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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 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 3 | 轮胎工业用更安全的操作油显示文摘在欧洲 ,立法和公众压力正在使欧洲市场上的操作油性质发生变化。这引起欧洲橡胶行业对不使用有潜在致癌危险芳香油的新型轮胎和橡胶配方进行评述。本文对这一状况进行了研究 ,并探讨了美国市场上可能出现的动态 ,介绍了不同产品的需求量以及北美操作油和润滑基油制造不断变化的局面。 | Paul W H T Juergen E P 吴淑华 | 2002 | 轮胎工业2002，22，5： | 3 |
| 4 | Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study显示文摘AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A 'low risk' category(lamotrigine or levetiracetam, n=16), an 'intermediate risk' category(carbamazepine, oxcarbazepine, phenytoin, or valproate, n=34) and a 'high risk' category(topiramate, n=5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant(P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category(P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient(ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient(linear regression analysis, P > 0.15) were observed. CONCLUSION Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects. | Tamar M van Veenendaal Dominique M IJff Albert P Aldenkamp Richard H C Lazeron Paul A M Hofman Anton J A de Louw Walter H Backes Jacobus F A Jansen | 2017 | World Journal of Radiology2017，9，6： | 2 |
| 5 | Anaerobic bacteria and intrahepatic stones: detections of Clostridium sp. and Bacteroides fragilis显示文摘To detect anaerobic bacteria Clostridium sp . and Bacteroides fragilis in intrahepatic stones by molecular genetic method Methods DNA was extracted from 59 stone samples and subjected to polymerase chain reaction (PCR) amplification targeting the 16S rRNA gene of Clostridium sp . and the glutamine synthetase gene of Bacteroides fragilis Single-strand conformational polymorphism (SSCP) analysis was performed to identify the Clostridium sp Results 16S rRNA gene sequences for Clostridium sp. were identified in 49 stones (83%, 49/59) The two most common groups were detected in 19 (41%) and 17 (37%) of the 46 samples using SSPC analysis, and 25/59 (42%) stones were tested positive for Bacteroides fragilis Conclusions Anaerobes such as Clostridium sp and Bacteroides fragilis present in intrahepatic stones and may play a role in stone formation PCR is a useful technique to detect fastidious pathogens, which are difficult to culture SSCP of PCR products is a rapid method in differentiating bacterial | LIU Yanlei Kan Lam Yajarayma J Tang Paul H Gumerlock Dong Ki Lee Myung Hwa Kim Sum P Lee Joseph SilvaJr Joseph W Leung | 2000 | Chinese Medical Journal2000，，9： | 2 |
| 6 | 细胞分离培养在实验室诊断眼部单纯疱疹病毒感染疾病的误诊和漏诊情况(英文)显示文摘目的:对比聚合酶链反应(PCR)和细胞分离培养在实验室诊断眼部单纯疱疹病毒(HSV)感染疾病的作用。方法:我们对连续患者的实验室结果(PCR实验,细胞分离培养及临床诊断)及病历进行回顾性研究在诊断眼部HSV感染疾病过程中,PCR检测结果、细胞分离培养及首诊结果进行了统计比较。结果:患者581例经过检查后,520例PCR检查阴性,细胞培养阴性(89.6%);0例PCR检查阴性,细胞培养阳性(0%);27例PCR检查阳性,细胞培养阴性(4.6%);34例PCR检查阳性,细胞培养阳性(5.8%)。PCR检测阳性率高于细胞分离培养(McNemars,P=0.0001)。47例PCR检查为HSV初诊感染阳性患者中,19例患者中有14例为细胞培养阴性结果(74%),5例HSV患者因缺PCR检测结果将被误诊;28例患者中有25例患者细胞培养阳性(占89%),3例HSV患者因缺PCR检测结果将被漏诊。结论:PCR诊断眼部HSV感染优于细胞分离培养。细胞分离培养对于眼部HSV感染的非典型表现不易诊断。 | Regis P Kowalski Paul P Thompson Tara H Cronin | 2010 | 国际眼科杂志2010，10，11： | 2 |
| 7 | Cladding of WC-12Co on low carbon steel using a pulsed Nd: YAG laser显示文摘 | Paul C P Alemohammad H Toyserkani E | 2007 | Materials Science and Engineering2007，464，： | 1 |
| 8 | Plant volatiles as a defense against insect herbivores 显示文摘 | PAUL W P JAMES H T | 1999 | Plant Physiology1999，121，： | 1 |
| 9 | Clopidogrel for coronary stenting response variability, drug resistance, and the effect of pretreatment platelet reactivity显示文摘 | PAUL A C KEVIN P B BONNIE L H et aI | 2003 | Circulation2003，107，： | 1 |
| 10 | Regional scale variation in forest structure and biomass in the Yucatan Peninsula, Mexico: Effects of forest disturbance 显示文摘 | TANIA U H PAUL M D CARLOS A P | 2007 | Forest Ecol Management2007，247，： | 1 |
| 11 | Cladding of WC-12Co on Low Carbon Steel Using a Pulsed Nd:YAG Laser显示文摘 | Paul C P Alemohammad H Toyserkani E | 2007 | Materials Science and Engineering A2007，464，： | 1 |
| 12 | Sequence comparison of open reading frames 2 to 5 of low and high virulence United Stated isolate of porcine reproductive and respiratory syndrome virus 显示文摘 | XIANG J M PAUL P S ALBOUR G H | 1995 | J Gen Virol1995，76，： | 1 |
| 13 | Maternal antibody inhibits both cellular and humoral immunity in response to measles vaccination at hirth显示文摘 | Mary P L Gregory H Paul R | 2006 | Virology2006，350，2： | 1 |
| 14 | Prehistoric and modem freshwater mussel (bivalvia:unionoidea) faunas of the Tennessee River:Alabama,Kentucky,and Tennessee显示文摘 | Mark H H Paul W P | 1999 | Regulated Rivers:Research & Management1999，15，13： | 1 |
| 15 | Death and Space in The Netherlands显示文摘 | PAUL J M STEEN V PELLENBARG P H | 2005 | Journal of Economic and Social Geography2005，97，5： | 1 |
| 16 | Biomass derived producer gas as a reciprocating engine fuel-an experimental analysis 显示文摘 | Sridhar G Paul P J Mukunda H S | 2001 | Biomass and Bioenergy2001，21，1： | 1 |
| 17 | Competitive and cooperative inventory policies in a two stage supply chain显示文摘 | GERARD P C PAUL H Z | 1999 | Management Science1999，45，7： | 1 |
| 18 | Ocular biometry in occludable angles and angle closure glaucoma: a population based survey 显示文摘 | George R Paul PG Baskaran M Ramesh SV Raju P Arvind H | 2003 | Br J Ophthalmol2003，87，4： | 1 |
| 19 | Modeling of cast systems using smoothed-particle hydrodynamics显示文摘 | Paul C Mahesh P Joseph H | 2004 | JOM2004，56，3： | 1 |
| 20 | Selective catalytic oxidation显示文摘 | KATRYNIOK B KIMURA H SKRZYIiSKA H GIRARDON J S FONGARLAND P CAPRON M DUCOULOMBIER R MIMURA N PAUL S DUMEIGNIL F | 2011 | Green Chem2011，13，8： | 1 |
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