Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Synergistic association of fluid overload and acute kidney injury on outcomes in pediatric cardiac ECMO: a retrospective analysis of the KIDMO database.

BACKGROUND: Acute kidney injury (AKI) and fluid overload (FO) are associated with poor outcomes in children receiving extracorporeal membrane oxygenation (ECMO). Our objective is to evaluate the impact of AKI and FO on pediatric patients receiving ECMO for cardiac pathology. METHODS: We performed a secondary analysis of the six-center Kidney Interventions During Extracorporeal Membrane Oxygenation (KIDMO) database, including only children who underwent ECMO for cardiac pathology. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. FO was defined as < 10% (FO-) vs. ≥ 10% (FO +) and was evaluated at ECMO initiation, peak during ECMO, and ECMO discontinuation. Primary outcomes were mortality and length of stay (LOS). RESULTS: Data from 191 patients were included. Non-survivors (56%) were more likely to be FO + than survivors at peak ECMO fluid status and ECMO discontinuation. There was a significant interaction between AKI and FO. In the presence of AKI, the adjusted odds of mortality for FO + was 4.79 times greater than FO- (95% CI: 1.52-15.12, p = 0.01). In the presence of FO + , the adjusted odds of mortality for AKI + was 2.7 times higher than AKI- [95%CI: 1.10-6.60; p = 0.03]. Peak FO + was associated with a 55% adjusted relative increase in LOS [95%CI: 1.07-2.26, p = 0.02]. CONCLUSIONS: The association of peak FO + with mortality is present only in the presence of AKI + . Similarly, AKI + is associated with mortality only in the presence of peak FO + . FO + was associated with LOS. Studies targeting fluid management have the potential to improve LOS and mortality outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Olfactomedin 4-Positive Neutrophils Are Upregulated after Hemorrhagic Shock.

Neutrophils are vital to both the inflammatory cascade and tissue repair after an injury. Neutrophil heterogeneity is well established but there is less evidence for significant, different functional roles for neutrophil subsets. OLFM4 (Olfactomedin-4) is expressed by a subset of neutrophils, and high expression of OLFM4 is associated with worse outcomes in patients with sepsis and acute respiratory distress syndrome. We hypothesized that an increased number of OLFM4+ neutrophils would occur in trauma patients with worse clinical outcomes. To test this, we prospectively enrolled patients who suffered a blunt traumatic injury. Blood was collected at the time of admission, Day 3, and Day 7 and analyzed for the percentage of neutrophils expressing OLFM4. We found that a subset of patients who suffered blunt traumatic injury upregulated their percentage of OLFM4+ neutrophils. Those who upregulated their OLFM4 had an increased length of stay, days in the ICU, and ventilator days. A majority of these patients also suffered from hemorrhagic shock. To establish a potential role for OLFM4+ neutrophils, we used a murine model of hemorrhagic shock because mice also express OLFM4 in a subset of neutrophils. These studies demonstrated that wild type mice had higher concentrations of cytokines in the plasma and myeloperoxidase in the lungs compared with OLFM4-null mice. In addition, we used an anti-OLFM4 antibody, which when given to wild type mice led to the reduction of myeloperoxidase in the lungs of mice. These findings suggest that OLFM4+ neutrophils are a unique subset of neutrophils that affect the inflammatory response after tissue injury.

A novel, composite measure of screen-based media use in young children (ScreenQ) and associations with parenting practices and cognitive abilities.

BACKGROUND: Screen-based media use is prevalent in children and is associated with health risks. American Academy of Pediatrics (AAP) recommendations involve access to screens, frequency, content, and co-viewing. The aim of this study was to test the ScreenQ, a composite measure of screen-based media use. METHODS: ScreenQ is a 15-item parent report measure reflecting AAP recommendations. Range is 0-26, higher scores reflecting greater non-adherence. With no "gold standard" available, four validated measures of skills and parenting practices cited as influenced by overuse were applied as the external criteria, including expressive language, speed of processing, emergent literacy, and cognitive stimulation at home. Psychometric analyses involved Rasch methods and Spearman's ρ correlations. RESULTS: Sixty-nine families were administered ScreenQ. Child age ranged from 36 to 63 months old (52 ± 8; 35 girls). Mean ScreenQ score was 9.6 (±5.0; 1-22). Psychometric properties were strong (rCo-α = 0.74). ScreenQ scores were negatively correlated with CTOPP-2 (Comprehensive Test of Phonological Processing, Second Edition) (rρ = -0.57), EVT-2 (Expressive Vocabulary Test, Second Edition) (rρ = -0.45), GRTR (Get Ready to Read!) (rρ = -0.30) and StimQ-P (rρ = -0.42) scores (all p ≤ 0.01). CONCLUSIONS: ScreenQ shows potential as a composite measure of screen-based media use in young children in the context of AAP recommendations. ScreenQ scores were correlated with lower executive, language and literacy skills, and less stimulating home cognitive environment.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy: a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to characterize continuous renal replacement therapy (CRRT) utilization on extracorporeal membrane oxygenation (ECMO) and to determine the association of both fluid overload (FO) at CRRT initiation and fluid removal during CRRT with mortality in a large multicenter cohort. METHODS: Retrospective chart review of all children < 18 years of age concurrently treated with ECMO and CRRT from January 1, 2007, to December 31, 2011, at six tertiary care children's hospital. Children treated with hemodialysis or peritoneal dialysis were excluded from the FO analysis. MEASUREMENTS AND MAIN RESULTS: A total of 756 of the 1009 children supported with ECMO during the study period had complete FO data. Of these, 357 (47.2%) received either CRRT or were treated with an in-line filter and thus entered into the final analysis. Survival to ECMO decannulation was 66.4% and survival to hospital discharge was 44.3%. CRRT initiation occurred at median of 1 day (IQR 0, 2) after ECMO initiation. Median FO at CRRT initiation was 20.1% (IQR 5, 40) and was significantly lower in ECMO survivors vs. non-survivors (15.3% vs. 30.5% p = 0.005) and in hospital survivors vs. non-survivors (13.5% vs. 25.9%, p = 0.004). Median FO at CRRT discontinuation was significantly lower in ECMO survivors (23% vs. 37.6% p = 0.002) and hospital survivors vs. non-survivors (22.6% vs. 36.1%, p = 0.002). In ECMO survivors, after adjusting for pH at CRRT initiation, non-renal complications, ECMO mode, support type, center, patient age and AKI, FO at CRRT initiation (p = 0.01), and FO at CRRT discontinuation (p = 0.0002) were independently associated with duration of ECMO. In a similar multivariable analysis, FO at CRRT initiation (adjusted adds ratio [aOR] 1.09, 95% CI 1.00-1.18, p = 0.045) and at CRRT discontinuation (aOR 1.11, 95% CI 1.03-1.19, p = 0.01) were independently associated with hospital mortality. CONCLUSIONS: In a multicenter pediatric ECMO cohort, this study demonstrates that severe FO was very common at CRRT initiation. We found an independent association between the degree of FO at CRRT initiation with adverse outcomes including mortality and increased duration of ECMO support. The results suggest that intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.

Impact of an Immersive Virtual Reality Curriculum on Medical Students' Clinical Assessment of Infants With Respiratory Distress.

OBJECTIVE: To determine whether exposure to an immersive virtual reality curriculum on pediatric respiratory distress improves medical students' recognition of impending respiratory failure. DESIGN: Randomized, controlled, prospective study conducted from July 2017 to June 2018. Evaluators blinded to student groupings. SETTING: Academic, free-standing children's hospital. PARTICIPANTS: All third-year medical students (n = 168) were eligible. The standard curriculum was delivered to all students during their pediatric rotation with optional inclusion of research data per Institutional Review Board review. A randomized selection of students was exposed to the virtual reality curriculum. INTERVENTION: All students received standard training on respiratory distress through didactics and high-fidelity mannequin simulation. Intervention students underwent an additional 30-minute immersive virtual reality curriculum, experienced through an OculusRift headset, with three simulations of an infant with 1) no distress, 2) respiratory distress, and 3) impending respiratory failure. MEASUREMENTS AND MAIN RESULTS: The impact of the virtual reality curriculum on recognition/interpretation of key examination findings, assignment of an appropriate respiratory status assessment, and recognition of the need for escalation of care for patients in impending respiratory failure was assessed via a free response clinical assessment of video vignettes at the end of the pediatric rotation. Responses were scored on standardized rubrics by physician experts. All eligible students participated (78 intervention and 90 control). Significant differences between intervention and control were demonstrated for consideration/interpretation of mental status (p < 0.01), assignment of the appropriate respiratory status assessment (p < 0.01), and recognition of a need for escalation of care (p = 0.0004). CONCLUSIONS: Exposure to an immersive virtual reality curriculum led to improvement in objective competence at the assessment of respiratory distress and recognition of the need for escalation of care for patients with signs of impending respiratory failure. This study represents a novel application of immersive virtual reality and suggests that it may be effective for clinical assessment training.

Pre-operative neutrophil-lymphocyte ratio predicts low cardiac output in children after cardiac surgery.

Neutrophil-lymphocyte ratio has been associated with clinical outcomes in several groups of cardiac patients, including patients with coronary artery disease, cardiac failure, and cardiac transplant recipients. We hypothesised that pre- and/or post-operative haematological cell counts are associated with clinical outcomes in children undergoing cardiac surgery for CHD. We performed a post hoc analysis of data collected as part of a prospective observational cohort study (n = 83, data available n = 47) of children evaluated for glucocorticoid receptor levels after cardiac surgery (July 2015-January 2016). The association of neutrophil-lymphocyte ratio with low cardiac output syndrome, time to inotrope free, and vasoactive-inotropic score was examined using proportional odds analysis, cox regression, and linear regression models, respectively. A majority (80%) of patients were infants (median/interquartile range 4.1/0.2-7.6 months) with conotruncal (36%) and left-sided obstructed lesions (28%). Two patients required mechanical circulatory support and three died. Higher pre-operative neutrophil-lymphocyte ratio was associated with higher cumulative odds of severe/moderate versus mild low cardiac output on post-operative day 1 (odds ratio 2.86; 95% confidence interval 1.18-6.93; p = 0.02). Pre-operative neutrophil-lymphocyte ratio was not significantly associated with time to inotrope free or vasoactive-inotrope score. Post-operative neutrophil-lymphocyte ratio was also not associated with outcomes. In children after congenital heart surgery, higher pre-operative neutrophil-lymphocyte ratio was associated with a higher chance of low cardiac output in the early post-operative period. Pre-operative neutrophil-lymphocyte ratio maybe a useful prognostic marker in children undergoing congenital heart surgery.

Utility of Diagnostic Studies for Upper Gastrointestinal Symptoms in Children with Orthostatic Intolerance.

OBJECTIVE: To assess the utility of gastrointestinal (GI) diagnostic studies in the evaluation of patients with orthostatic intolerance. STUDY DESIGN: Medical records of 103 consecutive children/young adults with orthostatic intolerance and gastrointestinal symptoms were reviewed. All patients had undergone antroduodenal manometry in conjunction with the tilt table test, autonomic testing, and upper gastrointestinal endoscopy (EGD). A gastric emptying study (GES) was performed in 81 patients. RESULTS: The median age of the cohort was 17 years (IQR, 15-19) with a female predominance (females:males, 3:1). As expected, the tilt table test was abnormal in all patients. Antroduodenal manometry was abnormal in 83 of 103 patients (81%), showing neurogenic intestinal dysmotility in 50%, rumination in 20%, and visceral hyperalgesia in 10%. The GES results were abnormal in 23 of 81 patients (28.4%), mostly (21 of 23) with delayed GES. None of the tilt table test or autonomic results were predictive of abnormal antroduodenal manometry or GES. Analysis of EGD biopsy samples revealed nonspecific esophagitis and/or gastritis in 16 of 103 patients (15%). CONCLUSIONS: Antroduodenal manometry with the tilt table test were the most insightful investigations in adolescents and young adults with orthostatic intolerance and gastrointestinal symptoms. GES and EGD provided limited information. Gastrointestinal symptoms were related more to functional rather than mucosal or organic etiologies, suggesting a limited role of endoscopy alone in evaluating patients with orthostatic intolerance presenting with gastrointestinal symptoms.

Fetal somatic growth trajectory differs by type of congenital heart disease.

BackgroundThe growth trajectories of common measurements, including estimated fetal weight (EFW), head circumference (HC), and abdominal circumference (AC), in fetuses with congenital heart disease (CHD) have not been described for different cardiac lesions. We hypothesized that (i) fetuses with CHD have differential growth in utero, and (ii) different categories of CHD demonstrate different in utero growth curves.MethodsWe performed a retrospective observational cohort study of pregnancies with known fetal CHD seen from January 2000 to June 2013. For analysis, the infants were divided into single ventricle (SV), biventricular conotruncal, d-transposition of great arteries (d-TGA), biventricular septal defects (SD; including atrial, ventricular, and atrioventricular SD), and all others (Other).ResultsA total of 194 newborns met inclusion criteria. There was significant differential growth of EFW in all CHD types, except d-TGA, starting with low z-scores before 25 weeks gestation, improving toward normal around 30-32 weeks gestation, and then again differential growth with advancing gestation. SV and SD groups had significant differential growth of HC starting early in gestation and linearly progressing negative z-scores with advancing gestation.ConclusionWe observed differences in the fetal growth curves throughout gestation for the major categories of CHD, including significant differential growth in even "simple" CHD, such as SD.

Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery.

OBJECTIVES: Postoperative administration of corticosteroids is common practice for managing catecholamine refractory low cardiac output syndrome. Since corticosteroid activity is dependent on the glucocorticoid receptor, we sought to characterize glucocorticoid receptor levels in children undergoing cardiac surgery and examined the association between glucocorticoid receptor levels and cardiovascular dysfunction. DESIGN: Prospective observational cohort study. SETTING: Large, tertiary pediatric cardiac center. SUBJECTS: Children undergoing corrective or palliative cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A prospective observational cohort study was conducted in 83 children with congenital heart disease. Total glucocorticoid receptor levels were measured in the peripheral WBCs using flow cytometry. In addition, blood samples were collected for total cortisol levels. The primary outcome studied was the time to being inotrope free. An increase in glucocorticoid receptor level from postoperative day 1 to postoperative day 3 was associated with a longer time to being inotrope free (hazard ratio, 0.49 [0.29-0.81]; p = 0.01) in the univariate analysis. This association remained significant after adjusting for age, weight, cardiopulmonary bypass time, cross clamp time, Risk Adjustment for Congenital Heart Surgery-1 score, and postoperative steroid use (hazard ratio, 0.53 [0.29-0.99]; p = 0.05). Postoperative day 3 glucocorticoid receptor level showed a trend to have longer time to being inotrope free (hazard ratio, 0.66 [0.42-1.02]; p = 0.0.06). The cortisol levels minimally increased during the study duration and did not correlate with glucocorticoid receptor levels. CONCLUSIONS: Increasing glucocorticoid receptor levels in peripheral WBCs of children undergoing cardiac surgery are associated with a longer time to being inotrope free. Cortisol levels minimally increased during the study duration. These results suggest that exposure to high-dose perioperative corticosteroids may suppress the hypothalamic-pituitary-adrenal axis leading to increase in glucocorticoid receptor levels in response to a low cortisol environment. Further studies are required to better delineate the interplay between glucocorticoid receptor levels, cortisol levels, corticosteroid exposure, and postoperative inotropic requirements.

Utility of Echocardiography in the Assessment of Left Ventricular Diastolic Function and Restrictive Physiology in Children and Young Adults with Restrictive Cardiomyopathy: A Comparative Echocardiography-Catheterization Study.

The aim of the study is to determine the utility of echocardiography in the assessment of diastolic function in children and young adults with restrictive cardiomyopathy (RCM). RCM is a rare disease with high mortality requiring frequent surveillance. Accurate, noninvasive echocardiographic measures of diastolic function may reduce the need for invasive catheterization. Single-center, prospective, observational study of pediatric and young adult RCM patients undergoing assessment of diastolic parameters by simultaneous transthoracic echocardiogram (TTE) and invasive catheterization. Twenty-one studies in 15 subjects [median (IQR) = 13.8 years (7.0-19.2), 60% female] were acquired with median left ventricular end-diastolic pressure (LVEDP) 21 (IQR 18-25) mmHg. TTE parameters of diastolic function, including pulmonary vein A wave duration (r s  = 0.79) and indexed left atrial volume (r s  = 0.49), demonstrated significant positive correlation, while mitral valve A (r s  = -0.44), lateral e' (r s  = -0.61) and lateral a' (r s  = -0.61) velocities showed significant negative correlation with LVEDP. Lateral a' velocity (≤0.042 m/s) and pulmonary vein A wave duration (≥156 m/s) both had sensitivity and specificity ≥80% for LVEDP ≥ 20 mmHg. In pediatric and young adult patients with RCM, lateral a' velocity and pulmonary vein A wave duration predicted elevated LVEDP with high sensitivity and specificity; however, due to technical limitations the latter was reliably measured in 12/21 patients. These noninvasive parameters may have utility in identifying patients that require further assessment with invasive testing. These findings require validation in a multicenter prospective cohort prior to widespread clinical implementation.

Fish and Shellfish Intake and Diabetes in a Costal Population of the Adriatic.

The objective of the study was to examine the association between fish and shellfish intake and diabetes in an island population, and the design of the study was Cross-sectional. Two independent population-based field surveys were conducted in Hvar Island of the eastern Adriatic coast of Croatia in May 2007 and May 2008, with a total of 1,379 adult participants. In multivariable logistic regression models, total fish intake was positively associated with diabetes prevalence in the total population (OR(Q4 vs. Q1) = 1.64; 95% CI = 1.01-2.66; p-trend = 0.09). Oily fish intake also exhibited a positive association with diabetes prevalence in the total population (OR(Q4 vs. Q1) = 2.22; 95% CI = 1.35-3.64; p-trend = 0.01) and in analyses stratified by body mass index, males and those with a high waist circumference. The study suggests an association between oily fish intake and diabetes in the population of the Hvar Island in Croatia. Longitudinal studies incorporating measures of persistent organic pollutants and local cooking practices are warranted to identify factors in fatty fish that may influence the development or persistence of diabetes.

Multiuser immersive virtual reality simulation for interprofessional sepsis recognition and management.

INTRODUCTION: Sepsis is a leading cause of pediatric mortality. While there has been significant effort toward improving adherence to evidence-based care, gaps remain. Immersive multiuser virtual reality (MUVR) simulation may be an approach to enhance provider clinical competency and situation awareness for sepsis. METHODS: A prospective, observational pilot of an interprofessional MUVR simulation assessing a decompensating patient from sepsis was conducted from January to June 2021. The study objective was to establish validity and acceptability evidence for the platform by assessing differences in sepsis recognition between experienced and novice participants. Interprofessional teams assessed and managed a patient together in the same VR experience with the primary outcome of time to recognition of sepsis utilizing the Situation Awareness Global Assessment Technique analyzed using a logistic regression model. Secondary outcomes were perceived clinical accuracy, relevancy to practice, and side effects experienced. RESULTS: Seventy-two simulations included 144 participants. The cumulative odds ratio of recognizing sepsis at 2 min into the simulation in comparison to later time points by experienced versus novice providers were significantly higher with a cumulative odds ratio of 3.70 (95% confidence interval: 1.15-9.07, p = .004). Participants agreed that the simulation was clinically accurate (98.6%) and will impact their practice (81.1%), with a high degree of immersion (95.7%-99.3%), and the majority of side effects were perceived as mild (70.4%-81.4%). CONCLUSIONS: Our novel MUVR simulation demonstrated significant differences in sepsis recognition between experienced and novice participants. This validity evidence along with the data on the simulation's acceptability supports expanded use in training and assessment.

Dietary patterns in adults from an Adriatic Island of Croatia and their associations with metabolic syndrome and its components.

Adriatic islanders have a high prevalence of metabolic syndrome (MetS) although they have traditionally practiced an active lifestyle and adhered to a Mediterranean diet. We performed a cross-sectional study to identify dietary patterns in a sample of 1442 adults from the island of Hvar, and determined whether MetS and its components: waist-circumference, serum triglycerides, fasting plasma glucose, HDL-cholesterol, and blood pressure, were related to an altered pattern of the traditional Mediterranean diet. Dietary intake was assessed by a food frequency questionnaire. MetS was defined using the International Diabetes Federation criteria. Our study showed that dietary patterns in this population have diversified from the traditional diet. Principal component analysis identified three major patterns. The meat, alcohol, and fish pattern (MAFp), sweets, grains, and fats pattern (SGFp), and an olive-oil, vegetables, and fruits pattern (OVFp) explained 30.6% of total dietary variance. The MAFp associated significantly with MetS (p = 0.027) and high plasma glucose (p = 0.006).

Tolerability and Acceptability of Autonomous Immersive Virtual Reality Incorporating Digital Twin Technology for Mass Training in Healthcare.

INTRODUCTION: As part of onboarding and systems testing for a clinical expansion, immersive virtual reality (VR) incorporating digital twin technology was used. While digital twin technology has been leveraged by industry, its use in health care has been limited with no prior application for onboarding or training. The tolerability and acceptability of immersive VR for use by a large population of healthcare staff were unknown. METHODS: A prospective, observational study of an autonomous immersive VR onboarding experience to a new clinical space was conducted from May to September 2021. Participants were healthcare staff from several critical care and acute care units. Primary outcomes were tolerance and acceptability measured by reported adverse effects and degree of immersion. Secondary outcomes were attitudes toward the efficacy of VR compared with standard onboarding experiences. RESULTS: A total of 1522 healthcare staff participated. Rates of adverse effects were low and those with prior VR experience were more likely to report no adverse effects. Odds of reporting immersion were high across all demographic groups, though decreased with increasing age. The preference for VR over low-fidelity methods was high across all demographics; however, preferences were mixed when compared with traditional simulation and real-time clinical care. CONCLUSIONS: Large-scale VR onboarding is feasible, tolerable, and acceptable to a diverse population of healthcare staff when using digital twin technology. This study also represents the largest VR onboarding experience to date and may address preconceived notions that VR-based training in health care is not ready for widespread adoption.

Reference Ranges for Bone Mineral Content and Density by Dual Energy X-Ray Absorptiometry for Young Children.

BACKGROUND: Assessment of bone health in young children has been hampered by limited reference values for bone mineral content (BMC) and areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA). OBJECTIVES: To identify age, sex, and population ancestry effects on BMC and aBMD and develop smoothed reference ranges for BMC and aBMD in young children. To quantify precision of bone measurements and influence of height-for-age Z-scores on bone Z-scores. METHODS: We recruited 484 healthy children ages 1 to 2 years or 4.5 to 5 years at 2 clinical centers, who were seen once or up to 7 times over a 3-year period. Lumbar spine, distal forearm, and whole-body subtotal (ages ≥ 3 years) BMC and aBMD were measured by DXA. These data were combined with data from the Bone Mineral Density in Childhood Study from children ages 5 to 8.9 years to create the smoothed reference curves. RESULTS: For 1- to 5-year-olds, BMC and aBMD at all skeletal sites increased with age. Age trends differed by sex for BMC and aBMD of the spine, distal one-third radius, ultradistal radius, and by ancestry (Black vs non-Black) for all measures. BMC and aBMD precision (% coefficient of variation) ranged from 1.0% to 4.4%. Height Z-scores were positively associated with bone Z-scores and accounted for 4% to 45% of the variance. CONCLUSIONS: We demonstrate the feasibility of bone density measurements in young children and provide robust reference ranges and stature adjustments for calculation of bone Z-scores at multiple skeletal sites to enable bone health assessments.

Associations between MRI T1 mapping, liver stiffness, quantitative MRCP, and laboratory biomarkers in children and young adults with autoimmune liver disease.

PURPOSE: Define relationships between quantitative magnetic resonance imaging (MRI) metrics and clinical/laboratory data in a pediatric and young adult cohort with autoimmune liver disease (AILD). MATERIALS AND METHODS: This prospective, cross-sectional study was institutional review board-approved. Patients enrolled in an institutional AILD registry were divided into groups: (1) autoimmune hepatitis (AIH) or (2) primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC). Participants underwent serum liver biochemistry testing and research MRI examinations, including 3D magnetic resonance cholangiopancreatography (MRCP), magnetic resonance elastography (MRE), and iron-corrected T1 mapping (cT1). MRCP + and LiverMultiScan (Perspectum Ltd., Oxford, UK) were used to post-process 3D MRCP and cT1 data. Multiple linear regression models were used to assess relationships. RESULTS: 58 patients, 35 male, median age 16 years were included; 30 in the AIH group, 28 in the PSC/ASC group. After statistical adjustments for patient age, sex, presence of inflammatory bowel disease (IBD), specific diagnosis (PSC/ASC vs. AIH), and time from diagnosis to MRI examination, left hepatic bile duct maximum diameter was a statistically significant predictor of whole liver mean cT1, cT1 interquartile range (IQR), and MRE liver stiffness (p = 0.01-0.04). Seven laboratory values were significant predictors of whole liver cT1 IQR (p < 0.0001-0.04). Eight laboratory values and right hepatic bile duct median and maximum diameter were significant predictors of liver stiffness (p < 0.0001-0.03). CONCLUSIONS: Bile duct diameters and multiple laboratory biomarkers of liver disease are independent predictors of liver stiffness and cT1 IQR in pediatric patients with AILD.

Acute Kidney Injury and Fluid Overload in Pediatric Extracorporeal Cardio-Pulmonary Resuscitation: A Multicenter Retrospective Cohort Study.

Acute kidney injury (AKI) and fluid overload (FO) are common complications of extracorporeal membrane oxygenation (ECMO). The purpose of this study was to characterize AKI and FO in children receiving extracorporeal cardiopulmonary resuscitation (eCPR). We performed a multicenter retrospective study of children who received eCPR. AKI was assessed during ECMO and FO defined as <10% [FO-] vs. ≥10% [FO+] evaluated at ECMO initiation and discontinuation. A composite exposure, defined by a four-group discrete phenotypic classification [FO-/AKI-, FO-/AKI+, FO+/AKI-, FO+/AKI+] was also evaluated. Primary outcome was mortality and hospital length of stay (LOS) among survivors. 131 patients (median age 29 days (IQR:9, 242 days); 51% men and 82% with underlying cardiac disease) were included. 45.8% survived hospital discharge. FO+ at ECMO discontinuation, but not AKI was associated with mortality [aOR=2.3; 95% CI: 1.07-4.91]. LOS for FO+ patients was twice as long as FO- patients, irrespective of AKI status [(FO+/AKI+ (60 days; IQR: 49-83) vs. FO-/AKI+ (30 days, IQR: 19-48 days); P = 0.01]. FO+ at ECMO initiation and discontinuation was associated with an adjusted 66% and 50% longer length of stay respectively. Prospective studies that target timing and strategy of fluid management, including its removal in children receiving ECPR are greatly needed.

Remote Virtual Reality Teaching: Closing an Educational Gap During a Global Pandemic.

OBJECTIVE: Resident physicians are expected to recognize patients requiring escalation of care on day 1 of residency, as outlined by the Association of American Medical Colleges. Opportunities for medical students to assess patients at the bedside or through traditional simulation-based medical education have decreased because of coronavirus disease 2019 restrictions. Virtual reality (VR) delivered remotely via video teleconferencing may address this educational gap. METHODS: A prospective pilot study targeting third-year pediatric clerkship students at a large academic children's hospital was conducted from April to December 2020. Groups of 6 to 15 students participated in a 1.5-hour video teleconferencing session with a physician facilitator donning a VR headset and screen sharing interactive VR cases of a hospitalized infant with respiratory distress. Students completed surveys assessing the immersion and tolerability of the virtual experience and reported its perceived effectiveness to traditional educational modalities. Comparisons were analyzed with binomial testing. RESULTS: Participants included third-year medical students on their pediatric clerkship. A total of 140 students participated in the sessions, with 63% completing the survey. A majority of students reported VR captured their attention (78%) with minimal side effects. Students reported remote VR training as more effective (P < .001) than reading and online learning and equally or more effective (P < .001) than didactic teaching. Most students (80%) rated remote VR as less effective than bedside teaching. CONCLUSIONS: This pilot reveals the feasibility of remote group clinical training with VR via a video conferencing platform, addressing a key experience gap while navigating coronavirus disease 2019 limitations on training.

Integration of a Pilot Oral Health Curriculum into a Medical School Pediatric Rotation.

Purpose: The purpose of this study was to assess changes in medical student knowledge, skills, and beliefs in oral health after participating in an oral health curriculum that included an online learning module, shadowing pediatric dental residents, and applying fluoride varnish. Methods: Third-year medical students completed a precurriculum questionnaire. After completing the online module and clinical experience, students completed a postcurriculum questionnaire. Data were analyzed via descriptive statistics, and outcomes were assessed. Results: There was an improvement in knowledge and oral health-related skills questions postcurriculum. All questions on beliefs toward oral health showed a more agreeable response following the oral health curriculum. Conclusion: Interprofessional collaboration and oral health curriculum integration lead to positively changing the knowledge, attitudes, and skills of medical students.