ABSTRACT
We present the first in-human transcatheter systemic atrioventricular valve-in-valve implantation in a 37-year-old patient with Ebstein anomaly, levo-transposition of the great arteries, and prior systemic valve replacement. She had severe bioprosthetic valve regurgitation and reduced systolic function. She had high surgical risk and was planned for transcatheter intervention. (Level of Difficulty: Advanced.).
ABSTRACT
Esophagopericardial fistulas are rare. Most reported cases are related to malignancy or prior surgical intervention. We report a case of an esophagopericardial fistula presenting as pneumopericardium and purulent pericarditis in a patient with a history of caustic ingestion and an esophageal stent.
Subject(s)
Burns, Chemical/complications , Caustics/adverse effects , Esophageal Fistula/complications , Esophagus/injuries , Fistula/complications , Pneumopericardium/etiology , Stents/adverse effects , Adult , Burns, Chemical/diagnosis , Burns, Chemical/surgery , Esophageal Fistula/diagnosis , Esophagus/diagnostic imaging , Esophagus/surgery , Fistula/diagnosis , Humans , Male , Pericardium/diagnostic imaging , Pneumopericardium/diagnosis , Radiography, Thoracic , Tomography, X-Ray ComputedABSTRACT
Classically Class IB phosphoinositide 3-kinase (PI3Kγ) plays a role in extracellular signal-regulated kinase (ERK) activation following G-protein coupled receptor (GPCR) activation. Knock-down of PI3Kγ unexpectedly resulted in loss of ERK activation to receptor tyrosine kinase agonists such as epidermal growth factor or insulin. Mouse embryonic fibroblasts (MEFs) or primary adult cardiac fibroblasts isolated from PI3Kγ knock-out mice (PI3KγKO) showed decreased insulin-stimulated ERK activation. However, expression of kinase-dead PI3Kγ resulted in rescue of insulin-stimulated ERK activation. Mechanistically, PI3Kγ sequesters protein phosphatase 2A (PP2A), disrupting ERK-PP2A interaction, as evidenced by increased ERK-PP2A interaction and associated PP2A activity in PI3KγKO MEFs, resulting in decreased ERK activation. Furthermore, ß-blocker carvedilol-mediated ß-arrestin-dependent ERK activation is significantly reduced in PI3KγKO MEF, suggesting accelerated dephosphorylation. Thus, instead of classically mediating the kinase arm, PI3Kγ inhibits PP2A by scaffolding and sequestering, playing a key parallel synergistic step in sustaining the function of ERK, a nodal enzyme in multiple cellular processes.
