2024
Gastrointestinal disease in systemic sclerosis: the neglected organ system?
McMahan Z, Pandolfino J, Perlman H, Del Galdo F, Hinchcliff M. Gastrointestinal disease in systemic sclerosis: the neglected organ system? Current Opinion In Rheumatology 2024 PMID: 39193877, DOI: 10.1097/bor.0000000000001052.Peer-Reviewed Original ResearchSystemic sclerosisClinical trial endpointsInflammatory bowel diseaseTrial endpointsAssessment of disease activityRisk stratification methodsGastrointestinal (GIDisease activityRisk stratificationEffective therapyImmune responseBowel diseaseDisease pathogenesisTherapeutic interventionsGastrointestinal diseasesOrgan systemsDiseaseMultidisciplinary teamPathogenesisFunctional studiesGut microbiomeEndpointSclerosisPOS0824 ARTIFICIAL INTELLIGENCE (DEEP NEURAL NETWORK ANALYSIS) AS A SKIN OUTCOME: RESULTS OF AN OPEN-LABEL BELUMOSUDIL TRIAL IN PATIENTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS
Gunes B, Duran Camacho L, Cowper S, Panse G, Page N, Bundschuh E, Williams A, Carns M, Aren K, Pradhan N, Bernstein E, Fantus S, Volkmann E, Bukiri H, Correia C, Wilson F, Mawe S, Mahoney J, Wang R, Hinchcliff M. POS0824 ARTIFICIAL INTELLIGENCE (DEEP NEURAL NETWORK ANALYSIS) AS A SKIN OUTCOME: RESULTS OF AN OPEN-LABEL BELUMOSUDIL TRIAL IN PATIENTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS. 2024, 1046.2-1047. DOI: 10.1136/annrheumdis-2024-eular.2892.Peer-Reviewed Original Research
2023
Prognostic significance of pericardial effusion in systemic sclerosis-associated pulmonary hypertension: analysis from the PHAROS Registry
Luo Y, Gordon J, Xu J, Kolstad K, Chung L, Steen V, Bernstein E, Csuka M, Derk C, Domsic R, Fischer A, Frech T, Goldberg A, Hant F, Hinchcliff M, Horn E, Hummers L, Hsu V, Kafaja S, Khanna D, Molitor J, Saketkoo L, Shapiro L, Silver R, Simms R. Prognostic significance of pericardial effusion in systemic sclerosis-associated pulmonary hypertension: analysis from the PHAROS Registry. Rheumatology 2023, 63: 1251-1258. PMID: 37478347, PMCID: PMC11065440, DOI: 10.1093/rheumatology/kead368.Peer-Reviewed Original ResearchPersistent pericardial effusionPericardial effusionPulmonary hypertensionSSc-PHSystemic sclerosisPrognostic significanceEffusion statusSystemic sclerosis-associated pulmonary hypertensionMultivariable Cox proportional hazards regressionCox proportional hazards regressionKaplan-Meier survival analysisProspective multicentre registryPulmonary Hypertension AssessmentRight heart catheterizationPredictors of survivalMultivariable-adjusted analysesProportional hazards regressionLog-rank testRecognition of OutcomesMulticentre registryPrognosticate survivalHeart catheterizationIndependent predictorsPrognostic impactSerial echocardiogramsPOS1258 RESULTS FROM A NOMINAL GROUP TECHNIQUE EXERCISE FOR THE CREATION OF A COMBINED RESPONSE INDEX FOR LIMITED CUTANEOUS SYSTEMIC SCLEROSIS: THE CRISTAL PROJECT
Lescoat A, Chen Y, Murphy S, Carroll L, Vann N, Didio P, Iya S, Phanhdone T, Farrington S, Allanore Y, Cella D, Chung L, Clements P, Del Galdo F, Denton C, Distler O, Hinchcliff M, Hughes M, Hummers L, Pauling J, Pope J, Steen V, Varga J, Buch M, Khanna D. POS1258 RESULTS FROM A NOMINAL GROUP TECHNIQUE EXERCISE FOR THE CREATION OF A COMBINED RESPONSE INDEX FOR LIMITED CUTANEOUS SYSTEMIC SCLEROSIS: THE CRISTAL PROJECT. 2023, 971.2-972. DOI: 10.1136/annrheumdis-2023-eular.4633.Peer-Reviewed Original ResearchClinical 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 modelingImpaired left-ventricular global longitudinal strain by feature-tracking cardiac MRI predicts mortality in systemic sclerosis
Feher A, Miller E, Peters D, Mojibian H, Sinusas A, Hinchcliff M, Baldassarre L. Impaired left-ventricular global longitudinal strain by feature-tracking cardiac MRI predicts mortality in systemic sclerosis. Rheumatology International 2023, 43: 849-858. PMID: 36894756, DOI: 10.1007/s00296-023-05294-6.Peer-Reviewed Original ResearchConceptsLate gadolinium enhancementLV-GLSSystemic sclerosisWorse survivalClinical indicationsImpaired left ventricular global longitudinal strainLeft ventricular global longitudinal strainPresence of LGECMR strainLV cardiac indexWorse LV-GLSLV ejection fractionCox regression analysisGlobal longitudinal strainLV cardiac outputGlobal radialCardiac indexOverall survivalRetrospective cohortEjection fractionPrognostic valueAdverse outcomesCardiac outputGadolinium enhancementRV strainThree Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients
Makinde H, Dunn JLM, Gadhvi G, Carns M, Aren K, Chung AH, Muhammad LN, Song J, Cuda CM, Dominguez S, Pandolfino JE, D'Amico J, Budinger GS, Assassi S, Frech TM, Khanna D, Shaeffer A, Perlman H, Hinchcliff M, Winter DR. Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients. Arthritis & Rheumatology 2023, 75: 595-608. PMID: 36281773, PMCID: PMC10165944, DOI: 10.1002/art.42380.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisNonclassical monocytesClassical monocytesSSc patientsTranscriptional signatureSystemic sclerosisSkin diseasesCharacteristic transcriptional signaturesRNA-seq dataSSc skin diseaseWorse lung functionCutaneous systemic sclerosisEarly systemic sclerosisActivity outcome measuresDistinct transcriptional profilesTranscriptional profilingRNA sequencingTranscriptional profilesProspective registryDisease activityLung functionComplex clinical phenotypeGene expressionPeripheral bloodMinority cell populationLearnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease
Higuero Sevilla J, Memon A, Hinchcliff M. Learnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease. Arthritis Research & Therapy 2023, 25: 118. PMID: 37422652, PMCID: PMC10329300, DOI: 10.1186/s13075-023-03090-y.Peer-Reviewed Original ResearchConceptsConnective tissue disease-associated interstitial lung diseaseInterstitial lung diseaseTreatment of patientsMycophenolate mofetilSSc-ILDLung diseaseClinical trialsScleroderma Lung Study IIPatient-reported outcome instrumentsIdiopathic inflammatory myositisClinical trial resultsInflammatory myositisIntravenous cyclophosphamideOral cyclophosphamideSubcutaneous tocilizumabGood tolerabilityLung functionSystemic sclerosisTreatment armamentariumRheumatoid arthritisPatient outcomesSimilar efficacyOutcome instrumentsPatientsUS Food
2022
Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis
Odell I, Steach H, Gauld S, Reinke-Breen L, Karman J, Carr T, Wetter J, Phillips L, Hinchcliff M, Flavell R. Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis. Science Immunology 2022, 7: eabq6691. PMID: 36490328, PMCID: PMC9840167, DOI: 10.1126/sciimmunol.abq6691.Peer-Reviewed Original ResearchConceptsLung fibrosisDendritic cellsImmune cellsDiffuse cutaneous systemic sclerosisPersistence of fibrosisCutaneous systemic sclerosisExtent of fibrosisType I interferonSystemic sclerosisAutoimmune diseasesAntifibrotic targetsTherapeutic administrationMouse modelI interferonLung samplesLung explantsFibrosisFibrotic tissueImmune signalsEpiregulin expressionPatient's skinExtracellular matrix productionGenetic deficiencyEpiregulinEGFR ligandsCirculating CTRP9 Is Associated With Severity of Systemic Sclerosis–Associated Interstitial Lung Disease
Yang MM, Balmert LC, Marangoni RG, Carns M, Hinchcliff M, Korman BD, Varga J. Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis–Associated Interstitial Lung Disease. Arthritis Care & Research 2022, 75: 152-157. PMID: 34251759, PMCID: PMC9233895, DOI: 10.1002/acr.24749.Peer-Reviewed Original ResearchConceptsC1q/tumor necrosis factor-related protein 9Interstitial lung diseaseSystemic sclerosisLung diseaseLung functionSystemic Sclerosis-Associated Interstitial Lung DiseaseSSc-associated interstitial lung diseasePulmonary function test dataLatent trajectory analysisVital capacity percentWorse lung functionPrimary outcome measureWorse pulmonary functionCause of morbidityRetrospective longitudinal studyAdipose tissue metabolismCross-sectional analysisAdipokine homeostasisDisease stabilityPulmonary functionSSc patientsSerum levelsPatient RegistryPredictive markerCapacity percentHuman dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis
Bhandari R, Yang H, Kosarek NN, Smith AE, Garlick JA, Hinchcliff M, Whitfield ML, Pioli PA. Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis. Rheumatology 2022, 62: si114-si124. PMID: 35946522, PMCID: PMC9910573, DOI: 10.1093/rheumatology/keac453.Peer-Reviewed Original ResearchConceptsFibroblast-derived exosomesSSc patientsMacrophage activationGender-matched control subjectsSSc fibroblastsDonor-derived macrophagesReciprocal activationUpregulated surface expressionMHC class IICo-cultured macrophagesHealthy control fibroblastsExtracellular matrix depositionCell typesSystemic sclerosisHealthy ageIL-10Production of collagenIL-12p40IL-6Control subjectsSkin biopsiesSSc skinTherapeutic targetingClass IIFlow cytometryDifferences in symptom experience among patients with systemic sclerosis: a cluster analytic approach to identifying subgroups
Murphy SL, Chen YT, Lee YC, Carns M, Aren K, Korman B, Hinchcliff M, Varga J. Differences in symptom experience among patients with systemic sclerosis: a cluster analytic approach to identifying subgroups. Rheumatology 2022, 62: si64-si73. PMID: 35920770, PMCID: PMC9910572, DOI: 10.1093/rheumatology/keac444.Peer-Reviewed Original ResearchConceptsSleep disturbancesSymptom experienceSymptom subgroupsSymptom clustersTreatment approachesSingle US academic medical centerLarge SSc cohortPatient-reported symptomsCo-occurring painUS academic medical centersSymptoms of peopleDistinct symptom clustersAcademic medical centerMain symptom clustersSimilar disease severityDifferent symptom presentationsSSc cohortSSc patientsSystemic sclerosisPain interferencePatient subgroupsModerate symptomsMedical CenterSymptom presentationDisease severityA 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
Cellular and Molecular Diversity in Scleroderma
Hinchcliff M, Garcia-Milian R, Di Donato S, Dill K, Bundschuh E, Galdo FD. Cellular and Molecular Diversity in Scleroderma. Seminars In Immunology 2021, 58: 101648. PMID: 35940960, DOI: 10.1016/j.smim.2022.101648.Peer-Reviewed Original ResearchConceptsSystemic sclerosisMedicine approachVariable clinical outcomesPrecision medicine approachPersonalized medicine approachClinical outcomesSame diagnosisDisease heterogeneityDisease riskCare promisesPatient heterogeneityRoutine integrationMolecular heterogeneityMolecular underpinningsSclerosisPatientsSclerodermaHistopathologyMolecular basisArmamentariumFindingsDiagnosisHeterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of “scleroderma esophagus”
Carlson DA, Prescott JE, Germond E, Brenner D, Carns M, Correia CS, Tetreault M, McMahan ZH, Hinchcliff M, Kou W, Kahrilas PJ, Perlman HR, Pandolfino JE. Heterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of “scleroderma esophagus”. Neurogastroenterology & Motility 2021, 34: e14284. PMID: 34709690, PMCID: PMC9046463, DOI: 10.1111/nmo.14284.Peer-Reviewed Original ResearchConceptsHigh-resolution manometryIneffective esophageal motilitySecondary peristalsisSystemic sclerosisFLIP panometryAbsent contractilityContractile responseDistensibility indexFunctional luminal imaging probe (FLIP) panometryEsophagogastric junction distensibility indexPattern of contractilityEGJ-DIScleroderma esophagusEsophageal dysmotilityReflux severitySSc patientsClinical outcomesEsophageal motilityManometric diagnosisPrimary peristalsisMotor abnormalitiesNormal peristalsisEsophageal functionChicago ClassificationPatientsEsophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis
Showalter K, Hoffmann A, Richardson C, Aaby D, Lee J, Dematte J, Agrawal R, Savas H, Wu X, Chang RW, Hinchcliff M. Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis. The Journal Of Rheumatology 2021, 48: 1830-1838. PMID: 34266985, PMCID: PMC8985598, DOI: 10.3899/jrheum.210533.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseInterstitial lung diseasePulmonary function testsSystemic sclerosisEsophageal dilationPulmonary function declineFVC declineClinical factorsEsophageal diameterFunction declineScl-70 positivitySSc-ILD patientsSubanalysis of patientsScl-70Function testsPrognostic implicationsVital capacityLung diseaseStudy criteriaI autoantibodiesRisk factorsPFT declineDiffusion capacityPatientsLinear mixed effects modelsImpaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography/Computed Tomography in Patients With Systemic Sclerosis.
Feher A, Boutagy NE, Oikonomou EK, Thorn S, Liu YH, Miller EJ, Sinusas AJ, Hinchcliff M. Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography/Computed Tomography in Patients With Systemic Sclerosis. The Journal Of Rheumatology 2021, 48: 1574-1582. PMID: 34266986, PMCID: PMC10275580, DOI: 10.3899/jrheum.210040.Peer-Reviewed Original ResearchConceptsReduced Myocardial Flow ReserveMyocardial flow reserveRaynaud's phenomenonPrimary Raynaud's phenomenonSecondary Raynaud's phenomenonPatient controlsHealthy participantsFlow reservePositron Emission Tomography/Computed TomographyEmission Tomography/Computed TomographyTomography/Computed TomographyPositron emission tomography/Impaired Myocardial Flow ReserveCoronary microvascular dysfunctionLarge prospective studiesMultivariable logistic regressionEmission tomography/PET/CTSSc-RPMicrovascular dysfunctionClinical predictorsIndependent predictorsSystemic sclerosisPrognostic valueProspective studyClinical 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 ResearchConceptsDiffuse 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-DIPredictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease
Assassi S, Li N, Volkmann ER, Mayes MD, Rünger D, Ying J, Roth MD, Hinchcliff M, Khanna D, Frech T, Clements PJ, Furst DE, Goldin J, Bernstein EJ, Castelino FV, Domsic RT, Gordon JK, Hant FN, Shah AA, Shanmugam VK, Steen VD, Elashoff RM, Tashkin DP. Predictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease. Arthritis & Rheumatology 2021, 73: 1005-1013. PMID: 33350170, PMCID: PMC8169525, DOI: 10.1002/art.41627.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBeta 2-MicroglobulinChemokine CCL19Chemokine CCL8Chemokine CXCL10Chemokine CXCL9CyclophosphamideFemaleHumansImmunosuppressive AgentsLung Diseases, InterstitialMaleMethotrexateMiddle AgedMycophenolic AcidObservational Studies as TopicPrognosisRandomized Controlled Trials as TopicReceptors, Tumor Necrosis Factor, Type IIScleroderma, SystemicVital CapacityConceptsInterstitial lung diseaseMycophenolate mofetilPredictive significanceCYC armILD courseMMF armSSc-ILDSystemic sclerosisLung diseaseHigh baseline C-reactive protein levelsTumor necrosis factor receptor type IIBaseline C-reactive protein levelsScleroderma Lung Study IIC-reactive protein levelsGood responseVital capacity percentChemotactic protein-2Receptor type IIActive immunosuppressionClinical predictorsCRP levelsObservational cohortProtein scoreActive treatmentTreatment armsA review and roadmap of the skin, lung and gut microbiota in systemic sclerosis
Teaw S, Hinchcliff M, Cheng M. A review and roadmap of the skin, lung and gut microbiota in systemic sclerosis. Rheumatology 2021, 60: 5498-5508. PMID: 33734316, PMCID: PMC8643452, DOI: 10.1093/rheumatology/keab262.Peer-Reviewed Original Research