简介：AIM:Toinvestigateifanimmuneimbalancemayaccountforthedevelopmentandprogressionofchronicradiationenteritis.WeanalyzedtheTh1/Th2immuneresponseprofileearlyand6moafterfractionatedcolorectalirradiation.METHODS:Aratmodeloffractionatedcolorectalγ-irradiation(4-Gyfractions,3fractionsperweek)wasdesignedtoinvestigatetheeffectsofcumulativedoseoninflammatorymediators(cytokinesandchemo-kines)andimmuneresponse(Th1/Th2profileandim-munosuppressivemediatorIL-10)duringacute(early)responseand6moaftertheendoffractionatedirradia-tion(chronicresponse).Analyseswereperformed1dafterthecumulativedosesof16Gyand36Gyand1d,3d,and26wkafterthecumulativedoseof52Gy.RESULTS:Withoutcausinghistologicaldamage,fractionatedradiationinducedelevatedexpressionofIL-1β,TNFα,MCP-1,andiNOSindistalcolonicmucosaduringtheearlypost-irradiationphase.Atthattime,aTh2profilewasconfirmedbyexpressionofboththeTh2-specifictranscriptionfactorGATA-3andthechemokinereceptorCCR4andbysuppressionoftheTh1cytokineIFNγ/IP-10throughouttheirradiationprotocol.After6mo,despitethe2-foldreductionofiNOSandMCP-1levels,theTh2profilepersisted,asshownbya50%reductionintheexpressionoftheTh1transcriptionfactorT-bet,thechemokinereceptorCCXCR3,andtheIFNγ/STAT1pathway.Atthesametime-point,theimmuno-suppressiveIL-10/STAT3pathway,knowntoregulatetheTh1/Th2balance,wasexpressed,inirradiatedrats,atapproximatelyhalfitslevelascomparedtocontrols.ThissuppressionwasassociatedwithanoverexpressionofSOCS3,whichinhibitsthefeedbackoftheTh1polarizationandregulatesIL-10production.CONCLUSION:ColorectalirradiationinducesTh2polarization,defectiveIL-10/STAT3pathwayactivationandSOCS3overexpression.Thesechanges,inturn,maintainaimmunologicalimbalancethatpersistsinthelongterm.

简介：AIM:ToinvestigatewhethertheevaluationoftumorbuddingcancomplementK-RASanalysistoimprovetheindividualizedpredictionofresponsetoanti-epidermalgrowthfactorreceptorbasedtherapiesinmetastaticcolorectalcancer(mCRC)patients.METHODS:Forty-threepatientswithmCRCtreatedwithcetuximaborpanitumumabwereenteredintothisstudy.AccordingtotheResponseEvaluationCriteriainSolidTumorscriteria,30patientshadstableorprogressivedisease(non-responsive),while13patientshadapartialresponse.Tumorbudswereevaluatedfromwholetissuesectionsstainedforpan-cytokeratin,evaluatedinthedensestregionusinga40×objectiveand'high-grade'tumorbuddingwasdefinedas15buds/high-powerfield.RESULTS:TumorbudsandK-RASmutationbothcorrectlyclassified68%ofpatients.AllpatientswithK-RASmutation(n=7)orhigh-gradetumorbudding(n=11)werenon-responsive,ofwhich4patientshadbothfeatures.All13partialresponderswereK-RASwild-typewithlow-gradetumorbudding.Combined,thepredictivevalueofK-RASandtumorbuddingwas80%.Additionally,high-gradetumorbuddingwassignificantlyrelatedtoworseprogression-freesurvival[HR(95%CI):2.8(1.3-6.0,P=0.008)].CONCLUSION:Ifconfirmedinlargercohorts,theadditionoftumorbuddingtoK-RASanalysismayrepresentaneffectiveapproachforindividualizedpatientmanagementinthemetastaticsetting.

简介：AIM:Tostudytheeffectsofglutamine(Gin)onthechangeofintestinalpermeabilityanditsrelationshiptosystemicinflammatoryresponseinearlyabdominalpostoperativepatients.METHODS:Aprospective,randomized,double-blindandcontrolledtrialwastaken.TwentypatientsundergoingabdominalsurgerywererandomizedintoGingroup(oraladministrationofglutamine,30g/d,for7d,n=10)andplacebogroup(oraladministrationofplacebo,30g/d,for7d,n=-10).Temperaturesandheartratesofallpatientsweredailyrecorded.Whitebloodcellcounts(WBC)andbiochemicalvariablesweremeasuredbeforeoperationand4and7dalterdrugadministration.Serumconcentrationsofglutamine,endotoxin,diamineoxidaseandmalondialdehydeandurinelactulose/mannito(L/M)ratioweremeasuredbeforeand7dalterdrugadministration.RESULTS:Thepatientsinthe2groupswerecomparablepriortodrugadministration.SerumGinconcentrationwassignificantlydecreasedintheplacebogroupandincreasedintheGingroup7dalterdrugadministration.UrineL/MratiowassignificantlyincreasedintheplacebogroupanddecreasedintheGingroup.Theserumconcentrationofendotoxin,diamineoxidaseandmalondialdehydewassignificantlydecreasedintheGingroupcomparedwiththoseintheplacebogroup.Temperatures,heartratesandWBCcountsweresignificantlylowerintheGingroupthanthoseintheplacebogroup.CONCLUSION:Gutisoneofthesourcesofsystemicinflammatoryresponseinabdominalpostoperativepatientsandglutaminecandecreaseintestinalpermeability,maintainintestinalbarrierandattenuatesystemicinflammatoryresponseinearlypostoperativepatients.

简介：AIM:Toevaluatetheimpactofsociodemographic/clinicalfactorsonearlyvirologicalresponse(EVR)topegin-terferon/ribavirinforchronichepatitisC(CHC)inclinicalpractice.METHODS:Weconductedamulticenter,cross-sectional,observationalstudyinHepatologyUnitsof91Spanishhospitals.CHCpatientstreatedwithpeginterferonα-2aplusribavirinwereincluded.EVRwasdefinedasundetectablehepatitisCvirus(HCV)-ribonucleicacid(RNA)or≥2logHCV-RNAdecreaseafter12wkoftreatment.AbivariateanalysisofsociodemographicandclinicalvariablesassociatedwithEVRwascarriedout.IndependentfactorsassociatedwithanEVRwereanalyzedusingamultipleregressionanalysisthatincludedthefollowingbaselinedemographicandclinicalvariables:age(≤40yearsvs>40years),gender,race,educationallevel,maritalstatusandfamilystatus,weight,alcoholandtobaccoconsumption,sourceofHCVinfection,alanineaminotransferase(ALT)andaspartateaminotransferase(AST)levels,andgammaglutamyltranspeptidase(GGT)(≤85IU/mLvs>85IU/mL),serumferritin,serumHCV-RNAconcentration(<400000vs≥400000),genotype(1/4vs3/4),cirrhoticstatusandribavirindose(800/1000/1200mg/d).RESULTS:Atotalof1014patientswereincludedinthestudy.Meanageofthepatientswas44.3±9.8years,70%weremale,and97%wereCaucasian.ThemainsourcesofHCVinfectionwereintravenousdrugabuse(25%)andbloodtransfusion(23%).SeventyeightpercentwereinfectedwithHCVgenotype1/4(68%hadgenotype1)and22%withgenotypes2/3.TheHCV-RNAlevelwas>400000IU/mLin74%ofpatients.ThemeanALTandASTlevelswere88.4±69.7IU/mLand73.9±64.4IU/mL,respectively,andmeanGGTlevelwas82±91.6IU/mL.Themeanferritinlevelwas266±284.8μg/L.Only6.2%ofpatientspresentedwithcirrhosis.Allpatientsreceived180mgofpeginterferonα-2a.Themostfrequentlyusedribavirindoseswere1000mg/d(41%)and1200mg/d(41%).Theplannedtreatm

简介：瞄准：估计临床，生物化学并且virological在长期的丙肝(CHC)的长期的结果有在加ribavirin的peginterferon(PEG-IFN)以后的持续virological回答(SVR)的病人联合治疗。方法：有在有PEG-IFN正ribavirin的治疗以后的SVR的一百和53个病人在一个单个西班牙的中心在5年的后续研究被包括，基于标准临床的实践。临床的回忆，生物化学的分析，丙肝病毒RNA和alpha-fetoprotein测量，ultrasonography和短暂elastography每年被执行。结果：153个病人的吝啬的后续经期是76??敦瑥吗？