2021
Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort
Jaafar S, Lescoat A, Huang S, Gordon J, Hinchcliff M, Shah AA, Assassi S, Domsic R, Bernstein EJ, Steen V, Elliott S, Hant F, Castelino FV, Shanmugam VK, Correia C, Varga J, Nagaraja V, Roofeh D, Frech T, Khanna D. Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort. Arthritis Research & Therapy 2021, 23: 170. PMID: 34127049, PMCID: PMC8201684, DOI: 10.1186/s13075-021-02548-1.Peer-Reviewed Original ResearchMeSH KeywordsCohort StudiesHumansLung Diseases, InterstitialMycophenolic AcidProspective StudiesScleroderma, DiffuseScleroderma, SystemicUnited StatesConceptsDiffuse cutaneous systemic sclerosisInterstitial lung diseaseImmunosuppressive therapyProgression of skinCardiac involvementSystemic sclerosisUS cohortAnti-RNA polymerase III antibodiesProgressive interstitial lung diseaseEarly diffuse systemic sclerosisMean HAQ-DIMulticenter prospective cohortMulticenter US cohortVital capacity declineMedian disease durationCurrent immunosuppressive therapiesCutaneous systemic sclerosisInternal organ involvementPolymerase III antibodiesDiffuse systemic sclerosisLimited cutaneous SScHigh case fatalityLongitudinal analysisBaseline mRSHAQ-DI
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 courseTowards a new classification of systemic sclerosis
Hinchcliff M, Mahoney JM. Towards a new classification of systemic sclerosis. Nature Reviews Rheumatology 2019, 15: 456-457. PMID: 31217541, DOI: 10.1038/s41584-019-0257-z.Peer-Reviewed Original Research
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 durationNormal Values of Esophageal Distensibility and Distension-Induced Contractility Measured by Functional Luminal Imaging Probe Panometry
Carlson DA, Kou W, Lin Z, Hinchcliff M, Thakrar A, Falmagne S, Prescott J, Dorian E, Kahrilas PJ, Pandolfino JE. Normal Values of Esophageal Distensibility and Distension-Induced Contractility Measured by Functional Luminal Imaging Probe Panometry. Clinical Gastroenterology And Hepatology 2018, 17: 674-681.e1. PMID: 30081222, PMCID: PMC6360138, DOI: 10.1016/j.cgh.2018.07.042.Peer-Reviewed Original ResearchMeSH KeywordsAdultElasticityEndoscopyEsophagusFemaleHealthy VolunteersHumansMaleManometryMuscle ContractionProspective StudiesReference ValuesConceptsRepetitive antegrade contractionsEGJ-DIFLIP panometryDistensibility plateauAntegrade contractionsEsophageal contractilityEsophagogastric junctionEsophageal distensibilityAsymptomatic volunteersClinical practiceFunctional luminal imaging probe (FLIP) panometryEGJ-distensibility indexSedated upper endoscopyTime of endoscopyProximal esophageal bodyRAC patternUpper endoscopyDistal esophagusEosinophilic esophagitisEsophageal bodyNormal findingsProspective studyEsophageal diseaseDistal bodyHealthy individualsMycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin
Hinchcliff M, Toledo DM, Taroni JN, Wood TA, Franks JM, Ball MS, Hoffmann A, Amin SM, Tan AU, Tom K, Nesbeth Y, Lee J, Ma M, Aren K, Carns MA, Pioli PA, Whitfield ML. Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin. Journal Of Investigative Dermatology 2018, 138: 1301-1310. PMID: 29391252, PMCID: PMC6590516, DOI: 10.1016/j.jid.2018.01.006.Peer-Reviewed Original ResearchConceptsMycophenolate mofetil treatmentMyeloid cell numbersMMF therapyMofetil treatmentSystemic sclerosisInflammatory scoreSkin biopsiesCell numberSkin myeloid cellsMyeloid dendritic cellsHalf of patientsRodnan skin scoreImmune cell numbersInflammatory gene signatureExpression of chemokinesProtein levelsCCL2 protein levelsCCL2 mRNA expressionInflammatory signatureDendritic cellsSkin scoreCCL2 mRNAEleven subjectsMonocyte migrationMyeloid cells
2017
Reliability and Validity of the Tender and Swollen Joint Counts and the Modified Rodnan Skin Score in Early Diffuse Cutaneous Systemic Sclerosis: Analysis from the Prospective Registry of Early Systemic Sclerosis Cohort.
Gordon JK, Girish G, Berrocal VJ, Zhang M, Hatzis C, Assassi S, Bernstein EJ, Domsic RT, Hant FN, Hinchcliff M, Schiopu E, Steen VD, Frech TM, Khanna D. Reliability and Validity of the Tender and Swollen Joint Counts and the Modified Rodnan Skin Score in Early Diffuse Cutaneous Systemic Sclerosis: Analysis from the Prospective Registry of Early Systemic Sclerosis Cohort. The Journal Of Rheumatology 2017, 44: 791-794. PMID: 28298560, PMCID: PMC5457319, DOI: 10.3899/jrheum.160654.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisSwollen joint countCutaneous systemic sclerosisRodnan skin scoreMusculoskeletal ultrasoundJoint countSkin scoreSystemic sclerosisEarly diffuse cutaneous systemic sclerosisModified Rodnan skin scoreSystemic sclerosis cohortProspective registryTJCExcellent interMRSSSJCSclerosisContent validityScoresCountRheumatologistsPatientsRegistryCohortAbnormalities
2016
Utility of B-type natriuretic peptides in the assessment of patients with systemic sclerosis-associated pulmonary hypertension in the PHAROS registry.
Chung L, Fairchild RM, Furst DE, Li S, Alkassab F, Bolster MB, Csuka ME, Derk CT, Domsic RT, Fischer A, Frech TM, Gomberg-Maitland M, Gordon JK, Hinchcliff M, Hsu V, Hummers LK, Khanna D, Medsger TAJ, Molitor JA, Preston IR, Schiopu E, Shapiro L, Hant F, Silver R, Simms R, Varga J, Steen VD, Zamanian RT. Utility of B-type natriuretic peptides in the assessment of patients with systemic sclerosis-associated pulmonary hypertension in the PHAROS registry. Clinical And Experimental Rheumatology 2016, 35 Suppl 106: 106-113. PMID: 27908301.Peer-Reviewed Original ResearchConceptsB-type natriuretic peptideNT-proBNP levelsPg/mLSSc-PHNT-proBNPPulmonary hypertensionSSc patientsSystemic sclerosisNatriuretic peptideBaseline B-type natriuretic peptideMedian B-type natriuretic peptideSystemic sclerosis-associated pulmonary hypertensionMulticenter prospective cohortNT-proBNP groupNatriuretic peptide levelsRight ventricular dysfunctionPredictors of mortalityPulmonary arterial hypertensionPredictors of progressionAssessment of patientsBaseline creatinineSSc-PAHArterial hypertensionPAH patientsVentricular dysfunction
2015
Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures
Taroni JN, Martyanov V, Huang CC, Mahoney JM, Hirano I, Shetuni B, Yang GY, Brenner D, Jung B, Wood TA, Bhattacharyya S, Almagor O, Lee J, Sirajuddin A, Varga J, Chang RW, Whitfield ML, Hinchcliff M. Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures. Arthritis Research & Therapy 2015, 17: 194. PMID: 26220546, PMCID: PMC4518531, DOI: 10.1186/s13075-015-0695-1.Peer-Reviewed Original ResearchConceptsSystemic sclerosisEsophageal biopsiesInflammatory signatureLarge inflammatory infiltratesConsecutive SSc patientsSmooth muscle atrophyAbsence of fibrosisSmooth muscle functionProliferative gene expression signatureGene expression subsetsSmooth muscle cellsEsophageal dilatationGene expression signaturesSSc patientsEsophageal fibrosisSerum autoantibodiesInflammatory infiltrateEsophageal pathologyImmune activationAutopsy studySSc pathogenesisSSc casesMolecular subsetsGene expressionMuscle atrophy
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 patientsSurvival and Predictors of Mortality in Systemic Sclerosis‐Associated Pulmonary Arterial Hypertension: Outcomes From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry
Chung L, Domsic RT, Lingala B, Alkassab F, Bolster M, Csuka ME, Derk C, Fischer A, Frech T, Furst DE, Gomberg‐Maitland M, Hinchcliff M, Hsu V, Hummers LK, Khanna D, Medsger TA, Molitor JA, Preston IR, Schiopu E, Shapiro L, Silver R, Simms R, Varga J, Gordon JK, Steen VD. Survival and Predictors of Mortality in Systemic Sclerosis‐Associated Pulmonary Arterial Hypertension: Outcomes From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry. Arthritis Care & Research 2014, 66: 489-495. PMID: 23983198, DOI: 10.1002/acr.22121.Peer-Reviewed Original ResearchConceptsPulmonary arterial hypertensionPulmonary Hypertension AssessmentCumulative survival rateRecognition of OutcomesSurvival rateScleroderma RegistryArterial hypertensionSSc patientsHypertension assessmentRoutine screeningWorld Health Organization group I PAHSystemic sclerosis associated pulmonary arterial hypertensionGroup I pulmonary arterial hypertensionSSc-associated pulmonary arterial hypertensionIncident pulmonary arterial hypertensionSSc centersRight-sided heart catheterizationDefinite pulmonary hypertensionIncident systemic sclerosisPredictors of mortalityMonths of enrollmentHeart catheterizationPAH diagnosisProspective registryPulmonary hypertension
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 patientsBaseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry
Bae S, Saggar R, Bolster MB, Chung L, Csuka ME, Derk C, Domsic R, Fischer A, Frech T, Goldberg A, Hinchcliff M, Hsu V, Hummers L, Schiopu E, Mayes MD, McLaughlin V, Molitor J, Naz N, Furst DE, Maranian P, Steen V, Khanna D. Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry. Annals Of The Rheumatic Diseases 2012, 71: 1335. PMID: 22307943, PMCID: PMC3398226, DOI: 10.1136/annrheumdis-2011-200546.Peer-Reviewed Original ResearchConceptsRight heart catheterisationPulmonary hypertensionSystemic sclerosisHigh-resolution CTNormal haemodynamicsBaseline characteristicsBorderline mean pulmonary arterial pressureHigh pulmonary vascular resistanceMean pulmonary arterial pressureRight ventricular systolic pressureAbnormal lung physiologyBaseline clinical characteristicsMean pulmonary pressureProspective longitudinal cohortPulmonary vascular resistancePulmonary arterial pressurePulmonary function testsRestrictive lung diseaseVentricular systolic pressureLong-term outcomesElevated mPAPHeart catheterisationVascular resistanceBaseline demographicsClinical characteristics