No abstract

BACKGROUND: A long-term trial showed that the oral prostacyclin (PGl 2) receptor (IP) agonist, selexipag, delayed disease progression in patients with pulmonary arterial hypertension (PAH). Transition to selexipag in patients treated with more burdensome inhaled therapies that target the prostacyclin pathway may be considered by patients and physicians. The Phase 3b, prospective, open-label TRANSIT-1 (Tolerability and Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Patients With Pulmonary Arterial Hypertension) study evaluated the safety and tolerability of transition from inhaled treprostinil to oral selexipag. METHODS: Patients receiving non-prostanoid oral PAH therapy and inhaled treprostinil at stable doses, in World Health Organization Functional Class II/III, with 6-minute walk distance ≥ 300 meters were enrolled. The 16-week main treatment period included downtitration of inhaled treprostinil over 8 weeks and parallel uptitration of selexipag over 12 weeks. Sustained treatment transition at Week 16 was defined as (1) receiving selexipag at Week 16; (2) no selexipag interruption(s) totaling ≥ 8 days; and (3) no inhaled treprostinil or other prostanoids after Week 8. Clinical parameters and patientreported treatment satisfaction outcomes were assessed at Week 16.

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status (SES) and/or POPH diagnosis were associated with treatment and healthcare utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n=344) and POPH (n=57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6 versus 34.9%, p=0.02) and more likely to be unemployed (54.7 versus 30.5%, p<0.001) and have an annual household income below poverty level (45.7 versus 19.0%, p<0.001). Patients with POPH had similar functional class, quality of life, 6MWD and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4 versus 62.2%, p=0.03) and endothelin receptor antagonists (ERAs) (28.6 versus 55.1%, p<0.001) at enrollment with similar treatment at follow-up. Patients with POPH had more emergency department (ED) visits (1.7±2.1 versus 0.9±1.2, p=0.009) and hospitalizations in the 6 months preceding enrollment (1.5±2.1 versus 0.8±1.1, p=0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of ED visits. Compared to IPAH, patients with POPH have lower SES, are less likely to receive initial combination therapy and ERAs but have similar treatment at follow-up and have increased healthcare utilization.

Secretory conglutinin-like factor (SKF) reacts directly with an unknown surface component of some, but not all, oral gram-positive organisms. The absorption of SKF by bacteria is EDTA-sensitive and cannot be blocked with immunoglobulins. High levels of SKF in EDTA extracts of washed salivary sediment reveal the direct in vivo reaction of SKF with oral bacteria. Mixed aggregation with alexinated erythrocytes showed the SKF corresponds to the secretory bacterial aggregating factor (SBAF) for Streptococcus mutans serotype c and also that for Streptococcus mitis. These reactions represent a cross-reaction between bacteria and complement component C3. SKF/SBAF non-mucin glycoproteins and immunoglobulins possess receptors for bacterial components while mucins are passive carriers of blood group determinants.