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1. Environmental Interaction of Resolved Human Cytomegalovirus Infection With Crohn's Disease Location

Author: Terri Shih, Susy Yusung, Rivkah Gonsky, Rhiannon Dutra-Clarke, David Ziring, Shervin Rabizadeh, Subra Kugathasan, Lee A Denson, Dalin Li, and Jonathan Braun
Subjects: Gastroenterology, Immunology and Allergy
Abstract: Lay Summary Active cytomegalovirus (CMV) infection complicates management of inflammatory bowel disease, but the relationship of resolved CMV infection to Crohn’s disease (CD) behavior or localization is unknown. This article reports a striking risk (9-fold) of Crohn’s disease localization to the colon with prior CMV infection. It also reports imputed mucosal cellular composition, HLA class 1, and KIR gene variants that delimit prior observations regarding HLA and KIR associations with Crohn’s disease risk and behavior.
Published: 2022

2. MULTIDISCIPLINARY MANAGEMENT, ANTI-TNF THERAPY, AND CLINICAL OUTCOMES OF INTERNALLY PENETRATING CROHN’S DISEASE COMPLICATION IN PEDIATRICS: INTERIM ANALYSES OF A MULTICENTER RETROSPECTIVE COHORT

Author: Brad Constant, Janet Okraku-Mantey, Kelly Kachelries, Sudha Anupindi, Jing Huang, Robert Baldassano, Frank Scott, Edwin de Zoeten, Ryan Morrow, Sabina Ali, Becca Trombler, Brad Pasternak, Amanda Kuehn, Jacob Kurowski, Jessica Barry, Jeremy Adler, Ibrahim Tarabishy, Whitney Sunseri, Erin Crawford, Jennifer Dotson, Shervin Rabizadeh, David Ziring, Jeannie Huang, Rusvelda Cruz, Cary Sauer, and Lindsey Albenberg
Subjects: Hepatology, Gastroenterology, Immunology and Allergy
Abstract: BACKGROUND Internally penetrating Crohn’s disease (CD) complications (IPCDC; i.e. abscess and/or inflammatory mass) confer significant morbidity to pediatric patients with CD. Management strategies are heterogenous. Anti-tumor-necrosis-factor-a biologics (anti-TNF) are the mainstay of penetrating CD therapy and are most effective early in the treatment course. However, anti-TNF use among patients with IPCDC is limited by hesitancy concerning infectious risk. Recent studies show that this risk may be overstated. We hypothesized that early anti-TNF following IPCDC diagnosis, in the context of infection control, is 1) safe and 2) effective in pediatric patients. Here, we present interim results of an observational multi-center study. METHODS We performed a retrospective cohort study of pediatric patients with IPCDC, across 12 tertiary children’s hospitals. Patients (age 6+ years) were identified via radiology, ICD-coding, and ImproveCareNow searches. Patients admitted for an IPCDC diagnosed via MRI or CT from 2007-2021, with 1+ year of follow-up were included. Patients were excluded if complications were due to a non-CD-related process, solely perianal, if admission followed outpatient or outside institution treatment failure, or if surgery was required within 7 days of IPCDC (n=7). First, we measured the safety effect of anti-TNF following IPCDC diagnosis, prior to IPCDC resolution, on infectious serious adverse events (SAE) (i.e. new or enlarging IPCDC, or infection, requiring hospitalization or surgery), within 30 days. Next, we measured the effectiveness of anti-TNF within 30 days of IPCDC diagnosis on CD-related SAEs (i.e. non-infectious CD-related hospitalization or surgery), within one year. Kaplan-Meier curves were generated to describe outcomes over time. RESULTS 95 patients were included. Cohort characteristics, multidisciplinary treatment strategies, and outcomes are presented in Table 1. Kaplan-Meier curves are presented in Figure 1. 80% of patients received anti-TNF within one year of IPCDC (median 37 days [IQR 7-68]). Infectious SAEs within 90 days of IPCDC occurred in 37% (median 20 days [IQR 10-26]). Among patients initiating anti-TNF prior to IPCDC resolution, 27% had an infectious SAE within 90 days, compared to 49% of those not initiating anti-TNF prior to IPCDC resolution. Non-infectious CD-related SAEs within one year occurred in 44% (median 51 days [IQR 27, 89]). Among patients initiating anti-TNF within 30 days of IPCDC, 47% had a CD-related SAE, compared to 43% in those not receiving anti-TNF within 30 days. CONCLUSION Among a large multicenter pediatric cohort, IPCDC are associated with high rates of both infectious and CD-related SAE. Further data collection, implementation of causal inference methods, and subgroup analyses will be critical in isolating the relationship between timing of anti-TNF post-IPCDC and SAEs. Values represent Number (Percent) for categorical variables and Median (Interquartile Range) for continuous variables. Kaplan-Meier Survival Analyses for A) Infectious Serious Adverse Events and B) Crohn's Disease-Related Serious Adverse Events, stratified by exposure status. No censoring for lost-to-followup occured, as all patients had at least 1 year of follow-up avaialble.
Published: 2023

3. S725 linical Utility of Precision-Guided Dosing Tool for Infliximab During Maintenance Therapy of Inflammatory Bowel Disease

Author: Bincy Abraham, Shervin Rabizadeh, Taha Qazi, Esther A. Torres, Ayesha Fatima, Ann D. Flynn, David Ziring, Robert Battat, Ryan Ungaro, Corey A. Siegel, Judith Gohndrone, Donald Lum, Adria A. Condino, Daniel J. Stein, Jana G. Hashash, Waseem Ahmed, Catherine Rowan, Brad Pasternak, Akash Pandey, Gil Y. Melmed, Jonathan Moses, Stephen B. Hanauer, Jean-Frederic Colombel, and Thierry Dervieux
Subjects: Hepatology, Gastroenterology
Published: 2022

4. Global multi-stakeholder endorsement of the MAFLD definition

Author: Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. Lee, Way Seah Lee, Yeong Yeh Lee, Diana Julie Leeming, Nathalie Carvalho Leite, Roberto Leon, Cosmas Rinaldi Adithya Lesmana, Junfeng Li, Qiong Li, Jun Li, Yang-Yang Li, Yufang Li, Lei Li, Min Li, Yiling li, Huiqing Liang, Tang Lijuan, Seng Gee Lim, Lee-Ling Lim, Shumei Lin, Han-Chieh Lin, Rita Lin, Rania Lithy, Yaru Liu, Yuanyuan Liu, Xin Liu, Wen-Yue Liu, Shourong Liu, Ken Liu, Tian Liu, Amedeo Lonardo, Mariana Bravo López, Eva López-Benages, Patricio Lopez-Jaramillo, Huimin Lu, Lun Gen Lu, Yan Lu, John Lubel, Rashid Lui, Iulianna Lupasco, Elena Luzina, Xiao-Hui Lv, Kate Lynch, Hong-Lei Ma, Mariana Verdelho Machado, Nonso Maduka, Katerina Madzharova, Russellini Magdaong, Sanjiv Mahadeva, Amel Mahfouz, Nik Ritza Kosai Nik Mahmood, Eman Mahmoud, Mohamed Mahrous, Rakhi Maiwall, Ammar Majeed, Avik Majumdar, Loey Mak, Madiha M Maklouf, Reza Malekzadeh, Claudia Mandato, Alessandra Mangia, Jake Mann, Hala Hussien Mansour, Abdellah Mansouri, Alessandro Mantovani, Jun qian Mao, Flor Maramag, Giulio Marchesini, Claude Marcus, Rui António Rocha Tato Marinho, Maria L Martinez-Chantar, Antonieta A. Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. Nersesov, Manuela Neuman, Masolwa Ng'wanasayi, Yan Ni, Amanda Nicoll, Takashi Niizeki, Dafina Nikolova, Wang Ningning, Madunil Niriella, K.A Nogoibaeva, Rozeena Nordien, Catherine O Sullivan, James O'Beirne, Solomon Obekpa, Ponsiano Ocama, Missiani Ochwoto, Michael Promise Ogolodom, Olusegun Ojo, Nana Okrostsvaridze, Claudia P. Oliveira, Raul Contreras Omaña, Omneya M. Omar, Hanaa Omar, Mabroka Omar, Salma Omran, Reham Omran, Marian Muse Osman, Nevin Owise, Theobald Owusu-Ansah, P. Martín Padilla- Machaca, Sirish Palle, Ziyan Pan, Xiao-Yan Pan, Qiuwei Pan, Apostolis Papaefthymiou, Feliciano Chanana Paquissi, Gabriella Par, Arit Parkash, Diana Payawal, Kevork M. Peltekian, Xuebin Peng, Liang Peng, Ying Peng, Rahul Pengoria, Martina Perez, José Luis Pérez, Norma Marlene Pérez, Marcello Persico, Mário Guimarães Pessoa, Salvatore Petta, Mathew Philip, Maria Corina Plaz Torres, Naveen Polavarapu, Jaime Poniachik, Piero Portincasa, Chunwen Pu, Tuğrul Pürnak, Edhie Purwanto, Xiaolong Qi, Xingshun Qi, Zibing Qian, Zhao Qiang, Zengpei Qiao, Liang Qiao, Alberto Queiroz, Atoosa Rabiee, Manal Radwan, Alain Marcel Rahetilahy, Yasmin Ramadan, Dina Ramadan, Anis Safura Ramli, Grant A. Ramm, Ao Ran, Ivan Rankovic, Huiying RAO, Sara Raouf, Sayantan Ray, Nancy Reau, Ahmed Refaat, Thomas Reiberger, Jose M Remes-Troche, Eira Cerda Reyes, Ben Richardson, Ezequiel Ridruejo, Sergio Riestra Jimenez, Ibrahim Rizk, Stuart Roberts, Juan Pablo Roblero, Jorge Alberto Prado Robles, Don Rockey, Manuel Rodríguez, Heriberto Rodríguez Hernández, Eva Román, Fernando Gomes Romeiro, Stefano Romeo, Jose Miguel Rosales-Zabal, Georgina R. Roshdi, Natalia Rosso, Andres Ruf, Patricia Cordero Ruiz, Nelia R. Runes, Andrea Ruzzenente, Marno Ryan, Ahmed Saad, Eman BE Sabbagh, Meriam Sabbah, Shimaa Saber, Reham Sabrey, Ramy Sabry, Maysaa Abdallah Saeed, Dina Said, Ebada M Said, Mohammad Amin Sakr, Yara Salah, Rabab Maamoun Salama, Asmaa Salama, Hussein Saleh, Ahmed Saleh, Ahmed Salem, Ahmed Thabet Salem, Alkassoum Salifou, Aso Faeq Salih, Abdallah Salman, Hanen Samouda, Faisal Sanai, Juan Francisco Sánchez-Ávila, Lakshumanan Sanker, Tomoya Sano, Miquel Sanz, Tobokalova Saparbu, Rohit Sawhney, Fatma Sayed, Sayed A. Sayed, Ashraf Othman Sayed, Manar Sayed, Giada Sebastiani, Laura Secadas, Khawaja Qamaruddin Sediqi, Sameh Seif, Nady Semida, Ebubekir Şenateş, Elena Daniela Serban, Lawrence Serfaty, Wai-Kay Seto, Ikram Sghaier, Min Sha, Hamada M. Shabaan, Lobna Shalaby, Inass Shaltout, Ala I. Sharara, Vishal Sharma, Isaac Thom Shawa, Ahmed Shawkat, Nehal Shawky, Osama Shehata, Sinead Sheils, Abate Bane Shewaye, Guojun Shi, Junping Shi, Shigeo Shimose, Tomotake Shirono, Lan Shou, Ananta Shrestha, Guanghou Shui, William Sievert, Solveig Sigurdardottir, Mostafa Mohamed Sira, Riyadh Siradj, Cecilia Sison, Linda Smyth, Reham Soliman, Jose D Sollano, Roger Sombie, Mark Sonderup, Siddharth Sood, German Soriano, Catherine A M Stedman, Oksana Stefanyuk, Davor Štimac, Simone Strasser, Pavel Strnad, Katherine Stuart, Wen Su, Minghua Su, Yoshio Sumida, Shuji Sumie, Dan-Qin Sun, Jing Sun, Hiroyuki Suzuki, Gianluca Svegliati-Baroni, Mohamed Osman Swar, S. TAHARBOUCHT, Zenab Taher, Saori Takamura, Lin Tan, Soek-Siam Tan, Tawesak Tanwandee, Sara Tarek, Ghelimici Tatiana, Federica Tavaglione, Gina Y. Tecson, Hoi-Poh Tee, Rolf Teschke, Mostafa Tharwat, Vo Duy Thong, Mark Thursz, Tulari Tine, Claudio Tiribelli, Ieva Tolmane, Jing Tong, Marco Tongo, Mamdouh Torkie, Aldo Torre, Esther A Torres, Meri Trajkovska, Sombat Treeprasertsuk, Tsubasa Tsutsumi, Thomas Tu, Josep A. Tur, Dilara Turan, Svetlana Turcan, Svetlana Turkina, Engin Tutar, Christian Tzeuton, Rose Ugiagbe, Ahmet Uygun, Michele Vacca, Pietro Vajro, David Van der Poorten, Laurens A. Van Kleef, Eliza Vashakidze, Carlos Moctezuma Velazquez, Mirtha Infante Velazquez, Sandro Vento, Veronique Verhoeven, Umberto Vespasiani-Gentilucci, Shireene Ratna Vethakkan, Josep Vilaseca, Libor Vítek, Ance Volkanovska, Michael Wallace, Wang Wan, Yan Wang, Ying Wang, Xiaolin Wang, Xuemei Wang, Chengyan Wang, Chunjiong Wang, Mingjie Wang, Pelden Wangchuk, Martin Weltman, MaryFrances White, Johannes Wiegand, Mohamed-Naguib Wifi, Alan Wigg, Markus Wilhelmi, Remon William, Henning Wittenburg, Shengjie Wu, Abdu Mohammed Wubeneh, Hongping Xia, Jian Xiao, Xiao Xiao, Wang Xiaofeng, Wanyuan Xiong, Liang Xu, Jie Xu, Weiguo Xu, Jing-Hang Xu, Keshu Xu, Yumin Xu, Shi-Hao Xu, Meng Xu, Aimin Xu, Chengfu Xu, Hongmei Yan, Jingyi Yang, Rui-Xu Yang, Yating Yang, Qinhe Yang, Naibin Yang, Jia Yao, Justine Yara, Serkan Yaraş, Nimet Yılmaz, Ramy Younes, Huda younes, Sona Young, Farah Youssef, Yanyan Yu, Ming-Lung Yu, Jing Yuan, Zhang Yue, Man-Fung Yuen, Wang Yun, Nonka Yurukova, Serag Zakaria, Samy Zaky, 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Strasser, S, Strnad, P, Stuart, K, Su, W, Su, M, Sumida, Y, Sumie, S, Sun, D, Sun, J, Suzuki, H, Svegliati-Baroni, G, Swar, M, Taharboucht, S, Taher, Z, Takamura, S, Tan, L, Tan, S, Tanwandee, T, Tarek, S, Tatiana, G, Tavaglione, F, Tecson, G, Tee, H, Teschke, R, Tharwat, M, Thong, V, Thursz, M, Tine, T, Tiribelli, C, Tolmane, I, Tong, J, Tongo, M, Torkie, M, Torre, A, Torres, E, Trajkovska, M, Treeprasertsuk, S, Tsutsumi, T, Tu, T, Tur, J, Turan, D, Turcan, S, Turkina, S, Tutar, E, Tzeuton, C, Ugiagbe, R, Uygun, A, Vacca, M, Vajro, P, Van der Poorten, D, Van Kleef, L, Vashakidze, E, Velazquez, C, Velazquez, M, Vento, S, Verhoeven, V, Vespasiani-Gentilucci, U, Vethakkan, S, Vilaseca, J, Vitek, L, Volkanovska, A, Wallace, M, Wan, W, Wang, Y, Wang, X, Wang, C, Wang, M, Wangchuk, P, Weltman, M, White, M, Wiegand, J, Wifi, M, Wigg, A, Wilhelmi, M, William, R, Wittenburg, H, Wu, S, Wubeneh, A, Xia, H, Xiao, J, Xiao, X, Xiaofeng, W, Xiong, W, Xu, L, Xu, J, Xu, W, Xu, K, Xu, Y, Xu, S, Xu, M, Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease
Subjects: Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract: Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)
Published: 2022

5. Decreased Antibody Responses to Ad26.COV2.S Relative to SARS-CoV-2 mRNA Vaccines in Patients With Inflammatory Bowel Disease

Author: Andrea Banty, Edward J. Feldman, Laura E. Raffals, Stephan R. Targan, Jonathan Braun, Erica R. Cohen, Susie Lee, Dermot P.B. McGovern, Gregory J. Botwin, Valeriya Pozdnyakova, Jason K. Hou, Theodore Stein, Emebet Mengesha, Nimisha K. Parekh, Corey A. Siegel, Mark C. Mattar, Joseph E. Ebinger, Jane Figuereido, John Prostko, Edwin C. Frias, Donald Lum, Kimia Sobhani, Sarah Sheibani, Ann D. Flynn, Mark Metwally, Aline Charabaty, Gaurav Syal, James L. Stewart, Swapna Reddy, Mark Lazarev, Rashmi Kumar, Keren L. Appel, Ziad Younes, Caroline Hwang, Gil Y. Melmed, Arthur Ostrov, David Ziring, David I. Fudman, Philip Debbas, John F. Valentine, Michael V. Chiorean, Rebecca Fausel, Brigid S. Boland, Melissa Hampton, Douglas C. Wolf, Christina Ha, Susan Cheng, Arash Horizon, Eric A. Vasiliauskas, and Shervin Rabizadeh
Subjects: 2019-20 coronavirus outbreak, Messenger RNA, COVID-19 Vaccines, Hepatology, Coronavirus disease 2019 (COVID-19), Ad26COVS1, business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Gastroenterology, COVID-19, medicine.disease, Inflammatory Bowel Diseases, Virology, Inflammatory bowel disease, Article, Antibody response, Antibody Formation, Medicine, Humans, RNA, Viral, In patient, business
Published: 2021

6. 656: POST-VACCINATION SYMPTOMS AFTER A THIRD DOSE OF SARS-COV-2 MRNA VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Author: Angela Mujukian, Dalin Li, Philip Debbas, Andrea Banty, Edward J. Feldman, Christina Ha, Susie Lee, Shervin Rabizadeh, Theodore Stein, Theodore Solomon, Gaurav Syal, Stephan R. Targan, Eric A. Vasiliauskas, David Ziring, Nirupama Bonthala, Melissa Hampton, Valeriya Pozdnyakova, Phillip Gu, Joseph Ebinger, Sandy Joung, Jane C. Figueiredo, Akil Merchant, Noah Merin, Karen L. Reckamp, Keren Appel, Rashmi Kumar, Brigid Boland, Aline Charabaty, Michael V. Chiorean, Erica Cohen, Ann D. Flynn, John F. Valentine, Adam C. Ehrlich, David Fudman, Sarah C. Glover, Arash A. Horizon, Dmitry Karayev, Benjamin Kretzmann, Jason K. Hou, Caroline Hwang, Mark Lazarev, Donald Lum, Rebecca Fausel, Swapna Reddy, Ryan McConnell, Mark Mattar, Mark Metwally, Arthur Ostrov, Parekh Nimisha, Laura H. Raffals, David T. Rubin, Sarah Sheibani, Corey A. Siegel, Douglas C. Wolf, Ziad H. Younes, Susan Cheng, Jonathan G. Braun, Dermot P.B. Mcgovern, and Gil Melmed
Subjects: Hepatology, Gastroenterology
Published: 2022

7. 653: PATIENTS WITH INFLAMMATORY BOWEL DISEASE HAVE IMPAIRED HUMORAL BUT PRESERVED CELLULAR RESPONSES TO SARS-COV-2 MRNA VACCINATION

Author: Dalin Li, Alexander Xu, Joseph Ebinger, Philip Debbas, Andrea Banty, Edward J. Feldman, Christina Ha, Susie Lee, Shervin Rabizadeh, Theodore Stein, Theodore Solomon, Gaurav Syal, Stephan R. Targan, Eric A. Vasiliauskas, David Ziring, Nirupama Bonthala, Melissa Hampton, Angela Mujukian, Valeriya Pozdnyakova, Phillip Gu, Sandy Joung, Keren Appel, Rashmi Kumar, Brigid S. Boland, Aline Charabaty, Michael V. Chiorean, Erica Cohen, Oriana M. Damas, Ann D. Flynn, John F. Valentine, Adam C. Ehrlich, David Fudman, Sarah C. Glover, Arash A. Horizon, Dmitry Karayev, Benjamin Kretzmann, Jason K. Hou, Caroline Hwang, Mark Lazarev, Donald Lum, Rebecca Fausel, Swapna Reddy, Ryan McConnell, Mark Mattar, Mark Metwally, Arthur Ostrov, Nimisha K. Parekh, Laura H. Raffals, David T. Rubin, Sarah Sheibani, Corey A. Siegel, Douglas C. Wolf, Ziad H. Younes, Ian M. Kaplan, John Prostko, Kimia Sobhani, Akil Merchant, Susan Cheng, Jonathan G. Braun, Dermot P.B. Mcgovern, and Gil Melmed
Subjects: Hepatology, Gastroenterology
Published: 2022

8. S824 Humoral Response to Ad26.COV2.S and SARS-CoV-2 mRNA Vaccines in Patients With Inflammatory Bowel Disease

Author: Valeriya Pozdnyakova, Gregory J. Botwin, Keren L. Appel, Rashmi Kumar, Nirupama Bonthala, Caroline Hwang, David Ziring, Melissa Hampton, Emebet Mengesha, Cindy D. Zamudio, Shane White, null CCRC, Philip Debbas, Diana Benliyan, Anzhelya Makaryan, Yin Li, Justina Ibrahim, Mary Hanna, Angela Mujukian, Susie K. Lee, Andrea Banty, Min Wu, Sandy Joung, Sarah Sternbach, Joseph Ebinger, Kimia Sobhani, Susan Cheng, Dermot McGovern, Jonathan Braun, and Gil Melmed
Subjects: 2019-20 coronavirus outbreak, Messenger RNA, Hepatology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Gastroenterology, Medicine, In patient, business, medicine.disease, Virology, Inflammatory bowel disease
Published: 2021

9. Ewing's Sarcoma in a Patient with Crohn's Disease Treated with Ustekinumab: A Case Report

Author: Rameshwar R. Rao, Fataneh Majlessipour, David Ziring, and Nicole Baca
Subjects: Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Epithelioid sarcoma, Sarcoma, Ewing, Crohn Disease, Ustekinumab, Medicine, Humans, B-cell lymphoma, Crohn's disease, business.industry, Cancer, Ewing's sarcoma, Sarcoma, Immunotherapy, medicine.disease, Dermatology, Oncology, Pediatrics, Perinatology and Child Health, Female, business, medicine.drug
Abstract: Biologic therapies have revolutionized the treatment of immune-mediated diseases. They are generally well tolerated; however, there are reports of malignancies associated with the use of these drugs. This case is of an adolescent with refractory Crohn's disease treated with ustekinumab, who subsequently developed Ewing's sarcoma. Patients treated with ustekinumab have reportedly developed B cell lymphoma, epithelioid sarcoma, as well as cancer of the lung, esophagus, ovary, testis, kidney, and thyroid. However, this is the first documented case of a patient treated with ustekinumab to develop Ewing sarcoma.
Published: 2020

10. Mucosal Inflammatory and Wound Healing Gene Programs Reveal Targets for Stricturing Behavior in Pediatric Crohn's Disease

Author: Susan S. Baker, David R. Mack, Phillip Minar, Ashish S. Patel, Neal S. Leleiko, Jennifer L. Dotson, Bruce J. Aronow, Suresh Venkateswaran, Samuel Tegge, Marla Dubinsky, Brianne Shuler, Scott B. Snapper, Dedrick E. Moulton, Yael Haberman, Robert Baldassano, Jeffrey S. Hyams, Ajay S. Gulati, Daniel Shapiro, David Ziring, Michael C. Stephens, Rebekah Karns, Richard Kellermayer, Ranjana Gokhale, Stanley A. Cohen, Thomas D. Walters, Sudhir Ghandikota, Maria Oliva-Hemker, Anthony R. Otley, Joshua D. Noe, Sandra C. Kim, Lee A. Denson, Tzipi Braun, Jonathan R. Dillman, Joel R. Rosh, Subra Kugathasan, Greg Gibson, Anne M. Griffiths, Melvin B. Heyman, Allison Ta, Phillip J. Dexheimer, James Markowitz, Anil G. Jegga, Stephen L. Guthery, and Steven J. Steiner
Subjects: 0301 basic medicine, medicine.medical_specialty, pediatric Crohn Disease, Clinical Sciences, small molecule, Crohn's Disease, Disease, Gastroenterology, Transcriptome, surgery, 03 medical and health sciences, 0302 clinical medicine, Paediatric Crohn disease, Clinical Research, Internal medicine, Gene expression, medicine, Genetics, Gene, Pediatric, Crohn's disease, Gastroenterology & Hepatology, business.industry, Inflammatory Bowel Disease, Mucous membrane, Original Articles, General Medicine, Gene signature, medicine.disease, Gene expression profiling, 030104 developmental biology, medicine.anatomical_structure, 030211 gastroenterology & hepatology, ileum, business, Digestive Diseases, transcriptome
Abstract: Background and Aims Ileal strictures are the major indication for resective surgery in Crohn’s disease [CD]. We aimed to define ileal gene programmes present at diagnosis and linked with future stricturing behaviour during 5-year follow-up, and to identify potential small molecules to reverse these gene signatures. Methods Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicentre paediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behaviour and for model testing to predict stricturing behaviour. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. Results A total of 19 of the 249 patients developed isolated B2 stricturing behaviour during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our previous report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix [ECM] gene expression, in those who developed stricturing complications. We further computationally prioritise small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by Year 5 after diagnosis {AUC (area under the curve) (95th CI [confidence interval]) = 0.82 [0.7–0.94)}. Conclusions An ileal gene programme for macrophage and fibroblast activation is linked to stricturing complications in treatment of naïve pediatric CD, and may inform novel small molecule therapeutic approaches.
Published: 2020

11. The Effect of Early-Life Environmental Exposures on Disease Phenotype and Clinical Course of Crohn's Disease in Children

Author: Marla Dubinsky, Melvin B. Heyman, Ashwin N. Ananthakrishnan, Scott B. Snapper, Anne M. Griffiths, Joel R. Rosh, James Markowitz, Livia Lindoso, Thomas D. Walters, Michael C. Stephens, Susan S. Baker, David R. Mack, Jeffrey S. Hyams, Dedrick E. Moulton, Ajay S. Gulati, Marian D. Pfefferkorn, Kajari Mondal, Maria Oliva-Hemker, Stephen L. Guthery, Suresh Venkateswaran, Anthony R. Otley, Cortney R. Ballengee, David J. Keljo, Jonathan Evans, Robert N. Baldassano, Ashish S. Patel, Lee A. Denson, Hari K. Somineni, Subra Kugathasan, Barbara S. Kirschner, Shervin Rabizadeh, Wallace Crandall, Joshua D. Noe, David Ziring, Stanley N. Cohen, Richard Kellermayer, and Neal S. LeLeiko
Subjects: Male, 0301 basic medicine, Time Factors, Adolescent, Colon, Constriction, Pathologic, Disease, Severity of Illness Index, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Pregnancy, Risk Factors, Severity of illness, medicine, Humans, Longitudinal Studies, Prospective Studies, Microbiome, Child, Immunologic Tolerance, Crohn's disease, Hepatology, business.industry, Smoking, Infant, Newborn, Gastroenterology, Environmental Exposure, medicine.disease, Phenotype, Hospitalization, Breast Feeding, 030104 developmental biology, Prenatal Exposure Delayed Effects, North America, Immunology, Disease Progression, Female, Tobacco Smoke Pollution, 030211 gastroenterology & hepatology, business, Follow-Up Studies
Abstract: Environmental factors play an important role in the pathogenesis of Crohn's Disease (CD). In particular, by virtue of the instability of the microbiome and development of immunologic tolerance, early life factors may exert the strongest influence on disease risk and phenotype.We used data from 1119 CD subjects recruited from RISK inception cohort to examine the impact of early life environment on disease progression. Our primary exposures of interest were breastfeeding in infancy and exposure to maternal, active, or passive smoke. Our primary outcomes were development of complicated (stricturing or penetrating) disease, and need for CD-related hospitalization, and surgery. Multivariable logistic regression models were used to define independent associations, adjusting for relevant covariates.Our study cohort included 1119 patients with CD among whom 15% had stricturing (B2) or penetrating disease (B3) by 3 years. 331 patients (35%) and 95 patients (10.6%) required CD-related hospitalizations and surgery respectively. 74.5% were breastfed in infancy and 31% were exposed to smoking among whom 7% were exposed to maternal smoke. On multivariable analysis, a history of breastfeeding was inversely associated with complicated (B2/B3 disease) 0.65, CI 95% 0.44-96; P = 0.03) in pediatric CD. Maternal smoking during pregnancy was associated with increased risk of hospitalization during the 3-year follow-up period (OR 1.75, CI 95% 1.05-2.89; P = 0.03).Early life environmental factors influence the eventual phenotypes and disease course in CD.
Published: 2018

12. MACHINE LEARNING FOR CROHN’S DISEASE PHENOTYPE MODELING USING BIOPSY IMAGES

Author: Scott B. Snapper, Joel R. Rosh, Shervin Rabizadeh, Ashish S. Patel, Christopher A. Moskaluk, Anne M. Griffiths, Stanley N. Cohen, Erin Bonkowski, Maria Oliva-Hemker, Joshua D. Noe, Dedrick E. Moulton, Richard Kellermayer, Jeffrey S. Hyams, Barbara S. Kirschner, Susan S. Baker, David R. Mack, David Ziring, Lee A. Denson, Sandra C. Kim, Ajay S. Gulati, Lubaina Ehsan, Anthony R. Otley, Subra Kugathasan, Thomas D. Walters, Jennifer L. Dotson, Marian D. Pfefferkorn, Jason Shapiro, Robert N. Baldassano, Saurav Sengupta, Stephen L. Guthery, James Markowitz, Melvin B. Heyman, and Sana Syed
Subjects: Crohn's disease, Pathology, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Biopsy, Gastroenterology, Medicine, Immunology and Allergy, business, medicine.disease, Phenotype
Abstract: Background Predicting Crohn’s disease (CD) phenotype development has proven challenging due to difficulties in biopsy image interpretation of histologically similar yet biologically distinct phenotypes. At initial diagnosis, mostly CD patients are classified as B1 (inflammatory behavior), they typically either retain B1 phenotype or develop more complicated B2 (stricturing), B3 (internal penetrating), or B2/B3 phenotypes (defined by Montreal Classification). Prediction of phenotype development based on baseline biopsies can radically improve our clinical care by altering disease management. Biopsy-based image analysis via Convolutional Neural Networks (CNNs) has been successful in cancer detection, but investigation into its utility for CD phenotypes is lacking. We applied a machine learning CNN model to classify CD phenotypes and histologically normal ileal controls. Methods Baseline hematoxylin & eosin (H&E) stained ileal biopsy slides were obtained from the Cincinnati Children’s Hospital Medical Center’s RISK validation sub cohort. At University of Virginia, biopsy slides were digitized, and a ResNet101 CNN model was trained. High resolution images were patched into 1000x1000 pixels with a 50% overlap and then resized to 256x256 pixels for training (80-20 split was kept between training and testing sets to ensure same patient patches were not mixed). Gradient Weighted Activating Mappings (GradCAMs) were used to visualize the model’s decision making process. Results We initially trained the model for CD vs. controls where it achieved 97% accuracy in detecting controls. We further trained it for classifying CD phenotypes (n=16 B1, n=16 B2, n=4 B3, n=13 B2/B3; phenotype decision at 5 year). It displayed a higher accuracy in detecting B2 (85%) while there were overlaps in the detection of other phenotypes (Figure 1). For B2, Grad-CAM heatmaps highlighted central pink areas within the lamina propria as the model’s regions of interests which were present when other phenotypes were misclassified as B2 (Figure 2). Conclusions: Here we highlight the potential utility of a machine learning image analysis model for describing CD phenotypes using H&E stained biopsies. Previous studies have shown B2 to be associated with increased activation for extracellular matrix genes (connective tissue component). Our GradCAM results support this finding as the pink central areas utilized by the model for classifying B2 could be connective tissue. Further confirmation via molecular phenotyping including Sirius Red immunohistochemistry is underway. Our work supports prediction of CD phenotypes using baseline biopsies at diagnosis and has potential to influence individualized care for children with CD.
Published: 2021

13. Sa482 MEGA-ANALYSIS REVEALS CLINICAL SEROLOGICAL AND GENETIC ASSOCIATIONS WITH EXTRAINTESTINAL MANIFESTATIONS IN IBD

Author: Shaohong Yang, David Hercules, Christina Ha, Gil Y. Melmed, Emebet Mengesha, Shishir Dube, Dalin Li, Gregory J. Botwin, Millie D. Long, Judy H. Cho, Shervin Rabizadeh, R. Balfour Sartor, Steven R. Brant, Bana Jabri, Richard H. Duerr, Eric A. Vasiliauskas, Ashwin N. Ananthakrishnan, William A. Faubion, David Ziring, John D. Rioux, Dermot P.B. McGovern, Stephan R. Targan, Michelle Khrom, Robert S. Sandler, L. Philip Schumm, Nirupama Bonthala, Mark S. Silverberg, Talin Haritunians, Subra Kugathasan, Sergio A. Lira, Rodney D. Newberry, Ramnik J. Xavier, and Gaurav Syal
Subjects: Hepatology, Immunology, Gastroenterology, Mega analysis
Published: 2021

14. Su521 USTEKINUMAB THERAPEUTIC DRUG MONITORING IN PEDIATRIC CROHN'S DISEASE AND ULCERATIVE COLITIS

Author: Lillian Du, David Ziring, Yvette Gonzales, Dermot P.B. McGovern, Shervin Rabizadeh, Yogesh Arora, and Keren Appel
Subjects: medicine.medical_specialty, Hepatology, medicine.diagnostic_test, Pediatric Crohn's disease, business.industry, Gastroenterology, medicine.disease, Ulcerative colitis, Dermatology, Therapeutic drug monitoring, Ustekinumab, medicine, business, medicine.drug
Published: 2021

15. Age-of-diagnosis dependent ileal immune intensification and reduced alpha-defensin in older versus younger pediatric Crohn Disease patients despite already established dysbiosis

Author: David Ziring, Stanley N. Cohen, Scott B. Snapper, Melvin B. Heyman, David J. Keljo, Jonathan Evans, Bruce J. Aronow, Richard Kellermayer, Dedrick E. Moulton, Steven J. Steiner, Mi-Ok Kim, Susan S. Baker, David R. Mack, Melanie Schirmer, Thomas D. Walters, Curtis Huttenhower, Joshua D. Noe, Barbara S. Kirschner, Phillip Dexheimer, Maria Oliva-Hemker, Lee A. Denson, Wallace Crandall, Ajay S. Gulati, Joel R. Rosh, James Markowitz, Yael Haberman, Robert N. Baldassano, Tzipi Braun, Stephen L. Guthery, Anne M. Griffiths, Ramnik J. Xavier, Jeffrey S. Hyams, Neal S. Leleiko, Marla Dubinsky, Subramaniam Kugathasan, Rebekah Karns, Anthony Otley, and Ashish S. Patel
Subjects: 0301 basic medicine, Male, Aging, Disease, Medical and Health Sciences, Alpha defensin, immune response, Pathogenesis, Cohort Studies, Peyer's Patches, 0302 clinical medicine, Crohn Disease, Immunology and Allergy, 2.1 Biological and endogenous factors, Aetiology, Child, Pediatric, Age Factors, Biological Sciences, medicine.anatomical_structure, Pediatric age-of-diagnosis, Child, Preschool, mucosal microbial profile and transcriptome, Female, Risk, alpha-Defensins, Adolescent, Immunology, digestive system, Article, 03 medical and health sciences, Immune system, Ileum, Clinical Research, medicine, Genetics, Humans, Preschool, business.industry, Prevention, Lachnospiraceae, Puberty, Inflammatory Bowel Disease, Gene signature, Th1 Cells, medicine.disease, 030104 developmental biology, Gene Expression Regulation, Paneth cell, Dysbiosis, business, Digestive Diseases, 030215 immunology
Abstract: Age-of-diagnosis associated variation in disease location and antimicrobial sero-reactivity has suggested fundamental differences in pediatric Crohn Disease (CD) pathogenesis. This variation may be related to pubertal peak incidence of ileal involvement and Peyer’s patches maturation, represented by IFNγ-expressing Th1 cells. However, direct mucosal evidence is lacking. We characterize the global pattern of ileal gene expression and microbial communities in 525 treatment-naive pediatric CD patients and controls (Ctl), stratifying samples by their age-of-diagnosis. We show a robust ileal gene signature notable for higher expression of specific immune genes including GM-CSF and INFγ, and reduced expression of antimicrobial Paneth cell α-defensins, in older compared to younger patients. Reduced α-defensin expression in older patients was associated with higher IFNγ expression. By comparison, the CD-associated ileal dysbiosis, characterized by expansion of Enterobacteriaceae and contraction of Lachnospiraceae and Ruminococcaceae, was already established within the younger group and did not vary systematically with increasing age-of-diagnosis. Multivariate analysis considering individual taxa, however did demonstrate negative associations between Lachnospiraceae and IFNγ, and positive associations between Bacteroides and α-defensin expression. These data provide evidence for maturation of mucosal Th1 immune responses and loss of epithelial antimicrobial α-defensins which are associated with specific taxa with increasing age-of-diagnosis in pediatric CD.
Published: 2019

16. Variation in care in the management of children with Crohn's disease: Data from a multicenter inception cohort study

Author: Lee A. Denson, Joshua D. Noe, Susan S. Baker, David R. Mack, David Keljo, Chenthan Krishnakumar, Anne M. Griffiths, Joel R. Rosh, Dedrick E. Moulton, Ranjana Gokhale, Marla Dubinsky, Stanley A. Cohen, Subra Kugathasan, Jeffrey S. Hyams, Maria Oliva-Hemker, Anthony R. Otley, Michael D. Kappelman, Marian D. Pfefferkorn, Mi-Ok Kim, David Ziring, Robert N. Baldassano, Richard Kellermayer, Shervin Rabizadeh, Jonathan Evans, Scott B. Snapper, Wallace Crandall, Chunyan Liu, Kajari Mondal, T Walters, Ashish S. Patel, Neal S. Leleiko, Cortney R. Ballengee, James Markowitz, Stephen L. Guthery, and Melvin B. Heyman
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Colonoscopy, Disease, Severity of Illness Index, Diagnostic modalities, 03 medical and health sciences, 0302 clinical medicine, Outcome variable, Crohn Disease, Risk Factors, Internal medicine, medicine, Humans, Immunologic Factors, Immunology and Allergy, Practice Patterns, Physicians', Child, Crohn's disease, medicine.diagnostic_test, business.industry, Gastroenterology, Antibodies, Monoclonal, Prognosis, medicine.disease, INCEPTION COHORT, 030104 developmental biology, Variation (linguistics), Cohort, Female, 030211 gastroenterology & hepatology, Patient Care, business, Follow-Up Studies
Abstract: Background: Variation in care is common in medical practice. Reducing variation in care is shown to improve quality and increase favorable outcomes in chronic diseases. We sought to identify factors associated with variation in care in children with newly diagnosed Crohn's disease (CD). Methods: Prospectively collected data from a 28-site multicenter inception CD cohort were analyzed for variations in diagnostic modalities, treatment, and follow-up monitoring practices, along with complicated disease outcomes over 3 years in 1046 children. Generalized linear mixed effects models were used to investigate the intercenter variations in each outcome variable. Results: The mean age at diagnosis was 12 years, and 25.9% were nonwhite. The number of participants ranged from 5 to 112 per site. No variation existed in the initial diagnostic approach. When medication exposure was analyzed, steroid exposure varied from 28.6% to 96.9% (P < 0.01) within 90 days, but variation was not significant over a 3-year period (P = 0.13). Early anti-tumor necrosis factor (anti-TNF) exposure (within 90 days) varied from 2.1% to 65.7% (P < 0.01), but variation was not significant over a 3-year period (P > 0.99). Use of immunomodulators (IMs) varied among centers both within 90 days (P < 0.01) and during 3 years of follow-up (P < 0.01). A significant variation was seen at the geographic level with follow-up small bowel imaging and colonoscopy surveillance after initial therapy. Conclusions: Intercenter variation in care was seen with the initial use of steroids and anti-TNF, but there was no difference in total 3-year exposure to these drugs. Variation in the initiation and long-term use of IMs was significant among sites, but further research with objective measures is needed to explain this variation of care. Small bowel imaging or repeat colonoscopy in CD patients was not uniformly performed across sites. As our data show the widespread existence of variation in care and disease monitoring at geographic levels among pediatric CD patients, future implementation of various practice strategies may help reduce the variation in care.
Published: 2019
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17. 761 MEGA-ANALYSIS REVEALS NOVEL GENETIC ASSOCIATIONS WITH EXTRAINTESTINAL MANIFESTATIONS IN IBD

Author: Gaurav Syal, L. Philip Schumm, Shervin Rabizadeh, Gil Y. Melmed, Shishir Dube, Dalin Li, Ramnik J. Xavier, Ashwin N. Ananthakrishnan, Talin Haritunians, Bana Jabri, Robert S. Sandler, Steven R. Brant, Sergio A. Lira, David Ziring, Dermot P.B. McGovern, Michelle Khrom, Gregory J. Botwin, Christina Ha, Emebet Mengesha, Rodney D. Newberry, Millie D. Long, Mark S. Silverberg, R. Balfour Sartor, Judy H. Cho, Nirupama Bonthala, Eric A. Vasiliauskas, John D. Rioux, Richard H. Duerr, William A. Faubion, Shaohong Yang, and Stephan R. Targan
Subjects: Hepatology, Evolutionary biology, Gastroenterology, Mega analysis
Published: 2020

18. Mo1859 CLINICAL, SEROLOGIC, AND GENOMIC PREDICTORS OF RESPONSE TO USTEKINUMAB IN CROHN'S DISEASE

Author: Gil Y. Melmed, Gregory J. Botwin, Nirupama Bonthala, Dermot P.B. McGovern, Linda Hwang, Talin Haritunians, David Ziring, Shervin Rabizadeh, Stephan R. Targan, Lillian Du, Gaurav Syal, Shaohong Yang, Christina Ha, Eric A. Vasiliauskas, and Dalin Li
Subjects: medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Ustekinumab, Gastroenterology, Medicine, business, medicine.disease, Dermatology, medicine.drug, Serology
Published: 2020

19. 935 PRE-TREATMENT MUCOSAL INFLAMMATORY AND WOUND HEALING GENE PROGRAMS REVEAL MECHANISMS ASSOCIATED WITH FUTURE STRICTURING BEHAVIOR DURING FIVE YEAR FOLLOW-UP IN PEDIATRIC CROHN'S DISEASE

Author: Robert N. Baldassano, Greg Gibson, David Ziring, Lee A. Denson, Michael C. Stephens, Rebekah Karns, Susan S. Baker, David R. Mack, Phillip Minar, Anne M. Griffiths, Ajay S. Gulati, Dedrick E. Moulton, Melvin B. Heyman, Jeffrey S. Hyams, Daniel Shapiro, Richard Kellermayer, Scott B. Snapper, Anthony R. Otley, Joshua D. Noe, Bruce J. Aronow, Marla Dubinsky, Ashish Patel, Neal S. Leleiko, Yael Haberman, Jennifer L. Dotson, Anil G. Jegga, Sudhir Ghandikota, Maria Oliva-Hemker, Ranjana Gokhale, Stephen L. Guthery, Sandra C. Kim, Steven J. Steiner, Stanley A. Cohen, Phillip J. Dexheimer, James Markowitz, Suresh Venkateswaran, Subra Kugathasan, Thomas D. Walters, Samuel Tegge, Brianne Shuler, and Tzipi Braun
Subjects: Pre treatment, medicine.medical_specialty, Hepatology, Pediatric Crohn's disease, business.industry, Internal medicine, Gastroenterology, Five year follow up, medicine, business, Wound healing
Published: 2020

20. Mo1907 REAL WORLD EXPERIENCE WITH USTEKINUMAB IN A PEDIATRIC CROHN'S DISEASE POPULATION

Author: Shervin Rabizadeh, Lillian Du, Dermot P.B. McGovern, David Ziring, and Yvette Gonzales
Subjects: Pediatrics, medicine.medical_specialty, education.field_of_study, Hepatology, Pediatric Crohn's disease, business.industry, Ustekinumab, Population, Gastroenterology, medicine, business, education, medicine.drug
Published: 2020

21. Su1988 ENVIRONMENTAL EFFECT OF RESOLVED HUMAN CMV INFECTION AND NK RECEPTOR GENETICS IN PEDIATRIC CROHN'S DISEASE SUSCEPTIBILITY AND PHENOTYPE

Author: Shervin Rabizadeh, Gregory J. Botwin, Dalin Li, Dermot P.B. McGovern, Terri Shih, Jonathan Braun, Rivkah Gonsky, David Casero, David Ziring, Subra Kugathasan, Susy Yusung, and Lee A. Denson
Subjects: Environmental effect, NK-receptor, Hepatology, Pediatric Crohn's disease, business.industry, Immunology, Gastroenterology, Medicine, business, Phenotype
Published: 2020

22. Pediatric Inflammatory Bowel Disease Clinical Innovations Meeting of the Crohn'sColitis Foundation: Charting the Future of Pediatric IBD

Author: K.T. Park, Laurie S. Conklin, Athos Bousvaros, Dale Lee, Caren Heller, Anthony R. Otley, David Ziring, Andrew B. Grossman, Andrew E. Mulberg, Alandra Weaver, Subra Kugathasan, Jeffrey S. Hyams, Joel R. Rosh, Joseph A. Picoraro, Michael D. Kappelman, and Lee A. Denson
Subjects: medicine.medical_specialty, Translational research, Disease, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, 030225 pediatrics, medicine, Immunology and Allergy, Humans, Colitis, Disease management (health), Leading off, Intensive care medicine, Child, Irritable bowel syndrome, Crohn's disease, business.industry, Tumor Necrosis Factor-alpha, Gastroenterology, Antibodies, Monoclonal, Disease Management, medicine.disease, Prognosis, Ulcerative colitis, digestive system diseases, Practice Guidelines as Topic, 030211 gastroenterology & hepatology, Colitis, Ulcerative, business
Abstract: The Crohn’s & Colitis Foundation has facilitated transformational research in pediatric inflammatory bowel disease (IBD), through the RISK and PROTECT studies, that has laid the groundwork for a comprehensive understanding of molecular mechanisms of disease and predictors of therapeutic response in children. Despite these advances, children have lacked timely and informed access to the latest therapeutic advancements in IBD. The Crohn's & Colitis Foundation convened a Pediatric Resource Organization for Kids with Inflammatory Intestinal Diseases (PRO-KIIDS) Clinical Innovations Meeting at the inaugural Crohn's and Colitis Congress in January 2018 to devise how to advance the care of children with IBD. The working group selected 2 priorities: (1) accelerating therapies to children with IBD and (2) stimulating investigator-initiated research while fostering sustainable collaboration; and proposed 2 actions: (a) the convening of a task force to specifically address how to accelerate pharmacotherapies to children with IBD and (b) the funding of a multicenter clinical and translational research study that incorporates the building of critical research infrastructure.10.1093/ibd/izy205_video1 izy205.video1 5799266615001
Published: 2018

23. Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease

Author: Iris Barshack, Batia Weiss, Lee A. Denson, Joel R. Rosh, Anne M. Griffiths, Stephen L. Guthery, Melvin B. Heyman, Dedrick E. Moulton, Anthony R. Otley, David Keljo, David Ziring, Yair Anikster, Robert N. Baldassano, Ayelet Di Segni, Marina BenShoshan, Phillip J. Dexheimer, Maria Oliva-Hemker, Joshua D. Noe, James Markowitz, Ashish S. Patel, Scott B. Snapper, Thomas D. Walters, Wallace Crandall, Tzipi Braun, Steven J. Steiner, Stanley A. Cohen, Susan S. Baker, David R. Mack, Camila Avivi, Yael Haberman, Bruce J. Aronow, Ajay S. Gulati, Jeffrey S. Hyams, Richard Kellermayer, Barbara S. Kirschner, Subra Kugathasan, and Neal S. LeLeiko
Subjects: 0301 basic medicine, Male, Myeloid, Messenger, Crohn's Disease, Gastroenterology, Crohn Disease, Gene expression, Immunology and Allergy, 2.1 Biological and endogenous factors, Gene Regulatory Networks, Aetiology, Child, Oligonucleotide Array Sequence Analysis, RNA expression, RNAseq, 3. Good health, Up-Regulation, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Hepatocyte Nuclear Factor 4, RNA, Long Noncoding, Female, Long Noncoding, Biotechnology, Cell type, medicine.medical_specialty, Adolescent, Clinical Sciences, Down-Regulation, long ncRNA, In situ hybridization, Biology, Autoimmune Disease, Article, 03 medical and health sciences, Downregulation and upregulation, Ileum, Internal medicine, medicine, Genetics, Humans, RNA, Messenger, Gene, Neoplastic, Gastroenterology & Hepatology, Gene Expression Profiling, Prevention, Inflammatory Bowel Disease, Human Genome, RNA, Gene signature, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Cancer research, Colitis, Ulcerative, Caco-2 Cells, Digestive Diseases, Basic Science Research
Abstract: Background Long noncoding RNAs (lncRNA) are key regulators of gene transcription and many show tissue-specific expression. We previously defined a novel inflammatory and metabolic ileal gene signature in treatment-naive pediatric Crohn disease (CD). We now extend our analyses to include potential regulatory lncRNA. Methods Using RNAseq, we systematically profiled lncRNAs and protein-coding gene expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RNA in situ hybridization was used to validate expression. Real-time polymerase chain reaction was used to test lncRNA regulation by IL-1β in Caco-2 enterocytes. Results We characterize widespread dysregulation of 459 lncRNAs in the ileum of CD patients. Using only the lncRNA in discovery and independent validation cohorts showed patient classification as accurate as the protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types 1showed that the upregulated LINC01272 is associated with a myeloid pro-inflammatory signature, whereas the downregulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We confirmed tissue-specific expression in biopsies using in situ hybridization, and validated regulation of prioritized lncRNA upon IL-1β exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusions We systematically define differentially expressed lncRNA in the ileum of newly diagnosed pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNAs, after mechanistic exploration, may serve as potential new tissue-specific targets for RNA-based interventions.
Published: 2018

24. Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study

Author: Joel R. Rosh, Nathan Gotman, Neal S. Leleiko, Vin Tangpricha, Francisco A. Sylvester, Marian Pfefferkorn, Jessie Wang, Jeffrey S. Hyams, Paul A. Rufo, Krista Spada, Keith J. Benkov, Michael D. Kappelman, Subra Kugathasan, David R. Mack, Jennifer A. Strople, David Ziring, Susan S. Baker, Anthony Otley, Robert N. Baldassano, Jose Serrano, Dedrick E. Moulton, Marla Dubinsky, Stephen L. Guthery, Brendan M. Boyle, Margaret H. Collins, Cary G. Sauer, David J. Keljo, Joshua D. Noe, Melvin B. Heyman, Jonathan Evans, Anne M. Griffiths, Maria Oliva-Hemker, Prateek Wali, Alison Marquis, Ashley Britt, Ashish S. Patel, Boris Sudel, James Markowitz, Thomas D. Walters, Suresh Venkateswaran, Sonia M. Davis, Lee A. Denson, and Bradley Saul
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, Psychological intervention, Anti-Inflammatory Agents, Administration, Oral, Ulcerative, Logistic regression, Oral and gastrointestinal, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Adrenal Cortex Hormones, Child, Mesalamine, Colectomy, Pediatric, Anti-Inflammatory Agents, Non-Steroidal, Remission Induction, Gastroenterology, Colitis, Ulcerative colitis, 3. Good health, Treatment Outcome, 6.1 Pharmaceuticals, Child, Preschool, Administration, 030211 gastroenterology & hepatology, Administration, Intravenous, Female, Non-Steroidal, Intravenous, Cohort study, Oral, medicine.medical_specialty, Adolescent, Autoimmune Disease, 03 medical and health sciences, Mesalazine, Clinical Research, Internal medicine, medicine, Humans, Preschool, Hepatology, business.industry, Evaluation of treatments and therapeutic interventions, Retrospective cohort study, medicine.disease, Surgery, 030104 developmental biology, chemistry, Colitis, Ulcerative, business, Digestive Diseases
Abstract: BackgroundPrevious retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis.MethodsThe PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4-17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10-30) oral corticosteroids (PUCAI 35-60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535.FindingsPatients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p
Published: 2017

25. Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study

Author: Francisco A. Sylvester, Joel R. Rosh, Jason Shapiro, Michael D. Kappelman, David Keljo, Lee A. Denson, Urko M. Marigorta, Scott B. Snapper, Dedrick E. Moulton, Marla Dubinsky, Anne M. Griffiths, Chunyan Liu, Susan S. Baker, David R. Mack, Thomas D. Walters, Judy H. Cho, Wallace Crandall, Joshua D. Noe, Anthony R. Otley, Robert N. Baldassano, Subra Kugathasan, Barbara S. Kirschner, Curtis Huttenhower, Maria Oliva-Hemker, Steven J. Steiner, Greg Gibson, Bruce C. Trapnell, Shervin Rabizadeh, David Ziring, Kajari Mondal, Stanley N. Cohen, Richard Kellermayer, Jonathan Evans, Bruce J. Aronow, Michael C. Stephens, Ramnik J. Xavier, Jeffrey S. Hyams, Ashish S. Patel, Melanie Schirmer, Melvin B. Heyman, Stephen L. Guthery, James Markowitz, and Mi-Ok Kim
Subjects: 0301 basic medicine, Male, Anti-Inflammatory Agents, Severity of Illness Index, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Crohn Disease, Prospective Studies, Prospective cohort study, Child, Crohn's disease, screening and diagnosis, Hazard ratio, Anti-Inflammatory Agents, Non-Steroidal, General Medicine, Prognosis, Detection, Disease Progression, 030211 gastroenterology & hepatology, Female, Non-Steroidal, medicine.drug, Cohort study, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Adolescent, Risk Assessment, Autoimmune Disease, 03 medical and health sciences, Clinical Research, Internal medicine, General & Internal Medicine, medicine, Adalimumab, Genetics, Humans, Propensity Score, business.industry, Tumor Necrosis Factor-alpha, Prevention, Inflammatory Bowel Disease, Gene signature, medicine.disease, Infliximab, Surgery, Gastrointestinal Microbiome, 030104 developmental biology, Complication, business, Digestive Diseases, Intestinal Obstruction
Abstract: Summary Background Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown. Methods We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. Findings Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51–82) and specificity of 63% (55–71), with a negative predictive value of 95% (94–97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10–0·89; p=0·0296) but not stricturing complication (1·13, 0·51–2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12–2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%. Interpretation Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy. Funding Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
Published: 2017

26. Increased Effectiveness of Early Therapy With Anti-Tumor Necrosis Factor-α vs an Immunomodulator in Children With Crohn's Disease

Author: Barbara S. Kirschner, Chunyan Liu, Anthony Otley, Maria Oliva-Hemker, Neal Leleiko, Lee A. Denson, James Markowitz, Wallace Crandall, Dedrick E. Moulton, Michael C. Stephens, Susan S. Baker, Stanley N. Cohen, Marla Dubinsky, Jonathan Evans, David R. Mack, Stephen L. Guthery, Melvin B. Heyman, Richard Kellermayer, Anne M. Griffiths, Jeffrey S. Hyams, Robert N. Baldassano, Subra Kugathasan, David Ziring, Ashish S. Patel, Marian Pfefferkorn, Mi-Ok Kim, Joel R. Rosh, Jonah Essers, Sandra C. Kim, and Thomas D. Walters
Subjects: Male, medicine.medical_specialty, Adolescent, Matched-Pair Analysis, Anti-Inflammatory Agents, Early Therapy, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Drug Administration Schedule, Child Development, Crohn Disease, Internal medicine, Azathioprine, medicine, Humans, Prospective Studies, Child, Propensity Score, Pediatric gastroenterology, Crohn's disease, Hepatology, biology, Mercaptopurine, business.industry, C-reactive protein, Adalimumab, Gastroenterology, Antibodies, Monoclonal, Induction Chemotherapy, medicine.disease, Infliximab, Surgery, Methotrexate, Treatment Outcome, Relative risk, Propensity score matching, biology.protein, Female, business, Body mass index, Immunosuppressive Agents, Follow-Up Studies, medicine.drug
Abstract: Background & Aims Standard therapy for children newly diagnosed with Crohn's disease (CD) includes early administration of immunomodulators after initial treatment with corticosteroids. We compared the effectiveness of early (≤3 mo after diagnosis) treatment with an anti-tumor necrosis factor (TNF)α with that of an immunomodulator in attaining clinical remission and facilitating growth of pediatric patients. Methods We analyzed data from the RISK study, an observational research program that enrolled patients younger than age 17 diagnosed with inflammatory (nonpenetrating, nonstricturing) CD from 2008 through 2012 at 28 pediatric gastroenterology centers in North America. Patients were managed by physician dictate. From 552 children (median age, 11.8 y; 61% male; 63% with pediatric CD activity index scores >30; and median C-reactive protein level 5.6-fold the upper limit of normal), we used propensity score methodology to identify 68 triads of patients matched for baseline characteristics who were treated with early anti-TNFα therapy, early immunomodulator, or no early immunotherapy. We evaluated relationships among therapies, corticosteroid and surgery-free remission (pediatric CD activity index scores, ≤10), and growth at 1 year for 204 children. Treatment after 3 months was a covariate. Results Early treatment with anti-TNFα was superior to early treatment with an immunomodulator (85.3% vs 60.3% in remission; relative risk, 1.41; 95% confidence interval [CI], 1.14-1.75; P = .0017), whereas early immunomodulator therapy was no different than no early immunotherapy (60.3% vs 54.4% in remission; relative risk, 1.11; 95% CI, 0.83-1.48; P = .49) in achieving remission at 1 year. Accounting for therapy after 3 months, early treatment with anti-TNFα remained superior to early treatment with an immunomodulator (relative risk, 1.51; 95% CI, 1.20-1.89; P = .0004), whereas early immunomodulator therapy was no different than no early immunotherapy (relative risk, 1.00; 95% CI, 0.75-1.34; P = .99). The mean height z-score increased compared with baseline only in the early anti-TNFα group. Conclusions In children newly diagnosed with comparably severe CD, early monotherapy with anti-TNFα produced better overall clinical and growth outcomes at 1 year than early monotherapy with an immunomodulator. Further data will be required to best identify children most likely to benefit from early treatment with anti-TNFα therapy.
Published: 2014

27. Sa1763 – A Multi-Protein Serum Test Predicts Mucosal Healing in Children with Ileocolonic Crohn's Disease

Author: Shervin Rabizadeh, David Ziring, Namita Singh, Marla Dubinsky, Kelly D. Hester, Anjali Jain, Larry Mimms, and Yogesh Arora
Subjects: Crohn's disease, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Mucosal healing, Gastroenterology, Medicine, business, medicine.disease
Published: 2019

28. Microbial Dysbiosis Associated with Disease Severity in Treatment Naive Pediatric Patients with New-Onset Ulcerative Colitis

Author: Melanie Schirmer, Dedrick E. Moulton, Ashish S. Patel, Ramnik J. Xavier, Boris Sudel, Neal S. Leleiko, Prateek Wali, Anne M. Griffiths, Maria Oliva-Hemker, Joel R. Rosh, Jennifer A. Strople, Keith J. Benkov, Jeffrey S. Hyams, David Ziring, Marian D. Pfefferkorn, Stephen L. Guthery, Paul A. Rufo, Robert N. Baldassano, Joshua D. Noe, David J. Keljo, Susan S. Baker, David R. Mack, Hera Vlamakis, James Markowitz, Brendan M. Boyle, Subra Kugathasan, Melvin B. Heyman, Cary G. Sauer, Thomas D. Walters, Curtis Huttenhower, Anthony R. Otley, Lee A. Denson, and Sonia M. Davis
Subjects: medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Microbial dysbiosis, medicine.disease, Ulcerative colitis, New onset, Therapy naive, Disease severity, Internal medicine, Medicine, business
Published: 2017

29. Proteomic Analysis Reveals Innate Immune Activity in Intestinal Transplant Dysfunction

Author: David Ziring, Xiaoxiao Li, Douglas G. Farmer, James LeBlanc, David Elashoff, Jonathan Braun, and Anjuli R. Kumar
Subjects: Adult, Graft Rejection, Proteomics, alpha-Defensins, Interleukin-1beta, Population, Perforation (oil well), Biology, Article, Interferon-gamma, Immune system, Immunity, Immunopathology, Granulocyte Colony-Stimulating Factor, Humans, Child, education, Transplantation, education.field_of_study, Innate immune system, Tumor Necrosis Factor-alpha, Interleukin-8, Enterostomy, Acquired immune system, Immunohistochemistry, Immunity, Innate, Intestines, Immunology, Cytokines
Abstract: Intestinal transplantation (ITx) offers a potential way of survival for patients with intestinal failure who have developed life-threatening complications (1). Overall, patient and graft survival rates have improved significantly over the past several years (2, 3). Nonetheless, acute cellular rejection (ACR) continues to pose major challenges in these patients, occurring in up to 50% of recipients and accounting for the majority of grafts loss. Currently, endoscopic biopsy is the only way for clinical assessment of ACR (4). Limitations of endoscopy include that it is invasive and associated with risks of bleeding, infection, or perforation. In addition, ACR is also often patchy (missed by ~30% of endoscopies) (5), and confounded by its presentation, which may be similar to infection. This creates challenges to both clinical management and biologic research (6). New noninvasive techniques to analyze ACR are thus needed to further advance the ITx field. The intestine is the largest immune organ in the body, with 80% of the total immune cells (7). Study of ITx recipients is further complicated by the presence of an immunogenic chimeric donor cell population (8, 9), and the underlying biology of ACR remains unclear. Recently, an underappreciated role of the innate immune system has been suggested in solid organ transplantation with evidence from both mouse models and human studies (10). Upregulation of proinflammatory mediators has been shown to occur independently of adaptive immunity, even before the T-cell response (11–14). Moreover, the profile of this early cytokine upregulation suggests it might be due to the epithelial stress response to tissue injury (12, 15). High-throughput proteomics allows simultaneous detection of a panel of proteins, which are differentially expressed in healthy and disease states. This technology has been successfully applied to profile proteins from different forms of clinical specimens (16), and protein combinations provide potentially innovative biomarkers which are useful in diagnosis or disease monitoring. In the search of biomarkers for ACR, various metabolites and proteins have been suggested as potential biomarkers for allograft monitoring in both human and mouse study (6, 17, 18). The purpose of this study was to evaluate the feasibility of using protein profiles of ostomy effluents as a strategy to monitor ACR, in particular those related to innate immune activation, which may represent a precondition of the graft for rejection. We used both high-throughput proteomic analysis and candidate immunoassay protein detection of ostomy effluents to search in a noninvasive manner for molecular profiles of epithelial stress and innate immunity during ACR. Our analyses uncovered several proteins that appeared to differ among patients with early ACR, notably the elevation of antimicrobial peptides and cytokines characteristic of early innate immune activation.
Published: 2011

30. 740 - Age-of-Onset Dependent Ileal Immune Maturation and Reduced Alpha-Defensin in Pediatric Crohn Disease with Already Established Dysbiosis

Author: Marla Dubinsky, David Ziring, Robert N. Baldassano, Lee A. Denson, Scott B. Snapper, Barbara S. Kirschner, Rebekah Karns, Tzipi Braun, Stanley N. Cohen, Joshua D. Noe, Anthony R. Otley, Melanie Schirmer, Dedrick E. Moulton, Phillip J. Dexheimer, James Markowitz, Anne M. Griffiths, Yael Haberman, Richard Kellermayer, Thomas D. Walters, Susan S. Baker, David R. Mack, Curtis Huttenhower, Ashish S. Patel, Maria Oliva-Hemker, Jonathan P. Evans, Ajay S. Gulati, Joel R. Rosh, David J. Keljo, Wallace Crandall, Subra Kugathasan, Bruce J. Aronow, Stephen L. Guthery, Melvin B. Heyman, Steven J. Steiner, Mi-Ok Kim, Jeffrey S. Hyams, Ramnik J. Xavier, and Neal S. Leleiko
Subjects: Immune system, Hepatology, business.industry, Crohn disease, Immunology, Gastroenterology, medicine, Age of onset, medicine.disease, business, Dysbiosis, Alpha defensin
Published: 2018

31. Su2017 - Predicting Response to Standardized Pediatric Colitis Therapy: The Protect Study

Author: Jessie Wang, Prateek Wali, Francisco A. Sylvester, Joel R. Rosh, Thomas D. Walters, Boris Sudel, Michael D. Kappelman, Dedrick E. Moulton, Stephen L. Guthery, Keith J. Benkov, Paul A. Rufo, Krista Spada, Mel Heyman, Marla Dubinsky, Anne M. Griffiths, Nathan Gotman, Vin Tangpricha, Maria Oliva-Hemker, Jose Serrano, Margaret H. Collins, Marian D. Pfefferkorn, David J. Keljo, Jonathan Evans, David Ziring, Anthony R. Otley, James Markowitz, Jennifer A. Strople, Ashish S. Patel, Subra Kugathasan, Robert N. Baldassano, Alison Marquis, Susan S. Baker, David R. Mack, Joshua D. Noe, Cary G. Sauer, Neal S. Leleiko, Jeffrey S. Hyams, Lee A. Denson, Suresh Venkateswaran, and Sonia M. Davis
Subjects: medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, Colitis, business
Published: 2018

32. Molecular Imaging of Murine Intestinal Inflammation With 2-Deoxy-2-[18F]Fluoro-d-Glucose and Positron Emission Tomography

Author: Sarah Brewer, Jonathan Braun, Stephan R. Targan, Michael McPherson, Olga Turovskaya, Daisuke Fujiwara, Ling Chen, Bo Wei, Hidetoshi Takedatsu, and David Ziring
Subjects: CD4-Positive T-Lymphocytes, Tumor Necrosis Factor Ligand Superfamily Member 15, Pathology, medicine.medical_specialty, Mice, Inbred Strains, Inflammation, Standardized uptake value, Lymphocyte Activation, Article, Mice, Piroxicam, Intestinal mucosa, Fluorodeoxyglucose F18, In vivo, Animals, Medicine, Intestinal Mucosa, Colitis, Mice, Knockout, Glucose Transporter Type 1, Mice, Inbred BALB C, Mice, Inbred C3H, Hepatology, medicine.diagnostic_test, business.industry, Macrophages, Anti-Inflammatory Agents, Non-Steroidal, Gastroenterology, Glucose transporter, medicine.disease, Intestines, carbohydrates (lipids), Positron emission tomography, Positron-Emission Tomography, Female, Radiopharmaceuticals, medicine.symptom, business
Abstract: 2-Deoxy-2-[(18)F]fluoro-d-glucose (FDG) uptake by positron emission tomography (PET), a measure of glucose transporter activity, has been used to detect mucosal inflammation. However, there is limited understanding of the biologic basis of mucosal FDG uptake.A contrast-based computed tomographic isocontour method was developed to identify intestinal anatomic regions, and FDG uptake was integrated over these regions to achieve reproducible quantification during longitudinal assessment of individual mice. Intestinal FDG uptake was compared with histologic scores and with glucose transporter 1 levels in mucosal immune cells by flow cytometry.Intestinal FDG uptake quantitatively correlated with disease activity in mild (C3H/HeJ.IL-10(-/-)) and severe (129.Galphai2(-/-), CD4(+) CD45RB(high), and Galphai2(-/-) CD3(+) transfer) murine colitis models at all time points examined (P.05) and was sufficiently sensitive to detect preclinical inflammation. FDG uptake was correlated by flow cytometric detection of glucose transporter 1 levels in mucosal CD4(+) T lymphocyte but not other intestinal immune cell types. CD4(+) T-cell transfer in vivo confirmed that mucosal FDG uptake was associated with the activated but not quiescent state. When intestinal inflammation was increased by treatment with piroxicam and decreased with anti-TL1A treatment, FDG uptake was correspondingly altered.This study clarifies the cellular basis of FDG signal in intestinal inflammation and introduces computed tomographic isocontour analysis of FDG-PET imaging for standardized quantitation of immune colitis.
Published: 2008

33. Oral Tacrolimus for Steroid-dependent and Steroid-resistant Ulcerative Colitis in Children

Author: Martin G. Martin, Marvin E. Ament, David Ziring, William S Mow, Mini Mehra, and Steven S. Wu
Subjects: Male, medicine.medical_specialty, Time Factors, Adolescent, medicine.drug_class, Drug Resistance, Administration, Oral, Azathioprine, Gastroenterology, Antimetabolite, Tacrolimus, Internal medicine, medicine, Humans, Colitis, Child, Retrospective Studies, Antibacterial agent, Dose-Response Relationship, Drug, business.industry, Remission Induction, Infant, medicine.disease, Mercaptopurine, Ulcerative colitis, Diarrhea, Treatment Outcome, Child, Preschool, Pediatrics, Perinatology and Child Health, Immunology, Colitis, Ulcerative, Female, Steroids, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract: To evaluate tacrolimus in 3 situations: for the induction of remission in children with severe steroid-resistant ulcerative colitis (UC); for steroid sparing in children with steroid-dependent UC in whom treatment with other immunosuppressants fails; and for the maintenance of remission in children with steroid-dependent and steroid-resistant UC.We retrospectively evaluated 18 consecutive patients (13 with pancolitis) who were treated with oral tacrolimus at our institution from May 1999 to October 2005. Nine patients had steroid-resistant UC and 9 patients were steroid-dependent. We started patients initially on tacrolimus 0.2 mg/kg divided twice daily, with a goal plasma trough level of 10 to 15 ng/mL for the first 2 weeks, and then titrated doses to achieve plasma levels between 7 and 12 ng/mL after induction.Of the 18 patients in this study, 17 showed a positive response to tacrolimus therapy (ie, cessation of diarrhea and other symptoms) and 5 showed a prolonged response to tacrolimus. The mean time from initiation of tacrolimus therapy until response was 8.5 days. The mean duration of response was 260 days. Eleven of 18 patients required colectomy, including all of the patients with steroid-resistant UC, but only 2 of 9 who were steroid-dependent. The mean time from initiation of tacrolimus until colectomy was 392 days.It is possible that tacrolimus may benefit selected patients with steroid-dependent UC, including those who are intolerant of 6-mercaptopurine or azathioprine. Conversely, patients with steroid-resistant UC are unlikely to sustain a prolonged clinical response to tacrolimus and seem to require colectomy eventually. Careful considerations of risk versus benefit, as well as close monitoring for adverse effects, are essential in all patients.
Published: 2007

34. Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping

Author: Jarod Prince, Thomas D. Walters, Dedrick E. Moulton, David J. Cutler, Joel R. Rosh, Susan S. Baker, Shervin Rabizadeh, David R. Mack, Michael E. Zwick, Promita Bose, Susan D. Thompson, Kajari Mondal, David Ziring, James Markowitz, Sampath Prahalad, David T. Okou, Wallace Crandall, Jonah Essers, Dhanya Ramachandran, Anne M. Griffiths, Marla Dubinsky, Jonathan P. Evans, Jeffrey S. Hyams, Subra Kugathasan, Maria Oliva-Hemker, Neal S. Leleiko, Scott B. Snapper, Stephen L. Guthery, Marian Pfefferkorn, Archana Kumar, John F. Bohnsack, Yael Haberman, David J. Keljo, Bruce J. Aronow, Michael C. Stephens, Michael D. Kappelman, Anthony R. Otley, Patel Ashish, Robert N. Baldassano, Melvin B. Heyman, Barbara S. Kirschner, Lee A. Denson, Stanley N. Cohen, Richard Kellermayer, and Joshua D. Noe
Subjects: Adult, Male, Genotype, Population, Nod2 Signaling Adaptor Protein, lcsh:Medicine, Genome-wide association study, Disease, Biology, digestive system, Polymorphism, Single Nucleotide, Crohn Disease, Genetic predisposition, Humans, Genetic Predisposition to Disease, Allele, Age of Onset, lcsh:Science, education, Child, Genotyping, Alleles, education.field_of_study, Multidisciplinary, Base Sequence, lcsh:R, Receptors, Interleukin, Sequence Analysis, DNA, digestive system diseases, 3. Good health, Immunology, lcsh:Q, Colitis, Ulcerative, Female, Age of onset, Research Article
Abstract: Background The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent. Methods We performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn’s disease; 121 ulcerative colitis and 86 IBD undetermined) and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset), this study replicated 4% (5 SNPs out of 136) of the SNPs identified in the Crohn’s disease (CD) cases and 0.8% (1 SNP out of 128) in the ulcerative colitis (UC) cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs) for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p< 0.03, R2= 0.007), but not for the smaller number of UC cases. Conclusions The allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD.
Published: 2015

35. A microRNA signature in pediatric ulcerative colitis: deregulation of the miR-4284/CXCL5 pathway in the intestinal epithelium

Author: Daniel W. Hommes, Efi Kokkotou, Georgios Koukos, Charalabos Pothoulakis, Angelos Oikonomopoulos, Renaisa Wahed, Dimitrios Iliopoulos, Jess L. Kaplan, David Ziring, Christos Polytarchou, and Harland S. Winter
Subjects: Male, Chemokine CXCL5, Crohn's Disease, Ulcerative, Inbred C57BL, Inflammatory bowel disease, Gastroenterology, Oral and gastrointestinal, Mice, Immunology and Allergy, 2.1 Biological and endogenous factors, Aetiology, Intestinal Mucosa, Child, 3' Untranslated Regions, In Situ Hybridization, Pediatric, Colitis, Prognosis, Intestinal epithelium, Real-time polymerase chain reaction, CXCL5, Female, Biotechnology, Adult, medicine.medical_specialty, Adolescent, Clinical Sciences, colonic epithelial cells, In situ hybridization, Real-Time Polymerase Chain Reaction, Autoimmune Disease, Article, noncoding RNA, Young Adult, In vivo, inflammatory bowel disease, Internal medicine, microRNA, medicine, Genetics, Animals, Humans, Nutrition, Gastroenterology & Hepatology, business.industry, Computational Biology, medicine.disease, Mice, Inbred C57BL, MicroRNAs, Gene Expression Regulation, Case-Control Studies, Colitis, Ulcerative, business, Digestive Diseases, Follow-Up Studies
Abstract: Author(s): Koukos, Georgios; Polytarchou, Christos; Kaplan, Jess L; Oikonomopoulos, Angelos; Ziring, David; Hommes, Daniel W; Wahed, Renaisa; Kokkotou, Efi; Pothoulakis, Charalabos; Winter, Harland S; Iliopoulos, Dimitrios | Abstract: BackgroundTwenty to 25% of the patients with inflammatory bowel disease (IBD) present the disease before the age of 18 to 20, with worse extent and severity, compared with adult-onset IBD. We sought to identify the differential expression of microRNAs in pediatric ulcerative colitis (UC) and their association with different clinical phenotypes.MethodsMicroRNA expression analysis was performed in colonic tissues derived from pediatric patients with UC and controls without IBD. MiR-4284 levels were verified by real-time quantitative polymerase chain reaction in 2 additional cohorts of pediatric patients with UC. Bioinformatics analysis was performed to predict the targets of miR-4284. In vitro experiments using luciferase reporter assays and real-time polymerase chain reaction evaluated the direct effect of miR-4284 on CXCL5 mRNA. In vivo experiments were performed in 2 mouse models of experimental colitis.ResultsA 24-microRNA signature was identified in colonic tissues derived from pediatric patients with UC. The most downregulated microRNA in the tissue of pediatric patients UC, relative to non-IBD controls, was miR-4284. In situ hybridization revealed that miR-4284 is present in colonic epithelial cells, and its levels correlate with the disease activity. Furthermore, we found that miR-4284 regulates CXCL5 mRNA expression through binding to its 3'UTR. CXCL5 had increased mRNA levels in colonic tissue from pediatric patients with UC and correlated with disease activity. Furthermore, we found an inverse correlation between miR-4284 and CXCL5 levels in the colonic pediatric UC tissues and in 2 mouse models of experimental colitis.ConclusionsOur data reveal a novel microRNA pediatric UC signature and provide evidence that miR-4284 directly regulates CXCL5 and correlates with the disease activity.
Published: 2015

36. Infectious Enteritis After Intestinal Transplantation: Incidence, Timing, and Outcome

Author: Sue V. McDiarmid, David Ziring, Jorge Vargas, Nupoor A. Gajjar, Galen Cortina, Ronald W. Busuttil, James D. Cherry, Susan Edelstein, Douglas G. Farmer, Robert Tran, Paul Krogstad, John F. Renz, and Marjorie J. Miller
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, medicine.disease_cause, Gastroenterology, Enteritis, Internal medicine, Rotavirus, medicine, Humans, Transplantation, Homologous, Survival rate, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Retrospective cohort study, Clostridium difficile, medicine.disease, Intestines, Survival Rate, Diarrhea, Treatment Outcome, Tissue Transplantation, Immunology, medicine.symptom, business, Follow-Up Studies
Abstract: Background. The study reviews the incidence, timing, and outcome of infectious enteritis (IE) after intestinal transplantation (ITx). Methods. A retrospective review of all patients who underwent ITx at a single institution between 1991 and 2003 was undertaken using database and medical records. Standard statistical analyses were performed. Results. Of 33 ITxrecipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of IE. Recipient demographics included the following: 10 males, median age 34 (10-585) months, 11 liver + intestine grafts, and two isolated intestine grafts. Infections were diagnosed a median of 76 days (32-1,800 days) after ITx. There were 14 viral (one cytomegalovirus, eight rotavirus, four adenovirus, one Epstein-Barr virus), three bacterial (Clostridium difficile), and three protozoal (one Giardia lamblia, two Cryptosporidium) infections. The bacterial infections tended to present earlier than the viral infections, and the most frequent presenting symptom was diarrhea. Complete resolution was achieved in 17 (94%) incidences with the appropriate antimicrobial or conservative therapy. It was interesting that there were seven rejection episodes documented by biopsy at the approximate time of diagnosis of IE. There were two graft losses: one because of adenoviral enteritis and one because of rejection after rotavirus enteritis. Three-year patient survival is 74% with no deaths directly attributable to IE. Conclusions. IE can occur in 39% of recipients after ITx. Viral agents are the cause in two thirds of the cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection on histopathology can be difficult and relies on cultures and immunostaining.
Published: 2005

37. 54 High Frequency of Non-Classical Endoscopic Findings in Children and Adolescents Diagnosed With Ulcerativ E.Coli Tis. The Protect Study

Author: Mel Heyman, Zhu Wang, Dedrick E. Moulton, Jeffrey S. Hyams, Anne M. Griffiths, Margaret H. Collins, Thomas D. Walters, Ashish S. Patel, Paul A. Rufo, Subra Kugathasan, Lee A. Denson, Stephen L. Guthery, Keith J. Benkov, David J. Keljo, Neal S. Leleiko, Joel R. Rosh, David Ziring, Boris Sudel, James Markowitz, Anthony R. Otley, Prateek Wali, Susan S. Baker, David R. Mack, Joshua D. Noe, Marian D. Pfefferkorn, Brendan M. Boyle, Cary G. Sauer, Jennifer A. Strople, Maria Oliva-Hemker, and Robert N. Baldassano
Subjects: medicine.medical_specialty, business.industry, Gastroenterology, medicine, Radiology, Nuclear Medicine and imaging, medicine.disease, business, Dermatology, Ulcerative colitis
Published: 2017

38. Suboptimal Early Outcomes following Standardized Induction Therapy in Children Newly Diagnosed with Ulcerative Colitis: The Protect Study

Author: Prateek Wali, Neal S. Leleiko, Anne M. Griffiths, Maria Oliva-Hemker, Brendan M. Boyle, Michael D. Kappelman, James Markowitz, Krista Spada, Mel Heyman, David Ziring, Susan S. Baker, David R. Mack, Joshua D. Noe, Stephen L. Guthery, Dedrick E. Moulton, Jeffrey S. Hyams, Marian D. Pfefferkorn, Sonia M. Davis, Keith J. Benkov, David J. Keljo, Jonathan Evans, Joel R. Rosh, Thomas D. Walters, Ashish S. Patel, Cary G. Sauer, Subra Kugathasan, Alison Marquis, Lee A. Denson, Boris Sudel, Paul A. Rufo, Nathan Gotman, Jennifer A. Strople, Robert N. Baldassano, and Anthony R. Otley
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Induction therapy, Gastroenterology, medicine, Newly diagnosed, medicine.disease, business, Ulcerative colitis, Surgery
Published: 2017

39. Greater Contribution of HLA to Risk for Pediatric-Onset Ulcerative Colitis Can be Narrowed to 3 Independent Classic HLA Variants and Corresponding Amino Acid Changes

Author: Jarod Prince, Joel R. Rosh, Boris Sudel, Stephen L. Guthery, Melvin B. Heyman, Dedrick E. Moulton, Cary G. Sauer, Kevin A. Hommel, Brendan M. Boyle, Lee A. Denson, Susan S. Baker, David R. Mack, Keith J. Benkov, Anthony R. Otley, David T. Okou, James Markowitz, Michael D. Kappelman, Neal S. Leleiko, Suresh Venkateswaran, Marian D. Pfefferkorn, Subra Kugathasan, Maria Oliva-Hemker, Sonia M. Davis, Thomas D. Walters, Pankaj Chopra, Joshua D. Noe, David J. Cutler, Jennifer A. Strople, Ashish S. Patel, Robert N. Baldassano, Paul A. Rufo, Prateek Wali, David Ziring, David J. Keljo, Jonathan Evans, Anne M. Griffiths, and Jeffrey S. Hyams
Subjects: chemistry.chemical_classification, Hepatology, chemistry, business.industry, Pediatric onset, Immunology, Gastroenterology, medicine, Human leukocyte antigen, medicine.disease, business, Ulcerative colitis, Amino acid
Published: 2017

40. Is Mesalamine Monotherapy Equally Effective in Inducing Remission in Mild Versus Moderate Pediatric Ulcerative Colitis at Diagnosis?

Author: Joshua D. Noe, David Ziring, Peter Townsend, Maria Oliva-Hemker, Cary G. Sauer, Dedrick E. Moulton, Thomas D. Walters, Stephen L. Guthery, Keith J. Benkov, Anne M. Griffiths, Mel Heyman, Joel R. Rosh, Brendan M. Boyle, Neal S. Leleiko, James Markowitz, Jennifer A. Strople, Anthony R. Otley, Alison Marquis, Boris Sudel, Paul A. Rufo, Robert N. Baldassano, Nathan Gotman, Subra Kugathasan, Susan S. Baker, David R. Mack, Ashish S. Patel, Sonia M. Davis, Lee A. Denson, Prateek Wali, David J. Keljo, Jonathan Evans, Marian D. Pfefferkorn, Michael D. Kappelman, and Jeffrey S. Hyams
Subjects: medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Gastroenterology, Medicine, Pediatric ulcerative colitis, business
Published: 2017

41. Lactobacillus bacteremia associated with probiotic use in a pediatric patient with ulcerative colitis

Author: Elaheh Vahabnezhad, Albert Brian Mochon, Laura Joyce Wozniak, and David Ziring
Subjects: Male, medicine.medical_specialty, Bacteremia, Gastroenterology, Microbiology, law.invention, Probiotic, Immunocompromised Host, Lactobacillus rhamnosus, law, Risk Factors, Lactobacillus, Internal medicine, RNA, Ribosomal, 16S, Medicine, Humans, Blood culture, Colitis, Gram-Positive Bacterial Infections, biology, medicine.diagnostic_test, business.industry, Lacticaseibacillus rhamnosus, Probiotics, food and beverages, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Ulcerative colitis, Anti-Bacterial Agents, Chills, Colitis, Ulcerative, medicine.symptom, business
Abstract: Probiotic strains of Lactobacillus are currently used in a variety of clinical practices with limited evidence to support their use. Lactobacillus species are a normal part of gastrointestinal flora, and bacteremia with probiotic strains of Lactobacillus is very uncommon. We describe a case of Lactobacillus bacteremia in a 17-year-old boy with ulcerative colitis managed with systemic corticosteroids and infliximab, who presented with fever to 102°F, flushing, and chills 1 week after starting Lactobacillus rhamnosus GG probiotics. Initial blood culture on day 2 of his fever was positive for Lactobacillus, however, subsequent blood cultures on day 3 and 5 were negative. He was treated empirically with antibiotics for 5 days and defervesced by day 8 of his illness. 16 S rRNA sequence analysis identified the organism from the patient's blood culture and probiotic capsule as L. rhamnosus with a 99.78% match for both the strains. This case report highlights the potential risk of Lactobacillus bacteremia in immunosuppressed patients with severe active ulcerative colitis.
Published: 2013

42. Predictors of Proctocolectomy in Children with Ulcerative Colitis

Author: Melvin B. Heyman, George D. Ferry, Harland S. Winter, Howard C. Jen, Lorraine I. Kelley-Quon, David Ziring, Benjamin D. Gold, Barbara S. Kirschner, Stanley A. Cohen, Stephen B. Shew, and Neera Gupta
Subjects: proctocolectomy, Male, Time Factors, medicine.medical_treatment, Restorative, Ulcerative, Gastroenterology, Medical and Health Sciences, Oral and gastrointestinal, Weight loss, Medicine, Hypoalbuminemia, Child, Pediatric, Proctocolectomy, Incidence (epidemiology), Incidence, Proctocolectomy, Restorative, Colitis, colectomy, Ulcerative colitis, Cyclosporine, Female, medicine.symptom, Risk assessment, Immunosuppressive Agents, medicine.medical_specialty, Calcineurin Inhibitors, Autoimmune Disease, Risk Assessment, Article, Tacrolimus, Clinical Research, Internal medicine, Weight Loss, Humans, Family, Genetic Predisposition to Disease, Serum Albumin, Nutrition, ulcerative colitis, Gastroenterology & Hepatology, business.industry, Prevention, Inflammatory Bowel Disease, medicine.disease, Surgery, Calcineurin, Pediatrics, Perinatology and Child Health, Colitis, Ulcerative, business, Digestive Diseases
Abstract: ObjectivesFew clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database.MethodsChildren diagnosed with UC at age
Published: 2012

43. 634 Serologic Reactivity Reflects Clinical and Genetic Expression of Ulcerative Colitis in Children. The Protect Study

Author: Suresh Venkateswaran, Anne M. Griffiths, Boris Sudel, Keith J. Benkov, Sonia M. Davis, Dedrick E. Moulton, Michael D. Kappelman, Joel R. Rosh, David Ziring, Brendan M. Boyle, Jeffrey S. Hyams, Lee A. Denson, Subra Kugathasan, Marla Dubinsky, Thomas D. Walters, Krista Spada, Mel Heyman, Maria Oliva-Hemker, Ashish S. Patel, Jonathan P. Evans, Marian D. Pfefferkorn, Jennifer A. Strople, Joshua D. Noe, Anthony R. Otley, Prateek Wali, Robert N. Baldassano, David J. Keljo, Alison Marquis, Cary G. Sauer, James Markowitz, Stephen L. Guthery, Susan S. Baker, David R. Mack, Paul A. Rufo, and Neal S. Leleiko
Subjects: Hepatology, business.industry, Gene expression, Immunology, Gastroenterology, Medicine, business, medicine.disease, Reactivity (psychology), Ulcerative colitis, Serology
Published: 2016

44. Postoperative complications and health care use in children undergoing surgery for ulcerative colitis

Author: Stephen B. Shew, Chi-Hong Tseng, Howard C. Jen, Lorraine I. Kelley-Quon, and David Ziring
Subjects: Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Patient Readmission, California, Cohort Studies, Postoperative Complications, medicine, Humans, Child, Colectomy, Retrospective Studies, Proctocolectomy, business.industry, General surgery, Proctocolectomy, Restorative, Retrospective cohort study, General Medicine, Odds ratio, Length of Stay, medicine.disease, Hospitals, Pediatric, Ulcerative colitis, Confidence interval, Surgery, Hospitalization, Logistic Models, Treatment Outcome, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Multivariate Analysis, Linear Models, Colitis, Ulcerative, Female, business, Cohort study
Abstract: Objectives Medical and surgical approaches toward children with ulcerative colitis (UC) vary and have differing implications for health care use. The goal of this study was to define hospital use and complications for children with UC before and after staged restorative proctocolectomy. Patients and Methods A retrospective study of the California Patient Discharge Dataset from 1999 to 2007 of children aged 2 to 18 years with UC who underwent colectomy was performed (N = 218). Surgical staging was determined alongside hospital type (children's vs non-children's) and surgical case volume. Postoperative complications and hospital length of stay were analyzed using multivariate regression. Results The cohort was mostly male (56%) and white (80%), had private insurance (78%), and underwent colectomy at a children's hospital (62%). Overall, 65% required a separate hospital admission before admission for colectomy. Single-, 2-, and 3-stage procedures were performed in 19 (9%), 144 (66%), and 38 (17%) children. The mean admissions per patient were 1.8 ± 2.4 before colectomy and 0.7 ± 1.6 after surgical completion. Surgical complications occurred in 100 (49%) children, with 39% being attributed to postoperative infection. Children with public insurance (odds ratio, 2.18; 95% confidence interval, 1.0-4.85) and those who underwent colectomy at a non–children's hospital (odds ratio, 2.53; 95% confidence interval, 1.0-6.37) had increased likelihood of surgical complications. Finally, nonwhite race, surgical staging, and undergoing colectomy at a low- or medium-volume hospital resulted in prolonged hospitalization ( P Conclusions Children with UC who undergo colectomy use a large number of hospital resources before surgery and exhibit decreased hospital use after surgical completion. Children undergoing colectomy at children's and high-volume hospitals experience fewer surgical complications and shorter hospitalization.
Published: 2012

45. Pediatric Inflammatory Bowel Disease Research: On the Cutting-Edge

Author: David Ziring and Jonathan Braun
Subjects: Computerized databases, medicine.medical_specialty, Research groups, Crohn disease, business.industry, Inflammatory Bowel Diseases, medicine.disease, Infant newborn, Inflammatory bowel disease, Article, Pediatrics, Perinatology and Child Health, Immunology, medicine, Intensive care medicine, business, Genotyping
Abstract: Recent groundbreaking collaborative efforts have brought the field of Pediatric inflammatory bowel disease (IBD) research to the threshold of a new era in our understanding of the pathogenesis and treatment of this condition. First, several multicenter collaborative research groups, each with computerized databases and large outcomes registries have agreed in principal to combine their efforts with regards to research in genetics, immunology, and infectious diseases. Our knowledge of the intestinal immune system and its communication with the resident luminal bacteria has increased dramatically. And genotyping technology has advanced to the point that it is now feasible to examine haplotype differences among thousands of patient samples in days and weeks instead of months and years.
Published: 2008

46. TNFα blockade in human diseases: An overview of efficacy and safety

Author: Elaine F. Reed, Sheetal B Desai, David Ziring, David W. Gjertson, Yael Korin, Sungjin Kim, Jan Lin, Jonathan Braun, Ram Singh, and Maida Wong
Subjects: medicine.medical_specialty, Immunology, Arthritis, Disease, Antibodies, Monoclonal, Humanized, Inflammatory bowel disease, Article, Receptors, Tumor Necrosis Factor, Etanercept, medicine, Adalimumab, Immunology and Allergy, Humans, Intensive care medicine, Inflammation, Latent tuberculosis, business.industry, Tumor Necrosis Factor-alpha, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, medicine.disease, Inflammatory Bowel Diseases, Infliximab, Rheumatoid arthritis, Immunoglobulin G, business, medicine.drug
Abstract: Tumor necrosis factor-alpha (TNFalpha) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn's disease and rheumatoid arthritis has led many investigators to propose a new, 'top down' paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNFalpha agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNFalpha antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or even exacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNFalpha antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNFalpha antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNFalpha antagonism.
Published: 2007

47. TNFα blockade in human diseases: Mechanisms and future directions

Author: Ram Singh, Maida Wong, Sungjin Kim, Jonathan Braun, Jan Lin, David W. Gjertson, David Ziring, Yael Korin, Elaine F. Reed, and Sheetal B Desai
Subjects: medicine.medical_treatment, Immunology, Inflammation, Antibodies, Monoclonal, Humanized, Certolizumab, Article, Receptors, Tumor Necrosis Factor, Etanercept, Arthritis, Rheumatoid, Immunology and Allergy, Medicine, Animals, Humans, Receptor, business.industry, Mechanism (biology), Tumor Necrosis Factor-alpha, Anti-Inflammatory Agents, Non-Steroidal, Adalimumab, Antibodies, Monoclonal, Immunotherapy, Inflammatory Bowel Diseases, Infliximab, Cytokine, Pegsunercept, Antirheumatic Agents, Immunoglobulin G, Cancer research, Cytokines, Tumor necrosis factor alpha, medicine.symptom, business, medicine.drug
Abstract: Tumor necrosis factor-alpha (TNFalpha) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFalpha antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFalpha antibodies are effective in other IMIDs. Early efforts at understanding how TNFalpha antagonists act in IMIDs centered on their ability to neutralize soluble TNFalpha or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFalpha blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFalpha antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFalpha antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFalpha antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations.
Published: 2007

48. Su1195 Simple Blood Testing Defines Severe New Onset Ulcerative Colitis in Children: The PROTECT Study

Author: Thomas D. Walters, David Ziring, Dedrick E. Moulton, Brendan M. Boyle, Anne M. Griffiths, Joel R. Rosh, Jonathan P. Evans, Stephen L. Guthery, Maria Oliva-Hemker, Melvin B. Heyman, Jeffrey S. Hyams, Prateek Wali, Keith J. Benkov, James Markowitz, Neal S. Leleiko, Joshua D. Noe, Subra Kugathasan, Anthony R. Otley, Marian D. Pfefferkorn, David J. Keljo, Jennifer A. Strople, Robert N. Baldassano, Cary G. Sauer, Alison Marquis, Ashish S. Patel, Boris Sudel, Susan S. Baker, David R. Mack, Sonia M. Davis, Lee A. Denson, Paul A. Rufo, Michael D. Kappelman, and Bradley Saul
Subjects: medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine.disease, Ulcerative colitis, New onset, Surgery, Internal medicine, medicine, business, Blood testing, Simple (philosophy)
Published: 2015

49. Sa1999 Patient Related Outcomes and Disease Activity Indices in New Onset Pediatric Ulcerative Colitis: The PROTECT Study

Author: Anthony R. Otley, Thomas D. Walters, Joel R. Rosh, Anne M. Griffiths, Keith J. Benkov, Marian D. Pfefferkorn, Melvin B. Heyman, David J. Keljo, Joshua D. Noe, Subra Kugathasan, Michael D. Kappelman, Neera Gupta, Dedrick E. Moulton, Cary G. Sauer, Krista Spada, Brendan M. Boyle, David Ziring, Prateek Wali, Jonathan P. Evans, Jennifer A. Strople, Robert N. Baldassano, Maria Oliva-Hemker, James Markowitz, Lee A. Denson, Jeffrey S. Hyams, Stephen L. Guthery, Neal S. Leleiko, Susan S. Baker, David R. Mack, Ashish S. Patel, Boris Sudel, and Paul A. Rufo
Subjects: Disease activity, medicine.medical_specialty, Psychoanalysis, Hepatology, media_common.quotation_subject, Gastroenterology, Physical therapy, medicine, Pediatric ulcerative colitis, Art, New onset, media_common
Abstract: Patient Related Outcomes and Disease Activity Indices in New Onset Pediatric Ulcerative Colitis: The PROTECT Study Thomas D. Walters, David R. Mack, Brendan Boyle, Anne M. Griffiths, Cary Sauer, Neal S. Leleiko, James Markowitz, David J. Keljo, Joel R. Rosh, Susan S. Baker, Melvin B. Heyman, Ashish S. Patel, Marian D. Pfefferkorn, Robert Baldassano, Joshua D. Noe, Maria Oliva-Hemker, Anthony R. Otley, Paul A. Rufo, Keith J. Benkov, David Ziring, Prateek Wali, Jonathan Evans, Dedrick E. Moulton, Boris Sudel, Stephen L. Guthery, Jennifer A. Strople, Michael Kappelman, Neera Gupta, Krista Spada, Subra Kugathasan, Lee Denson, Jeffrey S. Hyams
Published: 2015

50. Water load test in children

Author: Tsili Zangen, David Ziring, Lenore Schwankovsky, Anita Rowhani, Paul E. Hyman, Manu R. Sood, and Theresa Furtado
Subjects: Male, medicine.medical_specialty, Future studies, Body height, Drinking, Body weight, Satiety Response, Water consumption, Reference Values, Surveys and Questionnaires, medicine, Humans, Child, business.industry, Body Weight, Gastroenterology, Age Factors, Body Height, Self Efficacy, Surgery, Abdominal Pain, El Niño, Reference values, Pediatrics, Perinatology and Child Health, Physical therapy, Water load test, Female, business
Abstract: Objective: The purpose of this study was to estimate values for the water load test in healthy elementary school children. Methods: We measured the volume of water consumed by 176 children (71 boys and 105 girls) using the water load test at school. Children completed a questionnaire, which included self-efficacy and abdominal pain history. Then subjects drank water for 3 minutes or until full. Results: Children drank 630 ± 260 ml. Water consumption correlated with age, weight, and height. Children who believed they could drink a lot, drank more than those who thought they could not, P < 0.01. Conclusion: The water load test is a simple and inexpensive method to estimate onset of satiety and may be useful in future studies now that there are values for healthy children.
Published: 2002

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