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1帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) 2021中国肺癌杂志2021,24,9:34
2Passive expansion of sub-maximally dilated transjugular intrahepatic portosystemic shunts and assessment of clinical outcomes显示文摘AIM To assess for passive expansion of sub-maximally dilated transjugular intrahepatic portosystemic shunts(TIPS) and compare outcomes with maximally dilated TIPS.METHODS Polytetrafluoroethylene covered TIPS(Viatorr) from July 2002 to December 2013 were retrospectively reviewed at two hospitals in a single institution. Two hundred and thirty patients had TIPS maximally dilated to 10 mm(m TIPS), while 43 patients who were at increased risk for hepatic encephalopathy(HE), based on clinical evaluation or low pre-TIPS portosystemic gradient(PSG), had 10 mm TIPS sub-maximally dilated to 8 mm(sm TIPS). Group characteristics(age, gender, Model for End-Stage Liver Disease score, post-TIPS PSG and clinical outcomes were compared between groups, including clinical success(ascites or varices), primary patency,primary assisted patency, and severe post-TIPS HE. A subset of fourteen patients with sm TIPS underwent follow-up computed tomography imaging after TIPS creation, and were grouped based on time of imaging(< 6 mo and > 6 mo). Change in diameter and crosssectional area were measured with 3D imaging software to evaluate for passive expansion.RESULTS Patient characteristics were similar between the sm TIPS and m TIPS groups, except for pre-TIPS portosystemic gradient, which was lower in the sm TIPS group(19.4 mm Hg ± 6.8 vs 22.4 mm Hg ± 7.1, P = 0.01). Primary patency and primary assisted patency between sm TIPS and m TIPS was not significantly different(P = 0.64 and 0.55, respectively). Four of the 55 patients(7%) with sm TIPS required TIPS reduction for severe refractory HE, while this occurred in 6 of the 218 patients(3%) with m TIPS(P = 0.12). For the 14 patients with follow-up computed tomography(CT) imaging, the median imaging follow-up was 373 d. There was an increase in median TIPS diameter, median percent diameter change, median area, and median percent area change in patients with CT follow-up greater than 6 mo after TIPS placement compared to follow-up within 6 mo(8.45 mm, 5.58%, 56.04 mm^2, and 11.48%, respectively, P = 0.01).CONCLUSION Passive expansion of sm TIPS does occur but clinical outcomes of sm TIPS and m TIPS were similar. Sub-maximal dilation can prevent complications related to overshunting in select patients.Michael C Hsu Charles N Weber S William Stavropoulos Timothy W Clark Scott O Trerotola Richard D Shlansky Goldberg Michael C Soulen Gregory J Nadolski 2017World Journal of Hepatology2017,9,12:11
3Pathogenic mechanisms in en- dometriosis-associated infertility 显示文摘Gupta S Goldberg JM Aziz N 2008Fertil Steril2008,90,2:1
4Endotoxin and bacteria in portal blood显示文摘Jacob AI Goldberg PK Bloom N 1977Gastroenterology1977,72,:1
5Heat-shock proteins modulate the incidence of apoptosis and oxidative stress in reimplantation mouse embryos 显示文摘Esfandiari N Falcone T Goldberg JM 2007Fertil Steril2007,87,5:1
6Effects of peritoneal fluid on preimplantation mouse embryo development and apoptosis in vitro显示文摘ESFANDIARI N FALCONE T GOLDBERG J M 2005Reprod Biomed Online2005,11,5:1
7Linguistic features of noneoding DNA sequences 显示文摘Mantegna R N Buldyrev S V Goldberger A L 1994Physical Review Let- ters1994,73,23:1
8What is the best surgical margin for a Basal cell carcinoma: a meta-analysis of the literature显示文摘Gulleth Y Goldberg N Silverman RP 2010Plastic and Reconstructive Surgery2010,26,:1
9Management of exposure hydroxyapatite orbital implant 显示文摘Kim YD Goldberg RA Shrr N 1994Ophthalmologyy1994,101,11:1
10Security of the WEP algorithm显示文摘BORISOV N GOLDBERG 1 WAGNER D 2001ISAAC2001,36,3:1
11The validity oftwo versions of the GHQ in the WHO study of mental illness in general health care 显示文摘Goldberg DP Gater R Sartorius N 1997Psychol Med1997,27,:1
12The validity of two versions of the GHQ in the WHO study of mental illness in general health care 显示文摘Goldberg DP Gater R Sartorius N 1997Psychol Med1997,27,:1
13Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hyperclaolesterolemia 显示文摘Goldberg A C Hopkins P N Toth P P 2011Journal of clinical lipidology2011,5,3:1
14The transcaruncular approach in repair of orbital fractures : a retrospective study 显示文摘Garcia GH Goldberg RA Short N 1998Craniomaxillofac Trauma1998,4,1:1
15Processive degradation of proteins and other catalytic properties of the proteasorne from Ther-moplasma aeidophilum显示文摘Akopian T N Kisselev A F Goldberg A L 1997J Biol Chem1997,272,3:1
16Transcriptional and posttranscriptional regulation of soybean seed protein mRNA Level显示文摘Walling L Drews G N Goldberg R B 1986Proc Natl Acad sci1986,83,:1
17The validity of two versions of the GHQ in the WHO study of mental illness in general health care 显示文摘Goldberg DP Gater R Sartorius N 1997Psychol Med1997,27,:1
18Range of sizes of peptide products generated during degradation of different proteins by archaeal proteasomes显示文摘Kisselev A F Akopian T N Goldberg A L 1998J Biol Chem1998,273,4:1
19Orbital exenteration: resalts of an individualized approach 显示文摘Goldberg RA Kim JW Shorr N 2003Ophthalmol Plast Reconstr Surg2003,19,3:1
20Objective and subjective outcomes in surgery for chronic sinusitis显示文摘KENNEDY Q W WRIGHT E D GOLDBERG A N 2000Laryngoscope2000,110,:1
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