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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 | Long-term results of endoscopic balloon dilatation of lower gastrointestinal tract strictures in Crohn's disease:A prospective study显示文摘AIM:To examine the long-term results of endoscopic treatment in a prospective study conducted over a period of 10 years,1997 to January 2007.METHODS:A total of 25 patients(20 female and five male:aged 18-75 years),with at least one symptom of stricture not passable with the standard colonoscope and with a confirmed scarred Crohn's stricture of the lower gastrointestinal tract,were included in the study.The main symptom was abdominal pain.The endoscopic balloon dilatation was performed with an 18 mm balloon under endoscopic and radiological control.RESULTS:Eleven strictures were located in the colon,13 at the anastomosis after ileocecal resection,three at the Bauhin valve and four in the ileum.Four patients had two strictures and one patient had three strictures.Of the 31 strictures,in 30 was balloon dilatation successful in a single endoscopic session,so that eventually the strictures could be passed easily with the standard colonoscope.In one patient with a long stricture of the ileum involving the Bauhin valve and an additional stricture of the ileum which were 15 cm apart,sufficient dilatation was not possible.This patient therefore required surgery.Improvement of abdominal symptoms was achieved in all cases which had technically successful balloon dilatation,althoughin one case perforation occurred after dilatation of a recurrent stricture.Available follow-up was in the range of 54-118 mo(mean of 81 mo).The relapse rate over this period was 46%,but 64% of relapsing strictures could be successfully dilated again.Only in four patients was surgery required during this follow-up period.CONCLUSION:We conclude from these initial results that endoscopic balloon dilatation,especially for short strictures in Crohn's disease,can be performed with reliable success.Perforation is a rare complication.It is our opinion that in the long-term,the relapse rate is probably higher than after surgery,but usually a second endoscopic treatment can be performed successfully,leading to a considerable success rate of the endoscopic procedure. | Klaus Stienecker Daniel Gleichmann Ulrike Neumayer H Joachim Glaser Carolin Tonus | 2009 | World Journal of Gastroenterology2009，15，21： | 9 |
| 3 | Reelin induces EphB activation显示文摘进功能的 neuronal 网络的新生的神经原的集成在 neuronal 进程和与另外的神经原的 synaptic 接触的形成的发展中的大脑,生长和树枝状要求房间的移植到他们的最后的位置。在协调区别事件的这个复杂序列的信号之中的一个中央播放器是分泌 glycoprotein Reelin,它也调制 synaptic 粘性,学习并且在成年大脑的记忆形成。到 ApoER2 和 VLDL 受体的 Reelin 有约束力, LDL 受体家庭的二个成员,开始包含细胞内部的细胞质的适配器蛋白质 Disabled-1 的酷氨酸 phosphorylation 的发信号的串联,它指向 neuronal 细胞骨架并且最终控制在整个发展中的大脑放神经原。然而, Reelin 信号与另外的调停受体的发信号串联交往调整大脑开发和粘性的不同方面,是可能的。EphB 酷氨酸 kinases 经由通过 ephrin B transmembrane 蛋白质的双向发信号调整房间粘附和排斥依赖者过程。这里,我们证明 Reelin 绑在 EphB transmembrane 蛋白质的细胞外的领域,导致受体聚类和向前在神经原发信号的 EphB 的激活,独立于“古典”的 Reelin 受体, ApoER2 和 VLDLR。因此,鼠标缺乏 EphB1 和 EphB2 显示 CA3 海马趾的金字塔形的神经原的一个放的缺点,类似于那在 Reelin 缺乏的鼠标,和这房间迁居,缺点取决于 EphB 蛋白质的 kinase 活动。一起,我们的数据为在向前发信号的 Reelin 和 EphB 之间的信号集成提供生物化学、功能的证据。 | Elisabeth Bouche Mario I Romero-Ortega Mark Henkemeyer Timothy Catchpole Jost Leemhuis Michael Frotscher Petra May Joachim Herz Hans H Bock | 2013 | Cell Research2013，23，4： | 5 |
| 4 | Paraesophageal hernia and iron deficiency anemia:Mechanisms,diagnostics and therapy显示文摘There is ample clinical evidence suggesting that the presence of large axial or paraesophageal hernias may lead to iron deficiency anemia.So-called Cameron lesions,as well as other small mucosa erosions,in the sliding area of these diaphragmatic hernias lead to invisible chronic blood loss and consequently to iron depletion.While the spectrum of symptoms in these patients is large,anemia is often not the only indication and typically not the primary indication for surgical correction of diaphragmatic hernias.Drug treatment with proton pump inhibitors and iron substitution can alleviate anemia,but this is not always successful.To exclude other possible bleeding sources in the gastrointestinal tract,a comprehensive diagnostic program is necessary and reviewed in this manuscript.Additionally,we discuss controversies in the surgical management of paraesophageal hernias. | Christoph G Dietrich Dolores Hübner Joachim W Heise | 2021 | World Journal of Gastrointestinal Surgery2021，13，3： | 2 |
| 5 | Assessment of convection, hot-air combined with microwave- vacuum and freeze- drying methods for mushrooms with regard to product quality 显示文摘 | Dimitrios A Albert H Joachim M | 2011 | International Journal of Food Science and Technology2011，46，： | 1 |
| 6 | Association of eystatin C with mortality,cardiovascular events,and incident heart failure among persons with coronary heart disease - Data from the Heart and Soul Study显示文摘 | Ix Joachim H Shlipak MG Chertow GM | 2007 | Circulation2007，115，2： | 1 |
| 7 | Regular scintigraphic measurements of food transit following different types of reconstruction after total gastrectomy显示文摘 | Beatrix H Has-vdo Z Joachim MM | 1999 | Ardhieveof Surgery1999，134，11： | 1 |
| 8 | Virilixzing ovarian tumor of low malignant potential associated with antecedent tomaxifen use for breast cancer显示文摘 | Daniel VS Irene H Joachim T | 1998 | Gynecol Oncol1998，68，3： | 1 |
| 9 | Intrahepatic IL-8 producing Foxp3 + CD4 + regulatory T cells and fibrogenesis in chronic hepatitis C<!-- Doctopic: VH -->显示文摘 | Bettina Langhans Benjamin Kr?mer Marcell Louis Hans Dieter Nischalke Robert Hüneburg Andrea Staratschek-Jox Margarethe Odenthal Steffen Manekeller Michael Schepke J?rg Kalff Hans-Peter Fischer Joachim L. Schultze Ulrich Spengler | 2013 | Journal of Hepatology2013，，2： | 1 |
| 10 | Determinants of residentialw ater demand in Germany显示文摘 | Joachim S Thomas H | 2009 | Ecological Econom-ics2009，68，： | 1 |
| 11 | Permeability' Prediction Based on Fractal Pore-Space Geometry显示文摘 | Pape H Clauser C Joachim I | 1999 | Geophysics1999，64，5： | 1 |
| 12 | Ductility and impact resistance of powder-metallurgical molybdenum-rhenium alloys 显示文摘 | Leichtfried G Joachim H S Martin H | 2006 | Metall Mater Trans A2006，37，： | 1 |
| 13 | Investigation into the effect of pre-bulging during hydromechanical deep drawing with uniform pressure onto the blank显示文摘 | LANG L H JOACHIM D NIELSEN K B | 2004 | Intemational Journal of Machine Tools & Manufacture2004，，44： | 1 |
| 14 | Risks for Central Nervous System Diseases among Mobile Phone Subscribers: A Danish Retrospective Cohort Study 显示文摘 | Joachim S Gunhild W Jorgen H | 2009 | PLoS ONE2009，4，2： | 1 |
| 15 | High-performance gene name normalization with GeNo显示文摘 | Joachim W Katrin T Udo H | 2009 | Bioinformatics2009，25，6： | 1 |
| 16 | Flatness-based clutch control for automated manual transmissions显示文摘 | JOACHIM H JOACHIM B PETER M | 2003 | Control Engineering Practice2003，，11： | 1 |
| 17 | A fascinating method for the preparation of ultra thin fibers 显示文摘 | ANDREAS GREINERAN JOACHIM H WENDORFF | 2007 | Angew Chem Int Ed2007，46，： | 1 |
| 18 | CT imaging in acute pulmonary embolism:diagnostic strategies显示文摘 | Joachim E Andreas H Marco Das | 2005 | Eur Radial2005，15，10： | 1 |
| 19 | Spangenberg Ines Omann, Friedrich Hinterberger, Sustainable growth criteria: Minimum benchmarks and scenarios for employment and the environment显示文摘 | Joachim H | 2002 | Ecological Economics2002，42，： | 1 |
| 20 | Hepato-lenticular degeneration(Wilson's Disease) following splenectomy;Inter-realationship of the reticulo-endothelial and centralnervous systems显示文摘 | Rabiner AM Joachim H Freiman FI | 1941 | Annals of Internal Medicine1941，14，10： | 1 |
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