Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study.

Systemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity.

Serum IL-40 is elevated in systemic sclerosis and is linked to disease activity, gastrointestinal involvement, immune regulation and fibrotic processes.

Background: Interleukin 40 (IL-40) is a cytokine implicated in malignancies and rheumatic disorders. Its association with fibrotic mediators has been previously described. Since inflammation and fibrosis are hallmarks of systemic sclerosis (SSc), we aimed to analyze the role of IL-40 in SSc.

CRTAC1: a novel indicator of lung involvement in SSc.

Objectives: Interstitial lung disease (ILD) is the most frequent cause of mortality in patients with SSc. Cartilage acidic protein-1 (CRTAC1), secreted by alveolar type-2 epithelial cells, is a potential biomarker of lung health. This study explores CRTAC1's role in SSc, focusing on pulmonary involvement.

Sexual function and pelvic floor function in men with systemic sclerosis compared to healthy controls: a cross-sectional study.

Objectives: This cross-sectional study aimed to compare the sexual function (SF) and pelvic floor function of men with systemic sclerosis (SSc) with age-matched healthy controls (HC) and to identify the implications of clinical features on SF.

Material And Method: Twenty SSc males and 20 HC aged 18-70 years completed eleven questionnaires assessing SF [International Index of Erectile Function (IIEF), Male Sexual Health Questionnaire (MSHQ)]; sexual quality of life: Sexual Quality of Life Questionnaire-Male (SQoL-M); pelvic floor function: Pelvic Floor Impact Questionnaire-Short Form 7 (PFIQ-7), fatigue, depression, physical fitness, functional disability, and quality of life. Clinical data were collected.

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.

Objective: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment.

Methods: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14.

Correction: Štorkánová et al. Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin. 2021, , 650.

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S100A4-neutralizing monoclonal antibody 6B12 counteracts the established experimental skin fibrosis induced by bleomycin.

Objectives: Our previous studies have demonstrated that the Damage Associated Molecular Pattern (DAMP) protein, S100A4, is overexpressed in the involved skin and peripheral blood of patients with SSc. It is associated with skin and lung involvement, and disease activity. By contrast, lack of S100A4 prevented the development of experimental dermal fibrosis.

Effect of an 8-Week Tailored Physiotherapy Program on Sexual Health in Women with Scleroderma and Myositis: A Controlled Pilot Study.

Introduction: Systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) are very rare rheumatic diseases burdened by a high prevalence of sexual dysfunctions. However, no specific treatment has been proposed to date. To our knowledge, this is the first (pilot) study aiming to investigate the effect of an 8-week tailored physiotherapy program on the sexual health of women with SSc and IIM.

The effect of a 24-week physiotherapy and occupational therapy program in systemic sclerosis: a monocentric controlled study with follow-up.

Objectives: The structural and functional changes of the hands and face in systemic sclerosis (SSc) can be severely disabling. We aimed to assess the effect of a 24-week supervised physiotherapy and occupational therapy program (POTp) combined with home exercise on the function of hands/mouth of SSc patients, compared to a daily home exercise program in typical outpatient care.

Methods: Fifty-nine patients with SSc were consecutively and non-selectively enrolled in an intervention (IG, n=27) or control (CG, n=32) group.

Female Sexual Dysfunction and Pelvic Floor Muscle Function Associated with Systemic Sclerosis: A Cross-Sectional Study.

Only a few studies have addressed sexual health in patients with systemic sclerosis (SSc). This study aimed to compare female sexual function and pelvic floor muscle function in SSc patients with healthy controls (HC) matched by age, and to identify the potential implications of clinical features on sexual function. Our cohort included 90 women with SSc and 90 HC aged 18-70 years that completed six well-established and validated questionnaires assessing sexual function (Brief Index of Sexual Function for Women, Female Sexual Function Index, Sexual Quality of Life Questionnaire-Female, Sexual Function Questionnaire) and pelvic floor function (Pelvic Floor Impact Questionnaire-Short Form 7 and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form).

Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin.

Our previous study demonstrated that heat shock protein 90 (Hsp90) is overexpressed in the involved skin of patients with systemic sclerosis (SSc) and in experimental dermal fibrosis. Pharmacological inhibition of Hsp90 prevented the stimulatory effects of transforming growth factor-beta on collagen synthesis and the development of dermal fibrosis in three preclinical models of SSc. In the next step of the preclinical analysis, herein, we aimed to evaluate the efficacy of an Hsp90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in the treatment of established experimental dermal fibrosis induced by bleomycin.

Plasma Hsp90 levels in patients with systemic sclerosis and relation to lung and skin involvement: a cross-sectional and longitudinal study.

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis.

Secondary vasculitis - omitted manifestation of many diseases.

Secondary vasculitides usually accompany various common and rare conditions, Their clinical picture is very diverse, they can be loclaized or genaralized. Most frequently, we find parainfectious, drug-related and paraneoplastic vasculitides, less commonly in connective tissue diseases, after radiotherapy or transplantation. Vasculitides may be associated to infection of any origin.

Primary vasculitides - current diagnostics and therapy.

By term „vasculitis“ inflammatory disease of blood vessels is designated that leads to vessel wall destruction followed by proliferation and occlusion of their lumina. Basic condition for this diagnosis is that vessel wall is a primary site of the pathological process. Clinical syndromes are a consequence of this process resulting into ischaemia of tissues supplied by the affected vessels and with constitutional symptoms associated to the inflammatory disease.

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial.

Objectives: Riociguat is approved for pulmonary arterial hypertension and has antiproliferative, anti-inflammatory and antifibrotic effects in animal models of tissue fibrosis. We evaluated the efficacy and safety of riociguat in patients with early diffuse cutaneous systemic sclerosis (dcSSc) at high risk of skin fibrosis progression.

Methods: In this randomised, double-blind, placebo-controlled, phase IIb trial, adults with dcSSc of <18 months' duration and a modified Rodnan skin score (mRSS) 10-22 units received riociguat 0.

[Novel trends in monitoring and therapy of ANCA associated vasculitides].

Vasculitides with positivity of autoantibodies to neutrophil leukocytes cytoplasm (ANCA, AAV) belong to primary vasculitides involving small and less commonly medium size blood vessels. Three different clinical types of AAV can be distinguished: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. Since these autoantibodies seem to be weak activity biomarkers of AAV new molecules and factors start to come up, e.

Mapping and predicting mortality from systemic sclerosis.

Objectives: To determine the causes of death and risk factors in systemic sclerosis (SSc).

Methods: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database.

Molecular markers of systemic autoimmune disorders: the expression of MHC-located HSP70 genes is significantly associated with autoimmunity development.

Objectives: To analyse the expression regulation of two inducible HSP70 genes - HSPA1A and HSPA1B - located within the major histocompatibility complex (MHC) in patients with various systemic autoimmune diseases and to prove the reliability of MHC-located HSP70 genes as molecular markers reflecting the autoimmune process.

Methods: 94 adult patients with idiopathic inflammatory myopathy (IIM, n=31), systemic lupus erythematosus (SLE, n=31) or systemic sclerosis (SSc, n=32) and 37 healthy individuals were analysed. The mRNA expression level was determined using quantitative real-time PCR method.

Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease.

Objectives: IL-35 is a member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. IL-35 exerts immunomodulatory activities in experimental and human autoimmune inflammatory conditions. Our aim was to assess IL-35 expression in the skin and circulation of SSc patients and to characterize its potential association with SSc-related features.

Tribbles homologue 3 stimulates canonical TGF-β signalling to regulate fibroblast activation and tissue fibrosis.

Objectives: Tribbles homologue 3 (TRB3) is a pseudokinase that modifies the activation of various intracellular signalling pathways to control fundamental processes extending from mitosis and cell activation to apoptosis and modulation of gene expression. Here, we aimed to analyse the role of TRB3 in fibroblast activation in systemic sclerosis (SSc).

Methods: The expression of TRB3 was quantified by quantitative PCR, western blot and immunohistochemistry.

S100A4 amplifies TGF-β-induced fibroblast activation in systemic sclerosis.

Objectives: S100A4 is a calcium binding protein with regulatory functions in cell homeostasis, proliferation and differentiation that has been shown to promote cancer progression and metastasis. In the present study, we evaluated the role of S100A4 in fibroblast activation in systemic sclerosis (SSc).

Methods: The expression of S100A4 was analysed in human samples, murine models of SSc and in cultured fibroblasts by real-time PCR, immunohistochemistry and western blot.