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Rodríguez-Lago I, Casas-Deza D, Rimola J, Calafat M, Ferreiro-Iglesias R, Pellino G, Avellaneda N, Iborra M, Barreiro-de Acosta M, Gutiérrez Casbas A, Menchén L, Ordás I, Rodríguez-Moranta F, Zabana Y. Spanish Working Group in Crohn's Disease and Ulcerative Colitis (GETECCU) position paper for the management of non-perianal fistulizing Crohn's disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2025:502450. [PMID: 40250758 DOI: 10.1016/j.gastrohep.2025.502450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2025] [Accepted: 04/11/2025] [Indexed: 04/20/2025]
Abstract
Crohn's disease consists on a complex condition where, despite most patients initially present with an inflammatory behavior, a significant proportion develop complicated lesions such as strictures, fistulas, abscesses, or even perforations. These lesions progressively increase over time and are associated with a higher risk of surgery and hospitalization. Despite significant advances in their management after the introduction of biological therapies, particularly anti-TNF agents, these complications continue to pose challenges for the multiple professionals involved in their care. Fistulas that do not involve the perianal region (entero-enteric, entero-urinary, or entero-cutaneous) require a multidisciplinary strategy that combines medical, interventional, and surgical approaches. Their treatment ranges from general supportive measures to the use of antibiotics or, frequently, advanced therapies. Nevertheless, in cases of certain septic complications or those refractory to medical treatment, percutaneous drainage or surgical intervention remains essential. Although these lesions have a significant impact, evidence regarding the best strategies in this context, as well as the efficacy and safety of different therapies in these patients, remains limited. This is highlighted by the absence of specific recommendations in current guidelines. The objective of this document is to provide a comprehensive overview of non-perianal fistulizing Crohn's disease, addressing its epidemiological, clinical, and therapeutic aspects from a multidisciplinary perspective.
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Affiliation(s)
- Iago Rodríguez-Lago
- Servicio de Aparato Digestivo, Hospital Universitario de Galdakao; Instituto de Investigación Sanitaria Biobizkaia, Galdakao, Bizkaia, España.
| | - Diego Casas-Deza
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet; Instituto de Investigación Sanitaria de Aragón (IISA), Zaragoza, España
| | - Jordi Rimola
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, España
| | - Margalida Calafat
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol; Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España
| | - Rocío Ferreiro-Iglesias
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela; Fundación Galega de Investigación Sanitaria (IDIS), Santiago de Compostela, A Coruña, España
| | - Gianluca Pellino
- Servicio de Cirugía Colorrectal, Hospital Universitari Vall d'Hebron; Universitat Autònoma de Barcelona (UAB), Barcelona, España
| | - Nicolás Avellaneda
- Unidad de Investigación, Hospital Universitario CEMIC, Buenos Aires, Argentina
| | - Marisa Iborra
- Gastroenterología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Manuel Barreiro-de Acosta
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Santiago de Compostela; Fundación Galega de Investigación Sanitaria (IDIS), Santiago de Compostela, A Coruña, España
| | - Ana Gutiérrez Casbas
- Servicio de Aparato Digestivo, Hospital General Universitario Dr. Balmis; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL); Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Alicante, España
| | - Luis Menchén
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón; Instituto de Investigación Sanitaria Gregorio Marañón; Universidad Complutense, Madrid, España
| | - Ingrid Ordás
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Hospital Clínic, Barcelona; Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS); Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), España
| | - Francisco Rodríguez-Moranta
- Servicio de Aparato Digestivo, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa; Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Barcelona, España
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Salem DA, El-Ijla R, AbuMusameh RR, Zakout KA, Abu Halima AY, Abudiab MT, Banat YM, Alqeeq BF, Al-Tawil M, Matar K. Sex-related differences in profiles and clinical outcomes of Inflammatory bowel disease: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:425. [PMID: 39580396 PMCID: PMC11585250 DOI: 10.1186/s12876-024-03514-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/12/2024] [Indexed: 11/25/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that includes both Crohn's disease (CD) and ulcerative colitis (UC). The impact of sex on the disease course and the clinical outcomes not fully understood. Our systematic review and meta-analysis aims to explore the differences in the clinical outcomes in IBD. METHOD A systematic review and meta-analysis was done by searching in the PubMed /MEDLINE, Embase, and Scopus databases. We used the Random-Effects model to estimate risk ratios (RR) for binary outcomes and mean difference and hedges' g for continuous outcomes. RESULT A total of 44 unique studies were included. Our analysis revealed distinct sex differences in various outcomes of IBD. Anxiety was more prevalent in females (RR: 0.73; 95% CI [0.64, 0.82]) and females in the CD subgroup (RR: 0.76; 95% CI [0.62, 0.93]; p = 0.01. While depression was diagnosed more frequently in females (RR: 0.80; 95% CI [0.66, 0.97] in the total population of the study, subgroup analysis showed no sex difference. Additionally, quality of life scores were worse in females in the total population (Hedges' g: 0.24; 95% CI [0.05, 0.42]) with no significant difference in subgroup analyses. A significantly higher mortality risk was estimated in males (RR: 1.26; 95% CI [1.07, 1.48]) and in subgroup analysis for males with UC (RR: 1.48; 95% CI [1.19, 1.84]; p = 0.00) with no significant difference in CD. Regarding disease location, male patients were less likely to present with proctitis (RR: 0.67; 95% CI [0.50, 0.91]) when compared to females. Males had more frequent indications for surgery (RR: 1.10; 95% CI [1.01, 1.20]), however, no significant difference was found in subgroup analyses for CD or UC. Also, males were older at the time of admission (MD: 1.39 years; 95% CI [0.10, 2.68]). No significant sex differences were found in terms of hospitalization rates or disease behavior. CONCLUSION In conclusion, our meta-analysis shows that males face higher risks of early mortality and require more IBD surgeries, whereas females experience greater levels of anxiety and depression. These findings emphasize the need to consider sex disparities in IBD management.
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Affiliation(s)
- Dana A Salem
- Faculty of Medicine, Al-Quds University, Jerusalem, Palestine.
| | - Rawan El-Ijla
- Faculty of Medicine, Al-Quds University, Jerusalem, Palestine
| | | | - Khaled A Zakout
- Faculty of Medicine, Al-Quds University, Jerusalem, Palestine
| | | | | | - Yahya M Banat
- Faculty of Medicine, Al-Quds University, Jerusalem, Palestine
| | - Basel F Alqeeq
- Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine
| | | | - Khaled Matar
- Consultant Internal Medicine and Gastroenterology, European Gaza Hospital, Gaza, Palestine
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Caron B, Honap S, Peyrin-Biroulet L. Epidemiology of Inflammatory Bowel Disease across the Ages in the Era of Advanced Therapies. J Crohns Colitis 2024; 18:ii3-ii15. [PMID: 39475082 PMCID: PMC11522978 DOI: 10.1093/ecco-jcc/jjae082] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 05/12/2024] [Accepted: 05/31/2024] [Indexed: 11/02/2024]
Abstract
BACKGROUND AND AIMS The incidence of inflammatory bowel diseases [IBD] has risen over the past decade to become a global issue. The objectives of this review were to describe the incidence and/or prevalence of IBD in the era of advanced therapies, and to describe the association between environmental risk factors and both pathogenesis and disease course across the ages. METHODS We performed a search of English language publications listed in PubMed regarding the epidemiology of IBD and key environmental factors implicated in IBD from January 2000 to December 2023. RESULTS Annual incidence rates varied by geographical region with IBD estimates ranging from 10.5 to 46.14 per 100 000 in Europe, 1.37 to 1.5 per 100 000 in Asia and the Middle East, 23.67 to 39.8 per 100 000 in Oceania, 0.21 to 3.67 per 100 000 in South America, and 7.3 to 30.2 per 100 000 in North America. The burden of IBD among children and adolescents, and older people is rising globally. Key environmental factors implicated in IBD pathogenesis include exposure to tobacco smoking, antibiotics, non-steroidal anti-inflammatory drugs, oral contraceptives, infections, and ultra-high processed foods. Breastfeeding and a high-quality diet rich in fruit, vegetables, fish, and other fibre sources are important protective factors. Smoking has consistently been shown to negatively impact disease outcomes for Crohn's disease. CONCLUSION The epidemiology of IBD has undergone considerable change in recent decades, with an increase in the burden of disease worldwide. Optimally studying and targeting environmental triggers in IBD may offer future opportunities for disease modification.
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Affiliation(s)
- Bénédicte Caron
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
| | - Sailish Honap
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
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Herling A, Perluk TM, Freund O, Maharshak N, Cohen NA. Pulmonary Manifestations of IBD: Case Report and Review of the Literature. J Clin Med 2024; 13:5401. [PMID: 39336887 PMCID: PMC11432544 DOI: 10.3390/jcm13185401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 09/03/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
This article explores the pulmonary complications associated with inflammatory bowel disease (IBD). It presents a detailed case study of a 22-year-old male with Crohn's disease exhibiting pulmonary symptoms. The review delves into the spectrum of pulmonary involvement in IBD, covering clinical presentations, diagnostic challenges, underlying pathophysiology, and management strategies. It highlights the significance of these extraintestinal manifestations on patient outcomes and quality of life. The article underscores the need for heightened clinical awareness and a systematic approach to diagnosis and management, integrating the expertise of multiple specialists. The review identifies gaps in current research, suggesting avenues for future investigation to enhance the understanding and treatment of these complex manifestations.
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Affiliation(s)
- Amit Herling
- Faculty of Medicine, Ben-Gurion University of the Negev, Be'er Sheva 8410501, Israel
| | - Tal Moshe Perluk
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6139001, Israel
- The Pulmonary Institute, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
| | - Ophir Freund
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6139001, Israel
- The Pulmonary Institute, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
| | - Nitsan Maharshak
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6139001, Israel
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
| | - Nathaniel Aviv Cohen
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6139001, Israel
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Deodhar A, Blauvelt A, Lebwohl M, Feely M, Kronbergs A, Eberhart N, Zhu D, Inman E, Grace E, Holzkaemper T, Rahman P, Marzo-Ortega H, Papp KA, Merola JF, Gottlieb AB, Schwartzman S. Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials. Arthritis Res Ther 2024; 26:49. [PMID: 38347650 PMCID: PMC10860236 DOI: 10.1186/s13075-023-03257-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 12/27/2023] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND We report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA). METHODS This integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals. RESULTS Six thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0-1 to 4-5), PsA: 87 to 67.3 (year 0-1 to 2-3), axSpA: 82.1 to 55.4 (year 0-1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]). CONCLUSIONS In this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified. TRIAL REGISTRATION NCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.
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Affiliation(s)
- Atul Deodhar
- Oregon Health & Science University, Portland, OR, USA
| | | | | | - Meghan Feely
- Mount Sinai Hospital, New York, NY, USA
- Eli Lilly and Company, Indianapolis, IN, USA
- Mount Sinai West and Mount Sinai Morningside, New York, NY, USA
| | | | | | - Danting Zhu
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Elsa Inman
- Eli Lilly and Company, Indianapolis, IN, USA
| | - Elsie Grace
- Eli Lilly and Company, Indianapolis, IN, USA
| | | | - Proton Rahman
- Memorial University of Newfoundland, St. John's, NL, Canada
| | - Helena Marzo-Ortega
- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds Institute for Rheumatic and Musculoskeletal Medicine, The University of Leeds, Leeds, UK
| | - Kim A Papp
- Probity Medical Research and Alliance Clinical Trials, Waterloo, ON, Canada
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Joseph F Merola
- The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Alice B Gottlieb
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Cao L, Dayimu A, Guan X, Duan M, Zeng S, Wang H, Zong J, Sun C, Yang X, Yang X. Global evolving patterns and cross-country inequalities of inflammatory bowel disease burden from 1990 to 2019: a worldwide report. Inflamm Res 2024; 73:277-287. [PMID: 38184814 DOI: 10.1007/s00011-023-01836-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/30/2023] [Accepted: 12/09/2023] [Indexed: 01/08/2024] Open
Abstract
AIMS Inflammatory bowel disease (IBD) is a global disease. We aim to summarize the latest epidemiological patterns of IBD at the national, regional and global levels to give well-deserved attention and outline facilitating measures to reduce the disease burden. METHODS We collected the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of IBD in 204 countries and territories from 1990 to 2019 using data from the Global Burden of Disease Study 2019. We further calculated the estimated annual percentage change (EAPC) to qualify the temporal trends of IBD burden by sex, age and region over the past 30 years. RESULTS Globally, a total of 404.55 thousand incident cases, 4898.56 thousand prevalent cases, 41.00 thousand deaths and 1622.50 thousand DALYs of IBD were estimated in 2019. The age-standardized DALYs decreased from 27.2 in 1990 to 20.15 per 100,000 people in 2019, with an EAPC of -1.04. The high socio-demographic index regions presented pronounced age-standardized rates (ASRs) consistently over the last 30 years. The high-income North America had the highest ASRs in 2019, followed by Western Europe and Australasia. No gender difference was observed after being stratified by sex. CONCLUSIONS The accumulated IBD patients are expected to increase in the future due to the increased rate of IBD in developing countries, and social aging in developed countries. Understanding the changes in epidemiological patterns helps to provide evidence to mitigate the rising burden of IBD.
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Affiliation(s)
- Lina Cao
- Department of Health Management Center, Qilu Hospital of Shandong University, Jinan, China
| | - Alimu Dayimu
- Clinical Trial Unit, Department of Oncology, Univerisity of Cambridge, Cambridge, UK
| | - Xiao Guan
- Department of Health Management Center, Qilu Hospital of Shandong University, Jinan, China
| | - Miao Duan
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China
| | - Shuyan Zeng
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Wang
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, China
| | - Jiahao Zong
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, China
| | - Chunhua Sun
- Department of Health Management Center, Qilu Hospital of Shandong University, Jinan, China
| | - Xiaorong Yang
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, China.
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, China.
| | - Xiaoyun Yang
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, China.
- Clinical Epidemiology Unit, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, China.
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Festő B, Njers S, Dávid A, Horvát B, Sallay V, Molnár T, Rafael B, Martos T. [Health goals amongst patients with Crohn's disease.]. Orv Hetil 2023; 164:1102-1110. [PMID: 37454328 DOI: 10.1556/650.2023.32801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 05/03/2023] [Indexed: 07/18/2023]
Abstract
INTRODUCTION Inflammatory bowel diseases, including Crohn's disease, have a significant impact on patients' lifestyle, requiring lifelong attention to health behavior. OBJECTIVE The aim of our study was to investigate health-related goals, emotions related to health goals, the use of infocommunication tools and their associations. METHOD 79 patients with Crohn's disease (59.5% female, mean age 40.7 years, SD = 11.89) participated in the study. They answered demographic and health behaviour questions and completed the Personal Health Plans Questionnaire, which assessed their personal health goals, positive and negative emotions about health goal(s), support for personal health goals from their physician, negative and positive effects (barriers/support) of achieving health goals, and digital technology and internet use. RESULTS 70% of patients had at least 1 health goal. The health goals were classified into four categories: physical activity (43.6%), stress management (25.4%), nutrition (18%) and smoking cessation (7%). 71% of participants experienced at least average levels of positive emotions related to the health goal, but about 50% also experienced negative emotions. 51% of those with a health goal regularly use the internet and apps on smartphones. Infocommunication device use showed a medium-strength correlation with perceived health goal-related barrier/support (ρ = 0.55, p<0.01), support from the person's doctor (ρ = 0.45, p<0.05) and physical activity (ρ = 0.40, p<0.01). DISCUSSION More than two-thirds of patients had a health goal; most of the goals were related to health behaviours that are also relevant to Crohn's disease, but few had healthy eating and smoking cessation as health goals. Half of those with a health goal regularly use the internet and apps on smartphones. Among health behaviours, physical activity was associated with infocommunication device use. CONCLUSION It is recommended to investigate patients' health goals and infocommunication device use in the care of patients with Crohn's disease. This would allow the development of specific interventions to improve their health behaviour, which could increase the quality of life and disease prognosis. Orv Hetil. 2023; 164(28): 1102-1110.
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Affiliation(s)
- Blanka Festő
- 1 Szegedi Tudományegyetem, Egészségtudományi és Szociális Képzési Kar Szeged, Bal fasor 39-45., 6726 Magyarország
| | - Sanela Njers
- 2 Szegedi Tudományegyetem, Bölcsészet- és Társadalomtudományi Kar, Pszichológiai Intézet Szeged Magyarország
| | - Anett Dávid
- 3 Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Belgyógyászati Klinika Szeged Magyarország
| | - Barbara Horvát
- 2 Szegedi Tudományegyetem, Bölcsészet- és Társadalomtudományi Kar, Pszichológiai Intézet Szeged Magyarország
| | - Viola Sallay
- 2 Szegedi Tudományegyetem, Bölcsészet- és Társadalomtudományi Kar, Pszichológiai Intézet Szeged Magyarország
| | - Tamás Molnár
- 3 Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Belgyógyászati Klinika Szeged Magyarország
| | - Beatrix Rafael
- 4 Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Preventív Medicina Tanszék Szeged Magyarország
| | - Tamás Martos
- 2 Szegedi Tudományegyetem, Bölcsészet- és Társadalomtudományi Kar, Pszichológiai Intézet Szeged Magyarország
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Active smoking is associated with the development of adverse events of biological therapy in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2023; 35:15-20. [PMID: 36165073 DOI: 10.1097/meg.0000000000002445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Smoking has been associated with lower levels of anti-TNF agents, higher antibodies and a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate the possible association between smoking and adverse events (AEs) of biologics in patients with IBD. MATERIAL AND METHODS Consecutive IBD patients under biologics from a prospective, longitudinal registry of a tertiary center were included. A specially designed questionnaire including a wide range of AEs associated with biologics was also used. RESULTS A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5-56) years, Crohn's disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] who had completed the questionnaire forms for AEs were included. There were 52 (35%) active smokers and 33 (22.5%) ex-smokers. The prevalence of all AEs was 88% in smokers, 87% in ex-smokers and 79% in nonsmokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes ( P = 0.01 and 0.002, respectively). These correlations were the same for the CD and ulcerative colitis (UC), except for arthralgias where there was a significant correlation only with CD ( P = 0.001). There were no significant associations between smoking and other AEs ( P > 0.05). CONCLUSION Active smoking is associated with the development of dermatological manifestations (both in UC and CD) and arthralgias (in CD) in IBD patients under biologics.
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Attauabi M, Madsen GR, Bendtsen F, Wewer AV, Wilkens R, Ilvemark J, Vladimirova N, Jensen AB, Jensen FK, Hansen SB, Siebner HR, Nielsen YJW, Møller JM, Thomsen HS, Thomsen SF, Ingels HAS, Theede K, Boysen T, Bjerrum JT, Jakobsen C, Dorn-Rasmussen M, Jansson S, Yao Y, Burian EA, Møller FT, Fana V, Wiell C, Terslev L, Østergaard M, Bertl K, Stavropoulos A, Seidelin JB, Burisch J. Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study. BMJ Open 2022; 12:e055779. [PMID: 35760545 PMCID: PMC9237907 DOI: 10.1136/bmjopen-2021-055779] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 05/26/2022] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment. METHODS AND ANALYSIS IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis. ETHICS AND DISSEMINATION This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.
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Affiliation(s)
- Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Herlev Hospital, Herlev, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
| | - Gorm Roager Madsen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Anne Vibeke Wewer
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- The Paediatric Department, Hvidovre Hospital, Hvidovre, Denmark
| | - Rune Wilkens
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Johan Ilvemark
- Department of Gastroenterology and Hepatology, Herlev Hospital, Herlev, Denmark
| | - Nora Vladimirova
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark
| | - Annette Bøjer Jensen
- Department of Radiology, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark
| | - Frank Krieger Jensen
- Department of Radiology, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark
| | - Sanja Bay Hansen
- Department of Radiology, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark
| | - Hartwig Roman Siebner
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark
- Department of Neurology, Bispebjerg Hospital, Kobenhavn, Denmark
| | | | - Jakob M Møller
- Department of Radiology, Herlev Hospital, Herlev, Denmark
| | | | | | | | - Klaus Theede
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Trine Boysen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Jacob T Bjerrum
- Department of Gastroenterology and Hepatology, Herlev Hospital, Herlev, Denmark
| | - Christian Jakobsen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- The Paediatric Department, Hvidovre Hospital, Hvidovre, Denmark
| | - Maria Dorn-Rasmussen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- The Paediatric Department, Hvidovre Hospital, Hvidovre, Denmark
| | - Sabine Jansson
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- The Paediatric Department, Hvidovre Hospital, Hvidovre, Denmark
| | - Yiqiu Yao
- Department of Dermatology, Bispebjerg Hospital, Kobenhavn, Denmark
| | - Ewa Anna Burian
- Department of Dermatology, Bispebjerg Hospital, Kobenhavn, Denmark
| | - Frederik Trier Møller
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Kobenhavn, Denmark
| | - Viktoria Fana
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Kobenhavn, Denmark
| | - Charlotte Wiell
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Kobenhavn, Denmark
| | - Lene Terslev
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup, Glostrup, Denmark
| | - Mikkel Østergaard
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Kobenhavn, Denmark
| | - Kristina Bertl
- Department of Periodontology, Malmö Universitet, Malmo, Sweden
| | - Andreas Stavropoulos
- Malmo Universitet, Malmo, Sweden
- Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Jakob B Seidelin
- Department of Gastroenterology and Hepatology, Herlev Hospital, Herlev, Denmark
| | - Johan Burisch
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
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11
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Chen BC, Weng MT, Chang CH, Huang LY, Wei SC. Effect of smoking on the development and outcomes of inflammatory bowel disease in Taiwan: a hospital-based cohort study. Sci Rep 2022; 12:7665. [PMID: 35538186 PMCID: PMC9090732 DOI: 10.1038/s41598-022-11860-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 04/22/2022] [Indexed: 01/04/2023] Open
Abstract
Smoking influences the risks of inflammatory bowel disease (IBD). A hospital-based cohort was conducted to evaluate the effect of smoking on the development and outcomes of IBD, with age, sex and comorbidities matched non-IBD controls from the National Health Interview Survey database of Taiwan. 700 IBD patients (360 ulcerative colitis (UC), 340 Crohn’s disease (CD)) were analyzed for outcomes; and 575 patients (297 UC, 278 CD) were analyzed for prevalence. Smoking prevalence was significantly lower in UC patients than controls (20.9% vs. 30.4%, p < 0.01), but no difference between CD patients and controls (19.8% vs. 22.1%, p = 0.60). UC smokers had fewer admissions (1.6 vs. 2.5, p < 0.05) but higher rates of new cancer development (16% vs. 6.7%, p < 0.05) and mortality (16% vs. 4.9%, p < 0.01) than nonsmokers. CD smokers tended to have higher rates of stricturing and penetrating diseases (p < 0.05), and higher surgery risk (60.3% vs. 38.3%, p < 0.01) than nonsmokers. Smoking prevents UC occurrence and is associated with fewer hospitalization but increases risks of cancer and mortality. By contrast, smoking does not affect CD occurrence but is related to more aggressive behavior which results in a higher surgical rate.
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Affiliation(s)
- Bor-Cheng Chen
- School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Meng-Tzu Weng
- School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, HsinChu County, Taiwan
| | - Chin-Hao Chang
- Department of Medical Research, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Ling-Yun Huang
- Clinical Trial Center, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Shu-Chen Wei
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, National Taiwan University, No. 7 Chung-Shan South Road, Taipei, Taiwan.
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12
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Hua X, Lopes EW, Burke KE, Ananthakrishnan AN, Richter JM, Lo CH, Lochhead P, Chan AT, Khalili H. Smoking Behaviour Changes After Diagnosis of Inflammatory Bowel Disease and Risk of All-cause Mortality. J Crohns Colitis 2022; 16:1030-1038. [PMID: 35102373 PMCID: PMC9351977 DOI: 10.1093/ecco-jcc/jjac015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/30/2021] [Accepted: 01/25/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND AIMS We examined smoking behaviour changes after diagnoses of Crohn's disease [CD] and ulcerative colitis [UC] and evaluated their impact on mortality. METHODS Study population included incident CD or UC cases from three cohorts of the Nurses' Health Study [NHS], NHSII, and Health Professionals Follow-up Study. Smoking and other risk factors were prospectively assessed. Smoking behaviour changes were categorised as never, former [i.e., quit smoking before diagnosis], quitters [i.e., quit smoking after diagnosis], and current [i.e., continue smoking after diagnosis]. Follow-up for date and cause of death was completed through linkage to the National Death Index. Cox proportional hazard regression was used to estimate hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS Among 909 eligible CD and UC cases, 45% were never smokers, 38% were past smokers, and 16% were active smokers at the time of diagnosis. Among active smokers, 70% of patients with CD and 44% of patients with UC continued to smoke after diagnosis. In patients with CD, compared with current smokers, the multivariable-adjusted HRs [95% CI] of death were 0.19 [0.10 to 0.38] for never smokers, 0.31 [0.16 to 0.57] for former smokers, and 0.41 [0.18 to 0.93] for quitters. Similarly for UC, compared with current smokers, we observed a reduced risk of mortality for never smokers [HR = 0.23, 95% CI 0.10 to 0.51], former smokers [HR = 0.23, 95% CI 0.11 to 0.48], and quitters [HR = 0.28, 95% CI 0.11 to 0.72]. CONCLUSIONS In three cohorts of health professionals, a substantial proportion of patients with new diagnosis of CD and UC and history of smoking continued to smoke after diagnosis. Smoking cessation around the time of diagnosis was associated with a significant reduction in mortality.
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Affiliation(s)
- Xinwei Hua
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Emily W Lopes
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kristin E Burke
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Chun-Han Lo
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Paul Lochhead
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Hamed Khalili
- Corresponding author: Hamed Khalili, MD, MPH, Digestive Healthcare Center, Crohn’s and Colitis Center, Massachusetts General Hospital, 165 Cambridge Street, 9th Floor, Boston, MA 02114, USA. Tel.: 617 726 7933; fax: 617 726 3080;
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14
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Wu E, Duan M, Han J, Zhang H, Zhou Y, Cao L, Gong J, Guo Z, Li Y, Zhu W. Patients with Crohn's Disease Undergoing Abdominal Surgery: Clinical and Prognostic Evaluation Based on a Single-Center Cohort in China. World J Surg 2022; 46:450-460. [PMID: 34718840 DOI: 10.1007/s00268-021-06366-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The incidence and prevalence of Crohn's disease (CD) are increasing in China, but there are few reports on the characteristics of patients requiring abdominal surgery. This study aimed to evaluate the clinical characteristics of these patients and the potential risk factors for postoperative complications and surgical recurrence. METHODS In this observational, retrospective single-center cohort analysis, patients with CD who had undergone at least one abdominal surgery at our center from 2007 to 2020 were included. Data were collected from a prospectively maintained database. Clinical factors were assessed by logistic regression models, Kaplan-Meier methods, and Cox proportional hazards regression models. The predictive accuracy of the nomogram was determined by a concordance index (C-index) and calibration curve and was validated using bootstrap resampling. RESULTS In the 1639 patients, clinical characteristics were evaluated. In a multivariable logistic regression model, penetrating behavior (P = 0.002), emergency surgery (P = 0.010), and smoking status (P = 0.015) were significantly associated with an increased risk of postoperative septic complications. In contrast, staged surgery (P = 0.009) was inversely associated with postoperative complications. Upper gastrointestinal disease (P = 0.042), penetrating behavior (P = 0.027), emergency at initial surgery (P < 0.001) were significantly associated with an increased risk of surgical recurrence after the index surgery in our Cox regression model, whereas staged surgery (P = 0.036) was significantly associated with a decreased risk. The C-index of the nomogram for predicting recurrence was 0.744 (P = 0.015), and calibration curves showed good agreement between predictions of 3, 5, and 10 years of recurrence and actual observations. CONCLUSIONS There are several disease- and surgery-associated risk factors of postoperative adverse outcomes in patients with CD undergoing abdominal surgery. This is important in optimizing the management of CD which has evolved into a global disease with rising prevalence in newly industrialized countries including China.
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Affiliation(s)
- Enhao Wu
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Ming Duan
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Jianqiu Han
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Hanzhe Zhang
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Yan Zhou
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Lei Cao
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Jianfeng Gong
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Zhen Guo
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China
| | - Yi Li
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
| | - Weiming Zhu
- Department of General Surgery, Center for Inflammatory Bowel Diseases, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
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Kumar S, Kumar A. Microbial pathogenesis in inflammatory bowel diseases. Microb Pathog 2022; 163:105383. [PMID: 34974120 DOI: 10.1016/j.micpath.2021.105383] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 12/20/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal system. Previously, it is considered the disease of the western world but now the incidence and prevalence of IBD are increasing globally with urbanization and modernization. Additionally, the major problem is the highest incidence of IBD among children and adolescents. The precise etiology of IBD is unknown and there is no cure for IBD, which is also the reason for increasing the number of cases worldwide. The IBD is a complex interplay of environment, immune system, and microbiota in a genetically susceptible host. Among these factors, the alteration in intestinal microbiota has been detected in IBD patients. The bacterial species associated with IBD include Mycobacterium paratuberculosis, adherent-invasive E. coli (AIEC), Helicobacter pylori, and Campylobacter concisus. Moreover, the efficacy of antibiotics and probiotics further suggests the role of microbes in IBD. However, no study confirmed the bacterial species as a cause of IBD as per Koch's postulates. Thus, still controversies exist regarding the role of microbes in IBD. Therefore, this paper aims to review the current literature to evaluate the role of microbes in IBD that would be a useful inventory of researchers working in this area.
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Affiliation(s)
- Sunil Kumar
- Faculty of Biosciences, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh, India.
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India.
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16
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BOGALE K, VRANA K, KONSAVAGE W, WALTER V, STUART A, DALESSIO S, KOLTUN W, BERNASKO N, TINSLEY A, WILLIAMS E, CLARKE K, COATES M. Polysubstance use in inflammatory bowel disease. J Dig Dis 2021; 22:706-713. [PMID: 34724329 PMCID: PMC8688202 DOI: 10.1111/1751-2980.13064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/28/2021] [Accepted: 10/31/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We aimed to evaluate the incidence, predisposing factors and impacts of polysubstance use (PSU) (ie, the concurrent use or abuse of two or more drugs or substances) in inflammatory bowel disease (IBD). METHODS Data of patients enrolled between 1 January 2015 and 31 August 2019 from a single tertiary care referral center were retrospectively collected. Patients' baseline and clinical characteristics and their antidepressant and/or anxiolytic medications were abstracted. Associations between PSU and patients' characteristics were analyzed. Multivariate logistic regression models were fit, incorporating significant clinical factors. RESULTS Altogether 315 patients with IBD (166 women, 149 men; 214 with Crohn's disease and 101 ulcerative colitis) were enrolled. Of them, 66 (21.0%) exhibited PSU (CD 21.5%, UC 19.8%); 37.5% had moderate to severe disease activity, 34.3% with extraintestinal manifestations (EIM), 41.6% with an anxious or depressed state and 69.8% had used healthcare resources in the prior 12 months. Moreover, 71.2% used two substances, while 27.3% used three substances. In the total cohort, EIM (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.34, P = 0.019) and antidepressant or anxiolytic use (OR 2.51, 95% CI 1.45-4.39, P < 0.001) were positively associated with PSU on multivariate analysis. PSU was associated with increased rate of IBD-associated imaging (57.6% vs 47.0%, P < 0.05). CONCLUSIONS PSU is common in IBD. EIM, antidepressant and/or anxiolytic use and imaging studies were independently associated with PSU. This study reinforces the importance of screening patients with IBD for substance use, particularly those with EIM and using antidepressants and/or anxiolytics.
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Affiliation(s)
- Kaleb BOGALE
- Pennsylvania State University College of Medicine, Department of Medicine, Hershey, PA, U.S.A
| | - Kent VRANA
- Pennsylvania State University College of Medicine, Department of Pharmacology, Hershey, PA, U.S.A
| | - Wesley KONSAVAGE
- Pennsylvania State University College of Medicine, Department of Pharmacology, Hershey, PA, U.S.A
| | - Vonn WALTER
- Pennsylvania State University College of Medicine, Department of Public Health Sciences, Hershey, PA, U.S.A.,Pennsylvania State University College of Medicine, Department of Biochemistry, Hershey, PA, U.S.A
| | - August STUART
- Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
| | - Shannon DALESSIO
- Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
| | - Walter KOLTUN
- Pennsylvania State University College of Medicine, Department of Surgery, Division of Colorectal Surgery, Hershey, PA, U.S.A
| | - Nana BERNASKO
- Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
| | - Andrew TINSLEY
- Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
| | - Emmanuelle WILLIAMS
- Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
| | - Kofi CLARKE
- Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
| | - Matthew COATES
- Pennsylvania State University College of Medicine, Department of Pharmacology, Hershey, PA, U.S.A.,Pennsylvania State University College of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology, Hershey, PA, U.S.A
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17
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Park MY, Yoon YS, Kim HE, Lee JL, Park IJ, Lim SB, Yu CS, Kim JC. Surgical options for perianal fistula in patients with Crohn's disease: A comparison of seton placement, fistulotomy, and stem cell therapy. Asian J Surg 2021; 44:1383-1388. [PMID: 33966965 DOI: 10.1016/j.asjsur.2021.03.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 02/16/2021] [Accepted: 03/14/2021] [Indexed: 10/21/2022] Open
Abstract
OBJECTIVE This study was designed to assess the demographic characteristics of patients with Crohn's perianal fistula (CPF) who were treated at a tertiary referral institution. Surgical outcomes were compared in groups of patients who underwent seton placement, fistulotomy, and stem cell therapy. METHODS Patients who underwent surgery for CPF between 2015 and 2017 at Asan Medical Center, Seoul, Korea, were retrospectively evaluated. Patients were divided into groups who underwent seton placement, fistulotomy, and stem cell therapy. Their clinical variables and closure rates were compared. RESULTS This study included 156 patients who underwent a total of 209 operations. More than half of the operations consisted of seton placement (67%), followed by stem cell therapy (18%) and fistulotomy (15%) patients. Of the 209 fistulas, 153 (73%) were complex, with an overall closure rate of 38% during a median follow-up of 29 months. Closure rates following fistulotomy, stem cell therapy, and seton placement were 90%, 70%, and 18%. Seton placement was more significantly frequently used than the other procedures in patients with complex fistula and those with abscesses. Of the 79 fistulas that achieved complete closure, 11 (14%) recurred. The recurrence rates did not differ among the various techniques. CONCLUSION Surgical treatment of CPF is dependent on lesion type. Seton placement was the primary draining procedure for complex fistulas and abscesses, resulting in low closure rates. Fistulotomy was the definite procedure for low type and simple fistula. Stem cell therapy showed high closure rates as definitive treatment, even for complex fistulas.
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Affiliation(s)
- Min Young Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Sik Yoon
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hyoung Eun Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jong Lyul Lee
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - In Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seok-Byung Lim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Cheon Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Fiocchi C, Dragoni G, Iliopoulos D, Katsanos K, Ramirez VH, Suzuki K, Torres J, Scharl M. Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD-What, Why, and How. J Crohns Colitis 2021; 15:1410-1430. [PMID: 33733656 DOI: 10.1093/ecco-jcc/jjab051] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Many diseases that affect modern humans fall in the category of complex diseases, thus called because they result from a combination of multiple aetiological and pathogenic factors. Regardless of the organ or system affected, complex diseases present major challenges in diagnosis, classification, and management. Current forms of therapy are usually applied in an indiscriminate fashion based on clinical information, but even the most advanced drugs only benefit a limited number of patients and to a variable and unpredictable degree. This 'one measure does not fit all' situation has spurred the notion that therapy for complex disease should be tailored to individual patients or groups of patients, giving rise to the notion of 'precision medicine' [PM]. Inflammatory bowel disease [IBD] is a prototypical complex disease where the need for PM has become increasingly clear. This prompted the European Crohn's and Colitis Organisation to focus the Seventh Scientific Workshop on this emerging theme. The articles in this special issue of the Journal address the various complementary aspects of PM in IBD, including what PM is; why it is needed and how it can be used; how PM can contribute to prediction and prevention of IBD; how IBD PM can aid in prognosis and improve response to therapy; and the challenges and future directions of PM in IBD. This first article of this series is structured on three simple concepts [what, why, and how] and addresses the definition of PM, discusses the rationale for the need of PM in IBD, and outlines the methodology required to implement PM in IBD in a correct and clinically meaningful way.
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Affiliation(s)
- Claudio Fiocchi
- Department of Inflammation & Immunity, Lerner Research Institute, and Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence,Italy.,IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence,Italy
| | | | - Konstantinos Katsanos
- Division of Gastroenterology, Department of Internal Medicine, University of Ioannina School of Health Sciences, Ioannina,Greece
| | - Vicent Hernandez Ramirez
- Department of Gastroenterology, Xerencia Xestión Integrada de Vigo, and Research Group in Digestive Diseases, Galicia Sur Health Research Institute [IIS Galicia Sur], SERGAS-UVIGO, Vigo, Spain
| | - Kohei Suzuki
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX,USA
| | | | - Joana Torres
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
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19
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Con D, Parthasarathy N, Bishara M, Luber RP, Joshi N, Wan A, Rickard JA, Long T, Connoley DJ, Sparrow MP, Gibson PR, van Langenberg DR, Vasudevan A. Development of a Simple, Serum Biomarker-based Model Predictive of the Need for Early Biologic Therapy in Crohn's Disease. J Crohns Colitis 2021; 15:583-593. [PMID: 32949458 DOI: 10.1093/ecco-jcc/jjaa194] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Early or first-line treatment with biologics, as opposed to conventional immunomodulators, is not always necessary to achieve remission in Crohn's disease [CD] and may not be cost-effective. This study aimed to develop a simple model to predict the need for early biologic therapy, in order to risk-stratify CD patients and guide initial treatment selection. METHODS A model-building study using supervised statistical learning methods was conducted using a retrospective cohort across two tertiary centres. All biologic-naïve CD patients who commenced an immunomodulator between January 1, 2004 and December 31, 2016, were included. A predictive score was derived using Cox regression modelling of immunomodulator failure, and was internally validated using bootstrap resampling. RESULTS Of 410 patients [median age 37 years, 47% male, median disease duration 4.7 years], 229 [56%] experienced immunomodulator failure [39 required surgery, 24 experienced a new stricture, 44 experienced a new fistula/abscess, 122 required biologic escalation] with a median time to failure of 16 months. Independent predictors of treatment failure included raised C-reactive protein [CRP], low albumin, complex disease behaviour, younger age, and baseline steroids. Highest CRP and lowest albumin measured within the 3 months preceding immunomodulator initiation outperformed baseline measurements. After model selection, only highest CRP and lowest albumin remained and the resultant Crohn's Immunomodulator CRP-Albumin [CICA] index demonstrated robust optimism-corrected discriminative performance at 12, 24, and 36 months (area under the curve [AUC] 0.84, 0.83, 0.81, respectively). CONCLUSIONS The derived CICA index based on simple, widely available markers is feasible, internally valid, and has a high utility in predicting immunomodulator failure. This requires external, prospective validation.
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Affiliation(s)
- Danny Con
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
| | - Nina Parthasarathy
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
| | - Maria Bishara
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
| | - Raphael P Luber
- Department of Gastroenterology, Alfred Health, Melbourne, VIC, Australia
| | - Neetima Joshi
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Anna Wan
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - James A Rickard
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Tony Long
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
| | - Declan J Connoley
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health, Melbourne, VIC, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Health, Melbourne, VIC, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Daniel R van Langenberg
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Abhinav Vasudevan
- Department of Gastroenterology, Eastern Health, Melbourne, VIC, Australia
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20
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Yassin S, Isakov NF, Ron Y, Cohen NA, Hirsch A, Maharshak N. A watchful waiting approach for newly diagnosed Crohn's disease patients with an inflammatory phenotype. Int J Colorectal Dis 2021; 36:735-743. [PMID: 33404768 DOI: 10.1007/s00384-020-03811-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/23/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND An early treat-to-target approach in Crohn's disease (CD) patients is recommended to avoid complications. However, CD may not always progress despite lack of treatment, thus exposing some patients to unnecessary side effects. We aimed to examine whether newly diagnosed CD patients with an inflammatory phenotype can benefit from a watchful waiting approach. METHODS This retrospective cohort study followed CD patients with an inflammatory phenotype who were diagnosed between 2010 and 2015 and followed for at least 1 year. A watchful waiting approach was defined as maintenance therapy with 5-ASA medication only or no treatment during the first year of diagnosis or longer. Disease complications were defined as need for surgery or change in disease phenotype. RESULTS Eighty-six patients were included and followed-up for 57.0 ± 29.0 months. Thirty-seven patients were managed with a watchful waiting approach and 49 with an early therapeutic intervention. The majority of patients (83.8%) in the watchful waiting group did not develop disease complications. In this group, there was no difference in clinical disease severity (stools per day, 2.7 ± 1.7 vs 3.3 ± 1.0, P = 0.39; abdominal pain, 74.2 vs 50.0%, P = 0.24) between those who did not develop complications and those who did. Smoking was associated with a complicated course (multivariate analysis: OR = 1.98, 95% CI 1.06-3.71, P = 0.03). CONCLUSIONS A watchful waiting approach of newly diagnosed CD patients with an inflammatory phenotype may be a feasible option, with low long-term complication rate specifically in nonsmoking patients.
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Affiliation(s)
- Sharif Yassin
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel.,Department of Internal Medicine "B", Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Naomi Fliss Isakov
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Yulia Ron
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Nathaniel Aviv Cohen
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Ayal Hirsch
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel
| | - Nitsan Maharshak
- IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, 6423906, Tel Aviv, Israel.
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21
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Giudici F, Cavalli T, Luceri C, Russo E, Zambonin D, Scaringi S, Ficari F, Fazi M, Amedei A, Tonelli F, Malentacchi C. Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients. Mediators Inflamm 2021; 2021:8854916. [PMID: 33708009 PMCID: PMC7932801 DOI: 10.1155/2021/8854916] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND CARD15/NOD2 is the most significant genetic susceptibility in Crohn's disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the relationship between CARD15/NOD2 polymorphisms and the clinical CD behavior after a long-term follow-up, in order to identify potential clinical biomarkers of prognosis. METHODS 191 surgical CD patients were prospectively characterized both for the main single nucleotide polymorphisms of CARD15/NOD2 and for many other environmental risk factors connected with the severe disease form. After a mean follow-up of 7.3 years, the correlations between clinical features and CD natural history were analyzed. RESULTS CARD15/NOD2 polymorphisms were significantly associated with younger age at diagnosis compared to wild type cases (p < 0.05). Moreover, patients carrying a 3020insC polymorphism presented a larger Δ between diagnosis and surgery (p = 0.0344). Patients carrying an hz881 and a 3020insC exhibited, respectively, a lower rate of responsiveness to azathioprine (p = 0.012), but no difference was found in biologic therapy. Finally, the risk of surgical recurrence was significantly associated, respectively, to age at diagnosis, to familial CD history, to diagnostic delay, to arthritis, and to the presence of perioperative complications. CONCLUSIONS 3020insC CARD15 polymorphism is associated with an earlier CD onset, and age at CD diagnosis < 27 years was confirmed to have a detrimental effect on its clinical course. In addition, the familiarity seems to be connected with a more aggressive postoperative course. Finally, for the first time, we have observed a lower rate of responsiveness to azathioprine in patients carrying an hz881 and a 3020insC.
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Affiliation(s)
- Francesco Giudici
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Tiziana Cavalli
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Cristina Luceri
- Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), Italy
| | - Edda Russo
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Daniela Zambonin
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Stefano Scaringi
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Ferdinando Ficari
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Marilena Fazi
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Amedeo Amedei
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Francesco Tonelli
- Department of Clinical and Experimental Medicine, Surgical Unit, University of Florence, Italy
| | - Cecilia Malentacchi
- Department of Biomedical Experimental and Clinical Sciences, “Mario Serio”, Italy
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22
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Lee S, Kuenzig ME, Ricciuto A, Zhang Z, Shim HH, Panaccione R, Kaplan GG, Seow CH. Smoking May Reduce the Effectiveness of Anti-TNF Therapies to Induce Clinical Response and Remission in Crohn's Disease: A Systematic Review and Meta-analysis. J Crohns Colitis 2021; 15:74-87. [PMID: 32621742 DOI: 10.1093/ecco-jcc/jjaa139] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Cigarette smoking worsens prognosis of Crohn's disease [CD]. We conducted a systematic review and meta-analysis to examine the association between smoking and induction of clinical response or remission with anti-tumour necrosis factor [TNF] therapy. METHODS MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL [June 2019] were searched for studies reporting the effect of smoking on short-term clinical response and remission to anti-TNF therapy [≤16 weeks following the first treatment] in patients with CD. Risk ratios [RR] with 95% confidence intervals [CI] were calculated using random-effects models. RESULTS Eighteen observational studies and three randomised controlled trials [RCT] were included. Current smokers and non-smokers [never or former] had similar rates of clinical response [observational studies RR: 0.96; 95% CI: 0.88, 1.05; RCTs RR: 1.09; 95% CI: 0.84, 1.41]. When restricted to studies clearly defining the smoking exposure, smokers treated with anti-TNF were less likely to achieve clinical response than non-smokers [smokers defined as having ≥5 cigarettes/day for ≥6 months RR: 0.63; 95% CI: 0.48, 0.83; lifetime never smokers vs ever smokers excluding former smokers RR: 0.81; 95% CI: 0.71, 0.93]. Current smokers were also less likely to achieve clinical remission in observational studies [RR: 0.75; 95% CI: 0.57, 0.98], though this association was not seen in RCTs [RR: 1.04; 95% CI: 0.89, 1.21]. CONCLUSIONS Smoking is significantly associated with a reduction in the ability of infliximab or adalimumab to induce short-term clinical response and remission when pooling studies where smoking status was clearly defined. When patients with CD are treated with highly effective therapy, including anti-TNF agents, concurrent smoking cessation may improve clinical outcomes.
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Affiliation(s)
- Sangmin Lee
- Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - M Ellen Kuenzig
- CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.,Children's Hospital of Eastern Ontario [CHEO] Research Institute, Ottawa, ON, Canada.,Institute for Clinical Evaluative Sciences [ICES], Toronto, ON, Canada
| | - Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Ziyu Zhang
- Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Hang Hock Shim
- Department of Gastroenterology Hepatology, Singapore General Hospital, Bukit Merah, Singapore
| | - Remo Panaccione
- Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Inflammatory Bowel Disease Unit, University of Calgary, Calgary, AB, Canada
| | - Gilaad G Kaplan
- Community Health Sciences, University of Calgary, Calgary, AB, Canada.,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Inflammatory Bowel Disease Unit, University of Calgary, Calgary, AB, Canada
| | - Cynthia H Seow
- Community Health Sciences, University of Calgary, Calgary, AB, Canada.,Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Inflammatory Bowel Disease Unit, University of Calgary, Calgary, AB, Canada
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23
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Losurdo G, Todeschini A, Giorgio F, Piscitelli D, Giangaspero A, Ierardi E, Di Leo A. Human Leukocyte Antigen (HLA) Haplotype Does Not Influence the Inflammatory Pattern of Duodenal Lymphocytosis Linked to Irritable Bowel Syndrome. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:660. [PMID: 33260434 PMCID: PMC7761368 DOI: 10.3390/medicina56120660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/23/2020] [Accepted: 11/25/2020] [Indexed: 11/17/2022]
Abstract
Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten- and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFNγ), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFNγ, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 ± 7.7 vs. 36.0 ± 8.8, p < 0.001). A significant, direct correlation between IELs and duodenal expression of IFNγ was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (A.T.); (F.G.); (A.G.); (E.I.); (A.D.L.)
- PhD Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Alessia Todeschini
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (A.T.); (F.G.); (A.G.); (E.I.); (A.D.L.)
| | - Floriana Giorgio
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (A.T.); (F.G.); (A.G.); (E.I.); (A.D.L.)
| | - Domenico Piscitelli
- Section of Pathology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy;
| | - Antonio Giangaspero
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (A.T.); (F.G.); (A.G.); (E.I.); (A.D.L.)
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (A.T.); (F.G.); (A.G.); (E.I.); (A.D.L.)
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (A.T.); (F.G.); (A.G.); (E.I.); (A.D.L.)
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Le Berre C, Loy L, Lönnfors S, Avedano L, Piovani D. Patients' perspectives on smoking and inflammatory bowel disease: An online survey in collaboration with European Federation of Crohn's and Ulcerative Colitis Associations. World J Gastroenterol 2020; 26:4343-4355. [PMID: 32848338 PMCID: PMC7422536 DOI: 10.3748/wjg.v26.i29.4343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/25/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Smoking has detrimental effects on Crohn’s disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in inflammatory bowel diseases (IBD).
AIM To understand the patients’ perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients.
METHODS The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking.
RESULTS In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products.
CONCLUSION This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.
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Affiliation(s)
- Catherine Le Berre
- Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, Nantes 44000, France
| | - Laura Loy
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan 20089, Italy
| | - Sanna Lönnfors
- European Federation of Crohn's and Ulcerative Colitis Associations, Brussels B-1000, Belgium
| | - Luisa Avedano
- European Federation of Crohn's and Ulcerative Colitis Associations, Brussels B-1000, Belgium
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele MI, Milan 20090, Italy
- Humanitas Clinical and Research Center - IRCCS, Milan, Rozzano 20089, Italy
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Abstract
Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.
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Townsend CM, Nguyen TM, Cepek J, Abbass M, Parker CE, MacDonald JK, Khanna R, Jairath V, Feagan BG. Adalimumab for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2020; 5:CD012877. [PMID: 32413933 PMCID: PMC7386457 DOI: 10.1002/14651858.cd012877.pub2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Conventional medications for Crohn's disease (CD) include anti-inflammatory drugs, immunosuppressants and corticosteroids. If an individual does not respond, or loses response to first-line treatments, then biologic therapies such as tumour necrosis factor-alpha (TNF-α) antagonists such as adalimumab are considered for treating CD. Maintenance of remission of CD is a clinically important goal, as disease relapse can negatively affect quality of life. OBJECTIVES To assess the efficacy and safety of adalimumab for maintenance of remission in people with quiescent CD. SEARCH METHODS We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, and clinicaltrials.gov from inception to April 2019. SELECTION CRITERIA We considered for inclusion randomized controlled trials (RCTs) comparing adalimumab to placebo or to an active comparator. DATA COLLECTION AND ANALYSIS We analyzed data on an intention-to-treat basis. We calculated risk ratios (RRs) and corresponding 95% confidence intervals (95% CI) for dichotomous outcomes. The primary outcome was failure to maintain clinical remission. We define clinical remission as a Crohn's Disease Activity Index (CDAI) score of < 150. Secondary outcomes were failure to maintain clinical response, endoscopic remission, endoscopic response, histological remission and adverse events (AEs). We assessed biases using the Cochrane 'Risk of bias' tool. We used GRADE to assess the overall certainty of evidence supporting the primary outcome. MAIN RESULTS We included six RCTs (1158 participants). We rated four trials at low risk of bias and two trials at unclear risk of bias. All participants had moderate-to-severe CD that was in clinical remission. Four studies were placebo-controlled (1012 participants). Two studies (70 participants) compared adalimumab to active medication (azathioprine, mesalamine or 6-mercaptopurine) in participants who had an ileocolic resection prior to study enrolment. Adalimumab versus placebo Fifty-nine per cent (252/430) of participants treated with adalimumab failed to maintain clinical remission at 52 to 56 weeks, compared with 86% (217/253) of participants receiving placebo (RR 0.70, 95% CI 0.64 to 0.77; 3 studies, 683 participants; high-certainty evidence). Among those who received prior TNF-α antagonist therapy, 69% (129/186) of adalimumab participants failed to maintain clinical or endoscopic response at 52 to 56 weeks, compared with 93% (108/116) of participants who received placebo (RR 0.76, 95% CI 0.68 to 0.85; 2 studies, 302 participants; moderate-certainty evidence). Fifty-one per cent (192/374) of participants who received adalimumab failed to maintain clinical remission at 24 to 26 weeks, compared with 79% (149/188) of those who received placebo (RR 0.66, 95% CI 0.52 to 0.83; 2 studies, 554 participants; moderate-certainty evidence). Eighty-seven per cent (561/643) of participants who received adalimumab reported an AE compared with 85% (315/369) of participants who received placebo (RR 1.01, 95% CI 0.94 to 1.09; 4 studies, 1012 participants; high-certainty evidence). Serious adverse events were seen in 8% (52/643) of participants who received adalimumab and 14% (53/369) of participants who received placebo (RR 0.56, 95% CI 0.39 to 0.80; 4 studies, 1012 participants; moderate-certainty evidence) and withdrawal due to AEs was reported in 7% (45/643) of adalimumab participants compared to 13% (48/369) of placebo participants (RR 0.59, 95% CI 0.38 to 0.91; 4 studies, 1012 participants; moderate-certainty evidence). Commonly-reported AEs included CD aggravation, arthralgia, nasopharyngitis, urinary tract infections, headache, nausea, fatigue and abdominal pain. Adalimumab versus active comparators No studies reported failure to maintain clinical remission. One study reported on failure to maintain clinical response and endoscopic remission at 104 weeks in ileocolic resection participants who received either adalimumab, azathioprine or mesalamine as post-surgical maintenance therapy. Thirteen per cent (2/16) of adalimumab participants failed to maintain clinical response compared with 54% (19/35) of azathioprine or mesalamine participants (RR 0.23, 95% CI 0.06 to 0.87; 51 participants). Six per cent (1/16) of participants who received adalimumab failed to maintain endoscopic remission, compared with 57% (20/35) of participants who received azathioprine or mesalamine (RR 0.11, 95% CI 0.02 to 0.75; 51 participants; very low-certainty evidence). One study reported on failure to maintain endoscopic response at 24 weeks in ileocolic resection participants who received either adalimumab or 6-mercaptopurine (6-MP) as post-surgical maintenance therapy. Nine per cent (1/11) of adalimumab participants failed to maintain endoscopic remission compared with 50% (4/8) of 6-MP participants (RR 0.18, 95% CI 0.02 to 1.33; 19 participants). AUTHORS' CONCLUSIONS Adalimumab is an effective therapy for maintenance of clinical remission in people with quiescent CD. Adalimumab is also effective in those who have previously been treated with TNF-α antagonists. The effect of adalimumab in the post-surgical setting is uncertain. More research is needed in people with recent bowel surgery for CD to better determine treatment plans following surgery. Future research should continue to explore factors that influence initial and subsequent biologic selection for people with moderate-to-severe CD. Studies comparing adalimumab to other active medications are needed, to help determine the optimal maintenance therapy for CD.
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Affiliation(s)
| | | | - Jeremy Cepek
- Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada
| | - Mohamad Abbass
- Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada
| | | | - John K MacDonald
- Department of Medicine, University of Western Ontario, London, Canada
| | - Reena Khanna
- Department of Medicine, University of Western Ontario, London, Canada
- Robarts Clinical Trials, London, Canada
| | - Vipul Jairath
- Department of Medicine, University of Western Ontario, London, Canada
- Robarts Clinical Trials, London, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada
| | - Brian G Feagan
- Department of Medicine, University of Western Ontario, London, Canada
- Robarts Clinical Trials, London, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada
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Kirchgesner J, Nyboe Andersen N, Carrat F, Jess T, Beaugerie L. Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study. Gut 2020; 69:852-858. [PMID: 31446428 DOI: 10.1136/gutjnl-2019-318932] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 07/22/2019] [Accepted: 08/17/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Patients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD. DESIGN Patients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014. The risks of acute arterial events (including ischaemic heart disease, cerebrovascular disease and peripheral artery disease) were compared between thiopurines and anti-TNFs exposed and unexposed patients with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, traditional cardiovascular risk factors, comorbidities and IBD disease activity. RESULTS Among 177 827 patients with IBD (96 111 (54%) women, mean age at cohort entry 46.2 years (SD 16.3), 90 205 (50.7%) with Crohn's disease (CD)), 4145 incident acute arterial events occurred (incidence rates: 5.4 per 1000 person-years). Compared with unexposed patients, exposure to anti-TNFs (HR 0.79, 95% CI 0.66 to 0.95), but not to thiopurines (HR 0.93, 95% CI 0.82 to 1.05), was associated with a decreased risk of acute arterial events. The magnitude in risk reduction was highest in men with CD exposed to anti-TNFs (HR 0.54, 95% CI 0.40 to 0.72). CONCLUSION Exposure to anti-TNFs is associated with a decreased risk of acute arterial events in patients with IBD, particularly in men with CD.
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Affiliation(s)
- Julien Kirchgesner
- Department of Gastroenterology, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France .,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universite, Paris, France
| | - Nynne Nyboe Andersen
- Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.,Department of Gastroenterology, Zealand University Hospital Koge, Koge, Denmark
| | - Fabrice Carrat
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universite, Paris, France.,Department of Public Health, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Tine Jess
- Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark
| | - Laurent Beaugerie
- Department of Gastroenterology, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universite, Paris, France
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29
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Cox MA, Bassi C, Saunders ME, Nechanitzky R, Morgado-Palacin I, Zheng C, Mak TW. Beyond neurotransmission: acetylcholine in immunity and inflammation. J Intern Med 2020; 287:120-133. [PMID: 31710126 DOI: 10.1111/joim.13006] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 08/24/2019] [Accepted: 09/10/2019] [Indexed: 12/21/2022]
Abstract
Acetylcholine (ACh) is best known as a neurotransmitter and was the first such molecule identified. ACh signalling in the neuronal cholinergic system has long been known to regulate numerous biological processes (reviewed by Beckmann and Lips). In actuality, ACh is a ubiquitous signalling molecule that is produced by numerous non-neuronal cell types and even by some single-celled organisms. Within multicellular organisms, a non-neuronal cholinergic system that includes the immune system functions in parallel with the neuronal cholinergic system. Several immune cell types both respond to ACh signals and can directly produce ACh. Recent work from our laboratory has demonstrated that the capacity to produce ACh is an intrinsic property of T cells responding to viral infection, and that this ability to produce ACh is dependent upon IL-21 signalling to the T cells. Furthermore, during infection this immune-derived ACh is necessary for the T cells to migrate into infected tissues. In this review, we will discuss the various sources of ACh that are relevant during immune responses and describe how ACh acts on immune cells to influence their functions. We will also address the clinical implications of this fascinating aspect of immunity, focusing on ACh's role in the migration of T cells during infection and cancer.
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Affiliation(s)
- M A Cox
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - C Bassi
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - M E Saunders
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - R Nechanitzky
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - I Morgado-Palacin
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - C Zheng
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - T W Mak
- The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.,Ontario Institute for Cancer Research, Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.,Department of Immunology, University of Toronto, Toronto, ON, Canada.,Department of Pathology, University of Hong Kong, Hong Kong, Hong Kong
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30
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Should We Divide Crohn's Disease Into Ileum-Dominant and Isolated Colonic Diseases? Clin Gastroenterol Hepatol 2019; 17:2634-2643. [PMID: 31009791 PMCID: PMC6885453 DOI: 10.1016/j.cgh.2019.04.040] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 03/25/2019] [Accepted: 04/04/2019] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal tract. First described in 1932 as terminal ileitis or regional enteritis, it predominately involves the ileum with or without colonic involvement. Isolated colonic CD was first described in 1960 and since then the phenotypic classification of CD has evolved to stratify patients into isolated ileal, ileocolonic, or isolated colonic involvement. In the current review we evaluate the published literature regarding differences in epidemiology, natural history, pathogenesis, response to therapy, and disease monitoring, when stratified by disease location. Based on the available evidence consideration could be given to a new classification for CD, which splits it into ileum dominant (isolated ileal and ileocolonic) and isolated colonic disease. This may allow for a more optimized approach to clinical care and scientific research for CD.
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31
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Allez M, Auzolle C, Ngollo M, Bottois H, Chardiny V, Corraliza AM, Salas A, Perez K, Stefanescu C, Nancey S, Buisson A, Pariente B, Fumery M, Sokol H, Tréton X, Barnich N, Seksik P, Le Bourhis L. T cell clonal expansions in ileal Crohn's disease are associated with smoking behaviour and postoperative recurrence. Gut 2019; 68:1961-1970. [PMID: 30792246 DOI: 10.1136/gutjnl-2018-317878] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/21/2019] [Accepted: 01/22/2019] [Indexed: 12/14/2022]
Abstract
UNLABELLED T cell clonal expansions are present in the inflamed mucosa of patients with Crohn's disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection. METHODS T cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively. RESULTS TCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment. CONCLUSION Clonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven. TRIAL REGISTRATION NUMBER NCT03458195.
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Affiliation(s)
- Matthieu Allez
- Department of Gastroenterology, Hopital Saint Louis, Paris, France.,INSERM U1160, Hôpital Saint-Louis, Paris, France
| | - Claire Auzolle
- Department of Gastroenterology, Hopital Saint Louis, Paris, France
| | | | - Hugo Bottois
- INSERM U1160, Hôpital Saint-Louis, Paris, France
| | | | | | - Azucena Salas
- Hospital Clinic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Kevin Perez
- INSERM U1160, Hôpital Saint-Louis, Paris, France
| | - Carmen Stefanescu
- Service de Gastroentérologie, MICI et Assistance Nutritive, Hôpital Beaujon, Clichy, France
| | - Stéphane Nancey
- Department of Gastroenterology, Lyon Sud Hospital, Hospices Civils de Lyon, Pierre Benite, Lyon, France
| | - Anthony Buisson
- Gastroenterology Department, University Hospital Estaing, Clermont-Ferrand, France
| | - Benjamin Pariente
- Department of Gastroenterology, Hopital Claude huriez, Lille, France
| | - Mathurin Fumery
- Hepato-Gastroenterology Department, CHU Amiens, Amiens, France
| | - Harry Sokol
- Department of Gastroenterology, Hopital Saint-Antoine, Paris, Île-de-France, France
| | - Xavier Tréton
- Service de Gastroentérologie, MICI et Assistance Nutritive, Hopital Beaujon, Clichy, France
| | - Nicolas Barnich
- M2iSH, UMR Inserm U1071, USC INRA 2018, Université d'Auvergne, Clermont Ferrand, France
| | - Philippe Seksik
- Department of Gastroenterology, Hopital Saint-Antoine, Paris, Île-de-France, France
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Chong C, Rahman A, Loonat K, Sagar RC, Selinger CP. Current smoking habits in British IBD patients in the age of e-cigarettes. BMJ Open Gastroenterol 2019; 6:e000309. [PMID: 31297234 PMCID: PMC6590968 DOI: 10.1136/bmjgast-2019-000309] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/17/2019] [Accepted: 05/24/2019] [Indexed: 12/15/2022] Open
Abstract
Background Smoking has a detrimental effect on Crohn’s disease (CD) while data on ulcerative colitis (UC) are conflicting. Smoking habits have changed dramatically in the UK due to a public smoking ban and the advent of e-cigarettes. We describe current smoking rates in patients with inflammatory bowel disease (IBD) and any effects on disease course. Methods Self-reported smoking status was elicited in outpatients with IBD, and clinical data were extracted from patient records. Results Of 465 patients (58% CD, 42% UC), 247 (53.1%) were ever-smokers (37.4% ex-smokers, 15.7% current smokers). Electronic cigarettes (e-cigarettes) were ever used by 28 patients (15 current users). All e-cigarette users had previously smoked cigarettes and 13 had stopped smoking completely. Patients with CD were more likely to currently smoke (21.5% vs 7.7%, p<0.001) than those with UC. Ever use of biological therapy was higher in current smokers compared with never smokers (49% vs 35%, p=0.034). The need for surgery was higher in current smokers compared with never smokers (43% vs 25%, p=0.006). The risk of CD complications during 21-month prospective follow-up was numerically higher for current smoker versus e-cigarette users (53% vs 17%, p=0.19). Compared with the general population, the proportion of current cigarette smokers (14.9% vs 15.1%) and e-cigarette users was similar in our cohort (4.26% vs 5.5%). Conclusions Patients with IBD show similar smoking behaviour to the general population. E-cigarettes were used as replacement for cigarettes or by some as an intermediate step for smoking cessation. Larger, prospective studies are required to fully determine the effects of e-cigarettes on IBD.
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Affiliation(s)
- Chui Chong
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Anisha Rahman
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Khaleel Loonat
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Rebecca C Sagar
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Christian Philipp Selinger
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
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Sedano Muñoz R, Quera Pino R, Ibáñez Lazo P, Figueroa Corona C, Flores Pérez L. Aminosalicylates, thiopurines and methotrexate in inflammatory bowel disease: Is it possible to discontinue the treatment? GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 42:339-347. [PMID: 30954317 DOI: 10.1016/j.gastrohep.2019.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 01/15/2019] [Accepted: 01/16/2019] [Indexed: 06/09/2023]
Abstract
The current goals of treatment in inflammatory bowel disease, both Crohn's disease and ulcerative colitis, are to achieve clinical, endoscopic and ideally histological remission and improve the quality of life of these patients. Current therapies are effective in achieving remission in most cases, but there is a lack of clear guidelines on their optimal duration. This review aims to evaluate the current evidence on the withdrawal of therapy with 5-aminosalicylates, thiopurines and methotrexate. We also aim to identify which specific group of patients, while in remission and in the absence of risk factors, may be able to discontinue therapy without a significant risk of relapse.
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Affiliation(s)
- Rocío Sedano Muñoz
- Servicio de Gastroenterología, Hospital Clínico de la Universidad de Chile, Santiago, Chile
| | - Rodrigo Quera Pino
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile.
| | - Patricio Ibáñez Lazo
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile
| | - Carolina Figueroa Corona
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile
| | - Lilian Flores Pérez
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile
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Pittet V, Michetti P, Mueller C, Braegger CP, von Känel R, Schoepfer A, Macpherson AJ, Rogler G, Anderegg C, Bauerfeind P, Beglinger C, Begré S, Belli D, Bengoa JM, Biedermann L, Bigler B, Binek J, Blattmann M, Boehm S, Borovicka J, Braegger CP, Brunner N, Bühr P, Burnand B, Burri E, Buyse S, Cremer M, Criblez DH, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Dorta G, Egger M, Ehmann T, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Frei P, Frei PR, Fried M, Froehlich F, Funk C, Furlano RI, Gallot-Lavallée S, Geyer M, Girardin M, Golay D, Grandinetti T, Gysi B, Haack H, Haarer J, Helbling B, Hengstler P, Herzog D, Hess C, Heyland K, Hinterleitner T, Hiroz P, Hirschi C, Hruz P, Iwata R, Jost R, Juillerat P, Keller C, Knellwolf C, Knoblauch C, Köhler H, Koller R, Krieger-Grübel C, Kullak-Ublick G, Künzler P, Landolt M, Lange R, Lehmann FS, Macpherson A, Maerten P, Maillard MH, Manser C, Manz M, Marbet U, Marx G, Matter C, Meier R, Mendanova M, Michetti P, Misselwitz B, Morell B, Mosler P, Mottet C, Müller C, Müller P, Müllhaupt B, Münger-Beyeler C, Musso L, et alPittet V, Michetti P, Mueller C, Braegger CP, von Känel R, Schoepfer A, Macpherson AJ, Rogler G, Anderegg C, Bauerfeind P, Beglinger C, Begré S, Belli D, Bengoa JM, Biedermann L, Bigler B, Binek J, Blattmann M, Boehm S, Borovicka J, Braegger CP, Brunner N, Bühr P, Burnand B, Burri E, Buyse S, Cremer M, Criblez DH, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Dorta G, Egger M, Ehmann T, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Frei P, Frei PR, Fried M, Froehlich F, Funk C, Furlano RI, Gallot-Lavallée S, Geyer M, Girardin M, Golay D, Grandinetti T, Gysi B, Haack H, Haarer J, Helbling B, Hengstler P, Herzog D, Hess C, Heyland K, Hinterleitner T, Hiroz P, Hirschi C, Hruz P, Iwata R, Jost R, Juillerat P, Keller C, Knellwolf C, Knoblauch C, Köhler H, Koller R, Krieger-Grübel C, Kullak-Ublick G, Künzler P, Landolt M, Lange R, Lehmann FS, Macpherson A, Maerten P, Maillard MH, Manser C, Manz M, Marbet U, Marx G, Matter C, Meier R, Mendanova M, Michetti P, Misselwitz B, Morell B, Mosler P, Mottet C, Müller C, Müller P, Müllhaupt B, Münger-Beyeler C, Musso L, Nagy A, Neagu M, Nichita C, Niess J, Nydegger A, Obialo N, Oneta C, Oropesa C, Peter U, Peternac D, Petit LM, Piccoli-Gfeller F, Pilz JB, Pittet V, Raschle N, Rentsch R, Restellini RS, Richterich JP, Rihs S, Ritz MA, Roduit J, Rogler D, Rogler G, Rossel JB, Rueger V, Saner G, Sauter B, Sawatzki M, Schäppi M, Scharl M, Scharl S, Schelling M, Schibli S, Schlauri H, Uebelhart SS, Schnegg JF, Schoepfer A, Seibold F, Seirafi M, Semadeni GM, Semela D, Senning A, Sidler M, Sokollik C, Spalinger J, Spangenberger H, Stadler P, Steuerwald M, Straumann A, Straumann-Funk B, Sulz M, Suter A, Thorens J, Tiedemann S, Tutuian R, Vavricka S, Viani F, Vögtlin J, Von Känel R, Vonlaufen A, Vouillamoz D, Vulliamy R, Wermuth J, Werner H, Wiesel P, Wiest R, Wylie T, Zeitz J, Zimmermann D. Cohort Profile Update: The Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Int J Epidemiol 2019; 48:385-386f. [DOI: 10.1093/ije/dyy298] [Show More Authors] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Valérie Pittet
- Institute of Social & Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
| | - Pierre Michetti
- Crohn and Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland
- Division of Gastroenterology & Hepatology, Lausanne University Hospital, Lausanne, Switzerland
| | | | - Christian P Braegger
- Division of Gastroenterology and Nutrition, University Children's Hospital Zurich, Zurich, Switzerland
| | - Roland von Känel
- Department of Consultation-Liaison-Psychiatry and Psychosomatic Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Alain Schoepfer
- Division of Gastroenterology & Hepatology, Lausanne University Hospital, Lausanne, Switzerland
| | - Andrew J Macpherson
- University Clinic of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
- Maurice Muller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology & Hepatology, Zurich University Hospital, Zurich, Switzerland
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Oshima S, Watanabe M. Genetic and environmental factors drive personalized medicine for Crohn's disease. J Clin Invest 2018; 128:4758-4760. [PMID: 30320603 DOI: 10.1172/jci124303] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The introduction of anti-TNF antibody therapy has changed the course of treatment for Crohn's disease. However, the fundamental mechanism for the onset of Crohn's disease is still unknown, and the treatment strategy for this disease remains suboptimal. The assessment of the disease phenotype based on key environmental factors and genetic background may indicate options for the personalized treatment of Crohn's disease. In this issue of the JCI, Liu et al. show that consumption of tobacco and the mutation of ATG16L1T300A, a prevalent Crohn's disease susceptibility allele, drive defects in cells at the bottom of the intestinal crypt, the Paneth cells. These factors may provide novel targets for personalized medicine.
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Ouldali N, Hugot JP, Viala J, Damir M, Martinez-Vinson C, Meinzer U. Early Arthritis Is Associated With Failure of Immunosuppressive Drugs and Severe Pediatric Crohn's Disease Evolution. Inflamm Bowel Dis 2018; 24:2423-2430. [PMID: 29788152 DOI: 10.1093/ibd/izy137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic relapsing inflammatory disease. To optimize therapeutic decision making, it is essential to identify parameters that allow early prediction of a severe disease course. The aim of this study was to assess the link between arthritis and medium-term therapeutic failure in pediatric CD. METHODS We conducted a population-based cohort study with prospectively collected electronic data. To be included, patients must be younger than 17 years and have a confirmed CD diagnosed between 2005 and 2014. The primary outcome was the percentage of patients with at least 1 therapeutic failure of immunosuppressive drugs during the 2 years after the CD diagnosis, with a propensity score analysis. RESULTS We included 272 patients with CD. The median age was 12.1 years (interquartile [10.1-14.2]). Sixty-five patients (23.9%) developed arthritis, which predominantly occurred during the first year after CD diagnosis. We found a highly significant association between arthritis and therapeutic failure of immunosuppressive drugs after 2 years (OR = 6.9; 95% confidence interval [CI], 2.7-18.0; P < 0.0001; propensity score matching analysis). Arthritis was also significantly associated with introduction of biotherapy due to luminal disease 2 years after diagnosis (OR = 3.2, 95% CI, 1.8-6.0; P = 0.0001). Similar results were obtained after 4 years, and arthritis was significantly associated with a higher number of hospitalizations for luminal flare-up or complications after 4 years (OR = 2.2; 95% CI, 1.2-3.9; P = 0.007). CONCLUSIONS Arthritis was strongly associated with medium-term therapeutic failure of pediatric CD. Occurrence of arthritis early in the disease may justify closer follow-up visits or specific therapeutic management.
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Affiliation(s)
- Naïm Ouldali
- Unité d'Épidémiologie Clinique, Hôpital Robert Debré, APHP, Paris, France.,Inserm, CIC-EC 1426, Paris, France.,Service de Pédiatrie Générale, Maladies Infectieuses et Médicine Interne, Centre de Référence des Maladies Rhumatologiques et Auto-immunes Rares de l'Enfant (RAISE), Hôpital Robert Debré, APHP, Paris, France
| | - Jean-Pierre Hugot
- Service de Gastroentérologie, Centre de Références des Maladies Digestives Rares (MARDI), Hôpital Robert Debré, APHP, Paris, France.,Université Paris Diderot, INSERM UMR1149, Paris, France
| | - Jérôme Viala
- Service de Gastroentérologie, Centre de Références des Maladies Digestives Rares (MARDI), Hôpital Robert Debré, APHP, Paris, France
| | - Mohamed Damir
- Unité d'Épidémiologie Clinique, Hôpital Robert Debré, APHP, Paris, France.,Inserm, CIC-EC 1426, Paris, France
| | - Christine Martinez-Vinson
- Service de Gastroentérologie, Centre de Références des Maladies Digestives Rares (MARDI), Hôpital Robert Debré, APHP, Paris, France
| | - Ulrich Meinzer
- Université Paris Diderot, INSERM UMR1149, Paris, France.,Institut Pasteur, Unité Biologie et Génétique de la Paroi Bactérienne, Paris, France.,Service de Pédiatrie Générale, Maladies Infectieuses et Médicine Interne, Centre de Référence des Maladies Rhumatologiques et Auto-immunes Rares de l'Enfant (RAISE), Hôpital Robert Debré, APHP, Paris, France
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Laing B, Barnett MPG, Marlow G, Nasef NA, Ferguson LR. An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets. Expert Rev Gastroenterol Hepatol 2018; 12:969-983. [PMID: 30052094 DOI: 10.1080/17474124.2018.1505497] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.
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Affiliation(s)
- Bobbi Laing
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,b School of Nursing, Faculty of Medical and Health Sciences , The University of Auckland , Auckland , New Zealand
| | - Matthew P G Barnett
- c Food Nutrition & Health Team, Food & Bio-Based Products Group , AgResearch Limited , Palmerston North , New Zealand.,d Liggins Institute , The High-Value Nutrition National Science Challenge , Auckland , New Zealand.,e Riddet Institute , Massey University , Palmerston North , New Zealand
| | - Gareth Marlow
- f Institute of Medical Genetics , Cardiff University , Cardiff , Wales , UK
| | - Noha Ahmed Nasef
- e Riddet Institute , Massey University , Palmerston North , New Zealand.,g College of Health, Massey Institute of Food Science and Technology , Palmerston North , New Zealand
| | - Lynnette R Ferguson
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,h Auckland Cancer Research Society, Faculty of Medical and Health Sciences, Grafton Campus , The University of Auckland , Auckland , New Zealand
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Arieira C, Cúrdia Gonçaves T, Dias de Castro F, João Moreira M, Cotter J. Clinical course in Crohn's disease: factors associated with behaviour change and surgery. Scand J Gastroenterol 2018; 53:1222-1227. [PMID: 30345845 DOI: 10.1080/00365521.2018.1503709] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 07/14/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic and progressive disease that changes its behaviour over time. Transmural inflammation in CD leads to stricturing and/or penetrating complications. AIM To evaluate the frequency of long-term progression of CD phenotypes, the need of abdominal surgery, and the main factors associated with these outcomes. METHODS A retrospective study was conducted with a prospective follow-up. Montreal classification was assessed at the moment of the diagnosis and at the end of the follow-up period. RESULTS Two hundred and ninety patients were included, with mean follow-up duration of nine years. A change in behaviour was observed in 46 patients (15.9%). Ileocolic location (60.9% vs. 45.1%; p = .049), age at diagnosis <16 years (8.7% vs. 2.0%; p = .017), the use of steroids at diagnosis (43.2% vs. 27.0%; p = .031) and shorter exposure time to biological therapy (15.9 months vs 41.3 months; p < .001) were identified as risk factors for phenotype change. Regarding surgery, 70 patients (24.1%) were submitted to abdominal surgery. Smoking habits (41.3% vs. 26.9%; p = .048), stricturing behaviour (50% vs. 18.4%; p < .001), penetrating behaviour 34.8% vs. 7.8%; p < .001), hospitalisations in the first year of diagnosis (52.3% vs. 12.4%; p < .001), and use of steroids at diagnosis (61.4% vs. 23.6%; p < .001) were more frequently seen in patients subjected to surgery. Patients subjected to surgery were less frequently treated with biological therapy (8.7% vs. 23.4%; p < .025). CONCLUSIONS A behaviour progression was observed in about one-sixth of the patients. Progression to a stricturing pattern was the most frequent change in behaviour. Stricturing and penetrating behaviour, higher number of hospitalisations in the first year of diagnosis, use of steroids at diagnosis, smoking status, age at diagnosis <16 years and ileocolic disease location were associated with an unfavourable clinical evolution.
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Affiliation(s)
- Cátia Arieira
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine, Life and Health Sciences Research Institute, University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Tiago Cúrdia Gonçaves
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine, Life and Health Sciences Research Institute, University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Francisca Dias de Castro
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine, Life and Health Sciences Research Institute, University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Maria João Moreira
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine, Life and Health Sciences Research Institute, University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - José Cotter
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine, Life and Health Sciences Research Institute, University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
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Wang P, Hu J, Ghadermarzi S, Raza A, O′Connell D, Xiao A, Ayyaz F, Zhi M, Zhang Y, Parekh NK, Lazarev M, Parian A, Brant SR, Bedine M, Truta B, Hu P, Banerjee R, Hutfless SM. Smoking and Inflammatory Bowel Disease: A Comparison of China, India, and the USA. Dig Dis Sci 2018; 63:2703-2713. [PMID: 29862485 PMCID: PMC6435261 DOI: 10.1007/s10620-018-5142-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 05/28/2018] [Indexed: 01/12/2023]
Abstract
BACKGROUND Cigarette smoking is thought to increase the risk of Crohn's disease (CD) and exacerbate the disease course, with opposite roles in ulcerative colitis (UC). However, these findings are from Western populations, and the association between smoking and inflammatory bowel disease (IBD) has not been well studied in Asia. AIMS We aimed to compare the prevalence of smoking at diagnosis between IBD cases and controls recruited in China, India, and the USA, and to investigate the impact of smoking on disease outcomes. METHODS We recruited IBD cases and controls between 2014 and 2018. All participants completed a questionnaire about demographic characteristics, environmental risk factors and IBD history. RESULTS We recruited 337 participants from China, 194 from India, and 645 from the USA. In China, CD cases were less likely than controls to be current smokers (adjusted odds ratio [95% CI] 0.4 [0.2-0.9]). There was no association between current or former smoking and CD in the USA. In China and the USA, UC cases were more likely to be former smokers than controls (China 14.6 [3.3-64.8]; USA 1.8 [1.0-3.3]). In India, both CD and UC had similar current smoking status to controls at diagnosis. Current smoking at diagnosis was significantly associated with greater use of immunosuppressants (4.4 [1.1-18.1]) in CD cases in China. CONCLUSIONS We found heterogeneity in the associations of smoking and IBD risk and outcomes between China, India, and the USA. Further study with more adequate sample size and more uniform definition of smoking status is warranted.
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Affiliation(s)
- Peiqi Wang
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Jun Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Guangzhou, China
| | - Shadi Ghadermarzi
- Department of Internal Medicine, East Carolina University, Greenville, NC, USA
| | - Ali Raza
- Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, MD, USA
| | - Douglas O′Connell
- School of Medicine, Division of Gastroenterology, University of California, Irvine, USA
| | - Amy Xiao
- Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
| | - Faraz Ayyaz
- Services Institute of Medical Sciences, Lahore, Pakistan
| | - Min Zhi
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuanqi Zhang
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Nimisha K. Parekh
- School of Medicine, Division of Gastroenterology, University of California, Irvine, USA
| | - Mark Lazarev
- Department of Medicine, Division of Gastroenterology and Hepatology, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University, Baltimore, MD, USA
| | - Alyssa Parian
- Department of Medicine, Division of Gastroenterology and Hepatology, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University, Baltimore, MD, USA
| | - Steven R. Brant
- Department of Medicine, Division of Gastroenterology and Hepatology, Rutgers Health, Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Marshall Bedine
- Department of Medicine, Division of Gastroenterology and Hepatology, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University, Baltimore, MD, USA
| | - Brindusa Truta
- Department of Medicine, Division of Gastroenterology and Hepatology, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University, Baltimore, MD, USA
| | - Pinjin Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Susan M. Hutfless
- Division of Gastroenterology and Hepatology, Gastrointestinal Epidemiology Research Center, Johns Hopkins University, 600 N Wolfe St, Blalock 449, Baltimore, MD 21287, USA,Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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Harris KG, Chang EB. The intestinal microbiota in the pathogenesis of inflammatory bowel diseases: new insights into complex disease. Clin Sci (Lond) 2018; 132:2013-2028. [PMID: 30232239 PMCID: PMC6907688 DOI: 10.1042/cs20171110] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 08/30/2018] [Accepted: 09/04/2018] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel diseases (IBD) are a group of chronic diseases of increasing worldwide prevalence characterized by gastrointestinal (GI) inflammation leading to debilitating symptoms and complications. The contribution of the intestinal microbiota to the pathogenesis and etiology of these diseases is an area of active research interest. Here, we discuss key mechanisms underlying the chronic inflammation seen in IBD as well as evidence implicating the intestinal microbiota in the development and potentiation of that inflammation. We also discuss recently published work in areas of interest within the field of microbial involvement in IBD pathogenesis - the importance of proper microecology within the GI tract, the evidence that the intestinal microbiota transduces environmental and genetic risk factors for IBD, and the mechanisms by which microbial products contribute to communication between microbe and host. There is an extensive body of published research on the evidence for microbial involvement in IBD; the goal of this review is to highlight the growing edges of the field where exciting and innovative research is pushing the boundaries of the conceptual framework of the role of the intestinal microbiota in IBD pathogenesis.
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Affiliation(s)
| | - Eugene B Chang
- Department of Medicine, University of Chicago, Chicago, IL 60637, U.S.A.
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Lee S, Metcalfe A, Raman M, Leung Y, Aghajafari F, Letourneau N, Panaccione R, Kaplan GG, Seow CH. Pregnant Women with Inflammatory Bowel Disease Are at Increased Risk of Vitamin D Insufficiency: A Cross-Sectional Study. J Crohns Colitis 2018; 12:702-709. [PMID: 29546360 PMCID: PMC5972591 DOI: 10.1093/ecco-jcc/jjy030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 03/07/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Vitamin D insufficiency is prevalent in individuals with inflammatory bowel disease [IBD], as well as in pregnant women; however, the prevalence of vitamin D insufficiency in pregnant women with IBD is unknown. This study assessed the prevalence of vitamin D insufficiency in pregnant women with IBD and the adequacy of recommended supplementation. METHODS A cross-sectional study was conducted in pregnant women with inflammatory bowel disease [Crohn's disease = 61, ulcerative colitis = 41] and without inflammatory bowel disease [n = 574]. Chi square tests and log binomial regression were used to examine the prevalence of vitamin D insufficiency. Covariates included ethnicity and season. Adequacy of vitamin D supplementation during pregnancy was also assessed. RESULTS The prevalence of vitamin D insufficiency [25-OHD ≤75 nmol/L] in those with Crohn's disease was 50.8% (95% confidence interval [CI]: 38.4%-63.2%) and 60.9% [95% CI: 45.3%-74.7%] with ulcerative colitis compared with 17.4% [95% CI: 14.6%-20.8%] without inflammatory bowel disease. Women with inflammatory bowel disease were more likely to be vitamin D insufficient after adjusting for ethnicity and season (Crohn's disease-adjusted relative risk [aRR] = 2.98,;: 2.19-4.04; ulcerative colitis-aRR = 3.61; 95% CI: 2.65-4.93). Despite vitamin D supplementation, 32.3% [95% CI: 17.8%-51.2%] of those with Crohn's disease, 58.3% [95% CI: 37.1%-76.9%] of those with with ulcerative colitis, and 10.8% [95% CI: 6.9%-16.6%] of those without inflammatory bowel disease were still vitamin D insufficient. CONCLUSIONS Pregnant women with inflammatory bowel disease are at increased risk of vitamin D insufficiency compared with those without inflammatory bowel disease. The current guidelines for vitamin D supplementation may be inadequate for pregnant women with inflammatory bowel disease.
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Affiliation(s)
- Sangmin Lee
- University of Calgary Cumming School of Medicine, Community Health Sciences, Calgary, AB, Canada
| | - Amy Metcalfe
- University of Calgary Cumming School of Medicine, Calgary, AB, Canada,Obstetrics & Gynecology, Calgary, AB, Canada,Community Health Sciences, Medicine, Calgary, AB, Canada
| | - Maitreyi Raman
- University of Calgary Cumming School of Medicine, Medicine, Calgary, AB, Canada
| | - Yvette Leung
- University of British Columbia, Medicine, Vancouver, BC, Canada
| | - Fariba Aghajafari
- University of Calgary Cumming School of Medicine, Community Health Sciences, AB, Canada,Family Medicine, Calgary, AB, Canada
| | - Nicole Letourneau
- University of Calgary Cumming School of Medicine, Community Health Sciences, AB, Canada,University of Calgary Cumming School of Medicine, Medicine, AB, Canada,University of Calgary Cumming School of Medicine, Pediatrics & Psychiatry, AB, Canada,University of Calgary Faculty of Nursing, Nursing, Calgary, AB, Canada
| | - Remo Panaccione
- University of Calgary, Inflammatory Bowel Disease Clinic, Calgary, AB, Canada
| | - Gilaad G Kaplan
- University of Calgary, Division of Gastroenterology, Departments of Medicine, Calgary, AB, Canada
| | - Cynthia H Seow
- University of Calgary, Department of Medicine, Calgary, AB, Canada,Corresponding author: Dr Cynthia H. Seow, TRW building, Room 6D18, 3280 Hospital Drive NW, Calgary, AB, Canada, T2N 4Z6.
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Savin Z, Kivity S, Yonath H, Yehuda S. Smoking and the intestinal microbiome. Arch Microbiol 2018; 200:677-684. [DOI: 10.1007/s00203-018-1506-2] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Revised: 03/07/2018] [Accepted: 03/23/2018] [Indexed: 12/21/2022]
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Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol 2018; 113:481-517. [PMID: 29610508 DOI: 10.1038/ajg.2018.27] [Citation(s) in RCA: 898] [Impact Index Per Article: 128.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 01/11/2018] [Indexed: 02/06/2023]
Abstract
Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health-care providers should incorporate this guideline along with patient's needs, desires, and their values in order to fully and appropriately care for patients with Crohn's disease. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.
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Affiliation(s)
- Gary R Lichtenstein
- Department of Medicine, Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kim L Isaacs
- Department of Medicine, Division of Gastroenterology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA
| | - Miguel D Regueiro
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Lauren B Gerson
- Department of Medicine, Division of Gastroenterology, California Pacific Medical Center, San Francisco, California, USA
| | - Bruce E Sands
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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DNA polymorphisms predict time to progression from uncomplicated to complicated Crohn's disease. Eur J Gastroenterol Hepatol 2018; 30:447-455. [PMID: 29293112 DOI: 10.1097/meg.0000000000001055] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Most patients with Crohn's disease (CD) are diagnosed with the uncomplicated inflammatory form of the disease (Montreal stage B1). However, the majority of them will progress to complicated stricturing (B2) and penetrating (B3) CD during their lifetimes. The aim of our study was to identify the genetic factors associated with time to progression from uncomplicated to complicated CD. PATIENTS AND METHODS Patients with an inflammatory phenotype at diagnosis were followed up for 10 years. Genotyping was carried out using Illumina ImmunoChip. After quality control, association analyses, Bonferroni's adjustments, linear and Cox's regression, and Kaplan-Meier analysis were carried out for 111 patients and Manhattan plots were constructed. RESULTS Ten years after diagnosis, 39.1% of the patients still had the inflammatory form and 60.9% progressed to complicated disease, with an average time to progression of 5.91 years. Ileal and ileocolonic locations were associated with the complicated CD (P=1.08E-03). We found that patients with the AA genotype at single-nucleotide polymorphism rs16857259 near the gene CACNA1E progressed to the complicated form later (8.80 years) compared with patients with the AC (5.11 years) or CC (2.00 years) genotypes (P=3.82E-07). In addition, nine single-nucleotide polymorphisms (near the genes RASGRP1, SULF2, XPO1, ZBTB44, HLA DOA/BRD2, HLA DRB1/HLA DQA1, PPARA, PUDP, and KIAA1614) showed a suggestive association with disease progression (P<10). Multivariate Cox's regression analysis on the basis of clinical and genetic data confirmed the association of the selected model with disease progression (P=5.73E-16). CONCLUSION Our study confirmed the association between the locus on chromosome 1 near the gene CACNA1E with time to progression from inflammatory to stricturing or penetrating CD. Predicting the time to progression is useful to the clinician in terms of individualizing patients' management.
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Lang BM, Biedermann L, van Haaften WT, de Vallière C, Schuurmans M, Begré S, Zeitz J, Scharl M, Turina M, Greuter T, Schreiner P, Heinrich H, Kuntzen T, Vavricka SR, Rogler G, Beerenwinkel N, Misselwitz B. Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease. Aliment Pharmacol Ther 2018; 47:55-66. [PMID: 29052254 DOI: 10.1111/apt.14378] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 08/04/2017] [Accepted: 09/22/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. AIM To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. METHODS Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. RESULTS In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P<.05) and proctitis in ulcerative colitis (P<.05). CONCLUSIONS SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease.
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Affiliation(s)
- B M Lang
- Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.,Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
| | - L Biedermann
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - W T van Haaften
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland.,Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - C de Vallière
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - M Schuurmans
- Division of Pneumology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - S Begré
- Hohenegg Hospital, Meilen, Switzerland
| | - J Zeitz
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - M Scharl
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - M Turina
- Division of Visceral Surgery, University Hospital Zurich (USZ), Zurich, Switzerland
| | - T Greuter
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - P Schreiner
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - H Heinrich
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - T Kuntzen
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - S R Vavricka
- Division of Gastroenterology, Triemli Hospital Zurich, Zürich, Switzerland
| | - G Rogler
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
| | - N Beerenwinkel
- Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.,Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
| | - B Misselwitz
- Division of Gastroenterology, University Hospital Zurich (USZ) and Zurich University, Zurich, Switzerland
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Cepek J, Abbass M, Nguyen TM, Parker CE, MacDonald JK, Feagan BG, Jairath V, Khanna R. Adalimumab for maintenance of remission in Crohn's disease. Hippokratia 2017. [DOI: 10.1002/14651858.cd012877] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Jeremy Cepek
- University of Western Ontario; Schulich School of Medicine & Dentistry; London Canada
| | - Mohamad Abbass
- University of Western Ontario; Schulich School of Medicine & Dentistry; London Canada
| | - Tran M Nguyen
- Robarts Clinical Trials; Cochrane IBD Group; 100 Dundas Street, Suite 200 London ON Canada
| | - Claire E Parker
- Robarts Clinical Trials; 100 Dundas Street, Suite 200 London ON Canada N6A 5B6
| | - John K MacDonald
- Robarts Clinical Trials; Cochrane IBD Group; 100 Dundas Street, Suite 200 London ON Canada
- University of Western Ontario; Department of Medicine; London ON Canada
| | - Brian G Feagan
- Robarts Clinical Trials; Cochrane IBD Group; 100 Dundas Street, Suite 200 London ON Canada
- Robarts Clinical Trials; 100 Dundas Street, Suite 200 London ON Canada N6A 5B6
- University of Western Ontario; Department of Medicine; London ON Canada
- University of Western Ontario; Department of Epidemiology and Biostatistics; London ON Canada
| | - Vipul Jairath
- Robarts Clinical Trials; 100 Dundas Street, Suite 200 London ON Canada N6A 5B6
- University of Western Ontario; Department of Medicine; London ON Canada
- University of Western Ontario; Department of Epidemiology and Biostatistics; London ON Canada
| | - Reena Khanna
- Robarts Clinical Trials; 100 Dundas Street, Suite 200 London ON Canada N6A 5B6
- University of Western Ontario; Department of Medicine; London ON Canada
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Khasawneh M, Spence AD, Addley J, Allen PB. The role of smoking and alcohol behaviour in the management of inflammatory bowel disease. Best Pract Res Clin Gastroenterol 2017; 31:553-559. [PMID: 29195675 DOI: 10.1016/j.bpg.2017.10.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 09/11/2017] [Accepted: 10/20/2017] [Indexed: 02/09/2023]
Abstract
In the era of increasing use of immunosuppressive and biologic therapy for inflammatory bowel disease, environmental influences remain important independent risk factors to modify the course of the disease, affect the need for surgery and recurrence rates post-surgical resection. The effect of smoking on inflammatory bowel disease has been established over the decades, however the exact mechanism of how smoking affects remains as area of research. Alcohol is also among the socio-environmental factors which has been recognised to cause a flare of symptoms in inflammatory bowel disease patients. Nonetheless, the exact relation to date is not fully understood, and various paradoxical results from different studies are still a point of controversy.
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Affiliation(s)
- Mais Khasawneh
- South Eastern Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom
| | - Andrew D Spence
- Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Jennifer Addley
- South Eastern Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom
| | - Patrick B Allen
- South Eastern Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom.
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Abstract
The term inflammatory bowel disease (IBD) refers principally to two major categories of chronic relapsing inflammatory intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC). In the United States, it is currently estimated that about 1.5 million people suffer from IBD, causing considerable suffering, mortality and economic loss every year. Yet the cause of IBD is unknown, and until we understand more, prevention or cure will not be possible. There is a lot of variation in the incidence and prevalence of CD based on geographic region, environment, immigrant population, and ethnic groups. The annual incidence of CD in North America is reported to be 3.1-20.2 per 100,000 with a prevalence of 201 per 100,000 population. Based on the epidemiological, genetic and immunological data, CD is considered to be a heterogeneous disorder with multifactorial etiology in which genetics and environment interact to manifest the disease. Several genes have been studied so for with respect to CD, but thus far the strong and replicated associations have been identified with NOD2, IL23R and ATG16L1 genes. The risk factors implicated with CD include smoking, low fiber- high carbohydrate diet, altered microbiome and medications such as non-steroidal anti-inflammatory drugs. CD is typically characterized by transmural inflammation of the intestine and could affect any part of the gastrointestinal tract from mouth to perianal area. In terms of distribution of the disease 25% of the patients have colitis only, 25% is ileitis only and 50% have ileocolitis. The Montreal classification is based on the age at diagnosis (<16, 17-40, > 40), disease location (Ileal, colonic, Ileocolonic) and the disease behavior (nonstricturing/nonpenetrating, stricturing, penetrating). The key features for diagnosing CD comprises a combination of radiographic, endoscopic and pathological findings demonstrating focal, asymmetric, transmural or granulomatous features. Abdominal Computed tomography (CT) enterography is the most preferred first-line radiologic study used in the assessment of small bowel CD. The diagnostic accuracy of magnetic resonance enterography/enteroclysis is similar to that of CT scans and also prevents exposure to ionizing radiation. Endoscopic scores are considered to be the gold standard tool to measure the activity of CD and they are used more commonly in the clinical trials to measure the efficacy of various drugs on inducing and maintaining mucosal healing. The most common scoring systems used to measure clinical disease activity include Crohn's Disease Activity Index (CDAI), HBI- Harvey-Bradshaw index (HBI), short inflammatory bowel disease questionnaire (SIBDQ) and Lehmann score. Management of Crohn's disease has been seen as an evolving challenge owing to its widely heterogeneous manifestations, overlapping characteristics with other inflammatory disorders, often elusive extraintestinal manifestations and uncertain etiology. Therapeutic interventions are tailored to address symptomatic response and subsequent tolerance of the intervention. Chronology of treatment should favor treatment dose acute disease or "induction therapy", followed by maintenance of adequate response or remission, i.e. "maintenance therapy". The medications which are highly effective in inducing remission include steroids and Tumor Necrosis Factor (TNF) inhibitors. Medications used to maintain remission include 5-aminosalicyclic acid products, immunomodulators (Azathioprine, 6-mercaptopurine, methotrexate) and TNF inhibitors (infliximab, adalimumab, certolizumab and golimumab). Surgical interventions like bowel resection, stricturoplasty or drainage of abscess is required in up to two thirds of CD patients during their lifetime. The most common indications for surgical resection are medically refractory disease, perforation, persisting or recurrent obstruction, abscess not amenable to percutaneous drainage, intractable hemorrhage, dysplasia or cancer. Endoscopic recurrence in postoperative CD patients, as defined by Rutgeers score i2-i4 occur in 30-90% of the patients at the neoterminal ileum within 12 months of surgery and almost universally by 5 years. Treating CD requires a comprehensive care team including the patient, primary care provider, and gastroenterologist. In summary CD is a chronic inflammatory condition with a remitting and relapsing course primarily affecting relatively younger population with significant socioeconomic effects.
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Affiliation(s)
- Mahesh Gajendran
- Department of Internal Medicine, Texas Tech University Health Science Center El Paso, 2000B Transmountain Road, El Paso, TX 79911, United States.
| | - Priyadarshini Loganathan
- Department of Internal Medicine, Texas Tech University Health Science Center El Paso, 2000B Transmountain Road, El Paso, TX 79911, United States
| | - Anthony P Catinella
- Department of Family Medicine, Texas Tech University Health Science Center El Paso, 2000B Transmountain Road, El Paso, TX 79911, United States
| | - Jana G Hashash
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, M2, C Wing, 200 Lothrop Street, Pittsburgh, PA 15213, United States
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Development of a Novel Predictive Model for the Clinical Course of Crohn's Disease: Results from the CONNECT Study. Inflamm Bowel Dis 2017; 23:1071-1079. [PMID: 28410345 DOI: 10.1097/mib.0000000000001106] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND A considerable number of patients with Crohn's disease (CD) develop irreversible intestinal damage, although the early administration of immunomodulatory or biological therapies might prevent this. The aims of our study were to develop and validate a novel predictive model that can be used to predict the risk of surgical intervention in Korean patients with CD. METHODS The prognostic model was derived from the multicenter longitudinal CONNECT (CrOhn's disease cliNical NEtwork and CohorT) study cohort consisting of 1338 patients with CD, who were split into training and validation sets. The Korean Crohn's Disease Prediction (KCDP) model was developed with the training set data using the Cox proportional hazards model and multivariate analysis, and was then validated using the validation set. RESULTS A total of 1271 patients with CD were analyzed. During the follow-up period of 10,188 patient-years (median 7.1 yrs), 361 patients (28.4%) underwent CD-related surgery. Age at diagnosis, jejunal involvement, initial disease behavior, and perianal disease at diagnosis were associated with a poor prognosis and included in the KCDP model, which showed a modest discrimination ability with a Harrel's c-index of 0.731 at 5 years, and was well calibrated (Hosmer-Lemeshow χ = 8.230, P = 0.511). CONCLUSIONS This is the first validated surgery risk prediction model for Korean patients with CD; it provides accurate individualized estimates of the probability of surgery using clinical parameters collected at diagnosis. This model might guide appropriate patient selection for the early intensive treatment of CD.
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Li G, Guo G, Wang W, Wang K, Wang H, Dong F, Qian Y, Gong H, Xu G, Li Y, Pan L, Zhang B, Shan G. Association of prehypertension and cardiovascular risk factor clustering in Inner Mongolia: a cross-sectional study. BMJ Open 2017; 7:e015340. [PMID: 28667215 PMCID: PMC5734362 DOI: 10.1136/bmjopen-2016-015340] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVES To assess the clustering of cardiovascular disease (CVD) risk factors in Han and Mongolian adults with prehypertension or hypertension in Northern China. METHODS We selected 3227 Han and Mongolian participants (20-80 years old) using a multistage cluster sampling method in 2014. The participants were interviewed by standard questionnaires and underwent anthropometric measurement and biochemical testing. Han and Mongolian participants were divided into optimal, prehypertension, and hypertension groups based on blood pressure. A multinomial logit analysis was performed to explore relationships between CVD risk factor clustering and prehypertension or hypertension, and the heterogeneity between Han and Mongolian was evaluated by the Cochran Q test. The differences between the ethnic groups in the proportions of risk factors was tested with the χ2 test. RESULTS The clustering of two or three CVD risk factors in the prehypertension or hypertension groups was consistently higher than in the optimal group (Bonferroni, p<0.0167). The odds ratios (ORs) of prehypertension and hypertension increased with the number of CVD risk factors (ptrend <0.0001). In multivariate modelling, the adjusted ORs of one, two, and ≥3 CVD risk factors versus no risk factors was, respectively, 1.95, 2.25, and 2.28 in Han prehypertensive participants, and 1.73, 2.83, and 3.69 in Mongolian prehypertensive participants. In addition, the adjusted ORs were 3.15, 4.75, and 6.49 in Han hypertensive participants, and 1.90, 5.29, and 8.13 in Mongolian hypertensive participants (all p<0.05). There was no significant heterogeneity between Han and Mongolian participants in the prehypertension or hypertension groups. The age-standardised prevalence of ≥3 risk factors was 38.30% in Han men and 39.79% in Mongolian men. The rate was significantly lower in Han women than Mongolian women (9.18% vs 14.55%, p=0.002). CONCLUSIONS These findings showed clustering of CVD risk factors in prehypertensive Han and Mongolian adults, and showed prehypertension may be a useful target for intervention.
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Affiliation(s)
- Guoju Li
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Guanghong Guo
- Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing, China
| | - Wenrui Wang
- Inner Mongolia Center for Disease Control and Prevention, Hohhot, China
| | - Ke Wang
- Department of Obstetrics, Key Laboratory of 9 Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China 10 Second University Hospital, Sichuan University, Chengdu, China
| | - Hailing Wang
- Inner Mongolia Center for Disease Control and Prevention, Hohhot, China
| | - Fen Dong
- China-Japan Friendship Hospital, Beijing, China
| | - Yonggang Qian
- Inner Mongolia Center for Disease Control and Prevention, Hohhot, China
| | - Haiying Gong
- Fangshan District Center for Disease Control and Prevention, Beijing, China
| | - Guodong Xu
- China-Japan Friendship Hospital, Beijing, China
| | - Yanlong Li
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Li Pan
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Biao Zhang
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Guangliang Shan
- Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
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