生长抑素及其类似物联合质子泵抑制剂应用于急性非静脉曲张性上消化道出血的循证分析

目的 系统评价生长抑素及其类似物联合质子泵抑制剂（proton pump inhibitor，PPI）治疗急性非静脉曲张性上消化道出血（acute non-variceal upper gastrointestinal bleeding，ANVUGIB）的有效性和安全性，并分析其用药经济性。方法 采用循证医学方法搜集生长抑素及其类似物联合PPI治疗ANVUGIB的RCT、队列研究进行meta分析，得到相应的有效性及安全性分析结果，并进行成本-效果分析。结果 最终纳入6个RCT均未接受内镜治疗，共610例受试者。Meta分析结果显示，生长抑素及其类似物联合高、中、低剂量PPI治疗在以下方面均优于单用高、中、低剂量PPI治疗，差异有统计学意义，总有效率[OR=3.34，95%CI（2.03，5.47），P<0.000 01]、止血时间[MD=-9.04，95%CI（-11.69，-6.38），P<0.000 01]、输血量[MD=-1.10，95%CI（-1.46，-0.74），P<0.000 01]；在不良反应发生率方面，2组差异无统计学意义[OR=0.49，95%CI（0.11，2.12），P=0.34]。ANVUGIB患者予生长抑素联合高、中、低剂量奥美拉唑与单用高、中、低剂量奥美拉唑进行成本-效果分析，增量成本效果比分别为172.28，217.26，330.37，敏感性分析后显示结果稳定。而接受内镜治疗后应用生长抑素及其类似物联合PPI治疗仅1个队列研究，研究结果显示内镜治疗成功后联合治疗并不优于PPI单药治疗。结论 现有证据表明，生长抑素及其类似物联合PPI治疗未经内镜治疗的ANVUGIB患者为较有效的方案，两者安全性相当、耐受性较好，从药品直接成本考虑，高剂量PPI组联合治疗较中、低剂量PPI组联合治疗更具有成本效果性。而对于经内镜下止血治疗的患者两者疗效相当，可考虑单用PPI。     

A Snapshot of the Guidelines on Vesicoureteral Reflux in Children

The main goal in the management of patients with vesicoureteral reflux (VUR) is the preservation of kidney function by minimizing the risk of pyelonephritis. By defining and analyzing the risk factors for each patient depending on age, sex, grade of reflux, lower urinary tract dysfunction, anatomic abnormalities, and kidney status, it is possible to identify those patients with a potential risk of upper urinary tract infection and resulting renal scarring. This paper gives a brief overview of the European Association of Urology guidelines for the management and treatment of VUR in children. These guidelines are based on the best currently available knowledge and evidence.     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

程序性死亡蛋白-1抗体治疗晚期胃癌的临床研究新进展

目前化疗仍为晚期胃癌的标准治疗手段,而多数患者诊断时已接近晚期。近年新兴的免疫治疗手段程序性死亡蛋白-1(PD-1,programmed death l)抗体,通过阻断肿瘤细胞逃避自身免疫机制,重新激活自身免疫对肿瘤的杀伤作用,从而达到肿瘤的治疗作用。针对晚期胃癌的PD-1抗体治疗的临床研究已在国内外开展,大部分均有较好效果。本文对近年免疫治疗中的PD-1抗体在晚期胃癌的重要临床研究进展进行介绍。     

基于数据挖掘方法总结王树声教授治疗上尿路结石的用药经验

目的:运用中医传承辅助平台系统(V2.5)深入分析王树声教授治疗上尿路结石的用药经验，挖掘其核心经验 方组成和辨证用药规律。方法:收集王教授门诊治疗上尿路结石的治疗验方304 首，将方药信息录入系统，采用药物频次统计、 关联规则分析和熵聚类分析等方法分析处方用药规律。结果:304 首处方中涉及中药97 味，用药频次超过100 次的有14 味。所用药物药性多寒、温、平，药味多甘、苦，主归肝、肾、脾经；共得出25 组核心组合和9 首新处方。结论:王教授治疗 上尿路结石以益气固本、清热通淋为主，用药的关键在于“扶正固本”的把握和“祛邪通淋”的权衡，为临证用药和新方 开发提供参考。