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201437

Fournier Gangrene

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FournierGangrene
Author:VernonMPaisJr,MDChiefEditor:BradleyFieldsSchwartz,DO,FACSmore...
Updated:Mar7,2013

Background
Fourniergangrenewasfirstidentifiedin1883,whentheFrenchvenereologistJeanAlfredFournierdescribeda seriesinwhich5previouslyhealthyyoungmensufferedfromarapidlyprogressivegangreneofthepenisand scrotumwithoutapparentcause.Thiscondition,whichcametobeknownasFourniergangrene,isdefinedasa polymicrobialnecrotizingfasciitisoftheperineal,perianal,orgenitalareas(seetheimagebelow.)Incontrastto Fournier'sinitialdescription,thediseaseisnotlimitedtoyoungpeopleortomales,andacauseisnowusually identified.

PhotomicrographofFourniergangrene(necrotizingfasciitis),oilimmersionat1000Xmagnification.Notetheacute inflammatorycellsinthenecrotictissue.Bacteriaarelocatedinthehazinessoftheircytoplasm.CourtesyofBillieFife,MD, andThomasA.Santora,MD.

Impairedimmunity(eg,fromdiabetes)isimportantforincreasingsusceptibilitytoFourniergangrene.Traumato thegenitaliaisafrequentlyrecognizedvectorfortheintroductionofbacteriathatinitiatetheinfectiousprocess.[1] Formoreinformation,seetheMedscapeReferencearticlesTesticularTrauma,ScrotalTrauma,PenileFracture andTrauma,andUrethralTrauma.

Historicalbackground
In1764,Baurienneoriginallydescribedanidiopathic,rapidlyprogressivesofttissuenecrotizingprocessthatled togangreneofthemalegenitalia.However,thediseasewasnamedafterJeanAlfredFournier,aParisian venereologist,onthebasisofatranscriptfroman1883clinicallectureinwhichFournierpresentedacaseof perinealgangreneinanotherwisehealthyyoungman,addingthistoacompiledseriesof4additionalcases.[2]He differentiatedthesecasesfromperinealgangreneassociatedwithdiabetes,alcoholism,orknownurogenital trauma,althoughthesearecurrentlyrecognizedriskfactorsfortheperinealgangrenenowassociatedwithhis name. ThismanuscriptoutliningFourniersinitialseriesoffulminantperinealgangreneprovidesafascinatinginsightinto boththesocietalbackgroundandthepracticeofmedicineatthetime.Inanecdotes,Fournierdescribed recognizedcausesofperinealgangrene,includingplacementofamistressringaroundthephallus,ligationofthe prepuce(usedinanattempttocontrolenuresisorasanattemptedbirthcontroltechniquepracticedbyan adulterousmantoavoidimpregnatinghismarriedlover,placementofforeignbodiessuchasbeanswithinthe urethra,andexcessiveintercourseindiabeticandalcoholicpersons.Hecallsuponphysicianstobesteadfastin
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obtainingconfessionfrompatientsofobscenepractices.

Anatomy
ThecomplexanatomyofthemaleexternalgenitaliainfluencestheinitiationandprogressionofFourniergangrene. Thisinfectiousprocessinvolvesthesuperficialanddeepfascialplanesofthegenitalia.Asthemicroorganisms responsiblefortheinfectionmultiply,infectionspreadsalongtheanatomicalfascialplanes,oftensparingthe deepmuscularstructuresand,tovariabledegrees,theoverlyingskin. Thisphenomenonhasimplicationsforbothinitialdebridementandsubsequentreconstruction.Therefore,a workingknowledgeoftheanatomyofthemalelowerurinarytractandexternalgenitaliaiscriticalfortheclinician treatingapatientwithFourniergangrene.

Skinandsuperficialfascia
BecauseFourniergangreneispredominatelyaninfectiousprocessofthesuperficialanddeepfascialplanes, understandingtheanatomicrelationshipoftheskinandsubcutaneousstructuresoftheperineumandabdominal wallisimportant. TheskincephaladtotheinguinalligamentisbackedbyCamperfascia,whichisalayeroffatcontainingtissueof varyingthicknessandthesuperficialvesselstotheskinthatrunthroughit.Scarpafasciaformsanotherdistinct layerdeeptoCamperfascia.Intheperineum,ScarpafasciablendsintoCollesfascia(alsoknownasthe superficialperinealfascia),whileitiscontinuouswithDartosfasciaofthepenisandscrotum(seetheimage below).

Fascialenvelopmentoftheperineum(male).NotehowCollesfasciacompletelyenvelopsthescrotumandpenis.Colles fasciaisincontinuitycephaladtotheleveloftheclavicles.Intheinguinalregion,thisfasciallayerisknownasScarpa fascia.Understandingthetendencyofnecrotizingfasciitistospreadalongfascialplanesandthefascialanatomy,onecan seehowaprocessthatstartsintheperineumcanspreadtotheabdominalwall,theflank,andeventhechestwall.

Severalimportantanatomicrelationshipsshouldbeconsidered.ApotentialspacebetweentheScarpafasciaand thedeepfasciaoftheanteriorwall(externalabdominaloblique)allowsfortheextensionofaperinealinfectioninto theanteriorabdominalwall.Superiorly,ScarpaandCamperfasciacoalesceandattachtotheclavicles,ultimately limitingthecephaladextensionofaninfectionthatmayhaveoriginatedintheperineum. Collesfasciaisattachedtothepubicarchandthebaseoftheperinealmembrane,anditiscontinuouswiththe superficialDartosfasciaofthescrotalwall.Theperinealmembraneisalsoknownastheinferiorfasciaofthe urogenitaldiaphragmand,togetherwithCollesfascia,definesthesuperficialperinealspace. Thisspacecontainsthemembranousurethra,bulbarurethra,andbulbourethralglands.Inaddition,thisspaceis adjacenttotheanterioranalwallandischiorectalfossae.Infectiousdiseaseofthemaleurethra,bulbourethral glands,perinealstructures,orrectumcandrainintothesuperficialperinealspaceandcanextendintothe scrotumorintotheanteriorabdominalwalluptotheleveloftheclavicles.

Vascularsupplytotheskinofthelowerabdomenandgenitalia
Branchesfromtheinferiorepigastricanddeepcircumflexiliacarteriessupplytheloweraspectoftheanterior abdominalwall.Branchesoftheexternalandinternalpudendalarteriessupplythescrotalwall.Withtheexception oftheinternalpudendalartery,eachofthesevesselstravelswithinCamperfasciaandcanthereforebecome thrombosedintheprogressionofFourniergangrene. Thrombosisjeopardizestheviabilityoftheskinoftheanteriorscrotumandperineum.Often,theposterioraspect ofthescrotalwallsuppliedbytheinternalpudendalarteryremainsviableandcanbeusedinthereconstruction followingresolutionoftheinfection.
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Penisandscrotum
Thecontentsofthescrotum,namelythetesticles,epididymides,andcordstructures,areinvestedbyseveral fasciallayersdistinctfromtheDartosfasciaofthescrotalwall.Again,severalimportantanatomicrelationships shouldbeconsidered. Themostsuperficiallayerofthetestisandcordistheexternalspermaticfascia,whichiscontinuouswiththe externalaponeurosisofthesuperficialinguinalring(externalabdominaloblique).Thenextdeeperlayeristhe internalspermaticfascia,whichiscontinuouswiththetransversalisfascia.AdeepfasciatermedBuckfascia coverstheerectilebodiesofthepenis,thecorporacavernosa,andtheanteriorurethra.Buckfasciafusestothe densetunicaalbugineaofthecorporacavernosa,deepinthepelvis. Thefasciallayersdescribedinthissectiondonotbecomeinvolvedwithaninfectionofthesuperficialperineal spaceandcanlimitthedepthoftissuedestructioninanecrotizinginfectionofthegenitalia.Thecorpora cavernosa,urethra,testes,andcordstructuresareusuallysparedinFourniergangrene,whilethesuperficialand deepfasciaandtheskinaredestroyed.

Pathophysiology
LocalizedinfectionadjacenttoaportalofentryistheincitingeventinthedevelopmentofFourniergangrene. Ultimately,anobliterativeendarteritisdevelops,andtheensuingcutaneousandsubcutaneousvascularnecrosis leadstolocalizedischemiaandfurtherbacterialproliferation.Ratesoffascialdestructionashighas23cm/h havebeendescribed. Infectionofsuperficialperinealfascia(Collesfascia)mayspreadtothepenisandscrotumviaBuckanddartos fascia,ortotheanteriorabdominalwallviaScarpafascia,orviceversa.Collesfasciaisattachedtotheperineal bodyandurogenitaldiaphragmposteriorlyandtothepubicramilaterally,thuslimitingprogressioninthese directions.Testicularinvolvementisrare,asthetesticulararteriesoriginatedirectlyfromtheaortaandthushave abloodsupplyseparatefromtheaffectedregion. ThefollowingarepathognomonicfindingsofFourniergangreneuponpathologicevaluationofinvolvedtissue: Necrosisofthesuperficialanddeepfascialplanes Fibrinoidcoagulationofthenutrientarterioles Polymorphonuclearcellinfiltration Microorganismsidentifiedwithintheinvolvedtissues Infectionrepresentsanimbalancebetween(1)hostimmunity,whichisfrequentlycompromisedbyoneormore comorbidsystemicprocesses,and(2)thevirulenceofthecausativemicroorganisms.Theetiologicfactorsallow theportalforentryofthemicroorganismintotheperineum,thecompromisedimmunityprovidesafavorable environmenttoinitiatetheinfection,andthevirulenceofthemicroorganismpromotestherapidspreadofthe disease.Seetheimagebelow.

Necrotizinginfectionresultsfrominfectionwithanextremelyvirulentmicroorganismor,mostcommonly,froma combinationofmicroorganismsactingsynergisticallyinasusceptibleimmunocompromisedhost.

Microorganismvirulenceresultsfromtheproductionoftoxinsorenzymesthatcreateanenvironmentconducive torapidmicrobialmultiplication.[3]AlthoughMeleneyin1924attributedthenecrotizinginfectionstostreptococcal speciesonly,[4]subsequentclinicalserieshaveemphasizedthemultiorganismnatureofmostcasesof necrotizinginfection,includingFourniergangrene.[5,6,7,8,9] Presently,recoveringonlystreptococcalspeciesisunusual.[10]Rather,streptococcalorganismsarecultured alongwithasmanyas5otherorganisms. Thefollowingarecommoncausativemicroorganisms:


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Streptococcalspecies Staphylococcalspecies Enterobacteriaceae Anaerobicorganisms Fungi Mostauthoritiesbelievethatpolymicrobialinvolvementisnecessarytocreatethesynergyofenzymeproduction thatpromotesrapidmultiplicationandspreadofFourniergangrene.[3]Forexample,onemicroorganismmight producetheenzymesnecessarytocausecoagulationofthenutrientvessels.Thrombosisofthesenutrient vesselsreduceslocalbloodsupplythus,tissueoxygentensionfalls. Theresultanttissuehypoxiaallowsgrowthoffacultativeanaerobesandmicroaerophilicorganisms.Theselatter microorganisms,inturn,mayproduceenzymes(eg,lecithinase,collagenase),whichleadtodigestionoffascial barriers,thusfuelingtherapidextensionoftheinfection. Fascialnecrosisanddigestionarehallmarksofthisdiseaseprocessthisisimportanttoappreciatebecauseit providesthesurgeonwithaclinicalmarkeroftheextentoftissueinvolvement.Specifically,ifthefascialplane canbeseparatedeasilyfromthesurroundingtissuebybluntdissection,itisquitelikelytobeinvolvedwiththe ischemicinfectiousprocesstherefore,anysuchdissectedtissueshouldbeexcised. FaradvancedorfulminantFourniergangrenecanspreadfromthefascialenvelopmentofthegenitaliathroughout theperineum,alongthetorso,and,occasionally,intothethighs.

Etiology
Althoughoriginallydescribedasidiopathicgangreneofthegenitalia,Fourniergangrenehasanidentifiablecause in7595%ofcases.[11]Thenecrotizingprocesscommonlyoriginatesfromaninfectionintheanorectum,the urogenitaltract,ortheskinofthegenitalia.[12] AnorectalcausesofFourniergangreneincludeperianal,perirectal,andischiorectalabscessesanalfissuresand colonicperforations.Thesemaybeaconsequenceofcolorectalinjuryoracomplicationofcolorectalmalignancy, [13,14]inflammatoryboweldisease, [15]colonicdiverticulitis,orappendicitis. Urogenitaltractcausesincludeinfectioninthebulbourethralglands,urethralinjury,iatrogenicinjurysecondaryto urethralstricturemanipulation,epididymitis,orchitis,orlowerurinarytractinfection(eg,inpatientswithlongterm indwellingurethralcatheters). Dermatologiccausesincludehidradenitissuppurativa,ulcerationduetoscrotalpressure,andtrauma.Inabilityto practiceadequateperinealhygiene,suchasinparaplegicpatients,resultsinincreasedrisk. Accidental,intentional,orsurgicaltrauma[16]andthepresenceofforeignbodiesmayalsoleadtothedisease. Thefollowinghavebeenreportedintheliteratureasprecipitatingfactors: Bluntthoracictrauma Superficialsofttissueinjuries Genitalpiercings Penileselfinjectionwithcocaine[17] Urethralinstrumentation Prostheticpenileimplants Intramuscularinjections Steroidenemas(usedforthetreatmentofradiationproctitis) Rectalforeignbody [18] Inwomen,septicabortions,vulvarorBartholinglandabscesses,hysterectomy,andepisiotomyaredocumented sources.Inmen,analintercoursemayincreaseriskofperinealinfection,eitherfromblunttraumatotheareaor byspreadofrectallycarriedmicrobes. Inchildren,thefollowinghaveledtothedisease: Circumcision Strangulatedinguinalhernia Omphalitis Insectbites Trauma Urethralinstrumentation
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Perirectalabscesses Systemicinfections

Pathogens
WoundculturesfrompatientswithFourniergangrenerevealthatitisapolymicrobialinfectionwithanaverageof4 isolatespercase.Escherichiacoliisthepredominantaerobe,andBacteroides isthepredominantanaerobe. Othercommonmicrofloraincludethefollowing: Proteus Staphylococcus Enterococcus Streptococcus (aerobicandanaerobic) Pseudomonas Klebsiella Clostridium

Predispositiontodisease
AnyconditionthatdepressescellularimmunitymaypredisposeapatienttothedevelopmentofFournier gangrene.Examplesincludethefollowing: Diabetesmellitus(presentinasmanyas60%ofcases)[19] Morbidobesity Alcoholism Cirrhosis Extremesofage Vasculardiseaseofthepelvis Malignancy(eg,acutepromyelocyticleukemia,acutenonlymphoidleukemia,acutemyeloblasticleukemia)
[20,21]

Systemiclupuserythematosus [22] Crohndisease HIVinfection[23] Malnutrition Iatrogenicimmunosuppression(eg,fromlongtermcorticosteroidtherapy)

Epidemiology
Fourniergangreneisrelativelyuncommon,buttheexactincidenceofthediseaseisunknown.Inareviewof Fourniergangrenein1992,Patyandcoworkerscalculatedthatapproximately500casesoftheinfectionhave beenreportedintheliteraturesinceFourniers1883report,yieldingaprevalenceof1casein7500persons.[24]A retrospectivecasereviewrevealed1726casesdocumentedintheliteraturefrom19501999,withanaverageof 97casesperyearreportedfrom19891998.[25] Otherresearchershavereportedapproximately600casesofFourniergangreneintheworldliteraturesince1996. [26]ThefrequencyofFourniergangrenehasnotlikelychangedappreciablyrather,theapparentincreaseinthe numberofcasesintheliteraturemostlikelyresultsfromincreasedreporting. Noseasonalvariationoccurs.Fourniergangreneisnotindigenoustoanyregionoftheworld,althoughthelargest clinicalseriesoriginatefromtheAfricancontinent.[27]

Sexualandagerelateddifferencesinincidence
ThetypicalpatientwithFourniergangreneisanelderlymaninhissixthorseventhdecadeoflifewithcomorbid diseases.Themaletofemaleratioisapproximately10:1.Lowerincidenceinfemalesmaybecausedbybetter drainageoftheperinealregionthroughvaginalsecretions.Menwhohavesexwithmenmaybeathigherrisk, especiallyforinfectionscausedbycommunityassociatedmethicillinresistantStaphylococcusaureus (MRSA).
[28]

Mostreportedcasesoccurinpatientsaged3060years.Aliteraturereviewfoundonly56pediatriccases,with 66%ofthoseininfantsyoungerthan3months.
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Prognosis
Largescrotal,perineal,penile,andabdominalwallskindefectsmayrequirereconstructiveprocedureshowever, theprognosisforpatientsfollowingreconstructionforFourniergangreneisusuallygood.Thescrotumhasa remarkableabilitytohealandregenerateoncetheinfectionandnecrosishavesubsided.However,approximately 50%ofmenwithpenileinvolvementhavepainwitherection,oftenrelatedtogenitalscarring.Consultationwitha psychiatristmayhelpsomepatientsdealwiththeemotionalstressofanalteredbodyimage. Ifextensivesofttissueislost,lymphaticdrainagemaybeimpairedthus,dependentedemaandcellulitismay result.Useofexternalsupportmaybebeneficialtominimizethispostoperativeproblem. Todate,themajorityofstudiesofFourniergangrenehavebeenretrospectivereviews.[29,30]Therefore,theutility ofdrawingreliableprognosticinformationfromthesestudiesisverylimited. In1995,LaorandcolleaguesintroducedtheFournierGangreneSeverityIndex(FGSI).[31]TheFGSIisbasedon deviationfromreferencerangesofthefollowingclinicalparameters: Temperature Heartrate Respiratoryrate Whitebloodcellcount Hematocrit Serumsodium Serumpotassium Serumcreatinine Serumbicarbonate Eachparameterisassignedascorebetween0and4,withthehighervaluesindicatinggreaterdeviationfrom normal.TheFGSIrepresentsthesumofalltheparametersvalues. LaorandcolleaguesdeterminedthatanFGSIgreaterthan9correlatedwithincreasedmortality.[31]TheFGSIhas beenvalidatedinseveralretrospectivestudies.[32,33,34] In2010,YilmazlarandcolleaguesupdatedtheFGSI(UFGSI),addingtwoadditionalparametersageandextent ofdiseasetofurtherrefinetheprognosticutilityoftheFGSI.[35] These2groupsconcludethatthemortalityriskingeneralmaybedirectlyproportionaltotheageofthepatient andtheextentofdiseaseburdenandsystemictoxicityuponadmission.Factorsassociatedwithanimproved prognosisincludeageyoungerthan60years,localizedclinicaldisease,absenceofsystemictoxicity(eg,low FGSI),andsterilebloodcultures.[36,35] Mostrecently,Roghmannetalqueriedwhethertheseincreasinglycomplexscoringsystemsactually outperformed2existingandlessburdensomemorbidityscoringsystems,theageadjustedCharlsonComorbidity Index(ACCI)andthesurgicalAPGARscore(sAPGAR).[37]Theybothassessedthisretrospectivelythen prospectivelywitha30dayfollowup.TheynotedthatACCIandsAPGARperformedaswellastheFGSIand UFGSIandwereeasiertocalculateatthebedside.Again,increasingageandmedicalcomorbiditieswere associatedwithincreasedriskofdeath.[37] Surprisingly,diabetesandHIVinfectionarenotassociatedwithhighermortality.Insomestudies,Fournier gangrenethatoriginatesfromanorectaldiseasescarriesaworseprognosisthancasescausedbyotherfactors. ThereportedmortalityratesforFourniergangrenevarywidely,rangingashighas75%.However,inthe600 casesofFourniergangrenediscoveredduringaMedlinesearchdatingbackto1996,100deathsoccurred,fora mortalityrateof16.5%.Intheseriesthatincludedmorethan20patients,themortalityraterangedfrom454%, withmoststudiesreportingmortalityratesof2030%.[38,39] Factorsassociatedwithhighmortalityincludeananorectalsource,advancedage,extensivedisease(involving abdominalwallorthighs),shockorsepsisatpresentation,renalfailure,andhepaticdysfunction.[40] Deathusuallyresultsfromsystemicillness,suchassepsis(usuallygramnegative),coagulopathy,acuterenal failure,diabeticketoacidosis,ormultipleorganfailure.FataltetanusassociatedwithFourniergangrenehasbeen reportedintheliterature.

ContributorInformationandDisclosures
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Author VernonMPaisJr,MDAssistantProfessor,DepartmentofSurgery,SectionofUrology,DartmouthMedical School VernonMPaisJr,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,American UrologicalAssociation,EndourologicalSociety,SigmaXi,andSocietyofLaparoendoscopicSurgeons Disclosure:Nothingtodisclose. Coauthor(s) ThomasSantora,MDProfessorandViceChairforClinicalAffairs,DepartmentofSurgery,TempleUniversity Hospital,TempleUniversitySchoolofMedicine ThomasSantora,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationfortheSurgeryof Trauma,AmericanCollegeofSurgeons,AmericanTraumaSociety,AssociationforAcademicSurgery,and EasternAssociationfortheSurgeryofTrauma Disclosure:Nothingtodisclose. DanielBRukstalis,MDDirectorofUrologicalServices,GeisingerMedicalCenter,GeisingerMedicalGroup DanielBRukstalis,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationforthe AdvancementofScienceandAmericanUrologicalAssociation Disclosure:Nothingtodisclose. ChiefEditor BradleyFieldsSchwartz,DO,FACSProfessorofUrology,Director,CenterforLaparoscopyand Endourology,DepartmentofSurgery,SouthernIllinoisUniversitySchoolofMedicine BradleyFieldsSchwartz,DO,FACSisamemberofthefollowingmedicalsocieties:AmericanCollegeof Surgeons,AmericanUrologicalAssociation,AssociationofMilitaryOsteopathicPhysiciansandSurgeons, EndourologicalSociety,SocietyofLaparoendoscopicSurgeons,andSocietyofUniversityUrologists Disclosure:Nothingtodisclose. AdditionalContributors AndrewAAronson,MD,FACEPVicePresident,PhysicianPractices,BravoHealthAdvancedCareCenter ConsultingStaff,DepartmentofEmergencyMedicine,TaylorHospital AndrewAAronson,MD,FACEPisamemberofthefollowingmedicalsocieties:AmericanCollegeof EmergencyPhysicians,MassachusettsMedicalSociety,andSocietyofHospitalMedicine Disclosure:Nothingtodisclose. AlexJacocks,MDProgramDirector,Professor,DepartmentofSurgery,UniversityofOklahomaSchoolof Medicine Disclosure:Nothingtodisclose. RichardLavely,MD,JD,MS,MPHLecturerinHealthPolicyandAdministration,DepartmentofPublicHealth, YaleUniversitySchoolofMedicine RichardLavely,MD,JD,MS,MPHisamemberofthefollowingmedicalsocieties:AmericanCollegeof EmergencyPhysicians,AmericanCollegeofLegalMedicine,andAmericanMedicalAssociation Disclosure:Nothingtodisclose. EricLLegome,MDChief,DepartmentofEmergencyMedicine,KingsCountyHospitalCenterAssociate Professor,DepartmentofEmergencyMedicine,NewYorkMedicalCollege EricLLegome,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanAcademy ofEmergencyMedicine,AmericanCollegeofEmergencyPhysicians,CouncilofEmergencyMedicine ResidencyDirectors,andSocietyforAcademicEmergencyMedicine Disclosure:Nothingtodisclose. MichaelTMarynowski,DOStaffPhysician,DepartmentofEmergencyMedicine/InternalMedicine,Allegheny
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GeneralHospital Disclosure:Nothingtodisclose. DavidLMorris,MD,PhD,FRACSProfessor,DepartmentofSurgery,StGeorgeHospital,UniversityofNew SouthWales,Australia DavidLMorris,MD,PhD,FRACSisamemberofthefollowingmedicalsocieties:BritishSocietyof Gastroenterology Disclosure:RFAMedicalNoneDirectorMRCBiotecNoneDirector ErikDSchraga,MDStaffPhysician,DepartmentofEmergencyMedicine,MillsPeninsulaEmergency MedicalAssociates Disclosure:Nothingtodisclose. RichardHSinert,DOAssociateProfessorofEmergencyMedicine,ClinicalAssistantProfessorofMedicine, ResearchDirector,StateUniversityofNewYorkCollegeofMedicineConsultingStaff,Departmentof EmergencyMedicine,KingsCountyHospitalCenter RichardHSinert,DOisamemberofthefollowingmedicalsocieties:AmericanCollegeofPhysiciansand SocietyforAcademicEmergencyMedicine Disclosure:Nothingtodisclose. FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenter CollegeofPharmacyEditorinChief,MedscapeDrugReference Disclosure:MedscapeSalaryEmployment ToddThomsen,MDInstructorinMedicine,ConsultingStaff,DepartmentofEmergencyMedicine,Mount AuburnHospital ToddThomsen,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergency Physicians,MassachusettsMedicalSociety,PhiBetaKappa,andSocietyforAcademicEmergencyMedicine Disclosure:Nothingtodisclose.

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