Iron Overload Causes Oxidative Stress and Impaired Insulin Signaling in AML-12 Hepatocytes

Background

Iron overload is associated with increased severity of nonalcoholic fatty liver disease (NAFLD) including progression to nonalcoholic steatohepatitis and hepatocellular carcinoma.

Aims

To identify potential role(s) of iron in NAFLD, we measured its effects on pathways of oxidative stress and insulin signaling in AML-12 mouse hepatocytes.

Methods

Rapid iron overload was induced with 50 μM ferric ammonium citrate and 8-hydroxyquinoline. Insulin response was measured by Western blot of phospho-protein kinase B. Lipid content was determined by staining with Oil Red O. Reactive oxygen species (ROS) were measured by flow cytometry using 5-(and 6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate. Oxidative stress was measured by Western blots for phospho-jnk and phospho-p38.

Results

Iron increased ROS (p < 0.001) and oxidative stress (p < 0.001) and decreased insulin signaling by 33 % (p < 0.001). Treatment with stearic or oleic acids (200 μM) increased cellular lipid content and differentially modulated effects of iron. Stearic acid potentiated iron-induced ROS levels by two-fold (p < 0.05) and further decreased insulin response 59 % (p < 0.05) versus iron alone. In contrast, cells treated with oleic acid were protected against iron-mediated injury; ROS levels were decreased by half (p < 0.01) versus iron alone while insulin response was restored to control (untreated) levels. The anti-oxidant curcumin reduced effects of iron on insulin signaling, ROS, and oxidative stress (p < 0.01). Curcumin was similarly effective in cells treated with both stearic acid and iron.

Conclusions

An in vitro model of NAFLD progression is described in which iron-induced oxidative stress inhibits insulin signaling. Pathophysiological effects of iron were increased by saturated fat and decreased by curcumin.     

Patterns of Incident Reporting Across Clinical Sites in a Regionally Expanding Academic Radiation Oncology Department

PurposeWe evaluated patterns of event reporting across five clinical locations within an academic radiation oncology department, with the goal of better understanding variability across sites.Methods and MaterialsWe analyzed 1,351 events reported to a departmental incident learning system over 1 calendar year across the five locations with respect to volume of events, event type, process map location of origin and detection, and event reporter.ResultsWe found marked variability in reporting patterns, including reporting rate, event type, event severity, event location of origin and detection within the departmental process map, and discipline of event reporters. These differences relate both to variability in process and workflow (reflected by frequency of specific workflow events at each site) and in reporting culture (reflected by volume or rate of event reporting, and discipline of event reporter).ConclusionsThese data highlight the variability in reporting culture even within a single department, and therefore the need to tailor and individualize safety and quality programs to the unique clinical site, with the long-term goal of achieving a common culture of safety while supporting unique processes at individual locations. This work also raises concern about extrapolating single-institution incident learning system results without understanding the unique workflow and culture of clinical sites.     

Clinical Features of Adult COVID-19 Patients without Risk Factors before and after the Nationwide SARS-CoV-2 B.1.617.2 (Delta)-variant Outbreak in Korea: Experience from Gyeongsangnam-do

BackgroundData on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) delta variant virulence are insufficient. We retrospectively compared the clinical features of adult coronavirus disease 2019 (COVID-19) patients without risk factors for severe COVID-19 who entered residential treatment centers (RTCs) before and after the delta variant outbreak.MethodsWe collected medical information from two RTCs in South Korea. On the basis of nationwide delta variant surveillance, we divided the patients into two groups: 1) the delta-minor group (diagnosed from December 2020–June 2021, detection rate < 10%) and 2) the delta-dominant group (diagnosed during August 2021, detection rate > 90%). After propensity-score matching, the incidences of pneumonia, hospital transfer and need for supplemental oxygen were compared between the groups. In addition, risk factors for hospital transfer were analysed.ResultsA total of 1,915 patients were included. The incidence of pneumonia (14.6% vs. 9.2%, P = 0.009), all-cause hospital transfer (10.4% vs. 6.3%, P = 0.020) and COVID-19-related hospital transfer (7.5% vs. 4.8%, P = 0.081) were higher in the delta-dominant group than those in the delta-minor group. In the multivariate analysis, the delta-dominant group was an independent risk factor for all-cause (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.16–3.13; P = 0.011) and COVID-19-related hospital transfer (aOR, 1.86; 95% CI, 1.04–3.32; P = 0.036).ConclusionHospitalization rates were increased in the adult COVID-19 patients during the delta variant nationwide outbreak. Our results showed that the delta variant may be more virulent than previous lineages.     

Real-time management of incident learning reports in a radiation oncology department

Purpose

The optimal approach to managing incident learning system (ILS) reports remains unclear. Here, we describe our experience with prospective coding of events reported to the ILS with comparisons of risk scores on the basis of event type and process map location.

Stereotactic Ablative Radiotherapy (SABR/SBRT) for Hepatocellular Carcinoma

Purpose of Review

Liver-directed SABR (stereotactic ablative body radiotherapy) is emerging as an effective local therapy option for HCC (hepatocellular carcinoma). This review summarizes recent clinical progresses and proposes future directions.

Recent Findings

SABR is an effective and safe, non-invasive local therapy option for HCC in the primary and salvage treatment settings, as well as a bridge to liver transplantation in selected patients. Randomized trials comparing SABR with other locoregional modalities are currently ongoing.

Summary

Research efforts are being made toward better predicting normal tissue toxicity and tumor radiosensitivity for a tailored maximal safe treatment in HCC SABR. More recently, potential synergy with immunotherapies is of increasing interest in HCC.