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Scientific Reports Jun 2024Systemic sclerosis (SSc) is a multifaceted disease, and its diagnosis triggers substantial anxiety and uncertainty for those affected. Currently, there are no valid data... (Randomized Controlled Trial)
Randomized Controlled Trial
Systemic sclerosis (SSc) is a multifaceted disease, and its diagnosis triggers substantial anxiety and uncertainty for those affected. Currently, there are no valid data describing the impact of disease-specific patient education on the disease knowledge available. We created a two-day, online educational seminar to provide SSc patients with disease-specific information. The primary objective of the study was to observe the change in the disease-specific knowledge of the patients. A total of 118 patients were randomized into an intervention group and a waiting list control group. The change in knowledge was assessed using a multiple-choice test. The intervention group completed the questionnaire before, directly after, and 3 months after the seminar, while the waiting list control group also took the test 3 months before the seminar to rule out nonspecific learning. The primary outcome measure was the score difference between baseline and 3 months after baseline. The study was registered in the German Clinical Trials Register (protocol code DRKS00024915). The educational seminar resulted in a small, but measurable, increase in knowledge. While the two tests in the waiting list control group prior to the seminar did not show a nonspecific increase in disease knowledge, the intervention led to a numerical increase in knowledge (mean ± sd score difference 0.34 ± 1.31, 95% CI (- 0.23; 0.86), p = 0.26) that did not reach statistical significance. Multiple linear regression analysis showed that being a member of a self-help group (β = 1.12; p = 0.03) is a positive predictor of a higher disease knowledge. Although highly appreciated by participants, a two-day online seminar may not be the most appropriate format to generate measurable disease-specific knowledge. Self-help group membership was a positive predictor of a higher level of disease-specific knowledge prior to the educational seminar and should be recommended to every affected person.
Topics: Humans; Scleroderma, Systemic; Female; Male; Middle Aged; Patient Education as Topic; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; Adult; Aged; Internet
PubMed: 38877137
DOI: 10.1038/s41598-024-64532-4 -
Frontiers in Immunology 2024Integrin-dependent cell adhesion and migration play important roles in systemic sclerosis (SSc). The roles of integrin activating molecules including talins and...
BACKGROUND
Integrin-dependent cell adhesion and migration play important roles in systemic sclerosis (SSc). The roles of integrin activating molecules including talins and kindlins, however, are unclear in SSc.
OBJECTIVES
We aimed to explore the function of integrin activating molecules in SSc.
METHODS
Transcriptome analysis of skin datasets of SSc patients was performed to explore the function of integrin-activating molecules including talin1, talin2, kindlin1, kindlin2 and kindlin3 in SSc. Expression of talin1 in skin tissue was assessed by multiplex immunohistochemistry staining. Levels of talin1 in serum were determined by ELISA. The effects of talin1 inhibition were analyzed in human dermal fibroblasts by real-time PCR, western blot and flow cytometry.
RESULTS
We identified that talin1 appeared to be the primary integrin activating molecule involved in skin fibrosis of SSc. Talin1 was significantly upregulated and positively correlates with the modified Rodnan skin thickness score (mRSS) and the expression of pro-fibrotic biomarkers in the skin lesions of SSc patients. Further analyses revealed that talin1 is predominantly expressed in the dermal fibroblasts of SSc skin and promotes fibroblast activation and collagen production. Additionally, talin1 primarily exerts its effects through integrin β1 and β5 in SSc.
CONCLUSIONS
Overexpressed talin1 is participated in skin fibrosis of SSc, and talin1 appears to be a potential new therapeutic target for SSc.
Topics: Humans; Scleroderma, Systemic; Talin; Fibrosis; Skin; Fibroblasts; Female; Male; Middle Aged; Adult; Cells, Cultured
PubMed: 38863696
DOI: 10.3389/fimmu.2024.1400819 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2024To establish a diagnostic model for scleroderma by combining machine learning and artificial neural network based on mitochondria-related genes.
OBJECTIVE
To establish a diagnostic model for scleroderma by combining machine learning and artificial neural network based on mitochondria-related genes.
METHODS
The GSE95065 and GSE59785 datasets of scleroderma from GEO database were used for analyzing expressions of mitochondria-related genes, and the differential genes were identified by Random forest, LASSO regression and SVM algorithms. Based on these differential genes, an artificial neural network model was constructed, and its diagnostic accuracy was evaluated by 10-fold crossover verification and ROC curve analysis using the verification dataset GSE76807. The mRNA expressions of the key genes were verified by RT-qPCR in a mouse model of scleroderma. The CIBERSORT algorithm was used to estimate the bioinformatic association between scleroderma and the screened biomarkers.
RESULTS
A total of 24 differential genes were obtained, including 11 up-regulated and 13 down-regulated genes. Seven most relevant mitochondria-related genes (POLB, GSR, KRAS, NT5DC2, NOX4, IGF1, and TGM2) were screened using 3 machine learning algorithms, and the artificial neural network diagnostic model was constructed. The model showed an area under the ROC curves of 0.984 for scleroderma diagnosis (0.740 for the verification dataset and 0.980 for cross-over validation). RT-qPCR detected significant up-regulation of POLB, GSR, KRAS, NOX4, IGF1 and TGM2 mRNAs and significant down-regulation of NT5DC2 in the mouse models of scleroderma. Immune cell infiltration analysis showed that the differential genes in scleroderma were associated with follicular helper T cells, immature B cells, resting dendritic cells, memory activated CD4T cells, M0 macrophages, monocytes, resting memory CD4T cells and mast cell activation.
CONCLUSION
The artificial neural network diagnostic model for scleroderma established in this study provides a new perspective for exploring the pathogenesis of scleroderma.
Topics: Mice; Animals; Neural Networks, Computer; Mitochondria; Machine Learning; Algorithms; Scleroderma, Systemic; Humans; Biomarkers; Gene Expression Profiling; Computational Biology; ROC Curve; Disease Models, Animal
PubMed: 38862450
DOI: 10.12122/j.issn.1673-4254.2024.05.14 -
Journal of Cutaneous Medicine and... Jun 2024
PubMed: 38859662
DOI: 10.1177/12034754241260021 -
Scientific Reports Jun 2024Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis...
Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.
Topics: Humans; Scleroderma, Systemic; Female; Hypertension, Pulmonary; Middle Aged; Male; Aged; Retrospective Studies; Exercise Test; Exercise; Exercise Tolerance; Echocardiography; Oxygen Consumption; Cardiac Catheterization; Practice Guidelines as Topic; Vascular Resistance
PubMed: 38858443
DOI: 10.1038/s41598-024-63823-0 -
Echocardiography (Mount Kisco, N.Y.) Jun 2024Systemic Sclerosis (SSc), an intricate autoimmune disease causing tissue fibrosis, introduces cardiovascular complexities, notably pulmonary hypertension (PH), affecting...
BACKGROUND
Systemic Sclerosis (SSc), an intricate autoimmune disease causing tissue fibrosis, introduces cardiovascular complexities, notably pulmonary hypertension (PH), affecting both survival and quality of life. This study centers on evaluating echocardiographic parameters and endothelial function using flow-mediated dilatation (FMD) in SSc patients, aiming to differentiate those with and without pulmonary arterial hypertension (PAH). The emphasis lies in early detection, given the heightened vulnerability of the right ventricle (RV) in the presence of PH.
METHODS
Fifty-nine SSc patients and 48 healthy subjects participated, undergoing clinical examinations, echocardiography, FMD assessments, blood analyses, and right heart catheterization (RHC) according to the ESC/ERS guidelines for diagnosis and treatment of PH.
RESULTS
SSc-PAH patients displayed lower FMD, higher frequency of TAPSE < 18 mm, RA area > 18 cm, act RVOT < 105 ms and TRV > 280 cm/s compared to those without PAH and healthy controls. Resting resistivity index (RI) was higher in SSc patients, with no significant difference between those with and without PAH. Lower FMD% serves as a predictive marker for adverse cardiovascular outcomes in both SSc and SSc-PAH patients. Stratification by TRV levels and PAH presence reveals notable FMD% variations, emphasizing its potential utility.
CONCLUSIONS
Early identification of endothelial dysfunction and impaired RV echocardiographic parameters, such as TAPSE and TRV, could aid in predicting right ventricular dysfunction and PAH in SSc patients.
Topics: Humans; Female; Male; Scleroderma, Systemic; Middle Aged; Echocardiography; Hypertension, Pulmonary; Adult
PubMed: 38853623
DOI: 10.1111/echo.15853 -
Chest Jun 2024
Topics: Humans; Scleroderma, Systemic; Hypertension, Pulmonary
PubMed: 38852963
DOI: 10.1016/j.chest.2024.01.044 -
Seminars in Arthritis and Rheumatism Aug 2024We previously surveyed adults with systemic sclerosis (SSc) regarding COVID-19 vaccination in April-May 2021. The objective of the present study was to update through...
BACKGROUND/PURPOSE
We previously surveyed adults with systemic sclerosis (SSc) regarding COVID-19 vaccination in April-May 2021. The objective of the present study was to update through June-July 2022 and assess self-reported (1) COVID-19 vaccination rates, including boosters; (2) vaccine-related adverse events; (3) peri‑vaccination immunosuppressive medication management; (4) vaccine hesitancy; and (5) prevalence and severity of COVID-19 infections.
METHODS
In April-May 2021 and June-July 2022, SPIN Cohort participants completed surveys on COVID-19 vaccination and infection. Primary vaccine series was defined according to the standard for each COVID-19 vaccine; additional vaccine administrations were considered booster doses. Fully vaccinated was defined as having completed a primary vaccine series and at least one booster dose.
RESULTS
544 participants completed the 2021 survey only, 101 the 2022 survey only, and 388 both surveys. Among 489 participants with 2022 data, 437 (89 %) had received both primary and booster vaccines. Among all 1,033 participants, 960 (93 %) received at least one dose. At least one adverse reaction was reported by 34 % (330 of 960 participants) following first, 48 % (314 of 657 participants) following second, and 34 % (147 of 437 participants) following booster vaccine doses (primarily sore arm and fatigue); no severe adverse reactions were reported. SSc symptom worsening was reported in 6 % (53 of 960) after the first, 6 % after the second (39 of 657), and 4 % (17 of 437) after the booster dose. Of participants taking methotrexate or mycophenolate (including Cellcept or Myfortic), 34 of 266 (13 %) reported that they temporarily stopped or decreased their medication at the first dose, 32 of 215 (15 %) at the second dose, and 28 of 148 (19 %) for booster vaccination. Of 52 individuals not fully vaccinated with primary and booster doses in 2022, 29 (56 %) reported worry about vaccine related SSc flares. 172 of 489 (35 %) 2022 participants reported a history of at least one COVID-19 infection; 114 (66 %) occurred after receiving at least a primary vaccine series. Among initial COVID-19 infections, 9 (5 %) were asymptomatic, 66 (38 %) involved mild symptoms, 82 (48 %) moderate symptoms, and 15 (9 %) required hospitalization.
CONCLUSION
Most people with SSc in the study were fully vaccinated, and most continued their methotrexate or mycophenolate post-primary and booster vaccinations. Over half of vaccine-hesitant participants were concerned regarding risk of SSc flare; however, few vaccinated participants reported this. These data may be useful for counselling people with SSc regarding COVID-19 vaccine safety and outcomes.
Topics: Humans; Scleroderma, Systemic; Male; Female; COVID-19 Vaccines; COVID-19; Middle Aged; SARS-CoV-2; Aged; Adult; Vaccination; Cohort Studies; Immunosuppressive Agents; Vaccination Hesitancy; Immunization, Secondary
PubMed: 38851172
DOI: 10.1016/j.semarthrit.2024.152453 -
Journal of Cancer Research and Clinical... Jun 2024Systemic sclerosis (SSc) is a rare autoimmune disease associated with high morbidity and mortality. SSc treatment is still challenging, and evidence is scarce. In the...
PURPOSE
Systemic sclerosis (SSc) is a rare autoimmune disease associated with high morbidity and mortality. SSc treatment is still challenging, and evidence is scarce. In the last decades high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) has proven to be effective. However, treatment related morbidity and mortality (TRM) are high. We conducted a retrospective, single-center analysis of SSc patients following HD-ASCT focusing on TRM and risk factors.
METHODS
32 patients who underwent HD-ASCT at our hospital between June 2000 and September 2020 were included. Clinical characteristics were evaluated based on chart review before and after HD-ASCT. Analyses focused on overall survival (OS), TRM, and response to HD-ASCT.
RESULTS
Median OS was 81 months (range 0-243). Within one year, 20 of 32 (76.9%) patients responded to HD-ASCT. Overall, 6 patients (18.8%) died in the context of HD-ASCT. Patients with subjective response to HD-ASCT (p = 0.024) and those with shorter time to platelet engraftment (p = 0.047) had significantly longer OS. Impaired renal function, age at HD-ASCT ≥ 55, disease duration < 12 months, high Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and Charlton Comorbidity Index (CCI) scores were associated with higher TRM. Patients receiving conditioning chemotherapy with thiotepa needed longer time for neutrophil (p = 0.035) and platelet engraftment (p = 0.021).
CONCLUSION
This study confirms the efficacy of HD-ASCT for patients with SSc in a single center real-world setting. High TRM is still a challenge. However, TRM could be reduced by exclusion of high-risk patients and attention to prognostic parameters and scores as suggested in this study.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Female; Male; Middle Aged; Adult; Transplantation, Autologous; Prognosis; Aged; Scleroderma, Diffuse; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Young Adult; Combined Modality Therapy
PubMed: 38850365
DOI: 10.1007/s00432-024-05815-1 -
Acta Dermato-venereologica Jun 2024
Topics: Humans; Female; Aged; CREST Syndrome; Facial Dermatoses; Biopsy; Skin
PubMed: 38850086
DOI: 10.2340/actadv.v104.40419