Kunal Shah

Chronic pancreatitis is characterized by chronic inflammation and fibrosis, processes heightened by activated pancreatic stellate cells (PSCs). Recent publications have demonstrated that miR-15a, which targets YAP1 and BCL-2, is significantly downregulated in patients with chronic pancreatitis compared to healthy controls. We have utilized a miRNA modification strategy to enhance the therapeutic efficacy of miR-15a by replacing uracil with 5-fluorouracil (5-FU). We demonstrated increased levels of YAP1 and BCL-2 (both targets of miR-15a) in pancreatic tissues obtained from Ptf1aCre^ERTM and Ptf1aCre^ERTM;LSL-Kras^G12D mice after chronic pancreatitis induction as compared to controls. In vitro studies showed that delivery of 5-FU-miR-15a significantly decreased viability, proliferation, and migration of PSCs over six days compared to 5-FU, TGFβ1, control miR, and miR-15a. In addition, treatment of PSCs with 5-FU-miR-15a in the context of TGFβ1 treatment exerted a more substantial effect than TGFβ1 alone or when combined with other miRs. Conditioned medium obtained from PSC cells treated with 5-FU-miR-15a significantly inhibits the invasion of pancreatic cancer cells compared to controls. Importantly, we demonstrated that treatment with 5-FU-miR-15a reduced the levels of YAP1 and BCL-2 observed in PSCs. Our results strongly suggest that ectopic delivery of miR mimetics is a promising therapeutic approach for pancreatic fibrosis and that 5-FU-miR-15a shows specific promise.

Lactic acidosis is the most common anion gap metabolic acidosis in critically ill patients. Type B lactic acidosis is most commonly seen with hematological malignancies, especially lymphomas. It is considered an oncological emergency and is associated with high mortality and poor outcomes if not treated promptly. Here, we present the case of a 48-year-old male who developed Type B lactic acidosis secondary to newly diagnosed diffuse large B-cell lymphoma. This case highlights the importance of including Type B lactic acidosis in the differential diagnosis in a patient with unexplained lactic acidosis and hypoglycemia with otherwise vague symptoms and the need for a thorough search for quick diagnosis and early management.