UpdateonHGEin StefanClinicforSmallAnimalMedicine,LMU Outline大DefinitionofAHDS急 性腹瀉綜合征的定Updateonpathogenesis發(fā)病機(jī)理 進(jìn)roleofClostridiumperfringensandCltoxins產(chǎn)氣莢膜梭菌及其毒素起的作Updateontreatment治療 進(jìn)Background-Literature研究背Majorityofpatientswithunknowncauseforhaemorrhagicdiarrhoeadespiteextensivework-up>50%ofcaseswithacutehaemorrhagicdiarrhoeadeclaredidiopathic>50%的急性 犬性胃腸炎 研究方S.UNTERER,T.E.YOO,B.SCHULZ,K.ClinicofSmallAnimalMedicine,ilianUniversityMunich,JournalofVeterinaryInternalMedicine2008;22:1460)Background-Literature研究背景－文Idiopathicacutehaemorrhagicdiarrhoea自發(fā) firstdescribedin1972(Hill1972首次于1972definedasaspecificsyndromein1977:gastroenteritis(HGE)(Burrows, 性胃腸Background-Characteristics研究背景ToyandMiniaturebreeds(Hill,1972;Burrows,1977;PostandFeldman, Acutevomiting,oftenbloody急 ，常帶Acutehaemorrhagicdiarrhoea急 性腹(Burrows,1977;TrioloandLappin,Haematocrit (SpielmanandGarvey,Diagnosisofexclusion(ofcommoncausesforacutehaemorrhagicdiarrhoea)排除性診斷（排除急 性腹瀉的常見(jiàn)原因PatientwithHGErectalandurinarycatheterOutline大DefinitionofAHDS急 性腹瀉綜合征的定patientcharacteristics患犬特Updateonpathogenesis發(fā)病機(jī)理 研究進(jìn)roleofClostridiumperfringensandCl.產(chǎn)氣莢膜梭菌及其毒素所起的作Updateontreatment治療 進(jìn)Summaryofnew 研究方向簡(jiǎn)Question問(wèn)WhatWhatcharacterizeshaemorrhagicgastroenteritis(=acutehaemorrhagicdiarrhoeasyndrome)? 征犬的急 性腹瀉綜合征：108F.MORTIER,T.E.YOO,K.STROMEYER,K.HARTMANN,S.ClinicofSmallAnimalMedicine, ilianUniversityMunich,VetRec.2015Studygoals研究目DescriptionofsignalementclinicalcourselaboratorychangesIdentificationofparameterstodifferentiatebetweenHGEandotherdiseasescausinghaemorrhagic找出區(qū) MaterialandMethods材料和方Prospectivepatientrecruitment(n=預(yù)定病例招募數(shù)量Inclusioncriteria入選條件acutehaemorrhagicdiarrhoea(<3急 性腹瀉（<3天Exclusioncriteria排除條件knowncauseforhaemorrhagic已知引 性腹瀉的病Controlgroups對(duì)照12360patientsduringrecruitmentperiod招募期間12360只患MaterialsandMethods材料和方Diagnosticstoexcludeknowncausesofhaemorrhagicdiarrhoea排除已知病因引起的 物laboratorywork- 檢(haematology,chemistryincl.bileacidsandcPLI,coagulation（血液學(xué)檢查，生化檢查包括膽汁酸和犬胰腺炎，凝血功能檢查fecalexam糞(helminths,giardia, ,bacteria)（線蟲(chóng) 鞭毛蟲(chóng)，細(xì)小毒，細(xì)菌diagnosticimaging影像學(xué)診MaterialsandMethods:AHD- ActivityAppetite

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>MaterialsandMethods:AHD-材料與方法：急 ScoringSeverityScore得分0-4-6->notSummary小PraedispositionforAHDS:AHDS易youngtomiddleageddogs青年至中年toyandminiaturebreeds玩具和迷mostlypriortohaemorrhagicdiarrhoea大多數(shù)先 性腹瀉發(fā)Haematocritsignificantlyhigherthanincontroldogs顯著高于對(duì)照組only1/3ofdogs60只有1/3大于Goodprognosiswithintensivetherapy強(qiáng)化治療預(yù)后良Question問(wèn)WhichWhichmorphologicmucosalchangescanbefoundindogswithHGE?Endoscopicallyvisualizedlesions,histologicalfindingsandbacterialinvasioninthegastrointestinalmucosaofdogswithacutehemorrhagicdiarrheasyndrome急性 S.UNTERER,K.BUSCH,M.LEIPIG,W.HERMANNS,G.R.K.STRAUBINGER,K.ClinicofSmallAnimalMedicine,LMUMunich,InstituteofVeterinaryPathology,LMUMunich,InstituteforInfectiousDiseasesandZoonoses,LMUMunich,JournalofVeterinaryInternalMedicine2014;28:52-StudyGoal研究目Describe分type類ofendoscopicandhistologicchangesinthegastrointestinaltractofdogswithHGEHGE患犬胃腸道的內(nèi)窺鏡及組織學(xué)病MaterialsandMethods材料和方Prospectivepatientrecruitment10dogs預(yù)定病例Inclusioncriteriaacutehaemorrhagicdiarrhoea3daysExclusioncriteriaknowncauseofhemorrhagicdiarrhoea已知引起出MaterialsandMethods材料和方PatientshadtobestableforEndoscopicevaluationofgastrointestinaltractandretrivalofleast8biopsiesfromthefollowing stomachileumcolonResults–Endoscopic結(jié)果－內(nèi)窺鏡評(píng)GastricmucosanorelevantchangesareawithpronouncedchangeshighcasetocasevariabilityinseverityResults–Endoscopic結(jié)果－內(nèi)窺鏡評(píng)DuodenumshortenedDuodenumshortened腸絨毛縮necroticvilli腸hyperaemiain H&E,Colonnecrosisofaswellcryptlamina(PictureProf.W.Summary小GastricmucosanorelevanthistologicchangesDuodenalandcolonicmucosaacute,mostlynecrotisingseverityanddistributionvariablebetweenchangesincreaseinseverityfromproximaltointestinalOutline大DefinitionofAHDSAHDS的定Updateonpathogenesis發(fā)病機(jī)理 研究進(jìn)roleofClostridiumperfringensandCl.toxins產(chǎn)氣莢膜梭菌及其毒所起的作Updateontreatment治療 進(jìn)Summaryofnew 研究方向簡(jiǎn)Futureprojects/studies未來(lái)的研究課Question問(wèn)WhichroledoClostridiumspp.playinEndoscopicallyvisualizedlesions,histologicalfindingsandbacterialinvasioninthegastrointestinalmucosaofdogswithacutehemorrhagicdiarrheasyndrome急性 S.UNTERER,K.BUSCH,M.LEIPIG,W.HERMANNS,G.R.K.STRAUBINGER,K.ClinicofSmallAnimalMedicine,LMUMunich,GermanyInstituteofVeterinaryPathology,LMUMunich,GermanyInstituteforInfectiousDiseasesandZoonoses,LMUMunich,JournalofVeterinaryInternalMedicine2014;28:52-StudyGoal研究目DetectionofC.perfringenshistologyimmunhistologycultureinthesmallintestinaltractof10dogswithAHDS從10AHDS患犬的小腸中取MaterialsandMethods材料和方Biopsyforhistologyandendoscopyofsmallintestinessterilesingle-useforcepsinsertedthoughsterile通過(guò)無(wú)菌引導(dǎo)器插 firstduodenalbiopsyforculturesubmittedwithin30minutesof活檢樣本須在30分鐘內(nèi)送檢培Results–Histology結(jié)果－十二指腸組織學(xué)檢necroticnecroticvilli腸絨壞withinnecrosishighnumbersofshortdescribed?Clostridialtypebacteria“短桿菌，Giemsa(PictureProf.W.ResultsConfirmationofpresenceofClostridiumspp.insmallintestines(immunohistochemistryorculture確定小腸內(nèi)出現(xiàn)產(chǎn)氣莢膜梭菌（免疫組studygroupin10/10controlgroupin1/11Summary小C.perfringensseemstobeimportantinthediseasepathogenesisindogswithAHDS產(chǎn)氣莢膜梭菌似乎對(duì)犬significantlymoreoftenpresentinsmallintestinesindogsepitheliallesionscharacteristicforCperfringensinfectioninotherspecies上皮病灶符合典型的產(chǎn)氣莢膜梭菌特征（其它動(dòng)物種presenceofbacteriaandepitheliallesionscloselyassociated細(xì)菌noothercauseforepithelialnecrosisidentified沒(méi)有鑒別出其它導(dǎo)Question問(wèn)AreArespecificC.perfringensgenotypesresponsibleforAHDS?特 ofC.perfringensisolatesfromeightdogswithacutehaemorrhagicdiarrhoeasyndrome從8只AHDS患犬上分離出產(chǎn)氣莢膜梭 S.UNTERER,K.BUSCH,J.VERSPOHL,G.R.K.STRAUBINGER,K.ClinicofSmallAnimalMedicine,LMUMunich,InstituteforMicrobiologyandDepartmentofInfectiousDiseases,UniversityofVeterinaryMedicine,Hannover,GermanyInstituteforInfectiousDiseasesandZoonoses,LMUMunich,ECVIMcongress,StudyGoal研究目GenotyofC.perfringensstrainsisolatedfromduodenumindogswithAHDS對(duì)從AHDS患犬十二指腸獲得的產(chǎn)氣莢膜梭菌分離株進(jìn)行分型MaterialsandMethods材料和方Biopsyforbacterialculturesmallintestinalendoscopysterilesingle-useforcepsinsertedthroughsterile通過(guò)無(wú)菌引導(dǎo)器插 initialduodenumbiopsyforculturedonewithin30minutesof活檢樣本須在30分鐘內(nèi)送檢培8/11patientswithC.perfringensclassificationviaMALDI-TOFMS通過(guò)MALDI-TOFMaterialsandMethods材料和方MultiplexPCR多元PCRBaumsetalmajor

beta2 Results12345678(αtoxinα毒素++++++++(βtoxinβ毒素________(β2toxinβ2毒素_++++_+_(εtoxinε毒素________(ιtoxinι毒素________cpe________Summary小C.perfringenstypeAmostimportantgenotypeinAHDS型產(chǎn)氣莢膜梭菌是導(dǎo)致AHDS的最重要 ConclusionC.perfringensenterotoxinmostlikelynotresponsibleforepithelialdisruption產(chǎn)氣莢膜梭菌Outline大DefinitionofAHDSAHDS的定Updateonpathogenesis發(fā)病機(jī)理 進(jìn)roleofClostridiumperfringensandCltoxins產(chǎn)氣莢膜梭菌及其毒素起的作Updateontreatment治療 進(jìn)incidenceofbacteraemia菌血癥的發(fā)生indicationsforantibiotics使用抗生素的指Summaryofnewaspects新的研究方向簡(jiǎn)Futureprojects/studies未來(lái)的研究課Question問(wèn)AreArepatientswithAHDSatanincreasedriskforbacterialtranslocation/sepsis?Theclinicalsignificanceofbacterialtranslocationindogswithhaemorrhagicdiarrhoea急 性腹瀉綜合征患犬發(fā)生細(xì)菌遷移的臨床意S.UNTERER,E.LECHNER,R.S.MUELLER,G.R.K.STRAUBINGER,B.S.SCHULZ,K.ClinicofSmallAnimalMedicine,LMUMunich,InstituteforInfectiousDiseasesandZoonoses,LMUMunich,VetRec.2015StudyGoals研究目IncidenceofbacteriaemiaindogswithAHDSInfluenceofbacteraemiaonclinicalparametersselectedrelevantlaboratoryparameters有關(guān)的survivalrateMaterialsandMethodsBloodculture(studygroupn87controlgroupn21研究組87；對(duì)照組2sterilebloodsamplesdrawnfromjugularveinwithin30minutes30分鐘內(nèi)從頸靜脈抽取兩組無(wú)菌血液transfered intobloodculturesystems立即轉(zhuǎn)移到血液培養(yǎng)裝置ResultsPatientgroup14/87dogs(16%)withpositivein4/14dogscontaminants4/14例污incidenceofbacteraemia:11Controlgroup3/21dogs(14%)withpositivein0/3dogscontaminants0/3例污in3/3dogsbacterialtranslocation3/3例細(xì)菌遷incidenceofbacteriaemia:14ResultsDogswithAHDS(n10陽(yáng)性(n77陰性pHeartrateRespiratoryrateHospitalization33reportedasmedian記錄中ns:notsignificantafterBonferronins：用Bonferroni校正后差異不顯Results(n10(n77陰性pLeukocytesx109/l)Bandsx109/l)ALTU/LBilirubinμmol/lTotalproteing/l)Albuming/l)Glucosemmol/lreportedasmedian記錄中nsnotsignificantafterBonferronicorrectionns：用BonferroniSummary小IncidenceofbacteraemiaindogswithADHSlowandnotdifferenttothatinhealthydogsAHDS患犬的菌血癥發(fā)生率低與健康犬相較無(wú)差Bacteraemianoinfluenceonclinical菌血癥對(duì)病程發(fā)展無(wú)影ConclusionNodiagnosticvalueofbloodculturesindogswithADHSBenefitofantibioticsQuestion問(wèn)DoDopatientswithAHDSneedTreatmentofasepticdogswithhemorrhagicgastroenteritisamoxicillin/clavulanicacid:aprospectiveblinded使用阿莫西林克拉維酸鉀治療無(wú)菌 性胃腸炎犬：前瞻性單盲實(shí)S.UNTERER,K.STROHMEYER,B.D.KRUSE,C.SAUTER-LOUIS,ClinicofSmallAnimalMedicine,LMUMunich,ClinicforRuminants,LMUMunich,GermanyJournalofVeterinaryInternalMedicine;25:973-9StudyGoal研究目Evaluationofantibiotictreatmentwithamoxicillin/clavulanicacidindogswithAHDS MaterialsandMethods材料和方ProspectiveblindedtreatmentPatientgroupdogswithAHDS3 Placebo(n=Placebo(n=Treatment(n=AHDSpatients(n=60)AHDS患Results-Treatment結(jié)果－治療Nosignificantdifferenceinclinicalcourselengthofhospitalization(medianindays天數(shù)中值treatmentgroupplacebogroupstudydrop-outs/mortalityrate率Results-AHD結(jié)果－AHD指Placebo(n= Antibiotics(n=

DayDayDayDayDayDayDaySummary小Amoxicillin/ClavulanicacidhasnobenefitinpatientswiththathavenosignsofsepsisorasystemicinflammatoryAHDS患犬沒(méi)有幫Closepatientmonitoringnecessaryexclusionofbacterialinfectiondifficultriskofbacterialtranslocationsmallbutpresent細(xì)菌遷移的風(fēng)險(xiǎn)小NewInsights新的觀Clinicalpresentationandprogression臨床表現(xiàn)及病程發(fā)goodprognosiswithaggre