1,546 results on '"Halfvarson, Jonas"'
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2. Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study
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Mårild, Karl, Söderling, Jonas, Stephansson, Olof, Axelrad, Jordan, Halfvarson, Jonas, Bröms, Gabriella, Marsal, Jan, Olén, Ola, and Ludvigsson, Jonas F.
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- 2024
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3. Ustekinumab Versus Anti-tumour Necrosis Factor Alpha Agents as Second-Line Biologics in Crohn's Disease
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Eriksson, Carl, Söderling, Jonas, Karlqvist, Sara, Bröms, Gabriella, Everhov, Åsa H., Bergemalm, Daniel, Ludvigsson, Jonas F., Olén, Ola, and Halfvarson, Jonas
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- 2023
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4. Histologic Activity in Inflammatory Bowel Disease and Risk of Serious Infections: A Nationwide Study
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Olsson, Malin, Myrelid, Pär, Hjortswang, Henrik, Bengtsson, Jonas, Strid, Hans, Andersson, Marie, Jäghult, Susanna, Eberhardson, Michael, Nordenvall, Caroline, Björk, Jan, Rejler, Martin, Grip, Olof, Fagerberg, Ulrika L., Karling, Pontus, Mårild, Karl, Söderling, Jonas, Axelrad, Jordan, Halfvarson, Jonas, Forss, Anders, Olén, Ola, and Ludvigsson, Jonas F.
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- 2024
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5. Increasing Risk of Lymphoma Over Time in Crohn’s Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study
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Olsson, Malin, Myrelid, Pär, Hjortswang, Henrik, Bengtsson, Jonas, Strid, Hans, Andersson, Marie, Jäghult, Susanna, Eberhardson, Michael, Nordenvall, Caroline, Björk, Jan, Rejler, Martin, Grip, Olof, Fagerberg, Ulrika L., Karling, Pontus, Olén, Ola, Smedby, Karin E., Erichsen, Rune, Pedersen, Lars, Halfvarson, Jonas, Hallqvist-Everhov, Åsa, Bryder, Nicklas, Askling, Johan, Ekbom, Anders, Sachs, Michael C., Sørensen, Henrik Toft, and Ludvigsson, Jonas F.
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- 2023
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6. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis
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Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.
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- 2023
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7. Statin use and risk of colorectal cancer in patients with inflammatory bowel disease
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Sun, Jiangwei, Halfvarson, Jonas, Bergman, David, Ebrahimi, Fahim, Roelstraete, Bjorn, Lochhead, Paul, Song, Mingyang, Olén, Ola, and Ludvigsson, Jonas F.
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- 2023
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8. Ustekinumab Is Associated with Real-World Long-Term Effectiveness and Improved Health-Related Quality of Life in Crohn's Disease
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Forss, Anders, Clements, Mark, Myrelid, Pär, Strid, Hans, Söderman, Charlotte, Wagner, Agnieszka, Andersson, David, Hjelm, Fredrik, Olén, Ola, Halfvarson, Jonas, and Ludvigsson, Jonas F.
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- 2023
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9. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial
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Andrews, Jane, Sparrow, Miles, Leong, Rupert, Connor, Susan, Radforth-Smith, Graham, De Cruz, Peter, Preiss, Jan, Stallmach, Andrea, Liceni, Thomas, Grip, Olaf, Halfvarson, Jonas, Durai, Dharmaraj, Cummings, Fraser, Seilinger, Christian, Parkes, Miles, Lindsay, James, Lambrecht, Guy, Van Hootegem, Philippe, Rahier, Jean-François, Dewitte, Marie, Hebuterne, Xavier, Chanteloup, Elise, Altwegg, Romain, Nancey, Stephane, Bouguen, Guillaume, Pineton de Chambrun, Guillaume, Poullenot, Floriant, Roblin, Xavier, Louis, Edouard, Resche-Rigon, Matthieu, Laharie, David, Satsangi, Jack, Ding, Nik, Siegmund, Britta, D'Haens, Geert, Picon, Laurence, Bossuyt, Peter, Vuitton, Lucine, Irving, Peter, Viennot, Stephanie, Lamb, Christopher A, Pollok, Richard, Baert, Filip, Nachury, Maria, Fumery, Mathurin, Gilletta, Cyrielle, Almer, Sven, Ben-Horin, Shomron, Bouhnik, Yoram, Colombel, Jean-Frederic, and Hertervig, Erik
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- 2023
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10. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease
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Gornet, Jean-Marc, Beaugerie, Laurent, Shaji, Sebastian, Peyrin-Biroulet, Laurent, Reimund, Jean-Marie, Hebuterne, Xavier, Amiot, Aurélien, Armelao, Franco, Blanc, Pierre, Papi, Claudio, De Chambrun, Guillaume Pineton, Roblin, Xavier, Chu, Karmiris, Konstantinos, Shariq, Sohail, Viazis, Nikolaos, Limdi, Jimmy, Eder H, Piotr, Michalopoulos, Georgios, Bell, Andrew, Biancone, Livia, Dewitte, Marie, Mazhar, Zia, Franchimont, Denis, Nancey, Stephane, Macaigne, Gilles, Principi, Maria Beatrice, Fumery, Mathurin, Parkes, Gareth, Valats, Jean-Christophe, Doherty, Glen, Bouguen, Guillaume, Molnar, Tamás, Tsai, Hersin, Gangi, Mohsin, Pedersen, Natalia, Heluwaert, Frédéric, Shenderey, Richard, Zeissig, Sebastian, Butterworth, Jeffrey, Castiglione, Fabiana, Corless, Lynsey, Zallot, Camille, Baert, Filip, Singh, Salil, Sonwalkar, Sunil, Clayton, Elizabeth, Rahier, Jean-François, Vani, Deven, Bellaiche, Guy, De Vos, Martine, Kirchgesner, Julien, Kopylov, Uri, Lobaton, Triana, Locher, Christophe, Mantzaris, Gerassimos, Abouda, George, Smith, Katie, Sprakes, Michael, Theodoropoulou, Angeliki, Wesley, Emma, Bonnet, Joëlle, Elphick, David, Gilletta, Cyrielle, Gordon, John, Laharie, David, Nakad, Antoine, Orlando, Ambrogio, Dubois, Patrick, Hasselblatt, Peter, Michiels, Christophe, Preston, Cathryn, Staicu, Anca, Vuitton, Lucine, Kaassis, Mehdi, Speight, Ally, Ghosh, Deb, Löwenberg, Mark, Mathieu, Nicolas, Pelletier, Anne-Laure, Phillips, Anne, Magro, Fernando, Altwegg, Romain, Avni, Irit, biron, Landy, Jonathon, Nachury, Maria, Shenoy, Achuth, Trang, Caroline, Abitbol, Vered, Bamias, Georgios, Farkas, Klaudia, Maaser, Christian, Shitrit, Ariella, Siegmund, Britta, Filippi, Jérôme, O'morain, Colm, Yanai, Henit, Costes, Laurent, Hobday, David, Szepes, Zoltán, Calabrese, Emma, Dallal, Helen, Fung, Michael, Ramadas, Arvind, Baburajan, Bijay, Koss, Konrad, Barberis, Christophe, Buisson, Anthony, Amil, Morgane, Balestrieri, Paola, Johnson, Matthew, Tzouvala, Maria, Viennot, Stéphanie, Nagy, Ferenc, Thompson, Nick, Alric, Laurent, Samuel, Sunil, Bourrier, Anne, Chanteloup, Elise, Del Tedesco, Emilie, Harbord, Marcus, Lobo, Alan, Myers, Sally, Pollok, Richard, Ahmad, Tariq, Chaudhary, Rakesh, Karakoidas, Christos, Soliman, Ashraf, Stefanescu, Carmen, Theocharis, Georgios, Branden, Stijn Vanden, Beltran, Belén, Bouhnik, Yoram, Bourreille, Arnaud, Branco, Joana, Colleypriest, Ben, Eliakim, Rami, Knight, Paul, O'toole, Aoibhlinn, Robles, Virgina, Triantafyllou, Konstantinos, Bosca, Marta Maia, Lambrecht, Guy, Mosquera, Lucia Marquez, Panter, Simon, Pappa, Aikaterini, Simon, Marion, Sivaji, Ganesh, Bellanger, Christophe, Belle, Arthur, Borruel, Natalia, Egan, Laurence, Peeters, Harald, Sharpstone, Daniel, Arasaradnam, Ramesh, Benitez, José Manuel, Dahlerup, Jens Frederik, Giouleme, Olga, Gisbert, Javier P., Helwig, Ulf, Minguez, Miguel, Tsironi, Eftychia, Variola, Angela, Allen, Patrick, Boivineau, Lucille, Cole, Andy, Dib, Nina, Gomollon, Fernando, Johnston, Richard, Katsanos, Konstantinos, Kennedy, Nick, Kiszka-Kanowitz, Marianne, Marin-Jimenez, Ignacio, Miheller, Pál, Nos, Pilar, Saraj, Othman, Vinter-Jensen, Lars, Zittan, Eran, Baudry, Clotilde, Calvet, Xavier, Cazelles-Boudier, Marie-Christine, Coenegrachts, Jean-Louis, Cullen, Garret, Daperno, Marco, Dhar, Anjan, Gerard, Romain, Jensen, Nanna, Maharshak, Nitsan, Mcalindon, Mark, Mcloughlin, Simon, Parkes, Miles, Patel, Kamal, Peixoto, Armando, Polymeros, Dimitrios, Portela, Francisco, Rocca, Rodolfo, Seksik, Philippe, Subramanian, Sreedhar, Tennenbaum, Ruth, Atreya, Raja, Bachmann, Oliver, Berger, Arthur, Bor, Renáta, Buckley, Maire, Carpio, Daniel, Chaparro, María, Costa, Francesco, Domenech, Eugeni, Esteve, Maria, Foley, Stephen, Guardiola, Jordi, Koutroubakis, Ioannis, Kuehbacher, Tanja, Landman, Cécilia, Lavagna, Alessandro, Manceñido, Noemí, Mañosa, Míriam, Martín-Arranz, Maria Dolores, Plastaras, Laurianne, Scribano, Maria Lia, Sengupta, Subhasish, Teich, Nils, Tran-Minh, My-Linh, Zampeli, Evanthia, Amininejad, Leila, Arroyo, Teresa, Attar, Alain, Backman, Ann-Sofie, Bálint, Anita, Beckly, John, Ben Horin, Shomron, Bernardo, Sónia, Caillo, Ludovic, Caron, Bénédicte, Shanika de Silva, María, FábiáN, Anna, Fiorino, Gionata, Gutierrez, Ana, Lahat, Adi, Masmoudi, Mohamed, Mendolaro, Marco, Muls, Vinciane, Poullenot, Florian, Probert, Christopher, Reenaers, Catherine, Rutka, Mariann, Sarwari, Zaman, Sayer, Joanne, Sicilia, Beatriz, Sousa, Helena, van Kemseke, Catherine, Zabana, Yamile, Astegiano, Marco, Banim, Paul, Bettenworth, Dominik, Boualit, Médina, Brodersen, Jacob Broder, Christidou, Angeliki, Cooney, Rachel, Pinto, João Cortez, Cravo, Portugal Marília, Cremer, Anneline, Danese, Silvio, di Sabatino, Antonio, Fallingborg, Jan, Ferronato, Antonio, Planella, Esther Garcia, Gupta, Sanjay, Halfvarson, Jonas, Israeli, Eran, Kestenbaum, Samantha, Larsen, Lone, Macken, Elisabeth, Mathou, Nicoletta, Milassin, Ágnes, Pofelski, Joanna, Ricci, Chiara, Rodriguez-Moranta, Francisco, Schmidt-Lauber, Martin, Shaw, Ian, Soares, Marta, Soliman, Heithem, Triantos, Christos, Zografos, Konstantinos, Agrawal, Anurag, Armuzzi, Alessandro, Aubourg, Alexandre, Acosta, Manuel Barreiro-de, Barrio, Jesús, Bergemalm, Daniel, Bermejo, Fernando, Bodini, Giorgia, Bohr, Johan, Bossuyt, Peter, Christodoulou, Dimitrios, Claessens, Christophe, Collins, Paul, de Francisco, Ruth, Garcia, Santiago, Georgopoulos, Sotirios, Goutorbe, Felix, Kalantzis, Chrisostomos, Kourikou, Anastasia, Mace, Vincent, Malamut, Georgia, Ministro, Paula, Larmurier, Isabelle Nion, Ricart, Elena, Serrero, Mélanie, Sheridan, Juliette, Weimers, Petra, Andersen, Vibeke, Arroja, Bruno, Bokemeyer, Bernd, Bujanda, Luis, Degand, Thibault, Eriksson, Carl, Garceau, Cécile, Glerup, Henning, Goren, Idan, Jackson, Lucina, Koch, Stéphane, Mesonero, Francisco, Ordas, Ingrid, Riviere, Pauline, Saibeni, Simone, Soares, João, Tavernier, Noémie, Theede, Klaus, Ungar, Bella, Bästlein, Elke, Gasbarrini, Antonio, Protopapas, Andreas, Reindl, Wolfgang, Bossa, Fabrizio, Hart, Ailsa, Heil, Franz-Josef, O'Connor, Anthony, Oldenburg, Bas, Pastorelli, Luca, Stephen patchett, Ramakrishnan, Subramaniam, de Caestecker, John, Echarri, Ana, Kevans, David, Büning, Jürgen, Coelho, Rosa, Jansen, Jeroen, Koslowski, Benjamin, Wells, Christopher, Ceballos, Daniel, König, Ingrid, Padmanabhan, Hari, Patani, Timi, Qureshi, Raheel, Zagorowicz, Edyta, Allez, Matthieu, Archavlis, Emmanouil, Bonnet, Delphine, Guidi, Luisa, Mcnamara, Deirdre, Vernia, Piero, Weidenhiller, Michael, Alon, Lang, Boysen, Trine, Delattre, Charlotte, Farrell, Richard, Krüger, Rolf-Achim, Paupard, Thierry, Vind, Ida, Caprioli, Flavio, Gancho, Vladimir, Quentin, Vincent, Avidan, Benjamin, D’Haens, Geert, Mccarthy, Jane, Snook, Jonathon, Soufleris, Konstantinos, Zerbib, Frank, Carter, Dan, Depla, Annekatrien, Eisenbach, Thomas, Fries, Walter, Grammatikos, Nikolaos, Ilegems, Saskia, Lopez-Sanroman, Antonio, Moreau, Jacques, Riegler, Gabriele, Rietdijk, Svend, Rocha, Marta, Rosa, Isabelle, Ryan, Barbara, Yeremenko, Yelena, Boruchowicz, Arnaud, Damião, Filipe, Laoudi, Foteini, Lügering, Andreas, Macarri, Giampiero, Thomopoulos, Konstantinos, Barros, Luísa, Blixt, Thomas, Garros, Aurélien, Khorrami, Sam, Sokol, Harry, Sturm, Andreas, Livovsky, Dan, Maul, Jochen, Miks, Heinrich, Papadopoulos, Vasileios, Schmidt, Carsten, Snir, Yifat, Svenningsen, Lise, Ahmed, Wafaa, Broitman, Yelena, Cuillerier, Emmanuel, Kant, Prashant, Leyden, Jan, Lichtenstein, Lev, Lopes, Susana, Martineau, Chloé, Mulcahy, Hugh, Schweitzer, Axel, Van Schaik, Fiona, Banai, Hagar, Danion, Pauline, Dulery, Charlotte, Fidder, Herma, Gay, Claire, Hagege, Hervé, Harnois, Florence, Jørgensen, Søren Peter, Müller-Ziehm, Jens, Oikonomou, Michail, Palmela, Carolina, Schulze/Röske, Jörg, Smith, Mark, Thurm, Tamar, Bresso, Francesca, Brixi, Hedia, Jones, John, Macmathuna, Padraig, Painchart, Claire, Ron, Yulia, Vester-Andersen, Marianne, Alexandrino, Gonçalo, Börner, Norbert, Cardoso, Mariana, Chagas, Cristina, Dignaß, Axel, Dotan, Iris, Hedin, Charlotte, Karatzas, Pantelis, Kasapidis, Panagiotis, Palatka, Károly, Sakizlis, Georgios, Wilson, Ana, Bosanko, Nick, Caldeira, Paulo, Gagniere, Charlotte, Libier, Louise, Meunier, Camille, Moog, Gero, Pasquion, Audrey, Pica, Roberta, Akbar, Ayesha, Arab, Nadia, Cadiot, Guillaume, Carvalho, João, Charpignon, Claire, Fellermann, Laus, Fishman, Sigal, Fraser, Gerald, Gluck, Nathan, Hoesl, Mark, Kierkus, Jarosław, Klopocka, Maria, Arranz, Eduardo Martin, Menchen, Luis, Nikolaus, Susanna, Petrache, Anca, Ponsioen, Cyriel, Riestra, Sabino, Robledo, Pilar, Rodriguez, Cristina, Samer, Misheal, Tischer, Matthias, Wypych, Joanna, Baudon, Julien, Bezzio, Cristina, Boschetti, Gilles, Burisch, Johan, Creed, Tom, Demarzo, Maria Giulia, Festa, Stefano, Figueroa, Andrés, Julsgaard, Mette, Navarro, Pablo, Perez-Galindo, Pablo, Rouillon, Cléa, Sablich, Emanuele, Tosca, Joan, Vidon, Mathias, Vidon, Marine, Vitte, René-Louis, Wampach, Anne, Baumann, Cédric, Urmes, Isabelle Clerc, Rousseau, Hélène, Borie, Marc, Uzzan, Mathieu, Chatten, Kelly, Peter, Rimmer, Tariq, Iqbal, Cossignani, Marta, Cañete, Fiorella, Holvoet, Tom, Krasz, Susanne, Dias, Sandra, Abalia, Hadas, Abaza, Aziza, Abramovich, Gal, Ackzell, Ingrid, Adams, Carol, Addleton, Catherine, Alfambra, Erika, Algaba, Alicia, Allcock, Clare, Allison, Joanna, Amouriaux, Karine, Anderson, Julie, Anderson, Emma, Appelmans, Saskia, Armstrong, Lisa, Atkins, Stacey, Attaran-Bandarabadi, Masoumeh, Bailey, Yvonne, Bardot, Stephanie, Beck, Natasha, Bennett, Lillie, Bergfeld, Jonathan Phil, Berkane, Ramdane, Boey, Hanne, Bowlas, Louise, Bradley-Potts, Joanne, Brear, Tracy, Bretlander-Peters, Nicole, Brown, Ellen, Brown, Johanna, Buckingham, Elizabeth, Buellens, Katrien, Bull, Rhian, Burke, Maura, Burns, Leighanne, Burton, Julie, Bwalya, Agness, Cabanas, Karine, Callaghan, Muriel, Camou, Océane, Campbell, Debbie, Capoferro, Elvira, Carnahan, Mandy, Carnio, Cornelia, Carter, Anne, Clack, Concetta Casali, Chedouba, Leïla, Cipriano, Bessie, Claeys, Sophie, Closset, Manon, Coban, Dilek, Cococcia, Sara, Coe, Carolann, Cole, Helen, Collet, Emilie, Collins, Kayleigh, Combes, Isabelle, Connor, Emma, Constantin, Kathryn, Cooke, Susan, Cornet, Nathanaëlle, Corrihons, Estelle, Corsino, Pilar, Cortaville, Rosie, Cotterill, Donna, Cowton, Amanda, Cox, Harriet, Cripps, Viktoria, Crowder, Amanda, Cukier, Tzufit, Daniel, Amelia, Dawe, Chris, de Haan, Jose, Croix, Rosanna de la, Dejonckheere, Evva, Villanegro, Juan Delare, Delaval, Guillaume, Delliponti, Mariangela, Delommez, Aude, Detry, Emilie, Dhanaratne, Melanie, Galan, Laura Diez, Dodel, Marie, Dooks, Emma, Du Cheyron, Joseph, Duane, Linda, Vulgo Cochran, Jennifer Dulling, Dyer, Simona, Dymond, Harvey, Ekblad, Charlotte, Elliott, Kerry, Emmerson, Ingrid, Eugene-Jolchine, Irène, Fleming, Lorna, Fletcher, Eve, Ford, Sarah, Forshaw, Greg, Foulds, Angela, Francois, Caroline, Fuge, Nicole, Gafni, Gal, Ganon, Miri, Nuñez, Olga Garcia, Ramirez, Laura Garcia, Gelder, Sophie, Gettkowski, Raimonda, Gilardi, Daniela, Giuffrida, Paolo, Gobert, Vincent, Godden, Jo, Godwin, Nuala, Goulden, Kay, Graham, Sharon, Green, Charlotte, Green, Marie, Gueye, Aboubakar, Guler, Tuba, Gustavsson, Ida, Hadjisavvas, Helena, Hammonds, Fiona, Hantzi, Christina, Hauke, Marion, Haydock, Julie, Hayes, Orla, Nislev, Lizette Helbo, Hochstodter, Jessica, Hogg, Ashleigh, Hölbing, Manuela, Holland, Maureen, Holsbergen, Maartje, Howard, Linda, Hoyda, Aviya, Hull, Robert, Irish, Jane, Jackson, Wendy, Janssen, Wendy, Jeffrey, Lesley, Jourdan, Sofia, Jutrowska, Izabela, Kaniel, Chava, Karezos, Theofilos, Kelly, Niamh, Kelly, Jessica, Kennedy, Mary, Kennedy, Una, Kibaru, Joyce, Kirkman, Gemma, Klaproth, Janine, Kneese, Corinna, Koch, Andrea, Kokke, Kathleen, Koppelow, Martha, Krause, Sabine, Krauspe, Sabine, Kwakkenbos, Petra, Labarile, Nunzia, Lang, Hannah, Lassailly, Marianne, Leconte, Martine, Lepczynski, Linda, Levell, Emma, Levhar, Nina, Lindhort, Kerstin, Lisle, Jessica, Cauce, Beatriz Lopez, Lorenz, Gabriele, Lovati, Ambra, Lowry, Tracey, Lund, Margareta, Vorderbrügge, Anne Lutz, Maansson, Suzanne, Madapathage, Videsheka, Cheviakoff, Maelys, Magness, Alison, Manley, Orla, Manyoni, Catherine, Marg, Ingke, Marra, Antonella, Martins, Carole, Massella, Arianna, Mathias, Aurore, Mervyn, Danielle, Minsart, Charlotte, Mitchell, Sally, Monks, Kathleen, Montero, Mélanie, Moore, Alson, Moser, Maren, Moss, Alison, Mullen, Angela, Murciano, M. Francisca, Naylor, Deanna, Nehus, Ansgar, Nicholson, Anne, Nöding, Sarah, Nolan, Sinead, Nörenberg, Janet, Northcott, Clare, O'Connell, Jim, O’Kelly, Alison, Orbach-Zingboim, Noam, Orobitg, Judit, Otieno, Charlene, Owen, Charlotte, Patch, Sarah, Pauker, Maor, Pauli, Renate, Pearson, Harriet, Peggy, Falgon, Petit, Séverine, Petrissans, Christine, Piergallini, Simona, Pippard, Lucy, Pitt, Laura, Pócsik, Gabriella, Poher, Yoann, Pomes, Chloé, Pritchard, Lucy, Puchades, Laura, Quaid, Sheena, Rana, Aleem, Raynard, Dana, Reilly, Mykla, Reinert, Sonja, Reinknecht, Manuela, Renner, Baerbel, Reynolds, Rob, Rizzuto, Giulia, Robinson, Matthew, Robrechts, Joke, Rodriguez, Eva M., Rosenblum, Efrat, Russel, Tamlyn, Sadare, Ibiyemi, Salama, Noa, Schakel, Toos, Schauer, Anja, Schiavoni, Elisa, Shaw, Caroline, Shelton, Sarah, Sicart, Virginie, Siouville, Elodie, Smith, Orla, Soude, Théo, Stephenson, Sophie, Stephenson, Elaine, Steppe, Marjan, Sterkx, An, Stickley, Jo, Sugrue, Kathleen, Swietec, Natalia, Tasiaux, Charlotte, Thamu, Bhavneet, Thomas, Susane, Tobi, Ogwa, Touabi, Kahina, Tovi, Shifra, Tregonning, Julie, Turchini, Laura, Unkhoff, Julia, Unruh, Olesya, Uzun, Nurcan, Van Aert, Frauke, Bergh, Sandrine Vanden, Vandenbroucke, Louise, Vansteenkiste, Laura, Vardit, Shay, Vergriete, Valentin, Walker, Elaine, Warner, Eleanor, Watchorn, Olivia, Watson, Ekaterina, Wauthier, Marie-Claire, Weetman, Belgium Maria, Weston, Margaret, West-Petroschka, Wiebke, Wienecke, Susann, Wierling, Kerstin, Wiestler, Miriam, Wilcox, Rebecca, Wilhelmsen, Elva, Williams, Angharad, Williamson, Georgina, Wilson, Deborah, Wistance, Kate, Wortmann, Nicolas, Wurie, Subie, Yadgar, Karin, Young, Gail, Young, Megan, Aucouturier, Julien, Bertin, Marie- Jo, Bougrine, Hasnae, Coisnon, Marie, Defrance, Antoine, Gutierrez, Kati, Harouz, Amel, Jerber, Laure, Khlifi, Aida, Kirati, Amina, Liworo, Nasaladjine, Logoltat, Maude, Mailhat, Charlotte, M'Bayi, Chancely, Medane, Yasmina, Merkhoufa, Dalal, Elhad, Saouda Mohamed, Monthe, Bertille, Moyon, Fanny, Rabiega, Pascaline, Sekela, Jennifer, Thilloy, Charlotte, Hamamouche, Naima, Partisotti, Frederic, Blandin, Patrick, Mokhtari, Hocine, Coutard, Laure, and Doherty, Glen A.
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- 2023
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11. Long-term risk of arrhythmias in patients with inflammatory bowel disease: A population-based, sibling-controlled cohort study
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Sun, Jiangwei, Roelstraete, Bjorn, Svennberg, Emma, Halfvarson, Jonas, Sundström, Johan, Forss, Anders, Olén, Ola, and Ludvigsson, Jonas F.
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Medical research ,Medicine, Experimental ,Ulcerative colitis -- Care and treatment ,Comorbidity -- Care and treatment ,Antilipemic agents ,Arrhythmia -- Care and treatment ,Cardiac patients -- Care and treatment ,Biological sciences - Abstract
Background Although previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD. Methods and findings Through a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias. Conclusions In this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals., Author(s): Jiangwei Sun 1,*, Bjorn Roelstraete 1, Emma Svennberg 2, Jonas Halfvarson 3, Johan Sundström 4,5, Anders Forss 1,6, Ola Olén 7,8,9, Jonas F. Ludvigsson 1,10,11 Introduction Inflammatory bowel disease [...]
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- 2023
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12. Risk of heart failure in inflammatory bowel disease: a Swedish population-based study
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Sun, Jiangwei, primary, Yao, Jialu, additional, Olén, Ola, additional, Halfvarson, Jonas, additional, Bergman, David, additional, Ebrahimi, Fahim, additional, Rosengren, Annika, additional, Sundström, Johan, additional, and Ludvigsson, Jonas F, additional
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- 2024
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13. Histological remission in inflammatory bowel disease and risk of adverse pregnancy outcomes: A nationwide study
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Mårild, Karl, Söderling, Jonas, Stephansson, Olof, Axelrad, Jordan, Halfvarson, Jonas, Bröms, Gabriella, Marsal, Jan, Olén, Ola, and Ludvigsson, Jonas F.
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- 2022
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14. IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus
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Caron, Bénédicte, Abreu, Maria T., Siegel, Corey A., Panaccione, Remo, Sands, Bruce E., Dignass, Axel, Turner, Dan, Dotan, Iris, Hart, Ailsa L., Ahuja, Vineet, Allez, Matthieu, Ananthakrishnan, Ashwin N., Ghosh, Subrata, Griffiths, Anne M., Halfvarson, Jonas, Kaser, Arthur, Kotze, Paulo G., Koutroubakis, Ioannis E., Lakatos, Peter L., Levine, Arie, Lewis, James D., Magro, Fernando, Mantzaris, Gerassimos J., O’Morain, Colm, Ran, Zhihua, Reinisch, Walter, Rogler, Gerhard, Sachar, David B., Siegmund, Britta, Silverberg, Mark S., Sood, Ajit, Spinelli, Antonino, Steinwurz, Flavio, Tysk, Curt, Yamamoto-Furusho, Jesus K., Schreiber, Stefan, Rubin, David T., Sandborn, William J., Danese, Silvio, and Peyrin-Biroulet, Laurent
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- 2022
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15. Prevalence and Implications of Frailty in Older Adults With Incident Inflammatory Bowel Diseases: A Nationwide Cohort Study
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Olsson, Malin, Hjortswang, Henrik, Myrelid, Pär, Bengtsson, Jonas, Strid, Hans, Andersson, Marie, Jäghult, Susanna, Eberhardson, Michael, Nordenvall, Caroline, Björk, Jan, Fagerberg, Ulrika L., Rejler, Martin, Grip, Olof, Karling, Pontus, Halfvarson, Jonas, Kochar, Bharati, Jylhävä, Juulia, Söderling, Jonas, Ritchie, Christine S., Ludvigsson, Jonas F., Khalili, Hamed, and Olén, Ola
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- 2022
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16. Normal gastrointestinal mucosa at biopsy and subsequent cancer risk: nationwide population-based, sibling-controlled cohort study
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Sun, Jiangwei, Fang, Fang, Olén, Ola, Song, Mingyang, Halfvarson, Jonas, Roelstraete, Bjorn, Khalili, Hamed, and Ludvigsson, Jonas F.
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- 2022
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17. Faecal biomarkers for diagnosis and prediction of disease course in treatment‐naïve patients with IBD.
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Ling Lundström, Maria, Peterson, Christer, Hedin, Charlotte R. H., Bergemalm, Daniel, Lampinen, Maria, Magnusson, Maria K., Keita, Åsa V., Kruse, Robert, Lindqvist, Carl Mårten, Repsilber, Dirk, D'Amato, Mauro, Hjortswang, Henrik, Strid, Hans, Söderholm, Johan D., Öhman, Lena, Venge, Per, Halfvarson, Jonas, and Carlson, Marie
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CROHN'S disease ,RECEIVER operating characteristic curves ,BASIC proteins ,INFLAMMATORY bowel diseases ,ULCERATIVE colitis ,DISEASE progression - Abstract
Summary: Background: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). Aim: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. Methods: We included 65 patients with treatment‐naïve, new‐onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil‐derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. Results: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79–0.89) and MPO (AUC 0.85, 95% CI: 0.80–0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). Conclusions: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Spondyloarthritis in First-Degree Relatives and Spouses of Patients with Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study from Sweden.
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Shrestha, Sarita, Brand, Judith S, Osooli, Mehdi, Eriksson, Carl, Schoultz, Ida, Askling, Johan, Jess, Tine, Montgomery, Scott, Olén, Ola, and Halfvarson, Jonas
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Background and Aims Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We aimed to compare the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched, population-based, reference individuals. Methods We identified 147 080 FDRs and 25 945 spouses of patients with incident IBD [ N = 39 203] during 2006–2016, and 1 453 429 FDRs and 258 098 spouses of matched reference individuals [ N = 390 490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987–2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. Results During follow-up, 2430 FDRs of IBD patients [6.5/10 000 person-years] and 17 761 FDRs of reference individuals [4.8/10 000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95% CI:1.29, 1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR = 1.44; 95% CI:1.34,1.5 6] and of IBD patients aged <18 years at diagnosis [HR = 1.46; 95% CI: 1.27, 1.68]. IBD patients' spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs 3.5/10 000 person-years; HR = 1.22; 95% CI:1.09, 1.37]. No subgroup-specific risk pattern was identified among spouses. Conclusions The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Long-Term Risk of Myocarditis in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study in Sweden.
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Jiangwei Sun, Jialu Yao, Olén, Ola, Halfvarson, Jonas, Bergman, David, Ebrahimi, Fahim, Roelstraete, Bjorn, Rosengren, Annika, Sundström, Johan, and Ludvigsson, Jonas F.
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- 2024
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20. Histologic Activity in Inflammatory Bowel Disease and Risk of Serious Infections: A Nationwide Study
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Mårild, Karl, primary, Söderling, Jonas, additional, Axelrad, Jordan, additional, Halfvarson, Jonas, additional, Forss, Anders, additional, Olén, Ola, additional, Ludvigsson, Jonas F., additional, Olsson, Malin, additional, Myrelid, Pär, additional, Hjortswang, Henrik, additional, Bengtsson, Jonas, additional, Strid, Hans, additional, Andersson, Marie, additional, Jäghult, Susanna, additional, Eberhardson, Michael, additional, Nordenvall, Caroline, additional, Björk, Jan, additional, Rejler, Martin, additional, Grip, Olof, additional, Fagerberg, Ulrika L., additional, and Karling, Pontus, additional
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- 2024
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21. Long-Term Risk of Myocarditis in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study in Sweden
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Sun, Jiangwei, primary, Yao, Jialu, additional, Olén, Ola, additional, Halfvarson, Jonas, additional, Bergman, David, additional, Ebrahimi, Fahim, additional, Roelstraete, Bjorn, additional, Rosengren, Annika, additional, Sundström, Johan, additional, and Ludvigsson, Jonas F., additional
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- 2024
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22. Rectal Sensory and Compliance Testing: A Method Comparison Study between High-Resolution Anorectal Manometry and Barostat Investigations
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Marinica Grando, Lucian, primary, Halfvarson, Jonas, additional, and van Nieuwenhoven, Michiel, additional
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- 2024
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23. Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden
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Sun, Jiangwei, Fang, Fang, Olén, Ola, Song, Mingyang, Halfvarson, Jonas, Roelstraete, Bjorn, Khalili, Hamed, and Ludvigsson, Jonas F.
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Inflammatory bowel diseases -- Statistics -- Risk factors ,Gastrointestinal system -- Endoscopic surgery ,Biopsy -- Complications and side effects -- Statistics ,Biological sciences - Abstract
Background Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. Methods and findings In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD. Conclusions Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD., Author(s): Jiangwei Sun 1,*, Fang Fang 2, Ola Olén 3,4,5, Mingyang Song 6,7,8, Jonas Halfvarson 9, Bjorn Roelstraete 1, Hamed Khalili 7,8,10, Jonas F. Ludvigsson 1,11,12 Introduction Inflammatory bowel disease [...]
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- 2023
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24. Dynamics of the human gut microbiome in inflammatory bowel disease.
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Halfvarson, Jonas, Brislawn, Colin J, Lamendella, Regina, Vázquez-Baeza, Yoshiki, Walters, William A, Bramer, Lisa M, D'Amato, Mauro, Bonfiglio, Ferdinando, McDonald, Daniel, Gonzalez, Antonio, McClure, Erin E, Dunklebarger, Mitchell F, Knight, Rob, and Jansson, Janet K
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Feces ,Humans ,Colitis ,Ulcerative ,Inflammatory Bowel Diseases ,Crohn Disease ,Inflammation ,Leukocyte L1 Antigen Complex ,Cross-Sectional Studies ,Phenotype ,Adult ,Female ,Male ,Dysbiosis ,Gastrointestinal Microbiome ,Microbiology ,Medical Microbiology - Abstract
Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.
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- 2017
25. Rectal Sensory and Compliance Testing : A Method Comparison Study between High-Resolution Anorectal Manometry and Barostat Investigations
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Marinica Grando, Lucian, Halfvarson, Jonas, van Nieuwenhoven, Michiel A, Marinica Grando, Lucian, Halfvarson, Jonas, and van Nieuwenhoven, Michiel A
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Abnormal visceral perception and motor function are often observed in patients with fecal incontinence, evacuation disorders and irritable bowel syndrome. The international anorectal physiology working group has proposed a standardization for anorectal function assessment, where rectal sensitivity testing is performed using an elastic balloon attached to a high-resolution anorectal manometry (HRAM) catheter. Rectal compliance, another component of rectal function evaluation, is a pressure-volume relationship that refers to the rectum's ability to stretch and expand as it receives and holds fecal matter. There are no data available regarding the possibility of compliance testing using HRAM, although this is theoretically possible by correcting for the elastic balloon's intrinsic properties. The gold standard for measurement of visceral sensitivity and compliance is the rectal barostat, according to the procedure described by the European COST action GENIEUR group. Data on the agreement between the two different procedures are scarce. Hence, we performed a comparative study of the HRAM and barostat investigations in 26 healthy individuals. We hypothesized that by inflating the balloon before the examination, rectal compliance can be measured with HRAM investigations, and we examined correlations and levels of agreement between the methods. Our results demonstrate that assessing rectal compliance with HRAM is technically possible; however, a strong correlation with the rectal barostat was only observed at the maximum tolerable volume (Spearman's rho = 0.7, p = 0.02). We only found moderate correlations (Spearman's rho = 0.562, p = 0.019) for compliance according to the barostat methodology and for rectal sensibility testing (Spearman's rho = 0.57, p = 0.03 for maximum tolerable volume). Bland-Altman plots showed poor levels of agreement between the methods. We conclude that HRAM and the rectal barostat cannot be used interchangeably for compliance or sensitivity assess, This research was funded by the Research Committee Region Örebro County, grant numbers OLL-929762, OLL-935240 and OLL-978046, and the Research Fund of the Swedish Gastroenterological Society SLS-974222.
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- 2024
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26. Long-term risk of myocarditis in patients with inflammatory bowel disease : a nationwide cohort study in Sweden
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Sun, Jiangwei, Yao, Jialu, Olén, Ola, Halfvarson, Jonas, Bergman, David, Ebrahimi, Fahim, Roelstraete, Bjorn, Rosengren, Annika, Sundström, Johan, Ludvigsson, Jonas F., Sun, Jiangwei, Yao, Jialu, Olén, Ola, Halfvarson, Jonas, Bergman, David, Ebrahimi, Fahim, Roelstraete, Bjorn, Rosengren, Annika, Sundström, Johan, and Ludvigsson, Jonas F.
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OBJECTIVES: Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. METHODS: This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results. CONCLUSIONS: Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.
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- 2024
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27. Familial coaggregation of inflammatory bowel disease with cardiovascular disease : a nationwide multigenerational cohort study
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Sun, Jiangwei, Yao, Jialu, Olén, Ola, Halfvarson, Jonas, Bergman, David, Ebrahimi, Fahim, Sundström, Johan, Ludvigsson, Jonas F., Sun, Jiangwei, Yao, Jialu, Olén, Ola, Halfvarson, Jonas, Bergman, David, Ebrahimi, Fahim, Sundström, Johan, and Ludvigsson, Jonas F.
- Abstract
This study was supported by the European Crohn's and Colitis Organization (to JS; grant number: not applicable) and FORTE (to JFL; grant number: 2016-00424).
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- 2024
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28. Eosinophilic esophagitis is associated with increased risk of later inflammatory bowel disease in a nationwide Swedish population cohort
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Uchida, Amiko M., Garber, John J., Pyne, Ashley, Peterson, Kathryn, Roelstraete, Bjorn, Olén, Ola, Halfvarson, Jonas, Ludvigsson, Jonas F., Uchida, Amiko M., Garber, John J., Pyne, Ashley, Peterson, Kathryn, Roelstraete, Bjorn, Olén, Ola, Halfvarson, Jonas, and Ludvigsson, Jonas F.
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BACKGROUND: Earlier studies on the possible association between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have been contradictory. METHODS: Patients with biopsy-verified EoE diagnosed between 1990 and 2017 in Sweden (n = 1587) were age- and sex-matched with up to five general population reference individuals (n = 7808). EoE was defined using pathology reports from all 28 pathology centers in Sweden (the ESPRESSO study). Multivariate Cox regression then estimated hazard ratios for future IBD. IBD was defined based on the international classification of disease codes and histopathology codes. In secondary analyses, sibling comparators were used to further reduce potential familial confounding. Additionally, we performed logistic regression examining earlier IBD in EoE. RESULTS: During follow-up until 2020, 16 (0.01%) EoE patients and 21 (0.003%) general population reference individuals diagnosed with IBD, corresponding to a 3.5-fold increased risk of future IBD (aHR = 3.56; 95% CI 1.79-7.11). EoE was linked to Crohn's disease (aHR = 3.39 [95% CI 1.02-9.60]) but not to ulcerative colitis (aHR = 1.37; 95% CI 0.38-4.86). Compared to their siblings, patients with EoE were at a 2.48-fold increased risk of IBD (aHR = 2.48; 95% CI 0.92-6.70). Earlier IBD was 15 times more likely in EoE patients than in matched reference individuals (odds ratio, 15.39; 95% CI 7.68-33.59). CONCLUSION: In this nationwide cohort study, EoE was associated with a 3.5-fold increased risk of later IBD diagnosis. This risk increase may be due to shared genetic or early environmental risk factors, but also surveillance bias could play a role., AMU was supported by the Consortium of Eosinophilic GI Disease Researcher (CEGIR) Training Program. JFL was supported by Karolinska Institutet.
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- 2024
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29. Histologic activity in inflammatory bowel disease and risk of serious infections : A nationwide study
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Mårild, Karl, Söderling, Jonas, Axelrad, Jordan, Halfvarson, Jonas, Forss, Anders, Olén, Ola, Ludvigsson, Jonas F., Olsson, Malin, Myrelid, Pär, Hjortswang, Henrik, Bengtsson, Jonas, Strid, Hans, Andersson, Marie, Jäghult, Susanna, Eberhardson, Michael, Nordenvall, Caroline, Björk, Jan, Rejler, Martin, Grip, Olof, Fagerberg, Ulrika L., Karling, Pontus, Mårild, Karl, Söderling, Jonas, Axelrad, Jordan, Halfvarson, Jonas, Forss, Anders, Olén, Ola, Ludvigsson, Jonas F., Olsson, Malin, Myrelid, Pär, Hjortswang, Henrik, Bengtsson, Jonas, Strid, Hans, Andersson, Marie, Jäghult, Susanna, Eberhardson, Michael, Nordenvall, Caroline, Björk, Jan, Rejler, Martin, Grip, Olof, Fagerberg, Ulrika L., and Karling, Pontus
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BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear. METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses. RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61). CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD., Funding Agencies:ALF-funding from Region Västra GötalandUniversity of Gothenburg, SwedenBirgitta och Göran Karlssons foundationThe Swedish Society for Medical ResearchThe Swedish Research CouncilThe Swedish Society of MedicineKarolinska InstitutetSwedish Research CouncilThe Swedish Society of MedicineRegion Stockholm (ALF project)Crohn’s and Colitis FoundationJudith Stewart Colton Center for AutoimmunityNIH NIDDK Diseases
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30. Defining Comprehensive Disease Control for use as a Treatment Target for Ulcerative Colitis in Clinical Practice : International Delphi Consensus Recommendations
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Schreiber, Stefan, Danese, Silvio, Dignass, Axel, Domènech, Eugeni, Fantini, Massimo C., Ferrante, Marc, Halfvarson, Jonas, Hart, Ailsa, Magro, Fernando, Lees, Charlie W., Leone, Salvo, Pierik, Marieke J., Peters, Michele, Field, Polly, Fishpool, Helen, Peyrin-Biroulet, Laurent, Schreiber, Stefan, Danese, Silvio, Dignass, Axel, Domènech, Eugeni, Fantini, Massimo C., Ferrante, Marc, Halfvarson, Jonas, Hart, Ailsa, Magro, Fernando, Lees, Charlie W., Leone, Salvo, Pierik, Marieke J., Peters, Michele, Field, Polly, Fishpool, Helen, and Peyrin-Biroulet, Laurent
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BACKGROUND AND AIMS: Treatment of ulcerative colitis (UC) requires a patient-centric, definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process. METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before round 3. Consensus was met if ≥ 67% of the panel agreed. Statements without consensus in rounds 1 and 2 were revised or discarded after round 3. RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials (rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use), with additional patient-reported symptoms (bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance). The panel agreed on scoring systems and thresholds for many aspects. CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multi-component tool and adopt comprehensive disease control as a treatment target in clinical practice and trials.
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- 2024
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31. Atherosclerosis as a Risk Factor of Inflammatory Bowel Disease : A Population-Based Case-Control Study
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Faye, Adam S., Axelrad, Jordan, Sun, Jiangwei, Halfvarson, Jonas, Söderling, Jonas, Olén, Ola, Ludvigsson, Jonas F., Faye, Adam S., Axelrad, Jordan, Sun, Jiangwei, Halfvarson, Jonas, Söderling, Jonas, Olén, Ola, and Ludvigsson, Jonas F.
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Introduction: Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing. Methods: In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD. Results: There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even >= 5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition. Discussion: A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals.
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- 2024
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32. Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease : protocol for the Nordic inception cohort study (NORDTREAT)
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Fejrskov, Anja, Füchtbauer, Johannes David, Davíðsdóttir, Lóa G, Halfvarson, Jonas, Høivik, Marte Lie, Jensen, Michael Dam, Mortensen, Joachim Høg, Nielsen, Lene Nyholm, Rejler, Martin, Repsilber, Dirk, Söderholm, Johan D., Aalykke, Claus, Andersen, Vibeke, Christensen, Robin, Kjeldsen, Jens, Fejrskov, Anja, Füchtbauer, Johannes David, Davíðsdóttir, Lóa G, Halfvarson, Jonas, Høivik, Marte Lie, Jensen, Michael Dam, Mortensen, Joachim Høg, Nielsen, Lene Nyholm, Rejler, Martin, Repsilber, Dirk, Söderholm, Johan D., Aalykke, Claus, Andersen, Vibeke, Christensen, Robin, and Kjeldsen, Jens
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INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. C, Protocol.
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33. Prognostic potential of mucosal proteins in Ulcerative Colitis
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Salomon, Benita, Carlson, M., Bergemalm, Daniel, Hedin, C. R. H., Söderholm, J. D., Keita, Å. V., Carsten, A., Grip, O., Marsal, J., Eriksson, Carl, Strid, H., Lindqvist, C. M., Öhman, L., Magnusson, M. K., D'Amato, M., Repsilber, Dirk, Kruse, Robert, Halfvarson, Jonas, Salomon, Benita, Carlson, M., Bergemalm, Daniel, Hedin, C. R. H., Söderholm, J. D., Keita, Å. V., Carsten, A., Grip, O., Marsal, J., Eriksson, Carl, Strid, H., Lindqvist, C. M., Öhman, L., Magnusson, M. K., D'Amato, M., Repsilber, Dirk, Kruse, Robert, and Halfvarson, Jonas
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Background: Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value. Methods: Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of >2 courses of corticosteroids, or a cumulative dose of >2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC). Results: 117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MM
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34. The serum protein profile across the IBD spectrum : Results from the COLLIBRI consortium
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Salomon, Benita, Sudhakar, P., Verstockt, B., Ungaro, R. C., Aden, K., D'Haens, G. R., Silverberg, M. S., Repsilber, Dirk, Vermeire, S., Halfvarson, Jonas, Salomon, Benita, Sudhakar, P., Verstockt, B., Ungaro, R. C., Aden, K., D'Haens, G. R., Silverberg, M. S., Repsilber, Dirk, Vermeire, S., and Halfvarson, Jonas
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Background: Inflammatory bowel disease (IBD) is a heterogeneous disorder. Both subtypes, i.e., Crohn’s disease (CD) and ulcerative colitis (UC), differ in disease behaviour and inflamed gastrointestinal segments. Despite this, randomized controlled trials stratify patients based on CD and UC. Molecular characterization could uncover subtype-specific differences that could guide treatment and thereby overcome current therapeutic limitations. Therefore, we aimed to examine differences in serum inflammatory protein profiles across the IBD spectrum. Methods: This was a cross-sectional multicentre study of adult patients (≥18 years) with IBD from one Belgian and eight Swedish hospitals in the COLLIBRI consortium. IBD diagnosis and classification was based on international criteria, according to the Montreal classification. Relative serum protein levels were assessed using proximity extension assay technology (Olink Proteomics, Uppsala, Sweden; inflammation panel). We adopted smoothly clipped absolute deviation penalized logistic regression models to discriminate CD and UC patients. Using fitted CD vs UC logistic models, we estimated probability scores of CD vs UC for each patient based on their serum protein profiles. Scores ranged from 0 to 1, where lower scores indicated a higher molecular resemblance to UC. We evaluated the performance using leave-one-out cross-validation and the area under the curve (AUC). Results: Relative levels of 86 serum inflammatory proteins were available from 1,551 patients with IBD (CD, N=883; UC, N=639 and IBD-U, N=29) (Table 1). CD vs UC probability scores based on protein estimates for patients with UC, IBDU and different CD phenotypes (ileal CD, L1; colonic CD, L2; ileocolonic CD L3) are shown in Figure 1A. We observed a spectrum of IBD patients based on their CD vs CD probability scores with most pronounced differences between ileal CD and UC. Probability scores also differed significantly between colonic CD and ileal CD, but not betwee
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- 2024
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35. Depressive symptoms in ulcerative colitis and Crohn's disease - differences in improvement at 1 year follow-up
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Selin, K. A., Repsilber, Dirk, Strid, H., Lindqvist, C. M., Kruse, Robert, Magnusson, M. K., Öhman, L., Carlson, M., Keita, Å. V., Söderholm, J. D., Halfvarson, Jonas, Hedin, C. R. H., Selin, K. A., Repsilber, Dirk, Strid, H., Lindqvist, C. M., Kruse, Robert, Magnusson, M. K., Öhman, L., Carlson, M., Keita, Å. V., Söderholm, J. D., Halfvarson, Jonas, and Hedin, C. R. H.
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Background: Mental health (MH) has been reported to be poorer among patients with inflammatory bowel disease (IBD) than general population. However, it is not known whether MH is more driven by inflammation itself or related to gastrointestinal (GI) symptoms. Also, the dynamics of MH following IBD diagnosis is not well understood. Methods: In the Swedish Inception Cohort of IBD (SIC-IBD), patients with Crohn’s disease (CD), ulcerative colitis (UC) and unclassified IBD (IBD-U) as well as symptomatic controls (SC) and healthy controls (HC) filled in Patient Health Questionnaire-9 (PHQ-9), a validated screening tool for depression. Patients completed PHQ-9 at diagnosis and at one year follow-up while the controls completed it once. Disease outcome was defined at one year based on requirement of advanced treatments/ surgery. Results: In total, 286 individuals (16 HC, 89 SC, 62 CD, 104 UC, 15 IBD-U) completed the questionnaire at baseline. HC had significantly lower PHQ-9 score, (fewer depressive symptoms), at baseline compared to all the other groups (p<0.01). The baseline PHQ-9 score was not significantly different between SC and CD, UC and IBD-U patients (p=0.06). At one year follow-up, 38 CD and 53 UC patients completed the PHQ-9. Between baseline and follow-up, UC patients had a significant drop in their PHQ-9 score (p<0.0000001), whereas CD patients did not have any significant change in their PHQ-9 score (p=0.06). Furthermore, UC patients had significantly lower PHQ-9 score compared with CD patients at follow-up (p=0.04, Figure 1). Baseline PHQ-9 score was not correlated with calprotectin at baseline neither in UC nor CD patients (p=0.7 and 0.5 respectively). Also, there was no positive correlation between PHQ-9 score change and calprotectin change in either UC or CD patients, and neither baseline nor follow-up PHQ-9 scores were significantly different in patients with poor or good outcome (p>0.05). When analysed separately by sex, there was still no corr
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36. Observational study of tofacitinib in ulcerative colitis in Sweden (ODEN) - Interim analysis of clinical and biomarker data
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Nyberg, L., Söderling, J., Olén, O., Strid, H., Jäghult, S., Halfvarson, Jonas, Hedin, C., Jónsdóttir, S., Hjortswang, H., Cappelleri, J., Henrohn, D., Seddighzadeh, M., Marsal, J., Grip, O., Nyberg, L., Söderling, J., Olén, O., Strid, H., Jäghult, S., Halfvarson, Jonas, Hedin, C., Jónsdóttir, S., Hjortswang, H., Cappelleri, J., Henrohn, D., Seddighzadeh, M., Marsal, J., and Grip, O.
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Background: Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of moderate to severe ulcerative colitis (UC). ODEN is an ongoing Swedish multicentre prospective observational study regarding effectiveness of tofacitinib in UC. In this interim analysis, we aimed to assess the clinical outcomes during the first 16 weeks. Methods: Patients with active UC were enrolled 2020-2023 when starting tofacitinib as per clinical indication. Inclusion criteria were fecal (F) calprotectin >250 mg/kg or Mayo endoscopic score ≥2. Data were collected using an electronic case report form linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Data concerning inflammatory markers, endoscopic activity, partial (p) Mayo, extra intestinal manifestations, health-related quality of life measures, corticosteroid use, and colectomy rates were collected regardless of tofacitinib discontinuation. Information collected at week 8 and 16 is presented here. Intention-to-treat (ITT) analysis was applied and tofacitinib discontinuation was considered as treatment failure (i.e., no tofacitinib-induced clinical or laboratory response or remission). McNemar’s test was used for proportion differences. Results: The proportion of patients who previously had failed at least one biologic was 95% and at least two biologics, 62%. At inclusion, median p-Mayo was 5 and 39% of patients were on corticosteroids (Table 1a). Patients’ survival on drug is shown in Figure 1a. At week 8 and 16, 42% and 43%, respectively, achieved corticosteroid free clinical remission, Figure 1b. A 50% reduction in F-calprotectin was seen in 54% and 49% at week 8 and 16, respectively. The endpoint of Mayo endoscopic score 0 and/or F-calprotectin <100 mg/kg was achieved by 30% and 38% at week 8 and 16, respectively. Arthralgia frequency decreased significantly from baseline from 29% at inclusion to 13% and 11% at week 8 and 16 respectively. Three patients underwent colectomy the first
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37. Disease characteristics at time of diagnosis of adult onset inflammatory bowel disease and the risk of venous thromboembolism in the modern era - A Swedish nationwide cohort study 2007-2021
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Bröms, G., Forss, A., Eriksson, J., Linder, M., Eriksson, Carl, Askling, J., Halfvarson, Jonas, Ludvigsson, J. F., Olén, O., Bröms, G., Forss, A., Eriksson, J., Linder, M., Eriksson, Carl, Askling, J., Halfvarson, Jonas, Ludvigsson, J. F., and Olén, O.
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Background: Studies from mainly before the wide use of targeted therapies and guidelines for thromboprophylaxis indicate that patients with inflammatory bowel disease (IBD) are at a doubled risk of venous thromboembolism (VTE). We studied the risk of VTE in a modern-day cohort of patients with IBD, overall and in subgroups of disease characteristics. Methods: Using Swedish healthcare registers, we identified a nationwide population-based cohort of 55,252 patients with incident IBD between 2007 and 2021 with a median follow-up time of 6.5 years. Patients were matched by age, sex, calendar year and county of residence with up to ten reference individuals from the general population (N=536,067). The primary outcome was VTE, including pulmonary embolism and deep vein thrombosis. Incidence rates per 1,000 person-years and hazard ratios (HR) were calculated for IBD in general and according to disease subtype, sex, age and disease characteristics at diagnosis. HRs stratified by matching variables (model 1) and additionally adjusted for comorbidities and socioeconomic factors (model 2) were estimated by using Cox regression. Results: The incidence rate of VTE among patients with IBD was 5.03 per 1,000 person-years compared with 2.34 per 1,000 person-years among reference individuals (Table 1). This corresponded to a doubled incidence of VTE (HR=2.18, 95% confidence interval (CI)=2.07-2.29, model 1). Adjusting further for covariates in model 2 had only minor effects on the HR. The HR was consistent across IBD subtypes and sex. The relative risk was higher for those with younger age (18-39 years) at IBD diagnosis (HR 2.52, 95% CI: 2.22-2.83) with a risk difference of 1.25 per 1,000 person-years. The IR, 10.64 per 1,000 person-years, and risk difference, 5.42 per 1,000 person-years, was the highest for those with elderly onset (≥60 years) IBD. There was a stronger association for those with extensive ulcerative colitis (E3), primary sclerosing cholangitis, extraintestinal mani
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- 2024
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38. Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
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Grännö, O., Salomon, Benita, Lindqvist, C. M., Hedin, C. R. H., Carlson, M., Dannenberg, Katharina, Andersson, Erik, Söderholm, J. D., Keita, Å. V., Öhman, L., Magnusson, M. K., D'Amato, M., Eriksson, Carl, Hultdin, J., Kruse, Robert, Cao, Yang, Repsilber, Dirk, Bergemalm, Daniel, Grip, O., Karling, P., Halfvarson, Jonas, Grännö, O., Salomon, Benita, Lindqvist, C. M., Hedin, C. R. H., Carlson, M., Dannenberg, Katharina, Andersson, Erik, Söderholm, J. D., Keita, Å. V., Öhman, L., Magnusson, M. K., D'Amato, M., Eriksson, Carl, Hultdin, J., Kruse, Robert, Cao, Yang, Repsilber, Dirk, Bergemalm, Daniel, Grip, O., Karling, P., and Halfvarson, Jonas
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Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD). Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins. Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compa
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- 2024
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39. Observational study of tofacitinib in Ulcerative Colitis in Sweden (ODEN) - Interim analysis of health-related quality of life and fatigue
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Nyberg, L., Söderling, J., Olén, O., Strid, H., Jäghult, S., Halfvarson, Jonas, Hedin, C., Jónsdóttir, S., Hjortswang, H., Cappelleri, J. C., Henrohn, D., Seddighzadeh, M., Marsal, J., Grip, O., Nyberg, L., Söderling, J., Olén, O., Strid, H., Jäghult, S., Halfvarson, Jonas, Hedin, C., Jónsdóttir, S., Hjortswang, H., Cappelleri, J. C., Henrohn, D., Seddighzadeh, M., Marsal, J., and Grip, O.
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Background: Ulcerative colitis (UC) has a major impact on daily life. The Janus Kinas (JAK) inhibitor tofacitinib is effective in achieving remission in UC, but prospective real-world evidence concerning the effect on health-related quality of life (HRQoL) and fatigue are still scarce. Fatigue is a component of UC that is notoriously difficult to treat and not unambiguously related to inflammatory activity. ODEN is an ongoing Swedish multicentre prospective observational study of tofacitinib in UC. In this interim analysis, we assessed the effectiveness on HRQoL and fatigue during the first 16 weeks. Methods: Patients with UC and active inflammation were enrolled 2020-2023 when starting tofacitinib as per clinical indication. To measure various aspects of impairment of daily life, the validated questionnaires Short Health Scale (SHS), EQ-5D-5L [Swedish value set], and IBD-fatigue scale (IBD-F) were used. These data and information concerning clinical, biochemical, and endoscopic outcomes were collected in an e-CRF linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). For HRQoL outcomes, per protocol analysis was applied. Paired t-test and Wilcoxon’s signed-rank test were used for mean and median differences, respectively. Results: In total, 103 patients were included. Baseline data are shown in Table 1a. For patients still on tofacitinib treatment, all four dimensions of the SHS (symptoms, social function, disease related worry, and general well-being) improved significantly, Table 1b. A median decrease of one point from baseline was seen at week 8 in each of the parameters, which was maintained through week 16 with a tendency towards further improvement. EQ-5D-5L showed an impairment mainly in the aspects of pain/discomfort and ability to participate in common daily activities. Improvement in these dimensions was seen from baseline to week 16. The overall EQ-5D-5L index improved significantly from baseline (0.80) to week 8 (0.86)
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40. Comparative risk of serious infection with vedolizumab vs anti-TNF in Inflammatory Bowel Disease : Results from nationwide Swedish registers
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Karlqvist, Sara, Sachs, M., Eriksson, Carl, Cao, Yang, Montgomery, Scott, Ludvigsson, Jonas F., Olén, O., Halfvarson, Jonas, Karlqvist, Sara, Sachs, M., Eriksson, Carl, Cao, Yang, Montgomery, Scott, Ludvigsson, Jonas F., Olén, O., and Halfvarson, Jonas
- Abstract
Background: The real-world comparative safety of vedolizumab in inflammatory bowel disease (IBD) remains uncertain. We aimed to assess the risk of serious infection in IBD patients treated with vedolizumab, compared to (i) those treated with anti-tumour necrosis factor (TNF) treatment and (ii) the general population. Methods: In this nationwide cohort study, treatment episodes were identified from Swedish health registers (from 1 May 2014 – 31 December 2020). Patients were considered exposed from initiation of treatment until 90 days after discontinuation of treatment. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infection, defined as infection requiring hospital admission. Results: After propensity score matching, the cohorts were not materially different at baseline with regard to demographic, disease and treatment characteristics (Table 1). During 1376 treatment-episodes in patients with Crohn’s disease, there were 5.18 (95%CI: 3.98-6.63) serious infections per 100 person-years (PY) with vedolizumab vs 3.54 (95%CI: 2.50-4.85) per 100 PY with anti-TNF; HR 1.72 (95%CI: 1.12-2.65; Figure 1A). When examining site-specific infections in Crohn’s disease, vedolizumab was associated with an HR of 2.47 (95% CI: 0.96-6.39) for serious gastrointestinal infections. Compared to the rate of 0.75 (95%CI: 0.59-0.92) serious infections per 100 PY in the general population, vedolizumab demonstrated an increased HR of 7.00 (95%CI: 5.04-9.72). Across 1294 episodes among patients with ulcerative colitis there were 3.74 (95%CI: 2.66-5.11) serious infections per 100 PY with vedolizumab vs 3.42 (95%CI: 2.31-4.89) per 100 PY with anti-TNF, corresponding to HRs of 0.80 (95%CI: 0.47-1.36, Figure 1B) within the initial 1.1 years of treatment and 2.03 (95%CI: 0.65-6.32) after 1.1 years (follow-up truncated due to non-proportional hazards). In ulcerative colitis, there was no statistically significant association between ved
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- 2024
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41. Untargeted metabolomics profiling and hemoglobin normalization for archived newborn dried blood spots from a refrigerated biorepository
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Yu, Miao, Dolios, Georgia, Yong-Gonzalez, Vladimir, Björkqvist, Olle, Colicino, Elena, Halfvarson, Jonas, and Petrick, Lauren
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- 2020
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42. Genetic Epidemiology of Inflammatory Bowel Disease, Early Twin and Family Studies
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Halfvarson, Jonas, Hedin, Charlotte, editor, Rioux, John D., editor, and D'Amato, Mauro, editor
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- 2019
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43. Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study
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Turk, Niksa, Cukovic-Cavka, Silvija, Nicolaou, Anastasia, Lukas, Milan, Shonová, Olga, Blichfeldt, Birgitte, Marker, Dorte, Carlsen, Katrine, Weimers, Petra, Aalykke, Clays, Kudsk, Karen, Vind, Ida, Thorsgaard, Niels, Skamnelos, Alexandros, Politis, Dimitrios, Vegh, Zsuzsanna, Demenyi, Peterne, Nemethne Kramli, Szabina, Dal Piaz, Giualia, Santini, Alessia, Girardin, Giulia, Kupcinskas, Limas, Jonaitis, Laimas, Valantiene, Irena, Zykus, Romanas, Kucinskiene, Ruta, Lazar, Daniela, Nikulina, Inna, de Castro, Luisa, Pineda, Juan-Ramon, Pereira, Santos, Martinez-Cadilla, Jesus, Sanroman, Luciano, Figueira, Montserrat, Ares, David Martinez, Rodriguez-Prada, Jose-Ignacio, Carmona, Amalia, Gonzalez-Portela, Carlos, Widen, Ulla-Britt, Myers, Sally, Ashton, Katherine, Whitehead, Emma, Burisch, Johan, Vardi, Hillel, Schwartz, Doron, Friger, Michael, Kiudelis, Gediminas, Kupčinskas, Juozas, Fumery, Mathurin, Gower-Rousseau, Corinne, Lakatos, Laszlo, Lakatos, Peter L, D'Incà, Renata, Sartini, Alessandro, Valpiani, Daniela, Giannotta, Martina, Arebi, Naila, Duricova, Dana, Bortlik, Martin, Chetcuti Zammit, Stefania, Ellul, Pierre, Pedersen, Natalia, Kjeldsen, Jens, Midjord, Jóngerð Maria Miné, Nielsen, Kári Rubek, Winther Andersen, Karina, Andersen, Vibeke, Katsanos, Konstantinos H, Christodoulou, Dimitrios K, Domislovic, Viktor, Krznaric, Zeljko, Sebastian, Shaji, Oksanen, Pia, Collin, Pekka, Barros, Luisa, Magro, Fernando, Salupere, Riina, Kievit, Hendrika Adriana Linda, Goldis, Adrian, Kaimakliotis, Ioannis P, Dahlerup, Jens F, Eriksson, Carl, Halfvarson, Jonas, Fernandez, Alberto, Hernandez, Vicent, Turcan, Svetlana, Belousova, Elena, Langholz, Ebbe, Munkholm, Pia, and Odes, Selwyn
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- 2020
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44. Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study
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Olén, Ola, Erichsen, Rune, Sachs, Michael C, Pedersen, Lars, Halfvarson, Jonas, Askling, Johan, Ekbom, Anders, Sørensen, Henrik Toft, and Ludvigsson, Jonas F
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- 2020
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45. A User’s Guide to De-escalating Immunomodulator and Biologic Therapy in Inflammatory Bowel Disease
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Hirten, Robert P., Lakatos, Peter L., Halfvarson, Jonas, and Colombel, Jean Frederic
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- 2020
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46. Familial coaggregation of inflammatory bowel disease with cardiovascular disease: a nationwide multigenerational cohort study
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Sun, Jiangwei, primary, Yao, Jialu, additional, Olén, Ola, additional, Halfvarson, Jonas, additional, Bergman, David, additional, Ebrahimi, Fahim, additional, Sundström, Johan, additional, and Ludvigsson, Jonas F, additional
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- 2024
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47. A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn’s Disease and Human Gut Microbiome Composition
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Li, Dalin, Achkar, Jean-Paul, Haritunians, Talin, Jacobs, Jonathan P, Hui, Ken Y, D'Amato, Mauro, Brand, Stephan, Radford-Smith, Graham, Halfvarson, Jonas, Niess, Jan-Hendrik, Kugathasan, Subra, Büning, Carsten, Schumm, L Philip, Klei, Lambertus, Ananthakrishnan, Ashwin, Aumais, Guy, Baidoo, Leonard, Dubinsky, Marla, Fiocchi, Claudio, Glas, Jürgen, Milgrom, Raquel, Proctor, Deborah D, Regueiro, Miguel, Simms, Lisa A, Stempak, Joanne M, Targan, Stephan R, Törkvist, Leif, Sharma, Yashoda, Devlin, Bernie, Borneman, James, Hakonarson, Hakon, Xavier, Ramnik J, Daly, Mark, Brant, Steven R, Rioux, John D, Silverberg, Mark S, Cho, Judy H, Braun, Jonathan, McGovern, Dermot PB, and Duerr, Richard H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Nutrition and Dietetics ,Genetics ,Nutrition ,Inflammatory Bowel Disease ,Autoimmune Disease ,Human Genome ,Clinical Research ,Digestive Diseases ,Crohn's Disease ,Aetiology ,2.1 Biological and endogenous factors ,Oral and gastrointestinal ,Alleles ,Case-Control Studies ,Cation Transport Proteins ,Colitis ,Ulcerative ,Crohn Disease ,Female ,Gastrointestinal Microbiome ,Genetic Pleiotropy ,Genotype ,Humans ,Male ,Mutation ,Missense ,Risk Factors ,Inflammatory Bowel Diseases ,Microbiota ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsGenome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).MethodsGenotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.ResultsWe identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)).ConclusionsOur results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.
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- 2016
48. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.
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Rivas, Manuel, Graham, Daniel, Sulem, Patrick, Stevens, Christine, Desch, A, Goyette, Philippe, Gudbjartsson, Daniel, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Degenhardt, Frauke, Mucha, Sören, Kurki, Mitja, Li, Dalin, DAmato, Mauro, Annese, Vito, Vermeire, Severine, Weersma, Rinse, Halfvarson, Jonas, Paavola-Sakki, Paulina, Lappalainen, Maarit, Lek, Monkol, Cummings, Beryl, Tukiainen, Taru, Haritunians, Talin, Halme, Leena, Koskinen, Lotta, Ananthakrishnan, Ashwin, Luo, Yang, Heap, Graham, Visschedijk, Marijn, MacArthur, Daniel, Neale, Benjamin, Ahmad, Tariq, Anderson, Carl, Brant, Steven, Duerr, Richard, Silverberg, Mark, Cho, Judy, Palotie, Aarno, Saavalainen, Päivi, Kontula, Kimmo, Färkkilä, Martti, McGovern, Dermot, Franke, Andre, Stefansson, Kari, Rioux, John, Xavier, Ramnik, Daly, Mark, Barrett, J, de Lane, K, Edwards, C, Hart, A, Hawkey, C, Jostins, L, Kennedy, N, Lamb, C, Lee, J, Lees, C, Mansfield, J, Mathew, C, Mowatt, C, Newman, B, Nimmo, E, Parkes, M, Pollard, M, Prescott, N, Randall, J, Rice, D, Satsangi, J, Simmons, A, Tremelling, M, Uhlig, H, Wilson, D, Abraham, C, Achkar, J, Bitton, A, Boucher, G, Croitoru, K, Fleshner, P, Glas, J, Kugathasan, S, Limbergen, J, Milgrom, R, Proctor, D, Regueiro, M, Schumm, P, Sharma, Y, Stempak, J, Targan, S, and Wang, M
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Alleles ,Colitis ,Ulcerative ,Genetic Association Studies ,Genetic Predisposition to Disease ,Genetic Testing ,Humans ,Mutation ,Protein Transport ,RNA ,Messenger ,Reproducibility of Results ,Sequence Analysis ,DNA ,Ubiquitin-Protein Ligases - Abstract
Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
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- 2016
49. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci
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Ellinghaus, David, Jostins, Luke, Spain, Sarah L, Cortes, Adrian, Bethune, Jörn, Han, Buhm, Park, Yu Rang, Raychaudhuri, Soumya, Pouget, Jennie G, Hübenthal, Matthias, Folseraas, Trine, Wang, Yunpeng, Esko, Tonu, Metspalu, Andres, Westra, Harm-Jan, Franke, Lude, Pers, Tune H, Weersma, Rinse K, Collij, Valerie, D'Amato, Mauro, Halfvarson, Jonas, Jensen, Anders Boeck, Lieb, Wolfgang, Degenhardt, Franziska, Forstner, Andreas J, Hofmann, Andrea, Schreiber, Stefan, Mrowietz, Ulrich, Juran, Brian D, Lazaridis, Konstantinos N, Brunak, Søren, Dale, Anders M, Trembath, Richard C, Weidinger, Stephan, Weichenthal, Michael, Ellinghaus, Eva, Elder, James T, Barker, Jonathan NWN, Andreassen, Ole A, McGovern, Dermot P, Karlsen, Tom H, Barrett, Jeffrey C, Parkes, Miles, Brown, Matthew A, and Franke, Andre
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Biological Sciences ,Genetics ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Bayes Theorem ,Cholangitis ,Sclerosing ,Chronic Disease ,Colitis ,Ulcerative ,Comorbidity ,Crohn Disease ,Genetic Heterogeneity ,Genetic Pleiotropy ,Genetic Variation ,Genome-Wide Association Study ,Genotype ,Humans ,Inflammation ,Psoriasis ,Quantitative Trait Loci ,Spondylitis ,Ankylosing ,International IBD Genetics Consortium ,International Genetics of Ankylosing Spondylitis Consortium ,International PSC Study Group ,Genetic Analysis of Psoriasis Consortium ,Psoriasis Association Genetics Extension ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.
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- 2016
50. Disease signatures in the gut metagenome of a prospective family cohort of inflammatory bowel disease
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Ruehlemann, Malte Christoph, primary, Waschina, Silvio, additional, Wacker, Eike Matthias, additional, Rausch, Philipp, additional, Schaan, Ana, additional, Zafroon, Zaira, additional, Franzpoetter, Katrin, additional, Jacobs, Gunnar, additional, Ellinghaus, David, additional, Kruse, Robert, additional, Bergemalm, Daniel, additional, Halfvarson, Jonas, additional, Ziemann, Malte, additional, Goerg, Siegfried, additional, Lieb, Wolfgang, additional, Schreiber, Stefan, additional, Poyet, Mathilde, additional, Bang, Corinna, additional, Franke, Andre, additional, and Groussin, Mathieu, additional
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- 2023
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