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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 | Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic(type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease显示文摘AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM. | Bharat K Puchakayala Siddharth Verma Pushpjeet Kanwar John Hart Raghavendra R Sanivarapu Smruti R Mohanty | 2015 | World Journal of Hepatology2015，7，25： | 10 |
| 3 | Endoscopic management of postcholecystectomy biliary leakage显示文摘BACKGROUND: Biliary leak is an uncommon but significant complication following cholecystectomy. Endotherapy is an established method of treatment. However, the optimal intervention is not known. METHOD: Eighty-five patients with postcholecystectomy biliary leaks from July 2000 to March 2009 were retrospectively evaluated. RESULTS: The study population was 20 males and 65 females with a mean age of 42.47 years. Patients presented with abdominal pain (46), jaundice (23), fever (23), abdominal distension (42), or bilious abdominal drain (67). Endoscopic retrograde cholangiopancreatography detected a leak at the cystic duct stump in 45 patients, stricture with middle common bile duct leak in 4, leak from the right hepatic duct in 3, and a ligated common bile duct in 32. Twelve also had bile duct stones. One had a broken T-tube with stones Endotherapy was possible in 53 patients. Three patients with stones, one with a broken T-tube with stones, and 4 with stricture of the common bile duct with a leak were managed with sphincterotomy and stenting. Eight patients with a cystic duct stump leak with stones were managed with sphincterotomy and stone extraction. Three outpatients and 12 inpatients with a cystic duct stump leak were managed with sphincterotomy and stent and sphincterotomy and nasobiliary drain, respectively. Five patients with a cystic duct stump leak were managed with stenting. Sixteen with coagulopathy were managed with only nasobiliary drain (9) or stent (7). Leak closure was achieved in 100% patients Four developed mild pancreatitis which improved with conservative treatment.CONCLUSIONS: Endoscopic intervention is a safe and effective method of treatment of postcholecystectomy biliary leaks. However, management should be individualized based on factors such as outpatients or inpatients, presence of stone, stricture, ligature, or coagulopathy. | Virendra Singh Gurpreet Singh Ganga R Verma Rajesh Gupta | 2010 | Hepatobiliary & Pancreatic Diseases International2010，9，4： | 9 |
| 4 | Efficacy of sequential treatment of HCT116 colon cancer monolayers and xenografts with docetaxel,flavopiridol,and 5-fluorouracil显示文摘瞄准:有 docetaxel, flavopiridol,或 5 氟尿嘧啶(5-FU ) 的稳固的肿瘤的临床的治疗经常遇到不受欢迎的副作用和药抵抗。在 modulating chemosensitivity 并且更好与 docetaxel, flavopiridol,或 5-FU 评估联合治疗的潜在的角色的目的理解他们怎么可能临床上被使用的这研究。方法:HCT116 结肠癌房间在几不同行政时间表在试管内与 docetaxel, flavopiridol,和 5-FU 被对待,顺序或同时。房间幸存被 MTT 试金测量。caspase-3 的活动被 caspase-3 试金决定,软琼脂殖民地试金被用来在软琼脂测试 HCT116 房间的菌落形成。我们也建立了异种皮移植模型扩大在试管内观察到一个在活体内系统。结果:当人的结肠癌 HCT116 房间为 flavopiridol 为另一 24 h 为 24 h 和 5-FU 跟随的 1 h 与 docetaxel 被对待时,最大的细胞毒性被发现。这顺序的联合治疗不仅与另外的联合治疗相比更强烈禁止肿瘤细胞生长而且显著地在软琼脂减少菌落形成并且扩充 HCT116 细胞的 apoptosis。docetaxel 定序以后由 flavopiridol 跟随了 1 h,以后在异种皮移植模型由 5-FU 跟随了 24 h,也导致了推迟的肿瘤生长和更高的幸存率。结论:当把 docetaxel 与 flavopiridol 和 5-FU 相结合时,这些结果强调一张行政时间表的重要性,提供对它在临床的试用的发展的基本原理解释。 | Jun GUO An-wu ZHOU Yu-cai FW Udit N VERMA Debu TRIPATHY Eugene P FRENKEL Carlos R BECERRA | 2006 | Acta Pharmacologica Sinica2006，27，10： | 4 |
| 5 | Optimizing management in autoimmune hepatitis with liver failure at initial presentation显示文摘Autoimmune hepatitis (AIH) is a disease of unknown etiology,its hallmark being ongoing hepatic inflammation.By its very nature,it is a chronic condition,although increasingly,we are becoming aware of patients with acute presentations,some of whom may have liver failure.There are very limited published data on patients with AIH with liver failure at initial diagnosis,which consist mostly of small retrospective studies.As a consequence,the clinical features and optimal management of this cohort remain poorly defined.A subset of patients with AIH who present with liver failure do respond to corticosteroids,but for the vast majority,an urgent liver transplantation may offer the only hope of long-term survival.At present,there is uncertainty on how best to stratify such a cohort into responders and non-responders to corticosteroids as soon as possible after hospitalization,thus optimizing their management.This editorial attempts to answer some of the unresolved issues relating to management of patients with AIH with liver failure at initial presentation.However,it must be emphasized that,at present,this editorial is based mostly on small retrospective studies,and it is an understatement that multicenter prospective studies are urgently needed to address this important clinical issue. | Jonathan R Potts Sumita Verma | 2011 | World Journal of Gastroenterology2011，17，16： | 3 |
| 6 | A noval low-temperature synthesis of nanosized NiZn fetrite显示文摘 | Verma S Pradhan S D Pasricha R | 2005 | Journal of the American Chemical Society2005，88，： | 1 |
| 7 | Generalized system for relaxed cocoercive variational inequalities and its projection methods显示文摘 | Verma R U | 2004 | J Optim Theory Appl2004，121，1： | 1 |
| 8 | Hemorrhagic pleural effu- sion secondary to sarcoidosis:A brief review显示文摘 | Kumar S Verma SK Singh R Prasad R | 2009 | Ann Thorac Med2009，4，1： | 1 |
| 9 | Cardiac re-modeling and failure : from molecules to man ( Part 1 ) 显示文摘 | Fedak 1' W Verma S Weisel R D | 2005 | Cardiovasc: Pathol2005，14，： | 1 |
| 10 | Generalized System for Relaxed Cocoercive Variational Inequalities and Projection Methods显示文摘 | VERMA R U | 2004 | J Optim Theory Appl2004，121，1： | 1 |
| 11 | Crystallization behavior of nparaffins in Bombay-High middle-distillate wax/gel显示文摘 | Srivastava S P Tandon R S Verma P S | 1992 | Fuel1992，71，5： | 1 |
| 12 | Influence of Nd^3+ and Sm^3+ substitution on the magnetic properties of strontium ferrite sintered magnets显示文摘 | Puneet Sharma Amitabh Verma R K Sidhu O P Pandey | 2003 | Journal of Alloys and Compounds2003，361，： | 1 |
| 13 | Projection Methods, Algorithms, and a New System of Nonlinear Variational Inequalities 显示文摘 | VERMA R U | 2001 | Computers and Mathematics with Application2001，41，： | 1 |
| 14 | Soil CO2 fluxes and the carbon budget of a grassland显示文摘 | Norman J N R Garcia & S B Verma | 1992 | Journal Geophysical research1992，97，18： | 1 |
| 15 | Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis 显示文摘 | Lu H Forbes R A Verma A | 2002 | J Biol Chem2002，277，23： | 1 |
| 16 | L-asparaginase: a promising enzyme for treatment of acute lymphoblastic leukiemia显示文摘 | Jain R Zaidi K U Verma Y | 2012 | People J Sci Res2012，5，1： | 1 |
| 17 | Detecting subarach noid hemorrhage: comparison of combined FLAIR/SWI versus CT显示文摘 | Verma RK Kottke R Andereggen L | 2013 | Eur J Radiol2013，82，9： | 1 |
| 18 | Understanding gait control in post-stroke:implications for management显示文摘 | Verma R Arya KN Sharma P | | 0，，01： | 1 |
| 19 | A potential antitumor drug (arginine deiminase) reengineered for efficient oper- ation under physiological conditions 显示文摘 | ZHU LL VERMA R ROCCATANO D | 2010 | Chembioehem2010，11，16： | 1 |
| 20 | Energetic nitrogen-rich salts and ionic liquids显示文摘 | Singh R P Verma R D Meshri D T | 2006 | Angewandte Chemie-lnternational Edi- tion2006，45，22： | 1 |
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