Recent Changes in the Treatment of Helicobacter pylori Infection in Children and Adolescents

Treatments aimed at eradicating Helicobacter pylori (H. pylori) infections in children and adolescents should be clearly beneficial. According to the updated guidelines, a 14-day triple therapy or bismuth-based triple therapy is the first choice for treatment of children based on the results of antimicrobial sensitivity testing. Though culturing H. pylori using biopsy specimens is not always feasible, it should be performed for establishing empirical rescue therapy for patients not responding to first-line eradication therapy. The European and North American therapeutic strategies for children and adolescents with H. pylori infections may not be appropriate for treating children and adolescents in other countries owing to regional differences in epidemiological characteristics of H. pylori. The existence of clarithromycin-resistant H. pylori is an important factor involved in eradication failure. The development of new treatment-related allergies, treatment failure, side effects, and alteration of the gut microbiome have been highlighted as factors potentially outweighing the possible benefit of preventing future peptic ulcers or gastric cancer. Drug compliance can be improved by providing a detailed explanation of the reason for therapy, duration, and routes of drug administration. Physicians should understand the mechanisms underlying eradication treatment and explain drug prescriptions in detail to both parents and children to increase compliance. Herein, we reviewed the indications for and various modalities of eradication treatment in children with H. pylori infections in accordance with a review of recently published articles.

A Case of Congenital Common Bile Duct Web Treated with Balloon Dilation under Endoscopic Retrograde Cholangiopancreatography in a Young Child

Web in common bile duct (CBD web) is very rare. It is usually asymptomatic and detected incidentally during surgery for other causes in adults. It can be congenital or acquired, however congenital CBD web is extremely rare. Currently, despite its invasiveness and complications, endoscopic retrograde cholangiopancreatography (ERCP) is considered as a useful diagnostic and therapeutic modality in children with hepatobiliary pancreatic diseases as in adults. Herein we report a case of congenital CBD web presenting with acute pancreatitis and choledocholithiasis in a 4-year-old girl which was diagnosed and treated using balloon dilation under ERCP. After balloon dilation of the web, a common pancreatobiliary channel was observed. To the best of our knowledge, a case of congenital CBD web with pancreatobiliary junctional abnormality treated using ERCP in a child has not been reported to date.

Recent Changes in the Treatment of Helicobacter pylori Infection in Children and Adolescents

Treatments aimed at eradicating Helicobacter pylori (H. pylori) infections in children and adolescents should be clearly beneficial. According to the updated guidelines, a 14-day triple therapy or bismuth-based triple therapy is the first choice for treatment of children based on the results of antimicrobial sensitivity testing. Though culturing H. pylori using biopsy specimens is not always feasible, it should be performed for establishing empirical rescue therapy for patients not responding to first-line eradication therapy. The European and North American therapeutic strategies for children and adolescents with H. pylori infections may not be appropriate for treating children and adolescents in other countries owing to regional differences in epidemiological characteristics of H. pylori. The existence of clarithromycin-resistant H. pylori is an important factor involved in eradication failure. The development of new treatment-related allergies, treatment failure, side effects, and alteration of the gut microbiome have been highlighted as factors potentially outweighing the possible benefit of preventing future peptic ulcers or gastric cancer. Drug compliance can be improved by providing a detailed explanation of the reason for therapy, duration, and routes of drug administration. Physicians should understand the mechanisms underlying eradication treatment and explain drug prescriptions in detail to both parents and children to increase compliance. Herein, we reviewed the indications for and various modalities of eradication treatment in children with H. pylori infections in accordance with a review of recently published articles.

A Case of Congenital Common Bile Duct Web Treated with Balloon Dilation under Endoscopic Retrograde Cholangiopancreatography in a Young Child

Web in common bile duct (CBD web) is very rare. It is usually asymptomatic and detected incidentally during surgery for other causes in adults. It can be congenital or acquired, however congenital CBD web is extremely rare. Currently, despite its invasiveness and complications, endoscopic retrograde cholangiopancreatography (ERCP) is considered as a useful diagnostic and therapeutic modality in children with hepatobiliary pancreatic diseases as in adults. Herein we report a case of congenital CBD web presenting with acute pancreatitis and choledocholithiasis in a 4-year-old girl which was diagnosed and treated using balloon dilation under ERCP. After balloon dilation of the web, a common pancreatobiliary channel was observed. To the best of our knowledge, a case of congenital CBD web with pancreatobiliary junctional abnormality treated using ERCP in a child has not been reported to date.

Risk Factors and Effects of Severe LateOnset Hyponatremia on Long-Term Growth of Prematurely Born Infants / 대한소아소화기영양학회지

Purpose@#Sodium is an essential nutritional electrolyte that affects growth. A low serum sodium concentration in healthy premature infants beyond 2 weeks of life is called lateonset hyponatremia (LOH). Here, we investigated the association between LOH severity and growth outcomes in premature infants. @*Methods@#Medical records of premature infants born at ≤32 weeks of gestation were reviewed. LOH was defined as a serum sodium level <135 mEq/L regardless of sodium replacement after 14 days of life. Cases were divided into two groups, <130 mEq/L (severe) and ≥130 mEq/L (mild). Characteristics and growth parameters were compared between the two groups. @*Results@#A total of 102 premature infants with LOH were included. Gestational age ([GA] 27.7 vs. 29.5 weeks, p<0.001) and birth weight (1.04 vs. 1.34 kg, p<0.001) were significantly lower in the severe group. GA was a risk factor of severe LOH (odds ratio [OR], 1.328, p=0.022), and severe LOH affected the development of bronchopulmonary dysplasia (OR, 2.950, p=0.039) and led to a poor developmental outcome (OR, 9.339, p=0.049). Growth parameters at birth were lower in the severe group, and a lower GA and sepsis negatively affected changes in growth for 3 years after adjustment for time. However, severe LOH was not related to growth changes in premature infants. @*Conclusion@#Severe LOH influenced the development of bronchopulmonary dysplasia and developmental outcomes. However, LOH severity did not affect the growth of premature infants beyond the neonatal period.

Severe Gastrointestinal Hemorrhage in a Child after Taking an Improper Oral Rehydration Solution / 대한소아소화기영양학회지

Oral rehydration solution (ORS) is safe and effective for the prevention and treatment of dehydration in children. It has been commercially available as a small packaging unit that needs to be taken with a specified amount of water. Intake of incorrectly formulated ORS results in side effects, such as electrolyte imbalance and upper gastrointestinal (GI) disturbance. We experienced a case of severe GI hemorrhage from gastric and duodenal ulcers in a previously healthy child following intake of incorrectly formulated ORS. GI hemorrhage in children is often life threatening and reaching a diagnosis may be challenging. Commercially manufactured packets of powdered oral rehydration salts have been widely used and GI hemorrhage associated with an improperly diluted ORS has been rarely reported. Caution and education for proper preparation of ORS are imperative.

Changes in Seroprevalence of Helicobacter pylori Infection over 20 Years in Jinju, Korea, from Newborns to the Elderly

Background@#The objective of this study was to examine changes in the prevalence of cytotoxic-associated gene A (CagA) positive Helicobacter pylori infection in Jinju, Korea, over the last 20 years. @*Methods@#Three cross-sectional analyses were conducted concurrently. A total of 1,305 serum samples were collected from 1994–1995, 2004–2005, and 2014–2015, respectively. The presence of immunoglobulin (Ig) G, IgA, and IgM antibodies against H. pylori CagA protein was examined by western blotting. @*Results@#Overall, seropositivity for anti-CagA IgG antibody was significantly decreased from 63.2% to 42.5% over the last 20 years (P < 0.001). Anti-CagA IgG seropositivities in children and young adults aged 10–29 years decreased from 1994 (60.0%–85.0%) to 2015 (12.5%– 28.9%). The age when plateau of increasing IgG seropositivity was reached in each study period shifted from the 15–19 year-old group in 1994–1995 (85.0%) to the 40–49 year-old group in 2014–2015 (82.5%). Overall seropositive rates of anti-CagA IgA and IgM antibodies did not change significantly either over the last 20 years. @*Conclusion@#H. pylori infection rate in children and young adults declined over 20 years in Jinju, probably due to improved sanitation, housing, or economy.

A Case of Nephrogenic Diabetes Insipidus with a Rare X-linked Recessive Mutation in an Infant with Developmental and Growth Retardation Tracked by the Korean National Health Screening Program

Nephrogenic diabetes insipidus (DI) is a rare disease in which the patient cannot concentrate urine despite appropriate or high secretion of antidiuretic hormone. Congenital nephrogenic DI is caused by the arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2) gene mutation; the AVPR2 genetic mutation accounts for 90% of the cases. National health screening for infants and children was launched in 2007 in order to prevent accidents and promote public health in infants and children in Korea. The program has been widely used as a primary clinical service in Korea. We treated an infant with faltering growth and delayed development detected by the National health screening program, and diagnosed the problem as nephrogenic DI caused by a rare missense mutation of c.490T>C on the AVPR2 gene. This case can be a good educational nephrogenic DI with a rare AVPR2 mutation, which was well screened and traced by the national health screening program for infants and children in Korea.

Changes in the Treatment Strategies for Helicobacter pylori Infection in Children and Adolescents in Korea / 대한소아소화기영양학회지

The policies developed for the treatment of Helicobacter pylori infection in adults may not be the most suitable ones to treat children and adolescents. Methods used to treat children and adolescents in Europe and North America may not be appropriate for treating children and adolescents in Korea due to differences in epidemiological characteristics of H. pylori between regions. Moreover, the agreed standard guidelines for the treatment of H. pylori infection in children and adolescents in Korea have not been established yet. In this study, the optimal treatment strategy for H. pylori infection control in children and adolescents in Korea is discussed based on these guidelines, and recent progress on the use and misuse of antimicrobial agents is elaborated. Non-invasive as well as invasive diagnostic test and treatment strategy for H. pylori infection are not recommendable in children aged less than ten years or children with body weight under 35 kg, except in cases of clinically suspected or endoscopically identified peptic ulcers. The uncertainty, whether enough antimicrobial concentrations to eradicate H. pylori can be maintained when administered according to body weight-based dosing, and the costs and adverse effects outweighing the anticipated benefits of treatment make it difficult to decide to eradicate H. pylori in a positive non-invasive diagnostic test in this age group. However, adolescents over ten years of age or with a bodyweight of more than 35 kg can be managed aggressively as adults, because they can tolerate the adult doses of anti-H. pylori therapy. In adolescents, the prevention of future peptic ulcers and gastric cancers is expected after the eradication of H. pylori. Bismuth-based quadruple therapy (bismuth-proton pump inhibitor-amoxicillin/tetracycline-metronidazole) with maximal tolerable doses and optimal dose intervals of 14 days is recommended, because in Korea, the antibiotic susceptibility test for H. pylori is not performed at the initial diagnostic evaluation. If the first-line treatment fails, concomitant therapy plus bismuth can be attempted for 14 days as an empirical rescue therapy. Finally, the salvage therapy, if needed, must be administered after the H. pylori antibiotic susceptibility test.

Diagnosis of Helicobacter pylori Infection in Children and Adolescents in Korea / 대한소아소화기영양학회지

Helicobacter pylori plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma. In Korea, the guidelines for the diagnosis and treatment of H. pylori infection in adults were revised in 2013. The European Helicobacter and Microbiota Study Group and Consensus panel released the fifth edition of the Maastricht Consensus Report for the management of H. pylori infection in 2015, and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition released the updated joint guidelines for children and adolescents in 2016. Considering these recommendations and recent progress in our research and that of other research teams, this study aimed to discuss the diagnostic strategies for H. pylori infection in children and adolescents.

Cytomegalovirus-Associated Severe Direct Antiglobulin Test Negative Hemolytic Anemia: A Case Report / 임상소아혈액종양

Cytomegalovirus is a common virus that is mostly asymptomatic when infected, but rarely causes life-threatening hemolysis especially in immunocompromised children. We report a case of antiglobulin test negative severe hemolytic anemia caused by cytomegalovirus infection developed in an immune competent 9-year-old girl. The patient's hemoglobin level was 4.8 g/dL on the day of admission. The diagnosis was achieved by exclusion of other causes of hemolytic anemia and serological evidence of recent CMV infection. The patient was successfully treated with anti-viral agents and steroids resulting in recovery from anemia. Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in pediatric patients.

Pulmonary embolism presenting with acute abdominal pain in a girl with stable ankle fracture and inherited antithrombin deficiency

No abstract available.

Mild encephalopathy with a reversible splenial lesion in a girl with acute pyelonephritis / 소아과

We report the case of a 12-year-old girl who had mild encephalopathy with a reversible splenial lesion (MERS) associated with acutepyelonephritis caused by Escherichia coli. The patient was admitted with a high fever, and she was diagnosed with acute pyelonephritis based on pyuria and the results of urine culture, which detected cefotaxime-sensitive E. coli. Although intravenous cefotaxime and tobramycin were administered, her fever persisted and her C-reactive protein level increased to 307 mg/L. On day 3 of admission, she demonstrated abnormal neuropsychiatric symptoms, such as delirium, ataxia, and word salad. Magnetic resonance imaging (MRI) of the brain performed on day 4 showed marked hyperintensities in the bilateral corpus callosum and deep white matter on diffusion-weighted images, with corresponding diffusion restriction on apparent diffusion coefficient mapping. No abnormalities or pathogens were detected in the cerebrospinal fluid; however, lipopolysaccharides (LPS, endotoxin) were detected in plasma (41.6 pg/mL), associated with acute neurological deterioration. Her clinical condition gradually improved, and no neurological abnormalities were observed on day 6. Follow-up brain MRI performed 2 weeks later showed near-disappearance of the previously noted hyperintense lesions. In this patient, we first proved endotoxemia in a setting of MERS. The release of LPS following antibiotic administration might be related to the development of MERS in this patient. The possibility of MERS should be considered in patients who present with acute pyelonephritis and demonstrate delirious behavior.

Comparative study between an intensive small group teaching and a 1-year clinical practice on OSCE / 고신대학교의과대학학술지

OBJECTIVES: Our school introduced a new curriculum based on faculty-directed, intensive, small-group teaching of clinical skills in the third-year medical students. To examine its effects, we compared the mean scores on an OSCE between the third- and fourth-year medical students. METHODS: Third- and fourth-year students did rotations at the same five OSCE stations. They then completed a brief self-reporting questionnaire survey to examine the degree of satisfaction with new curriculum in the third-year students and clinical practice in the fourth-year students, as well as their perception of confidence and preparedness. We analyzed the OSCE data obtained from 158 students, 133 of whom also completed the questionnaire. RESULTS: Mean OSCE scores on the breast examination and wet smear stations were significantly higher in the third-year group (P < 0.001). But mean OSCE scores of motor-sensory examination and lumbar puncture were significantly higher in the fourth-year group (P < 0.05). The mean OSCE scores had no significant correlation with satisfaction. In addition, the self-ratings of confidence had a high degree of correlation with satisfaction with new curriculum (r = 0.673) and clinical practice (r = 0.692). Furthermore, there was a moderate degree of correlation between satisfaction and preparedness in both groups (r = 0.403 and 0.449). CONCLUSIONS: There is no significant difference in the effect on the degree of clinical performance and confidence between an intensive-small group teaching and a 1-year clinical practice. If combined, intensive small group teaching and clinical practice would be useful to improve the degree of ability and confidence in medical students.

Characterization of Specific IgA Response to Antigenic Determinants of Helicobacter pylori Urease Encoded by ureA and ureB in Children

Helicobacter pylori (H. pylori), a causative agent of chronic gastritis and gastric cancer, has several virulent factors for own survival and progression toward gastric diseases in human stomach. Of those, H. pylori produces mainly urease (10~15% total protein weight) that neutralize the gastric acid for survival. Here, we identified the antigenic epitope of urease and then developed an ELISA using the antigen including the epitope of urease. We identified the antigenic epitope of urease that induces IgA antibodies in human using truncated mutants. Eight kinds of serially-truncated mutant of UreA and UreB were prepared and subjected to immunoblot using pooled sera of patients with gastric disorders. UreBEnd protein containing UreB epitope was produced and investigated its diagnostic value via ELISA in children. As a result, mutants having last 24 amino acid residues of UreB carboxyl terminus deleted did not show IgA-reactive band. The clones that contained the downstream of 448(th) amino acid in UreB showed IgA-reactive band. The serodiagnostic value of the UreBEnd recombinant protein including identified epitope was confirmed via IgA ELISA and shown to have 97% sensitivity and 100% specificity. These results demonstrated that carboxyl terminal region of UreB carries an antigenic epitope for IgA response in human. It may be useful for detecting H. pylori infection with improved test accuracy and minimum use of endoscopy.

Eradication Therapy for Pediatric Helicobacter pylori Infection

In children, Helicobacter pylori infection causes gastritis, peptic ulcer, and extraintestinal manifestations such as refractory iron deficiency anemia, failure to thrive, and chronic idiopathic thrombocytopenia. The outcomes of recommendations for H. pylori eradication therapy in children are not comparable with the eradication rates of those in adults because of the low level of evidence, including randomized placebo-controlled treatment trials. In South Korea, no standard guideline for the management of children with H. pylori infection has been established yet. Herein, we reviewed the indications for and various modalities of eradication therapy in children with H. pylori infection in accordance with a review of published articles. H. pylori-associated peptic ulcer is the only one indication for eradication therapy. A proton pump inhibitor based on a combination of two antibiotics has been considered as the standard eradication therapy in children, but no consensus has been reached regarding the modality of eradication therapy in children.

National Survey Assessing Treatment of Helicobacter pylori Infection in Korean Children: A Pilot Study

BACKGROUND/AIMS: The standard guideline for the management Helicobacter pylori infection in Korean children is not present until now. In present study, we conducted the questionnaire survey to investigate the real situation of H. pylori eradication in children. MATERIALS AND METHODS: Questionnaire concerning the indications of H. pylori eradication, the first choice of treatment modality, the decision method of eradication result, experience of eradication failure, the second choice of treatment modality was sent to doctors who are members of the Korean Society for Pediatric Gastorenterology, Hepatology, and Nutrition. RESULTS: A total of 28 doctors (90.3%) answered the questionnaires among 31 doctors. The most common indication for eradication of H. pylori was peptic ulcer (n=24) followed by chronic abdominal pain (n=17) and positive family history of gastric cancer (n=12). The most common choice of first-line eradication therapy was omeprazole, amoxicillin, clarithromycin triple therapy (n=21) and followed by bismuth subsalicylate, amoxicillin, metronidazole, clarithromycin quadruple therapy (n=7). The results of treatment were judged by C13-urea breath test after 2 months later in 19 doctors (67.8%). Twenty four (85.7%) out of 28 doctors had experienced treatment failure. The most common second-line therapy was the sequential therapy (58.3%, 14 doctors among 24). CONCLUSIONS: This was the first study for the survey of the treatment of H. pylori infection to Korean pediatricians. The results of this study showed that most pediatric gastroenterologists used to treat H. pylori infection according to the textbook and the common use of bismuth-based quadruple therapy for the first-line treatment was notable.

Helicobacter pylori Antigens Inducing Early Immune Response in Infants

To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4–11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease β subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants.

The Application of Bacterial Meningitis Score for Bacterial Meningitis and Enteroviral Meningitis in Pediatric Patients

PURPOSE: Bacterial meningitis score (BMS) has been introduced as a clinical predictive parameter for diagnosing cerebrospinal fluid (CSF) pleocytosis in children at very low risk of bacterial meningitis in the postconjugate vaccine era. This study aimed to examine the usefulness of the BMS and to identify an additional index to distinguish between enteroviral meningitis and bacterial meningitis. METHODS: We retrospectively included 289 patients with enteroviral meningitis and 10 patients with bacterial meningitis between the aged 2 months to 16 years. We applied the BMS to all the included patients, and compared the initial laboratory and clinical characteristics between the two groups. RESULTS: Of the 210 patients categorized as having a very low risk of bacterial meningitis based on BMS, 2 (1%) had bacterial meningitis, both of whom were younger than 3 months. The sensitivity, specificity, and negative predictive value of the BMS for bacterial meningitis were 80%, 72%, and 99%, respectively. Compared with patients with enteroviral meningitis, those with bacterial meningitis were younger (0.3 years vs. 5.0 years, P<0.01), had higher leukocyte count (530/mm³ vs. 43/mm³, P=0.04), neutrophil count (490/mm³ vs. 20/mm³, P<0.01), and protein level (106 mg/dL vs. 30 mg/dL, P<0.01) in the CSF, and increased serum C-reactive protein (CRP) level (79 mg/L vs. 4.5 mg/L, P<0.01). CONCLUSION: Although the BMS is a useful clinical predictive parameter for identifying children with CSF pleocytosis who are at very low risk of bacterial meningitis, it should be applied with caution in young infants. In addition to applying BMS, clinical parameters such as CSF profiles and serum CRP levels are useful in clinical decision making for the management of children with CSF pleocytosis.

The Application of Bacterial Meningitis Score for Bacterial Meningitis and Enteroviral Meningitis in Pediatric Patients

PURPOSE: Bacterial meningitis score (BMS) has been introduced as a clinical predictive parameter for diagnosing cerebrospinal fluid (CSF) pleocytosis in children at very low risk of bacterial meningitis in the postconjugate vaccine era. This study aimed to examine the usefulness of the BMS and to identify an additional index to distinguish between enteroviral meningitis and bacterial meningitis. METHODS: We retrospectively included 289 patients with enteroviral meningitis and 10 patients with bacterial meningitis between the aged 2 months to 16 years. We applied the BMS to all the included patients, and compared the initial laboratory and clinical characteristics between the two groups. RESULTS: Of the 210 patients categorized as having a very low risk of bacterial meningitis based on BMS, 2 (1%) had bacterial meningitis, both of whom were younger than 3 months. The sensitivity, specificity, and negative predictive value of the BMS for bacterial meningitis were 80%, 72%, and 99%, respectively. Compared with patients with enteroviral meningitis, those with bacterial meningitis were younger (0.3 years vs. 5.0 years, P<0.01), had higher leukocyte count (530/mm³ vs. 43/mm³, P=0.04), neutrophil count (490/mm³ vs. 20/mm³, P<0.01), and protein level (106 mg/dL vs. 30 mg/dL, P<0.01) in the CSF, and increased serum C-reactive protein (CRP) level (79 mg/L vs. 4.5 mg/L, P<0.01). CONCLUSION: Although the BMS is a useful clinical predictive parameter for identifying children with CSF pleocytosis who are at very low risk of bacterial meningitis, it should be applied with caution in young infants. In addition to applying BMS, clinical parameters such as CSF profiles and serum CRP levels are useful in clinical decision making for the management of children with CSF pleocytosis.