Seroprevalence of Helicobacter pylori infection among schoolchildren in southern Taiwan-A 20-year longitudinal follow-up.

BACKGROUND: Helicobacter pylori infection is primarily acquired in childhood and can lead to peptic ulcer diseases and gastric cancer. The prevalence of H. pylori infection varies widely in different countries. The aim of this study was to explore the change of pediatric H. pylori seroprevalence in the past two decades and to investigate the risk factors for pediatric H. pylori seropositivity in southern Taiwan. MATERIALS AND METHODS: This study enrolled children aged 7-12 years in Tainan City in 2018 and compared the result with our previous data in 1998, 2005, and 2010. Parents of the participants were invited to fill out questionnaires, including information of personal history, family history of peptic ulcer diseases, annual household income, and source of drinking water. Blood samples were analyzed for anti-H. pylori IgG by enzyme-linked immunosorbent assay. RESULTS: A total of 391, 629, 618, and 488 elementary school students in Tainan City were enrolled in 1998, 2005, 2010, and 2018, respectively. There was a significant decline in H. pylori seroprevalence from 9.2% in 1998, 7.8% in 2005, 6.2% in 2010 to 4.7% in 2018 (p < 0.001). Neither gender difference nor age difference was found in H. pylori seropositivity in each year of enrollment. Low household income was significantly associated with pediatric H. pylori seropositivity. CONCLUSIONS: The seroprevalence of H. pylori infection among elementary schoolchildren has remarkably declined in southern Taiwan in the past two decades. Low household income was a risk factor for pediatric H. pylori seropositivity.

NR1H4 mutation and rapid progressive intrahepatic cholestasis in infancy: A case report and literature review.

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.

The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.

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.

Combining Panel-Based Next-Generation Sequencing and Exome Sequencing for Genetic Liver Diseases.

OBJECTIVES: To determine how advanced genetic analysis methods may help in clinical diagnosis. STUDY DESIGN: We report a combined genetic diagnosis approach for patients with clinical suspicion of genetic liver diseases in a tertiary referral center, using tools either tier 1: Sanger sequencing on SLC2SA13, ATP8B1, ABCB11, ABCB4, and JAG1 genes, tier 2: panel-based next generation sequencing (NGS), or tier 3: whole-exome sequencing (WES) analysis. RESULTS: In a total of 374 patients undergoing genetic analysis, 175 patients received tier 1 Sanger sequencing based on phenotypic suspicion, and pathogenic variants were identified in 38 patients (21.7%). Tier 2 included 216 patients (39 of tier 1-negative patients) who received panel-based NGS, and pathogenic variants were identified in 60 (27.8%). In tier 3, 41 patients received WES analysis, and 20 (48.8%) obtained genetic diagnosis. Pathogenic variants were detected in 6 of 19 (31.6%) who tested negative in tier 2, and a greater detection rate in 14 of 22 (63.6%) patients with deteriorating/multiorgan disease receiving one-step WES (P = .041). The overall disease spectrum is comprised of 35 genetic defects; 90% of genes belong to the functional categories of small molecule metabolism, ciliopathy, bile duct development, and membrane transport. Only 13 (37%) genetic diseases were detected in more than 2 families. A hypothetical approach using a small panel-based NGS can serve as the first tier with diagnostic yield of 27.8% (98/352). CONCLUSIONS: NGS based genetic test using a combined panel-WES approach is efficient for the diagnosis of the highly diverse genetic liver diseases.

Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan.

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.

The accuracy of magnetic resonance cholangiopancreatography in the diagnosis of biliary atresia in preterm infants with cholestasis.

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.

Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication.

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 < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

MOCHI: a comprehensive cross-platform tool for amplicon-based microbiota analysis.

MOTIVATION: Microbiota analyses have important implications for health and science. These analyses make use of 16S/18S rRNA gene sequencing to identify taxa and predict species diversity. However, most available tools for analyzing microbiota data require adept programming skills and in-depth statistical knowledge for proper implementation. While long-read amplicon sequencing can lead to more accurate taxa predictions and is quickly becoming more common, practitioners have no easily accessible tools with which to perform their analyses. RESULTS: We present MOCHI, a GUI tool for microbiota amplicon sequencing analysis. MOCHI preprocesses sequences, assigns taxonomy, identifies different abundant species and predicts species diversity and function. It takes either taxonomic count table or FASTQ of partial 16S/18S rRNA or full-length 16S rRNA gene as input. It performs analyses in real time and visualizes data in both tabular and graphical formats. AVAILABILITY AND IMPLEMENTATION: MOCHI can be installed to run locally or accessed as a web tool at https://mochi.life.nctu.edu.tw. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Characteristics and Risk Factors of Asparaginase-Associated Pancreatitis in Pediatric Acute Lymphoblastic Leukemia.

OBJECTIVE: This study aimed to elucidate the characteristics and the risk factors for asparaginase-associated pancreatitis (AAP) in pediatric acute lymphoblastic leukemia (ALL) under the Taiwan Pediatric Oncology Group (TPOG)-ALL regimen. METHODS: The study was conducted by reviewing the chart records of 191 patients aged 1 to 18 years treated with TPOG-ALL (2002 and 2013) protocols at the National Cheng Kung University Hospital, Tainan, Taiwan, from 2002 to 2019. The disease incidence, clinical presentations, laboratory data, complications, and outcomes of AAP were investigated. RESULTS: The incidence of AAP was 4.7%. The incidence was significantly higher in children treated with the TPOG-ALL-2013 (n = 62) than TPOG-ALL-2002 (n = 129) protocol (11.3% vs 1.6%, P = 0.006). Multivariate analysis identified using TPOG-ALL-2013 protocol was an independent risk factor for AAP. Pancreatic necrosis or pseudocysts developed in 7 patients (78%). Notably, 1 AAP case (11%) developed diabetes mellitus and 4 (44%) had chronic pancreatitis during a 1-year observational period. None were mortality. CONCLUSIONS: The incidence of AAP was 4.7% in ALL patients treated with TPOG-ALL protocol. Although a higher cumulative dose of asparaginase in TPOG-ALL-2013 may attribute to the pancreatic toxicity, unidentified factors such as genetic predisposition or other drugs still need further study.

A Culture-Based Strategy Is More Cost Effective Than an Empiric Therapy Strategy in Managing Pediatric Helicobacter pylori Infection.

Background: Helicobacter 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. Methods: We retrospectively enrolled patients aged <18 years with a diagnosis of H. pylori infection who received esophagogastroduodenoscopy at two medical centers in southern Taiwan from 1998 to 2018. Patients with positive cultures and minimum inhibitory concentration test results were allocated to a culture-based strategy, and those with negative cultures or without culture as an empiric therapy strategy. We collected demographic data and eradication rates, and calculated the total essential costs of treating a hypothetical cohort of 1,000 pediatric patients based on the two strategies. Results: Ninety-six patients were enrolled, of whom 55 received a culture-based strategy and 41 received an empiric therapy strategy. The eradication rates with the first treatment were 89.1 and 75.6% in the culture-based and empiric therapy strategy, respectively. There were no significant differences in age, sex, and endoscopic diagnosis between the two strategies. For every 10% increase in those receiving a culture-based strategy, the total cost would have been reduced by US$466 in a hypothetical cohort of 1,000 patients. For every 10% increase in successful eradication rate, the total cost was reduced by US$24,058 with a culture-based strategy and by US$20,241 with an empiric therapy strategy. Conclusions: A culture-based strategy was more cost effective than an empiric therapy strategy in treating pediatric H. pylori-infected patients.

Atrophic gastritis in Helicobacter pylori-infected children.

BACKGROUND: Helicobacter pylori infection is the leading cause of peptic ulcer and chronic gastritis and may initiate gastric carcinogenesis following the Correa cascade. Another lineage of metaplasia, spasmolytic peptide-expressing metaplasia (SPEM) has recently been found to be an alternative precursor to gastric cancer. To date, few reports have investigated gastric precancerous lesions among children with H. pylori infection. This study aimed to evaluate the histopathological pattern of H. pylori atrophic gastritis in children and the extent of precancerous lesions. MATERIALS AND METHODS: This study enrolled pediatric patients with H. pylori infection from 1998 to 2019. During esophagogastroduodenoscopy examinations, biopsy fragments were collected from the gastric antrum and corpus for rapid urease test, culture, and histology evaluation. The presence and degree of chronic inflammation, activity of gastritis, H. pylori density, atrophy, and intestinal metaplasia (IM) were assessed according to the modified Updated Sydney System. Trefoil factor 2 (TFF2) immunohistochemistry was also performed to assess SPEM in the gastric tissues collected from each case using rabbit anti-human TFF2 antibodies. RESULTS: A total of 92 children with H. pylori infection and adequate gastric mucosa biopsies were enrolled. Esophagogastroduodenoscopy showed that 39 (42.4%) had duodenal ulcers, 11 (12.0%) had gastric ulcers, 41 (44.6%) had gastritis, and 1 (1.1%) had negative findings. Mild-to-moderate IM was identified in 4 patients (4.3%). SPEM was found in 8 patients (8.7%) with a significantly higher incidence among female patients (15.8% vs. 8.7%, p = .031). Gastric glandular atrophy presented in 28 patients (30.4%), and high-grade atrophy was more common in female patients (3.2% vs. 1.9%, p = .031). CONCLUSIONS: The prevalence rates of atrophic gastritis in the children with H. pylori infection were 30.4% for gastric glandular atrophy, 4.3% for IM and 8.7% for SPEM. SPEM and high-grade atrophy were more common in female patients.

Differential H. pylori-Induced MAPK Responses Regulate Lewis Antigen Expression and Colonization Density on Gastric Epithelial Cells Between Children and Adults.

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.

Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia.

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.

Successful Montelukast Treatment in an Infant with Steroid-Resistant Eosinophilic Colitis.

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.

Case Report: Successful Use of Biliary Stent for Iatrogenic Esophageal Perforation Following Balloon Dilation in a 7-Month-Old Infant.

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.

Probiotics-Containing Yogurt Ingestion and H. pylori Eradication Can Restore Fecal Faecalibacterium prausnitzii Dysbiosis in H. pylori-Infected Children.

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-ß1 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.

Changes in epidemiology and antimicrobial susceptibility of nontyphoid Salmonella in children in southern Taiwan, 1997-2016.

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.

Maternal H. pylori seropositivity is associated with gestational hypertension but is irrelevant to fetal growth and development in early childhood.

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 (< 35 ng/ml, 70.0% vs. 40.7%, p = 0.02) and IGFBP-3 (< 1120 ng/ml, 100.0% vs. 76.3%, p = 0.02) compared with the seronegative women. No significant impacts on birth weight, childhood growth and cognitive development were found to be correlated with maternal H. pylori seropositivity during pregnancy. CONCLUSIONS: Maternal H. pylori infection during pregnancy was more likely to lead to the development of GH, but was not correlated with fetal and childhood growth and development. In addition to close monitoring of hypertension, H. pylori eradication can be considered for mothers with H. pylori infection.

The relationship between nonalcoholic fatty liver disease and pediatric congenital hypothyroidism patients.

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 (X2 linear-by-linear = 5.9, P < .05). The multivariate regression analysis showed obesity (ß-coefficient = 5.52, P < .05), CHT (ß-coefficient = 2.92, P < .05) and mean TSH levels (ß-coefficient = 0.24, P < .05) were independent risk factors for NAFLD. A positive correlation was found between TSH level and lipid profiles. CHT patients had higher risk of NAFLD despite treatment being initiated early in life. Close monitoring of metabolic profiles is warranted. Further research should examine ways to optimize the treatment for CHT patients in terms of prevention against NAFLD.