Unmet Workplace Support Needs and Lost Productivity of Workers With Systemic Sclerosis: A Path Analysis Study.

OBJECTIVE: Few studies have examined how workplace support can address work productivity loss among individuals with systemic sclerosis (SSc). The objective was to 1) examine the relationship between unmet workplace support needs and work productivity loss among workers with SSc, and 2) determine whether SSc symptom severity, fatigue, active disease periods, and workplace activity limitations mediate the relationship between unmet workplace support needs and work productivity loss. METHODS: A cross-sectional survey was conducted of employed individuals with SSc who were recruited through rheumatology clinics. Information on work productivity loss (i.e., absenteeism, presenteeism, job disruptions) and the need, availability, and use of workplace supports was collected. SSc symptom severity (e.g., workplace activity limitations, active disease periods, fatigue, and overall SSc symptom severity) and demographic, health, and work context characteristics were collected. Three Bayesian path models examined the association between unmet workplace support needs and each work productivity loss outcome. SSc symptom severity variables were examined as mediators in each model. RESULTS: A total of 110 employed participants were recruited (mean ± SD ages 49 ± 12.9 years). More than three-fourths of participants were female (77%) and worked full-time (77%). The most needed workplace supports included extended health benefits (84%), special equipment (63%), and flextime (59%). Additionally, 61% reported unmet workplace support needs. Path models indicated that indirect relationships between unmet workplace support needs and work productivity loss were significant. For all models, workplace activity limitations mediated the relationship between unmet workplace support needs and productivity loss. CONCLUSION: To foster productive employment of individuals with SSc, interventions need to address symptom severity and meet workplace support needs.

Fatigue and Its Association With Social Participation, Functioning, and Quality of Life in Systemic Sclerosis.

OBJECTIVE: Fatigue is consistently ranked as one of the most problematic symptoms of systemic sclerosis (SSc), but the impact of fatigue on daily life is not well characterized. The purpose of this study was to examine the contribution of fatigue to deficits in social participation, functioning, and quality of life. METHODS: Baseline data from a sample undertaking a clinical trial were utilized (n = 267). Fatigue, pain interference, depressive symptoms, physical function, and social participation were assessed by measures from the Patient-Reported Outcomes Measurement Information System. Hierarchical linear regressions were performed to determine the unique contribution of fatigue to social participation, physical function, and quality of life above and beyond the effects of demographic and clinical variables, pain interference, and depressive symptoms. RESULTS: The sample was predominantly female (91%), with an average age of 53.7 years, average disease duration of 9 years, and a mean fatigue T score of 58.7. Of all outcomes, fatigue was most strongly associated with deficits in social participation, explaining 48% of the variance beyond demographic and clinical factors, which is similar to the amount of variance contributed by pain interference and depressive symptoms combined (49%). Fatigue also accounted for significant amounts of variance in physical function and quality of life (R2 = 0.27 and 0.33, respectively) above and beyond the effects of demographic and clinical factors. CONCLUSION: Fatigue is an important clinical problem in SSc and is strongly associated with decreased participation in social roles and activities. Rehabilitation interventions that focus on fatigue management may be necessary to maximize participation.

Assessment of esophageal body peristaltic work using functional lumen imaging probe panometry.

The goal of this study was to conceptualize and compute measures of "mechanical work" done by the esophagus using data generated during functional lumen imaging probe (FLIP) panometry and compare work done during secondary peristalsis among patients and controls. Eighty-five individuals were evaluated with a 16-cm FLIP during sedated endoscopy, including asymptomatic controls (n = 14) and those with achalasia subtypes I, II, and III (n = 15, each); gastroesophageal reflux disease (GERD; n = 13); eosinophilic esophagitis (EoE; n = 9); and systemic sclerosis (SSc; n = 5). The FLIP catheter was positioned to have its distal segment straddling the esophagogastric junction (EGJ) during stepwise distension. Two metrics of work were assessed: "active work" (during bag volumes ≤ 40 mL where contractility generates substantial changes in lumen area) and "work capacity" (for bag volumes ≥ 60 mL when contractility cannot substantially alter the lumen area). Controls showed median [interquartile range (IQR)] of 7.3 (3.6-9.2) mJ of active work and 268.6 (225.2-332.3) mJ of work capacity. Patients with all achalasia subtypes, GERD, and SSc showed lower active work done than controls (P ≤ 0.003). Patients with achalasia subtypes I and II, GERD, and SSc had lower work capacity compared with controls (P < 0.001, 0.004, 0.04, and 0.001, respectively). Work capacity was similar between controls and patients with achalasia type III and EoE. Mechanical work of the esophagus differs between healthy controls and patient groups with achalasia, EoE, SSc, and GERD. Further studies are needed to fully explore the utility of this approach, but these work metrics would be valuable for device design (artificial esophagus), to measure the efficacy of peristalsis, to gauge the physiological state of the esophagus, and to comment on its pumping effectiveness.NEW & NOTEWORTHY Functional lumen imaging probe (FLIP) panometry assesses esophageal response to distension and provides a simultaneous assessment of pressure and dimension during contractility. This enables an objective assessment of "mechanical work" done by the esophagus. Eighty-five individuals were evaluated, and two work metrics were computed for each subject. Controls showed greater values of work compared with individuals with achalasia, gastroesophageal reflux disease (GERD), and systemic sclerosis (SSc). These values can quantify the mechanical behavior of the distal esophagus and assist in the estimation of muscular integrity.

Electrocardiogram and heart rate variability assessment in patients with common autoimmune diseases: a methodological review.

The aim of this article was to summarize current knowledge about the potential clinical utility of electrocardiogram (ECG) and heart rate variability (HRV) measures in patients with 4 common autoimmune diseases (ADs): rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet's disease (BD), and systemic sclerosis (SSc). A search was conducted of the PubMed, Embase, and Scopus databases using terms and a controlled vocabulary associated with these ADs, ECG, and HRV. The available, full-text articles published in English were considered. In all, 20 publications that examined the direct effect of these diseases on the heart were selected according to a systematic review protocol. Time-frequency domain analysis revealed that HRV parameters were lower in patients with the selected ADs in comparison with control groups. An increased QT dispersion and heart rate corrected QT, which are well-known as risk factors for sudden cardiac death, were observed in the patient group. In some studies, a correlation was seen between the duration of the disease and its activity, while others did not report such an association. Heart rate turbulence parameters were also examined. Turbulence onset was increased in SLE and SSc patients, while the turbulence slope was decreased in SLE patients. There was no significant change in these parameters in BD patients. Patients with ADs demonstrate abnormal HRV and ECG parameters, which indicates an autonomic cardiac functional impairment. Measurement of these parameters can be a useful clinical tool in the diagnosis and prediction of some disorders in patients with ADs. Both of these signals can provide helpful information for physicians to trace the efficacy of prescribed medicines.

Quantitative computed tomography assessment for systemic sclerosis-related interstitial lung disease: comparison of different methods.

OBJECTIVES: To compare the previously defined six different histogram-based quantitative lung assessment (QLA) methods on high-resolution CT (HRCT) in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: The HRCT images of SSc patients with ILD were reviewed, and the visual ILD score (semiquantitative) and the severity of ILD (limited or extensive) were calculated. The QLA score of ILD was evaluated using the previously defined six different methods and parameters (different lung attenuation ranges, skewness, kurtosis, mean lung attenuation, and standard deviation [SD]). Pulmonary function tests (PFTs) were also performed on all patients. Relationships among variables were evaluated using Spearman's correlation coefficient (r). Diagnostic performance of quantitative methods for the ability to differentiate the limited from extensive ILD was calculated using ROC analysis. RESULTS: Fifty-five patients were included in the study. There was a significant correlation between all quantitative and semiquantitative measurement results (p < 0.0001). The QLA scores revealed a significant correlation with PFT results. The kurtosis value of the voxels between - 200 and - 1024 Hounsfield unit (HU) (Method-5) showed the best correlation with semiquantitative evaluation (r = - 0.740, p < 0.0001). The ROC analysis demonstrated the best performance of SD of the voxels between - 400 and - 950 HU (Method-6) for histogram analysis method and Method-3 (voxels between - 260 and - 600 HU were calculated as ILD) for CT density cutoff methods. CONCLUSIONS: All the QLA methods are applicable in assessing the ILD score in SSc patients and have potential importance to differentiate limited from extensive ILD. KEY POINTS: • Quantitative interstitial lung disease assessment helps clinicians to assess systemic sclerosis patients with interstitial lung disease. • Quantitative lung assessment methods are applicable in assessing the interstitial lung disease score in systemic sclerosis patients. • Quantitative lung assessment methods have potential importance in the management of patients.

Ability of the COPD Assessment Test to evaluate the lung-specific quality of life in systemic sclerosis-associated interstitial lung disease.

INTRODUCTION: The COPD Assessment Test (CAT) is utilised to evaluate the treatment outcome regarding the health status in idiopathic interstitial pneumonia (IIP). However, the ability of the CAT to evaluate the lung-specific quality of life in systemic sclerosis-associated interstitial lung disease (SSc-ILD) is not established. Therefore, we investigated whether CAT scores can be used to evaluate SSc-ILD as they are for IIP. METHODS: A total of 150 patients with IIP or SSc-ILD who were evaluated by the CAT were retrospectively assigned to this study. Clinical data at the visit for the CAT were analysed. RESULTS: The forced vital capacity and distance walked during the 6-minute walk test (6MWD) were significantly correlated with the CAT score for SSc-ILD and IIP, and the CAT scores were similarly distributed in SSc-ILD and IIP. The CAT score of SSc-ILD patients was negatively affected by pulmonary arterial hypertension, but not by corticosteroids, which affected it in IIP patients. CAT scores of patients with either disease receiving home oxygen therapy were poor. In multiple regression analysis, pulmonary arterial hypertension and 6MWD were independent predictors for the CAT score in patients with SSc-ILD, while corticosteroid administration was selected as an independent factor in patients with IIP. CONCLUSIONS: Our study suggests that the CAT can be applied to evaluate the lung-specific quality of life in SSc-ILD similar to IIP regarding the pulmonary function, but it should be noted that pulmonary arterial hypertension in SSc-ILD influences the CAT score.

Multicenter Qualitative Study Exploring the Patient Experience of Digital Ulcers in Systemic Sclerosis.

OBJECTIVE: Digital ulcers (DUs) are a major cause of disease-related morbidity and are a difficult-to-treat vascular complication of systemic sclerosis (SSc). Demonstrating treatment efficacy has traditionally focused on clinician assessment of DUs alone. No existing patient-reported outcome (PRO) instrument captures the multifaceted impact of SSc-DU. We report the findings of a multicenter qualitative research study exploring the patient experience of SSc-DU. METHODS: Patient focus groups were conducted across 3 scleroderma units, following a topic guide devised by SSc patients, experts, and experienced qualitative researchers. A purposive sampling framework ensured that the experiences of a diverse group of patients were captured. Focus groups were audio recorded, and information was transcribed, anonymized, and analyzed using inductive thematic analysis. We continued focus groups until thematic saturation was achieved. RESULTS: Twenty-nine SSc patients with a history of DU disease participated in 4 focus groups across the UK (Bath, Manchester, and London). Five major interrelated themes (and subthemes) were identified that encompass the patient experience of SSc-DU: disabling pain and hypersensitivity; deep and broad-ranging emotional impact; impairment of physical and social activity; factors aggravating occurrence, duration, and impact; and mitigating, managing, and adapting. CONCLUSION: The patient experience of SSc-DU is multifaceted and comprises a complex interplay of experiences associated with significant pain and morbidity. Patient experiences of SSc-DU are not captured using existing SSc-DU outcomes. Our findings will inform the development of a novel PRO instrument to assess the severity and impact of SSc-DU for use in future SSc-DU clinical trials.

The role of high-resolution manometry in the assessment of upper gastrointestinal involvement in systemic sclerosis: a systematic review.

Systemic sclerosis (SSc) affects the upper gastrointestinal (GI) system in 90% of patients. High-resolution manometry (HRM) assesses esophageal dysmotility, but its role in diagnosis and follow-up remains unclear. The objectives of this systematic review were to investigate the role of HRM in the assessment of SSc-associated upper GI involvement and to evaluate the correlation between HRM abnormalities and clinical characteristics and the effects of therapeutic interventions on HRM findings. Fifteen articles were included. Most (11/15) studies were of very good or good quality. Most studies assessed correlations between esophageal symptoms and esophageal dysmotility. Two studies assessed the effectiveness of buspirone and reported HRM findings. Studies assessing upper GI symptoms using validated questionnaires, such as the University of California Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 or Gastrointestinal Symptoms Severity Index score, found an association between absent contractility on HRM and upper GI symptoms, but even asymptomatic patients often have esophageal body dysmotility on HRM. Esophageal dysmotility positively correlates with the presence of interstitial lung disease on high-resolution computed tomography and reduced diffusion capacity (< 0.8 of predicted value). Trials investigating the effect of buspirone demonstrate both increased lower esophageal sphincter resting pressure and reduced upper GI symptoms. Most studies report on limited patient numbers and retrospective data. Potential bias was minimized using quality appraisal. HRM findings correlate to upper GI symptoms when assessed by validated questionnaires and can detect response to therapy in buspirone trials. Esophageal body dysmotility on HRM positively correlates with the presence of interstitial lung disease. KEY POINTS: • Esophageal body dysmotility on HRM correlates with presence of ILD. • HRM findings seem to correspond to clinical symptom alleviation in interventional trials, but data are still limited. • At present HRM, a procedure with a high negative burden to the patient, offers little to no role in the therapeutic strategy.

Durometry as an alternative tool to the modified Rodnans skin score in the assessment of diffuse systemic sclerosis patients: a cross-sectional study

Abstract Background The reproducibility and reliability of the modified Rodnan's Skin Score (mRSS) are debated due to investigator-related subjectivity. Here, we evaluate if durometry correlates with mRSS in patients with diffuse systemic sclerosis (SSc). Methods This cross-sectional study was conducted from December 2018 to June 2019, including 58 diffuse SSc patients. Two certified researchers, blind to each other's scores, performed the mRSS, followed by durometry at 17 predefined skin sites. For durometry and mRSS, individual scores per skin site were registered. Durometry and mRSS results measured by each researcher, as well as scores from different researchers, were compared. Skin thickness measurements from forearm skin biopsies were available in a subset of the patients, for comparisons. Statistical analyses included Cohen's Kappa Coefficient, Intraclass Correlation Coefficient, Kendall's Coefficient and Spearman's test. Results Mean (standard deviation, SD) patient age was 44.8 (12.9) years, and 88% were female. Inter-rater agreement varied from 0.88 to 0.99 (Intraclass correlation coefficient) for durometry, and 0.54 to 0.79 (Cohen's Kappa coefficient) for mRSS, according to the specific evaluated sites. When data were compared with skin thickness assessed in forearm biopsies, durometry correlated better with skin thickness than mRSS. Conclusion Durometry may be considered as an alternative method to quantify skin involvement in patients with diffuse SSc. The strong inter-rater agreement suggests that the method may be useful for the assessment of patients by multiple researchers, as in clinical trials.(AU)

Sidestream Dark Field (SDF) imaging of oral microcirculation in the assessment of systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic disease characterised by abnormalities in small blood vessels, skin and organ fibrosis. It is assessed using generalised skin thickening scores, autoantibodies and nailfold capillaroscopy. Sidestream Dark Field imaging (SDF) is a non-invasive imaging tool that assesses microcirculation. This study aims to investigate the potential of using SDF as a diagnostic tool in SSc. METHOD: Oral microcirculation of 20 patients with SSc was compared to 20 age and gender matched controls using SDF imaging. Sublingual, buccal and incisor regions of the mouth were examined. All volunteers were female averaging 48.0 (24-64) years old. Vasculature was assessed by calculating the De Backer score and Functional Capillary Density (FCD) on an imaging software. RESULTS: At all regions of the mouth, SSc patients had a significantly lower De Backer score compared to controls (SSc 3.484 ±â€¯0.1361/mm vs Control 5.184 ±â€¯0.1896/mm, unpaired t-test p < 0.0001). The SSc patients showed significantly lower FCDs compared to controls at all areas as well (SSc 19.65 ±â€¯0.9445% vs Control 29.45 ±â€¯1.681%, unpaired t-test, p < 0.0001). The incisor regions had significantly higher De Backer and FCD scores than buccal and sublingual regions in both control and SSc patients (one way anova, p < 0.05). De Backer/FCD scores showed significant correlation against Rodnan Skin Scores in patients with SSc (Pearson correlation, p < 0.05). CONCLUSIONS: SSc patients showed decreased oral vasculature compared to controls. SDF imaging has shown the ability to be a useful diagnostic tool in the assessment of SSc.

Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary circulation in patients with systemic sclerosis.

PURPOSE: Pulmonary hypertension (PH) is an ominous complication in systemic sclerosis patients (SSc) and echocardiography is a screening tool for its detection. The goal of this study was to assess the reliability of resting and exercise echo Doppler parameters with data obtained by right heart catheterization (RHC). MATERIAL AND METHODS: We included 91 patients (84 F, 53.3 ± 15.2 years) with SSc. Transthoracic echocardiography followed by exercise Doppler-echocardiography (EDE) were performed. A positive EDE was defined as a ≥20 mmHg increase in tricuspid regurgitation peak gradient (TRPG). RHC with exercise was performed in positive EDE patients and/or in subjects with resting TRPG > 31 mmHg. RESULTS: Finally, RHC was performed in 20 patients. The correlation for the echocardiography and invasive measurement of systolic (sPAP) and mean (mPAP) pulmonary artery pressure was r = 0.66 (p = 0.001) and r = 0.7 (p = 0.001), respectively. We also found significant correlation between echocardiography and invasive measurement of exercise sPAP r = 0.68 (p = 0.001) and exercise mPAP r = 0.67 (p = 0.002). There was a correlation between pulmonary vascular resistance (PVR) assessed by echocardiography and measured by RHC r = 0.49, p = 0.027. The equation derived within our population was: PVR by echocardiography = 9.6*TRV/TVIRVOT+0.068. We also performed ROC analysis to predict PVR > 2 WU. Our results highlight that sPAP has the highest AUC (0.802, 95% CI 0.585-1). CONCLUSION: Doppler resting and exercise echocardiography may provide a reliable, noninvasive method for determining resting and exercise sPAP, mPAP, and PVR in SSc patients, although it may underestimate or overestimate these values in some individuals. Doppler echocardiography does not replace RHC for definite hemodynamic assessment of suspected PH.

Comparison of non-invasive assessment of arrhythmias, conduction disturbances and cardiac autonomic tone in systemic sclerosis and systemic lupus erythematosus.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are connective tissue diseases presenting cardiac complications including different arrhythmias, then direct electrocardiographic comparison may be useful in everyday clinical decision making. We examined 86 adult SSc patients, 76 with SLE and 45 healthy controls. Among other examinations all subjects underwent 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence evaluation. Patients with various co-existing conditions which might markedly influence arrhythmias and autonomic modulation were excluded from further analysis (SSc n = 12, SLE n = 6). Finally, 76 SSc and 70 SLE subjects were eligible for this study, mean age 51.9 ± 13.1 and 46.5 ± 12.7 years (p = 0.11), with median disease duration 6.0 and 8.5 years (p = 0.15), respectively. As compared to SLE, patients with SSc were characterised by more frequent incidence of various supraventricular and ventricular arrhythmias. As compared to SSc, patients with SLE presented prolonged corrected QT intervals and also significant correlations between corrected QT length and heart rate variability indices. Both SSc and SLE subjects presented impaired sympathetic cardiac autonomic modulation, while indices associated with parasympathetic activity in SLE were not diminished. Disease duration was not associated with arrhythmias' occurrence (except for ventricular tachycardia in SSc, p = 0.02) and also with autonomic function in both groups of patients. Patients with SSc and SLE differ in terms of arrhythmias, conduction disturbances and cardiac autonomic tone. Regular Holter monitoring should be considered as a part of routine evaluation in connective tissue diseases patients, especially in systemic sclerosis.

The role of inflammatory markers in assessment of disease activity in systemic sclerosis.

OBJECTIVES: The role of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in systemic sclerosis (SSc) remains controversial. We sought to evaluate the relationship between clinical features of SSc and raised inflammatory markers and to determine if changes in ESR and CRP reflect changes in other disease features over time. METHODS: One thousand, five hundred and forty-five patients enrolled in the Australian Scleroderma Cohort Study were observed over a mean 3.52±2.91 years and assessed at 6,119 study visits. Generalised estimating equations were used to determine the relationship between ESR≥20mm/hr and CRP≥5mg/L and features of disease. The associations between change in inflammatory markers and change in skin scores and respiratory function tests were analysed. RESULTS: Overall, there was a significant association between raised ESR and forced vital capacity (FVC)<80% predicted, diffusing capacity of the lung (DLCO)<80% predicted, pulmonary arterial hypertension (PAH), body mass index (BMI), proximal muscle strength, anaemia, and hypocomplementaemia (p<0.05). Raised CRP was significantly associated with modified Rodnan Skin Score>20, FVC<80%, DLCO<80%, PAH, digital ulcers, BMI, synovitis, tendon friction rub, anaemia, and hypocomplementaemia (p<0.05). A significant deterioration in respiratory function tests (RFTs) was associated with a 2-fold increase in both ESR and CRP (p<0.05). CONCLUSIONS: Raised inflammatory markers are associated with pulmonary, cutaneous and musculoskeletal manifestations of SSc. Rising inflammatory markers are correlated with declining respiratory function tests. This suggests inflammatory markers have a role in the assessment of SSc disease activity.

Association of low socioeconomic status and physician assessment of disease severity with oral health-related quality of life in patients with systemic sclerosis: a pilot study from Croatia, a country in transition.

OBJECTIVE: This study was performed to identify a possible association of the clinical parameters of systemic sclerosis (SSc) and the socioeconomic status (SES) with oral health-related quality of life (OHrQoL) as measured by the Oral Health Impact Profile 49 (OHIP 49), taking into account the effect of educational level (as a proxy of SES) on oral health. METHODS: Subjects were recruited from the Croatian SSc Center of Excellence cohort. Detailed dental and clinical examinations were performed according to standardized protocols. The associations of OHrQoL with disease characteristics and socioeconomic status were examined. RESULTS: Thirty-one consecutive patients with SSc were enrolled (29 women; mean age, 56.45 ± 13.60 years). OHIP 49 scores were significantly correlated with disease activity and severity. Furthermore, OHrQoL was positively correlated with skin involvement as evaluated by the modified Rodnan skin score. Impaired OHrQoL was positively correlated with the severity of general, skin, gastrointestinal, and joint/tendon involvement. The OHIP 49 score differed between patients who were positive and negative for anti-topoisomerase I antibody. Higher OHIP 49 scores were detected in patients with lower SES (primary school educational level). CONCLUSION: Collaboration between rheumatologists and dental professionals is required to improve dental care and oral health outcomes of SSc.

Determinants of health-related quality of life in a multinational systemic sclerosis inception cohort.

OBJECTIVES: To evaluate health-related quality of life (HRQoL) and its determinants in a systemic sclerosis (SSc) multinational inception cohort. We performed a meta-analysis of data from individual countries, and compared the meta-analysis to individual country results by pooling data from each of the countries. METHODS: SSc patients within 2 years of disease onset were recruited from 5 countries participating in the International Systemic Sclerosis Inception Cohort (INSYNC). Data from each country's database were exported for analysis using a harmonised platform. HRQoL was assessed using the Medical Outcomes Short Form-36 (SF-36). Multivariate linear regression assessed associations between HRQoL and predictors in cohorts separately and meta-analyzed to generate pooled estimates. The analyses were repeated using individual patient data. RESULTS: Of the 637 SSc patients recruited, the majority was female (80.2%-83.3%), aged between 52.4-56.7 years with limited cutaneous disease subtype (48.6%-66.7%). HRQoL scores were lower for SSc patients than the general population (SF-36 physical component summary (PCS) score (36.4-39.6), mental component summary (MCS) score (41.0-46.4)). Determinants of SF-36 PCS by meta-analysis included increasing age (ß=-0.1, 95%CI -0.2, -0.01), diffuse cutaneous disease subtype (ß=-8.4, 95%CI -10.6, -6.3), and pulmonary arterial hypertension (ß=-10.9, 95%CI -16.6, -5.3). Increasing age (ß=0.09, 95%CI 0.0, 0.18) was the only variable associated with SF-36 MCS. Analyses using individual patient data revealed similar results to those of the meta-analysis of cohort data. CONCLUSIONS: Our study provides estimates of HRQoL in a large inception SSc cohort and provides evidence that individual patient data analysis is valid in the INSYNC dataset.

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement.

NEW FINDINGS: What is the central question of this study? Do systemic sclerosis patients exhibit impaired nitric oxide-mediated vascular function of the lower limb and are these decrements correlated with plasma biomarkers for inflammation and oxidative stress? What is the main finding and its importance? Findings indicate impaired nitric oxide-mediated vascular function, linked to the incidence of digital ulcers and a milieu of inflammation and oxidative stress. However, the absence of significant correlations between individual biomarkers and blood flow responses suggests that the vasculopathy observed in systemic sclerosis may not be solely the result of derangements in the redox balance or inflammatory signalling. ABSTRACT: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, which may be the consequence of inflammation and oxidative stress that ultimately leads to a reduced nitric oxide (NO) bioavailability. Passive leg movement (PLM) is a novel methodology for assessing lower limb vascular function that is predominantly NO dependent. We combined this vascular assessment with a comprehensive panel of plasma biomarkers to assess the axis of inflammation, oxidative stress and NO in SSc patients (n = 12; 62 ± 11 years of age) compared with healthy control subjects (n = 17; 60 ± 16 years of age). The PLM-induced changes in leg blood flow (LBF; 191 ± 104 versus 327 ± 217 ml min-1 ) and LBF area under the curve (39 ± 104 versus 125 ± 131 ml) were reduced in SSc compared with control subjects. Stratification of patients according to history of digital ulcer (DU) formation revealed a further reduction in LBF area under the curve in DU (-13 ± 83 ml) versus non-DU (91 ± 102 ml) patients. Biomarkers of inflammation (C-reactive protein) and oxidative stress (malondialdehyde and protein carbonyl) were all elevated in SSc (C-reactive protein, 3299 ± 2372 versus 984 ± 565 ng ml-1 ; malondialdehyde, 3.2 ± 1.1 versus 1.1 ± 0.7 µm; and protein carbonyl, 0.15 ± 0.05 versus 0.12 ± 0.03 nmol mg-1 ), and C-reactive protein was further elevated in patients with a history of DU (4551 ± 2752 versus 2047 ± 1019 ng ml-1 ) compared with non-DU, although these were not individually correlated with changes in LBF. These findings of impaired NO-mediated vascular function, linked to DU and a milieu of inflammation and oxidative stress, suggest that redox balance plays an important, but not necessarily deterministic, role in the vascular pathophysiology of SSc.

Automated assessment of absolute nailfold capillary number on videocapillaroscopic images: Proof of principle and validation in systemic sclerosis.

BACKGROUND: Absolute nailfold capillary number should be a putative biomarker in selected rheumatic diseases but could be time-consuming and not highly repeatable. OBJECTIVE: To validate an automated software for absolute nailfold capillary number and density evaluation, on NVC images in SSc. METHODS: An automated software to count nailfold capillary number (AUTOCAPI) had been constructed, through an exploratory image set. Subsequently, application rules have been created to define the ROI in NVC images, through a training images set. The software reliability was assessed through calculation of the ICC between automatic and manual counting, by four independent observers, on the same NVC images. RESULTS: The following ICC's were obtained per observer, for the patients with SSc (40 images), the healthy (20 images), and the PRP subgroups (20 images), respectively: 0.94, 0.81, and 0.62 (observer 1); 0.94, 0.91, and 0.67 (observer 2); 0.88, 0.56, and 0.64 (observer 3); and 0.88, 0.85, and 0.85 (observer 4). CONCLUSIONS: The validation of an automated software for measuring absolute nailfold capillary number and density in SSc was achieved. The integration into the pre-existing imaging software should make the assessment of the capillary number in NVC easier, quicker, and standardized.

Chest CT texture analysis for response assessment in systemic sclerosis.

PURPOSE: To evaluate the role of CT-textural features for monitoring lung involvement in subjects with systemic sclerosis(SSc) undergoing autologous stem cell transplantation(SCT) by comparison with semi-quantitative chest-CT, pulmonary function tests(PFT) and clinical parameters (modified Rodnan skin score[mRSS]). METHODS: In a retrospective single centre analysis, we identified 23 consecutive subjects(11male) with SSc between 07/2005 and 11/2016 that underwent chest CTs before, 6 and 12 months post-SCT. Response to therapy was defined at 6 months after transplantation as stabilisation or improvement in FVC > 10% and DLCOSB > 10%. CT-texture analysis(CTTA) including mean, entropy and uniformity were calculated. RESULTS: PFT classified the subjects into responders(18/23;78%) and non-responders(5/23;22%). mRSS improved in responders from 28.46 ±â€¯9.53 to 15.70 ±â€¯10.07 6 months after auto-SCT(p = .001) whereas in non-responders no significant improvement was registered. Fibrosis score increased significantly(mean2.33 ±â€¯1.23 vs.1.41 ±â€¯0.78; p = .005) in non-responders after 6 and 12months. Significant lower mean intensity and entropy of skewness and higher uniformity of skewness was found in responders vs. non-responders at baseline. Significant changes in CTTA-parameters were found in both responders and non-responders at 6months and only in responders also at 12months post-SCT. CONCLUSIONS: Changes in CT-textural features after SCT are associated with visual CT evaluation of SSc-related lung abnormalities, but complementary provide information about therapy-induced, structural pulmonary changes.