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Abstract Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag‐treated PAH‐CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH‐CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety‐eight selexipag‐treated patients had follow‐up information; 178 (26%) had PAH‐CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate‐low, 40% intermediate‐high, and 30% high risk of 1‐year mortality, according to the ESC/ERS 4‐strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post‐baseline. Over a median (Q1−Q3) selexipag exposure period of 8.6 (2.5−17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH‐related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH‐CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH‐CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.

Abstract Background The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. Methods/design In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a “total neoadjuvant” therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. Trial registration NCT04090463 at clinicaltrials.gov.

While previous research on inhibition in people with Down syndrome (DS) reported contradictory results, with no explicit theoretical model, on the other hand, a more homogeneous impaired profile on the delay of gratification skills emerged. The main goal of the present study was to investigate response inhibition, interference suppression, and delay of gratification in 51 individuals with DS matched for a measure of mental age (MA) with 71 typically developing (TD) children. Moreover, we cross-sectionally explored the strengths and weaknesses of these components in children and adolescents vs. adults with DS with the same MA. A battery of laboratory tasks tapping on inhibitory sub-components and delay of gratification was administrated. Results indicated that individuals with DS showed an overall worse performance compared to TD children on response inhibition and delay of gratification, while no differences emerged between the two samples on the interference suppression. Additionally, our results suggested that older individuals with DS outperformed the younger ones both in response inhibition and in the delay of gratification, whereas the interference suppression still remains impaired in adulthood. This study highlights the importance of evaluating inhibitory sub-components considering both MA and chronological age in order to promote more effective and evidence-based training for this population.

The present study aims to investigate inhibition in individuals with Down Syndrome compared to typically developing children with different inhibitory tasks tapping response inhibition and interference suppression. Previous studies that aimed to investigate inhibition in individuals with Down Syndrome reported contradictory results that are difficult to compare given the different types of inhibitory tasks used and the lack of reference to a theoretical model of inhibition that was tested in children (see Bunge et al., 2002; Gandolfi et al., 2014). Three groups took part in the study: 32 individuals with Down Syndrome (DS) with a mean age of 14 years and 4 months, 35 typically developing children 5 years of age (5TD), and 30 typically developing children 6 years of age (6TD). No difference emerged among the groups in fluid intelligence. Based on a confirmatory factor analysis, two different inhibition factors were identified (response inhibition and interference suppression), and two composite scores were calculated. An ANOVA was then executed with the composite inhibitory scores as dependent variables and group membership as the between-subject variable to explore the group differences in inhibition components. The 6TD group outperformed the 5TD group in both response inhibition and interference suppression component scores. No differences were found in both inhibition components between the DS group and 5TD. In contrast, the 6TD group outperformed the DS group in both response inhibition and in the interference suppression component's scores. Summarizing, our findings show that both response inhibition and interference suppression significantly increased during school transition and that individuals with DS showed a delay in both response inhibition and interference suppression components compared to typically developing 6-year-olds, but their performance was similar to typically developing 5-year-olds.