Aortic pulse wave velocity in children with Cushing syndrome: A window into a marker of early cardiovascular disease.

OBJECTIVE: To investigate early signs of cardiovascular arterial remodelling in paediatric patients with Cushing syndrome (CS) in comparison with normative values from healthy children. STUDY DESIGN: The metrics used to assess cardiac health were from thoracic aorta and carotid MRI. Scans were performed on 18 children with CS (mean: 12.5 ± 3.1 years, range: 6.0-16.8 years, 10 female). Pulse wave velocity (PWV), aortic distensibility (AD) and carotid intima-media thickness (cIMT), well-validated measurements of cardiac compromise, were measured from the images and compared to normative age-matched values where available. RESULTS: Patients with CS had significantly higher PWV compared to age-adjusted normal median control values (4.0 ± 0.7 m/s vs. 3.4 ± 0.2 m/s, respectively, P = 0.0115). PWV was positively correlated with midnight plasma cortisol (r = 0.56, P = 0.02). Internal and common cIMT were negatively correlated with ascending AD (r = -0.75, P = 0.0022, r = -0.69, P = 0.0068, respectively). CONCLUSION: Pulse wave velocity data indicate that paediatric patients with CS have early evidence of cardiovascular remodelling. The results suggest the opportunity for monitoring as these changes begin in childhood.

Germline USP8 Mutation Associated With Pediatric Cushing Disease and Other Clinical Features: A New Syndrome.

BACKGROUND: Somatic mutations in the ubiquitin-specific peptidase 8 (USP8) gene are common in corticotropinomas of children with Cushing disease (CD). We report a unique patient with a germline USP8 mutation who presented with CD and a constellation of other findings that constitute an intriguing genetic syndrome. CASE DESCRIPTION: We describe a 16-year-old female with CD, developmental delay, dysmorphic features, ichthyosiform hyperkeratosis, chronic lung disease, chronic kidney disease, hyperglycemia, dilated cardiomyopathy with congestive heart failure, and previous history of hyperinsulinism and partial GH deficiency. She was diagnosed with CD at 14 years old and underwent transsphenoidal surgery. Despite initial improvement, she developed recurrent CD. METHODS: DNA was extracted from peripheral blood and tumor DNA; whole-exome and Sanger confirmatory sequencing were performed. Immunohistochemistry was performed on the resected adenoma. RESULTS: A de novo germline heterozygous USP8 mutation (c.2155T>C, p.S719P) in the critical 14-3-3 binding motif hot spot locus of the gene was identified in both the peripheral blood and tumor DNA. Histopathologic evaluation of the resected tumor confirmed an ACTH-secreting adenoma. CONCLUSION: Somatic USP8 mutations are common in adenomas causing CD, but to date, no germline defects have been reported. We describe a patient with a de novo germline USP8 mutation with recurrent CD and multiple other medical problems. This unique patient informs us of the multitude of signaling events that may be controlled by USP8.

Facilitating the Timely Discharge of Well Newborns by Using Quality Improvement Methods.

BACKGROUND AND OBJECTIVES: Discharges are a key driver of hospital throughput. Our pediatric hospitalist team sought to improve newborn nursery throughput by increasing the percentage of newborns on our service with a discharge order by 11 am. We hypothesized that implementing a discharge checklist would result in earlier discharge times for newborns who met discharge criteria. METHODS: We identified barriers to timely discharge through focus groups with key stakeholders, chart reviews, and brainstorming sessions. We subsequently created and implemented a discharge checklist to identify and address barriers before daily rounds. We tracked mean monthly discharge order times. Finally, we performed chart reviews to determine causes for significantly delayed discharge orders and used this information to modify rounding practices during a second plan-do-study-act cycle. RESULTS: During the 2-year period before the intervention, 24% of 3224 newborns had a discharge order entered by 11 am. In the 20 months after the intervention, 39% of 2739 newborns had a discharge order by 11 am, a 63% increase compared with the baseline. Observation for group B Streptococcus exposure was the most frequent reason for a late discharge order. CONCLUSIONS: There are many factors that affect the timely discharge of well newborns. The development and implementation of a discharge checklist improved our ability to discharge newborns on our pediatric hospitalist service by 11 am. Future studies to identify nonphysician barriers to timely newborn discharges may lead to further improvements in throughput between the labor and delivery and maternity suites units.