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1.  The Lewis score or the capsule endoscopy Crohn’s disease activity index: which one is better for the assessment of small bowel inflammation in established Crohn’s disease? 
Therapeutic Advances in Gastroenterology  2018;11:1756283X17747780.
Background
Small-bowel capsule endoscopy (CE) is a prime modality for evaluation of the small bowel. The Lewis score (LS) and the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) are validated endoscopic indices for quantification of small-bowel inflammation on CE. It is unclear whether these indexes are interchangeable for the evaluation of mucosal inflammation in established Crohn’s disease (CD). The aim of this study was to compare the quantitative evaluation of small- bowel inflammation by LS and CECDAI.
Methods
Patients with known quiescent small-bowel CD for at least 3 months (Crohn’s disease activity index < 150) were prospectively recruited and underwent CE. The LS was calculated using RAPID 8 capsule-reading software and the CECDAI was calculated manually. Cumulative LS (C-LS) was calculated by summation of individual tertile LS. Fecal calprotectin (FCP) and C-reactive protein (CRP) levels were measured and correlated with the scores.
Results
A total of 50 patients were included in the study. There was a moderate correlation between the worst segment LS and CECDAI (Pearson’s r = 0.66, p = 0.001), and a strong correlation between C-LS and CECDAI (r = 0.81, p = 0.0001). CECDAI < 5.4 corresponded to mucosal healing (LS < 135), while CECDAI > 9.2 corresponded to moderate-to-severe inflammation (LS ⩾ 790). There was a moderate correlation between capsule scores and FCP levels (r = 0.39, p = 0.002 for LS, r = 0.48, p = 0.001 for C-LS, and r = 0.53, p = 0.001 for CECDAI, respectively). CRP levels were not significantly correlated with either score.
Conclusions
CECDAI and C-LS are strongly correlated and perform similarly for quantitative assessment of mucosal inflammation in established CD.
doi:10.1177/1756283X17747780
PMCID: PMC5788095
capsule endoscopy; fecal calprotectin; Crohn’s disease
2.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
3.  Factors associated with the achievement of mucosal healing in Crohn’s disease: the benefit of endoscopic monitoring in treating to target 
Background:
Mucosal healing (MH), the proposed treat to target in Crohn’s disease (CD), is associated with improved disease outcomes. There are still scant data on factors associated with achieving MH in clinical practice. We evaluated the probability of achieving MH and identified factors predictive of subsequent MH in patients with CD.
Methods:
This was a retrospective, observational cohort study. A total of 272 patients with CD with serial endoscopy assessment and subsequent therapeutic management were reviewed. The primary outcome was MH. The cumulative incidence of MH and endoscopic improvement was estimated using the Kaplan–Meier method. Factors independently associated with MH were identified using the Cox proportional hazards model.
Results:
Of the 272 patients, 126 (46.32%) achieved MH after a median follow-up period of 33 months (interquartile range: 27–38 months). Factors independently associated with MH by multivariate analysis were time between endoscopic procedures within 26 weeks (hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.05–3.39), adjustment of medical therapy when MH was not achieved (HR: 2.07; 95% CI: 1.26–2.33), prior enteric fistula (HR: 0.22; 95% CI: 0.06–0.91), perianal disease at CD diagnosis (HR: 0.58; 95% CI: 0.35–0.95), and C-reactive protein normalization within 12 weeks (HR: 3.23; 95% CI: 1.82–5.88). Similar factors have also been identified for endoscopic improvement.
Conclusions:
Performing serial endoscopic procedures at a 26-week interval and subsequent adjustment in medical treatment are helpful in achieving MH. Endoscopic monitoring plays an important role in the treating to target of CD.
doi:10.1177/1756283X17698089
PMCID: PMC5424871
Crohn’s disease; endoscopic; mucosal healing; treat to target
4.  The Impact of Magnetic Resonance Enterography and Capsule Endoscopy on the Re-classification of Disease in Patients with Known Crohn’s Disease: A Prospective Israeli IBD Research Nucleus (IIRN) Study 
Journal of Crohn's & Colitis  2016;10(5):525-531.
Background and aims:
The classification of Crohn’s disease (CD) is usually determined at initial diagnosis and is frequently based on ileocolonoscopic and cross-sectional imaging data. Advanced endoscopic and imaging techniques such as small-bowel video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) may provide additional data regarding disease extent and phenotype. Our aim was to examine whether VCE or MRE performed after the initial diagnosis may alter the original disease classification.
Methods:
Consecutive patients with known small-bowel CD in clinical remission or mild disease were prospectively recruited and underwent MRE and VCE (if small-bowel patency was confirmed by a patency capsule (PC). Montreal classifications before and after evaluation were compared.
Results:
Seventy-nine patients underwent MRE and VCE was performed in 56. Previously unrecognized disease locations were detected with VCE and MRE in 51 and 25%, respectively (p < 0.01) and by both modalities combined in 44 patients (55%). Twenty-two patients (27%) were reclassified as having an advanced phenotype (B2/B3). MRE and VCE reclassified the phenotype in 26 and 11% of cases, respectively (p < 0.05). Overall, both modalities combined altered the original Montreal classification in 49/76 patients (64%).
Conclusion:
VCE and MRE may lead to reclassification of the original phenotype in a significant percentage of CD patients in remission. VCE was more sensitive for detection of previously unrecognized locations, while MRE was superior for detection of phenotype shift. The described changes in the disease classification may have an important impact on both clinical management and long-term prognosis in these patients.
doi:10.1093/ecco-jcc/jjw006
PMCID: PMC4957453  PMID: 26748404
Capsule endoscopy; Crohn’s disease; magnetic resonance enterography; Montreal classification; phenotype
5.  Thalidomide induces clinical remission and mucosal healing in adults with active Crohn’s disease: a prospective open-label study 
Background:
Thalidomide is effective in inducing and maintaining clinical remission in children and adolescents with refractory Crohn’s disease (CD). However, little is known about the efficacy and safety of thalidomide for adult patients with CD.
Methods:
We conducted a prospective open-label cohort study between January 2013 and April 2015. A total of 47 adult patients with active CD who were dependent/resistant or intolerant to corticosteroids and/or immunomodulators or biologics received 50–100 mg of thalidomide daily. Primary outcome was clinical remission evaluated at week 8. Endoscopic assessment was performed at week 24 and defined as endoscopic response (decrease in Crohn’s Disease Endoscopic Index of Severity [CDEIS] score > 5 points from baseline CDEIS of 6 or more), complete endoscopic remission (CDEIS score < 3), and mucosal healing (MH) (no ulceration).
Results:
A total of 47 adults with active CD were enrolled. The clinical remission rate was 14.9% and 23.4% at week 4 and week 8, but increased to 46.8% at week 12 and 53.2% at week 24 out of all the 47 patients included (intention-to-treat analysis). Altogether 32 patients consented and underwent ileocolonoscopy at week 24. The rate of endoscopic response and complete endoscopic remission were 68.4% and 43.8%. MH (no ulceration) was achieved in 28.1% of patients. Adverse events occurred in 27/47 (57.4%) patients but necessitated therapy discontinuation in only 5/47 (10.6%) of patients.
Conclusions:
Low-dose thalidomide was effective and tolerated for inducing and maintaining clinical remission in adult patients with active CD, but the optimal time frame for thalidomide to induce clinical remission may be longer than previously appreciated and is probably optimal at 12 weeks. MH could reasonably be achievable with thalidomide.
doi:10.1177/1756283X17698910
PMCID: PMC5415099
mucosal healing; refractory Crohn’s disease; thalidomide
6.  Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis: A global survey of physicians' practice 
World Journal of Gastroenterology  2017;23(16):2995-3002.
AIM
To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates (5ASA) with corticosteroids (CS) versus corticosteroids alone for patients with active ulcerative colitis (UC).
METHODS
A cross-sectional questionnaire exploring physicians’ attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents’ agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses.
RESULTS
Six hundred and sixty-four questionnaires were distributed and 349 received (52.6% response rate). Of 340 eligible respondents, 221 (65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108 (32%) would stop the 5ASA (P < 0.001), and 11 (3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340 (41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most (94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS.
CONCLUSION
Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.
doi:10.3748/wjg.v23.i16.2995
PMCID: PMC5413795
Inflammatory bowel disease; Corticosteroids; 5-aminosalicylates; Ulcerative colitis
7.  Helicobacter pylori prevalence and clinical significance in patients with quiescent Crohn’s disease 
BMC Gastroenterology  2017;17:27.
Background
Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn’s disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures.
Methods
Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed.
Results
Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative.
CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication.
Conclusions
The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.
doi:10.1186/s12876-017-0588-7
PMCID: PMC5307850  PMID: 28193167
Crohn’s disease; Helicobacter pylori; Video capsule endoscopy; Prevalence; Eradication
9.  Over-reaching beyond disease activity: the influence of anxiety and medical economic burden on health-related quality of life in patients with inflammatory bowel disease 
Purpose
Many patients with inflammatory bowel disease (IBD) have impaired health-related quality of life (HRQOL). The influence of psychological and economic factors on HRQOL has not been fully elucidated in IBD. Therefore, we aimed to identify the predictors of HRQOL in an IBD cohort.
Patients and methods
This was a cross-sectional cohort study of patients presenting to our tertiary IBD center. HRQOL was measured using the 36-item Short Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Perceived stress and perceived social support were also assessed by standardized scales. Demographic, socioeconomic and clinical data were obtained from a prespecified questionnaire and patients’ medical records. Univariate analyses and multiple regression analysis were performed to identify predictors of HRQOL.
Results
A total of 242 IBD patients were recruited, and the questionnaire return rate was 90.5% (219/242). The prevalence rates of anxiety and depression were 24.7% and 17.4%, respectively. In all, 30.6% of the patients spent over half of their income to cover medical costs. Multivariate analysis revealed that anxiety symptoms (P<0.001), active disease (P<0.001) and higher medical expenditures (P=0.001) were strong and independent predictors of reduced HRQOL.
Conclusion
Psychological factors and costs of medical care strongly impair HRQOL in IBD, independent of the disease activity. Psychological counseling and socioeconomic support programs should be considered for integration into the management of IBD patients.
doi:10.2147/PPA.S118589
PMCID: PMC5189695  PMID: 28053510
inflammatory bowel disease; Crohn’s disease; health-related quality of life; anxiety; depression; stress
10.  Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assays 
Background:
There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays.
Methods:
Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs.
Results:
The three assays showed 81–96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 µg/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 µg/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 µg/ml. However, in samples with high levels of ADAs (>25 µg/ml) interference was only observed at IFX concentrations higher than 100 µg/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA- and IFX-/ADAs+ were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination.
Conclusions:
All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs-) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances.
doi:10.1177/1756283X16658223
PMCID: PMC5076767  PMID: 27803733
anti-infliximab antibodies; anti-Infliximab antibody methodologies; infliximab trough levels; therapeutic drug monitoring
11.  Surgical management of inflammatory bowel disease in China: a systematic review of two decades 
Intestinal Research  2016;14(4):322-332.
Background/Aims
The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China.
Methods
We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures.
Results
A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010.
Conclusions
The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.
doi:10.5217/ir.2016.14.4.322
PMCID: PMC5083261  PMID: 27799883
Inflammatory bowel disease; General surgery; China; Systematic review
12.  Magnetic resonance enterography versus capsule endoscopy activity indices for quantification of small bowel inflammation in Crohn’s disease 
Background:
Video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) are the prime modalities for the evaluation of small bowel (SB) Crohn’s disease (CD). Mucosal inflammation on VCE is quantified using the Lewis score (LS). Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows for accurate assessment of SB inflammation without administration of intravenous contrast material. The Magnetic Resonance Index of Activity (MaRiA) and the Clermont index are quantitative activity indices validated for contrast-enhanced MRE and DW-MRE, respectively. The aim of this study was to compare the quantification of distal SB inflammation by VCE and MR-related activity indices.
Methods:
Patients with known quiescent SB CD were prospectively recruited and underwent MRE and VCE. LS, MaRIA and Clermont scores were calculated for the distal SB.
Results:
Both MRI-based indices significantly correlated with the LS and the Clermont index (r = 0.50, p = 0.001 and r = 0.53, p = 0.001, respectively). Both MaRIA and Clermont scores were significantly lower in patients with mucosal healing (LS < 135). The area under the curve (AUC) with both MR scores was moderate for prediction of any mucosal inflammation (LS ⩾ 135) and excellent for prediction of moderate-to-severe inflammation (LS ⩾ 790) (0.71 and 0.74 versus 0.93 and 0.91 for MaRIA and Clermont score, respectively).
Conclusions:
Modest correlation between VCE- and MRE-based quantitative indices of inflammation in patients with quiescent SB CD was observed. Between-modality correlation was higher in patients with endoscopically severe disease. DW-MRE gauged by Clermont score was at least as accurate as contrast-enhanced MRE for quantification of SB inflammation.
doi:10.1177/1756283X16649143
PMCID: PMC4984327  PMID: 27582877
Crohn’s disease; diffusion-weighted MRI; magnetic resonance enterography; videocapsule endoscopy
13.  Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells 
Background
To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5+ B cells in MSC therapy.
Methods
The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4+ T helper (Th) cell subgroups and CD5+ regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5+ B cells were isolated for in vitro co-culture and adaptive transfer.
Results
HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5+ B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5+ B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5+ B cells also inhibited T-cell proliferation and produced interleukin (IL)-10.
Conclusions
HUC-MSCs protected against experimental colitis by boosting the numbers of CD5+ B cells and IL-10-producing CD5+ Bregs, and correcting Treg/Th17/Th1 imbalances.
Electronic supplementary material
The online version of this article (doi:10.1186/s13287-016-0376-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s13287-016-0376-2
PMCID: PMC4981968  PMID: 27515534
Mesenchymal stem cells; Colitis; Crohn’s disease; B regulatory cell; T helper cell
14.  Magnetic resonance enterography or video capsule endoscopy – what do Crohn’s disease patients prefer? 
Patient preference and adherence  2016;10:1043-1050.
Background
Despite differences in the information obtained by capsule endoscopy (CE) and magnetic resonance enterography (MRE), one of these modalities is usually needed when evaluating disease activity. There are no data on patients’ preference that would help guide the choice between these two modalities in these instances.
Aim
To compare patients’ tolerance and preference to MRE versus CE.
Patients and methods
Patients with known small bowel Crohn’s disease (CD) in clinical remission (Crohn’s disease activity index [CDAI] <150) or with mild symptoms (CDAI <220) were prospectively recruited. All patients underwent MRE followed by CE. Patients were asked to fill out a questionnaire addressing specific points regarding inconvenience during the preparation for the procedures, the procedures, and postprocedures. Side effects and procedure preference were addressed. Questionnaires were included for analysis only when more than 95% of the items were addressed.
Results
Fifty-six patients fulfilled inclusion criteria. Pre-exam discomfort, during-exam discomfort, nausea, vomiting, bloating, and abdominal pain were all significantly more prominent in MRE as compared to CE (P<0.0001, P<0.0001, P<0.0001, P=0.009, P=0.0002, P<0.0001, respectively). MRE was perceived as a more difficult procedure (P<0.0001). Furthermore, MRE was associated with a specific adverse event – claustrophobia. Seventy-eight percent of patients (44 patients) preferred to repeat CE as compared to 22% (P<0.0001) who preferred MRE.
Conclusion
CE was better tolerated by CD patients compared to MRE and was preferred by 78% of patients. The superior tolerability of CE should be considered along with the diagnostic features, and more data sought when choosing between these two modalities for CD patients for long-term follow-up.
doi:10.2147/PPA.S99690
PMCID: PMC4908937  PMID: 27354774
inflammatory bowel disease; Crohn’s imaging; MRE; capsule endoscopy; patients’ preference
15.  Optimizing biologic treatment in IBD: objective measures, but when, how and how often? 
BMC Gastroenterology  2015;15:178.
Background
The advent of biologic agents for the treatment of inflammatory bowel disease (IBD) was accompanied in parallel with emerging understanding of persisting underlying inflammation and ensuing bowel damage that can occur even in patients with seeming clinical remission. This lead to the concepts of mucosal healing and deep remission gaining acceptance as the more desired goals for therapy within an ambitious disease-control therapeutic approach, namely, treat-to-target strategy. However, how to practically monitor IBD patients, which objective measures to follow, at what time-points and whether to act upon results in asymptomatic patients are all questions that remain disputed.
Methods and result
In this concise review we aim to provide an overview of objective measures for monitoring of IBD patients, focusing on the challenging group of patients treated by infliximab, adalimumab, vedolizumab and other biologics. These objective measures are discussed in the context of the different common clinical scenarios wherein the clinician may contemplate their use. Specifically, we will delineate the role of objective parameters to be monitored during induction phase of treatment, during maintenance therapy, at loss of response and after elective cessation of therapy in patients in remission.
Conclusion
Coupled with the non-negligible costs of therapy, and the over-all worse prognosis of moderate-severe patients who are the usual recipients of biologic therapies, this challenging patients seem to be the first candidates for this more proactive strategy combining inflammatory and pharmacokinetic monitoring of objective inflammatory and pharmacokinetic measures. More data is still desirable to better define the exact parameters to be followed and their optimal thresholds, and to delineate the optimal cost-effective interventions for these patients.
doi:10.1186/s12876-015-0408-x
PMCID: PMC4683713  PMID: 26678147
16.  Infliximab-Related Infusion Reactions: Systematic Review 
Journal of Crohn's & Colitis  2015;9(9):806-815.
Objective:
Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur.
Methods:
We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients.
Results:
We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies.
Conclusions:
There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms.
doi:10.1093/ecco-jcc/jjv096
PMCID: PMC4558633  PMID: 26092578
Infliximab; infusion reactions; adverse drug reaction; drug hypersensitivity; drug allergy; drug toxicity; inflammatory bowel disease; Crohn’s disease; ulcerative colitis
17.  Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure 
Medicine  2015;94(18):e673.
Supplemental Digital Content is available in the text
Abstract
Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.
To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.
One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17–0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13–0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15–0.65, P = 0.002; OR 0.42 95% CI 0.18−0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07−16.1, p = 0.04, OR 4.45 95% CI 1.2−16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14−0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07–16.1, P = 0.04; OR 4.45, 95% CI 1.2–16.6, P = 0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14–0.96, P = 0.04).
Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.
doi:10.1097/MD.0000000000000673
PMCID: PMC4602524  PMID: 25950682
18.  Significance of low level infliximab in the absence of anti-infliximab antibodies 
AIM: To evaluate the prevalence of double negative (DN) sera and the mechanisms responsible for DN status.
METHODS: Sera of inflammatory bowel disease patients treated with infliximab (IFX) were tested for drug/antibodies to infliximab (ATI) trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA (with labeled IFX as the detection antibody) and an anti-lambda ELISA (with anti-human lambda chain detection antibody). Repeat testing with lower than customary serum dilution (1:10) was performed. Patients with DN status were matched with IFX+/ATI- controls and were followed-up for subsequent development of non-transient ATI to investigate if DN status precedes ATI.
RESULTS: Of 67 sera obtained at time of loss of response, only 6/67 (9%) were DN by anti-lambda ELISA compared to 27/67 (40%) with double antigen ELISA (P < 0.001, Fisher’s Exact test). Of the latter 27 sera, 22% were also DN by anti-lambda ELISA, whereas 44% were actually IFX positive (IFX+ATI-), 30% were ATI positive (IFX-ATI+) and 4% were double positive (IFX+ATI+). Re-testing using a 1:10 dilution converted most DN results into IFX+ and /or ATI+ status. Patients with DN status had shorter survival free of non-transient ATI compared with matched controls (log rank test, P < 0.001). In 9/30 (30%) of these patients, non transient ATI occurred before and after the event at which the DN serum was obtained, supporting the view that a DN result may represent a particular time-point along the two curves of ATI titer rise and infliximab drug level decline.
CONCLUSION: DN status may result from false negative detection of IFX or ATI by double antigen ELISA, suggesting a transitional state of low-level immunogenicity, rather than non-immunological clearance.
doi:10.3748/wjg.v21.i6.1907
PMCID: PMC4323470  PMID: 25684959
Inflammatory bowel disease; Biological therapy; Infliximab; Immunology; Drug response
19.  Magnetic resonance enterography in pregnant women with Crohn’s disease: case series and literature review 
BMC Gastroenterology  2014;14:146.
Background
Evaluation of pregnant women with known or suspected Crohn’s disease (CD) remains a challenge. Magnetic Resonance Enterography (MRE) is a promising diagnostic tool in these patients; however, the clinical data on MRE utilization in pregnancy is scarce. The aim of the study was to describe the experience with MRE in pregnant CD patients in a tertiary referral center.
Methods
We retrospectively reviewed MRE studies performed in pregnant women with known or suspected CD that were performed between January 2007 and November 2012. Imaging findings, clinical management and outcome were extracted from patient’s file and electronic records. Image quality was evaluated.
Results
Ten studies of 9 patients were included. MRE protocol was modified to maximize maternal and fetal safety, and intravenous gadolinium was not used. In 7 patients, CD diagnosis was previously established; six were admitted with clinical symptoms consistent with CD exacerbation, and an additional patient with a recurrent groin abscess without apparent luminal symptoms. In all seven patients, imaging features consistent with active CD were detected; new penetrating complications were detected in 4 patients. Two patients underwent MRE for suspected CD which was not comforted by study results. The clinical management was significantly impacted by MRE results in all positive cases. The image quality of the fast MRE sequences obtained without gadolinium was satisfactory and allowed meaningful interpretation.
Conclusion
MRE with an adapted protocol for pregnancy is a reliable imaging modality to manage in pregnant women with known or suspected CD.
doi:10.1186/1471-230X-14-146
PMCID: PMC4141584  PMID: 25129422
Crohn’s disease; Pregnancy; Magnetic resonance enterography; MRI
20.  Partners of patients with inflammatory bowel disease: how important is their support? 
Background
Chronic inflammatory bowel disease (IBD) causes significant distress for patients and their families. Data assessing the need of these patients for support and sharing with their partners are scarce. The aim of this study was to assess patients’ views regarding sharing of information with their partners.
Methods
Ambulatory IBD patients treated at the Chaim Sheba Medical Center between January 2011 and January 2013 were asked to complete an anonymous questionnaire. Patients who had a stable partner and completed more than 95% of the questionnaire were included.
Results
Of 134 patients who agreed to complete the questionnaire, 101 met the inclusion criteria, 53 were men (mean age 45±15 years), and 50% had academic education. Only 42% of patients reported that their partner accompanied them to the doctor. However, 93% shared health problems with their partner, 64% would have liked their partner to receive more medical information, and 70% would like their partner to be more involved. The majority (88%) believed that more partner involvement could help them deal better with the disease, and 70% thought that support groups for partners should be established. No association was found between patients’ demographic data and their answers. Patients who felt that partner involvement could help them to deal with the disease tended to share medical information with their partners and wanted them to be more involved in health care decision-making (P<0.001).
Conclusion
Most IBD patients in our study wanted their partner to be more involved with their health problems, and believed that greater partner involvement could help them deal better with their disease. Therefore, more attention should be focused on gaining better cooperation from patients’ families.
doi:10.2147/CEG.S62173
PMCID: PMC4122224  PMID: 25114579
inflammatory bowel disease; Crohn’s disease; ulcerative colitis; partner; psychological support; coping
21.  Antiviral therapy in cytomegalovirus-positive ulcerative colitis: A systematic review and meta-analysis 
AIM: To evaluate the impact of antiviral treatment on cytomegalovirus (CMV)-positive ulcerative colitis patients.
METHODS: We performed a systematic review and meta-analysis (MA) of comparative cohort and case-control studies published between January 1966 and March 2013. Studies focusing on colectomy series and studies including only less than 3 patients in the treated or non-treated arm were excluded. The primary outcome was colectomy within 30 d of diagnosis. Secondary outcomes included colectomy during the follow-up period Subgroup analyses by method of detection of CMV, study design, risk of bias and country of origin were performed. Quality of studies was evaluated according to modified New-Castle Ottawa Scale.
RESULTS: After full-text review, nine studies with a total of 176 patients were included in our MA. All the included studies were of low to moderate quality. Patients who have received antiviral treatment had a higher risk of 30-d colectomy (OR = 2.40; 95%CI: 1.05-5.50; I2 = 37.2%). A subgroup analysis including only patients in whom CMV diagnosis was based did not demonstrate a significant difference between the groups (OR = 3.41; 95%CI: 0.39-29.83; I2 = 56.9%). Analysis of long-term colectomy rates was possible for 6 studies including 110 patients. No statistically significant difference was found between the treated and untreated groups (OR = 1.71; 95%CI: 0.71-4.13; 6 studies, I2 = 0%). Analysis of mortality rate was not possible due to a very limited number of cases. Stratification of the outcomes by disease severity was not possible.
CONCLUSION: No positive association between antiviral treatment and a favorable outcome was demonstrated. These findings should be interpreted cautiously due to primary studies’ quality and potential biases.
doi:10.3748/wjg.v20.i10.2695
PMCID: PMC3949279  PMID: 24627606
Ulcerative colitis; Cytomegalovirus; Colectomy; Antiviral treatment; Gancyclovir; Foscarnet
22.  Therapeutic drug monitoring in inflammatory bowel disease 
Tumor necrosis factor (TNF)-α inhibitors and thiopurines are among the most important classes of medications utilized in the clinical management of Crohn’s disease and ulcerative colitis. A significant proportion of patients loses response to these agents or develops adverse effects during the course of the treatment. Monitoring of drug levels and anti-drug antibodies (for TNF-α inhibitors) and metabolite levels (for thiopurines) can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients. This review summarizes the current knowledge on the clinical implications of therapeutic drug monitoring in inflammatory bowel disease patients treated with TNF-α inhibitors and thiopurines.
PMCID: PMC4188926  PMID: 25331715
Inflammatory bowel disease; Crohn’s disease; ulcerative colitis; biologics; thiopurines
23.  Cytomegalovirus positive ulcerative colitis: A single center experience and literature review 
AIM: To compare the clinical outcome of cytomegalovirus (CMV)-positive ulcerative colitis (UC) patients with and without antiviral therapy.
METHODS: This was a retrospective case-controlled study. The database of UC patients in our institution was scanned for documented presence of CMV on colonic biopsies. Demographics, clinical data, endoscopy findings and pathology reports were extracted from the patients’ charts and electronic records. When available, the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also extracted. The primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the follow-up.
RESULTS: Thirteen patients were included in the study, 7 (53.5%) of them were treated with gancyclovir and 6 (46.5%) were not. Patients treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir, while none of the patients without antivirals required rescue therapy. One patient died and another patient underwent urgent colectomy during hospitalization, both of them from the gancyclovir-treatment group. For the entire follow-up time (13 ± 13 mo), a total of 3 colectomies and one death occurred, all among the antiviral-treated patients (for colectomy: 3/7 vs 0/6 patients, P = 0.19; for combined adverse outcome: 4/7 vs 0/6 patients, P = 0.07). In 9/13 patients, immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient only.
CONCLUSION: Gancyclovir-treated patients had a more severe disease and outcome, probably unrelated to antiviral therapy. Immunohistochemistry-CMV-positive patients with mild disease may recover without antiviral therapy.
doi:10.4291/wjgp.v4.i1.18
PMCID: PMC3627461  PMID: 23596551
Ulcerative colitis; Cytomegalovirus; Gancyclovir; Cyclosporine; Immunohistochemistry
24.  Familial ulcerative colitis in Israeli Jews: its prevalence and clinical severity compared to sporadic disease 
Background
A family history of inflammatory bowel disease (IBD) is present in some ulcerative colitis (UC) patients. We aimed to investigate the familial occurrence of UC and its impact on disease severity.
Methods
A structured questionnaire was distributed to patients with UC. Parameters pertaining to disease severity were compared for patients with or without positive family history of IBD.
Results
The study group consisted of 168 UC patients with a total of 952 first degree relatives. Positive family history for IBD in a first degree relative was reported in 24 patients (14%). Six of the 336 parents (1.8%) had IBD (all with UC). There were 13 siblings with IBD (4 CD, 9 UC) out of 249 (5.4%). Seven of 376 (1.9%) offsprings had IBD (4 CD, 3 UC). Familial patients were more commonly females and have reported significantly more disease exacerbations than the sporadic group (17.7±15 versus 6.8±11, respectively, p=0.006). On multivariate analysis, familial disease was significantly and independently associated with both female sex (OR 4.1, 95% CI 1.1-14.9, p=0.04) and more exacerbations per year (annual OR 1.05, 95% CI 1.01-1.1, p=0.02). However, similar proportions of sporadic and familial patients wherever hospitalized, underwent colectomy or were treated by immune-suppressors.
Conclusions
Familial occurrence of UC is not uncommon among Jewish patients in Israel. The familial-genetic component may preferentially influence disease occurrence among females, and is possibly associated with more disease flares although other parameters of disease severity do not seem to be impacted.
PMCID: PMC3959319  PMID: 24713724
Crohn’s disease; ulcerative colitis; inheritance
25.  Flare-up of ulcerative colitis after systemic corticosteroids: A strong case for Strongyloides 
Super-imposed infection with intestinal organisms can mimic a flare-up of underlying disease in patients with inflammatory bowel disease (IBD). We report a case of patient with long standing ulcerative colitis (UC), who presented with abdominal pain, diarrhea and low-grade fever after receiving systemic corticosteroids for an unrelated disorder. Despite a negative stool examination, a peripheral eosinophilia reappeared upon tapering down of a corticosteroid dose. Subsequently, duodenal biopsies showed evidence for Strongyloides, presumably acquired 20 years ago when the patient was residing in Brazil. The patient fully recovered following anti-helmintic therapy. This case underscores the importance of considering Strongyloides in the work-up of flaring-up IBD patients, even if a history of residing or traveling to endemic areas is in the distant past.
doi:10.3748/wjg.14.4413
PMCID: PMC2731200  PMID: 18666337
Ulcerative colitis; Infection; Parasites; Eosinophilia; Strongyloides

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