Provider Communication and Fever Protocol for Children With Sickle Cell Disease in the Emergency Department.

OBJECTIVE: We assessed whether prior communication between pediatric hematologists and emergency department (ED) providers reduced time to administration of parenteral antibiotics for children with sickle cell disease presenting with fever. METHODS: Patients 2 months to 21 years of age were retrospectively identified if they were followed up at our center's pediatric hematology clinic and presented to the pediatric ED with fever. Emergency department-hematology communication before patient arrival was ascertained by chart review. The primary outcome was time to administration of parenteral antibiotics after ED arrival, with 60 minutes being the recommended maximum. RESULTS: Forty-nine patients were included in the analysis. Prior communication occurred in 43% of cases, with a median time to antibiotic administration of 79 minutes in this group (interquartile range, 59-142), compared with 136 minutes for patients without prior communication (interquartile range, 105-181 minutes; P = 0.012). The groups did not differ in hospital length of stay at the index visit. CONCLUSIONS: Advance communication between the pediatric hematologist and ED physician was associated with reduced time to antibiotic administration for febrile children with sickle cell disease. Further interventions should be explored to achieve timely antibiotics administration within 60 minutes of ED arrival.

Arsenic is more potent than cadmium or manganese in disrupting the INS-1 beta cell microRNA landscape.

Diabetes is a metabolic disorder characterized by fasting hyperglycemia and impaired glucose tolerance. Laboratory and population studies have shown that inorganic arsenic (iAs) can impair these pathways. Other metals including cadmium (Cd) and manganese (Mn) have also been linked to diabetes phenotypes. MicroRNAs, short non-coding RNAs that regulate gene expression, have emerged as potential drivers of metabolic dysfunction. MicroRNAs responsive to metal exposures in vitro have also been reported in independent studies to regulate insulin secretion in vivo. We hypothesize that microRNA dysregulation may associate with and possibly contribute to insulin secretion impairment upon exposure to iAs, Cd, or Mn. We exposed insulin secreting rat insulinoma cells to non-cytotoxic concentrations of iAs (1 µM), Cd (5 µM), and Mn (25 µM) for 24 h followed by small RNA sequencing to identify dysregulated microRNAs. RNA sequencing was then performed to further investigate changes in gene expression caused by iAs exposure. While all three metals significantly inhibited glucose-stimulated insulin secretion, high-throughput sequencing revealed distinct microRNA profiles specific to each exposure. One of the most significantly upregulated microRNAs post-iAs treatment is miR-146a (~ + 2-fold), which is known to be activated by nuclear factor κB (NF-κB) signaling. Accordingly, we found by RNA-seq analysis that genes upregulated by iAs exposure are enriched in the NF-κB signaling pathway and genes down-regulated by iAs exposure are enriched in miR-146a binding sites and are involved in regulating beta cell function. Notably, iAs exposure caused a significant decrease in the expression of Camk2a, a calcium-dependent protein kinase that regulates insulin secretion, has been implicated in type 2 diabetes, and is a likely target of miR-146a. Further studies are needed to elucidate potential interactions among NF-kB, miR-146a, and Camk2a in the context of iAs exposure.