|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease显示文摘Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P < 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA 'resistant') in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P < 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources. | Luis R Lopez Kirk E Guyer Ignacio Garcia De La Torre Kelly R Pitts Eiji Matsuura Paul RJ Ames | 2014 | World Journal of Diabetes2014，5，2： | 13 |
| 3 | Ultrasound-assessed non-culprit and culprit coronary vessels differ by age and gender显示文摘AIM: To investigate age-and gender-related differences in non-culprit versus culprit coronary vessels assessed with virtual histology intravascular ultrasound (VH-IVUS). METHODS: In 390 patients referred for coronary angiography to a single center (Luzerner Kantonsspital, Switzerland) between May 2007 and January 2011, 691 proximal vessel segments in left anterior descending, circumflex and/or right coronary arteries were imaged by VH-IVUS. Plaque burden and plaque composition(fibrous, fibro-fatty, necrotic core and dense calcium volumes) were analyzed in 3 age tertiles, according to gender and separated for vessels containing non-culprit or culprit lesions. To classify as vessel containing a culprit lesion, the patient had to present with an acute coronary syndrome, and the VH-IVUS had to be performed in a vessel segment containing the culprit lesion according to conventional coronary angiography. RESULTS: In non-culprit vessels the plaque burden increased significantly with aging (in men from 37% ± 12% in the lowest to 46% ± 10% in the highest age tertile, P < 0.001; in women from 30% ± 9% to 40% ± 11%, P < 0.001); men had higher plaque burden than women at any age (P < 0.001 for each of the 3 age tertiles). In culprit vessels of the lowest age tertile, plaque burden was significantly higher than that in non- culprit vessels (in men 48% ± 6%, P < 0.001 as compared to non-culprit vessels; in women 44% ± 18%, P = 0.004 as compared to non-culprit vessels). Plaque burden of culprit vessels did not significantly change during aging (plaque burden in men of the highest age tertile 51% ± 9%, P = 0.523 as compared to lowest age tertile; in women of the highest age tertile 49% ± 8%, P = 0.449 as compared to lowest age tertile). In men, plaque morphology of culprit vessels became increasingly rupture-prone during aging (increasing percentages of necrotic core and dense calcium), whereas plaque morphology in non-culprit vessels was less rupture-prone and remained constant during aging. In women, necrotic core in non-culprit vessels was very low at young age, but increased during aging resulting in a plaque morphology that was very similar to men. Plaque morphology in culprit vessels of young women and men was similar. CONCLUSION: This study provides evidence that age-and gender-related differences in plaque burden and plaque composition significantly depend on whether the vessel contained a non-culprit or culprit lesion. | Andreas W Schoenenberger Nadja Urbanek Stefan Toggweiler Andreas E Stuck Thérèse J Resink Paul Erne | 2013 | World Journal of Cardiology2013，5，3： | 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 | Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘 | C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer | 2003 | Ophthalmology2003，，9： | 4 |
| 6 | Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression显示文摘 | Victoria G Weis Josane F Sousa Bonnie J LaFleur Ki Taek Nam Jared A Weis Paul E Finke Nadia A Ameen James G Fox James R Goldenring | 2013 | Gut2013，，9： | 3 |
| 7 | Adenoma detection with cap-assisted colonoscopy versus regular colonoscopy: a randomised controlled trial显示文摘 | Thomas R de Wijkerslooth Esther M Stoop Patrick M Bossuyt Elisabeth M H Mathus-Vliegen Jan Dees Kristien M A J Tytgat Monique E van Leerdam Paul Fockens Ernst J Kuipers Evelien Dekker | 2012 | Gut2012，，10： | 3 |
| 8 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 9 | Current debate in the oncologic management of rectal cancer显示文摘Despite the considerable amount of research in the field,the management of locally advanced rectal cancer remains a subject to debate.To date,effective treatment centers on surgical resection with the standard approach of total mesorectal resection.Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence.While it is accepted that a multimodality treatment regimen is indicated,there remains significant debate for how best to accomplish this in regards to order,dosing,and choice of agents.Preoperative radiation is the standard of care,yet remains debated with the option for chemoradiation,short course radiation,and even ongoing studies looking at the possibility of leaving radiation out altogether.Chemotherapy was traditionally incorporated in the adjuvant setting,but recent reports suggest the possibility of improved efficacy and tolerance when given upfront.In this review,the major studies in the management of locally advanced rectal cancer will be discussed.In addition,future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy,inclusion of radiation,and nonoperative management. | Trish Millard Paul R Kunk Erika Ramsdale Osama E Rahma | 2016 | World Journal of Gastrointestinal Oncology2016，8，10： | 3 |
| 10 | Randomized controlled trial of domici-liary noninvasive positive pressure ventilation and physical train ing in severe chronic obstructive pulmonary disease显示文摘 | Garrod R Mikelsons C Paul E A | 2000 | Am J Respir Crit Med2000，162，： | 2 |
| 11 | Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘 | C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer | 2003 | Ophthalmology2003，，9： | 2 |
| 12 | Carbon-13 nuclear magnetic resonance of 5-substituted uracils 显示文摘 | Paul D E Dunlap R B Polllard A L | 1973 | Amer Chem Soc1973，95，13： | 2 |
| 13 | Leptospirosis: a zoonotic disease of global importance显示文摘 | Ajay R Bharti Jarlath E Nally Jessica N Ricaldi Michael A Matthias Monica M Diaz Michael A Lovett Paul N Levett Robert H Gilman Michael R Willig Eduardo Gotuzzo Joseph M Vinetz | 2003 | The Lancet Infectious Diseases2003，，12： | 2 |
| 14 | GATA3 controls Foxp3^sup +^ regulatory T cell fate during inflammation in mice显示文摘 | Wohlfert Elizabeth A Grainger John R Bouladoux Nicolas Konkel Joanne E Oldenhove Guillaume Ribeiro Carolina Hager Hall Jason A Yagi Ryoji Naik Shruti Bhairavabhotla Ravikiran Paul William E Bosselut Remy Wei Gang Zhao Keji Oukka Mohamed Zhu | 2011 | Journal of Clinical Investigation2011，，11： | 2 |
| 15 | The design and fabrication of a 40 cm diameter,SiC coated,normal incidence telescope and spectrometer显示文摘 | Stephan R McCandliss Mel E Martinez Paul D Feldman | 1994 | SPIE1994，2011，： | 1 |
| 16 | Stabilization mechanisms of soil organic matter: Implications for C-saturation of soils显示文摘 | Six J Conant R T Paul E A | 2002 | Plant Soil2002，241，： | 1 |
| 17 | Nitrogen-linked diphosphine ligands with ethers attached to nitrogen for chromium-catalyzed ethylene ti- and tetramerizations显示文摘 | Paul R E Cassandra M Pringle P G | 2006 | Organometallics2006，25，22： | 1 |
| 18 | Cell cycle control, checkpoint mechanisms, and genotoxie strees 显示文摘 | Shackelford R E Kaufmann W K Paules R S | 1999 | Environ Health Perspect1999，107，1： | 1 |
| 19 | Kinematics Control Equations for Simple Manipulator显示文摘 | Paul R P Shirnanno B E Mayer G | 1981 | IEEEE Trans SMC1981，11，6： | 1 |
| 20 | Stabilization mechanisms of soil organic matter:Implications for C-saturation of soils显示文摘 | Six J Conant R T Paul E A | 2002 | Plant and Soil2002，241，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员