新英格兰示范摘要精读讲解Word格式.docx

新英格兰示范摘要精读讲解Word格式.docx

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MethodsToevaluatetheefficacyofstrontiumranelateinpreventingvertebralfracturesinaphase3trial,werandomlyassigned1649postmenopausalwomenwithosteoporosis（lowbonemineraldensity）andatleastonevertebralfracturetoreceive2goforalstrontiumranelateperdayorplaceboforthreeyears.WegavecalciumandvitaminDsupplementstobothgroupsbeforeandduringthestudy.Vertebralradiographswereobtainedannually,andmeasurementsofbonemineraldensitywereperformedeverysixmonths.

ResultsNewvertebralfracturesoccurredinfewerpatientsinthestrontiumranelategroupthanintheplacebogroup,withariskreductionof49percentinthefirstyearoftreatmentand41percentduringthethree-yearstudyperiod（relativerisk,0.59;

95percentconfidenceinterval,0.48to0.73）.Strontiumranelateincreasedbonemineraldensityatmonth36by14.4percentatthelumbarspineand8.3percentatthefemoralneck（P<

0.001forbothcomparisons）.Therewerenosignificantdifferencesbetweenthegroupsintheincidenceofseriousadverseevents.

ConclusionsTreatmentofpostmenopausalosteoporosiswithstrontiumranelateleadstoearlyandsustainedreductionsintheriskofvertebralfractures.

2.Effusive–ConstrictivePericarditis

BackgroundEffusive–constrictivepericarditisisanuncommonpericardialsyndromecharacterizedbyconcomitanttamponade,causedbytensepericardialeffusion,andconstriction,causedbythevisceralpericardium.Weconductedaprospectivestudyofitsclinicalevolutionandmanagement.

MethodsFrom1986through2001,allpatientswitheffusive–constrictivepericarditiswereprospectivelyevaluated.Combinedpericardiocentesisandcardiaccatheterizationwereperformedinallpatients,andpericardiectomywasperformedinthosewithpersistentconstriction.Follow-uprangedfrom1monthto15years（median,7years）.

ResultsAtotalof1184patientswithpericarditiswereevaluated,218ofwhomhadtamponade.Ofthese218,190underwentcombinedpericardiocentesisandcatheterization.Fifteenofthesepatientshadeffusive–constrictivepericarditisandwereincludedinthestudy.Allpatientspresentedwithclinicaltamponade;

however,concomitantconstrictionwasrecognizedinonlysevenpatients.Atcatheterization,allpatientshadelevatedintrapericardialpressure（median,12mmHg;

interquartilerange,7to18）andelevatedrightatrialandend-diastolicrightandleftventricularpressures.Afterpericardiocentesis,theintrapericardialpressuredecreased（medianvalue,–5mmHg;

interquartilerange,–5to0）,whereasrightatrialandend-diastolicrightandleftventricularpressures,althoughslightlyreduced,remainedelevated,withadip–plateaumorphology.Thecauseswerediverse,anddeathwasmainlyrelatedtotheunderlyingdisease.Pericardiectomywasrequiredinsevenpatients,allofwhomhadinvolvementofthevisceralpericardium.Threepatientshadspontaneousresolution.

ConclusionsEffusive–constrictivepericarditisisanuncommonpericardialsyndromethatmaybemissedinsomepatientswhopresentwithtamponade.Althoughevolutiontopersistentconstrictionisfrequent,idiopathiccasesmayresolvespontaneously.Inouropinion,extensiveepicardiectomyistheprocedureofchoiceinpatientsrequiringsurgery.

3.EffectofEculizumabonHemolysisandTransfusionRequirementsinPatientswithParoxysmalNocturnalHemoglobinuria

BackgroundParoxysmalnocturnalhemoglobinuria（PNH）arisesfromasomaticmutationofthePIG-Ageneinahematopoieticstemcellandthesubsequentproductionofbloodcellswithadeficiencyofsurfaceproteinsthatprotectthecellsagainstattackbythecomplementsystem.Wetestedtheclinicalefficacyofeculizumab,ahumanizedantibodythatinhibitstheactivationofterminalcomplementcomponents,inpatientswithPNH.

MethodsEleventransfusion-dependentpatientswithPNHreceivedinfusionsofeculizumab（600mg）everyweekforfourweeks,followedoneweeklaterbya900-mgdoseandthenby900mgeveryotherweekthroughweek12.Clinicalandbiochemicalindicatorsofhemolysisweremeasuredthroughoutthetrial.

ResultsMeanlactatedehydrogenaselevelsdecreasedfrom3111IUperliterbeforetreatmentto594IUperliterduringtreatment（P=0.002）.ThemeanpercentageofPNHtypeIIIerythrocytesincreasedfrom36.7percentofthetotalerythrocytepopulationto59.2percent（P=0.005）.Themeanandmediantransfusionratesdecreasedfrom2.1and1.8unitsperpatientpermonthto0.6and0.0unitsperpatientpermonth,respectively（P=0.003forthecomparisonofthemedianrates）.Episodesofhemoglobinuriawerereducedby96percent（P<

0.001）,andmeasurementsofthequalityoflifeimprovedsignificantly.

ConclusionsEculizumabissafeandwelltoleratedinpatientswithPNH.ThisantibodyagainstterminalcomplementproteinC5reducesintravascularhemolysis,hemoglobinuria,andtheneedfortransfusion,withanassociatedimprovementinthequalityoflifeinpatientswithPNH.

4.UseofB-TypeNatriureticPeptideintheEvaluationandManagementofAcuteDyspnea

BACKGROUNDB-typenatriureticpeptidelevelsarehigherinpatientswithcongestiveheartfailurethaninpatientswithdyspneafromothercauses.　　

METHODSWeconductedaprospective,randomized,controlledstudyof452patientswhopresentedtotheemergencydepartmentwithacutedyspnea:

225patientswererandomlyassignedtoadiagnosticstrategyinvolvingthemeasurementofB-typenatriureticpeptidelevelswiththeuseofarapidbedsideassay,and227wereassessedinastandardmanner.Thetimetodischargeandthetotalcostoftreatmentweretheprimaryendpoints.

　RESULTSBase-linedemographicandclinicalcharacteristicswerewellmatchedbetweenthetwogroups.TheuseofB-typenatriureticpeptidelevelsreducedtheneedforhospitalizationandintensivecare:

75percentofpatientsintheB-typenatriureticpeptidegroupwerehospitalized,ascomparedwith85percentofpatientsinthecontrolgroup（P=0.008）,and15percentofthoseintheB-typenatriureticpeptidegrouprequiredintensivecare,ascomparedwith24percentofthoseinthecontrolgroup（P=0.01）.Themediantimetodischargewas8.0daysintheB-typenatriureticpeptidegroupand11.0daysinthecontrolgroup（P=0.001）.Themeantotalcostoftreatmentwas$5,410（95percentconfidenceinterval,$4,516to$6,304）intheB-typenatriureticpeptidegroup,ascomparedwith$7,264（95percentconfidenceinterval,$6,301to$8,227）inthecontrolgroup（P=0.006）.Therespective30-daymortalityrateswere10percentand12percent（P=0.45）.

　CONCLUSIONSUsedinconjunctionwithotherclinicalinformation,rapidmeasurementofB-typenatriureticpeptideintheemergencydepartmentimprovedtheevaluationandtreatmentofpatientswithacutedyspneaandtherebyreducedthetimetodischargeandthetotalcostoftreatment.

5.ImpairedMitochondrialActivityintheInsulin-ResistantOffspringofPatientswithType2Diabetes

BackgroundInsulinresistanceappearstobethebestpredictorofthedevelopmentofdiabetesinthechildrenofpatientswithtype2diabetes,butthemechanismresponsibleisunknown.

MethodsWeperformedhyperinsulinemic–euglycemicclampstudiesincombinationwithinfusionsof[6,6-2H2]glucoseinhealthy,young,lean,insulin-resistantoffspringofpatientswithtype2diabetesandinsulin-sensitivecontrolsubjectsmatchedforage,height,weight,andphysicalactivitytoassessthesensitivityofliverandmuscletoinsulin.Proton（1H）magneticresonancespectroscopystudieswereperformedtomeasureintramyocellularlipidandintrahepatictriglyceridecontent.Ratesofwhole-bodyandsubcutaneousfatlipolysiswereassessedbymeasuringtheratesof[2H5]glycerolturnoverincombinationwithmicrodialysismeasurementsofglycerolreleasefromsubcutaneousfat.Weperformed31Pmagneticresonancespectroscopystudiestoassesstheratesofmitochondrialoxidative-phosphorylationactivityinmuscle.

ResultsTheinsulin-stimulatedrateofglucoseuptakebymusclewasapproximately60percentlowerintheinsulin-resistantsubjectsthanintheinsulin-sensitivecontrolsubjects（P<

0.001）andwasassociatedwithanincreaseofapproximately80percentintheintramyocellularlipidcontent（P=0.005）.Thisincreaseinintramyocellularlipidcontentwasmostlikelyattributabletomitochondrialdysfunction,asreflectedbyareductionofapproximately30percentinmitochondrialphosphorylation（P=0.01forthecomparisonwithcontrols）,sincetherewerenosignificantdifferencesinsystemicorlocalizedratesoflipolysisorplasmaconcentrationsoftumornecrosisfactor

interleukin-6,resistin,oradiponectin.

ConclusionsThesedatasupportthehypothesisthatinsulinresistanceintheskeletalmuscleofinsulin-resistantoffspringofpatientswithtype2diabetesisassociatedwithdysregulationofintramyocellularfattyacidmetabolism,possiblybecauseofaninheriteddefectinmitochondrialoxidativephosphorylation.

6.CirculatingAngiogenicFactorsandtheRiskofPreeclampsia

BackgroundThecauseofpreeclampsiaremainsunclear.Limiteddatasuggestthatexcesscirculatingsolublefms-liketyrosinekinase1（