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1. 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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2. Differences in Outcomes Reported by Patients With Inflammatory Bowel Diseases vs Their Health Care Professionals

Author

Valérie E.H. Pittet, Michel H. Maillard, Thomas Simonson, Nicolas Fournier, Gerhard Rogler, Pierre Michetti, Claudia Anderegg, Peter Bauerfeind, Christoph Beglinger, Stefan Begré, Dominique Belli, José M. Bengoa, Luc Biedermann, Beat Bigler, Janek Binek, Mirjam Blattmann, Stephan Boehm, Jan Borovicka, Christian P. Braegger, Nora Brunner, Patrick Bühr, Bernard Burnand, Emanuel Burri, Sophie Buyse, Matthias Cremer, Dominique H. Criblez, Philippe de Saussure, Lukas Degen, Joakim Delarive, Christopher Doerig, Barbara Dora, Gian Dorta, Mara Egger, Tobias Ehmann, Ali El-Wafa, Matthias Engelmann, Jessica Ezri, Christian Felley, Markus Fliegner, Montserrat Fraga, Pascal Frei, Remus Frei, Michael Fried, Florian Froehlich, Christian Funk, Raoul Ivano Furlano, Suzanne Gallot-Lavallée, Martin Geyer, Marc Girardin, Delphine Golay, Tanja Grandinetti, Beat Gysi, Horst Haack, Johannes Haarer, Beat Helbling, Peter Hengstler, Denise Herzog, Cyrill Hess, Klaas Heyland, Thomas Hinterleitner, Philippe Hiroz, Claudia Hirschi, Petr Hruz, Rika Iwata, Res Jost, Pascal Juillerat, Céline Keller, Christina Knellwolf, Christoph Knoblauch, Henrik Köhler, Rebekka Koller, Claudia Krieger-Grübel, Gerd Kullak-Ublick, Patrizia Künzler, Markus Landolt, Rupprecht Lange, Frank Serge Lehmann, Andrew Macpherson, Philippe Maerten, Christine Manser, Michael Manz, Urs Marbet, George Marx, Christoph Matter, Rémy Meier, Martina Mendanova, Benjamin Misselwitz, Bernhard Morell, Patrick Mosler, Christian Mottet, Christoph Müller, Pascal Müller, Beat Müllhaupt, Claudia Münger-Beyeler, Leilla Musso, Andreas Nagy, Michaela Neagu, Cristina Nichita, Jan Niess, Andreas Nydegger, Nicole Obialo, Carl Oneta, Cassandra Oropesa, Ueli Peter, Daniel Peternac, Laetitia Marie Petit, Franziska Piccoli-Gfeller, Julia Beatrice Pilz, Valérie Pittet, Nadia Raschle, Ronald Rentsch, Sophie Restellini, Jean-Pierre Richterich, Sylvia Rihs, Marc Alain Ritz, Jocelyn Roduit, Daniela Rogler, Jean-Benoît Rossel, Vanessa Rueger, Gaby Saner, Bernhard Sauter, Mikael Sawatzki, Michela Schäppi, Michael Scharl, Sylvie Scharl, Martin Schelling, Susanne Schibli, Hugo Schlauri, Sybille Schmid Uebelhart, Jean-François Schnegg, Alain Schoepfer, Frank Seibold, Mariam Seirafi, Gian-Marco Semadeni, David Semela, Arne Senning, Marc Sidler, Christiane Sokollik, Johannes Spalinger, Holger Spangenberger, Philippe Stadler, Michael Steuerwald, Alex Straumann, Bigna Straumann-Funk, Michael Sulz, Alexandra Suter, Joël Thorens, Sarah Tiedemann, Radu Tutuian, Stephan Vavricka, Francesco Viani, Jürg Vögtlin, Roland Von Känel, Alain Vonlaufen, Dominique Vouillamoz, Rachel Vulliamy, Jürg Wermuth, Helene Werner, Paul Wiesel, Reiner Wiest, Tina Wylie, Jonas Zeitz, Dorothee Zimmermann, and Petit, Laëtitia Marie

Subjects
PRO, Adult, Diarrhea, Male, medicine.medical_specialty, Abdominal pain, SF-36, Adolescent, Disease, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Quality of life, Crohn Disease, Internal medicine, Physicians, Health care, medicine, Humans, Immunologic Factors, Patient Reported Outcome Measures, Antidiarrheals, Aged, Aged, 80 and over, Crohn's disease, ddc:618, Hepatology, business.industry, Gastroenterology, Middle Aged, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Management, Abdominal Pain, 030220 oncology & carcinogenesis, Cohort, Quality of Life, 030211 gastroenterology & hepatology, Patient-reported outcome, Colitis, Ulcerative, Female, Tumor Necrosis Factor Inhibitors, Disease Activity Index, medicine.symptom, business, Fecal Incontinence
Abstract

Background & Aims Inflammatory bowel disease (IBD) scoring systems combine patient-reported data with physicians’ observations to determine patient outcomes, but these systems are believed to have limitations. We used real-world data from a large IBD cohort in Switzerland to compare results between patients and healthcare professionals from scoring systems for Crohn’s disease (CD) and ulcerative colitis (UC). Methods We collected data from the Swiss IBD cohort, beginning in 2006, using 2453 reports for 1385 patients (52% female, 58% with CD). During office visits, physicians asked patients about signs and symptoms and recorded their answers (health care professional-reported outcomes). On a later date, patients received a questionnaire at home (independently of the medical visit), complete it, and sent it back to the data center. Patients also completed the short form 36 and IBD quality of life (QoL) questionnaires. We calculated Cohen’s kappa (κ) statistics to assess the level of agreement in scores between patients and health care professionals (Δt between reports collected less than 2 months apart). We used Spearman correlation coefficients (ρ) to compare general well-being (GWB) and QoL scores determined by patients vs health care professionals. Our primary aim was to investigate the overall and individual level of agreement on signs and symptoms reported by health care professionals vs patients. Results The best level of agreement (although moderate) was observed for number of stools last week in patients with CD (κ = 0.47), and nocturnal diarrhea in patients with UC (κ = 0.52). Agreement was low on level of abdominal pain (κ = 0.31 for patients with CD and κ = 0.37 for patients with UC) and GWB (κ = 0.23 for patients with CD and κ = 0.26 for patients with UC). Patients reported less severe abdominal pain and worse GWB (CD) or better GWB (UC) than that determined by health care professionals. Patient self-rated GWB correlated with IBD quality of life (ρ = 0.68 for patients with CD and ρ = 0.70 for patients with UC) and SF-36 physical scores (ρ = 0.55 for patients with CD and ρ = 0.60 for patients with UC); there was no correlation between health care professional-rated GWB and QoL. Conclusions In a comparison of patient vs health care provider-reported outcomes in a Swiss IBD cohort, we found that health care professionals seem to misinterpret patients’ complaints. Patients self-rated GWB correlated with QoL scores, indicating that reporting GWB in a single question is possible and relevant, but can vary based on how the data are collected.

Published
2018

3. Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease

Author

Antonina Mikocka-Walus, Valerie Pittet, Jean-Benoît Rossel, Roland von Känel, Claudia Anderegg, Peter Bauerfeind, Christoph Beglinger, Stefan Begré, Dominique Belli, José M. Bengoa, Luc Biedermann, Beat Bigler, Janek Binek, Mirjam Blattmann, Stephan Boehm, Jan Borovicka, Christian P. Braegger, Nora Brunner, Patrick Bühr, Bernard Burnand, Emanuel Burri, Sophie Buyse, Matthias Cremer, Dominique H. Criblez, Philippe de Saussure, Lukas Degen, Joakim Delarive, Christopher Doerig, Barbara Dora, Gian Dorta, Mara Egger, Tobias Ehmann, Ali El-Wafa, Matthias Engelmann, Jessica Ezri, Christian Felley, Markus Fliegner, Nicolas Fournier, Montserrat Fraga, Pascal Frei, Remus Frei, Michael Fried, Florian Froehlich, Christian Funk, Raoul Ivano Furlano, Suzanne Gallot-Lavallée, Martin Geyer, Marc Girardin, Delphine Golay, Tanja Grandinetti, Beat Gysi, Horst Haack, Johannes Haarer, Beat Helbling, Peter Hengstler, Denise Herzog, Cyrill Hess, Klaas Heyland, Thomas Hinterleitner, Philippe Hiroz, Claudia Hirschi, Petr Hruz, Rika Iwata, Res Jost, Pascal Juillerat, Vera Kessler Brondolo, Christina Knellwolf, Christoph Knoblauch, Henrik Köhler, Rebekka Koller, Claudia Krieger-Grübel, Gerd Kullak-Ublick, Patrizia Künzler, Markus Landolt, Rupprecht Lange, Frank Serge Lehmann, Andrew Macpherson, Philippe Maerten, Michel H. Maillard, Christine Manser, Michael Manz, Urs Marbet, George Marx, Christoph Matter, Valérie McLin, Rémy Meier, Martina Mendanova, Christa Meyenberger, Pierre Michetti, Benjamin Misselwitz, Darius Moradpour, Bernhard Morell, Patrick Mosler, Christian Mottet, Christoph Müller, Pascal Müller, Beat Müllhaupt, Claudia Münger-Beyeler, Leilla Musso, Andreas Nagy, Michaela Neagu, Cristina Nichita, Jan Niess, Natacha Noël, Andreas Nydegger, Nicole Obialo, Carl Oneta, Cassandra Oropesa, Ueli Peter, Daniel Peternac, Laetitia Marie Petit, Franziska Piccoli-Gfeller, Julia Beatrice Pilz, Valérie Pittet, Nadia Raschle, Ronald Rentsch, Sophie Restellini, Jean-Pierre Richterich, Sylvia Rihs, Marc Alain Ritz, Jocelyn Roduit, Daniela Rogler, Gerhard Rogler, Markus Sagmeister, Gaby Saner, Bernhard Sauter, Mikael Sawatzki, Michela Schäppi, Michael Scharl, Martin Schelling, Susanne Schibli, Hugo Schlauri, Sybille Schmid Uebelhart, Jean-François Schnegg, Alain Schoepfer, Frank Seibold, Mariam Seirafi, Gian-Marco Semadeni, David Semela, Arne Senning, Marc Sidler, Christiane Sokollik, Johannes Spalinger, Holger Spangenberger, Philippe Stadler, Michael Steuerwald, Alex Straumann, Bigna Straumann-Funk, Michael Sulz, Joël Thorens, Sarah Tiedemann, Radu Tutuian, Stephan Vavricka, Francesco Viani, Jürg Vögtlin, Roland Von Känel, Alain Vonlaufen, Dominique Vouillamoz, Rachel Vulliamy, Jürg Wermuth, Helene Werner, Paul Wiesel, Reiner Wiest, Tina Wylie, Jonas Zeitz, and Dorothee Zimmermann

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Anxiety, Hospital Anxiety and Depression Scale, Inflammatory bowel disease, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Switzerland/epidemiology, Recurrence, Internal medicine, medicine, Humans, Prospective Studies, Depression (differential diagnoses), Aged, Aged, 80 and over, Crohn's disease, ddc:618, Hepatology, business.industry, Depression, Inflammatory Bowel Diseases/complications/psychology, Anxiety/epidemiology/pathology, Gastroenterology, Depression/epidemiology/pathology, Middle Aged, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, Crohn's Disease Activity Index, digestive system diseases, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Physical therapy, 030211 gastroenterology & hepatology, Female, medicine.symptom, business, Switzerland
Abstract

Background & Aims We examined the relationship between symptoms of depression and anxiety and clinical recurrence of inflammatory bowel disease (IBD) in a large patient cohort. We considered the progression of depression and anxiety over time. Methods We collected clinical and treatment data on 2007 adult participants of the Swiss IBD study (56% with Crohn's disease [CD], 48% male) performed in Switzerland from 2006 through 2015. Depression and anxiety symptoms were quantified by using the Hospital Anxiety and Depression Scale. The relationship between depression and anxiety scores and clinical recurrence was analyzed by using survival-time techniques. Results We found a significant association between symptoms of depression and clinical recurrence over time (for all patients with IBD, P = .000001; for subjects with CD, P = .0007; for subjects with ulcerative colitis, P = .005). There was also a significant relationship between symptoms of anxiety and clinical recurrence over time in all subjects with IBD ( P = .0014) and in subjects with CD ( P = .031) but not ulcerative colitis ( P = .066). Conclusions In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

Published
2016

4. Long-standing type II diabetes mellitus is not a risk factor for slow gastric emptying in critically ill patients

Author

Ross N. Butler, Nam Q. Nguyen, Richard H. Holloway, Geoffrey P. Davidson, Marianne J. Chapman, Betty Zacharakis, Laura K. Bryant, Robert J. Fraser, Marc A Ritz, Nguyen, Nam, Chapman, Marianne, Fraser, R, Ritz, Marc, Bryant, L, Butler, Ross Norman, Davidson, Geoffrey, Zacharakis, B, and Holloway, R

Subjects
Male, medicine.medical_specialty, critically ill, Critical Illness, Clinical Sciences, Gastric emptying, Type 2 diabetes, Critical Care and Intensive Care Medicine, Gastroenterology, Risk Factors, Internal medicine, Intensive care, Diabetes mellitus, medicine, Humans, Risk factor, APACHE, Retrospective Studies, Breath test, Chi-Square Distribution, medicine.diagnostic_test, APACHE II, business.industry, breath test, Stomach, Middle Aged, medicine.disease, Respiration, Artificial, medicine.anatomical_structure, Endocrinology, Breath Tests, Diabetes Mellitus, Type 2, Gastric Emptying, Case-Control Studies, diabetes mellitus, Female, business
Abstract

Delayed gastric emptying (GE) is common both in critical illness and in patients with diabetes mellitus (DM). The effect of DM on the incidence of slow GE in these patients is unknown. We evaluated the effect of DM on liquid GE in critically ill patients. Retrospective analysis of GE using a standard [13C]octanoic acid breath test in 12 type 2 DM patients compared with (a) 44 critically ill patients without DM, including (b) a subgroup of 15 age- and sex-matched patients and (c) 15 healthy volunteers. We determined the gastric emptying coefficient (GEC) and the gastric half-emptying time (t 50). Mean APACHE II scores, blood glucose levels and use of morphine were similar between patient groups. GE was faster in critically ill patients with DM (t 50 122 ± 11 min, GEC: 3.8 ± 0.3) than in patients without DM (t 50 168 ± 16 min, GEC 2.8 ± 0.1) and in age- and sex-matched controls (t 50 165 ± 13 min, GEC 2.7 ± 0.2) and was similar to that in healthy volunteers (t 50 148 ± 13 min, GEC 3.5 ± 0.1). The proportion of patients with slow emptying (GEC

Published
2006
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5. Erythromycin dose of 70 mg accelerates gastric emptying as effectively as 200 mg in the critically ill

Author

Deborah Rea, Marc A Ritz, Mark E. Finnis, Geoffrey P. Davidson, Robert J. Fraser, Marianne J. Chapman, Ross N. Butler, Patricia Cmielewski, Butler, Ross Norman, Ritz, Marc, Chapman, Marianne, Fraser, Robert, Finnis, M, Cmielewski, P, Davidson, Geoffrey, and Rea, Deborah

Subjects
Adult, Male, Critical Care, medicine.medical_treatment, Clinical Sciences, Erythromycin, Critical Care and Intensive Care Medicine, gastric emptying, Enteral Nutrition, Double-Blind Method, Gastrointestinal Agents, Intensive care, medicine, critical illness, Humans, Infusions, Intravenous, Saline, Aged, Antibacterial agent, Breath test, Gastrointestinal agent, Dose-Response Relationship, Drug, Gastric emptying, medicine.diagnostic_test, business.industry, breath test, Stomach, Middle Aged, Intensive Care Units, nutrition, medicine.anatomical_structure, Breath Tests, Gastric Emptying, erythromycin, Anesthesia, enteral feeding, Female, business, medicine.drug
Abstract

To compare the effectiveness of 70-mg and 200-mg doses of intravenous erythromycin in improving gastric emptying in critically ill patients. Gastric emptying was measured on consecutive days; day 1 (pre-treatment), day 2 (post-treatment) after an intravenous infusion of either 70 or 200 mg erythromycin or saline placebo (0.9%), in a randomized double-blind fashion. Mixed medical/surgical intensive care unit, tertiary referral. Thirty-five randomly selected, mechanically ventilated, enterally fed critically ill patients (median APACHE II score 19 on admission). On day 2 either 70 or 200 mg erythromycin or saline was administered intravenously over 20 min. Gastric emptying was measured using the [13C]octanoic acid breath test. The gastric emptying coefficient (GEC) and half-emptying time (t1/2) were calculated from the area under the 13CO2-recovery curve. Pre-treatment gastric emptying measurements were similar in all three patient groups. Treatment with both doses of erythromycin significantly reduced the gastric t1/2: 70 mg, 98 min (IQR 88–112); 200 mg, 86 min (75–104); vs. placebo, 122 min (102–190) (p

Published
2005
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6. Delayed gastric emptying in ventilated critically ill patients: Measurement by 13C-octanoic acid breath test

Author

Robert J. Fraser, Marianne J. Chapman, Jean-Pierre Tournadre, John Dent, Geoff Davidson, Marc A Ritz, Ross N. Butler, Patricia Cmielewski, Addolorata C. Di Matteo, and Nicholas A. Edwards

Subjects
Adult, Male, Artificial ventilation, medicine.medical_specialty, Critical Care, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Enteral administration, Enteral Nutrition, Intensive care, medicine, Humans, Intensive care medicine, APACHE, Aged, Aged, 80 and over, Mechanical ventilation, Breath test, medicine.diagnostic_test, Gastric emptying, Critically ill, business.industry, Carbon Dioxide, Middle Aged, Respiration, Artificial, Breath Tests, Gastric Emptying, Case-Control Studies, Anesthesia, Female, Caprylates, business
Abstract

To measure gastric emptying in ventilated critically ill patients with a new noninvasive breath test.Single-center, open study.Combined medical and surgical intensive care unit of a university hospital.Thirty unselected mechanically ventilated critically ill patients receiving gastric feeding and 22 healthy volunteers.None.After 4 hrs without feeding, intragastric infusion of 100 mL of a liquid meal (Ensure) labeled with 100 microL 13C-octanoic acid. End-expiratory breath samples were collected into evacuated tubes from the respirator circuit every 5 mins for the first hour, then every 15 mins for 3 hrs. End-expiratory breath samples were also collected from volunteers studied supine after an overnight fast following an identical infusion via a nasogastric tube. Breath 13CO2 was measured with an isotope ratio mass spectrometer.Performance of the breath test posed no difficulty or interference with patient care. The CO2 level was1% in 1297/1300 breath samples, indicating satisfactory end-expiratory timing. Data are median and interquartile range. Gastric emptying was slower in patients compared with volunteers: gastric emptying coefficient 2.93 (2.17-3.39) vs. 3.58 (3.18-3.79), p.001 and gastric half emptying time, derived from the area under the 13CO2 curve, 155 min (130-220) vs. 133 min (120-145), p.008. Fourteen of the 30 patients had a gastric emptying coefficient95% of all volunteers and 11 had a gastric half emptying time longer than 95% of all volunteers. The Acute Physiology and Chronic Health Evaluation (APACHE II) score (median 22, range 13-43) either at admission or on the day of the study did not correlate with gastric emptying coefficient.Gastric emptying of a calorie-dense liquid meal is slow in 40% to 45% of unselected mechanically ventilated patients in a combined medical and surgical intensive care unit. The 13C-octanoic acid breath test is a novel and useful bedside technique to measure gastric emptying in these patients.

Published
2001
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7. Impacts and patterns of disturbed gastrointestinal function in critically ill patients

Author

Marc A Ritz, Robert J. Fraser, John Dent, and William Tam

Subjects
medicine.medical_specialty, Critical Illness, Gastroenterology, Intestinal absorption, law.invention, Enteral Nutrition, Gastrointestinal Agents, law, Internal medicine, medicine, Humans, Gastrointestinal Transit, Intensive care medicine, Gastrointestinal agent, Hepatology, Gastric emptying, business.industry, medicine.disease, Intensive care unit, Intensive Care Units, Parenteral nutrition, Pulmonary aspiration, Gastric Emptying, Intestinal Absorption, Gastrointestinal Motility, Gastrointestinal function, business, Digestive System, Abnormal gastrointestinal motility
Abstract

Disordered upper gastrointestinal tract motility occurs frequently in intensive care unit patients and often represents a substantial treatment challenge. In addition to specific complications such as pulmonary aspiration and diarrhea, abnormal gastrointestinal motility is a limiting factor for delivery and success of enteral nutrition. The pathophysiologies involved are incompletely understood because of the difficulties of making measurements of gastrointestinal function in critically ill patients. With the recent development of techniques that overcome some of these difficulties, the prospects are brighter for significant advances in this field.

Published
2000
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8. The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects

Author

Pius Hildebrand, Jürgen Drewe, Pierre Schneider, Marc Alain Ritz, Christoph Beglinger, Najiba Lahlou, and Annette Ziel

Subjects
Adult, Male, medicine.medical_specialty, Gallbladder Emptying, Time Factors, Antineoplastic Agents, Administration, Cutaneous, Drug Administration Schedule, Gastric Acid, Placebos, chemistry.chemical_compound, Double-Blind Method, Internal medicine, Gastrins, medicine, Humans, Pharmacology (medical), Infusion Pumps, Gastrin, Cholecystokinin, Pharmacology, Vapreotide, Cross-Over Studies, Gastric emptying, business.industry, Gallbladder, Hydrogen-Ion Concentration, medicine.anatomical_structure, Somatostatin, Endocrinology, chemistry, Gastric acid, Original Article, business
Abstract

Aims Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. Methods Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day−1 s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. Results After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide’s effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. Conclusions The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.

Published
1999
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9. Haemodynamic and endocrinological effects of noninvasive mechanical ventilation in respiratory failure

Author

J. B. Thorens, M Vallotton, C Reynard, A Righetti, Philippe Jolliet, Marc A Ritz, U Kyle, J.-C. Chevrolet, and H Favre

Subjects
Male, Pulmonary and Respiratory Medicine, Cardiac output, medicine.medical_treatment, Positive pressure, Cardiac index, Hemodynamics, Nerve Tissue Proteins, Plasma renin activity, Intermittent Positive-Pressure Ventilation, Hypercapnia, Natriuretic Peptide, Brain, medicine, Edema, Humans, Pulmonary Wedge Pressure, Mechanical ventilation, Ejection fraction, business.industry, Middle Aged, Water-Electrolyte Balance, Hormones, Respiratory failure, Case-Control Studies, Anesthesia, Body Composition, Ventricular Function, Right, Female, Respiratory Insufficiency, business, Atrial Natriuretic Factor
Abstract

The aim of this study was to investigate the haemodynamic and endocrinological effects of noninvasive positive pressure ventilation (NIPPV). Eleven patients with oedema and recent hypercapnic and hypoxaemic worsening of a chronic respiratory insufficiency were included. Echocardiography, cardiac radionuclide assessment, blood catecholamines, salt and water handling hormones were measured at admission and discharge (long study (LS)). To discriminate between the action of NIPPV and other treatments, measurements were performed on the fourth day, for 4 h without NIPPV and 4 h with NIPPV (short study (SS)). NIPPV entailed a correction of P(a,CO2) and an increase of P(a,O2) in LS and SS. Oedema disappeared. Body weight decreased (from 85+/-42 to 81+/-40 kg) during LS. Systolic and mean pulmonary arterial pressure decreased in LS and SS. Right ventricular ejection fraction increased in LS. Left ventricular ejection fraction did not change. Cardiac index was normal on admission and then decreased. Natriuretic peptides and catecholamines were increased on admission, whereas plasma renin activity, aldosterone and vasopressin were normal. We suggest that in these patients, oedema can occur independently of renin-angiotensin-aldosterone-vasopressin and with a normal cardiac output. Noninvasive positive pressure ventilation allowed a correction of blood gases, associated with the resolution of oedema, a decrease in pulmonary arterial pressures and an increase in right ventricular ejection fraction.

Published
1997
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10. Nitric oxide and prostacyclin as test agents of vasoreactivity in severe precapillary pulmonary hypertension: predictive ability and consequences on haemodynamics and gas exchange

Author

Jean-Claude Chevrolet, P Bulpa, J B Thorens, Marc A Ritz, and P. Jolliet

Subjects
Pulmonary and Respiratory Medicine, Nifedipine, Hypertension, Pulmonary, Hemodynamics, Vasodilation, Prostacyclin, Nitric Oxide, medicine.artery, medicine, Humans, Antihypertensive Agents, Pulmonary Gas Exchange, business.industry, Calcium Channel Blockers, medicine.disease, Epoprostenol, Pulmonary hypertension, medicine.anatomical_structure, Blood pressure, Anesthesia, Papers, Pulmonary artery, Vascular resistance, business, medicine.drug
Abstract

BACKGROUND: In patients with primary pulmonary hypertension who respond to vasodilators acutely, survival can be improved by the long term use of calcium channel blockers. However, testing for such a response with calcium channel blockers or prostacyclin (PGI2) may cause hypotension and adversely affect gas exchange. Nitric oxide (NO), which does not have these effects, could be a better test agent. METHODS: NO (10, 20, and 40 ppm for 15 minutes), PGI2 (1-->10 ng/kg/min), and oral nifedipine (10 mg, then 20 mg/h) were administered sequentially to 10 patients after determination of the 24 hour spontaneous variability of their pulmonary and systemic mean arterial pressures. Patients were considered responders if the mean pulmonary artery pressure or pulmonary vascular resistance decreased by 20% or more. RESULTS: Six patients (60%) responded to all three agents, and three to none of the agents. One patient responded to PGI2 only. In those who responded to vasodilators, NO had no major effect on gas exchange or systemic haemodynamics, while PGI2 and nifedipine both induced systemic hypotension (mean (SD) systemic arterial pressure 72 (14) versus 89 (19) mm Hg with PGI2 and 72 (15) versus 86 (17) mm Hg with nifedipine, p < 0.05) and hypoxaemia (PaO2 8.7 (1.4) versus 10.8 (1.0) kPa with PGI2 and 8.6 (1.4) versus 10.2 (1.5) kPa with nifedipine, p < 0.05) and increased venous admixture (28 (9) versus 14 (4)% with PGI2 and 22 (9) versus 13 (5)% with nifedipine, p < 0.05). CONCLUSIONS: NO inhalation can accurately predict a vasodilator response to nifedipine in patients with severe pulmonary hypertension without adverse effects on systemic haemodynamics and gas exchange. This absence of side effects may make it a more appropriate agent for testing the vasodilator response.

Published
1997
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11. Evaluation of the 13C-triolein breath test for fat malabsorption in adult patients with cystic fibrosis

Author

Patricia Cmielewski, Addolorata C. Di Matteo, Hugh Greville, Ross N. Butler, Geoff Davidson, Robert J. Fraser, Marc A Ritz, Butler, Ross Norman, Ritz, Marc, Fraser, Robert, Di Matteo, Addolorata, Greville, Hugh, Cmielewski, P, and Davidson, G.P

Subjects
Adult, Male, medicine.medical_specialty, Pancreatic disease, Malabsorption, Cystic Fibrosis, malabsorption, Duodenum, Clinical Sciences, Administration, Oral, Enzyme Therapy, Gastroenterology, cystic fibrosis, gastric emptying, Malabsorption Syndromes, C-triolein, Internal medicine, Humans, Medicine, Ingestion, Pancreas, Breath test, Carbon Isotopes, Cross-Over Studies, Hepatology, Gastric emptying, medicine.diagnostic_test, business.industry, breath test, Middle Aged, medicine.disease, Dietary Fats, Crossover study, Effective dose (pharmacology), Fat malabsorption, Endocrinology, Breath Tests, Gastric Emptying, Female, business, Triolein, pancreatic exocrine failure
Abstract

Background and Aims: A simple non-invasive test not requiring the use of radioactive isotopes is required to assess fat malabsorption in adult cystic fibrosis (CF) patients. Breath tests using substrates labeled with 13 C meet these conditions. The 14 C-triolein breath test is sensitive and specific for measuring fat malabsorption, but involves radiation exposure. The aim of this study was to examine the utility of a test using a 13 C label and to determine whether pancreatic replacement therapy would return the test to the values of a normal control group. Methods: 13 CO 2 recovery was assessed after an overnight fast in six adult patients with CF, both with and without pancreatic enzyme replacement therapy (PERT) in the usual dose for a light snack, in a randomized order, on different days. Studies were also performed in eight healthy volunteers after oral ingestion. Subjects drank 50 mL of a liquid meal mixed with 200 μL 13 C-triolein and breath samples were collected by blowing through a straw into collection tubes every 30 min for 6 h. The effect of gastric emptying was assessed by comparison of oral ingestion with intraduodenal infusion. Intra-individual variability was assessed in nine volunteers by repeating the breath test after drinking the test meal on a separate day. Results: Compared with healthy subjects there was virtually no recovery of 13 CO 2 in CF patients without PERT. The median (interquartile range) cumulative percentage dose recovery (cPDR) at 6 h was 3% (0-8) in CF patients compared with 28% (22-41) in healthy controls (P< 0.01). Fat absorption was normalized (37%) (36-43) after ingestion of PERT. Gastric emptying delayed the peak in 13 CO 2 recovery, but there was no difference in the cPDR at 6 h. There was no difference in recovery between days 1 and 2. Conclusions: The 13 C-triolein breath test is a simple and reproducible method to measure fat malabsorption. The test provides a screening technique for fat malabsorption in adult CF patients and may be useful for monitoring the lowest effective dose of PERT.

Published
2004

12. Additive beneficial effects of the prone position, nitric oxide, and almitrine bismesylate on gas exchange and oxygen transport in acute respiratory distress syndrome

Author

Jean-Claude Chevrolet, José Enrique Ema López, Philippe Jolliet, Marc A Ritz, Bara Ricou, and Pierre Bulpa

Subjects
Adult, Male, Cardiac output, Almitrine, Supine position, Adolescent, Respiratory System Agents, Critical Care and Intensive Care Medicine, Nitric Oxide, Nitric oxide, chemistry.chemical_compound, medicine, Prone Position, Humans, Prospective Studies, Pulmonary wedge pressure, APACHE, Aged, Aged, 80 and over, Respiratory Distress Syndrome, business.industry, Pulmonary Gas Exchange, Oxygen transport, Hemodynamics, Oxygenation, Middle Aged, Oxygen, Prone position, chemistry, Anesthesia, Female, business, medicine.drug
Abstract

To test the hypothesis that prone position ventilation, nitric oxide, and almitrine bismesylate, each acting by a different mechanism to improve arterial oxygenation, could exert additive beneficial effects when used in combination in patients with severe acute respiratory distress syndrome (ARDS). Prospective, nonrandomized, interventional study. Medical and surgical intensive care units at a university tertiary care center. Twelve patients with ARDS and severe hypoxemia, defined as PaO2/FIO2 of or=to0.6, with pulmonary artery occlusion pressure of or=to10 torr (>or=to1.3 kPa) or a gain in the PaO2/FIO2 ratio of >or=to20 was observed. Seven patients (58%) responded to being turned prone. Compared with supine baseline conditions, nitric oxide and supine position increased arterial oxygen saturation from 89 +/- 4 (SD) % to 92 +/- 3% (p

Published
1997

13. Distal small bowel motility and lipid absorption in patients following abdominal aortic aneurysm repair surgery

Author

Jim Burnett, Robert K. Foreman, Monika Kwiatek, Brendan M. Stanley, John Dent, Addolorata C. Di Matteo, Marc A Ritz, Robert J. Fraser, Rosalie Vozzo, Jack Walsh, and Paul Jury

Subjects
Adult, medicine.medical_specialty, Ileum, Enteral administration, Intestinal absorption, Aortic aneurysm, Clinical Research, Intestine, Small, medicine, Humans, cardiovascular diseases, Aged, business.industry, Gastroenterology, General Medicine, Middle Aged, Lipid Metabolism, medicine.disease, Abdominal aortic aneurysm, Small intestine, Surgery, medicine.anatomical_structure, Parenteral nutrition, Intestinal Absorption, cardiovascular system, Gastrointestinal Motility, business, Aortic Aneurysm, Abdominal, Abdominal surgery
Abstract

AIM: To investigate distal small bowel motility and lipid absorption in patients following elective abdominal aortic aneurysm (AAA) repair surgery. METHODS: Nine patients (aged 35-78 years; body mass index (BMI) range: 23-36 kg/m2) post-surgery for AAA repair, and seven healthy control subjects (20-50 years; BMI range: 21-29 kg/m2) were studied. Continuous distal small bowel manometry was performed for up to 72 h, during periods of fasting and enteral feeding (Nutrison®). Recordings were analyzed for the frequency, origin, length of migration, and direction of small intestinal burst activity. Lipid absorption was assessed on the first day and the third day post surgery in a subset of patients using the 13C-triolein-breath test, and compared with healthy controls. Subjects received a 20-min intraduodenal infusion of 50 mL liquid feed mixed with 200 μL 13C-triolein. End-expiratory breath samples were collected for 6 h and analyzed for 13CO2 concentration. RESULTS: The frequency of burst activity in the proximal and distal small intestine was higher in patients than in healthy subjects, under both fasting and fed conditions (P

Published
2006
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14. Evaluation of miniature manometric techniques for the measurement of esophageal body pressure waves

Author

Richard H. Holloway, Ganes Shanmuganathan, Taher Omari, Marc A Ritz, and Addolorata C. Di Matteo

Subjects
Adult, Male, Pressure wave, Miniaturization, Hepatology, Manometry, business.industry, Gastroenterology, Esophageal body, Rise rate, Anatomy, Esophagus, medicine.anatomical_structure, Perfusion rate, Pressure, Humans, Medicine, Female, Peristalsis, Esophageal peristalsis, business, Perfusion, Biomedical engineering
Abstract

Background and Aims: Perfused miniature manometric assemblies with lumina of 0.4-0.5 mm i.d. have been developed. Reduced luminal size offers the advantages of reduced assembly bulk and increased assembly complexity with greater numbers of lumina and lower manometric infusion volumes because of a slower perfusion rate. This study investigated the recording fidelity of miniature manometric assemblies in the measurement of esophageal peristalsis. Methods: Four miniature manometric assemblies, each containing manometric lumina of either 0.4 or 0.5 mm i.d., were evaluated at 100 and 180 cm lengths. The fidelity of miniature manometric luminal recordings were evaluated in vivo during esophageal peristalsis by using a simultaneous comparison with the standard lumina and an intraluminal strain gauge. Results: During esophageal peristalsis, miniature manometric lumina recorded the peak amplitude of pressure waves, with an accuracy at perfusion rates of 0.04 mL/min (0.4 mm, i.d) and 0.15 mL/min (0.5 mm, i.d.). Conclusion: Miniature manometric assemblies of lengths that are practical for use in humans are suitable for recording esophageal peristalsis.

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