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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 | Spontaneous fungal peritonitis: Micro-organisms, management and mortality in liver cirrhosis-A systematic review显示文摘BACKGROUND Spontaneous peritonitis is an infection of ascitic fluid without a known intraabdominal source of infection. spontaneous fungal peritonitis (SFP) is a potentially fatal complication of decompensated cirrhosis, defined as fungal infection of ascitic fluid in the presence of ascitic neutrophil count of greater than 250 cells/mL. AIM To determine the prevalence of fungal pathogens, management and outcomes (mortality) of SFP in critically ill cirrhotic patients. METHODS Studies were identified using PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Scopus databases until February 2019. Inclusion criteria included intervention trials and observation studies describing the association between SFP and cirrhosis. The primary outcome was in-hospital, 1-mo, and 6- mo mortality rates of SFP in cirrhotic patients. Secondary outcomes were fungal microorganisms identified and in hospital management by anti-fungal medications. The National Heart, Lung and Blood Institute quality assessment tools were used to assess internal validity and risk of bias for each included study. RESULTS Six observational studies were included in this systematic review. The overall quality of included studies was good. A meta-analysis of results could not be performed because of differences in reporting of outcomes and heterogeneity of the included studies. There were 82 patients with SFP described across all the included studies. Candida species, predominantly Candida albicans was the fungal pathogen in majority of the cases (48%-81.8%) followed by Candida krusei (15%- 25%) and Candida glabrata (6.66%-20%). Cryptococcus neoformans (53.3%) was the other major fungal pathogen. Antifungal therapy in SFP patients was utilized in 33.3% to 81.8% cases. The prevalence of in hospital mortality ranged from 33.3% to 100%, whereas 1-mo mortality ranged between 50% to 73.3%. CONCLUSION This systematic review suggests that SFP in end stage liver disease patient is associated with high mortality both in the hospital and at 1-mo, and that antifungal therapy is currently underutilized. | Tooba Tariq Furqan B Irfan Mehdi Farishta Brian Dykstra Eric Martin Sieloff Archita P Desai | 2019 | World Journal of Hepatology2019，11，7： | 7 |
| 3 | Platelet-rich plasma for muscle injuries: A systematic review of the basic science literature显示文摘BACKGROUND Platelet-rich plasma(PRP) is an increasingly used biologic adjunct for muscle injuries, as it is thought to expedite healing. Despite its widespread use, little is known regarding the mechanisms by which PRP produces its efficacious effects in some patients.AIM To clarify the effects of PRP on muscular pathologies at the cellular and tissue levels by evaluating the basic science literature.METHODS A systematic review of PubMed/MEDLINE and EMBASE databases was performed using the Preferred Reporting Items for Systematic Reviews and MetaAnalyses(PRISMA) guidelines and checklist. Level III in vivo and in vitro studies examining PRP effects on muscles, myocytes and/or myoblasts were eligible for inclusion. Extracted data included PRP preparation methods and study results.RESULTS Twenty-three studies were included(15 in vivo, 6 in vitro, 2 in vitro/in vivo). Only one reported a complete PRP cytology(platelets, and red and white blood cell counts). Five in vitro studies reported increased cellular proliferation, four reported increased gene expression, and three reported increased cellular differentiation. Five in vivo studies reported increased gene expression, three reported superior muscle regeneration, and seven reported improved histological quality of muscular tissue.CONCLUSION The basic science literature on the use of PRP in muscle pathology demonstrates that PRP treatment confers several potentially beneficial effects on healing in comparison to controls. Future research is needed to determine optimal cytology,dosing, timing, and delivery methods of PRP for muscle pathologies. | Kyle N Kunze Charles P Hannon Jared D Fialkoff Rachel M Frank Brian J Cole | 2019 | World Journal of Orthopedics2019，10，7： | 6 |
| 4 | A gene expression estimator of intramuscular fat percentage for use in both cattle and sheep显示文摘Background:The expression of genes encoding proteins involved in triacyglyceride and fatty acid synthesis and storage in cattle muscle are correlated with intramuscular fat(IMF)%.Are the same genes also correlated with IMF%in sheep muscle,and can the same set of genes be used to estimate IMF%in both species?Results:The correlation between gene expression(microarray) and IMF%in the longissimus muscle(LM) of twenty sheep was calculated.An integrated analysis of this dataset with an equivalent cattle correlation dataset and a cattle differential expression dataset was undertaken.A total of 30 genes were identified to be strongly correlated with IMF%in both cattle and sheep.The overlap of genes was highly significant,8 of the 13 genes in the TAG gene set and 8 of the 13 genes in the FA gene set were in the top 100 and 500 genes respertively most correlated with IMF%in sheep,P-value = 0.Of the 30 genes,CIDEA,THRSP,ACSM1,DGAT2 and FABP4 had the highest average rank in both species.Using the data from two small groups of Brahman cattle(control and Hormone growth promotant-treated[known to decrease IMF%in muscle]) and 22 animals in total,the utility of a direct measure and different estimators of IMF%(ultrasound and gene expression) to differentiate between the two groups were examined.Directly measured IMF%and IMF%estimated from ultrasound scanning could not discriminate between the two groups.However,using gene expression to estimate IMF%discriminated between the two groups.Increasing the number of genes used to estimate IMF%from one to five significantly increased the discrimination power;but increasing the number of genes to 15 resulted in little further improvement.Conclusion:We have demonstrated the utility of a comparative approach to identify robust estimators of IMF%in the LM in cattle and sheep.We have also demonstrated a number of approaches(potentially applicable to much smaller groups of animals than conventional methods) to using gene expression to rank animals for IMF%within a single farm/treatment,or to estimate differences in IMF%between two farms/treatments. | Bing Guo Kritaya Kongsuwan Paul L Greenwood Guanghong Zhou Wangang Zhang Brian P Dalrymple | 2014 | Journal of Animal Science and Biotechnology2014，5，4： | 6 |
| 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 | Experimental and modeling study of de novo formation of PCDD/PCDF on MSW fly ash显示文摘polychlorinateddibenzo-p-dioxins ( PCDD )和 polychlorinated dibenzo呋喃( PCDF )的形成上的硫二氧化物( SO2 )的效果在模仿的浪费燃烧 conditions.A chlorinationmodel basedon 下面在anentrained流动反应堆( EFR )被学习了有条件的概率被采用评估 PCDD andPCDFs.Results revealedthat 的相当或相同事物模式 SO2 的存在尽管 SO2suppressed PCDD/F formation.The 预言模型 ofPCDF 显示出好 ag 。 | LI Xiao-dong ZHANG Ji YAN Jian-hua CEN Ke-fa RYAN Shawn P GULLETT Brian K LEE Chunwai | 2007 | Journal of Environmental Sciences2007，19，1： | 6 |
| 7 | 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 |
| 8 | Role of self-expanding metal stents in the management ofvariceal haemorrhage:Hype or hope?显示文摘Despite the advances of medical,endoscopic and radiological therapy over recent years the mortality rates of acute variceal haemorrhage are still 16%-20% and the medium term outcome has not improved in the last 25 years. Early transjugular intrahepatic portosystemic shunt has proved to be an effective therapy for selected groups of patients with a high risk of re-bleeding and moderate liver disease. However,there is an unmet need for a therapy that can be applied in patients with a high risk of re-bleeding and advanced liver disease either as definitive therapy or as a bridge to permanent therapy. Selfexpanding metal stents can be placed without the need for endoscopic or fluoroscopic control and,once in place,will provide effective haemostasis and allow a route for oral fluids and nutrition. They can remain in place whilst liver function recovers and secondary prophylaxis is initiated. We review the results of 6 case series including a total of 83 patients and the first randomised controlled trial of self-expanding metal stents vs balloon tamponade(BT) in the management of refractory variceal haemorrhage. We report that self-expanding metal stents provide effective haemostasis and perform better than BT in refractory bleeding,where they are associated with fewer complications. Whilst the most effective place for self-expanding metal stents in the management algorithm needs to be determined by further randomised controlled trials,currently they provide an effective alternative to BT in selected patients. | Brian J Hogan James P O’Beirne | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，1： | 5 |
| 9 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 10 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 11 | Metabolomic and elemental profiling of blood serum in bladder cancer显示文摘Bladder cancer(BC)is one of the most frequently diagnosed types of urinary cancer.Despite advances in treatment methods,no specific biomarkers are currently in use.Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls(NCs),with external validation,was attempted using three analytical methods,i.e.,nuclear magnetic resonance,gold and silver-109 nanoparticle-based laser desorption/ionization mass spectrometry(LDI-MS),and inductively coupled plasma optical emission spectrometry(ICP-OES).All results were subjected to multivariate statistical analysis.Four potential serum biomarkers of BC,namely,isobutyrate,pyroglutamate,choline,and acetate,were quantified with proton nuclear magnetic resonance,which had excellent predictive ability as judged by the area under the curve(AUC)value of 0.999.Two elements,Li and Fe,were also found to distinguish between cancer and control samples,as judged from ICP-OES data and AUC of 0.807(in validation set).Twenty-five putatively identified compounds,mostly related to glycans and lipids,differentiated BC from NCs,as detected using LDI-MS.Five serum metabolites were found to discriminate between tumor grades and nine metabolites between tumor stages.The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection,staging,and grading of BC. | Krzysztof Ossolinski Tomasz Ruman Valerie Copie Brian P.Tripet Leonardo B.Nogueira Katiane O.P.C.Nogueira Artur Kołodziej Aneta Płaza-Altamer Anna Ossolinska Tadeusz Ossolinski Joanna Nizioł | 2022 | Journal of Pharmaceutical Analysis2022，12，6： | 2 |
| 12 | Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study显示文摘 | Ana Ignjatovic James E East Noriko Suzuki Margaret Vance Thomas Guenther Brian P Saunders | 2009 | Lancet Oncology2009，，： | 2 |
| 13 | Efficient bump mapping hardware 显示文摘 | Mark P John A Brian C | 1997 | Computer Graphics Proceedings Annual Conference Series ACM S IGGRA PH Los Angeles California1997，1997，： | 1 |
| 14 | Phosphorus-31 nuclear magnetic resonance spectroscopic determination of phytate in foods显示文摘 | Eugene P M Brian Q P Barbara F H | 1986 | Journal of Agricultural and Food Chemistry1986，34，1： | 1 |
| 15 | Use of plasma brain natriuretic peptide concentration to aid in the diagnosis of heart failure显示文摘 | Shapiro MD Homg H | 2003 | Mayo clinproe2003，78，6： | 1 |
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