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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 | 抗炎介质表达缺陷参与中性粒细胞型支气管哮喘发病机制:半乳糖凝集素-3和白细胞介素-1RA/白细胞介素-1beta比例显著下降显示文摘支气管哮喘(哮喘)是具有异质性的气道炎症性疾病,其主要特点表现为气道高反应和可变的气流受限。在哮喘的发病机制中,过敏原诱导的TH2淋巴细胞激活以及IL-5介导的嗜酸粒细胞渗出起到重要的作用。近年来发现超过50%的哮喘患者气道的嗜酸粒细胞水平并不增高,并将这种亚型定义为非嗜酸粒细胞型哮喘。其中部分患者表现为气道中性粒细胞明显增高,称为中性粒细胞型哮喘。 | 高鹏 Peter G Gibson Katherine J Baines Ian A Yang John W Upham Paul N Reynolds Sandra Hodge Alan L James Christine Jenkins Matthew J Peters 张捷 Jodie L Simpson | 2016 | 中华结核和呼吸杂志2016，39，11： | 5 |
| 3 | Prostate cancer upgrading or downgrading of biopsy Gleason scores at radical prostatectomy:prediction of'regression to the mean'using routine clinical features with correlating biochemical relapse rates显示文摘Recommendations for managing clinically localized prostate cancer are structured around clinical risk criteria,with prostate biopsy(PB)Gleason score(GS)being the most important factor.Biopsy to radical prostatectomy(RP)specimen upgrading/downgrading is welldescribed,and is often the ratio nale for costly imaging or genomic studies.We prese nt simple,no-cost an a lyses of clinical parametersto predict which GS 6 and GS 8 patients will change to GS 7 at prostatectomy.From May 2006 to December 2012,1590 patientsunderwent robot-assisted radical prostatectomy(RARP).After exclusions,we identified a GS 6 cohort of 374 patients and a GS 8cohort of 91 patients.During this era,>1000 additional patients were enrolled in an active surveillanee(AS)program.For GS 6,265(70.9%)of 374 patients were upgraded,and the cohort included 183(48.9%)patients eligible for AS by the Prostate Cancer ResearchInternational Active Surveillance Study(PRIAS)standards,of which 57.9%were upgraded.PB features that predicted a>90%chanceof upgrading included≥7 cores positive,maximum foci length≥8 mm in any core,and total tumor involvement≥30%.For GS 8,downgrading occurred in 46(50.5%),which was significantly higher for single core versus multiple cores(80.4%vs 19.6%,P=0.011).Biochemical recurre nee(BCR)occurred in 3.4%of GS 6 upgraded versus 0%non upgraded,and in GS 8,19.6%downgraded versus42.2%nondown graded.In coun seling men with clin ically localized prostate can cer,the odds of GS cha nge should be presented,andcertain men with high-volume GS 6 or low-volume GS 8 can be counseled with GS 7-based recommendations. | Muammer Altok Patricia Troncoso Mary F Achim Surena F Matin Graciela N Gonzalez John W Davis | 2019 | Asian Journal of Andrology2019，21，6： | 4 |
| 4 | Continuous internal counterpulsation as a bridge to recovery in acute and chronic heart failure显示文摘Cardiac recovery from cardiogenic shock(CS) and end-stage chronic heart failure(HF) remains anoften insurmountable therapeutic challenge. The counterpulsation technique exerts numerous beneficial effects on systemic hemodynamics and left ventricular mechanoenergetics, rendering it attractive for promoting myocardial recovery in both acute and chronic HF. Although a recent clinical trial has questioned the clinical effectiveness of short-term hemodynamic support with intra-aortic balloon pump(IABP, the main representative of the counterpulsation technique) in CS complicating myocardial infarction, the issue remains open to further investigation. Moreover, preliminary data suggest that long-term IABP support in patients with end-stage HF is safe and may mediate recovery of left- or/and right-sided cardiac function, facilitating long-term weaning from mechanical support or enabling the application of other permanent, life-saving solutions. The potential of long-term counterpulsation could possibly be enhanced by implementation of novel, fully implantable counterpulsation devices. | Christos D Kontogiannis Konstantinos Malliaras Chris J Kapelios Jay W Mason John N Nanas | 2016 | World Journal of Transplantation2016，6，1： | 4 |
| 5 | ACC/AHA guidelines for the management of patients with unstable angina and non–st-segment elevation myocardial infarction显示文摘 | Eugene Braunwald Elliott M Antman John W Beasley Robert M Califf Melvin D Cheitlin Judith S Hochman Robert H Jones Dean Kereiakes Joel Kupersmith Thomas N Levin Carl J Pepine John W Schaeffer Earl E Smith David E Steward Pierre Theroux Raymond J Gibbons J | 2000 | Journal of the American College of Cardiology2000，，3： | 4 |
| 6 | Challenges facing early detection of acute kidney injury in the critically ill显示文摘Recent advances in the detection of acute kidney injury(AKI) afford the possibility of early intervention. Proteomics and genomics have identified many markers of tubular cell injury, some of which are manifest in the urine. One trial has used novel injury biomarkers to recruit patients to an intervention prior to an elevation in plasma creatinine. This trial and other recent studies have shown that the use of biomarkers of injury will depend on the time the patient presents following insult to the kidney, the likely cause of that insult, and the pre-injury renal function of that patient. The definition of AKI is likely to change in the near future to include a measure of injury. We anticipate novel therapies becoming available following successful trials that utilize the methodology of early intervention following an elevated injury biomarker. | John W Pickering Zoltán H Endre John Pickering | 2012 | World Journal of Critical Care Medicine2012，1，3： | 4 |
| 7 | Reproducibility of the diagnosis of dysplasia in Barrett esophagus: A reaffirmation显示文摘 | Elizabeth Montgomery Mary P Bronner John R Goldblum Joel K Greenson Marian M Haber John Hart Laura W Lamps Gregory Y Lauwers Audrey J Lazenby David N Lewin Marie E Robert Alicia Y Toledano Yu Shyr Kay Washington | 2001 | Human Pathology2001，，4： | 3 |
| 8 | Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing显示文摘 | Chan K C Allen Jiang Peiyong Zheng Yama W L Liao Gary J W Sun Hao Wong John Siu Shing Shun N Chan Wing C Chan Stephen L Chan Anthony T C Lai Paul B S Chiu Rossa W K Lo Y M D | 2013 | Clinical Chemistry2013，，1： | 2 |
| 9 | Ecological Linkages Between Aboveground and Belowground Biota显示文摘 | DAVID A W RICHARD D B JOHN N K | 2004 | Science2004，304，： | 1 |
| 10 | Ni-and Zn-promotion of γ-Al2O3 for the hydrolysis of COS under mild conditions显示文摘 | JOHN W WILIAMS B P YOUNG N | 2001 | Catalysis Communications2001，，2： | 1 |
| 11 | The aerodynamic instability and disintegration of viscous liquid sheets显示文摘 | Dombrowski N Johns W R | 1963 | Chem Eng Sci1963，18，： | 1 |
| 12 | The aerodynamic instability and disintegration of viscous liquid sheets显示文摘 | Dombrowski N Johns W R | 1963 | Chem Eng Sci1963，18，： | 1 |
| 13 | Increase glutathione hiosynthesis plays a role in nickel tolerance in thlaspi nickel hyperaecumulas显示文摘 | John L F Michael W P Ken N | 2004 | The Plant Cell2004，16，： | 1 |
| 14 | The stability of vegetation boundaries and the propagation of desertification in the American Southwest : A modeling approach显示文摘 | Eva N John W Anthony J | 2007 | Ecological Modeling2007，208，： | 1 |
| 15 | 显示文摘 | Barns T J Britton John N H Coffey W J | 2000 | Canadian Economic Geographer2000，44，1： | 1 |
| 16 | The aerodynamic instability and dis- integration of viscous liquid sheets显示文摘 | Dombrowski N Johns W R | 1963 | Chemieal Engineering Sci- e nce1963，18，3： | 1 |
| 17 | Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial显示文摘 | Helen M Colhoun D John Betteridge Paul N Durrington Graham A Hitman H Andrew W Neil Shona J Livingstone Margaret J Thomason Michael I Mackness Valentine Charlton-Menys John H Fuller | 2004 | The Lancet . 2004 (9435)2004，，9435： | 1 |
| 18 | Advanced graphics behind medical virtual realiy:evolution of algorithms,hardware,and software interfaces显示文摘 | Soferman Z Blythe D John N W | | 0，，03： | 1 |
| 19 | The Kuroshio east of Taiwan:Modes of variability and relationship to interior ocean mesoscale eddies显示文摘 | ZHANG Dong Xiao LEE T N JOHNS W E | 2001 | J Phys Oceanogr2001，31，4： | 1 |
| 20 | Validation of a Chinese version of the Epworth sleepiness scale显示文摘 | Chen N H Johns M W Li H Y | 2002 | Qual Life Res2002，11，8： | 1 |
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