Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Effect of Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 on Acute Watery Diarrhea: A Randomized Double-Blind Placebo-Controlled Study in Indian Children.

PURPOSE: To assess the effect of combination probiotic Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 in outpatient management of acute watery diarrhea in children. METHODS: A randomized double-blind placebo-controlled study was conducted in 180 participants aged six months to five years with acute mild to moderate diarrhea. All were enrolled from six centers across India and centrally randomized to receive S. boulardii CNCM-I 3799 and B. subtilis CU-1 or a placebo along with oral rehydration salts and zinc supplementation. Each participant was followed up for three months to assess recurrence of diarrhea. RESULTS: The mean duration of diarrhea in the probiotic and placebo groups were 54.16 hours and 59.48 hours, respectively. The difference in the duration of diarrhea in those administered with probiotic or placebo within 24 hours of diarrhea onset was 25.21 hours. Furthermore, the difference in duration of diarrhea was 13.84 hours (p<0.05) for participants who were administered with probiotics within 48 hours. There were no significant differences in the stool frequencies between the two arms. After three months, 15% in the probiotic group and 18.5% in the placebo group reported episodes of diarrhea. The mean duration of diarrhea was considerably lower in the probiotic group, 31.02 hours versus 48 hours in placebo (p=0.017). CONCLUSION: S. boulardii CNCM-I 3799 and B. subtilis CU-1 combination was effective in reducing the duration of diarrhea when administered within 48 hours of diarrhea onset. Similarly, it reduced recurrence of diarrhea and its intensity in the subsequent three months.

Efficacy of polyethylene glycol 3350 as compared to lactulose in treatment of ROME IV criteria-defined pediatric functional constipation: A randomized controlled trial.

BACKGROUND AND AIMS: Functional constipation is a common childhood problem, with a prevalence of approximately 3% worldwide. The aim of the study was to compare the efficacy of polyethylene glycol (PEG) 3350 and lactulose in the treatment of pediatric functional constipation. METHODS: A total of 100 subjects with functional constipation were enrolled and centrally randomized to receive PEG 3350 (0.7-1.5 mg/kg/day) or lactulose (0.7-2.0 g/kg/day). RESULTS: There was a significant increase in median (min, max) stool frequency within 1 week in the PEG 3350 group as compared to the lactulose group (1 [0, 3] to 8 [3, 39] vs. 1 [0, 3] to 7 [1, 17]) (p-value < 0.01). The trend was maintained at week 2, week 3 (p-value < 0.01), and week 4 (p-value = 0.05) with the PEG 3350 group reporting higher weekly median stool frequency than the lactulose group. The PEG group reported significant reduction in painful bowel movements from 68.8% subjects at baseline to 43.8% at the end of first week, whereas the lactulose group reported an increase from 48.9% to 73.3% (p-value = 0.05). Other parameters of constipation, i.e. straining, large diameter stool, and large fecal mass as reported subjectively by parents, significantly decreased from baseline to the end of the study in the PEG 3350 arm compared to those in the lactulose arm. At the end of week 4, there was a statistically significant reduction in all the ROME IV-defined criteria between the two groups. CONCLUSION: This study proved that the PEG 3350 treatment group had early symptom relief and significant improvement compared to the lactulose group in pediatric functional constipation. TRIAL REGISTRATION: Clinical Trials Registry India (CTRI/2018/01/011061).

Achalasia Cardia in a Young Infant.

Achalasia cardia is an esophageal motility disorder rarely reported in children and more so in young infants. Common clinical presentations include vomiting, dysphagia, regurgitation, recurrent pulmonary aspiration and failure to thrive. Diagnosis is made by barium swallow study and esophageal manometry, which is the gold standard test. Pharmocological management and endotherapy often fails and results in recurrence of symptoms. Laparoscopic Hellers myotomy, with or without anti-reflux procedure is the standard treatment of choice for children. Per-oral endoscopic myotomy is utilized for treatment of achalasia in adults, but its safety, efficacy, and feasibility is not studied in children.

Hemosuccus Pancreaticus.

BACKGROUND: Gastrointestinal bleeding in children has diverse etiologies. CASE CHARACTERISTICS: Two children (age 3y and 7y) with recurrent gastrointestinal bleeding. Computed tomography demonstrated features of chronic pancreatitis but no vessel abnormality. Conventional angiography revealed bleeding from gastroduodenal artery in both cases. OUTCOME: Coil embolization of gastroduodenal vessels was performed, and there was no recurrence of bleeding. MESSAGE: Hemosuccus pancreaticus is to be considered in children with chronic pancreatitis presenting with recurrent gastrointestinal bleeding and conventional angiography with coil embolization is helpful.