854 results on '"Assassi, Shervin"'
Search Results
2. Combining Clinical and Biological Data to Predict Progressive Pulmonary Fibrosis in Patients With Systemic Sclerosis Despite Immunomodulatory Therapy.
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Volkmann, Elizabeth, Wilhalme, Holly, Assassi, Shervin, Kim, Grace, Kuwana, Masataka, Tashkin, Donald, Roth, Michael, and Goldin, Jonathan
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OBJECTIVE: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD). METHODS: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling. RESULTS: Among 112 participants with follow-up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C-index of 0.72 (95% confidence interval 0.60-0.84). CONCLUSION: The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc-ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc-ILD cohorts to confirm its predictive power.
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- 2023
3. Genetic Factors
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Assassi, Shervin, Martin, Javier, Allanore, Yannick, Allanore, Yannick, editor, Varga, John, editor, Denton, Christopher P., editor, Kuwana, Masataka, editor, Chung, Lorinda, editor, and Shah, Ami A., editor
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- 2024
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4. Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease.
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Roofeh, David, Brown, Kevin, Kazerooni, Ella, Tashkin, Donald, Assassi, Shervin, Martinez, Fernando, Wells, Athol, Raghu, Ganesh, Denton, Christopher, Chung, Lorinda, Hoffmann-Vold, Anna-Maria, Distler, Oliver, Johannson, Kerri, Allanore, Yannick, Matteson, Eric, Kawano-Dourado, Leticia, Pauling, John, Seibold, James, Volkmann, Elizabeth, Walsh, Simon, Oddis, Chester, White, Eric, Barratt, Shaney, Bernstein, Elana, Domsic, Robyn, Dellaripa, Paul, Conway, Richard, Rosas, Ivan, Bhatt, Nitin, Hsu, Vivien, Ingegnoli, Francesca, Kahaleh, Bashar, Garcha, Puneet, Gupta, Nishant, Khanna, Surabhi, Korsten, Peter, Lin, Celia, Mathai, Stephen, Strand, Vibeke, Doyle, Tracy, Steen, Virginia, Zoz, Donald, Ovalles-Bonilla, Juan, Rodriguez-Pinto, Ignasi, Shenoy, Padmanabha, Lewandoski, Andrew, Belloli, Elizabeth, Lescoat, Alain, Nagaraja, Vivek, Ye, Wen, Huang, Suiyuan, Maher, Toby, and Khanna, Dinesh
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connective tissue disease interstitial lung disease ,systemic sclerosis associated interstitial lung disease subsets ,systemic sclerosis interstitial lung disease ,Humans ,Lung Diseases ,Interstitial ,Scleroderma ,Systemic ,Vital Capacity ,Tomography ,X-Ray Computed ,Severity of Illness Index ,Lung - Abstract
OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.
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- 2023
5. Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts.
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Estrada-Y-Martin, Rosa, Skaug, Brian, Mayes, Maureen, Tashkin, Donald, Assassi, Shervin, Wareing, Nancy, Mohan, Vishnu, Taherian, Rana, Volkmann, Elizabeth, Lyons, Marka, Wilhalme, Holly, and Roth, Michael
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Humans ,Neutrophils ,Lymphocytes ,Scleroderma ,Systemic ,Disease Progression ,Skin ,Lymphocyte Count - Abstract
OBJECTIVE: To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). METHODS: Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. RESULTS: Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b = -4.74, P = 0.009 and b = -2.68, P = 0.028, respectively) and higher serially obtained MRSS (b = 4.07, P
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- 2023
6. Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression.
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Khanna, Dinesh, Maher, Toby, Volkmann, Elizabeth, Allanore, Yannick, Smith, Vanessa, Assassi, Shervin, Kreuter, Michael, Hoffmann-Vold, Anna-Maria, Kuwana, Masataka, Stock, Christian, Alves, Margarida, Sambevski, Steven, and Denton, Christopher
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Autoimmune Diseases ,Pulmonary Fibrosis ,Scleroderma ,Systemic ,Therapeutics ,Humans ,Fibrosis ,Lung Diseases ,Interstitial ,Risk Factors ,Scleroderma ,Systemic - Abstract
OBJECTIVE: To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC. METHODS: The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (
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- 2023
7. Sex differences in clinical outcomes and biological profiles in systemic sclerosis-associated interstitial lung disease: a post-hoc analysis of two randomised controlled trials.
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Volkmann, Elizabeth, Tashkin, Donald, Silver, Richard, Bostwick, Carol, Assassi, Shervin, Frost, DeAnna, Leng, Mei, Wilhalme, Holly, Kim, Grace, Roth, Michael, and Goldin, Jonathan
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BACKGROUND: Observational studies have shown that men with systemic sclerosis have an increased risk of interstitial lung disease (ILD) and mortality compared with women. However, previous studies have not controlled for treatment effect or evaluated the biological mechanism or mechanisms underlying this sex difference. We aimed to compare ILD progression and long-term morbidity and mortality outcomes in male and female participants of two randomised controlled trials for systemic sclerosis-associated ILD. METHODS: For this post-hoc analysis, data from all participants in the Scleroderma Lung Study (SLS) I and SLS II were analysed. The primary objective was to explore the effect of sex on the course of the percentage predicted forced vital capacity (FVC) during and after active treatment over the 24-month study periods. In SLS I, 158 participants (111 women, 47 men) were randomly assigned to receive oral cyclophosphamide (cyclophosphamide; ≤2 mg/kg daily) or placebo; in SLS II, 142 participants (105 women, 37 men) were randomly assigned to receive oral mycophenolate mofetil (1500 mg twice daily) or oral cyclophosphamide (≤2 mg/kg daily). Sex (ie, male or female) was self-reported in both studies by the participants. Changes in radiographic fibrosis and time to death and respiratory failure were secondary outcomes of the present analysis. Baseline levels of biomarkers implicated in the pathobiology of systemic sclerosis-associated ILD were measured in bronchoalveolar lavage fluid in SLS I. FINDINGS: In the SLS I placebo group, the rate of decline in percentage predicted FVC from 3 months to 12 months was greater in men than in women, but the difference was not significant (estimated effect -0·29 [95% CI -0·67 to 0·10]; p=0·14). In SLS II, the rate of decline in percentage predicted FVC from 3 months to 12 months was significantly worse in men treated with either cyclophosphamide (estimated effect -0·72; [95% CI -1·14 to -0·31]; p=0·00060) or mycophenolate mofetil (estimated effect -0·34 [-0·58 to -0·10]; p=0·0051) than in women. A greater proportion of men had a decline in percentage predicted FVC of 10% or greater compared with women for the pooled active treatment groups from SLS I and SLS II and the placebo group of SLS I. Men had worse radiographic outcomes at 2 years than women in SLS II, even after adjusting for baseline disease severity and treatment arm assignment. Long-term survival was worse in men in SLS I (log-rank test p=0·080) and SLS II (log-rank test p=0·030). In SLS II, male sex was independently associated with increased mortality (hazard ratio 2·42 [95% CI 1·16 to 5·04]; p=0·018). In bronchoalveolar lavage fluid, men had increased concentrations of pro-fibrotic mediators (eg, matrix metalloproteinase-13 and tissue inhibitor of metallopeptidase 1), whereas women had increased pro-inflammatory mediators (eg, interleukin [IL]-12, IL-7, and granulocyte-colony stimulating factor). INTERPRETATION: In two randomised controlled trials, men with systemic sclerosis-associated ILD had a less favourable course of ILD both with and without active treatment, as well as worse long-term survival. Sex differences in pro-fibrotic or inflammatory mediators of disease might account for these differences and warrant future study. FUNDING: US National Institutes of Health; US National Heart, Lung, and Blood Institute; US National Institute of Arthritis and Musculoskeletal and Skin Diseases; Bristol Myers Squibb; and Hoffmann-LaRoche.
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- 2022
8. Understanding diagnostic pathways in systemic sclerosis and systemic sclerosis-associated interstitial lung disease: A retrospective cohort study.
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Assassi, Shervin, Shao, Nan, Yin, Ziwei, Volkmann, Elizabeth, Zoz, Donald, and Leonard, Thomas
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Cohort Studies ,Humans ,Lung ,Lung Diseases ,Interstitial ,Retrospective Studies ,Scleroderma ,Systemic - Abstract
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is usually detected in a patient known to have SSc but may be diagnosed prior to SSc. We probed an insurance database to investigate documentation of ILD prior to SSc. Using Optums Clinformatics® Data Mart Database, we identified patients with an SSc index date between January 1, 2010, and September 30, 2015, based on International Classification of Diseases (ICD)-9-Clinical Modification (CM) codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥3 years of continuous enrollment prior to SSc index date (ICD-9-CM cohort). We identified an ICD-10-CM cohort comprising patients with an SSc index date between October 1, 2017, and June 30, 2019, based on ICD-10-CM codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥2 years of continuous enrollment prior to SSc index date. ILD was defined as ≥2 medical claims associated with ILD on different dates. The ICD-9-CM and ICD-10-CM cohorts comprised 1779 and 1032 patients, respectively. In these cohorts, respectively, 7.6% and 9.3% of patients had their second medical claim associated with ILD prior to their SSc index date, and 4.3% and 5.6% of patients had their second medical claim associated with ILD >1 year prior to the SSc index date. In this analysis, 4% to 6% of patients with SSc had claims for ILD >1 year prior to a claim for SSc. These data show that SSc can affect the lung early and demonstrate the importance of screening patients with SSc for ILD and patients with ILD for SSc.
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- 2022
9. A Prospective Observational Study of Disease Severity and Mortality in Hispanic American Patients With Systemic Sclerosis
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Jandali, Bochra, Lyons, Marka, Charles, Julio, Zhang, Meng, Theodore, Samuel, Pedroza, Claudia, Mayes, Maureen D., and Assassi, Shervin
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- 2024
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10. Peripheral blood gene expression profiling shows predictive significance for response to mycophenolate in systemic sclerosis-related interstitial lung disease
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Assassi, Shervin, Volkmann, Elizabeth R, Zheng, W Jim, Wang, Xuan, Wilhalme, Holly, Lyons, Marka A, Roth, Michael D, and Tashkin, Donald P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Autoimmune Disease ,Rare Diseases ,Clinical Research ,Genetics ,Scleroderma ,Lung ,Inflammatory and immune system ,Cyclophosphamide ,Gene Expression Profiling ,Humans ,Immunosuppressive Agents ,Inflammation ,Lung Diseases ,Interstitial ,Mycophenolic Acid ,Scleroderma ,Systemic ,Vital Capacity ,scleroderma ,systemic ,pulmonary fibrosis ,autoimmune diseases ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectivesTo characterise the peripheral blood cell (PBC) gene expression changes ensuing from mycophenolate mofetil (MMF) or cyclophosphamide (CYC) treatment and to determine the predictive significance of baseline PBC transcript scores for response to immunosuppression in systemic sclerosis (SSc)-related interstitial lung disease (ILD).MethodsPBC RNA samples from baseline and 12-month visits, corresponding to the active treatment period of both arms in Scleroderma Lung Study II, were investigated by global RNA sequencing. Joint models were created to examine the predictive significance of baseline composite modular scores for the course of forced vital capacity (FVC) per cent predicted measurements from 3 to 12 months.Results134 patients with SSc-ILD (CYC=69 and MMF=65) were investigated. CYC led to an upregulation of erythropoiesis, inflammation and myeloid lineage-related modules and a downregulation of lymphoid lineage-related modules. The modular changes resulting from MMF treatment were more modest and included a downregulation of plasmablast module. In the longitudinal analysis, none of the baseline transcript module scores showed predictive significance for FVC% course in the CYC arm. In contrast, in the MMF arm, higher baseline lymphoid lineage modules predicted better subsequent FVC% course, while higher baseline myeloid lineage and inflammation modules predicted worse subsequent FVC% course.ConclusionConsistent with the primary mechanism of action of MMF on lymphocytes, patients with SSc-ILD with higher baseline lymphoid module scores had better FVC% course, while those with higher myeloid cell lineage activation score had poorer FVC% course on MMF.
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- 2022
11. Fibroblast Subpopulations in Systemic Sclerosis: Functional Implications of Individual Subpopulations and Correlations with Clinical Features
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Zhu, Honglin, Luo, Hui, Skaug, Brian, Tabib, Tracy, Li, Yi-Nan, Tao, Yongguang, Matei, Alexandru-Emil, Lyons, Marka A., Schett, Georg, Lafyatis, Robert, Assassi, Shervin, and Distler, Jörg H.W.
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- 2024
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12. Proteomic aptamer analysis reveals serum markers that characterize preclinical systemic sclerosis (SSc) patients at risk for progression toward definite SSc
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Bellocchi, Chiara, Assassi, Shervin, Lyons, Marka, Marchini, Maurizio, Mohan, Chandra, Santaniello, Alessandro, and Beretta, Lorenzo
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- 2023
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13. Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis
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Hwang, Mark, Assassi, Shervin, Zheng, Jim, Castillo, Jessica, Chavez, Reyna, Vanarsa, Kamala, Mohan, Chandra, and Reveille, John
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- 2023
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14. A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc.
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Saketkoo, Lesley, Frech, Tracy, Varjú, Cecília, Domsic, Robyn, Farrell, Jessica, Gordon, Jessica, Mihai, Carina, Sandorfi, Nora, Shapiro, Lee, Poole, Janet, Volkmann, Elizabeth, Lammi, Monika, McAnally, Kendra, Alexanderson, Helene, Pettersson, Henrik, Hant, Faye, Kuwana, Masataka, Shah, Ami, Smith, Vanessa, Hsu, Vivien, Kowal-Bielecka, Otylia, Assassi, Shervin, Cutolo, Maurizio, Kayser, Cristiane, Shanmugam, Victoria, Vonk, Madelon, Fligelstone, Kim, Baldwin, Nancy, Connolly, Kerri, Ronnow, Anneliese, Toth, Beata, Suave, Maureen, Farrington, Sue, Bernstein, Elana, Crofford, Leslie, Czirják, László, Jensen, Kelly, Hinchclif, Monique, Hudson, Marie, Lammi, Matthew, Mansour, Jennifer, Morgan, Nadia, Mendoza, Fabian, Nikpour, Mandana, Pauling, John, Riemekasten, Gabriela, Russell, Anne-Marie, Scholand, Mary, Seigart, Elise, Rodriguez-Reyna, Tatiana, Hummers, Laura, Walker, Ulrich, and Steen, Virginia
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Disability ,Interstitial lung disease ,Pulmonary fibrosis ,Pulmonary hypertension ,Quality of life ,Renal crisis ,Scleroderma ,Symptom burden ,Systemic sclerosis ,Humans ,Hypertension ,Pulmonary ,Lung ,Lung Diseases ,Interstitial ,Patient Care ,Scleroderma ,Systemic - Abstract
Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.
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- 2021
15. Predictive Significance of Serum Interferon-Inducible Protein Score for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease.
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Assassi, Shervin, Li, Ning, Volkmann, Elizabeth, Mayes, Maureen, Rünger, Dennis, Ying, Jun, Roth, Michael, Hinchcliff, Monique, Khanna, Dinesh, Frech, Tracy, Clements, Philip, Furst, Daniel, Goldin, Jonathan, Bernstein, Elana, Castelino, Flavia, Domsic, Robyn, Gordon, Jessica, Hant, Faye, Shah, Ami, Shanmugam, Victoria, Steen, Virginia, Elashoff, Robert, and Tashkin, Donald
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Adult ,Aged ,Chemokine CCL19 ,Chemokine CCL8 ,Chemokine CXCL10 ,Chemokine CXCL9 ,Cyclophosphamide ,Female ,Humans ,Immunosuppressive Agents ,Lung Diseases ,Interstitial ,Male ,Methotrexate ,Middle Aged ,Mycophenolic Acid ,Observational Studies as Topic ,Prognosis ,Randomized Controlled Trials as Topic ,Receptors ,Tumor Necrosis Factor ,Type II ,Scleroderma ,Systemic ,Vital Capacity ,beta 2-Microglobulin - Abstract
OBJECTIVE: Response to immunosuppression is highly variable in systemic sclerosis (SSc)-related interstitial lung disease (ILD). This study was undertaken to determine whether a composite serum interferon (IFN)-inducible protein score exhibits predictive significance for the response to immunosuppression in SSc-ILD. METHODS: Serum samples collected in the Scleroderma Lung Study II, a randomized controlled trial of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC), were examined. Results were validated in an independent observational cohort receiving active treatment. A composite score of 6 IFN-inducible proteins IFNγ-inducible 10-kd protein, monokine induced by IFNγ, monocyte chemotactic protein 2, β2 -microglobulin, tumor necrosis factor receptor type II, and macrophage inflammatory protein 3β) was calculated, and its predictive significance for longitudinal forced vital capacity percent predicted measurements was evaluated. RESULTS: Higher baseline IFN-inducible protein score predicted better response over 3 to 12 months in the MMF arm (point estimate = 0.41, P = 0.001) and CYC arm (point estimate = 0.91, P = 0.009). In contrast, higher baseline C-reactive protein (CRP) levels were predictive of a worse ILD course in both treatment arms. The predictive significance of the IFN-inducible protein score and CRP levels remained after adjustment for baseline demographic and clinical predictors. During the second year of treatment, in which patients in the CYC arm were switched to placebo, a higher IFN-inducible protein score at 12 months showed a trend toward predicting a worse ILD course (point estimate = -0.61, P = 0.068), while it remained predictive of better response to active immunosuppression in the MMF arm (point estimate = 0.28, P = 0.029). The predictive significance of baseline IFN-inducible protein score was replicated in the independent cohort (rs = 0.43, P = 0.028). CONCLUSION: A higher IFN-inducible protein score in SSc-ILD is predictive of better response to immunosuppression and could potentially be used to identify patients who may derive the most benefit from MMF or CYC.
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- 2021
16. Large-Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis.
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Bellocchi, Chiara, Ying, Jun, Goldmuntz, Ellen, Keyes-Elstein, Lynette, Varga, John, Hinchcliff, Monique, Lyons, Marka, McSweeney, Peter, Furst, Daniel, Nash, Richard, Crofford, Leslie, Welch, Beverly, Goldin, Jonathan, Pinckney, Ashley, Mayes, Maureen, Sullivan, Keith, and Assassi, Shervin
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Adult ,Chemokines ,Cytokines ,Female ,Fibrosis ,Humans ,Lung ,Male ,Middle Aged ,Pulmonary Fibrosis ,Scleroderma ,Systemic ,Skin ,Skin Diseases ,Transcriptome - Abstract
OBJECTIVE: To provide a large-scale assessment of serum protein dysregulation in diffuse cutaneous systemic sclerosis (dcSSc) and to investigate serum protein correlates of SSc fibrotic features. METHODS: We investigated serum protein profiles of 66 participants with dcSSc at baseline who were enrolled in the Scleroderma: Cyclophosphamide or Transplant Trial and 66 age- and sex-matched healthy control subjects. A panel of 230 proteins, including several cytokines and chemokines, was investigated. Whole blood gene expression profiling in concomitantly collected samples was performed. RESULTS: Among the participants with dcSSc, the mean disease duration was 2.3 years. All had interstitial lung disease (ILD), and none were being treated with immunosuppressive agents at baseline. Ninety proteins were differentially expressed in participants with dcSSc compared to healthy control subjects. Similar to previous global skin transcript results, hepatic fibrosis, granulocyte and agranulocyte adhesion, and diapedesis were the top overrepresented pathways. Eighteen proteins correlated with the modified Rodnan skin thickness score (MRSS). Soluble epidermal growth factor receptor was significantly down-regulated in dcSSc and showed the strongest negative correlation with the MRSS, being predictive of the scores course over time, whereas α1 -antichymotrypsin was significantly up-regulated in dcSSc and showed the strongest positive correlation with the MRSS. Furthermore, higher levels of cancer antigen 15-3 correlated with more severe ILD, based on findings of reduced forced vital capacity and higher scores of disease activity on high-resolution computed tomography. Only 14 genes showed significant differential expression in the same direction in serum protein and whole blood RNA gene expression analyses. CONCLUSION: Diffuse cutaneous SSc has a distinct serum protein profile with prominent dysregulation of proteins related to fibrosis and immune cell adhesion/diapedesis. The differential expression for most serum proteins in SSc is likely to originate outside the peripheral blood cells.
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- 2021
17. Racial Disparities in Systemic Sclerosis: Short- and Long-Term Outcomes Among African American Participants of SLS I and II.
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Volkmann, Elizabeth, Steen, Virginia, Li, Ning, Roth, Michael, Clements, Philip, Furst, Daniel, Assassi, Shervin, Khanna, Dinesh, Kim, Grace-Hyun, Goldin, Jonathan, Elashoff, Robert, and Tashkin, Donald
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OBJECTIVE: To evaluate short- and long-term outcomes of African American (AA) participants of Scleroderma Lung Studies (SLS) I and II. METHODS: SLS I randomized 158 participants with systemic sclerosis-interstitial lung disease (SSc-ILD) to 1 year of oral cyclophosphamide (CYC) versus placebo. SLS II randomized 142 participants with SSc-ILD to 1 year of oral CYC followed by 1 year of placebo versus 2 years of mycophenolate (MMF). Joint models compared the course of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) between AA and non-AA, and Cox proportional hazard models assessed long-term morbidity and mortality outcomes. RESULTS: In SLS I, there was no difference in the course of the FVC or DLCO between AA and non-AA in either treatment arm. In SLS II, AA had an improved course of the FVC compared with non-AA in the CYC arm; in the MMF arm, there was no difference in FVC course. There was no difference in DLCO course in either arm. Time to death and respiratory failure were similar for AA and non-AA in SLS I. There was a trend for improved survival and time to respiratory failure in AA compared with non-AA in SLS II. AA race was not independently associated with mortality in the SLS I or II in the Cox models. CONCLUSION: Data from two randomized controlled trials demonstrated that AA patients with SSc-ILD have similar morbidity and mortality outcomes compared with non-AA patients. These findings contrast with the racial disparities described in prior observational studies and warrant further investigation.
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- 2021
18. Patterns of patient-reported symptoms and association with sociodemographic and systemic sclerosis disease characteristics: a scleroderma Patient-centered Intervention Network (SPIN) Cohort cross-sectional study
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Adams, Claire E., Henry, Richard S., Fortuné, Catherine, Gottesman, Karen, Guillot, Geneviève, Hummers, Laura K., Lawrie-Jones, Amanda, Mayes, Maureen D., Richard, Michelle, Sauvé, Maureen, Assassi, Shervin, El-Baalbaki, Ghassan, Fligelstone, Kim, Frech, Tracy, Gietzen, Amy, Harel, Daphna, Hinchcliff, Monique, Johnson, Sindhu R., Larche, Maggie, Leite, Catarina, Nguyen, Christelle, Nielsen, Karen, Pope, Janet, Rannou, François, Rodriguez-Reyna, Tatiana Sofia, Schouffoer, Anne A., Suarez-Almazor, Maria E., Agard, Christian, Abdallah, Nassim Ait, André, Marc, Bernstein, Elana J., Berthier, Sabine, Bissonnette, Lyne, Bruns, Alessandra, Carreira, Patricia, Casadevall, Marion, Chaigne, Benjamin, Chung, Lorinda, Crichi, Benjamin, Denton, Christopher, Domsic, Robyn, Dunne, James V., Dunogue, Bertrand, Fare, Regina, Farge-Bancel, Dominique, Fortin, Paul R., Gordon, Jessica, Granel-Rey, Brigitte, Guffroy, Aurélien, Gyger, Genevieve, Hachulla, Eric, Hoa, Sabrina, Ikic, Alena, Kafaja, Suzanne, Khalidi, Nader, Lakin, Kimberly, Lambert, Marc, Launay, David, Lee, Yvonne C., Maillard, Hélène, Maltez, Nancy, Manning, Joanne, Marie, Isabelle, Lopez, Maria Martin, Martin, Thierry, Masetto, Ariel, Maurier, François, Mekinian, Arsene, Díaz, Sheila Melchor, Nikpour, Mandana, Olagne, Louis, Poindron, Vincent, Proudman, Susanna, Régent, Alexis, Rivière, Sébastien, Robinson, David, Almazar, Esther Rodríguez, Roux, Sophie, Smets, Perrine, Sobanski, Vincent, Spiera, Robert, Steen, Virginia, Sutton, Evelyn, Thorne, Carter, Varga, John, Wilcox, Pearce, Ayala, Mara Cañedo, Cook, Vanessa, Hu, Sophie, Matthews, Bianca, Nassar, Elsa-Lynn, Neyer, Marieke Alexandra, Nordlund, Julia, Provencher, Sabrina, Wojeck, Robyn K., Knisely, Mitchell R., Bailey, Donald E., Somers, Tamara J., Kwakkenbos, Linda, Carrier, Marie-Eve, Nielson, Warren R., Bartlett, Susan J., Malcarne, Vanessa L., Hudson, Marie, Levis, Brooke, Benedetti, Andrea, Mouthon, Luc, Thombs, Brett D., and Silva, Susan G.
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- 2023
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19. Validity, Reliability, and Differential Item Functioning of English and French Versions of the 10‐Item Connor‐Davidson Resilience Scale in Systemic Sclerosis: A Scleroderma Patient‐Centered Intervention Network Cohort Study
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Neyer, Marieke A., Henry, Richard S., Carrier, Marie‐Eve, Kwakkenbos, Linda, Wojeck, Robyn K., Gietzen, Amy, Gottesman, Karen, Guillot, Geneviève, Lawrie‐Jones, Amanda, Mayes, Maureen D., Mouthon, Luc, Nielson, Warren R., Richard, Michelle, Worron‐Sauvé, Maureen, Harel, Daphna, Malcarne, Vanessa L., Bartlett, Susan J., Thombs, Brett D., Fortuné, Catherine, Hudson, Marie, Benedetti, Andrea, Hummers, Laura K., Adams, Claire Elizabeth, Ayala, Mara Cañedo, Cook, Vanessa, Hu, Sophie, Matthews, Bianca, Nassar, Elsa‐Lynn, Nordlund, Julia, Provencher, Sabrina, Assassi, Shervin, El‐Baalbaki, Ghassan, Fligelstone, Kim, Frech, Tracy, Hinchcliff, Monique, Johnson, Sindhu R., Larche, Maggie, Khalidi, Nader, Leite, Catarina, Nguyen, Christelle, Rannou, François, Nielsen, Karen, Pope, Janet, Rodriguez‐Reyna, Tatiana Sofia, Schouffoer, Anne A., Suarez‐Almazor, Maria E., Agard, Christian, André, Marc, Olagne, Louis, Bernstein, Elana J., Berthier, Sabine, Bissonnette, Lyne, Bruns, Alessandra, Masetto, Ariel, Roux, Sophie, Cacciatore, Carlotta, Crichi, Benjamin, Farge‐Bancel, Dominique, Carreira, Patricia, Fare, Regina, Lopez, Maria Martin, Díaz, Sheila Melchor, Almazar, Esther Rodríguez, Casadevall, Marion, Chaigne, Benjamin, Dunogue, Bertrand, Régent, Alexis, Chung, Lorinda, Domsic, Robyn, Dunne, James V., Wilcox, Pearce, Fortin, Paul R., Ikic, Alena, Gordon, Jessica, Lakin, Kimberly, Spiera, Robert, Granel‐Rey, Brigitte, Guffroy, Aurélien, Martin, Thierry, Poindron, Vincent, Gyger, Genevieve, Hachulla, Eric, Hoa, Sabrina, Jones, Niall, Lambert, Marc, Launay, David, Maillard, Hélène, Sobanski, Vincent, Lee, Yvonne C., Maltez, Nancy, Manning, Joanne, Marie, Isabelle, Maurier, François, Mekinian, Arsene, Rivière, Sébastien, Nikpour, Mandana, Proudman, Susanna, Robinson, David, Smets, Perrine, Steen, Virginia, Sutton, Evelyn, and Thorne, Carter
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- 2023
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20. Evaluation of Measurement Properties and Differential Item Functioning in the English and French Versions of the University of California, Los Angeles, Loneliness Scale‐6: A Scleroderma Patient‐Centered Intervention Network (SPIN) Study
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S. Rapoport, Chelsea, Choi, Alyssa K., Kwakkenbos, Linda, Carrier, Marie‐Eve, Henry, Richard S., Mouthon, Luc, Roesch, Scott C., Thombs, Brett D., Malcarne, Vanessa L., Fortuné, Catherine, Gietzen, Amy, Guillot, Geneviève, Lewis, Nancy, Nielsen, Karen, Sauvé, Maureen, Richard, Michelle, Welling, Joep, Varga, John, Adams, Claire E., Ayala, Mara Cañedo, Cook, Vanessa, Hu, Sophie, Nassar, Elsa‐Lynn, Neyer, Marieke Alexandra, Nordlund, Julia, Provencher, Sabrina, Bartlett, Susan J., Hudson, Marie, Benedetti, Andrea, Gottesman, Karen, Hummers, Laura K., Lawrie‐Jones, Amanda, Mayes, Maureen D., Assassi, Shervin, Nielson, Warren R., El‐Baalbaki, Ghassan, van den Ende, Cornelia, Fligelstone, Kim, Frech, Tracy, Harel, Daphna, Hinchcliff, Monique, Johnson, Sindhu R., Larche, Maggie, Khalidi, Nader, Leite, Catarina, Nguyen, Christelle, Rannou, François, Pope, Janet, Reyna, Tatiana Sofia Rodriguez, Schouffoer, Anne A., Suarez‐Almazor, Maria E., Agard, Christian, Abdallah, Nassim Ait, Crichi, Benjamin, Farge‐Bancel, Dominique, André, Marc, Olagne, Louis, Smets, Perrine, Bernstein, Elana J., Berthier, Sabine, Bissonnette, Lyne, Bruns, Alessandra, Masetto, Ariel, Roux, Sophie, Carreira, Patricia, Fare, Regina, Martin, Maria, Díaz, Sheila Melchor, Almazar, Esther Rodríguez, Casadevall, Marion, Chaigne, Benjamin, Dunogue, Bertrand, Régent, Alexis, Chung, Lorinda, Denton, Christopher, Domsic, Robyn, Dunne, James V., Wilcox, Pearce, Fortin, Paul R., Ikic, Alena, Gordon, Jessica, Lakin, Kimberly, Spiera, Robert, Granel‐Rey, Brigitte, Guffroy, Aurélien, Martin, Thierry, Poindron, Vincent, Gyger, Genevieve, Hachulla, Eric, Lambert, Marc, Launay, David, Maillard, Hélène, Sobanski, Vincent, Hoa, Sabrina, Jones, Niall, Kafaja, Suzanne, Lee, Yvonne C., Maltez, Nancy, Manning, Joanne, Marie, Isabelle, Maurier, François, Mekinian, Arsene, Rivière, Sébastien, Nikpour, Mandana, Proudman, Susanna, Robinson, David, Steen, Virginia, Sutton, Evelyn, Thorne, Carter, and Varga, John
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- 2023
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21. Methods for objective assessment of skin involvement in systemic sclerosis
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Desai, Ruhani, Chawla, Harshdeep, Larin, Kirill, and Assassi, Shervin
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- 2023
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22. The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis.
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Volkmann, Elizabeth R, Tashkin, Donald P, Roth, Michael D, Li, Ning, Charles, Julio, Mayes, Maureen, Kim, Grace, Goldin, Jonathan, Pourzand, Lila, Clements, Philip J, Furst, Daniel E, Khanna, Dinesh, Elashoff, Robert M, and Assassi, Shervin
- Subjects
Lung ,Humans ,Lung Diseases ,Interstitial ,Scleroderma ,Systemic ,Mycophenolic Acid ,Cyclophosphamide ,Immunosuppressive Agents ,Vital Capacity ,Mucin-5B ,Biomarkers ,Genetics ,Interstitial lung disease ,Mycophenolate mofetil ,Polymorphism ,Systemic sclerosis ,Scleroderma ,Clinical Research ,Autoimmune Disease ,Rare Diseases ,Orphan Drug ,Aetiology ,2.1 Biological and endogenous factors ,Respiratory ,Inflammatory and immune system ,Clinical Sciences ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveTo investigate the prevalence of the MUC5B promoter variant rs35705950 in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) and whether its presence predicts response to immunosuppression with cyclophosphamide (CYC) and mycophenolate (MMF).MethodsSSc-ILD patients who participated in Scleroderma Lung Study (SLS) II (MMF versus CYC) were included in this study (N = 142). TaqMan Genotyping Assays were used to determine the MUC5B rs35705950 single nucleotide polymorphism. Joint models were created to examine how the presence of this variant affected the course of the forced vital capacity (FVC) over 2 years. Linear regression models were used to investigate the relationship between the presence of this variant and the change in quantitative radiographic fibrosis.ResultsAmong 128 participants who were tested for this variant, 18% possessed at least one copy of the MUC5B minor allele. Patients with at least one copy of this allele were similar to those without the allele with respect to age, sex, SSc subtype, ILD disease severity; however, this variant was rare among African Americans (3.7%). The presence of the MUC5B variant did not affect the course of the FVC, nor the change in quantitative radiographic fibrosis, ground glass or ILD scores in either treatment arm.ConclusionIn the context of a randomized controlled trial for SSc-ILD, the presence of the MUC5B variant did not predict disease severity, nor affect treatment response to MMF or CYC. Future studies are needed to determine whether this variant affects ILD progression in other SSc cohorts and in patients receiving anti-fibrotic therapy.
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- 2020
23. Predictors of progression in systemic sclerosis patients with interstitial lung disease.
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Distler, Oliver, Assassi, Shervin, Cottin, Vincent, Cutolo, Maurizio, Danoff, Sonye, Denton, Christopher, Distler, Jörg, Hoffmann-Vold, Anna-Maria, Johnson, Sindhu, Müller Ladner, Ulf, Smith, Vanessa, Volkmann, Elizabeth, and Maher, Toby
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Biomarkers ,Carbon Monoxide ,Disease Progression ,Humans ,Lung ,Lung Diseases ,Interstitial ,Respiratory Function Tests ,Scleroderma ,Systemic ,Tomography ,X-Ray Computed - Abstract
Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc.There are no valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients clinical courses are variable and difficult to predict, although certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, although there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD.There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or a decline in FVC of 5-9% in association with a decline in diffusing capacity of the lung for carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1-2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.
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- 2020
24. Progression of Interstitial Lung Disease in Systemic Sclerosis: The Importance of Pneumoproteins Krebs von den Lungen 6 and CCL18.
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Volkmann, Elizabeth R, Tashkin, Donald P, Kuwana, Masataka, Li, Ning, Roth, Michael D, Charles, Julio, Hant, Faye N, Bogatkevich, Galina S, Akter, Tanjina, Kim, Grace, Goldin, Jonathan, Khanna, Dinesh, Clements, Philip J, Furst, Daniel E, Elashoff, Robert M, Silver, Richard M, and Assassi, Shervin
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Lung ,Humans ,Lung Diseases ,Interstitial ,Scleroderma ,Systemic ,Disease Progression ,Mycophenolic Acid ,Cyclophosphamide ,Chemokines ,CC ,Immunosuppressive Agents ,Respiratory Function Tests ,Vital Capacity ,Adolescent ,Adult ,Aged ,Middle Aged ,Female ,Male ,Randomized Controlled Trials as Topic ,Mucin-1 ,Young Adult ,Autoimmune Disease ,Rare Diseases ,Scleroderma ,Inflammatory and immune system ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveTo investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD).MethodsPatients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm.ResultsBaseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only).ConclusionIn a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.
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- 2019
25. Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis
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Sapao, Paulene, Roberson, Elisha D.O., Shi, Bo, Assassi, Shervin, Skaug, Brian, Lee, Fred, Naba, Alexandra, Perez White, Bethany E., Córdova-Fletes, Carlos, Tsou, Pei-Suen, Sawalha, Amr H., Gudjonsson, Johann E., Ma, Feiyang, Verma, Priyanka, Bhattacharyya, Dibyendu, Carns, Mary, Strauss, Jerome F., III, Sicard, Delphine, Tschumperlin, Daniel J., Champer, Melissa I., Campagnola, Paul J., Teves, Maria E., and Varga, John
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- 2023
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26. Deletion of adipocyte Sine Oculis Homeobox Homolog 1 prevents lipolysis and attenuates skin fibrosis.
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Wareing, Nancy, primary, Mills, Tingting W, additional, Collum, Scott, additional, Wu, Minghua, additional, Revercomb, Lucy, additional, Girard, Rene, additional, Lyons, Marka, additional, Skaug, Brian, additional, Bi, Weizhen, additional, Ali, Meer A., additional, Koochak, Haniyeh, additional, Flores, Anthony R, additional, Yang, Yuntao, additional, Zheng, W Jim, additional, Swindell, William, additional, Assassi, Shervin, additional, and Karmouty-Quintana, Harry, additional
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- 2024
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27. Myeloablation Followed by Hematopoietic Stem Cell Transplantation and Long‐Term Normalization of Systemic Sclerosis Molecular Signatures
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Wareing, Nancy, primary, Wang, Xuan, additional, Keyes‐Elstein, Lynette, additional, Goldmuntz, Ellen A., additional, Lyons, Marka A., additional, McSweeney, Peter, additional, Furst, Daniel E., additional, Nash, Richard A., additional, Crofford, Leslie J., additional, Welch, Beverly, additional, Pinckney, Ashley, additional, Mayes, Maureen D., additional, Sullivan, Keith M., additional, and Assassi, Shervin, additional
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- 2024
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28. EphB2 receptor promotes dermal fibrosis in systemic sclerosis
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Egal, Erika SA, primary, Kamdem, Severin Donald, additional, Yoshigi, Masaaki, additional, Yang, Ching‐Chu, additional, Pellizzari, Sarah, additional, Kameni, Ernest M, additional, Helms, My N, additional, Assassi, Shervin, additional, Henkemeyer, Mark, additional, Frech, Tracy M, additional, and Mimche, Patrice N, additional
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- 2024
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29. Skin involvement in early diffuse cutaneous systemic sclerosis: an unmet clinical need
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Herrick, Ariane L., Assassi, Shervin, and Denton, Christopher P.
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- 2022
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30. False positive anti-Topoisomerase I (Scl-70) antibody results in clinical practice: A case series from a scleroderma referral center
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Lam, Brian H., Assassi, Shervin, Charles, Julio, Taherian, Rana, Lyons, Marka A., Jandali, Bochra, Mayes, Maureen D., and Skaug, Brian
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- 2022
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31. Safety and tolerability of nintedanib in patients with interstitial lung diseases in subgroups by sex: a post-hoc analysis of pooled data from four randomised controlled trials
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Hoffmann-Vold, Anna-Maria, Volkmann, Elizabeth R, Allanore, Yannick, Assassi, Shervin, de Vries-Bouwstra, Jeska K, Smith, Vanessa, Tschoepe, Inga, Loaiza, Lazaro, Kanakapura, Madhu, and Distler, Oliver
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- 2022
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32. Predictors of Perceived Functional Status in Early Systemic Sclerosis: A Prospective Longitudinal Study of an Early Disease Cohort
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Chernis, Julia, Buni, Maryam, Kazzaz, Sarah, Ying, Jun, Lyons, Marka, Assassi, Shervin, and Mayes, Maureen
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- 2023
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33. Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
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Kerick, Martin, Acosta-Herrera, Marialbert, Simeón-Aznar, Carmen Pilar, Callejas, José Luis, Assassi, Shervin, Proudman, Susanna M., Nikpour, Mandana, Hunzelmann, Nicolas, Moroncini, Gianluca, de Vries-Bouwstra, Jeska K., Orozco, Gisela, Barton, Anne, Herrick, Ariane L., Terao, Chikashi, Allanore, Yannick, Fonseca, Carmen, Alarcón-Riquelme, Marta Eugenia, Radstake, Timothy R. D. J., Beretta, Lorenzo, Denton, Christopher P., Mayes, Maureen D., and Martin, Javier
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- 2022
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34. PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation.
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Sanchez, Santiago, McDowell-Sanchez, Aaron K., Al-Meerani, Sharaz B., Cala-Garcia, Juan D., Waich Cohen, Alan R., Ochsner, Scott A., McKenna, Neil J., Celada, Lindsay J., Wu, Minghua, Assassi, Shervin, Rosas, Ivan O., and Tsoyi, Konstantin
- Abstract
Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in the progression of SSc through the induction of extracellular matrix (ECM) proteins and myofibroblast differentiation. Here, we demonstrate that 4'-(cyclopropylmethyl)-N2-4-pyridinyl-[4,5'-bipyrimidine]-2,2'-diamine (PIK-III), known as class III phosphatidylinositol 3-kinase (PIK3C3/VPS34) inhibitor, exerts potent antifibrotic effects in human dermal fibroblasts (HDFs) by attenuating transforming growth factor-beta 1 (TGF-β1)-induced ECM expression, cell contraction and myofibroblast differentiation. Unexpectedly, neither genetic silencing of PIK3C3 nor other PIK3C3 inhibitors (e.g., SAR405 and Autophinib) were able to mimic PIK-III-mediated antifibrotic effect in dermal fibroblasts, suggesting that PIK-III inhibits fibroblast activation through another signaling pathway. We identified that PIK-III effectively inhibits p38 activation in TGF-β1-stimulated dermal fibroblasts. Finally, PIK-III administration significantly attenuated dermal and lung fibrosis in bleomycin-injured mice. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Unraveling the role of MiR‐181 in skin fibrosis pathogenesis by targeting NUDT21.
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Mills, Tingting W., Wu, Minghua, Alonso, Jerry, Puente, Hydia, Charles, Julio, Chen, Zheng, Yoo, Seung‐hee, Mayes, Maureen D., and Assassi, Shervin
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- 2024
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36. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.
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Johnson, Sindhu R., Bernstein, Elana J., Bolster, Marcy B., Chung, Jonathan H., Danoff, Sonye K., George, Michael D., Khanna, Dinesh, Guyatt, Gordon, Mirza, Reza D., Aggarwal, Rohit, Allen, Aberdeen, Assassi, Shervin, Buckley, Lenore, Chami, Hassan A., Corwin, Douglas S., Dellaripa, Paul F., Domsic, Robyn T., Doyle, Tracy J., Falardeau, Catherine Marie, and Frech, Tracy M.
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MEDICAL protocols ,PULMONARY function tests ,BIOPSY ,OXYGEN saturation ,PROFESSIONAL associations ,INTERSTITIAL lung diseases ,CHEST X rays ,SYSTEMATIC reviews ,VOTING ,AUTOIMMUNE diseases ,PATIENT monitoring ,BRONCHOSCOPY ,RHEUMATISM ,DISEASE risk factors ,DISEASE complications - Abstract
Objective: We provide evidence‐based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. Results: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high‐resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6‐minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. Conclusion: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs. [ABSTRACT FROM AUTHOR]
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- 2024
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37. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.
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Johnson, Sindhu R., Bernstein, Elana J., Bolster, Marcy B., Chung, Jonathan H., Danoff, Sonye K., George, Michael D., Khanna, Dinesh, Guyatt, Gordon, Mirza, Reza D., Aggarwal, Rohit, Allen, Aberdeen, Assassi, Shervin, Buckley, Lenore, Chami, Hassan A., Corwin, Douglas S., Dellaripa, Paul F., Domsic, Robyn T., Doyle, Tracy J., Falardeau, Catherine Marie, and Frech, Tracy M.
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RHEUMATISM treatment ,AUTOIMMUNE disease treatment ,MEDICAL protocols ,INTERSTITIAL lung diseases ,DESCRIPTIVE statistics ,SYSTEMATIC reviews ,PHYSICIANS ,DATA analysis software ,ADULTS - Abstract
Objective: We provide evidence‐based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. Results: Thirty‐five recommendations were generated (including two strong recommendations) for first‐line SARD‐ILD treatment, treatment of SARD‐ILD progression despite first‐line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis–ILD as a first‐line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first‐line ILD treatment in all other SARDs. Conclusion: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Blood Neutrophil Count and Neutrophil‐to‐Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts
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Wareing, Nancy, Mohan, Vishnu, Taherian, Rana, Volkmann, Elizabeth R., Lyons, Marka A., Wilhalme, Holly, Roth, Michael D., Estrada‐y‐Martin, Rosa M., Skaug, Brian, Mayes, Maureen D., Tashkin, Donald P., and Assassi, Shervin
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- 2023
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39. Dysregulation of Type I Interferon Signaling in Systemic Sclerosis: a Promising Therapeutic Target?
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Wu, Minghua and Assassi, Shervin
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- 2021
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40. Ethnicity and disease severity in ankylosing spondylitis a cross-sectional analysis of three ethnic groups
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Jamalyaria, Farokh, Ward, Michael M, Assassi, Shervin, Learch, Thomas J, Lee, MinJae, Gensler, Lianne S, Brown, Matthew A, Diekman, Laura, Tahanan, Amirali, Rahbar, Mohammad H, Weisman, Michael H, and Reveille, John D
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Arthritis ,Adult ,Black or African American ,Black People ,Blood Sedimentation ,Cross-Sectional Studies ,Disease Progression ,Female ,HLA-B27 Antigen ,Hispanic or Latino ,Humans ,Longitudinal Studies ,Male ,Middle Aged ,Prospective Studies ,Reproducibility of Results ,Severity of Illness Index ,Spine ,Spondylitis ,Ankylosing ,White People ,Young Adult ,Ankylosing spondylitis ,Blacks ,Disease severity ,HLA-B27 ,Latinos ,Arthritis & Rheumatology ,Clinical sciences ,Immunology ,Allied health and rehabilitation science - Abstract
The purpose of this study is to compare disease severity in ankylosing spondylitis (AS) in three ethnic groups. We assessed 925 AS patients (57 Blacks, 805 Whites, 63 Latinos) enrolled in the longitudinal Prospective Study of Outcomes in AS (PSOAS) for functional impairment, disease activity, and radiographic severity. Comparisons of clinical characteristics and HLA-B27 frequency for each group were performed, in two multivariable regression models, we compared the baseline Bath Ankylosing Spondylitis Radiographic Index (BASRI) and modified Stokes Ankylosing Spondylitis Spine Score (mSASSS) by ethnicity, adjusting for covariates. Blacks had greater functional impairment (Bath Ankylosing Spondylitis Functional Index) (median 62.5 vs. 27.8 in Whites and 38.1 in Latinos; p
- Published
- 2017
41. Pain levels and associated factors in the Scleroderma Patient-centered Intervention Network (SPIN) cohort: a multicentre cross-sectional study
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Henry, Richard S., Gottesman, Karen, Hudson, Marie, Hummers, Laura K., Malcarne, Vanessa L., Mayes, Maureen D., Nielson, Warren R., Riggs, Robert, Assassi, Shervin, El-Baalbaki, Ghassan, Ells, Carolyn, Fligelstone, Kim, Fortuné, Catherine, Frech, Tracy, Gietzen, Amy, Guillot, Geneviève, Harel, Daphna, Hinchcliff, Monique, Johnson, Sindhu R., Larche, Maggie, Leite, Catarina, Nguyen, Christelle, Nielsen, Karen, Pope, Janet, Rannou, François, Richard, Michelle, Rodriguez-Reyna, Tatiana Sofia, Schouffoer, Anne A., Suarez-Almazor, Maria E., Agard, Christian, Ait Abdallah, Nassim, Albert, Alexandra, André, Marc, Bernstein, Elana J., Berthier, Sabine, Bissonnette, Lyne, Bruns, Alessandra, Carreira, Patricia, Casadevall, Marion, Chaigne, Benjamin, Chung, Lorinda, Correia, Chase, Crichi, Benjamin, Denton, Christopher, Domsic, Robyn, Dunne, James V., Dunogue, Bertrand, Fare, Regina, Farge-Bancel, Dominique, Fortin, Paul R., Gordon, Jessica, Granel-Rey, Brigitte, Gyger, Genevieve, Hachulla, Eric, Herrick, Ariane L, Hoa, Sabrina, Ikic, Alena, Jones, Niall, Kafaja, Suzanne, Khalidi, Nader, Lambert, Marc, Launay, David, Maillard, Hélène, Maltez, Nancy, Manning, Joanne, Marie, Isabelle, Martin, Maria, Martin, Thierry, Masetto, Ariel, Maurier, François, Mekinian, Arsene, Melchor, Sheila, Nikpour, Mandana, Olagne, Louis, Poindron, Vincent, Proudman, Susanna, Régent, Alexis, Rivière, Sébastien, Robinson, David, Rodriguez, Esther, Roux, Sophie, Smets, Perrine, Sobanski, Vincent, Spiera, Robert, Steen, Virginia, Sutton, Evelyn, Thorne, Carter, Wilcox, Pearce, Bourgeault, Angelica, Cañedo Ayala, Mara, Carboni Jiménez, Andrea, Discepola, Marie-Nicole, Gagarine, Maria, Nordlund, Julia, Østbø, Nora, Lee, Yvonne C, Fox, Rina S, Kwakkenbos, Linda, Levis, Brooke, Carrier, Marie-Eve, Welling, Joep, Sauvé, Maureen, Mouthon, Luc, Benedetti, Andrea, Bartlett, Susan J, Varga, John, and Thombs, Brett D
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- 2021
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42. Investigating vascular changes in systemic sclerosis using optical coherence tomography angiography
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Nikitin, Pavel V., primary, Chawla, Harshdeep S., additional, Singh, Manmohan, additional, Aglyamov, Salavat R., additional, Theodore, Samuel, additional, Assassi, Shervin, additional, and Larin, Kirill V., additional
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- 2024
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43. Comparison of optical coherence elastography and ultrasound elastography for detecting systemic sclerosis: preliminary results from a prospective clinical trial
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Chawla, Harshdeep Singh, primary, Desai, Ruhani, additional, Nikitin, Pavel, additional, Zhang, Meng, additional, Theodore, Samuel, additional, Singh, Manmohan, additional, Aglyamov, Salavat R., additional, Larin, Kirill V., additional, and Assassi, Shervin, additional
- Published
- 2024
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44. Sine Oculis Homeobox Homolog 1 Modulates Early Features of Systemic Sclerosis Skin Fibrosis
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Wareing, Nancy, primary, Mills, Tingting, additional, Collum, Scott D., additional, Wu, Minghua, additional, Revercomb, Lucy, additional, Girard, Rene, additional, Lyons, Marka, additional, Skaug, Brian, additional, Bi, Weizhen, additional, Ali, Meer, additional, Koochack, Haniyeh, additional, Flores, Anthony, additional, Yang, Yuntao, additional, Zheng, Jim W., additional, Swindell, William, additional, Assassi, Shervin, additional, and Karmouty-Quintana, Harry, additional
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- 2024
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45. Type 1 interferon activation in systemic sclerosis: a biomarker, a target or the culprit
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Kakkar, Vishal, Assassi, Shervin, Allanore, Yannick, Kuwana, Masataka, Denton, Christopher P., Khanna, Dinesh, and Del Galdo, Francesco
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- 2022
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46. Factors associated with fears due to COVID-19: A Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 cohort study
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Fortuné, Catherine, Gietzen, Amy, Guillot, Geneviève, Lewis, Nancy, Richard, Michelle, Sauvé, Maureen, Welling, Joep, Fligelstone, Kim, Gottesman, Karen, Leite, Catarina, Pérez, Elisabet, Baron, Murray, Malcarne, Vanessa, Mayes, Maureen D., Nielson, Warren R., Riggs, Robert, Assassi, Shervin, Ells, Carolyn, van den Ende, Cornelia, Frech, Tracy, Harel, Daphna, Hinchcliff, Monique, Hudson, Marie, Johnson, Sindhu R., Larche, Maggie, Nguyen, Christelle, Pope, Janet, Rannou, François, Reyna, Tatiana Sofia Rodriguez, Schouffoer, Anne A., Suarez-Almazor, Maria E., Agard, Christian, Albert, Alexandra, Bernstein, Elana J., Berthier, Sabine, Bissonnette, Lyne, Bruns, Alessandra, Carreira, Patricia, Chaigne, Benjamin, Chung, Lorinda, Correia, Chase, Denton, Christopher, Domsic, Robyn, Dunne, James V., Dunogue, Bertrand, Farge-Bancel, Dominique, Fortin, Paul R., Gordon, Jessica, Granel-Rey, Brigitte, Hatron, Pierre-Yves, Herrick, Ariane L., Hoa, Sabrina, Jones, Niall, Fernandes, Artur Jose de B., Kafaja, Suzanne, Khalidi, Nader, Launay, David, Manning, Joanne, Marie, Isabelle, Martin, Maria, Mekinian, Arsene, Melchor, Sheila, Nikpour, Mandana, Olagne, Louis, Proudman, Susanna, Régent, Alexis, Rivière, Sébastien, Robinson, David, Rodriguez, Esther, Roux, Sophie, Sobanski, Vincent, Steen, Virginia, Sutton, Evelyn, Thorne, Carter, Wilcox, Pearce, Ayala, Mara Cañedo, Carboni-Jiménez, Andrea, Gagarine, Maria, Nordlund, Julia, Østbø, Nora, Rice, Danielle B., Turner, Kimberly A., Culos-Reed, Nicole, Dyas, Laura, El-Baalbaki, Ghassan, Hebblethwaite, Shannon, Bustamante, Laura, Duchek, Delaney, Ellis, Kelsey, Wu, Yin, Kwakkenbos, Linda, Henry, Richard S., Carrier, Marie-Eve, Harb, Sami, Bourgeault, Angelica, Tao, Lydia, Negeri, Zelalem, Patten, Scott, Bartlett, Susan J., Mouthon, Luc, Varga, John, Benedetti, Andrea, and Thombs, Brett D.
- Published
- 2021
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47. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial
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Highland, Kristin B, Distler, Oliver, Kuwana, Masataka, Allanore, Yannick, Assassi, Shervin, Azuma, Arata, Bourdin, Arnaud, Denton, Christopher P, Distler, Jörg H W, Hoffmann-Vold, Anna Maria, Khanna, Dinesh, Mayes, Maureen D, Raghu, Ganesh, Vonk, Madelon C, Gahlemann, Martina, Clerisme-Beaty, Emmanuelle, Girard, Mannaig, Stowasser, Susanne, Zoz, Donald, and Maher, Toby M
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- 2021
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48. 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.
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Gordon, Jessica K, Girish, Gandikota, Berrocal, Veronica J, Zhang, Meng, Hatzis, Christopher, Assassi, Shervin, Bernstein, Elana J, Domsic, Robyn T, Hant, Faye N, Hinchcliff, Monique, Schiopu, Elena, Steen, Virginia D, Frech, Tracy M, and Khanna, Dinesh
- Subjects
Joints ,Skin ,Humans ,Scleroderma ,Diffuse ,Disability Evaluation ,Physical Examination ,Severity of Illness Index ,Registries ,Prospective Studies ,Reproducibility of Results ,Adult ,Middle Aged ,Female ,Male ,Young Adult ,DIAGNOSTIC IMAGING ,INFECTIONS AND ARTHRITIS ,JOINT COUNT ,OUTCOME MEASURES ,SYSTEMIC SCLEROSIS ,ULTRASONOGRAPHY ,Clinical Research ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveTo determine the inter/intraobserver reliability of the tender and swollen joint counts (TJC, SJC) and the modified Rodnan Skin Score (mRSS) in diffuse cutaneous systemic sclerosis (dcSSc) and to assess content validity of the TJC/SJC.MethodsTen rheumatologists completed the SJC, TJC, and mRSS on 7 patients. Musculoskeletal ultrasound (MSUS) was performed.ResultsInterobserver and intraobserver reliability for the TJC was 0.97 and 0.99, for the SJC was 0.24 and 0.71, and for the mRSS was 0.81 and 0.94, respectively. MSUS abnormalities did not correspond with SJC/TJC.ConclusionWe demonstrate excellent inter- and intraobserver reliability for the mRSS and TJC in dcSSc. However, the SJC and TJC did not correspond to MSUS.
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- 2017
49. Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease.
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Volkmann, Elizabeth R, Tashkin, Donald P, Roth, Michael D, Clements, Philip J, Khanna, Dinesh, Furst, Daniel E, Mayes, Maureen, Charles, Julio, Tseng, Chi-Hong, Elashoff, Robert M, and Assassi, Shervin
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Humans ,Lung Diseases ,Interstitial ,Scleroderma ,Systemic ,Disease Progression ,Mycophenolic Acid ,Cyclophosphamide ,Platelet Factor 4 ,Immunosuppressive Agents ,Respiratory Function Tests ,Enzyme-Linked Immunosorbent Assay ,Double-Blind Method ,Adult ,Aged ,Middle Aged ,Female ,Male ,Biomarkers ,Chemokines ,Immunosuppression ,Pulmonary fibrosis ,Systemic sclerosis ,Arthritis & Rheumatology ,Clinical Sciences ,Immunology ,Public Health and Health Services - Abstract
BackgroundIncreased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD.MethodsA total of 142 SSc-ILD patients from Scleroderma Lung Study (SLS) II were randomized in a double-blind, parallel-arm trial, to receive mycophenolate (MMF) for 2 years or oral cyclophosphamide (CYC) for 1 year followed by 1 year of placebo. Plasma CXCL4 levels were measured at baseline, 12 months, and 24 months in SLS II participants (N = 136) and at a single time point in healthy controls (N = 67). A mixed-effects model evaluated the relationship between change in CXCL4 levels and SSc-ILD progression. The primary outcome was the course of the forced vital capacity.ResultsBaseline CXCL4 levels were significantly higher in SSc-ILD patients compared with healthy controls (2699 ± 1489 ng/ml vs 2233 ± 1351 ng/ml (mean ± SD); P = 0.019). However, no significant correlations were identified between CXCL4 levels and extent of ILD at baseline, as measured by the forced vital capacity, diffusing capacity of carbon monoxide, or radiographic extent of ILD. Plasma CXCL4 decreased significantly from baseline to 12 months in all patients (CYC: P
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- 2016
50. Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity.
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Lofgren, Shane, Hinchcliff, Monique, Carns, Mary, Wood, Tammara, Aren, Kathleen, Arroyo, Esperanza, Cheung, Peggie, Kuo, Alex, Valenzuela, Antonia, Haemel, Anna, Wolters, Paul J, Gordon, Jessica, Spiera, Robert, Assassi, Shervin, Boin, Francesco, Chung, Lorinda, Fiorentino, David, Utz, Paul J, Whitfield, Michael L, and Khatri, Purvesh
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Scleroderma ,Autoimmune Disease ,Orphan Drug ,Clinical Research ,Rare Diseases ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Inflammatory and immune system - Abstract
Systemic sclerosis (SSc) is a rare autoimmune disease with the highest case-fatality rate of all connective tissue diseases. Current efforts to determine patient response to a given treatment using the modified Rodnan skin score (mRSS) are complicated by interclinician variability, confounding, and the time required between sequential mRSS measurements to observe meaningful change. There is an unmet critical need for an objective metric of SSc disease severity. Here, we performed an integrated, multicohort analysis of SSc transcriptome data across 7 datasets from 6 centers composed of 515 samples. Using 158 skin samples from SSc patients and healthy controls recruited at 2 centers as a discovery cohort, we identified a 415-gene expression signature specific for SSc, and validated its ability to distinguish SSc patients from healthy controls in an additional 357 skin samples from 5 independent cohorts. Next, we defined the SSc skin severity score (4S). In every SSc cohort of skin biopsy samples analyzed in our study, 4S correlated significantly with mRSS, allowing objective quantification of SSc disease severity. Using transcriptome data from the largest longitudinal trial of SSc patients to date, we showed that 4S allowed us to objectively monitor individual SSc patients over time, as (a) the change in 4S of a patient is significantly correlated with change in the mRSS, and (b) the change in 4S at 12 months of treatment could predict the change in mRSS at 24 months. Our results suggest that 4S could be used to distinguish treatment responders from nonresponders prior to mRSS change. Our results demonstrate the potential clinical utility of a novel robust molecular signature and a computational approach to SSc disease severity quantification.
- Published
- 2016
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