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.

Percutaneous Electrical Nerve Field Stimulation in Children and Adolescents With Functional Dyspepsia-Integrating a Behavioral Intervention.

OBJECTIVES: Functional dyspepsia (FD) includes postprandial distress and epigastric pain syndrome. Percutaneous electrical nerve field stimulation (PENFS) in addition to behavioral interventions (BI) has shown benefits in children with functional abdominal pain but not specifically in FD. We aimed to assess the efficacy of PENFS for treating FD and compare the outcomes with those who received the combination of PENFS + BI. MATERIALS AND METHODS: Charts of patients with FD who completed four weeks of PENFS were evaluated. A subset of patients received concurrent BI. Demographic data, medical history, and symptoms were documented. Outcomes at different time points included subjective symptom responses and validated questionnaires collected clinically (Abdominal Pain Index [API], Nausea Severity Scale [NSS], Functional Disability Inventory [FDI], Pittsburgh Sleep Quality Index [PSQI], Children's Somatic Symptoms Inventory [CSSI], Patient-Reported Outcomes Measurement Information Systems [PROMIS] Pediatric Anxiety and Depression scales). RESULT: Of 84 patients, 61% received PENFS + BI, and 39% received PENFS alone. In the entire cohort, API (p < 0.0001), NSS (p = 0.001), FDI (p = 0.001), CSSI (p < 0.0001), PSQI (p = 0.01), PROMIS anxiety (p = 0.02), and depression (p = 0.01) scores improved from baseline to three weeks and at three months. Subjective responses showed nausea improvement (p = 0.01) and a trend for improvement in abdominal pain (p = 0.07) at week three. Abdominal pain subjectively improved at week three and three months (p = 0.003 and 0.02, respectively), nausea at week three and three months (p = 0.01 and 0.04, respectively), and a trend for improvement in sleep disturbances at week three and three months (p = 0.08 and p = 0.07, respectively) in the PENFS + BI group vs PENFS alone. CONCLUSION: Abdominal pain, nausea, functioning, somatization, sleep disturbances, anxiety, and depression improved at three weeks and three months after PENFS in pediatric FD. Subjective pain and nausea improvement were greater in the PENFS + BI group than in the group with PENFS alone, suggesting an additive effect of psychologic therapy.

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.

Acute Kidney Injury, Fluid Overload, and Renal Replacement Therapy Differ by Underlying Diagnosis in Neonatal Extracorporeal Support and Impact Mortality Disparately.

INTRODUCTION: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. METHODS: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. RESULTS: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14-8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11-1.30) and RRT receipt (OR 2.12, 95% CL 1.20-3.73) were independently associated with mortality. DISCUSSION/CONCLUSIONS: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.

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.

The Impact of Fluid Overload on Outcomes in Children Treated With Extracorporeal Membrane Oxygenation: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To characterize the epidemiology of fluid overload and its association with mortality and duration of extracorporeal membrane oxygenation in children treated with extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Six tertiary children's hospital ICUs. PATIENTS: Seven hundred fifty-six children younger than 18 years old treated with extracorporeal membrane oxygenation for greater than or equal to 24 hours from January 1, 2007, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall survival to extracorporeal membrane oxygenation decannulation and hospital discharge was 74.9% (n = 566) and 57.7% (n = 436), respectively. Median fluid overload at extracorporeal membrane oxygenation initiation was 8.8% (interquartile range, 0.3-19.2), and it differed between hospital survivors and non survival, though not between extracorporeal membrane oxygenation survivors and non survivors. Median peak fluid overload on extracorporeal membrane oxygenation was 30.9% (interquartile range, 15.4-54.8). During extracorporeal membrane oxygenation, 84.8% had a peak fluid overload greater than or equal to 10%; 67.2% of patients had a peak fluid overload of greater than or equal to 20% and 29% of patients had a peak fluid overload of greater than or equal to 50%. The median peak fluid overload was lower in patients who survived on extracorporeal membrane oxygenation (27.2% vs 44.4%; p < 0.0001) and survived to hospital discharge (24.8% vs 43.3%; p < 0.0001). After adjusting for acute kidney injury, pH at extracorporeal membrane oxygenation initiation, nonrenal complications, extracorporeal membrane oxygenation mode, support type, center and patient age, the degree of fluid overload at extracorporeal membrane oxygenation initiation (p = 0.05), and the peak fluid overload on extracorporeal membrane oxygenation (p < 0.0001) predicted duration of extracorporeal membrane oxygenation in survivors. Multivariable analysis showed that peak fluid overload on extracorporeal membrane oxygenation (adjusted odds ratio, 1.09; 95% CI, 1.04-1.15) predicted mortality on extracorporeal membrane oxygenation; fluid overload at extracorporeal membrane oxygenation initiation (adjusted odds ratio, 1.13; 95% CI, 1.05-1.22) and peak fluid overload (adjusted odds ratio, 1.18; 95% CI, 1.12-1.24) both predicted hospital morality. CONCLUSIONS: Fluid overload occurs commonly and is independently associated with adverse outcomes including increased mortality and increased duration of extracorporeal membrane oxygenation in a broad pediatric extracorporeal membrane oxygenation population. These results suggest that fluid overload is a potential target for intervention to improve outcomes in children on extracorporeal membrane oxygenation.

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.

The Incidence of Acute Kidney Injury and Its Effect on Neonatal and Pediatric Extracorporeal Membrane Oxygenation Outcomes: A Multicenter Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Study Group.

OBJECTIVE: In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation; to describe the prevalence and timing of acute kidney injury utilizing a consensus acute kidney injury definition and investigate the association of acute kidney injury with outcomes (length of extracorporeal membrane oxygenation and mortality). DESIGN: Multicenter retrospective observational cohort study. SETTING: Six pediatric extracorporeal membrane oxygenation centers. PATIENTS: Pediatric patients (age, < 18 yr) on extracorporeal membrane oxygenation at six centers during a period of January 1, 2007, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Complete data were analyzed for 832 patients on extracorporeal membrane oxygenation. Sixty percent of patients had acute kidney injury utilizing the serum creatinine Kidney Disease Improving Global Outcomes criteria (AKI) and 74% had acute kidney injury using the full Kidney Disease Improving Global Outcomes criteria including renal support therapy (AKI). Of those who developed acute kidney injury, it was present at extracorporeal membrane oxygenation initiation in a majority of cases (52% AKI and 65% AKI) and present by 48 hours of extracorporeal membrane oxygenation support in 86% (AKI) and 93% (AKI). When adjusted for patient age, center of support, mode of support, patient complications and preextracorporeal membrane oxygenation pH, the presence of acute kidney injury by either criteria was associated with a significantly longer duration of extracorporeal membrane oxygenation support (AKI, 152 vs 110 hr; AKI, 153 vs 99 hr) and increased adjusted odds of mortality at hospital discharge (AKI: odds ratio, 1.77; 1.22-2.55 and AKI: odds ratio, 2.50; 1.61-3.90). With the addition of renal support therapy to the model, acute kidney injury was associated with a longer duration of extracorporeal membrane oxygenation support (AKI, 149 vs 121 hr) and increased risk of mortality at hospital discharge (AKI: odds ratio, 1.52; 1.04-2.21). CONCLUSION: Acute kidney injury is present in 60-74% of neonatal-pediatric patients supported on extracorporeal membrane oxygenation and is present by 48 hours of extracorporeal membrane oxygenation support in 86-93% of cases. Acute kidney injury has a significant association with increased duration of extracorporeal membrane oxygenation support and increased adjusted odds of mortality at hospital discharge.

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.

Impact of a relocation to a new critical care building on pediatric safety events.

BACKGROUND: Cincinnati Children's Hospital Medical Center (CCHMC) relocated the pediatric, cardiac, and neonatal intensive care units (PICU, CICU and NICU) to a newly constructed critical care building (CCB) in November 2021. Simulation and onboarding sessions were implemented before the relocation, aimed at mitigating latent safety threats. OBJECTIVE: To evaluate the impact of ICU relocation to the CCHMC CCB on patient safety as measured by the quantity, rate, severity score, and category of safety reports. METHODS: This retrospective, cross-sectional, observational study compared safety reports filed in a 90-day period before and following the CCB relocation. The primary outcome was pre- and postrelocation safety report rates per 100 patient-days. Secondary outcomes included safety report severity, category, and rate of hospital acquired conditions (HACs). RESULTS: Total safety report incidence increased by 16% across all ICUs postrelocation with no difference in post- versus prerelocation odds ratio between ICUs. Three isolated instances of special cause variation were found, one in NICU and two in CICU. No special cause variation was found in the PICU. There were no statistical differences in assigned safety report severity pre- to postrelocation for all ICUs, and only lab specimen/test related safety reports showed a statistically significant increase postrelocation. Overall rates of HACs were low, with six occurring prerelocation and eight postrelocation. CONCLUSIONS: All three ICUs were relocated to the new CCB with minimal changes in the incidence, severity, or category of safety reports filed, suggesting staff training and preparations ahead of the relocation mitigated latent safety threats.

Safety and Effectiveness of Prucalopride in Children with Functional Constipation with and without Upper Symptoms.

INTRODUCTION: Pediatric prucalopride studies for treatment of gastrointestinal (GI) disorders have reported mixed results. We aimed to assess the safety and effectiveness of prucalopride in functional constipation (FC) with and without upper GI symptoms. METHODS: Retrospective data on patients with FC receiving combined prucalopride and conventional therapy was compared with those receiving conventional therapy alone within 12 months. Thirty patients on combined therapy and those on conventional therapy were each matched on the basis of age, gender, race, and presence of fecal soiling. Response (complete, partial, or no resolution) was compared. Similarly, response to concurrent functional upper GI symptoms (postprandial pain, bloating, weight loss, vomiting, early satiety, or nausea) and dysphagia, as well as adverse effects, were evaluated in the combined group. RESULTS: Mean age of 57 cases was 14.7 ± 4.9 years and 68% were female. Comorbidities included functional upper GI (UGI) symptoms (84%), dysphagia (12%), mood disorders (49%), and hypermobility spectrum disorder (37%). Unmatched cases reported 63% improvement to FC; response did not differ between the matched cohorts (70% versus 76.6%, p = 0.84). Cases showed a 56% improvement in functional UGI symptoms and 100% in dysphagia. Adverse effects were reported in 30%, abdominal cramps being most common. Four (7%) patients with a known mood disorder reported worsened mood, of which two endorsed suicidal ideation. CONCLUSION: Prucalopride efficaciously treated concurrent UGI symptoms and dysphagia in constipated pediatric patients and was overall well tolerated. Preexisting mood disorders seemed to worsen in a small subset of cases.

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.

Revisiting Post-ICU Admission Fluid Balance Across Pediatric Sepsis Mortality Risk Strata: A Secondary Analysis of a Prospective Observational Cohort Study.

OBJECTIVES: Post-ICU admission cumulative positive fluid balance (PFB) is associated with increased mortality among critically ill patients. We sought to test whether this risk varied across biomarker-based risk strata upon adjusting for illness severity, presence of severe acute kidney injury (acute kidney injury), and use of continuous renal replacement therapy (CRRT) in pediatric septic shock. DESIGN: Ongoing multicenter prospective observational cohort. SETTING: Thirteen PICUs in the United States (2003-2023). PATIENTS: Six hundred and eighty-one children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cumulative percent PFB between days 1 and 7 (days 1-7 %PFB) was determined. Primary outcome of interest was complicated course defined as death or persistence of greater than or equal to two organ dysfunctions by day 7. Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II biomarkers were used to assign mortality probability and categorize patients into high mortality (n = 91), intermediate mortality (n = 134), and low mortality (n = 456) risk strata. Cox proportional hazard regression models with adjustment for PERSEVERE-II mortality probability, presence of sepsis-associated acute kidney injury on day 3, and use of CRRT, demonstrated that time-dependent variable days 1-7%PFB was independently associated with an increased hazard of complicated course. Risk-stratified analyses revealed that each 10% increase in days 1-7 %PFB was associated with increased hazard of complicated course only among patients with high mortality risk strata (adjusted hazard ratio 1.24 (95% CI, 1.08-1.43), p = 0.003). However, this association was not causally mediated by PERSEVERE-II biomarkers. CONCLUSIONS: Our data demonstrate the influence of cumulative %PFB on the risk of complicated course in pediatric septic shock. Contrary to our previous report, this risk was largely driven by patients categorized as having a high mortality risk based on PERSEVERE-II biomarkers. Incorporation of such prognostic enrichment tools in randomized trials of restrictive fluid management or early initiation of de-escalation strategies may inform targeted application of such interventions among at-risk patients.