Uma Padhye Phatak

Two-day bowel preparation with polyethylene glycol 3350 and bisacodyl: a new, safe, and effective regimen for colonoscopy in children.

Objectives: To assess the safety, efficacy, and acceptance of a 2-day bowel preparation with polyethylene glycol (PEG) 3350 without electrolytes and bisacodyl for colonoscopy in children. Patients and Methods: In a prospective study, 111 children of mean age 11.9 years were given 2 g/kg of PEG and a 5-mg tablet of bisacodyl daily for 2 days before colonoscopy. Stool frequency, consistency, and adverse effects were monitored for the duration of the bowel preparation. Compliance and quality of colonic preparation were assessed on the day of the colonoscopy. Results: The average daily stool frequency increased from a baseline of 2, to 4* on day 1, and 6.5* on day 2 of the bowel preparation (*P < 0.001 for difference vs baseline). The colonic preparations were rated as excellent or good in 92% and 93% of the patients in the right and left colon, respectively. Adverse effects were mild nausea (19%), abdominal pain (11%), and vomiting (4%). The compliance was rated as excellent in 95% of the patients. Conclusions: A 2-day bowel preparation with PEG and bisacodyl is safe, effective, and well accepted for colonoscopy in children without any major adverse effects.

Prevalence of functional gastrointestinal disorders in obese and overweight children

Objective:To compare the prevalence of functional gastrointestinal disorders such as functional constipation (FC), functional abdominal pain (FAP), functional abdominal pain syndrome (FAPS) and irritable bowel syndrome (IBS) between a large cohort of healthy obese/overweight children and normal-weight children.Methods:Healthy children between the ages of 4 and 18 years were eligible for recruitment from the Yale Pediatric Primary Care clinic, Yale Adolescent clinic and a local private practice in Orange, CT, USA. Study subjects or their parents were interviewed using a questionnaire based on the ROME III standardized criteria for diagnosing functional gastrointestinal disorders. Medical records were reviewed to collect information about age, gender, height, weight, body mass index (BMI), ethnicity and chronic medical conditions. Children were classified into obese, overweight and normal-weight based on their BMI for age and gender. Data were analyzed to compare the prevalence of FC, FAP, FAPS and IBS between obese/overweight children and normal-weight children.Results:A total of 450 children (45% males) were recruited. There were 191 (42%) obese/overweight children and 259 (58%) normal-weight children. FAPS (odds ratio (OR) =2.1, 95% confidence interval (CI): 1.21–3.64, P=0.007), FC (OR=1.83, 95% CI: 1.12–2.98, P=0.01), and IBS (OR=2.59, 95% CI: 1.40–4.79, P=0.003) were significantly more prevalent in the obese/overweight children than in the normal-weight children. Of the obese/overweight children, 47% had at least one functional gastrointestinal disorder compared with 27% of the normal-weight children (P⩽0.001). Only 36% of the children with functional gastrointestinal disorders sought medical attention for their symptoms.Conclusions:Obese/overweight children have a higher prevalence of functional gastrointestinal disorders than normal-weight children. Almost half of the obese/overweight children had at least one functional gastrointestinal disorder.

Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology.

BACKGROUND & AIMS In children with liver failure, as many as half remain of indeterminate aetiology. This hinders timely consideration of optimal treatment options. We posit that a significant subset of these children harbour known inherited metabolic liver diseases with atypical presentation or novel inborn errors of metabolism. We investigated the utility of whole-exome sequencing in three children with advanced liver disease of indeterminate aetiology. METHODS Patient 1 was a 10 year-old female diagnosed with Wilson disease but no detectable ATP7B mutations, and decompensated liver cirrhosis who underwent liver transplant and subsequently developed onset of neurodegenerative disease. Patient 2 was a full-term 2 day-old male with fatal acute liver failure of indeterminate aetiology. Patient 3 was an 8 year-old female with progressive syndromic cholestasis of unknown aetiology since age 3 months. RESULTS Unbiased whole-exome sequencing of germline DNA revealed homozygous mutations in MPV17 and SERAC1 as the disease causing genes in patient 1 and 2, respectively. This is the first demonstration of SERAC1 loss-of-function associated fatal acute liver failure. Patient 1 expands the phenotypic spectrum of the MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. Patient 3 was found to have syndromic cholestasis due to bi-allelic NOTCH2 mutations. CONCLUSIONS Our findings validate the application of whole-exome sequencing in the diagnosis and management of children with advanced liver disease of indeterminate aetiology, with the potential to enhance optimal selection of treatment options and adequate counselling of families. Moreover, whole-exome sequencing revealed a hitherto unrecognized phenotypic spectrum of inherited metabolic liver diseases.

Mycophenolate mofetil-induced colitis in children.

Mycophenolate Mofetil (MMF) is a frequently used medication for the maintenance of immunosuppression in pediatric renal transplant patients. It is known to cause mild gastrointestinal side effects. Severe colitis due to MMF is rare and is only described in adults. We report 2 children who presented with severe colitis due to MMF. Infectious and other causes of diarrhea were ruled out. Our patients had diverse histologic findings on colonic biopsies. Patient 1 had histologic features similar to inflammatory bowel disease and patient 2 to graft versus host disease. Withdrawal of MMF resulted in the complete resolution of symptoms in both patients suggesting a causal association. These cases underscore the importance of considering MMF-induced colitis in any patient who presents with diarrhea while on MMF therapy.

Acute Necrotizing Pancreatitis in Children

OBJECTIVE To describe the etiologic factors, course, and outcome of acute necrotizing pancreatitis in children. STUDY DESIGN We performed a retrospective study of children with necrotizing pancreatitis diagnosed during the last 21 years at Yale-New Haven Childrens Hospital. Computed tomography (CT) criteria were used to diagnose necrotizing pancreatitis and to assess severity index. Charts were reviewed to collect demographics, etiology, details of hospital stay, complications, and outcome. RESULTS Seven children (mean age, 11.6 years; range, 4-17.8 years) had necrotizing pancreatitis. Etiologic factors were medications, diabetes, and gallstones. All had prolonged hospitalization (9-40 days; mean, 20 days) and 5 patients required admission to the pediatric intensive care unit. During the hospital stay, patients developed complications involving the respiratory, hematologic, renal, metabolic, and circulatory systems. All patients had aggressive supportive medical therapy, and none required surgery. There were no deaths attributable to pancreatitis. Late complications after hospital discharge occurred in 5 patients and included pseudocysts, transient hyperglycemia, diabetes, and pancreatic exocrine insufficiency. The CT severity index correlated with the risk of complications. CONCLUSIONS A cute necrotizing pancreatitis has a variable etiology in children. CT scan is useful in the diagnosis and assessment of severity. Necrotizing pancreatitis in children is associated with severe acute and late complications and requires intensive medical therapy.

Celiac disease in a child with ulcerative colitis: a possible genetic association.

Celiac disease and inflammatory bowel disease including ulcerative colitis (UC) and Crohns disease are both immune-mediated enteropathies. It is rare for both celiac disease and inflammatory bowel disease to occur together in an individual patient. This association has been reported in adults, however, very rarely in children. Here, we report an unusual case of an 8-year-old child with a history of anemia and failure to thrive who presented with bloody diarrhea. His evaluation showed anemia, elevated inflammatory markers, and positive celiac antibodies. Endoscopic evaluation revealed partial duodenal villous atrophy and pancolitis. He was diagnosed with celiac disease and UC and responded well to a gluten-free diet and steroid/mesalamine therapy. The patients genetic testing revealed markers showing susceptibility for both celiac disease and UC. It is important to be aware of this association as both conditions can present with similar clinical features, however, require different therapeutic approaches.

Prevalence and Patterns of Marijuana Use in Young Adults with Inflammatory Bowel Disease.

Objectives: Recent studies in adults report symptom relief with marijuana use in patients with inflammatory bowel disease (IBD). We assessed the prevalence, pattern, effects, and adverse effects of marijuana use in young adults with IBD. Methods: We conducted a prospective questionnaire survey study at a pediatric IBD clinic. All patients (18–21 years of age) answered anonymous questionnaires about demographics, IBD, medications, and marijuana use. Results: Fifty-three patients (mean age 18.7 years, 32 boys) were enrolled. Thirty-seven patients (70%) reported using marijuana currently or in the past. There was no statistically significant difference between the users and nonusers of marijuana regarding demographics, disease activity, or medications. Despite prolonged use of marijuana, 70% of patients did not discuss it with their gastroenterologists. Twenty-four patients used marijuana medicinally for IBD symptoms in addition to medical therapy. Although majority found marijuana to be moderately/very helpful, complete relief of symptoms such as abdominal pain, poor appetite, nausea, and diarrhea was seen in 29%, 37%, 14%, and 10% of patients, respectively. Only half of patients reported knowledge of possible adverse effects of marijuana and 19% of patients reported mild neuropsychiatric adverse effects. Overall, 98% of patients supported legalization of marijuana and 85% were interested in using medical marijuana if it became legally available. Conclusions: We found a high rate of marijuana use in our cohort of young adults with IBD. Majority of users report symptom improvement but do not inform physicians. Future well-controlled studies are necessary to assess role of marijuana in IBD therapy.

Role of Polyethylene Glycol in Childhood Constipation

Constipation is a common and chronic problem in children worldwide. Long-term use of laxatives is necessary for successful treatment of chronic constipation. Commonly used laxatives in children include milk of magnesia, lactulose, mineral oil, and polyethylene glycol (PEG). Recent studies report the efficacy and safety of PEG for the long-term treatment of constipation in children. Because of its excellent patient acceptance, PEG is being used widely in children for constipation. In this commentary, we review the recently published pediatric literature on the efficacy, safety, and patient acceptance of PEG. We also assess the role of PEG in childhood constipation by comparing it with other laxatives in terms of efficacy, safety, patient acceptance, and cost.

Recurrent acute pancreatitis in a child with primary hyperparathyroidism.

Hypercalcemia is an important etiology to consider in the evaluation of acute pancreatitis. Not only is it a treatable cause, but understanding the basis for this etiology may provide new insight into the common biochemical mechanisms involved in the pathogenesis of pancreatitis. We report a case of an 11-year-old girl with hypercalcemia due to primary hyperparathyroidism who developed recurrent pancreatitis. We review clinical and experimental data that implicate hypercalcemia as the cause and discuss mechanisms for the association.

P-220 To Assess the Rate of Adequate Immune Response to Primary Hepatitis B Vaccination Series in Patients with IBD

Background:Patients with inflammatory bowel disease (IBD) are often placed on immunosuppressive medications which put them at a potential risk for reactivation of hepatitis B (hep B). Immune response following hep B vaccination is reported to be around 90% in children from the general population. The aim of this study was to assess the rate of adequate immune response to primary hep B vaccination series in patients with IBD. Methods:We performed a retrospective chart review of patients with IBD who had serologic samples tested for hepatitis B surface antigen (HbsAg) and hepatitis B surface antibody (HbsAb) from February 2012 to July 2015. The study was conducted at Yale New Haven Childrens hospital. Patients up to 22 years of age were included. Adequate immune response to hep B was considered to be present when the HbsAb level was above ≥8 mIU/mL by our laboratory standard. Age, gender, BMI (presence of obesity), type of IBD, and medications were noted to assess association of these factors with inadequate response to hep B vaccination. Results:HbsAg and HbsAb levels were tested in 98 children with IBD. Mean age of the patients was 16 (±3) years; 37 females and 61 males. Thirty-seven patients had ulcerative colitis and 61 patients had Crohns disease. None of the patients had a positive HbsAg. Sixty-three (64%) patients were found to be non-immune to hep B with HbsAb level less than 8 mIU/mL. In 35 children with an adequate immune response, the mean level of HbsAb was 91 mIU/mL (range 9 to 560 mIU/mL). Sixty one percent of patients receiving anti-TNF therapy had an inadequate immune response to Hep B. Use of infliximab (24% in non-immune group versus 16% in immune group) or immunomodulators (15% in non-immune group versus 8% in immune group) was not significantly different between the 2 groups. Factors such as gender, type of IBD, presence of obesity were also not significantly different in the non-immune and immune group. Conclusions:Immunity to hepatitis B after primary vaccination series is lower in patients with IBD as compared to the known immune response in the general population (64% versus 90% respectively). Use of immunomodulator or anti-TNF therapy is not associated with lack of immune response to hepatitis B vaccine.