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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis显示文摘AIM To investigate whether the use of proton pump inhibitors(PPIs) increases the incidence of spontaneous bacterial peritonitis(SBP) in patients with cirrhosis and ascites.METHODS An historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm3 without evidence of an intraabdominal, surgically treatable source of infection.RESULTS Of 738 cirrhotic patients, 582(58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection(36.2%) and alcohol abuse(25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299(51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP(22.5%). Among 107 non-users of PPIs, 23 developed SBP(21.5%)(HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh(CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo(Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP(58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP(P = 0.34). CONCLUSION In conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites. | Suelen A S Miozzo Jorge A John Marcelo C Appel-da-Silva Isabella A Dossin Cristiane V Tovo Angelo A Mattos | 2017 | World Journal of Hepatology2017，9，35： | 5 |
| 3 | 深部俯冲板片三维构造重建及其几何学、运动学研究——以汤加—克马德克地区俯冲板片为例显示文摘西南太平洋板块与澳大利亚板块之间的汤加-克马德克俯冲带,是研究地球动力学最重要的区域之一.本文研究根据MIT~P08地震数据,结合板块构造边界、地震活动分布、海岸地形数据等,基于GOCAD软件平台建立三维地震层析成像,对西南太平洋板块的汤加-克马德克俯冲板片进行三维解释.地震层析成像显示汤加-斐济地区地幔至少存在三个“高速”异常体.早期汤加-克马德克俯冲板片穿过地幔转换带,并进入下地幔,最大深度达1600km.三维构造模型揭示了汤加克马德克板片在深度600~800km处存在断折形变,该俯冲板片去褶皱恢复后,测量其俯冲的最大位移达2600km.汤加-克马德克板片开始快速俯冲的时间至少在30Ma之前,平均移动速率约为68~104mrn/a.俯冲板片三维构造重建和恢复,可以有效揭示俯冲板片几何学、运动学,为研究深源地震成因、地球深部变化过程和动力学机制提供约束. | 鲁人齐 John Suppe 何登发 Jonny Wu Ravi V S Kanda 刘波 陈于高 | 2013 | 地球物理学报2013，56，11： | 3 |
| 4 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 5 | 2009年南极冰穹A的双色天光背景统计和分析显示文摘天光背景是天文台址的一个重要指标。利用2009年位于南极冰穹A的CSTAR望远镜两个波段的观测数据,对南极冰穹A的天光背景进行了统计和分析。结果表明约74%的g波段天光背景的ADU值小于每像素100/s;90.5%的r波段的天光背景的ADU值小于每像素100/s。在不考虑大气消光的情况下,定标后的结果为2009年冰穹A的观测数据中天光背景亮度的中值:g波段为19.9 mag/arcsec2,r波段为20.1 mag/arcsec2。 | 宗伟凯 付建宁 牛家树 Ashley Michael C B 宫雪非 Lawrence J S 刘强 Luong-Van Daniel Pennypacker C R Storey John W V 王灵芝 王力帆 杨惠根 袁祥岩 York Donald G 朱镇熹 | 2014 | 天文研究与技术2014，11，1： | 2 |
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| 9 | Synthesis and size control of gold nanoparticles stabilized by poly(methyl- phenylphosphazene)显示文摘 | Walker C H John J V S Wisian Neilson P | 2001 | J Am Chem Soc2001，123，16： | 1 |
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