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2. 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

5. The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation

Author

Tcymbarevich I, Eloranta J, Spalinger M, Cosin-Roger J, Lang S, Kullak-Ublick G, Wagner C, Seuwen K, Ruiz P, de Valliere C, Abdelrahman K, Ademi G, Aepli P, Thomas A, Anderegg C, Antonino A, Archanioti E, Arrigoni E, de Jong D, Balsiger B, Basturk P, Bauerfeind P, Becocci A, Belli D, Bengoa J, Biedermann L, Binek J, Blattmann M, Boehm S, Boldanova T, Borovicka J, Braegger C, Brand S, Brugger L, Brunner S, Buhr P, Burnand B, Burk S, Burri E, Buyse S, Cao D, Carstens O, Criblez D, Cunningham S, D'Angelo F, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Drerup S, Egger M, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Franc Y, Frei P, Frei R, Fried M, Froehlich F, Furlano R, Garzoni L, Geyer M, Girard L, Girardin M, Golay D, Good I, Bigler U, Gysi B, Haarer J, Halama M, Haldemann J, Heer P, Heimgartner B, Helbling B, Hengstler P, Herzog D, Hess C, Hessler R, Heyland K, Hinterleitner T, Hirschi C, Hruz P, Juillerat P, Khalid-de Bakker C, Kayser S, Keller C, Knellwolf-Grieger C, Knoblauch C, Kohler H, Koller R, Krieger-Grubel C, Kunzler P, Kusche R, Lehmann F, Macpherson A, Maillard M, Manz M, Marot A, Meier R, Meyenberger C, Meyer P, Michetti P, Misselwitz B, Mosler P, Mottet C, Muller C, Mullhaupt B, Musso L, Neagu M, Nichita C, Niess J, Nydegger A, Obialo N, Ollo D, Oropesa C, Peter U, Peternac D, Petit L, Pittet V, Pohl D, Porzner M, Preissler C, Raschle N, Rentsch R, Restellini A, Restellini S, Richterich J, Ris F, Risti B, Ritz M, Rogler G, Rohrich N, Rossel J, Rueger V, Rusticeanu M, Sagmeister M, Saner G, Sauter B, Sawatzki M, Scharl M, Schelling M, Schibli S, Schlauri H, Schluckebier D, Schmid D, Schmid-Uebelhart S, Schnegg J, Schoepfer A, Seematter V, Seibold F, Seirafi M, Semadeni G, Senning A, Sokollik C, Sommer J, Spalinger J, Spangenberger H, Stadler P, Staub P, Staudenmann D, Stenz V, Steuerwald M, Straumann A, Strebel B, Stulz A, Sulz M, Tatu A, Tempia-Caliera M, Thorens J, Truninger K, Tutuian R, Urfer P, Vavricka S, Viani F, Vogtlin J, Von Kanel R, Vouillamoz D, Vulliamy R, Wiesel P, Wiest R, Wohrle S, Zamora S, Zander S, Wylie T, Zeitz J, Zimmermann D, and Swiss IBD Cohort Study Grp

Subjects
UC, pH-sensing, cAMP, IBD, Acidic pH, RhoA, Inflammatory bowel diseases, CD
Abstract

BackgroundTissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161.Methods1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured.ResultsIn our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele.ConclusionsThe T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift.

Published
2019

7. Necrotising Fasciitis: Restitutio ad integrum after early diagnosis, aggressive surgical treatment and vacuum therapy

Author

Zundel, S, Lemaréchal, A, Spalinger, J, and Szavay, P

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Necrotising fasciitis is a severe, life-threatening infectious condition. Bacterial invasion of the subcutaneous tissues with subsequent release of endotoxins and exotoxins causes tissue ischemia and liquefactive necrosis. Subsequent systemic inflammation is common, morbidity and mortality[for full text, please go to the a.m. URL], 133. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2016
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10. Empfehlungen zu Prä- und Probiotika in Säuglingsanfangsnahrungen

Author

Böhles, H, Fusch, C, Genzel-Boroviczény, O, Henker, J, Kersting, M, Koletzko, B, Lentze, M, Maaser, R, Mihatsch, W, Przyrembel, H, Wabitsch, M, Deutsch, J, Haiden, N, Hauer, A, Pietschnig, B, Pollak, A N, Rock, I, Scholl-Bürgi, S, Skladal, D, Sperl, W, Widhalm, K, Zwiauer, K, Baehler, P, Baenziger, O, Belli, D, Braegger, C, Délèze, G, Furlano, R, Laimbacher, J, Spalinger, J, Studer, P, University of Zurich, and Koletzko, B

Subjects
10036 Medical Clinic, 610 Medicine & health, 2735 Pediatrics, Perinatology and Child Health, 2746 Surgery
Published
2009
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13. Commission de nutrition

Author

Braegger, C, Baehler, P, Baenziger, O, Belli, D, Délèze, G, Furlano, R, Laimbacher, J, Roulet, M, Spalinger, J, Studer, P, and University of Zurich

Subjects
10036 Medical Clinic, 610 Medicine & health
Published
2009

14. Empfehlungen zum Verzehr zuckerhaltiger Getränke durch Kinder und Jugendliche : Ernährungskommission der Deutschen Gesellschaft für Kinder- und Jugendmedizin (DGKJ); Ernährungskommission der Österreichischen Gesellschaft für Kinder- und Jugendheilkunde (ÖGKJ); Ernährungskommission der Schweizerischen Gesellschaft für Pädiatrie (SGP)

Author

Böhles, H, Fusch, C, Genzel-Boroviczény, O, Henker, J, Koletzko, B, Kersting, M, Lentze, M, Maaser, R, Mihatsch, W, Przyrembel, H, Wabitsch, M, Deutsch, J, Haiden, N, Hauer, A, Pietschnig, B, Pollak, A, Rock, I, Scholl-Bürgi, S, Skladal, D, Sperl, W, Widhalm, K, Zwiauer, K, Baehler, P, Baenziger, O, Belli, D, Braegger, C, Délèze, G, Furlano, R, Laimbacher, J, Spalinger, J, Studer, P, and University of Zurich

Subjects
10036 Medical Clinic, 610 Medicine & health, 2735 Pediatrics, Perinatology and Child Health, 2746 Surgery
Published
2008
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15. Empfehlungen für die Säuglingsernährung 2008

Author

Baehler, P, Baenziger, O, Belli, D, Braegger, C, Délèze, G, Furlano, R, Laimbacher, J, Roulet, M, Spalinger, J, Studer, P, and University of Zurich

Subjects
10036 Medical Clinic, 610 Medicine & health
Published
2008

18. Biliary atresia: Swiss national study 1994-2004

Author

Wildhaber, B. E., Majno, Pietro, Birraux, J., Mayr, Johannes, Furlano, R. Ι., Zachariou, Zacharias, Schibli, S., Hohlfeld, Judith, Roulet, M., Schwoebel, M., Spalinger, J., Kistler, Walter, Marx, G., Meuli, Martin, Braegger, C., Mentha, Gilles, Belli, Dominique, Chardot, C., Zachariou, Zacharias [0000-0001-8305-8037], Majno, Pietro [0000-0002-8676-3214], and Kistler, Walter [0000-0002-9289-6953]

Subjects
General & internal medicine
Abstract

136 10S 10S

Published
2006

22. Psychosomatic Symptoms in Asthmatic Children and Adolescents

Author

M. Weder, Richard Kraemer, Speck S, Spalinger J, and C. Casaulta Aebischer

Subjects
Childhood asthma, medicine.diagnostic_test, business.industry, Total ige, CBCL, Physical examination, Disease, medicine.disease, respiratory tract diseases, Asthmatic children, immune system diseases, Medicine, business, Psychosocial, Clinical psychology, Asthma
Abstract

In order to identify different patterns of association between physical and psychical symptoms in childhood asthma 102 children have been investigated. Somatic investigations included clinical examination, whole-body plethysmography, total IgE and RAST of specific allergens such as pollens, mites and animals. Psychosocial assessment comprised a semi-structured interview and questionnaires (Achenbach, CBCL and Olson, FACES II). There were typical psychosocial patterns in function of aetiopathogenetic groups. The infection-induced asthma was accompanied by high anxiety and here the most school problems were found. Children with seasonal asthma were psychologically healthy whereas those with perennial asthma showed important psycho-vegetative difficulties secondary to chronic somatic disease. Atypical asthma was found to be most often associated with real psychiatric symptoms. We concluded that psychosocial findings are heterogeneous and should be interpreted in relation to somatic manifestations.

Published
1993
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29. Successful treatment of bilateral renal fungal balls with liposomal amphotericin B and fluconazole in an extremely low birth weight infant.

Author

Stocker, Martin, Caduff, Jürg H., Spalinger, Johannes, Berger, Thomas M., Stocker, M, Caduff, J H, Spalinger, J, and Berger, T M

Subjects
BIRTH weight, KIDNEY disease treatments, INFANT disease treatment, HEALTH
Abstract

Unlabelled: At the age of 8 weeks, an extremely low birth weight infant (gestational age 26 0/7 weeks, birth weight 740 g) had non-obstructing bilateral renal fungal balls. Urine cultures had repeatedly grown Candida albicans. Combination therapy with liposomal amphotericin B intravenously and fluconazole orally was administered for 6 weeks. Monotherapy with fluconazole was then continued until complete resolution of the renal fungal balls.Conclusion: Combination therapy with liposomal amphotericin B and fluconazole was successful in eliminating non-obstructing bilateral renal fungal balls and obviated the need for surgical intervention. [ABSTRACT FROM AUTHOR]

Published
2000
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30. The personality traits activity, self-reproach, and negative affect jointly predict clinical recurrence, depressive symptoms, and low quality of life in inflammatory bowel disease patients

Author

Sebastian Bruno Ulrich, Jordi, Brian Matthew, Lang, Jacqueline, Wyss, Bianca, Auschra, Bahtiyar, Yilmaz, Niklas, Krupka, Thomas, Greuter, Philipp, Schreiner, Luc, Biedermann, Martin, Preisig, Roland, von Känel, Gerhard, Rogler, Stefan, Begré, Benjamin, Misselwitz, Dorothee, Zimmermann, Swiss IBD cohort study group, Anderegg, C., Bauerfeind, P., Beglinger, C., Begré, S., Belli, D., Bengoa, J.M., Biedermann, L., Bigler, B., Binek, J., Blattmann, M., Boehm, S., Borovicka, J., Braegger, C.P., Brunner, N., Bühr, P., Burnand, B., Burri, E., Buyse, S., Cremer, M., Criblez, D.H., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Dorta, G., Egger, M., Ehmann, T., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Frei, P., Frei, R., Fried, M., Froehlich, F., Funk, C., Furlano, R.I., Gallot-Lavallée, S., Geyer, M., Girardin, M., Golay, D., Grandinetti, T., Gysi, B., Haack, H., Haarer, J., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Heyland, K., Hinterleitner, T., Hiroz, P., Hirschi, C., Hruz, P., Iwata, R., Jost, R., Juillerat, P., Brondolo, V.K., Knellwolf, C., Knoblauch, C., Köhler, H., Koller, R., Krieger-Grübel, C., Kullak-Ublick, G., Künzler, P., Landolt, M., Lange, R., Lehmann, F.S., Macpherson, A., Maerten, P., Maillard, M.H., Manser, C., Manz, M., Marbet, U., Marx, G., Matter, C., McLin, V., Meier, R., Mendanova, M., Meyenberger, C., Michetti, P., Misselwitz, B., Moradpour, D., Morell, B., Mosler, P., Mottet, C., Müller, C., Müller, P., Müllhaupt, B., Münger-Beyeler, C., Musso, L., Nagy, A., Neagu, M., Nichita, C., Niess, J., Noël, N., Nydegger, A., Obialo, N., Oneta, C., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Piccoli-Gfeller, F., Pilz, J.B., Pittet, V., Raschle, N., Rentsch, R., Restellini, S., Richterich, J.P., Rihs, S., Ritz, M.A., Roduit, J., Rogler, D., Rogler, G., Rossel, J.B., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Schäppi, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Uebelhart, S.S., Schnegg, J.F., Schoepfer, A., Seibold, F., Seirafi, M., Semadeni, G.M., Semela, D., Senning, A., Sidler, M., Sokollik, C., Spalinger, J., Spangenberger, H., Stadler, P., Steuerwald, M., Straumann, A., Straumann-Funk, B., Sulz, M., Thorens, J., Tiedemann, S., Tutuian, R., Vavricka, S., Viani, F., Vögtlin, J., von Känel, R., Vonlaufen, A., Vouillamoz, D., Vulliamy, R., Wermuth, J., Werner, H., Wiesel, P., Wiest, R., Wylie, T., Zeitz, J., and Zimmermann, D.

Subjects
Cohort Studies, Humans, Personality Inventory, Quality of Life, Depression/epidemiology, Personality, Chronic Disease, Inflammatory Bowel Diseases, Five-factor model, Flares, IBD, NEO-FFI, Depression, Gastroenterology, 610 Medicine & health
Abstract

Background The bidirectional “gut-brain axis” has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). While the influence of stress and depressive symptoms on IBD is well-characterized, the role of personality remains insufficiently investigated. Methods Personality was assessed in 1154 Swiss IBD cohort study (SIBDCS) patients via the NEO-Five-Factor Inventory (NEO-FFI) as well as in 2600 participants of the population-based CoLaus¦PsyCoLaus cohort study (NEO-FFI-revised). The NEO-FFI subcomponents activity, self-reproach and negative affect were associated with higher IBD disease activity and were combined to a NEO-FFI risk score. This risk score was validated and its effect on clinical IBD course and psychological endpoints was analysed in time-to-event and cumulative incidence analyses. Results In time-to-event analyses, a high NEO-FFI risk score was predictive for the clinical endpoints of new extraintestinal manifestation [EIM, adjusted hazard ratio (aHR) = 1.64, corrected p value (q) = 0.036] and two established composite flare endpoints (aHR = 1.53–1.63, q = 0.003–0.006) as well as for the psychological endpoints depressive symptoms (aHR = 7.06, q q r = 0.03–0.14). Conclusions Personality assessed by the NEO-FFI contained considerable predictive power for disease recurrence, depressive symptoms and low quality of life in IBD patients. Nevertheless, the personalities of IBD patients did not substantially differ from the general population.

Published
2022
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31. Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

Author

Yoganathan, Priyatharsan, Rossel, Jean-Benoit, Jordi, Sebastian Bruno Ulrich, Franc, Yannick, Biedermann, Luc, Misselwitz, Benjamin, Hausmann, Martin, Rogler, Gerhard, Scharl, Michael, Frey-Wagner, Isabelle, Swiss IBD cohort study group, Marot, Astrid, Ris, Frédéric, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, University of Zurich, Frey-Wagner, Isabelle, Swiss IBD cohort study group, Abdelrahman, K., Ademi, G., Aepli, P., Thomas, A., Anderegg, C., Antonino, A.T., Archanioti, E., Arrigoni, E., de Jong, D.B., Balsiger, B., Bastürk, P., Bauerfeind, P., Becocci, A., Belli, D., Bengoa, J.M., Biedermann, L., Binek, J., Blattmann, M., Boehm, S., Boldanova, T., Borovicka, J., Braegger, C.P., Brand, S., Brügger, L., Brunner, S., Bühr, P., Burnand, B., Burk, S., Burri, E., Buyse, S., Cao, D.T., Carstens, O., Criblez, D.H., Cunningham, S., D'Angelo, F., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Drerup, S., Egger, M., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Franc, Y., Frei, P., Frei, R., Fried, M., Froehlich, F., Furlano, R.I., Garzoni, L., Geyer, M., Girard, L., Girardin, M., Golay, D., Good, I., Bigler, U.G., Gysi, B., Haarer, J., Halama, M., Haldemann, J., Heer, P., Heimgartner, B., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Hessler, R., Heyland, K., Hinterleitner, T., Hirschi, C., Hruz, P., Juillerat, P., Bakker, C.K., Kayser, S., Keller, C., Grieger, C.K., Knoblauch, C., Köhler, H., Koller, R., Krieger-Grübel, C., Künzler, P., Kusche, R., Lehmann, F.S., Macpherson, A., Maillard, M.H., Manz, M., Marot, A., Meier, R., Meyenberger, C., Meyer, P., Michetti, P., Misselwitz, B., Mosler, P., Mottet, C., Müller, C., Müllhaupt, B., Musso, L., Neagu, M., Nichita, C., Niess, J., Nydegger, A., Obialo, N., Ollo, D., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Pittet, V., Pohl, D., Porzner, M., Preissler, C., Raschle, N., Rentsch, R., Restellini, A., Restellini, S., Richterich, J.P., Ris, F., Risti, B., Ritz, M.A., Rogler, G., Röhrich, N., Rossel, J.B., Rueger, V., Rusticeanu, M., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Schluckebier, D., Schmid, D., Uebelhart, S.S., Schnegg, J.F., Schoepfer, A., Seematter, V., Seibold, F., Seirafi, M., Semadeni, G.M., Senning, A., Sokollik, C., Sommer, J., Spalinger, J., Spangenberger, H., Stadler, P., Staub, P., Staudenmann, D., Stenz, V., Steuerwald, M., Straumann, A., Strebel, B., Stulz, A., Sulz, M., Tatu, A., Tempia-Caliera, M., Thorens, J., Truninger, K., Tutuian, R., Urfer, P., Vavricka, S., Viani, F., Vögtlin, J., Von Känel, R., Vouillamoz, D., Vulliamy, R., Wiesel, P., Wiest, R., Wöhrle, S., Zamora, S., Zander, S., Wylie, T., Zeitz, J., and Zimmermann, D.

Subjects
Genotype, NLR Proteins, 610 Medicine & health, Single-nucleotide polymorphism, RC799-869, Disease, Polymorphism, Single Nucleotide, Inflammatory bowel disease, Pyrin domain, Cohort Studies, NLR Family, Pyrin Domain-Containing 3 Protein, Genetic variation, medicine, Humans, 2715 Gastroenterology, Genetic Predisposition to Disease, Allele, Gene, Genetic Association Studies, integumentary system, ddc:617, Clinical characteristics, 10179 Institute of Medical Microbiology, business.industry, Gastroenterology, Pyrin Domain, Single nucleotide polymorphisms, General Medicine, Diseases of the digestive system. Gastroenterology, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Colitis, Ulcerative/genetics, Switzerland, NLRP3 inflammasome, 10219 Clinic for Gastroenterology and Hepatology, 10036 Medical Clinic, Immunology, Colitis, Ulcerative, 610 Medizin und Gesundheit, business, Research Article
Abstract

Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

Published
2021
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32. Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management

Author

Luc Biedermann, Alexander Siebenhüner, Philipp Schreiner, René Roth, Benjamin Misselwitz, Martina Ledergerber, Brian M. Lang, Niklas Krupka, Thomas Greuter, Henriette Heinrich, Stefan Begré, Andreas Rickenbacher, Stephan R. Vavricka, Jonas Zeitz, Matthias Turina, Niko Beerenwinkel, Gerhard Rogler, Swiss IBD Cohort Study Group, Anderegg, C., Bauerfeind, P., Beglinger, C., Begré, S., Belli, D., Bengoa, J.M., Biedermann, L., Bigler, B., Binek, J., Blattmann, M., Boehm, S., Borovicka, J., Braegger, C.P., Brunner, N., Bühr, P., Burnand, B., Burri, E., Buyse, S., Cremer, M., Criblez, D.H., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Dorta, G., Egger, M., Ehmann, T., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Frei, P., Frei, R., Fried, M., Froehlich, F., Funk, C., Furlano, R.I., Gallot-Lavallée, S., Geyer, M., Girardin, M., Golay, D., Grandinetti, T., Gysi, B., Haack, H., Haarer, J., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Heyland, K., Hinterleitner, T., Hiroz, P., Hirschi, C., Hruz, P., Iwata, R., Jost, R., Juillerat, P., Brondolo, V.K., Knellwolf, C., Knoblauch, C., Köhler, H., Koller, R., Krieger-Grübel, C., Kullak-Ublick, G., Künzler, P., Landolt, M., Lange, R., Lehmann, F.S., Macpherson, A., Maerten, P., Maillard, M.H., Manser, C., Manz, M., Marbet, U., Marx, G., Matter, C., McLin, V., Meier, R., Mendanova, M., Meyenberger, C., Michetti, P., Misselwitz, B., Moradpour, D., Morell, B., Mosler, P., Mottet, C., Müller, C., Müller, P., Müllhaupt, B., Münger-Beyeler, C., Musso, L., Nagy, A., Neagu, M., Nichita, C., Niess, J., Noël, N., Nydegger, A., Obialo, N., Oneta, C., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Piccoli-Gfeller, F., Pilz, J.B., Pittet, V., Raschle, N., Rentsch, R., Restellini, S., Richterich, J.P., Rihs, S., Ritz, M.A., Roduit, J., Rogler, D., Rogler, G., Rossel, J.B., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Schäppi, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Uebelhart, S.S., Schnegg, J.F., Schoepfer, A., Seibold, F., Seirafi, M., Semadeni, G.M., Semela, D., Senning, A., Sidler, M., Sokollik, C., Spalinger, J., Spangenberger, H., Stadler, P., Steuerwald, M., Straumann, A., Straumann-Funk, B., Sulz, M., Thorens, J., Tiedemann, S., Tutuian, R., Vavricka, S., Viani, F., Vögtlin, J., Von Känel, R., Vonlaufen, A., Vouillamoz, D., Vulliamy, R., Wermuth, J., Werner, H., Wiesel, P., Wiest, R., Wylie, T., Zeitz, J., Zimmermann, D., University of Zurich, and Misselwitz, Benjamin

Subjects
0301 basic medicine, Crohn’s disease, Abdominal pain, medicine.medical_specialty, 610 Medicine & health, Disease, Polymorphism, Single Nucleotide, Inflammatory bowel disease, Gastroenterology, Single-nucleotide polymorphisms, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Abdominal Pain/genetics, Colitis, Ulcerative/complications, Colitis, Ulcerative/genetics, Humans, Inflammatory Bowel Diseases/complications, Inflammatory Bowel Diseases/genetics, Irritable Bowel Syndrome/complications, Irritable Bowel Syndrome/genetics, Nucleotides, Irritable bowel syndrome, Ulcerative colitis, Internal medicine, medicine, 2715 Gastroenterology, lcsh:RC799-869, 10217 Clinic for Visceral and Transplantation Surgery, Crohn's disease, business.industry, General Medicine, Hepatology, Inflammatory Bowel Diseases, medicine.disease, 10219 Clinic for Gastroenterology and Hepatology, 030104 developmental biology, 10036 Medical Clinic, Colitis, Ulcerative, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, medicine.symptom, 610 Medizin und Gesundheit, business, Research Article, Cohort study
Abstract

Background Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear. Methods Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models. Results In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P, BMC Gastroenterology, 21 (1), ISSN:1471-230X

Published
2021
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33. Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Author

Serra, Eva Gonçalves, Schwerd, Tobias, Moutsianas, Loukas, Cavounidis, Athena, Fachal, Laura, Pandey, Sumeet, Kammermeier, Jochen, Croft, Nicholas M, Posovszky, Carsten, Rodrigues, Astor, Russell, Richard K, Barakat, Farah, Auth, Marcus K H, Heuschkel, Robert, Zilbauer, Matthias, Fyderek, Krzysztof, Braegger, Christian, Travis, Simon P, Satsangi, Jack, Parkes, Miles, Thapar, Nikhil, Ferry, Helen, Matte, Julie C, Gilmour, Kimberly C, Wedrychowicz, Andrzej, Sullivan, Peter, Moore, Carmel, Sambrook, Jennifer, Ouwehand, Willem, Roberts, David, Danesh, John, Baeumler, Toni A, Fulga, Tudor A, Karaminejadranjbar, Mohammad, Ahmed, Ahmed, Wilson, Rachel, Barrett, Jeffrey C, Elkadri, Abdul, Griffiths, Anne M, Snapper, Scott B, Shah, Neil, Muise, Aleixo M, Wilson, David C, Uhlig, Holm H, Anderson, Carl A, Marlen, Zurek, Caterina, Strisciuglio, Mamoun, Elawad, Bernice, Lo, Carolina, Arancibia-Carcamo, Adam, Bailey, Ellie, Barnes, Elizabeth Louise, Bird-Lieberman, Oliver, Brain, Barbara, Braden, Jane, Collier, James, East, Lucy, Howarth, Satish, Keshav, Paul, Klenerman, Simon, Leedham, Rebecca, Palmer, Fiona, Powrie, Alison, Simmons, Matthew, Walker, Zoe, Tolkien, Stephen, Kaptoge, David, Allen, Susan, Mehenny, Jonathan, Mant, Emanuele, Di Angelantonio, Simon G, Thompson, Bahtiyar, Yilmaz, Pascal, Juillerat, Markus, Geuking, Reiner, Wiest, Andrew J, Macpherson, Francisco Damian, Bravo, Lukas, Brügger, Ove, Carstens, Ulrike Graf, Bigler, Benjamin, Heimgartner, Monica, Rusticeanu, Sybille, Schmid-Uebelhart, Bruno, Strebel, Aurora, Tatu, Radu, Tutuian, Ove, Øyås, Charlotte, Ramon, Jörg, Stelling, Yannick, Franc, Nicolas, Fournier, Valerie E H, Pittet, Bernard, Burnand, Mara, Egger, Delphine, Golay, Astrid, Marot, Leilla, Musso, Valérie, Pittet, Jean-Benoît, Rossel, Vivianne, Seematter, Joachim, Sommer, Rachel, Vulliamy, Pierre, Michetti, Michel H, Maillard, Céline, Keller, Andreas, Nydegger, Alain, Schoepfe, Eva, Archanioti, Jessica, Ezri, Montserrat, Fraga, Alain, Schoepfer, Christoph, Müller, Gerhard, Rogler, Luc, Biedermann, Mirjam, Blattmann, Sabine, Burk, Barbara, Dora, Michael, Fried, Benjamin, Misselwitz, Beat, Müllhaupt, Nicole, Obialo, Daniel, Pohl, Nadia, Raschle, Michael, Scharl, Stephan, Vavricka, Roland, Von Känel, Jonas, Zeitz, Karim, Abdelrahman, Gentiana, Ademi, Jan, Borovicka, Stephan, Brand, Remus, Frei, Johannes, Haarer, Christina, Knellwolf-Grieger, Claudia, Krieger-Grübel, Patrizia, Künzler, Christa, Meyenberger, Pamela, Meyer, Nina, Röhrich, Mikael, Sawatzki, Martin, Schelling, Gian-Marco, Semadeni, Michael, Sulz, Dorothee, Zimmermann, Patrick, Aepli, Dominique H, Criblez, Cyrill, Hess, Jean-Pierre, Richterich, Johannes, Spalinger, Dominic, Staudenmann, Andreas, Stulz, Stefanie, Wöhrle, Amman, Thomas, Claudia, Anderegg, Henrik, Köhler, Rachel, Kusche, Anca-Teodora, Antonino, Eviano, Arrigoni, José M, Bengoa, Sophie, Cunningham, Philippe, de Saussure, Laurent, Girard, Diana Bakker, de Jong, Polat, Bastürk, Simon, Brunner, Lukas, Degen, Petr, Hruz, Carolina, Khalid-de Bakker, Jan, Niess, Bruno, Balsiger, Janine, Haldemann, Gaby, Saner, Frank, Seibold, Peter, Bauerfeind, Andrea, Becocci, Dominique, Belli, Janek, Binek, Peter, Hengstler, Stephan, Boehm, Tujana, Boldanov, Patrick, Bühr, Rebekka, Koller, Vanessa, Rueger, Arne, Senning, Emanuel, Burri, Sophie, Buyse, Dahlia-Thao, Cao, Fabrizia, D'Angelo, Joakim, Delarive, Christopher, Doerig, Roxane, Hessler, Claudia, Preissler, Ronald, Rentsch, Branislav, Risti, Marc Alain, Ritz, Michael, Steuerwald, Jürg, Vögtlin, Markus, Sagmeister, Bernhard, Sauter, Susanne, Schibli, Christiane, Sokollik, Hugo, Schlauri, Jean-François, Schnegg, Mariam, Seirafi, Holger, Spangenberger, Philippe, Stadler, Peter, Staub, Volker, Stenz, Michela, Tempia-Caliera, Joël, Thorens, Kaspar, Truninger, Patrick, Urfer, Francesco, Viani, Dominique, Vouillamoz, Silvan, Zander, Tina, Wyli, L, Jostins, N A, Kennedy, T, Ahmad, C A, Lamb, C, Edwards, A, Hart, C, Hawkey, J C, Mansfield, C, Mowat, W G, Newman, A, Simmons, M, Tremelling, J C, Lee, N J, Prescott, C G, Mathew, C W, Lees, D P B, McGovern, S R, Targan, G, Botwin, E, Mengesha, P, Fleshner, C, Landers, D, Li, J D, Rioux, A, Bitton, J, Côté-Daigneault, M J, Daly, R, Xavier, K, Morris, G, Boucher, J H, Cho, C, Abraham, M, Merad, B, Sands, I, Peter, K, Hao, Y, Itan, R H, Duerr, L, Konnikova, M B, Schwartz, S, Proksell, E, Johnston, V, Miladinova, W, Chen, S R, Brant, L, Datta, M S, Silverberg, L P, Schumm, S, Birch, M, Giri, K, Gettler, Y, Sharma, C, Stevens, M, Lazarev, T, Haritunians, Fachal, Laura [0000-0002-7256-9752], Croft, Nicholas M [0000-0002-1519-6435], Posovszky, Carsten [0000-0002-9487-8812], Russell, Richard K [0000-0001-7398-4926], Zilbauer, Matthias [0000-0002-7272-0547], Travis, Simon P [0000-0002-2690-4361], Matte, Julie C [0000-0001-5642-648X], Wedrychowicz, Andrzej [0000-0003-1448-167X], Fulga, Tudor A [0000-0002-1056-0082], Karaminejadranjbar, Mohammad [0000-0002-7770-2065], Ahmed, Ahmed [0000-0001-6509-2581], Muise, Aleixo M [0000-0001-9624-3346], Wilson, David C [0000-0003-0879-1129], Apollo - University of Cambridge Repository, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Croft, Nicholas M. [0000-0002-1519-6435], Russell, Richard K. [0000-0001-7398-4926], Travis, Simon P. [0000-0002-2690-4361], Matte, Julie C. [0000-0001-5642-648X], Fulga, Tudor A. [0000-0002-1056-0082], Muise, Aleixo M. [0000-0001-9624-3346], Wilson, David C. [0000-0003-0879-1129], Eva Gonçalves, Serra, Tobias, Schwerd, Loukas, Moutsiana, Athena, Cavounidi, Laura, Fachal, Sumeet, Pandey, Jochen, Kammermeier, Nicholas M, Croft, Carsten, Posovszky, Astor, Rodrigue, Richard K, Russell, Farah, Barakat, Marcus K H, Auth, Robert, Heuschkel, Matthias, Zilbauer, Krzysztof, Fyderek, Christian, Braegger, Simon P, Travi, Jack, Satsangi, Miles, Parke, Nikhil, Thapar, Helen, Ferry, Julie C, Matte, Kimberly C, Gilmour, Andrzej, Wedrychowicz, Peter, Sullivan, Carmel, Moore, Jennifer, Sambrook, Willem, Ouwehand, David, Robert, John, Danesh, Toni A, Baeumler, Tudor A, Fulga, Mohammad, Karaminejadranjbar, Ahmed, Ahmed, Rachel, Wilson, Jeffrey C, Barrett, Abdul, Elkadri, Anne M, Griffith, Scott B, Snapper, Neil, Shah, Aleixo M, Muise, David C, Wilson, Holm H, Uhlig, Carl A, Anderson, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Arancibia-Carcamo, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Elizabeth Louise, Brain, Oliver, Braden, Barbara, Collier, Jane, East, Jame, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Powrie, Fiona, Simmons, Alison, Walker, Matthew, Tolkien, Zoe, Kaptoge, Stephen, Allen, David, Mehenny, Susan, Mant, Jonathan, Di Angelantonio, Emanuele, Thompson, Simon G, Yilmaz, Bahtiyar, Juillerat, Pascal, Geuking, Marku, Wiest, Reiner, Macpherson, Andrew J, Bravo, Francisco Damian, Brügger, Luka, Carstens, Ove, Bigler, Ulrike Graf, Heimgartner, Benjamin, Rusticeanu, Monica, Schmid-Uebelhart, Sybille, Strebel, Bruno, Tatu, Aurora, Tutuian, Radu, Øyås, Ove, Ramon, Charlotte, Stelling, Jörg, Franc, Yannick, Fournier, Nicola, Pittet, Valerie E H, Burnand, Bernard, Egger, Mara, Golay, Delphine, Marot, Astrid, Musso, Leilla, Pittet, Valérie, Rossel, Jean-Benoît, Seematter, Vivianne, Sommer, Joachim, Vulliamy, Rachel, Michetti, Pierre, Maillard, Michel H, Keller, Céline, Nydegger, Andrea, Schoepfe, Alain, Archanioti, Eva, Ezri, Jessica, Fraga, Montserrat, Schoepfer, Alain, Müller, Christoph, Rogler, Gerhard, Biedermann, Luc, Blattmann, Mirjam, Burk, Sabine, Dora, Barbara, Fried, Michael, Misselwitz, Benjamin, Müllhaupt, Beat, Obialo, Nicole, Pohl, Daniel, Raschle, Nadia, Scharl, Michael, Vavricka, Stephan, Von Känel, Roland, Zeitz, Jona, Abdelrahman, Karim, Ademi, Gentiana, Borovicka, Jan, Brand, Stephan, Frei, Remu, Haarer, Johanne, Knellwolf-Grieger, Christina, Krieger-Grübel, Claudia, Künzler, Patrizia, Meyenberger, Christa, Meyer, Pamela, Röhrich, Nina, Sawatzki, Mikael, Schelling, Martin, Semadeni, Gian-Marco, Sulz, Michael, Zimmermann, Dorothee, Aepli, Patrick, Criblez, Dominique H, Hess, Cyrill, Richterich, Jean-Pierre, Spalinger, Johanne, Staudenmann, Dominic, Stulz, Andrea, Wöhrle, Stefanie, Thomas, Amman, Anderegg, Claudia, Köhler, Henrik, Kusche, Rachel, Antonino, Anca-Teodora, Arrigoni, Eviano, Bengoa, José M, Cunningham, Sophie, de Saussure, Philippe, Girard, Laurent, de Jong, Diana Bakker, Bastürk, Polat, Brunner, Simon, Degen, Luka, Hruz, Petr, Khalid-de Bakker, Carolina, Niess, Jan, Balsiger, Bruno, Haldemann, Janine, Saner, Gaby, Seibold, Frank, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Binek, Janek, Hengstler, Peter, Boehm, Stephan, Boldanov, Tujana, Bühr, Patrick, Koller, Rebekka, Rueger, Vanessa, Senning, Arne, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, D'Angelo, Fabrizia, Delarive, Joakim, Doerig, Christopher, Hessler, Roxane, Preissler, Claudia, Rentsch, Ronald, Risti, Branislav, Ritz, Marc Alain, Steuerwald, Michael, Vögtlin, Jürg, Sagmeister, Marku, Sauter, Bernhard, Schibli, Susanne, Sokollik, Christiane, Schlauri, Hugo, Schnegg, Jean-Françoi, Seirafi, Mariam, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Stenz, Volker, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Urfer, Patrick, Viani, Francesco, Vouillamoz, Dominique, Zander, Silvan, Wyli, Tina, Jostins, L, Kennedy, N A, Ahmad, T, Lamb, C A, Edwards, C, Hart, A, Hawkey, C, Mansfield, J C, Mowat, C, Newman, W G, Simmons, A, 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, Côté-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, Carrami, Eli M [0000-0002-7770-2065], COLORS in IBD group investigators, Oxford IBD cohort study investigators, INTERVAL Study, Swiss IBD cohort investigators, UK IBD Genetics Consortium, NIDDK IBD Genetics Consortium, 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., Brügger, L., Carstens, O., Bigler, U.G., Heimgartner, B., Rusticeanu, M., Schmid-Uebelhart, S., Strebel, B., Tatu, A., Tutuian, R., Øyås, O., Ramon, C., Stelling, J., Franc, Y., Fournier, N., Pittet, VEH, Burnand, B., Egger, M., Golay, D., Marot, A., Musso, L., Pittet, V., 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., Müller, C., Rogler, G., Biedermann, L., Blattmann, M., Burk, S., Dora, B., Fried, M., Misselwitz, B., Müllhaupt, B., Obialo, N., Pohl, D., Raschle, N., Scharl, M., Vavricka, S., Von Känel, R., Zeitz, J., Abdelrahman, K., Ademi, G., Borovicka, J., Brand, S., Frei, R., Haarer, J., Knellwolf-Grieger, C., Krieger-Grübel, C., Künzler, P., Meyenberger, C., Meyer, P., Röhrich, 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., Wöhrle, S., Thomas, A., Anderegg, C., Köhler, H., Kusche, R., Antonino, A.T., Arrigoni, E., Bengoa, J.M., Cunningham, S., de Saussure, P., Girard, L., de Jong, D.B., Bastürk, P., Brunner, S., Degen, L., Hruz, P., Bakker, C.K., Niess, J., Balsiger, B., Haldemann, J., Saner, G., Seibold, F., Bauerfeind, P., Becocci, A., Belli, D., Binek, J., Hengstler, P., Boehm, S., Boldanov, T., Bühr, 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., Vögtlin, 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, DPB, Targan, S.R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J.D., Bitton, A., Côté-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., and Haritunians, T.

Subjects
0301 basic medicine, Male, Multifactorial Inheritance, General Physics and Astronomy, 631/208/1516, 13, Inflammatory bowel disease, Whole Exome Sequencing, Adult, Age of Onset, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Female, Genes, Recessive, Genetic Predisposition to Disease, Genetic Variation, Humans, Infant, Infant, Newborn, Inflammatory Bowel Diseases/etiology, Inflammatory Bowel Diseases/genetics, Loss of Function Mutation, Mosaicism, Mutation, NADPH Oxidase 2/genetics, Pedigree, Primary Immunodeficiency Diseases/complications, Primary Immunodeficiency Diseases/genetics, Risk Factors, 0302 clinical medicine, Primary Immunodeficiency Disease, Medicine, lcsh:Science, Exome sequencing, 49/31, education.field_of_study, Multidisciplinary, Medical genetics, article, 692/699/249/1570, 631/250/249/2510/257, 631/208/248, 3. Good health, NADPH Oxidase 2, 030211 gastroenterology & hepatology, Case-Control Studie, Human, medicine.medical_specialty, Science, Primary Immunodeficiency Diseases, Population, 45/22, 45/23, digestive system, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immunological deficiency syndromes, Exome Sequencing, Immunogenetics, Allele, education, 45, business.industry, Risk Factor, Inflammatory Bowel Disease, Case-control study, General Chemistry, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, 49, 030104 developmental biology, Immunology, Primary immunodeficiency, lcsh:Q, Age of onset, Cohort Studie, business
Abstract

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P, Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Published
2020
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34. Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

Author

Klöti S, Schaad J, Spalinger J, Schibli S, Hart L, Sokollik C, and Righini-Grunder F

Subjects
Humans, Retrospective Studies, Male, Child, Female, Biopsy, Child, Preschool, Adolescent, Autoantibodies blood, Protein Glutamine gamma Glutamyltransferase 2, GTP-Binding Proteins immunology, Treatment Outcome, Follow-Up Studies, Infant, Patient Compliance, Celiac Disease diagnosis, Celiac Disease diet therapy, Celiac Disease blood, Celiac Disease immunology, Diet, Gluten-Free, Transglutaminases immunology, Immunoglobulin A blood
Abstract

Objectives: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN., Methods: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models., Results: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach., Conclusions: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Published
2024
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35. Drug-Related Adverse Events Necessitating Treatment Discontinuation in Pediatric Inflammatory Bowel Disease Patients.

Author

Salzmann M, von Graffenried T, Righini-Grunder F, Braegger C, Spalinger J, Schibli S, Schoepfer A, Nydegger A, Pittet V, and Sokollik C

Subjects
Humans, Child, Adolescent, Cohort Studies, Infliximab adverse effects, Adalimumab adverse effects, Tumor Necrosis Factor-alpha, Tumor Necrosis Factor Inhibitors, Inflammatory Bowel Diseases drug therapy, Crohn Disease drug therapy, Colitis, Ulcerative drug therapy
Abstract

Objectives: Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients., Methods: We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments, and related AE. We analyzed the frequency, type, and risk factors for AE necessitating drug discontinuation., Results: A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least 1 drug-related AE that required drug cessation. Immunomodulators [methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)] followed by tumor necrosis factor (TNF)-alpha antagonists [adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)] accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE [odds ratio = 2.50, 95% confidence interval (1.50-4.17)] in all pediatric IBD patients., Conclusions: Drug-related AE necessitating discontinuation are common in pediatric and adolescent IBD patients. Caution needs to be taken in the case of concomitant drug use., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Published
2022
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36. Impact of Overweight and Obesity on Disease Outcome in the Pediatric Swiss Inflammatory Bowel Disease Cohort.

Author

von Graffenried T, Schoepfer AM, Rossel JB, Greuter T, Safroneeva E, Godat S, Henchoz S, Vavricka SR, Sokollik C, Spalinger J, Braegger CP, and Nydegger A

Abstract

Given the paucity of data, we aimed to assess the impact of obesity on disease activity, complications, and quality of life (QoL) in pediatric inflammatory bowel disease (IBD) patients., Methods: Prospective analysis of pediatric IBD patients. Patients were categorized into 4 groups according to the World Health Organization (WHO) child growth standards: obese, overweight, normal weight, and underweight., Results: Three hundred twenty-seven pediatric patients were included (146 with Crohn's disease [CD], 181 with ulcerative colitis of whom 13 [4%] were underweight, 272 [83.2%] had normal weight, 22 [6.7%] were overweight, and 20 [6.1%] were obese). Compared with normal weight patients, obese ulcerative colitis had a significantly higher clinical but not biological disease activity nor severity. Compared with normal weight patients, overweight/obese CD patients did not have higher clinical or biological disease activity nor severity. Perianal abscesses and surgery for this purpose were more frequently observed in overweight/obese CD patients compared with normal weight controls. Overweight/obese IBD patients were similarly hospitalized in the last 12 months compared with normal weight controls., Conclusions: Prevalence of overweight/obesity was 12.8% in pediatric IBD patients. Obesity was not associated with a decrease in disease remission rates nor an increase in the risk of complicated disease progression in IBD pediatric patients, except for the occurrence of perianal abscesses and related surgery in CD patients., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Published
2022
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37. Newborns with Bloody Stools-At the Crossroad between Efficient Management of Necrotizing Enterocolitis and Antibiotic Stewardship.

Author

Heyne-Pietschmann M, Lehnick D, Spalinger J, Righini-Grunder F, Buettcher M, Lehner M, and Stocker M

Abstract

The onset of bloody stools in neonates often results in antibiotic treatment for suspected necrotizing enterocolitis (NEC). Food protein-induced allergic proctocolitis (FPIAP) is an often-neglected differential diagnosis. We performed a retrospective analysis of antibiotic exposure at our tertiary center from 2011 to 2020 that included three time periods of differing antimicrobial stewardship goals. We compared these data with the conventional treatment guidelines (modified Bell's criteria). In our cohort of 102 neonates with bloody stools, the length of antibiotic exposure was significantly reduced from a median of 4 to 2 days. The proportion of treated neonates decreased from 100% to 55% without an increase in negative outcomes. There were 434 antibiotic days. Following a management strategy according to modified Bell's criteria would have led to at least 780 antibiotic days. The delayed initiation of antibiotic treatment was observed in 7 of 102 cases (6.9%). No proven NEC case was missed. Mortality was 3.9%. In conclusion, with FPIAP as a differential diagnosis of NEC, an observational management strategy in neonates with bloody stools that present in a good clinical condition seems to be justified. This may lead to a significant reduction of antibiotic exposure. Further prospective, randomized trials are needed to prove the safety of this observational approach.

Published
2021
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38. Impact of Diagnostic Delay on Disease Course in Pediatric- versus Adult-Onset Patients with Ulcerative Colitis: Data from the Swiss IBD Cohort.

Author

Schoepfer AM, Tran VDC, Rossel JB, Sokollik C, Spalinger J, Safroneeva E, von Graffenried T, Godat S, Hahnloser D, Vavricka SR, Braegger C, and Nydegger A

Abstract

Introduction: Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years)., Methods: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs)., Results: A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group ( p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay ( p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia ( p = 0.023), EIMs ( p < 0.001), and more specifically arthritis/arthralgias ( p < 0.001) and ankylosing spondylitis/sacroiliitis ( p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias ( p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization., Conclusions: As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

Published
2021
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39. Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps.

Author

Zysset D, Montani M, Spalinger J, Schibli S, Zlobec I, Mueller C, and Sokollik C

Subjects
Adolescent, Case-Control Studies, Child, Child, Preschool, Colonic Polyps metabolism, Colonoscopy, Cytokines metabolism, Eosinophils pathology, Female, Humans, Inflammatory Bowel Diseases metabolism, Leukocyte L1 Antigen Complex metabolism, Male, RNA, Messenger analysis, Recurrence, T-Lymphocytes pathology, Colonic Polyps pathology, Eosinophils metabolism, Inflammatory Bowel Diseases pathology, T-Lymphocytes metabolism
Abstract

Introduction: Solitary juvenile polyps (JP) are characterized by a benign disease course with low recurrence rate but present with signs of intestinal inflammation. To better understand the underlying pathogenesis, we performed histological and molecular evaluation targeting distinct immune mechanisms., Methods: Pediatric patients with JP (n = 12), with treatment-naïve inflammatory bowel disease (IBD; [n = 41]) as inflammatory control, and non-IBD controls (n = 14) were investigated. For a comparative analysis of infiltrating immune cells, a next-generation tissue microarray of biopsies was assembled, immunostained, and scored. Targeted transcriptional profiling was performed using a customized immunology panel., Results: In JP, a predominant accumulation of neutrophils and eosinophils was observed. RNA expression profiles revealed increased levels of CXCL8, CXCL5, and CCL11 transcripts in JP, indicating an enhanced recruitment of neutrophils and eosinophils. Moreover, messenger RNA levels of the proinflammatory cytokine IL1b and the inflammation-amplifying receptor TREM1 were higher in JP, whereas we could not find signs of a functionally polarized Tcell response in JP when compared with IBD., Discussion: Patients with JP and patients with treatment-naïve IBD have distinct cell infiltrates during active disease. The ample presence of eosinophils in JP supports neutrophil accumulation, which is responsible for the elevated release of calprotectin. Intriguingly, however, we were not able to identify a functionally polarized T-cell response in JP, which indicates that during the acute onset of inflammation in JP, a potent adaptive immune memory is not established. This may explain the low reoccurrence rate of JP., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Published
2021
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40. Comparative study of preterm infants fed new and existing human milk fortifiers showed favourable markers of gastrointestinal status.

Author

Rigo J, Hascoët JM, Picaud JC, Mosca F, Rubio A, Saliba E, Radkë M, Simeoni U, Guillois B, Hays NP, Hartweg M, Billeaud C, and Spalinger J

Subjects
Belgium, Biomarkers, Food, Fortified, France, Germany, Humans, Infant, Infant, Newborn, Italy, Switzerland, Weight Gain, Infant, Premature, Milk, Human
Abstract

Aim: This study examined the influence of different human milk fortifiers on biomarkers of gastrointestinal immaturity and inflammation in preterm infants., Methods: We report secondary outcomes from a controlled, double-blind, randomised, parallel group study conducted from 2011 to 2014 in neonatal intensive care units at 11 metropolitan hospitals in France, Belgium, Germany, Switzerland and Italy. Preterm infants born at up to 32 weeks or weighing up to 1500 g were randomised to a new powdered human milk fortifier (n = 77) or a control fortifier (n = 76) for a minimum of 21 days. We analysed faecal markers of gut inflammation, namely alpha-1 antitrypsin and calprotectin, and maturity, namely elastase-1., Results: Faecal alpha-1 antitrypsin was slightly lower in the new than control fortifier group after 21 days of full enteral feeding, with a geometric mean and standard deviation of 1.52 ± 1.32 vs 1.82 ± 1.44 mg/g stools (P = .01). There was no significant difference in faecal calprotectin (median [Q1-Q3] of 296 [136-565] μg/g stools in both groups combined at study day 21). Faecal elastase-1 was lower in the new fortifier than control fortifier group (202.5 ± 1.6 vs 257.7 ± 1.5 μg/g stools, P = .016)., Conclusion: Mean values for each parameter were within the ranges in healthy term infants, indicating favourable markers of gastrointestinal status in both groups. In addition, for faecal calprotectin, the relatively high concentration observed in preterm infants fed fortified human milk suggests that the threshold level for detecting necrotising enterocolitis should be revised., (© 2019 Société des Produits Nestlé SA. Acta Paediatrica Published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Published
2020
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41. Systematic Analysis of the Impact of Diagnostic Delay on Bowel Damage in Paediatric Versus Adult Onset Crohn's Disease.

Author

Schoepfer A, Santos J, Fournier N, Schibli S, Spalinger J, Vavricka S, Safroneeva E, Aslan N, Rogler G, Braegger C, and Nydegger A

Subjects
Adolescent, Adult, Age of Onset, Child, Crohn Disease complications, Crohn Disease pathology, Female, Humans, Intestines pathology, Male, Switzerland, Time Factors, Young Adult, Crohn Disease diagnosis, Delayed Diagnosis adverse effects
Abstract

Background and Aims: Length of diagnostic delay is associated with bowel strictures and intestinal surgery in adult patients with Crohn's disease [CD]. Here we assessed whether diagnostic delay similarly impacts on the natural history of paediatric CD patients., Methods: Data from the Swiss IBD Cohort Study were analysed. Frequency of CD-related complications [bowel stenosis, perianal fistula, internal fistula, any fistula, resection surgery, fistula/abscess surgery, any complication] at diagnosis and in the long term [up to 30 years after CD diagnosis] was compared between paediatric patients [diagnosed <18 years] and adult patients [diagnosed ≥18 years] using multivariate Cox proportional hazard regression modelling., Results: From 2006 to 2016, 387 paediatric and 1163 adult CD patients were included. Median [interquartile range: IQR] diagnostic delay was 3 [1-9] for the paediatric and 6 [1-24] months for the adult group, respectively. Adult onset CD patients presented at diagnosis more frequently with bowel stenosis [p <0.001] and bowel surgery [p <0.001] compared with paediatric CD patients. In the long term, length of diagnostic delay was significantly associated with bowel stenosis [p = 0.001], internal fistula [p = 0.038], and any complication [p = 0.024] in the adult onset CD population. No significant association between length of diagnostic delay and CD-related outcomes in the long term was observed in the paediatric population., Conclusions: Adult CD patients have longer diagnostic delay compared with paediatric CD patients and present at diagnosis more often with bowel stenosis and surgery. Length of diagnostic delay was found to be predictive for CD-related complications only in the adult but not in the paediatric CD population., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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42. Management of Juvenile Polyposis Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group.

Author

Cohen S, Hyer W, Mas E, Auth M, Attard TM, Spalinger J, Latchford A, and Durno C

Subjects
Adolescent, Child, Colonoscopy standards, Consensus, Evidence-Based Medicine, Gastrointestinal Neoplasms etiology, Gastrointestinal Neoplasms prevention & control, Genetic Testing methods, Humans, Intestinal Polyposis complications, Intestinal Polyposis diagnosis, Intestinal Polyposis genetics, Intestinal Polyposis therapy, Mutation, Missense, Neoplastic Syndromes, Hereditary complications, Neoplastic Syndromes, Hereditary genetics, Genetic Testing standards, Intestinal Polyposis congenital, Neoplastic Syndromes, Hereditary diagnosis, Neoplastic Syndromes, Hereditary therapy
Abstract

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Polyposis Working Group developed recommendations to assist clinicians and health care providers with appropriate management of patients with juvenile polyposis. This is the first juvenile polyposis Position Paper published by ESPGHAN with invited experts. Many of the published studies were descriptive and/or retrospective in nature, consequently after incorporating a modified version of the GRADE system many of the recommendations are based on expert opinion. This ESPGHAN Position Paper provides a guide for diagnosis, assessment, and management of juvenile polyposis syndrome in children and adolescents, and will be helpful in the appropriate management and timing of procedures in children and adolescents. The formation of international collaboration and consortia is proposed to monitor patients prospectively to advance our understanding of juvenile polyposis conditions.

Published
2019
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43. PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn's disease.

Author

Horn MP, Peter AM, Righini Grunder F, Leichtle AB, Spalinger J, Schibli S, and Sokollik C

Subjects
Adolescent, Adult, Antibodies, Antineutrophil Cytoplasmic immunology, Child, Colitis, Ulcerative immunology, Colitis, Ulcerative pathology, Crohn Disease immunology, Crohn Disease pathology, Diagnosis, Differential, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Myeloblastin immunology, Pediatrics, Prognosis, Antibodies, Antineutrophil Cytoplasmic blood, Colitis, Ulcerative blood, Crohn Disease blood, Inflammatory Bowel Diseases blood, Myeloblastin blood
Abstract

Background: Accurate classification of patients with inflammatory bowel disease into the subtypes ulcerative colitis (UC) and Crohn's disease (CD) is still a challenge, but important for therapy and prognosis., Objectives: To evaluate the diagnostic utility of anti-neutrophil cytoplasmic antibodies specific for proteinase-3 (PR3-ANCA) for ulcerative colitis (UC) and the value of an antibody panel incorporating PR3-ANCA to differentiate between Crohn's disease (CD) and UC., Study Design: In this cohort study, 122 pediatric and adolescent individuals were retrospectively included (61 IBD patients of two clinical centers, 61 non-IBD controls). All subjects had a comprehensive antibody profile done from stored sera taken close to time of diagnosis. By employing quasi-exhaustive logistic regression the best discriminative model for UC and CD,subjects was determined in a training cohort and confirmed in a validation cohort., Results: PR3-ANCA was specifically associated with UC (odds ratio (OR), 17.6; 95% confidence interval (CI); 3.6, 87); P < .001). A four antibody-panel including PR3-ANCA had an AUC of 90.81% (95%CI; 81.93, 99.69) to distinguish between UC and CD in the training cohort. In a smaller external validation cohort, the AUC was 84.13% (95%CI; 64.21, 100) for accurate diagnosis of CD and UC., Conclusion: PR3-ANCA is highly specific for UC. The differentiating capability of a panel, which contains PR3-ANCA and weighs broadly available antibodies, is superior and utilization of the panel can support accurate classification in the work-up of pediatric and adolescent patients with IBD patients., Competing Interests: The authors have declared that no competing interests exist.

Published
2018
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44. The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease.

Author

Sokollik C, Fournier N, Rizzuti D, Braegger CP, Nydegger A, Schibli S, and Spalinger J

Subjects
Administration, Cutaneous, Administration, Oral, Adolescent, Child, Cohort Studies, Female, Humans, Male, Medical Records, Retrospective Studies, Severity of Illness Index, Treatment Outcome, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Inflammatory Bowel Diseases, Mesalamine administration & dosage
Abstract

Background: In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn's disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease., Materials and Methods: Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed., Results: Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%., Conclusions: In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy.

Published
2018
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45. Change of treatment modalities over the last 10 years in pediatric patients with inflammatory bowel disease in Switzerland.

Author

Guilcher K, Fournier N, Schoepfer A, Schibli S, Spalinger J, Braegger C, and Nydegger A

Subjects
Adolescent, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Child, Colitis, Ulcerative surgery, Crohn Disease surgery, Drug Therapy trends, Female, Humans, Male, Retrospective Studies, Switzerland, Tumor Necrosis Factor-alpha antagonists & inhibitors, Adrenal Cortex Hormones therapeutic use, Biological Products therapeutic use, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Immunosuppressive Agents therapeutic use, Mesalamine therapeutic use
Abstract

Background and Aim: During the past decade, several new drugs were approved for the treatment of pediatric inflammatory bowel disease (IBD). We aimed to evaluate if and how pharmacologic treatment options for pediatric IBD in Switzerland have changed over time., Patients and Methods: Data from the pediatric Swiss IBD Cohort Study, a national prospective cohort study initiated in 2006, were analyzed. Patients were divided into two groups: patients with IBD diagnosis until 2009 (168 patients) and patients with IBD diagnosis in 2010 and after (210 patients). Both groups were analyzed regarding the past and the current therapies as well as need for surgery., Results: Overall, 378 pediatric patients with IBD were analyzed, of which 51.9% had Crohn's disease (CD) and 48.1% had ulcerative colitis/indeterminate colitis. Median age at diagnosis was 12 years. The majority (65.4%) of the patients with ulcerative colitis experienced pancolitis, whereas 45.4% of patients with CD presented with ileocolonic disease at diagnosis. A decreased use of corticosteroids in pediatric patients with CD can be found after 2010 (P=0.041). Use of 5-aminosalicylic acid for patients with CD was dramatically reduced after the year 2010 (33.5 vs. 67.7% after 6 years of disease). A significant shift toward earlier use of biologicals could be shown after 2010 (P<0.001). However, there was no significant decrease of surgery rate after 5 years of disease., Conclusion: In the past decade, a significant earlier use of anti-tumor necrosis factor-α agents in pediatric patients with IBD was observed with steroid-sparing effect in patients with CD. However, this change was not associated with reduction of surgery.

Published
2018
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46. Nutrient intake of Swiss toddlers.

Author

Brunner TA, Casetti L, Haueter P, Müller P, Nydegger A, and Spalinger J

Subjects
Child, Preschool, Dietary Fats administration & dosage, Dietary Proteins administration & dosage, Europe, Female, Humans, Infant, Male, Micronutrients, Diet standards, Energy Intake physiology, Nutritional Requirements, Recommended Dietary Allowances
Abstract

Purpose: During the first years of life, food preferences are shaped that might last throughout a person's entire life affecting his/her health in the long term. However, knowledge on early feeding habits is still limited for toddlers. Therefore, the goal of the present study was to: (1) assess toddlers' nutrient intake; (2) compare the findings to past studies as well as to national feeding recommendations and (3) identify major food sources for energy and macronutrients., Methods: A food survey using a 4-day diary was conducted. The dietary software nut.s ® was used to analyse the data., Results: A cohort of 188 healthy toddlers (aged 1-3 years) was analysed. The energy intake of most toddlers was below the recommended daily intake (RDI) but in accordance with earlier studies. Protein intake was three- to fourfold higher than the RDI and reached the proposed upper limit of 15% of total energy intake. Fat intake was in accordance with the RDI, but the balance of saturated and unsaturated fatty acids should be improved. Carbohydrate intake met the RDI. For the micronutrients, iron and vitamin D intakes showed critical values., Conclusion: As in other European countries, the diet of Swiss toddlers in general seems adequate but does not meet all nutritional requirements. In particular, the quality of the fats and vitamin D supplementation should be improved. For proteins and iron, additional research is needed to gain more confidence in the recommendations.

Published
2018
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47. Age at disease onset of inflammatory bowel disease is associated with later extraintestinal manifestations and complications.

Author

Herzog D, Fournier N, Buehr P, Rueger V, Koller R, Heyland K, Nydegger A, Spalinger J, Schibli S, Petit LM, and Braegger CP

Subjects
Adolescent, Adult, Age of Onset, Anemia epidemiology, Arthralgia epidemiology, Bone Diseases, Metabolic epidemiology, Child, Cholangitis, Sclerosing epidemiology, Colitis, Ulcerative diagnosis, Colitis, Ulcerative therapy, Crohn Disease diagnosis, Crohn Disease therapy, Disease Progression, Female, Humans, Male, Prevalence, Prognosis, Prospective Studies, Registries, Retrospective Studies, Risk Factors, Severity of Illness Index, Spondylitis, Ankylosing epidemiology, Stomatitis, Aphthous epidemiology, Switzerland epidemiology, Time Factors, Colitis, Ulcerative epidemiology, Crohn Disease epidemiology
Abstract

Introduction: A small but increasing number of patients with inflammatory bowel disease are diagnosed during childhood or adolescence, and disease distribution and severity at onset vary according to the age at diagnosis. Clinical factors present at the time of diagnosis can be predictive of the disease course., Aim: The aim of this study was to characterize disease behavior and the cumulative complications and extraintestinal manifestations 10 years after the diagnosis and to assess their association with age at diagnosis., Patients and Methods: Data of patients participating with the Swiss IBD cohort study registry, a disease duration of 10 years and a complete data set were analyzed. The outcome was defined as the cumulative change of disease behavior, the occurrence of extra-intestinal manifestations or complications, and the necessity for medical or surgical interventions., Results: A total of 481 patients with Crohn's disease (CD) and 386 patients with ulcerative colitis (UC), grouped according to disease onset before 10, 17, 40, or after 40 years of age, were analyzed. Despite differences in sex, initial disease location, and smoking habits, at 10 years after the diagnosis, no difference was found regarding disease behavior in CD or regarding progression of disease extension in UC. Similarly, no age-of-onset-dependent cumulative need for medical or surgical therapies was found. However, higher rates of anemia and lower rates of arthralgia and osteopenia were found in both pediatric-onset CD and UC, and a tendency toward higher rates of stomatitis in pediatric-onset CD, and of primary sclerosing cholangitis and ankylosing spondylitis in pediatric-onset UC., Conclusion: After 10 years of disease evolution, age at disease onset is not anymore associated with disease behavior but only with a small difference in the occurrence of specific extraintestinal manifestations and complications.

Published
2018
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48. Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.

Author

Rigo J, Hascoët JM, Billeaud C, Picaud JC, Mosca F, Rubio A, Saliba E, Radkë M, Simeoni U, Guillois B, de Halleux V, Jaeger J, Ameye L, Hays NP, and Spalinger J

Subjects
Biomarkers metabolism, Dietary Fats, Dietary Proteins, Double-Blind Method, Female, Humans, Infant, Newborn, Infant, Premature metabolism, Infant, Very Low Birth Weight metabolism, Male, Nutrition Assessment, Outcome Assessment, Health Care, Weight Gain, Food, Fortified, Infant Care methods, Infant Nutritional Physiological Phenomena, Infant, Premature growth & development, Infant, Very Low Birth Weight growth & development, Milk, Human, Nutritional Status
Abstract

Objectives: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid., Methods: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored., Results: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g · kg · day (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events., Conclusions: nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.

Published
2017
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49. Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

Author

Greuter T, Bertoldo F, Rechner R, Straumann A, Biedermann L, Zeitz J, Misselwitz B, Scharl M, Rogler G, Safroneeva E, Ali RAR, Braegger C, Heyland K, Mueller P, Nydegger A, Petit LM, Schibli S, Furlano RI, Spalinger J, Schäppi M, Zamora S, Froehlich F, Herzog D, Schoepfer AM, and Vavricka SR

Subjects
Adolescent, Anti-Inflammatory Agents therapeutic use, Child, Child, Preschool, Cholangitis, Sclerosing diagnosis, Cholangitis, Sclerosing drug therapy, Cholangitis, Sclerosing epidemiology, Colitis, Ulcerative diagnosis, Colitis, Ulcerative drug therapy, Crohn Disease diagnosis, Crohn Disease drug therapy, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Joint Diseases diagnosis, Joint Diseases drug therapy, Joint Diseases epidemiology, Logistic Models, Male, Prevalence, Retrospective Studies, Skin Diseases diagnosis, Skin Diseases drug therapy, Skin Diseases epidemiology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Uveitis diagnosis, Uveitis drug therapy, Uveitis epidemiology, Cholangitis, Sclerosing etiology, Colitis, Ulcerative complications, Crohn Disease complications, Joint Diseases etiology, Skin Diseases etiology, Uveitis etiology
Abstract

Background: There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD)., Methods: Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively., Results: A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%)., Conclusions: In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy.

Published
2017
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50. Changes in health-related quality of life over a 1-year follow-up period in children with inflammatory bowel disease.

Author

Werner H, Landolt MA, Buehr P, Koller R, Nydegger A, Spalinger J, Heyland K, Schibli S, and Braegger CP

Subjects
Adolescent, Child, Chronic Disease, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Prospective Studies, Surveys and Questionnaires, Time Factors, Inflammatory Bowel Diseases psychology, Quality of Life psychology
Abstract

Purpose: Little is known about disease-specific health-related quality-of-life (HRQoL) changes over time in paediatric patients with inflammatory bowel disease (IBD), and about their associations with baseline medical characteristics., Methods: In this study, 153 paediatric patients with IBD from the multicentre prospective Swiss IBD cohort study were included at baseline. Of these, 90 patients were analysed at a 1-year follow-up. Medical data were extracted from hospital records, while HRQoL data were measured using the standardized, self-report disease-specific IMPACT-III questionnaire., Results: The IBD diagnosis of the included children was made an average of 2.0 years before their baseline assessment. Over the 1-year follow-up period, a significant increase in overall HRQoL and in the HRQoL domain 'physical functioning' was evident. On multivariate analysis, overall HRQoL changes over time were predicted by baseline HRQoL, baseline disease activity, and disease activity changes over time. HRQoL improvements were significantly associated with decreases in physician-assessed disease activity. Children reporting a low baseline HRQoL and children with inactive or mildly-active disease experienced greater improvements., Conclusions: Children with more severe baseline disease activity had the greatest risk for HRQoL deterioration over the 1-year follow-up period. However, among possible factors that might influence HRQoL changes over time, the child's medical characteristics explained only a small proportion of their variability in our sample. We, therefore, recommend that researchers and clinicians focus on factors that are not incorporated within the multidimensional HRQoL concept if they seek to gain better insights into factors that influence HRQoL changes over time in children with IBD.

Published
2017
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