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1. Current Guidelines and Future Strategies for the Management of Cow’s Milk Allergy

Author

Vandenplas Y, Brough HA, Fiocchi A, Miqdady M, Munasir Z, Salvatore S, Thapar N, Venter C, Vieira MC, and Meier R

Subjects
amino acid formula, challenge test, cow milk allergy, hydrolysate, plant-based drink, rice hydrolysate, soy formula, Immunologic diseases. Allergy, RC581-607
Abstract

Yvan Vandenplas,1 Helen A Brough,2– 4 Alessandro Fiocchi,5 Mohamad Miqdady,6 Zakiudin Munasir,7 Silvia Salvatore,8 Nikhil Thapar,9 Carina Venter,10 Mario C Vieira,11 Rosan Meier12,13 1Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium; 2Department Women and Children’s Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Children’s Allergy Service, Evelina Children’s Hospital, Guy’s and St. Thomas’s NHS Foundation Trust, London, UK; 5Translational Research in Pediatric Specialities Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, Rome, Italy; 6Department of Pediatrics, Sheikh Khalifa Medical City, College of Medicine & Health Sciences, Khalifa University, Khalifa, United Arab Emirates; 7Department of Child Health, Ciptomangunkusumo Hospital-Medical Faculty Universitas Indonesia, Jakarta, Indonesia; 8Pediatric Department, Hospital “F. Del Ponte”, University of Insubria, Varese, Italy; 9Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland, Australia; 10University of Colorado, Children’s Hospital Colorado, Denver, CO, USA; 11Center for Pediatric Gastroenterology -Hospital Pequeno Príncipe, Curitiba, Brazil; 12Department of Paediatrics, Imperial College, London, UK; 13Department Nutrition and Dietetics, University of Winchester, Winchester, UKCorrespondence: Yvan VandenplasVrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, BelgiumEmail Yvan.vandenplas@uzbrussel.beAbstract: Exclusive breast feeding is recommended in all guidelines as the first choice feeding. Cow milk allergy (CMA) can be diagnosed by a diagnostic elimination diet for 2 to 4 weeks with a hypo-allergenic formula, followed by a challenge test with intact cow milk protein. The most often used hypo-allergenic formula for the diagnostic elimination diet and the therapeutic diet is a CM based extensive hydrolysate. CM-based partial hydrolysates cannot be recommended in the management of CMA because of insufficient efficacy and possible reactions, but about half of the infants with CMA may tolerate a partial hydrolysate. The pros and cons of other dietary options are discussed in this paper. The use of an amino acid-based formula and/or rice based hydrolysate formula during the diagnostic elimination and therapeutic diet is debated. When available, there is sufficient evidence to consider rice hydrolysates as an adequate alternative to CM-based hydrolysates, since some infants will still react to the CM hydrolysate. The pros and cons of dietary options such as soy formula, buckwheat, almond, pea or other plant based dietary products are discussed. Although the majority of the plant-based beverages are nutritionally inadequate, some are nutritionally adapted for toddlers. However, accessibility and content vary by country and, thus far there is insufficient evidence on the efficacy and tolerance of these plant-based drinks (except for soy formula and rice hydrolysates) to provide an opinion on them.Conclusion: A diagnostic elimination diet, followed by a challenge remains the diagnostic standard. The use of an awareness tool may result in a decrease of delayed diagnosis. Breastmilk remains the ideal source of nutrition and when not available a CM extensively hydrolyzed formula, rice hydrolysate or amino acid formula should be recommended. More evidence is needed regarding plant-based drinks.Keywords: amino acid formula, challenge test, cow milk allergy, hydrolysate, plant-based drink, rice hydrolysate, soy formula

Published
2021

2. Radiopaque marker colonic transit study in the pediatric population BSPGHAN Motility Working Group consensus statement.

Author

Papadopoulos, M., Mutalib, M., Nikaki, K., Volonaki, E., Rybak, A., Thapar, N., Lindley, K., Borrelli, O., Das, A., Crespi, D., Cleeve, S., and Athanasakos, E.

Subjects
CHILD patients, PEDIATRIC gastroenterology, CONSTIPATION, HEPATOLOGY, COLON (Anatomy)
Abstract

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
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5. Liquid-liquid dispersions from in-line rotor-stator mixers

Author

Thapar, N. and Brown, D. E.

Subjects
620.106
Abstract

Experiments were performed on an industrial scale Silverson in-line rotor-stator mixer to investigate its liquid-liquid dispersion capabilities. A non-coalescing kerosene-water system was used in the tests and the effect of stator geometry, rotor-speeds, flowrates and dispersed phase concentrations on the droplet size distribution was investigated. The rotor-speed and the dispersed phase concentration were found to have the most influence on droplet size. Drop sizes were also seen to increase with an increase in open area. No differences were observed in the droplet sizes or power draw of the stators with the smallest and similar open areas (Emulsor Screens and Square Hole High Shear screen). The power supplied to the fluid was proportional to N3 indicating the mixer was operating under turbulent conditions. d32 was correlated against the rotor speed and dispersed phase and the relationship was found to be close to that described by Chen and Middleman (1967). This analysis suggested that inertial stresses in the viscous sub-range were mainly responsible for drop break-up. d32 = 2x109 (1 + 20(D)(We Re4)-'" An estimation of the average energy dissipation rate was made in order to determine the Kolomogov length scale. The droplet sizes ranged from below the Kolmogorov length scale to significantly higher, suggesting that droplet break-up is due to inertial and viscous sub-range eddies. The Re could be defined in different regions within the mixer these values were used along with the nominal residence times in each region to determine where in the mixer the main drop break-up was occurring. The residence times for each region were in the following order: Shear Gap < Stator < Inlet < Rotor < Volute. The relatively long residence times and the magnitude of the stresses indicated that droplet break-up in a single pass through the in-line rotor-stator mixer is predominately determined by the viscous and inertial stresses in the rotor region.

Published
2004

6. Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (Nature Communications, (2020), 11, 1, (995), 10.1038/s41467-019-14275-y)

Author

Serra E. G., Schwerd T., Moutsianas L., Cavounidis A., Fachal L., Pandey S., Kammermeier J., Croft N. M., Posovszky C., Rodrigues A., Russell R. K., Barakat F., Auth M. K. H., Heuschkel R., Zilbauer M., Fyderek K., Braegger C., Travis S. P., Satsangi J., Parkes M., Thapar N., Ferry H., Matte J. C., Gilmour K. C., Wedrychowicz A., Sullivan P., Moore C., Sambrook J., Ouwehand W., Roberts D., Danesh J., Baeumler T. A., Fulga T. A., Carrami E. M., Ahmed A., Wilson R., Barrett J. C., Elkadri A., Griffiths A. M., Zurek M., Strisciuglio C., Elawad M., Lo B., Arancibia-Carcamo C., Bailey A., Barnes E., Bird-Lieberman E. L., Brain O., Braden B., Collier J., East J., Howarth L., Keshav S., Klenerman P., Leedham S., Palmer R., Powrie F., Simmons A., Walker M., Tolkien Z., Kaptoge S., Allen D., Mehenny S., Mant J., Di Angelantonio E., Thompson S. G., Yilmaz B., Juillerat P., Geuking M., Wiest R., Macpherson A. J., Bravo F. D., Brugger L., Carstens O., Bigler U. G., Heimgartner B., Rusticeanu M., Schmid-Uebelhart S., Strebel B., Tatu A., Tutuian R., Oyas O., Ramon C., Stelling J., Franc Y., Fournier N., Pittet V. E. H., Burnand B., Egger M., Golay D., Marot A., Musso L., Rossel J. -B., Seematter V., Sommer J., Vulliamy R., Michetti P., Maillard M. H., Keller C., Nydegger A., Schoepfe A., Archanioti E., Ezri J., Fraga M., Schoepfer A., Muller C., Rogler G., Biedermann L., Blattmann M., Burk S., Dora B., Fried M., Misselwitz B., Mullhaupt B., Obialo N., Pohl D., Raschle N., Scharl M., Vavricka S., Von Kanel R., Zeitz J., Abdelrahman K., Ademi G., Borovicka J., Brand S., Frei R., Haarer J., Knellwolf-Grieger C., Krieger-Grubel C., Kunzler P., Meyenberger C., Meyer P., Rohrich N., Sawatzki M., Schelling M., Semadeni G. -M., Sulz M., Zimmermann D., Aepli P., Criblez D. H., Hess C., Richterich J. -P., Spalinger J., Staudenmann D., Stulz A., Wohrle S., Thomas A., Anderegg C., Kohler H., Kusche R., Antonino A. -T., Arrigoni E., Bengoa J. M., Cunningham S., de Saussure P., Girard L., de Jong D. B., Basturk P., Brunner S., Degen L., Hruz P., Bakker C. K. -D., Niess J., Balsiger B., Haldemann J., Saner G., Seibold F., Bauerfeind P., Becocci A., Belli D., Binek J., Hengstler P., Boehm S., Boldanov T., Buhr P., Koller R., Rueger V., Senning A., Burri E., Buyse S., Cao D. -T., D'Angelo F., Delarive J., Doerig C., Hessler R., Preissler C., Rentsch R., Risti B., Ritz M. A., Steuerwald M., Vogtlin J., Sagmeister M., Sauter B., Schibli S., Sokollik C., Schlauri H., Schnegg J. -F., Seirafi M., Spangenberger H., Stadler P., Staub P., Stenz V., Tempia-Caliera M., Thorens J., Truninger K., Urfer P., Viani F., Vouillamoz D., Zander S., Wyli T., Jostins L., Kennedy N. A., Ahmad T., Lamb C. A., Edwards C., Hart A., Hawkey C., Mansfield J. C., Mowat C., Newman W. G., Tremelling M., Lee J. C., Prescott N. J., Mathew C. G., Lees C. W., McGovern D. P. B., Targan S. R., Botwin G., Mengesha E., Fleshner P., Landers C., Li D., Rioux J. D., Bitton A., Cote-Daigneault J., Daly M. J., Xavier R., Morris K., Boucher G., Cho J. H., Abraham C., Merad M., Sands B., Peter I., Hao K., Itan Y., Duerr R. H., Konnikova L., Schwartz M. B., Proksell S., Johnston E., Miladinova V., Chen W., Brant S. R., Datta L., Silverberg M. S., Schumm L. P., Birch S., Giri M., Gettler K., Sharma Y., Stevens C., Lazarev M., Haritunians T., Snapper S. B., Shah N., Muise A. M., Wilson D. C., Uhlig H. H., Anderson C. A., Serra, E. G., Schwerd, T., Moutsianas, L., Cavounidis, A., Fachal, L., Pandey, S., Kammermeier, J., Croft, N. M., Posovszky, C., Rodrigues, A., Russell, R. K., Barakat, F., Auth, M. K. H., Heuschkel, R., Zilbauer, M., Fyderek, K., Braegger, C., Travis, S. P., Satsangi, J., Parkes, M., Thapar, N., Ferry, H., Matte, J. C., Gilmour, K. C., Wedrychowicz, A., Sullivan, P., Moore, C., Sambrook, J., Ouwehand, W., Roberts, D., Danesh, J., Baeumler, T. A., Fulga, T. A., Carrami, E. M., Ahmed, A., Wilson, R., Barrett, J. C., Elkadri, A., Griffiths, A. M., Zurek, M., Strisciuglio, C., Elawad, M., Lo, B., Arancibia-Carcamo, C., Bailey, A., Barnes, E., Bird-Lieberman, E. L., Brain, O., Braden, B., Collier, J., East, J., Howarth, L., Keshav, S., Klenerman, P., Leedham, S., Palmer, R., Powrie, F., Simmons, A., Walker, M., Tolkien, Z., Kaptoge, S., Allen, D., Mehenny, S., Mant, J., Di Angelantonio, E., Thompson, S. G., Yilmaz, B., Juillerat, P., Geuking, M., Wiest, R., Macpherson, A. J., Bravo, F. D., Brugger, L., Carstens, O., Bigler, U. G., Heimgartner, B., Rusticeanu, M., Schmid-Uebelhart, S., Strebel, B., Tatu, A., Tutuian, R., Oyas, O., Ramon, C., Stelling, J., Franc, Y., Fournier, N., Pittet, V. E. H., Burnand, B., Egger, M., Golay, D., Marot, A., Musso, L., Rossel, J. -B., Seematter, V., Sommer, J., Vulliamy, R., Michetti, P., Maillard, M. H., Keller, C., Nydegger, A., Schoepfe, A., Archanioti, E., Ezri, J., Fraga, M., Schoepfer, A., Muller, C., Rogler, G., Biedermann, L., Blattmann, M., Burk, S., Dora, B., Fried, M., Misselwitz, B., Mullhaupt, B., Obialo, N., Pohl, D., Raschle, N., Scharl, M., Vavricka, S., Von Kanel, R., Zeitz, J., Abdelrahman, K., Ademi, G., Borovicka, J., Brand, S., Frei, R., Haarer, J., Knellwolf-Grieger, C., Krieger-Grubel, C., Kunzler, P., Meyenberger, C., Meyer, P., Rohrich, N., Sawatzki, M., Schelling, M., Semadeni, G. -M., Sulz, M., Zimmermann, D., Aepli, P., Criblez, D. H., Hess, C., Richterich, J. -P., Spalinger, J., Staudenmann, D., Stulz, A., Wohrle, S., Thomas, A., Anderegg, C., Kohler, H., Kusche, R., Antonino, A. -T., Arrigoni, E., Bengoa, J. M., Cunningham, S., de Saussure, P., Girard, L., de Jong, D. B., Basturk, P., Brunner, S., Degen, L., Hruz, P., Bakker, C. K. -D., Niess, J., Balsiger, B., Haldemann, J., Saner, G., Seibold, F., Bauerfeind, P., Becocci, A., Belli, D., Binek, J., Hengstler, P., Boehm, S., Boldanov, T., Buhr, P., Koller, R., Rueger, V., Senning, A., Burri, E., Buyse, S., Cao, D. -T., D'Angelo, F., Delarive, J., Doerig, C., Hessler, R., Preissler, C., Rentsch, R., Risti, B., Ritz, M. A., Steuerwald, M., Vogtlin, J., Sagmeister, M., Sauter, B., Schibli, S., Sokollik, C., Schlauri, H., Schnegg, J. -F., Seirafi, M., Spangenberger, H., Stadler, P., Staub, P., Stenz, V., Tempia-Caliera, M., Thorens, J., Truninger, K., Urfer, P., Viani, F., Vouillamoz, D., Zander, S., Wyli, T., Jostins, L., Kennedy, N. A., Ahmad, T., Lamb, C. A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Tremelling, M., Lee, J. C., Prescott, N. J., Mathew, C. G., Lees, C. W., Mcgovern, D. P. B., Targan, S. R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J. D., Bitton, A., Cote-Daigneault, J., Daly, M. J., Xavier, R., Morris, K., Boucher, G., Cho, J. H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R. H., Konnikova, L., Schwartz, M. B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S. R., Datta, L., Silverberg, M. S., Schumm, L. P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., Haritunians, T., Snapper, S. B., Shah, N., Muise, A. M., Wilson, D. C., Uhlig, H. H., and Anderson, C. A.

Published
2022

9. Drugs in Focus: Proton Pump Inhibitors

Author

Orel, R. Benninga, M.A. Broekaert, I.J. Gottrand, F. Papadopoulou, A. Ribes-Koninckx, C. Thomson, M. Wilschanski, M. Thapar, N.

Abstract

Proton pump inhibitors (PPIs) are amongst the most commonly prescribed drugs in infants and children with the last decades witnessing a dramatic rise in their utilization. Although PPIs are clearly effective when used appropriately and have been regarded as safe drugs, there is growing evidence regarding their potential adverse effects. Although, largely based on adult data it is clear that many of these are also relevant to pediatrics. PPI use potentially affects gastrointestinal microbiota composition and function, decreases defence against pathogens resulting in increased risk for infections, interferes with absorption of minerals and vitamins leading to specific deficiencies and increased risk for bone fractures as well as interferes with protein digestion resulting in increased risk of sensitization to allergens and development of allergic diseases and eosinophilic esophagitis. An association with gastric, liver and pancreatic cancer has also been inferred from adult data but is tenuous and causation is not proven. Overall, evidence for these adverse events is patchy and not always compelling. Overall, the use of PPIs, for selected indications with a good evidence base, has significant potential benefit but carries more caution in infants and children. Pediatricians should be aware of the concerns regarding the potential adverse events associated with their use. Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Published
2021

10. Systematic review and meta-analysis: the incidence and prevalence of paediatric coeliac disease across Europe

Author

Roberts, SE, Morrison-Rees, S, Thapar, N, Benninga, MA, Borrelli, O, Broekaert, I, Dolinsek, J, Martín-de-Carpi J, Mas, E, Miele, E, Pienar, C, Ribes-Koninckx, C, Thomassen, RA, Thomson, M, Tzivinikos, C, Thorne, K, John, A, and Williams, JG

Abstract

Background Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. Aim To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. Methods Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. Results The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages Paediatric coeliac disease incidence and prevalence have risen across Europe and appear highest in Scandinavia, Finland and Spain. The most recent evidence shows large increases in incidence in most regions, but stabilisation in some (notably Sweden and Finland). Sharp increases in the age at diagnosis may reflect increases in milder and asymptomatic cases diagnosed since reliable serology testing became widely used, through endomysial antibodies after 1990 and tissue transglutaminase antibodies around 2000.

Published
2021

11. The Use of Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee

Author

Koninckx CR, Donat E, Benninga MA, Broekaert IJ, Gottrand F, Kolho KL, Lionetti P, Miele E, Orel R, Papadopoulou A, Pienar C, Schäppi MG, Wilschanski M, and Thapar N

Subjects
fluids and secretions, inflammation, inflammatory bowel disease, Crohn disease, intestine, fecal calprotectin, position paper, ulcerative colitis
Abstract

The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children.

Published
2021

12. Management of Gastrointestinal and Nutritional Problems in Children With Neurological Impairment: A Survey of Practice

Author

Romano, C. Dipasquale, V. Van Winckel, M. Hulst, J. Broekaert, I. Bronsky, J. Dall'Oglio, L. Mis, N.F. Hojsak, I. Orel, R. Papadopoulou, A. Schaeppi, M. Thapar, N. Wilschanski, M. Sullivan, P. Gottrand, F.

Abstract

OBJECTIVES: The main aim of this study was to determine the impact on clinical practice of the first European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper on the diagnosis and management of nutritional and gastrointestinal problems in children with neurological impairment (NI). METHODS: In this pilot-study, a web-based questionnaire was distributed between November, 2019 and June, 2020, amongst ESPGHAN members using the ESPGHAN newsletter. Fifteen questions covered the most relevant aspects on nutritional management and gastrointestinal issues of children with NI. A descriptive analysis of responses was performed. RESULTS: A total of 150 health professionals from 23 countries responded to the survey. A considerable variation in clinical practice concerning many aspects of nutritional and gastrointestinal management of children with NI was observed. The most frequently used method for diagnosing oropharyngeal dysfunction was the direct observation of meals with or without the use of standardised scores (n = 103). Anthropometric measurements were the most commonly used tools for assessing nutritional status (n = 111). The best treatment for gastroesophageal reflux disease (GERD) was considered to be proton pump inhibitor therapy by most (n = 116) participants. Regarding tube feeding, nearly all respondents (n = 114) agreed that gastrostomy is the best enteral access to be used for long-term enteral feeding. Fundoplication was indicated at the time of gastrostomy placement especially in case of uncontrolled GERD. CONCLUSIONS: More studies are required to address open questions on adequate management of children with NI. Identifying knowledge gaps paves the way for developing updated recommendations and improving patient care. Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Published
2021

16. Drugs in Focus: The Use of Racecadotril in Paediatric Gastrointestinal Disease

Author

Pienar C, Benninga MA, Broekaert IJ, Dolinsek J, Mas E, Miele E, Orel R, Ribes-Koninckx C, Thomassen RA, Thomson M, Tzivinikos C, and Thapar N

Subjects
racecadotril, adjuvant, digestive, oral, and skin physiology, gastroenteritis
Abstract

Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant anti-diarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant anti-diarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.

Published
2020

23. A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe

Author

Roberts, S E, primary, Thorne, K, additional, Thapar, N, additional, Broekaert, I, additional, Benninga, M A, additional, Dolinsek, J, additional, Mas, E, additional, Miele, E, additional, Orel, R, additional, Pienar, C, additional, Ribes-Koninckx, C, additional, Thomson, M, additional, Tzivinikos, C, additional, Morrison-Rees, S, additional, John, A, additional, and Williams, J G, additional

Published
2020
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25. White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies

Author

Burns, A.J., Goldstein, A.M., Newgreen, D.F., Stamp, L., Schäfer, K.H., Metzger, M., Hotta, R., Young, H.M., Andrews, P.W., Thapar, N., Belkind-Gerson, J., Bondurand, N., Bornstein, J.C., Chan, W.Y., Cheah, K., Gershon, M.D., Heuckeroth, R.O., Hofstra, R.M., Just, L., Kapur, R.P., King, S.K., McCann, C.J., Nagy, N., Ngan, E., Obermayr, F., Pachnis, V., Pasricha, P.J., Sham, M.H., Tam, P., Berghe, P.V., Publica, Surgery, and Clinical Genetics

Subjects
Hirschsprung disease, cell replacement therapy, Intestinal Pseudo-Obstruction, Cell- and Tissue-Based Therapy, Guidelines as Topic, Cell Biology, Article, Gastrointestinal Tract, Disease Models, Animal, enteric nervous system, Neural Stem Cells, stem cells, ddc:570, Animals, Humans, ddc:610, enteric neuropathies, Molecular Biology, Stem Cell Transplantation, Developmental Biology
Abstract

Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts’ views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.

Published
2016
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28. The use of jejunal tube feeding in children: A position paper by the gastroenterology and nutrition committees of the European Society for paediatric Gastroenterology, hepatology, and nutrition 2019

Author

Broekaert, I.J. Falconer, J. Bronsky, J. Gottrand, F. Dall'Oglio, L. Goto, E. Hojsak, I. Hulst, J. Kochavi, B. Papadopoulou, A. Ribes-Koninckx, C. Schaeppi, M. Werlin, S. Wilschanski, M. Thapar, N.

Abstract

Objectives: Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety. Methods: A group of members of the Gastroenterology and Nutrition Committees of the European Society of Paediatric Gastroenterology Hepatology and Nutrition and of invited experts in the field was formed in September 2016 to produce this clinical guide. Seventeen clinical questions treating indications and contraindications, investigations before placement, techniques of placement, suitable feeds and feeding regimen, weaning from JTF, complications, long-term care, and ethical considerations were addressed. A systematic literature search was performed from 1982 to November 2018 using PubMed, the MEDLINE, and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalized. In the absence of evidence from randomized controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 33 recommendations were voted on using the nominal voting technique. Conclusions: JTF is a safe and effective means of enteral feeding when gastric feeding is insufficient to meet caloric needs or is not possible. The decision to place a jejunal tube has to be made by close cooperation of a multidisciplinary team providing active follow-up and care. © ESPGHAN and NASPGHAN. All rights reserved.

Published
2019

29. The Use of Jejunal Tube Feeding in Children: A Position Paper by the Gastroenterology and Nutrition Committees of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition 2019

Author

Broekaert IJ, Falconer J, Bronsky J, Gottrand F, Dall'Oglio L, Goto E, Hojsak I, Hulst J, Kochavi B, Papadopoulou A, Ribes-Koninckx C, Schaeppi M, Werlin S, Wilschanski M, and Thapar N

Subjects
children, recommendations, jejunal tube, multidisciplinary team, clinical guide, feeding
Abstract

Jejunal tube feeding (JTF) is increasingly becoming the standard of care for children in whom gastric tube feeding is insufficient to achieve caloric needs. Given a lack of a systematic approach to the care of JTF in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimize its utility and safety.

Published
2019

31. Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitor

Author

Urbani L, Camilli C, Phylactopoulos DE, Crowley C, Natarajan D, Scottoni F, Maghsoudlou P, McCann CJ, Pellegata AF, Urciuolo A, Aruta S, Signorelli MC, Kiely D, Hannon E, Deguchi K, Trevisan M, Wong R, Baradez MO, Moulding D, Khalaf S, Virasami A, Gjinovci A, Loukogeorgakis S, Mantero S, Thapar N, Sebire N, Eaton S, Lowdell M, Cossu G, Bonfanti P* and De Coppi P

Published
2018
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32. Chapter 5.3.2. Some Things Have Moved in the World of Motility

Author

Benninga, M., Annamaria Staiano, Milla, P., Thapar, N., Paediatric Gastroenterology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Amsterdam Reproduction & Development (AR&D), and Pediatric surgery

Published
2018

37. A new role for the Ret receptor tyrosine kinase in intestinal epithelia

Author

Perea, D, Guiu, J, Hudry, B, Konstantinidou, C, Milona, A, Hadjieconomou, D, Carroll, T, Hoyer, N, Natarajan, D, Kallijärvi, J, Walker, JA, Soba, P, Thapar, N, Burns, AJ, Jensen, KB, Miguel-Aliaga, I, Commission of the European Communities, and Wellcome Trust

Subjects
08 Information And Computing Sciences, 11 Medical And Health Sciences, 06 Biological Sciences, Developmental Biology
Published
2017

38. Role of Polyethylene Glycol in the Treatment of Functional Constipation in Children

Author

Koppen, I.J.N. Broekaert, I.J. Wilschanski, M. Papadopoulou, A. Ribes-Koninckx, C. Thapar, N. Gottrand, F. Orel, R. Lionetti, P. Benninga, M.A.

Subjects
technology, industry, and agriculture
Abstract

According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered. © 2017 ESPGHAN and NASPGHAN. All rights reserved.

Published
2017

41. European Society for Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children with Neurological Impairment

Author

Romano, C. Van Wynckel, M. Hulst, J. Broekaert, I. Bronsky, J. Dall'Oglio, L. Mis, N.F. Hojsak, I. Orel, R. Papadopoulou, A. Schaeppi, M. Thapar, N. Wilschanski, M. Sullivan, P. Gottrand, F.

Abstract

Objectives: Feeding difficulties are frequent in children with neurological impairments and can be associated with undernutrition, growth failure, micronutrients deficiencies, osteopenia, and nutritional comorbidities. Gastrointestinal problems including gastroesophageal reflux disease, constipation, and dysphagia are also frequent in this population and affect quality of life and nutritional status. There is currently a lack of a systematic approach to the care of these patients. With this report, European Society of Gastroenterology, Hepatology and Nutrition aims to develop uniform guidelines for the management of the gastroenterological and nutritional problems in children with neurological impairment. Methods: Thirty-one clinical questions addressing the diagnosis, treatment, and prognosis of common gastrointestinal and nutritional problems in neurological impaired children were formulated. Questions aimed to assess the nutritional management including nutritional status, identifying undernutrition, monitoring nutritional status, and defining nutritional requirements; to classify gastrointestinal issues including oropharyngeal dysfunctions, motor and sensory function, gastroesophageal reflux disease, and constipation; to evaluate the indications for nutritional rehabilitation including enteral feeding and percutaneous gastrostomy/jejunostomy; to define indications for surgical interventions (eg, Nissen Fundoplication, esophagogastric disconnection); and finally to consider ethical issues related to digestive and nutritional problems in the severely neurologically impaired children. A systematic literature search was performed from 1980 to October 2015 using MEDLINE. The approach of the Grading of Recommendations Assessment, Development, and Evaluation was applied to evaluate the outcomes. During 2 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation using the nominal voting technique. Expert opinion was applied to support the recommendations where no randomized controlled trials were available. Copyright © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Published
2017

45. EPI-506 (ralaniten acetate), a novel androgen receptor (AR) N-terminal domain (NTD) inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC): Phase 1 update on safety, tolerability, pharmacokinetics and efficacy

Author

Vaishampayan, U., primary, Montgomery, R.B., additional, Gordon, M.S., additional, Smith, D.C., additional, Barber, K., additional, de Haas-Amatsaleh, A., additional, Thapar, N., additional, Chandhasin, C., additional, Perabo, F., additional, and Chi, K.N., additional

Published
2017
Full Text
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46. In vivo transplantation of fetal human gut‐derived enteric neural crest cells

Author

Cooper, J. E., Natarajan, D., McCann, C. J., Choudhury, S., Godwin, H., Burns, A. J., and Thapar, N.

Subjects
neural crest cells, Mice, Knockout, Hot Topic, human enteric neural stem cells, Enteric Nervous System, Intestines, Mice, Neural Stem Cells, Neural Crest, Animals, Humans, cell transplantation, enteric neuropathies, Cells, Cultured, Embryonic Stem Cells, Stem Cell Transplantation
Abstract

The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75NTR were lentivirally labeled with either GFP or calcium‐sensitive GCaMP and transplanted into the hindgut of Rag2 − /γc − /C5 −‐immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut‐derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections.

Published
2016

47. Functional gastro-intestinal disorder algorithms focus on early recognition, parental reassurance and nutritional strategies

Author

Vandenplas, Y. Benninga, M. Broekaert, I. Falconer, J. Gottrand, F. Guarino, A. Lifschitz, C. Lionetti, P. Orel, R. Papadopoulou, A. Ribes-Koninckx, C. Ruemmele, F.M. Salvatore, S. Shamir, R. Schäppi, M. Staiano, A. Szajewska, H. Thapar, N. Wilschanski, M.

Abstract

Up to 50% of infants present with symptoms of regurgitation, infantile colic and/or constipation during the first 12 months of life. Although they are often classed as functional disorders, there is an overlap with cows' milk allergy. We present practical algorithms for the management of such disorders, based on existing evidence and general consensus, with a particular focus on primary health care. Management consists of early recognition of warning signs of organic disease, parental reassurance and nutritional strategies. Conclusion The proposed algorithms aim to help healthcare providers manage frequent gastrointestinal and cows' milk-related symptoms in infants safely and effectively. ©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd.

Published
2016

48. An international consensus report on a new algorithm for the management of infant diarrhoea

Author

Lo Vecchio, A. Vandenplas, Y. Benninga, M. Broekaert, I. Falconer, J. Gottrand, F. Lifschitz, C. Lionetti, P. Orel, R. Papadopoulou, A. Ribes-Koninckx, C. Salvatore, S. Shamir, R. Schäppi, M. Staiano, A. Szajewska, H. Thapar, N. Wilschanski, M. Guarino, A.

Abstract

Aim: Implementing international guidelines guarantees high standards of clinical care. A group of experts developed an algorithm to drive the management of common gastrointestinal symptoms in infancy by paediatricians and general practitioners. Methods: The algorithm started from the evidence-based recommendations of the European Society of Gastroenterology, Hepatology and Nutrition and the European Society of Pediatric Infectious Diseases and an updated review of the literature. We used the structured quantitative method of nominal group technique to reach a consensus. Results: A practical algorithm for the management of infants with acute diarrhoea was designed based on the consensus reached for each statement. The management of an infant with acute diarrhoea should include a sequence of actions: (i) a semiquantitative estimate of infant dehydration through validated clinical scores, (ii) rehydration therapy and early refeeding with breast milk or regular formula and (iii) effective agents to reduce the severity and duration of the diarrhoea. Finally, in children with prolonged diarrhoea, the search for aetiology should include persistent infections or reinfections, cows' milk protein allergy and coeliac diseases. Lactose should always be withdrawn. Conclusion: This algorithm provides an evidence-based sequence of interventions to optimise the management of infants with acute diarrhoea. ©2016 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd

Published
2016

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