16 results on '"Becker, Mike Oliver"'
Search Results
2. Pain chronification and the important role of non-disease-specific symptoms in patients with systemic sclerosis
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Evers, Caroline, Jordan, Suzana, Maurer, Britta, Becker, Mike Oliver, Mihai, Carina, Dobrota, Rucsandra, Hoederath, Petra, and Distler, Oliver
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- 2021
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3. Performance of the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument as a clinical decision aid in the routine clinical care of patients with systemic sclerosis
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Zampatti, Norina, Garaiman, Alexandru, Jordan, Suzana, Dobrota, Rucsandra, Becker, Mike Oliver, Maurer, Britta, Distler, Oliver, and Mihai, Carina
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- 2021
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4. Intrapatient competition of VEXAS syndrome and CML clones
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Djerbi, Nadia, Zimmermann, Kathrin, Roncador, Marco, Becker, Mike Oliver, Manz, Markus G., and Balabanov, Stefan
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- 2023
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5. Vision transformer assisting rheumatologists in screening for capillaroscopy changes in systemic sclerosis: an artificial intelligence model.
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Garaiman, Alexandru, Nooralahzadeh, Farhad, Mihai, Carina, Gonzalez, Nicolas Perez, Gkikopoulos, Nikitas, Becker, Mike Oliver, Distler, Oliver, Krauthammer, Michael, and Maurer, Britta
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DIGITAL image processing ,DEEP learning ,PREDICTIVE tests ,NAILS (Anatomy) ,DERMATOMYOSITIS ,CAPILLARIES ,ANGIOSCOPY ,SYSTEMIC scleroderma ,ARTIFICIAL intelligence ,RHEUMATOLOGISTS ,DESCRIPTIVE statistics ,RECEIVER operating characteristic curves ,SENSITIVITY & specificity (Statistics) ,LONGITUDINAL method - Abstract
Objectives The first objective of this study was to implement and assess the performance and reliability of a vision transformer (ViT)-based deep-learning model, an 'off-the-shelf' artificial intelligence solution, for identifying distinct signs of microangiopathy in nailfold capilloroscopy (NFC) images of patients with SSc. The second objective was to compare the ViT's analysis performance with that of practising rheumatologists. Methods NFC images of patients prospectively enrolled in our European Scleroderma Trials and Research group (EUSTAR) and Very Early Diagnosis of Systemic Sclerosis (VEDOSS) local registries were used. The primary outcome investigated was the ViT's classification performance for identifying disease-associated changes (enlarged capillaries, giant capillaries, capillary loss, microhaemorrhages) and the presence of the scleroderma pattern in these images using a cross-fold validation setting. The secondary outcome involved a comparison of the ViT's performance vs that of rheumatologists on a reliability set, consisting of a subset of 464 NFC images with majority vote–derived ground-truth labels. Results We analysed 17 126 NFC images derived from 234 EUSTAR and 55 VEDOSS patients. The ViT had good performance in identifying the various microangiopathic changes in capillaries by NFC [area under the curve (AUC) from 81.8% to 84.5%]. In the reliability set, the rheumatologists reached a higher average accuracy, as well as a better trade-off between sensitivity and specificity compared with the ViT. However, the annotators' performance was variable, and one out of four rheumatologists showed equal or lower classification measures compared with the ViT. Conclusions The ViT is a modern, well-performing and readily available tool for assessing patterns of microangiopathy on NFC images, and it may assist rheumatologists in generating consistent and high-quality NFC reports; however, the final diagnosis of a scleroderma pattern in any individual case needs the judgement of an experienced observer. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Vision transformer assisting rheumatologists in screening for capillaroscopy changes in systemic sclerosis: an artificial intelligence model
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Garaiman, Alexandru, primary, Nooralahzadeh, Farhad, additional, Mihai, Carina, additional, Gonzalez, Nicolas Perez, additional, Gkikopoulos, Nikitas, additional, Becker, Mike Oliver, additional, Distler, Oliver, additional, Krauthammer, Michael, additional, and Maurer, Britta, additional
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- 2022
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7. Additional file 1 of Performance of the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument as a clinical decision aid in the routine clinical care of patients with systemic sclerosis
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Zampatti, Norina, Garaiman, Alexandru, Jordan, Suzana, Dobrota, Rucsandra, Becker, Mike Oliver, Maurer, Britta, Distler, Oliver, and Mihai, Carina
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Data_FILES - Abstract
Additional file 1.
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- 2021
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8. Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model
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Wu, Wanlong, Jordan, Suzana, Becker, Mike Oliver, Dobrota, Rucsandra, Maurer, Britta, Fretheim, Håvard, Ye, Shuang, Siegert, Elise, Allanore, Yannick, Hoffmann-Vold, Anna-Maria, Distler, Oliver, University of Zurich, and Distler, Oliver
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2403 Immunology ,Rheumatology ,1300 General Biochemistry, Genetics and Molecular Biology ,2745 Rheumatology ,General Biochemistry ,Immunology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,2723 Immunology and Allergy ,Immunology and Allergy ,610 Medicine & health ,Genetics and Molecular Biology ,General Biochemistry, Genetics and Molecular Biology - Abstract
ObjectivesTo identify the predictive clinical characteristics and establish a prediction model for the progression of mild interstitial lung disease (ILD) in patients with systemic sclerosis (SSc).MethodsPatients with SSc from two independent prospective cohorts were included in this observational study. All patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria, had mild ILD at baseline diagnosed by High-Resolution Computed Tomography (HRCT), available baseline and ≥1 annual follow-up pulmonary function tests and no concomitant pulmonary hypertension or airflow obstruction. ILD progression was defined as a relative decrease in forced vital capacity (FVC)%≥15%, or FVC%≥10% combined with diffusing capacity for carbon monoxide %≥15% at 1-year follow-up. Candidate predictors for multivariate logistic regression were selected by expert opinion based on clinical significance. A prediction model for ILD progression was established in the derivation cohort and validated in the multinational validation cohort.ResultsA total of 25/98 and 25/117 patients with SSc showed ILD progression in the derivation cohort and the validation cohort, respectively. Lower SpO2 after 6 min walk test (6MWT) and arthritis ever were identified as independent predictors for ILD progression in both cohorts. The optimal cut-off value of SpO 2 after 6MWT for predicting ILD progression was determined as 94% by receiver operating characteristic curve analysis. The derived SPAR model combining both predictors (SPO2 and ARthritis) increased the prediction rate from 25.5% to 91.7% with an area under the curve (95% CI) of 0.83 (0.73 to 0.93).ConclusionsThe evidence-based SPAR prediction model developed in our study might be helpful for the risk stratification of patients with mild SSc-ILD in clinical practice and cohort enrichment for future clinical trial design. This article has been accepted for publication in 'Annals of the Rheumatic Diseases', 2018 following peer review, and the Version of Record can be accessed online at https://doi.org/10.1136/annrheumdis-2018-213201. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.
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- 2018
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9. Does therapy with immunosuppressive drugs improve gastrointestinal symptoms in patients with systemic sclerosis?
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Stamm L, Garaiman A, Becker MO, Bruni C, Dobrota R, Elhai M, Ismail S, Jordan S, Zampatti N, Tatu AM, Distler O, and Mihai C
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- Humans, Female, Male, Middle Aged, Aged, Treatment Outcome, Severity of Illness Index, Adult, Scleroderma, Systemic drug therapy, Scleroderma, Systemic complications, Immunosuppressive Agents therapeutic use, Gastrointestinal Diseases etiology
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Objectives: While important progress was made regarding the treatment of systemic sclerosis (SSc), there is still no evidence-based disease-modifying treatment available for SSc-related gastrointestinal (GI) manifestations. We aimed to identify an association between immunosuppressive therapy and the the severity of GI symptoms, measured by the University of California at Los Angeles/Scleroderma Clinical Trial Consortium Gastro-Intestinal Tract instrument 2.0 (GIT)., Methods: We selected patients with SSc who had at least two visits (further referred to as 'baseline' and 'follow-up') with completed GITs, within an interval of 12±3 months. The study outcome was the GIT score at follow-up. We used multivariable linear regression with the following covariates: immunosuppressive therapy during observation, immunosuppressive therapy before baseline, baseline GIT and several baseline parameters selected by clinical judgement as potentially influencing GI symptoms., Results: We included 209 SSc patients (82.3% female, median age 59.0 years, median disease duration 6.0 years, 40 (19.1%) diffuse cutaneous SSc, median baseline GIT 0.19). Of these, 71 were exposed to immunosuppressive therapy during the observation period, and, compared with unexposed patients, had overall more severe SSc and a higher prevalence of treatment with proton pump inhibitors. In multivariable linear regression, immunosuppressive therapy during the period of observation and lower baseline GIT scores were significantly associated with lower (better) GIT scores at follow-up., Conclusion: Immunosuppressive treatment was associated with lower GIT scores in our cohort, which suggests the potential effects of immunosuppressants on GI manifestations in patients with SSc, requiring confirmation in prospective randomised clinical trials., Competing Interests: Competing interests: MB has received consultancy fees from GSK, Amgen, Novartis and Vifor. CB has received consultancy fees from Boehringer Ingelheim, grants/research support from Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), EMDO foundation. Educational grants from AbbVie and Wellcome Trust, and congress support from Boehringer Ingelheim. RD has received speaker and/or consultancy fees from Actelion, Boehringer-Ingelheim; grant/research support from: Pfizer, Actelion, Iten-Kohaut; and congress participation support from Amgen and Otsuka. She also received the Walter and Sigrid Siegenthaler Fellowship. ME has received congress support from Janssen and Astra-Zeneca and research support from Novartis outside of the submitted work. She also received the Walter and Sigrid Siegenthaler Fellowship. SI has received a EULAR scientific long-term training grant for young fellows. OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Cantargia AB, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Prometheus, Redxpharma, Roivant, EMD Serono, Topadur and UCB. Patent issued 'mir-29 for the treatment of systemic sclerosis' (US8247389, EP2331143). Cofounder of CITUS AG. CM received speaker and/or consultancy fees from Janssen-Cilag AG, Boehringer Ingelheim, MED Talks Switzerland, Medbase, Mepha, Novartis and PlayToKnow AG and travel support for congress from Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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10. Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.
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Windirsch K, Jordan S, Becker MO, Bruni C, Dobrota R, Elhai M, Garaiman IA, Mihai CM, Iudici M, Hasler P, Ribi C, Maurer B, Gabrielli A, Hoffmann-Vold AM, and Distler O
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- Humans, Immunosuppressive Agents therapeutic use, Rituximab therapeutic use, Methotrexate therapeutic use, Mycophenolic Acid therapeutic use, Prospective Studies, Switzerland, Fibrosis, Scleroderma, Systemic complications, Scleroderma, Systemic chemically induced, Lung Diseases, Interstitial drug therapy, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial diagnosis, Antirheumatic Agents therapeutic use
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Objectives: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations., Methods: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%., Results: A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation., Conclusion: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.
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- 2024
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11. Management of giant-cell arteritis in Switzerland: an online national survey.
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Iudici M, Hemmig AK, Stegert M, Courvoisier DS, Adler S, Becker MO, Berger CT, Dan D, Finckh A, Mahr A, Neumann T, Reichenbach S, Ribi C, Seitz L, Villiger P, Wildi L, and Daikeler T
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- Humans, Switzerland, Temporal Arteries, Positron Emission Tomography Computed Tomography, Glucocorticoids therapeutic use, Giant Cell Arteritis diagnostic imaging, Giant Cell Arteritis drug therapy
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Aims of the Study: To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools., Methods: We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics., Results: Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice., Conclusions: This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas.
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- 2023
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12. Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model.
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Garaiman A, Steigmiller K, Gebhard C, Mihai C, Dobrota R, Bruni C, Matucci-Cerinic M, Henes J, de Vries-Bouwstra J, Smith V, Doria A, Allanore Y, Dagna L, Anić B, Montecucco C, Kowal-Bielecka O, Martin M, Tanaka Y, Hoffmann-Vold AM, Held U, Distler O, and Becker MO
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- Humans, Platelet Aggregation Inhibitors therapeutic use, Fingers, Skin Ulcer etiology, Skin Ulcer complications, Scleroderma, Systemic complications, Scleroderma, Systemic drug therapy
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Objective: To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor., Methods: We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors., Results: Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs., Conclusion: The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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13. Visual assessment of digital ulcers in systemic sclerosis analysed by eye tracking: implications for wound assessment.
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Moser T, Lohmeyer Q, Meboldt M, Distler O, and Becker MO
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- Fingers, Humans, Ulcer, Scleroderma, Systemic, Skin Ulcer
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Objectives: The assessment of digital ulcers (DUs) in systemic sclerosis (SSc) depends crucially on visual aspects. However, little is known about the differences in visual assessment of these wounds between experts and non-experts or medical lay persons (novices). To develop potential training recommendations for the visual assessment of digital ulcers in SSc, we analysed gaze pattern data during assessment of digital ulcers between assessors with different levels of expertise., Methods: Gaze pattern data from 36 participants were collected with a mobile eye tracking device. 20 pictures from digital ulcers of SSc patients were presented to each participant. The analysis comprised the scan path, the dwell times (for areas of interest), fixation counts and the entry time for each picture and subject., Results: Most significant differences were found between novices and medically educated groups. Dwell times in the wound area for novices differed statistically significantly from all medically educated groups (1.76s-3.1s less). Above all, novices had lower dwell times in wound margin and wound surrounding and spent more time in other areas (up to 1.92s longer). Correspondingly, they had less fixation points and longer overall scan paths in wound areas. Similar gaze pattern data were generated for medically educated groups., Conclusions: For the first time, we could analyse the visual assessment of digital ulcers in SSc and detected differences according to levels of medical education and expertise. Adequate training on proper interpretation of changes in all wound areas are warranted to improve wound assessment in digital ulcers.
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- 2020
14. Does angiotensin and endothelin receptor blockade have an impact on lung function? An analysis from the EUSTAR database.
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Radic M, Becker MO, Distler O, Huscher D, Siegert E, and Riemekasten G
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- Blood Pressure, Humans, Receptor, Endothelin B, Angiotensin Receptor Antagonists pharmacology, Endothelin Receptor Antagonists pharmacology, Lung drug effects, Lung physiology
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- 2019
15. Serum cytokines and their predictive value in pulmonary involvement of systemic sclerosis.
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Becker MO, Radic M, Schmidt K, Huscher D, Riedlinger A, Michelfelder M, Meisel C, Ewert R, Burmester GR, and Riemekasten G
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- Adult, Aged, Biomarkers blood, Disease Progression, Female, Humans, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial immunology, Lung Diseases, Interstitial mortality, Male, Middle Aged, Predictive Value of Tests, Prognosis, Pulmonary Arterial Hypertension diagnosis, Pulmonary Arterial Hypertension immunology, Pulmonary Arterial Hypertension mortality, Retrospective Studies, Risk Assessment, Risk Factors, Scleroderma, Systemic diagnosis, Scleroderma, Systemic immunology, Scleroderma, Systemic mortality, Cytokines blood, Lung Diseases, Interstitial blood, Pulmonary Arterial Hypertension blood, Scleroderma, Systemic blood
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Objective: To identify serum cytokines which predict mortality and/or disease progression in patients with systemic sclerosis, especially with pulmonary involvement., Methods: Serum cytokines (IL-6, IL-7, IL-8, IL-10, CCL2, CCL4, TGF-β, TNF-α) were measured in 125 SSc patients, who were recruited and observed in our outpatient clinic. Of these, 60 had pulmonary involvement, classified as either interstitial lung disease (ILD, 43 patients), pulmonary arterial hypertension (PAH, 7 patients) or pulmonary hypertension and ILD (PH-ILD, 10 patients). The association of serum cytokines with clinical features was analysed and their correlation with BAL cytokines measured in a subset of SSc patients with ILD., Results: Serum cytokines were detected at different levels: high (TGF-β, median 287.5 pg/ml; CCL2, median 89.7 pg/ml; CCL4, median 104.2 pg/ml), low (IL-6, median 3.2 pg/ml; IL-7 median 2.3 pg/ml; IL-8, median 5.2 pg/ml; TNF-α, median 0 pg/ml but with a bimodal distribution) and very low (IL-10, median 0.4 pg/ml). IL-6 and IL-7 were predictive for death in a Cox regression analysis in all SSc patients as well as in all patients with pulmonary involvement; IL-6 was predictive for mortality in SSc-ILD patients. In a multivariate analysis, cytokine levels could also predict a change in lung function, e.g. IL-7 was a predictor for a decline of diffusion capacity (DLCO) by 20 or 30% in ILD patients. In a subset of ILD patients, serum cytokines were compared to BAL cytokines, but revealed only few correlations., Conclusion: In conclusion, the analysis of serum cytokines implicates a role as biomarkers, distinct from BAL., (Copyright: © 2019.)
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- 2019
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16. Angiotensin receptor type 1 and endothelin receptor type A on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis patients.
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Günther J, Kill A, Becker MO, Heidecke H, Rademacher J, Siegert E, Radić M, Burmester GR, Dragun D, and Riemekasten G
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- Adult, Autoantibodies immunology, Chemokines, CC immunology, Chemotaxis, Leukocyte, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Interleukin-18 immunology, Male, Middle Aged, Monocytes metabolism, Real-Time Polymerase Chain Reaction, Receptor, Angiotensin, Type 1 immunology, Receptor, Endothelin A immunology, Scleroderma, Systemic metabolism, Cell Movement, Chemokines, CC biosynthesis, Interleukin-18 biosynthesis, Monocytes immunology, Receptor, Angiotensin, Type 1 metabolism, Receptor, Endothelin A metabolism, Scleroderma, Systemic immunology
- Abstract
Introduction: Agonistic autoantibodies (Aabs) against the angiotensin II receptor type 1 (AT1R) and the endothelin receptor type A (ETAR) have been identified in patients with systemic sclerosis (SSc). In our present study, we examined the expression of the AT1R and the ETAR in human immune cells and the pathological effects mediated through these receptors by their corresponding Aabs., Methods: Protein expression of AT1R and ETAR on peripheral blood mononuclear cells (PBMCs) from healthy individuals and SSc patients was analyzed using flow cytometry, and mRNA expression of both receptors in PBMCs from healthy donors was examined by real-time PCR. In addition, PBMCs from healthy donors were stimulated in vitro with affinity-purified immunoglobulin G (IgG) fractions from SSc patients positive for AT1R and ETAR Aabs, as well as with IgG from healthy donors serving as controls. Alterations in cell surface marker expression, cytokine secretion and chemotactic motility were analyzed using flow cytometry, enzyme-linked immunosorbent assays and chemotaxis assays, respectively. The results were correlated with the characteristics and clinical findings of the IgG donors., Results: Both AT1R and ETAR were expressed on PBMCs in humans. Protein expression of both receptors was decreased in SSc patients compared with that of healthy donors and declined during the course of disease. IgG fractions of SSc patients positive for AT1R and ETAR Aabs induced T-cell migration in an Aab level-dependent manner. Moreover, IgG of SSc patients stimulated PBMCs to produce more interleukin 8 (IL-8) and chemokine (C-C motif) ligand 18 (CCL18) than did the IgG of healthy donors. All effects were significantly reduced by selective AT1R and ETAR antagonists. Statistical analysis revealed an association of SSc-IgG induced high IL-8 concentrations with an early disease stage and of high CCL18 concentrations with lung fibrosis onset and vascular complications in the respective IgG donors., Conclusion: In our present study, we could demonstrate the expression of both AT1R and ETAR on human peripheral T cells, B cells and monocytes. The decreased receptor expression in SSc patients, the inflammatory and profibrotic effects upon Aab stimulation of PBMCs in vitro and the associations with clinical findings suggest a role for Aab-induced activation of immune cells mediated by the AT1R and the ETAR in the pathogenesis or even the onset of the disease.
- Published
- 2014
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