Portopulmonary hypertension (POPH) is a type of pulmonary arterial hypertension occurring exclusively in those with portal hypertensive liver disease. Liver transplantation (LT) can significantly improve outcomes. Current guidelines counsel against immediate adjustments to targeted therapy after LT and suggest routine echocardiography as sufficiently informative to guide therapeutic adjustments. Current practice patterns for adjusting targeted therapy after LT in POPH, and how they compare with guidelines, are not well established. To answer this question, we performed an institutional review board–approved, cross‐sectional mixed‐methods survey‐based study of US POPH providers. Anonymized requests to complete the survey were sent through professional networks between January 20, 2022, and April 20, 2022. Responses were compared between cardiologists and pulmonologists using Fisher's exact tests, at a significance of 0.05. A total of 85 POPH physicians were included in the final analysis (66% pulmonologists and 34% cardiologists). Following LT, the majority of respondents routinely used a combination of standard cardiopulmonary assessment modalities to guide adjustment of targeted therapy following LT. Most respondents (69%) started by adjusting parenteral prostacyclins with small titrations and frequent reassessments within 3 months of LT, but some (19.7%) adjusted targeted therapy immediately after LT. Our results showed that the majority of respondents favored serial integrated cardiopulmonary testing (including routine right heart catheterization) to guide the adjustment of targeted therapy in POPH after LT, and almost one‐fifth of respondents weaned therapy immediately after LT. Our study demonstrates heterogeneity in POPH practice patterns after LT, highlights differences between current practice patterns and the most recent guidelines, emphasizes the need for additional research, and supports a team‐based approach to standardize care for these high‐risk patients and optimize post‐LT outcomes.
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women, causing cystic remodelling of the lung and progressive respiratory failure. The cellular composition, microenvironment and cellular interactions within the LAM lesion remain unclear. To facilitate data sharing and collaborative LAM research, we performed an integrative analysis of single-cell data compiled from lung, uterus and kidney of patients with LAM from three research centres and developed an LAM Cell Atlas (LCA) Web-Portal. The LCA offers a variety of interactive options for investigators to search, visualise and reanalyse comprehensive single-cell multiomics data sets to reveal dysregulated genetic programmes at transcriptomic, epigenomic and cell–cell connectome levels.
Abstract Cyanides are among the most acutely toxic of all industrial chemicals and are produced in large quantities and used in many different applications. However, they cause few serious accidents or deaths. This is partly because the word cyanide is synonymous with a highly poisonous substance and a certain amount of care in handling is thereby ensured. The cyanides and nitriles are a disparate group of substances characterized by the presence of a cyanide (CN) group in their molecular structure. The cyanide group consists of a carbon bonded to a nitrogen. In those cases where the cyanide group is readily available, toxicity is likely to have similarity to hydrogen cyanide (HCN). The chemical and physical characteristics of the compound will affect the potential availability of the cyanide group and therefore, the hazards associated with different chemical species. For purposes of the toxicologist, cyanides and nitriles can be classified into groups based on their common properties. Group 1, inorganic cyanides, includes hydrogen cyanide, cyanogen, and simple salts such as sodium, potassium, calcium, and ammonium cyanide of hydrogen cyanide that dissociate readily to release CN −1 ions. Group 2 includes halogenated compounds such as cyanogen chloride or bromide. Group 3 comprises simple and complex salts such as cobalt cyanide trihydrate, cupric and cuprous cyanide, silver cyanide, and ferricyanide and ferrocyanide salts of hydrogen cyanide that do not dissociate readily to release CN −1 ions. Group 4, organic cyanides, includes cyanide glycosides produced by plants such as amygdalin and linamarin. Group 5, nitriles, have a general structure R‐CNO, and include compounds such as acetonitrile (methyl cyanide), acrylonitrile, and isobutyronitrile.
Lymphangioleiomyomatosis (LAM) is a metastasizing neoplasm of reproductive age women that causes cystic lung remodeling and progressive respiratory failure. The source of LAM cells that invade the lung and the reasons that LAM targets women have remained elusive. We employed single cell and single nuclei RNA sequencing on LAM lesions within explanted LAM lungs, known to contain smooth muscle like cells bearing mTOR activating mutations in TSC1 or TSC2, and identified a unique population of cells that were readily distinguished from those of endogenous lung cells. LAM CORE cells shared closest transcriptomic similarity to normal uterus and neural crest. Immunofluorescence microscopy demonstrated the expression of LAMCORE cell signature genes within LAM lesions in both lung and uterus. Serum aptamer proteomics and ELISA identified biomarkers predicted to be secreted by LAM CORE cells. Single cell transcriptomics strongly supports a uterine neural crest origin of LAM CORE cells; providing insights into disease pathogenesis and informing future treatment strategies for LAM.
OBJECTIVES/GOALS: To describe team science training that can be tailored to specific audiences, in this case, Clinical Research Professionals (CRP) using discipline-specific vignettes, and to highlight the benefits of audience-specific training in team science. METHODS/STUDY POPULATION: Translational science teams are comprised of members from various disciplines. All members can benefit from team science training. Our education team has incorporated discipline-specific training into educational offerings. This project focuses on education tailored to CRPs and their role in clinical research. Historically, team science training has been focused on faculty and trainees. The exclusion of CRPs can limit the impact of this training. We’ve created workshops specifically geared toward CRPs. This presentation demonstrates how we tailor team science training to CRPs by using relevant examples and real-world vignettes to highlight concepts. RESULTS/ANTICIPATED RESULTS: The team science workshops conducted specifically for CRPs have been well received. CRPs have been eager to engage with team science-related material. The number of team science workshops requested by CRP groups is continuing to increase. We will share both quantitative and qualitative evaluation results from several team science workshops conducted to-date. The inclusion of scenarios that relate to common situations encountered by CRPs has been especially helpful in demonstrating team science concepts they have personally experienced. DISCUSSION/SIGNIFICANCE: Helping CRPs directly apply team science concepts to their work is very valuable for improving high-functioning team behavior. CRPs can use new knowledge and skills to enhance efficiency and reduce stress and burnout. The impact of team science is maximized when all members of the team are trained.
