Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial.

OBJECTIVE: Pediatric irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with variable response to various therapeutic agents. Psyllium has been proven to be effective in adults; however, there is no study in children. The objective of this study is to evaluate the efficacy of psyllium husk as compared to placebo in pediatric IBS patients. METHODS: In this double-blind randomized controlled trial, 43 children were assigned to psyllium arm (Group A) and 38 into placebo arm (Group B). Severity is assessed at baseline and after 4 weeks of treatment using IBS severity scoring scale (IBS-SSS) and classified into mild, moderate, and severe categories. Categorical data was compared with chi-square test and paired categorical variable was compared with McNemer test. RESULTS: Mean ages (±SD; in years) of Groups A and B were 9.87 (2.7) and 9.82 (3.17), respectively, with median duration of illness of 12 months. At baseline, type, severity, and parameters (IBS-SSS) of IBS were equally distributed in 2 groups. There was a significant reduction in median interquartile range (IQR) of total IBS-SSS in psyllium versus placebo [75 (42.5-140) vs 225 (185-270); P < 0.001] at 4 weeks. Similarly 43.9% in Group A versus 9.7% in Group B attained remission [IBS-SSS < 75 ( P < 0.0001)]. The mean difference in IBS-SSS between Group A and Group B was -122.85 with risk ratio of 0.64 (95% CI; 0.42-0.83; P = 0.001) and absolute risk reduction of 32% (NNT = 3). CONCLUSIONS: Psyllium husk is effective for the therapy of pediatric IBS when compared with placebo in short term.

Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology.

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Low Osmolarity Oral Rehydration Salt Solution (LORS) in Management of Dehydration in Children.

JUSTIFICATION: The IAP last published the guidelines "Comprehensive Management of Diarrhea" in 2006 and a review in 2016. The WHO in 2002 and the Government of India in 2004 recommended low osmolarity rehydration solution (LORS) as the universal rehydration solution for all ages and all forms of dehydration. However, the use of LORS in India continues to be unacceptably low at 51%, although awareness about ORS has increased from a mere 14% in 2005 to 69% in 2015. Availability of different compositions of ORS and brands in market added to the confusion. PROCESS: The Indian Academy of Pediatrics constituted a panel of experts from the fields of pediatrics, pediatric gastroenterology and nutrition to update on management of dehydration in children with particular reference to LORS and issue a current practice guideline. The committee met twice at CIAP HQ to review all published literature on the aspect. Brief presentations were made, followed by discussions. The draft paper was circulated by email. All relevant inputs and suggestions were incorporated to arrive at a consensus on this practice guideline. OBJECTIVES: To summarize latest literature on ORT and empower pediatricians, particularly those practicing in rural areas, on management of dehydration by augmenting LORS use. RECOMMENDATIONS: It was stressed that advantages of LORS far out-weigh its limitations. Increased use of LORS can only be achieved by promoting better awareness among public and health-care providers across all systems of medicine. LORS can also be useful in managing dehydration in non-diarrheal illness. More research is required to modify ORS further to make it safe and effective in neonates, severe acute malnutrition, renal failure, cardiac and other co-morbidities. There is an urgent need to discourage production and marketing all forms of ORS not in conformity with WHO approved LORS, under a slogan "One India, one ORS".

Endovascular Transjugular Occlusion of Congenital Intrahepatic Portosystemic Venous Shunt Using Simultaneous Fluoroscopy and Transabdominal Ultrasound Guidance: Report of 2 Cases.

Congenital intrahepatic portosystemic venous shunts (CIPVS) are rare anomalies that can be detected before birth or in early infancy or later in life. Symptomatic shunts are treated as they carry high risk of complications like hepatic encephalopathy. Various treatment options include surgery, endovascular embolization, and percutaneous closure devices. We treated 2 infants with CIPVS successfully by endovascular embolization of the shunt using vascular plug through transjugular route. Transabdominal ultrasound guidance in addition to fluoroscopy was used at the time of vascular plug placement. We emphasize that the use of transabdominal ultrasound during endovascular occlusion enhances the safety and technical success rate.

Effect of gluten-free diet and compliance on quality of life in pediatric celiac disease patients.

BACKGROUND: Quality of life (QOL) in children with celiac disease (CD) has been sparsely studied. AIMS: We aimed to study QOL in pediatric CD and the effect of a gluten-free diet (GFD) in a North Indian population. METHODS: QOL was assessed at baseline and 6 months after GFD using a pediatric symptom checklist (PSC) score. The effect of GFD was assessed using a CD-specific questionnaire on domains such as dietary compliance, parental behavior and perceptions, children's feeling, and difficulty identifying gluten-free foods. RESULTS: A total of 60 CD children (age 6.03 ± 0. 42 years, range: 2-12 years, M:F 2:1) were prospectively enrolled. The median PSC score at baseline was 11.5 (2-35), which showed a statistically significant improvement after GFD to 2.5 (0-34) (P < 0.001). Significant concerns regarding specific domains emerged: difficulty in maintaining GFD 26.2%, at school 14.3%, at parties 43.2%, poor taste 11.4%, special diet a burden 28.5%, felt left out at school or friend's home 40.9%, felt different from other kids 40.9%, felt embarrassed to bring GFD to parties 54.6%, felt angry about following a special diet 56.8%, felt not invited out for meals because of CD 13.6%, and difficulty determining if food available was gluten free in 75%. CONCLUSION: GFD has a significant impact on emotional, behavioral, and psychosocial domains in children with CD. Proper labeling of commercially available food items, counseling, and patient support groups are the need of the hour.

Diet and inflammatory bowel disease: The Asian Working Group guidelines.

INTRODUCTION: These Asian Working Group guidelines on diet in inflammatory bowel disease (IBD) present a multidisciplinary focus on clinical nutrition in IBD in Asian countries. METHODOLOGY: The guidelines are based on evidence from existing published literature; however, if objective data were lacking or inconclusive, expert opinion was considered. The conclusions and 38 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. RESULTS: Diet has an important role in IBD pathogenesis, and an increase in the incidence of IBD in Asian countries has paralleled changes in the dietary patterns. The present consensus endeavors to address the following topics in relation to IBD: (i) role of diet in the pathogenesis; (ii) diet as a therapy; (iii) malnutrition and nutritional assessment of the patients; (iv) dietary recommendations; (v) nutritional rehabilitation; and (vi) nutrition in special situations like surgery, pregnancy, and lactation. CONCLUSIONS: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 38 recommendations.

Niemann-Pick Disease: An Underdiagnosed Lysosomal Storage Disorder.

Lysosomal storage disorders (LSDs) collectively constitute a significant public health burden in developing countries. Commoner LSDs include Gaucher, Fabry, and Niemann-Pick disease (NPD), but many cases remain undiagnosed. With the high incidence of consanguineous marriages, South East Asian countries are expected to have high prevalence of these LSDs. Here we report 4 cases of NPD type A/B in 3 families presenting with hepatosplenomegaly and cytopenias including one family with two sibs having hypertension and mitral valve prolapse. The diagnosis of NPD was proven by mutation analysis with identification of novel mutations, including a novel 4 bp insertion mutation (C>CCTGG) in exon 2 of the SMPD1 gene. We also had two cases of NPD type C, confirmed on mutation analysis.

In-silico analysis of novel p.(Gly14Ser) variant of ATOX1 gene: plausible role in modulating ATOX1-ATP7B interaction.

Clinical heterogeneity is commonly observed in Wilson disease (WD), including cases with identical ATP7B mutations. It is thought to be an outcome of impairment in other genes involved in cellular copper homeostasis in addition to the mutations in the ATP7B gene. ATOX1, a copper chaperone that delivers copper to ATP7B, is a potential genetic modifier of WD. In the present study, we analyzed the genetic variations in the ATOX1 gene in 50 WD patients and 60 controls. We identified four novel variants, of which, the coding region variant c.40G > A, p.(Gly14Ser) was observed in 2% alleles. Interestingly, p.(Gly14Ser) was seen with an early onset age, reduced serum ceruloplasmin level and manifestations of liver and brain in a WD patient unlike the other having identical ATP7B mutation but normal ATOX1 alleles. Further, computational analysis predicted that p.(Gly14Ser) substitution, in the critical copper binding motif (MXCXG14C) of the protein, affects the protein-protein interaction involved in copper sharing and transfer between ATOX1 and ATP7B-MBD4. Our findings suggest that p.(Gly14Ser) variant of ATOX1 might play a role as a genetic modifier leading to phenotypic variation in WD.

Role of Diagnostic Endoscopic Ultrasound in Idiopathic Acute Pancreatitis and Acute Recurrent Pancreatitis in Children.

OBJECTIVES: Endoscopic ultrasound (EUS) is a minimally invasive pancreatic imaging modality. We evaluated children with idiopathic acute pancreatitis (IAP) and acute recurrent pancreatitis (ARP) for changes of chronicity (Rosemont criteria) and biliary risk factors. Diagnostic yield of simultaneously performed transabdominal ultrasonography (TUS) was compared with EUS. METHODS: This was a prospective observational study. Patients underwent EUS and TUS after 2 months of pancreatitis attack. RESULTS: Forty-five (18 IAP, 27 ARP) patients underwent EUS and TUS. Mean (standard deviation) age and weight were 9.1 (2.6) years and 32.66 (12.43) kg in IAP, whereas these were 12.2 (3.1) years and 44.84 (15.12) kg in ARP, respectively. Endoscopic ultrasound demonstrated morphological abnormality in 33.3% and 40.7% of IAP and ARP, respectively (P = 0.61), whereas 16.6% and 25.9% were abnormal in TUS. Endoscopic ultrasound showed unequivocal changes of chronicity (11.1% vs 0%) and risk factors only among ARP (25.9% vs 0%; P = 0.03) and demonstrated slightly higher odds ratio (95% confidence interval) as compared with TUS to detect abnormalities in both IAP (2.43 [0.49-14.17], P = 0.28) and ARP (1.94 [0.60-6.47], P = 0.26). CONCLUSIONS: Applying EUS, changes of chronicity and risk factors were noted only in ARP. Endoscopic ultrasound performed better than TUS in detecting chronicity.

An improved and easy protocol for primary epithelial cell culture from atretic tissue in biliary atresia.

Biliary atresia (BA) is a lethal disease of infancy with obscure etiology. Insight into the pathogenesis of this disorder is limited by lack of availability of adequate epithelial tissue. Primary culture of human biliary epithelium may help to provide material for diagnostic and research purposes. However, culture of these cells from atretic tissue is a challenging task. We aimed to develop a reliable and easier protocol for culture of human biliary epithelial cells from excised atretic extrahepatic bile duct. An explant culture was performed using tissue obtained from 30 children with diseases of biliary tract. The culture showed florid cell growth in less than 3 weeks. Epithelial nature and biliary origin of cultured cells was confirmed using pancytokeratin and cytokeratin -7 antibodies. The protocol showed 100% success rate as cells could be cultured in all 30 patients. Moreover, the cells remained viable for a duration of over 3 months in most of the cases. This easier culture technique is likely to have an impact on the study of biliary cell pathophysiology, particularly in BA.

Incomplete functional and morphological recovery after acute and acute recurrent pancreatitis in children.

BACKGROUND AND AIM: There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery. METHODS: All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (µg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DIo ) (mmol/L) (ß-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters. RESULTS: At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 ± 150.94 (AP), 135.70 ± 103.80 (ARP), 46.56 ± 30.20 (CP), and 240.00 ± 181.83 (HC) (P < 0.001; anova) (AP vs CP, ARP vs CP, and CP vs HC; P < 0.001). Prediabetes due to insulin resistance was seen in 16.6% and 22.6% (P = 0.56) of AP and ARP. Median (interquartile range) DIo (mmol/L) was comparable between AP (4.20 [2.36, 8.3]) and HC (5.20 [2.89, 8.68]), but was low in ARP (2.97 [1.80, 5.12]), which was comparable with CP (1.91 [1.20, 2.83]). Endoscopic ultrasound demonstrated morphological changes in 25% and 37% (P = 0.34) of AP and ARP, respectively. CONCLUSION: There was high frequency of biochemical evidence of exocrine insufficiency. ß-Cell function (DIo ) was preserved among AP but was poor in ARP. Nearly one-third showed morphological changes in imaging.

Correction to: Diet and inflammatory bowel disease: The Asian Working Group guidelines.

The recommendations 31 which recommend "VSL#3®", refer only to the product used in the cited literature and equivalent products independent from the present product labelings. This product is now known by the generic name "De Simone Formulation".

Characterization of mutation spectrum and identification of novel mutations in ATP7B gene from a cohort of Wilson disease patients: Functional and therapeutic implications.

Wilson disease (WD), a copper metabolism disorder, occurs due to the presence of mutations in the gene encoding ATP7B, a protein that primarily facilitates hepatic copper excretion. A better understanding of spectrum and functional significance of ATP7B variants is critical to formulating targeted and personalized therapies. Henceforth, we screened and sequenced 21 exons of ATP7B gene from 50 WD patients and 60 healthy subjects. We identified 28 variants comprising, seven novels in 20% alleles, while eight variations affecting 23% alleles were first time reported in Indian cohort. The c.813C>A, p.(Cys271*) (10%) was the most frequent mutation. Bioinformatics analysis revealed five of seven novel variants viz. c.1600C>A, p.(Pro534Thr); c.1616C>A, p.(Pro539His); c.1924G>T, p.(Asp642Tyr); c.2168G>C, p.(Arg723Thr); c.2174G>C, p.(Arg725Thr) resulted in protein misfolding. Sequence conservation analysis of ATP7B regions containing novel variants documented an evolutionarily conserved nature. Functional analysis of these novel variants in five different cell lines lacking inherent ATP7B expression demonstrated sensitivity to CuCl2 -treatment, experiencing augmented cellular copper retention and decreased copper excretion as well as ceruloplasmin secretion to that of wildtype-ATP7B expressing cells. Interestingly, pharmacological chaperone 4-phenylbutyrate, a clinically approved compound, partially restored protein function of ATP7B mutants. These findings might enable novel treatment strategies in WD by clinically enhancing the protein expression of mutant ATP7B with residual copper export activity.

Bertiella studeri Infection-A Rare Cause of Chronic Abdominal Pain in a Child from North India.

Bertiella is a common parasite seen in non-human primates. It is rarely seen in humans. We present the case of a 2-year-old child with bertiellosis. He had recurrent abdominal pain, and worm fragments were found in stool, which were refractory to albendazole therapy.

Solitary Peutz-Jeghers Polyp of Jejunum: A Rare Cause of Childhood Intussusception.

An extremely rare case of solitary jejunal Peutz-Jeghers polyp causing intussusception in an 8-year-old boy is reported. The polyp was excised by laparoscopic-assisted surgery. This appears to be only the fourth and the youngest patient with such a polyp reported in the indexed English language literature.

An Unusual Cause of Fever, Generalized Lymphadenopathy and Eosinophilia in a HCV-Positive 6-Year-Old Boy.

A 6-year-old boy presented with a 3-month history of high-grade fever and night-sweats but without chills/rigors. On examination, he had moderate hepatosplenomegaly with multiple enlarged cervical and axillary lymph nodes. His hemogram revealed anemia and marked eosinophilia. Initial investigations were negative, except anti-HCV IgG antibodies, that were positive. Bone marrow aspirate showed a single histiocyte containing suspicious intracellular yeast-like forms. Cervical lymph node aspiration revealed a heavy load of intra- and extra-cellular Histoplasma spp. Disseminated histoplasmosis remains an unusual cause of peripheral eosinophilia and diagnosis can often be rendered fairly easily by cytomorphological evaluation. The case illustrates how Indian pathologists must maintain a high index of suspicion for unexpected infectious disorders in cases with eosinophilia.

Acceptability and Efficacy of Locally Produced Ready-to-Use Therapeutic Food Nutreal in the Management of Severe Acute Malnutrition in Comparison With Defined Food: A Randomized Control Trial.

BACKGROUND: Severe acute malnutrition (SAM) is a salient health problem in India. Federation of Indian Chamber of Commerce and Industry (FICCI) Research and Analysis Centre, New Delhi, prepared nutreal equivalent to ready-to-use therapeutic food by World Health Organization (WHO) for the management of SAM and defined food like homemade diet. OBJECTIVE: To compare acceptability and efficacy of nutreal over defined food for the management of SAM. METHODS: One hundred twelve children aged less than 5 years with SAM were enrolled as per the standard of WHO. Children were randomized into 2 groups to receive nutreal (n = 56) and defined food (n = 56) in unlimited amounts for 42 consecutive days and extended by 2 weeks as per demand. Calorie and protein intake, weight, and mid-upper arm circumference (MUAC) were recorded daily. RESULTS: Age range was 8 to 45 months. Ninety-three percent of children eagerly accepted nutreal but 7% does not. Whereas in the defined food group, 68% accepted eagerly, 30% did not accept eagerly, and 1.8% accepted poorly ( P = .004). At enrollment, mean weight in the nutreal group was 6.44 ± 1.60 kg and in the defined food group was 8.69 ± 1.76 kg, with MUAC in the nutreal group being 11.12 ± 0.47 cm and in the defined food group being 11.54 ± 0.34 cm. Mean weight in the nutreal and defined food groups at eighth week of intervention was 7.97 ± 1.8 kg and 9.71 ± 1.8 kg ( P < .001), respectively. Mid-upper arm circumference at eighth week was 12.10 ± 0.29 cm in the nutreal group and 12.49 ± 0.50 cm in the defined group ( P < .001). CONCLUSION: Acceptability, mean weight gain, and MUAC in the nutreal group are greater than the defined food.

Hepatobiliary Scintigraphy Findings Lead to the Diagnosis of Spontaneous Common Bile Duct Rupture in an Infant.

Hepatobiliary scintigraphy is a widely used functional imaging modality for diagnosis of a variety of liver diseases, as well as for detecting biliary tract abnormalities. Neonates or infants with persistent jaundice beyond the physiological period are usually evaluated with hepatobiliary scintigraphy. The authors present a 5-month-old girl with neonatal jaundice, ascites, and umbilical and bilateral inguinal hernias in whom spontaneous rupture of the biliary duct resulted in intraperitoneal bile leak with passage of tracer into bilateral inguinal hernial sacs.