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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 | Bone mineral density and disorders of mineral metabolism in chronic liver disease显示文摘AIM:To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis.METHODS:The study was performed on 72 Indian patients with cirrhosis(63 male, 9 female;aged < 50 years).Etiology of cirrhosis was alcoholism(n = 37), hepatitis B(n = 25) and hepatitis C(n = 10).Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C.Secondary causes for metabolic bone disease and osteoporosis were ruled out.Sunlight exposure, physical activity and dietary constituents were calculated.Complete metabolic profiles were derived, and bone mineral density(BMD) was measured using dual energy X ray absorptiometry.Low BMD was defined as a Z score below-2.RESULTS:Low BMD was found in 68% of patients.Lumbar spine was the most frequently and severely affected site.Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass.Calcium intake was adequate, with unfavorable calcium:protein ratio and calcium:phosphorus ratio.Vitamin D deficiency was highly prevalent(92%).There was a high incidence of hypogonadism(41%).Serum estradiol level was elevated significantly in patients with normal BMD.Insulin-like growth factor(IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups.IGF-1 was signiflcantly lower in patients with low BMD.Serum osteocalcin level was low(68%) and urinary deoxypyridinoline to creatinine ratio was high(79%), which demonstrated low bone formation with high resorption.CONCLUSION:Patients with cirrhosis have low BMD.Contributory factors are reduced physical activity, low lean body mass, vitamin D def iciency and hypogonadism and low IGF-1 level. | Joe George Hosahithlu K Ganesh Shrikrishna Acharya Tushar R Bandgar Vyankatesh Shivane Anjana Karvat Shobna J Bhatia Samir Shah Padmavathy S Menon Nalini Shah | 2009 | World Journal of Gastroenterology2009，15，28： | 15 |
| 3 | An electromagnetic interaction modeling advisor显示文摘 | JOE L GEORGE I | 1991 | IEEE Trans on EMC1991，33，3： | 1 |
| 4 | An electromagnetic interaction modeling advisor显示文摘 | Joe L George I | 1991 | IEEE Trans on EMC1991，33，3： | 1 |
| 5 | Multiresidue analysis of seventeen pesticides in wine by gas chromatography with mass-selective detection显示文摘 | George J Soleas Joe Yan | 2000 | Journal of Chromatography A2000，882，6： | 1 |
| 6 | Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe显示文摘 | Bradley L. Urquhart Joseph A. Ware Rommel G. Tirona Richard H. Ho Brenda F. Leake Ute I. Schwarz Hani Zaher Joe Palandra Jamie C. Gregor George K. Dresser Richard B. Kim | 2008 | Pharmacogenetics and Genomics2008，，5： | 1 |
| 7 | Anxiety, depression and quality of life among Chinese breast cancer patients during adjuvant therapy显示文摘 | Winnie K.W. So Gene Marsh W.M. Ling F.Y. Leung Joe C.K. Lo Maggie Yeung George K.H. Li | 2009 | European Journal of Oncology Nursing2009，，1： | 1 |
| 8 | A comparative study between endoscopic middle meatal antrostomy and caldwell-Iuc surgery in the treatment of chronic maxillary sinusitis 显示文摘 | Joe Jacob K George S Preethi S | 2011 | Indian J Otolaryngol Head Neck Surg2011，63，3： | 1 |
| 9 | Assessing Respiration-Induced Tumor Motion and Internal Target Volume Using Four-Dimensional Computed Tomography for Radiotherapy of Lung Cancer显示文摘 | H. Helen Liu Peter Balter Teresa Tutt Bum Choi Joy Zhang Catherine Wang Melinda Chi Dershan Luo Tinsu Pan Sandeep Hunjan George Starkschall Isaac Rosen Karl Prado Zhongxing Liao Joe Chang Ritsuko Komaki James D. Cox Radhe Mohan Lei Dong | 2007 | International Journal of Radiation Oncology Biology Physics2007，，2： | 1 |
| 10 | Assessing Respiration-Induced Tumor Motion and Internal Target Volume Using Four-Dimensional Computed Tomography for Radiotherapy of Lung Cancer显示文摘 | H. Helen Liu Peter Balter Teresa Tutt Bum Choi Joy Zhang Catherine Wang Melinda Chi Dershan Luo Tinsu Pan Sandeep Hunjan George Starkschall Isaac Rosen Karl Prado Zhongxing Liao Joe Chang Ritsuko Komaki James D. Cox Radhe Mohan Lei Dong | 2007 | International Journal of Radiation Oncology Biology Physics2007，，2： | 1 |
| 11 | Primary hyperparathyroidism in children and adolescents显示文摘 | Joe George Shrikrishna V. Acharya Tushar R. Bandgar Padma S. Menon Nalini S. Shah | 2010 | The Indian Journal of Pediatrics2010，，2： | 1 |
| 12 | PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ显示文摘 | Kelly-Ann Sheppard Lori J. Fitz Julie M. Lee Christina Benander Judith A. George Joe Wooters Yongchang Qiu Jason M. Jussif Laura L. Carter Clive R. Wood Divya Chaudhary | 2004 | FEBS Letters2004，，1： | 1 |
| 13 | An electromagnetic interaction modeling advisor显示文摘 | Joe L George I | 1991 | IEEE Trans on EMC1991，33，3： | 1 |
| 14 | Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe显示文摘 | Bradley L. Urquhart Joseph A. Ware Rommel G. Tirona Richard H. Ho Brenda F. Leake Ute I. Schwarz Hani Zaher Joe Palandra Jamie C. Gregor George K. Dresser Richard B. Kim | 2008 | Pharmacogenetics and Genomics2008，，5： | 1 |
| 15 | A comparative study between endoscopic middle meatal antrostomy and Caldwell-Luc surgery in the treatment of chronic maxillary sinusitis 显示文摘 | Joe Jacob K George S Preethi S | 2011 | Indian J Otolaryngol Head Neck Surg2011，63，3： | 1 |
| 16 | Multiresidue analysis of seventeen pesticides in wine by gas chromatography with mass-selective detection显示文摘 | George J Soleas Joe Yan Kirby Hom | 2000 | Journal of Chromatography A2000，882，2000： | 1 |
| 17 | A comparative study be- tween endoscopic middle meatal antrostomy and Caldwell-Luc surgery in the treatment of chronic maxillary sinusitis 显示文摘 | Joe Jacob K George S Preeth S | 2011 | Indian J Octolaryngol Head Neck Surg2011，63，3： | 1 |
| 18 | Practice Guidelines for the manage-ment of patients with histoplasmosis显示文摘 | George S David M | 2000 | Clin Infectious Diseases2000，30，： | 1 |
| 19 | Pancreatic carcinoma is associated with delayed gastric emptying显示文摘 | Jamie S. Barkin MD FACP Robert I. Goldberg MD George N. Sfakianakis MD Joe Levi MD | 1986 | Digestive Diseases and Sciences1986，，3： | 1 |
| 20 | Azithromycin Exerts Bactericidal Activity and Enhances Innate Immune Mediated Killing of MDR Achromobacter xylosoxidans显示文摘Azithromycin(AZM),the most commonly prescribed antibiotic in the United States,is thought to have no activity against multidrugresistant Gram-negative pathogens such as Achromobacter xylosoxidans(AX)per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton Broth.Here we provide the first report of AZM bactericidal activity against carbapenemresistant isolates of AX,with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human environment.This pharmaceutical activity,evident in eukaryotic tissue culture media,is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood,serum,and neutrophils.Additionally,AZM monotherapy inhibited preformed AX biofilm growth in a dose-dependent manner together with a reduction in viable bacteria.In an illustrative case,AZM in combination with piperacillin-tazobactam exerted clear therapeutic effects in a patient with carbapenem-resistant AX mediastinitis,sternal osteomyelitis,and aortic graft infection.Our study reinforces how current antimicrobial testing practices fail to recapitulate the host environment or host-pathogen interactions and may misleadingly declare complete resistance to useful agents,adversely affecting patient outcomes.We conclude that AZM merits further exploration in the treatment of drug-resistant AX infections.Novel approaches to antimicrobial susceptibility testing that better recapitulate the host environment should be considered,especially as infections caused by multidrug-resistant Gram-negative bacterial pathogens are expanding globally with high morbidity and mortality. | Erlinda R.Ulloa Armin Kousha Hannah Tsunemoto Joe Pogliano Carmelo Licitra John J.LiPuma George Sakoulas Victor Nizet Monika Kumaraswamy | 2020 | Infectious Microbes & Diseases2020，2，1： | 0 |
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