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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 | Achalasia: A review of clinical diagnosis, epidemiology,treatment and outcomes显示文摘Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function.Historically,annual achalasia incidence rates were believed to be low,approximately 0.5-1.2 per 100000.More recent reports suggest that annual incidence rates have risen to 1.6 per 100000 in some populations.The aetiology of achalasia is still unclear but is likely to be multi-factorial.Suggested causes include environmental or viral exposures resulting in inflammation of the oesophageal myenteric plexus,which elicits an autoimmune response.Risk of achalasia may be elevated in a sub-group of genetically susceptible people.Improvement in the diagnosis of achalasia,through the introduction of high resolution manometry with pressure topography plotting,has resulted in the development of a novel classification system for achalasia.This classification system can evaluate patient prognosis and predict responsiveness to treatment.There is currently much debate over whether pneumatic dilatation is a superior method compared to the Heller’s myotomy procedure in the treatment of achalasia.A recent com-parative study found equal efficacy,suggesting that patient preference and local expertise should guide the choice.Although achalasia is a relatively rare condition,it carries a risk of complications,including aspiration pneumonia and oesophageal cancer.The risk of both squamous cell carcinoma and adenocarcinoma of the oesophagus is believed to be significantly increased in patients with achalasia,however the absolute excess risk is small.Therefore,it is currently unknown whether a surveillance programme in achalasia patients would be effective or cost-effective. | Orla M O'Neill Brian T Johnston Helen G Coleman | 2013 | World Journal of Gastroenterology2013,19,35: | 26 |
| 3 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014,2,3: | 7 |
| 4 | 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 |
| 5 | 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 |
| 6 | Ovarian autoimmune disease: clinical concepts and anima models显示文摘卵巢不是一个 immunologically 给予优惠的机关,但是在为卵巢特定的抗原的 tolerogenic 机制的一个故障在生育力上有灾难性的后果在里面女人,和这在自体免疫的疾病的鼠科的模型被复制。孤立的卵巢的自体免疫的疾病在女人是稀罕的,由于疾病和无能到的严厉可能播送越过代授与卵巢的疾病的基因信息。尽管如此,自体免疫的卵巢炎经常与另外的自体免疫的疾病联合被观察,特别地自体免疫的肾的疾病,并且在社会和单个健康上拿使用费。在老鼠的研究揭示了保护卵巢免受自体免疫的攻击的伤害的至少二机制。这些机制为自体免疫的管理者(亚耳河) 由导出胸腺的规章的 T 房间,以及一个角色包括 autoreactive T 房间的控制,在髓的 thymic 导致限制织物的抗原的表示的一个 transcriptional 管理者上皮的房间在 T 房间的开发期间。尽管后者机制不完全地被定义,也的失败导致自体免疫调停指向和卵巢的滤泡的弄空,这很好被建立。在这评论,我们将探讨自体免疫调停的临床的特征和后果在女人的卵巢的不孕,以及由动物揭示了的疾病的可能的机制当模特儿。 | Bryce D Warren William K Kinsey Lynda K McGinnis Lane K Christenson Susmita Jasti Anne M Stevens Brian K Petroff Margaret G Petroff | 2014 | Cellular & Molecular Immunology2014,11,6: | 3 |
| 7 | 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 |
| 8 | Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial显示文摘 | Brian I Rini Bernard Escudier Piotr Tomczak Andrey Kaprin Cezary Szczylik Thomas E Hutson M Dror Michaelson Vera A Gorbunova Martin E Gore Igor G Rusakov Sylvie Negrier Yen-Chuan Ou Daniel Castellano Ho Yeong Lim Hirotsugu Uemura Jamal Tarazi David Cella | 2011 | The Lancet . 2011 (9807)2011,,9807: | 2 |
| 9 | Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial显示文摘 | Brian I Rini Bernard Escudier Piotr Tomczak Andrey Kaprin Cezary Szczylik Thomas E Hutson M Dror Michaelson Vera A Gorbunova Martin E Gore Igor G Rusakov Sylvie Negrier Yen-Chuan Ou Daniel Castellano Ho Yeong Lim Hirotsugu Uemura Jamal Tarazi David Cella | 2011 | The Lancet2011,,9807: | 2 |
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| 12 | Comparative application of indices of biotic integrity basedon periphyton, macroinvertebrates, and fish to southernRocky Mountain streams显示文摘 | MICHAEL B G BRIAN H H FRANK H M | 2005 | Ecological Indicators2005,5,: | 1 |
| 13 | DNA immunization of dairy cows with the clumping factor A of Staph- ylococcus aureus显示文摘 | ADEL N M NOUR EL-DIN LULZIM SHKRETA BRIAN G TALBOT | 2006 | Vaccine2006,24,: | 1 |
| 14 | Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma显示文摘 | Matthias L?hr Anne Hoffmeyer Jens-Christian Kr?ger Mathias Freund Johannes Hain Albrecht Holle Peter Karle Wolfram T Kn?fel Stefan Liebe Petra Müller Horst Nizze Matthias Renner Robert M Saller Thomas Wagner Karlheinz Hauenstein Walter H Günzburg Brian Sa | 2001 | The Lancet2001,,9268: | 1 |
| 15 | The influence of water level fluctuations on the growth of four emergent macrophyte species 显示文摘 | Brian M D Sean D W George G G | 2007 | Aquatic Botany2007,86,4: | 1 |
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| 18 | Reliability and Validity of the Functional Analysis Screening Tool 显示文摘 | lwata Brian A Deleon Iser G Roscoe Eileen M | 2013 | Journal of Applied Behavior Analysis2013,,46: | 1 |
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