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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 | Early acute kidney injury after liver transplantation: Predisposing factors and clinical implications显示文摘AIM To investigate the additional clinical impact of hepatic ischaemia reperfusion injury(HIRI) on patients sustaining acute kidney injury(AKI) following liver transplantation.METHODS This was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation(OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT(> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration(CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase(AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor(< 1000 IU/L), moderate(1000-5000 IU/L) or severe(> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications(AKI and HIRI) alone and then as a combined outcome. RESULTS Out of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustainedmoderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively(P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation(P < 0.001) and intensive care length of stay(P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication(P = 0.049). CONCLUSION HIRI has an important role in the development of AKI post-OLT and has a negative impact on patient outcomes, especially when occurring alongside AKI. | Suehana Rahman Susan V Mallett Brian R Davidson | 2017 | World Journal of Hepatology2017，9，18： | 6 |
| 3 | Endoscopic retrograde cholangiography for pediatric choledocholithiasis: Assessing the need for endoscopic intervention显示文摘AIM:To assess pediatric patients for choledocholithiasis.We applied current adult guidelines to identify predictivefactors in children.METHODS:A single-center retrospective analysis was performed at a tertiary children's hospital.We evaluated 44 consecutive pediatric patients who underwent endoscopic retrograde cholangiography(ERCP) for suspected choledocholithiasis.Patients were stratified into those with common bile duct stones(CBDS) at ERCP vs those that did not using the American Society of Gastrointestinal Endoscopy(ASGE) guidelines(Very Strong and Strong criteria) for suspected CBDS.RESULTS:CBDS were identified in 84% at the time of ERCP.Abdominal ultrasound identified CBDS in 36% of patients.Conjugated bilirubin ≥ 0.5 mg/d L was an independent risk factor for CBDS(P = 0.003).The Very Strong(59.5%) and Strong(48.6%) ASGE criteria identified the majority of patients(P = 0.0001).A modified score using conjugated bilirubin had a higher sensitivity(81.2% vs 59.5%) and more likely to identify a stone than the standard criteria,odds ratio of 25.7 compared to 8.8.Alanine aminotransferase and gamma-glutamyl transferase values identified significant differences in a subset of patients with odds ratio of 4.1 and 3.25,respectively.CONCLUSION:Current adult guidelines identified the majority of pediatric patients with CBDS,but specific pediatric guidelines may improve detection,thus decreasing risks and unnecessary procedures. | Douglas S Fishman Bruno P Chumpitazi Isaac Raijman Cynthia Man-Wai Tsai E O’Brian Smith Mark V Mazziotti Mark A Gilger | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，11： | 6 |
| 4 | Advances in endovascular aneurysm management: coiling and adjunctive devices显示文摘Endovascular coil embolisation continues to evolve and remains a valid modality in managing ruptured and unruptured cerebral aneurysms.Technological advances in coil properties,adjunctive devices and interventional techniques continue to improve long-term aneurysm occlusion rates.This review elaborates on the latest advances in next-generation endovascular coils and adjunctive coiling techniques for treating cerebral aneurysms. | Jessica K Campos Brian V Lien Alice S Wang Li-Mei Lin | 2020 | Stroke & Vascular Neurology2020，5，1： | 5 |
| 5 | Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma:Results from the FINBAR study显示文摘AIM:To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS:This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients,227 oesophageal adenocarcinoma patients and 260 controls.All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS:Gastro-oesophageal reflux was associated with Barrett's [OR 12.0(95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48(95% CI 2.25-5.41)].Oesophageal adenocarcinoma patients were more likely than controls to be ex-or current smokers [OR 1.72(95% CI 1.06-2.81)and OR 4.84(95% CI 2.72-8.61)respectively] and to have a high body mass index [OR 2.69(95% CI 1.62-4.46)].No significant associations were observed between these risk factors and Barrett's oesophagus.Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50(95% CI 0.30-0.86)].CONCLUSION:A high body mass index,a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma. | Lesley A Anderson RG Peter Watson Seamus J Murphy Brian T Johnston Harry Comber Jim Mc Guigan John V Reynolds Liam J Murray | 2007 | World Journal of Gastroenterology2007，13，10： | 5 |
| 6 | Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma显示文摘 | Ijichi Hideaki Chytil Anna Gorska Agnieszka E Aakre Mary E Bierie Brian Tada Motohisa Mohri Dai Miyabayashi Koji Asaoka Yoshinari Maeda Shin Ikenoue Tsuneo Tateishi Keisuke Wright Christopher V E Koike Kazuhiko Omata Masao Moses Harold L | 2011 | Journal of Clinical Investigation2011，，10： | 3 |
| 7 | Ultra high magnification endoscopy: Is seeing really believing?显示文摘Endoscopy is an indispensible diagnostic and thera-peutic instrument for gastrointestinal diseases. Endo-cytoscopy and confocal endomicroscopy are two types of ultra high magnification endoscopy techniques.Standard endoscopy allows for 50 × magnification,whereas endocytoscopy can magnify up to 1400 × and confocal endomicroscopy can magnify up to 1000 ×.These methods open the realm of real time micros copicevaluation of the GI tract, including cellular and subcellular structures. Confocal endomicroscopy has the additional advantage of being able to visualize subsurface structures. The use of high magnification endoscopy inconjunction with standard endoscopy allows for a real-time microscopic assessment of areas with macroscopic abnormalities, providing 'virtual biopsies' with valuable information about cellular and subcellular changes. Thiscan minimize the number of biopsies taken at the time of endoscopy. The use of this technology may assistin detecting premalignant or malignant changes at anearlier state, allowing for earlier intervention and treatment. High magnification endoscopy has shown promising results in clinical trials for Barrett's esophagus,esophageal adenocarcinoma, esophageal squamous cell cancer, gastric cancer, celiac disease, colorectalcancer, and inflammatory bowel disease. As the use of high magnification endoscopy techniques increases,the clinical applications will increase as well. Of the two systems, only confocal endomicroscopy is currently commercially available. Like all new technologies there will be an initial learning curve before operators become proficient in obtaining high quality images and discerning abnormal from normal pathology. Validatedcriteria for the diagnosis of the various gastrointestinal diseases will need to be developed for each method. Inthis review, the basic principles of both modalities are discussed, along with their clinical applic ability and limitations. | Aman V Arya Brian M Yan | 2012 | World Journal of Gastrointestinal Endoscopy2012，4，10： | 2 |
| 8 | 显示文摘 | Ryan Muszynski Brian Seger Prashant V | 2008 | Journal of Physical Chemistry C2008，112，： | 1 |
| 9 | Accurate prediction of the response of freshwater fish to a mixture of estrogenic chemicals 显示文摘 | BRIAN J V HARRIS C A SCHOLZE M | 2005 | Environ Health Perspect2005，113，： | 1 |
| 10 | The use of sub-surface constructed wetlands for wastewater treatment in the Czech Republic : 10 years experience 显示文摘 | Brian V J | 2006 | Ecol Eng2006，18，5： | 1 |
| 11 | A Study on the Optimization of Integral Fuel Burnable Absorbers Using the Genetic Algorithm Based CIGARO Fuel Management System显示文摘 | Brian V H Madeline A F | 1997 | Ann Nucl Energy1997，24，6： | 1 |
| 12 | Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model显示文摘 | Brian B C Huang Y Goettl V M | 2005 | Brain Res2005，1041，1： | 1 |
| 13 | Contribution to the determination of kinetic parameters of the sol-gel transformation by rheological measurements显示文摘 | Peter J D Brian V Elizabeth W | 2000 | J Colloid Interface Sci2000，221，： | 1 |
| 14 | Combinatorial biosynthesis of lipopeptide antibiotics in Streptomyces roseosporus 显示文摘 | Baltz R H Brian P Miao V | 2006 | J Ind Microbiol Biotechnol2006，33，： | 1 |
| 15 | A method for assessing hydrologic alteration within ecosystems显示文摘 | Brian D Riehter Jeffrey V Baumgartner David P Braun | 1996 | Conservation Biology1996，10，4： | 1 |
| 16 | Accurate prediction of the response of freshwater fish to a mixture of estrogenic chemicals 显示文摘 | BRIAN V HARRIS C A SCHOLZE M | 2005 | Environ Health Perspect2005，113，6： | 1 |
| 17 | The effect of seat geometry on gate valve noise显示文摘 | Smith Bruce A W Luloff Brian V | 2000 | Pressure Vessel Technology2000，122，4： | 1 |
| 18 | Urine biomarkers predict the cause of glomerular disease显示文摘 | SANJU A V BRIAN P MILOS N B | 2007 | J Am Soc Nephrol2007，18，： | 1 |
| 19 | A Method for Assessing Hydrologic Alteration Within Ecosystems显示文摘 | Brian D Richter J eff rey V Baumgartner J ennifer Powell | 1996 | Conservation Biology1996，10，4： | 1 |
| 20 | Daptomycin biosynthesis in Streptomyces roseosporus : cloning and analysis of the gene cluster and revision of peptide stereochemistry 显示文摘 | Miao V Coeffet- LeGal MF Brian P | 2005 | Microbiology2005，151，5： | 1 |
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