Delayed intracranial hemorrhage in elderly anticoagulated patients sustaining a minor fall.

BACKGROUND: Falls are a common cause of hospitalization, morbidity, and mortality among the elderly in the United States. Evidence-based imaging recommendations for evaluation of delayed intracranial hemorrhage (DICH) are not generally agreed upon. The purpose of this project was to evaluate the incidence of DICH detected by head computer tomography (CT) among an elderly population on pre-injury anticoagulant or antiplatelet (ACAP) therapy. METHODS: Data from a Level 1 Trauma Center trauma registry was used to assess the incidence of DICH in an elderly population of patients (≥65 years) who sustained a minor fall while on pre-injury ACAP medications. Counts and percentages are reported. RESULTS: Data on 1076 elderly trauma patients were downloaded, of which 838 sustained a minor fall and 513 were found to be using a pre-injury ACAP medication. One patient (0.46%) with a DICH was identified out of 218 patients who received a routine repeat head CT. Aspirin and warfarin were the most common pre-injury ACAP medications and 19.27% (42/218) of patients were found to be using multiple ACAP medications. CONCLUSIONS: Universal screening protocols promote immediate-term patient safety, but do so at a great expense with respect to health expenditures and increased radiation exposure. This analysis highlights the need for an effective risk assessment tool for DICH that would reduce the burden of unnecessary screenings while still identifying life-threatening intracranial hemorrhages in affected patients

Hepatocyte Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 4 Regulates Stress Signaling, Fibrosis, and Insulin Sensitivity During Development of Steatohepatitis in Mice

Background & aimsReactive oxidative species (ROS) are believed to be involved in the progression of nonalcoholic steatohepatitis (NASH). However, little is known about the sources of ROS in hepatocytes or their role in disease progression. We studied the effects of nicotinamide adenine dinucleotide phosphate reduced oxidase 4 (NOX4) in liver tissues from patients with NASH and mice with steatohepatitis.MethodsLiver biopsy samples were obtained from 5 patients with NASH, as well as 4 patients with simple steatosis and 5 patients without steatosis (controls) from the University of California, Davis Cancer Center Biorepository. Mice with hepatocyte-specific deletion of NOX4 (NOX4(hepKO)) and NOX4(floxp+/+) C57BL/6 mice (controls) were given fast-food diets (supplemented with high-fructose corn syrup) or choline-deficient l-amino acid defined diets to induce steatohepatitis, or control diets, for 20 weeks. A separate group of mice were given the NOX4 inhibitor (GKT137831). Liver tissues were collected and immunoblot analyses were performed determine levels of NOX4, markers of inflammation and fibrosis, double-stranded RNA-activated protein kinase, and phospho-eIF-2α kinase-mediated stress signaling pathways. We performed hyperinsulinemic-euglycemic clamp studies and immunoprecipitation analyses to determine the oxidation and phosphatase activity of PP1C.ResultsLevels of NOX4 were increased in patients with NASH compared with controls. Hepatocyte-specific deletion of NOX4 reduced oxidative stress, lipid peroxidation, and liver fibrosis in mice with diet-induced steatohepatitis. A small molecule inhibitor of NOX4 reduced liver inflammation and fibrosis and increased insulin sensitivity in mice with diet-induced steatohepatitis. In primary hepatocytes, NOX4 reduced the activity of the phosphatase PP1C, prolonging activation of double-stranded RNA-activated protein kinase and phosphorylation of extracellular signal-regulated kinase-mediated stress signaling. Mice with hepatocyte-specific deletion of NOX4 and mice given GKT137831 had increased insulin sensitivity.ConclusionsNOX4 regulates oxidative stress in the liver and its levels are increased in patients with NASH and mice with diet-induced steatohepatitis. Inhibitors of NOX4 reduce liver inflammation and fibrosis and increase insulin sensitivity, and might be developed for treatment of NASH