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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 | 内侧固定平台单髁置换术后的冠状面下肢力线是翻修的影响因素显示文摘膝关节单髁置换术(unicompartmental knee arthroplasty,UKA)后患者冠状面的下肢力线被认为是影响手术长期疗效的一个重要因素,但关于最佳的UKA术后下肢力线还没有形成明确共识。一些研究主张术后下肢力线应保持在中立位,而另一些研究认为即使术后下肢力线存在10°的内翻也可获得良好的临床效果。 | Sean E Slaven John P Cody Robert A Sershon Henry Ho Robert H Hopper Jr Kevin B Fricka 李亚坤(整理) 张民(整理) | 2020 | 实用骨科杂志2020，26，12： | 15 |
| 3 | Vanishing bile duct syndrome in human immunodeficiency virus infected adults:A report of two cases显示文摘Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes. | Ana Paula Oppenheimer Christopher Koh Mary McLaughlin John C Williamson Thomas D Norton Jennifer Laudadio Theo Heller David E Kleiner Kevin P High Caryn G Morse | 2013 | World Journal of Gastroenterology2013，19，1： | 8 |
| 4 | Meeting report:a hard look at the state of enamel research显示文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines(ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research(NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3 D cell culture/organoids. Scientists from a number of disciplines,representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field. | ophir d klein olivier duverger wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer | 2017 | International Journal of Oral Science2017，9，4： | 3 |
| 5 | 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 |
| 6 | Serum zonulin levels in patients with liver cirrhosis:Prognostic implications显示文摘BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis.Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study.Serum zonulin levels,clinical,radiological and biochemical data were collected at baseline.Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTS We enrolled 116 cirrhotics[mean Child-Turcotte-Pugh(CTP)score:6.2±1.6;model for end-stage liver disease score:11±3.9].The causes of cirrhosis were viral hepatitis(39%),alcohol(30%),non-alcoholic fatty liver disease(17%),and other(14%).At baseline,53% had decompensated cirrhosis,48% had ascites,and 32% had history of hepatic encephalopathy.Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2±2.4 ng/dL vs 3.5±0.9 ng/dL,P=0.038),with than without ascites(P=0.006),and with than without history of encephalopathy(P=0.011).Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P=0.039),with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation.Higher CTP score(P=0.021)and portal vein diameter(P=0.022)were independent predictors of mortality.CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation. | Theodoros A Voulgaris Dimitrios Karagiannakis E Hadziyannis Spilios Manolakopoulos Georgios P Karamanolis George Papatheodoridis John Vlachogiannakos | 2021 | World Journal of Hepatology2021，13，10： | 2 |
| 7 | Effect of donor–recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis显示文摘 | Mary Eapen John P Klein Guillermo F Sanz Stephen Spellman Annalisa Ruggeri Claudio Anasetti Maria Brown Richard E Champlin Joan Garcia-Lopez Gareth Hattersely Gesine Koegler Mary J Laughlin Gerard Michel Samir K Nabhan Franklin O Smith Mary M Horowitz Eli | 2011 | Lancet Oncology2011，，13： | 2 |
| 8 | Analysis of joint action of insecticides against housefly显示文摘 | Sun Y P John E R | 1960 | Journal of Economic Entomology1960，53，5： | 1 |
| 9 | Adaptation of HIV-1to human leukocyte antigen class I显示文摘 | Kawashima Y Pfafferott K Frater J Matthews P Payne R Addo M Gatanaga H Fujiwara M Hachiya A Koizumi H Kuse N Oka S Duda A Prendergast A Crawford H Leslie A Brumme Z Brumme C Allen T Brander C Kaslow R Tang J Hunter E Allen S Mulenga J Branch S Roach T John M Mallal S Ogwu A Shapiro R Prado J G Fidler S Weber J Pybus O G Klenerman P Ndung'u T Phillips R Heckerman D Harrigan P R Walker B D Takiguchi M Goulder P | 2009 | Nature2009，458，7238： | 1 |
| 10 | Uncertainty quantification using evidence theory in multidisciplinary design optimization 显示文摘 | Harish A John E R Evan L P | 2004 | Reliability Engineering and System Safety2004，85，13： | 1 |
| 11 | IAEA activities on passive safety systems and overviewof international development 显示文摘 | JOHN P E KUPITZ J CLEVELAND J | 2000 | Nucl Eng Des2000，201，： | 1 |
| 12 | Hemodilution reduces early reperfusion injury in an ex vivo rabbit lung preservation model 显示文摘 | John D P Oka T Mayer E Edward A | 1994 | Ann Thorac Surg1994，57，： | 1 |
| 13 | Transient expression and insertional mutagenesis of Puccinia triticina using biolistics显示文摘 | CRAIG A W LES J S GUUS B CLARKE G RICHARD C S MERLE E JOHN P F | 2005 | Functional & Integrative Genomics2005，12，： | 1 |
| 14 | Resistance of Rosa microtubule polymerization to colchicines results from a low-affinity interation of colchicine and tubulin显示文摘 | MORE JOHN L C BUREARU T E TOCCHI L P | 1987 | Planta1987，28，1： | 1 |
| 15 | Emulsifying Properties of Protein: Evaluation of a Turbidimetric Technique显示文摘 | | 1978 | J Agric Food Chem1978，26，3： | 1 |
| 16 | Natriuretic peptide receptor 1 expression influences blood pressures of mice in a dose-dependent manner显示文摘 | OLIVER P M JOHN S W PURDYK E | 1998 | PNAS1998，95，5： | 1 |
| 17 | Guidelines for the implementation of the CWELD and ACM2 spot weld models in structural dynamics 显示文摘 | Matteo P Michael I F John E M | 2004 | Finite Ele ments in Analysis and Design2004，41，2： | 1 |
| 18 | Generalizedgradient approximation made simple显示文摘 | JOHN P P KIERON B MATTHIAS E | 1996 | Phys Rev Lett1996，77，18： | 1 |
| 19 | Phytoestrogen intake and endometrial cancer risk 显示文摘 | HORNROSS P L JOHN E M CANCHOLA A J | 2003 | Natl Cancer2003，95，： | 1 |
| 20 | Measurement of effective saturation concentration for gas transfer显示文摘 | Gulliver J S Hibbs D E Mcdonald John P | 1997 | Journal of Hydraulic Engineering1997，123，2： | 1 |
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