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1. 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

3. 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

6. ALKOHOL-MANUAL

Author

Aeschbach C, null NSchaub, Steuerwald M, and Wanner J

Published
2011

7. Treatment of chronic hepatitis C genotype 1 with triple therapy comprising telaprevir or boceprevir.

Author

Swiss Association for the Study of the Liver, Moradpour, D., Helbling, B., Cerny, A., De Gottardi, A., Heim, MH., Majno, P., Müllhaupt, B., Negro, F., Rubbia-Brandt, L., Semela, D., Vilei, SB., Bernsmeier, C., Bihl, F., Borovicka, J., Dill, M., Dufour, JF., Filipowicz, M., Geier, A., Gerlach, T., Giostra, E., Gonvers, JJ., Goossens, N., Gubler, C., Hadengue, A., Hellstern, M., Hirschi, C., Jochum, W., Krähenbühl, S., Kullak-Ublick, G., Lange, C., Lavanchy, D., Malinverni, R., McLin, V., Mentha, G., Mertens, JC., Nasser, S., Oneta, C., Pache, I., Sauter, B., Spahr, L., Steuerwald, M., Stickel, F., Stieger, B., Wehr, K., Zala, G., Swiss Association for the Study of the Liver, Moradpour, D., Helbling, B., Cerny, A., De Gottardi, A., Heim, MH., Majno, P., Müllhaupt, B., Negro, F., Rubbia-Brandt, L., Semela, D., Vilei, SB., Bernsmeier, C., Bihl, F., Borovicka, J., Dill, M., Dufour, JF., Filipowicz, M., Geier, A., Gerlach, T., Giostra, E., Gonvers, JJ., Goossens, N., Gubler, C., Hadengue, A., Hellstern, M., Hirschi, C., Jochum, W., Krähenbühl, S., Kullak-Ublick, G., Lange, C., Lavanchy, D., Malinverni, R., McLin, V., Mentha, G., Mertens, JC., Nasser, S., Oneta, C., Pache, I., Sauter, B., Spahr, L., Steuerwald, M., Stickel, F., Stieger, B., Wehr, K., and Zala, G.

Abstract

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Two first-generation protease inhibitors, telaprevir and boceprevir, have recently been approved for the treatment of chronic hepatitis C genotype 1. Triple therapy comprising pegylated interferon-α, ribavirin and telaprevir or boceprevir increases sustained virological response rates to ~70% and allows to shorten treatment duration in ~½ of treatment-naïve patients with chronic hepatitis C genotype 1. Sustained virological response rates in treatment-experienced patients depend on the response to previous treatment, ranging from >80% in previous relapsers to ~30% in previous null responders. These advances come at the expense of new adverse effects and increased cost. In addition, treatment of chronic hepatitis C will become more complex. In these times of changing medical practice, the present expert opinion statement by the Swiss Association for the Study of the Liver shall provide guidance on the treatment of chronic hepatitis C with triple therapy comprising telaprevir or boceprevir.

Published
2012

18. Interferon-α (IFN) induction dosing and ribavirin (R) in IFN non-responders (NR) with chronic hepatitis C (CHC): Interim analysis of an ongoing study (SASL 10)

Author

Renner-Schneiter, E.C., primary, Dufour, J-F., additional, Fried, R., additional, Gonvers, J.J., additional, Knoblauch, M., additional, Malè, P.J., additional, Negro, F., additional, Reichen, J., additional, Rohner, C., additional, Steuerwald, M., additional, and Renner, E.L., additional

Published
2000
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21. Pilot Study of Interferon-α with and without Amantadine for the Treatment of Hepatitis C in HIV Co-infected Individuals on Antiretroviral Therapy.

Author

Sax, H., Friedl, A., Renner, E., Steuerwald, M. H., and Weber, R.

Subjects
INTERFERONS, AMANTADINE, HEPATITIS C, THERAPEUTICS, ANTIRETROVIRAL agents, DRUG interactions
Abstract

Background: Concurrent potent therapy of hepatitis C (HCV) and HIV includes at least five antiviral drugs. Drug interactions, toxicity, tolerance and acceptance by patients of such treatment regimens are unknown. Study design: A prospective open randomized pilot trial was conducted to test interferon-α (6 million units/day for the 1st month followed by 6 million thrice weekly) and amantadine versus interferon-α monotherapy for tolerability and feasibility among HIV and HCV co-infected patients on stable antiretroviral combination therapy. Results: 1,013 HIV-infected patients were consecutively evaluated. 314 were anti-HCV antibody positive; only eight (2.4%) were eligible. Major reasons for exclusion were: normal. transaminase levels (34%), ongoing intravenous drug use (33%), or recent change in antiretroviral. therapy (31%). Study drugs were stopped in all of the seven patients enrolled because of side effects and/or failure of anti-HCV therapy. CD4 lymphocyte counts and HIV-1 RNA remained stable. Conclusion: Among patients on highly active antiretroviral. therapy, the addition of interferon-α with or without amantadine was inefficient and poorly tolerated, but had no negative influence on HIV infection. Eligibility for the study was unexpectedly low. [ABSTRACT FROM AUTHOR]

Published
2001
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22. HIV--Enteropathy and Bile Acid Malabsorption: Response to Cholestyramine.

Author

Steuerwald, M., Bucher, H. C., Gyr, K., Müller-Brand, J., Götze, M., and Roser, H. W.

Subjects
DIARRHEA, INTESTINAL diseases, WEIGHT loss, AIDS patients, SPRUE, BILE acids, MALABSORPTION syndromes
Abstract

Chronic diarrhea and weight loss are common in patients with AIDS. We report on an AIDS patient with chronic diarrhea, steatorrhea, and marked weight loss. A 75SeHCAT test demonstrated that the diarrhea was mainly due to bile acid malabsorption. Therapy with cholestyramine dramatically reduced bowel movements and led to significant reversal of weight loss. [ABSTRACT FROM AUTHOR]

Published
1995

23. 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

24. 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

25. 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

26. 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

27. Initiation of Inhaled Nitric Oxide by an Air Transport Team in Adult Coronavirus Disease 2019 Respiratory Failure.

Author

Brown CJ, Rubel N, Lai J, Ward C, McLean J, Wheelock M, Steuerwald M, and Cathers A

Subjects
Administration, Inhalation, Adult, Humans, Nitric Oxide therapeutic use, COVID-19, Respiratory Distress Syndrome therapy, Respiratory Insufficiency therapy
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused a significant increase in the volume of critical care flight transports between outlying referral hospitals and tertiary care facilities. Because of the tropism of severe acute respiratory syndrome coronavirus 2, flight crews are often asked to transport mechanically ventilated patients in refractory hypoxemic respiratory failure. The authors present a case series of 5 patients with COVID-19 acute respiratory distress syndrome (ARDS) who were initiated on inhaled nitric oxide (iNO) by the transport team before rotor wing transport and survived the journey in stable or improved condition upon arrival. Previously, no case reports have described adults with COVID-19 ARDS transported after iNO initiation by the transport team. This case series shows the feasibility of iNO initiation by trained air medical transport teams and suggests a short-term stabilizing effect of iNO in patients with ARDS from COVID-19., (Copyright © 2022 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Published
2022
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28. Comparison of Hyperangulated and Standard Geometry Video Laryngoscopy Tracheal Intubation for Prehospital Care in a Manikin: A Randomized Controlled Crossover Trial.

Author

Lepa N, Cathers A, Emmerich K, Galgon R, Jennett B, Schroeder KM, and Steuerwald M

Subjects
Cross-Over Studies, Humans, Intubation, Intratracheal, Laryngoscopy, Manikins, Video Recording, Emergency Medical Services, Laryngoscopes
Abstract

Objective: The purpose of this study was to investigate the efficacy of hyperangulated video laryngoscopy (HAVL) versus standard geometry video laryngoscopy (SGVL) in the simulated prehospital environment using a manikin. There is consensus that video laryngoscopy (VL) can be very useful in the emergency department when difficult intubations are predicted. Emergency medical service (EMS) providers are also often faced with difficult, rapidly deteriorating airway management situations that not only involve patient and operator factors but also include challenging unique environmental factors, such as nonoptimized positions in transport vehicles (eg, helicopters and ambulances) or at ground level or entrapped positions. To our knowledge, there has never been a study purposefully investigating the efficacy of hyperangulated geometry versus standard geometry VL techniques in the prehospital environment., Methods: A single-center, randomized controlled crossover trial was performed using attending physician helicopter EMS providers. Physicians were randomized to perform 5 HAVL or SGVL intubations followed by the subsequent technique. Intubations were performed on ground level and then repeated in the helicopter with the first location also randomized. A manikin airway management trainer was used to simulate intubation in each environment. The time to intubation (primary outcome) as well as first-pass success and the Cormack-Lehane view were recorded for each attempt. Qualitative data were also obtained for physician preference and perceived difficulty., Results: There was no statistically significant difference in the time to intubation with HAVL versus SGVL (ground: 15.02 vs. 14.88 seconds, P = .86; helicopter: 16.11 vs. 16.14 seconds, P = .93). First-pass success was 100% for both techniques in both scenarios. More Grade 1 views were obtained with HAVL (147/150 vs. 134/150). Moreover, most physicians preferred HAVL overall and felt that HAVL required less force (9/15 grounded manikin and 10/15 helicopter manikin) and led to the best chance for first-pass success (11/15 grounded manikin and 10/15 helicopter manikin)., Conclusion: The results of this study are limited because of the static and highly favorable anatomy of a manikin versus the variability and often difficult anatomy of individual patients. Our results suggest that both techniques are efficacious when the patient is both on the ground or in the helicopter, although provider preference does seem to vary., (Published by Elsevier Inc.)

Published
2021
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31. Patients' and providers' perceptions of asthma and asthma care: a qualitative study.

Author

Mowrer JL, Tapp H, Ludden T, Kuhn L, Taylor Y, Courtlandt C, Alkhazraji T, Reeves K, Steuerwald M, Andrew M, and Dulin M

Subjects
Focus Groups, Health Expenditures, Humans, Medication Adherence, Patient Care Planning, Patient Education as Topic, Primary Health Care, Professional-Patient Relations, Qualitative Research, Self Care, Asthma psychology, Asthma therapy, Health Personnel psychology, Patients psychology
Abstract

Background: Differences in patients' and providers' perceptions of asthma and asthma care can create barriers to successful treatment. The primary goal of this qualitative study was to further explore patient and provider perceptions of asthma and asthma care as part of a larger Asthma Comparative Effectiveness Study., Methods: Focus groups held every 6 months for 3 years were designed to have a mix of both patients and providers allowing for unique understanding around asthma care., Results: The discussion centered on goal setting, asthma action plans and prevention strategies for asthma exacerbations. Three overarching themes, with a variety of subthemes, emerged as the main findings of this study. The three main themes were Cost/Economic Barriers/Process, Self-Governance/Adherence and Education., Conclusions: These themes indicated a strong need for patient educational interventions around asthma as well as education for providers around cost, insurance coverage and patient-centered communication. Specifically, education on learning to use inhalers properly, avoiding triggers and understanding the importance of a controller medication will benefit patients in the long-term management of asthma.

Published
2015
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32. Critical management of deadly pelvic injuries.

Author

Gerecht R, Larrimore A, and Steuerwald M

Subjects
Accidents, Traffic, Humans, Emergency Medical Services organization & administration, Emergency Treatment, Fractures, Bone therapy, Multiple Trauma therapy, Pelvic Bones injuries
Published
2014

33. Adapting community based participatory research (CBPR) methods to the implementation of an asthma shared decision making intervention in ambulatory practices.

Author

Tapp H, Kuhn L, Alkhazraji T, Steuerwald M, Ludden T, Wilson S, Mowrer L, Mohanan S, and Dulin MF

Subjects
Adolescent, Asthma diagnosis, Child, Child Welfare, Child, Preschool, Female, Health Plan Implementation, Humans, Male, Physician-Patient Relations, Risk Assessment, Severity of Illness Index, United States, Vulnerable Populations, Young Adult, Ambulatory Care methods, Asthma drug therapy, Community-Based Participatory Research methods, Decision Making, Outcome Assessment, Health Care
Abstract

Objective: Translating research findings into clinical practice is a major challenge to improve the quality of healthcare delivery. Shared decision making (SDM) has been shown to be effective and has not yet been widely adopted by health providers. This paper describes the participatory approach used to adapt and implement an evidence-based asthma SDM intervention into primary care practices., Methods: A participatory research approach was initiated through partnership development between practice staff and researchers. The collaborative team worked together to adapt and implement a SDM toolkit. Using the RE-AIM framework and qualitative analysis, we evaluated both the implementation of the intervention into clinical practice, and the level of partnership that was established. Analysis included the number of adopting clinics and providers, the patients' perception of the SDM approach, and the number of clinics willing to sustain the intervention delivery after 1 year., Results: All six clinics and physician champions implemented the intervention using half-day dedicated asthma clinics while 16% of all providers within the practices have participated in the intervention. Themes from the focus groups included the importance of being part the development process, belief that the intervention would benefit patients, and concerns around sustainability and productivity. One year after initiation, 100% of clinics have sustained the intervention, and 90% of participating patients reported a shared decision experience., Conclusions: Use of a participatory research process was central to the successful implementation of a SDM intervention in multiple practices with diverse patient populations.

Published
2014
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34. Use of community-based participatory research in primary care to improve healthcare outcomes and disparities in care.

Author

Tapp H, White L, Steuerwald M, and Dulin M

Subjects
Asthma therapy, Child, Child Welfare, Diabetes Mellitus therapy, Exercise Therapy statistics & numerical data, Female, Health Services Accessibility standards, Healthcare Disparities, Humans, Interprofessional Relations, Male, Maternal Welfare, Obesity therapy, Outcome Assessment, Health Care, Pregnancy, Program Evaluation, Vulnerable Populations, Community-Based Participatory Research statistics & numerical data, Primary Health Care standards
Abstract

Community-based participatory research (CBPR) has emerged to bridge the gap between research and primary-care practice through community engagement and social action to increase health equity. It is widely acknowledged that access to high-quality primary care services is important to the overall health of a community. Here, CBPR studies in a primary care setting are reviewed to assess the use of CBPR associated with common health problems seen in primary care such as access to care and disparities in chronic disease management across vulnerable populations. CBPR involves building relationships with local communities, determining areas of need and establishing priorities for health concerns. Studies showing improved access to care for a Hispanic population, reduced asthma symptoms and weight loss are highlighted.

Published
2013
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35. Incidence and predictors of repeated computed tomographic pulmonary angiography in emergency department patients.

Author

Kline JA, Courtney DM, Beam DM, King MC, and Steuerwald M

Subjects
Adult, Aged, Angiography statistics & numerical data, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Pulmonary Embolism epidemiology, Recurrence, Risk Factors, Tomography, X-Ray Computed statistics & numerical data, Angiography methods, Emergency Service, Hospital statistics & numerical data, Pulmonary Embolism diagnostic imaging, Tomography, X-Ray Computed methods
Abstract

Study Objective: Use of contrast-enhanced computed tomography (CT) of the pulmonary arteries to evaluate for pulmonary embolism has increased, raising concern about radiation and contrast toxicity. We sought to measure the frequency of repeat CT pulmonary angiography in emergency department (ED) patients., Methods: This was a prospective, longitudinal follow-up of ED patients who underwent first-time CT pulmonary angiography as part of a research protocol for diagnosis of pulmonary embolism in 2001 to 2002. Two authors (DMB and MCK) searched electronic medical record databases to measure the frequency of repeated CT scans performed within 5 years. Primary outcome was greater than or equal to 1 repeated CT pulmonary angiography examination. Radiologist-written interpretations of CT pulmonary angiography were categorized by 2 observers (DMB and JAK). Cox regression was used to estimate hazard ratios for 24 clinical variables., Results: A cohort of 675 ED patients was observed for a median of 1,989 days: 226 of 675 (33%) had at least 1 additional CT pulmonary angiography scan, and 60 died with no repeated CT pulmonary angiography, leading to a mortality-adjusted frequency of repeated CT pulmonary angiography scanning of 226 of 615, or 37%. Seventy-three percent of the cohort had 1 or more subsequent CT scans of any body part, and 31 patients (5%) had 5 or more repeated CT pulmonary angiography scans. The pulmonary embolism (positive) prevalence was 57 of 675 (8.4%; 95% confidence interval [CI] 6.5% to 10.8%) on the first CT pulmonary angiography versus 8 of 226 (3.5%; 95% CI 1.5% to 6.9%) on the second CT pulmonary angiography scan. Hazard ratios indicated that respiratory rate, active malignancy, previous coronary artery disease, and previous or new diagnosis of venous thromboembolism were positively associated with repeated CT pulmonary angiography scanning., Conclusion: At least one third of ED patients who undergo CT pulmonary angiography scanning will have a second CT pulmonary angiography result that will be negative for pulmonary embolism. New methods are needed to exclude pulmonary embolism recurrence without use of ionizing radiation.

Published
2009
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36. Palmoplantar pustulosis and acrodermatitis in a patient treated with infliximab for Crohn's sacroiliitis.

Author

Wermuth J, Kind F, and Steuerwald M

Subjects
Acrodermatitis pathology, Adult, Anti-Inflammatory Agents therapeutic use, Antibodies, Monoclonal therapeutic use, Female, Humans, Infliximab, Skin Diseases, Infectious pathology, Acrodermatitis etiology, Anti-Inflammatory Agents adverse effects, Antibodies, Monoclonal adverse effects, Crohn Disease drug therapy, Skin Diseases, Infectious etiology
Published
2009
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37. [Esophageal intramural pseudodiverticulosis].

Author

Manz M, Meier R, Schaub N, Toia D, and Steuerwald M

Subjects
Aged, Candidiasis complications, Candidiasis diagnosis, Diagnosis, Differential, Dilatation, Diverticulosis, Esophageal complications, Esophageal Stenosis complications, Esophageal Stenosis therapy, Esophagitis complications, Esophagitis diagnosis, Esophagoscopy, Female, Humans, Male, Middle Aged, Treatment Outcome, Deglutition Disorders etiology, Diverticulosis, Esophageal diagnosis, Esophageal Stenosis diagnosis
Abstract

We report two cases of esophageal intramural pseudodiverticulosis (EIPD). EIPD is a rare condition characterized by multiple flask-shaped outpouchings in the esophageal wall representing dilated excretory ducts of submucosal glands. Dysphagia is the leading symptom. On endoscopy, minute openings in the esophageal wall, and sometimes a segmental candida esophagitis or a benign stenosis not originating from an erosive reflux esophagitis are found.

Published
2007
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38. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis.

Author

Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, Zala JF, Helbling B, Steuerwald M, and Zimmermann A

Subjects
Adolescent, Adult, Aged, Biopsy, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Liver Cirrhosis enzymology, Liver Cirrhosis pathology, Male, Middle Aged, Retrospective Studies, Transaminases blood, Treatment Outcome, Cholagogues and Choleretics therapeutic use, Liver Cirrhosis drug therapy, Ursodeoxycholic Acid therapeutic use, Vitamin E therapeutic use, Vitamins therapeutic use
Abstract

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy. UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective. This study tested their combination., Methods: Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were randomly assigned to receive UDCA 12-15 mg.kg-1.day-1 with vitamin E 400 IU twice a day (UDCA/Vit E), UDCA with placebo (UDCA/P), or placebo/placebo (P/P). After 2 years, they underwent a second liver biopsy. Biopsy specimens were collected, blinded, and scored by a single liver pathologist., Results: Forty eight patients were included, 15 in the UDCA/Vit E group, 18 in the UDCA/P group, and 15 in the P/P group; 8 patients dropped out, none because of side effects. Baseline parameters were not significantly different between the 3 groups. Body mass index remained unchanged during the study. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels diminished significantly in the UDCA/Vit E group. Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group. Histologically, the activity index was unchanged at the end of the study in the P/P and UDCA/P groups, but it was significantly better in the UDCA/Vit E group, mostly as a result of regression of steatosis., Conclusions: Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH. Larger trials are warranted.

Published
2006
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39. End expiratory oxygen concentrations to predict central venous oxygen saturation: an observational pilot study.

Author

Jones AE, Kuehne K, Steuerwald M, and Kline JA

Abstract

Background: A non-invasive surrogate measurement for central venous oxygen saturation (ScVO2) would be useful in the ED for assessing therapeutic interventions in critically ill patients. We hypothesized that either linear or nonlinear mathematical manipulation of the partial pressure of oxygen in breath at end expiration (EtO2) would accurately predict ScVO2., Methods: Prospective observational study of a convenience sample of hemodialysis patients age > 17 years with existing upper extremity central venous catheters were enrolled. Using a portable respiratory device, we collected both tidal breathing and end expiratory oxygen and carbon dioxide concentrations, volume and flow on each patient. Simultaneous ScVO2 measurements were obtained via blood samples collected from the hemodialysis catheter. Two models were used to predict ScVO2: 1) Best-fit multivariate linear regression equation incorporating all respiratory variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume using the least squares method to estimate the pO2 that would occur at <20% of total lung capacity., Results: From 21 patients, the correlation between EtO2 and measured ScVO2 yielded R2 = 0.11. The best fit multivariate equation included EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute difference from the measured ScVO2 of 8 +/- 6% (range -18 to +17%). The predicted ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling of the EtO2 curve did not accurately predict ScVO2 at any lung volume., Conclusion: We found no significant correlation between EtO2 and ScVO2. A linear equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for ScVO2.

Published
2006
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40. First case of ivermectin-induced severe hepatitis.

Author

Veit O, Beck B, Steuerwald M, and Hatz C

Subjects
Adult, Animals, Cameroon, Female, Humans, Loa isolation & purification, Microfilariae isolation & purification, Antiparasitic Agents adverse effects, Chemical and Drug Induced Liver Injury etiology, Ivermectin adverse effects, Loiasis drug therapy
Abstract

Loiasis, caused by the filarial parasite Loa loa, is endemic in West and Central Africa. Ivermectin has been shown to be an effective treatment of loiasis. We report the case of a 20-year-old woman originally from Cameroon who was infected by the L. loa parasite and developed severe hepatitis, identified 1 month after a single dose of ivermectin. Liver biopsy showed intralobular inflammatory infiltrates, confluent necrosis and apoptosis, compatible with drug-induced liver disease. To our knowledge, this is the first case of ivermectin-induced severe liver disease published in the literature.

Published
2006
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41. Place of probiotics.

Author

Meier R and Steuerwald M

Subjects
Colitis, Ulcerative diet therapy, Crohn Disease diet therapy, Dysentery diet therapy, Humans, Inflammatory Bowel Diseases diet therapy, Perioperative Care methods, Pouchitis diet therapy, Critical Care methods, Gastrointestinal Diseases diet therapy, Probiotics therapeutic use
Abstract

Purpose of Review: This review reports on the recent progress understanding mechanisms of action and clinical applications of probiotics., Recent Findings: New insights on regulating mechanisms of intestinal commensal bacteria to prevent and treat different gastrointestinal diseases have been reported. Some probiotics, though not all, exert beneficial effects by modulating the mucosal barrier function and immune activity. It seems that a combination of different probiotics is more effective than a single strain. It was demonstrated that not only viable bacteria administered to the intestinal tract but also isolated probiotic DNA is active, even if injected subcutaneously. There is reasonable evidence to recommend probiotics in infectious diarrhoea for prevention and treatment (mainly in children) and to prevent antibiotic-induced gastrointestinal side effects. Furthermore, probiotics are effective in maintaining remission in ulcerative colitis and preventing and treating pouchitis. Promising positive effects were published in major surgery patients (gastric resection, pancreatic resection, liver transplantation) and in severe necrotising acute pancreatitis., Summary: Increasing knowledge on probiotics is exciting, but in the near future it must be defined which probiotics (single strains or a combination) are most effective in specific diseases. Well-designed, randomized clinical trials are still required to further define the role of probiotics as preventive and therapeutic agents.

Published
2005
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42. Obstructive jaundice caused by enteropathy-associated T-cell lymphoma in a patient with celiac sprue.

Author

Buess M, Steuerwald M, Wegmann W, and Rothen M

Subjects
Biopsy, Duodenal Neoplasms complications, Gallbladder Diseases complications, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Tomography, X-Ray Computed, Celiac Disease complications, Jaundice, Obstructive etiology, Lymphoma, T-Cell complications
Abstract

Patients with celiac sprue carry a considerable risk of gastrointestinal malignancies; in particular, non-Hodgkin's lymphoma. These malignancies represent the most serious complications of celiac disease. Commonly, patients present with deteriorating symptoms of the underlying disease, which makes an early diagnosis difficult. We report a patient with a 13-year history of celiac sprue presenting with painless jaundice and a Courvoisier gallbladder. Abdominal computed tomography (CT) scan showed thickening of the duodenal wall, suggesting a neoplastic infiltration of the papilla of Vater, causing biliary obstruction. Biopsies taken on endoscopy revealed enteropathy-associated T-cell lymphoma of the duodenum. Biliary obstruction is a rare clinical finding in enteropathy-associated T-cell lymphoma. To our knowledge, this is the first reported case of this unusual manifestation in celiac disease.

Published
2004
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43. [Fever, malaise and new onset mitral valve insufficiency. Subacute Streptococcus bovis mitral valve endocarditis ].

Author

Burri E, Laffer R, Steuerwald M, Cathomas G, and Zimmerli W

Subjects
Diagnosis, Differential, Echocardiography, Endocarditis, Subacute Bacterial diagnostic imaging, Endocarditis, Subacute Bacterial pathology, Humans, Male, Middle Aged, Mitral Valve Insufficiency diagnostic imaging, Streptococcal Infections diagnostic imaging, Streptococcal Infections pathology, Endocarditis, Subacute Bacterial diagnosis, Fever of Unknown Origin etiology, Mitral Valve Insufficiency etiology, Streptococcal Infections diagnosis, Streptococcus bovis
Abstract

A 62-year-old patient with low grade fever, fatigue, arthralgia and newly discovered mitral regurgitation was diagnosed with subacute endocarditis. Streptococcus bovis grew from all six blood culture bottles. Streptococcus bovis is known to be associated with gastrointestinal neoplasias. Therefore a colonoscopy was performed and two polyps were removed. Histological analysis revealed a tubulovillous adenoma and a serrated adenoma. Colonoscopy is mandatory for all patients with Streptococcus bovis endocarditis even without any symptoms for colorectal neoplasia. The significance of Streptococcus bovis for the carcinogenesis of colorectal neoplasias and the possible alternative pathway for colorectal carcinomas through serrated adenomas will be discussed.

Published
2004
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44. The role of nutrition in diarrhoea syndromes.

Author

Meier R, Burri E, and Steuerwald M

Subjects
Acute Disease, Anti-Bacterial Agents adverse effects, Child, Enteral Nutrition adverse effects, Female, Fluid Therapy, Humans, Male, Probiotics therapeutic use, Zinc therapeutic use, Diarrhea prevention & control, Diarrhea therapy
Abstract

Purpose of Review: Diarrhoea is a common and worldwide problem, accounting for significant morbidity and mortality, especially in children. This paper reviews recent advances in the field of nutritional intervention for the prevention and treatment of diarrhoeal diseases., Recent Findings: In the developing countries, the incidence of diarrhoeal diseases remains unchanged, whereas in industrialized areas a decrease has been reported. In acute diarrhoea, oral rehydration therapy is the treatment of first choice. Newer oral rehydration solutions with amylase-resistant starch or partially hydrolysed guar gum have been tested and found to be useful. Promising new data on supplementation with zinc in acute diarrhoea were published last year. The use of prebiotics and probiotics in the prevention and the treatment of diarrhoea is still controversial. However, new data and meta-analyses with probiotics are available, showing benefits in the treatment of acute diarrhoea as a co-treatment with oral rehydration. The same benefits were found to apply to antibiotic-associated diarrhoea syndromes. The co-administration of probiotics to patients receiving antibiotics seems to be a promising approach for reducing the incidence of antibiotic-associated diarrhoea. New evidence suggests that fibre reduces diarrhoea associated with enteral tube feeding. Furthermore, a new probiotic mixture (VSL-3, viable lyophilized bacteria of 4 strains of Lactobacillus, 3 strains of Bifidobacterium and 1 strain of Streptococcus thermophilus (VSL Pharmaceuticals, Inc,. Ft. Lauderdale, FL. USA)) was of benefit in the treatment of bacterial overgrowth and in the prevention of diarrhoea after pelvic radiation treatment., Summary: Oral rehydration is still the first line of treatment for acute diarrhoea. Zinc supplements have been shown to have a beneficial effect on acute diarrhoea in children. Probiotics and fibre have proved to be useful in the prevention and treatment of several diarrhoea syndromes. Because of the small numbers of patients and shortcomings in design and analysis, additional large placebo-controlled trials of the effects of fibre and probiotics, or a combination of both, in diarrhoea syndromes are needed.

Published
2003
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45. [Cystic space-occupying lesion of the liver as an incidental finding. Symptomatic Echinococcus granulosus cyst of the right hepatic lobe].

Author

Burri E, Steuerwald M, Maurer CA, Toia D, Cathomas G, and Meier R

Subjects
Adult, Diagnosis, Differential, Female, Humans, Hypertrophy, Intestines diagnostic imaging, Lymph Nodes pathology, Male, Mesentery diagnostic imaging, Middle Aged, Ultrasonography, Intestinal Diseases diagnostic imaging, Lymph Nodes diagnostic imaging
Published
2003
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46. Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial.

Author

Helbling B, Stamenic I, Viani F, Gonvers JJ, Dufour JF, Reichen J, Cathomas G, Steuerwald M, Borovicka J, Sagmeister M, and Renner EL

Subjects
Adult, Amantadine adverse effects, Amantadine economics, Antiviral Agents adverse effects, Antiviral Agents economics, Cost-Benefit Analysis, Double-Blind Method, Female, Humans, Interferon alpha-2, Interferon-alpha adverse effects, Interferon-alpha economics, Male, Middle Aged, Placebos, Recombinant Proteins, Treatment Outcome, Amantadine therapeutic use, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Interferon-alpha therapeutic use
Abstract

Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.

Published
2002
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47. Pilot study of interferon-alpha with and without amantadine for the treatment of hepatitis C in HIV coinfected individuals on antiretroviral therapy.

Author

Sax H, Friedl A, Renner E, Steuerwald MH, and Weber R

Subjects
Adult, Amantadine administration & dosage, Amantadine adverse effects, Antiviral Agents administration & dosage, Antiviral Agents adverse effects, CD4 Lymphocyte Count, Drug Interactions, Female, Hepatitis C etiology, Humans, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Male, Middle Aged, Patient Compliance, Patient Selection, Prospective Studies, Amantadine pharmacology, Antiviral Agents pharmacology, HIV Infections complications, Hepatitis C drug therapy, Interferon-alpha pharmacology
Abstract

Background: Concurrent potent therapy of hepatitis C (HCV) and HIV includes at least five antiviral drugs. Drug interactions, toxicity, tolerance and acceptance by patients of such treatment regimens are unknown., Study Design: A prospective open randomized pilot trial was conducted to test interferon-alpha (6 million units/day for the 1st month followed by 6 million thrice weekly) and amantadine versus interferon-alpha monotherapy for tolerability and feasibility among HIV and HCV co-infected patients on stable antiretroviral combination therapy., Results: 1,013 HIV-infected patients were consecutively evaluated. 314 were anti-HCV antibody positive; only eight (2.4%) were eligible. Major reasons for exclusion were: normal transaminase levels (34%), ongoing intravenous drug use (33%), or recent change in antiretroviral therapy (31%). Study drugs were stopped in all of the seven patients enrolled because of side effects and/or failure of anti-HCV therapy. CD4 lymphocyte counts and HIV-1 RNA remained stable., Conclusion: Among patients on highly active antiretroviral therapy, the addition of interferon-alpha with or without amantadine was inefficient and poorly tolerated, but had no negative influence on HIV infection. Eligibility for the study was unexpectedly low.

Published
2001
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48. A prospective study of endoscopy in HIV-associated diarrhea.

Author

Kearney DJ, Steuerwald M, Koch J, and Cello JP

Subjects
Adult, Biopsy, Colon pathology, Diarrhea microbiology, Diarrhea pathology, Duodenum pathology, Female, HIV Enteropathy microbiology, HIV Enteropathy pathology, Humans, Ileum pathology, Male, Middle Aged, Prospective Studies, Sensitivity and Specificity, AIDS-Related Opportunistic Infections diagnosis, Diarrhea etiology, Endoscopy, Gastrointestinal, HIV Enteropathy diagnosis
Abstract

Objective: Diarrhea commonly occurs in persons with human immunodeficiency virus (HIV) infection. The optimal use of endoscopic procedures remains poorly studied for patients with HIV-related diarrhea. The purpose of this study is to compare the diagnostic yield of a complete endoscopic work-up including an esophagogastroduodenoscopy and colonoscopy to a more limited approach of biopsies obtainable by flexible sigmoidoscopy., Methods: A prospective study of 79 patients with HIV-related diarrhea. Upper endoscopy and colonoscopy were performed with tissue biopsies labelled according to location within the colon or small intestine., Results: A new infection was diagnosed in 22 of 79 patients (28%). Biopsy of the left colon yielded an enteric pathogen in 17 of 22 patients (sensitivity: 77%) and in 15 of 15 patients with cytomegalovirus colitis (sensitivity: 100%). Combined left and right colonic biopsies had a sensitivity of 82%. Combined colonic and terminal ileum biopsies missed no pathogens. Duodenal biopsies yielded no additional pathogens beyond those identified by colonoscopy and terminal ileal biopsy. Patients with a new pathogen diagnosed had significantly lower CD4 lymphocyte counts as compared to patients without a new pathogen (p = 0.001)., Conclusions: For patients with CD4 counts < 100/mm3 and unexplained AIDS-related diarrhea, flexible sigmoidoscopy with biopsy is a sufficiently thorough endoscopic evaluation.

Published
1999
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49. The Fas receptor in HIV infection: expression on peripheral blood lymphocytes and role in the depletion of T cells.

Author

Gehri R, Hahn S, Rothen M, Steuerwald M, Nuesch R, and Erb P

Subjects
Animals, Antigens, CD biosynthesis, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Cytotoxicity, Immunologic, Flow Cytometry, Humans, Lymphocyte Cooperation, Mice, T-Lymphocytes, Cytotoxic immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, fas Receptor biosynthesis
Abstract

Objective: To analyse the role of the apoptosis-inducing Fas receptor in the depletion of CD4+ and CD8+ T cells in HIV-infected individuals., Methods: Peripheral blood lymphocytes (PBL) obtained from HIV-infected subjects of all 1993 Centers for Disease Control and Prevention (CDC) stages and from non-infected controls were examined. A two-colour cytofluorometry was employed using monoclonal antibodies against Fas receptor (CD95) in combination with the surface markers CD4, CD8, CD28, CD26 and CD45RO. CD4+ and CD8+ T-cell-enriched PBL were used as target cells to assess their susceptibility to lysis by CD4+ cytotoxic T lymphocytes (CTL) which kill via the Fas pathway., Results: Fas+PBL are more elevated in HIV-infected individuals than in HIV-negative controls and increase significantly from CDC stages A to C. Whereas Fas+CD4+ and Fas-CD4+ T-cell populations decline in parallel with the progression of HIV infection, the Fas+CD8+, but not of the Fas-CD8+ fraction, significantly increases. The Fas+CD8+ lymphocytes are susceptible to Fas-mediated lysis as they are efficiently killed by Fas-ligand+CD4+CTL., Conclusion: The Fas receptor may contribute, but not as a unique cause, to the decline of CD4+ T cells in HIV-infected individuals. This and the significant increase of the number of Fas+ CD8+ T cells indicates that Fas-mediated immune regulation is disturbed.

Published
1996

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