Importance High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration isrctn.org Identifier:ISRCTN54371254

https://jamanetwork.com/journals/jama/articlepdf/1883019/joi140072.pdf

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Purpose
Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk for atherosclerosis and cardiovascular disease. Our objective was to perform a systematic review and meta-analysis to determine if atherosclerosis is increased in patients with SSc compared to healthy individuals.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/art.30380

Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis.

Smoke and autoimmunity: The fire behind the disease.

Objective

To examine cancer incidence in patients with systemic sclerosis (SSc) through a meta-analysis of population-based cohort studies.



Methods

Five different databases (Medline, Scopus, CINAHL [Cumulative Index to Nursing and Allied Health Literature], Web of Science, and Cochrane Collaboration) were searched for articles published between January 1966 and May 2012; review articles and the reference lists from the articles that resulted from the search were also evaluated. Population-based cohort studies with data relevant to the determination of cancer risk in patients with SSc were included. All articles that met strict inclusion criteria were analyzed for data on population size, time of followup, and observed-to-expected cancer ratios, also known as standardized incidence ratios (SIRs).



Results

Six articles met criteria and were included in the meta-analysis. The pooled SIR for the incidence of cancer overall was 1.41 (95% confidence interval [95% CI] 1.18–1.68), and significant heterogeneity was observed as a consequence of variability in the participants, outcome, study design, and risk of bias among the studies. Men had a significantly higher pooled SIR (1.85 [95% CI 1.49–2.31]) than women (SIR 1.33 [95% CI 1.18–1.49]) (P < 0.01), and stratification for sex eliminated heterogeneity, which indicates that variability among the studies greatly contributed to differences between the sexes. There were no differences between limited cutaneous SSc and diffuse cutaneous SSc (P = 0.77). Significant increases were observed in the risk of cancer of the lung, liver, hematologic system, and bladder, as well as of non-Hodgkin's lymphoma and leukemia.



Conclusion

SSc is associated with an increased risk of cancer, particularly lung, liver, hematologic, and bladder cancers, although absolute risk is relatively low. Men with SSc have a higher risk of developing cancer than women.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.37969

Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies.

Tobacco smoking has been linked to an increased risk of multiple sclerosis. However, to date, results from the few studies on the impact of smoking on the progression of disability are conflicting. The aim of this study was to investigate the effects of smoking on disability progression and disease severity in a cohort of patients with clinically definite multiple sclerosis. We analysed data from 895 patients (270 male, 625 female), mean age 49 years with mean disease duration 17 years. Forty-nine per cent of the patients were regular smokers at the time of disease onset or at diagnosis (ever-smokers). Average disease severity as measured by multiple sclerosis severity score was greater in ever-smokers, by 0.68 (95% confidence interval: 0.36–1.01). The risk of reaching Expanded Disability Status Scale score milestones of 4 and 6 in ever-smokers compared to never-smokers was 1.34 (95% confidence interval: 1.12–1.60) and 1.25 (95% confidence interval: 1.02–1.51) respectively. Current smokers showed 1.64 (95% confidence interval: 1.33–2.02) and 1.49 (95% confidence interval: 1.18–1.86) times higher risk of reaching Expanded Disability Status Scale scores 4 and 6 compared with non-smokers. Ex-smokers who stopped smoking either before or after the onset of the disease had a significantly lower risk of reaching Expanded Disability Status Scale scores 4 (hazard ratio: 0.65, confidence interval: 0.50–0.83) and 6 (hazard ratio: 0.69, confidence interval: 0.53–0.90) than current smokers, and there was no significant difference between ex-smokers and non-smokers in terms of time to Expanded Disability Status Scale scores 4 or 6. Our data suggest that regular smoking is associated with more severe disease and faster disability progression. In addition, smoking cessation, whether before or after onset of the disease, is associated with a slower progression of disability.

/pdf/tobacco-smoking-and-disability-progression-in-multiple-4xqd9g9g3m.pdf

Tobacco smoking and disability progression in multiple sclerosis: United Kingdom cohort study

Objective

To determine the effects of cigarette smoking on vascular, gastrointestinal, and respiratory outcomes in patients with systemic sclerosis (SSc).



Methods

Subjects were patients enrolled in the Canadian Scleroderma Research Group cohort. Smoking history was obtained by patient self-report. The effect of smoking was assessed using multiple regression analysis of each SSc clinical outcome of interest (vascular, gastrointestinal, and respiratory). Smoking was modeled both as categorical variables (current, past, and never) and using the Comprehensive Smoking Index (CSI), which integrates smoking intensity, duration of smoking, and time since cessation into a single covariate of smoking effect. All regression models were adjusted for age, sex, disease duration, and limited or diffuse skin involvement.



Results

This study included 606 patients with SSc, of whom 87% were women and 90% were white, and the mean age was 55 years, mean disease duration was 11 years, and 36% had diffuse disease. Of these patients, 16% were current smokers, 42% were past smokers, and 42% were never smokers. The regression analyses showed that smoking had a significant negative effect on almost all vascular, gastrointestinal, and respiratory outcomes. The effects of smoking were in some cases long-lasting (e.g., persistent respiratory abnormalities), and smoking cessation appeared beneficial with respect to some outcomes (e.g., reduced severity of Raynaud's phenomenon).



Conclusion

Physicians caring for patients with SSc should prioritize smoking cessation as a recommendation to patients, and resources directed to supporting smoking cessation in patients with SSc should be more readily available.

Cigarette smoking in patients with systemic sclerosis

Objective. Systemic sclerosis (SSc) is a multisystem disease associated with significant morbidity and increased mortality. Little is known about work disability in SSc. We undertook this study to determine the prevalence and demographic and clinical correlates of work disability in a large cohort of patients with SSc.

Methods. Cross-sectional, multicenter study of patients from the Canadian Scleroderma Research Group Registry. Patients were assessed with detailed clinical histories, medical examinations, and self-administered questionnaires. The primary outcome was self-reported work disability. Multiple logistic regression was used to assess the relationship between selected demographic and clinical variables and work disability.

Results. Of the 643 patients available for this study, 133 (21%) reported that they were work disabled. Work disability in SSc was common, even in people with short disease duration, and increased steadily with increasing disease duration: among those who were ≤ 65 years and who reported being either disabled or working, 28.0% and 44.8% of patients with disease duration of < 2 and 10–15 years, respectively, reported that they were work-disabled. The significant correlates of work disability included co-morbidities, disease duration, diffuse disease, disease severity, pain, fatigue, and physical function.

Conclusion. Work disability is prevalent, occurs early, and is associated with markers of disease severity and functional status. Further research is needed to identify other, potentially modifiable, risk factors for work disability in SSc.

https://www.jrheum.org/content/jrheum/36/11/2481.full.pdf

Work disability in systemic sclerosis.

Objective. Systemic sclerosis (SSc) is a multisystem disease associated with impaired health-related quality of life (HRQOL). Our objective was to identify the clinical characteristics that correlate with the physical health status of patients with SSc, as assessed by the Medical Outcomes Trust Short Form-36 (SF-36).

Methods. Cross-sectional, multicenter study of 416 patients from the Canadian Scleroderma Research Group Registry. Patients were assessed with detailed clinical histories, medical examinations, and self-administered SF-36. Multiple linear regression was used to assess the relationship between selected demographic and clinical variables and the SF-36 Physical Component Summary (PCS) score.

Results. The greatest impairments in the SF-36 were in the domains measuring physical health, and the mean SF-36 PCS score was 37.5 (± 11.2). In multivariate analysis, significant clinical predictors of the SF-36 PCS were shortness of breath, number of gastrointestinal problems, skin score, swollen joint count, and age. The final model explained 47% of the variance in the SF-36 PCS.

Conclusion. Clinical characteristics identified as significant correlates of the self-reported physical health status in SSc should each be targets of intervention in order to improve the HRQOL of patients with this disease.

https://www.jrheum.org/content/jrheum/36/6/1226.full.pdf

Clinical Correlates of Self-reported Physical Health Status in Systemic Sclerosis

BACKGROUND
Mild cognitive impairment (MCI) is the prodromal stage of dementia. In this stage, reasonable intervention measures can help to delay the decline of cognitive function. Supplementation of n-3 polyunsaturated fatty acids (n-3PUFAs) may be beneficial to delay the decline of cognitive function in the elderly.


OBJECTIVE
To investigate the effectiveness of docosapentaenoic acid (DHA) or/and eicosapentaenoic acid (EPA) supplements in the elderly with MCI.


METHODS
Eight electronic databases, PubMed, Cochrane Library, Embase, VIP, SinoMed, Web of Science, CNKI, and WANFANG DATA, were searched for related articles from inception until January 2022. Subgroup analyses and sensitivity analyses were performed to detect confounding variables. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots. Stata12.0 was used for Begg's and Egger's test to quantify whether publication bias. Linear relationship between global cognition and covariates was examined in meta-regression analysis.


RESULTS
Twelve studies (n = 1,124) were included. The methodological quality of research is mostly medium. Compared with placebo, n-3PUFAs supplements have benefits on global cognition [SMD = 0.51, 95% CI(0.12, 0.91), p = 0.01]. No significant differences were observed between intervention group and placebo on language fluency, executive functions, and depression.


CONCLUSION
Our findings indicated DHA and/or EPA supplements have benefits on global cognition, and it may also reduce the level of blood amyloid-β (Aβ)-related biomarkers (e.g., Aβ 40, Aβ 42) and inflammatory factors (e.g., 1L-6, 1L-10). Since there are only two relative articles, more research is needed in the future to clarify the relationship.

/pdf/n-3-polyunsaturated-fatty-acids-in-elder-with-mild-cognitive-pwx10ni5.pdf

Ying Lu

Papers

Cigarette smoking in patients with systemic sclerosis

Work disability in systemic sclerosis.

Clinical Correlates of Self-reported Physical Health Status in Systemic Sclerosis

N-3 Polyunsaturated Fatty Acids in Elder with Mild Cognitive Impairment: A Systemic Review and Meta-Analysis.