- Email: [email protected]
Tu1138 Genes of Alcohol Metabolism in Patients With Simple Steatosis and NASH
Tu1136 Pilot Study of Hypoallergenic Formula With Lactobacillus GG: Impact on Crying Time, Inflammatory Biomarkers and Microbiota in Infants With Colic Nicole Y. Fatheree, Yuying Liu, Michael J. Ferris, Marcela Zozaya, Valarie McMurtry, Chunyan Cai, Mohammad H. Rahbar, Manouchehr Ardjomand-Hessabi, Ta Vu, Christine Wong, Melissa R. Van Arsdall, Juleen Min, Dat Q. Tran, Fernando Navarro, Wallace Gleason, Sara Gonzalez, Jon M. Rhoads BACKGROUND: Colic affects 5-19% of otherwise normal infants. In a previous study of infants with colic, we suggested that gut inflammation was associated with a less diverse fecal microbiota. Early colonization of the immature intestine with Lactobacillus rhamnosus GG (LGG), given in the infant's formula, has been proposed to reduce colic symptoms in formula-fed infants. OBJECTIVE: We hypothesized that LGG would become established as a component of the intestinal microbial community and alter biomarkers associated with colic. METHODS: This study was a prospective, double-blind, placebo-controlled trial in otherwise healthy infants with colic. The study was conducted and completed at the University of Texas clinics. We screened 74, randomized 30, and were able to completely follow and analyze 20 infants: 9 in the treatment group (casein hydrolysate formula plus LGG , minimum 3x10^7 CFU's daily) and 11 infants in the placebo group (casein hydrolysate formula without probiotic). Crying and fussing times, fecal calprotectin, and fecal microbiota were measured. RESULTS: Both groups demonstrated similar, steady declines in crying plus fussing time, although 20% of infants continued to have colic beyond 4 months. Fecal calprotectin was high and variable in both groups and did not show a parallel decline with crying + fussing time. Serum cytokine levels were detectable but similar in both groups. Microbiota analysis showed that in colicky infants, the most abundant genera were Blautia (22%), Escherichia/ Shigella (17%), Enterococcus (15%), Streptococcus (14%) and Coprobacillus (13%). The mean percent abundance of Enterococcus (p=0.001) and Bacilli (p=0.0121) were significantly increased in colicky infants with an average crying and fussing time of >180 minutes compared to colicky infants with a crying and fussing time <180 min. In the LGG+ group, L. rhamnosus abundance increased 2 weeks after treatment, but decreased thereafter while the infants were still receiving formula with LGG. CONCLUSIONS: We conclude that most infants in this age range have low-level intestinal inflammation that is not systemic in nature and that infants with colic have alterations in fecal microbiota which need further investigation. Infants with colic on either formula generally had resolution of symptoms by 6 weeks.
Tu1134 Are ESPGHAN 2011 Guidelines for Celiac Disease Also Suitable for Asymptomatic Patients? Chiara Maria Trovato, Francesco Valitutti, Ilaria Celletti, Stefania Leoni, Silvia Gatti, Donatella Iorfida, Monica Montuori, Caterina Anania, Anna Rita Vestri, Maria Barbato, Salvatore Cucchiara Introduction: In 2011, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has released its updated guidelines on celiac disease (CD) diagnosis. According to these new guidelines, symptomatic children with anti-transglutaminase (antitTG2) antibody levels ≥ 10 times upper limit normal (ULN) could avoid duodenal biopsies if the HLA test and serum anti-endomysial antibodies (EMA) are positive. So far, both symptomatic patients with anti-tTG2 titer <10 times ULN and those asymptomatic should undergo upper endoscopy with multiple duodenal biopsies to confirm a suspected CD. Objective: The aim of this study was to assess the accuracy of serological tests in asymptomatic patients to diagnose CD. Methods: We retrospectively assessed 286 children and adolescents (mean age: 8,3 years; age range: 10 months-17 years) who had received a CD diagnosis based on elevated titer of anti-tTG2, EMA positivity, histology and HLA typing. All patients (95 boys, 191 girls) were positive for anti-tTG2 and EMA. Patients were distinguished between symptomatic and asymptomatic while histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Statistical evaluation was made with the Fisher exact test. Results: Among the 286 EMA positive biopsied children, 196 (68.53%) had anti-tTG2 titers ≥ 10 times ULN. Among them, a group of 156 (54.54 %) children also had symptoms suggestive of CD (namely "high-titer" symptomatic children); of these, 142 (91.02%) showed severe lesion degree (3a, 3b, 3c MO). On the contrary, 40 out of 196 (13.98%) children were asymptomatic (namely "high-titer" asymptomatic children); 37 (92,5%) of them showed severe lesion degree (3a,3b, 3c MO). No difference was found between "high-titer" symptomatic children and "high-titer" asymptomatic children with regards to histological damage (Fisher exact test p=1,000). Conclusion: Our results indicate that the absence of symptoms in children with anti-tTG2 titers >10 times ULN and positive EMA antibodies does not undermine a "biopsy-sparing" CD diagnosis. The "biopsy-sparing" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG2 titer >10 times ULN, positive EMA and HLA-DQ2/DQ8.
Tu1137 Teaching Residents in a "Flipped Classroom" on an Inpatient Pediatric Gastroenterology Rotation Benjamin Sahn, Candi Jump, Danielle Wendel, Amanda Muir, Samantha Fish, Marianne Augustine, Allison Ballantine, Henry C. Lin, Lindsey Albenberg Background: Balancing quality subspecialty medical education during resident rotations with resident responsibilities and work hour restrictions is challenging. It is difficult to identify the ideal time for teaching and the ideal teaching format. A previous survey of the housestaff at the Children's Hospital of Philadelphia (CHOP), a tertiary care center with a large residency program, indicated a need for improved gastroenterology (GI) education. Traditional didactic formats are not efficient or high-yield and targeted adult-learning strategies are needed. "Flipped Classroom" is a method in which students learn new content by watching video tutorials and then the actual time in the "classroom" is spent working on problems in an interactive setting with the teacher. Hypothesis: Institution of a "Flipped Classroom" on an inpatient pediatric GI rotation will improve the perceived benefits of teaching sessions by the housestaff. Methods: A pre-study needs-assessment survey was distributed to 120 CHOP residents to assess the importance of subspecialty education and the ideal timing and methodology of teaching. Based on responses, a "Flipped Classroom" format was instituted. 10-minute-long online videos were created on GI symptom-based topics. One video was assigned to the inpatient residents each week, followed by a 30minute fellow-led, interactive teaching session, in which topic-specific cases and pediatric board-style questions were discussed. The residents completed pre- and post-rotation surveys. Results: The majority of residents prefer <30 minutes of subspecialty teaching per day. Directed learning either during rounds or through interactive cases is favored. On the postrotation survey, 100% of residents felt that the value of teaching sessions improved with the "Flipped Classroom." Additionally, 80% of respondents felt that fellows did a better job of teaching residents using the "Flipped Classroom" format. Despite the fact that the videos are short, 50% of residents felt that it was not easy to find time to watch the videos. Conclusion: Finding a balance between productivity and teaching is a major challenge facing resident education today. This is the first report of a "Flipped Classroom" method in graduate medical education. "Flipped Classroom" improves the value of resident educational sessions.
Tu1135 Anti-Transglutaminase Title, Marsh-Oberhuber Grading and Bone Mineral Density in Children With Celiac Disease At Diagnosis Chiara Maria Trovato, Stefania Leoni, Ilaria Celletti, Silvia Gatti, Francesco Valitutti, Donatella Iorfida, Costanza Cavallini, Monica Montuori, Caterina Anania, Carlina V. Albanese, Maria Barbato, Salvatore Cucchiara Introduction: Metabolic bone disease remains a significant and common complication of celiac disease (CD). Several studies have demonstrated low bone mineral density (BMD) at the time of celiac disease diagnosis in both children and adults. Low bone density in children and adolescents is defined as an areal BMD (aBMD) less than 2 SD below the age-adjusted mean value (Z-score <−2 SD). The pathogenesis of bone loss in celiac disease has not been completely elucidated: two major causal factors are malabsorption and inflammation. Calcium and Vitamin D might be poorly absorbed substances in celiacs. Several studies demonstrated an increased RANKL/OPG ratio in vitro and an increased osteoclastogenesis in untreated celiac patients due to chronic release of pro-inflammatory cytokines. Objectives: Aim of our study was to correlate Z-score value and anti-tissue transglutaminase type 2 (anti-tTG2) antibody title and Z-score value and Marsh-Oberhuber grade (MO) in children with CD at diagnosis. Methods: We enrolled 99 celiac patients (M 35; F 64; age-range: 4-15 years). All patients had positive test results for anti-tTG2 antibodies; histological lesions were graded according to MO classification; all of them underwent lumbar DEXA performed by Lunar Prodigy Advance (GE Healthcare, USA). Bone mineral density was estimated by Z-score. The linear correlation between the anti-tTg2 title and Z-score value and between MO grade and Z-score was evaluated by the Pearson product-moment correlation coefficient (Pearson's r). Results: Anti-tTG2 antibody titers ≥10 times the upper limit of normal were found in 65 of 99 patients. 84 patients showed severe lesion degree (3c + 3b + 3a) in Marsh-Oberhuber classification, 3 patients showed MO2, 4 MO1, 4 no lesions and 4 didn't undergo conventional upper GI (diagnosed according to the "biopsy-sparing" ESPGHAN 2012 criteria). Low BMD (Z-score ≤−2DS) was found in 13 (13.13%) patients; 20 (20.20%) patients showed −2< Zscore <−1; 43 (43.43%) patients showed -1≤ Z-score <0 and Z score ≥0 was detected in 23 (23.23%) patients. No correlations were found between Z-score value and anti-tTG2 title (Pearson's r = -0.06 ) and between Z-score value and MO degree (Pearson's r = 0.07). Conclusion: Low bone mineral density does not correlate to the anti-tTG2 title and to MarshOberhuber grading in a cohort of Italian children at CD diagnosis.
Tu1138 Genes of Alcohol Metabolism in Patients With Simple Steatosis and NASH Ghanim Aljomah, Susan S. Baker, Wensheng Liu, Rafal Kozielski, Robert D. Baker, Lixin Zhu Purpose: Non-alcoholic steatohepatitis (NASH) is a serious form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, and variable degrees of fibrosis. NASH and alcoholic steatohepatitis share many histological features. The increased gene expression of alcohol-catabolism related genes in NASH was reported in children, suggesting that alcohol may play a role in NASH. Our previous studies suggest that gut microbiome is a source of endogenous alcohol. The purpose of this study is to examine the gene expression of alcohol-catabolism related genes in simple steatosis patients, in comparison to NASH patients and normal controls and to determine the role of alcohol in the natural progression of NASH. Methods: NASH was diagnosed according to Kleiner's criteria. The mRNA expression of alcohol-catabolism related genes (ADH4, ADH6, ADH1C, CYP2E1 and Catalase) in the livers of normal controls, simple steatosis and NASH patients were examined
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AGA Abstracts
AGA Abstracts
substantial amount (27%) of children presenting with FDDs at a tertiary care center have positive scores on ASD screening questionnaires. Although only a small number meet criteria for a classic ASD, the majority meets criteria for other DSM-IV diagnoses. Further studies are needed to determine whether particular autistic-like behaviors, such as disruptive behaviors, are associated with particular phenotypes of FDDs or different outcomes. Physicians dealing with children with FDD need to be vigilant to uncover possible associated behavioral disturbances.
AGA Abstracts
by quantitative real-time PCR (qRT-PCR). ANOVA test was applied to analyze the data. Results: There was a statistically significant difference in mRNA expression of the alcohol related genes among the three groups (p< 0.05, ANOVA) for ADH4, ADH1C, CYP2E1 and Catalase. The gene expression of (ADH4, ADH6, ADH1C, CYP2E1 and Catalase) was higher in NASH and simple steatosis compare to NC (p< 0.05). No statistical significance was found between the simple steatosis and the NASH patients. Conclusions: Increased expression of alcohol metabolizing genes suggests that alcohol metabolism is elevated in patients with NASH and with simple steatosis. Alcohol metabolism may contribute to the pathogenesis of steatosis and steatohepatitis in a mechanism similar to the pathogenesis of alcoholic steatohepatitis.
susceptibility is different depending on the country or region, it is necessary to consider the regional characteristics to eradicate H. pylori. Tu1141 The Effect of Sleep on the Frequency and Characteristics of GER Events and Symptom Associations in NICU Neonates Aslam Qureshi, Alecia Wagner, Xiaoyu Gao, Sudarshan Jadcherla BACKGROUND: Sleep is a reversible physiological state, during which protection of the aero-digestive tract is vital for survival. Infants spend nearly 80% of their time sleeping and it is well known that gastroesophageal reflux (GER) is highly prevalent in the NICU setting. The correlation between sleep and GER events, as well as the role of symptoms during this time is unclear. AIM: 1) To distinguish the characteristics and prevalence of GER events stratified based on sleep state or wakeful state in infants 2) To differentiate the symptom characteristics between these categories. METHODS: Fourteen infants (6 males), were evaluated for apparent life threatening events involving concurrent pH-Impedance (Ohmega, MMS) and video polysomnography (Grass Technologies) testing at 41.6 ± 3.4 wks postmenstrual age (born at 34.9 ± 4.9 wks). Infants were referred mainly for apnea and desaturation. Concurrent video polysomnography was performed for 6 hours during 24-hr pH-impedance study at bedside and included EEG, EOG, Submental EMG, and respiratory inductance plethysmography. GER events were classified as: acidic when pH was ≤ 4 reaching at least two consecutive impedance channels, pH only events (POE) when pH was ≤4 with no impedance event or reaching only one impedance channel and weakly acid when impedance was seen in at least two consecutive impedance channels with pH >4 but <7. Sleep study was scored on 30-sec epochs, and separated into either sleep or wake. Bolus clearance time (BCT) was defined as time taken in seconds for bolus to return to the baseline and ACT was defined as the time taken for the pH to return to >4 for >3s. Symptom index (SI) and symptom sensitivity index (SSI) were calculated if a GER occurred 120 seconds before or 120 seconds after symptom onset. Symptoms were further grouped into: Cardiorespiratory-aerodigestive (cough, bradycardia, tachycardia, desaturation, sneezing, gagging), sensory (emesis, flushing, grimace, grunting), and physical (arching, irritability). RESULTS: A total of 362 reflux events were analyzed from 89 hours of recordings, of which 34 hours (38%) were spent in sleep and 55 hours (62%) were spent in wakeful state. Reflux characteristics are shown in Table 1. Symptom associations are shown in Table 2. CONCLUSIONS: Wakeful state is associated with a higher frequency of GER that is predominantly comprised of weakly acid reflux events and a greater proximal extent, while sleep state has significantly fewer GER events that are more evenly distributed between acid and weakly acid events, with few events reaching the proximal channels. Symptom generation functions are similar in sleep and wakeful states. Neonates have the ability to perceive esophageal sensitivity during sleep (Table 2). *Supported in part by 2RO1DK 068158 (Jadcherla). Table 1: Reflux Characteristics in Sleep versus Wake
Tu1139 Narrow Band Imaging (NBI) Combined to Water Immersion Technique (WIT): Any Diagnostic Yield for Celiac Disease? a Pediatric Prospective Study Francesco Valitutti, Donatella Iorfida, Salvatore Oliva, Ilaria Celletti, Stefania Leoni, Silvia Gatti, Chiara Maria Trovato, Maria Barbato, Monica Montuori, Caterina Anania, Antonio Tiberti, Giovanni Di Nardo, Salvatore Cucchiara Background and Aims: Upper GI endoscopies are still required to diagnose the majority of celiac children, notwithstanding the recently updated ESPGHAN criteria. The "multiplebiopsy" approach both in the duodenum and in the bulb has been suggested by several guidelines as the best strategy to confirm the diagnosis of celiac disease (CD); however, this approach increases the invasiveness of the endoscopic procedure itself and is fairly timeconsuming. Our aim was to evaluate the diagnostic yield of a single biopsy guided by narrowband imaging (NBI) combined to water immersion technique (WIT), in the assessment of CD in a prospective, single center, pediatric study. Methods: We enrolled 43 children (12 males; mean age: 7.2 years; age range: 1.25-15.25 years) with suspected CD (positive antitransglutaminase and antiendomisial antibodies) undergoing upper GI endoscopy to compare single "NBI plus WIT"-guided biopsy versus the standard, duodenal and bulbar, "multiplebiopsy" approach (2 random biopsies in the bulb, 4 random biopsies in the 2nd-3rd duodenal portion). "NBI-plus-WIT" endoscopic severity was classified on a Likert scale as normal, altered with mild modifications (nodular mucosa, scalloping) or clearly altered (reduction and flattening of "plicae"); inter-observer variability between two different physicians was also assessed with regards to endoscopic judgments. Histology was graded according to the Marsh-Oberhuber classification. Results: Diagnosis of CD was confirmed in 40 out of 43 children (the remaining 3 were diagnosed as potential CD). "NBI plus WIT" approach correctly diagnosed 35 out of 40 celiac children, with a diagnostic sensitivity of 87.5 % (C.I.: 77.3-97.7); none among the studied patients showed an exclusive, "NBI plus WIT"detected histological damage. Clearly altered pattern at "NBI plus WIT" endoscopic visualization was significantly associated to villous atrophy both at "NBI plus WIT"-guided biopsy and at multiple biopsy sampling (Spearman Rho 0.637 and 0.496). High anti-transglutaminase antibody titer (≥10 times upper limit normal) was also associated to clearly altered pattern at "NBI plus WIT" endoscopic visualization. Concordance of "NBI plus WIT" endoscopic assessments was fairly high between two different operators (K: 0.884). After the passage through the pylorus of the endoscope, mean NBI plus WIT procedure time was 53.6 sec (DS: 12.7 sec), whereas mean time for multiple biopsy sampling was 218.2 sec (DS: 38.3 sec) (p≤0,0001). Conclusions: Albeit time- and resource- saving, single "NBI plus WIT"guided biopsy is not as effective as the well established "multiple-biopsy" approach in confirming the diagnosis of CD. Tu1140 Primary Antibiotics Susceptibility and Efficacy of Susceptibility-Guided Triple Therapy for Helicobacter pylori Among Japanese Children in the Last Decade A Multi-Center Observational Study Hiroyuki Yamada, Yuri Etani, Yoshiko Nakayama, Yousuke Shima, Shingo Kurasawa, Sawako Kato, Nao Hidaka, Akira Horiuchi, Shinobu Ida Background: Recently, the prevalence of Helicobacter pylori infection in Japanese children has been reduced to 3-5%. However not a few patients showed difficulties to eradication because of the high incidence of drug susceptibility. Therefore it is quite important to choose appropriate regimen for certain eradication and avoid conduction of further drug resistance. The present study aimed to analyze the drug resistance rate and the eradication rate of H. pylori in the last 10 years in Japanese children. The efficacy of antimicrobial susceptibilityguided triple eradication therapy for H. pylori is also evaluated. SUBJECTS and METHODS: From April 2003 to March 2012, in Japanese three facilities, total 74 (mean age 12.3 years ± 3.2 SD, male 47.3%) children and adolescents under 18 years old who had no history of eradication therapy in the past were included in this study. H. pylori culture was performed using biopsy specimens from gastric antrum and corpus, and then the drug susceptibility was evaluated. Patients were treated with susceptibility-based triple therapy and were examined the rate of eradication. Successfulness of eradication was evaluated by the 13C-urea breath test and/or stool antigen test at least 8 weeks later after the end of treatment. Result: H.pylori susceptibility test showed that 47.2% of resistance (MIC^1) to clarithromycin (CAM) and 30.1% (MIC^16) to metronidazole (MNZ), respectively. Susceptibility of amoxicillin (AMPC) (MIC^0.06) was 21.3%, but MIC^1 was only 2 strains. The MIC 50 of CAM during the first five-years of study period was 0.12 and resistance rate was 44.4%. On the other hand, in the latter five-years period, MIC 50 of CAM was 2.0 and resistance rate was elevated to 52.2%, thus it was speculated that the rate of CAM-resistant strain showed increasing trend in Japan. The overall eradication rate was 89.4% (59/66) by intention-totreat analysis (ITT) and 96.7% by per-protocol analysis (PP). The PPI, AMPC and CAM regimen was the first choice for CAM susceptible strain. The ITT and PP eradication rates were 91.7% (33/36) and 100% (33/33), respectively. The PPI, AMPC and MNZ regimen was the first choice for CAM resistant strain and the ITT and PP eradication rates were 91.3% (21/23) and 100% (21/21), respectively. Conclusions: An antimicrobial susceptibilityguided triple eradication therapy for H. pylori was quite effective in Japanese children with very high, approximately 50%, CAM resistance rate. It showed comparable to or greater efficacy than the previously described sequential therapy in western countries. The drug
AGA Abstracts
Data are stated as median (IQR) or mean ± SEM. Table 2: Symptoms Relating with Reflux Events in Sleep versus Wakeful State.
Data are stated as median (IQR) or mean ± SEM. CRE- Cardiorespiratory-aerodigestive . * P-value <0.05 comparing wake and sleep.
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Tu1134 Are ESPGHAN 2011 Guidelines for Celiac Disease Also Suitable for Asymptomatic Patients? Chiara Maria Trovato, Francesco Valitutti, Ilaria Celletti, Stefania Leoni, Silvia Gatti, Donatella Iorfida, Monica Montuori, Caterina Anania, Anna Rita Vestri, Maria Barbato, Salvatore Cucchiara Introduction: In 2011, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has released its updated guidelines on celiac disease (CD) diagnosis. According to these new guidelines, symptomatic children with anti-transglutaminase (antitTG2) antibody levels ≥ 10 times upper limit normal (ULN) could avoid duodenal biopsies if the HLA test and serum anti-endomysial antibodies (EMA) are positive. So far, both symptomatic patients with anti-tTG2 titer <10 times ULN and those asymptomatic should undergo upper endoscopy with multiple duodenal biopsies to confirm a suspected CD. Objective: The aim of this study was to assess the accuracy of serological tests in asymptomatic patients to diagnose CD. Methods: We retrospectively assessed 286 children and adolescents (mean age: 8,3 years; age range: 10 months-17 years) who had received a CD diagnosis based on elevated titer of anti-tTG2, EMA positivity, histology and HLA typing. All patients (95 boys, 191 girls) were positive for anti-tTG2 and EMA. Patients were distinguished between symptomatic and asymptomatic while histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Statistical evaluation was made with the Fisher exact test. Results: Among the 286 EMA positive biopsied children, 196 (68.53%) had anti-tTG2 titers ≥ 10 times ULN. Among them, a group of 156 (54.54 %) children also had symptoms suggestive of CD (namely "high-titer" symptomatic children); of these, 142 (91.02%) showed severe lesion degree (3a, 3b, 3c MO). On the contrary, 40 out of 196 (13.98%) children were asymptomatic (namely "high-titer" asymptomatic children); 37 (92,5%) of them showed severe lesion degree (3a,3b, 3c MO). No difference was found between "high-titer" symptomatic children and "high-titer" asymptomatic children with regards to histological damage (Fisher exact test p=1,000). Conclusion: Our results indicate that the absence of symptoms in children with anti-tTG2 titers >10 times ULN and positive EMA antibodies does not undermine a "biopsy-sparing" CD diagnosis. The "biopsy-sparing" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG2 titer >10 times ULN, positive EMA and HLA-DQ2/DQ8.
Tu1137 Teaching Residents in a "Flipped Classroom" on an Inpatient Pediatric Gastroenterology Rotation Benjamin Sahn, Candi Jump, Danielle Wendel, Amanda Muir, Samantha Fish, Marianne Augustine, Allison Ballantine, Henry C. Lin, Lindsey Albenberg Background: Balancing quality subspecialty medical education during resident rotations with resident responsibilities and work hour restrictions is challenging. It is difficult to identify the ideal time for teaching and the ideal teaching format. A previous survey of the housestaff at the Children's Hospital of Philadelphia (CHOP), a tertiary care center with a large residency program, indicated a need for improved gastroenterology (GI) education. Traditional didactic formats are not efficient or high-yield and targeted adult-learning strategies are needed. "Flipped Classroom" is a method in which students learn new content by watching video tutorials and then the actual time in the "classroom" is spent working on problems in an interactive setting with the teacher. Hypothesis: Institution of a "Flipped Classroom" on an inpatient pediatric GI rotation will improve the perceived benefits of teaching sessions by the housestaff. Methods: A pre-study needs-assessment survey was distributed to 120 CHOP residents to assess the importance of subspecialty education and the ideal timing and methodology of teaching. Based on responses, a "Flipped Classroom" format was instituted. 10-minute-long online videos were created on GI symptom-based topics. One video was assigned to the inpatient residents each week, followed by a 30minute fellow-led, interactive teaching session, in which topic-specific cases and pediatric board-style questions were discussed. The residents completed pre- and post-rotation surveys. Results: The majority of residents prefer <30 minutes of subspecialty teaching per day. Directed learning either during rounds or through interactive cases is favored. On the postrotation survey, 100% of residents felt that the value of teaching sessions improved with the "Flipped Classroom." Additionally, 80% of respondents felt that fellows did a better job of teaching residents using the "Flipped Classroom" format. Despite the fact that the videos are short, 50% of residents felt that it was not easy to find time to watch the videos. Conclusion: Finding a balance between productivity and teaching is a major challenge facing resident education today. This is the first report of a "Flipped Classroom" method in graduate medical education. "Flipped Classroom" improves the value of resident educational sessions.
Tu1135 Anti-Transglutaminase Title, Marsh-Oberhuber Grading and Bone Mineral Density in Children With Celiac Disease At Diagnosis Chiara Maria Trovato, Stefania Leoni, Ilaria Celletti, Silvia Gatti, Francesco Valitutti, Donatella Iorfida, Costanza Cavallini, Monica Montuori, Caterina Anania, Carlina V. Albanese, Maria Barbato, Salvatore Cucchiara Introduction: Metabolic bone disease remains a significant and common complication of celiac disease (CD). Several studies have demonstrated low bone mineral density (BMD) at the time of celiac disease diagnosis in both children and adults. Low bone density in children and adolescents is defined as an areal BMD (aBMD) less than 2 SD below the age-adjusted mean value (Z-score <−2 SD). The pathogenesis of bone loss in celiac disease has not been completely elucidated: two major causal factors are malabsorption and inflammation. Calcium and Vitamin D might be poorly absorbed substances in celiacs. Several studies demonstrated an increased RANKL/OPG ratio in vitro and an increased osteoclastogenesis in untreated celiac patients due to chronic release of pro-inflammatory cytokines. Objectives: Aim of our study was to correlate Z-score value and anti-tissue transglutaminase type 2 (anti-tTG2) antibody title and Z-score value and Marsh-Oberhuber grade (MO) in children with CD at diagnosis. Methods: We enrolled 99 celiac patients (M 35; F 64; age-range: 4-15 years). All patients had positive test results for anti-tTG2 antibodies; histological lesions were graded according to MO classification; all of them underwent lumbar DEXA performed by Lunar Prodigy Advance (GE Healthcare, USA). Bone mineral density was estimated by Z-score. The linear correlation between the anti-tTg2 title and Z-score value and between MO grade and Z-score was evaluated by the Pearson product-moment correlation coefficient (Pearson's r). Results: Anti-tTG2 antibody titers ≥10 times the upper limit of normal were found in 65 of 99 patients. 84 patients showed severe lesion degree (3c + 3b + 3a) in Marsh-Oberhuber classification, 3 patients showed MO2, 4 MO1, 4 no lesions and 4 didn't undergo conventional upper GI (diagnosed according to the "biopsy-sparing" ESPGHAN 2012 criteria). Low BMD (Z-score ≤−2DS) was found in 13 (13.13%) patients; 20 (20.20%) patients showed −2< Zscore <−1; 43 (43.43%) patients showed -1≤ Z-score <0 and Z score ≥0 was detected in 23 (23.23%) patients. No correlations were found between Z-score value and anti-tTG2 title (Pearson's r = -0.06 ) and between Z-score value and MO degree (Pearson's r = 0.07). Conclusion: Low bone mineral density does not correlate to the anti-tTG2 title and to MarshOberhuber grading in a cohort of Italian children at CD diagnosis.
Tu1138 Genes of Alcohol Metabolism in Patients With Simple Steatosis and NASH Ghanim Aljomah, Susan S. Baker, Wensheng Liu, Rafal Kozielski, Robert D. Baker, Lixin Zhu Purpose: Non-alcoholic steatohepatitis (NASH) is a serious form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, and variable degrees of fibrosis. NASH and alcoholic steatohepatitis share many histological features. The increased gene expression of alcohol-catabolism related genes in NASH was reported in children, suggesting that alcohol may play a role in NASH. Our previous studies suggest that gut microbiome is a source of endogenous alcohol. The purpose of this study is to examine the gene expression of alcohol-catabolism related genes in simple steatosis patients, in comparison to NASH patients and normal controls and to determine the role of alcohol in the natural progression of NASH. Methods: NASH was diagnosed according to Kleiner's criteria. The mRNA expression of alcohol-catabolism related genes (ADH4, ADH6, ADH1C, CYP2E1 and Catalase) in the livers of normal controls, simple steatosis and NASH patients were examined
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AGA Abstracts
AGA Abstracts
substantial amount (27%) of children presenting with FDDs at a tertiary care center have positive scores on ASD screening questionnaires. Although only a small number meet criteria for a classic ASD, the majority meets criteria for other DSM-IV diagnoses. Further studies are needed to determine whether particular autistic-like behaviors, such as disruptive behaviors, are associated with particular phenotypes of FDDs or different outcomes. Physicians dealing with children with FDD need to be vigilant to uncover possible associated behavioral disturbances.
AGA Abstracts
by quantitative real-time PCR (qRT-PCR). ANOVA test was applied to analyze the data. Results: There was a statistically significant difference in mRNA expression of the alcohol related genes among the three groups (p< 0.05, ANOVA) for ADH4, ADH1C, CYP2E1 and Catalase. The gene expression of (ADH4, ADH6, ADH1C, CYP2E1 and Catalase) was higher in NASH and simple steatosis compare to NC (p< 0.05). No statistical significance was found between the simple steatosis and the NASH patients. Conclusions: Increased expression of alcohol metabolizing genes suggests that alcohol metabolism is elevated in patients with NASH and with simple steatosis. Alcohol metabolism may contribute to the pathogenesis of steatosis and steatohepatitis in a mechanism similar to the pathogenesis of alcoholic steatohepatitis.
susceptibility is different depending on the country or region, it is necessary to consider the regional characteristics to eradicate H. pylori. Tu1141 The Effect of Sleep on the Frequency and Characteristics of GER Events and Symptom Associations in NICU Neonates Aslam Qureshi, Alecia Wagner, Xiaoyu Gao, Sudarshan Jadcherla BACKGROUND: Sleep is a reversible physiological state, during which protection of the aero-digestive tract is vital for survival. Infants spend nearly 80% of their time sleeping and it is well known that gastroesophageal reflux (GER) is highly prevalent in the NICU setting. The correlation between sleep and GER events, as well as the role of symptoms during this time is unclear. AIM: 1) To distinguish the characteristics and prevalence of GER events stratified based on sleep state or wakeful state in infants 2) To differentiate the symptom characteristics between these categories. METHODS: Fourteen infants (6 males), were evaluated for apparent life threatening events involving concurrent pH-Impedance (Ohmega, MMS) and video polysomnography (Grass Technologies) testing at 41.6 ± 3.4 wks postmenstrual age (born at 34.9 ± 4.9 wks). Infants were referred mainly for apnea and desaturation. Concurrent video polysomnography was performed for 6 hours during 24-hr pH-impedance study at bedside and included EEG, EOG, Submental EMG, and respiratory inductance plethysmography. GER events were classified as: acidic when pH was ≤ 4 reaching at least two consecutive impedance channels, pH only events (POE) when pH was ≤4 with no impedance event or reaching only one impedance channel and weakly acid when impedance was seen in at least two consecutive impedance channels with pH >4 but <7. Sleep study was scored on 30-sec epochs, and separated into either sleep or wake. Bolus clearance time (BCT) was defined as time taken in seconds for bolus to return to the baseline and ACT was defined as the time taken for the pH to return to >4 for >3s. Symptom index (SI) and symptom sensitivity index (SSI) were calculated if a GER occurred 120 seconds before or 120 seconds after symptom onset. Symptoms were further grouped into: Cardiorespiratory-aerodigestive (cough, bradycardia, tachycardia, desaturation, sneezing, gagging), sensory (emesis, flushing, grimace, grunting), and physical (arching, irritability). RESULTS: A total of 362 reflux events were analyzed from 89 hours of recordings, of which 34 hours (38%) were spent in sleep and 55 hours (62%) were spent in wakeful state. Reflux characteristics are shown in Table 1. Symptom associations are shown in Table 2. CONCLUSIONS: Wakeful state is associated with a higher frequency of GER that is predominantly comprised of weakly acid reflux events and a greater proximal extent, while sleep state has significantly fewer GER events that are more evenly distributed between acid and weakly acid events, with few events reaching the proximal channels. Symptom generation functions are similar in sleep and wakeful states. Neonates have the ability to perceive esophageal sensitivity during sleep (Table 2). *Supported in part by 2RO1DK 068158 (Jadcherla). Table 1: Reflux Characteristics in Sleep versus Wake
Tu1139 Narrow Band Imaging (NBI) Combined to Water Immersion Technique (WIT): Any Diagnostic Yield for Celiac Disease? a Pediatric Prospective Study Francesco Valitutti, Donatella Iorfida, Salvatore Oliva, Ilaria Celletti, Stefania Leoni, Silvia Gatti, Chiara Maria Trovato, Maria Barbato, Monica Montuori, Caterina Anania, Antonio Tiberti, Giovanni Di Nardo, Salvatore Cucchiara Background and Aims: Upper GI endoscopies are still required to diagnose the majority of celiac children, notwithstanding the recently updated ESPGHAN criteria. The "multiplebiopsy" approach both in the duodenum and in the bulb has been suggested by several guidelines as the best strategy to confirm the diagnosis of celiac disease (CD); however, this approach increases the invasiveness of the endoscopic procedure itself and is fairly timeconsuming. Our aim was to evaluate the diagnostic yield of a single biopsy guided by narrowband imaging (NBI) combined to water immersion technique (WIT), in the assessment of CD in a prospective, single center, pediatric study. Methods: We enrolled 43 children (12 males; mean age: 7.2 years; age range: 1.25-15.25 years) with suspected CD (positive antitransglutaminase and antiendomisial antibodies) undergoing upper GI endoscopy to compare single "NBI plus WIT"-guided biopsy versus the standard, duodenal and bulbar, "multiplebiopsy" approach (2 random biopsies in the bulb, 4 random biopsies in the 2nd-3rd duodenal portion). "NBI-plus-WIT" endoscopic severity was classified on a Likert scale as normal, altered with mild modifications (nodular mucosa, scalloping) or clearly altered (reduction and flattening of "plicae"); inter-observer variability between two different physicians was also assessed with regards to endoscopic judgments. Histology was graded according to the Marsh-Oberhuber classification. Results: Diagnosis of CD was confirmed in 40 out of 43 children (the remaining 3 were diagnosed as potential CD). "NBI plus WIT" approach correctly diagnosed 35 out of 40 celiac children, with a diagnostic sensitivity of 87.5 % (C.I.: 77.3-97.7); none among the studied patients showed an exclusive, "NBI plus WIT"detected histological damage. Clearly altered pattern at "NBI plus WIT" endoscopic visualization was significantly associated to villous atrophy both at "NBI plus WIT"-guided biopsy and at multiple biopsy sampling (Spearman Rho 0.637 and 0.496). High anti-transglutaminase antibody titer (≥10 times upper limit normal) was also associated to clearly altered pattern at "NBI plus WIT" endoscopic visualization. Concordance of "NBI plus WIT" endoscopic assessments was fairly high between two different operators (K: 0.884). After the passage through the pylorus of the endoscope, mean NBI plus WIT procedure time was 53.6 sec (DS: 12.7 sec), whereas mean time for multiple biopsy sampling was 218.2 sec (DS: 38.3 sec) (p≤0,0001). Conclusions: Albeit time- and resource- saving, single "NBI plus WIT"guided biopsy is not as effective as the well established "multiple-biopsy" approach in confirming the diagnosis of CD. Tu1140 Primary Antibiotics Susceptibility and Efficacy of Susceptibility-Guided Triple Therapy for Helicobacter pylori Among Japanese Children in the Last Decade A Multi-Center Observational Study Hiroyuki Yamada, Yuri Etani, Yoshiko Nakayama, Yousuke Shima, Shingo Kurasawa, Sawako Kato, Nao Hidaka, Akira Horiuchi, Shinobu Ida Background: Recently, the prevalence of Helicobacter pylori infection in Japanese children has been reduced to 3-5%. However not a few patients showed difficulties to eradication because of the high incidence of drug susceptibility. Therefore it is quite important to choose appropriate regimen for certain eradication and avoid conduction of further drug resistance. The present study aimed to analyze the drug resistance rate and the eradication rate of H. pylori in the last 10 years in Japanese children. The efficacy of antimicrobial susceptibilityguided triple eradication therapy for H. pylori is also evaluated. SUBJECTS and METHODS: From April 2003 to March 2012, in Japanese three facilities, total 74 (mean age 12.3 years ± 3.2 SD, male 47.3%) children and adolescents under 18 years old who had no history of eradication therapy in the past were included in this study. H. pylori culture was performed using biopsy specimens from gastric antrum and corpus, and then the drug susceptibility was evaluated. Patients were treated with susceptibility-based triple therapy and were examined the rate of eradication. Successfulness of eradication was evaluated by the 13C-urea breath test and/or stool antigen test at least 8 weeks later after the end of treatment. Result: H.pylori susceptibility test showed that 47.2% of resistance (MIC^1) to clarithromycin (CAM) and 30.1% (MIC^16) to metronidazole (MNZ), respectively. Susceptibility of amoxicillin (AMPC) (MIC^0.06) was 21.3%, but MIC^1 was only 2 strains. The MIC 50 of CAM during the first five-years of study period was 0.12 and resistance rate was 44.4%. On the other hand, in the latter five-years period, MIC 50 of CAM was 2.0 and resistance rate was elevated to 52.2%, thus it was speculated that the rate of CAM-resistant strain showed increasing trend in Japan. The overall eradication rate was 89.4% (59/66) by intention-totreat analysis (ITT) and 96.7% by per-protocol analysis (PP). The PPI, AMPC and CAM regimen was the first choice for CAM susceptible strain. The ITT and PP eradication rates were 91.7% (33/36) and 100% (33/33), respectively. The PPI, AMPC and MNZ regimen was the first choice for CAM resistant strain and the ITT and PP eradication rates were 91.3% (21/23) and 100% (21/21), respectively. Conclusions: An antimicrobial susceptibilityguided triple eradication therapy for H. pylori was quite effective in Japanese children with very high, approximately 50%, CAM resistance rate. It showed comparable to or greater efficacy than the previously described sequential therapy in western countries. The drug
AGA Abstracts
Data are stated as median (IQR) or mean ± SEM. Table 2: Symptoms Relating with Reflux Events in Sleep versus Wakeful State.
Data are stated as median (IQR) or mean ± SEM. CRE- Cardiorespiratory-aerodigestive . * P-value <0.05 comparing wake and sleep.
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