2023
Clinical Phenotypes of Patients With Systemic Sclerosis With Distinct Molecular Signatures in Skin
Yang M, Goh V, Lee J, Espinoza M, Yuan Y, Carns M, Aren K, Chung L, Khanna D, McMahan ZH, Agrawal R, Nelson L, Shah SJ, Whitfield ML, Hinchcliff M. Clinical Phenotypes of Patients With Systemic Sclerosis With Distinct Molecular Signatures in Skin. Arthritis Care & Research 2023, 75: 1469-1480. PMID: 35997480, PMCID: PMC9947190, DOI: 10.1002/acr.24998.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseInterstitial lung diseaseHigher mRSSSSc patientsSerum autoantibodiesClinical phenotypeHealthy participantsScl-70 antibodyPresent multicenter studySimilar disease durationSystemic sclerosis patientsDistinct clinical phenotypesSkin gene expressionValuable clinical informationDcSSc patientsDisease durationIdentifies patientsSystemic sclerosisSclerosis patientsMulticenter studyLung diseaseSkin fibrosisSimilar prevalenceClinical dataMultivariable modeling
2022
A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis
Franks JM, Toledo DM, Martyanov V, Wang Y, Huang S, Wood TA, Spino C, Chung L, Denton C, Derrett-Smith E, Gordon JK, Spiera R, Domsic R, Hinchcliff M, Khanna D, Whitfield ML. A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis. Rheumatology 2022, 62: 19-28. PMID: 35751592, PMCID: PMC9788818, DOI: 10.1093/rheumatology/keac344.Peer-Reviewed Original ResearchConceptsMolecular subsetsIntrinsic subsetInflammatory subsetBaseline demographicsSSc patientsWhite/Caucasian patientsBaseline clinical demographicsAverage disease durationRodnan skin scoreAfrican American/BlackASSET trialUnique gene expression signatureDisease durationGene expression signaturesClinical demographicsParticipant seraSkin scoreSystemic sclerosisValidation cohortClinical variablesCaucasian patientsSpecific therapyAmerican/BlackSkin biopsiesDisease pathogenesis
2021
Large‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis
Bellocchi C, Ying J, Goldmuntz EA, Keyes‐Elstein L, Varga J, Hinchcliff ME, Lyons MA, McSweeney P, Furst DE, Nash R, Crofford LJ, Welch B, Goldin JG, Pinckney A, Mayes MD, Sullivan KM, Assassi S. Large‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis. Arthritis & Rheumatology 2021, 73: 660-670. PMID: 33131208, PMCID: PMC8005427, DOI: 10.1002/art.41570.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisInterstitial lung diseaseSerum protein profilesHealthy control subjectsControl subjectsSex-matched healthy control subjectsRodnan skin thickness scoreSevere interstitial lung diseaseCutaneous systemic sclerosisMean disease durationDiffuse cutaneous SScWhole blood gene expression profilingSkin thickness scoreBlood gene expression profilingPeripheral blood cellsCancer antigen 15Epidermal growth factor receptorSoluble epidermal growth factor receptorSerum proteinsGrowth factor receptorDisease activityDisease durationSystemic sclerosisCutaneous SScImmunosuppressive agents
2020
Calcinosis is associated with ischemic manifestations and increased disability in patients with systemic sclerosis
Valenzuela A, Baron M, Rodriguez-Reyna TS, Proudman S, Khanna D, Young A, Hinchcliff M, Steen V, Gordon J, Hsu V, Castelino FV, Schoenfeld S, Li S, Wu JY, Fiorentino D, Chung L. Calcinosis is associated with ischemic manifestations and increased disability in patients with systemic sclerosis. Seminars In Arthritis And Rheumatism 2020, 50: 891-896. PMID: 32898758, PMCID: PMC8205269, DOI: 10.1016/j.semarthrit.2020.06.007.Peer-Reviewed Original ResearchConceptsSSc patientsSystemic sclerosisDigital ischemiaHealth Assessment Questionnaire Disability IndexCochin Hand Functional ScaleACR/EULAR criteriaSubcutaneous calcium depositionConsecutive SSc patientsSubset of patientsMedian T-scoreDisability IndexFinger/thumbCommon complicationDisease durationEULAR criteriaIschemic manifestationsAcro-osteolysisMultivariable analysisPhysical examinationHand functionClinical correlationHand dysfunctionClear historyHigh burdenBone densitometry
2019
Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile
Skaug B, Khanna D, Swindell WR, Hinchcliff ME, Frech TM, Steen VD, Hant FN, Gordon JK, Shah AA, Zhu L, Zheng WJ, Browning JL, Barron AMS, Wu M, Visvanathan S, Baum P, Franks JM, Whitfield ML, Shanmugam VK, Domsic RT, Castelino FV, Bernstein EJ, Wareing N, Lyons MA, Ying J, Charles J, Mayes MD, Assassi S. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals Of The Rheumatic Diseases 2019, 79: annrheumdis-2019-215894. PMID: 31767698, PMCID: PMC7386329, DOI: 10.1136/annrheumdis-2019-215894.Peer-Reviewed Original ResearchConceptsImmune cell signaturesEarly diffuse systemic sclerosisDiffuse systemic sclerosisLonger disease durationSystemic sclerosisDisease durationCell signatureSSc patientsT cellsEarly diffuse cutaneous systemic sclerosisScleroderma Outcome Study cohortDiffuse cutaneous systemic sclerosisShorter disease durationCutaneous systemic sclerosisRodnan skin scoreCD8 T cellsB cell signaturesCD4 T cellsSystemic sclerosis cohortImmune cell markersClinical trial designDiffuse SSc patientsBiopsy RNAProspective registryClinical course
2018
Risk Factors for Mortality and Cardiopulmonary Hospitalization in Systemic Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry
Hsu VM, Chung L, Hummers LK, Shah A, Simms R, Bolster M, Hant FN, Silver RM, Fischer A, Hinchcliff ME, Varga J, Goldberg AZ, Derk CT, Schiopu E, Khanna D, Shapiro LS, Domsic RT, Medsger T, Mayes MD, Furst D, Csuka ME, Molitor JA, Saketkoo LA, Salazar CR, Steen VD. Risk Factors for Mortality and Cardiopulmonary Hospitalization in Systemic Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry. The Journal Of Rheumatology 2018, 46: 176-183. PMID: 30275260, DOI: 10.3899/jrheum.180018.Peer-Reviewed Original ResearchConceptsExercise oxygen desaturationPulmonary hypertensionCardiopulmonary hospitalizationsPericardial effusionSystemic sclerosisOxygen desaturationMale sexRisk factorsSSc-pulmonary arterial hypertensionSystolic pulmonary arterial pressurePredictors of hospitalizationRight heart catheterizationPredictors of mortalityProspective cohort studyPulmonary arterial pressurePulmonary function testingSystemic sclerosis patientsBaseline clinical measuresProportional hazards modelPH patientsArterial hypertensionDyspnea scoreHeart catheterizationCohort studyDisease durationSAT0486 Myeloablation followed by autologous stem cell rescue leads to normalisation of serum il-6 levels in patients with systemic sclerosis
Bellocchi C, Sullivan K, Goldmuntz E, Ying J, Keyes-Elstein L, Varga J, Hinchcliff M, McSweeney P, Furst D, Nash R, Crofford L, Welch B, Pinckney A, Mayes M, Assassi S. SAT0486 Myeloablation followed by autologous stem cell rescue leads to normalisation of serum il-6 levels in patients with systemic sclerosis. Annals Of The Rheumatic Diseases 2018, 77: 1100. DOI: 10.1136/annrheumdis-2018-eular.3731.Peer-Reviewed Original ResearchSerum IL-6 levelsHematopoietic stem cell transplantationIL-6 levelsStem cell transplantationSystemic sclerosisIL-6IL-12IL-1βSCOT trialDisease durationSSc pathogenesisAutologous hematopoietic stem cell transplantationPro-inflammatory Th1 cytokinesAutologous stem cell rescueAutologous stem cell transplantationSerum IFN-γ levelsBaseline clinical featuresMean disease durationStem cell rescueRodnan skin scoreSerum IL-6Diffuse systemic sclerosisMajority of patientsAvailable serum samplesIFN-γ levels
2016
Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study
Valenzuela A, Baron M, Group C, Herrick AL, Proudman S, Stevens W, Group A, Rodriguez-Reyna TS, Vacca A, Medsger TA, Hinchcliff M, Hsu V, Wu JY, Fiorentino D, Chung L. Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study. Seminars In Arthritis And Rheumatism 2016, 46: 344-349. PMID: 27371996, PMCID: PMC5500288, DOI: 10.1016/j.semarthrit.2016.05.008.Peer-Reviewed Original ResearchMeSH KeywordsAcro-OsteolysisAdultAgedAntibodies, AntinuclearAutoantibodiesCalcinosisCohort StudiesDNA Topoisomerases, Type IFemaleFingersHeart DiseasesHumansHypertension, PulmonaryLogistic ModelsMaleMiddle AgedMultivariate AnalysisNuclear ProteinsOdds RatioOsteoporosisRetrospective StudiesRibonucleoprotein, U1 Small NuclearRNA Polymerase IIIScleroderma, SystemicSkin UlcerTelangiectasisConceptsScleroderma Clinical Trials ConsortiumDigital ulcersSystemic sclerosisOdds ratioMultivariate analysisAnti-PM/SclRetrospective cohort studyQuarter of patientsLonger disease durationClinical Trials ConsortiumStrong associationMulticenter collaborative effortsGastrointestinal involvementAnticardiolipin antibodiesPulmonary hypertensionCohort studyDisease durationClinical factorsAcro-osteolysisClinical featuresUnivariate analysisCardiac diseasePatientsCalcinosisUlcersEsophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study
Richardson C, Agrawal R, Lee J, Almagor O, Nelson R, Varga J, Cuttica MJ, Dematte J, Chang RW, Hinchcliff ME. Esophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study. Seminars In Arthritis And Rheumatism 2016, 46: 109-114. PMID: 27033049, PMCID: PMC5500283, DOI: 10.1016/j.semarthrit.2016.02.004.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseSSc interstitial lung diseaseInterstitial lung diseaseSystemic sclerosisCross-sectional studyEsophageal diameterEsophageal dilatationLung diseaseProgression of ILDSSc disease subtypesPulmonary function testsRodnan skin scoreErythrocyte sedimentation rateSecondary outcome variablesBody mass indexGround-glass opacitiesProton pump inhibitorsLow lung volumesSemi-quantitative scoreRegistry patientsDisease durationLow DLCOSkin scoreMedication useSerum autoantibodies
2014
Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study
Hsu VM, Chung L, Hummers LK, Wigley F, Simms R, Bolster M, Silver R, Fischer A, Hinchcliff ME, Varga J, Goldberg AZ, Derk CT, Schiopu E, Khanna D, Shapiro LS, Domsic RT, Medsger T, Mayes MD, Furst D, Csuka ME, Molitor JA, Alkassab F, Steen VD. Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study. Seminars In Arthritis And Rheumatism 2014, 44: 55-62. PMID: 24709277, DOI: 10.1016/j.semarthrit.2014.03.002.Peer-Reviewed Original ResearchConceptsSystolic pulmonary arterial pressureRight heart catheterizationExercise-induced hypoxiaPulmonary hypertensionPulmonary arterial hypertensionPulmonary function testingSystemic sclerosisCohort studyDisease durationHigher systolic pulmonary arterial pressureProspective longitudinal cohort studyFVC/DLcoNew pulmonary hypertensionPulmonary Hypertension AssessmentDiffusion lung capacityPulmonary arterial pressureOngoing prospective studyKaplan-Meier survivalHigh-risk populationKaplan-Meier estimatesLongitudinal cohort studyHigh-risk factorsRecognition of OutcomesPFT criteriaPH patients
2012
Prevalence, prognosis, and factors associated with left ventricular diastolic dysfunction in systemic sclerosis.
Hinchcliff M, Desai CS, Varga J, Shah SJ. Prevalence, prognosis, and factors associated with left ventricular diastolic dysfunction in systemic sclerosis. Clinical And Experimental Rheumatology 2012, 30: s30-7. PMID: 22338601, PMCID: PMC3507505.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedChi-Square DistributionChicagoComorbidityDiastoleEchocardiography, DopplerFemaleHumansLinear ModelsMaleMiddle AgedMultivariate AnalysisPrevalencePrognosisProportional Hazards ModelsProspective StudiesRegistriesRetrospective StudiesRisk AssessmentRisk FactorsScleroderma, SystemicSystoleTime FactorsVentricular Dysfunction, LeftVentricular Function, LeftConceptsLV diastolic dysfunctionLeft ventricular diastolic dysfunctionVentricular diastolic dysfunctionDiastolic dysfunctionRisk of deathSystemic sclerosisDisease durationEarly mitral annular velocityMultivariable Cox regression analysisSSc disease durationTissue Doppler eLV systolic dysfunctionPulmonary function testsMitral annular velocityCoronary artery diseaseCox regression analysisMultivariable linear regressionSystemic hypertensionSystolic dysfunctionClinical characteristicsDoppler EImpaired relaxationArtery diseaseClinical factorsConsecutive patients
2011
Validity of two new patient‐reported outcome measures in systemic sclerosis: Patient‐reported outcomes measurement information system 29‐item health profile and functional assessment of chronic illness therapy–dyspnea short form
Hinchcliff M, Beaumont JL, Thavarajah K, Varga J, Chung A, Podlusky S, Carns M, Chang RW, Cella D. Validity of two new patient‐reported outcome measures in systemic sclerosis: Patient‐reported outcomes measurement information system 29‐item health profile and functional assessment of chronic illness therapy–dyspnea short form. Arthritis Care & Research 2011, 63: 1620-1628. PMID: 22034123, PMCID: PMC3205420, DOI: 10.1002/acr.20591.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge of OnsetAgedChronic DiseaseCross-Sectional StudiesDyspneaFemaleHealth StatusHealth Status IndicatorsHumansMaleMichiganMiddle AgedPredictive Value of TestsPrognosisRegistriesReproducibility of ResultsScleroderma, SystemicSelf ReportSeverity of Illness IndexTime FactorsYoung AdultConceptsOutcomes Measurement Information SystemComposite severity scoreMeasurement Information SystemSeverity scorePRO instrumentsPROMIS-29SSc patientsHealth profileFunctional assessmentHealth statusPatient-reported outcome measuresPatient-reported outcome instrumentsRaynaud's phenomenon symptomsSSc disease durationSystemic sclerosis trialMean patient ageNew patient-reported outcome measurePatient-Reported Outcomes Measurement Information SystemPhysical functioning scoresCross-sectional studyDisease severity scoreShort formNew PRO instrumentComplicated scoring systemsDisease duration