Whole phenotype of patients with systemic sclerosis and sicca manifestations: Comparison with sicca manifestations from other causes.

INTRODUCTION & OBJECTIVES: This study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes. METHODS: Sixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc). RESULTS: SSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure. CONCLUSION: SjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets.

Phenotypic and proteomic analysis of plasma extracellular vesicles highlights them as potential biomarkers of primary Sjögren syndrome.

Sjögren syndrome (SjS) is an autoimmune disease characterized by the destruction of the exocrine gland epithelia, causing a dryness of mucosa called sicca symptoms, and whose main life-threatening complication is lymphoma. There is a need for new biomarkers in this disease, notably diagnostic biomarkers for patients with genuine sicca symptoms that do not meet current criteria, and prognostic biomarkers for patients at risk of lymphoma. Plasma extracellular vesicles (EVs) are promising biomarker candidates in several diseases, but their potential has not yet been explored in SjS. In this proof-of-concept study, we characterized EVs from primary SjS patients (pSS, n=12) at the phenotypic and proteomic levels, compared to EVs from healthy donor (HD, n=8) and systemic lupus erythematosus patients (SLE, n=12). Specific plasma EVs subpopulations, derived from neutrophils, endothelial, and epithelial cells, were found increased in pSS. We also identified a pSS proteomic signature in plasma EVs, including neutrophil-, epithelial-, and endothelial-related proteins, such as integrin alpha M (ITGAM), olfactomedin-4 (OLFM4), Ras-related protein RAB10, and CD36. Overall, our results support the relevance of plasma EVs as biomarkers in SjS.

Should we really include systemic sclerosis specific antibodies in the classification criteria of Sjogren's disease?

We have read with great interest the results from Marketos et al. regarding the positivity of specific systemic sclerosis auto-antibodies in patients with sicca symptoms. Based on complementary data from the literature, we rather believe scleroderma-associated antibodies should be considered either as a yellow flag for an association between scleroderma and Sjogren, or a potential undiagnosed scleroderma, rather than an isolated Sjogren's disease.

Sicca syndrome in systemic sclerosis: a narrative review on a neglected issue.

SSc is an auto-immune disease characterized by life-threatening manifestations such as lung fibrosis or pulmonary arterial hypertension. Symptoms with a detrimental impact on quality of life are also reported and sicca syndrome (xerostomia, xeropthalmia) is present in up to 80% of patients with SSc. Sicca syndrome can occur in the absence of overlap with Sjögren's disease and recent studies highlight that fibrosis of minor and major salivary glands, directly linked to the pathogenesis of SSc, could be a major contributor of xerostomia in SSc. This narrative review provides an overview of the clinical presentation, diagnostic strategies, management and future perspectives on sicca syndrome in patients with SSc.

Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: an international collaborative scoping review.

OBJECTIVES: The aim of this study was to comprehensively identify instruments within relevant domains employed to assess lcSSc since the endorsement of its consensus definition in 1988. The overall objective is to inform the creation of a Combined Response Index for Scleroderma Trials Assessing lcSSc (CRISTAL). METHODS: MEDLINE and Embase were searched using terms selected to comprehensively retrieve titles and abstracts mentioning both lcSSc and dcSSc, along with those only mentioning lcSSc, SSc sine scleroderma, limited SSc and/or CREST/CRST. Because our initial assessment of the literature revealed that very few studies included only lcSSc subjects, we also assessed literature that included both cutaneous subsets. A total of 3964 titles and abstracts were screened by two reviewers, and 270 articles were selected for data extraction. RESULTS: We identified 27 domains encompassing 459 instruments. Instruments from 'Skin involvement', 'Pulmonary involvement' and 'Health-related quality of life and general functioning' were the most frequently retrieved. Among the 15 most represented instruments announced as primary end points in efficacy or effectiveness studies, 7 were clinician-reported outcomes (ROs), 7 were patient ROs, and one was a performance outcome (6 min-walk test). The mean proportion of lcSSc patients in studies of lcSSc, including studies that mention both lcSSc and dcSSc, was 56.4%, demonstrating that this subset is underrepresented in the literature, given that the prevalence of lcSSc ranges from 60% to 80% in national registries and international cohorts. CONCLUSION: This scoping literature review provides a comprehensive identification of domains and outcomes used to assess lcSSc. Our results also highlight that lcSSc is underrepresented in the literature.

Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes.

Systemic sclerosis (SSc; systemic scleroderma) is characterized by a heterogeneous range of clinical manifestations. SSc is classified into limited cutaneous SSc (lcSSc) and diffuse cutaneous subgroups (dcSSc) based on the extent of skin involvement. Randomized controlled trials in scleroderma have mainly focused on dcSSc partly because the measurement of skin involvement, critical for evaluating a therapeutic intervention is more dynamic in this subset. Nonetheless, lcSSc, the most common cutaneous subset (about 2/3), is also associated with significant morbidity and detrimental impact on health-related quality of life. The lack of interventional studies in lcSSc is partly due to a lack of relevant outcome measures to evaluate this subgroup. Combining several clinically meaningful outcomes selected specifically for lcSSc may improve representativeness in clinical trials and responsiveness of outcomes measured in randomized controlled trials. A composite index dedicated to lcSSc combining such relevant outcomes could advance clinical trial development for lcSSc by providing the opportunity to test and select among candidate drugs that could act as disease-modifying treatments for this neglected subgroup of SSc. This proposed index would include items selected by expert physicians and patients with lcSSc across domains grounded in the lived experience of lcSSc. This article reviews the reasons behind the relative neglect of lcSSc, discusses the current state of outcome measures for lcSSc, identifies challenges, and proposes a roadmap for a combined lcSSc-specific treatment response index.

Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: a scoping review protocol.

INTRODUCTION: Limited cutaneous systemic sclerosis (lcSSc) is the most frequent subset of systemic sclerosis. Despite this, lcSSc is not the major focus of clinical studies. The lack of interventional studies in lcSSc is due, in part, to a paucity of relevant outcome measures to effectively evaluate this subset. A combined response index dedicated to lcSSc would facilitate development of well-designed trials and approval of new drugs. The objective of this scoping review is to perform a broad and comprehensive identification of the outcome measures (core set items) within relevant domains, which have been used so far to assess lcSSc. METHODS AND ANALYSIS: The planned scoping review will be based on the approach proposed by Arksey et al and further developed by Levac et al. Development and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews checklist and guidelines. The development of the search strategy was guided by the concepts of domains and outcomes based on the Outcome Measures in Rheumatology approach and by the different names and definitions of SSc, with a specific emphasis on their occurrence in clinical trial studies. Two databases will be searched: MEDLINE and Embase. Studies in English, published from the year 1988 onwards, will be included, since 1988 corresponds to the publication of LeRoy's first consensus definition of lcSSc. Data will be extracted and analysed using a standardised charting tool. ETHICS AND DISSEMINATION: No ethical approval is required for this study. The results will be submitted to an international peer-reviewed journal and scientific conferences, informing the discussion on which items should be included in a combined response index dedicated to lcSSc (the CRISTAL project: Combined Response Index for Scleroderma Trial Assessing lcSSc).

Improving the work environment in the fluorescent lamp recycling sector by optimizing mercury elimination.

One of the main issues in the fluorescent lamp recycling sector is the mercury contamination of output fractions and occupational exposure associated with recycling operations. The aim of this study is to carry out effective mercury mass balance determinations and improve mercury recovery by finding the optimal levels for the recycling process parameters. These optimizations will allow upstream mercury emissions to be reduced, which will help to avoid mercury exposure among WEEE recycling workers. Firstly, the distribution of mercury was assessed in new and spent lamps. For new fluorescent tubes, the mean percentage of mercury in the solid phase is lower in new fluorescent tubes (19.5% with 5.5% in glass, 9.7% in end caps and 4.3% in luminescent powder) than in spent tubes (33.3% with 8.3% in glass, 12.9% in end caps and 12.1% in luminescent powder). The parametric study also shows that the finer the grains of glass, the higher the concentration of mercury (1.2 µg Hg/g for glass size particle >1000 µm and 152.0 µg Hg/g for glass size particle <100 µm); the crushing time required for the optimal removal of mercury from spent tubes is 24 h; on average 71% of the mercury is desorbed at a temperature of 400 °C. The effects of air flow rate, rotation speed and number of balls could not be determined due to wide variations in the results. It is recommended that recycling companies employ processes combining as heating and mixing techniques for the recovery of mercury from lamps in order to both (i) remove as much of the mercury as possible in vapor form and (ii) avoid adsorption of the mercury at new sites created during the crushing process.

Exposure to hazardous substances in Cathode Ray Tube (CRT) recycling sites in France.

The Waste Electrical and Electronic Equipment (WEEE) or e-waste recycling sector has grown considerably in the last fifteen years due to the ever shorter life cycles of consumables and an increasingly restrictive policy context. Cathode Ray Tubes (CRTs) from used television and computer screens represent one of the main sources of e-waste. CRTs contain toxic materials such as lead, cadmium, barium, and fluorescent powders which can be released if recycling of CRTs is not appropriate. Exposure to these harmful substances was assessed in nine workshops where CRT screens are treated. Particulate exposure levels were measured using a gravimetric method and metals were analysed by plasma emission spectrometry. The maximum levels of worker exposure were 8.8mg/m(3), 1504.3µg/m(3), 434.9µg/m(3), 576.3µg/m(3) and 2894.3µg/m(3) respectively for inhalable dust, barium, cadmium, lead and yttrium. The maximum levels of airborne pollutants in static samples were 39.0mg/m(3), 848.2µg/m(3), 698.4µg/m(3), 549.3µg/m(3) and 3437.9µg/m(3) for inhalable dust, barium, cadmium, lead and yttrium. The most harmful operations were identified, and preventive measures for reducing the chemical risk associated with screen recycling were proposed. Workplace measurements were used to define recommendations for reducing the chemical risks in CRT screens recycling facilities and for promoting the design and development of "clean and safe" processes in emerging recycling channels.

Occupational exposure in the fluorescent lamp recycling sector in France.

The fluorescent lamp recycling sector is growing considerably in Europe due to increasingly strict regulations aimed at inciting the consumption of low energy light bulbs and their end-of-life management. Chemical risks were assessed in fluorescent lamp recycling facilities by field measurement surveys in France, highlighting that occupational exposure and pollutant levels in the working environment were correlated with the main recycling steps and processes. The mean levels of worker exposure are 4.4 mg/m(3), 15.4 µg/m(3), 14.0 µg/m(3), 247.6 µg/m(3), respectively, for total inhalable dust, mercury, lead and yttrium. The mean levels of airborne pollutants are 3.1mg/m(3), 9.0 µg/m(3), 9.0 µg/m(3), 219.2 µg/m(3), respectively, for total inhalable dust, mercury, lead and yttrium. The ranges are very wide. Surface samples from employees' skin and granulometric analysis were also carried out. The overview shows that all the stages and processes involved in lamp recycling are concerned by the risk of hazardous substances penetrating into the bodies of employees, although exposure of the latter varies depending on the processes and tasks they perform. The conclusion of this study strongly recommends the development of a new generation of processes in parallel with more information sharing and regulatory measures.

The ultrasound-assisted oxidative scission of monoenic fatty acids by ruthenium tetroxide catalysis: influence of the mixture of solvents.

Carboxylic acids and diacids were synthesized from monoenic fatty acids by using RuO4 catalysis, under ultrasonic irradiation, in various mixtures of solvents. Ultrasound associated with Aliquat 336 have promoted in water, the quantitative oxidative cleavage of the CH=CH bond of oleic acid. A design of experiment (DOE) shows that the optimal mixture of solvents (H2O/MeCN, ratio 1/1, 2.2% RuCl3/4.1 eq. NaIO4) gives 81% azelaic acid and 97% pelargonic acid. With the binary heterogeneous mixture H2O/AcOEt, the oxidation of the oleic acid leads to a third product, the alpha-dione 9,10-dioxostearic acid.