854572 of PON-1 were detected using SNaPshot single-nucleotide polymorphism typing technology. Results: The rs854572 polymorphism of the PON-1 gene showed a significant correlation with IS, and its GG genotype reduced the risk of IS (recessive model, p = 0.001). The GG genotype was also associated with mild stroke (p = 0.032). No association was observed between rs854560 and IS. Conclusion:PON-1 rs854572 polymorphism was related to the risk of IS and could be a biomarker to access the severity of IS.

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.