Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon: a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database

Objective. To assess patients with SSc who present without circulating ANAs or RP. Methods. Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire. Results. Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure. Conclusion. We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patient

Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12\ub13 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trial

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. / Methods: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. / Results: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. / Conclusion: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis

Martensitic Transformation in CuAlMn and CuAlNi Melt Spun Ribbons

The martensitic transformation was studied in CuAlMn and CuAlNi alloys transforming at elevated temperatures i.e. 70 - 250 °C. All alloys possessed mixed 18R and 2H structure of martensite. Splat quenching caused a direct formation of martensite and a considerable decrease of the grain size from about 100 µm in the bulk (in spite of TiB additions) down to about 2 µm. The martensite was less prone to stabilization as in bulk water quenched alloys. The DO3 domains size was not altered in ribbons due to insufficient cooling in the solid state after casting. Their size was considerably lowered in ribbons cooled directly in water after casting. Martensitic transformation temperatures were shifted to lower temperatures by 20 - 50 °C, but the transformation hysteresis was 10 - 20 °C broader in all alloys investigated. Transmission electron microscope (TEM) in-situ heating/cooling experiments allowed one to follow the nucleation of martensite in splat quenched ribbons due to their fine grain size. It appeared that martensite needles nucleated at the grain boundaries. Growing needles, approaching grain boundaries induce formation of other plates at adjacent grains

An X-ray photoelectron spectroscopic study of the B-N-Ti system

Composite nitrides (such as BN, TiN) are widely used in various industrial applications because of their extreme wear and corrosion resistance, thermal and electrical properties. In order to obtain composite materials with these optimal properties, it is important to elucidate whether any chemical reactions occur at nitride/metal interfaces, e.g., those involving BN-Ti/TiN. Materials of interest include the deposition by PVD of Ti and TiN on BN substrates. Some of these systems were then subjected to varying degrees of physical and thermal alteration. Detailed X-ray photoelectron spectroscopy (XPS) has therefore been rendered of these interfaces using cross-sectional display and sputter etching. Resulting structural and morphological features have been investigated with transmission electron microscopy (TEM) and X-ray diffraction (XRD). Diffusion of the nitridation, oxynitride formation and interfacial growth are of general interest

Znaczenie topografii powierzchni dla biologicznych właściwości warstw azotowanych dyfuzyjnie wytwarzanych na stopie tytanu Ti6Al4V

Diffusion nitrided layers produced on titanium and its alloys are widely studied in terms of their application for cardiac and bone implants. The influence of the structure, the phase composition, topography and surface morphology on their biological properties is being investigated. The article presents the results of a study of the topography (nanotopography) of the surface of TiN+Ti2N+αTi(N) nitrided layers produced in low-temperature plasma on Ti6Al4V titanium alloy and their influence on the adhesion of blood platelets and their aggregates. The TEM microstructure of the produced layers have been examined and it was demonstrated that the interaction between platelets and the surface of the titanium implants subjected to glow-discharge nitriding can be shaped via modification of the roughness parameters of the external layer of the TiN titanium nitride nanocrystalline zone.Dyfuzyjne warstwy azotowane na tytanie i jego stopach są szeroko badane m. in. w aspekcie zastosowań na implanty kardiologiczne i kostne. Stąd też analizowany jest wpływ struktury składu fazowego, topografii i morfologii powierzchni na ich właściwości biologiczne. W artykule przedstawiono wyniki badań wpływu topografii (nanotopografii) powierzchni warstw azotowanych –TiN+Ti2N+αTi(N) wytwarzanych w niskotemperaturowej plazmie na stopie tytanu Ti6Al4V na adhezję płytek krwi i ich aglomeratów. Omówiono mikrostrukturę (TEM) wytwarzanych warstw i wykazano, że poprzez stan chropowatości powierzchni zewnętrznej strefy warstwy azotowanej – nanokrystalicznego azotku tytanu (TiN) można kształtować oddziaływanie płytek krwi z powierzchnią implantów tytanowych poddanych procesowi azotowania jarzeniowego

Properties of electrodeposited Ni-Mo coatings

W artykule przedstawiono badania powłok Ni-Mo osadzanych metodą elektrochemiczną. Analizowano właściwości mechaniczne i tribologiczne powłok Ni-Mo wytwarzanych przy gęstościach prądu osadzania z zakresu 0,5–5 A/dm2. Badane powłoki charakteryzują się twardością od 6,4 do 7,8 GPa oraz modułem sprężystości Younga 180–260 GPa. W zależności od stosowanych parametrów prądowych podczas osadzania uzyskane powłoki znacząco różniły się charakterem deformacji występujących na skutek odkształceń sprężysto-plastycznych lub kruchego pękania oraz odpornością na zużycie. Duże różnice we właściwościach powłok tłumaczono ich różną mikrostrukturą, którą wyznaczono z użyciem mikroskopii SEM i TEM.Mechanical and tribological properties of electrodeposited Ni-Mo coating were studied. Coatings of 30 žm thickness were deposited under different cathodic current densities 0.5-5 A/dm2 on steel disc substrates. Microhardness and Young's modulus of electrodeposits were measured by Vickers instrumented microindentation method. Tested coatings have a hardness from 6.4 to 7.8 GPa and Young's modulus of 180-260 GPa. Coatings show significantly different characters of deformation from elastic-plastic to brittle fracture that were found from spherical indentation test results. Wear tests done on ball-on-disc tribometer indicate that coatings produced at a current density higher than 3 A/dm2 have a higher wear resistance of several times, which corresponds to the decrease of the coefficient of friction from 0.8 to 0.25. Large differences in hardness and wear resistance of Ni-Mo coatings were explained by significant differences in Mo content and the surface roughness of coatings obtained at different current densities. Microstructure and stresses of electrodeposits were performed using SEM and X-ray diffraction techniques. Properties of Ni-Mo coatings were compared with the hard chromium coating that is used in industry - WSK-PZL Rzeszow