Untargeted, High-Resolution Metabolomics in Pediatric Eosinophilic Esophagitis.

BACKGROUND/OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory disease of unclear etiology. The aim of this study was to use untargeted plasma metabolomics to identify metabolic pathway alterations associated with EoE to better understand the pathophysiology. METHODS: This prospective, case-control study included 72 children, aged 1-17 years, undergoing clinically indicated upper endoscopy (14 diagnosed with EoE and 58 controls). Fasting plasma samples were analyzed for metabolomics by high-resolution dual-chromatography mass spectrometry. Analysis was performed on sex-matched groups at a 2:1 ratio. Significant differences among the plasma metabolite features between children with and without EoE were determined using multivariate regression analysis and were annotated with a network-based algorithm. Subsequent pathway enrichment analysis was performed. RESULTS: Patients with EoE had a higher proportion of atopic disease (85.7% vs 50%, P = 0.019) and any allergies (100% vs 57.1%, P = 0.0005). Analysis of the dual chromatography features resulted in a total of 918 metabolites that differentiated EoE and controls. Glycerophospholipid metabolism was significantly enriched with the greatest number of differentiating metabolites and overall pathway enrichment ( P < 0.01). Multiple amino and fatty acid pathways including linoleic acid were also enriched, as well as pyridoxine metabolism ( P < 0.01). CONCLUSIONS: In this pilot study, we found differences in metabolites involved in glycerophospholipid and inflammation pathways in pediatric patients with EoE using untargeted metabolomics, as well as overlap with amino acid metabolome alterations found in atopic disease.

Single-Center Retrospective Review of the Presentation and Initial Care of Esophageal Button Battery Impactions 2007-2020.

OBJECTIVE: The aims of this study were to characterize the patient population and initial presentation and care of esophageal button battery ingestion and provide descriptive data including factors affecting accurate diagnosis, duration of battery exposure, and battery removal. METHODS: This was a retrospective cohort study from 2007 to 2020 at a single-center, large-volume, urban academic pediatric hospital system. Included participants were children 6 months to 18 years old who underwent removal of an esophageal button battery impaction at our institution. RESULTS: Our cohort comprised 63 patients; ages ranged from 7 to 87 months with a median of 27 months. Median button battery size was 2.12 cm with 59% lodged in the proximal esophagus. A prolonged impaction, greater than 12 hours, occurred in 46% of patients. Risk ratio analysis demonstrated that lack of caregiver suspicion of ingestion was associated with prolonged impaction (risk ratio, 3.39; confidence interval, 2.15-5.34). Misdiagnosis of button battery ingestion occurred in 10% of cases. The majority of patients, 87%, required transfer from a referring facility with a median total distance of 37 miles (range, 1.4-160 miles) from home to facility where battery was removed. CONCLUSION AND RELEVANCE: This study describes the initial presentation and care of a large cohort of pediatric esophageal button battery ingestion. It emphasizes the continued need for primary prevention, prompt identification, and removal of these batteries. There are many challenges in caring for these patients involving multiple pediatric disciplines, and guidelines encompassing a multidisciplinary approach would be beneficial.

Comparing Eosinophilic Esophagitis in a Black and Non-Black Pediatric Cohort.

OBJECTIVES: To compare presenting symptoms, comorbidities, disease, and treatment characteristics of a black pediatric eosinophilic esophagitis (EoE) group to a non-black pediatric EoE group. METHODS: A retrospective chart review consisting of pediatric patients diagnosed with EoE between the years of 2010 and 2018 at a single urban pediatric hospital system comprising 143 black pediatric patients compared with 142 non-black pediatric patients with similar distribution of age and sex. RESULTS: Both groups were majority male, and the median age of diagnosis between the black and non-black group was 5.1 and 6.7 years old, respectively. Comorbidities more commonly seen in the black group included food allergies, atopic dermatitis, asthma, and allergic rhinitis. Black patients were more likely to present with failure to thrive (FTT)/poor growth, whereas non-black patients were more likely to present with abdominal pain. There was no statistically significant difference between the groups in achieving remission using current therapies. The black group had higher rates of nonadherence to medical therapies. CONCLUSIONS: This is the largest study to date comparing a black versus non-black pediatric EoE population. The black population had more atopic comorbidities and FTT at presentation and had significantly more issues with nonadherence. This new knowledge describing EoE in a minority population will hopefully improve awareness, diagnosis, and management of EoE in this population.

High-Powered Magnet Exposures in Children: A Multi-Center Cohort Study.

BACKGROUND AND OBJECTIVES: High-powered magnets were effectively removed from the US market by the Consumer Product Safety Commission (CPSC) in 2012 but returned in 2016 after federal court decisions. The United States Court of Appeals for the 10th Circuit cited imprecise data among other reasons as justification for overturning CPSC protections. Since then, incidence of high-powered magnet exposure has increased markedly, but outcome data are limited. In this study, we aim to describe the epidemiology and outcomes in children seeking medical care for high-powered magnets after reintroduction to market. METHODS: This is a multicenter, retrospective cohort study of patients aged 0 to 21 years with a confirmed high-powered magnet exposure (ie, ingestion or insertion) at 25 children's hospitals in the United States between 2017 and 2019. RESULTS: Of 596 patients with high-powered magnet exposures identified, 362 (60.7%) were male and 566 (95%) were <14 years of age. Nearly all sought care for magnet ingestion (n = 574, 96.3%), whereas 17 patients (2.9%) presented for management of nasal or aural magnet foreign bodies, 4 (0.7%) for magnets in their genitourinary tract, and 1 patient (0.2%) had magnets in their respiratory tract. A total of 57 children (9.6%) had a life-threatening morbidity; 276 (46.3%) required an endoscopy, surgery, or both; and 332 (55.7%) required hospitalization. There was no reported mortality. CONCLUSIONS: Despite being intended for use by those >14 years of age, high-powered magnets frequently cause morbidity and lead to high need for invasive intervention and hospitalization in children of all ages.

Management of esophageal button battery ingestions: resource utilization and outcomes.

PURPOSE: Institutions are adopting the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines for pediatric esophageal button battery ingestion (EBBI). Our objective was to evaluate the guidelines' impact on in-hospital resource utilization and short-term clinical outcomes in hemodynamically stable patients after endoscopic battery removal. METHODS: A single-center retrospective review of all EBBI admissions from 2010 to 2020. Patients were divided into two groups based on adoption of national guidelines: pre-guideline (2010-2015) and post-guideline (2016-2020). RESULTS: Sixty-five patients were studied (pre-guideline n = 23; post-guideline n = 42). Compared with pre-guideline, post-guideline use of magnetic resonance imaging (MRI) increased (2/23 [8.7%]; 30/42 [71.4%]; p < 0.001). Post-guideline increases resulted for median days (IQR) receiving antibiotics (0 [0, 4]; 6 [3, 8]; p = 0.01), total pediatric intensive care unit admission (0 [0, 1]; 3 [0, 6]; p < 0.001), and total hospital length of stay (5 [2, 11]; 11.5 [4, 17]; p = 0.02). Two patients in the post-guideline group had delayed presentations despite normal imaging: one with TEF and one with aorto-esophageal fistula. All survived to discharge. CONCLUSION: In EBBI cases managed using the consensus based NASPHAGN guidelines, we report increased resource utilization without improved patient outcomes. Further research should evaluate post-guideline costs and resource utilization.

Evolving Clinical Care in Esophageal Button Batteries: Impact of Expert-Opinion Guideline Adoption and Continued Gaps in Care.

BACKGROUND/OBJECTIVES: Esophageal button battery impactions (BBI) in children pose a significant danger to children. Although there are expert-opinion guidelines to help manage this population, few studies detail the impact of guidelines on the clinical care of these patients. With this study, we aimed to describe the care of these patients before and following adoption of guidelines at a single center. METHODS: Retrospective cohort study of patients with esophageal BBI at a single center, large volume, urban academic pediatric hospital system before adoption of expert-opinion guidelines (2007-2017) and following adoption (2018-2020). RESULTS: Cohort was comprised of 31 patients before adoption and 32 patients following adoption of guidelines. Patient characteristics did not differ between groups. After 2018, significantly more patients received acetic acid irrigation, initial cross-sectional imaging, and serial cross-sectional imaging. There was also an increase in intensive care unit (ICU) stays, number of intubations, nil per os time, and hospital length of stay. There was no difference in patient outcomes. CONCLUSION: This study describes a large cohort of pediatric esophageal BBI before and following adoption of guidelines. Findings detail increased adherence to guidelines resulting in more cross-sectional imaging which led to ICU stays, longer length of stays, and more nil per os time. This study emphasizes the need for multi-disciplinary guidelines as well as further multi-institutional study.

PRO-C3, a Serological Marker of Fibrosis, During Childhood and Correlations With Fibrosis in Pediatric NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease in children and may lead to cirrhosis requiring liver transplant. Thus, prompt diagnosis of advanced fibrosis is essential. Our objectives were to examine PRO-C3 (a neo-epitope pro-peptide of type III collagen formation) levels across childhood/adolescence and associations with advanced fibrosis in pediatric NAFLD. This cross-sectional study included 88 children and adolescents with biopsy-proven NAFLD (mean age: 13.9 ± 2.9 years, 71% male) and 65 healthy participants (11.8 ± 4.5 years, 38% male). PRO-C3, and the bone remodeling biomarkers C-terminal telopeptide of type I collagen (CTX-I; bone resorption) and osteocalcin (N-MID; bone formation), were measured in serum by enzyme-linked immunosorbent assay. Fibrosis was assessed by liver biopsy in participants with NAFLD, who were categorized as having advanced (Ishak score ≥ 3) or none/mild fibrosis (Ishak score ≤ 2). Overall, PRO-C3 was similar in participants with NAFLD (median [interquartile range]: 20.6 [15.8, 25.9] ng/mL) versus healthy participants (19.0 [13.8, 26.0] ng/mL), but was significantly lower in older adolescents ≥ 15 years old (16.4 [13.0, 21.2] ng/mL) compared with children ≤ 10 years old (22.9 [18.1, 28.4] ng/mL; P < 0.001) or 11-14 years old (22.4 [18.3, 31.2] ng/mL; P < 0.001). PRO-C3 was also directly correlated with levels of CTX-I and N-MID (r = 0.64 and r = 0.62, respectively; both P < 0.001). Among participants with NAFLD, PRO-C3 was higher in those with advanced fibrosis (median [IQR]: 28.5 [21.6, 37.6]) compared with none/mild fibrosis (20.3 [18.2, 22.8]; P = 0.020) in models adjusted for age, sex, and body mass index z-score. However, associations were attenuated after additionally adjusting for bone-remodeling CTX-I (P = 0.09) or N-MID (P = 0.08). Conclusion: Collectively, these findings show that PRO-C3 levels are higher in children with advanced fibrosis in NAFLD, but are also influenced by age and pubertal growth spurt, assessed by bone remodeling biomarkers, and therefore may not be a reliable biomarker for liver fibrosis in pediatric NAFLD until late adolescence.

Development and repair of aorto-esophageal fistula following esophageal button battery impaction: A case report.

BACKGROUND: Complications from esophageal button battery impactions remain a real fear for practicing pediatric gastroenterologists and surgeons. This case describes a child who developed an aorto-esophageal fistula 25 days after initial battery ingestion and survived due to prompt placement of an aortic stent via minimally invasive surgery, avoiding an open procedure. CASE PRESENTATION: A 6-year-old female presented acutely with a mid-esophageal button battery impaction witnessed by her parents. Presenting symptoms included chest pain and emesis. Button battery location and size were confirmed on X-ray. She underwent removal with flexible esophagogastroduodenoscopy (EGD) and rigid esophagoscopy. She was admitted to the hospital and received conservative medical management, with serial cross-sectional imaging via chest MRIs to assess the evolution of her injury according to available national guidelines, and was discharged after 12 days of close inpatient monitoring. Despite these measures the patient represented 25 days post-ingestion with hematemesis from a new aorto-esophageal fistula, requiring emergent cardiac catheterization with successful, life-saving aortic stent placement. She remained admitted for an additional 12 days of monitoring as her diet was advanced slowly post-catheterization. Since this second hospitalization she continues to do well, with outpatient follow-up by multiple subspecialists. CONCLUSIONS: This case highlights the continued uncertainty regarding the risk of developing this complication, as well as gaps in the current literature and guidelines for managing these patients following ingestion and esophageal injury. It also details the unique course following development of this complication and its surgical repair.

Serial MRI Findings After Endoscopic Removal of Button Battery From the Esophagus.

OBJECTIVE. The purpose of this study was to evaluate findings at serial MRI after endoscopic removal of a button battery from the esophagus in a series of pediatric patients. MATERIALS AND METHODS. Serial MRI examinations after removal of a button battery from the esophagus were reviewed retrospectively for the presence of mediastinal edema; imaging characteristics of the aorta and arteries; imaging characteristics of the trachea; and imaging characteristics of the esophageal wall at the level of injury. RESULTS. A total of 48 MRI examinations were performed on 19 patients, 89% (17/19) in the first 48 hours after battery removal. Serial MRI was performed for 84% (16/19) of patients. Initial MRI showed extensive mediastinal edema in all 17 patients who underwent MRI in the first 48 hours. Edema directly abutted major arteries in all 17 patients and abutted the airway in all 10 patients with proximal esophageal injury. Arterial vascular changes were seen in 30% (3/10) of patients with proximal esophageal injury and 57% (4/7) of patients with mid or distalesophageal injury. Airway changes were seen in 80% (8/10) of patients with proximal esophageal injury. Serial MRI showed improvement of airway changes in all patients and improvement in vessel wall changes in all but one (25%, 1/4) of the patients who had mid or distal esophageal injury. Four patients (21% [4/19]) had contained esophageal leak on esophagrams. No patients in our series developed a tracheoesophageal or vascular-enteric fistula. CONCLUSION. Our case series provides important information on natural history of MRI findings in children after endoscopic removal of a button battery from the esophagus. Further studies are needed to determine the imaging findings most sensitive and specific for severe complications, such as tracheoesophageal fistula and vascular-enteric fistula.

Predicting the impacts of sea level rise in sea turtle nesting habitat on Bioko Island, Equatorial Guinea.

Sea level is expected to rise 44 to 74 cm by the year 2100, which may have critical, previously un-investigated implications for sea turtle nesting habitat on Bioko Island, Equatorial Guinea. This study investigates how nesting habitat will likely be lost and altered with various increases in sea level, using global sea level rise (SLR) predictions from the Intergovernmental Panel on Climate Change. Beach profiling datasets from Bioko's five southern nesting beaches were used in GIS to create models to estimate habitat loss with predicted increases in sea level by years 2046-2065 and 2081-2100. The models indicate that an average of 62% of Bioko's current nesting habitat could be lost by 2046-2065 and 87% by the years 2081-2100. Our results show that different study beaches showed different levels of vulnerability to increases in SLR. In addition, on two beaches erosion and tall vegetation berms have been documented, causing green turtles to nest uncharacteristically in front of the vegetation line. We also report that development plans are currently underway on the beach least susceptible to future increases in sea level, highlighting how anthropogenic encroachment combined with SLR can be particularly detrimental to nesting turtle populations. Identified habitat sensitivities to SLR will be used to inform the government of Equatorial Guinea to consider the vulnerability of their resident turtle populations and projected climate change implications when planning for future development. To our knowledge this is the first study to predict the impacts of SLR on a sea turtle nesting habitat in Africa.

Shared Reading Practices and Early Literacy Promotion in the First Year of Life.

Limited research exists on family reading practices, the impact of counseling, and book distribution in the first 6 months of life, despite recommendations from the American Academy of Pediatrics and Reach Out and Read promoting shared reading from birth. OBJECTIVE: To describe infant home reading trajectories and environments in the first year and to assess whether receiving books starting in the newborn period, compared with starting at 6 months, alters these trajectories. METHODS: Two study groups were enrolled in a quasi-experimental sequential cohort study; both groups received shared reading counseling starting in the newborn period and completed surveys throughout the first year. The Standard group received books starting at 6 months, whereas the Early Books group received books starting at 2 weeks. Reading trajectories were assessed both overall and between the study groups. RESULTS: At the 2-week visit, less than half of families in each group had started shared reading with their infant, which rose to >97% by 12 months. Approximately two-thirds of families owned >10 children's books at 2 weeks, which increased to >80% at 12 months. Incorporating shared reading into bedtime routines also increased during the first year. Early versus standard book distribution did not alter these trajectories. CONCLUSION: Over the first year of life, families almost universally initiated shared reading and increased the number of books in the home. Reading habits established during this time were maintained in both groups. Literacy promotion beginning at the earliest well-child visits may help establish routines that will persist throughout childhood.

Home Literacy Environment and Shared Reading in the Newborn Period.

: In 2014, the American Academy of Pediatrics and Reach Out and Read formally emphasized counseling families on shared reading starting at birth. However, little data exist on the home reading practices and environments of newborn infants. OBJECTIVE: To characterize the home reading practices and environments of 2-week-old infants. METHODS: We distributed writtens self-administered surveys to 223 families seen for 2-week well-child visits. The survey assessed the frequency of shared reading, "favorite activities" with infants (including shared reading), number of books in the home, and sources of reading information. Descriptive and multivariate statistics were computed to assess the frequency of primary outcomes and sociodemographic associations. RESULTS: At the 2-week well-child visit, 57.7% of families had not yet started reading with their infants. A minority of families (29.1%) reported shared reading as a favorite activity. Thirty-five percent of families reported having ≤10 books in the home. Non-white race and having lived outside the United States were significantly associated with having ≤10 books in the home. Parents who reported not always enjoying reading were less likely to have started reading to their infant. CONCLUSION: Differences in both book ownership and having initiated shared reading are present from the newborn period. Findings suggest an opportunity for the provision of children's books in early infancy through primary care, particularly for immigrant and minority families. Engaging parents to incorporate language-rich activities, including shared reading, with their infants may be especially important for those who have a history of not being read to or who do not report enjoying reading.