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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 | Levels of CMV-reactive antibodies correlate with the induction of CD28^null T cells and systemic inflammation in chronic obstructive pulmonary disease (COPD)显示文摘 | Dino BA Tan Fathiah S Amran Teck-Hui Teo Patricia Price Yuben P Moodley | 2016 | Cellular & Molecular Immunology2016，13，4： | 8 |
| 3 | Outcomes of critically ill cancer patients with Acinetobacter baumannii infection显示文摘AIM: To describe the intensive care unit(ICU) outcomes of critically ill cancer patients with Acinetobacter baumannii(AB) infection.METHODS: This was an observational study that included 23 consecutive cancer patients who acquired AB infections during their stay at ICU of the National Cancer Institute of Mexico(INCan), located in Mexico City. Data collection took place between January 2011, and December 2012. Patients who had AB infections before ICU admission, and infections that occurred during the first 2 d of ICU stay were excluded. Data were obtained by reviewing the electronic health record of each patient. This investigation was approved by the Scientific and Ethics Committees at INCan. Because of its observational nature, informed consent of the patients was not required.RESULTS: Throughout the study period, a total of 494 critically ill patients with cancer were admitted to the ICU of the INCan, 23(4.6%) of whom developed AB infections. Sixteen(60.9%) of these patients had hematologic malignancies. Most frequent reasons for ICU admission were severe sepsis or septic shock(56.2%) and postoperative care(21.7%). The respiratory tract was the most frequent site of AB infection(91.3%). The most common organ dysfunction observed in our group of patients were the respiratory(100%), cardiovascular(100%), hepatic(73.9%) and renal dysfunction(65.2%). The ICU mortality of patients with 3 or less organ system dysfunctions was 11.7%(2/17) compared with 66.6%(4/6) for the group of patients with 4 or more organ system dysfunctions(P = 0.021). Multivariate analysis identified blood lactate levels(BLL) as the only variable independently associated with inICU death(OR = 2.59, 95%CI: 1.04-6.43, P = 0.040). ICU and hospital mortality rates were 26.1% and 43.5%, respectively.CONCLUSION: The mortality rate in critically ill patients with both HM, and AB infections who are admitted to the ICU is high. The variable most associated with increased mortality was a BLL ≥ 2.6 mmol/L in the first day of stay in the ICU. | Silvio A ?amendys-Silva Paulina Correa-García Francisco J García-Guillén María O González-Herrera Américo Pérez-Alonso Julia Texcocano-Becerra Angel Herrera-Gómez Patricia Cornejo-Juárez Abelardo Meneses-García | 2015 | World Journal of Critical Care Medicine2015，4，3： | 3 |
| 4 | Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells显示文摘 | Patricia DA Lima Megan M Tu Mir Munir A Rahim Annie R Peng B Anne Croy Andrew P Makrigiannis | 2014 | Cellular & Molecular Immunology2014，11，5： | 3 |
| 5 | Distribution of the P2X2 receptor and chemical coding in ileal enteric neurons of obese male mice(ob/ob)显示文摘AIM:To investigate the colocalization,density and profile of neuronal areas of enteric neurons in the ileum of male obese mice.METHODS:The small intestinal samples of male mice in an obese group(OG)(C57BL/6J ob/ob)and a control group(CG)(+/+)were used.The tissues were analyzed using a double immunostaining technique for immunoreactivity(ir)of the P2X2 receptor,nitric oxide synthase(NOS),choline acetyl transferase(ChAT)and calretinin(Calr).Also,we investigated the density and profile of neuronal areas of the NOS-,ChAT-and Calrir neurons in the myenteric plexus.Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method.RESULTS:The analysis demonstrated that the P2X2receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG.Neuronal density values(neuron/cm2)decreased 31%(CG:6579±837;OG:4556±407)and 16.5%(CG:7796±528;OG:6513±610)in the NOS-ir and calretininir neurons in the OG,respectively(P<0.05).Density of ChAT-ir(CG:6200±310;OG:8125±749)neurons significantly increased 31%in the OG(P<0.05).Neuron size studies demonstrated that NOS,ChAT,and Calr-ir neurons did not differ significantly between the CG and OG groups.The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG.CONCLUSION:Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir,ChAT-ir and CalR-ir myenteric neurons. | Márcia Sanae Mizuno Amanda Rabello Crisma Primavera Borelli Bárbara Tavares Schfer Mariana Póvoa Silveira Patricia Castelucci | 2014 | World Journal of Gastroenterology2014，20，38： | 3 |
| 6 | Relation of atrophic gastritis with Helicobacter pylori-CagA^+ and interleukin-1 gene polymorphisms显示文摘AIM: To determine the association of Helicobacter pylori (H pylori) CagA+ infection and pro-inflammatory poly-morphisms of the genes interleukin (IL)-1RN and IL-1B with the risk of gastric atrophy and peptic ulcers in a dyspeptic population in Costa Rica, a country with high incidence and mortality of gastric cancer. METHODS: Seven biopsy specimens, a fasting blood sample and a questionnaire concerning nutritional and sociodemographic factors were obtained from 501 con-secutive patients who had undergone endoscopy for dyspeptic symptoms. A histopathological diagnosis was made. Pepsinogen concentrations were analyzed by enzyme linked immunosorbent assay (ELISA). Infection with H pylori CagA+ was determined by serology and polymerase chain reaction (PCR). IL-1B and IL-1RN polymorphisms genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP)and PCR respectively. RESULTS: In this dyspeptic population, 86% were H pylori positive and of these, 67.8% were positive for CagA. Atrophic antral gastritis (AAG) was associated with CagA+ status [odd ratio (OR) = 4.1; P < 0.000] and fruit consumption (OR = 0.3; P < 0.00). Atrophic body gastritis (ABG) was associated with pepsinogen PGI/PGII < 3.4 (OR = 4.9; P < 0.04) and alcohol consumption (OR = 7.3; P < 0.02). Duodenal ulcer was associated with CagA+ (OR = 2.9; P < 0.04) and smoking (OR = 2.4; P < 0.04). PGI < 60 μg/L as well as PGI/PGII < 3.4 were associated with CagA+. CONCLUSION: In a dyspeptic population in Costa Rica, H pylori CagA+ is not associated with ABG, but it is a risk factor for AAG. The pro-inflammatory cytokine poly-morphisms IL-1B + 3945 and IL-1RN are not associated with the atrophic lesions of this dyspeptic population. | Rafaela Sierra Clas Une Vanessa Ramírez Warner Alpízar-Alpízar María I González José A Ramírez Antoine de Mascarel Patricia Cuenca Guillermo Pérez-Pérez Francis Mégraud | 2008 | World Journal of Gastroenterology2008，14，42： | 2 |
| 7 | Uncommon features of pulmonary Langerhans' cell histiocytosis: analysis of 11 cases and a review of the literature显示文摘 | LING Chun-hua JI Cheng Daniel P Raymond Patricia A Bourne XU Hao-dong | 2010 | Chinese Medical Journal2010，，4： | 2 |
| 8 | Effects of Ischemia and Reperfusion on Subpopulations of Rat Enteric Neurons Expressing the P2X7 Receptor显示文摘 | Kelly Palombit Cristina Eusébio Mendes Wothan Tavares-de-Lima Mariana Póvoa Silveira Patricia Castelucci | 2013 | Digestive Diseases and Sciences2013，，12： | 2 |
| 9 | Silent diabetic nephropathy显示文摘AIM: To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy(DN) and its possible associated factors.METHODS: Clinical and histological data of 60 patients diagnosed with diabetic nephropathy were retrospectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The final event was defined as renal replacement therapy(RRT) initiation or progression of chronic kidney disease(CKD), according to the KDIGO 2012 definition of a decrease in CKD category and a decrease in GFR of 25% or more. RESULTS: A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a median age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, although in 13 patients, it was less than 5 years. A total of 62% of patients reached the final event in a mean period of 3.4 years(95%CI: 2.1-4.7), with 21 of them requiring dialysis. The factors that were independently associated with renal survival were estimated glomerular filtration rate(e GFR) at the time of biopsy, cardiovascular disease(CVD) history and Hb A1 c less than 7%. Therefore, for each 10 m L/min per 1.73 m2 reduction in e GFR, we obtained a DN progression risk of HR = 2(1.3-3.0)(P = 0.001); patients with CVD were at greater risk for DN progression(HR = 2.8, 1.1-7.1, P = 0.032), and CKD patients with Hb A1 c < 7% demonstrated greater renal risk than patients with Hb A1 c ≥ 7%, with an HR of 2.9(1.0-8.4)(P = 0.054).CONCLUSION: A past history of CVD is a risk factor for DN progression. Levels of Hb A1 c less than 7% could favor an e GFR decrease in these patients. | Katia López-Revuelta Patricia Pea Galdo Ramona Stanescu Leticia Parejo Carmen Guerrero Elia Pérez-Fernández | 2014 | World Journal of Nephrology2014，3，1： | 2 |
| 10 | Thymosin-beta4 modulates corneal matrix metalloproteinase levels and polymorphonuclear celt infiltration after alkali injury 显示文摘 | Sosne G Patricia L Christopherson P L | 2005 | Invest Ophthalmol Vis Sci2005，46，7： | 1 |
| 11 | Determination of As, Sb, Se, Te and Bi in milk by slurry sampling hydride atomic fluorescence spectrometry 显示文摘 | Patricia C M Luisa C Agustin P | 2004 | Talanta2004，62，1： | 1 |
| 12 | Variations in microbial community composition through two soil depth profiles显示文摘 | NOAH F JOSHUA P S PATRICIA A H | 2003 | Soil Biol Biochem2003，35，1： | 1 |
| 13 | Casts of Aporrectodea caliginosa (Savigny) and Lumbricus rubellus (Hoffmeister) differ in microbial activity,nutrient availability and aggregate stability显示文摘 | Richard J H Patricia M F Jacqueline E P | 2003 | Pedobiologia2003，47，： | 1 |
| 14 | Large-scale HCV RNA screening in first time blood donors: the first step towards genomic screening of blood donations显示文摘 | Juraj P Patricia H John B | 1999 | Vox Sang1999，76，3： | 1 |
| 15 | Structural mechanism for STI571 inhibition of Abelson tyrosine kinase显示文摘 | Thomas S William B Patricia P | 2000 | Science2000，289，15： | 1 |
| 16 | Variations in microbial communitycomposition through two soil depth profiles显示文摘 | NOAH F JOSHUA P S PATRICIA A H | 2003 | Soil Biology and Biochemistry2003，35，1： | 1 |
| 17 | Regulatory Implication of Credit Risk Modeling 显示文摘 | Patricia J William P | 2000 | Journal of Banking and Finance2000，，24： | 1 |
| 18 | The effect of ionic products from bioactive glass dissolution on osteoblast proliferation and collagen production显示文摘 | Patricia V Marivalda M P Alfredo M G | 2004 | Biomaterials2004，25，： | 1 |
| 19 | An examination of the nature of trust in buyer- seller relationships显示文摘 | PATRICIA M DONEY JOSEPH P CANNON | 1997 | Journal of marketing1997，61，2： | 1 |
| 20 | MAS NMR,TPR and TEM studies of the interaction of NiMo with alumina and silicaalumina supports显示文摘 | Qu L L Zhang W P Patricia J | | 0，，： | 1 |
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