Left ventricle phenotyping utilizing tissue doppler imaging in premature infants with varying severity of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s\u27, e\u27, a\u27), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI at three time periods from 32 and 36 weeks, postmenstrual age through one year of age. We also measured post systolic motion (PSM), a marker of myocardial dysfunction that results from asynchronous movement of the ventricular walls, and not previously described in preterm infants. Patients were stratified into groups according to BPD severity and the presence of PH and compared over time. Conventional TDI measures of the LV function were similar between groups, but the septal PSM was significantly prolonged over the first year of age in patients with BPD-PH. PSM provides a novel objective way to assess the hemodynamic impact of lung and pulmonary vascular disease severity on LV function in preterm infants with BPD and PH

A unique high-output cardiac hypertrophy phenotype arising from low systemic vascular resistance in Cantu syndrome

Background Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high-output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities. Methods and Results We sought to systematically characterize high-output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain-of-function variants i

Maturational patterns of left ventricular rotational mechanics in pre-term infants through 1 year of age

BACKGROUND: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures. METHODS: Pre-term infants (\u3c29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus. RESULTS: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p \u3c 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p \u3c 0.05). CONCLUSION: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age

Impact of Risk-based Sexually Transmitted Infection Screening in the Emergency Department

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents. METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing recommendations. Patient answers and testing recommendations were integrated in real-time into the electronic health record. Patients who tested positive received treatment according to our standard-of-care practices. All patients 15-21 years of age were asked to complete this on an opt-out basis, regardless of the reason for their ED visit. Exclusions included those unable to independently use a tablet, severe illness, sexual assault, or non-English speaking. Our primary outcome was to describe STI-testing recommendations and test results among ACASI participants. We also compared STI testing between ACASI participants and those who were eligible but did not use it. RESULTS: In the first 13 months, 28.9% (1788/6194) of eligible adolescents completed the ACASI and 44.2% (321/790) accepted recommended STI testing. The mean age of participants was 16.6 ± 1.3 years, with 65.4% (1169) being female. Gonorrhea/chlamydia testing was significantly higher among participants vs. non-participants (20.1% [359/1788] vs 4.8% [212/4406]; p \u3c 0.0001). The proportion of positive STI tests was similar between the two groups: 24.8% (89/359) vs. 24.5% (52/212; p = 0.94) were positive for chlamydia and/or gonorrhea, while 0.6% (2/354) participants vs. 0% non-participants (p \u3e 0.99) were positive for HIV. Among participants whose chief complaints were unlikely to be related to STIs but accepted recommended testing, 20.9% (37/177) were positive for gonorrhea or chlamydia. CONCLUSIONS: Our program facilitated STI testing in the ED and identified many adolescents with STIs, even when their ED complaint was for unrelated reasons. More rigorous implementation is needed to determine the impact of deployment of ACASI to all eligible adolescents and addressing barriers to accepting STI testing recommendations

Monitoring of the central blood pressure waveform via a conformal ultrasonic device.

Continuous monitoring of the central-blood-pressure waveform from deeply embedded vessels, such as the carotid artery and jugular vein, has clinical value for the prediction of all-cause cardiovascular mortality. However, existing non-invasive approaches, including photoplethysmography and tonometry, only enable access to the superficial peripheral vasculature. Although current ultrasonic technologies allow non-invasive deep-tissue observation, unstable coupling with the tissue surface resulting from the bulkiness and rigidity of conventional ultrasound probes introduces usability constraints. Here, we describe the design and operation of an ultrasonic device that is conformal to the skin and capable of capturing blood-pressure waveforms at deeply embedded arterial and venous sites. The wearable device is ultrathin (240 μm) and stretchable (with strains up to 60%), and enables the non-invasive, continuous and accurate monitoring of cardiovascular events from multiple body locations, which should facilitate its use in a variety of clinical environments

A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome

BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic β cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions.RESULTSDantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, β cell functions were not significantly improved, but there was a significant correlation between baseline β cell functions and change in β cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1β, TNF-α, and isoprostane, were elevated in subjects.CONCLUSIONThis study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02829268FUNDINGNIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs