Clinical Predictors and Outcomes for Recurrent Pneumatosis Intestinalis in Children: A Case Control Study.

INTRODUCTION: Pneumatosis intestinalis (PI) is air collections within the wall of the intestine that can be associated with life threatening conditions. Recurrent episodes of PI have been reported; however, little is known about risks for recurrent disease. This study aims to identify predictors of recurrent PI and evaluate long-term outcomes in patients with recurrent PI. METHODS: This retrospective case-control study evaluated patients, ages 6 months to 18 years, with imaging evidence of PI over a 30-month period. Images were analyzed by consensus to confirm PI. Recurrent PI was defined as new findings of PI after resolution by imaging and/or at least 1-month interval between episodes of PI. Univariate and multivariable analyses were performed using logistic regression, with significance set to P < 0.05. RESULTS: Forty-six children were included. Recurrent PI occurred in 17 (37%) patients, with a total of 39 episodes. Predictors of recurrent PI all related to the segment of bowel involved with small bowel PI predictive of recurrent PI (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.01, 2.4) and colonic PI protective (OR 0.6; 95% CI 0.4, 0.87) after adjusting for age. Predictors for surgical intervention included cerebral palsy (OR 17; 95% CI 1.7, 167) and PI involving small bowel (OR 19; 95% 3.1, 114). CONCLUSION: Location of PI is predictive of recurrence. Clinical outcomes were similar between groups with single episode and recurrent PI.

The Impact of COVID-19 on Job Prospects and Educational Training for Pediatric Gastroenterology Fellows.

OBJECTIVES: The COVID-19 pandemic has significantly affected graduate medical education with redistribution of trainees, altered clinical care, and decreased research. For graduating trainees, there remains concern that financial stability of health systems will affect the availability of new positions and hiring practices. This survey aims to evaluate the pandemic's impact from pediatric gastroenterology fellows' perspectives. METHODS: An anonymous survey was distributed by e-mail from June 11 to July 1, 2020 to all North American pediatric gastroenterology and advanced training fellows. The survey was tailored for the fellows' year of training including questions on education, clinical experience, research, and job outlook. RESULTS: Of the 434 pediatric gastroenterology fellows, 145 completed the survey. Of all respondents, negative impact was reported in 52% on clinical training, 46% research projects, and 41% procedural confidence. A majority (93%) of third-year respondents had a job contract signed at the time of the survey; however, 18% of those contracts were subsequently altered with 5 respondents having job contracts rescinded due to hiring freezes. Fifty-four percent of first- and second-year fellow respondents reported concern regarding finding a job with the majority being second-year fellows (78%). CONCLUSIONS: The COVID-19 pandemic continues to affect the medical system and healthcare professionals. This survey identified significant impact on job acquisition for graduating pediatric gastroenterology fellows and other critical components of training, which are likely applicable to other pediatric trainees. The survey results raise questions about potential strategies to improve medical education and job search success for graduating trainees.

Fully quantitative pixel-wise analysis of cardiovascular magnetic resonance perfusion improves discrimination of dark rim artifact from perfusion defects associated with epicardial coronary stenosis.

BACKGROUND: Dark rim artifacts in first-pass cardiovascular magnetic resonance (CMR) perfusion images can mimic perfusion defects and affect diagnostic accuracy for coronary artery disease (CAD). We evaluated whether quantitative myocardial blood flow (MBF) can differentiate dark rim artifacts from true perfusion defects in CMR perfusion. METHODS: Regadenoson perfusion CMR was performed at 1.5 T in 76 patients. Significant CAD was defined by quantitative invasive coronary angiography (QCA) ≥ 50% diameter stenosis. Non-significant CAD (NonCAD) was defined as stenosis by QCA < 50% diameter stenosis or computed tomographic coronary angiography (CTA) < 30% in all major epicardial arteries. Dark rim artifacts had study specific and guideline-based definitions for comparison purposes. MBF was quantified at the pixel-level and sector-level. RESULTS: In a NonCAD subgroup with dark rim artifacts, stress MBF was lower in the subendocardial than midmyocardial and epicardial layers (2.17 ± 0.61 vs. 3.06 ± 0.75 vs. 3.24 ± 0.80 mL/min/g, both p < 0.001) and was also 30% lower than in remote regions (2.17 ± 0.61 vs. 2.83 ± 0.67 mL/min/g, p < 0.001). However, subendocardial stress MBF in dark rim artifacts was 37-56% higher than in true perfusion defects (2.17 ± 0.61 vs. 0.95 ± 0.43 mL/min/g, p < 0.001). Absolute stress MBF differentiated CAD from NonCAD with an accuracy ranging from 86 to 89% (all p < 0.001) using pixel-level analyses. Similar results were seen at a sector level. CONCLUSION: Quantitative stress MBF is lower in dark rim artifacts than remote myocardium but significantly higher than in true perfusion defects. If confirmed in larger series, this approach may aid the interpretation of clinical stress perfusion exams. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00027170 ; first posted 11/28/2001; updated 11/27/2017.

Quantitative pixel-wise measurement of myocardial blood flow: the impact of surface coil-related field inhomogeneity and a comparison of methods for its correction.

BACKGROUND: Surface coil-related field inhomogeneity potentially confounds pixel-wise quantitative analysis of perfusion CMR images. This study assessed the effect of surface coil-related field inhomogeneity on the spatial variation of pixel-wise myocardial blood flow (MBF), and assessed its impact on the ability of MBF quantification to differentiate ischaemic from remote coronary territories. Two surface coil intensity correction (SCIC) techniques were evaluated: 1) a proton density-based technique (PD-SCIC) and; 2) a saturation recovery steady-state free precession-based technique (SSFP-SCIC). METHODS: 26 subjects (18 with significant CAD and 8 healthy volunteers) underwent stress perfusion CMR using a motion-corrected, saturation recovery SSFP dual-sequence protocol. A proton density (PD)-weighted image was acquired at the beginning of the sequence. Surface coil-related field inhomogeneity was approximated using a third-order surface fit to the PD image or a pre-contrast saturation prepared SSFP image. The estimated intensity bias field was subsequently applied to the image series. Pixel-wise MBF was measured from mid-ventricular stress images using the two SCIC approaches and compared to measurements made without SCIC. RESULTS: MBF heterogeneity in healthy volunteers was higher using SSFP-SCIC (24.8 ± 4.1%) compared to PD-SCIC (20.8 ± 3.0%; p = 0.009), however heterogeneity was significantly lower using either SCIC technique compared to analysis performed without SCIC (36.2 ± 6.3%). In CAD patients, the difference in MBF between remote and ischaemic territories was minimal when analysis was performed without SCIC (0.06 ± 0.91 mL/min/kg), and was substantially lower than with either PD-SCIC (0.50 ± 0.63 mL/min/kg; p = 0.013) or with SSFP-SCIC (0.63 ± 0.89 mL/min/kg; p = 0.005). In 6 patients, MBF quantified without SCIC was artifactually higher in the stenosed coronary territory compared to the remote territory. PD-SCIC and SSFP-SCIC had similar differences in MBF between remote and ischaemic territories (p = 0.145). CONCLUSIONS: This study demonstrates that surface coil-related field inhomogeneity can confound pixel-wise MBF quantification. Whilst a PD-based SCIC led to a more homogenous correction than a saturation recovery SSFP-based technique, this did not result in an appreciable difference in the differentiation of ischaemic from remote coronary territories and thus either method could be applied.

What Do We C in Children With Scurvy? A Case Series Focused on Musculoskeletal Symptoms.

OBJECTIVES: Vitamin C deficiency in children commonly presents with musculoskeletal symptoms such as gait disturbance, refusal to bear weight, and bone or joint pain. We aimed to identify features that could facilitate early diagnosis of scurvy and estimate the cost of care for patients with musculoskeletal symptoms related to scurvy. METHODS: We conducted a retrospective chart review of patients at a single site with diagnostic codes for vitamin C deficiency, ascorbic acid deficiency, or scurvy. Medical records were reviewed to identify characteristics including presenting symptoms, medical history, and diagnostic workup. The Pediatric Health Information System was used to estimate diagnostic and hospitalization costs for each patient. RESULTS: We identified 47 patients with a diagnosis of scurvy, 49% of whom had a neurodevelopmental disorder. Sixteen of the 47 had musculoskeletal symptoms and were the focus of the cost analysis. Three of the 16 had moderate or severe malnutrition, and 3 had overweight or obesity. Six patients presented to an emergency department for care, 11 were managed inpatient, and 3 required critical care. Diagnostic workups included MRI, computed tomography, echocardiogram, endoscopy, lumbar puncture, and/or EEG. Across all patients evaluated, the cost of emergency department utilization, imaging studies, diagnostic procedures, and hospitalization totaled $470 144 (median $14 137 per patient). CONCLUSIONS: Children across the BMI spectrum, particularly those with neurodevelopmental disorders, can develop vitamin C deficiency. Increased awareness of scurvy and its signs and symptoms, particularly musculoskeletal manifestations, may reduce severe disease, limit adverse effects related to unnecessary tests/treatments, and facilitate high-value care.

Patient-Reported Outcomes Correlate With Microbial Community Composition Independent of Mucosal Inflammation in Pediatric Inflammatory Bowel Disease.

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

Case report: Pulmonary hypertensive crisis leading to cardiac arrest during endoscopic evaluation in a 6-year-old boy with autism, severe malnutrition, and undiagnosed scurvy.

Pediatric gastroenterologists are often responsible for the evaluation of malnutrition in the setting of selective eating. Endoscopic evaluation for conditions including eosinophilic esophagitis and celiac disease can help to identify and treat mucosal disease contributing to food selectivity. However, undiagnosed micronutrient deficiencies can cause cardiovascular derangements that significantly increase a patient's anesthetic risk. Vitamin C deficiency in particular, alone or in combination with severe malnutrition, is associated with a severe but reversible form of pulmonary arterial hypertension that, while life threatening in the acute phase, may significantly improve within days of starting ascorbic acid replacement therapy. Here we present a case of a 6-year-old boy with autism spectrum disorder (ASD), severe malnutrition, and undiagnosed chronic vitamin C deficiency who developed a pulmonary hypertensive crisis after induction of general anesthesia leading to cardiac arrest during endoscopic evaluation. While the association between food selectivity among youth with neurodevelopmental differences and vitamin C deficiency is well-described, and pulmonary hypertension is a recognized rare complication of scurvy, extant literature has not addressed next steps to improve patient outcomes. Using this case report as a foundation, we discuss specific patient populations to screen and treat for micronutrient deficiencies prior to anesthesia and propose a novel clinical algorithm for pre-anesthesia risk stratification and mitigation in patients specifically at risk for scurvy and associated pulmonary hypertension.

Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease.

BACKGROUND: Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. MATERIALS AND METHODS: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq, and the ileal microbial community composition was characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. RESULTS: After controlling for ileal location, baseline ileal LN (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), increasing serum albumin (OR, 4; 95% CI, 1.3-12.3), and anti-Saccharomyces cerevisiae antibodies IgG serology (OR, 0.97; 95% CI, 0.95-1) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (area under the curve, 0.86; positive predictive value, 80%; negative predictive value, 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate-producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and the genus Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, and Aggregatibacter and Blautia bacteria were associated with reduced extracellular matrix gene expression. CONCLUSIONS: Pediatric patients with CD with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.

Mucosal Inflammatory and Wound Healing Gene Programs Reveal Targets for Stricturing Behavior in Pediatric Crohn's Disease.

BACKGROUND AND AIMS: Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures. METHODS: Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. RESULTS: 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94)). CONCLUSION: An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches.

Diagnostic Performance of Fully Automated Pixel-Wise Quantitative Myocardial Perfusion Imaging by Cardiovascular Magnetic Resonance.

OBJECTIVES: The authors developed a fully automated framework to quantify myocardial blood flow (MBF) from contrast-enhanced cardiac magnetic resonance (CMR) perfusion imaging and evaluated its diagnostic performance in patients. BACKGROUND: Fully quantitative CMR perfusion pixel maps were previously validated with microsphere MBF measurements and showed potential in clinical applications, but the methods required laborious manual processes and were excessively time-consuming. METHODS: CMR perfusion imaging was performed on 80 patients with known or suspected coronary artery disease (CAD) and 17 healthy volunteers. Significant CAD was defined by quantitative coronary angiography (QCA) as ≥70% stenosis. Nonsignificant CAD was defined by: 1) QCA as <70% stenosis; or 2) coronary computed tomography angiography as <30% stenosis and a calcium score of 0 in all vessels. Automatically generated MBF maps were compared with manual quantification on healthy volunteers. Diagnostic performance of the automated MBF pixel maps was analyzed on patients using absolute MBF, myocardial perfusion reserve (MPR), and relative measurements of MBF and MPR. RESULTS: The correlation between automated and manual quantification was excellent (r = 0.96). Stress MBF and MPR in the ischemic zone were lower than those in the remote myocardium in patients with significant CAD (both p < 0.001). Stress MBF and MPR in the remote zone of the patients were lower than those in the normal volunteers (both p < 0.001). All quantitative metrics had good area under the curve (0.864 to 0.926), sensitivity (82.9% to 91.4%), and specificity (75.6% to 91.1%) on per-patient analysis. On a per-vessel analysis of the quantitative metrics, area under the curve (0.837 to 0.864), sensitivity (75.0% to 82.7%), and specificity (71.8% to 80.9%) were good. CONCLUSIONS: Fully quantitative CMR MBF pixel maps can be generated automatically, and the results agree well with manual quantification. These methods can discriminate regional perfusion variations and have high diagnostic performance for detecting significant CAD. (Technical Development of Cardiovascular Magnetic Resonance Imaging; NCT00027170).

Comparison of Infant Gut and Skin Microbiota, Resistome and Virulome Between Neonatal Intensive Care Unit (NICU) Environments.

Background: There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Study Design: Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus. Metagenomic sequencing was performed and data analyzed by CosmosID bioinformatics software package. Results: There were no significant differences between the cohorts in gestational age, length of stay, and delivery mode; infants in the old NICU received significantly more antibiotics (p = 0.03). Differentially abundant antimicrobial resistance genes and virulence associated genes were found between the cohorts in stool and skin, with more differentially abundant antimicrobial resistance genes in the new NICU. The entire bacterial microbiota analyzed to the genus level significantly differed between cohorts in skin (p = 0.0001) but not in stool samples. There was no difference in alpha diversity between the two cohorts. DNA viruses and fungi were detected but did not differ between cohorts. Conclusion: Differences were seen in the resistome and virulome between the two cohorts with more differentially abundant antimicrobial resistance genes in the new NICU. This highlights the influence that different NICU environments can have on the neonatal microbiota. Whether the differences were due to the new NICU being a single-family NICU or located in a newly constructed building warrants exploration. Long term health outcomes from the differences observed must be followed longitudinally.

The Microbiome in Necrotizing Enterocolitis: A Case Report in Twins and Minireview.

Our case describes the serial microbiome changes in twins discordant for necrotizing enterocolitis (NEC), who shared similar intrauterine and early environmental exposures. The key findings were that the 2 neonates had distinctly different microbiome compositions from the first stool samples collected. Also, in the twin who developed NEC there was a decrease in bacterial diversity and an increase in Proteobacteria a week before developing any clinical symptoms, suggesting an early role of the intestinal microbiome in the development of NEC. Here we briefly review the literature on the role of the intestinal microbiome in NEC and how a greater understanding of the neonatal microbiome and host interactions may help mitigate this devastating disease.