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Tukek NB, Bakkaloglu OK, Sen G, Hatemi İ, Celik AF, Erzin YZ. The effects of biologics on ulcerative colitis-related colectomy rate: results of a 22-year study. Scand J Gastroenterol 2025; 60:548-557. [PMID: 40302309 DOI: 10.1080/00365521.2025.2497954] [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: 01/02/2025] [Revised: 02/25/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND To assess the impact of the biological era on colectomy rates in ulcerative colitis (UC) patients and identify factors associated with the necessity for colectomy in a large cohort from Eastern Europe. METHODS A retrospective cohort study was conducted on UC patients followed at a tertiary care center covering 1999 to 2021. Patients who underwent colectomy due to disease activity were compared to those who did not. Factors related to colectomy and the influence of the biological era were analyzed. RESULTS Among 1197 patients with a median follow-up of 3.3 years, 18% received biological agents and 5.3% underwent colectomy due to disease activity. The colectomy rate was lower in the biological era compared to the pre-biological era (2% vs. 12%; p < 0.001). Independent predictors of colectomy included steroid dependency, steroid resistance, lack of mucosal remission, and elevated CRP levels. Patients who achieved and maintained mucosal remission and had CRP levels below 3 mg/L had a significantly lower risk of colectomy. CONCLUSIONS The biological era has significantly reduced colectomy rates in UC patients. Achieving mucosal remission and maintaining low CRP levels are essential for preventing colectomy and improving long-term outcomes.
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Affiliation(s)
- Nur Beyza Tukek
- Clinic of Internal Medicine, Tekirdag Dr Ismail Fehmi Cumalioglu City Hospital, Tekirdag, Turkey
| | - Oguz Kagan Bakkaloglu
- Division of Gastroenterology, Department of Internal Medicine, Kosuyolu High Specialization Research and Education Hospital, Istanbul, Turkey
| | - Gozde Sen
- Clinic of Internal Medicine, Istanbul Bahcelievler State Hospital, Istanbul, Turkey
| | - İbrahim Hatemi
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
| | - Aykut Ferhat Celik
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
| | - Yusuf Ziya Erzin
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
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Du X, Yu W, Chen F, Jin X, Xue L, Zhang Y, Wu Q, Tong H. HDAC inhibitors and IBD: Charting new approaches in disease management. Int Immunopharmacol 2025; 148:114193. [PMID: 39892171 DOI: 10.1016/j.intimp.2025.114193] [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: 09/08/2024] [Revised: 12/14/2024] [Accepted: 01/27/2025] [Indexed: 02/03/2025]
Abstract
Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. Despite substantial advances in our understanding of IBD pathogenesis, the currently available therapeutic options remain limited in their efficacy and often come with significant side effects. Therefore, there is an urgent need to explore novel approaches for the management of IBD. One promising avenue of investigation revolves around the use of histone deacetylase (HDAC) inhibitors, which have garnered considerable attention for their potential in modulating gene expression and curbing inflammatory responses. This review emphasizes the pressing need for innovative drugs in the treatment of IBD, and drawing from a wealth of preclinical studies and clinical trials, we underscore the multifaceted roles and the therapeutic effects of HDAC inhibitors in IBD models and patients. This review aims to contribute significantly to the understanding of HDAC inhibitors' importance and prospects in the management of IBD, ultimately paving the way for improved therapeutic strategies in this challenging clinical landscape.
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Affiliation(s)
- Xueting Du
- College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, China
| | - Weilai Yu
- Department of Gastroenterology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China
| | - Fangyu Chen
- College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, China
| | - Xiaosheng Jin
- Department of Gastroenterology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China
| | - Liwei Xue
- Department of Gastroenterology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China
| | - Ya Zhang
- College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, China; Hepatology Diagnosis and Treatment Center & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China
| | - Qifang Wu
- College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, China.
| | - Haibin Tong
- College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, China.
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Hall JC, Hall AK, Lozko Y, Hui C, Baniel CC, Jackson S, Vitzthum LK, Chang DT, Rahimy E, Pollom EL. Safety of Pelvic and Abdominal Radiation Therapy for Patients With Inflammatory Bowel Disease: A Dosimetric Analysis of Acute Bowel Toxicity. Int J Radiat Oncol Biol Phys 2025; 121:442-451. [PMID: 39270827 DOI: 10.1016/j.ijrobp.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 07/15/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024]
Abstract
PURPOSE Inflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) because of the potential greater risk of RT-induced toxicities. This study aimed to assess acute toxicity outcomes in patients with IBD treated with abdominal/pelvic RT. METHODS AND MATERIALS After institutional review board approval, patients with IBD who received RT to the abdomen/pelvis were identified from an institutional research repository, and their electronic medical records were reviewed. The IBD cohort was matched 1:1 with controls according to all of the following: RT, gender, disease site, age, and year of RT. Acute toxicity was defined as toxicity occurring within 3 months of RT. Primary outcomes were assessed via univariable logistic regression models and the predicted probability of acute toxicity and acute gastrointestinal (GI) toxicity were plotted for the most significant covariates. IBD and control cohorts were compared on demographic and toxicity variables using χ2/Fisher exact tests and Kruskal-Wallis tests where appropriate. RESULTS We identified 62 patients with a median age of 64 years (IQR, 54-70 years) who received RT from 2006 to 2022. Patients were treated with intensity modulated RT (38; 61.3%), 3-dimensional conformal RT (12; 19.4%), and stereotactic body RT/brachytherapy (12; 19.4%). After RT, 28 (45.2%) and 23 (37.1%) patients experienced grade ≥2 acute (any) and acute GI toxicity, respectively. Higher overall RT dose and RT dose to small bowel were found to be significantly associated with increased risk of grade ≥2 acute toxicities (OR, 1.041 per unit Gy; 95% CI, 1.005-1.084; P = .034 and OR, 1.046; 95% CI, 1.018-1.082; P = .003, respectively). Between IBD and control cohorts, there were no significant differences in grade ≥2 acute (any) and acute GI toxicities (P = .710 and P = .704, respectively). CONCLUSIONS In patients with IBD treated with abdominal/pelvic RT for malignancy, RT was effective and well-tolerated. RT treatment planning should carefully consider the location(s) of IBD inflammation and dose to bowel structures, in particular, dose to the small bowel.
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Affiliation(s)
- Jennifer C Hall
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Abbie K Hall
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Yuliia Lozko
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Caressa Hui
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Claire C Baniel
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Scott Jackson
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Lucas K Vitzthum
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Daniel T Chang
- Department of Radiation Oncology, Michigan University School of Medicine, Ann Arbor, Michigan
| | - Elham Rahimy
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
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Okabe M, Yamamoto S, Shiokawa M, Hisamatsu T, Yamazaki H, Nakanishi R, Hamada K, Kitamoto H, Kuwada T, Uza N, Sakatani A, Fujii T, Ohno M, Matsuura M, Shibuya T, Ohmiya N, Ooi M, Hoshi N, Moriya K, Tsuchiya K, Yamaguchi Y, Kunisaki R, Takahara M, Takagi T, Takehara T, Hirai F, Kakimoto K, Esaki M, Nakase H, Kinjo F, Torisu T, Kanmura S, Narimatsu K, Matsuoka K, Hiraga H, Yokoyama K, Honzawa Y, Naganuma M, Saruta M, Kodama Y, Chiba T, Seno H. Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study. J Gastroenterol 2025; 60:86-95. [PMID: 39607498 PMCID: PMC11717824 DOI: 10.1007/s00535-024-02176-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study. METHODS We measured V6 Ab titers in patients definitively diagnosed with UC, Crohn's disease (CD), or other gastrointestinal disorders (OGDs). The primary outcome was the diagnostic value of V6 Ab. Secondary outcomes were factors associated with false-negative results in patients with UC and false-positive results in patients without UC and the heterogeneity of the diagnostic value of V6 Ab among the participating facilities. RESULTS We enrolled 1241, 796, and 206 patients with UC, CD, and OGD, respectively, from 28 Japanese high-volume referral centers. The diagnostic sensitivity of V6 Ab for UC was 87.7%, and its specificities for CD and OGDs were 82.0% and 87.4%, respectively. Multivariable logistic regression analysis showed that false-negative results were associated with older age at the time of sample collection, current smokers, lower partial Mayo score, and not receiving advanced therapies in patients with UC, and false-positive results were associated with colonic CD in patients with CD. No factor was associated with false-positive results in patients with OGDs. There were no significant differences in the diagnostic value of V6 Ab among the centers. CONCLUSIONS The diagnostic value of V6 Ab for UC was validated in the large-scale nationwide multicenter study.
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Affiliation(s)
- Makoto Okabe
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Shuji Yamamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Masahiro Shiokawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, 181-8611, Japan.
| | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan
| | - Risa Nakanishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kensuke Hamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hiroki Kitamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takeshi Kuwada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Norimitsu Uza
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Aki Sakatani
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, 078-8510, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan
| | - Masashi Ohno
- Department of Medicine, Shiga University of Medical Science, Otsu, 520-2192, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan
| | - Naoki Ohmiya
- Department of Advanced Endoscopy, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan
| | - Makoto Ooi
- Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan
| | - Namiko Hoshi
- Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan
| | - Kei Moriya
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara, 630-8581, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, 305-8576, Japan
| | - Yoshiharu Yamaguchi
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, 232-0024, Japan
| | - Masahiro Takahara
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, 700-8558, Japan
| | - Tomohisa Takagi
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
| | - Fumihito Hirai
- Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan
| | - Kazuki Kakimoto
- Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, 569-8686, Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, 849-8501, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan
| | - Fukunori Kinjo
- Center for Gastroenterology, Urasoe General Hospital, Urasoe, 901-2102, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
| | - Shuji Kanmura
- Division of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan
| | - Kazuyuki Narimatsu
- Department of Internal Medicine, National Defence Medical College, Tokorozawa, 359-8513, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, 285-8741, Japan
| | - Hiroto Hiraga
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8563, Japan
| | - Kaoru Yokoyama
- Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, 252-0375, Japan
| | - Yusuke Honzawa
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Osaka, 573-1010, Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Osaka, 573-1010, Japan
| | - Masayuki Saruta
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, 105-8471, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan
| | - Tsutomu Chiba
- Department of Gastroenterology and Hepatology, Kansai Electric Power Hospital, Fukushima-ku, Osaka, 553-0003, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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Xiao L, Ma J, Chen R, Chen J, Wang Q, Tang N, Zhao X, Zhang H, Jiao C. The Impact of Cytomegalovirus Infection on Ulcerative Colitis Relapse: A Multicenter Retrospective Cohort Study. J Inflamm Res 2024; 17:9059-9070. [PMID: 39583855 PMCID: PMC11585274 DOI: 10.2147/jir.s479663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 11/13/2024] [Indexed: 11/26/2024] Open
Abstract
Purpose Cytomegalovirus (CMV) infection exacerbates intestinal inflammation in ulcerative colitis (UC) patients, yet the effect of CMV infection on UC relapse has not been fully elucidated. This study aimed to investigate the impact of CMV infection on UC relapse and identify associated risk factors. Patients and Methods This multicenter retrospective cohort study included UC patients who visited research centers from January 2016 to December 2020. Univariate and multivariate Cox regression analyses were conducted to explore risk factors for UC relapse. Propensity score matching was used to balance the differences in the clinical characteristics between the groups. Results A total of 298 UC patients participated in this study, including 19 with CMV colitis, 37 with CMV viremia, and 242 CMV-negative patients. The 2-year cumulative recurrence rate was higher in patients with CMV colitis than that in CMV-negative patients (84.21% vs 51.65%, p = 0.01). Univariate and multivariate Cox regression analyses confirmed that fecal calprotectin ≥ 250 µg/g, Montreal classification E3, CMV colitis, duration > 48 months, and serum albumin < 30 g/L were independent risk factors for UC relapse at 2 years, whereas the use of biologics for induction of remission was identified as an independent protective factor. Conclusion Our study suggests that the risk of relapse increases among UC patients with CMV colitis over two years. Risk factors for UC relapse at 2 years include fecal calprotectin ≥ 250 μg/g, Montreal classification E3, CMV colitis, UC duration > 48 months, and albumin < 30 g/L, whereas the use of biologics during induction is a protective factor.
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Affiliation(s)
- Linmei Xiao
- Department of Liver Disease, Wuxi No.5 People’s Hospital Affiliated to Jiangnan University, Wuxi, People’s Republic of China
| | - Jingjing Ma
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Ruidong Chen
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Jie Chen
- Northern Jiangsu People’s Hospital/Northern Jiangsu People’s Hospital of Jiangsu Province, Yangzhou, Jiangsu Province, People’s Republic of China
| | - Qiang Wang
- Jiangsu Shengze Hospital, Suzhou, Jiangsu Province, People’s Republic of China
| | - Nana Tang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Xiaojing Zhao
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Hongjie Zhang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Chunhua Jiao
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
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Ginard D, Barreiro-de Acosta M, Nos P, Moraleja I, Muñoz Nuñez F, Aldeguer X, Echarri A, Villoria A, Riestra S, Boscá Watts MM, González-Lama Y, Royo V, Ferreiro-Iglesias R, Iborra M, Elorza A, Fernandez-Pordomingo A, Sans M, on behalf of the Becalcu Study. Efficacy of Beclomethasone Dipropionate in Lowering Fecal Calprotectin Levels in Patients with Ulcerative Colitis in Clinical Remission and at Risk of Relapse: The Becalcu Randomized, Controlled Trial. Dig Dis 2024; 42:600-609. [PMID: 39173598 PMCID: PMC11614308 DOI: 10.1159/000540792] [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: 04/19/2024] [Accepted: 08/05/2024] [Indexed: 08/24/2024]
Abstract
INTRODUCTION Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse. METHODS This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission treated with 5-aminosalicylic acid and with FC levels ≥250 μg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 μg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9. RESULTS Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 μg/g (p value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p value = 0.049). Both treatment groups showed a favorable safety profile, with the most common adverse events being gastrointestinal disorders. CONCLUSION In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.
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Affiliation(s)
- Daniel Ginard
- Gastroenterology Unit, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears, Palma de Mallorca, Spain
| | | | - Pilar Nos
- Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | | | | | - Xavier Aldeguer
- Hospital Universitario Doctor Josep Trueta de Girona, Girona, Spain
| | - Ana Echarri
- Complejo Hospitalario Universitario de Ferrol, Ferrol, Spain
| | | | - Sabino Riestra
- Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | | | | | - Vanesa Royo
- Gastroenterology Unit, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears, Palma de Mallorca, Spain
| | | | - Marisa Iborra
- Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | | | | | - Miquel Sans
- Gastroenterology Unit, ISADMU, Centro Médico Teknon Barcelona, Barcelona, Spain
| | - on behalf of the Becalcu Study
- Gastroenterology Unit, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears, Palma de Mallorca, Spain
- Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
- Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Hospital Galdakao-Usansolo, Galdakao, Spain
- Hospital Universitario de Salamanca, Salamanca, Spain
- Hospital Universitario Doctor Josep Trueta de Girona, Girona, Spain
- Complejo Hospitalario Universitario de Ferrol, Ferrol, Spain
- Corporación sanitaria Parc Taulí, Sabadell, Spain
- Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
- Hospital Clínico Universitario de Valencia, Valencia, Spain
- Hospital Universitario Puerta de Hierro, Madrid, Spain
- Gastroenterology Unit, ISADMU, Centro Médico Teknon Barcelona, Barcelona, Spain
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7
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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Zhang H, Kalla R, Chen J, Zhao J, Zhou X, Adams A, Noble A, Ventham NT, Wellens J, Ho GT, Dunlop MG, Nowak JK, Ding Y, Liu Z, Satsangi J, Theodoratou E, Li X. Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease. Nat Commun 2024; 15:595. [PMID: 38238335 PMCID: PMC10796384 DOI: 10.1038/s41467-024-44841-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 01/04/2024] [Indexed: 01/22/2024] Open
Abstract
This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10-10) and UC (P < 2 × 10-16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10-8) and UC (P = 1.04 × 10-4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10-6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.
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Affiliation(s)
- Han Zhang
- Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Rahul Kalla
- Edinburgh IBD Science Unit, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Jie Chen
- Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jianhui Zhao
- Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xuan Zhou
- Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Alex Adams
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Alexandra Noble
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Nicholas T Ventham
- Academic Coloproctology, University of Edinburgh, Western General Hospital, Edinburgh, UK
| | - Judith Wellens
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
- Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Gwo-Tzer Ho
- Edinburgh IBD Science Unit, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Malcolm G Dunlop
- Cancer Research UK Scotland Centre and Medical Research Council Human Genetics Unit, University of Edinburgh, Edinburgh, UK
| | - Jan Krzysztof Nowak
- Department of Paediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhanju Liu
- Center for IBD Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Jack Satsangi
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK.
| | - Evropi Theodoratou
- Cancer Research UK Scotland Centre and Medical Research Council Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
| | - Xue Li
- Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
- Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, UK.
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Santiago P, Coelho-Prabhu N, Lennon R, Rui S, Rajauria P, Friton J, Raffals LE, Deepali F, Daoud N, Farraye FA, Tuck J, Malik T, Leleiko NS, Shapiro J, Shah SA, Sands BE, Ungaro RC. Baseline Clinical Factors Are Associated With Risk of Complications in Crohn's Disease: Appraisal of the American Gastroenterological Association Clinical Care Pathway. Am J Gastroenterol 2024; 119:147-154. [PMID: 37713528 DOI: 10.14309/ajg.0000000000002498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 08/18/2023] [Indexed: 09/17/2023]
Abstract
INTRODUCTION The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related-hospitalization, (ii) any inflammatory bowel disease-related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0-1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71-4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11-3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.
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Affiliation(s)
- Priscila Santiago
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ryan Lennon
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Shumin Rui
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Palak Rajauria
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jessica Friton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Fnu Deepali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nader Daoud
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Jaclyn Tuck
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Talha Malik
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Neal S Leleiko
- Division of Pediatric Gastroenterology, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA
| | - Jason Shapiro
- Department of Pediatric Gastroenterology, Warren Alpert Medical School of Brown University, Providence
| | - Samir A Shah
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence
| | - Bruce E Sands
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ryan C Ungaro
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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10
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Cui Z, Amevor FK, Zhao X, Mou C, Pang J, Peng X, Liu A, Lan X, Liu L. Potential therapeutic effects of milk-derived exosomes on intestinal diseases. J Nanobiotechnology 2023; 21:496. [PMID: 38115131 PMCID: PMC10731872 DOI: 10.1186/s12951-023-02176-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/25/2023] [Indexed: 12/21/2023] Open
Abstract
Exosomes are extracellular vesicles with the diameter of 30 ~ 150 nm, and are widely involved in intercellular communication, disease diagnosis and drug delivery carriers for targeted disease therapy. Therapeutic application of exosomes as drug carriers is limited due to the lack of sources and methods for obtaining adequate exosomes. Milk contains abundant exosomes, several studies have shown that milk-derived exosomes play crucial roles in preventing and treating intestinal diseases. In this review, we summarized the biogenesis, secretion and structure, current novel methods used for the extraction and identification of exosomes, as well as discussed the role of milk-derived exosomes in treating intestinal diseases, such as inflammatory bowel disease, necrotizing enterocolitis, colorectal cancer, and intestinal ischemia and reperfusion injury by regulating intestinal immune homeostasis, restoring gut microbiota composition and improving intestinal structure and integrity, alleviating conditions such as oxidative stress, cell apoptosis and inflammation, and reducing mitochondrial reactive oxygen species (ROS) and lysosome accumulation in both humans and animals. In addition, we discussed future prospects for the standardization of milk exosome production platform to obtain higher concentration and purity, and complete exosomes derived from milk. Several in vivo clinical studies are needed to establish milk-derived exosomes as an effective and efficient drug delivery system, and promote its application in the treatment of various diseases in both humans and animals.
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Affiliation(s)
- Zhifu Cui
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China
| | - Felix Kwame Amevor
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, P. R. China
| | - Xingtao Zhao
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Sichuan, P. R. China
| | - Chunyan Mou
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China
| | - Jiaman Pang
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China
| | - Xie Peng
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China
| | - Anfang Liu
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China
| | - Xi Lan
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China.
| | - Lingbin Liu
- College of Animal Science and Technology, Southwest University, Chongqing, P. R. China.
- College of Animal Science and Technology, Chongqing Key Laboratory of Forage & Herbivore, Chongqing Engineering Research Center for Herbivores Resource Protection and Utilization, Southwest University, Beibei, Chongqing, 400715, P. R. China.
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11
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Tang YZ, Liu Y, Chen YP, Feng TT, Liu YY, Wang Y, Zhang JP, Xu WH. Citropten alleviates acute and recurrent colitis via blockage of NF-κB and JAK/STAT3 pathways. Int Immunopharmacol 2023; 125:111102. [PMID: 37922567 DOI: 10.1016/j.intimp.2023.111102] [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: 08/16/2023] [Revised: 10/10/2023] [Accepted: 10/18/2023] [Indexed: 11/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD.
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Affiliation(s)
- Yu Zhen Tang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Ying Liu
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, PR China
| | - Ya Ping Chen
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Ting Ting Feng
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Ya Yi Liu
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China
| | - Yan Wang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China
| | - Jun Ping Zhang
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
| | - Wei Heng Xu
- College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China; School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
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12
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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13
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Burisch J. Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort. APMIS 2023; 131 Suppl 147:1-46. [PMID: 37336790 DOI: 10.1111/apm.13334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
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Li DF, Yang MF, Xu J, Xu HM, Zhu MZ, Liang YJ, Zhang Y, Tian CM, Nie YQ, Shi RY, Wang LS, Yao J. Extracellular Vesicles: The Next Generation Theranostic Nanomedicine for Inflammatory Bowel Disease. Int J Nanomedicine 2022; 17:3893-3911. [PMID: 36092245 PMCID: PMC9462519 DOI: 10.2147/ijn.s370784] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 08/25/2022] [Indexed: 12/02/2022] Open
Abstract
The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment.
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Affiliation(s)
- De-feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Mei-feng Yang
- Department of Hematology, Yantian District People’s Hospital, Shenzhen, People’s Republic of China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Hao-ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Min-zheng Zhu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Yu-jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, People’s Republic of China
| | - Cheng-mei Tian
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Yu-qiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, People’s Republic of China
| | - Rui-yue Shi
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Li-sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China
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15
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Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis. J Transl Med 2022; 20:354. [PMID: 35962454 PMCID: PMC9373544 DOI: 10.1186/s12967-022-03569-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 08/01/2022] [Indexed: 11/10/2022] Open
Abstract
Objective To compare efficacy and safety of fecal microbiota transplantation (FMT) with glucocorticoid as induction therapy in ulcerative colitis (UC). Methods The patients with active mild to moderate UC were recruited into the single-center, prospective cohort study. The patients were treated with either FMT (FMT group) or glucocorticoids (GCs group). Patients received FMT administration for 3 days. The primary outcome was clinical and endoscopic remission at week 12. Inflammatory parameters were assessed by routine blood tests. Safety was assessed by adverse events recorded. The serum levels of TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10 IL-8, IL-12p70, IL-13, IL-17A and IL-23 following FMT were measured by Luminex multiplex assay. Results Of the 122 patients, 62 patients were treated with FMT and 60 with glucocorticoids. 34 patients in FMT group (54.8%) and 29 in GCs group (48.3%) reached the primary outcome (p = 0.30). The incidence of adverse events in GCs group (35/60, 58.3%) was significantly higher than that in FMT group (14/62, 22.6%) and two serious adverse events were observed following GCs. Patients in FMT group were stratified into responders (RE) and non-responders (NR) groups. The level of TNF-α and IL-6 decreased significantly in RE group, while IL-10 decreased significantly in NR group. Conclusion FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events. The modification of serum TNF-α, IL-6 and IL-10 might be related to the efficacy of FMT in UC. Trial registration This study was registered with ClinicalTrials.gov (NCT02435160). Registered on 6 April, 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT02435160&cntry=&state=&city=&dist=
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16
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Elhag DA, Kumar M, Saadaoui M, Akobeng AK, Al-Mudahka F, Elawad M, Al Khodor S. Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response. Int J Mol Sci 2022; 23:ijms23136966. [PMID: 35805965 PMCID: PMC9266456 DOI: 10.3390/ijms23136966] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/05/2022] [Accepted: 06/06/2022] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.
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Affiliation(s)
- Duaa Ahmed Elhag
- Research Department, Sidra Medicine, Doha 26999, Qatar; (D.A.E.); (M.K.); (M.S.)
| | - Manoj Kumar
- Research Department, Sidra Medicine, Doha 26999, Qatar; (D.A.E.); (M.K.); (M.S.)
| | - Marwa Saadaoui
- Research Department, Sidra Medicine, Doha 26999, Qatar; (D.A.E.); (M.K.); (M.S.)
| | - Anthony K. Akobeng
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha 26999, Qatar; (A.K.A.); (F.A.-M.); (M.E.)
| | - Fatma Al-Mudahka
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha 26999, Qatar; (A.K.A.); (F.A.-M.); (M.E.)
| | - Mamoun Elawad
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha 26999, Qatar; (A.K.A.); (F.A.-M.); (M.E.)
| | - Souhaila Al Khodor
- Research Department, Sidra Medicine, Doha 26999, Qatar; (D.A.E.); (M.K.); (M.S.)
- Correspondence:
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Ge C, Lu Y, Shen H, Zhu L. Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis. Scand J Gastroenterol 2022; 57:513-524. [PMID: 34994661 DOI: 10.1080/00365521.2021.2022193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Ulcerative colitis is a chronic recurrent intestinal inflammatory disease, and its recurrence is difficult to predict. In this review, we summarized the objective indicators that can be used to evaluate intestinal inflammation, the purpose is to better predict the clinical recurrence of UC, formulate individualized treatment plan during remission of UC, and improve the level of diagnosis and treatment of UC.Methods: Based on the search results in the PUBMED database, we explored the accuracy and value of these methods in predicting the clinical recurrence of UC from the following three aspects: endoscopic and histological scores, serum biomarkers and fecal biomarkers.Results: Colonoscopy with biopsy is the gold standard for assessing intestinal inflammation, but it is invasive, inconvenient and expensive. At present, there is no highly sensitive and specific endoscopic or histological score to predict the clinical recurrence of UC. Compared with serum biomarkers, fecal biomarkers have higher sensitivity and specificity because they are in direct contact with the intestine and are closer to the site of intestinal inflammation. Fecal calprotectin is currently the most studied and meaningful fecal biomarker. Lactoferrin and S100A12, as novel biomarkers, have no better performance than FC in predicting the recurrence of UC.Conclusions: FC is currently the most promising predictive marker, but it lacks an accurate cut-off value. Combining patient symptoms, incorporating multiple indicators to construct a UC recurrence prediction model, and formulating individualized treatment plans for high recurrence risk patients will be the focus of UC remission management.
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Affiliation(s)
- Changchang Ge
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Lu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Zhu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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18
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Hao Y, Yzet C, McBride RB, Stock A, Tiratterra E, D'Errico A, Belluzzi A, Scaioli E, Gionchetti P, Roda G, Ungaro R, Colombel JF, Harpaz N, Ko HM. Baseline Histological Findings Do Not Predict the Risk of Subsequent Extension in Patients with Limited Ulcerative Colitis. Dig Dis Sci 2022; 67:1311-1319. [PMID: 33934255 DOI: 10.1007/s10620-021-06970-y] [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: 08/21/2020] [Accepted: 03/24/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Among patients with limited ulcerative colitis (UC), 30% ultimately extend to pancolitis and are at increased risk of adverse clinical outcomes. Risk of endoscopic extension has been found to correlate with clinical features such as early age of onset. AIMS We sought to determine whether histologic features correlate with disease extension. METHODS The study population consisted of 40 patients with UC from two large academic centers diagnosed between 2006 and 2017. Eligible cases had a diagnosis of endoscopically limited UC (Montreal E1 or E2) at baseline and ≥ 2 subsequent endoscopic examinations with biopsies. Severity of inflammation was scored using both the Mount Sinai Activity Index and Nancy Histological Index. RESULTS Patients were divided into two cohorts: those who progressed to pancolitis (Montreal E3) were defined as "Extenders" (n = 21), whereas "Non-extenders" (n = 19) were cases without progression in the follow-up period. The median follow-up time was 58.4 months. The histologic scores in the endoscopically involved mucosa of the index biopsies were not associated with subsequent extension of disease, overall. However, among extender cohort, the index histology scores correlated with biopsy scores at extension (r = 0.455, P = 0.044) and index severity was associated with a shorter time to extension (r = - 0.611, P = 0.003). Furthermore, female patients had a shorter time to extension (P = 0.013). CONCLUSIONS Histological severity of limited UC is not an independent predictor of extension in UC. However, among patients who subsequently extend, severe inflammation at baseline correlates with shorter progression time and severe inflammation when extension occurs. Patients with limited UC but severe histologic inflammation may warrant more frequent endoscopic surveillance.
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Affiliation(s)
- Yansheng Hao
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Clara Yzet
- Department of Gastroenterology, Amiens University Hospital, Picardie University, Amiens, France
| | - Russell B McBride
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Aryeh Stock
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Elisa Tiratterra
- Department of Medical and Surgical Sciences (DIMEC), Gastroenterology and Endoscopy Unit, Sant'Orsola University Hospital, University of Bologna, Bologna, Italy
| | - Antonietta D'Errico
- 'F Addarii'' Institute of Oncology and Transplantation Pathology, Sant'Orsola Hospital, University of Bologna, Bologna, Italy
| | - Andrea Belluzzi
- Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Eleonora Scaioli
- Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Giulia Roda
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Humanitas Clinical and Research Center -IRCCS, Milan, Italy
| | - Ryan Ungaro
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jean-Frederic Colombel
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Noam Harpaz
- Departments of Pathology and Medicine (Gastroenterology), Icahn School of Medicine At Mount Sinai, New York, NY, USA
| | - Huaibin Mabel Ko
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
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19
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Lamb CA, Saifuddin A, Powell N, Rieder F. The Future of Precision Medicine to Predict Outcomes and Control Tissue Remodeling in Inflammatory Bowel Disease. Gastroenterology 2022; 162:1525-1542. [PMID: 34995532 PMCID: PMC8983496 DOI: 10.1053/j.gastro.2021.09.077] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/20/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease is characterized by significant interindividual heterogeneity. With a wider selection of pharmacologic and nonpharmacologic interventions available and in advanced developmental stages, a priority for the coming decade is to determine accurate methods of predicting treatment response and disease course. Precision medicine strategies will allow tailoring of preventative and therapeutic decisions to individual patient needs. In this review, we consider the future of precision medicine in inflammatory bowel disease. We discuss the critical need to extend from research focused on short-term symptomatic response to integrative multi-omic systems biology strategies to identify and validate biomarkers that underpin precision approaches. Crucially, the international community has collective responsibility to provide well-phenotyped and -curated longitudinal datasets for scientific discovery and validation. Research must also study broader aspects of the immune response, including components of the extracellular matrix, to better understand biological pathways initiating and perpetuating tissue fibrosis and longer-term disease complications.
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Affiliation(s)
- Christopher A Lamb
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Gastroenterology, Newcastle upon Tyne Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom.
| | - Aamir Saifuddin
- St Mark's Academic Institute, London North West University Hospitals National Health Service Trust, London, United Kingdom; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Nick Powell
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Florian Rieder
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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20
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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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21
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Magro F, Alves C, Santiago M, Ministro P, Lago P, Correia L, Gonçalves R, Carvalho D, Portela F, Dias CC, Dignass A, Danese S, Peyrin‐Biroulet L, Estevinho MM, Moreira P, on behalf GEDII (Portuguese IBD Group). Composite outcomes in observational studies of ulcerative colitis: A systematic review and meta-analysis. United European Gastroenterol J 2022; 10:54-72. [PMID: 34907660 PMCID: PMC8830283 DOI: 10.1002/ueg2.12183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 11/18/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes. OBJECTIVE This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes. METHODS A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest. RESULTS A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased. CONCLUSION The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.
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Affiliation(s)
- Fernando Magro
- Department of GastroenterologySão João University Hospital Center (CHUSJ)PortoPortugal
- Department of BiomedicineUnit of Pharmacology and TherapeuticsFaculty of MedicineUniversity of PortoPortoPortugal
- Department of Clinical PharmacologySão João University Hospital Center (CHUSJ)PortoPortugal
| | | | - Mafalda Santiago
- Center for Health Technology and Services Research (CINTESIS)PortoPortugal
| | - Paula Ministro
- Department of GastroenterologyTondela‐Viseu Hospital CentreViseuPortugal
| | - Paula Lago
- Department of GastroenterologySanto António University Hospital Center (CHUPorto)PortoPortugal
| | - Luís Correia
- Department of GastroenterologyLisbon North Hospital CentreSanta Maria HospitalLisbonPortugal
| | | | - Diana Carvalho
- Department of GastroenterologySanto António dos Capuchos Hospital at Centro Hospitalar Lisboa CentralLisbonPortugal
| | - Francisco Portela
- Department of GastroenterologyUniversity Hospital Centre of CoimbraCoimbraPortugal
| | - Cláudia Camila Dias
- Center for Health Technology and Services Research (CINTESIS)PortoPortugal
- Department of Community Medicine, Information and Health Decision SciencesFaculty of MedicineUniversity of PortoPortoPortugal
| | - Axel Dignass
- Agaplesion Markus HospitalDepartment of Medicine IFrankfurtGermany
| | - Silvio Danese
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- Inflammatory Bowel Disease (IBD) CenterDepartment of GastroenterologyHumanitas Clinical and Research Center (IRCCS)MilanItaly
| | - Laurent Peyrin‐Biroulet
- Department of Gastroenterology and Inserm NGERE U1256University Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
| | - Maria Manuela Estevinho
- Department of BiomedicineUnit of Pharmacology and TherapeuticsFaculty of MedicineUniversity of PortoPortoPortugal
- Department of GastroenterologyCentro Hospitalar Vila Nova de Gaia/EspinhoVila Nova de GaiaPortugal
| | - Paula Moreira
- Department of Clinical PharmacologySão João University Hospital Center (CHUSJ)PortoPortugal
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22
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Singh S, Jain R, Singh V, Naik AK, Chakrabarty B, Ranjan P, Kumar P. Causes, frequencies, and predictors of relapse in patients with ulcerative colitis on long-term follow-up in a tertiary care hospital of Northern India. JOURNAL OF MARINE MEDICAL SOCIETY 2022. [DOI: 10.4103/jmms.jmms_182_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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23
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Malibary NH, Ezzat MA, Mogharbel AM, Kouzaba KA, Alkadi AA, Malki UH, Gharib SM, Altowairqi FM, Saadah OI, Mosli MH. Factors Affecting Ulcerative Colitis Flare-Ups: Associations With Smoking Habits and Other Patient Characteristics. Cureus 2021; 13:e19834. [PMID: 34824952 PMCID: PMC8610210 DOI: 10.7759/cureus.19834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2021] [Indexed: 12/03/2022] Open
Abstract
Background and study aims Currently, there are no studies conducted in the Kingdom of Saudi Arabia (KSA) that have assessed the relationship between ulcerative colitis (UC) flare-ups and smoking. The present study aims to assess the risk of UC flare-ups and evaluate the relationship between UC flare-ups and smoking in adult patients following up at King Abdulaziz University Hospital in Jeddah, KSA. Patients and methods This was a retrospective study involving patients with confirmed UC between January 2015 and December 2020. Various information was examined, including demographic, clinical, endoscopic, radiologic, and laboratory data. Descriptive statistics were used for summarizing findings and a logistic regression analysis was applied to test for possible associations. Results Eighty-nine patients with UC were included in the study. Almost half (48.3%) had recurrent UC flare-ups during follow-up. A non-significant relationship was found between recurrent UC flares and all types of smoking habits (cigarette smoking, P = 0.15; shisha smoking, P = 0.88; and vape smoking, P = 0.09). Participants who were underweight (P = 0.041), had family history of UC (P = 0.013), depression (P = 0.033), fecal incontinence (P = 0.003), iron deficiency anemia (P = 0.009), or a malignancy (P = 0.039) had a significantly higher probability of experiencing recurrent flares. Binary logistic regressions revealed that family history of UC (OR = 5.3, P = 0.007) and fecal incontinence (OR = 4.7, P = 0.006) were associated significantly with recurrent flares. Conclusion There was no clear association between smoking and recurrent UC flares identified in this cohort. Of the variables considered, UC patients with fecal incontinence or family history of UC were at the highest risk of developing recurrent flares.
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Affiliation(s)
- Nadim H Malibary
- Visceral and General Surgery, Hautepierre Hospital, Strasbourg, FRA.,Surgery, King Abdulaziz University Hospital, Jeddah, SAU
| | | | | | | | | | - Usama H Malki
- Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| | | | | | - Omar I Saadah
- Pediatric Gastroenterology, King Abdulaziz University Hospital, Jeddah, SAU
| | - Mahmoud H Mosli
- Gastroenterology, King Abdulaziz University Hospital, Jeddah, SAU
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24
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Yu J, Park J, Kang EA, Park SJ, Park JJ, Kim TI, Kim WH, Cheon JH. Prognostic Value of Terminal Ileal Inflammation in Patients with Ulcerative Colitis. Gut Liver 2021; 15:858-866. [PMID: 33767032 PMCID: PMC8593494 DOI: 10.5009/gnl20294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 11/19/2020] [Accepted: 12/18/2020] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND/AIMS Few studies have investigated terminal ileal lesions and their prognostic value in patients with ulcerative colitis (UC). We evaluated the clinical significance of these lesions as a prognostic factor in patients with UC who were in clinical remission. METHODS We retrospectively selected 567 of 4,066 colonoscopy reports that included positive findings from orificial observations of the terminal ileum (TI) and appendix in patients with UC. We finally recruited patients who were in clinical remission (n=204). We compared the clinical courses, including relapse and other prognostic parameters associated with UC, between the groups. RESULTS The baseline patient characteristics were not significantly different between patients with (n=69, TI+ group) and without TI lesions (n=135, TI- group), although there were more never-smokers in the TI+ group (n=57 [82.6%] in the TI+ group; n=86 [63.7%] in the TI- group; p=0.005). Of note, appendiceal orifice inflammation (AOI) was less frequently found in the TI+ group (14.5%) than in the TI- group (71.9%, p<0.001). The cumulative relapse rate was numerically higher in the TI- group, but it was not significantly different according to the Kaplan-Meier analysis (p=0.116). Multivariate Cox regression analysis also revealed advanced age at diagnosis as the most significant factor (adjusted hazard ratio, 0.964; 95% confidence interval, 0.932 to 0.998; p=0.037), but neither TI inflammation nor AOI were significantly associated with the cumulative relapse rate in patients with UC in clinical remission. CONCLUSIONS For patients with UC in clinical remission, neither terminal ileal lesions nor AOI had significant clinical or predictive value for future relapse.
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Affiliation(s)
- Jongwook Yu
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jihye Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Ae Kang
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Jung Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Jun Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Il Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Won Ho Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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25
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Pedersen KM, Çolak Y, Vedel-Krogh S, Kobylecki CJ, Bojesen SE, Nordestgaard BG. Risk of ulcerative colitis and Crohn's disease in smokers lacks causal evidence. Eur J Epidemiol 2021; 37:735-745. [PMID: 34091767 DOI: 10.1007/s10654-021-00763-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 05/13/2021] [Indexed: 11/24/2022]
Abstract
Smoking has been associated with opposing risks of ulcerative colitis and Crohn's disease. Whether these observational associations reflect actual causal associations, confounding, or reverse causation is unclear. Using a Mendelian randomization approach, we tested the hypothesis that smoking protects against ulcerative colitis and is a cause of Crohn's disease. We included 118,683 white Danes aged ≥ 20 from the Copenhagen General Population Study (2003-2015) and the Copenhagen City Heart Study (1991-94 and 2001-03). During follow-up until 2018, we investigated the association of smoking and CHRNA3 rs1051730, where the T-allele is strongly associated with nicotine dependence, with risk of ulcerative colitis and Crohn's disease. We identified 1312 cases of ulcerative colitis and 671 cases of Crohn's disease. Compared to never-smokers, multivariable adjusted hazard ratios (HRs) for ulcerative colitis were 1.69(95% confidence interval [CI] 1.32-2.15) in former smokers and 2.27(1.74-2.96) in current smokers. Corresponding HRs for Crohn's disease were 1.31(0.93-1.84) and 1.93(1.34-2.78), respectively. Among ever-smokers when compared to non-carriers of the CHRNA3 rs1051730 T-allele, age and sex adjusted HRs for risk of ulcerative colitis were 1.03(95%CI 0.89-1.18) in heterozygotes and 0.91(0.72-1.16) in homozygotes. Corresponding HRs for Crohn's disease were 1.05(0.87-1.28) and 1.02(0.74-1.41), respectively. In a meta-analysis combined with UK Biobank, there was no evidence that CHRNA3 rs1051730 was associated with risk of ulcerative colitis or Crohn's disease. In conclusion, current versus never-smoking was associated with unexpected 2.3-fold risk of ulcerative colitis and expected 1.9-fold risk of Crohn's disease in prospective analyses; however, genetic evidence of lifelong increased smoking intensity did not support causal relationships.
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Affiliation(s)
- Kasper Mønsted Pedersen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Yunus Çolak
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Signe Vedel-Krogh
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Camilla Jannie Kobylecki
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Stig Egil Bojesen
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,The Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg, Denmark
| | - Børge Grønne Nordestgaard
- Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark. .,The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark. .,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. .,The Copenhagen City Heart Study, Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg, Denmark.
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26
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Abstract
BACKGROUND Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. METHODS Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence. RESULTS Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group. CONCLUSIONS These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.
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Juliao-Baños F, Puentes F, López R, Saffon M, Reyes G, Parra V, Galiano M, Barraza M, Molano J, Álvarez E, Corrales R, Vargas L, Gil F, Álvarez P, Limas L, Prieto R, Yance P, Díaz F, Bareño J, Juliao-Baños F, Arrubla M, Camargo J, Puentes F, Arango L, López R, García R, Mendoza B, Saffon MA, Roldan LF, Zuleta J, Reyes G, Parra V, Flórez C, Nuñez E, Galiano MT, Barraza M, Sanchez IC, Molano JL, Lizarazo JI, Cuellar I, Álvarez E, Corrales R, Gil F, Vargas LE, Álvarez P, Limas LM, Prieto R, Ballén H, Delgado L, Yance P, Díaz F. Characterization of inflammatory bowel disease in Colombia: Results of a national register. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2021. [DOI: 10.1016/j.rgmxen.2020.05.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Prevalence of cardiovascular risk factors in a nationally representative adult population with inflammatory bowel disease without atherosclerotic cardiovascular disease. Am J Prev Cardiol 2021; 6:100171. [PMID: 34327497 PMCID: PMC8315477 DOI: 10.1016/j.ajpc.2021.100171] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/01/2021] [Accepted: 03/07/2021] [Indexed: 01/08/2023] Open
Abstract
Background and aims Chronic inflammation is associated with premature atherosclerotic cardiovascular disease (ASCVD). We studied the prevalence of cardiovascular risk factors (CRFs) amongst individuals with IBD who have not developed ASCVD. Methods Our study population was derived from the 2015 – 2016 National Health Interview Survey. Those with ASCVD (defined as myocardial infarction, angina or stroke) were excluded. The prevalence of CRFs among individuals with IBD was compared with those without IBD. The odds CRFs among adults with IBD was assessed using logistic regression models. Results In our study population of 60,155 individuals, 786 (1.3%) had IBD. IBD was associated with increased odds hypertension (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.39–2.09), diabetes (OR 1.68, 95% CI 1.22–2.32), hypercholesterolemia (OR 1.62, 95% CI 1.32–2.99) and insufficient physical activity (OR 1.38, 95% CI 1.16–1.66). Conclusion IBD is associated with higher prevalence of CRFs. Early screening and risk mitigation strategies are warranted.
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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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30
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Martí-Aguado D, Ballester MP, Mínguez M. Risk factors and management strategies associated with non-response to aminosalicylates as a maintenance treatment in ulcerative colitis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:447-453. [PMID: 33569968 DOI: 10.17235/reed.2021.7797/2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Aminosalicylates (5-ASA) are used as the first-line maintenance treatment in patients with mild-moderate ulcerative colitis (UC). Early identification of patients at high risk for 5-ASA non-response and appropriate therapeutic escalation are essential to avoid disease progression. However, the absence of a standardized definition for treatment success makes this a challenging task. The focus of the current review was to describe the risk factors and management strategies associated with 5-ASA non-response. Rates of 5-ASA failure can vary from 17 % to 75 % according to different success definitions, of which clinical relapse is the most prevalent and studied condition. Younger age and endoscopic activity at diagnosis, extensive colitis, early need for corticosteroids, elevated inflammatory markers and non-adherence are consistent risk factors of 5-ASA failure. Given the effectiveness, safety profile and tolerability of this medication, therapy optimization is critical before treatment escalation. Combined use of systemic and topical therapy at an appropriate dose in a once-daily administration and control of adherence could improve success rates.
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Affiliation(s)
| | | | - Miguel Mínguez
- Medicina Digestiva, Hospital Clínico Universitario de Valencia, España
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31
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Gazel U, Ayan G, Solmaz D, Akar S, Aydin SZ. Comment on: The impact of smoking on prevalence of psoriasis and psoriatic arthritis: reply. Rheumatology (Oxford) 2021; 60:e27. [PMID: 32995878 DOI: 10.1093/rheumatology/keaa559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 08/03/2020] [Indexed: 11/14/2022] Open
Affiliation(s)
- Ummugulsum Gazel
- Rheumatology, University of Ottawa Faculty of Medicine.,Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Gizem Ayan
- Rheumatology, University of Ottawa Faculty of Medicine.,Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Dilek Solmaz
- Department of Internal Medicine, Division of Rheumatology, Izmir Katip Celebi University, Izmir, Turkey
| | - Servet Akar
- Department of Internal Medicine, Division of Rheumatology, Izmir Katip Celebi University, Izmir, Turkey
| | - Sibel Zehra Aydin
- Rheumatology, University of Ottawa Faculty of Medicine.,Ottawa Hospital Research Institute, Ottawa, ON, Canada
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32
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Monstad IL, Solberg IC, Cvancarova M, Hovde O, Henriksen M, Huppertz-Hauss G, Gunther E, Moum BA, Stray N, Vatn M, Hoie O, Jahnsen J. Outcome of Ulcerative Colitis 20 Years after Diagnosis in a Prospective Population-based Inception Cohort from South-Eastern Norway, the IBSEN Study. J Crohns Colitis 2020; 15:969-979. [PMID: 33367569 PMCID: PMC8218709 DOI: 10.1093/ecco-jcc/jjaa232] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS The long-term course of ulcerative colitis [UC] is difficult to predict. Mortality, colectomy, cancer, and hospitalisation represent hard outcomes of disease. Moreover, knowledge on the risk of relapses and need for potent medication add important information about living with UC. We aimed to evaluate the course and prognosis of UC during the first 20 years after diagnosis, and to identify early prognostic risk factors. METHODS From 1990 to 1994, a population-based inception cohort of patients with inflammatory bowel disease was enrolled in South-Eastern Norway. A systematic follow-up [FU] was conducted at 1,5, 10, and 20 years after diagnosis. Clinical outcomes were recorded continuously, and possible relationships between early disease characteristics and outcomes were analysed using multiple regression analysis. RESULTS Among 519 UC patients, 119 died, 60 were lost to FU, and 340 were included in the FU cohort. The 20-year cumulative risk of colectomy was 13.0% (95% confidence interval [CI] [11.4-14.6]). Extensive colitis at diagnosis was independently associated with an increased risk of colectomy compared with proctitis (hazard ratio [HR] = 2].8, 95% CI [1.3-6.1]). In contrast, mucosal healing at 1-year FU was independently associated with reduced risk of colectomy [HR = 0.4, 95% CI [0.2-0.8]), and inversely associated with subsequent risk of relapse [adjusted HR = 0.5, 95% CI [0.3-0.7]). CONCLUSIONS The overall risk of colectomy in our cohort was lower than expected from previous studies, although considerable for patients with extensive colitis at diagnosis. Early mucosal healing was associated with better disease outcomes 20 years after diagnosis.
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Affiliation(s)
- Iril Lovise Monstad
- Department of Gastroenterolgy, Oslo University Hospital, Ulleval, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway,Corresponding author: Dr Iril L. Monstad, Lovisenberg Diaconal Hospital, Lovisenberg Street 17, 1456 Oslo, Norway. Tel.: + 47 984 48 423;
| | | | | | - Oistein Hovde
- Department of Gastroenterology, Innlandet Hospital Trust, Gjøvik, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Magne Henriksen
- Department of Gastroenterology, Østfold Hospital, Fredrikstad, Norway
| | | | - Eva Gunther
- Department of Gastroenterology, Østfold Hospital, Fredrikstad, Norway
| | - Bjørn Allan Moum
- Department of Gastroenterolgy, Oslo University Hospital, Ulleval, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Njaal Stray
- Department of Internal Medicine, Diakonhjemmet Hospital, Oslo, Norway
| | - Morten Vatn
- EpiGen Institute, Akershus University Hospital, Lørenskog, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ole Hoie
- Department of Internal Medicine, Hospital of Southern Norway, Arendal, Norway
| | - Jørgen Jahnsen
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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Alkhatry M, Al-Rifai A, Annese V, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani R, Taha MS, Limdi JK. First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases: A 2020 Delphi consensus. World J Gastroenterol 2020; 26:6710-6769. [PMID: 33268959 PMCID: PMC7684461 DOI: 10.3748/wjg.v26.i43.6710] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 07/15/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.
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Affiliation(s)
- Maryam Alkhatry
- Gastroenterology and Endoscopy Department, Ibrahim Bin Hamad Obaid Allah Hospital, Ministry of Health and Prevention, Ras Al Khaiman, United Arab Emirates
| | - Ahmad Al-Rifai
- Department of Gastroenterology, Sheikh Shakbout Medical City, Abu Dhabi, United Arab Emirates
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
- Department of Gastroenterology and Endoscopy, American Hospital, Dubai, United Arab Emirates
| | | | - Ahmad N Jazzar
- Gastroenterology Division, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Ahmed M Khassouan
- Digestive Disease Unit, Rashid Hospital, Dubai, United Arab Emirates
| | - Zaher Koutoubi
- Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | - Rahul Nathwani
- Department of Gastroenterology, Mediclinic City Hospital, Dubai, United Arab Emirates
- Department of Gastroenterology, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | - Mazen S Taha
- Gastroenterology and Hepatology, Tawam Hospital, Al Ain, United Arab Emirates
| | - Jimmy K Limdi
- Department of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester Academic Health Sciences, University of Manchester, Manchester M8 5RB, United Kingdom
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Kang EA, Chun J, Kim JH, Han K, Soh H, Park S, Hong SW, Moon JM, Lee J, Lee HJ, Park JB, Im JP, Kim JS. Periodontitis combined with smoking increases risk of the ulcerative colitis: A national cohort study. World J Gastroenterol 2020; 26:5661-5672. [PMID: 33088159 PMCID: PMC7545388 DOI: 10.3748/wjg.v26.i37.5661] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/07/2020] [Accepted: 09/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Periodontitis is a chronic inflammation of periodontal tissues. The effect of periodontitis on the development of inflammatory bowel disease (IBD) remains unclear. AIM To assessed the risk of IBD among patients with periodontitis, and the risk factors for IBD related to periodontitis. METHODS A nationwide population-based cohort study was performed using claims data from the Korean National Healthcare Insurance Service. In total, 9950548 individuals aged ≥ 20 years who underwent national health screening in 2009 were included. Newly diagnosed IBD [Crohn's disease (CD), ulcerative colitis (UC)] using the International Classification of Disease 10th revision and rare intractable disease codes, was compared between the periodontitis and non-periodontitis groups until 2017. RESULTS A total of 1092825 individuals (11.0%) had periodontitis. Periodontitis was significantly associated with older age, male gender, higher body mass index, quitting smoking, not drinking alcohol, and regular exercise. The mean age was 51.4 ± 12.9 years in the periodontitis group and 46.6 ± 14.2 years in the non-periodontitis group (P < 0.01), respectively. The mean body mass index was 23.9 ± 3.1 and 23.7 ± 3.2 in the periodontitis and non-periodontitis groups, respectively (P < 0.01). Men were 604307 (55.3%) and 4844383 (54.7%) in the periodontitis and non-periodontitis groups, respectively. The mean follow-up duration was 7.26 years. Individuals with periodontitis had a significantly higher risk of UC than those without periodontitis [adjusted hazard ratio: 1.091; 95% confidence interval (CI): 1.008-1.182], but not CD (adjusted hazard ratio: 0.879; 95% confidence interval: 0.731-1.057). The risks for UC were significant in the subgroups of age ≥ 65 years, male gender, alcohol drinker, current smoker, and reduced physical activity. Current smokers aged ≥ 65 years with periodontitis were at a 1.9-fold increased risk of UC than non-smokers aged ≥ 65 years without periodontitis. CONCLUSION Periodontitis was significantly associated with the risk of developing UC, but not CD, particularly in current smokers aged ≥ 65 years.
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Affiliation(s)
- Eun Ae Kang
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, South Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06229, South Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Bundang CHA Medical Center, CHA University School of Medicine, Seoul 13496, South Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, South Korea
| | - Hosim Soh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Seona Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Seung Wook Hong
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Jung Min Moon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Jooyoung Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Hyun Jung Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Jun-Beom Park
- Department of Periodontics, the Catholic University of Korea College of Medicine, Seoul 06591, South Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
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Opening a Window on Attention: Adjuvant Therapies for Inflammatory Bowel Disease. Can J Gastroenterol Hepatol 2020; 2020:7397523. [PMID: 32850517 PMCID: PMC7441453 DOI: 10.1155/2020/7397523] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 01/17/2020] [Accepted: 01/27/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), most commonly known as Crohn's disease (CD) and ulcerative disease (UC), is a chronic and relapsing intestinal disease which cannot be cured completely. The prevalence of IBD in Europe and in North America has increased over the past 20 years. As most IBD patients are young at onset, their quality of life (QOL) can be influenced to varying degrees. Thus, current treatment goals are typically focused on preventing complications, including maintaining clinical remission and improving the QOL. Adjuvant therapies have been widely concerned as an effective treatment in alleviating IBD symptoms, including dietary intervention, traditional Chinese medicine, smoking, alcohol, and physical activities. This review focuses on different ancillary therapies for IBD treatments, in particular the mechanism of reducing inflammation based on the actual data from research studies. Moreover, comparing the latest data, this review also presented potential future prospect for adjuvant therapies.
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37
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Juliao-Baños F, Puentes F, López R, Saffon MA, Reyes G, Parra V, Galiano MT, Barraza M, Molano J, Álvarez E, Corrales R, Vargas LE, Gil F, Álvarez P, Limas L, Prieto R, Yance P, Díaz F, Bareño J. Characterization of inflammatory bowel disease in Colombia: Results of a national register. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2020; 86:153-162. [PMID: 32723624 DOI: 10.1016/j.rgmx.2020.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 04/29/2020] [Accepted: 05/14/2020] [Indexed: 02/07/2023]
Abstract
AIM To determine the clinical, sociodemographic, and treatment characteristics of inflammatory bowel disease (IBD) in a Colombian population register. METHODS A descriptive, analytic, observational, cross-sectional, multicenter study on patients with IBD from 17 hospital centers in 9 Colombian cities was conducted. RESULTS A total of 2,291 patients with IBD were documented, 1,813 (79.1%) of whom presented with ulcerative colitis (UC), 456 (19.9%) with Crohn's disease (CD), and 22 with IBD unclassified (0.9%). The UC/CD ratio was 3.9:1. A total of 18.5% of the patients with UC and 47.3% with CD received biologic therapy. Patients with extensive UC had greater biologic therapy use (OR = 2.78, 95% CI: 2.10-3.65, p = 0.000), a higher surgery rate (OR = 5.4, 95% CI: 3.5-8.3, p = 0.000), and greater frequency of hospitalization (OR = 4.34, 95% CI: 3.47-5.44, p = 0.000). Patients with severe UC had greater biologic therapy use (OR = 5.04, 95% CI: 3.75-6.78, p = 0.000), a higher surgery rate (OR = 8.64, 95% CI: 5.4-13.78, p = 0.000), and greater frequency of hospitalization (OR = 28.45, 95% CI: 19.9-40.7, p = 0.000). CD patients with inflammatory disease behavior (B1) presented with a lower frequency of hospitalization (OR = 0.12, 95% CI: 0.07-0.19, p = 0.000), a lower surgery rate (OR = 0.08, 95% CI: 0.043-0.15, p = 0.000), and less biologic therapy use (OR = 0.26, 95% CI: 0.17-0.41, p = 0.000). CONCLUSION In Colombia, there is a predominance of UC over CD (3.9:1), as occurs in other Latin American countries. Patients with extensive UC, severe UC, or CD with noninflammatory disease behavior (B2, B3) have a worse prognosis.
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Affiliation(s)
- F Juliao-Baños
- Clínica de Enfermedad Inflamatoria Intestinal, Hospital Pablo Tobón Uribe, Medellín, Colombia.
| | - F Puentes
- Unidad de Cirugía Gastrointestinal, Cirujanos Unidos, Manizales, Colombia
| | - R López
- Unidad de Gastroenterología y Patología, Fundación Santa Fe, Bogotá, Colombia
| | - M A Saffon
- Unidad de Gastroenterología, Instituto Gastroclínico, Medellín, Colombia
| | - G Reyes
- Unidad de Gastroenterología, Clínica Colombia, Bogotá, Colombia
| | - V Parra
- Unidad de Gastroenterología, Gastroadvanced, Bogotá-Medellín, Colombia
| | - M T Galiano
- Unidad de Gastroenterología, MTG Servimed SAS, Bogotá, Colombia
| | - M Barraza
- Unidad de Gastroenterología, Endodigestivos, Pereira, Colombia
| | - J Molano
- Unidad de Gastroenterología, Emdiagnóstica SAS, Bogotá, Colombia
| | - E Álvarez
- Unidad de Gastroenterología, IMAT, Montería, Colombia
| | - R Corrales
- Unidad de Gastroenterología, Clínica Intermedios, Montería, Colombia
| | - L E Vargas
- Unidad de Gastroenterología, Clínica La Misericordia, Barranquilla, Colombia
| | - F Gil
- Unidad de Gastroenterología, Clínica Colombia, Bogotá, Colombia
| | - P Álvarez
- Unidad de Gastroenterología, Clínica La Carolina, Bogotá, Colombia
| | - L Limas
- Unidad de Cirugía Gastrointestinal, LIMEQ, Tunja, Colombia
| | - R Prieto
- Unidad de Gastroenterología, Hospital Central de la Policía, Bogotá, Colombia
| | - P Yance
- Unidad de Gastroenterología, Gastrosalud, Santa Marta, Colombia
| | - F Díaz
- Unidad de Gastroenterología, Hospital Universitario del Caribe, Cartagena, Colombia
| | - J Bareño
- Centro de Epidemiología, Universidad CES, Medellín, Colombia
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Primary Humoral Immune Deficiencies: Overlooked Mimickers of Chronic Immune-Mediated Gastrointestinal Diseases in Adults. Int J Mol Sci 2020; 21:ijms21155223. [PMID: 32718006 PMCID: PMC7432083 DOI: 10.3390/ijms21155223] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/20/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022] Open
Abstract
In recent years, the incidence of immune-mediated gastrointestinal disorders, including celiac disease (CeD) and inflammatory bowel disease (IBD), is increasingly growing worldwide. This generates a need to elucidate the conditions that may compromise the diagnosis and treatment of such gastrointestinal disorders. It is well established that primary immunodeficiencies (PIDs) exhibit gastrointestinal manifestations and mimic other diseases, including CeD and IBD. PIDs are often considered pediatric ailments, whereas between 25 and 45% of PIDs are diagnosed in adults. The most common PIDs in adults are the selective immunoglobulin A deficiency (SIgAD) and the common variable immunodeficiency (CVID). A trend to autoimmunity occurs, while gastrointestinal disorders are common in both diseases. Besides, the occurrence of CeD and IBD in SIgAD/CVID patients is significantly higher than in the general population. However, some differences concerning diagnostics and management between enteropathy/colitis in PIDs, as compared to idiopathic forms of CeD/IBD, have been described. There is an ongoing discussion whether CeD and IBD in CVID patients should be considered a true CeD and IBD or just CeD-like and IBD-like diseases. This review addresses the current state of the art of the most common primary immunodeficiencies in adults and co-occurring CeD and IBD.
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Papoutsopoulou S, Satsangi J, Campbell BJ, Probert CS. Review article: impact of cigarette smoking on intestinal inflammation-direct and indirect mechanisms. Aliment Pharmacol Ther 2020; 51:1268-1285. [PMID: 32372449 DOI: 10.1111/apt.15774] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 04/13/2020] [Accepted: 04/16/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The inflammatory bowel diseases, Crohn's disease and ulcerative colitis are related multifactorial diseases. Their pathogenesis is influenced by each individual's immune system, the environmental factors within exposome and genetic predisposition. Smoking habit is the single best-established environmental factor that influences disease phenotype, behaviour and response to therapy. AIM To assess current epidemiological, experimental and clinical evidence that may explain how smoking impacts on the pathogenesis of inflammatory bowel disease. METHODS A Medline search for 'cigarette smoking', in combination with terms including 'passive', 'second-hand', 'intestinal inflammation', 'Crohn's disease', 'ulcerative colitis', 'colitis'; 'intestinal epithelium', 'immune system', 'intestinal microbiota', 'tight junctions', 'mucus', 'goblet cells', 'Paneth cells', 'autophagy'; 'epigenetics', 'genes', 'DNA methylation', 'histones', 'short noncoding/long noncoding RNAs'; 'carbon monoxide/CO' and 'nitric oxide/NO' was performed. RESULTS Studies found evidence of direct and indirect effects of smoking on various parameters, including oxidative damage, impairment of intestinal barrier and immune cell function, epigenetic and microbiota composition changes, that contribute to the pathogenesis of inflammatory bowel disease. CONCLUSIONS Cigarette smoking promotes intestinal inflammation by affecting the function and interactions among intestinal epithelium, immune system and microbiota/microbiome.
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Affiliation(s)
- Stamatia Papoutsopoulou
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Jack Satsangi
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Barry J Campbell
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Chris S Probert
- Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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40
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Chiba M, Nakane K, Tsuji T, Tsuda S, Ishii H, Ohno H, Watanabe K, Obara Y, Komatsu M, Sugawara T. Relapse Prevention by Plant-Based Diet Incorporated into Induction Therapy for Ulcerative Colitis: A Single-Group Trial. Perm J 2020; 23:18-220. [PMID: 31050638 DOI: 10.7812/tpp/18-220] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CONTEXT No known previous study has focused on plant-based diet (PBD) to prevent relapse of ulcerative colitis (UC) except our previous educational hospitalization study. OBJECTIVE To describe the relapse rate in a large case series of UC after incorporation of PBD into induction therapy. DESIGN All patients with UC between 2003 and 2017 were admitted for induction therapy. Patients receiving educational hospitalization or treated with infliximab were excluded. A lacto-ovo-semivegetarian diet (PBD) together with medication prescribed according to UC guidelines was provided during hospitalization. MAIN OUTCOME MEASURES The primary endpoint was relapse during follow-up. The secondary endpoint was change over time in the plant-based diet score (PBDS), which evaluated adherence to the PBD. RESULTS Ninety-two cases were studied, of which 51 were initial episodes and 41 were relapses. Cases varied in severity (31 mild, 48 moderate, 13 severe) and extent (15 proctitis, 22 left-sided colitis, 55 extensive colitis). More severe cases existed among the relapse cases than among the initial episode cases. Cumulative relapse rates at 1- and 5-year follow-up (Kaplan-Meier analysis) were 14% and 27%, respectively, for the initial episode cases, and 36% and 53%, respectively, for relapse cases. At long-term follow-up (6 years 4 months), PBDS was significantly higher than baseline PBDS (p < 0.0001). CONCLUSION Relapse rates in UC after induction therapy with PBD were far lower than those previously reported with conventional therapy. Adherence to PBD was significantly higher than baseline even at 6-year follow-up. We conclude PBD is effective for preventing UC relapse.(Study identification no.: UMIN000019061: Registration: www.umin.ac.jp).
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Affiliation(s)
- Mitsuro Chiba
- Inflammatory Bowel Disease Section, Akita City Hospital, Japan
| | - Kunio Nakane
- Gastroenterology Division, Akita City Hospital, Japan
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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: 106] [Impact Index Per Article: 21.2] [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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Borg-Bartolo SP, Boyapati RK, Satsangi J, Kalla R. Precision medicine in inflammatory bowel disease: concept, progress and challenges. F1000Res 2020; 9:F1000 Faculty Rev-54. [PMID: 32047622 PMCID: PMC6993839 DOI: 10.12688/f1000research.20928.1] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2020] [Indexed: 12/12/2022] Open
Abstract
Crohn's disease and ulcerative colitis are increasingly prevalent, relapsing and remitting inflammatory bowel diseases (IBDs) with variable disease courses and complications. Their aetiology remains unclear but current evidence shows an increasingly complex pathophysiology broadly centring on the genome, exposome, microbiome and immunome. Our increased understanding of disease pathogenesis is providing an ever-expanding arsenal of therapeutic options, but these can be expensive and patients can lose response or never respond to certain therapies. Therefore, there is now a growing need to personalise therapies on the basis of the underlying disease biology and a desire to shift our approach from "reactive" management driven by disease complications to "proactive" care with an aim to prevent disease sequelae. Precision medicine is the tailoring of medical treatment to the individual patient, encompassing a multitude of data-driven (and multi-omic) approaches to foster accurate clinical decision-making. In IBD, precision medicine would have significant benefits, enabling timely therapy that is both effective and appropriate for the individual. In this review, we summarise some of the key areas of progress towards precision medicine, including predicting disease susceptibility and its course, personalising therapies in IBD and monitoring response to therapy. We also highlight some of the challenges to be overcome in order to deliver this approach.
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Affiliation(s)
- Simon P. Borg-Bartolo
- Department of Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
| | - Ray Kiran Boyapati
- Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia
- Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia
| | - Jack Satsangi
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Rahul Kalla
- Department of Gastroenterology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK
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43
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Jones DP, Richardson TG, Davey Smith G, Gunnell D, Munafò MR, Wootton RE. Exploring the Effects of Cigarette Smoking on Inflammatory Bowel Disease Using Mendelian Randomization. CROHN'S & COLITIS 360 2020; 2:otaa018. [PMID: 33506196 PMCID: PMC7809707 DOI: 10.1093/crocol/otaa018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Previous observational evidence has suggested an association between smoking and inflammatory bowel disease (IBD). METHODS We used observational techniques followed by Mendelian randomization to explore whether smoking is a causal factor in the development of IBD and its subtypes. RESULTS In those who have ever smoked, we observed increased risk of IBD and, in current smokers, we observed increased risk of Crohn disease and decreased risk of ulcerative colitis. However, our Mendelian randomization analyses found little evidence that smoking affects the development of IBD. CONCLUSION Overall, our results suggest that smoking does not causally influence the risk of IBD.
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Affiliation(s)
- Daniel P Jones
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- Southmead Hospital, Westbury-on-Trym, Bristol, UK
| | - Tom G Richardson
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit, Bristol, UK
| | - George Davey Smith
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- MRC Integrative Epidemiology Unit, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
| | - David Gunnell
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
| | - Marcus R Munafò
- MRC Integrative Epidemiology Unit, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
- UK Centre for Tobacco and Alcohol Studies, University of Bristol, Bristol, UK
- School of Psychological Science, University of Bristol, Bristol, UK
| | - Robyn E Wootton
- MRC Integrative Epidemiology Unit, Bristol, UK
- NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
- School of Psychological Science, University of Bristol, Bristol, UK
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Chiba M, Tsuji T, Nakane K, Tsuda S, Ishii H, Ohno H, Obara Y, Komatsu M, Tozawa H. High Remission Rate with Infliximab and Plant-Based Diet as First-Line (IPF) Therapy for Severe Ulcerative Colitis: Single-Group Trial. Perm J 2020; 24:1-10. [PMID: 33482946 DOI: 10.7812/tpp/19.166] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION About one-third of patients with severe ulcerative colitis (UC) do not respond to corticosteroid therapy and receive rescue therapy with infliximab or cyclosporine. Up to 20% of such patients fail to respond to rescue therapy and undergo colectomy. OBJECTIVE We investigated the outcomes of infliximab and a plant-based diet (PBD) as first-line therapy for severe UC. METHODS Patients with severe UC defined by the Truelove and Witts criteria were admitted and given standard induction therapy with infliximab (5.0 mg/kg-7.5 mg/kg) at 0, 2, and 6 weeks. Additionally, they received a PBD. The primary endpoint was remission or colectomy in the induction phase and 1 year after discharge. Secondary endpoints were changes in inflammatory markers in the induction phase and the PBD score at baseline and follow-up. A higher PBD score indicates greater adherence to a PBD. RESULTS Infliximab and PBD as first-line therapy was administered in 17 cases. The remission rate was 76% (13/17), and the colectomy rate was 6% (1/17) in the induction phase. C-reactive protein values and the erythrocyte sedimentation rate significantly decreased at week 6 from 9.42 mg/dL to 0.33 mg/dL and from 59 to 17 mm/h, respectively (p < 0.0001). At 1-year follow-up, the cumulative relapse rate was 25%, and there were no additional colectomy cases. Mean PBD scores of 27.7 at 1 year and 23.8 at 4 years were significantly higher than baseline scores of 8.3 and 9.9, respectively (p < 0.0001 and p = 0.0391). CONCLUSION This new first-line therapy for severe UC demonstrated a higher remission rate and lower colectomy rate than with the current modality.
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Affiliation(s)
- Mitsuro Chiba
- Gastroenterology Division, Akita City Hospital, Akita, Japan
| | | | - Kunio Nakane
- Gastroenterology Division, Akita City Hospital, Akita, Japan
| | - Satoko Tsuda
- Gastroenterology Division, Akita City Hospital, Akita, Japan
| | - Hajime Ishii
- Gastroenterology Division, Akita City Hospital, Akita, Japan
| | - Hideo Ohno
- Gastroenterology Division, Akita City Hospital, Akita, Japan
| | - Yu Obara
- Gastroenterology Division, Akita City Hospital, Akita, Japan
| | | | - Haruhiko Tozawa
- Gastroenterology Division, Nakadori General Hospital, Akita, Japan
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Kevans D, Kirsch R, Dargavel C, Kabakchiev B, Riddell R, Silverberg MS. Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis. Inflamm Bowel Dis 2019; 26:1722-1729. [PMID: 31883337 PMCID: PMC8243631 DOI: 10.1093/ibd/izz308] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC. METHODS Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy. RESULTS Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2-118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse. CONCLUSIONS In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC.
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Affiliation(s)
- David Kevans
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada,Division of Gastroenterology, Department of Medicine, Toronto, Ontario, Canada,Address correspondence to: Mark Silverberg, MD, Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology, Mount Sinai Hospital, 600 University Ave. Room 437, Toronto, ON M5G 1X5, Canada ()
| | - Richard Kirsch
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada,Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Callum Dargavel
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada,Division of Gastroenterology, Department of Medicine, Toronto, Ontario, Canada
| | - Boyko Kabakchiev
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Robert Riddell
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada,Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Mark S Silverberg
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada,Division of Gastroenterology, Department of Medicine, Toronto, Ontario, Canada
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46
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Hibi T, Naganuma M, Oda E, Yamada Y, Chujoh Y, Yoshihara R, Watanabe M. Predictive factors for achievement of mucosal healing by budesonide 2-mg foam in ulcerative colitis: a pooled analysis of data from two clinical trials. Intest Res 2019; 18:56-68. [PMID: 31813214 PMCID: PMC7000644 DOI: 10.5217/ir.2019.00064] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 11/15/2019] [Indexed: 01/03/2023] Open
Abstract
Background/Aims Mucosal healing (MH) of distal lesions in ulcerative colitis (UC) has recently been confirmed with budesonide 2-mg foam (BF) treatment in 2 clinical trials; however, few studies have investigated the predictive factors for complete MH. Methods We conducted a post hoc analysis using pooled data from phase II and III clinical trials evaluating the efficacy and safety of BF for UC. Additionally, we analyzed the relationships between complete MH and baseline factors and clinical symptoms from baseline to week 6. Results Among the 291 Japanese patients from the 2 pooled clinical studies, 119 patients in the BF twice a day group and 117 in the placebo group were included in the full analysis set. The proportion of patients with a rectal bleeding (RB) subscore of 0 was significantly higher in the BF group than in the placebo group after a 5-day treatment (P<0.05). After a 2-day treatment, significantly more patients in the BF group had a stool frequency (SF) subscore of 0 than patients in the placebo group (P<0.05). Multivariate analysis showed that complete MH at week 6 was influenced by baseline SF subscore and 5-aminosalicylic acid (5-ASA) enema or suppository use (P=0.0086 and P=0.0015, respectively). The relationship between complete MH at week 6 and RB subscore after week 2 was also confirmed. Conclusions Normal SF at baseline, history of 5-ASA topical product use, and elimination of RB after week 2 are suggested predictors of complete MH at week 6 with twice-daily BF treatment.
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Affiliation(s)
- Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Eisei Oda
- Medical Statistics Division, AC Medical Inc., Tokyo, Japan
| | - Yoji Yamada
- Clinical Development Department, EA Pharma Co., Ltd., Tokyo, Japan
| | | | | | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, and TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1510] [Impact Index Per Article: 251.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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48
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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49
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Marti-Aguado D, Ballester MP, Tosca J, Bosca-Watts MM, Navarro P, Anton R, Pascual I, Mora F, Minguez M. Long-term follow-up of patients treated with aminosalicylates for ulcerative colitis: Predictive factors of response: An observational case-control study. United European Gastroenterol J 2019; 7:1042-1050. [PMID: 31662861 PMCID: PMC6794696 DOI: 10.1177/2050640619854277] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/05/2019] [Indexed: 01/19/2023] Open
Abstract
Background Knowing patients' ulcerative colitis history is essential to selecting the appropriate therapy according to risk stratification. Objective To evaluate and identify predictive factors of non-response to aminosalicylates judged as the need for a step-up approach over time. Methods A case-control study of ulcerative colitis patients treated with aminosalicylates after the diagnosis of disease flare included in the ENEIDA single-centre registry from 1997 to 2017. Long-term treatment maintenance with aminosalicylates and higher therapeutic requirements were recorded. The cumulative incidence of treatment escalation was estimated using Kaplan-Meier curves and compared by the log-rank test. Cox regression analysis was performed to identify predictive factors of treatment with immunomodulators, biological agents or surgery. Results A total of 457 patients were included, of whom 28% (n = 126) were non-responders to aminosalicylates. The cumulative probability for a step-up approach within 20 years of follow up was 35%, mainly due to steroid-dependent colitis. Risk factors for treatment escalation were age ≤27 years (hazard ratio 2.31, 95% confidence interval 1.36-3.92), extensive colitis (hazard ratio 1.65, 95% confidence interval 1.04-2.60), Mayo endoscopic subscore ≥2 (hazard ratio 1.45, 95% confidence interval 1.02-2.06) and extraintestinal manifestations (hazard ratio 2.04, 95% confidence interval 1.03-4.05). Conclusions Aminosalicylates represent an effective maintenance therapy. Younger age, extensive colitis, endoscopic disease severity and extraintestinal manifestations are risk factors for higher therapeutic requirements.
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Affiliation(s)
- David Marti-Aguado
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
| | - María Pilar Ballester
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
| | - Joan Tosca
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
| | | | - Pablo Navarro
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
| | - Rosario Anton
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
| | - Isabel Pascual
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
- University of Valencia, Valencia,
Spain
| | - Francisco Mora
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
- University of Valencia, Valencia,
Spain
| | - Miguel Minguez
- Digestive Disease Department, University
Clinic Hospital of Valencia, Valencia, Spain
- University of Valencia, Valencia,
Spain
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50
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Spooren CEGM, Wintjens DSJ, de Jong MJ, van der Meulen-de Jong AE, Romberg-Camps MJ, Becx MC, Maljaars JP, van Bodegraven AA, Mahmmod N, Markus T, Hameeteman WM, Masclee AAM, Winkens B, Jonkers DMAE, Pierik MJ. Risk of impaired nutritional status and flare occurrence in IBD outpatients. Dig Liver Dis 2019; 51:1265-1269. [PMID: 31213405 DOI: 10.1016/j.dld.2019.05.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 05/20/2019] [Accepted: 05/23/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients are at risk of an impaired nutritional status. The impact thereof on the IBD relapse risk is clinically relevant, though sparsely investigated. AIM The aim was to explore the association between an impaired nutritional status risk and the occurrence of disease flares in IBD outpatients participating in a longitudinal telemedicine study. METHODS IBD outpatients were recruited from the myIBDcoach study cohort, with one year clinical follow-up. Through myIBDcoach, a telemedicine tool, patients reported on disease activity and risk of impaired nutritional status (i.e. Short Nutritional Assessment Questionnaire >1 and/or BMI < 18.5 kg/m2) every one to three months. Data was analysed by generalized estimating equation modelling. RESULTS In total, 417 patients were included. During follow-up, 49 patients (11.8%) flared after initial clinical remission and 53 patients (12.7%) showed an increased risk of impaired nutritional status. The risk of impaired nutritional status was associated with flare occurrence (OR 2.61 (95% CI 1.02-6.69)). CONCLUSIONS The risk of an impaired nutritional status was associated with subsequent flares in IBD outpatients. This emphasizes the importance of monitoring disease activity in IBD patients at risk of impaired nutritional status.
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Affiliation(s)
- Corinne E G M Spooren
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands.
| | - Dion S J Wintjens
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Marin J de Jong
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands
| | | | - Mariëlle J Romberg-Camps
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Centre, Sittard-Geleen-Heerlen, The Netherlands
| | - Marco C Becx
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Jeroen P Maljaars
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Ad A van Bodegraven
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Centre, Sittard-Geleen-Heerlen, The Netherlands
| | - Nofel Mahmmod
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Tineke Markus
- CCUVN, Dutch IBD Patients Organization, Woerden, Netherlands
| | - Wim M Hameeteman
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Ad A M Masclee
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics, Maastricht University, Maastricht, The Netherlands
| | - Daisy M A E Jonkers
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Marie J Pierik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands
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