There are increasing reports of the effects of COVID-19 on the pancreas. Pancreatitis, as a result of hypertriglyceridemia, has also been reported. Hypothesized mechanisms include hemophagocytic lymph Show more
There are increasing reports of the effects of COVID-19 on the pancreas. Pancreatitis, as a result of hypertriglyceridemia, has also been reported. Hypothesized mechanisms include hemophagocytic lymphohistiocytosis (HLH) syndrome and acquired lipoprotein lipase (LPL) inhibitors. We present a 51-year-old female patient who presented with nausea, vomiting, and epigastric abdominal pain radiating to the back. On examination, she had generalized abdominal tenderness without guarding or rebound tenderness. Our workup revealed elevated lipase of 1150 units/L, triglycerides (TG) of 11340 mg/dL, and mild pancreatitis on an abdominal computed tomography (CT) scan. On day 2, she developed a new oxygen requirement and tested positive for COVID-19. She was treated with fluids and opiates for pancreatitis, plasmapheresis, and an insulin infusion to treat her hypertriglyceridemia. She was treated with remdesivir for an acute COVID-19 infection. Triglycerides decreased to <500 mg/dL with treatment, and she was discharged home on oral lipid-lowering agents. By discussing this case, we aim to shed light on the association between COVID-19 and hypertriglyceridemia, which can further lead to life-threatening complications such as acute pancreatitis. Further studies are needed to identify the exact mechanisms, preventive measures, and long-term effects of COVID-19 on triglycerides and the pancreas. Show less
Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF- Show more
Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF-β) and RAS, signaling through SMAD and RAS-responsive element-binding protein 1 (RREB1), jointly trigger expression of EMT and fibrogenic factors as two discrete arms of a common transcriptional response in carcinoma cells. Here, we demonstrate that both arms come together to form a program for lung adenocarcinoma metastasis and identify chromatin determinants tying the expression of the constituent genes to TGF-β and RAS inputs. RREB1 localizes to H4K16acK20ac marks in histone H2A.Z-loaded nucleosomes at enhancers in the fibrogenic genes interleukin-11 (IL11), platelet-derived growth factor-B (PDGFB), and hyaluronan synthase 2 (HAS2), as well as the EMT transcription factor SNAI1, priming these enhancers for activation by a SMAD4-INO80 nucleosome remodeling complex in response to TGF-β. These regulatory properties segregate the fibrogenic EMT program from RAS-independent TGF-β gene responses and illuminate the operation and vulnerabilities of a bifunctional program that promotes metastatic outgrowth. Show less