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Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressures that can lead to right heart failure and death. No cure exists for this disease, but therapeutic advancements have extended its median survival from 2 to 7 years. Mechanistic research in PAH has been limited by factors including that a) animal models do not fully recapitulate the disease or provide insights into its pathogenesis, and b) cellular material from PAH patients is primarily obtained from donor lungs during autopsy or transplantation, which reflect end-stage disease. Therefore, there is a need to identify tools that can elucidate the specific mechanisms of human disease in individual patients, a critical step to guide treatment decisions based on specific pathway abnormalities. Here we demonstrate a simple method to isolate and culture circulating endothelial cells (CECs) obtained at the time of right heart catheterization in PAH patients. We tested these CECs using transcriptomics and found that they have typical traits of PAH, including those involving key treatment pathways, i.e. nitric oxide, endothelin, prostacyclin and BMP/activin pathways. CECs show important gene expression changes in other central PAH disease pathways. In summary, we present a new cellular model for the ex-vivo mechanistic evaluation of critical PAH pathways that participate in the pathogenesis of the disease and may help personalized therapeutic decisions. [ABSTRACT FROM AUTHOR]

Background: It remains unknown whether the cutaneous microvascular responses are different between patients with scleroderma‐associated pulmonary arterial hypertension (SSc‐PAH) and SSc without pulmonary hypertension (PH). Methods: We included 59 patients with SSc between March 2013 and September 2019. We divided patients into 4 groups: (a) no PH by right heart catheterization (RHC) (n = 8), (b) no PH by noninvasive screening tests (n = 16), (c) treatment naïve PAH (n = 16), and (d) PAH under treatment (n = 19). Microvascular studies using laser Doppler flowmetry (LDF) were done immediately after RHC or at the time of an outpatient clinic visit (group b). Results: The median (IQR) age was 59 (54–68) years, and 90% were females. The responses to local thermal stimulation and postocclusive reactive hyperemia, acetylcholine, and sodium nitroprusside iontophoresis were similar among groups. The microvascular response to treprostinil was more pronounced in SSc patients without PH by screening tests (% change: 340 (214–781)) compared with SSc‐PAH (naïve + treatment) (Perfusion Units (PU) % change: 153 (94–255) % [p =.01]). The response to A‐350619 (a soluble guanylate cyclase (sGC) activator) was significantly higher in patients with SSc without PH by screening tests (PU % change: 168 (46–1,296)) than those with SSc‐PAH (PU % change: 22 (15–57) % [p =.006]). The % change in PU with A350619 was directly associated with cardiac index and stroke volume index (R: 0.36, p =.03 and 0.39, p =.02, respectively). Conclusions: Patients with SSc‐PAH have a lower cutaneous microvascular response to a prostacyclin analog treprostinil and the sGC activator A‐350619 when compared with patients with SSc and no evidence of PH on screening tests, presumably due to a peripheral reduction in prostacyclin receptor expression and nitric oxide bioavailability. [ABSTRACT FROM AUTHOR]

Objective: To assess volatile organic compounds (VOCs) in breath samples collected non-invasively from preterm and full-term infants., Methods: This was a pilot study included preterm and full-term infants who were not intubated or suspected or diagnosed with metabolic or gastrointestinal disorders. The samples were analyzed for VOCs using a selected-ion flow-tube mass spectrometer., Results: Twenty infants were included; ten preterm and ten full-term infants. Twenty-two VOCs were detected and measurable in all samples. There was a significant difference between preterm and full-term infants for the 2-propanol, acetaldehyde, acetone, acetonitrile, benzene, ethanol, isoprene, pentane, 3-methylhexane, 2-nonene, ethane, triethylamine, and trimethylamine compounds., Conclusion: It is feasible to measure VOCs in breath samples of preterm and full-term non-intubated infants. Full-term infants express different concentrations than preterm infants. Further studies are needed to examine the utility and reproducibility of measuring VOCs to identify neonatal diseases and predict outcomes., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)