Search

Effective educational strategies to train and assess residents' skills in behavioral health competencies have been limited. We hypothesized that a training curriculum using virtual reality (VR) simulations would enhance residents' evidence-based skills related to behavioral health anticipatory guidance (BHAG) and motivational interviewing (MI).We conducted a randomized controlled pilot trial of our curriculum within an urban academic clinic. Intervention and control groups received four 15-minute, monthly didactics on BHAG and MI followed by VR simulations to 1) deliberately practice delivering BHAG by verbally counseling avatars, who responded real-time (intervention group) or 2) assessing pediatric respiratory distress (control group). Two months post-VR training, all residents participated in a unique VR behavioral health scenario which was recorded and coded by pediatric psychologists via an observation instrument to assess residents' skills. Differences in BHAG and MI competencies were assessed via independent samples t tests for continuous variables and Fisher's exact tests for categorical variables.Sixty-six percent (n = 55) of eligible residents completed all study protocols comprising 35 intervention and 20 control participants. Intervention participants demonstrated an increase in BHAG skills (P = .002), percentage of open-ended questions asked (P = .04), and percentage of MI adherent behaviors (P = .04) when compared to the control group.VR may be an effective educational strategy for residents to acquire BHAG and MI skills though deliberate practice. Next steps will focus on assessing the generalizability of the VR curriculum as well as exploring the opportunities to enhance its scalability through artificial intelligence.

In pediatric heart transplantation, donor: recipient weight ratio (DRWR) has long been the sole metric for size matching. Total cardiac volume (TCV)-based size matching has emerged as a novel method to precisely identify an upper limit of donor organ size of a heart transplant recipient while minimizing the risk of complications from oversizing. The clinical adoption of donor: recipient volume ratio (DRVR) to prevent short-term adverse outcomes of oversizing is unknown. The purpose of this single-center study is to determine the relationship of DRWR and DRVR to the risk of post-operative complications from allograft oversizing.Recipient TCV was measured from imaging studies and donor TCV was calculated from published TCV prediction models. DRVR was defined as donor TCV divided by recipient TCV. The primary outcome was short-term post-transplant complications (SPTC), a composite outcome of delayed chest closure and prolonged intubation7 days. A multivariable logistic regression model of DRWR (cubic spline), DRVR (linear) and linear interaction between DRWR and DRVR was used to examine the probability of experiencing a SPTC over follow-up as a function of DRWR and DRVR.A total of 106 transplant patients' records were reviewed. Risk of the SPTC increased as DRVR increased. Both low and high DRWR was associated with the SPTC. A logistic regression model including DRWR and DRVR predicted SPTC with an AUROC curve of 0.74. [95% CI 0.62 0.85]. The predictive model identified a "low-risk zone" of donor-recipient size match between a weight ratio of 0.8 and 2.0 and a TCV ratio less than 1.0.DRVR in combination with DRWR predicts short-term post-transplant adverse events. Accepting donors with high DRWR may be safely performed when DRVR is considered.

Colorectal cancer (CRC) incidence is increasing in young patients without a clear etiology. Emerging data have implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC is poorly defined.We performed a meta-analysis of fecal metagenomics sequencing data from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate features of the fecal metagenome associated with CRC. We hypothesized that known carcinogenic virulence factors (colibactin, fadA) and species abundance may be differentially enriched in young CRC patients relative to older CRC patients and controls.Summary odds ratios (OR) for CRC were increased with the presence of colibactin (OR 1.92 95% CI 1.08-3.38), fadA (OR 4.57 95% CI 1.63-12.85), and F. nucleatum (OR 6.93 95% CI 3.01-15.96) in meta-analysis models adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of Fusobacterium nucleatum (OR = 1.40 [1.18; 1.65]) and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. Species relative abundance was differentially enriched in young CRC patients for five species-Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis.In this study, we observed strong associations with CRC status for colibactin, fadA, and Fusobacterium nucleatum with CRC relative to controls. In addition, we identified several microbial species differentially enriched in young colorectal cancer patients. Studies targeting the young CRC patients are warranted to elucidate underlying preclinical mechanisms.

Background Inflammatory bowel diseases (IBDs) involve an aberrant host response to intestinal microbiota causing mucosal inflammation and gastrointestinal symptoms. Patient-reported outcomes (PROs) are increasingly important in clinical care and research. Our aim was to examine associations between PROs and fecal microbiota in patients 0 to 22 years of age with IBD. Methods A longitudinal, prospective, single-center study tested for associations between microbial community composition via shotgun metagenomics and PROs including stool frequency and rectal bleeding in ulcerative colitis (UC) and abdominal pain and stool frequency in Crohn’s disease (CD). Mucosal inflammation was assessed with fecal calprotectin. A negative binomial mixed-effects model including clinical characteristics and fecal calprotectin tested for differentially abundant species and metabolic pathways by PROs. Results In 70 CD patients with 244 stool samples, abdominal pain correlated with increased relative abundance of Haemophilus and reduced Clostridium spp. There were no differences relative to calprotectin level. In 23 UC patients with 76 samples, both rectal bleeding and increased stool frequency correlated with increased Klebsiella and reduced Bacteroides spp. Conversely, UC patients with lower calprotectin had reduced Klebsiella. Both UC and CD patients with active symptoms exhibited less longitudinal microbial community stability. No differences in metabolic pathways were observed in CD. Increased sulfoglycolysis and ornithine biosynthesis correlated with symptomatic UC. Conclusions Microbial community composition correlated with PROs in both CD and UC. Metabolic pathways differed relative to PROs in UC, but not CD. Data suggest that microbiota may contribute to patient symptoms in IBD, in addition to effects of mucosal inflammation.

Supplemental Figure 2. A) LEfSe comparing differentially abundant taxa according to 8-OH status.

Supplemental figure legends

Supplemental Figure 1. A) Non-metric dimensional scaling of the Bray-Curtis metric according to CIN status (ADONIS p=0.30; stress=0.09).

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn’s susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells., The pathogenesis of biliary atresia remains poorly understood. Here, the authors report that maternal butyrate treatment alters the gut microbiome and glutamine/hypoxanthine metabolites similar to human subjects, and suppresses biliary atresia in newborn mice.

Introduction: After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. Methods: In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after four weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise (peak oxygen consumption, peak VO2). We also aimed to assess the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Results: Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401±428 to 1428±436 mL/min, p=0.128), but VO2 at the anaerobic threshold increased (1087 + 313 to 1115 + 302 mL/min, p= 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 + 4.5 to 20.6 + 3.0 mmHg, p=0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 + 0.4 to 2.1 + 0.5 m/s, p=0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Conclusions: Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend towards lower liver stiffness. Larger, longer studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation. Clinical Trial Registration: URL: https//clinicaltrials.gov. Unique identifier: NCT04297241

Rhythm-symptom correlation in pediatric patients with syncope/palpitations or at risk cohorts can be difficult, but important given potential associations with treatable or malignant arrhythmia. We sought to evaluate the use, efficacy and outcomes of implantable loop recorders (ILR) in pediatrics. We conducted a retrospective study of pediatric patients (21 years) with implanted ILR. Patient/historical characteristics and ILR indication were obtained. Outcomes including symptom documentation, arrhythmia detection and ILR based changes in medical care were identified. Comparison of outcomes were performed based on implant indication. Additional sub-analyses were performed in syncope-indication patients comparing those with and without changes in clinical management. A total of 116 patients with ILR implant were identified (79 syncope/37 other). Symptoms were documented 58% of patients (syncope 68% vs nonsyncope 35%; p = 0.002). A total of 37% of patients had a documented clinically significant arrhythmia and 25% of patients had a resultant change in clinical management independent of implant indication. Arrhythmia type was dependent on implant indication with nonsyncope patients having more ventricular arrhythmias. Pacemaker/defibrillator implantation and mediation management were the majority of the clinical changes. In conclusion, IRL utilization in selected pediatric populations is associated with high efficacy and supports clinical management. ILR efficacy is similar regardless of indication although patients with nonsyncope indications had a higher frequency of ventricular arrhythmias as opposed to asystole and heart block in syncope indications. The majority of arrhythmic findings occurred in the first 12 months, and new technology that would allow for less invasive monitoring for 6 to 12 months may be of value.

Socioeconomic status (SES) affects a range of health outcomes but has not been extensively explored in the single ventricle population. We investigate the impact of community-level deprivation on morbidity and mortality for infants with single ventricle heart disease in the first year of life. Retrospective cohort analysis of infants enrolled in the National Pediatric Cardiology Improvement Collaborative who underwent staged single ventricle palliation examining mortality and length of stay (LOS) using a community-level deprivation index (DI). 974 patients met inclusion criteria. Overall mortality was 20.5%, with 15.7% of deaths occurring between the first and second palliations. After adjusting for clinical risk factors, the DI was associated with death (log relative hazard $${\chi }_{3}^{2}$$ = 8.92, p = 0.030) and death or transplant (log relative hazard $${\chi }_{3}^{2}$$ = 8.62, p = 0.035) in a non-linear fashion, impacting those near the mean DI. Deprivation was associated with LOS following the first surgical palliation (S1P) (p = 0.031) and overall hospitalization during the first year of life (p = 0.018). For every 0.1 increase in the DI, LOS following S1P increased by 3.35 days (95% confidence interval 0.31–6.38) and total hospitalized days by 5.08 days (95% CI 0.88–9.27). Community deprivation is associated with mortality and LOS for patients with single ventricle congenital heart disease. While patients near the mean DI had a higher hazard of one year mortality compared to those at the extremes of the DI, LOS and DI were linearly associated, demonstrating the complex nature of SES factors.

Coronary angiography remains the standard for diagnosis of cardiac transplant vasculopathy (CAV), but it is invasive. Non-invasively derived left ventricle (LV) global myocardial work (GMW) indices have not been evaluated. We aimed to assess for correlations between LV GMW and the presence of CAV in a pediatric population. 24 heart transplant patients and 24 normal controls were prospectively enrolled. Patients were age-matched into groups with: orthotopic heart transplant and CAV (OHT-CAV; 6 patients, 33% male, mean age 13.5 years [SD 4.2]), orthotopic heart transplant without CAV (OHT; 18 patients, 67% male, mean age 11.1 years [SD 4.8]), and normal healthy controls (42% male, mean age 12.8 years [SD 5.0]). Transplant patients underwent cardiac catheterization with coronary angiography within 3 months of echocardiogram. Post-processing of echocardiograms with speckle-tracking echocardiography and derivation of GMW indices was performed. OHT-CAV patients had decreased global work efficiency (GWE) compared to OHT (mean difference = 7.01 [1.76, 12.25], adjusted p

Objective The aim of the study was to assess whether responses to a standardized social risk screen administered during pediatric well-child visits (WCV) were associated with emergency department (ED) or urgent care (UC) utilization. Methods This was a retrospective cohort study of 26,509 children younger than 13 years with a WCV between January 1, 2012, and December 31, 2013. Exposure was positive response(s) on a standardized social risk screening questionnaire at the index WCV. Primary outcome was number of ED or UC visits in the 12 months after the WCV. Results The cohort was 50.9% male and 65.7% black, with a median age of 3.6 years. More than 20% had a positive response to at least one question on the social risk screen. For those reporting any social risk, 46.7% had 1 or more EDs or UC visit within 12 months. Each additional reported risk was associated with a 4% increase in the rate of ED utilization (incidence rate ratio = 1.04, 95% confidence interval = 1.02-1.07) and a 16% increase in the rate of hospitalizations (incidence rate ratio = 1.16, 95% confidence interval = 1.08-1.24). Similar patterns were noted for those visiting the ED 4 times or more (adjusted odds ratio = 1.09, 1.03-1.15) and hospitalization 2 times or more (adjusted odds ratio = 1.19, 1.04-1.35) in the year after the WCV. Those who screened positive on food insecurity, safety, and desire to meet with a social worker questions also had higher odds of ED or UC utilization. Conclusions Families reporting a social concern on a standardized screen during a WCV had increased acute care utilization in the subsequent year. Identifying socially at-risk families may allow for the creation of more effective strategies to prevent future utilization.

Background: Omega-3 fatty acid supplementation has been investigated in treating elevated triglycerides (TGs), nonalcoholic fatty liver disease (NAFLD), and low high-density lipoprotein cholesterol...

Objective Using a nested, cluster-randomized trial, we tested the hypothesis that a shared decision-making intervention, as part of consent, would improve study-related knowledge. Methods We developed a shared decision-makingintervention then randomized sites in a clinical trial to intervention or control (standard consent). We collected participants’ knowledge (primary outcome) and decisional support data. Other data came from a clinical registry and research coordinator surveys. We compared outcomes between study arms using generalized estimating equation models, accounting for clustering. We used qualitative description to understand variation in intervention use. Results 265 individuals, from 34 sites, enrolled in the parent trial during our study period. Of those, 241 participants completed our survey. There was no knowledge difference between arms (mean difference = 0.56 (95 %CI: -3.8, 4.9)). Both groups had a considerable number of participants with misunderstandings. We also found no difference for decisional support (mean difference = 1.5 (95 %CI: -1.8, 4.8)) or enrollment rate between arms. Clinician use of the intervention varied between sites. Conclusions We found no differences in outcomes but demonstrated the feasibility and acceptability of incorporating a shared decision-making intervention into consent. Practice implications Future work should consider adapting our intervention to other trials and more robust measurement strategies.

The gut microbiome plays an essential role in regulating lipid metabolism. However, little is known about how gut microbiome modulates sex differences in lipid metabolism. The present study aims to determine whether gut microbiota modulates sexual dimorphism of lipid metabolism in mice fed a high-fat diet (HFD). Conventional and germ-free male and female mice were fed an HFD for four weeks, and lipid absorption, plasma lipid profiles, and apolipoprotein levels were then evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. After 4-week HFD consumption, the females exhibited less body weight gain and body fat composition and significantly lower triglyceride levels in very-low-density lipoprotein (VLDL) and cholesterol levels in high-density lipoprotein (HDL) compared to male mice. The fecal microbiota analysis revealed that the male mice were associated with reduced gut microbial diversity. The female mice had considerably different microbiota composition compared to males, e.g., enriched growth of beneficial microbes (e.g., Akkermansia) and depleted growth of Adlercreutzia and Enterococcus. Correlation analyses suggested that the different compositions of the gut microbiota were associated with sexual dimorphism in body weight, fat mass, and lipid metabolism in mice fed an HFD. Our findings demonstrated significant sex differences in lipid metabolism and the microbiota composition at baseline (during LFD), along with sex-dependent responses to HFD. A comprehensive understanding of sexual dimorphism in lipid metabolism modulated by microbiota will help to develop more sex-specific effective treatment options for dyslipidemia and metabolic disorders in females.

Non-invasive imaging markers in patients with repaired tetralogy of Fallot (rTOF) are still being investigated to inform clinical decision making. Atrial function is a prognostic indicator in many acquired and congenital heart diseases. We sought to examine the relationship between cardiac MRI (CMR)-derived indices of left atrial (LA) function, native left ventricular (LV) T1 values, biventricular systolic function, and exercise capacity in rTOF. Sixty-six patients with rTOF without prior pulmonary valve replacement who underwent CMR (median age 18.5 years) were identified. Twenty-one adult rTOF patients (age range 19–32 years) were compared with 20 age-matched healthy volunteers (age range 19–34 years). LA reservoir, conduit, and pump global longitudinal strain (GLS) and strain rate (SR) were determined by tissue tracking. Native LV T1 values were measured on rTOF patients. Pearson correlations were performed to determine bivariate associations. Adult rTOF patients had higher pump GLS, pump:conduit, and pump:reservoir GLS ratios, and lower conduit:reservoir GLS ratio, LV ejection fraction (EF), and right ventricular EF compared to controls (p

Residential relocation (RR) is associated with behavior problems and cognitive delays in school-age children. Little is known regarding effects of RR on early childhood development. The data from this study were collected from 2011 to 2016 through the Cincinnati Home Injury Prevention and Literacy Promotion Trial. The purpose of the current study was to identify factors associated with RR and determine effects of RR on early childhood development in a cohort of mother/child dyads (n = 424). High RR was relocating ≥ 3 times over the 24-month study period. Differences in baseline characteristics and early childhood development, measured by the Ages and Stages Questionnaire (ASQ) and MacArthur Bates Communicative Development Inventory, according to relocations, were estimated by negative binomial regression and logistic regression, respectively. Participants moved on average 1.46 times over 24 months. Relocations decreased by 0.05 for each year of increasing maternal age. Mothers with college degrees moved 0.72 fewer times than those with a high school diploma or less. Mothers living alone moved 0.47 fewer times than their counterparts. Mothers who could not count on someone to loan them $1000 and those with food insecurity more (0.41) than their counterparts (0.50). Odds of scoring in the bottom-tertile for the communication domain of the ASQ was significantly higher in those relocating ≥ 3 times. High RR was associated with concern for delayed language development at 24-month follow-up in some, but not all models. Early intervention may be more successful if primary care physicians and community health professionals collaborate to link families at risk of high RR to relevant community based resources.

BACKGROUND Fetal hypoxia has been implicated in fetal growth restriction in congenital heart disease (CHD) and leads to stress erythropoiesis in utero. The objective is to assess erythropoiesis and its association with growth in newborns with CHD. METHODS Fetuses with prenatally diagnosed CHD from 2013 to 2018 were retrospectively reviewed. Pregnancies with multiple gestation, genetic abnormalities, major extra-cardiac anomalies, and placental abruption were excluded. Complete blood count tests at birth were compared to published normative values. Spearman correlation assessed associations of red blood cell (RBC) indices with birth anthropometrics and prenatal Doppler measures. RESULTS A total of 160 newborns were included. Median gestational age was 38.3 (37.3, 39.0) weeks. Infants ≥37 weeks gestation had lower hemoglobin (Hgb), hematocrit, and elevated nucleated RBC (nRBC), mean corpuscular volume, and mean corpuscular hemoglobin compared to reference. No differences in RBC indices were observed in infants

Pacemakers are a mainstay of therapy for patients with congenital and acquired heart block, but ventricular pacing is related to ventricular dysfunction. We sought to evaluate patient and device characteristics associated with ventricular dysfunction in pediatric patients with chronic ventricular pacing. This was a retrospective cohort of pediatric patients with heart block and chronic ventricular pacing. Patient, ECG, and device characteristics were analyzed to determine factors associated with ventricular dysfunction. Longitudinal ECG and echocardiogram parameters were obtained to track changes in QRS and systemic ventricular systolic function over time. In total, 82 patients were included (median age at implant 0.81 years). Over a follow-up time of 6.1 years, 18% developed ventricular dysfunction. Patients with dysfunction had greater current QRS duration (p = 0.002) compared to those with preserved function with a similar time from device implantation. There was no difference between lead location or age at device implantation. QRS duration increased with time from implant and the resultant ΔQRS was associated with ventricular dysfunction (p = 0.01). QRS duration >162 ms was associated with a 5.8 (2–9)-fold increased risk for dysfunction. Transvenous leads were associated with longer QRS duration with no difference compared to epicardial leads in development of ventricular dysfunction. This study demonstrated that the absolute paced QRS duration and Δpaced QRS were association with long-term ventricular dysfunction independent of how long a given patient was paced. Patients in high-risk categories may benefit from close echocardiographic monitoring. Whether permissive junctional rhythm or His bundle/biventricular pacing decreases the rate of dysfunction needs further study.

ObjectiveElevated central venous pressure (CVP) plays an important role in the development of adverse Fontan outcomes. Peripheral venous pressure (PVP) has been validated as a surrogate for CVP in Fontan patients. We hypothesised that PVP in response to exercise will be associated with a greater prevalence of Fontan morbidity.MethodsAdult Fontan patients had cardiopulmonary exercise testing (CPET) with PVP monitoring in the upper extremity between 2015 and 2018. PVP at rest, during unloaded cycling and at peak exercise was compared between those with and without adverse Fontan outcomes including arrhythmia, unscheduled hospital admissions, heart failure requiring diuretics, need for reintervention and a composite outcome of the above morbidities, heart transplantation and death.ResultsForty-six patients with a mean age at CPET of 26.9±9.5 years. During exercise, PVP increased from 13.6±3.5 mm Hg at rest, to 16.5±3.9 mm Hg during unloaded cycling, to 23.0±5.5 mm Hg at peak exercise. Unloaded and peak PVP were more strongly associated than resting PVP with all adverse outcomes, except reintervention (composite outcome: resting PVP: OR 2.8, p=0.023; unloaded PVP: OR 6.1, p=0.001; peak PVP: OR 4.0, pConclusionHigher PVP at unloaded and peak exercise was strongly associated with a higher prevalence of adverse Fontan outcomes. Minimally invasive PVP monitoring during CPET may serve as a useful tool for risk stratifying individuals with a Fontan.

Respiratory microbiome is an understudied area of research compared to other microbiomes of the human body. The respiratory tract is exposed to an array of environmental pollutants, including microbes. Yet, we know very little about the relationship between environmental and respiratory microbiome. The primary aim of our study was to compare the mycobiomes and bacteriomes between three sample types from the same participants, including home dust, saliva, and sputum. Samples were collected from 40 adolescents in a longitudinal cohort. We analyzed the samples using 16s bacterial rDNA and ITS fungal rDNA gene sequencing, as well as quantitative PCR with universal fungal and bacterial primers. Results showed that home dust had the greatest alpha diversity between the three sample types for both bacteria and fungi. Dust had the highest total fungal load and the lowest total bacterial load. Sputum had greater bacterial diversity than saliva, but saliva had greater fungal diversity than sputum. The distribution of major bacterial phyla differed between all sample types. However, the distribution of major fungal classes differed only between sputum and saliva. Future research should examine the biological significance of the taxa found in each sample type based on microbial ecology and associations with health effects.

To assess atrial function in Fontan patients using cardiac MRI (CMR) and determine the relationships between atrial function, hemodynamics, and clinical outcomes. Two center chart review identified all Fontan patients with technically adequate CMR to assess atrial function within 1 year of cardiac catheterization and age-matched controls with CMR. Atrial reservoir, conduit, and pump global longitudinal strain and strain rate measurements were determined by CMR. Univariate and stepwise multivariable analysis were conducted to detect associations of atrial function measures with ventricular end diastolic pressure (EDP), cardiac index (CI), exercise capacity, liver stiffness and a composite outcome of heart transplantation, ventricular assist device or death. The study cohort was comprised of 33 Fontan patients and 30 age-matched controls. Fontan patients had lower atrial reservoir and conduit strain, and lower reservoir, conduit, and pump strain rate compared to age-matched controls. Atrial conduit strain was negatively associated with EDP and lower atrial pump-to-conduit strain ratio was associated with lower cardiac index in multivariable analysis. Lower atrial pump strain was associated with lower exercise capacity (per 1% increase: β = 2.3 ± 0.9, p = 0.03) and higher liver stiffness (per 1% increase: β = − 0.12 ± 0.03, p = 0.002). Higher atrial pump strain (HR per 1% increase = 0.53 [95% confidence interval 0.22, 0.83], p = 0.002) and ventricular ejection fraction (HR per 1% increase = 0.90 [95% confidence interval 0.80, 0.98], p = 0.02) were associated with lower risk for the composite adverse outcome. Atrial function is impaired in Fontan patients and is associated with worse CI, EDP, exercise performance, liver stiffness, and a higher risk for adverse outcomes.

Objectives To examine the association between maternal body dissatisfaction and mother's (mis)perception of their infant's weight classification among families from low-income households. Methods Mother-infant dyads were recruited during well-child visits from two urban primary care clinics. Maternal body dissatisfaction was measured using the Stunkard Figure Rating Scale. Perception of infant weight was assessed using a 5-point Likert scale. Infant weight-for-length (WFL) percentiles were calculated using WHO growth charts. Associations between maternal body dissatisfaction score and mother's (mis)perception of their infant's weight classification were examined using logistic regression allowing for non-linear associations via restricted cubic splines. Results Mothers (n=180) were 26.6 ± 5.1 years old and 72% Black; infants were 8.8 ± 2.1 months old. Mean infant WFL percentile was 64 ± 26. On average, mothers wanted to be one body figure smaller than their perceived current body size. Most mothers (82%) accurately perceived their infant's weight classification while few overestimated (7%) or underestimated (11%) their child's weight category. The probability of mothers misperceiving their infant's weight classification increased as maternal body dissatisfaction increased in either extreme in unadjusted (p Conclusions Increased maternal body dissatisfaction may be associated with mother's misperception of infant weight classification. Future studies should examine this relationship in a heterogeneous population.

Objectives To assess clinically asymptomatic infants with single-ventricle physiology (SVP) for sleep-disordered breathing (SDB) in the supine and car seat positions using polysomnography. Polysomnography results also were compared with results of a standard Car Seat Challenge to measure the dependability of the standard Car Seat Challenge. Study design This was an observational study of 15 infants with SVP. Polysomnography data included Obstructive Index, Central Index, Arousal Index, Apnea Hypopnea Index, and sleep efficiency. Polysomnography heart rate and oxygen saturation data were used to compare polysomnography with the standard Car Seat Challenge. Results Polysomnography demonstrated that all 15 infants had SDB and 14 had obstructive sleep apnea (Obstructive Index ≥1/hour) in both the supine and car seat positions. Infants with SVP had a statistically significant greater median Obstructive Index in the car seat compared with supine position (6.3 vs 4.2; P = .03), and median spontaneous Arousal Index was greater in the supine position compared with the car seat (20.4 vs 15.2; P = .01). Comparison of polysomnography to standard Car Seat Challenge results demonstrated 5 of 15 (33%) of infants with SVP with abnormal Obstructive Index by polysomnography would have passed a standard Car Seat Challenge. Conclusions Infants with SVP without clinical symptoms of SDB may be at high risk for SDB that appears worse in the car seat position. The standard Car Seat Challenge is not dependable in the identification of infants with SVP and SDB. Further studies are warranted to further delineate its potential impact of SDB on the clinical outcomes of infants with SVP.

Although the strongest predictor of human papillomavirus (HPV) vaccination is a high-quality recommendation, physicians often provide weak recommendations. Thus, the authors developed Virtual Immersive Communication Training on Recommending Immunizations (VICTORI), a virtual reality (VR)‒based intervention that provided physicians the opportunity to deliberately practice recommendation behaviors. VICTORI included VR simulations during which participants counseled caregiver avatars hesitant to vaccinate. Before participation in VICTORI, participants reviewed a smartphone application on recommendation behaviors. A nonrandomized control trial of VICTORI was conducted with licensed and resident physicians. The intervention group completed the application and VICTORI simulations, whereas a comparison group completed only the application. The hypothesis was that HPV vaccination rates would increase for patients in the intervention group. The preintervention period was defined as the 6 months before allocated training (February 1, 2020-July 31, 2020), and the postintervention period was the 6 months after (October 1, 2020-March 31, 2021). The primary outcome was a change in the rates of human papillomavirus vaccine initiation among eligible patients presenting to clinic before and after. Of 142 eligible physicians, 134 (94%) chose to participate, with 93 of /97 (96%) intervention and 30 of 37 (81%) comparison participants completing study protocols. There was a statistically significant increase in patients' HPV vaccine initiation rates after training within the intervention group (54.3%‒72.4%; 18.1% difference [95% CI=11.0, 25.8]; p0.001) but not within the comparison group (59.5%‒63.4%; 3.9% difference [95% CI= -11.0, 19.0]; p=0.609). In conclusion, HPV vaccine initiation increased after VR training, and further study is warranted.

Pulmonary arterial hypertension (PAH) is a progressive, ultimately fatal cardiopulmonary disease associated with a number of physiologic changes, which is believed to result in imbalances in the intestinal microbiota. To date, comprehensive investigational analysis of the intestinal microbiota in human subjects is still limited. To address this, we performed a pilot study of the intestinal microbiome in 20 PAH and 20 non-PAH healthy control subjects, recruited from a single center, with each PAH subject recruited simultaneously with a cohabitating non-PAH control subject. Shotgun metagenomic sequencing was used to analyze the microbiome profiles. There were no differences between PAH and non-PAH subjects across several measures of microbial abundance and diversity (Alpha Diversity, Beta Diversity, F/B ratio). The relative abundance of

Background: Vedolizumab for inflammatory bowel disease (IBD) is often intensified based on distinct pharmacokinetics in children. Prior adult-specific population pharmacokinetic models have identified limited covariates of drug clearance. Aims: To establish a population pharmacokinetic model for children and young adults to identify novel covariates of drug clearance to better account for paediatric-specific inter-patient variability in vedolizumab pharmacokinetics; a key secondary exploratory aim was to identify microbial signatures of pharmacokinetic outcomes in a subset of patients. Methods: The study included data from 463 observed vedolizumab concentrations (59 peaks and 404 troughs) from 74 patients with IBD (52 with Crohn's disease and 22 with ulcerative colitis or unclassified IBD, median age 16 years). Pharmacokinetic analysis was conducted with non-linear mixed effects modelling. For the evaluation of the exposure–response relationship, clinical outcomes were evaluated by trough levels, clearance and vedolizumab exposure. Whole-genome metagenomic sequencing was conducted at baseline and week 2. Results: A two-compartment population pharmacokinetic model was identified with a clear correlation between CL and weight, erythrocyte sedimentation rate, and hypoalbuminemia. Trough concentrations before infusion 3 (37 μg/ml) and before infusion 4 (20 μg/ml) best predicted steroid-free clinical remission at infusion 4. Using faecal metagenomics, we identified an early (baseline and week 2) abundance of butyrate-producing species and pathways that were associated with an infusion 4 trough concentration >20 μg/ml. Conclusions: This novel paediatric vedolizumab pharmacokinetic model could inform precision dosing. While additional studies are needed, an abundance of faecal butyrate producers is associated with early response to vedolizumab, suggesting that microbial analysis may be beneficial to biological selection.

Introduction: After the Fontan operation, decreased venous capacitance (venoconstriction) and elevated central venous pressure may result in worse clinical outcomes, worse exercise capacity, and increased liver stiffness. This pilot study evaluated the acute effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. Methods: In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after four weeks of treatment with ISDN. Cardiopulmonary exercise testing was performed to assess exercise tolerance, with a primary outcome of peak oxygen consumption (peak VO 2 ). The secondary outcome included VO 2 at the anaerobic threshold (AT VO 2 ), PVP at rest and peak exercise and liver stiffness measured by ultrasound prior to the exercise test. Repeated measure t-test was used to test for differences in outcomes in response to ISDN. Results: The mean age was 23.5 ± 9.2 years (range 11.2-30.6 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO 2 from baseline (1401±428 to 1428±436 ml/min, p=0.128), but there was an improvement in AT VO 2 (1087 ± 313 to 1115 ±302 mL/min, p= 0.03). Treatment with ISDN was associated with lower peak exercise PVP (22.5 ±4.5 to 20.6 ± 2.99 mmHg, p=0.015) without a notable difference in the resting PVP (p=0.357). There was a trend towards lower liver stiffness with ISDN (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p=0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Conclusions: Treatment with ISDN for 4 weeks is well-tolerated except for headache and appears safe in patients with a Fontan circulation. ISDN therapy was associated with improvements in certain exercise and hemodynamic parameters as well as a trend towards lowering liver stiffness. Larger studies will be necessary to validate these physiologic findings and further evaluate the effects of nitrates on meaningful clinical outcomes.

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty‐two US pediatric institutions participated in a 10‐year review (2008–2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract‐based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community deprivation were obtained. Data for 947 cases showed median age at diagnosis of 9 years; 51% and 56% identified as male and non‐White, respectively. Most (89%) had health insurance and were first diagnosed in the United States (82%). Only 13% reported travel to an endemic region before diagnosis. Although 96% of patients were prescribed secondary prophylaxis, only 58% were prescribed intramuscular benzathine penicillin G. Higher deprivation was associated with increasing disease severity (odds ratio, 1.25; 95% CI, 1.08–1.46). Conclusions The majority of recent US cases of ARF and RHD are endemic rather than the result of foreign exposure. Children who live in more deprived communities are at risk for more severe disease. This study demonstrates a need to improve guideline‐based treatment for ARF/RHD with respect to secondary prophylaxis and to increase research efforts to better understand ARF and RHD in the United States.

Coronary angiography remains the standard for diagnosis of cardiac transplant vasculopathy (CAV), but it is invasive. Non-invasively derived left ventricle (LV) global myocardial work (GMW) indices have not been evaluated. We aimed to assess for correlations between LV GMW and the presence of CAV in a pediatric population. 24 heart transplant patients and 24 normal controls were prospectively enrolled. Patients were age-matched into groups with: orthotopic heart transplant and CAV (OHT-CAV; 6 patients, 33% male, mean age 13.5 years [SD 4.2]), orthotopic heart transplant without CAV (OHT; 18 patients, 67% male, mean age 11.1 years [SD 4.8]), and normal healthy controls (42% male, mean age 12.8 years [SD 5.0]). Transplant patients underwent cardiac catheterization with coronary angiography within 3 months of echocardiogram. Post-processing of echocardiograms with speckle-tracking echocardiography and derivation of GMW indices was performed. OHT-CAV patients had decreased global work efficiency (GWE) compared to OHT (mean difference = 7.01 [1.76, 12.25], adjusted p 0.01). LV global longitudinal strain (GLS) and LV ejection fraction were not different between groups. Both global work index and GWE were decreased in OHT-CAV and OHT when compared to normal controls (OHT-CAV 1311.23 mmHg% vs OHT 1426.22 mmHg% vs controls 1802.81 mmHg%, adjusted p 0.01; OHT-CAV 83.87% vs. OHT 90.87% vs. controls 95.41%, adjusted p 0.01). GWE correlated negatively with the presence of CAV (r = - 0.44 [- 0.72, - 0.05]). This pilot study demonstrates decreased GWE correlates with pediatric CAV. This supports the need for further investigation of this promising diagnostic tool.

Left ventricular (LV) mass is a major determining tool for myocardial injury in hypertensive patients. Issues with LV mass calculations exist given that there are multiple methods to assess mass, including from the parasternal long axis (PLA), parasternal short axis (PSA), and 2-dimensional (2D) volumetric methods. The aim of this study was to compare the agreement of LV mass calculations using the PLA, PSA, and 2D volumetric methods. This study retrospectively reviewed 200 consecutive, initial echocardiograms for the indication of hypertension. A single reader calculated the LV mass in each patient via the PLA, PSA, and 2D volumetric methods. Percent differences for each study were calculated. LV mass threshold cutoffs of 51 g/m2.7 (cardiac organ injury) and 38.6 g/m2.7 (elevated LV mass) were used to compare categorical differences between the different measurement methods. Paired comparisons demonstrated an absolute mean percent difference of 8.46% to 9.41% among the different methods. LV mass calculated by the 2D volumetric method was less compared with PLA and PSA methods (31.64 vs 33.90 vs 35.51 g/m2.7; p

ObjectivesCalcific aortic valve disease (CAVD) is a progressive disease ranging from aortic valve (AoV) sclerosis to AoV stenosis (AS), characterised by severe calcification with impaired leaflet function. Due to the lack of early symptoms, the pathological progression towards valve dysfunction is poorly understood. The early patterns of AoV calcification and altered extracellular matrix (ECM) organisation were analysed in individuals postmortem without clinical AS compared with clinical AS.MethodsHistological patterns of calcification and ECM organisation in postmortem AoV leaflets without clinical AS obtained from a tissue repository and surgical specimens obtained from individuals with clinical AS were compared with in vivo imaging prior to transcatheter AoV implantation.ResultsAoV calcification was detected in all samples from individuals >50 years old, with severity increasing with age, independent of known CAVD risk factors. Two distinct types of calcification were identified: ‘Intrinsic’, primarily found at the leaflet hinge of postmortem leaflets, accompanied by abnormal collagen and proteoglycan deposition; and ‘Nodular’, extending from the middle to the tip regions in more severely affected postmortem leaflets and surgical specimens, associated with increased elastin fragmentation and loss of elastin integrity. Even in the absence of increased thickening, abnormalities in ECM composition were observed in postmortem leaflets without clinical AS and worsen in clinical AS.ConclusionsTwo distinct phenotypes of AoV calcification are apparent. While the ‘nodular’ form is recognised on in vivo imaging and is present with CAVD and valve dysfunction, it is unclear if the ‘intrinsic’ form is pathological or detected on in vivo imaging.

Objective To determine the impact of a curriculum that included parent feedback, via the Communication Assessment Tool (CAT), on resident communication skills. Methods In a prospective, controlled study, categorical pediatric residents in continuity clinic were divided into control and intervention groups based on clinic day. Parent feedback was obtained for all residents at the beginning and end of the year using the CAT, a validated survey to assess physician communication. Intervention residents participated in learning conferences that reviewed communication best practices and received parental feedback via individual and group CAT scores. Scores were dichotomized as 5 (excellent) versus 1 to 4 (less than excellent) and reported as percentage of items rated excellent. Curriculum impact was assessed by comparing score changes between groups. Residents’ scores in both arms were combined to assess changes from the beginning of the year to the end. Statistical testing was performed using generalized linear mixed-effects models. Results All residents (N = 68) participated. Intervention (n = 38) and control (n = 30) residents received at least 10 CATs at the beginning and end of the year. The percentage of parents rating all items as excellent increased by similar percentages in intervention and control groups (60.9%–73.8% vs 61.1%–69.8; P = .38). When scores of residents in both arms were combined, improvement was found from the beginning to the end of the year for all CAT items (P Conclusions A curriculum including parent feedback from CATs did not significantly impact communication skills. However, communication skills improved over the year in intervention and control groups, suggesting that communication training occurs in multiple settings.

Background Exposure to particulate matter has been shown to increase the adhesion of bacteria to human airway epithelial cells. However, the impact of traffic-related air pollution (TRAP) on the respiratory microbiome is unknown. Methods Forty children were recruited through the Cincinnati Childhood Allergy and Air Pollution Study, a longitudinal cohort followed from birth through early adolescence. Saliva and induced sputum were collected at age 14 years. Exposure to TRAP was characterized from birth through the time of sample collection using a previously validated land-use regression model. Sequencing of the bacterial 16S and ITS fungal rRNA genes was performed on sputum and saliva samples. The relative abundance of bacterial taxa and diversity indices were compared in children with exposure to high and low TRAP. We also used multiple linear regression to assess the effect of TRAP exposure, gender, asthma status, and socioeconomic status on the alpha diversity of bacteria in sputum. Results We observed higher bacterial alpha diversity indices in sputum than in saliva. The diversity indices for bacteria were greater in the high TRAP exposure group than the low exposure group. These differences remained after adjusting for asthma status, gender, and mother’s education. No differences were observed in the fungal microbiome between TRAP exposure groups. Conclusion Our findings indicate that exposure to TRAP in early childhood and adolescence may be associated with greater bacterial diversity in the lower respiratory tract. Asthma status does not appear to confound the observed differences in diversity. These results demonstrate that there may be a TRAP-exposure related change in the lower respiratory microbiota that is independent of asthma status.