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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
2Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers显示文摘Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide,due to late detection and high recurrence rates.Today,these cancers have a heavy socioeconomic burden,for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets.Osteopontin (OPN) is overexpressed in most patients with gastric and liver cancers.Over the past decade,emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers,indicating its potential as an independent prognostic indicator in such patients.Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo .Furthermore,OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment,in which many details need further exploration.OPN signaling results in various functions,including prevention of apoptosis,modulation of angiogenesis,malfunction of tumor-associated macrophages,degradation of extracellular matrix,activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways,which lead to tumor formation and progression,particularly in gastric and liver cancers.This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression,its potential as a therapeutic target,and putative mechanisms in gastric and liver cancers.Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.Dong-Xing Cao Zhi-Jie Li Xiao-Ou Jiang Yick Liang Lum Ester Khin Nikki P Lee Guo-Hao Wu John M Luk 2012World Journal of Gastroenterology2012,18,30:29
3China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design显示文摘Rachel P Dreyer Xi Li Xue Du Nicholas S Downing Li Li Hai-Bo Zhang Fang Feng Wen-Chi Guan Xiao Xu Shu-Xia Li Zhen-Qiu Lin Frederick A Masoudi John A Spertus Harlan M Krumholz Li-Xin Jiang 2016Chinese Medical Journal2016,,1:13
4Dickkopfs and Wnt/β-catenin signalling in liver cancer显示文摘Liver cancer is the fifth and seventh most common cause of cancer in men and women,respectively.Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma(HCC).Based on the current understanding,this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC.Furthermore,we will discuss the role of dickkopfs(DKKs)in regulating Wnt/β-catenin signalling,which is poorly understood and understudied.DKKs are a family of secreted proteins that comprise at least four members,namely DKK1-DKK4,which act as inhibitors of Wnt/β-catenin signalling.Nevertheless,not all members antagonize Wnt/β-catenin signalling.Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis.Because of the important oncogenic roles,there are an increasing number of therapeutic molecules targetingβ-catenin and the Wnt/β-catenin pathway for potential therapy of HCC.Sarwat Fatima Nikki P Lee John M Luk 2011World Journal of Clinical Oncology2011,2,8:11
5Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus显示文摘Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.Niall A Smyth Christopher D Murawski Amgad M Haleem Charles P Hannon Ian Savage-Elliott John G Kennedy 2012World Journal of Orthopedics2012,3,7:8
6National trends in resection of the distal pancreas显示文摘AIM:To investigate national trends in distal pancreatectomy(DP) through query of three national patient care databases.METHODS:From the Nationwide Inpatient Sample(NIS,2003-2009),the National Surgical Quality Improvement Project(NSQIP,2005-2010),and the Surveillance Epidemiology and End Results(SEER,2003-2009) databases using appropriate diagnostic and procedural codes we identified all patients with a diagnosis of a benign or malignant lesion of the body and/or tail of the pancreas that had undergone a partial or distal pancreatectomy.Utilization of laparoscopy was defined in NIS by the International Classification of Diseases,Ninth Revision correspondent procedure code;and in NSQIP by the exploratory laparoscopy or unlisted procedure current procedural terminology codes.In SEER,patients were identified by the International Classification of Diseases for Oncology,Third Edition diagnosis codes and the SEER Program Code Manual,third edition procedure codes.We analyzed the databases with respect to trends of inpatient outcome metrics,oncologic outcomes,and hospital volumes in patients with lesions of the neck and body of the pancreas that underwent operative resection.RESULTS:NIS,NSQIP and SEER identified 4242,2681 and 11 082 DP resections,respectively.Overall,laparoscopy was utilized in 15%(NIS) and 27%(NSQIP).No significant increase was seen over the course of the study.Resection was performed for malignancy in 59%(NIS) and 66%(NSQIP).Neither patient Body mass index nor comorbidities were associated with operative approach(P = 0.95 and P = 0.96,respectively).Mortality(3% vs 2%,P = 0.05) and reoperation(4% vs 4%,P = 1.0) was not different between laparoscopy and open groups.Overall complications(10% vs 15%,P < 0.001),hospital costs [44 741 dollars,interquartile range(IQR) 28 347-74 114 dollars vs 49 792 dollars,IQR 13 299-73 463,P = 0.02] and hospital length of stay(7 d,IQR 4-11 d vs 7 d,IQR 6-10,P < 0.001) were less when laparoscopy was utilized.One and two year survival after resection for malignancy were unchanged over the course of the study(ductal adenocarinoma 1-year 63.6% and 2-year 35.1%,P = 0.53;intraductal papillary mucinous neoplasm and nueroendocrine 1-year 90% and 2-year 84%,P = 0.25).The majority of resections were performed in teaching hospitals(77% NIS and 85% NSQIP),but minimally invasive surgery(MIS) was not more likely to be used in teaching hospitals(15% vs 14%,P = 0.26).Hospitals in the top decile for volume were more likely to be teaching hospitals than lower volume deciles(88% vs 43%,P < 0.001),but were no more likely to utilize MIS at resection.Complication rate in teaching and the top decile hospitals was not significantly decreased when compared to non-teaching(15% vs 14%,P = 0.72) and lower volume hospitals(14% vs 15%,P = 0.99).No difference was seen in the median number of lymph nodes and lymph node ratio in N1 disease when compared by year(P = 0.17 and P = 0.96,respectively).CONCLUSION:There appears to be an overall underutilization of laparoscopy for DP.Centralization does not appear to be occurring.Survival and lymph node harvest have not changed.Armando Rosales-Velderrain Steven P Bowers Ross F Goldberg Tatyan M Clarke Mauricia A Buchanan John A Stauffer Horacio J Asbun 2012World Journal of Gastroenterology2012,18,32:8
7Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model显示文摘AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect model.METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then assessed.RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.Lorraine A Boakye Keir A Ross John M Pinski Niall A Smyth Amgad M Haleem Charles P Hannon Lisa A Fortier John G Kennedy 2015World Journal of Orthopedics2015,6,11:7
8It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis显示文摘Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis.Jason P Appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg Philip M Bath for the ENOS investigators 2019Stroke & Vascular Neurology2019,4,1:6
9针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) 2020英国医学杂志中文版2020,23,9:5
10Hepatic tight junctions:From viral entry to cancer metastasis显示文摘The tight junction (TJ) is a critical cellular component for maintenance of tissue integrity, cellular interactions and cell-cell communications, and physiologically functions as the 'great wall' against external agents and the surrounding hostile environment. During the host-pathogen evolution, viruses somehow found the key to unlock the gate for their entry into cells and to exploit and exhaust the host cells. In the liver, an array of TJ molecules is localized along the bile canaliculi forming the blood-biliary barrier, where they play pivotal roles in paracellular permeability, bile secretion, and cell polarity. In pathology, certain hepatic TJ molecules mediate virus entry causing hepatitis infection; deregulation and functional abnormality of the TJ have also been implicated in triggering liver cancer development and metastasis. All these findings shed new insights on the understanding of hepatic TJs in the development of liver disease and provide new clues for potential intervention.Nikki P Lee John M Luk 2010World Journal of Gastroenterology2010,16,3:4
11Cost benefit analysis of the use of tranexamic acid in primary lower limb arthroplasty: A retrospective cohort study显示文摘AIM: To examine the cost benefit conferred by the perioperative administration of intravenous tranexamic acid(TXA) in lower limb arthroplasty.METHODS: This study evaluates the use of TXA in 200 consecutive lower limb arthroplasties performed in a single surgeon series. The initial 100 patients(control group) underwent surgery without perioperative administration of TXA while the subsequent 100 patients(TXA group) all received 1 g TXA at the time of induction of anaesthesia. Pre- and post-operative haemoglobin, platelet count, haematocrit, the use of blood product post-operatively, length of stay were examined. A financial analysis of both groups was then undertaken. RESULTS: The mean age of patients in both groups was 63 ± 13 years. There were no significant differences between groups in terms of gender(P = 0.47), proportion of total hip replacement to total knee replacement(P = 0.25) or pre-operative haemoglobin(P = 0.43). In the control group, the transfusion rate was 22%. In the TXA group, the transfusion rate dropped to 2%(P < 0.001). The mean post-operative haemoglobin was 10.82 ± 1.55g/dL in the control group vs 11.33 ± 1.27 g/dL in the TXA group(P = 0.01). The total cost of transfused blood products was €11055 and €603 respectively. The mean length of stay in the control group was 6.53 ± 5.93 d vs 5.47 ± 4.26 d in the TXA group(P = 0.15) leading to an estimated financial saving of €114586. There was one pulmonary embolus in the control group and one deep venous thrombosis in the TXA group.CONCLUSION: Intravenous TXA reduces blood loss in lower limb arthroplasty. This leads to lower transfusion rates, shorter length of stay in hospital and significant financial savings.Niall P McGoldrick Eabhann M O'Connor Nikos Davarinos Rose Galvin John F Quinlan 2015World Journal of Orthopedics2015,6,11:3
12Reproducibility 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 2001Human Pathology2001,,4:3
13Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus显示文摘AIM: To compare the gene expression profile in a pair of HBV-infected twins.METHODS: The gene expression profile was compared in a pair of HBV-infected twins.RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV,whereas the other became a chronic HBV carrier. Eightyeight and forty-six genes were found to be up- or downregulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RTPCR. However, upon HBV core antigen stimulation,TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins.CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV.Marie C Lin Nikki P Lee Ning Zheng Pai-Hao Yang Oscar G Wong Hsiang-Fu Kung Chee-Kin Hui John M Luk George Ka-Kit Lau 2005World Journal of Gastroenterology2005,11,48:3
14The Use of Simvastatin for the Prevention of Gallstones in the Lithogenic Prairie Dog Model显示文摘Kurt G Davis MD Thomas M Wertin MD John P Schriver MD FACS 2003Obesity Surgery2003,,6:2
15Narrow band imaging to differentiate neoplastic and non-neoplastic colorectal polyps in real time: a meta-analysis of diagnostic operating characteristics显示文摘Sarah K McGill Evangelos Evangelou John P A Ioannidis Roy M Soetikno Tonya Kaltenbach 2013Gut2013,,12:2
16Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit?显示文摘David D Waters John R Guyton David M Herrington Mary P McGowan Nanette K Wenger Charles Shear 2004The American Journal of Cardiology2004,,2:2
17Effect 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 2011Lancet Oncology2011,,13:2
18Effective primary isolation of wild-type canine distemper virus in MDCK,MV1 Lu and Vero cells without nucleotide sequence changes within the entire haemagglutinin protein gene and in subgenomic sections of the fusion and phospho protein genes显示文摘John A L Thomas P M Michael J K 2004Virology2004,118,:1
19Copper Treatment of Containers Influences Root Development of Longleaf Pine Seedlings Proceedings of the Longleaf Pine Container显示文摘James P John M M 2001Production Workshop2001,6,:1
20Assessment of erosion haz- ard with the USLE and GIS A ease study of the Upper Ewaso Nglro North basin of Kenya显示文摘Bancy M Mati Royston P C Morgan Francis N Gichuki John N Quinton Tim R Brewer Hans P l iniger 2000lnternation Journal of Applied Earth Ob- servation and Geoinformation2000,2,2:1
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