2024
Sex Differences in Tryptophan Metabolism via the Kynurenine Pathway in Acute Ischemic Stroke
Dylla L, Higgins H, Poisson S, Vu T, Reisz J, Herson P, Monte A. Sex Differences in Tryptophan Metabolism via the Kynurenine Pathway in Acute Ischemic Stroke. Clinical Therapeutics 2024 PMID: 39603869, DOI: 10.1016/j.clinthera.2024.10.015.Peer-Reviewed Original ResearchAcute ischemic strokeQuinolinic acid levelsLevels of tryptophanNIHSS scoreTryptophan metabolismMetabolite levelsKynurenine pathwayLinear regression modelsIncreased lifetime risk of strokeLifetime risk of strokeMass spectrometry-based metabolomicsPotential sex differencesDownstream kynurenine metabolitesAssociated with poor outcomesIschemic strokeKynurenine pathway metabolitesDecreased tryptophan concentrationsIncreased lifetime riskRegression modelsMultivariate linear regression modelSex differencesExperience worse outcomesRisk of strokeAcid levelsKynurenine metabolitesNanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts
Li Y, Saba L, Scheinman R, Banda N, Holers M, Monte A, Dylla L, Moghimi S, Simberg D. Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts. ACS Nano 2024, 18: 28649-28658. PMID: 39395006, DOI: 10.1021/acsnano.4c05087.Peer-Reviewed Original ResearchConceptsPegylated liposomal doxorubicinComplement activationPredictive valuePlasma concentrationsC-reactive protein levelsAnti-PEG IgGTriggers proinflammatory responsesAnti-PEG IgMEfficacy of nanomedicinesPoor predictive valueAnti-PEG antibodiesLiposomal doxorubicinIron oxide nanowormsHealthy donorsHigher complement activationAcute infectionInflammatory disease conditionsChronic inflammationProinflammatory responseSystemic administrationComplement cascadeComplement factorsComplement responseIgMProtein levelsSex Differences in the Blood Metabolome During Acute Response to Ischemic Stroke
Dylla L, Higgins H, Stephenson D, Reisz J, Vu T, Poisson S, Herson P, Monte A. Sex Differences in the Blood Metabolome During Acute Response to Ischemic Stroke. Journal Of Women's Health 2024, 33: 1378-1384. PMID: 38946610, PMCID: PMC11564668, DOI: 10.1089/jwh.2023.1133.Peer-Reviewed Original ResearchIschemic strokeLinear regression modelsMass spectrometry-based metabolomicsLifetime risk of strokeAssociated with neurological outcomeDifferentially expressed metabolitesRegression modelsAcute ischemic strokeRisk of strokeComprehensive stroke centerBlood metabolomeNeurological outcomeAcute treatmentMetabolomic profilesLifetime riskNeurological functionIndividual metabolitesTherapeutic potentialStroke centersAcute responseResults:</i></b>Study objectiveMetabolomicsStrokeNIHSSIdentification of specific recommendations for prehospital stroke care associated with shorter door-to-CT times – An analysis of Get with the Guidelines-Stroke registry and prehospital data
Dylla L, Higgins H, Wham C, Leppert M, Ravare B, Jeppson K, Bina H, Monte A, Poisson S. Identification of specific recommendations for prehospital stroke care associated with shorter door-to-CT times – An analysis of Get with the Guidelines-Stroke registry and prehospital data. Frontiers In Stroke 2024, 3: 1355889. DOI: 10.3389/fstro.2024.1355889.Peer-Reviewed Original ResearchDoor-to-CT timeAmerican Heart AssociationGuidelines-Stroke registryAmerican Heart Association recommendationsPrehospital careStroke patientsEmergency medical services documentationIschemic stroke patientsDoor-to-computed tomographyCare of stroke patientsPrehospital medical recordsPrehospital Stroke ScaleCare of strokeMultivariate linear regression modelPrehospital providersPrehospital dataProvider educationStroke signsPotential confoundersLinear regression modelsTreatment of acute strokeComprehensive stroke centerDescriptive statisticsSuspected strokeMedical recordsOptimized Enzyme-Linked Immunosorbent Assay for Anti-PEG Antibody Detection in Healthy Donors and Patients Treated with PEGylated Liposomal Doxorubicin
Li Y, Ettah U, Jacques S, Gaikwad H, Monte A, Dylla L, Guntupalli S, Moghimi S, Simberg D. Optimized Enzyme-Linked Immunosorbent Assay for Anti-PEG Antibody Detection in Healthy Donors and Patients Treated with PEGylated Liposomal Doxorubicin. Molecular Pharmaceutics 2024, 21: 3053-3060. PMID: 38743264, DOI: 10.1021/acs.molpharmaceut.4c00278.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayLiposomal doxorubicinHealthy donorsPatients treated with pegylated liposomal doxorubicinEnzyme-linked immunosorbent assay signalCancer patientsAnti-PEG IgGPegylated liposomal doxorubicinImmunosorbent assayOptimized ELISAEnzyme-linked immunosorbent assay protocolsAnti-PEG antibodiesChemotherapy cyclesBetween-assay variabilityPEGylated liposomesCutoff valueAccelerated clearanceTreatment cyclesDrug delivery systemsAntibody titersComplement activationInfused drugAnti-PEGOptimized assayPatientsValidation of dot blot immunoassay for measurement of complement opsonization of nanoparticles
Li Y, Monte A, Dylla L, Moghimi S, Simberg D. Validation of dot blot immunoassay for measurement of complement opsonization of nanoparticles. Journal Of Immunological Methods 2024, 528: 113668. PMID: 38574804, PMCID: PMC11023749, DOI: 10.1016/j.jim.2024.113668.Peer-Reviewed Original ResearchConceptsDeposition of C3Complement activation markersSurface C3 depositionMembrane attack complex C5b-9Activation markersDot blot immunoassayC3 depositionAnaphylatoxins C3aImmune responseNanomedicine researchC5b-9Complement attackComplement activationBlot immunoassayFluid phase markerMarkersPhase markersImmunoassaySurface resultsPathway specificityAssembly of C3 convertaseComplementNanoparticlesAbstract 106: Circulating Interleukin-6 Levels Early During Active Stroke Estimate Time of Stroke Onset: Potential New Clinical Biomarker Tool From a Mobile Stroke Unit
Kowalski R, Ledreux A, Violette J, Neumann R, Grotta J, Ornelas D, Thompson J, Monte A, Dylla L, Coughlan C, Yu X, Graner M, Jones W. Abstract 106: Circulating Interleukin-6 Levels Early During Active Stroke Estimate Time of Stroke Onset: Potential New Clinical Biomarker Tool From a Mobile Stroke Unit. Stroke 2024, 55: a106-a106. DOI: 10.1161/str.55.suppl_1.106.Peer-Reviewed Original ResearchInterleukin-6 levelsMobile stroke unitInterleukin-6Symptom onsetLesion volumeAcute strokeHealthy controlsMobile stroke unit patientsDevelopment of immunomodulatory therapiesMedian interleukin-6Circulating interleukin-6 levelsMeasurement of interleukin-6Associated with lesion volumeMedian initial NIHSS scoreDWI lesion volumeCirculating interleukin-6Plasma interleukin-6Stroke patientsOnset timeIL-6 responseTime of stroke onsetImmunomodulatory therapyMedian ageThrombolysis windowNIHSS score
2023
Provider Perceptions of Oxygenation Strategies for Critically Ill Trauma Patients With and Without Moderate-to-Severe Traumatic Brain Injury
Dylla L, Douin D, Cwik J, Steinwand A, Rice J, Jackson C, Anderson E, Higgins H, Monte A, Ginde A. Provider Perceptions of Oxygenation Strategies for Critically Ill Trauma Patients With and Without Moderate-to-Severe Traumatic Brain Injury. Military Medicine 2023, 188: 166-175. PMID: 37948260, PMCID: PMC11022338, DOI: 10.1093/milmed/usad076.Peer-Reviewed Original ResearchConceptsCritically ill trauma patientsCritical care providersTraumatic brain injuryCare providersTrauma patientsSupplemental oxygenNon-TBI patientsCross-sectional surveyUniversity of Colorado HospitalCase-based scenariosProviders' perceptionsProvider practicesCritically ill TBI patientsProviders' viewsOxygen useProvider typeAdministration of supplemental oxygenTargeted educationAssociated with increased mortalityBrain injuryOxygen saturation thresholdsModerate-to-severeSupplemental oxygen useFisher's exact testCritically ill patientsResponse to: Acute ischemic stroke and cardioemboli: Does sex matter?
Higgins H, Chen L, Ravare B, Jeppson K, Bina H, Herson P, Monte A, Poisson S, Dylla L. Response to: Acute ischemic stroke and cardioemboli: Does sex matter? The American Journal Of Emergency Medicine 2023, 74: 170-171. PMID: 37867013, PMCID: PMC10792528, DOI: 10.1016/j.ajem.2023.10.014.Peer-Reviewed Original ResearchSex differences in acute ischemic stroke presentation are a matter of infarct location
Higgins H, Chen L, Ravare B, Jeppson K, Bina H, Herson P, Monte A, Poisson S, Dylla L. Sex differences in acute ischemic stroke presentation are a matter of infarct location. The American Journal Of Emergency Medicine 2023, 74: 95-99. PMID: 37802001, PMCID: PMC10843056, DOI: 10.1016/j.ajem.2023.09.046.Peer-Reviewed Original ResearchConceptsEmergency medical servicesMultivariate logistic regressionStroke symptomsFrequency of patient presentationLogistic regressionStroke screening toolElectronic health recordsRecognition of strokeAcute ischemic strokeInfarct locationClassic symptomsEmergency department treatmentDistribution of strokeIschemic strokeIschemic stroke presentingHealth recordsRetrospective cohort studyMedical servicesUnilateral weaknessAnterior circulation infarctionCohort studyScreening toolStroke presentationEtiology of strokePosterior circulation infarctionCorrection to: A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation
Monte A, Vest A, Reisz J, Berninzoni D, Hart C, Dylla L, D’Alessandro A, Heard K, Wood C, Pattee J. Correction to: A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation. Journal Of Medical Toxicology 2023, 19: 416-416. PMID: 37365428, PMCID: PMC10522543, DOI: 10.1007/s13181-023-00957-z.Peer-Reviewed Original ResearchA Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation
Monte A, Vest A, Reisz J, Berninzoni D, Hart C, Dylla L, D’Alessandro A, Heard K, Wood C, Pattee J. A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation. Journal Of Medical Toxicology 2023, 19: 255-261. PMID: 37231244, PMCID: PMC10212224, DOI: 10.1007/s13181-023-00951-5.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTricarboxylic acid cycleMitochondrial energy productionLiver injuryGenomic dataALT elevationIdentification of genesTherapeutic doses of APAPAlanine aminotransferase elevationPredicting liver injuryDose of APAPMaltose metabolismAPAP-induced liver injuryMechanism of injuryAssociation studiesGenetic analysisRandomized controlled trialsAminotransferase elevationGenetic variantsAcid cycleClinical outcomesTherapeutic dosesMultiomics approachGenetic controlAPAP liver injuryAbstract TP47: Impact Of Prehospital Care And Patient Presentation On In-hospital Treatment Of Acute Ischemic Stroke
DYLLA L, Higgins H, Ravare B, Jeppson K, Bina H, Rice J, Herson P, Monte A, Poisson S. Abstract TP47: Impact Of Prehospital Care And Patient Presentation On In-hospital Treatment Of Acute Ischemic Stroke. Stroke 2023, 54: atp47-atp47. DOI: 10.1161/str.54.suppl_1.tp47.Peer-Reviewed Original ResearchEmergency medicine servicesDoor-to-CT timeAmerican Heart AssociationLinear regression modelsDoor-to-computed tomographyIn-hospital quality of careQuality-of-care metricsGuideline concordant careQuality of careAcute stroke careDoor-to-CTIn-hospital careRegression modelsMultivariate linear regression modelConcordant careProvider compliancePrehospital careStroke careStroke guidelinesIschemic stroke patientsMedicine serviceStroke symptomsIn-hospital outcomesComprehensive stroke centerAcute ischemic stroke patientsHyperoxia is associated with a greater risk for mortality in critically ill traumatic brain injury patients than in critically ill trauma patients without brain injury
Douin D, Dylla L, Anderson E, Rice J, Jackson C, Bebarta V, Neumann R, Schauer S, Ginde A. Hyperoxia is associated with a greater risk for mortality in critically ill traumatic brain injury patients than in critically ill trauma patients without brain injury. Science Progress 2023, 106: 00368504231160416. PMID: 36879502, PMCID: PMC10450323, DOI: 10.1177/00368504231160416.Peer-Reviewed Original ResearchConceptsTraumatic brain injury statusTraumatic brain injuryIntensive care unitTraumatic brain injury patientsIn-hospital mortalityCritically ill trauma patientsTrauma patientsState Trauma RegistryNon-TBI patientsRisk of mortalityIntensive care unit daysCritically ill TBI patientsRegional trauma centerRetrospective cohort studyIntensive care unit length of stayLength of stayBrain injuryIntensive care unit lengthTrauma registryInjured adultsSecondary analysisBrain injury patientsCohort studyPatient observationSecondary outcomes
2022
Sex as a biological variable in determining the metabolic changes influencing acute ischemic stroke outcomes—Where is the data: A systematic review
Dylla L, Higgins H, Piper C, Poisson S, Herson P, Monte A. Sex as a biological variable in determining the metabolic changes influencing acute ischemic stroke outcomes—Where is the data: A systematic review. Frontiers In Neurology 2022, 13: 1026431. PMID: 36504643, PMCID: PMC9729945, DOI: 10.3389/fneur.2022.1026431.Peer-Reviewed Original ResearchResponse to acute ischemic strokeAcute ischemic strokeIschemic strokeSystematic reviewNeurological outcomePathophysiology of acute ischemic strokePreclinical rat modelClinical cohort studyFull-text reviewNational Institutes of Health (NIHWeb of ScienceAcute stroke researchClinical research studiesSubgroup analysisCohort studyRat modelBiological variablesResearch studiesSex differencesSex-based differencesOvid MEDLINEStudy designLifetime morbidityMetabolic changesPatient outcomesMetabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine Protein Adduct Formation with Therapeutic Acetaminophen Administration: Sex-based Physiologic Differences
Arnold C, Dylla L, Monte A, Heard K, Heard S, D’Alessandro A, Reynolds K, Dart R, Rumack B, Sonn B. Metabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine Protein Adduct Formation with Therapeutic Acetaminophen Administration: Sex-based Physiologic Differences. Journal Of Medical Toxicology 2022, 18: 297-310. PMID: 35751009, PMCID: PMC9492831, DOI: 10.1007/s13181-022-00903-5.Peer-Reviewed Original ResearchConceptsTherapeutic APAP dosingAdduct formationN-acetyl-p-benzoquinone imineFalse discovery rate correctionAPAP doseProtein adduct formationAdduction groupLiquid chromatography mass spectrometryUltra-high performance liquid chromatography mass spectrometryMetabolite expressionN-acetyl-p-benzoquinoneAlanine aminotransferaseChromatography mass spectrometrySeverity of hepatic injuryMethodsThis retrospective studyProtein adductsMass spectrometryAdductsAdduct productionAPAP-protein adductsT-testTransaminase elevationMetabolomics evaluationIndependent of sexRetrospective studyAnalysis of stroke care among 2019-2020 national emergency medical services information system encounters
Dylla L, Rice J, Poisson S, Monte A, Higgins H, Ginde A, Herson P. Analysis of stroke care among 2019-2020 national emergency medical services information system encounters. Journal Of Stroke And Cerebrovascular Diseases 2022, 31: 106278. PMID: 34998044, PMCID: PMC8851983, DOI: 10.1016/j.jstrokecerebrovasdis.2021.106278.Peer-Reviewed Original ResearchConceptsNational Emergency Medical Services Information SystemEmergency medicine servicesGuideline-concordant carePrehospital stroke careImpression of strokeStroke careService information systemImprove prehospital stroke careAmerican Stroke Association (ASA) guidelinesGuideline-compliant careMinority of patientsMultivariate logistic regressionInitiation of treatmentPotential targeted interventionsGuideline-concordantMedicine serviceSuspected strokeCareLogistic regressionPatient outcomesPrimary outcomeAssess compliancePatient characteristicsASA guidelinesGender-based differences
2021
A multicenter cluster randomized, stepped wedge implementation trial for targeted normoxia in critically ill trauma patients: study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen (SAVE-O2) trial
Dylla L, Douin D, Anderson E, Rice J, Jackson C, Bebarta V, Lindsell C, Cheng A, Schauer S, Ginde A. A multicenter cluster randomized, stepped wedge implementation trial for targeted normoxia in critically ill trauma patients: study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen (SAVE-O2) trial. Trials 2021, 22: 784. PMID: 34749762, PMCID: PMC8574946, DOI: 10.1186/s13063-021-05688-6.Peer-Reviewed Original ResearchConceptsCritically ill trauma patientsImplementation trialStatistical analysis planMultimodal interventionTrauma patientsTraining periodStudy protocolTargeted normoxiaVentilator-free daysOne-month training periodGlasgow Outcome ScoreAnalysis planLevel 1 trauma centerCombat casualty careUsual carePre-implementationInjured trauma patientsSupplemental oxygenPost-implementationReduced logistical burdensIntervention phaseOutcome measuresCasualty careMulticenter clusterOutcome scoresResponse to: “Does statistical difference in a pre/post quasiexperimental study mean utility of a multimodal education intervention in targeted normoxia in critically ill trauma patients?”
Dylla L, Rice J, Ginde A. Response to: “Does statistical difference in a pre/post quasiexperimental study mean utility of a multimodal education intervention in targeted normoxia in critically ill trauma patients?”. Journal Of Trauma And Acute Care Surgery 2021, 91: s270-s270. PMID: 34039928, DOI: 10.1097/ta.0000000000003299.Peer-Reviewed Original ResearchAssociation Between Hyperoxia, Supplemental Oxygen, and Mortality in Critically Injured Patients
Douin D, Anderson E, Dylla L, Rice J, Jackson C, Wright F, Bebarta V, Schauer S, Ginde A. Association Between Hyperoxia, Supplemental Oxygen, and Mortality in Critically Injured Patients. Critical Care Explorations 2021, 3: e0418. PMID: 34036272, PMCID: PMC8133168, DOI: 10.1097/cce.0000000000000418.Peer-Reviewed Original ResearchIn-hospital mortalityAdult trauma patientsInjured patientsCohort studyRisk scoreTrauma patientsEmergency department arrivalLevel I trauma centerOutcome of in-hospital mortalityICU admissionMechanism of injuryRisk of mortalityRetrospective cohort studyBlunt trauma mechanismHigh oxygen administrationOxygen administrationSecondary outcomesPrimary outcomeOxygen saturationLevel IIIVentilator-free daysHospital-free daysDays of hospitalizationCritically ill patientsPeriod of hyperoxia