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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 | Cholangiocarcinoma:A 7-year experience at a single center in Greece显示文摘AIM: To evaluate survival rate and clinical outcome of cholangiocarcinoma.METHODS: The medical records of 34 patients with cholangiocarcinoma,seen at a single hospital between the years 1999-2006,were retrospectively reviewed.RESULTS: Thirty-four patients with a median age of 75 years were included.Seventeen (50%) had painless jaundice at presentation.Sixteen (47.1%) were perihilar,15 (44.1%) extrahepatic and three (8.8%) intrahepatic.Endoscopic retrograde cholangiography (ERCP) and/or magnetic resonance cholangiography (MRCP) were used for the diagnosis.Pathologic confirmation was obtained in seven and positive cytological examination in three.Thirteen patients had co-morbidities (38.2%).Four cases were managed with complete surgical resection.All the rest of the cases (30) were characterized as non-resectable due to advanced stage of the disease.Palliative biliary drainage was performed in 26/30 (86.6%).The mean follow-up was 32 mo (95% CI,20-43 mo).Overall median survival was 8.7 mo (95% CI,2-16 mo).The probability of 1-year,2-year and 3-year survival was 46%,20% and 7%,respectively.The survival was slightly longer in patients who underwent resection compared to those who did not,but this difference failed to reach statistical significance.Patients who underwent biliary drainage had an advantage in survival compared to those who did not (probability of survival 53% vs 0% at 1 year,respectively,P = 0.038).CONCLUSION: Patients with cholangiocarcinoma were usually elderly with co-morbidities and/or advanced disease at presentation.Even though a slight amelioration in survival with palliative biliary drainage was observed,patients had dismal outcome without resection of the tumor. | Alexandra Alexopoulou Aspasia Soultati Spyros P Dourakis Larissa Vasilieva Athanasios J Archimandritis | 2008 | World Journal of Gastroenterology2008，14，40： | 3 |
| 3 | Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats显示文摘AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration. | Larissa Lucena Périco Vinícius Peixoto Rodrigues Rie Ohara Gabriela Bueno Vania Vasti Alfieri Nunes Raquel Cássia dos Santos Ana Carolina Lima Camargo Luis Antuio Justulin Joior Sérgio Faloni de Andrade Viviane Miranda Bispo Steimbach Luísa Mota da Silva Lúcia Regina Machado da Rocha Wagner Vilegas Catarina dos Santos Clélia Akiko Hiruma-Lima | 2018 | World Journal of Gastroenterology2018，24，38： | 3 |
| 4 | Production of free fatty acids from waste oil by application of ultrasound 显示文摘 | Larissa P L Francisco F S Enio C | 2012 | Biomass Conversion and Biorefinery2012，，2： | 1 |
| 5 | Cream cheese as a symbiotic food carrier using B ifidobacterium animalis B b‐12 and L actobacillus acidophilus L a‐5 and inulin显示文摘 | Larissa L Alves Neila S P S Richards Paula Mattanna Diego F Andrade Adriano P S Rezer Liana I G Milani Adriano G Cruz José A F Faria | 2012 | Int J Dairy Technol2012，，1： | 1 |
| 6 | IFI16 Induction by Glucose Restriction in Human Fibroblasts Contributes to Autophagy through Activation of the ATM/AMPK/p53Pathway显示文摘 | Xin D Larissa P Sudhakar V | 2011 | PLo S One2011，，19： | 1 |
| 7 | Beyond traditional surveillance:applying syndromic surveillance to developing settings-opportunities and challenges显示文摘 | Larissa M Jean C Julie P | | 0，，1： | 1 |
| 8 | Reverse knowledge trans- fer in MNES: subsidiary innovativeness and entry modes显示文摘 | RAM M LUCIA P LARISSA R | 2014 | Long Range Planning2014，47，1： | 1 |
| 9 | Census of the Viral Metagenome within an Activated Sludge Microbial Assemblage显示文摘 | Larissa C P Erin J C Stephen J | 2010 | Applied and Environmental Microbiology2010，76，8： | 1 |
| 10 | Associations of FASN gene polymorphisms with economical traits in Nellore cattle 显示文摘 | Fabio R P S Milena G C Larissa F S F | 2012 | Molecular Biology Reports2012，39，10： | 1 |
| 11 | Notch receptor and Notch ligand expression in developing avian cartilage显示文摘 | Rebecca Wil iams Larissa Nelson Gary P Dowthwaite | | 0，，： | 1 |
| 12 | Syntheses and structure-activity relationships of novel 3'-difluoromethyl and 3'-trifluoromethyl-taxoids显示文摘 | LARISSA V K ANTONELLA P IOANA M U | 2008 | Journal of Fluorine Chemistry2008，129，9： | 1 |
| 13 | Synthesis ofa thinl- 13-cyclodextrin, a polential ag,ent for con/rolling enzymatic browning in fruits and vegetables 显示文摘 | Carmen M Gabriela P A Larissa G | 2013 | Journal of Agricuhural and Food Chemistu2013，61，11： | 1 |
| 14 | Relationships between water vapor path and precipitation over the tropical oceans显示文摘 | CHRISTOPHER S B MATTHEW E P LARISSA E B | 2004 | J Clim2004，17，7： | 1 |
| 15 | Image quality in a low radiation exposure protocol for retrospectively ECG-gated coronary CT angiog- raphy 显示文摘 | Tobias P Larissa K Dieter R | 2009 | A JR Am J Roentgenol2009，192，4： | 1 |
| 16 | Image quality in alow radiation exposure protocal for retrospectively ECG-gated coronary CT angiography 显示文摘 | Tobiss P Larissa R Dieter R | 2009 | AJR2009，192，4： | 1 |
| 17 | Effect of salt additives on protein partion in polythylene glycolsodium sulfate aqueous two-phase systems 显示文摘 | Luisa Ferreira Pedro P Madeira Larissa Mikheeva | 2013 | Biochimica et Biophysica Acta2013，1834，12： | 1 |
| 18 | Mechanical properties of nylon-6/brazilian clay nanocomposites 显示文摘 | Amanda M D L Larissa F M Osanildo D P | 2010 | Journal of Alloys and Compounds2010，95，2： | 1 |
| 19 | Predicting utility of a model for end stage liver disease in alcoholic liver disease显示文摘瞄准:作为短术语(30 d 和 90 d ) 的预言者为结束阶段肝疾病验证 Maddrey 判别式函数分数和模型的统计实用程序在有含酒精的肝炎并且到的病人的死亡与含酒精的肝炎在临床的特征和病人的实验室变量之中估计预示的因素。方法:有含酒精的肝炎的诊断的 34 个病人承认从 2000 ~ 2005 的雅典的大学医院在当前的回顾的学习被估计,统计分析被进行到 Hippokration。结果:30-d 和 90-d 死亡率在 5.9% 点被报导(2/34 ) 并且 14.7%(5/34 ) 分别地。重要关联为结束阶段肝疾病为模型被表明( P30 = 0.094 , P90 = 0.046 )并且 Maddrey 判别式功能分数( P30 = 0.033 , P90 = 0.038 )与 30-d 和 90-d 死亡而一个重要协会也为丙氨酸 aminotransferase 被建立( P = 0.057 ),血纤维蛋白降级产品( P = 0.048 )并且C反应的蛋白质( P = 0.067 )与 90-d 死亡。为 30-d 死亡,在曲线下面的区域是 0.969 (95%CI:0.902-1.036, P = 0.028 ) 为为结束阶段肝疾病 20 和 0.984 的模型(95%CI:0.942-1.027, P = 0.023 ) 为 Maddrey 判别式功能分数与最佳割掉 30.5 的点(敏感 1,特性 0.937 ) 并且 108.68 (敏感 1,特性 0.969 ) 分别地。因此,为 90-d 死亡,在曲线下面的区域是 0.762 (95%CI:0.559-0.965, P = 0.065 ) 为为结束阶段肝疾病 20 和 0.752 的模型(95%CI:0.465-1.038, P = 0.076 ) 为 Maddrey 判别式功能分数与最佳割掉 19 的点(敏感 0.6,特性 0.6 ) 并且 92 (敏感 0.6,特性 0.946 ) 分别地。为不同分数范畴的观察 Kaplan Meier 幸存率与木头等级测试和更高的分数相比价值与更低的幸存被相关。结论:为结束阶段肝疾病和 Maddrey 判别式功能分数的模型的相等被当前的学习暗示,由阴谋的接收装置起作用的曲线和估计的幸存率验证了。90-d 死亡的独立预言者也被验证了的 C 反应的蛋白质,血纤维蛋白降级产品和丙氨酸 aminotransferase 的一个统计上重要的实用程序。 | Aspasia S Soultati Spyridon P Dourakis Alexandra Alexopoulou Melanie Deutsch Larissa Vasilieva Athanasios J Archimandritis | 2006 | World Journal of Gastroenterology2006，12，25： | 1 |
| 20 | Idiopathic type 1 diabetes in Dallas, Texas 显示文摘 | Antonic P P Larissa A S Litonjua P | 2001 | Diabetes Care2001，24，： | 1 |
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