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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 | Relationship between the exocrine and endocrine pancreas after acute pancreatitis显示文摘AIM:To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.METHODS:Relevant literature cited in three major biomedical journal databases(EMBASE,MEDLINE,and Scopus)was reviewed independently by two authors.There were no language constraints but the search was limited to human studies.Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis.Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus,pancreatic exocrine insufficiency,or chronic pancreatitis.The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis.Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed withdiabetes mellitus only.Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted.Pooled prevalence and corresponding 95%confidence intervals were calculated for all outcome measures and P-values<0.05 were deemed statistically significant.RESULTS:Eight clinical studies comprising of 234patients met all eligibility criteria.The pooled prevalence of newly diagnosed prediabetes or diabetes in individuals after acute pancreatitis was 43%(95%CI:30%-56%).The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29%(95%CI:19%-39%).The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40%(95%CI:25%-55%).The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41%(95%CI:12%-75%)and 39%(95%CI:28%-51%),respectively.Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis.CONCLUSION:Pancreatic exocrine insufficiency occurs in 40%of individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.Further studies are needed to investigate the pathogenesis of diabetes in this setting. | Stephanie L M Das James I C Kennedy Rinki Murphy Anthony R J Phillips John A Windsor Maxim S Petrov | 2014 | World Journal of Gastroenterology2014，20，45： | 9 |
| 3 | Ever-increasing diversity of drug-induced pancreatitis显示文摘With over 100000 hospital admissions per annum,acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has farreaching impact well beyond.It has become increasingly recognized that druginduced pancreatitis(DIP),despite accounting for less than 3%of all cases,represents an important and growing though often inconspicuous cause of acute pancreatitis.Nevertheless,knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents,especially for nonprescription medications.Indeed,the majority of available data is derived from case reports,case series,or case control studies.Furthermore,the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established(<10%of cases).Several classification systems have been proposed,but no single system has been widely adopted,and periodic updates are required in light of ongoing pharmacologic expansion.Moreover,infrequently prescribed medications or those available over-thecounter(including herbal and other alternative remedies)are often overlooked as a potential culprit of acute pancreatitis.Herein,we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity.We believe this manuscript will aid in increasing both primary and secondary prevention of DIP,thus ultimately facilitating more expedient diagnosis and a decrease in DIPrelated morbidity. | Simcha Weissman Muhammad Aziz Ryan B Perumpail Tej I Mehta Rutwik Patel James H Tabibian | 2020 | World Journal of Gastroenterology2020，26，22： | 8 |
| 4 | 评估清晨或夜晚服用降压药对24h动态血压的影响:清晨或夜间服用降压药的希腊英国联合研究显示文摘观察数据显示,临床血压水平与随后的主要不良心血管事件之间存在强烈的线性关系。然而,动态血压监测显示,夜间血压水平比24h或白天血压水平更能预测主要的不良心血管事件。此外,夜间与白天的血压比值和杓型状态也是心血管结局的重要独立预测因素。这些发现可能对抗高血压药物的最佳给药时间有影响,一些研究表明,夜晚服用降压药可能较白天服药减少心血管事件。 | Poulter NR Savopoulos C Anjum A Apostolopoulou M Chapman N Cross M Falaschetti E Fotiadis S James RM Kanellos I Szigeti M Thom S Sever P Thompson D Hatzitolios AI 赵狄 练桂丽 | 2018 | 中华高血压杂志2018，26，10： | 7 |
| 5 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 6 | Patterns of in-hospital mortality and bleeding complications following PCI for very elderly patients: insights from the Dartmouth Dynamic Registry显示文摘BackgroundVery 老病人(年龄 85 年) 是人口的一个很快增加的片断。作为一个组,他们经历跟随经皮的冠的干预(一种总线标准) 的在里面医院死亡和流血复杂并发症的高率。然而,在流血和死亡在之间的关系老 unknown.MethodsRetrospective 评论在 Dartmouth-Hitchcock 从 2000 ~ 2015 在 17,378 连续一种总线标准过程上被执行医学中心。在索引一种总线标准承认期间流血的发生(流血要求的输送,存取地点 hematoma > 5 厘米, pseudoaneurysm,和 retroperitoneal 流血)? 并且在里面医院死亡为四个年龄组被报导(< 65 年, 65-74 年, 75-84 年,和 85 年) 。承受了谁的流血复杂并发症和那些的病人的死亡被计算, multivariate 分析为在里面医院被执行死亡。最后,知道流血的预言者在病人年龄之间被比较 < 85 年和年龄 17,378 个病人学习了的 85 years.ResultsOf,(5.9%) 1019 经历了流血,(2.1%) 369 死了在里面医院追随者一种总线标准。流血和在里面医院死亡的发生与增加年龄 monotonically 增加了(死亡:0.94% , 2.27% , 4.24% 和 4.58% ;流血:3.96% , 6.62% , 10.68% 和 13.99% 好久 < 65, 65-74, 75-84 和 85 年,分别地) 。除了病人年龄 85 年,在 multivariate 分析上,流血为所有年龄组与增加的死亡被联系[机会比率(95% CI ) :变老 < 65 年, 3.65 (1.99-6.74 ) ;年龄 65-74 年, 2.83 (1.62-4.94 ) ;年龄 75-84 年, 3.86 (2.56-5.82 ) ,年龄 85 年:1.39 (0.49-3.95 )] 有增加的 .ConclusionsBleeding 和死亡追随者一种总线标准增加变老。为老尽管有流血的高率,流血在里面医院死亡追随者一种总线标准不再是预兆的。 | Shawn X Li Hannah I Chaudry Jiyong Lee Theodore B Curran Vishesh Kumar Kendrew K Wong Bruce W Andrus James T DeVries | 2018 | Journal of Geriatric Cardiology2018，15，2： | 6 |
| 7 | Colonoscopy quality with Entonox? vs intravenous conscious sedation:18608 colonoscopy retrospective study显示文摘AIM To compare colonoscopy quality with nitrous oxide gas(Entonox?) against intravenous conscious sedation using midazolam plus opioid.METHODS A retrospective analysis was performed on a prospectively held database of 18608 colonoscopies carried out in Lothian health board hospitals between July 2013 and January 2016.The quality of colonoscopies performed with Entonox was compared to intravenous conscious sedation(abbreviated in this article as IVM).Furthermore,the quality of colonoscopies performed with an unmedicated group was compared to IVM.The study used the following key markers of colonoscopy quality:(1) patient comfort scores;(2) caecal intubation rates(CIRs); and (3) polyp detection rates (PDRs).We used binary logistic regression to model the data.RESULTS There was no difference in the rate of moderate-toextreme discomfort between the Entonox and IVM groups (17.9% vs 18.8%; OR = 1.06,95%CI: 0.95-1.18,P = 0.27).Patients in the unmedicated group were less likely to experience moderate-to-extreme discomfort than those in the IVM group(11.4% vs 18.8%; OR = 0.71,95%CI: 0.60-0.83,P < 0.001).There was no difference in caecal intubation between the Entonox and IVM groups(94.4% vs 93.7%; OR = 1.08,95%CI: 0.92-1.28,P = 0.34).There was no difference in caecal intubation between the unmedicated and IVM groups (94.2% vs 93.7%; OR = 0.98,95%CI: 0.79-1.22,P = 0.87).Polyp detection in the Entonox group was not different from IVM group (35.0% vs 33.1%; OR = 1.01,95%CI: 0.93-1.10,P = 0.79).Polyp detection in the unmedicated group was not significantly different from the IVM group (37.4% vs 33.1%; OR = 0.97,95%CI: 0.87-1.08,P = 0.60).CONCLUSION The use of Entonox was not associated with lower colonoscopy quality when compared to intravenous conscious sedation using midazolam plus opioid. | Alexander R Robertson Nicholas A Kennedy James A Robertson Nicholas I Church Colin L Noble | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，9： | 3 |
| 8 | 直接评估吗啡刺激糖尿病人隐静脉内皮一氧化氮释放减少显示文摘to directly measure in real time basal and stimulated levels of NO released from human saphenous vein endothelium and to quantify the expression of the μopiate receptor, which has been linked with NO release. METHODS: Saphenous vein segments from patients with type 2 diabetes ( n = 12) and patients without diabetes (n =8) were obtained. The release of NO was measured directly from the endothelium using a NO-specific amperometric probe. NΩ-nitro-L-arginine methyl ester (L-NAME, 0.1 mmol/L), a NO synthase (NOS) inhibitor, or morphine (1 μmol/L), a stimulant, was administered and the measurements were repeated. Values were reported relative to the mean initial measurement of NO release from diabetic endothelium, which was defined as the relative zero level of NO release. A RT-PCR was then performed on the endothelium to measureμ opiate receptor expression. RESULTS: Diabetic patients (n = 12) showed a relative and significantly diminished basal level of released NO, (0.049± 0.012) nmol/L, compared | Thomas V BILHNGER, James A VOSSWINKEL, Patrick CADET, Christos M RIALAS, Harold I MAGAZINE, George B STEFANO(Division of Cardiothoracic Surgery, Department of Surgery, University Hospital and Medical Center, HSC, T19-080, Stony Brook, New York 11794-8191 Neuroscience Research Institute, State University of New York College at Old Westbury, Old Westbury, New York , USA) | 2002 | Acta Pharmacologica Sinica2002，23，2： | 3 |
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