Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease.

BACKGROUND: We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers. METHODS: Clinical response was assessed by Pediatric Crohn's Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls. RESULTS: Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls. CONCLUSIONS: Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.

Therapeutics for Inflammatory Bowel Diseases in Children and Adolescents: A Focus on Biologics and an Individualized Treatment Paradigm.

Pharmacologic treatment of children and adolescents with inflammatory bowel diseases (IBD) [Crohn's disease and ulcerative colitis] requires consideration of disease and medication effects on growth and nutrition, the importance of durability of biologics, and concerns for long-term sequelae of disease and therapies. Achieving early remission in children with Crohn's disease correlates with improved outcomes and therefore allows a window of opportunity for maximizing growth. Thus, there is a great need to treat children and adolescents with the right drug at the right time while achieving adequate exposure. Improved understanding of disease phenotypes, disease natural history, and risk stratification will play a critical role in treatment selection for children, particularly as more therapeutic options become available. Here we summarize data supporting newer concepts of treating the individual child with IBD through targeted early biologic treatment, including utilization of therapeutic drug monitoring to optimize treatment effects and the use of early antitumor necrosis factor (TNF)-α therapies to mitigate long-term sequelae of the disease. Recent inception cohort studies provide important data regarding the risk stratification of children and adolescents with IBD, which support a move toward a personalized therapeutic approach to IBD in children and adolescents.

Epidemiology and healthcare utilization of inpatient admissions in children with pediatric intestinal pseudo-obstruction.

BACKGROUND: Pediatric intestinal pseudo-obstruction is a rare disorder affecting gastrointestinal motility leading to chronic symptoms and hospitalizations. There is limited understanding of the epidemiology and healthcare burden. METHODS: We analyzed data from Kids' Inpatient Database from 2016, which includes inpatient discharge records from US hospitals. ICD-10 codes were used to identify patients 0-18 years with pediatric intestinal pseudo-obstruction and comorbid conditions. Multivariable logistic regression and Wilcoxon rank-sum test were used. RESULTS: In 2016, there were 1671 inpatient discharges from US hospitals for patients 0-18 years of age with this diagnosis. The incidence of inpatient admission was 29/100 000 patients. After controlling for age, race, income status, and insurance, males vs females (adjusted odds ratio, aOR: 1.10; 95% CI: 0.94-1.28; P = .241) and caucasians vs other races (aOR: 1.55; 95% CI: 1.27-1.88; P < .001) were more likely to be admitted. Inpatient admissions incurred significant healthcare burden; median (inter quartile range IQR) cost of hospitalization of US$ 52 079 (US$ 23 530-120 961) and a median (IQR) length of stay of 6 days (3-14 days). Gastrostomy (32%) and ileostomy (12.6%) status appeared to incur lower healthcare burden. Parenteral nutrition, malnutrition, and central line/bloodstream infections resulted in higher healthcare burden. CONCLUSIONS: Pediatric intestinal pseudo-obstruction is a rare diagnosis with a high incidence of inpatient admissions and healthcare burden. An aggressive multidisciplinary management is crucial in reducing inpatient admissions in this cohort.

Aerodigestive Approach to Chronic Cough in Children.

PURPOSE OF REVIEW: Chronic cough is the most common presenting complaint in a pediatric aerodigestive clinic. The etiology of chronic cough is varied and often includes more than one organ system. This review aims to summarize the current literature for a multidisciplinary approach when evaluating a child with chronic cough. RECENT FINDINGS: There is very little medical literature focused on a multidisciplinary approach to chronic cough. In the limited data available, multidisciplinary clinics have been shown to be more cost-efficient for the families of children with complex medical problems, and also increase the likelihood of successfully obtaining a diagnosis. SUMMARY: There is no consensus in the literature on how to work-up a child with chronic cough presenting to an aerodigestive clinic. Current studies from these clinics have shown improved outcomes related to cost-effectiveness and identifying definitive diagnoses. Future studies evaluating clinical outcomes are necessary to help delineate the utility of testing routinely performed, and to demonstrate the impact of interventions from each specialty on quality of life and specific functional outcome measures.

Do pediatric gastroenterology doctors address pediatric obesity?

OBJECTIVES: To assess how often obesity is acknowledged at pediatric gastroenterology outpatient visits. METHODS: A retrospective chart review was performed to identify obese children seen at a gastroenterology subspecialty clinic over a 1-year period of time; 132 children were identified. Demographics, obesity comorbidities, reasons for referral, diagnosis of obesity, and a plan to address obesity were abstracted. Chi-square or Fisher's exact tests were used to examine statistical associations. RESULTS: Only 49% of children were given a diagnosis of obesity. In total, 52% of children were given a body mass index reduction plan. Those diagnosed with obesity were more likely to receive a body mass index reduction plan (p < 0.0001). Younger children and males were more likely to receive an obesity diagnosis (p = 0.002 and p = 0.02, respectively). Diagnosis of obesity was more likely in patients with obesity-related comorbidities (p = 0.0004) and those referred for obesity or related comorbidities (p = 0.01). CONCLUSION: Obesity is diagnosed less than 50% of the time in pediatric gastroenterology outpatient clinics. To increase opportunities for addressing childhood obesity in the pediatric gastroenterology outpatient setting, further investigation of barriers and optimal provider education is urgently required.