Fetal Doppler Echocardiographic Assessment Predicts Severe Postnatal Obstruction in Total Anomalous Pulmonary Venous Connection.

BACKGROUND: Obstructed total anomalous pulmonary venous connection (TAPVC) is a form of critical congenital heart disease that usually requires urgent postnatal intervention. Knowing which patients have severe obstruction can aid delivery planning. The authors previously developed a novel quantitative metric of pulmonary venous flow, the pulmonary venous variability index (PVVI). The aim of this study was to test the hypothesis that fetal PVVI and vertical vein Doppler velocities are associated with severe pulmonary vein obstruction postnatally. METHODS: A retrospective cohort study of neonates with prenatally diagnosed TAPVC was performed. Patients who underwent fetal echocardiography at the Children's Hospital of Philadelphia with Doppler interrogation of the vertical vein were included for analysis. Twenty-nine patients met criteria (21 with heterotaxy, 18 with supracardiac TAPVC). The latest gestation fetal echocardiogram was used. Severe pulmonary vein obstruction was defined as preoperative death or urgent surgery or catheter-based intervention (first day of life). Measurements of PVVI, defined as (maximum velocity - minimum velocity)/mean velocity, were made offline. Wilcoxon rank sum models were used to assess the associations of severe obstruction and PVVI and maximum, mean, and minimum velocities. RESULTS: The mean gestational age at the latest fetal echocardiographic examination was 35 weeks (range, 30-39 weeks). Twelve of the 29 patients (41%) met criteria for severe pulmonary vein obstruction. Lower PVVI was associated with greater risk for severe pulmonary venous obstruction (P = .008). The maximum, mean, and minimum velocities in the vertical vein were all significantly associated with severe pulmonary venous obstruction (P = .03, P = .03, and P = .007, respectively). Qualitative assessment of obstruction was not significantly associated with the outcome. Interobserver reliability for all vertical vein Doppler metrics was high (intraclass correlation coefficient > 0.9). CONCLUSIONS: Fetal PVVI and maximum, mean, and minimum velocities are associated with severe postnatal pulmonary vein obstruction in TAPVC. Accurate prediction of obstructed TAPVC could allow safer delivery planning. Further research with larger sample sizes is needed to identify the ideal cutoff values for these Doppler measures.

Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Patient Awareness of Reported Adverse Effects Associated with Proton Pump Inhibitors in a Medically Underserved Community.

Reports of adverse effects associated with proton pump inhibitors (PPIs) are concerning because of high usage and over-the-counter availability. We sought to determine the awareness of PPI adverse effects among our patient population, which is medically underserved, low-income, and racially diverse. A 21-item survey was administered to gastroenterology-clinic outpatients. It collected information about age, gender, education, race, specialty of the prescriber, specific PPI, indication, knowledge of dose, adherence, duration of use and awareness of any risks. Medical records were reviewed to verify survey responses pertaining to indication, dosing, and adherence. A vast majority (96%) of 101 participants were not aware of PPI adverse effects. In total, 63% of the patients completed a high school education or less, which was associated with a higher risk of long-term PPI use than completion of at least an undergraduate degree (p = 0.05). In contrast to other studies, the shockingly low patient awareness about PPI adverse effects in our patient population is particularly concerning, especially as it is tied to their demographic attributes. This may lead to long-term and high-dose PPI use. Our study highlights the need for effective provider-driven education regarding medication risks, especially in the communities with significant health disparities.

A standardized imaging protocol improves quality and reduces practice variability in echocardiographic assessment of ventricular function by first-year pediatric cardiology fellows.

BACKGROUND: Echocardiography education for pediatric cardiology fellows has been a recent focus leading to the implementation of "boot camps." Less is described about continuing education through fellowship and improving image quality. We noticed practice variation in echocardiograms assessing ventricular function performed on nights and weekends. Thus, we implemented a standardized protocol and assessed its impact on imaging and reporting completeness. METHODS: We created an imaging protocol for the assessment of ventricular function in the acute setting. The protocol included demographic information, a list of images to be obtained, and the methods to quantify ventricular function. The protocol was explained to first-year fellows and distributed on an electronic quick reference card. Echocardiograms independently performed by first-year fellows during their first 4 months of on-call time were assessed pre- and postintervention using a standard rubric. RESULTS: Compliance with demographic reporting was high pre- and postintervention, but significantly improved after the standardized protocol (P < 0.001). Use of the protocol increased the median number of unique images obtained per echocardiogram from 13 to 17 (out of 23 required views, P < 0.001). Particularly improved was the performance of quantitative evaluations of function, including Simpson's method for left ventricular ejection fraction (four chamber: 40% vs 67%, P < 0.001; two chamber: 33% vs 67%, P < 0.001) and tricuspid annular plane systolic excursion (45% vs 80%, P < 0.001). CONCLUSIONS: The introduction of a standardized imaging protocol and its distribution to first-year fellows resulted in improvements in echocardiographic reporting completeness and increased the quality of information obtained by providing more quantitative assessments of ventricular function.

Echocardiographic Assessment of Diastolic Function in Children with Incident Systemic Lupus Erythematosus.

The timing and etiology of diastolic impairment in pediatric-onset systemic lupus erythematosus (SLE) are poorly understood. We compared echocardiographic metrics of left ventricular diastolic function in children at SLE diagnosis to controls and identified factors associated with diastolic indices. Echocardiograms of children aged 5-18 years within 1 year of SLE diagnosis and age-/sex-matched controls were retrospectively read by blinded cardiologists. Clinical characteristics were abstracted separately. Z-scores for diastolic indices (E/A, e', E/e', and isovolumetric relaxation time (IVRT)) were calculated using published normative data and study controls, and compared using linear mixed-effects models adjusted for blood pressure. Pericardial effusions and valvular disease were also evaluated. Linear regression was used to identify factors associated with diastolic measures. 85 children with incident SLE had echocardiograms performed a median of 6 days after diagnosis (interquartile range (IQR) 1-70). Prior cumulative prednisone exposure was minimal (median 60 mg, IQR 0-1652). SLE cases had lower E/A, lower e', higher E/e', and longer IVRT compared to controls. Though none met criteria for Grade I diastolic dysfunction, Z-scores for e', E/e', and IVRT were abnormal in 30%, 25%, and 6% of SLE cases, respectively. Greater disease activity was associated with lower septal e' (p < 0.01), higher E/e' (p = 0.02), and longer IVRT (p < 0.01). Children with incident SLE have worse diastolic indices at diagnosis compared to peers without SLE, independent of blood pressure and prior to significant prednisone exposure. Longitudinal studies will determine whether diastolic dysfunction develops in this population over time.

Echocardiographic Assessment of Right Ventricular Function in Clinically Well Pediatric Heart Transplantation Patients and Comparison With Normal Control Subjects.

BACKGROUND: Echocardiographic follow-up after pediatric heart transplantation is important because of the lifelong risk for rejection and resultant ventricular dysfunction. Although adult studies have shown that echocardiographic measures of right ventricular function are changed after transplantation, similar results have not been reported in the pediatric population. METHODS: A single-center retrospective study of echocardiograms obtained among pediatric heart transplant recipients was conducted. All echocardiograms were selected remote from transplantation, rejection, or graft vasculopathy. These criteria identified 127 patients. Right ventricular systolic function was measured using tricuspid annular plane systolic excursion, fractional area change (FAC), and peak systolic tricuspid annular tissue velocity (S'). Results were compared with those in 380 healthy age-matched echocardiographic control subjects. RESULTS: Tricuspid annular plane systolic excursion values in pediatric heart transplant recipients were significantly lower than in control subjects at all ages (P < .0001), with a mean Z score of -3.38. FAC and S' did not vary by age in control patients >6 months of age. FAC values in transplantation patients were significantly decreased compared with those in control subjects (P < .0001), but 83% of transplantation patients had FAC values within the control-derived normal range. S' values were also significantly lower in transplantation patients than control subjects (P < .0001). CONCLUSIONS: Heart transplantation patients have significantly decreased quantitative metrics of right ventricular function relative to healthy control subjects; longitudinal shortening (tricuspid annular plane systolic excursion and S') is particularly affected. FAC is relatively preserved and may be a better metric in this population. These results establish nomograms of RV function in pediatric heart transplantation patients and in normal pediatric control subjects, which may allow quantification of changes in this vulnerable population.

Development of a national cosmic-ray dose monitoring system with Health Canada's Fixed Point Surveillance network.

This work explores the application of Health Canada's Fixed Point Surveillance (FPS) network for cosmic ray monitoring and dose estimation purposes. This network is comprised of RS250 3 inch by 3 inch Sodium Iodide (NaI) spectroscopic dosimeters distributed throughout Canada. The RS250's high channel count rate responds to the electromagnetic and muonic components of cosmic ray shower. These count rates are used to infer cosmic ray doses throughout FPS locations. The derived dose was found to have an accuracy within 6.5% deviation relative to theoretical calculation. The solar cycle effect and meteorologically induced fluctuation can be realistically reflected in the estimated dose. This work may serve as a basis to enable the FPS network to monitor and report both terrestrial and cosmic radiation in quasi-real time.

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making.

Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

Teaching Antimicrobial Stewardship to Infectious Disease Fellows Through Simulated Interdisciplinary Scenarios.

Introduction: While several approaches have been described to teach antimicrobial stewardship (AS) practices, fewer have been aimed at infectious disease physicians. We developed a series of simulated AS meetings to train infectious disease fellows in the synthesis of AS interventions. Methods: Three simulated AS committee scenarios were developed. Background lectures were given 1 week prior to the simulation during which multidisciplinary roles were assigned. Precourse work included review of primary literature pertinent to the scenario. Simulations were conducted over 1.5 hours. Individual and team performances were evaluated. Pre- and postsurveys were collected from fellows and faculty members to assess the format. Results: Six infectious disease fellows participated in the series. Fellows demonstrated information synthesis and improvements in individual and team performance. Eighty-three percent of fellows before the simulation series and 100% postseries reported educating others on AS principles in the previous month. Fellows were satisfied with the series and requested more scenarios. Eight faculty members completed surveys. Thirty-eight percent of faculty before the series and 63% after completion reported that fellows viewed antimicrobial preauthorization as useful or necessary. Faculty supported the format, found it useful in evaluation of learners, and perceived that fellows benefited from the approach. Discussion: Simulation is an effective and enjoyable way to train infectious disease fellows in AS and team utilization. Fellows demonstrated improvement in AS knowledge, skills, and attitudes and developed evidence-based interdisciplinary plans to solve AS challenges. Faculty also viewed this strategy as effective and sustainable.

Efficient uncertainty minimization for fuzzy spectral clustering.

Spectral clustering uses the global information embedded in eigenvectors of an inter-item similarity matrix to correctly identify clusters of irregular shape, an ability lacking in commonly used approaches such as k -means and agglomerative clustering. However, traditional spectral clustering partitions items into hard clusters, and the ability to instead generate fuzzy item assignments would be advantageous for the growing class of domains in which cluster overlap and uncertainty are important. Korenblum and Shalloway [Phys. Rev. E 67, 056704 (2003)] extended spectral clustering to fuzzy clustering by introducing the principle of uncertainty minimization. However, this posed a challenging nonconvex global optimization problem that they solved by a brute-force technique unlikely to scale to data sets having more than O(10;{2}) items. Here we develop a method for solving the minimization problem, which can handle data sets at least two orders of magnitude larger. In doing so, we elucidate the underlying structure of uncertainty minimization using multiple geometric representations. This enables us to show how fuzzy spectral clustering using uncertainty minimization is related to and generalizes clustering motivated by perturbative analysis of almost-block-diagonal matrices. Uncertainty minimization can be applied to a wide variety of existing hard spectral clustering approaches, thus transforming them to fuzzy methods.