Submaximal Exercise Response is Associated with Future Hypertension in Patients with Coarctation of the Aorta.

Hypertension (HTN) is common in patients with a history of coarctation of the aorta (CoA) and remains underrecognized and undertreated. Studies in the non-coarctation otherwise healthy adult population have correlated an exaggerated blood pressure response during mild to moderate exercise with subsequent diagnosis of HTN. The goal of this study was to determine if blood pressure response to submaximal exercise in normotensive CoA patients correlated with development of HTN.Retrospective chart review was performed in individuals ≥ 13 years old with CoA and no diagnosis of HTN at time of cardiopulmonary exercise testing (CPET). Systolic blood pressure (SBP) during CPET at rest, submax 1 (stage 1 Bruce or minute 2 bicycle ramp), submax 2 (stage 2 Bruce or minute 4 bicycle ramp), and peak were recorded. The primary composite outcome was HTN diagnosis or initiation of anti-hypertensive medications at follow up.There were 177 patients (53% female, median age 18.5 years), of whom 38 patients (21%) met composite outcome during a median follow up of 46 months. Men were more likely to develop hypertension. Age at repair and age at CPET were not significant covariates. At each stage of CPET, SBP was significantly higher in those who met the composite outcome. Submax 2 SBP ≥ 145 mmHg was 75% sensitive, 71% specific in males and 67% sensitive, 76% specific in females for development of composite outcome.Our study shows an exaggerated SBP response to submaximal exercise may portend an increased risk of developing hypertension during short- to mid-term follow up.

Improving the Pediatric Emergency Department Learning Experience: A Simulation-Based Orientation for Pediatric PGY 1 Residents.

Introduction: Rotations in the pediatric emergency department (PED) may expose residents to very few critically ill patients. In our previous work, interns at our institution showed low self-confidence in decision-making and preparedness to stabilize acutely ill patients. In order to improve this, we designed a new, peer-led, simulation-based orientation to the PED rotation for interns focusing on workflow and decision-making. The cases presented learners with practical and generalizable challenges, such as ordering initial labs and medications and defining the ultimate disposition for the patient. Methods: This orientation curriculum was designed for first-year residents using high-fidelity simulation mannequins. In the first of two cases, learners managed a 10-year-old boy presenting with status asthmaticus who required continuous albuterol and parenteral magnesium to achieve stability for admission. In the second case, a 4-year-old girl with short gut syndrome and an indwelling central line presented with fever, was found to be septic, but responded well to fluid resuscitation and antibiotic therapy. Results: Over 2 years of implementation, 39 residents participated. Pre- and postintervention Likert-based survey evaluations showed significant increases in confidence in decision-making and preparedness to stabilize acutely ill children that were not seen in a control group during the pilot year. A subsequent class-wide implementation showed similar significant improvements, as well as increased comfort initiating treatment prior to staffing. Discussion: Using simulation mannequins in a case-based orientation can improve PGY 1 residents' self-confidence and sense of preparedness during their first rotation in the PED.

Human Metapneumovirus Infection in Hospitalized Children.

BACKGROUND: Most children are exposed to human metapneumovirus (HMPV) by the age of 5 y. This study aimed to describe the morbidity associated with HMPV infections in a cohort of children in the Midwest of the United States. METHODS: This was a retrospective 2-center cohort study including children (0-17 y old) hospitalized with HMPV infections at 2 tertiary care pediatric hospitals from 2009 to 2013. Demographics, chronic medical conditions, viral coinfections, and hospitalization characteristics, including the need for respiratory support, high-flow nasal cannula, CPAP, bi-level positive airway pressure, invasive mechanical ventilation, pediatric ICU admission, acute kidney injury (AKI), use of extracorporeal membrane oxygenation, and length of stay, were collected. RESULTS: In total, 131 subjects were included. Those with one or more comorbidities were older than their otherwise healthy counterparts, with a median age of 2.8 y (interquartile range [IQR] 1.1-7.0) compared to 1.3 y (IQR 0.6-2.0, P < .001), respectively. Ninety-nine (75.6%) subjects required respiratory support; 72 (55.0%) subjects required nasal cannula, simple face mask, or tracheostomy mask as their maximum support. Additionally, 1 (0.8%) subject required high-flow nasal cannula, 1 (0.8%) subject required CPAP, 2 (1.5%) subjects required bi-level positive airway pressure, 15 (11.5%) subjects required invasive mechanical ventilation, 4 (3.1%) subjects required high-frequency oscillatory or jet ventilation, and 4 (3.1%) subjects required extracorporeal membrane oxygenation. Fifty-one (38.9%) subjects required pediatric ICU admission, and 16 (12.2%) subjects developed AKI. Subjects with AKI were significantly older than those without AKI at 5.4 y old (IQR 1.6-11.7) versus 1.9 y old (IQR 0.7-3.5, P = .003). After controlling for the presence of at least one comorbidity and cystic fibrosis, each year increase in age led to a 16% increase in the odds of AKI (P = .01). The median length of stay for the entire cohort was 4.0 d (IQR 2.7-7.0). CONCLUSIONS: Children hospitalized with HMPV may be at risk for AKI. Risk of HMPV-associated AKI appears to increase with age regardless of severity of respiratory illness or presence of comorbidities.

Laser ablation of the zebrafish pronephros to study renal epithelial regeneration.

Acute kidney injury (AKI) is characterized by high mortality rates from deterioration of renal function over a period of hours or days that culminates in renal failure. AKI can be caused by a number of factors including ischemia, drug-based toxicity, or obstructive injury. This results in an inability to maintain fluid and electrolyte homeostasis. While AKI has been observed for decades, effective clinical therapies have yet to be developed. Intriguingly, some patients with AKI recover renal functions over time, a mysterious phenomenon that has been only rudimentally characterized. Research using mammalian models of AKI has shown that ischemic or nephrotoxin-injured kidneys experience epithelial cell death in nephron tubules, the functional units of the kidney that are made up of a series of specialized regions (segments) of epithelial cell types. Within nephrons, epithelial cell death is highest in proximal tubule cells. There is evidence that suggests cell destruction is followed by dedifferentiation, proliferation, and migration of surrounding epithelial cells, which can regenerate the nephron entirely. However, there are many unanswered questions about the mechanisms of renal epithelial regeneration, ranging from the signals that modulate these events to reasons for the wide variation of abilities among humans to regenerate injured kidneys. The larval zebrafish provides an excellent model to study kidney epithelial regeneration as its pronephric kidney is comprised of nephrons that are conserved with higher vertebrates including mammals. The nephrons of zebrafish larvae can be visualized with fluorescence techniques because of the relative transparency of the young zebrafish. This provides a unique opportunity to image cell and molecular changes in real-time, in contrast to mammalian models where nephrons are inaccessible because the kidneys are structurally complex systems internalized within the animal. Recent studies have employed the aminoglycoside gentamicin as a toxic causative agent for study of AKI and subsequent renal failure: gentamicin and other antibiotics have been shown to cause AKI in humans, and researchers have formulated methods to use this agent to trigger kidney damage in zebrafish. However, the effects of aminoglycoside toxicity in zebrafish larvae are catastrophic and lethal, which presents a difficulty when studying epithelial regeneration and function over time. Our method presents the use of targeted cell ablation as a novel tool for the study of epithelial injury in zebrafish. Laser ablation gives researchers the ability to induce cell death in a limited population of cells. Varying areas of cells can be targeted based on morphological location, function, or even expression of a particular cellular phenotype. Thus, laser ablation will increase the specificity of what researchers can study, and can be a powerful new approach to shed light on the mechanisms of renal epithelial regeneration. This protocol can be broadly applied to target cell populations in other organs in the zebrafish embryo to study injury and regeneration in any number of contexts of interest.