Long-term Memory of Sensory Experiences from the First Pregnancy, its Peri-partum and Post-partum in Women with Autism Spectrum Disorders without Intellectual Disabilities: A Retrospective Study

Purpose: To explore the recalled experience of pregnancy and motherhood in women diagnosed with Autism Spectrum Disorders (ASD) without intellectual disabilities, focusing on sensory perceptions and mood. Methods: We retrospectively evaluated, through an ad-hoc structured interview, the sensory sensitivity during the pre-partum, the peri-partum, and the post-partum of thirty-three mothers with ASD and thirty-two neurotypical mothers. Participants also underwent a psychometric assessment about autistic traits, general sensory sensitivity, and post-partum depressive symptomatology. Results: Mothers with ASD recalled a higher sensitivity than the comparison group across the three time-points; however, during the peri-partum their recalled hypersensitivity decreases, and in the post-partum it returned as high as before childbirth. The difference in the length of recall between groups did not statistically influence our results. Higher levels of autistic traits correlated with higher depressive post-partum symptomatology. Conclusions: Mothers with ASD seem to recall their experience of pregnancy, childbirth, and post-partum period differently from neurotypical mothers, particularly in terms of hypersensitivity. The correlation with depressive symptoms and the potential role of oxytocin and of long-term memory (encoding and recollection) are discussed. Further exploring these aspects might give fundamental hints to provide tailored support to mothers with ASD during pregnancy and motherhood

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

Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database

Objectives: To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. Methods: 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan–Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. Results: The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. Conclusion: Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening

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

Phenotypes determined by cluster analysis and their survival in the prospective european scleroderma trials and research cohort of patients with systemic sclerosis

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

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±3 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 trials.status: publishe

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.status: publishe

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= 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