Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Characterization of pharyngeal contractile integral using pharyngeal manometry in children.

OBJECTIVES: Pharyngeal contractile integral (PhCI) is the product of mean pharyngeal contractile amplitude, length, and duration, and provides a single metric for the vigor of entire pharyngeal contraction. A major limitation in children is lack of characterization of PhCI on high-resolution pharyngeal manometry. We aimed to determine and compare the values of PhCI in children with the abnormal and normal videofluoroscopic study of swallow (VFSS). METHODS: Children who underwent high-resolution pharyngeal and esophageal manometry (HRPM/HREM), as well as VFSS, were divided into two groups; "normal VFSS" and "abnormal VFSS" groups. PhCI was calculated from the pharyngo-esophageal manometry analysis software (MMS, v9.5, Laborie Medical Technologies), and compared in these two groups. RESULTS: Of 67 children, 9 had abnormal VFSS (mean age 64 ± 50 months; 66.7% males), while 58 had normal VFSS (mean age 123 ± 55 months; 47% males). The mean PhCI in abnormal and normal VFSS groups was 82.00 ± 51.90 and 147.28 ± 53.89 mmHg.s.cm, respectively (p = 0.001). Subjects with abnormal VFSS were significantly younger than those with normal VFSS (p = 0.003). However, after adjusting for the VFSS result, age was no longer related to PhCI (p = 0.364). In subgroup analysis of children presenting with dysphagia, the mean PhCI in abnormal (9 subjects) and normal (36 subjects) VFSS groups was 82.00 ± 51.90 and 141.86 ± 50.39 mmHg.s.cm, respectively (p = 0.003). CONCLUSIONS: PhCI was significantly lower in children with abnormal VFSS than in those with normal VFSS. We did not find a significant impact of age on PhCI in our pediatric populations.

A comparison of the success rate of pneumatic reduction in intussusception between general anesthesia and deep sedation: a randomized controlled trial.

PURPOSE: This study was aimed to compare the success rate between patients who underwent general anesthesia and deep sedation. METHODS: Patients who were diagnosed with intussusception and had no contraindications would receive non-operative treatment first by undergoing pneumatic reduction. The patients were then split in to two groups: one group underwent general anesthesia (GA group), while the other underwent deep sedation (SD group). This study was a randomized controlled trial which compared success rate between two groups. RESULTS: A total of 49 episodes diagnosed with intussusception were random into 25 episodes in GA group and 24 episodes in SD group. There was no significant difference in baseline characteristic between the two groups. The success rates of GA group and SD group were equally 88.0% (p = 1.00). Sub-analysis of the success rate was lower in the patients with high-risk score for failed reduction. (Chiang Mai University Intussusception (CMUI) failed score in success VS failed = 6.9 ± 3.2 vs. 10.3 ± 3.0 p = 0.017). CONCLUSION: General anesthesia and deep sedation offered similar success rates. In cases of high risk of failure, general anesthesia should be considered to accommodate the switch to surgical management in the same setting if the non-operative approach fails. The appropriate treatment and sedative protocol also increase the success of reduction.

Evaluation of Chronic Constipation in Children With Autism Spectrum Disorder.

OBJECTIVES: Chronic constipation occurs frequently in children with autism spectrum disorder (ASD). The primary objective was to determine whether chronic constipation is associated with a higher rate of abnormal colonic motor activity in ASD children than in non-ASD children. A secondary goal was to determine if clinical variables could identify children with ASD at risk for possessing abnormal colonic motility. METHODS: A retrospective, propensity-matched, case-control study compared colonic manometry (CM) of an ASD cohort and non-ASD controls with chronic constipation. Clinical variables were evaluated as potential predictors for abnormal colonic motility. RESULTS: Fifty-six patients with ASD and 123 controls without the diagnosis of ASD who underwent CM were included. Propensity score resulted in 35 matched cohorts of ASD and controls. The rate of abnormal CM findings between ASD and matched controls (24% vs 20%, P = 0.78) did not differ significantly. A prediction model of abnormal CM that included ASD diagnosis, duration of constipation, and soiling achieved a sensitivity of 0.94 and specificity of 0.65. The risk for abnormal colonic motility increased 11% for every 1-year increase in duration of constipation. Odds for abnormal motility were 30 times higher in ASD children with soiling than controls with soiling (P < 0.0001). CONCLUSIONS: Chronic constipation does not appear to be associated with a higher rate of abnormal colonic motility in children with ASD. Clinical information of disease duration and presence of soiling due to constipation show promise in identifying patients with ASD at a greater risk for abnormal colonic motility.

Novel Variants and Phenotypes in NEUROG3-Associated Syndrome.

CONTEXT: Biallelic pathogenic variants in the NEUROG3 gene cause malabsorptive diarrhea, insulin-dependent diabetes mellitus (IDDM), and rarely hypogonadotropic hypogonadism. With only 17 reported cases, the clinical and mutational spectra of this disease are far from complete. OBJECTIVE: To identify the underlying genetic etiology in 3 unrelated Thai patients who presented with early-onset malabsorptive diarrhea, endocrine abnormalities, and renal defects and to determine the pathogenicity of the newly identified pathogenic variants using luciferase reporter assays and western blot. METHODS: Three unrelated patients with congenital diarrhea were recruited. Detailed clinical and endocrinological features were obtained. Exome sequencing was performed to identify mutations and in vitro functional experiments including luciferase reporter assay were studied to validate their pathogenicity. RESULTS: In addition to malabsorptive diarrhea due to enteric anendocrinosis, IDDM, short stature, and delayed puberty, our patients also exhibited pituitary gland hypoplasia with multiple pituitary hormone deficiencies (Patient 1, 2, 3) and proximal renal tubulopathy (Patient 2, 3) that have not previously reported. Exome sequencing revealed that Patient 1 was homozygous for c.371C > G (p.Thr124Arg) while the other 2 patients were homozygous for c.284G > C (p.Arg95Pro) in NEUROG3. Both variants have never been previously reported. Luciferase reporter assay demonstrated that these 2 variants impaired transcriptional activity of NEUROG3. CONCLUSIONS: This study reported pituitary gland hypoplasia with multiple pituitary hormone deficiencies and proximal renal tubulopathy and 2 newly identified NEUROG3 loss-of-function variants in the patients with NEUROG3-associated syndrome.

Effect of percutaneous electrical nerve field stimulation on mechanosensitivity, sleep, and psychological comorbidities in adolescents with functional abdominal pain disorders.

BACKGROUND: Percutaneous electrical nerve field stimulation (PENFS) improves symptoms in adolescents with functional abdominal pain disorders (FAPDs). However, little is known about its impact on sleep and psychological functioning. We evaluated the effects of PENFS on resting and evoked pain and nausea, sleep and psychological functioning, and long-term outcomes. METHODS: Patient ages 11-19 years with FAPD requiring PENFS as standard care were recruited. Evoked pain was elicited by a Water Load Symptom Provocation Task (WL-SPT) before and after four weeks of treatment. Pain, gastrointestinal symptoms, sleep, somatic symptoms, and physical and psychological functioning were assessed. Actigraphy was used to measure daily sleep-wake patterns. KEY RESULTS: Twenty patients (14.3 ± 2.2 years old) with FAPD were enrolled. Most patients were females (70%) and white (95%). During pain evoked by WL-SPT, visual analog scale (VAS) pain intensity and nausea were lower following PENFS compared with baseline (p = 0.004 and p = 0.02, respectively). After PENFS, resting VAS pain unpleasantness (p = 0.03), abdominal pain (p < 0.0001), pain catastrophizing (p = 0.0004), somatic complaints (0.01), functional disability (p = 0.04), and anxiety (p = 0.02) exhibited significant improvements, and some were sustained long-term. Self-reported sleep improved after PENFS (p's < 0.05) as well as actigraphy-derived sleep onset latency (p = 0.03). CONCLUSIONS AND INFERENCES: We demonstrated improvements in resting and evoked pain and nausea, sleep, disability, pain catastrophizing, somatic complaints, and anxiety after four weeks of PENFS therapy. Some effects were sustained at 6-12 months post-treatment. This suggests that PENFS is a suitable alternative to pharmacologic therapy.

Effects of Provocative Testing on Phase III Migrating Motor Complex in Children.

OBJECTIVES: Antroduodenal manometry (ADM) is used to evaluate antral and small intestinal motility, with the presence of phase III migrating motor complexes (MMCs) indicating an intact enteric neuromuscular system. The lack of evidence-based or consensus-driven established norms for MMC in fasting phase and after provocative testing marks a major limitation in the interpretation of ADM studies. We aimed to determine the characteristics of MMC in fasting and post-provocative phase in children. METHODS: Data from subjects ages <20 years with ADM results evaluated at neuro-gastroenterology and Motility Disorders Center, Cincinnati Children's Hospital Medical Center from January 2018 to March 2019 were analyzed. RESULTS: Forty-eight ADM tracings that did not demonstrate abnormal patterns were included; the mean age was 10.00 ±â€Š5.72 years and 50% were male. Indications for ADM included: vomiting (27.1%), feeding intolerance (27.1%), abdominal pain (16.6%), nausea (14.6%), and abdominal distension (14.6%). Thirty-seven percent of subjects had enteral access for feeds. During fasting, one-third of all MMC originated in the antrum. Azithromycin-induced MMC occurred in 28% of subjects and two-thirds of these originated in the antrum with antral contractions of significantly higher frequency and amplitude compared to fasting. Octreotide significantly increased frequency, amplitude, and duration of MMC compared to fasting, with 76% originating in the antrum. Both azithromycin and octreotide induced more than one MMC in a third of subjects. CONCLUSIONS: We describe the characteristics of antral and small intestinal motility during fasting and after provocative testing in children. These values will help standardize our interpretation of pediatric ADM studies.

Pharyngeal and upper esophageal sphincter motor dynamics during swallow in children.

BACKGROUND: Motor abnormalities of pharyngeal contraction or upper esophageal sphincter (UES) relaxation can lead to swallowing problems. METHODS: We reviewed high-resolution esophageal manometry of children ≤18 years and classified into two groups based on the results of videofluoroscopic study of swallow (VFSS), as normal or abnormal. The UES metrics (integrated relaxation pressure [IRP], resting pressure [URP], and nadir pressure [UNP]), as well as peak pharyngeal pressure (velopharyngeal and meso-hypopharyngeal), were analyzed. RESULTS: UES metrics: There were 142 and 19 subjects in the normal and abnormal groups, respectively. In the normal group, the median UES-IRP at 0.2, 0.4, 0.6, 0.8 seconds, URP, and UNP were 1.0, 4.0, 11.0, 18.0, 53.5, and -1.0 mm Hg while in the abnormal group were 10.0, 13.0, 21.0, 25.5, 47.0, and 8.0 mm Hg. The UES-IRP at 0.2, 0.4, 0.6 seconds, and UNP was significantly higher in the abnormal group. Pharyngeal metrics: We included 58 subjects in normal and 10 subjects in the abnormal group. The median of peak velopharyngeal and meso-hypopharyngeal pressures were lower in the abnormal group; 188.50 vs 210.50, P = .185 and 110.00 vs 144.75 mm Hg, P = .065. CONCLUSIONS AND INFERENCES: The UES-IRP was lower than adults, URP was higher than preterm but less than adults, and UNP was lower than neonates but similar to adults. The pharyngeal pressures were higher than those reported for neonates and adults. Our data indicate that motor dynamics of swallowing may change from neonates to adulthood and reflect a maturational process. The subjects with abnormal VFSS had significantly higher UES-IRP and UNP compared to normal VFSS.

Clearance of jaundice after the modified Kasai`s operation predicts survival outcomes in patients with biliary atresia.

Tamgal J, Damrongmanee A, Khorana J, Tepmalai K, Ukarapol N. Clearance of jaundice after the modified Kasai`s operation predicts survival outcomes in patients with biliary atresia. Turk J Pediatr 2019; 61: 7-12. The aim of this study was to assess the probability of survival with native liver (SNL) and the rate of esophageal variceal bleeding (EVB) as well as their potential risk factors, in patients diagnosed with Biliary Atresia (BA), who underwent the hepaticoportoenterostomy (HPE) by retrospectively reviewing medical records between 2007 and 2016. The subjects were classified as poor outcomes if they died or a liver transplant (LT) was performed. A total of 73 cases were enrolled. The average age at HPE was 106.2 +/- 58.5 days. Poor outcome was observed in 27.4%, 54.8% survived with native liver and 17.8% were lost to follow-up. The principal cause of death was sepsis, followed by massive upper GI hemorrhage. The overall 10-year SNL was 66.8%. Only total bilirubin (TB) > 3 mg/dL at 3, 6 months after HPE and presence of associated anomalies negatively affected SNL (p=0.0155, 0.0042 and 0.001, respectively). Most of the patients experienced EVB within 3 years of age, in which TB > 9 mg/dL at 12 months after HPE was significantly associated with probability of the EVB outcome. Any interventions to improve jaundice clearance after HPE should be strongly pursued in order to improve outcomes in BA patients, particularly in centers where liver transplantation (LT) is not available. Surveillance esophagogastroduodenoscopy around the age of 1.5 years in patients having TB > 9 mg/dL may be beneficial to identify large varices having potential fatal bleeding.

Adenovirus infection: A potential risk for developing intussusception in pediatric patients.

The pathogenesis of intussusception without obvious anatomical leading points remains unclear. The objective of this study was to determine a feasibility of association between certain gastroenteritis viruses and intussusception. This was a prospective cohort study. Forty intussusception cases and 136 acute gastroenteritis controls with comparable age and gender were separately consecutively enrolled and relevant clinical data of both groups were recorded. The clinical specimens collected from all patients were screened for adenovirus, rotavirus, norovirus, and astrovirus by PCR and RT-PCR using specific primers. The genomes of detected viruses were characterized further to identify their genotypes by nucleotide sequencing. In 40 intussusception cases, adenovirus, rotavirus, and norovirus were detected in 12 (30.0%), 2 (5.0%), and 2 (5.0%), respectively while astrovirus was undetectable. In contrast, 136 acute gastroenteritis patients, adenovirus, rotavirus, and norovirus were detected in 11 (8.1%), 24 (17.7%), and 24 (17.7%) patients, respectively and again astrovirus was undetectable. The detection of adenovirus in intussusception patients was significantly higher than those in the control group (P < 0.001) with an odd ratio of 4.87 (95%CI: 1.95, 12.16). Interestingly, molecular analysis of adenovirus genome demonstrated that all of adenovirus detected in intussusception patients belonged to adenovirus C. This could be a potential risk factor or pathogenesis for developing intussusception in the cases of those without apparent anatomical leading points. J. Med. Virol. 88:1930-1935, 2016. © 2016 Wiley Periodicals, Inc.

Risk of stricture after endoscopic submucosal dissection for large rectal neoplasms.

BACKGROUND AND STUDY AIMS: Improvements in the endoscopic submucosal dissection (ESD) technique have made circumferential ESD in the rectum possible. However, little is known about the clinical course after extensive ESD in the rectum. The aim of this study was to determine the stricture risk in the rectum after total or subtotal circumferential ESD. PATIENTS AND METHODS: A total of 69 patients with 69 rectal tumors that required ≥ 75 % circumferential resection were identified at Kobe University Hospital and an affiliated hospital between April 2005 and May 2014. Among the patients, 61 were available for evaluation of stricture development, either by follow-up colonoscopy or by surgical specimens. The rate and possible risk factors of post-ESD strictures were investigated. RESULTS: Post-ESD rectal strictures developed in 12 patients (19.7 %). Patients who underwent total circumferential ESD developed a stricture (5/7, 71.4 %) more frequently than those with subtotal (≥ 90 %) ESD (7/16, 43.8 %). Patients undergoing an ESD procedure that involved < 90 % of the circumference did not develop strictures. The strictures were membranous or < 10 mm long in all cases. Of the patients with stricture, 11 received endoscopic balloon dilation and one received bougie with short-caliber-tip transparent hood; all strictures improved following dilation therapy. Statistical analysis revealed that ≥ 90 % circumferential resection was an independent risk factor for stricture, whereas morphology and size were not. CONCLUSIONS: Patients who underwent total or subtotal circumferential ESD of a rectal tumor had a high risk of stricture formation. Dilation helped to alleviate the stenosis.Study registered at University Hospital Medical Information Network (UMIN 000016559).

Incidence of antibiotic-associated diarrhea in a pediatric ambulatory care setting.

BACKGROUND: Although antibiotic-associated diarrhea (AAD) is a common adverse event in children receiving oral antibiotics, few epidemiological studies have investigated this issue. OBJECTIVE: To determine the incidence of AAD in children who received oral antibiotics at the Pediatric Outpatient Department, Chiang Mai University Hospital. MATERIAL AND METHOD: Children who were prescribed oral antibiotics between September 2004 and June 2005 were randomly enrolled. Subjects with immunodeficiencies, acute/chronic diarrhea, and a history of having taken antibiotics within two weeks prior to this visit were excluded Patients' characteristics including age, gender principal diagnosis, and type of antibiotics were recorded. Parents were asked to observe stool frequency and consistency until one week after discontinuing antimicrobial agents and fill out an appropriate questionnaire. AAD was defined if there were at least three loose or liquid stools per day for two consecutive days. Risk factors including age, type, and dosage of the antibiotics used, were analyzed RESULTS: Two hundred and twenty-five children were eligible for data analysis. The mean age was 4.1 years (0.3-14.5 years). Pharyngotonsillitis was the most common diagnosis (53.8%), and amoxicillin and cloxacillin comprised the most common antibiotics prescribed in the present cohort. The incidence ofAAD was 6.2%. All episodes were presented while the patients were taking antibiotics with a mean (+/- SD) onset and duration of occurrence of 2.28 +/- 1.13 and 2.64 +/- 1.15 days, respectively. Premature discontinuation of antimicrobial agents was reported in nine patients (64.3%). There was a trend towards a higher incidence of AAD in the amoxicillin/clavulanate group (16.7%) compared to amoxicillin (6.9%) and erythromycin (11.1%) groups, although it was not statistically significant. In addition, the present study could not demonstrate an association between younger age or the high dosage of antibiotics used, and the development ofAAD. CONCLUSION: AAD was not uncommon in a pediatric ambulatory care setting. It tended to occur in younger children receiving amoxicillin/clavulanate.