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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 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018，24，12： | 5 |
| 3 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 4 | The spectrum of neuromyelitis optica显示文摘 | Dean M Wingerchuk Vanda A Lennon Claudia F Lucchinetti Sean J Pittock Brian G Weinshenker | 2007 | Lancet Neurology2007，，9： | 3 |
| 5 | Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population显示文摘AIM:To evaluate the accuracy of two non-invasivetests in a population of Alaska Native persons. Highrates of Helico bacter pylori(H. pylori) infection,H. pylori treatment failure,and gastric cancer in this population necessitate documentation of infection status atmultiple time points over a patient's life.METHODS:In 280 patients undergoing endoscopy,H. pylori was diagnosed by culture,histology,rapidurease test,13C urea breath test(UBT) ,and immuno-globulin G antibodies to H. pylori in serum. The performances of 13C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori testby culture or,in case of a negative culture result,bypositive histology and a positive rapid urease test.RESULTS:The sensitivity and specificity of the 13C-UBT were 93% and 88%,respectively,relative to thegold standard. The antibody test had an equivalents ensitivity of 93% with a reduced specificity of 68%.The false positive results for the antibody test were as-sociated with previous treatment for an H. pylori infection [relative risk(RR) = 2.8]. High levels of antibodiesto H. pylori were associated with chronic gastritis and male gender,while high scores in the 13C-UBT testwere associated with older age and with the H. pyloribacteria load on histological examination(RR = 4.4) .CONCLUSION:The 13C-UBT out performed the anti-body test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment out come or when monitoring for reinfection. | Dana L Bruden Michael G Bruce Karen M Miernyk Julie Morris Debby Hurlburt Thomas W Hennessy Helen Peters Frank Sacco Alan J Parkinson Brian J McMahon | 2011 | World Journal of Gastroenterology2011，17，42： | 3 |
| 6 | Long-term outcome in patients with apical hypertrophic cardiomyopathy显示文摘 | Maria J Eriksson Brian Sonnenberg Anna Woo Paul Rakowski Thomas G Parker E.Douglas Wigle Harry Rakowski | 2002 | Journal of the American College of Cardiology2002，，4： | 2 |
| 7 | Setup, deposition, and sedimentary characteristics of two storm overwash deposits, Abrahams Bosom Beach, Southeastern Australia显示文摘 | Adam D S Brian G J | 2008 | Journal of Coastal Research2008，，： | 1 |
| 8 | On Cloaking for Elasticity and Physical Equations with A Transformation Invariant Form 显示文摘 | Milton G W Briane M Willis J R | 2006 | New J Phys2006，8，： | 1 |
| 9 | Ileal ureter substitution: a contemporary series显示文摘 | Brian R Matlaga Ojas D Shah Lois J Hart Dean G Assimos | 2003 | Urology2003，，6： | 1 |
| 10 | Modifiable Factors Associated With Improved Cardiac Arrest Survival in a Multicenter Basic Life Support/Defibrillation System: OPALS Study Phase I Results显示文摘 | Ian G Stiell George A Wells Valerie J DeMaio Daniel W Spaite Brian J Field Douglas P Munkley Marion B Lyver Lorraine G Luinstra Roxanne Ward | 1999 | Annals of Emergency Medicine1999，，： | 1 |
| 11 | Tacrolimus for the treatment of fistulas in patients with crohn’s disease: a randomized, placebo-controlled trial显示文摘 | William J Sandborn Daniel H Present Kim L Isaacs Douglas C Wolf Eugene Greenberg Stephen B Hanauer Brian G Feagan Lloyd Mayer Therese Johnson Joseph Galanko Christopher Martin Robert S Sandler | 2003 | Gastroenterology2003，，2： | 1 |
| 12 | Comparison of the effects of di-(2-ethylhexyl)adipate on hepatic peroxisome proliferation and cell replication in the rat and mouse 1 Presented in part at the Annual Meeting of the Society of Toxicology, Dallas, Texas, March 13–17, 1994. 1显示文摘 | Brian G Lake Roger J Price Morag E Cunninghame David G Walters | 1997 | Toxicology1997，，3： | 1 |
| 13 | A comparison of detection per formance for several track-before detect algorithms显示文摘 | Samuel J D Mark G R Brian C | 2008 | Journal on Advances in Signal Processing2008，，： | 1 |
| 14 | Substrate-assisted catalysis in sialic acid aldolase 显示文摘 | Brian J S Michael C L Joao A R G B | 1999 | J Org Chem1999，64，： | 1 |
| 15 | Determinants of mortality and type of repair in neonates with pulmonary atresia and intact ventricular septum显示文摘 | David A Ashburn Eugene H Blackstone Winfield J Wells Richard A Jonas Frank A Pigula Peter B Manning Gary K Lofland William G Williams Brian W McCrindle | 2004 | The Journal of Thoracic and Cardiovascular Surgery2004，，4： | 1 |
| 16 | Alteration of brain default network in subacute phase of injury in concussed individuals: Resting-state fMRI study显示文摘 | Brian J Kai Z Michael G | 2012 | Neuroimage2012，59，1： | 1 |
| 17 | On estimating the exponent of power-law frequency distribution显示文摘 | Ethan P W Brian J E Jessica L G | 2008 | Ecology2008，89，4： | 1 |
| 18 | A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis显示文摘 | Vanda A Lennon Dean M Wingerchuk Thomas J Kryzer Sean J Pittock Claudia F Lucchinetti Kazuo Fujihara Ichiro Nakashima Brian G Weinshenker | 2004 | 2004 (9451)2004，，9451： | 1 |
| 19 | Transoral Incisionless Fundoplication: 2-year Results from the Prospective Multicenter U.S. Study显示文摘 | Bell Reginald C W Barnes William E Carter Bart J Sewell Robert W Mavrelis Peter G Ihde Glenn M Hoddinott Kevin M Fox Mark A Freeman Katherine D Gunsberger Tanja Hausmann Mark G Dargis David Gill Brian DaCosta Wilson Erik Trad Karim S | 2014 | The American Surgeon2014，，11： | 1 |
| 20 | A metal-free organic-inorganic aqueous flow battery显示文摘 | Huskinson Brian Marshak Michael P Suh Changwon Er Süleyman Gerhardt Michael R Galvin Cooper J Chen Xudong Aspuru-Guzik Alán Gordon Roy G Aziz Michael J | 2014 | Nature2014，505，7482： | 1 |
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