Impact of Coronavirus disease 2019 pandemic in children with functional abdominal pain disorders: Data from long-term follow-up.

OBJECTIVE: We aimed to compare symptom frequency and severity in children with functional abdominal pain disorders (FAPDs) and to evaluate anxiety, quality of life (QoL) and global health during Coronavirus disease 2019 (COVID-19) related quarantine and after 17 months. METHODS: Children diagnosed with FAPDs between October 2019 and February 2020 at 5 different centers were enrolled and prospectively interviewed during the COVID-19 quarantine and 17 months later when schools, hospital services, and routine activities had re-opened to the public. The patients were asked to complete the Rome IV questionnaire, the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale, the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and global health questionnaires. Data about COVID-19 infection and its clinical outcome were also collected. RESULTS: Ninety-nine out of 180 (55%) children completed the follow-up. The number of patients reporting a worsening of their symptoms was significantly higher at follow-up when compared to the quarantine period (24/99 [24.2%] vs. 12/99 [12.1%]; p = 0.04). The PedsQL 4.0 subtotal score at follow-up significantly decreased at 17 months of follow-up (65.57 [0-100]) when compared to the quarantine (71 [0-100], p = 0.03). Emotional functioning was the most significantly reduced (Follow-up: 64.7 [0-100] vs. Quarantine: 75 [0-100]; p = 0.006). We did not identify significant differences in symptoms and QoL between COVID-19 infected children and the remaining cohort at the two time points. CONCLUSIONS: An improvement of symptoms and QoL was observed during the quarantine, followed by a worsening at-follow-up. These findings reinforce the hypothesis that the nest effect overweighted COVID-19 fears during the quarantine and highlight the importance of psychological factors in symptom exacerbation.

Impact of Coronavirus Disease 2019 on the Pediatric Population with Aerodigestive Disease.

OBJECTIVE: To determine the impact of the coronavirus disease 2019 (COVID-19) quarantine on baseline health, medication use, health anxiety, and healthcare use in pediatric patients with aerodigestive disease and to evaluate for associations of commonly prescribed medications with the risk of COVID-19 illness. STUDY DESIGN: Prospective study of patients presenting in person to pediatric neurogastroenterology clinics between July 2020 and March 2021. RESULTS: Of 202 recruited patients, 71.3% were seen in the aerodigestive diseases center and 28.7% in the functional abdominal pain (FAP)/motility clinic. Of all patients, 25.1% reported improved overall health during quarantine; patients with aerodigestive disease (35.3%) reported higher rates of improved overall health compared with patients with FAP/motility disorders (3.6%, P = .0001). Patients with aerodigestive disease had fewer airway symptoms (P < .05) and less medication use during quarantine (inhaled steroids, P < .05 and albuterol, P < .05). Despite objective improvement, there was significant health-related anxiety, with greater anxiety scores reported during and at the end of quarantine (P < .05), with no difference between patient groups (P > .11). Patients continued to access healthcare during quarantine. In total, 28.7% of patients were seen in the emergency department (patients with FAP more than patients with aerodigestive disease, P = .02), and 19.8% were hospitalized. COVID-19 testing was performed in 58.4% of patients and 2.0% (n = 4) of the entire cohort tested positive. CONCLUSIONS: Patients with aerodigestive disease show improvement of airway symptoms and decreased use of medications during the pandemic, despite increased health-related anxiety. Despite complexities of accessing care due to the widespread lockdown, all patient groups continued to access healthcare.

Overall Impact of Coronavirus Disease 2019 Outbreak in Children With Functional Abdominal Pain Disorders: Results From the First Pandemic Phase.

OBJECTIVE: We aimed to assess how the first phase of coronavirus disease 2019 (COVID-19) pandemic influenced symptoms in children with functional abdominal pain disorders (FAPDs) and to characterize their quality of life (QoL), anxiety and global health. METHODS: This was a multicenter, observational, international study conducted between April and July 2020 at six different referral centers. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group). Patients were asked to complete PedsQL 4.0 Generic Core Scale and PROMIS Anxiety and Global Health questionnaires. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group. RESULTS: Three-hundred-fifty-six children were enrolled of whom 180 (mean age at diagnosis: 14 ±â€Š2.8 years) in the Quarantine group and 176 (mean age at diagnosis: 13 ±â€Š2.8 years) in the Control group. At 4 months of follow-up, we observed a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline, in both groups (Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001). The Quarantine group had median QoL values of 84.8 with 16.6% of children showing high anxiety values and 55% having decreased global health score. CONCLUSIONS: We demonstrated symptoms' improvement at 4 months of follow-up in both cohorts. During the first months of the COVID-19 quarantine children with FAPDs showed satisfactory QoL and anxiety scores, suggesting positive effects of school closure and increased parental attention.

Pediatric Collagenous Gastritis: Clinical and Histologic Outcomes in a Large Pediatric Cohort.

OBJECTIVE: The aim of the study was to present the clinical characteristics, treatment, and outcomes of pediatric collagenous gastritis (CG). METHOD: This is a retrospective cohort study. Patients were identified via query of the institutional pathology database. Clinical data was obtained by review of medical records. RESULTS: Forty patients (57.5% female) were identified, mean age 11.3 ±â€Š3.7 years (2-16years). Isolated CG was present in 66.7%, coexisting collagenous duodenitis (CD) in 17.5%, collagenous colitis (CC) in 7.5%, and collagenous ileitis in 2.5%. Atopic comorbidities were found in 25%, autoimmune comorbidities in 12.5%. PRESENTING SYMPTOMS: Abdominal pain (77.5%), vomiting (65%), anemia (57.5%), nausea (55.5%), diarrhea (32.5%), anorexia (25.0%), weight loss (25%), gastrointestinal bleed (22.5%), poor growth (20%), poor weight gain (12.5%). ENDOSCOPIC FINDINGS: All had abnormal endoscopic findings on esophago-gastro-duodenoscopy (EGD), most commonly gastric nodularity (77.5%), visible blood (20%), erosions/superficial ulcerations (10%), ulcers (7.5%). Histologically, all patients had increased subepithelial collagen deposition. TREATMENT: A variety of medications aimed towards inflammation and symptomatic treatment were used. Patients with anemia received iron supplementation and responded. Otherwise, there was no significant association of clinical or histologic improvement with specific treatments. CLINICAL AND HISTOLOGIC OUTCOMES: 87.5% reported improvement or resolution of symptoms at the last follow-up (34.8 ±â€Š27.0 months). Persistent sub-epithelial collagen was noted in 73.1% on the last EGD. CONCLUSIONS: Despite persistent findings of increased sub-epithelial collagen deposition during the follow-up period, most patients with CG show remission or resolution of clinical symptoms. Anemia responds to iron supplementation in all patients.

Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls.

OBJECTIVES: Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D. METHODS: Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations. RESULTS: Mean age was 14.7 ±â€Š2.5 years (42.3% female) in IBS-D and 12.6 ±â€Š2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002). CONCLUSIONS: Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D.

Healthcare spending and utilization for pediatric Irritable Bowel Syndrome in a commercially insured population.

BACKGROUND: Pediatric Irritable Bowel Syndrome (IBS) is common and can be associated with disabling gastrointestinal symptoms. Comprehensive data regarding utilization and cost of pediatric IBS are lacking. Our aim was to determine the annual all-cause spending and healthcare utilization in pediatric IBS. METHODS: Cross-sectional cohort study using a national claims database of commercially insured individuals. 932,592 members, age 8-18 years, were included. Members were selected based on PheWas codes and continuous enrollment in 2014. Linear and binomial regression models were used to calculate healthcare spending and compare comorbidities between IBS subjects and controls. KEY RESULTS: 1215 members with claims for IBS (68.4% female) and 931,377 controls (55.7% female) were included. Mean age was 15.03 ± 2.83 (median 16) years in the IBS group and 13.14 ± 3.12 (median 13) years in controls. Mental health and chronic pain comorbidities were more prevalent in the IBS cohort. Healthcare spending: The mean annual all-cause incremental spending of members with IBS was $6,364.60 compared to controls when adjusting for age and gender. Healthcare utilization: Members with IBS had increased healthcare utilization including higher rates of inpatient, outpatient, and emergency room visits, and higher rates of health service utilization including medical care, radiology/laboratory services, surgery, anesthesia, mental health, and physical therapy. General pediatrics was more frequently consulted by controls. All subspecialty consultations, with the exception of dental medicine and endocrinology, were sought more frequently by IBS patients. CONCLUSION: Patients with IBS incur significant annual spending through increased healthcare utilization.

Perceptions of Pain Treatment in Pediatric Patients With Functional Gastrointestinal Disorders.

OBJECTIVES: Individual understanding of and expectations for chronic pain treatment can influence treatment adherence and thus success, but little is known about these critical factors in parents and children presenting with pain-predominant functional gastrointestinal disorders. The aim of this study was to identify parent and patient understanding of pain-predominant functional gastrointestinal disorders, expectations for treatment, and interventions utilized before presenting to a multidisciplinary clinic. MATERIALS AND METHODS: This was a prospective study of patients evaluated in a Multidisciplinary Functional Abdominal Pain Program. Before the clinic visit, parents and patients completed questionnaires regarding their understanding of chronic pain, perceptions of abdominal pain contributors, expectations regarding treatment, and identification of previous interventions utilized. RESULTS: Participants were knowledgeable regarding the biology of chronic pain. Perceptions of contributors to abdominal pain included a sensitive stomach, general stress, and nerves/worry. Most had attempted to treat their pain with medication, exercise or physical therapy, or a psychological treatment. Participants reported that receiving a definite diagnosis would be the most helpful intervention, followed by psychological treatment. DISCUSSION: Participants were knowledgeable regarding chronic pain, but still indicated that receiving a definite diagnosis would be the most helpful intervention. Most had tried multiple interventions and did not believe that further medication, testing, or surgery would solve their pain. Instead, parents presenting at this Functional Abdominal Pain Program appeared most hopeful about the benefits of multidisciplinary treatment approaches including psychological interventions, a focus on activity and functioning, and complementary and alternative medicine interventions.

Pediatric Collagenous Gastroenterocolitis Successfully Treated with Methotrexate.

A two-and-one-half-year-old previously healthy female presented with a ten-week history of watery diarrhea, nonbilious and nonbloody emesis, and low-grade fevers. She was found to have severe hypoalbuminemia and hypogammaglobulinemia. Her symptoms persisted, and she became dependent on parenteral nutrition. Biopsies obtained during subsequent endoscopic and colonoscopic studies revealed findings consistent with collagenous gastroenterocolitis. She responded to an empiric course of prednisone, but her symptoms recurred shortly after transitioning to oral budesonide. After successful reinduction with intravenous prednisone, intramuscular methotrexate was initiated. She remained asymptomatic during a 15-month course of therapy, and she continued to do well clinically until approximately nine months after weaning off methotrexate. At that point, she experienced a recurrence of diarrhea, and repeat endoscopic evaluation confirmed collagenous colitis. This responded nicely to a short course of oral budesonide, and she has since remained asymptomatic and off any therapy.

Risk of Serious Infections Associated with Biologic Agents in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analyses.

OBJECTIVE: To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). STUDY DESIGN: A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta-analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. RESULTS: In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor-alpha inhibitors [n = 814 patients], 3 for interleukin-6 inhibitors [n = 318], 6 for interleukin-1 inhibitors [n = 353], and 1 for selective T-lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. CONCLUSIONS: In this systematic review and meta-analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.

Multidisciplinary Treatment Reduces Pain and Increases Function in Children With Functional Gastrointestinal Disorders.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents, frequently resulting in extensive testing, school absenteeism, disability, and poor quality of life.1-3 FGIDs result from a complex interplay between genetic predisposition, biological triggers, and psychosocial triggers, and are best explained by the biopsychosocial model.1 Although this implies the necessity of multidisciplinary treatment, studies showing the efficacy of such an intervention are lacking. We describe the outcome of children with severe FGIDs treated in a multidisciplinary program.

Are We Using Abdominal Radiographs Appropriately in the Management of Pediatric Constipation?

OBJECTIVE: To identify the reasons why pediatric gastroenterologists obtain abdominal radiographs in the management of pediatric constipation. STUDY DESIGN: This was a prospective study surveying providers regarding their rationale, interpretation, resultant change, and confidence in their management before and after obtaining KUBs in patients seen for suspected constipation. Demographics and clinical findings were obtained from medical records. RESULTS: A total of 24 providers were surveyed after 72 patient encounters. Reasons for obtaining an abdominal radiograph included evaluation of stool burden (70%), need for a clean out (35%), fecal impaction (27%), cause of abdominal pain (24%), demonstration of stool burden to families (14%), assessment of response to therapy (13%), or encopresis (10%). The plan was changed in 47.6% of cases based on radiographic findings. In cases in which a plan was outlined before obtaining the radiograph (69%), the initial plan was implemented on average in 52.5%. In cases with no plans before obtaining the radiograph, previously unconsidered plans were implemented in 8.7%. Provider confidence in the management plan increased from 2.4 ± 2.7 to 4.1 ± 1.8 (P < .05) after the abdominal radiograph. CONCLUSION: Abdominal radiographs commonly are obtained by pediatric gastroenterologists in the evaluation and management of constipation. The majority used it to make a diagnosis, and nearly one-half changed their management based on the imaging findings. Overall, they reported an improved confidence in their management plan, despite evidence that radiographic findings poorly correlate with clinical severity. This study highlights the need for further provider education regarding the recommendations delineated in existing constipation guidelines.

A 10-Month-Old With Intermittent Hypotonia and Paralysis.

A 10-month-old boy presented with a 1-day history of flaccid quadriplegia and dysconjugate gaze. His history was remarkable for stereotyped episodes of flaccid quadriplegia or hemiplegia, oculomotor abnormalities, and limb or neck posturing, beginning in the first days of life and becoming more frequent and more prolonged over time. The patient was healthy and developmentally normal between episodes. Results of extensive laboratory evaluations, including EEG and brain imaging studies, were negative. The patient's history, diagnostic evaluation, and final diagnosis are reviewed. This case illustrates the importance of a fundamental understanding of neurologic localization in pediatric care and a focused diagnostic approach to an infant with paroxysmal neurologic signs.

MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. To identify novel candidates for targeted therapy, we performed a comprehensive transcriptome analysis identifying MondoA (MLXIP) - a transcription factor regulating glycolysis - to be overexpressed in ALL compared to normal tissues. Using microarray-profiling, gene-set enrichment analysis, RNA interference and functional assays we show that MondoA overexpression increases glucose catabolism and maintains a more immature phenotype, which is associated with enhanced survival and clonogenicity of leukemia cells. These data point to an important contribution of MondoA to leukemia aggressiveness and make MondoA a potential candidate for targeted treatment of ALL.