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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | 颅内出血患者抗栓药逆转指南美国神经重症监护学会和美国重症医学会对医疗卫生专业人员的声明显示文摘背景抗栓药的使用,包括抗凝药、抗血小板药和溶栓药,在过去10年中日益增多并且预计将继续上升。虽然抗栓药相关性颅内出血可能是灾难性的,但快速逆转凝血功能障碍可能有助于限制血肿增大和改善转归。方法美国神经重症监护学会联合美国重症医学会组建了一个国际性多机构委员会,涉及的专业领域包括神经重症监护、神经内科、神经外科、卒中、血液学、血液病理学、急诊医学、药学、护理和指南制定,目的是进行文献评价并制定一份循证实践指南。该委员会进行了正式的文献检索,并对符合标准的研究进行了评价。结果利用GRADE方法学,委员会提出了在颅内出血情况下逆转维生素K拮抗药、直接Xa因子拮抗药、直接凝血酶抑制药、普通肝素、低分子肝素、类肝素、戊多糖、溶栓药和抗血小板药的推荐意见。结论该指南提供了及时和循证的抗栓药逆转策略以协助临床医生治疗抗栓药相关性颅内出血。 | Jennifer A. Frontera John J. Lewin Ⅲ Alejandro A. Rabinstein Imo P. Aisiku Anne W. Alexandrov Aaron M. Cook Gregory J. del Zoppo Monisha A. Kumar Ellinor I. B. Peerschke Michael F. Stiefel Jeanne S Teitelbaum Katja E. Wartenberg Cindy L. Zerfoss 杨一萍 谢丽丽 宁小金 季宇腾 柯开富 | 2016 | 国际脑血管病杂志2016，24，11： | 24 |
| 3 | 皮质下小血管病诊断的共识声明显示文摘血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病(Binswanger's disease, BD)的进行性白质损害患者构成了从单纯血管性疾病到合并神经变性病变的疾病谱。BD患者是一个相对同质性的亚组,存在缺氧缺血、腔隙性梗死和炎症,它们协同作用破坏血脑屏障和髓鞘。通过临床、脑脊液、神经心理学和影像学检查获得的多模式疾病标记物能促进该亚组患者的鉴别。本共识声明确定了一系列基于基础病理学改变的潜在生物学标记物,这将有助于诊断以及将来协作性治疗试验的患者选择。 | Gary A Rosenberg Anders Wallin Joanna M Wardlaw Hugh S Markus Joan Montaner Leslie Wolfson Costantino Iadecola Berislav V Zlokovic Anne Joutel Martin Dichgans Marco Duering Reinhold Schmidt Amos D Korczyn Lea T Grinberg Helena C Chui Vladimir Hachinski 王训师 张劼 陈涵丰 俞娅美 徐子奇 罗本燕 | 2016 | 国际脑血管病杂志2016，24，6： | 18 |
| 4 | Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice显示文摘AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal motility.Peristaltic activity of distal colonic segments was studied in vitro using a modified Trendelenburg set-up.Cytokine profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction. RESULTS:Intracolonic injection of TNBS caused severe colitis.Treatment with S.mansoni proteins significantly ameliorated colonic inflammation after 5 d.TNBS did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of colitis.Treatment with S.mansoni proteins ameliorated these in vivo and in vitro motility disturbances.In addition,TNBS injection caused a downregulation of effector T cell cytokines after 5 d,whereas a S.mansoni protein effect was no longer observed at this time point. CONCLUSION:Treatment with S.mansoni proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experimental colitis. | Nathalie E Ruyssers Benedicte Y De Winter Joris G De Man Natacha D Ruyssers Ann J Van Gils Alex Loukas Mark S Pearson Joel V Weinstock Paul A Pelckmans Tom G Moreels | 2010 | World Journal of Gastroenterology2010，16，6： | 11 |
| 5 | Mucosal healing progression after acute colitis in mice显示文摘BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin(Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSION This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators. | Sandra Vidal-Lletjós Mireille Andriamihaja Anne Blais Marta Grauso Patricia Lepage Anne-Marie Davila Claire Gaudichon Marion Leclerc Francois Blachier Annaig Lan | 2019 | World Journal of Gastroenterology2019，25，27： | 5 |
| 6 | Pancreatitis in patients with pancreas divisum:Imaging features at MRI and MRCP显示文摘AIM:To determine the magnetic resonance cholangiopancreatography(MRCP)and magnetic resonance imaging(MRI)features of pancreatitis with pancreas divisum(PD)and the differences vs pancreatitis without divisum.METHODS:Institutional review board approval was obtained and the informed consent requirement was waived for this HIPAA-compliant study.During one year period,1439 consecutive patients underwent successful MRCP without injection of secretin and abdominal MRI studies for a variety of clinical indications using a 1.5 T magnetic resonance scanner.Two experienced radiologists retrospectively reviewed all the studies in consensus.Disputes were resolved via consultation with a third experienced radiologist.The assessment included presence and the imaging findings of PD,pancreatitis,and distribution of abnormalities.The pancreatitis with divisum constituted the study group while the pancreatitis without divisum served as the control group.MRCP and MRI findings were correlated with final diagnosis.Fisher exact tests and Pearson × 2 tests were performed.RESULTS:Pancreatitis was demonstrated at MRCP and MRI in 173 cases(38 cases with and 135 cases without divisum)among the 1439 consecutive cases.The recurrent acute pancreatitis accounted for 55.26%(21 of 38)in pancreatitis patients associated with PD,which was higher than 6.67%(9 of 135)in the control group,whereas the chronic pancreatitis was a dominant type in the control group(85.19%,115 of 135)when compared to the study group(42.11%,16 of 38)(χ 2 = 40.494,P < 0.0001).In cases of pancreatitis with PD,the dorsal pancreatitis accounted for a much higher percentage than that in pancreatitis without PD(17 of 38,44.74% vs 30 of 135,22.22%)(χ 2 = 7.257,P < 0.05).CONCLUSION:MRCP and MRI can depict the features of pancreatitis associated with divisum.Recurrent acute pancreatitis and isolated dorsal involvement are more common in patients with divisum. | Deng-Bin Wang Jinxing Yu Ann S Fulcher Mary A Turner | 2013 | World Journal of Gastroenterology2013，19，30： | 5 |
| 7 | Update on Cardiovascular Implantable Electronic Device Infections and Their Management: A Scientific Statement From the American Heart Association显示文摘 | Larry M. Baddour Andrew E. Epstein Christopher C. Erickson Bradley P. Knight Matthew E. Levison Peter B. Lockhart Frederick A. Masoudi Eric J. Okum Walter R. Wilson Lee B. Beerman Ann F. Bolger N A. Mark Estes Michael Gewitz Jane W. Newburger Eleanor B. S | 2010 | Circulation2010，，3： | 4 |
| 8 | Brain changes in diabetes mellitus patients withgastrointestinal symptoms显示文摘Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system(CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal(GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testingmainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes,especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation. | Anne M Drewes Eirik Søfteland Georg Dimcevski Adam D Farmer Christina Brock Jens B Frøkjær Klaus Krogh Asbjørn M Drewes | 2016 | World Journal of Diabetes2016，7，2： | 4 |
| 9 | Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study显示文摘 | Timothy Iveson Ross C Donehower Irina Davidenko Sergey Tjulandin Andrzej Deptala Mark Harrison Somanath Nirni Kuntegowdanahalli Lakshmaiah Anne Thomas Yizhou Jiang Min Zhu Rui Tang Abraham Anderson Sarita Dubey Kelly S Oliner Elwyn Loh | 2014 | Lancet Oncology2014，，9： | 3 |
| 10 | Cost-utility of molecular adsorbent recirculating system treatment in acute liver failure显示文摘AIM:To determine the short-term cost-utility of mo-lecular adsorbent recirculating system(MARS) treatment in acute liver failure(ALF).METHODS:A controlled retrospective study was conducted with 90 ALF patients treated with MARS from 2001 to 2005.Comparisons were made with a historical control group of 17 ALF patients treated from 2000 to 2001 in the same intensive care unit(ICU) specializing in liver diseases.The 3-year outcomes and number of liver transplantations were recorded.All direct liver disease-related medical expenses from 6 mo before to 3 years after ICU treatment were determined for 31 MARS patients and 16 control patients.The health-related quality of life(HRQoL) before MARS treatment was estimated by a panel of ICU doctors and after MARS using a mailed 15D(15-dimensional generic healthrelated quality of life instrument) questionnaire.The HRQoL,cost,and survival data were combined and the incremental cost/quality-adjusted life years(QALYs) was calculated.RESULTS:In surviving ALF patients,the health-related quality of life after treatmeant was generally high and comparable to the age-and gender-matched general Finnish population.Compared to the controls,the average cost per QALY was considerably lower in the MARS group(64 732€ vs 133 858€) within a timeframe of 3.5 years.The incremental cost of standard medical treatment alone compared to MARS was 10 928€,and the incremental number of QALYs gained by MARS was 0.66.CONCLUSION:MARS treatment combined with standard medical treatment for ALF in an ICU setting is more cost-effective than standard medical treatment alone. | Taru Kantola Suvi Mklin Anna-Maria Koivusalo Pirjo Rsnen Anne Rissanen Risto Roine Harri Sintonen Krister Hckerstedt Helena Isoniemi | 2010 | World Journal of Gastroenterology2010，16，18： | 3 |
| 11 | Wilson’s disease显示文摘 | Aftab Ala Ann P Walker Keyoumars Ashkan James S Dooley Michael L Schilsky | 2007 | The Lancet . 2007 (9559)2007，，9559： | 3 |
| 12 | Noninvasive In Vivo Liver Fibrosis Evaluation Using Supersonic Shear Imaging: A Clinical Study on 113 Hepatitis C Virus Patients显示文摘 | éric Bavu Jean-Luc Gennisson Mathieu Couade Jeremy Bercoff Vincent Mallet Mathias Fink Anne Badel Ana?s Vallet-Pichard Bertrand Nalpas Micka?l Tanter Stanislas Pol | 2011 | Ultrasound in Medicine & Biology2011，，9： | 3 |
| 13 | Regulatory macrophages induced by infliximab are involved in healing in vivo and in vitro显示文摘 | Anne Christine W.Vos Manon E.Wildenberg IngridArijs MarjolijnDuijvestein Auke P.Verhaar Gertde Hertogh SéverineVermeire PaulRutgeerts Gijs R.van den Brink Daniel W.Hommes | 2012 | Inflamm Bowel Dis2012，，3： | 2 |
| 14 | Phytoplankton functional groups as indicators of human impacts along the River Loire (France)显示文摘 | András Abonyi Maria Leit?o Anne Marie Lan?on Judit Padisák | 2012 | Hydrobiologia2012，，1： | 2 |
| 15 | Challenges for land system science显示文摘 | Mark D.A. Rounsevell Bas Pedroli Karl-Heinz Erb Marc Gramberger Anne Gravsholt Busck Helmut Haberl S?ren Kristensen Tobias Kuemmerle Sandra Lavorel Marcus Lindner Hermann Lotze-Campen Marc J. Metzger David Murray-Rust Alexander Popp Marta Pérez-Soba Anett | 2012 | Land Use Policy2012，，4： | 2 |
| 16 | Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor显示文摘 | Anne Brunet Azad Bonni Michael J Zigmond Michael Z Lin Peter Juo Linda S Hu Michael J Anderson Karen C Arden John Blenis Michael E Greenberg | 1999 | Cell1999，，6： | 2 |
| 17 | B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy显示文摘 | Vijay K Kuchroo Mercy Prabhu Das Julia A Brown Ann M Ranger Scott S Zamvil Raymond A Sobel Howard L Weiner Nasrin Nabavi Laurie H Glimcher | 1995 | Cell1995，，5： | 2 |
| 18 | Statistically designed two step response surface optimization of enzymatic prepress treatment to increase juice yield and lower turbidity of elderberry juice显示文摘 | Anne Katrine Landbo Karl Kaack Anne S Meyer | 2007 | Innovative Food Science and Emerging Technologies2007，8，1： | 1 |
| 19 | Strategic Momentum: The Effects of Repetitive, Positional, and Contex- tual Momentum on Merger Activity显示文摘 | AMBURGEY TERRY L ANNE S MINER | 1992 | Strategic Management Journal1992，13，5： | 1 |
| 20 | Magnetic manipulation of copper-tin nanowires capped with nickel ends显示文摘 | ANNE K B JEREMY S T ARTHUR B E WENDY C C | 2004 | Nano Letters2004，4，3： | 1 |
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