Acute Pancreatitis in the Emergency Department

Introduction: Acute pancreatitis (AP) is a common emergency department (ED) presentation with a variety of outcomes. Stratifying AP severity with scoring systems can allow physicians to effectively manage patient disposition. Objective: To identify ED pancreatitis patients who will likely be admitted to the ICU or be discharged within 48 hours, and to validate existing pancreatitis severity scores. Methods: Patients with a final ED diagnosis of AP and/or lipase ≥ 3 times the upper limit of normal were enrolled in a prospective, observational chart review study. Parametric and non-parametric descriptive statistics were used to describe the patient population. Area under receiver operating curve (AUC) was used to determine the predictive accuracy of existing pancreatitis scores. Results: Ranson criteria, Glasgow-Imrie (GI) criteria, Bedside Index of Severity in Acute Pancreatitis (BISAP), and Harmless Acute Pancreatitis Score (HAPS) were assessed. GI criteria (AUC = 0.77) had the highest predictive accuracy for ICU admission, while Ranson criteria (AUC = 0.62) had the highest predictive accuracy for early discharge. Mean scores of ICU patients were significantly (p \u3c 0.05) higher than those of non-ICU patients in all four scoring systems; however, mean scores in ICU patients failed to meet the severe case threshold for all four scoring systems. Discussion: Existing pancreatitis scoring systems cannot consistently predict AP severity in ED patients. The small difference in mean ICU and non-ICU patient scores illustrates the difficulty of using scoring systems to stratify AP severity in the ED. Further efforts to develop an ED-specific scoring system could allow physicians to more efficiently admit patients

Ouabain-Stimulated Trafficking Regulation of the Na/K-ATPase and NHE3 in Renal Proximal Tubule Cells

We have demonstrated that ouabain regulates protein trafficking of the Na/K-ATPase a1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this mechanism is species-specific, ouabain-induced regulation of the a1 subunit and NHE3 as well as transcellular 22Na? transport were compared in three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 in which the pig a1 was replaced by ouabain-resistant rat a1). Ouabain-induced inhibition of transcellular 22Na? transport is due to an ouabain-induced redistribution of the a1 subunit and NHE3. In LLC-PK1 cells, ouabain also inhibited the endocytic recycling of internalized NHE3, but has no significant effect on recycling of endocytosed a1 subunit. These data indicated that the ouabain-induced redistribution of the a1 subunit and NHE3 is not a species-specific phenomenon, and ouabain-activated Na/K-ATPase signaling influences NHE3 regulation

Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC)

Abstract The landscape of head and neck squamous cell carcinoma (HNSCC) has been changing rapidly due to growing proportion of HPV-related disease and development of new therapeutic agents. At the same time, there has been a constant need for individually tailored treatment based on genetic biomarkers in order to optimize patient survival and alleviate treatment-related toxicities. In this regard, aberrations of PI3K pathway have important clinical implications in the treatment of HNSCC. They frequently constitute ‘gain of function’ mutations which trigger oncogenesis, and PI3K mutations can also lead to emergence of drug resistance after treatment with EGFR inhibitors. In this article, we review PI3K pathway as a target of treatment for HNSCC and summarize PI3K/mTOR inhibitors that are currently under clinical trials. In light of recent advancement of immune checkpoint inhibitors, consideration of PI3K inhibitors as potential immune modulators is also suggested