摘要：Glioblastoma (GBM) is the most common primary brain malignancy in adults and has a poor prognosis despite standard of care treatment. The mainstay of GBM treatment has relied on maximum surgical resection and chemotherapy and radiation. Cancer immunotherapy has made great strides since the advent of anti-PD-1, anti-CTLA-4, and other immune checkpoint inhibitors. With the advancement of novel therapeutics, more clinical trials for patients have opened as well. An important future direction of clinical trials is the ability to identify appropriate patients to optimize treatment response and minimize toxicities. This review describes considerations in designing future GBM clinical trials in not only immunotherapy but also with other promising treatments. We will discuss factors, such as pseudoprogression, genetic and circulating biomarkers, and the commensal microbiome of patients in the setting of clinical trial design.

摘要：Background:Olmesartan,an angiotensin Ⅱ receptor blocker(ARB),is associated with gastrointestinal symptoms resembling sprue-like *** have proposed that enteropathy may be a class effect rather than *** performed a systematic review to identify literature of sprue-like enteropathy for all ***:Case reports,case series and comparative studies of ARBs were searched on PubMed and Embase databases through 21 November 2018 and then ***:A total of 82 case reports and case series as well as 5 comparative studies,including 248 cases,were selected and *** ARBs listed in the case reports were olmesartan(233 users;94.0%),telmisartan(5 users;2.0%),irbesartan(4 users;1.6%),valsartan(3 users;1.2%),losartan(2 users;0.8%)and eprosartan(1 user;0.4%).The periods between ARB initiation and onset of symptoms ranged from 2 weeks to 13 *** results were reported in 218 cases,in which 201 cases(92.2%)were villous atrophy and 131 cases(60.1%)were intraepithelial *** leucocyte antigen(HLA)testing was performed in 147 patients,among whom 105(71.4%)had HLA-DQ2 or HLA-DQ8 *** antibodies were tested in 169 patients,among whom 167(98.8%)showed negative *** exclusion from the diet failed to relieve symptoms of enteropathy in 127(97.7%)of 130 patients with *** remission of symptoms after discontinuation of ARB was reported in 233(97.4%)of the 239 patients with *** cases(2.8%)reported recurrence of symptoms after restarting olmesartan;rechallenge was not reported for the non-olmesartan *** retrospective studies conducted worldwide had inconsistent study designs(*** in periods of study and case definition)and ***:Although enteropathy is rare,clinicians should remain vigilant of this potential adverse event even years after medication initiation.

摘要：背景:巴西里约热内卢,中等收入地区,成人的HIV感染率约为1%。目标:评价里约热内卢市的DOTS项目成本-效益。设计:根据里约热内卢市卫生局的成本数据和以项目结果为基础的流行病学模型进行成本-效益分析研究。按零售市场价格估算成本数据,并从公开发表的文献采集流行病学数据。结果:10年自服药形式(SAT)的结核病项目服务262000人口的成本约为580271$,而DOTS形式结核病项目的成本则为1047886$。DOTS预算的最大部分是人员成本和病人成本,各占28%。而SAT预算的最大部分是药物成本,占34%。从SAT形式到DOTS形式可以减少1558 例结核病人(不确定范围[UR]:1418-1704)和143例结核病死亡病人(不确定范围[UR]:131-155)。DOTS的边际成本-效益比(ICER)为300$/减少一例病人(不确定范围[UR]:289-312),3270$/减少一例结核病死亡(不确定范围[UR]:3123-3435)。如果采用失能调整年指标(DALYS),DOTS可减少5426个DALYs损失(不确定范围[UR]:4906-5961)。DOTS的边际成本-效益比为86$/DALY(不确定范围[UR]:74-100)。结论:在巴西,DOTS是具有高度成本-效益比的卫生干预措施。

摘要：目的：报告1例萎缩性黄斑病变患者，经双眼局限性黄斑转位术后视力改善，并讨论选择该方法可能的候选者。设计：病例报告。结果：78岁女性，双眼萎缩性黄斑病变，无脉络膜新生血管形成，右眼至少17个月、左眼25个月有缓慢进展的视力丧失。经双眼局限性黄斑转位术，右眼采用巩膜内折叠法（infolding），左眼用巩膜外折叠（outpouching）法。黄斑转位后，最佳矫正视力，右眼从20／200提高到20／30，左眼从20／180到20／100。右眼随访30个月、左眼随访22个月，保持稳定。结论：黄斑转位可能使经选择的萎缩性黄斑病变患者的视力恢复，即使视力变坏经过较长时间。

摘要：Objective: To determine which features of incomplete or “nonclassic”forms of cystic fibrosis (CF) are associated with deleterious CF transmembrane conductan ce regulator gene (CFTR) mutations, and to explore other etiologies for features not associated with deleterious CFTR mutations. Study design: Clinical features were compared between 57 patients with deleterious mutations in each CFTR and 6 3 with no deleterious mutations. The Shwachman Bodian Diamond syndrome gene (SBD S) was sequenced to search for mutations in patients with no deleterious CFTR mu tations and steatorrhea to determine if any had unrecognized Shwachman-Diamond syndrome (SDS). Results: The presence of a common CF-causi ng mutation, absence of the vas deferens, and Pseudomona aeruginosa in the sputu m correlated with the presence of two deleterious CFTR mutations, whereas sweat chloride concentration, diagnostic criteria for CF, and steatorrhea did not. How ever, sweat chloride concentration correlated with CFTR mutation status in patie nts infected with P aeruginosa. One patient had disease-causing mutations in ea ch SBDS. Conclusions: Presence of a common CF-causing mutation, absence of the vas deferens and/or P aeruginosa infection in a patient with features of nonclas sic CF are predictive of deleterious mutations in each CFTR, whereas steatorrhea in the same context is likely to have etiologies other than CF transmembrane co nductance regulator (CFTR) dysfunction.

摘要：目的:调查巴西圣埃斯皮里图州维多利亚市肺结核发病空间模型及其与社会经济状况的关系。设计:2002—2006年在维多利亚进行为期4年的、基于地区的新发肺结核患者监测回顾性研究,并使用空间聚集分析[Anselin局部空间相关指标(LISA)和Getis-Ord Gi*统计值]、平滑化后的经验贝叶斯估计和模型预测的发病率3种方法来比较疾病发病的空间模型。并用空间泊松模型检验结核发病和社会经济状况的关系。结果:78个社区共报告了651例结核患者,其报告率从0到129/10万不等。Moran’sI表明发病率中有很强的空间自相关(0.399,P<0.0001),LISA和Gi*统计值发现了4个高发病区域。平滑化后经验贝叶斯估计展示了其中的2个区域,发病率由70/10万至90/10万变化,而另外2个地区变化范围为40~70/10万。结核发病和社会经济有显著性曲线相关关系(P=0.02)。结论:空间统计工具提取的数据可以帮助结核病控制规划将结核病资源分配到高发病危险的人群和结核病控制规划需要加以关注的目标地区。

摘要：目的发布欧洲重症医学学会(European Society of Intensive Care medicine, ESICM)关于神经重症监护患者液体治疗的专家共识和临床实践推荐意见。设计在2016年10月召开的ESICM LIVE 2016会议上召集了一个由22名国际专家组成的共识委员会,随后委员会成员通过电话会议和在线讨论制定本专家共识。方法回顾人群、干预、对比和结局(population, intervention,comparison, and outcomes, PICO)问题,根据需要进行更新并得到证据概要。本共识关注3个主要议题:(1)神经重症监护患者的液体复苏和维持;(2)高渗液体在颅内压控制中的应用;(3)蛛网膜下腔出血后迟发性脑缺血的液体管理。经过广泛的文献检索,应用推荐分级的评估、制订与评价(Gradingof Recommendations Assessment, Development and Evaluation, GRADE)系统原则评估证据质量(从高到极低),制定治疗推荐(强或弱),并在适用时发布最佳实践声明。基于文献和专家意见提供的综合证据,应用改良德尔菲方法(使用序贯方法以避免偏倚和误解)产生最终共识声明。结果最终共识包含总共32条声明,其中13条为强推荐,17条为弱推荐,另外2条声明未提供推荐意见。结论我们发布了一份关于神经重症监护患者液体治疗的共识声明和临床实践推荐。