Pub Date : 2019-09-01DOI: 10.1097/MPG.0000000000002413
S. Ling, Wen Ye, D. Leung, O. Navarro, A. Weymann, W. Karnsakul, A. J. Freeman, J. Magee, M. Narkewicz
OBJECTIVES Early identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and non-invasive liver fibrosis indices correlate with liver US patterns and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease. METHODS We studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3-12y, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous liver pattern on US (HTG, n = 62) were matched 1:2 in design with children with normal US (NL, n = 122). Analyses included children with nodular (NOD, n = 22) and homogeneous hyperechoic (HMG, n = 38) livers. RESULTS Univariate analysis showed significant differences between US groups for standard blood tests, spleen size, and non-invasive liver fibrosis indices. Multivariable models discriminated NOD vs. NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG vs. NL (AUROC 0.76), NOD vs. HTG (0.78), and HMG vs NL (0.79). CONCLUSION Liver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL vs NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.
目的:早期识别有严重肝脏疾病(CFLD)风险的囊性纤维化(CF)患儿，将有助于开展针对性的预防性治疗研究。CFLD没有金标准测试。超声检查(US)用于识别CFLD，但其诊断准确性值得关注。我们的目的是确定标准血液检查、影像学变量和非侵入性肝纤维化指数的差异是否与肝脏US模式相关，从而为异质US模式反映临床相关肝病提供支持性证据。方法:我们研究了244名年龄3-12岁的胰腺功能不全CF儿童的基线研究腹部US和血液检查，这些儿童参加了一项US预测CF肝硬化能力的前瞻性研究(PUSH研究)。在设计中，异质肝型US患儿(HTG, n = 62)与正常US患儿(NL, n = 122) 1:2匹配。分析包括结节性(NOD, n = 22)和均匀性高回声(HMG, n = 38)肝患儿。结果单因素分析显示，美国两组在标准血液检查、脾脏大小和非侵入性肝纤维化指标方面存在显著差异。多变量模型区分NOD和NL的准确率很高(AUROC为0.96)。模型还可以区分HTG与NL (AUROC为0.76)、NOD与HTG(0.78)以及HMG与NL(0.79)。结论CF患儿肝脏US型与血小板计数、脾脏大小及肝纤维化指标相关。这些生物标志物的多变量模型对NL和NOD有很好的区分能力，对其他US模式也有很好的区分能力，提示US模式与临床相关肝脏疾病相关。
{"title":"Liver Ultrasound Patterns in Children with Cystic Fibrosis Correlate with Non-Invasive Tests of Liver Disease.","authors":"S. Ling, Wen Ye, D. Leung, O. Navarro, A. Weymann, W. Karnsakul, A. J. Freeman, J. Magee, M. Narkewicz","doi":"10.1097/MPG.0000000000002413","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002413","url":null,"abstract":"OBJECTIVES\u0000Early identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and non-invasive liver fibrosis indices correlate with liver US patterns and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease.\u0000\u0000\u0000METHODS\u0000We studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3-12y, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous liver pattern on US (HTG, n = 62) were matched 1:2 in design with children with normal US (NL, n = 122). Analyses included children with nodular (NOD, n = 22) and homogeneous hyperechoic (HMG, n = 38) livers.\u0000\u0000\u0000RESULTS\u0000Univariate analysis showed significant differences between US groups for standard blood tests, spleen size, and non-invasive liver fibrosis indices. Multivariable models discriminated NOD vs. NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG vs. NL (AUROC 0.76), NOD vs. HTG (0.78), and HMG vs NL (0.79).\u0000\u0000\u0000CONCLUSION\u0000Liver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL vs NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85108277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-22DOI: 10.1097/MPG.0000000000002573
A. Di Sessa, G. R. Umano, G. Cirillo, P. Marzuillo, M. Arienzo, M. Pedullà, E. M. Giudice
We first investigated in obese children the protective role of the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567:TA variant in liver damage. Six hundred eighty-five obese children were genotyped for HSD17B13, patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) was calculated. The population was clustered in two genetic risk groups based on the numbers of steatogenic alleles (low: carriers up to 3 risk alleles, high:4-6 risk alleles).Carriers of the HSD17B13 rare A allele showed lower percentage of hepatic steatosis and both lower serum transaminase and PNFI levels than noncarriers, even after adjustments for confounders. These findings were also confirmed in both risk groups.We demonstrated the protective effect of the rs72613567:TA HSD17B13 variant in reducing liver damage in obese children regardless of genetic predisposition.
{"title":"The rs72613567: TA Variant in the Hydroxysteroid 17-beta Dehydrogenase 13 Gene Reduces Liver Damage in Obese Children.","authors":"A. Di Sessa, G. R. Umano, G. Cirillo, P. Marzuillo, M. Arienzo, M. Pedullà, E. M. Giudice","doi":"10.1097/MPG.0000000000002573","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002573","url":null,"abstract":"We first investigated in obese children the protective role of the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567:TA variant in liver damage. Six hundred eighty-five obese children were genotyped for HSD17B13, patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) was calculated. The population was clustered in two genetic risk groups based on the numbers of steatogenic alleles (low: carriers up to 3 risk alleles, high:4-6 risk alleles).Carriers of the HSD17B13 rare A allele showed lower percentage of hepatic steatosis and both lower serum transaminase and PNFI levels than noncarriers, even after adjustments for confounders. These findings were also confirmed in both risk groups.We demonstrated the protective effect of the rs72613567:TA HSD17B13 variant in reducing liver damage in obese children regardless of genetic predisposition.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83549490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-22DOI: 10.1097/MPG.0000000000002470
Jenny Koo, Averyl Narvasa, L. Bode, J. H. Kim
BACKGROUND Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies. METHODS We thickened donor human milk (DHM) and formula using various thickeners: starch-based thickeners (SBT) (Thick It®, rice cereal), and gum-based thickeners (GBT) (xanthan gum: Simply Thick®, Thicken Up Clear®; carob gum: GelMix®). We also assessed formula with added starches marketed for reflux, including Similac Spit Up® (SSU) and Enfamil AR® (EAR). The viscosity of each sample was measured over time using a rotary viscometer. Additional variables, including acidity, temperature, and the addition of human milk fortifier, were tested. RESULTS Formula can be effectively thickened with all tested thickeners, but the viscosities of thickened formula increase over time. On the other hand, DHM does not effectively thicken with SBT. Autoclaving DHM inactivates digestive enzymes, thus allowing SBT to successfully thicken autoclaved DHM. GBT effectively thickened both DHM and formula but reached higher viscosities than intended based on manufacturer recommendations. Adding acid to xanthan-gum thickened DHM resulted in phase separation and formation of solid precipitant. CONCLUSIONS Current thickening strategies of preterm infant feeding produces highly variable results in final feed viscosity. The unpredictable properties of gum-based thickeners raise questions about their safety profile. Objective measures of liquid viscosity and careful consideration of acidity and time are recommended for adequate comparisons of thickening regimens. Human milk continues to be the most challenging feed type to thicken.
背景:胃食管反流病(GERD)是新生儿的常见问题，目前增稠人乳的方式产生不一致的结果。本体外研究的目的是测量不同增稠策略的粘度效应。方法:采用多种增稠剂对供体母乳(DHM)和配方奶进行增稠:淀粉基增稠剂(SBT) (Thick It®，米粉)和胶基增稠剂(GBT)(黄原胶:simple Thick®，Thicken Up Clear®;角豆胶:GelMix®)。我们还评估了市场上用于反流的添加淀粉的配方，包括Similac Spit Up®(SSU)和Enfamil AR®(EAR)。使用旋转粘度计测量每个样品的粘度随时间的变化。测试了其他变量，包括酸度、温度和人乳强化剂的添加。结果所有增稠剂均能有效增稠配方，但增稠配方的粘度随时间增加而增加。另一方面，DHM不能有效增厚SBT。高压灭菌DHM使消化酶失活，从而使SBT成功地使高压灭菌DHM增稠。GBT有效地增稠了DHM和配方，但达到了比制造商建议的更高的粘度。在黄原胶中加入酸使DHM增稠，导致相分离和固体沉淀的形成。结论目前的增稠策略对早产儿的最终饲料粘度有很大的影响。胶基增稠剂不可预测的特性引起了人们对其安全性的质疑。对于增稠方案的充分比较，建议采用液体粘度的客观测量，并仔细考虑酸度和时间。人乳仍然是最具挑战性的增稠饲料类型。
{"title":"Through Thick and Thin: The In Vitro Effects of Thickeners On Infant Feed Viscosity.","authors":"Jenny Koo, Averyl Narvasa, L. Bode, J. H. Kim","doi":"10.1097/MPG.0000000000002470","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002470","url":null,"abstract":"BACKGROUND\u0000Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies.\u0000\u0000\u0000METHODS\u0000We thickened donor human milk (DHM) and formula using various thickeners: starch-based thickeners (SBT) (Thick It®, rice cereal), and gum-based thickeners (GBT) (xanthan gum: Simply Thick®, Thicken Up Clear®; carob gum: GelMix®). We also assessed formula with added starches marketed for reflux, including Similac Spit Up® (SSU) and Enfamil AR® (EAR). The viscosity of each sample was measured over time using a rotary viscometer. Additional variables, including acidity, temperature, and the addition of human milk fortifier, were tested.\u0000\u0000\u0000RESULTS\u0000Formula can be effectively thickened with all tested thickeners, but the viscosities of thickened formula increase over time. On the other hand, DHM does not effectively thicken with SBT. Autoclaving DHM inactivates digestive enzymes, thus allowing SBT to successfully thicken autoclaved DHM. GBT effectively thickened both DHM and formula but reached higher viscosities than intended based on manufacturer recommendations. Adding acid to xanthan-gum thickened DHM resulted in phase separation and formation of solid precipitant.\u0000\u0000\u0000CONCLUSIONS\u0000Current thickening strategies of preterm infant feeding produces highly variable results in final feed viscosity. The unpredictable properties of gum-based thickeners raise questions about their safety profile. Objective measures of liquid viscosity and careful consideration of acidity and time are recommended for adequate comparisons of thickening regimens. Human milk continues to be the most challenging feed type to thicken.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89655282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-20DOI: 10.1097/MPG.0000000000002465
Mary Shull, Tracy R. Ediger, I. Hill, R. L. Schroedl
OBJECTIVES Celiac disease (CD) is a common chronic condition with potential adverse physical and psychosocial implications for affected children. The study purpose was to characterize health-related quality of life (HRQOL) in a large sample of pediatric patients with newly diagnosed CD using the PedsQL™ 4.0 Generic Core Scales, and compare it to that of healthy children and children with non-celiac GI conditions using historic data. METHODS The PedsQL™ was administered to 159 children with newly diagnosed CD and their parents at either the time of diagnostic esophagogastroduodenoscopy or prior to their initial dietitian appointment for gluten-free diet teaching. Mean parent-report and self-report PedsQL™ summary and subscale scores were calculated, then compared to published means from a sample of healthy children and a sample of children with non-celiac GI symptoms using one-sample t-tests. RESULTS Compared to the healthy children, those with newly diagnosed CD had lower Total Scores, Physical Health, Psychosocial Health, Emotional Functioning, and School Functioning on parent-report (p < 0.008) with similar findings on self-report. Within the CD sample, clinically significant scores were found in 55.9% for School Functioning, 62.7% for Physical Health, 54.4% for Emotional Functioning, 43.7% for Social Functioning, and 49% for Total Score. CONCLUSIONS Children and adolescents with newly diagnosed CD had lower HRQOL than healthy children and similar HRQOL to that of patients with non-celiac GI conditions. Patients with deficits in domains such as school or emotional functioning may benefit from early interventions including a Section 504 plan or meeting with a psychologist or social worker.
{"title":"Health-related Quality of Life in Newly Diagnosed Pediatric Celiac Disease Patients.","authors":"Mary Shull, Tracy R. Ediger, I. Hill, R. L. Schroedl","doi":"10.1097/MPG.0000000000002465","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002465","url":null,"abstract":"OBJECTIVES\u0000Celiac disease (CD) is a common chronic condition with potential adverse physical and psychosocial implications for affected children. The study purpose was to characterize health-related quality of life (HRQOL) in a large sample of pediatric patients with newly diagnosed CD using the PedsQL™ 4.0 Generic Core Scales, and compare it to that of healthy children and children with non-celiac GI conditions using historic data.\u0000\u0000\u0000METHODS\u0000The PedsQL™ was administered to 159 children with newly diagnosed CD and their parents at either the time of diagnostic esophagogastroduodenoscopy or prior to their initial dietitian appointment for gluten-free diet teaching. Mean parent-report and self-report PedsQL™ summary and subscale scores were calculated, then compared to published means from a sample of healthy children and a sample of children with non-celiac GI symptoms using one-sample t-tests.\u0000\u0000\u0000RESULTS\u0000Compared to the healthy children, those with newly diagnosed CD had lower Total Scores, Physical Health, Psychosocial Health, Emotional Functioning, and School Functioning on parent-report (p < 0.008) with similar findings on self-report. Within the CD sample, clinically significant scores were found in 55.9% for School Functioning, 62.7% for Physical Health, 54.4% for Emotional Functioning, 43.7% for Social Functioning, and 49% for Total Score.\u0000\u0000\u0000CONCLUSIONS\u0000Children and adolescents with newly diagnosed CD had lower HRQOL than healthy children and similar HRQOL to that of patients with non-celiac GI conditions. Patients with deficits in domains such as school or emotional functioning may benefit from early interventions including a Section 504 plan or meeting with a psychologist or social worker.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80844794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-13DOI: 10.1097/MPG.0000000000002472
K. Penniston, Eve Palmer, Riley J Medenwald, Sarah Johnson, L. M. John, David J. Beshensky, I. Saeed
OBJECTIVES Patients requiring oral and/or enteral nutrition support, delivered via nasogastric, gastric, or intestinal routes, have a relatively high incidence of calcium oxalate (CaOx) kidney stones. Nutrition formulas are frequently made from corn and/or or soy, both of which contain ample oxalate. Excessive oxalate intake contributes to hyperoxaluria (>45 mg urine oxalate/d) and CaOx stones especially when 1) unopposed by concomitant calcium intake, 2) gastrointestinal malabsorption is present, and/or 3) oxalate degrading gut bacteria are limiting or absent. Our objective was to assess the oxalate content of commonly used commercial enteral nutrition formulas. METHODS Enteral nutrition formulas were selected from the formulary at our clinical inpatient institution. Multiple samples of each were assessed for oxalate concentration with ion chromatography. RESULTS Results from 26 formulas revealed highly variable oxalate concentration ranging from 4-140 mg oxalate/L of formula. No definitive patterns for different types of formulas (e.g., flavored vs. unflavored, high protein vs. not) were evident. CV for all formulas ranged from 0.68 to 43% (mean±SD 19 ± 12%; median 18%). CONCLUSIONS Depending on the formula and amount delivered, patients requiring nutrition support could obtain anywhere from 12-150 mg oxalate/d or more and are thus at risk for hyperoxaluria and CaOx stones.
{"title":"Oxalate Content of Enteral Nutrition Formulas.","authors":"K. Penniston, Eve Palmer, Riley J Medenwald, Sarah Johnson, L. M. John, David J. Beshensky, I. Saeed","doi":"10.1097/MPG.0000000000002472","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002472","url":null,"abstract":"OBJECTIVES\u0000Patients requiring oral and/or enteral nutrition support, delivered via nasogastric, gastric, or intestinal routes, have a relatively high incidence of calcium oxalate (CaOx) kidney stones. Nutrition formulas are frequently made from corn and/or or soy, both of which contain ample oxalate. Excessive oxalate intake contributes to hyperoxaluria (>45 mg urine oxalate/d) and CaOx stones especially when 1) unopposed by concomitant calcium intake, 2) gastrointestinal malabsorption is present, and/or 3) oxalate degrading gut bacteria are limiting or absent. Our objective was to assess the oxalate content of commonly used commercial enteral nutrition formulas.\u0000\u0000\u0000METHODS\u0000Enteral nutrition formulas were selected from the formulary at our clinical inpatient institution. Multiple samples of each were assessed for oxalate concentration with ion chromatography.\u0000\u0000\u0000RESULTS\u0000Results from 26 formulas revealed highly variable oxalate concentration ranging from 4-140 mg oxalate/L of formula. No definitive patterns for different types of formulas (e.g., flavored vs. unflavored, high protein vs. not) were evident. CV for all formulas ranged from 0.68 to 43% (mean±SD 19 ± 12%; median 18%).\u0000\u0000\u0000CONCLUSIONS\u0000Depending on the formula and amount delivered, patients requiring nutrition support could obtain anywhere from 12-150 mg oxalate/d or more and are thus at risk for hyperoxaluria and CaOx stones.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73990856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-13DOI: 10.1097/MPG.0000000000002474
Ahmed M El-Lekawy, D. Abdallah, H. El-Abhar
OBJECTIVES Alanyl-glutamine (AG) is a dipeptide that fuels enterocytes and has a co-adjuvant role during gut healing. The current study aimed to investigate the potential ulcer-healing effect of AG in indomethacin-induced gastropathy. METHODS Animals (n = 10 rats/group) were randomly allocated into 5 groups. Gastric ulcerated rats were administered AG, AG + dexamethasone (DEXA), or pantoprazole post indomethacin exposure. RESULTS Comparable to pantoprazole, AG inhibited H-KATPase pump and elevated the pH of gastric juice. Moreover, the dipeptide increased the serum/mucosal contents of GLP-1, pS473-Akt, and cyclin-D1. On the other hand, AG abated serum TNF-α and gastric mucosal content of pS45-β catenin, pS9-GSK3β, pS133-CREB, pS536-NF-κB, H2O2, claudin-1, and caspase-3. The administration of DEXA prior to AG hampered its effect on almost all the measured parameters. CONCLUSIONS AG confers its anti-ulcerogenic/anti-secretory potentials by repressing the proton pump to increase the gastric juice pH via boosting p-CREB, p-Akt, p-GSK-3β, and GLP-1. Also, it inhibits apoptosis through suppressing NF-κB/TNF-α/H2O2/claudin-1 cue. This trajectory contributes to loosen the tight junction priming AG-mediated GLP-1/β-catenin/cyclin-D1 that results in pronounced increase in gastric mucosa proliferation. Therefore, the crosstalk between multiple pathways orchestrates the action of AG against gastric ulceration.
{"title":"Alanyl-glutamine heals indomethacin induced gastric ulceration in rats via anti-secretory and anti-apoptotic mechanisms.","authors":"Ahmed M El-Lekawy, D. Abdallah, H. El-Abhar","doi":"10.1097/MPG.0000000000002474","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002474","url":null,"abstract":"OBJECTIVES\u0000Alanyl-glutamine (AG) is a dipeptide that fuels enterocytes and has a co-adjuvant role during gut healing. The current study aimed to investigate the potential ulcer-healing effect of AG in indomethacin-induced gastropathy.\u0000\u0000\u0000METHODS\u0000Animals (n = 10 rats/group) were randomly allocated into 5 groups. Gastric ulcerated rats were administered AG, AG + dexamethasone (DEXA), or pantoprazole post indomethacin exposure.\u0000\u0000\u0000RESULTS\u0000Comparable to pantoprazole, AG inhibited H-KATPase pump and elevated the pH of gastric juice. Moreover, the dipeptide increased the serum/mucosal contents of GLP-1, pS473-Akt, and cyclin-D1. On the other hand, AG abated serum TNF-α and gastric mucosal content of pS45-β catenin, pS9-GSK3β, pS133-CREB, pS536-NF-κB, H2O2, claudin-1, and caspase-3. The administration of DEXA prior to AG hampered its effect on almost all the measured parameters.\u0000\u0000\u0000CONCLUSIONS\u0000AG confers its anti-ulcerogenic/anti-secretory potentials by repressing the proton pump to increase the gastric juice pH via boosting p-CREB, p-Akt, p-GSK-3β, and GLP-1. Also, it inhibits apoptosis through suppressing NF-κB/TNF-α/H2O2/claudin-1 cue. This trajectory contributes to loosen the tight junction priming AG-mediated GLP-1/β-catenin/cyclin-D1 that results in pronounced increase in gastric mucosa proliferation. Therefore, the crosstalk between multiple pathways orchestrates the action of AG against gastric ulceration.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75095175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-06DOI: 10.1097/MPG.0000000000002461
S. Kansal, A. Catto-Smith, Karen Boniface, Sarah Thomas, D. Cameron, M. Oliver, G. Alex, C. Kirkwood, J. Wagner
OBJECTIVES Crohn's Disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. About 30-60% of CD patients have antibodies to Saccharomyces cerevisiae (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype. METHODS Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity and clinical characteristics. RESULTS ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease and long-term risk of surgery. Microbial alpha and beta diversity were similar in CD patients with or without ASCA, but significantly less when compared to non-IBD controls. Microbial richness was similar across all three groups. Fourteen bacterial species were associated with ASCA positive CD patients and 14 species with ASCA negative patients (p < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterolitica 61 remained significantly associated with CD ASCA positivity (p = 0.0178), while Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (p = 0.0178 and 0.0342). CONCLUSION ASCA positive and ASCA negative CD patients have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.
{"title":"Variation of Gut Mucosal Microbiome with ASCA Status in Pediatric Crohn's Disease.","authors":"S. Kansal, A. Catto-Smith, Karen Boniface, Sarah Thomas, D. Cameron, M. Oliver, G. Alex, C. Kirkwood, J. Wagner","doi":"10.1097/MPG.0000000000002461","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002461","url":null,"abstract":"OBJECTIVES\u0000Crohn's Disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. About 30-60% of CD patients have antibodies to Saccharomyces cerevisiae (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype.\u0000\u0000\u0000METHODS\u0000Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity and clinical characteristics.\u0000\u0000\u0000RESULTS\u0000ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease and long-term risk of surgery. Microbial alpha and beta diversity were similar in CD patients with or without ASCA, but significantly less when compared to non-IBD controls. Microbial richness was similar across all three groups. Fourteen bacterial species were associated with ASCA positive CD patients and 14 species with ASCA negative patients (p < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterolitica 61 remained significantly associated with CD ASCA positivity (p = 0.0178), while Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (p = 0.0178 and 0.0342).\u0000\u0000\u0000CONCLUSION\u0000ASCA positive and ASCA negative CD patients have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76197201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-22DOI: 10.1097/MPG.0000000000002450
K. Mysore, B. Shneider, S. Harpavat
Biliary atresia (BA) is the most common reason for pediatric liver transplant. BA's varied presentation, natural history, and treatment with the KP have been well described; however, when BA starts relative to birth has not been clearly defined. In this review, we discuss laboratory, imaging, and clinical data which suggest that most if not all forms of BA may start before birth. This early onset has implications in terms of delivering treatments earlier and identifying possible factors underlying BA's etiology.
{"title":"Biliary Atresia as a Disease Starting In Utero: Implications for Treatment, Diagnosis, and Pathogenesis.","authors":"K. Mysore, B. Shneider, S. Harpavat","doi":"10.1097/MPG.0000000000002450","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002450","url":null,"abstract":"Biliary atresia (BA) is the most common reason for pediatric liver transplant. BA's varied presentation, natural history, and treatment with the KP have been well described; however, when BA starts relative to birth has not been clearly defined. In this review, we discuss laboratory, imaging, and clinical data which suggest that most if not all forms of BA may start before birth. This early onset has implications in terms of delivering treatments earlier and identifying possible factors underlying BA's etiology.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88434839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-10DOI: 10.1097/MPG.0000000000002445
D. Ley, M. Bridenne, F. Gottrand, J. Lemale, B. Hauser, A. Lachaux, L. Rebouissoux, J. Viala, P. Fayoux, L. Michaud
OBJECTIVES Research on long-term use of mitomycin C (MC) for recurrent oesophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent oesophageal stenoses in children. METHODS This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4-196.0) at the time of MC application. The aetiologies of stenosis were oesophageal atresia (n = 25), caustic ingestion (n = 9), congenital oesophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child (range: 2-26)) over a median period of 7 months (range: 2.6-49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC. RESULTS For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years (range: 0.6-8.5)). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and oesophageal atresia type III. CONCLUSIONS This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent oesophageal stenosis in children.
{"title":"Efficacy and safety of the local application of mitomycin C to recurrent oesophageal strictures in children.","authors":"D. Ley, M. Bridenne, F. Gottrand, J. Lemale, B. Hauser, A. Lachaux, L. Rebouissoux, J. Viala, P. Fayoux, L. Michaud","doi":"10.1097/MPG.0000000000002445","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002445","url":null,"abstract":"OBJECTIVES\u0000Research on long-term use of mitomycin C (MC) for recurrent oesophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent oesophageal stenoses in children.\u0000\u0000\u0000METHODS\u0000This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4-196.0) at the time of MC application. The aetiologies of stenosis were oesophageal atresia (n = 25), caustic ingestion (n = 9), congenital oesophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child (range: 2-26)) over a median period of 7 months (range: 2.6-49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC.\u0000\u0000\u0000RESULTS\u0000For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years (range: 0.6-8.5)). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and oesophageal atresia type III.\u0000\u0000\u0000CONCLUSIONS\u0000This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent oesophageal stenosis in children.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79010703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-10DOI: 10.1097/MPG.0000000000002435
Emma Kortekangas, Rebecca T. Young, Y. Cheung, Yue-Mei Fan, J. Jorgensen, A. Kamng’ona, D. Chaima, U. Ashorn, K. Dewey, K. Maleta, P. Ashorn
OBJECTIVES The determinants of gut microbiota composition and its effects on common childhood illnesses are only partly understood, especially in low-income settings. The aim of the present study was to investigate whether morbidity predicts gut microbiota composition in Malawian children and whether microbiota predicts subsequent morbidity. We tested the hypothesis that common infectious disease symptoms would be predictive of lower microbiota maturity and diversity. METHODS We used data from 631 participants in a randomized-controlled nutrition intervention trial, in which a small-quantity lipid-based nutrient supplement was provided to pregnant and lactating mothers and their children at 6 to 18 months of age. Fecal samples were collected from the children at 6, 12, 18, and 30 months of age and analyzed using 16S rRNA sequencing. Microbiota variables consisted of measures of microbiota diversity (Shannon Index), microbiota maturity (microbiota-for-age z score), and the relative abundances of taxa. Morbidity variables included gastrointestinal and respiratory symptoms and fever. RESULTS Diarrhea and respiratory symptoms from 11 to 12 months were predictive of lower microbiota-for-age z score and higher Shannon Index, respectively (P = 0.035 and P = 0.023). Morbidity preceding sample collection was predictive of the relative abundances of several bacterial taxa at all time points. Higher microbiota maturity and diversity at 6 months were predictive of a lower incidence rate of fever in the subsequent 6 months (P = 0.007 and P = 0.031). CONCLUSIONS Our findings generally do not support the hypothesis that morbidity prevalence predicts a subsequent decrease in gut microbiota maturity or diversity in rural Malawian children. Certain morbidity symptoms may be predictive of microbiota maturity and diversity and relative abundances of several bacterial taxa. Furthermore, microbiota diversity and maturity may be associated with the subsequent incidence of fever.
{"title":"A Prospective Study on Child Morbidity and Gut Microbiota in Rural Malawi.","authors":"Emma Kortekangas, Rebecca T. Young, Y. Cheung, Yue-Mei Fan, J. Jorgensen, A. Kamng’ona, D. Chaima, U. Ashorn, K. Dewey, K. Maleta, P. Ashorn","doi":"10.1097/MPG.0000000000002435","DOIUrl":"https://doi.org/10.1097/MPG.0000000000002435","url":null,"abstract":"OBJECTIVES\u0000The determinants of gut microbiota composition and its effects on common childhood illnesses are only partly understood, especially in low-income settings. The aim of the present study was to investigate whether morbidity predicts gut microbiota composition in Malawian children and whether microbiota predicts subsequent morbidity. We tested the hypothesis that common infectious disease symptoms would be predictive of lower microbiota maturity and diversity.\u0000\u0000\u0000METHODS\u0000We used data from 631 participants in a randomized-controlled nutrition intervention trial, in which a small-quantity lipid-based nutrient supplement was provided to pregnant and lactating mothers and their children at 6 to 18 months of age. Fecal samples were collected from the children at 6, 12, 18, and 30 months of age and analyzed using 16S rRNA sequencing. Microbiota variables consisted of measures of microbiota diversity (Shannon Index), microbiota maturity (microbiota-for-age z score), and the relative abundances of taxa. Morbidity variables included gastrointestinal and respiratory symptoms and fever.\u0000\u0000\u0000RESULTS\u0000Diarrhea and respiratory symptoms from 11 to 12 months were predictive of lower microbiota-for-age z score and higher Shannon Index, respectively (P = 0.035 and P = 0.023). Morbidity preceding sample collection was predictive of the relative abundances of several bacterial taxa at all time points. Higher microbiota maturity and diversity at 6 months were predictive of a lower incidence rate of fever in the subsequent 6 months (P = 0.007 and P = 0.031).\u0000\u0000\u0000CONCLUSIONS\u0000Our findings generally do not support the hypothesis that morbidity prevalence predicts a subsequent decrease in gut microbiota maturity or diversity in rural Malawian children. Certain morbidity symptoms may be predictive of microbiota maturity and diversity and relative abundances of several bacterial taxa. Furthermore, microbiota diversity and maturity may be associated with the subsequent incidence of fever.","PeriodicalId":16725,"journal":{"name":"Journal of Pediatric Gastroenterology & Nutrition","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76527051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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