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.
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.
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.
A 16-year-old boy with recent weight loss and elevated inflammatory markers presented to the emergency department with abdominal pain. CT abdomen revealed ileal perforation, fluid collection in the right lower quadrant, and multiple areas of small and large bowel inflammation, suspicious for Crohn disease. He was treated with IV antibiotics and gut rest. During antibiotic therapy, he developed bone lesions in the vertebra most consistent with chronic recurrent multifocal osteomyelitis (CRMO) (Fig. 1). After he underwent surgical drainage for persistent fluid collection, Crohn disease was confirmed with endoscopy and biopsies; anti-tumor necrosis factor a therapy was initiated. He clinically improved with weight gain and normalization of inflammatory markers. A year later, repeat imaging showed complete resolution of the bone lesions (Fig. 2).CRMO (now referred as chronic noninfectious osteomyelitis) has been described in literature as a rare extraintestinal manifestation of IBD (1,2). It is an aseptic inflammation of the metaphyses of long bones, although any part of the skeleton may be affected. It is considered autoimmune in etiology and has been described in association with other autoimmune diseases (3,4,5). When it occurs in association with IBD, often the bone lesions predate the gut symptoms (1). The lesions are always sterile and respond to antiinflammatory therapy (2,6,7).
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.
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