Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

中西医结合护理干预妊娠晚期合并急性单纯性阑尾炎患者的临床观察

目的:探讨中西医结合护理干预妊娠晚期合并急性单纯性阑尾炎的临床疗效。方法:将2017 年9 月—2018 年12月于我院接受中西医结合保守治疗的31 例妊娠晚期合并急性单纯性阑尾炎患者作为研究对象，按随机数表法随机分为中西医结合护理组(观察组16 例)与常规护理组(对照组15 例)，对照组采取常规护理措施，观察组在对照组的基础上增加中西医结合护理措施，对比两组患者的临床疗效。结果:观察组患者的心理状态变化、新生儿体质状况以及临床疗效等指标等情况均明显优于对照组，且组间对比差异显著有统计学意义(P ＜ 0.05)。结论:中西医结合护理对妊娠晚期合并急性单纯性阑尾炎有较好的临床效果，可减少、甚至避免孕妇因合并急性阑尾炎而造成的打击和创伤。     

临床药师工作评价初探综述

随着我国医疗机构临床药师队伍的不断壮大，其在医疗服务中发挥着越来越重要的作用，对其工作进行绩效考核也是当今医疗领域的重要内容。以现有文献为基础，对国内外临床药师绩效考核体系进行分析，发现现有体系可分为为基于临床药师职责、基于临床药师业务流程、国外临床药师绩效考核体系三个方面；通过结合医疗机构的实际情况对现有绩效考核体系进行分析，发现存在考核指标和标准确定困难、考核难以做到实时性和延续性等问题，并针对这些问题提出清晰职责定位、重视临床药师价值体现等修改说明。     

Heterogeneity in amount of growth factors secreted by platelets in platelet-rich plasma samples from alopecia patients

Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFβ1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.     

Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

临床护理路径用于ICU重症颅脑损伤患者护理中的价值

目的 探讨临床护理路径用于ICU重症颅脑损伤患者护理中的价值。方法 选择2017年11月～2018年10月进行ICU重症颅脑损伤治疗的患者100例作为对象,随机数字表法分为对照组(n=50)和观察组(n=50)。对照组给予常规护理,观察组在其基础上应用临床护理路径,15 d护理后比较患者依从性情况、对患者护理前后心理状态进行评分,对不良并发症产生情况进行比较。结果 观察组康复锻炼依从、按时用药依从及饮食依从高于对照组(P0.05)。护理前两组SDS与SAS评分比较差异无统计学意义(P0.05),护理后,观察组SDS与SAS评分低于对照组(P0.05)。观察组出现压疮、泌尿感染、以及发热的发生率显著低于对照组(P0.05)。结论 将临床护理路径用于ICU重症颅脑损伤患者的护理中,提高了患者的护理依从性,减少了不良情绪以及不良并发症的产生,有助于患者整体治疗,值得推广应用。