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Abstract Farnesoid X receptor (FXR) is a nuclear bile acid receptor encoded by the NR1H4 gene, a vital regulator of bile acid homeostasis. Pathogenic mutations of NR1H4 manifest as low gamma‐glutamyl transferase (GGT) cholestasis with rapid progression to liver failure, which is referred to as progressive familial intrahepatic cholestasis 5 (PFIC‐5). Herein, we present a case with rapid progressive cholestasis, liver failure in early infancy with the NR1H4 termination mutation.

Background/purpose(s): Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear. Methods: We recruited exclusively breastfeeding mothers from among the donors of the human milk bank established at National Cheng-Kung University Hospital. The donor mothers provided 35 BM samples at three months (3 M; before introducing children to complementary feeding) and 23 BM samples at six months (6 M; after introducing children to complementary feeding) postpartum. At both time points, samples from different body sites, including nasal swabs, oral swabs and stool, were collected from the mothers and their infants. Results: Maternal BMI was inversely associated with coagulase-negative Staphylococcus (CoNS) abundance in breastmilk. Staphylococcus caprae representation in BM CoNS showed a negative correlation with Streptococcus abundance. Network analysis revealed that infants fed Staphylococcus-dominated BM had better gut and nasal microbiota networks than infants fed Streptococcus-abundant BM during early infancy. Conclusion: Our work suggests that maternal metabolic status plays a crucial role in Staphylococcus/Streptococcus competition in BM, which in turn can impact the development of the infant microbiota. Our microbiota co-occurrence network analysis might serve as a helpful bioinformatic tool to monitor microbiota maturation during early infancy.

Background: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. Methods: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. Results: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%–40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P

Background: Magnetic resonance cholangiopancreatography (MRCP) is a useful and non-invasive method to diagnose biliary atresia (BA) in term infants, however few studies have investigated its use in preterm infants. This study aimed to evaluate the accuracy of MRCP in the diagnosis of BA in preterm infants with cholestasis. Methods: Infants aged less than 6 months who received MRCP for cholestasis at a tertiary medical center were enrolled from 2011 to 2020. Demographic and laboratory data were retrospectively obtained. One pediatric radiologist reviewed the MRCP images. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRCP to diagnose BA based on surgical proof or at least 6 months of follow-up were assessed. Results: A total of 80 infants (36 preterm and 44 term) were analyzed. The mean post-chronological age was 1.8 months, and the female-to-male ratio was 0.78. Six (16.7%) preterm and 16 (36.4%) term infants were confirmed to have BA. BA was obscured by a choledochal cyst preoperatively in two term infants. In the preterm infants, the sensitivity, specificity, PPV, NPV, and accuracy of MRCP to diagnose BA were 100%, 77%, 46%, 100%, and 81%, respectively, compared to 81%, 86%, 76%, 89%, and 84% in the term infants. Using MRCP to differentiate BA from other cholestasis in the preterm infants had superior sensitivity (100% vs. 81%) and NPV (100% vs. 89%), and lower specificity (77% vs. 86%) and PPV (46% vs. 76%) than in the term infants. Conclusions: Negative MRCP findings can be used to exclude BA in preterm infants with cholestasis based on a favorable NPV.

Background: Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multi-systemic involvement, with no disease-modifying treatment available. Olipudase alfa is an investigational enzyme product developed to replace the deficient acid sphingomyelinase in ASMD patients. Several clinical trials have reported promising safety and efficacy results in adult and pediatric patients. However, no data have been reported outside of the clinical trial setting yet. This study aimed to evaluate major outcomes in pediatric chronic ASMD patients receiving olipudase alfa in the real-world setting. Materials and methods: Two children with type A/B (chronic neuropathic) ASMD have received olipudase alfa treatment since May 2021. Clinical parameters, including height, weight, complete blood count, liver function tests, lipid profiles, biomarkers, abdominal ultrasonography with shear wave elastography, chest computed tomography, nerve conduction studies, neurodevelopmental evaluations, and six-minute walk tests, were checked at baseline and every three to six months in the first year of enzyme replacement therapy (ERT) to assess its efficacy and safety. Results: The two patients in our study started olipudase alfa treatment at the age of 5 years and 8 months and 2 years and 6 months. During the first year of treatment, both patients saw a reduction in their hepatic and splenic volumes as well as liver stiffness. Height z-score, weight z-score, lipid profiles, biomarker levels, interstitial lung disease scores, and bone mineral densities also improved over time. The six-minute walk test showed a gradual increase in walking distance in both patients. There were no obvious improvements or deterioration in neurocognitive function and peripheral nerve conduction velocities after treatment. No severe infusion-associated reactions were noted during the first year of treatment. One patient had two episodes of transient but significantly elevated liver enzymes during the dose-escalation phase. The patient was asymptomatic, and the impaired liver function resolved spontaneously within two weeks. Conclusion: Our results provide real-world experience that olipudase alfa is safe and effective in improving major systemic clinical outcomes for pediatric chronic ASMD patients. Monitoring of liver stiffness by shear wave elastography is a noninvasive procedure that can monitor treatment efficacy during ERT.

BackgroundHelicobacter pylori infection is a major cause of peptic ulcers and gastric cancer. This study aimed to compare the eradication rate and essential costs of culture-based and empiric therapy strategies in treating pediatric H. pylori infection.MethodsWe retrospectively enrolled patients aged

Eosinophilic colitis (EC) belongs to a group of idiopathic diseases called eosinophilic gastrointestinal disorders, which are characterized by eosinophil-predominant inflammation in the gastrointestinal tract. Corticosteroids is the first-line pharmacotherapy for EC refractory to diet therapy. We report an infant with steroid-resistant EC, who successfully returned to a healthy growth trajectory under the combined therapy of montelukast and ketotifen. An 8-month-old boy presented with bloody diarrhea, anemia, and failure to thrive (FTT) that started 6 days after birth. The patient has no known allergies. A trial of elementary diet was unsuccessful. The results of several stool cultures were unremarkable. Similarly, lower gastrointestinal series failed to identify anything significant. At 3 months of age, an esophagogastroduodenoscopy with biopsies from the distal duodenum and proximal jejunum were unremarkable. The diarrhea and FTT persisted. A rectosigmoidoscopy with biopsies was performed; the results led to the diagnosis of EC at 5 months of age. Oral prednisolone 1 mg/kg/day was prescribed; however, 3 months into the treatment, persistent bloody diarrhea and FTT were still noted. Montelukast and ketotifen were added, after which diarrhea and weight gain started to improve. Prednisolone and montelukast/ketotifen were tapered off 6 months after. He remains symptom free and has normal growth and development in a 5-year follow-up.

Helicobacter pylori causes gastrointestinal diseases, the manifestations of diseases are more serious in adults than in children. Lewis antigen expressions on the gastric epithelium serves as receptors targeted by H. pylori. Moreover, the MAPK signaling pathway involves glycoprotein synthesis of Lewis antigens. We aimed to investigate whether differences in H. pylori-induced MAPK responses mediate gastric Lewis antigens expression and colonization density differently in children and adults. We used human stomach fetal epithelium (HSFE) and SV40-immortalized human normal gastric epithelial (GES-1) cell lines to mimic primary gastric epithelium of children and adults, respectively. H. pylori colonization intensity and Lewis antigens were significantly higher in GES-1 than in HSFE cells, whereas IL-8 and IL-6 levels were significantly higher in HSFE than in GES-1 cells after infection. c-Jun N-terminal kinase (JNK) siRNA and inhibitor (SP600125) experiments showed that Lewis antigen expression and H. pylori colonization were reduced in GES-1 cells but increased in HSFE cells. Furthermore, p-p38 intensity was significantly higher in the superficial epithelium of the children than in the adults with/without H. pylori infection. The overexpression of p38 in GES-1 cells downregulated H. pylori-induced JNK activity mimicking H. pylori infection in children. In conclusion, a higher p38 expression in gastric epithelium counteracting JNK activity in children may contribute to lower Lewis antigen expression and colonization density than in adults after H. pylori infection.

Background: This study aimed to investigate the changing trends in serogroup distribution and antimicrobial susceptibility of nontyphoid Salmonella (NTS) isolated from children in the past two decades in Taiwan. Methods: This retrospective study enrolled patients aged younger than 18 years with culture-proven NTS infection in a tertiary medical center from 1997 to 2016. Data on age, Salmonella serogroup, culture sample, and antimicrobial susceptibility were obtained from medical records. The rates of Salmonella serogroups and antimicrobial resistance were compared between period 1 (1997–2006) and period 2 (2007–2016). Results: A total of 2075 NTS isolates were identified from 1997 to 2016 (1036 in period 1, 1039 in period 2). The major isolates were from feces (89.1%) and blood (10.4%). The most common serogroup was serogroup B (54.8%), followed by serogroup D (18.8%). There was a significant decline in the proportion of serogroup B with a concomitant rise in serogroup D in the past two decades. In period 2, resistance to cefotaxime and cefixime increased remarkably among serogroup B, whereas resistance to ampicillin increased notably among serogroup D. Furthermore, the incidence of multidrug-resistant (≥3 antibiotics) NTS significantly decreased in both serogroup B and serogroup D in period 2. Conclusion: This study revealed a significant rise in serogroup D with a concomitant decline in serogroup B NTS infection in Taiwanese children. Moreover, antimicrobial resistance to third-generation cephalosporins increased in serogroup B. Continuous surveillance of NTS serogroup distribution and antimicrobial susceptibility is mandatory to formulate therapeutic strategies for NTS infections.

Abstract Background Helicobacter pylori infection is known to alter growth-related hormones and affect growth in young children. However, it is still unknown whether maternal H. pylori infection has an impact on the levels of cord blood growth-related hormones and whether this can predict intrauterine growth restriction and poor physical and neurodevelopmental outcomes in children. This study aimed to examine associations between maternal H. pylori infection and pregnancy-related adverse events, fetal growth and early childhood development. Methods In this prospective cohort study, we recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015. Seropositivity for H. pylori was defined as > 12 U/ml of anti-H. pylori IgG in maternal serum. Demographic data and pregnancy-related medical issues of the cohort were documented. Cord blood levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA. The growth of the included neonates was monitored annually for up to 3 years, and cognitive development was assessed using the comprehensive developmental inventory for infants and toddlers (CDIIT) test 3 years after birth. Results Of the 106 enrolled women, 25 (23.6%) were H. pylori-seropositive. Maternal H. pylori seropositivity was correlated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p = 0.04) and lower cord blood levels of IGF-1 (

Abstract Previous studies have shown hypothyroidism was independently associated with nonalcoholic fatty liver disease (NAFLD) in adults, but few studies examined their relationships in pediatric populations. This study aimed to investigate the prevalence of NAFLD in pediatric congenital hypothyroidism (CHT) patients and to identify the association between CHT and NAFLD. This study enrolled pediatric CHT patients receiving levothyroxine treatment at one medical center from 2013 to 2014. Euthyroid subjects (ET) and transient hypothyroidism (THT) patients weaned off medication successfully after age 3 were selected for further comparison. Laboratory data including thyroid functions, liver functions, and metabolic profiles were obtained. The major outcome was the occurrence of NAFLD, diagnosed based on the findings of abdominal ultrasonography. One‐hundred and twenty‐nine subjects (47 in CHT, 47 in THT, and 35 in ET groups) were enrolled. The analysis showed higher fasting serum glucose, insulin, thyroxine (T4), and mean thyroid‐stimulating hormone (TSH) levels in the CHT group. NAFLD prevalence was higher in the CHT (23.4%) group than in the THT (8.5%) and the ET (5.7%) groups, demonstrating an increasing trend across three strata (X2linear‐by‐linear = 5.9, P

Abstract Aims/Introduction Helicobacter pylori infection is associated with insulin resistance and glycemia in non‐diabetes. However, the relationship between H. pylori infection and glycemia in diabetes remains inconclusive. Therefore, we explored the effect of H. pylori infection status and its eradication on glycemic control and antidiabetic therapy in type 2 diabetes patients. Materials and Methods A total of 549 diabetes patients were recruited for sequential two‐step approach (immunoglobulin G [IgG] serology followed by 13C‐urea breath test [UBT]) to discriminate “active” (IgG+ and UBT+) from “non‐active” (UBT− or IgG−) H. pylori infection, and “past” (IgG+ but UBT−) from “never/remote” (IgG−) infection. The differences in hemoglobin A1c (A1C) and antidiabetic regimens between groups were compared. In the “active” infection group, the differences in A1C changes between participants with and without 10‐day eradication therapy were compared after 3 months. Results Despite no between‐group difference in A1C, the “active” infection group (n = 208) had significantly more prescriptions of oral antidiabetic drug classes (2.1 ± 1.1 vs 1.8 ± 1.1, P = 0.004) and higher percentages of sulfonylurea use (67.3% vs 50.4%, P

Esophageal perforation is a rare but critical emergency that requires early detection and prompt management. In the pediatric population, iatrogenic injury is the most common etiology of esophageal perforation, and the majority of cases come from stricture dilation. Treatment options include medical management, endoscopic therapy, and surgery. Usually, conservative treatment is appropriate in most carefully selected patients, especially in the setting of early diagnosis and with the absence of severe sepsis. A surgical approach is reserved for a large tear with mediastinum contamination, or clinical deterioration after unsuccessful conservative management. With the advancement of the endoscopy technique, endoscopy therapy using esophageal stents is an available choice for adult populations who have a complicated protracted healing course or comorbidities precluding surgical attempts. However, this procedure is seldom implemented in children, especially in young infants, owing to unavailable equipment and experts. We report our successful use of a fully-covered self-expandable metal biliary stent in managing esophageal perforation in a seven-month-old infant. In light of this encouraging achievement, this model can be applied to more children who have the same problem.

Background: The clinical presentation of cow's milk protein allergy (CMPA) in children varies. This retrospective study aimed to investigate the prevalence and clinical manifestations of CMPA in young children who visited for evaluation of iron deficiency anemia (IDA). Methods: Patients aged

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

Abstract Background Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls. Methods A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls. Results The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p

Huge amount microorganisms resides in human intestine, and many contribute to the maturation and homeostasis of immune system. The diversity of gut ecology are affected by the gestational age, delivery type, feeding sources, and antibiotics use in neonates. Recent studies pointed out that disturbance of gut microbiota, so called dysbiosis, could result in several pediatric diseases including obesity, non-alcoholic fatty liver disease (NAFLD), metabolic syndromes, allergic diseases, and inflammatory bowel diseases. However, there are no single species can be proven to play a key factor in pediatric obesity and NAFLD at present. Various probiotics may confer benefit to these gut microbiota-related pediatric diseases. The clinical application is still limited. This review article aimed to elucidate evidently the relationship between gut microbiota and pediatric obesity/NAFLD and to discuss the potential probiotics use in pediatric obesity and NAFLD. Keywords: Microbiota, Obesity, Non-alcoholic fatty liver disease, Immunity, Probiotics

This study investigated the compositional differences in fecal microbiota between children with and without H. pylori infection and tested whether probiotics-containing yogurt and bacterial eradication improve H. pylori-related dysbiosis. Ten H. pylori-infected children and 10 controls ingested probiotics-containing yogurt for 4 weeks. Ten-day triple therapy plus yogurt was given to the infected children on the 4th week. Fecal samples were collected at enrollment, after yogurt ingestion, and 4 weeks after successful H. pylori eradication for cytokines and microbiota analysis using ELISA and metagenomic sequencing of the V4 region of the 16S rRNA gene, respectively. The results showed H. pylori-infected children had significantly higher levels of fecal TGF-β1 than those who were not infected. Eight of 295 significantly altered OTUs in the H. pylori-infected children were identified. Among them, the abundance of F. prausnitzii was significantly lower in the H. pylori-infected children, and then increased after yogurt ingestion and successful bacterial eradication. We further confirmed probiotics promoted F. prausnitzii growth in vitro and in ex vivo using real-time PCR. Moreover, F. prausnitzii supernatant significantly ameliorated lipopolysaccharide-induced IL-8 in HT-29 cells. In conclusions, Probiotics-containing yogurt ingestion and H. pylori eradication can restore the decrease of fecal F. prausnitzii in H. pylori-infected children.

Colonoscopy of the lower gastrointestinal tract has diagnostic and therapeutic value. This retrospective study aimed to investigate the indications, complications, and diagnostic yield of diagnostic colonoscopy among Taiwanese children. Methods: The application of colonoscopy performed on children aged < 18 years between 1998 and 2010 in a referral tertiary center in Southern Taiwan was reviewed. Data on age, gender, indications, complications, and colonoscopic and final diagnoses were collected and analyzed. Results: One hundred and ninety-two children with 201 colonoscopies and 27 sigmoidoscopies were enrolled. The rate of successful ileocecal approach was 77.5%. The most common indication was lower gastrointestinal bleeding (LGIB; 53.5%), followed by chronic abdominal pain (20.6%), iron deficiency anemia (IDA; 11.8%), and chronic diarrhea (11.4%). There were 144 patients (75%) with a conclusive diagnosis in their first colonoscopy, including nonspecific colitis (23.4%), polyp (20.4%), and inflammatory bowel disease (8.3%). The diagnostic yields of colonoscopy according to the major indications were 77.3% in LGIB, 68.1% in chronic abdominal pain, 66.7% in IDA, and 79.2% in chronic diarrhea. Among the patients with LGIB, juvenile polyp (26.4%) was the most common etiology. There were no major procedure-related complications. Conclusion: LGIB is the most common indication for pediatric colonoscopy. Pediatric colonoscopy is most effective in diagnosing pediatric LGIB and chronic diarrhea.

An increase in group D Salmonella isolates with high antimicrobial resistant rates is being seen in Taiwan. This study aimed to determine the multidrug-resistant (MDR, more than three antibiotics) phenotype, genotype, and the correlation between the presence of class 1 integrons and its invasiveness of Salmonella panama and Salmonella enteritidis isolated from children. Methods: Twenty S. panama and 59 S. enteritidis isolates were examined for minimal inhibitory concentrations of ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline by agar dilution method. The presence of blaPSE-1, floR, aadA2, sul1, and tet(G) resistance genes, class 1 integrons, and Salmonella genomic island 1 (SGI1) was identified by polymerase chain reaction. The adhesion and invasion assays of S. panama to Caco-2 cells were determined using the pour plate method. Results: All S. panama and 15 (25.4%) of the S. enteritidis isolates displayed MDR phenotype. Furthermore, MDR genotype was present in 70.0% of S. panama and 6.8% of S. enteritidis. Class 1 integrons were present in 40.0% of S. panama and 11.9% of S. enteritidis. None contained SGI1 or SGI1 variants. Strains carrying class 1 integrons were more frequently isolated from bacteria with MDR (73.3% vs. 37.5%; odds ratio, 4.6; 95% confidence interval, 1.3-16.0; p=0.01) and isolated from blood and cerebrospinal fluid (46.7% vs. 21.9%; odds ratio, 3.1; 95% confidence interval, 1.0-10.1; p=0.05) than noncarriers. S. panama carrying class 1 integrons were more invasive to Caco-2 cells than those without (p=0.01). Conclusion: S. panama and S. enteritidis with class 1 integrons are significantly related to the presence of MDR phenotype. Moreover, S. panama with class 1 integrons may present more invasiveness than those without.

Allergic colitis (AC) is an inflammatory condition characterized by eosinophils infiltrating the colonic wall. It can be a benign and/or severe illness among gastrointestinal diseases in infants. Methods: We report five infants who, since January 2009, in whom AC under fibrotic endoscopic examinations has been diagnosed. The criterion for histopathologic diagnosis of AC in this study was five or more eosinophils per high-power field. Patients’ clinical symptoms, pathologic findings, and immunologic studies, such as specific antibodies against component of cow’s milk protein, were compared with those of allergic children without AC and those of nonatopic control children. Results: Histopathologic examinations of biopsy specimens revealed acute inflammation with characteristic eosinophilic infiltration of lamina propria (5–15 eosinophils per high-power field) in all five patients. They all had strongly positive skin prick tests against milk protein, which were not correlated with in vitro allergen-specific immunoglobulin (Ig) E levels. In contrast, there were significantly higher levels of IgE antibodies, and lower specific IgG4 and IgA levels to components and whole milk proteins in AC, as compared to control children without AC. Conclusion: Endoscopic biopsy specimens of intestine confirm the diagnosis of AC. However, allergen skin prick test and IgE antibody to milk protein components also provide helpful diagnostic tools for this rare disease in children.

The innate immune response is characterized by activation of transcription factors, nuclear factor kappa B and activator protein-1 and their downstream targets, the pro-inflammatory cytokines including interleukin 1β and interleukin 6. Normal development of this response in the intestine is critical to survival of the human neonate and delays can cause the onset of devastating inflammatory diseases such as necrotizing enterocolitis. Previous studies have addressed the role of nuclear factor kappa B in the development of the innate immune response in the enterocyte, however despite its central role in the control of multiple pro-inflammatory cytokine genes, little is known on the role of Activator Protein 1 in this response in the enterocyte. Here we show that the canonical Activator Protein 1 members, cJun and cFos and their upstream kinases JNK and p38 play an essential role in the regulation of interleukin 6 in the immature enterocyte. Our data supports a model whereby the cFos/cJun heterodimer and the more potent cJun homodimer downstream of JNK are replaced by less efficient JunD containing dimers, contributing to the decreased responsiveness to interleukin 1β and decreased interleukin 6 secretion observed in the mature enterocyte. The tissue specific expression of JunB in colonocytes and colon derived tissues together with its ability to repress Interleukin-1β induction of an Interleukin-6 gene reporter in the NCM-460 colonocyte suggests that induction of JunB containing dimers may offer an attractive therapeutic strategy for the control of IL-6 secretion during inflammatory episodes in this area of the intestine.

Peptic ulcer disease (PUD) in children is relatively rare as compared with adults. This study aimed to assess the etiology, clinical and histological characteristics, and treatment of PUD in children. Methods: All children aged < 18 years with an endoscopic diagnosis of PUD were enrolled in a tertiary referral center. The demographic data, clinical, endoscopic, and histological findings were compared between patients with different causes of PUD. Results: From 1234 endoscopic examinations, 67 (5.4%) children (median age, 11.4 years) with gastric ulcer (GU; n = 27) or duodenal ulcer (DU; n = 40) were included. Thirty-two (47.7%) of them had Helicobacter pylori infection and 11 (16.5%) had previous use of non-steroidal anti-inflammatory drugs (NSAIDs). Non-H. pylori, non-NSAID PUD was found in 24 (35.8%) patients. Children with H. pylori-related PUD had a significantly higher mean age, antral chronic inflammatory score, rate of familial PUD, and presence of DU and nodular gastritis than those with NSAID-related and non-H. pylori, non-NSAID PUD (p < 0.01). In contrast, children with NSAID-related PUD had a higher rate of upper gastrointestinal bleeding, associated with acute febrile disease, than those with H. pylori-related and non-H. pylori, non-NSAID PUD (p < 0.05). All but two patients with non-H. pylori, non-NSAID PUD were disease free after H. pylori eradication and proton pump inhibitor treatment for 1–2 months. Conclusion: In children, H. pylori-related PUD is associated with familial peptic ulcer and the presence of DU. However, short-term NSAID use is correlated highly with GU. The outcome of childhood PUD is good.

Pseudomembranous colitis after short-course antibiotics is rare in children. We report a 14-month-old girl who presented with rectal prolapse complicated with Clostridium difficile–associated pseudomembranous colitis after a 4-day course of oral cefuroxime for treatment of acute otitis media. Abdominal sonogram showed a pelvic mass, and computed tomography revealed thickened wall of the rectum. Sigmoidoscopy demonstrated discrete yellowish plaques adherent to an edematous mucosa. Stool cultures for C difficile were positive and C difficile toxins A and B were detected in her stool. Histological examination of colonic biopsy showed superficial erosion of the mucosa and the adherent pseudomembranes. She achieved a full recovery after discontinuing cefuroxime. Our case implied that C difficile infection should be considered in children presenting with rectal prolapse, especially when they are taking or have recently received antibiotic therapy. Supportive therapy and discontinuation of antibiotics are generally sufficient for patients with C difficile–associated pseudomembranous colitis who present with mild diarrheal illness.

BACKGROUND: Infantile hepatitis B after neonatal immunoprophylaxis is a rare yet distinct disease. This study aimed to analyze the long-term outcomes and risk factors in immunized infants with hepatitis B. METHODS: The clinical parameters and outcomes of 41 infants born after universal immunization, and admitted for HBV-positive hepatitis were studied. All patients were followed for at least 6 months (median = 4.4 years, range 0.6-18.1 years). Patient survival, changes of HBsAg and HBeAg status, and complications were analyzed. RESULTS: Among the 41 cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20 with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses revealed younger age of onset (age

As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D). Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.

Purpose: To date, there is no region-specific guideline for pediatric endoscopy training. This study aimed to illustrate the current status of pediatric endoscopy training in Asia-Pacific region and identify opportunities for improvement. Methods: A cross-sectional survey, using a standardized electronic questionnaire, was conducted among medical schools in the Asia-Pacific region in January 2024. Results: A total of 57 medical centers in 12 countries offering formal Pediatric Gastroenterology training programs participated in this regional survey. More than 75% of the centers had an average case load of <10 cases per week for both diagnostic and therapeutic endoscopies. Only 36% of the study programs employed competency-based outcomes for program development, whereas nearly half (48%) used volume-based curricula. Foreign body retrieval, polypectomy, percutaneous endoscopic gastrostomy, and esophageal variceal hemostasis, that is, sclerotherapy or band ligation (endoscopic variceal sclerotherapy and endoscopic variceal ligation), comprised the top four priorities that the trainees should acquire in the autonomous stage (unconscious) of competence. Regarding the learning environment, only 31.5% provided formal hands-on workshops/simulation training. The direct observation of procedural skills was the most commonly used assessment method. The application of a quality assurance (QA) system in both educational and patient care (Pediatric Endoscopy Quality Improvement Network) aspects was present in only 28% and 17% of the centers, respectively. Conclusion: Compared with Western academic societies, the limited availability of cases remains a major concern. To close this gap, simulation and adult endoscopy training are essential. The implementation of reliable and valid assessment tools and QA systems can lead to significant development in future programs. [ABSTRACT FROM AUTHOR]