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假体周围关节感染的诊断与治疗的现状及展望（2024）假体周围关节感染的诊断与治疗的现状及展望（2024）CurrentStatusandPerspectivesofDiagnosisandTreatmentofPeriprostheticJointInfectionZhouH,YangY,ZhangY,LiF,ShenY,QinL,HuangW.CurrentStatusandPerspectivesofDiagnosisandTreatmentofPeriprostheticJointInfection[J].InfectDrugResist,2024,17:2417-2429.转载文章的原链接1：https://pubmed.ncbi.nlm.nih.gov/38912221/转载文章的原链接2：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192293/AbstractPeriprostheticjointinfection(PJI)isacatastrophiccomplicationfollowingjointreplacementsurgery,posingsignificantchallengestoorthopedicsurgeons.Duetothelackofadefinitivediagnosticgoldstandard,timelytreatmentinitiationisproblematic,resultinginsubstantialeconomicburdensonpatientsandsociety.Inthisreview,wethoroughlyanalyzethecomplexitiesofPJIandemphasizetheimportanceofaccuratediagnosisandeffectivetreatment.Thearticlespecificallyfocusesontheadvancementsindiagnostictechniques,rangingfromtraditionalpathogenculturetoadvancedmoleculardiagnostics,anddiscussestheirroleinenhancingdiagnosticaccuracy.Additionally,wereviewthelatestsurgicalmanagementstrategies,includingeverythingfromdebridementtorevisionsurgeries.OursummaryaimstoprovidepracticalinformationforthediagnosisandtreatmentofPJIandencouragesfurtherresearchtoimprovediagnosticaccuracyandtreatmentoutcomes.假体周围感染(PJI)是关节置换术后的一种灾难性并发症，给骨科医生带来了巨大的挑战。由于缺乏明确的诊断金标准，及时开始治疗存在困难，导致患者和社会承受了巨大的经济负担。在这篇综述中，我们全面分析了PJI的复杂性，强调了准确诊断和有效治疗的重要性。文章特别关注了诊断技术的进步，从传统的病原体培养到先进的分子诊断，并讨论了它们在提高诊断准确性方面的作用。此外，我们还回顾了最新的手术管理策略，包括从清创到翻修手术的一切内容。我们的总结旨在为PJI的诊断和治疗提供实用信息，并鼓励进一步的研究以提高诊断准确性和治疗效果。Keywords:arthroplasty,periprostheticjointinfection,PJI,moleculardiagnosis,pathogenesisdiagnosis,antibioticapplication,recurrenceofinfectionIntroductionProstheticjointinfection(PJI)isacommoncomplicationfollowingjointreplacementsurgery,withanincidencerateofonly1–3%,yetitoftenleadstodisastrousconsequences.1Approximately15%ofrevisionsurgeriesafterjointreplacementareduetoinfections(Figure1A).2Furthermore,StaphylococcusaureusisthemostprevalentpathogenincasesofPJI,accountingforover60%ofinstances.3ItshighvirulenceandpropensitytorecurposesignificantchallengestothetreatmentofPJI.3,4TheoccurrenceofPJInotonlyseverelydamagespatients’physicalandmentalhealthbutalsoimposessubstantialeconomicburdensonfamiliesandthehealthcaresystem.5,6ItisestimatedthatthetotalcostofsecondaryrevisionsurgeriesforPJIismorethandoublethatofasepticrevisions.7PreventionisknowntobethemosteffectivestrategyforPJI,buttimelyandaccuratediagnosisofPJIremainscriticalforeffectivetreatment.ThebiologyofthecausativemicroorganismsandtheindividualizedinflammatoryresponseofthepatientposesignificantchallengestotheaccuratediagnosisofPJI.DespitethefactthatauthoritativeorganizationsincludingtheMusculoskeletalInfectionSociety(MSIS),8theEuropeanBoneandJointInfectionSociety(EBJIS),9andtheAmericanAcademyofOrthopaedicSurgeons(AAOS)havepublishedandregularlyupdatednumerousdiagnosticcriteriaforperiprostheticjointinfection(PJI),10thereremainsalackofaunified,widelyrecognizedgoldstandardfortheaccuratediagnosisofPJI.11–14Ofcourse,intermsoftreatment,howtoavoidrecurrenceofinfectionwhilerestoringthefunctionoftheaffectedlimbistheultimategoalofPJItreatment.OngoingeffortsbymedicalandscientificprofessionalshaveledtonotableadvancementsinPJIdiagnosisandtreatmentinrecentyears.Basedonthecurrentstateofresearchandclinicalreview,thisarticlefocusesonthemoleculardiagnosisandpathogendetectionofPJIaswellasitscurrentmainstreamtherapeuticstrategies(Figure1).8.PJ,TlT,GK,etal.The2018definitionofperiprosthetichipandkneeinfection:anevidence-basedandvalidatedcriteria.JArthroplasty.2018;33(5).doi:10.1016/j.arth.2018.02.0789.McNallyM,SousaR,Wouthuyzen-BakkerM,etal.TheEBJISdefinitionofperiprostheticjointinfection.BoneJtJ.2021;103-B(1):18–25.doi:10.1302/0301-620X.103B1.BJJ-2020-1381.R110.TubbCC,PolkowksiGG,KrauseB.Diagnosisandpreventionofperiprostheticjointinfections.JAmAcadOrthopSurg.2020;28(8):e340.doi:10.5435/JAAOS-D-19-00405Figure1DiagnosisandepidemiologyofPeriprostheticjointinfection(PJI).(A)EpidemiologyofPJI.(B)MolecularbiologyandPathogendiagnosisprocessinPJI.(C)SerologicTestingofPJI.(D)JointAspirationandSynovialFluidAnalysis.(E–G)CT/BoneScintigraphy/MRIimageofPJIpatient.MaterialsandMethodsInthisnarrativereview,weutilizedthecriteriafromtheScalefortheAssessmentofNarrativeReviewArticles(SANRA)asastandardtoenhancethequalityofourmanuscriptmethodologically.15Thisarticlefocusesonaddressingseveralkeyquestions:HowdothelatestmoleculardiagnostictechniquesimprovethedetectionratesofPJI?HowcanimprovementsinetiologicalexaminationmethodsleadtofasterandmoreaccurateidentificationofthepathogensresponsibleforPJI?WhataretheadvancementsinsurgicaltechniquesandantibioticstrategiesinthemanagementofPJI?Forourliteraturesearch,weusedthefollowingkeywords:“PeriprostheticJointInfection”,“Diagnosis”,“MolecularDiagnostics”,“Biofilm”,“SurgicalManagement”,“Antibiotic”inthePubMeddatabasetoidentifyarticlesrelevanttoourtopic.Afterrigorousrelevancescreening,thesearticleswereultimatelyincludedinourreview.DiagnosisToenhancetheaccuracyofdiagnosingPJI,manyexpertsandorganizationshavedevelopedaseriesofdiagnosticcriteria.8–10Typically,thesecriteriaencompassbloodmarkers(C-reactiveprotein,sedimentationrate,etc.),jointfluidanalysis,bacterialcultures,andotherspecificmicrobiologicallaboratorytests.Despitethesecriteriaandguidelines,diagnosingPJIcontinuestobechallengingduetothelimitationsofexistingtests,thebiologyofcausativemicroorganisms,patientclinicalpresentationvariability,andotherfactors.Moreover,nosingletestexiststhatcanperfectlydiagnosePJI.ClinicalSignsWiththecontinuousadvancementoftechnology,theaccuracyoflaboratorydiagnosticsandradiologicaltechniquesforPJIhassignificantlyimproved.Nevertheless,theevaluationofassociatedclinicalsymptomsandsignsremainsthecornerstonefortheearlyassessmentofPJIconditions.InallrelevantPJIdiagnosticcriteria,asinustractcommunicatingwiththeprosthesisorjointisconsideredaspecificclinicalmanifestationofPJI.9,16BesidesfocusingonthespecificclinicalmanifestationsofPJI,clinicalfeaturessuchasfever,erythema,swelling,pain,andjointdysfunction,althoughnotuniquetoPJI,indeedincreasethelikelihoodofinfectionwhenpresent.17,18Rapidrecognitionofthesesymptomsandpromptinitiationoffurtherevaluationarecriticalforachievingoptimaltreatmentoutcomesinpatientswithperiprostheticjointinfections.MolecularDiagnosisofPeriprostheticJointInfectionSerologicTestingInrecentyears,biomarkershaveemergedasaresearchhotspotinPJIdiagnosisresearch.Previously,themainserologicindicatorstoassistinthediagnosiswereerythrocytesedimentationrate(ESR),C-reactiveprotein(CRP),interleukin-6(IL-6),etc.19,20(Figure1B)Yet,theseindicatorslackspecificityforpathogenicinfections,makingitchallengingforclinicianstomakedefinitivejudgments.21Recently,D-dimer,aproductoffibrindegradation,hasbeenidentifiedasapromisingmarkerfordiagnosingPJI.22Incurrentclinicalapplications,D-dimerisusedtoassesswhetherpatientsarehypercoagulableandtopredicttheriskofdeepveinthrombosisinthelowerextremities.23Fibrincanintensifytheinflammatoryresponse.ElevatedD-dimerlevelshavebeenlinkedtoinfectionsorsepsisinpatients.8Iskanderetalnotedthatinfection-inducedendothelialcelldamageleadstoplateletandmonocyteactivation,disruptingthefibrinolyticsystemandpotentiallycausingmicrothrombosisinmicrovessels,indicatedbyincreasedcirculatingD-dimerlevels.24Therefore,thereisasolidtheoreticalbasisforusingD-dimerasamarkertopredictpathogenicinfections.PannuetalshowedinacohortanalysisthatserumD-dimerlevelsweresignificantlyhigherinpatientswithPJIcomparedtothosewithasepticlooseningfollowingarthroplasty,identifying850ng/mLastheoptimalcutoffvalueforPJIdiagnosis.25Meanwhile,ourstudyalsoexpandedtheapplicationofD-dimer,analyzingitsuseinpatientswithcommonchronicPJI.WedeterminedthattheoptimalthresholdfordiagnosingchronicPJIusingD-dimeris1170ng/mL,withasensitivityof92.73%andaspecificityof74.63%.26Intherevised2018PJIdiagnosticcriteria,D-dimerwasincludedasasecondaryadjunctivediagnosticstandard.27However,inthecurrentstudy,thediagnosticspecificityofD-dimerasanovelserummarkerforPJIwasfoundtobeunsatisfactory.28Therefore,refiningthediagnosticspecificityofPJIcontinuestobeafocalpointinongoingresearch.JointAspirationandSynovialFluidAnalysisPreoperativearthrocentesisplaysapivotalroleindiagnosingPJI.Unlikeserology,jointfluiddetectionisdistinctasserummarkerscanbeinfluencedbyacuteorchronicinflammatorydiseasesinvariousorgansandsystemsofthebody,whereasinflammatoryanalysisofjointfluid,owingtoitslimitedfluidityandcontainmentwithinthejointcapsule,offersatruerreflectionofthelocalinflammatorycondition(Figure1C).29Preoperativesynovialfluidaspirationinpatientswithsuspectedinfectionsallowsforthedetectionofleukocytecountandpolymorphonuclearcellpercentage,aswellaspathogenculture.30,31Thisimprovesdiagnosticaccuracyandprovidesessentialinformationforformulatingtargetedtreatmentplans.32Zaharetalreportedthatthesensitivityofsynovialfluidleukocytecountsandpolymorphonuclearcellpercentagesfordiagnosisexceeds80%,indicatingsubstantialdiagnosticvalue.33Additionally,advancementsinsynovialfluidresearchhaveledtotheidentificationofnumerousbiomarkers.34,35Deirmengianetalobservedthatthelevelsofvariousbiomarkers,includingIL-1,IL-6,andGranulocyteColony-StimulatingFactor(G-CSF),areelevatedinthesynovialfluidofpatientswithPJI,demonstratinghighsensitivityandspecificity.36ThesenovelcytokineshavesignificantlyenhancedthediagnosticaccuracyforPJI.36ItshouldbenotedthatCRP,acommonlyusedserologicalindicator,rapidlyrespondstotissueinjuryorinfection,demonstratinghighsensitivitybutlimitedspecificityforlocalizedoccultinfections.However,detectingCRPinjointfluidhasbeenfoundtoenhanceitsdiagnosticspecificityforPJI.HuangWei’sgroupdiscoveredthatusingacombinationofserumandsynovialfluidCRP(serumCRP＞10.2mg/LandsynovialfluidCRP＞7.26mg/L)todiagnosePJIachievesasensitivityof97.44%andaspecificityof100%.Thisapproachnotonlyenhancesdiagnosticaccuracybutalsoreducesmedicalcosts.37Thetest’sspecificityreached100%,enhancingaccuracyandreducingmedicalcostssimultaneously.ExplorationofnovelmolecularmarkersforPJIcontinues,includingα-defensin,CD14,TREM-1,TLR2,andtheCD64index,whichhaveshownhighpotentialfordiagnosis.Furthervalidationthroughadditionalresearchisnecessary.38–40MolecularBiologyAlthoughthecurrentmolecularmarkerdiagnosisofPJIhasachievedexcellentresults.Thereisstillnomarkerthatcandirectlyconfirmthediagnosis,somorescholarscontinuetoexplorenewmethodstoaccelerateandaccuratelydiagnosePJIandidentifythepathogenicorganisms.Advancementsinmolecularbiologytechniqueshavebeenparticularlynotable(Figure1D).PolymeraseChainReaction(PCR)PCRtechnologyplaysacrucialroleinthediagnosisofmicrobesandisextensivelyusedinthefieldofPJIduetoitshighsensitivityandspecificity.41Thistechnique,byemployingspeciallydesignedprimers,amplifiestargetgenesthousandstomillionsoftimes,enablingthedetectionofpathogengenesevenatverylowlevelsinsamples.ItprovidesavitalbasisforthediagnosisofPJI.PCRcanbebroadlycategorizedintospecificPCR,multiplexPCR,andbroad-rangePCRbasedonthedifferentprimersused.42SpecificPCRSpecificPCRdesignsprimersforparticulargenefragmentsofspecificbacteriaandamplifiesthem.43Althoughithashighsensitivityandspecificity,theprimersinthespecificPCRreactionsystemaresingular,makingitdifficulttoscreenforPJI.Therefore,itisrarelyusedclinically.44MultiplexPCRTheprincipleofmultiplexPCRtechnologyisbasedonincorporatingmultiplesetsofprimersintothesamePCRreactionsystem,allowingthesimultaneousparallelamplificationofmultipletargetDNAfragmentsinasingleexperiment.44Thismethodcansimultaneouslydetectavarietyofcommonpathogenicmicroorganismsandtheirassociatedresistancegenes(suchasmecA,vanA,vanB),45,46greatlyimprovingdetectionefficiencyandspecificity.IthasbeenwidelyappliedinthefieldofPJI.47–50RenzetalhavefoundthatmultiplexPCRisparticularlyeffectiveatdetectinglow-virulencepathogens,outperformingtraditionalculturingmethodsinidentifyingpathogenssuchasCutibacteriumspp.andcoagulase-negativestaphylococci.49Horcajadaetalhaveappliedultrasonicationtoremovedprostheticcomponents,followedbymultiplexPCRonthesonicatedfluid,furtherenhancingthesensitivity(96%)andspecificity(100%)ofmultiplexPCR.48However,thelimitationofmultiplexPCRliesinitsabilitytoonlydetectspecificpathogenstargetedbytheprimers,posingchallengesinidentifyingPJIscausedbyrarepathogens.Malandainetalalsoobservedinaretrospectivemulticenterstudythat,of276culture-positivesamples,only119(47%)werepositiveinmultiplexPCR,suggestinglimitationsinitspracticalapplication.50Moreover,theuseofmultipleprimerpairsinmultiplexPCRreactionscanleadtoprimercross-reactionsandincreasesthecomplexityofsettingreactionconditions.51Broad-RangePCRBroad-rangePCR,whichtargetsthehighlyconserved16srDNAgeneinbacteria,simplifiesthereactionsystem.43Followinggeneamplification,Sangersequencingisusedtoidentifythespecificbacterialspecies.Pateletalhaveprocessedprostheticcomponentsremovedduringrevisionsurgerieswithultrasonication,followedbymultiplexPCR,andfoundthatbroad-rangePCRandcultureofsonicatefluidshowedsimilardiagnosticperformance,withasensitivityof70.4%andspecificityof97.8%fordiagnosingPJI.52ZhangetalinaretrospectivestudyfoundthatusingjointfluidandsonicatedfluidassamplesforPCRprovideshighersensitivity(83.0%and84.9%,respectively)comparedtousingperiprosthetictissue(34.0%).53Theresultsofbroad-rangePCRareoftenaffectedbyvariousfactors,includingdifferenttestingsamplesandreagents,showingconsiderablevariabilityandahigherrateoffalsepositives.Additionally,issuessuchascontaminationwithforeignbacterialDNAcanimpacttheaccuracyofresults.54AlthoughcurrentstudieshavemethodstodealwiththisforeignDNA,suchasusingultravioletirradiationorreducingthenumberofPCRcycles,thesecancompromisesensitivitytosomeextent.54Therefore,theresultsofbroad-rangePCRinthediagnosisofPJIneedtobecarefullyconsidered.Recently,othertechniqueshavebeenusedinconjunctionwithPCRwithgoodresults,suchasthemicrofluidicplatformdevelopedbyWen-HsinChangwhichallowsrapiddetectionandtypingofviablebacteriainpatients’jointfluids.Inaddition,themicrofluidicsystemisautomatedandrequireslittlehumanintervention,allowingrapiddiagnosisofPJIintheoperatingroom,withpotentialclinicalapplications.55MetagenomicNextGenerationSequencingTheadventofnextgenerationsequencingtechnologiesbasedonmetagenomicshasprovidedanewapproachtothediagnosisofPJI.Metagenomicnextgenerationsequencing(mNGS)referstothesequencingoftheentireDNAorRNAofasamplewithouttheuseofspecificprimersorprobes,incomparisonwithmicrobialgeneticdatabases.56Theuseofmetagenomicnextgenerationsequencing(mNGS)technologynotonlyidentifiesthespeciesofmicroorganismsthatcausedisease,butalsodetectsresistancegenesintheseinfectedmicroorganisms,whichcanhelpjointsurgeonschoosemorefavorabletreatmentoptions.Inmoststudy,mNGSshowedhighdiagnosticvalueinthediagnosisofperiprosthetictissueinfections,withahighsensitivityof95%andspecificityof90%.57,58However,thepresenceofhumannucleicacidsaswellassynovialmicrobiomeintissue-derivedsamplescanleadtomorecomplexdataanalysisbymNGSandmayresultinmissedmicrobialsequencesortypingerrors.59EffectiveenrichmentofmicrobialDNAwillthereforebekeytoimprovingthesensitivityofmacrogenomicapproaches.Currently,theuseofmethylatedCpG-specificbindingproteinMBD2,whichisfusedtohumanIgGFcfragments,andtheuseofproteinA-bindingmagneticbeadstoselectivelybindtohumanDNAcanachievetheeffectofremovinghumanDNA.AswellastheuseofchaotropicreagentsthatselectivelydisrupthumancellsanduseDNaseenzymestodegradetheDNAreleasedfromcelldisruptionbeforeextractingthemicrobialDNA.BothofthesemethodshelptoreducethebackgroundinthesequencingdataandhelptoanalyzethemicrobialDNAinamorefocusedmanner.MatthewThoendelusedbothofthesemethodstotreatprostheticAftersonicationofthefluid,itwasshownthatthelatterwasmoreefficientinenrichment,butmayhavethelimitationofbeingdifficulttoapplydirectlyonsolidtissuesamplesagain.60Inadditiontothesemolecularmethods,therecentadventofmatrixassistedlaserdesorption/ionizationtime-of-flightmassspectrometry(MALDI-TOFMS)forrapididentificationofmicroorganismsusingproteomics,aswellasthedevelopmentandadvancementofanti-biofilmantibodies,fluorescenceinsituhybridization,andgenechipshavebeenaboontopatientswithPJI.However,itisstillalongtimebeforethesetechniquescanbeimplementedinmostmedicalinstitutions,andthehighcostofmedicaltreatmentisalsoaconcernforhealthcareprofessionals.61–63PathogenDetectionTissueCultureCulturingthepathogeninthetissuesurroundingtheprosthesisisthestrongestevidenceforthediagnosisofPJI.However,theaccuracyoftissuecultureisaffectedbythesamplingmethod,sampletype,samplesize,andtypeofculturemedium;therefore,effectiveavoidanceoftheseproblemsduringthecultureprocesswillhelptoincreasetheculturepositivityrate.Intraoperativesamplingandcultureisamorereliablemethodofidentifyinginfectiousagentsthanpreoperativesynovialfluidaspiration.Inaretrospectivestudyinvolving167incidentPJIs,NoraRenz’steamfoundthattheconcordancebetweenpreoperativeculturesandintraoperativecultureswasonly52%,andthatupto38%ofcaseshadnegativepreoperativeculturesbutpositiveintraoperativecultures.64Inaddition,swabcollectionshouldbeavoidedwhencollectingsamplesbecauseswabsincreasetheriskofcross-contaminationwhencollectingsamplesandhavedifficultyreachingdeeptissues,whichcangreatlyinterferewiththeresultsofcultures.Austinetal,bycomparingintraoperativecollectionoftissuesamplesversusswabcollectionofculturesinthediagnosisofPJI,foundthattheintraoperativesamplingculturegrouphadasensitivity(93%versus70%),specificity(98%versus89%),NPV(93%versus68%),PPV(98%versus90%)werehigherthanthoseoftheswabculturegroup,andalsocametothesameconclusionsasabove.65Inaddition,whencollectingsamplesintraoperatively,fourtosixtissuesamples四到六个组织样本shouldbecollectedfrommultiplesites,inordertoincreasethesensitivityoftheculture.Aprospectivemulticenterstudyrecommendedthatbestpracticeistocollectculturesfromtissuesincontactwithmaterialandjointfluidandtohavethesurgeoninoculatethemdirectlyintobloodculturebottles血培养瓶,whicharethensenttothelaboratoryforculture.66However,antibiotictherapyforPJIposesasignificantchallengetothetraditionalintraoperativeculturemodel.Antibioticadministrationreducesbacterialloadandmediatesbacterialdormancy细菌休眠leadingtofalse-negativeresults.Berbarifoundthat53%ofpatientswithCulture-negativePJIreceivedantibiotictherapypriortodiagnosisofPJI.67Furthermore,withoutadefinitivepathogendiagnosis,choosingtheappropriateantibioticbecomesmoredifficultanduncertain.Therefore,inconjunctionwiththerecommendationsoftheAmericanAcademyofOrthopaedicSurgeonsandtheInfectiousDiseasesSocietyofAmericapracticeguidelines,antibioticsshouldbediscontinuedatleast14days14天priortoculturinginpatientsingoodgeneralcondition.UltrasonicandChemicalTreatmentofCulture超声波和化学处理的培养Theabilityofpathogenstoformclosedbiofilms封闭的生物膜onprostheticandbonesurfacessignificantlycomplicatestraditionalculturemethods.Consequently,toenhancediagnosticaccuracy,scientistsareexploringinnovativeculturetechniques,withsonicationandchemicaltreatmentshowingpromisingadvantages.Ultrasonicationisamethodinwhichsurgicallyremovedimplantsaretreatedwithlow-frequencyultrasoundandthentheultrasonicatedsolutionisinoculatedforculture.Ultrasoundcandirectlydisruptthebiofilmstructureformedbypathogensandreleasethebacteria,thuseffectivelyincreasingthesensitivityoftheculture.ThemostclassicalultrasoundmethodwasproposedbyTrampuzA.68Thesurgicallyremovedimplantwasplacedinacontainercontaining400mLofLactatedRinger’ssolution.Then,itwasvortexed,sonicated,andvortexedagaininsequence.Thesolutionwastheninoculatedontoaerobicandanaerobicbloodagarplatesforcultureaspertissueculture.Finally,microorganismswerecountedandclassifiedusingconventionalmicrobiologicaltechniques(Figure1D).68Optimalsensitivity82%(76–87%),andspecificity99%(98–100%)isachievedwhenathresholdvalue≥5CFUisused.69AlthoughseveralstudieshavenowdemonstratedthatthesensitivityofculturesafterultrasoundtreatmentissignificantlyimprovedinPJIcomparedtoconventionaltissueculture(61%versus79%).69However,AndrewJ.Brentpointedoutthattherearefewstudiescomparingultrasoundtreatmenttotherecommended4to6tissuesamplesortoautomatedculturemethodsthathavebeenshowntooptimizeculturesensitivity.Whereastheirresultsshowedthatthesensitivityoftissueculturewas69%(63–75%)betterthanthesensitivityofultrasoundculture57%(50–63%),inthatstudy,apositiveultrasoundculturewasplaced＞50CFU/mL,andthethresholdwas10CFU/mL,whichwouldhavehadsomeimpactonthesensitivityoftheculture.70Withadeeperunderstandingofculturetechniques,researchershavedevelopedavarietyofstrategiestoenhancetheefficacyofsonication.ZhangetalrecommendtheuseoftheBDBactecsystemforculturingsonicatedsamples,animprovementthatcanincreasesensitivityto88%.71Similarly,LiCaoandothersfoundthatultrasoundtreatmentofremovedprostheticcomponentsandtheirsurroundingsofttissuesinsmallmetalcontainersdirectlyduringsurgery,followedbyincubationinbloodcultureflasksintheoperatingroomandculturingintheBACT/ALERT3DBloodCultureSystemnotonlyincreasedthesensitivityrateto91.7%,butalsosimplifiedthetraditionalultrasoundtreatmentprocessandreducedtheriskofpotentialcontamination.66Chemicalmethodsoftreatmentrefertotheuseofstrongreducingagentssuchasdithiothreitol(DTT)toimprovethesensitivityoftheculturebydestabilizingthebiofilm,therebyseparatingthebacteriafromthebiofilm.Dithiothreitolisasulfhydrylcompound,firstproposedbyLorenzoDragoItcanbeusedforthetreatmentofPJIsamples,itcanreducethedisulfidebondsofproteinsinthebiofilm,whichwillnotharmthebacteriawhiledestabilizingthebiofilm’sandhasahighsensitivityof85.7%andspecificityof94%.72Theadvantageofthismethodoverultrasonictreatmentisthatitdoesnotrequirespecializedtreatmentequipmentandcomplextreatmentprocesses.However,thereisadebateabouttheadvantagesanddisadvantagesbetweenchemicalandultrasonictreatmentsforculture,whichstillneedstobeexploredinfurtherstudies.ImagingPlainRadiographsPlainfilmsshouldbetheimagingstudyofchoiceforevaluatingthelikelihoodofPJIinpatients.Plainfilmsareusefulinprovidingareferenceforidentifyingsymptomaticinfectiousandnoninfectiousconditions,suchasperiprostheticfractures,prostheticdislocation,andheterotopicossification.Thepresenceofanirregularlycontouredtranslucentbandaroundtheprosthesis,looseningordisplacementoftheprosthesis,anddestructionofthelateralbonewithperiostealnewboneformationareoftenindicativeofinfectionwhenobservedatanearlystage.Althoughthesensitivityandspecificityoftheseimagingmanifestationsarenothigh,theyprovideimportantclues,soahighdegreeofvigilanceisstillneededwhenconfrontedwiththesesigns.73CT/MRIComputedtomography(CT)andmagneticresonanceimaging(MRI)havetheadvantageofshowingfinebonystructuresandaccuratelyassessingtheextentofosteolysis(Figure1Eand?andG).G).TheyhavebettersensitivityandspecificityforPJIdiagnosisthanX-ray,buttheproblemofmetalartifactsthatcannotbecompletelyeliminatedandthehighcostofdetectionmakeitdifficulttoclarifytheadditionalbenefitsoftheapplicationofthesetechniques.Basedontheresultsofthecurrentstudy,thereisnotenoughevidencetosupporttheinclusionofCT/MRIinthediagnosticcriteriaforPJI.BoneScintigraphyBonescintigraphyisatechniquethatutilizesradioisotopestoassessthestateofthebone.A99mTc-labeledbisphosphonatecompound,whichisreadilyabsorbedbynewbonetissue,istypicallyused,followedbyatriphasicbonescintigraphyscan(Figure1F).Thetechniqueishighlysensitivetotheboneremodelingprocess,makingitextremelysensitivetoPJI,andiswidelyusedbecauseofitsrapidityandcost-effectiveness.74However,itsspecificityislow,asotherpathologiessuchasfracturehealing,asepticloosening,andheterotopicossificationcanleadtosimilarimagingresults.FDG-PET/CTFDGPETcanbehelpfulinthediagnosisofPJIbasedonitsdetectionofhighglucosemetabolismratesininflammatorycellsandmicroorganisms.ThetechniqueworksbyinjectingpatientswithFDG,aglucoseanalogthatcontainsaradiolabeledFDG.Asinflammatorycellsandmicroorganismsininfectedareas,suchasPJI,haveahigherrateofglucoseconsumption,FDGaccumulatesintheseareas.Subsequently,signalsfromradioactiveFDGintheseareascanbecapturedbyPETscanning,whichcanhelpphysiciansidentifyandlocalizetheinfection.75TheadvantageofFDGPEToverBSisthatitcanprovidehigherqualityimagesinashorterperiodoftime.However,duetothelackofharmonizedstandardsregardingthediagnosisofPJIwithFDGPET,aswellasthepresenceofmetalartifacts,andthehighcost,theroleofthistechniqueinthediagnosisofPJIneedstobeevaluatedinfurtherstudies.TreatmentofPJICurrently,thetreatmentoptionsforPJIincludesoleantibioticsuppression,debridement,antibioticsandimplantretention(DAIR),one-stagerevision,two-stagerevision,jointfusion,andamputation.AlthoughtherearenumerousmethodsfortreatingPJI,thereisconsiderabledebateovertheselectionandeffectivenessofthesestrategies.AntibiotictreatmentservesasacornerstonethroughoutthePJItreatmentprocess.Foreachpatient,thechoiceoftreatmentshouldbedeterminedbasedontheirindividualsituationandtheseverityoftheircondition.Debridement,AntibioticsandImplantRetention(DAIR)DAIRinvolvesthoroughlyremovingnon-viabletissuesduringsurgery,excisingsynovialtissuesandinflammatorytissues,andthenrepeatedlysoakingandrinsingwithhydrogenperoxide,iodine,andsaline.Componentsmaybereplacedifnecessary,whilestillretainingtheprosthesis.Afterthesurgery,antibiotictreatmentiscontinuedwiththeaimofcompletelyeradicatingpathogenicmicroorganisms.DAIRtreatmentforPJIhasadvantagessuchaslowcost,simplesurgicaloperation,shorthospitalstay,andtheabilitytoretaintheprosthesiswhileclearingtheinfection.Aprerequisiteisthattheprosthesisisfirmlyfixedandlocalsofttissueconditionsaregood.Variabilityindebridementmethods,perioperativemanagement,andsurgicalindicationsacrossmedicalcenterscontributestodifferingDAIRsuccessrates,whichrangefrom46%to89%.76SomestudiesindicatethatDAIRconductedwithinaweekofinfectiononsetcanyieldpositiveoutcomes.However,thetypeofinfectingmicroorganismsignificantlyinfluencesthesuccessofdebridementfollowingjointreplacementPJI.Specifically,DAIR’ssuccessratefallsbelow30%incasesofMRSAinfections.40MultiplefactorsinfluenceDAIR’ssuccess,encompassingdebridementmethods,antimicrobialadministration,andthepatient’soverallhealth.Thus,decision-makingshouldnotbebasedsolelyonsurgerytimingorsymptomduration.77ForDAIRsurgery,thetimingofdebridementiscrucial,andanydelaywillreducethelikelihoodofsuccessfullyretainingtheprosthesis.Additionally,DAIRsurgeryismoresuitableforpatientswithlow-virulencepathogensandnoaccompanyingdiseases.Ifthefirstdebridementfails,asecondattemptshouldbemadewithgreatcaution,astheprobabilityoffailuredoesnotdiminishwithsubsequentattempts.Therefore,multipledebridementsurgeriesaregenerallynotrecommended.RevisionSurgeryRevisionsurgeryisaneffectivetreatmentforPJI.Thefundamentaltreatmentprincipleistothoroughlyeradicatetheinfectionandthenreconstructastableandwell-functioningjoint.However,theoptimaltimingforprosthesisreplacementandwhethertochooseasingle-stagerevisionorthemoreconservativetwo-stagerevisionremainhotlydebatedtopics..Intermsofsurgicalmethods,asingle-stagerevisioninvolvesfirstclearingthepurulenttissuearoundtheprosthesis,thenremovingtheoriginalprosthesis,thoroughlydebridingagain,andfinallyimplantinganewprosthesis,followedbyadjunctiveantibiotictreatment.Incontrast,atwo-stagerevisioninvolvesthoroughlyclearinginflammatorytissue,bonecement,andotherforeignmaterialswhileremovingtheoriginalprosthesisinthefirststage,followedbyimplantinganantibioticcementspacerandprovidingantibiotictreatment.Aftertheinfectioniscontrolled,thejointreplacementisdoneinthesecondstage.Comparedtotwo-stagerevisions,single-stagerevisionshaveadvantagessuchasfewersurgeries,shorterhospitalstays,lowercosts,lessjointdamage,quickerpostoperativejointfunctionrecovery,andhigherpatientsatisfaction.78Tominimizepostoperativeinfectionrecurrence,itiscrucialtostrictlyadheretotheindicationsandcontraindicationsforrevisionsurgery.Single-stagerevisionsurgeryiswidelyacceptedunderconditionswherethetissuesaroundthesurgicalincisionareingoodcondition,bonelossisminimal,clearmicrobiologicalcultureevidenceexists,andthepatient’sgeneralconditionisfavorable.79Incaseslackingmicrobiologicalevidence,withmulti-drugresistantorspecificbacterialinfections,sinustractformation,orpoorskinconditionsmakingwoundclosuredifficult,maximuminfectioncontrolcanbeachievedthroughatwo-stagerevision.80Althoughtwo-stagerevisionsprovideamoreforgivingspaceandalongeranti-infectionwindow,withadvancesinsurgicaltechniques,optimizationofantibioticuse,andhigherdemandsforpatientfunctionalrecovery,theindicationsforsingle-stagerevisionsaregraduallyexpandingandachievingsatisfactoryresults.Contrarytomostresearch,studiesfromENDO-Kliniksuggestthatsingle-stagerevisionremainsaviabletreatmentoptionevenincasesofrecurrenceofinfection.81Single-stagerevisionsgenerallyachievebetterfunctionalrecoverythantwo-stagerevisionswheninfectioncontrolratesarecomparable.Oussedikcomparedthetreatmentoutcomesof11patientsundergoingsingle-stagereplacementand39undergoingtwo-stagereplacement.82After5yearsoffollow-up,bothgroupsachievedgoodinfectioncontrolrates.TheHarrishipscore(HHS)aftersingle-stagereplacementwassignificantlyhigherthanthataftertwo-stagereplacement(87.8versus75.5).Similarly,Haddadetalcomparedthetherapeuticeffectsofsingle-stageandtwo-stagerevisionsurgeriesforchronickneePJI,findingthatsingle-stagerevisionsachievedaninfectioncontrolrateof100%,comparedto93%fortwo-stagerevisions.83Additionally,patientsundergoingsingle-stagerevisionsrecordedhigherKneeSocietyScores(KSS)comparedtothoseundergoingtwo-stagerevisions,withscoresof88versus76,respectively.However,moststudiesonsingle-stagerevisionforPJIhaveissuessuchassmallsamplesizes,shortfollow-upperiods,andlaxinclusioncriteria.Consequently,moreclinicalevidenceisnecessarytoguidetheselectionofrevisionsurgerytype.Presently,two-stagerevisionisconsideredthegoldstandardfortreatingchronicPJI.84It’sworthnotingthathowlongonewaitsaftertheinitialsurgerytoperformthesecondsurgeryiskeytothesuccessofatwo-stagerevision.Butthere’scurrentlynounifiedstandardforthiswaitingperiod.In2013,IDSArecommendedinthePJItreatmentguidelinesthataftertheone-stagespacersurgery,treatmentwithsensitiveantibioticsshouldbegivenfor4–6weeksbeforeproceedingwithatwo-stagerevisionsurgery.85Somescholarsbelievethatduringtheentiretransitionperiodofthetwo-stagerevision,theantibioticusetimeshouldlastatleast12weeks.86Infact,thecurrentdebatebetweensingle-stageandtwo-stagerevisionsessentiallyboilsdowntoabalancebetweenpathogeneradicationandlimbfunction.Thisinvolvesthestandardproceduresofdebridementsurgeriesandthecourseandmethodofantibioticapplication.Surgicaldebridementinvolvestheremovalofallsuspiciouslyinfectedstructuresinthesurgicalfield,whichwillnotbediscussedfurtherhere.Antibiotics,asthebasicsafeguardforPJItreatment,arenotrecommendedforusewithoutsurgery.Whetherchoosingsingle-stageortwo-stagerevision,thetreatmentwithantibioticsdeservesdeepexploration.AntibioticscommonlyusedtotreatPJIincluderifampicin,vancomycin,fluoroquinolones,daptomycin,andlinezolid利福平，万古霉素，氟喹诺酮类，达托霉素，利奈唑胺.ForPJIpatientswithoutpositivebacterialcultureorpendingdrugsensitivityresults,there’snoconsensusonthespecificchoiceofempiricalantibiotictreatment,butvancomyciniscommonlyusedforculture-negativecases.87Currently,therecommendeduseofantibioticsforPJIinvolvesacombinationofintravenousandoralroutes.Interestingly,theinfectionrecurrencerateduetosystemicantibioticusedoesnotsignificantlydifferbetweensingle-stageandtwo-stagerevisions.88Consequently,giventheuniquestructureofthejointcavity,numerousresearchershavebegunexploringthemethodoflocalantibioticapplication.Thisapproachsignificantlyreducesthesideeffectsassociatedwithsystemicantibioticuseandenhancestheantimicrobialconcentrationatthejointsite,effectivelyincreasingthesuccessrateofantibiotictreatment.89Eveninpatientswithinfectionscausedbymultidrug-resistantpathogens,Lietalhaveachieveda100%microbialcureratethroughtheinjectionofantibioticsdirectlyintothejointcavity.90However,traditionalantibiotictreatmentsstillpresentsignificantlimitations:1)Long-termanduncontrolleduseofantibioticscancauseseriousharmtothebody,suchasliverandkidneyfailure,andhemolyticanemia;2)Continuedpressureonbacteriamaypromotetheformationofresistantstrains,therebycomplicatingtreatment;3)Bacteriamayevadethekillingeffectsofantibioticsthroughmechanismssuchasbiofilmformationandintracellularinfection生物膜形成和细胞内感染.91–93Therefore,thesecomplexresistancemechanismsmakethetreatmentofbacterialinfectionsmorechallenging,andtheyhavespurredglobalresearcherstoacceleratethedevelopmentofnewantibioticsandalternativetreatmentmethods.94–96SummarizingandLookingForwardPJI,asa“catastrophic”complicationfollowingjointarthroplasty,hasalwaysbeenachallengethatorthopedicsurgeonsmustovercome.Currently,issuessuchasmoleculardiagnosisofPJI,antibioticapplication,andthechoiceofsurgicalmethodsremainthefocusofresearchinthisfield.Withadeeperunderstandingofmicrobiology,continuousinnovationsindiagnostictechnology,thedevelopmentofantimicrobialmaterials,andtheoptimizationofantibioticuse,theclinicalchallengesposedbyPJIwilleventuallyberesolved.It’sworthnotingthatforpathogenswithlatentinfections,howtoaccuratelyidentifythetypeofpathogenandgraspthetiminganddosageofantibioticapplicationremainurgentclinicalandresearchissuestotackle.PJI（关节置换术后的“灾难性”并发症）一直是骨科医生必须克服的挑战。目前，PJI的分子诊断、抗生素应用以及手术方法的选择仍然是这一领域的研究重点。随着对微生物学的深入了解，诊断技术的不断创新，抗微生物材料的发展以及抗生素使用的优化，PJI带来的临床挑战最终将得到解决。值得注意的是，对于潜伏性感染的病原体，如何准确识别病原体类型并把握抗生素应用的时机和剂量仍然是亟待解决的临床和研究问题。北京潞河医院骨关节科科普号
单髁置换手术适应症与禁忌证单髁置换UKA的适应症从初级阶段的UKA到现在，UKA的适应症一直在扩大，禁忌症越来越少。以前认为年龄、肥胖、髌股关节损伤等都属于UKA的禁忌症。随着科学技术的发展，UKA材料和设计不断改进，目前公认的UKA最佳适应症包括：1、前内侧骨关节炎（AMOA），股骨内侧髁或胫骨内侧平台骨坏死2、前交叉韧带ACL完好、内侧副韧带MCL功能完好3、外侧软骨正常或轻微退4、内翻畸形<15°，屈膝畸形<15°，膝关节可主动屈曲≥90°UKA的禁忌症目前对于UKA的禁忌症，多数并没有科学试验数据的直接依据，而只是绝大多数专家学者根据临床经验做出的符合一般规律的推断。主要包括：1、ACL、MCL缺失或严重损伤2、关节内畸形不能被手动矫正3、屈膝畸形>15°，麻醉下膝关节被动屈曲<100°4、外侧间室软骨缺损5、炎症性关节炎（类风湿性关节炎、化脓性关节炎、色绒炎等）孙胜医生的科普号