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

Socio-economic analysis of development regions in Romania

Regional development is a priority objective of the EU. Reducing gaps and inequalities between European countries or regions requires coordinated efforts through a regional development policy. To make the implementation of regional political measures more efficient, the European territory was divided into regions according to certain territorial division criteria, NUTS. Considering this context, the paper aims to carry out a socio-economic analysis at the regional level, using the Tempo Online statistical database of the National Institute of Statistics (INS). For this purpose, indicators were used regarding the labor force, the level of living and economic statistics of the development regions in Romania

Optimization of Functional Toothpaste Formulation Containing Nano-Hydroxyapatite and Birch Extract for Daily Oral Care

This research work aims to develop functional toothpastes with combined enamel remineralization and antibacterial effects using nano-hydroxyapatites (nHAPs) and birch extract. Eleven toothpastes (notated as P1–P11) were designed featuring different concentrations of birch extract and a constant concentration of pure nHAPs or substituted nHAPs (HAP-5%Zn, HAP-0.23%Mg-3.9%Zn-2%Si-10%Sr, and HAP-2.5%Mg-2.9%Si-1.34%Zn). In vitro assessments involved treating artificially demineralized enamel slices and analyzing surface repair and remineralization using Atomic Force Microscopy (AFM). The Agar Disk Diffusion method was used to measure antibacterial activity against Enterococcus faecalis, Escherichia coli, Porphyromonas gingivalis, Streptococcus mutans, and Staphylococcus aureus. Topographic images of enamel structure and surface roughness, as well as the ability of nHAP nanoparticles to form self-assembled layers, revealed excellent restorative properties of the tested toothpastes, with enamel nanostructure normalization occurring as soon as 10 days after treatment. The outcomes highlighted enamel morphology improvements due to the toothpaste treatment also having various efficacious antibacterial effects. Promising results were obtained using P5 toothpaste, containing HAP-5%Zn (3.4%) and birch extract (1.3%), indicating notable remineralization and good antibacterial properties. This study represents a significant advancement in oral care by introducing toothpaste formulations that simultaneously promote enamel health through effective remineralization and bacterial inhibition

Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort

Objective: In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods: We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. Centres were asked for supplementary data on traditional cardiovascular risk factors. We analysed the cross-sectional relationship between gangrene and its potential risk factors by univariable and multivariable logistic regression. Longitudinal data were analysed by Cox proportional hazards regression. Results: 1757 patients were analysed (age 55.9 [14.5] years, disease duration 7.9 [10.3] years, male sex 16.7%, 24.6% diffuse cutaneous subset [dcSSc]). At inclusion, 8.9% of patients had current or previous digital gangrene, 16.1% had current digital ulcers (DUs) and 42.7% had ever had DUs (current or previous). Older age, DUs ever and dcSSc were statistically significant risk factors for gangrene in the cross-sectional multivariable model. During a median follow-up of 13.1 months, 16/771 (0.9%) patients developed gangrene. All 16 patients who developed gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the dcSSc subset and longer disease duration. Conclusion: In unselected SSc patients, gangrene occurs in about 9% of SSc patients. DUs ever and, to a lesser extent, the dcSSc subset are strongly and independently associated with gangrene, while traditional cardiovascular risk factors could not be identified as risk factors

A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: A EUSTAR prospective study

Objectives. In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. Method. We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results. 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p<0.001), a higher frequency of digital ulcers (OR: 1.28 (1.11 to 1.47); p<0.001) and pulmonary hypertension (OR: 3.01 (1.47 to 6.20); p<0.003). In the longitudinal analysis (n=4499), after a mean follow-up of 4.9 (±2.7) years, male sex was predictive of new onset of pulmonary hypertension (HR: 2.66 (1.32 to 5.36); p=0.006) and heart failure (HR: 2.22 (1.06 to 4.63); p=0.035). 908 deaths were recorded, male sex predicted deaths of all origins (HR: 1.48 (1.19 to 1.84); p<0.001), but did not significantly account for SSc-related deaths. Conclusions. Although more common in women, SSc appears as strikingly more severe in men. Our results obtained through the largest worldwide database demonstrate a higher risk of severe cardiovascular involvement in men. These results raise the point of including sex in the management and the decisionmaking process

Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: A EUSTAR analysis

none194Dobrota, Rucsandra; Maurer, Britta; Graf, Nicole; Jordan, Suzana; Mihai, Carina; Kowal-Bielecka, Otylia; Allanore, Yannick; Distler, Oliver; Cerinic, Marco Matucci; Guiducci, Serena; Walker, Ulrich; Lapadula, Giovanni; Iannone, Florenzo; Becvar, Radim; Sierakowsky, Stanislaw; Cutolo, Maurizio; Sulli, Alberto; Valentini, Gabriele; Cuomo, Giovanna; Vettori, Serena; Riemekasten, Gabriela; Siegert, Elise; Rednic, Simona; Nicoara, Ileana; Kahan, André; Vlachoyiannopoulos, P.; Montecucco, C.; Caporali, Roberto; Carreira, Patricia E.; Novak, Srdan; Czirják, László; Varju, Cecilia; Chizzolini, Carlo; Kucharz, Eugene J.; Kotulska, Anna; Kopec-Medrek, Magdalena; Widuchowska, Malgorzata; Cozzi, Franco; Rozman, Blaz; Mallia, Carmel; Coleiro, Bernard; Gabrielli, Armando; Farge, Dominique; Wu, Chen; Marjanovic, Zora; Faivre, Helene; Hij, Darin; Dhamadi, Roza; Airò, Paolo; Hesselstrand, Roger; Wollheim, Frank; Wuttge, Dirk M.; Andréasson, Kristofer; Martinovic, Duska; Balbir-Gurman, Alexandra; Braun-Moscovici, Yolanda; Trotta, F.; Monaco, Andrea Lo; Hunzelmann, Nicolas; Pellerito, Raffaele; Mauriziano, Ospedale; Bambara, Lisa Maria; Caramaschi, Paola; Black, Carol; Denton, Christopher; Damjanov, Nemanja; Henes, Jörg; Santamaria, Vera Ortiz; Heitmann, Stefan; Krasowska, Dorota; Seidel, Matthias; Burkhardt, Harald; Himsel, Andrea; Salvador, Maria J.; Da Silva, José Antonio Pereira; Stamenkovic, Bojana; Stankovic, Aleksandra; Tikly, Mohammed; Ananieva, Lidia P.; Denisov, Lev N.; Müller-Ladner, Ulf; Frerix, Marc; Tarner, Ingo; Scorza, Raffaella; Engelhart, Merete; Strauss, Gitte; Nielsen, Henrik; Damgaard, Kirsten; Mendoza, Antonio Zea; de la Puente, Carlos; Giraldo, Walter A. Sifuentes; Midtvedt, Øyvind; Reiseter, Silje; Hachulla, Eric; Launay, David; Valesini, Guido; Riccieri, Valeria; Ionescu, Ruxandra Maria; Opris, Daniela; Groseanu, Laura; Cornateanu, Roxana Sfrent; Ionitescu, Razvan; Gherghe, Ana Maria; Soare, Alina; Gorga, Marilena; Bojinca, Mihai; Schett, Georg; Distler, Jörg H.W.; Beyer, Christian; Meroni, Pierluigi; Ingegnoli, Francesca; Mouthon, Luc; Keyser, Filip De; Smith, Vanessa; Cantatore, Francesco P.; Corrado, Ada; Pozzi, Maria R.; Eyerich, Kilian; Hein, Rüdiger; Knott, Elisabeth; Wiland, Piotr; Szmyrka-Kaczmarek, Magdalena; Sokolik, Renata; Morgiel, Ewa; Madej, Marta; Krummel-Lorenz, Brigitte; Saar, Petra; Aringer, Martin; Günther, Claudia; Westhovens, Rene; de Langhe, Ellen; Lenaerts, Jan; Anic, Branimir; Baresic, Marko; Mayer, Miroslav; Radominski, Sebastião C.; de Souza Müller, Carolina; Azevedo, Valderílio F.; Agachi, Svetlana; Groppa, Liliana; Chiaburu, Lealea; Russu, Eugen; Popa, Sergei; Zenone, Thierry; Stebbings, Simon; Highton, John; Stamp, Lisa; Chapman, Peter; O'Donnell, John; Solanki, Kamal; Doube, Alan; Veale, Douglas; O'Rourke, Marie; Loyo, Esthela; Li, Mengtao; Rosato, Edoardo; Amoroso, Antonio; Gigante, Antonietta; Tanaseanu, Cristina-Mihaela; Popescu, Monica; Dumitrascu, Alina; Tiglea, Isabela; Foti, Rosario; Chirieac, Rodica; Ancuta, Codrina; Villiger, Peter; Adler, Sabine; de la Peña Lefebvre, Paloma García; Rubio, Silvia Rodriguez; Exposito, Marta Valero; Sibilia, Jean; Chatelus, Emmanuel; Gottenberg, Jacques Eric; Chifflot, Hélène; Litinsky, Ira; Venalis, Algirdas; Butrimiene, Irena; Venalis, Paulius; Rugiene, Rita; Karpec, Diana; Saketkoo, Lesley Ann; Lasky, Joseph A.; Kerzberg, Eduardo; Montoya, Fabiana; Cosentino, Vanesa; Limonta, Massimiliano; Brucato, Antonio Luca; Lupi, Elide; Spertini, François; Ribi, Camillo; Buss, Guillaume; Pasquali, Jean Louis; Martin, Thierry; Gorse, AudreyDobrota, Rucsandra; Maurer, Britta; Graf, Nicole; Jordan, Suzana; Mihai, Carina; Kowal Bielecka, Otylia; Allanore, Yannick; Distler, Oliver; Cerinic, Marco Matucci; Guiducci, Serena; Walker, Ulrich; Lapadula, Giovanni; Iannone, Florenzo; Becvar, Radim; Sierakowsky, Stanislaw; Cutolo, Maurizio; Sulli, Alberto; Valentini, Gabriele; Cuomo, Giovanna; Vettori, Serena; Riemekasten, Gabriela; Siegert, Elise; Rednic, Simona; Nicoara, Ileana; Kahan, André; Vlachoyiannopoulos, P.; Montecucco, Carlomaurizio; Caporali, Roberto; Carreira, Patricia E.; Novak, Srdan; Czirják, László; Varju, Cecilia; Chizzolini, Carlo; Kucharz, Eugene J.; Kotulska, Anna; Kopec Medrek, Magdalena; Widuchowska, Malgorzata; Cozzi, Franco; Rozman, Blaz; Mallia, Carmel; Coleiro, Bernard; Gabrielli, Armando; Farge, Dominique; Wu, Chen; Marjanovic, Zora; Faivre, Helene; Hij, Darin; Dhamadi, Roza; Airò, Paolo; Hesselstrand, Roger; Wollheim, Frank; Wuttge, Dirk M.; Andréasson, Kristofer; Martinovic, Duska; Balbir Gurman, Alexandra; Braun Moscovici, Yolanda; Trotta, F.; Monaco, Andrea Lo; Hunzelmann, Nicolas; Pellerito, Raffaele; Mauriziano, Ospedale; Bambara, Lisa Maria; Caramaschi, Paola; Black, Carol; Denton, Christopher; Damjanov, Nemanja; Henes, Jörg; Santamaria, Vera Ortiz; Heitmann, Stefan; Krasowska, Dorota; Seidel, Matthias; Burkhardt, Harald; Himsel, Andrea; Salvador, Maria J.; Da Silva, José Antonio Pereira; Stamenkovic, Bojana; Stankovic, Aleksandra; Tikly, Mohammed; Ananieva, Lidia P.; Denisov, Lev N.; Müller Ladner, Ulf; Frerix, Marc; Tarner, Ingo; Scorza, Raffaella; Engelhart, Merete; Strauss, Gitte; Nielsen, Henrik; Damgaard, Kirsten; Mendoza, Antonio Zea; de la Puente, Carlos; Giraldo, Walter A. Sifuentes; Midtvedt, Øyvind; Reiseter, Silje; Hachulla, Eric; Launay, David; Valesini, Guido; Riccieri, Valeria; Ionescu, Ruxandra Maria; Opris, Daniela; Groseanu, Laura; Cornateanu, Roxana Sfrent; Ionitescu, Razvan; Gherghe, Ana Maria; Soare, Alina; Gorga, Marilena; Bojinca, Mihai; Schett, Georg; Distler, Jörg H. W.; Beyer, Christian; Meroni, Pierluigi; Ingegnoli, Francesca; Mouthon, Luc; Keyser, Filip De; Smith, Vanessa; Cantatore, Francesco P.; Corrado, Ada; Pozzi, Maria R.; Eyerich, Kilian; Hein, Rüdiger; Knott, Elisabeth; Wiland, Piotr; Szmyrka Kaczmarek, Magdalena; Sokolik, Renata; Morgiel, Ewa; Madej, Marta; Krummel Lorenz, Brigitte; Saar, Petra; Aringer, Martin; Günther, Claudia; Westhovens, Rene; de Langhe, Ellen; Lenaerts, Jan; Anic, Branimir; Baresic, Marko; Mayer, Miroslav; Radominski, Sebastião C.; de Souza Müller, Carolina; Azevedo, Valderílio F.; Agachi, Svetlana; Groppa, Liliana; Chiaburu, Lealea; Russu, Eugen; Popa, Sergei; Zenone, Thierry; Stebbings, Simon; Highton, John; Stamp, Lisa; Chapman, Peter; O'Donnell, John; Solanki, Kamal; Doube, Alan; Veale, Douglas; O'Rourke, Marie; Loyo, Esthela; Li, Mengtao; Rosato, Edoardo; Amoroso, Antonio; Gigante, Antonietta; Tanaseanu, Cristina Mihaela; Popescu, Monica; Dumitrascu, Alina; Tiglea, Isabela; Foti, Rosario; Chirieac, Rodica; Ancuta, Codrina; Villiger, Peter; Adler, Sabine; de la Peña Lefebvre, Paloma García; Rubio, Silvia Rodriguez; Exposito, Marta Valero; Sibilia, Jean; Chatelus, Emmanuel; Gottenberg, Jacques Eric; Chifflot, Hélène; Litinsky, Ira; Venalis, Algirdas; Butrimiene, Irena; Venalis, Paulius; Rugiene, Rita; Karpec, Diana; Saketkoo, Lesley Ann; Lasky, Joseph A.; Kerzberg, Eduardo; Montoya, Fabiana; Cosentino, Vanesa; Limonta, Massimiliano; Brucato, Antonio Luca; Lupi, Elide; Spertini, François; Ribi, Camillo; Buss, Guillaume; Pasquali, Jean Louis; Martin, Thierry; Gorse, Audre

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study.

Objective To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. Methods We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. Results 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)&gt;10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p&lt;0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). Conclusion Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial