Improving Situational Awareness to Decrease Emergency ICU Transfers for Hospitalized Pediatric Cardiology Patients.

Introduction: Failure to recognize and mitigate critical patient deterioration remains a source of serious preventable harm to hospitalized pediatric cardiac patients. Emergency transfers (ETs) occur 10-20 times more often than code events outside the intensive care unit (ICU) and are associated with morbidity and mortality. This quality improvement project aimed to increase days between ETs and code events on an acute care cardiology unit (ACCU) from a baseline median of 17 and 32 days to ≥70 and 90 days within 12 months. Methods: Institutional leaders, cardiology-trained physicians and nurses, and trainees convened, utilizing the Institution for Healthcare Improvement model to achieve the project aims. Interventions implemented focused on improving situational awareness (SA), including a "Must Call List," evening rounds, a visual management board, and daily huddles. Outcome measures included calendar days between ETs and code events in the ACCU. Process measures tracked the utilization of interventions, and cardiac ICU length of stay was a balancing measure. Statistical process control chart methodology was utilized to analyze the impact of interventions. Results: Within the study period, we observed a centerline shift in primary outcome measures with an increase from 17 to 56 days between ETs and 32 to 62 days between code events in the ACCU, with sustained improvement. Intervention utilization ranged from 87% to 100%, and there was no observed special cause variation in our balancing measure. Conclusions: Interventions focused on improving SA in a particularly vulnerable patient population led to sustained improvement with reduced ETs and code events outside the ICU.

Usefulness of Echocardiography in Children with New-Onset Supraventricular Tachycardia.

BACKGROUND: Supraventricular tachycardia (SVT) is the most common sustained arrhythmia in children. Infants with SVT and ventricular preexcitation (Wolff-Parkinson-White syndrome) are known to have up to 30% prevalence of congenital heart disease (CHD). Infants without ventricular preexcitation who present with SVT at <1 year of age have a similar prevalence of CHD. However, for children without ventricular preexcitation who present with SVT at older ages, the prevalence of CHD is not known. The aim of this study was to determine the prevalence of CHD in older children and adolescents presenting with SVT without ventricular preexcitation, with the goal of providing guidance regarding the usefulness of echocardiography in this patient population. METHODS: Children aged 2 to 18 years presenting with confirmed SVT between January 2011 and December 2015 were included in this retrospective review. Patients with any history of ventricular preexcitation or preexisting heart disease were excluded. Medical records were reviewed, and electrocardiographic and echocardiographic findings were classified as normal, incidental, or abnormal. RESULTS: Two hundred ninety patients met the inclusion criteria. Echocardiographic examinations were completed on 224 patients. Only one patient was found to have CHD, a moderate primum atrial septal defect. This patient was noted to have electrocardiographic abnormalities consistent with primum atrial septal defect. CONCLUSIONS: For older children and adolescents with no known heart disease presenting with SVT without ventricular preexcitation, echocardiography may not be a necessary part of initial evaluation when the results of physical examination and electrocardiography are normal.

Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer.

Inhibitors of histone deacetylases (HDACs) induce growth arrest, differentiation, and apoptosis of colon cancer cell lines in vitro and have demonstrated anti-cancer efficacy in clinical trials. Whereas a role for HDAC1 and -2 in mediating components of the HDAC inhibitor response has been reported, the role of HDAC3 is unknown. Here we demonstrate increased protein expression of HDAC3 in human colon tumors and in duodenal adenomas from Apc1638(N/+) mice. HDAC3 was also maximally expressed in proliferating crypt cells in normal intestine. Silencing of HDAC3 expression in colon cancer cell lines resulted in growth inhibition, a decrease in cell survival, and increased apoptosis. Similar effects were observed for HDAC2 and, to a lesser extent, for HDAC1. HDAC3 silencing also selectively induced expression of alkaline phosphatase, a marker of colon cell maturation. Concurrent with its effect on cell growth, overexpression of HDAC3 and other Class I HDACs inhibited basal and butyrate-induced p21 transcription in a Sp1/Sp3-dependent manner, whereas silencing of HDAC3 stimulated p21 promoter activity and expression. However, the magnitude of the effects elicited by silencing of individual Class I HDACs was significantly less than that induced by HDAC inhibitors. These findings identify HDAC3 as a gene deregulated in human colon cancer and as a novel regulator of colon cell maturation and p21 expression. These findings also demonstrate that multiple Class I HDACs are involved in repressing p21 and suggest that the growth-inhibitory and apoptotic effects induced by HDAC inhibitors are probably mediated through the inhibition of multiple HDACs.

Gene expression profiling of intestinal epithelial cell maturation along the crypt-villus axis.

BACKGROUND & AIMS: To define the genetic reprogramming that drives intestinal epithelial cell maturation along the crypt-villus axis, enterocytes were sequentially isolated from the villus tip to the crypts of mouse small intestine. METHODS: Changes in gene expression were assessed using 27,405-element complementary DNA microarrays (14,685 unique genes) and specific changes validated by Western blotting. RESULTS: A total of 1113 genes differentially expressed between the crypt and villus were identified. Among these, established markers of absorptive and goblet cell differentiation were up-regulated in villus cells, whereas Paneth cell markers were maximally expressed in crypt cells. The 1113 differentially expressed genes were significantly enriched for genes involved in cell cycle progression, RNA processing, and translation (all predominantly down-regulated during maturation) and genes involved in cytoskeleton assembly and lipid uptake (predominantly up-regulated during maturation). No enrichment for apoptosis-regulating genes was observed. We confirmed that Wnt signaling was maximal in the proliferative compartment and observed a decrease in MYC and an increase in MAD and MAX expression during the maturation program. Consistent with these changes, the 1113 genes were enriched for MYC targets, establishing the importance of this network in intestinal cell maturation. CONCLUSIONS: This database serves as a resource for understanding the molecular mechanisms of intestinal cell maturation and for dissection of how perturbations in the maturation process can lead to changes in gastrointestinal physiology and pathology, particularly intestinal tumorigenesis.