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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 | 最新AD研究用诊断标准:IWG-2标准显示文摘在过去的8年中,国际工作组织(IWG)和美国国立老化研究院-阿尔茨海默协会(NIA-AA)建立了阿尔茨海默病(AD)诊断标准,它能更好地定义AD的临床表型,整合了生物标记物于诊断流程中,并覆盖了疾病的全程。本意见书充分地权衡了IWG标准的优缺点,建议改进诊断框架。依据这些改进,AD的诊断变得简单,只要有恰当的AD临床表型(典型或不典型)和与AD的病理相一致的病理生理学生物标志物出现。我们认为疾病的下游的定位性生物标志,如容积性磁共振成像(MRI)和氟脱氧葡萄糖-正电子发射型计算机断层成像(FDG-PET)等,适合更好地测量和监测疾病过程。本文还详述了非典型性AD、混合性AD和AD临床前期的特异诊断标准。 | 陈刚 曹雯炜 俞羚 糜建华 Dubois B Feldman HH Jacova C Hampel H Molinuevo JL Blennow K DeK osky ST Gauthier S Selkoe D Bateman R Cappa S Crutch S Engelborghs S Frisoni GB Fox NC Galasko D Habert MO Jicha GA Nordberg A Pasquier F Rabinovici G Robert P Rowe C Salloway S Sarazin M Epelbaum S de Souza LC Vellas B Visser PJ Schneider L Stern Y Scheltens P Cummings JL | 2014 | 神经病学与神经康复学杂志2014，11，3： | 31 |
| 3 | Chronic stress sensitizes rats to pancreatitis induced by cerulein:Role of TNF-α显示文摘AIM:To investigate chronic stress as a susceptibility factor for developing pancreatitis,as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer.METHODS:Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation.Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats.RESULTS:In vitro exposure of pancreatic acini toTNF-α disorganized the actin cytoskeleton.This was further increased by TNF-α/CCK treatment,which additionally reduced amylase secretion,and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner.TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release,induced ATP loss,and augmented the ADP/ATP ratio.In vivo,rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels.Serum,pancreatic,and lung inflammatory parameters,as well as caspases' activity in pancreatic and lung tissue,were substantially enhanced in stressed/cerulein-treated rats,which also experienced tissues' ATP loss and greater ADP/ATP ratios.Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema,hemorrhage and leukocyte infiltrate,and pancreatic necrosis.Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-αantibody,which diminished all inflammatory parameters,histopathological scores,and apoptotic/necrotic markers in stressed/cerulein-treated rats.CONCLUSION:In rats,chronic stress increases susceptibility for developing pancreatitis,which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. | Marcelo G Binker Andres A Binker-Cosen Daniel Richards Herbert Y Gaisano Rodica H de Cosen Laura I Cosen-Binker | 2010 | World Journal of Gastroenterology2010，16，44： | 7 |
| 4 | Endoscopic ultrasound-guided vs endoscopic retrograde cholangiopancreatography biliary drainage for obstructed distal malignant biliary strictures: A systematic review and meta-analysis显示文摘BACKGROUND For palliation of malignant biliary obstruction(MBO), the gold-standard method of biliary drainage is endoscopic retrograde cholangiopancreatography(ERCP)with the placement of metallic stents. Endoscopic ultrasound(EUS)-guided drainage is an alternative that is typically reserved for cases of ERCP failure.Recently, however, there have been robust randomized clinical trials(RCTs)comparing EUS-guided drainage and ERCP as primary approaches to MBO.AIM To compare EUS guidance and ERCP in terms of their effectiveness and safety in palliative biliary drainage for MBO.METHODS This was a systematic review and meta-analysis, in which we searched the MEDLINE, Excerpta Medica, and Cochrane Central Register of Controlled Trials databases. Only RCTs comparing EUS and ERCP for primary drainage of MBO were eligible. All of the studies selected provided data regarding the rates of technical and clinical success, as well as the duration of the procedure, adverse events, and stent patency. We assessed the risk of biases using the Jadad score and the quality of evidence using the Grading of Recommendations Assessment,Development and Evaluation criteria.RESULTS The database searches yielded 5920 records, from which we selected 3 RCTs involving a total of 222 patients(112 submitted to EUS and 110 submitted to ERCP). In the EUS and ERCP groups, the rate of technical success was 91.96%n and 91.81%, respectively, with a risk difference(RD) of 0.00%(95%CI:-0.07, 0.07;P = 0.97; I^2 = 0%). The clinical success was 84.81% and 85.53% in the EUS and ERCP groups, respectively, with an RD of-0.01%(95%CI:-0.12, 0.10; P = 0.90; I^2 =0%). The mean difference(MD) for the duration of the procedure was-0.12%(95%CI:-8.20, 7.97; P = 0.98; I^2 = 84%). In the EUS and ERCP groups, there were14 and 25 adverse events, respectively, with an RD of-0.06%(95%CI:-0.23, 0.12; P= 0.54; I^2 = 77%). The MD for stent patency was 9.32%(95%CI:-4.53, 23.18; P =0.19; I^2 = 44%). The stent dysfunction rate was significantly lower in the EUS t group(MD =-0.22%; 95 CI:-0.35,-0.08; P = 0.001; I^2 = 0%).CONCLUSION EUS represents an interesting alternative to ERCP for MBO drainage,demonstrating lower stent dysfunction rates compared with ERCP. Technical and clinical success, duration, adverse events and patency rates were similar. | Fernanda P Logiudice Wanderlei M Bernardo Facundo Galetti Vitor M Sagae Carolina O Matsubayashi Antonio C Madruga Neto Vitor O Brunaldi Diogo T H de Moura Tomazo Franzini Spencer Cheng Sergio E Matuguma Eduardo G H de Moura | 2019 | World Journal of Gastrointestinal Endoscopy2019，11，4： | 6 |
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