Journal of Scleroderma and Related Disorders最新文献

Introduction/objective: The Scleroderma Patient-centered Intervention Network Support group Leader EDucation Program was found in a randomized controlled trial to substantially improve leader self-efficacy. Whether the program is effective for leaders with different levels of experience, including candidate leaders with no prior experience and leaders with ⩽3 years experience or ⩾4 years experience, is not known. The objective of the present post hoc secondary analysis was to evaluate outcomes by leader experience, age, and education.

Methods: The trial was a pragmatic, two-arm partially nested randomized controlled trial with 1:1 allocation to intervention or waitlist control. Eligible participants were existing or candidate support group leaders. The 13-session leader training was delivered in groups of five to six participants weekly via videoconference in 60- to 90-min sessions. The primary outcome was leader self-efficacy, measured by the Support Group Leader Self-efficacy Scale (SGLSS) immediately post-intervention. Secondary outcomes were Support Group Leader Self-efficacy Scale scores 3 months post-intervention and emotional distress, leader burnout, and volunteer satisfaction post-intervention and 3 months post-intervention. Leaders were classified as having no experience, ⩽3 years experience, or ⩾4 years experience.

Results: A total of 148 participants were randomized to intervention (N = 74) or waitlist (N = 74). Compared to leaders with ⩾4 years of experience, Support Group Leader Self-efficacy Scale scores were non-statistically significantly higher post-intervention for leaders with 0-3 years experience and lower for leaders with no experience. The 3 months post-intervention Support Group Leader Self-efficacy Scale scores were significantly lower for leaders without experience and similar for leaders with 0-3 years to those with ⩾4 years experience. There were no differences by experience on other outcomes or by age and education on any outcomes.

Conclusion: Support group leader education improved leader self-efficacy but was most effective for leaders with experience prior to initiating the program.

Trial registration: NCT03965780; registered on May 29, 2019.

Introduction: Vitamin D may be capable of interfering with the pathophysiological pathways involved in systemic sclerosis, by virtue of its well-known immunomodulatory effects. In this study, we aimed at evaluating the differences and the correlations between vitamin D levels in systemic sclerosis patients versus patients with very early systemic sclerosis.

Methods: One hundred twenty-six patients (80 definite systemic sclerosis and 46 very early systemic sclerosis) were included in this case control study. Anthropometric, clinical, biochemical, and instrumental data were recorded and correlated with serum vitamin D levels.

Results: Briefly, systemic sclerosis patients and very early systemic sclerosis subjects significantly differed for telangectasias, scleredema, autoantibody profile, and videocapillaroscopic pattern. In addition, the mean vitamin D levels were significantly lower in systemic sclerosis patients when compared to those of very early systemic sclerosis subjects. When systemic sclerosis patients were divided into two groups, that is, those with ⩽20 ng/ml versus >20 ng/ml vitamin D serum levels, significantly higher serum vitamin D levels were observed in patients with a lesser skin and vascular involvement. With regard to very early systemic sclerosis subjects, who exhibited baseline satisfactory vitamin D levels, only the autoantibody profile was found to correlate with vitamin D serum levels.

Conclusion: Vitamin D serum levels were found to be generally satisfactory in very early systemic sclerosis subjects, but they were reduced in systemic sclerosis patients. Advanced skin and microvascular involvement were found to predispose to hypovitaminosis D. Due to the well-documented immunomodulatory properties of vitamin D, studies are needed to determine whether vitamin D supplementation may prevent the subsequent evolution of very early systemic sclerosis into definite systemic sclerosis.

Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.

The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples. Similarly, any inference on epithelial-to-mesenchymal transition occurrence driven from preclinical models should consider the limitations of cell cultures and animal models. Notwithstanding, while the occurrence or the relevance of this phenomenon in scleroderma-related interstitial lung disease have not been directly and conclusively demonstrated until now, pre-clinical and clinical evidence supports the potential role of epithelial-to-mesenchymal transition in the development and progression of lung fibrosis. Evidence consolidation on scleroderma-related interstitial lung disease epithelial-to-mesenchymal transition would pave the way for new therapeutic opportunities to prevent, slow or even reverse lung fibrosis, drawing lessons from current research lines in neoplastic epithelial-to-mesenchymal transition.

Objective: Cold-induced transient myocardial ischemia has been described in patients with systemic sclerosis. The clinical impact of cold exposure in systemic sclerosis patients with acute cardiac conditions is unknown. We compared the seasonal variation of acute cardiac hospitalizations in patients with and without systemic sclerosis.

Methods: We performed a retrospective cross-sectional study using the National Inpatient Sample from 2016 to 2019. The primary outcome was acute cardiac hospitalization primarily due to heart failure, acute myocardial infarction, or cardiac arrhythmias. We compared the proportion of acute cardiac hospitalizations in each season in patients with and without systemic sclerosis. We also performed a subgroup analysis by US geographic region (Northeast, Midwest, South, West).

Results: There were a total of 10,118,002 acute cardiac hospitalizations over the 4-year study period. Compared to those without systemic sclerosis, patients with systemic sclerosis who were hospitalized for acute cardiac care were younger (mean age 67 ± 13 vs 70 ± 14 years, p < 0.01), a greater proportion were female (82% vs 45%, p < 0.01), and a smaller proportion were Caucasian (68% vs 71%, p < 0.01). There was a lesser proportion of traditional cardiovascular risk factors in systemic sclerosis compared to non-systemic sclerosis patients. There was no significant difference in the proportion of winter admissions between systemic sclerosis and non-systemic sclerosis patients for total acute cardiac hospitalizations (26.4% vs 25.9%, p = 0.51), heart failure (27.0% vs 26.5%, p = 0.64), acute myocardial infarction (26.9% vs 25.5%, p = 0.50), or arrhythmias (24.3% vs 25.0%, p = 0.68). The results were consistent across all four US geographic regions.

Conclusion: Our study did not support that patients with systemic sclerosis had a disproportionally higher risk of acute cardiac hospitalization in winter compared to the general population. We found that systemic sclerosis patients hospitalized for acute cardiac care had a lower burden of traditional cardiovascular risk factors than their non-systemic sclerosis counterparts.

Objectives: Pulmonary hypertension is one of the leading causes of death in systemic sclerosis. Early detection and treatment of pulmonary hypertension in systemic sclerosis is crucial. Nailfold capillaroscopy microscopy, vascular autoantibodies AT1R and ETAR, and several candidate-biomarkers have the potential to serve as noninvasive tools to identify systemic sclerosis patients at risk for developing pulmonary hypertension. Here, we explore the classifying potential of nailfold capillaroscopy microscopy characteristics and serum levels of selected candidate-biomarkers in a sample of systemic sclerosis patients with and without different forms of pulmonary hypertension.

Methods: A total of 81 consecutive systemic sclerosis patients were included, 40 with systemic sclerosis pulmonary hypertension and 41 with no pulmonary hypertension. In each group, quantitative and qualitative nailfold capillaroscopy microscopy characteristics, vascular autoantibodies AT1R and ETAR, and serum levels of 24 soluble serum factors were determined. For evaluation of the nailfold capillaroscopy microscopy characteristics, linear regression analysis accounting for age, sex, and diffusing capacity of the lungs for carbon monoxide percentage predicted was used. Autoantibodies and soluble serum factor levels were compared using two-sample t test with equal variances.

Results: No statistically significant differences were observed in quantitative or qualitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibody ETAR and AT1R titer between systemic sclerosis-pulmonary hypertension and systemic sclerosis-no pulmonary hypertension. In contrast, several serum levels of soluble factors differed between groups: Endostatin, sVCAM, and VEGFD were increased, and CXCL4, sVEGFR2, and PDGF-AB/BB were decreased in systemic sclerosis-pulmonary hypertension. Random forest classification identified Endostatin and CXCL4 as the most predictive classifiers to distinguish systemic sclerosispulmonary hypertension from systemic sclerosis-no pulmonary hypertension.

Conclusion: This study shows the potential for several soluble serum factors to distinguish systemic sclerosis-pulmonary hypertension from systemic sclerosis-no pulmonary hypertension. We found no classifying potential for qualitative or quantitative nailfold capillaroscopy microscopy characteristics, or vascular autoantibodies.