Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on MRI 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 (MRI) at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T MRI scan between 39 through 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, preeclampsia, 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: 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=0.02), primarily driven by increased white matter injury/abnormality scores (p=0.01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (p=0.02) 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.

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.

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.

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.

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.

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.

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.

Percutaneous electrical nerve field stimulation compared to standard medical therapy in adolescents with functional abdominal pain disorders.

Introduction: Standard medical therapy (SMT) in children with functional abdominal pain disorders (FAPD) includes cyproheptadine and amitriptyline. While percutaneous electrical nerve field stimulation (PENFS) has shown benefit, no study has compared outcomes of PENFS to SMT. We aimed to examine changes in abdominal pain, nausea and disability before and after treatment and compare outcomes between treatments. Methods: The records of FAPD patients ages 11-21 years, treated with 4 weeks of PENFS, cyproheptadine or amitriptyline were reviewed. Outcomes were evaluated using validated questionnaires [Abdominal Pain Index (API), Nausea Severity Scale (NSS), and the Functional Disability Inventory (FDI)] at baseline and follow-up within 3 months (FU). Result: Of 101 patients, 48% received PENFS, 31% cyproheptadine and 21% received amitriptyline. Median ages were 17 (15-19), 16 (15-18) and 15 (11-16) years respectively and the majority were females (75%, 90% and 52% respectively). In the PENFS group, API (p = 0.001), NSS (p = 0.059) and FDI (p = 0.048) were significantly lower at FU. API (p = 0.034) but not NSS and FDI (p > 0.05) decreased significantly at FU in the amitriptyline group. API, NSS and FDI did not change significantly with cyproheptadine at FU (p > 0.05). FU API scores were lower in PENFS vs. cyproheptadine (p = 0.04) but not vs. amitriptyline (p = 0.64). The FDI scores were significantly lower in the amitriptyline vs. cyproheptadine group (p = 0.03). Conclusion: Therapy with PENFS showed improvements in abdominal pain, nausea and disability while amitriptyline showed improvements in abdominal pain within 3 months of treatment. PENFS was more effective than cyproheptadine in improving abdominal pain. Amitriptyline improved disability scores more than cyproheptadine and showed promise for treatment. PENFS may be a good non-pharmacologic alternative for FAPD.

Revisiting post-ICU admission fluid balance across pediatric sepsis mortality risk strata: A secondary analyses from a prospective observational cohort study.

Introduction: 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 (AKI), and use of renal replacement therapy (CRRT) in pediatric septic shock. Design: Ongoing multi-center prospective observational cohort. Setting: Thirteen pediatric ICUs in the United States (2003-2023). Patients: Six hundred and eighty-one children with septic shock. Interventions: None. Measurements and Main Results: Cumulative percent positive fluid balance between day 1-7 (Day 1-7%PFB) was determined. Primary outcome of interest was complicated course defined as death or persistence of ≥ 2 organ dysfunctions by day 7. PERSEVERE-II biomarkers were used to assign mortality probability and categorize patients into high (n = 91), intermediate (n = 134), and low (n = 456) mortality risk strata. Cox proportional hazard regression models with adjustment for PERSEVERE-II mortality probability, presence of sepsis associated acute kidney injury (SA-AKI) on Day 3, and any use of CRRT, demonstrated that time-dependent variable Day 1-7%PFB was independently associated with increased hazard of complicated course in the cohort. Risk stratified analyses revealed that each 10% increase in Day 1-7%PFB was independently associated with increased hazard of complicated course among patients with high mortality risk strata (adj HR of 1.24 (95%CI: 1.08-1.42), p = 0.002), but not among those categorized as intermediate- or low- mortality risk. Conclusions: Our data demonstrate the independent influence of cumulative %PFB on the risk of complicated course. Contrary to our previous report, this risk was largely driven by patients categorized as having a high-mortality risk based on PERSEVERE-II biomarkers. Further research is necessary to determine whether this subset of patients may benefit from targeted deployment of restrictive fluid management or early initiation of de-escalation therapies upon resolution of shock.

Virtual Reality to Assess Resident Recognition of Impending Respiratory Failure During COVID-19.

OBJECTIVES: To assess the performance of pediatric residents in recognizing a decompensating patient with impending respiratory failure and appropriately escalating care using a virtual reality (VR) simulated case of an infant with bronchiolitis after an extended period of decreased clinical volumes during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Sixty-two pediatric residents at a single academic pediatric referral center engaged in a 30-minute VR simulation on respiratory failure in a 3-month-old admitted to the pediatric hospital medicine service with bronchiolitis. This occurred in a socially distant manner across the Zoom platform during the COVID-19 pandemic (January-April 2021). Residents were assessed on their ability to (1) recognize altered mental status (AMS), (2) designate clinical status as "(impending) respiratory failure," and (3) escalate care. Statistical differences between and across postgraduate year (PGY) levels were examined using χ2 or Fisher's exact test, followed by pairwise comparison and posthoc multiple testing using the Hochberg test. RESULTS: Among all residents, 53% successfully recognized AMS, 16% identified respiratory failure, and 23% escalated care. No significant differences were seen across PGY levels for recognizing AMS or identifying respiratory failure. PGY3+ residents were more likely to escalate care than PGY2 residents (P = .05). CONCLUSIONS: In the setting of an extended period with decreased clinical volumes during the COVID-19 pandemic, pediatric residents across all PGY levels demonstrated challenges with identifying (impending) respiratory failure and appropriately escalating care during VR simulations. Though limited, VR simulation may serve as a safe adjunct for clinical training and assessment during times of decreased clinical exposure.

The microbiome in adolescents with irritable bowel syndrome and changes with percutaneous electrical nerve field stimulation.

BACKGROUND: Irritable bowel syndrome (IBS), a disorder of the gut-brain axis, is affected by the microbiome. Microbial studies in pediatric IBS, especially for centrally mediated treatments, are lacking. We compared the microbiome between pediatric IBS patients and healthy controls (HC), in relation to symptom severity, and with percutaneous electrical nerve field stimulation (PENFS), a non-invasive treatment targeting central pain pathways. METHODS: We collected a stool sample, questionnaires and a 1-2 week stool and pain diary from 11 to 18 years patients with IBS. A patient subset completed 4 weeks of PENFS and repeated data collection immediately after and/or 3 months after treatment. Stool samples were collected from HC. Samples underwent metagenomic sequencing to evaluate diversity, composition, and abundance of species and MetaCyc pathways. KEY RESULTS: We included 27 cases (15.4 ± 2.5 year) and 34 HC (14.2 ± 2.9 year). Twelve species including Firmicutes spp., and carbohydrate degradation/long-chain fatty acid (LCFA) synthesis pathways, were increased in IBS but not statistically significantly associated with symptom severity. Seventeen participants (female) who completed PENFS showed improvements in pain (p = 0.012), disability (p = 0.007), and catastrophizing (p = 0.003). Carbohydrate degradation and LCFA synthesis pathways decreased post-treatment and at follow-up (FDR p-value <0.1). CONCLUSIONS AND INFERENCES: Firmicutes, including Clostridiaceae spp., and LCFA synthesis pathways were increased in IBS patients suggesting pain-potentiating effects. PENFS led to marked improvements in abdominal pain, functioning, and catastrophizing, while Clostridial species and LCFA microbial pathways decreased with treatment, suggesting these as potential targets for IBS centrally mediated treatments.

Novel sensory trigger for gastrocolonic response.

BACKGROUND: Gastrocolonic response (GCR) is a physiologic increase in motor activity of the colon following meal ingestion. The presence of GCR, in colonic manometry (CM) studies, is used as a marker of normal colonic motor activity. Our aim was to investigate whether GCR could be induced by sensory stimulation (visual or olfactory) prior to food ingestion, and to describe the characteristics of patients with this response. METHODS: We prospectively marked time of meal presence and initiation on CM tracings of patients with idiopathic constipation. We reviewed electronic medical records and normal CM studies. Presence of sensory GCR was defined as an increase by at least 25% of the baseline motility index (MI) after exposure to meal, prior to food ingestion. Manometry characteristics of patients with a sensory GCR response were compared to those without. KEY RESULTS: Eighty-nine patients, (47% females, median age 9 years) met the inclusion criteria. Forty-seven (52.8%) patients had a positive sensory GCR. This cohort had a higher proportion of postprandial GCR (93.6% vs. 76.2%, p-value = 0.02) and lower fasting MI (2.08 mm Hg vs. 3.54 mm Hg, p < 0.01). Thirteen (14.6%) patients who had no postprandial GCR had higher baseline MI (median of 3.69 vs. 2.46 mm Hg, p < 0.05). CONCLUSIONS & INFERENCES: Visualizing or smelling food resulted in a significant increase in baseline MI in more than 50% of patients. Our findings propose a novel, alternate pathway that can induce GCR. This central sensory pathway may have clinical relevance in the diagnosis and management of patients with colonic dysmotility.

Children from disadvantaged neighborhoods experience disproportionate injury from interpersonal violence.

BACKGROUND: Disparities in pediatric injury have been widely documented and are driven, in part, by differential exposures to social determinants of health (SDH). Here, we hypothesized that neighborhood socioeconomic deprivation and specific sociodemographic characteristics would be associated with interpersonal violence-related injury admission. METHODS: We conducted a retrospective cohort study of all patients ≤16 years, residing in Hamilton County, admitted to our level 1 pediatric trauma center. Residential addresses were geocoded to link admissions with a census tract-level socioeconomic deprivation index. Admissions were categorized as resulting from interpersonal violence or not - based on a mechanism of injury (MOI) of abuse or assault. The percentage of interpersonal violence-related injury admissions was compared across patient demographics and neighborhood deprivation index tertiles. These factors were then evaluated with multivariable regression analysis. RESULTS: Interpersonal violence accounted for 6.2% (394 of 6324) of all injury-related admissions. Interpersonal violence-related injury admission was associated with older age, male sex, Black race, public insurance, and living in tertiles of census tracts with higher socioeconomic deprivation. Those living in the most deprived tertile experienced 62.2% of all interpersonal violence-related injury admissions but only 36.9% of non-violence related injury admissions (p < 0.001). After adjustment, insurance and neighborhood deprivation accounted for much of the increase in interpersonal violence-related admissions for Black compared to White children. CONCLUSIONS: Children from higher deprivation neighborhoods, who are also disproportionately Black and publicly insured, experience a higher burden of interpersonal violence-related injury admissions. Level of evidence Level III.

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.

Relationships between socioeconomic deprivation and pediatric firearm-related injury at the neighborhood level.

BACKGROUND: Disparities in pediatric injury are widely documented and partly driven by differential exposures to social determinants of health (SDH). Here, we examine associations between neighborhood-level SDH and pediatric firearm-related injury admissions as a step to defining specific targets for interventions to prevent injury. METHODS: We conducted a retrospective review of patients 16 years or younger admitted to our Level I pediatric trauma center (2010-2019) after a firearm-related injury. We extracted patients' demographic characteristics and intent of injury. We geocoded home addresses to enable quantification of injury-related admissions at the neighborhood (census tract) level. Our population-level exposure variable was a socioeconomic deprivation index for each census tract. RESULTS: Of 15,686 injury-related admissions, 140 were for firearm-related injuries (median age, 14 years; interquartile range, 11-15 years). Patients with firearm-related injuries were 75% male and 64% Black; 66% had public insurance. Nearly half (47%) of firearm-related injuries were a result of assault, 32% were unintentional, and 6% were self-inflicted; 9% died. At the neighborhood level, the distribution of firearm-related injuries significantly differed by deprivation quintile ( p < 0.05). Children from the highest deprivation quintile experienced 25% of injuries of all types, 57% of firearm-related injuries, and 70% of all firearm-related injuries from assault. They had an overall risk of firearm-related injury 30 times that of children from the lowest deprivation quintile. CONCLUSION: Increased neighborhood socioeconomic deprivation is associated with more firearm-related injuries requiring hospitalization, at rates far higher than injury-related admissions overall. Addressing neighborhood-level SDH may help prevent pediatric firearm-related injury. LEVEL OF EVIDENCE: Prognostic and epidemiological, Level III.

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.

Effect of percutaneous electrical nerve field stimulation on mechanosensitivity, sleep, and psychological comorbidities in adolescents with functional abdominal pain disorders.

BACKGROUND: Percutaneous electrical nerve field stimulation (PENFS) improves symptoms in adolescents with functional abdominal pain disorders (FAPDs). However, little is known about its impact on sleep and psychological functioning. We evaluated the effects of PENFS on resting and evoked pain and nausea, sleep and psychological functioning, and long-term outcomes. METHODS: Patient ages 11-19 years with FAPD requiring PENFS as standard care were recruited. Evoked pain was elicited by a Water Load Symptom Provocation Task (WL-SPT) before and after four weeks of treatment. Pain, gastrointestinal symptoms, sleep, somatic symptoms, and physical and psychological functioning were assessed. Actigraphy was used to measure daily sleep-wake patterns. KEY RESULTS: Twenty patients (14.3 ± 2.2 years old) with FAPD were enrolled. Most patients were females (70%) and white (95%). During pain evoked by WL-SPT, visual analog scale (VAS) pain intensity and nausea were lower following PENFS compared with baseline (p = 0.004 and p = 0.02, respectively). After PENFS, resting VAS pain unpleasantness (p = 0.03), abdominal pain (p < 0.0001), pain catastrophizing (p = 0.0004), somatic complaints (0.01), functional disability (p = 0.04), and anxiety (p = 0.02) exhibited significant improvements, and some were sustained long-term. Self-reported sleep improved after PENFS (p's < 0.05) as well as actigraphy-derived sleep onset latency (p = 0.03). CONCLUSIONS AND INFERENCES: We demonstrated improvements in resting and evoked pain and nausea, sleep, disability, pain catastrophizing, somatic complaints, and anxiety after four weeks of PENFS therapy. Some effects were sustained at 6-12 months post-treatment. This suggests that PENFS is a suitable alternative to pharmacologic therapy.

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.

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.