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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 | High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients显示文摘AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate. | Tan To Cheung Sheung Tat Fan See Ching Chan Kenneth SH Chok Ferdinand SK Chu Caroline R Jenkins Regina CL Lo James YY Fung Albert CY Chan William W Sharr Simon HY Tsang Wing Chiu Dai Ronnie TP Poon Chung Mau Lo | 2013 | World Journal of Gastroenterology2013，19，20： | 23 |
| 3 | Non-invasive means of measuring hepatic fat content显示文摘Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance (MR) techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo 1H MRS is a fast, safe, non-invasive method forthe quantification of intrahepatocellular lipid (IHCL) levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis (e.g. non-alcoholic fatty liver disease), or in testing new treatments for these conditions. | Sanjeev R Mehta E Louise Thomas Jimmy D Bell Desmond G Johnston Simon D Taylor-Robinson | 2008 | World Journal of Gastroenterology2008，14，22： | 21 |
| 4 | Current status and recent advances of liver transplantation from donation after cardiac death显示文摘The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably 'prematurely' of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures. | M Thamara PR Perera Simon R Bramhall | 2011 | World Journal of Gastrointestinal Surgery2011，3，11： | 16 |
| 5 | Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation显示文摘Liver transplantation(LT)is the best treatment for endstage hepatic failure,with an excellent survival rates over the last decade.Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death.Ischaemic cholangiopathy(IC)is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis.It commonly presents with cholestasis and cholangitis resulting in higher readmission rates,longer length of stay,repeated therapeutic interventions,and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs.The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time,donation after circulatory death(DCD),rejection,and cytomegalovirus infection.The majority of IC occurs within 12 mo after LT.Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC.Biliary complications and IC rates are between 16%and 29%in DCD grafts com-pared to between 3%and 17%in donation after brain death(DBD)grafts.The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation.However,there are many other risk factors for IC that should be considered.The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation.Careful donor selection and procurement might help to optimize the utilization of DCD grafts. | Moustafa Mabrouk Mourad Abdullah Algarni Christos Liossis Simon R Bramhall | 2014 | World Journal of Gastroenterology2014，20，20： | 16 |
| 6 | Psychological controversies in gastroparesis: A systematic review显示文摘AIM To systematically review literature addressing three key psychologically-oriented controversies associated with gastroparesis. METHODS A comprehensive search of Pub Med, CINAHL, and PsycI NFO databases was performed to identify literature addressing the relationship between gastroparesis and psychological factors. Two researchers independently screened all references. Inclusion criteria were: an adult sample of gastroparesis patients, a quantitative methodology, and at least one of the following:(1) evaluation of the prevalence of psychopathology;(2) an outcome measure of anxiety, depression, or quality of life; and(3) evidence of a psychological intervention. Case studies, review articles, and publications in languages other than English were excluded from the current review. RESULTS Prevalence of psychopathology was evaluated by three studies(n = 378), which found that combined anxiety/depression was present in 24% of the gastroparesis cohort, severe anxiety in 12.4%, depression in 21.8%-23%, and somatization in 50%. Level of anxiety and depression was included as an outcome measure in six studies(n = 1408), and while limited research made it difficult to determine the level of anxiety and depression in the cohort, a clear positive relationship with gastroparesis symptom severity was evident.Quality of life was included as an outcome measure in 11 studies(n = 2076), with gastroparesis patients reporting lower quality of life than population norms, and a negative relationship between quality of life and symptom severity. One study assessed the use of a psychological intervention for gastroparesis patients(n = 120) and found that depression and gastric function were improved in patients who received psychological intervention, however the study had considerable methodological limitations. CONCLUSION Gastroparesis is associated with significant psychological distress and poor quality of life. Recommendations for future studies and the development of psychological interventions are provided. | Sally Woodhouse Geoff Hebbard Simon R Knowles | 2017 | World Journal of Gastroenterology2017，23，7： | 12 |
| 7 | 使用cDNA微阵列和组织微阵列对三种上皮性卵巢肿瘤基因表达的分析显示文摘背景与目的卵巢癌是在妇科恶性肿瘤中死亡率最高的肿瘤,主要原因是由于缺乏有效的早期诊断方法。为了发现新的、特异性癌基因和进一步探索上皮性卵巢癌的临床意义,本文探索出一种新方法,通过结合cDNA微阵列和RNA原位杂交冰冻组织微阵列的方法寻找特异性卵巢癌基因。方法利用cDNA微阵列筛选在3种不同卵巢癌中(卵巢浆液性交界性肿瘤、卵巢浆液性腺癌和卵巢子宫内膜样腺癌)显示有意义表达的基因,并由RNA原位杂交冰冻组织微阵列证实其结果。结果40个基因和ESTs显示出在卵巢浆液性交界性肿瘤、浆液性和子宫内膜样卵巢癌3种类型之间基因表达有明显的差异;EPHB6、PTPRF、GFER、ERG25、PLRP1,FLJ22060和WISP2被进一步用于RNA原位杂交冰冻组织微阵列研究,其结果与cDNA微阵列研究结果相符合。结论cDNA微阵列和RNA原位杂交冰冻组织微阵列相结合是一种理想的寻找癌相关基因的方法,EPHB6,PTPRF,GFER,ERG25,PLRP1,FLJ22060和WISP2有可能成为新的上皮性卵巢癌候选基因。 | 郑敏 Simon R Kononen J Sauter G Mihatsch MJ Moch H | 2004 | 癌症2004，23，7： | 8 |
| 8 | Inhibition of Navl.7 channels by methyl eugenol as a mechanism underlying its antinociceptive and anesthetic actions显示文摘目的: 甲基 eugenol 是从中国植物 Asari 根值 et 根茎提取的一个主要活跃部件,它被用来治疗牙疼和其它疼痛。以前的在里面 vivo 研究证明了甲基 eugenol 有麻药和 antinociceptive 效果。这研究的目的是决定在神经系统混乱上位于它的效果下面的可能的机制。 | Ze-Jun WANG Boris TABAKOFF Simon R LEVINSON Thomas HEINBOCKEL | 2015 | Acta Pharmacologica Sinica2015，36，7： | 7 |
| 9 | Pancreatitis: Preventing catastrophic haemorrhage显示文摘Pancreatitis represents nearly 3% of acute admissions to general surgery in United Kingdom hospitals and has a mortality of around 1%-7% which increases to around 10%-18% in patients with severe pancreatitis. Patients at greatest risk were those identified to have infected pancreatic necrosis and/or organ failure. This review seeks to highlight the potential vascular complications associated with pancreatitis that despite being relatively uncommon are associated with mortality in the region of 34%-52%. We examine the current evidence base to determine the most appropriate method by which to image and treat pseudo-aneurysms that arise as the result of acute and chronic inflammation of pancreas. We identify how early recognition of the presence of a pseudo-aneurysm can facilitate expedited care in an expert centre of a complex pathology that may require angiographic, percutaneous, endoscopic or surgical intervention to prevent catastrophic haemorrhage. | Richard PT Evans Moustafa Mabrouk Mourad Gunraj Pall Simon G Fisher Simon R Bramhall | 2017 | World Journal of Gastroenterology2017，23，30： | 6 |
| 10 | A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform显示文摘 | Bence Sipos Simone M?ser Holger Kalthoff Virag T?r?k Matthias L?hr Günter Kl?ppel | 2003 | Virchows Archiv2003，，5： | 4 |
| 11 | Imaging of liver cancer显示文摘Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identif ication and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality. | Ben Ariff Claire R Lloyd Sameer Khan Mohamed Shariff Andrew V Thillainayagam Devinder S Bansi Shahid A Khan Simon D Taylor-Robinson Adrian KP Lim | 2009 | World Journal of Gastroenterology2009，15，11： | 4 |
| 12 | Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival显示文摘AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS:In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro . By contrast,the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2-/- mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation. | Sheena M Cruickshank Louise Wakenshaw John Cardone Peter D Howdle Peter J Murray Simon R Carding | 2008 | World Journal of Gastroenterology2008，14，38： | 3 |
| 13 | Characterization of colonic dendritic cells in normal and colitic mice显示文摘AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC.METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis.RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+,B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40,and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN).The majority (>85%) of DC in the colon and MLN of IL2-/-mice were type 1 myeloid, and expressed high levels of MHC class Ⅱ, CD80, CD86, CD 40, DEC 205, and CCR5molecules and were of low endocytic activity consistent with mature DC.CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon. | Sheena M Cruickshank Nicholas R English Peter J Felsburg Simon R Carding | 2005 | World Journal of Gastroenterology2005，11，40： | 3 |
| 14 | Cholangiocarcinoma显示文摘 | Shahid A Khan Howard C Thomas Brian R Davidson Simon D Taylor-Robinson | 2005 | The Lancet . 2005 (9493)2005，，： | 3 |
| 15 | The Index of a Projection 显示文摘 | Avron J Seiler R Simon B | 1994 | J Funct Anal1994，120，1： | 2 |
| 16 | Anisotropic Gaussian Schell-model beams: passage through optical systems and associated invariants显示文摘 | Simon R Sudarshan E C G Mukunda N | 1985 | Phys Rev A1985，46，4： | 2 |
| 17 | Use of Anesthetic Agents in Neonates and Young Children显示文摘 | R Daniel Mellon Arthur F. Simone Bob A. Rappaport | 2007 | Anesthesia & Analgesia2007，，3： | 2 |
| 18 | A comparison of hirudin with heparin in the prevention of rest enosis after coronary angioplasty显示文摘 | Serruys PW Herrman JR Simon R | 1995 | N Eng J Med1995，333，12： | 2 |
| 19 | Ventricular repolarization components on the electrocardiogram显示文摘 | Gan-Xin Yan Ramarao S Lankipalli James F Burke Simone Musco Peter R Kowey | 2003 | Journal of the American College of Cardiology2003，，： | 2 |
| 20 | Anticoagulation and antiplatelets as prophylaxis for hepatic artery thrombosis after liver transplantation显示文摘Hepatic artery thrombosis(HAT) is the most serious vascular complication after liver transplantation. Multiple risk factors have been identified to impact its development. Changes in haemostasis associated with end stage liver disease and the disturbance of the coagulation and anticoagulation cascades play an important role in development of this lethal complication. Early recognition and therapeutic intervention is mandatory to avoid its consequences. Pharmacological prophylaxis, by the use of antiplatelet or anticoagulant agents, is an important tool to reduce its incidence and prevent graft loss. Only a few studies have shown a clear benefit of antiplatelet agents in reducing HAT occurrence, however, these studies are limited by being retrospective and by inhomogeneous populations. The use of anticoagulants such as heparin is associated with an improvement in the outcomes mainly when used for a high-risk patients like living related liver recipients. The major concern when using these agents is the tendency to increase bleeding complications in a setting of already unstable haemostasis. Hence, monitoring of their administration and careful selection of patients to be treated are of great importance. Well-designed clinical studies are still needed to further explore their effects and to formulate proper protocols that can be implemented safely. | Abdullah A Algarni Moustafa M Mourad Simon R Bramhall | 2015 | World Journal of Hepatology2015，7，9： | 2 |
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