|
1
|
Bencardino S, Allocca M, Furfaro F, D’Amico F, Parigi TL, Danese S, Zilli A. Multiple Ileal and Colonic Stenoses: Is It Always Crohn's Disease? J Crohns Colitis 2025; 19:jjae174. [PMID: 39679549 PMCID: PMC12087567 DOI: 10.1093/ecco-jcc/jjae174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
A 62-year-old woman presented with multiple ileal and colonic stenoses, initially suspected to be Crohn's disease. Despite unremarkable endoscopic biopsies, surgery was performed due to clinical deterioration, and histological analysis confirmed the presence of metastatic breast cancer. This case highlights the importance of considering metastatic disease in the differential diagnosis of gastrointestinal (GI) strictures, particularly when inflammatory bowel disease markers are inconclusive or marginal. Clinicians should be aware of the potential for breast cancer to metastasize to the GI tract, which may present with symptoms mimicking primary GI diseases.
Collapse
Affiliation(s)
- Sarah Bencardino
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| |
Collapse
|
|
2
|
Qin J, Ma L, Zhou MY, Li WB, Xiao MS, Niu ZH, Yang H, Zhu QL. Determining the Accuracy and Interobserver Agreement of 4 Ultrasound Scores in Crohn's Disease Assessment: Correlations With Endoscopy. Clin Transl Gastroenterol 2025; 16:e00812. [PMID: 39791555 PMCID: PMC12020696 DOI: 10.14309/ctg.0000000000000812] [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: 06/04/2024] [Accepted: 12/20/2024] [Indexed: 01/12/2025] Open
Abstract
INTRODUCTION Gastrointestinal ultrasound (GIUS) is recommended for monitoring Crohn's disease (CD). GIUS scores are used to quantify CD activity. Among them, International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), Bowel Ultrasound Score (BUSS), Simple Ultrasound Score, and Simple Ultrasound Score for Crohn's Disease are most commonly used. The aim of this study was to compare and correlate the performance of such indicators with endoscopic activity and to calculate interobserver agreement. METHODS Consecutive patients with CD at our hospital between June 2015 and July 2021 were retrospectively enrolled. All patients underwent ileocolonoscopy after medical treatment. GIUS was performed within 2 weeks, and 4 GIUS scores were independently calculated. Receiver operating characteristic curve analyses were used to determine a cutoff value. Cohen kappa (κ) coefficient was calculated to estimate the agreement between GIUS findings. RESULTS A total of 106 patients with CD were enrolled. 80.2% (85/106) were endoscopic active (Simple Endoscopic Score for Crohn's disease ≥3), and 8.49% (9/106) were severe cases (Simple Endoscopic Score for Crohn's disease ≥9). All GIUS features (bowel wall thickness, color Doppler signs, bowel wall stratification, inflammatory signals at the mesentery) were statistically significant in assessing CD activity ( P < 0.05). IBUS-SAS showed the highest area under the curve (0.98; 95% CI: 0.96-1.00) and specificity (95.2%) for a cutoff value of 46.50. However, IBUS-SAS had only moderate agreement (Cohen κ = 0.427; P < 0.001). BUSS had substantial interobserver agreement (Cohen κ = 0.947; P < 0.001), with a similar diagnostic value (sensitivity, 100.0%; accuracy, 95.3%; area under the curve of 0.96 [95% CI: 0.91-1.00] for a cutoff value of 4.58). DISCUSSION GIUS score is an efficient and reliable method to assess CD activity. BUSS achieved a high accuracy and excellent interobserver agreement, which is more suitable for treatment assessment.
Collapse
Affiliation(s)
- Jing Qin
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Ma
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Meng-Yuan Zhou
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen-Bo Li
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Meng-Su Xiao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zi-Han Niu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qing-Li Zhu
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
3
|
Boaz E, Ledder O, Bar-Gil Shitrit A, Dagan A, Freund MR, Koslowsky B, Lujan R, Greenfeld S, Kariv R, Loewenberg Weisband Y, Lederman N, Matz E, Dotan I, Turner D, Yellinek S. Ethnic Disparities in the Management of Inflammatory Bowel Disease in Israel and Impact on Outcomes. CROHN'S & COLITIS 360 2025; 7:otaf025. [PMID: 40321840 PMCID: PMC12048840 DOI: 10.1093/crocol/otaf025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Indexed: 05/08/2025] Open
Abstract
Background In this nationwide study, we aimed to explore healthcare services utilization, medical management, and disease outcomes of inflammatory bowel diseases (IBD) across the 2 major ethnic groups in Israel. Methods We utilized a cohort including all patients diagnosed with IBD in Israel since 2005. The primary outcome was steroid dependency, with secondary outcomes including use of biologics, time to surgery, and hospitalizations. Outcomes were controlled for possible inherent differences in disease course and phenotype. Results Of the 32 491 included patients, 18 252 (56%) had Crohn's disease (CD) and 14 239 (44%) had ulcerative colitis (UC); 10% were Arabs and 90% were Jews. Jewish ethnicity was associated with lower rates of steroid dependency compared to Arab ethnicity in both CD (HR = 0.7 [95% CI, 0.6-0.8]) and UC (HR = 0.7 [95% CI, 0.6-0.8]). The risk of IBD-related surgery in CD was higher in the Arab group at both 3 and 5 years (13% vs. 10%, 16% vs 14%, respectively, P = .005). Arabs had more frequent IBD-related hospitalizations than Jews at 5 years (28% vs. 19% with at least 2 hospitalizations, P < .001). In contrast, Jewish ethnicity was associated with more frequent use of biologics during the first year from diagnosis in patients with CD (HR = 1.3 [95% CI, 1.1-1.6]) but not with UC. Conclusions Arab ethnicity is associated with higher rates of hospitalizations, steroid dependency, and surgeries, and, on the other side, with lower utilization of biologics. Healthcare practitioners and policymakers should address potential cultural and systemic barriers in healthcare delivery in order to improve care across all populations.
Collapse
Affiliation(s)
- Elad Boaz
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Oren Ledder
- Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Ariella Bar-Gil Shitrit
- Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Amir Dagan
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Michael R Freund
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Benjamin Koslowsky
- Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Rona Lujan
- Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Shira Greenfeld
- Maccabi Health Services, The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, IsraelTel-Aviv, Israel
- The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - Revital Kariv
- Maccabi Health Services, The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, IsraelTel-Aviv, Israel
- The Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | | | | | - Eran Matz
- Leumit Health Services, Tel-Aviv, Israel
| | - Iris Dotan
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Shlomo Yellinek
- Department of General Surgery, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| |
Collapse
|
|
4
|
Venkatachalam P, Muthu M, Gopal J. Reviewing the audacity of elixirs of inflammatory bowel disease from mushroom β-glucans: The solved and unresolved. Carbohydr Polym 2025; 348:122832. [PMID: 39562106 DOI: 10.1016/j.carbpol.2024.122832] [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: 07/18/2024] [Revised: 10/01/2024] [Accepted: 10/03/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Mushrooms are known as the elixirs of life, they are packed with various bioactive compounds that make them not only tasty but also healthy. Thus, they not just fall within the category of nutritional foods, but also functional foods. When medicinal bioactive components are sought after from every other available resource, these natural reservoirs are easily accessible therapeutic sources. Of the various bioactive that mushrooms have to offer, β-glucans are the most enriching. METHODS β-glucans are available in other sources as well, but their relative abundance is higher in mushrooms. Amidst the cascade of biological benefits from β-glucans, anti-inflammatory benefits are highly promising. In this present review, the anti-inflammatory properties of mushroom β-glucans have been discussed and its specific contributions against inflammatory bowel disease have been reviewed. DISCUSSION What is known regarding the modulus operandi of β-glucans against inflammatory bowel disease has been summarized and the gaps and lapses in the current understanding highlighted. This is the first state-of-the-art review that presents a comprehensive executive summary and discussion in this subject area.
Collapse
Affiliation(s)
- Prasanth Venkatachalam
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, Tamil Nadu, India
| | - Manikandan Muthu
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, Tamil Nadu, India
| | - Judy Gopal
- Department of Research and Innovation, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602105, Tamil Nadu, India.
| |
Collapse
|
|
5
|
Kumar S, Rao N, Bhagwanani A, Parry T, Hameed M, Rahman S, Fitzke HE, Holmes J, Barrow B, Bard A, Menys A, Bennett D, Mallett S, Taylor SA. Volumetric measurement of terminal ileal Crohn's disease by magnetic resonance enterography: a feasibility study. Eur Radiol 2025; 35:117-126. [PMID: 39028375 PMCID: PMC11632055 DOI: 10.1007/s00330-024-10880-8] [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: 01/23/2024] [Revised: 04/04/2024] [Accepted: 05/02/2024] [Indexed: 07/20/2024]
Abstract
OBJECTIVES Magnetic resonance enterography (MRE) interpretation of Crohn's disease (CD) is subjective and uses 2D analysis. We evaluated the feasibility of volumetric measurement of terminal ileal CD on MRE compared to endoscopy and sMARIA, and the responsiveness of volumetric changes to biologics. METHODS CD patients with MRE and contemporaneous CD endoscopic index of severity-scored ileocolonoscopy were included. A centreline was placed through the terminal ileum (TI) lumen defining the diseased bowel length on the T2-weighted non-fat saturated sequence, used by two radiologists to independently segment the bowel wall to measure volume (phase 1). In phase 2, we measured disease volume in patients treated with biologics, who had undergone pre- and post-treatment MRE, with treatment response classified via global physician assessment. RESULTS Phase 1 comprised 30 patients (median age 29 (IQR 24, 34) years). Phase 2 included 12 patients (25 years (22, 38)). In phase 1, the mean of the radiologist-measured volumes was used for analysis. The median disease volume in those with endoscopically active CD was 20.9 cm3 (IQR 11.3, 44.0) compared to 5.7 cm3 (2.9, 9.8) with normal endoscopy. The mean difference in disease volume between the radiologists was 3.0 cm3 (limits of agreement -21.8, 15.9). The median disease volume of patients with active CD by sMARIA was 15.0 cm3 (8.7, 44.0) compared to 2.85 cm3 (2.6, 3.1) for those with inactive CD. Pre- and post-treatment median disease volumes were 28.5 cm3 (26.4, 31.2), 11 cm3 (4.8, 16.6), respectively in biological responders, vs 26.8 cm3 (12.3, 48.7), 40.1 cm3 (10, 56.7) in non-responders. CONCLUSION Volumetric measurement of terminal ileal CD by MRE is feasible, related to endoscopy and sMARIA activity, and responsive to biologics. CLINICAL RELEVANCE STATEMENT Measuring the whole volume of diseased bowel on MRE in CD is feasible, related to how biologically active the disease is when assessed by endoscopy and by existing MRE activity scores, and is sensitive to treatment response. KEY POINTS MRE reporting for CD is subjective and uses 2D images rather than assessing the full disease volume. Volumetric measurement of CD relates to endoscopic activity and shows reduced disease volumes in treatment responders. This technique is an objective biomarker that can assess disease activity and treatment response, warranting validation.
Collapse
Affiliation(s)
- Shankar Kumar
- Centre for Medical Imaging, University College London (UCL), London, UK
| | - Nikhil Rao
- Department of Radiology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Anisha Bhagwanani
- Department of Radiology, Frimley Health NHS Foundation Trust, Frimley, United Kingdom
| | - Thomas Parry
- Centre for Medical Imaging, University College London (UCL), London, UK
| | - Maira Hameed
- Centre for Medical Imaging, University College London (UCL), London, UK
| | - Safi Rahman
- Department of Radiology, Frimley Health NHS Foundation Trust, Frimley, United Kingdom
| | - Heather E Fitzke
- Centre for Medical Imaging, University College London (UCL), London, UK
| | - Judith Holmes
- Centre for Medical Imaging, University College London (UCL), London, UK
| | | | | | - Alex Menys
- Motilent Limited, London, United Kingdom
| | | | - Sue Mallett
- Centre for Medical Imaging, University College London (UCL), London, UK
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London (UCL), London, UK.
| |
Collapse
|
|
6
|
Calvo Bernal MDM, Pérez Campos E, Aparicio Mota A, Hernández Martínez Á. Assessment of the quality of life of patients with inflammatory bowel disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502192. [PMID: 38719182 DOI: 10.1016/j.gastrohep.2024.502192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 05/28/2024]
Abstract
INTRODUCTION Ulcerative colitis (UC) and Crohn's disease (CD) are diseases that cause a significant impact on patients' quality of life. The aim of this study is to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQoL). MATERIAL AND METHODS Observational, descriptive, cross-sectional study, carried out at Torrecárdenas Hospital (Almería). Patients over 14 years of age diagnosed with CD or UC were included. For the assessment of HRQoL, the reduced 9-item IBDQ-9 questionnaire was used. RESULTS 106 patients with a mean age of 44 years were included, with a female predominance. Forty-five percent of the patients in the sample had UC compared to 55% with CD. Of the patients, 69.8% were in clinical remission. The median questionnaire score was 60.8 points out of 100. Statistically significant differences were observed between sexes, with worse HRQoL for females. No differences were observed between patients with UC and CD. Differences were also detected between patients who underwent surgery and those who did not. A negative association was observed between the number of flares and the questionnaire score. CONCLUSIONS In our study population, there is an acceptable HRQoL, with no differences observed between CD and UC. Female sex, absence of clinical remission, number of previous outbreaks, and surgery have a negative association with HRQoL.
Collapse
Affiliation(s)
| | - Elena Pérez Campos
- Servicio de Aparato Digestivo, Hospital Universitario Torrecárdenas, Almería, España
| | - Adrián Aparicio Mota
- Unidad de asesoramiento estadístico Indexa Geodata. Hospital Universitario Torrecárdenas, Almería, España
| | | |
Collapse
|
|
7
|
Fujita Y, Kumagai H, Yamaguchi T, Suzuki K, Ishida K, Akemoto Y, Yoshihara S. Partial Enteral Nutrition for Treating Anal Fistulas in a Boy With Crohn's Disease Without Luminal Involvement: A Case Report. Cureus 2025; 17:e76898. [PMID: 39902008 PMCID: PMC11789204 DOI: 10.7759/cureus.76898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/03/2025] [Indexed: 02/05/2025] Open
Abstract
Crohn's disease (CD) has various clinical manifestations, including anal fistulae and perianal abscesses. While perianal abscesses typically occur during infancy, pediatricians should remain alert to the possibility of CD when perianal abscesses appear outside the usual age of onset. We report the case of a three-year-old boy with refractory anal fistulas who exhibited no gastrointestinal symptoms or growth failure at presentation. Gastrointestinal endoscopy revealed no significant mucosal abnormalities, but histopathological examination identified noncaseating epithelioid cell granulomas in the terminal ileum. Based on the presence of characteristic perianal lesions and these granulomas, the patient was diagnosed with CD. Partial enteral nutrition (PEN) therapy led to significant improvement in the anal fistulas. CD presenting solely with perianal fistulas and no luminal involvement is rare, particularly in young patients. This case underscores the importance of histopathological evaluation, including step biopsies, in patients with anal fistulas, even in the absence of gastrointestinal symptoms or endoscopic abnormalities. Additionally, it highlights the potential efficacy of PEN therapy for managing perianal fistulas without luminal involvement, as demonstrated by the patient's marked improvement with this approach alone.
Collapse
Affiliation(s)
- Yuji Fujita
- Department of Pediatrics, Dokkyo Medical University, Mibu, JPN
| | - Hideki Kumagai
- Department of Pediatrics, Jichi Medical University, Shimotsuke, JPN
| | - Takeshi Yamaguchi
- Division of Pediatric Surgery, Surgical Oncology Graduate School of Medicine, Dokkyo Medical University, Mibu, JPN
| | - Kan Suzuki
- Division of Pediatric Surgery, Surgical Oncology Graduate School of Medicine, Dokkyo Medical University, Mibu, JPN
| | - Kazuyuki Ishida
- Department of Diagnostic Pathology, Dokkyo Medical University, Mibu, JPN
| | - Yui Akemoto
- Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, JPN
| | - Shigemi Yoshihara
- Department of Pediatrics, Dokkyo Medical University Hospital, Mibu, JPN
| |
Collapse
|
|
8
|
Tews HC, Schmelter F, Kandulski A, Büchler C, Schmid S, Schlosser S, Elger T, Loibl J, Sommersberger S, Fererberger T, Gunawan S, Kunst C, Gülow K, Bettenworth D, Föh B, Maaß C, Solbach P, Günther UL, Derer S, Marquardt JU, Sina C, Müller M. Unique Metabolomic and Lipidomic Profile in Serum From Patients With Crohn's Disease and Ulcerative Colitis Compared With Healthy Control Individuals. Inflamm Bowel Dis 2024; 30:2405-2417. [PMID: 38156773 PMCID: PMC11630276 DOI: 10.1093/ibd/izad298] [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: 05/17/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease. METHODS Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale. RESULTS Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2. CONCLUSIONS Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.
Collapse
Affiliation(s)
- Hauke Christian Tews
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Franziska Schmelter
- Institute of Nutritional Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Arne Kandulski
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Christa Büchler
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Stephan Schmid
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Sophie Schlosser
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Tanja Elger
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Johanna Loibl
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Stefanie Sommersberger
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Tanja Fererberger
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Stefan Gunawan
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Claudia Kunst
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Karsten Gülow
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Dominik Bettenworth
- Department of Medicine B—Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
- Practice for Internal Medicine, Münster, Germany
| | - Bandik Föh
- Department of Medicine I, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Carlos Maaß
- Department of Medicine I, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Philipp Solbach
- Department of Medicine I, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Ulrich L Günther
- Institute of Chemistry and Metabolomics, University of Lübeck, Lübeck, Germany
| | - Stefanie Derer
- Institute of Nutritional Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Jens U Marquardt
- Department of Medicine I, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Christian Sina
- Institute of Nutritional Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
- Department of Medicine I, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
- Fraunhofer Research Institution for Individualized and Cell-Based Medical Engineering, Lübeck, Germany
| | - Martina Müller
- Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| |
Collapse
|
|
9
|
Ullah H, Alioui Y, Ali M, Ali S, Farooqui NA, Siddiqui NZ, Alsholi DM, Ilyas M, Rahman MU, Xin Y, Wang L. Sea conch ( Rapana venosa) peptide hydrolysate regulates NF-κB pathway and restores intestinal immune homeostasis in DSS-induced colitis mice. Food Sci Nutr 2024; 12:10070-10086. [PMID: 39723032 PMCID: PMC11666983 DOI: 10.1002/fsn3.4410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 07/30/2024] [Accepted: 08/01/2024] [Indexed: 12/28/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Sea conch peptide hydrolysate (CPH) was produced by enzymatic digestion of fresh conch meat with trypsin enzyme. To analyze the molecular composition, functional groups, and structural morphology of the hydrolysate, we employed liquid chromatography-mass spectrometry (LC-MS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Results confirmed that crude protein could be effectively digested by enzymes to generate peptides. In this study, we evaluated the bioactivities of CPH on dextran sulfate solution (DSS)-induced colitis in mice. The findings demonstrated that CPH supplementation improved body weight, food and water intake, and colon length. The therapeutic efficacy and immunoregulatory effect of CPH were further determined. Our results exhibited that CPH treatment significantly ameliorated pathological symptoms by enhancing intestinal integrity, mucin production, and goblet cell count. Moreover, the immunoregulatory effect of CPH on mRNA expression levels of different pro- and anti-inflammatory cytokines was determined. Results exhibited a decrease in the expression of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines in the colon. Additionally, the CPH administration modulates the nuclear factor kappa B (NF-κB) pathway, preventing DNA damage and cell death. Assays for apoptosis and DNA damage revealed that CPH reduced oxidative DNA damage and apoptosis. These findings highlight the immunomodulatory and treatment amelioration effect of CPH in reducing the severity of colitis.
Collapse
Affiliation(s)
- Hidayat Ullah
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Yamina Alioui
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Muhsin Ali
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Sharafat Ali
- Department of Biochemistry and Molecular Biology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Nabeel Ahmed Farooqui
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Nimra Z. Siddiqui
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Duaa M. Alsholi
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Muhammad Ilyas
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Mujeeb U. Rahman
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Yi Xin
- Department of Biotechnology, College of Basic Medical ScienceDalian Medical UniversityDalianChina
| | - Liang Wang
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine CenterThe First Affiliated Hospital of Dalian Medical UniversityDalianChina
| |
Collapse
|
|
10
|
Ling Lundström M, Peterson C, Hedin CRH, Bergemalm D, Lampinen M, Magnusson MK, Keita ÅV, Kruse R, Lindqvist CM, Repsilber D, D'Amato M, Hjortswang H, Strid H, Söderholm JD, Öhman L, Venge P, Halfvarson J, Carlson M. Faecal biomarkers for diagnosis and prediction of disease course in treatment-naïve patients with IBD. Aliment Pharmacol Ther 2024; 60:765-777. [PMID: 38997818 DOI: 10.1111/apt.18154] [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: 02/28/2024] [Revised: 04/07/2024] [Accepted: 06/28/2024] [Indexed: 07/14/2024]
Abstract
BACKGROUND Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). AIM To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. METHODS We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. RESULTS All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). CONCLUSIONS This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.
Collapse
Affiliation(s)
- Maria Ling Lundström
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Christer Peterson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Charlotte R H Hedin
- Karolinska Institute, Department of Medicine Solna, Stockholm, Sweden
- Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Daniel Bergemalm
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Maria Lampinen
- Department of Pharmacy, Uppsala University, Uppsala, Sweden
| | - Maria K Magnusson
- Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Åsa V Keita
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Robert Kruse
- Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Carl Mårten Lindqvist
- Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Dirk Repsilber
- Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Mauro D'Amato
- Gastrointestinal Genetics Lab, CIC BioGUNE-BRTA, Derio, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Henrik Hjortswang
- Department of Health, Medicine, and Caring Sciences, Linköping University, Linkoping, Sweden
| | - Hans Strid
- Gastroenterology Unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Johan D Söderholm
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Surgery, Linköping University, Linköping, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Per Venge
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marie Carlson
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
11
|
Fu Y, Liu X, Xu J, Zhong T, Jiang J, Fu T, Cao Q, Jiang Z. A Combination of Pathological Features Identifies Crohn's Disease in Surgical Bowel Resection Specimens. Int J Surg Pathol 2024; 32:738-747. [PMID: 37715659 DOI: 10.1177/10668969231195028] [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] [Indexed: 09/18/2023]
Abstract
BACKGROUND Diagnosis of Crohn's disease is challenging. This study aims to compare the histological features of Crohn's disease and non-Crohn's disease (other intestinal inflammatory diseases) in surgical specimens to identify a set of histologic features distinguishing Crohn's disease from non-Crohn's disease. METHODS Patients with Crohn's disease (N = 171) and patients with non-Crohn's disease (N = 215) diagnosed between 2010 and 2015 who had surgical bowel resection were identified. The frequency of histological features in surgical resection specimens was compared between these two groups. RESULTS Univariate analysis revealed that transmural inflammation, subserosal lymphoid aggregates, fissures or sinus-like structures, granulomas or granuloma-like nodules, abnormalities of the enteric nervous system, and mucosa structure alterations (muscularis mucosa thickening or mucosal atrophy with pseudopyloric gland metaplasia) were more frequent in Crohn's disease than non-Crohn's disease cases (p < 0.001 for all). Some of the above histologic features were further grouped as chronic inflammatory change which includes granulomas or granuloma-like nodules, lymphoid aggregates in the muscularis propria or subserosa, fissures or sinus-like structures, and architectural abnormality which is defined as the presence of abnormal enteric nervous system and/or mucosa structural alterations (muscularis mucosa thickening or mucosal atrophy with pseudopyloric gland metaplasia). A combination of transmural inflammation, chronic inflammatory change, and architectural abnormality had a sensitivity of 92.4% and a specificity of 97.7% for Crohn's disease. CONCLUSIONS In surgical bowel resection specimens, a combination of transmural inflammation, chronic inflammatory change, and architectural abnormality help diagnose Crohn's disease.
Collapse
Affiliation(s)
- Yujuan Fu
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiuli Liu
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA
| | - Jiaqi Xu
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tingting Zhong
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junchang Jiang
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tianhong Fu
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhinong Jiang
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| |
Collapse
|
|
12
|
Fernández-Clotet A, Ordás I, Masamunt MC, Caballol B, Rodríguez S, Gallego M, Barastegui R, Saavedra AC, Panés J, Ricart E, Rimola J. Magnetic resonance enterography findings 46 weeks after initiation of biological therapy predict long-term adverse outcomes in Crohn's disease. Aliment Pharmacol Ther 2024; 59:1435-1445. [PMID: 38650481 DOI: 10.1111/apt.17968] [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: 10/18/2023] [Revised: 03/11/2024] [Accepted: 03/13/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND AND AIMS Magnetic resonance enterography (MRE) depicts transmural changes in response to biological treatment for Crohn's disease (CD); however, the long-term prognostic significance of these findings is unknown. The primary objective of this study was to identify findings on MRE 46 weeks after initiating biological treatment that predict adverse long-term outcomes. METHODS Patients with CD underwent MRE 46 weeks after initiating biological treatment and were prospectively followed for 2 years. A logistic regression analysis was performed to assess the prognostic value of different radiologic findings for various predefined adverse outcomes. RESULTS Of the 89 patients included, 46 (51.7%) had ≥1 adverse outcome during follow-up: 40 (44.9%) had clinical recurrence; 18 (20.2%) required surgery, 8 (9%) endoscopic balloon dilation, 12 (13.5%) hospitalization and 7 (7.8%) required corticosteroids. In the multivariate analysis, persistence of severe lesions (MaRIA ≥11) in any intestinal segment was associated with an increased risk of surgery [OR 11.6 (1.5-92.4)], of surgery and/or endoscopic balloon dilation [OR 6.3 (1.3-30.2)], and of clinical relapse [OR 4.6 (1.6-13.9)]. Penetrating lesions were associated with surgery [OR 3.4 (1.2-9.9)]. Creeping fat with hospitalization [OR 5.1 (1.1-25.0)] and corticosteroids requirement [OR 16.0 (1.2-210.0)]. The presence of complications (stricturing and/or penetrating lesions) was associated with having ≥1 adverse outcome [OR 3.35 (1.3-8.5)]. CONCLUSION MRE findings at week-46 after initiating biological therapy can predict long-term adverse outcomes in CD. Therapeutic intervention may be required in patients with persistence of severe inflammatory lesions, CD-associated complications, or creeping fat.
Collapse
Affiliation(s)
- Agnès Fernández-Clotet
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Ingrid Ordás
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Maria Carme Masamunt
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Berta Caballol
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Sonia Rodríguez
- IBD Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Marta Gallego
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Rebeca Barastegui
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| | | | - Julián Panés
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Elena Ricart
- IBD Unit, Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Jordi Rimola
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- IBD Unit, Radiology Department, Hospital Clinic de Barcelona, Barcelona, Spain
| |
Collapse
|
|
13
|
Jayasooriya N, Saxena S, Blackwell J, Bottle A, Creese H, Petersen I, Pollok RCG. Associations between prior healthcare use, time to diagnosis, and clinical outcomes in inflammatory bowel disease: a nationally representative population-based cohort study. BMJ Open Gastroenterol 2024; 11:e001371. [PMID: 38802264 PMCID: PMC11131120 DOI: 10.1136/bmjgast-2024-001371] [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: 02/03/2024] [Accepted: 04/23/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Timely diagnosis and treatment of inflammatory bowel disease (IBD) may improve clinical outcomes. OBJECTIVE Examine associations between time to diagnosis, patterns of prior healthcare use, and clinical outcomes in IBD. DESIGN Using the Clinical Practice Research Datalink we identified incident cases of Crohn's disease (CD) and ulcerative colitis (UC), diagnosed between January 2003 and May 2016, with a first primary care gastrointestinal consultation during the 3-year period prior to IBD diagnosis. We used multivariable Cox regression to examine the association of primary care consultation frequency (n=1, 2, >2), annual consultation intensity, hospitalisations for gastrointestinal symptoms, and time to diagnosis with a range of key clinical outcomes following diagnosis. RESULTS We identified 2645 incident IBD cases (CD: 782; UC: 1863). For CD, >2 consultations were associated with intestinal surgery (adjusted HR (aHR)=2.22, 95% CI 1.45 to 3.39) and subsequent CD-related hospitalisation (aHR=1.80, 95% CI 1.29 to 2.50). For UC, >2 consultations were associated with corticosteroid dependency (aHR=1.76, 95% CI 1.28 to 2.41), immunomodulator use (aHR=1.68, 95% CI 1.24 to 2.26), UC-related hospitalisation (aHR=1.43, 95% CI 1.05 to 1.95) and colectomy (aHR=2.01, 95% CI 1.22 to 3.27). For CD, hospitalisation prior to diagnosis was associated with CD-related hospitalisation (aHR=1.30, 95% CI 1.01 to 1.68) and intestinal surgery (aHR=1.71, 95% CI 1.13 to 2.58); for UC, it was associated with immunomodulator use (aHR=1.42, 95% CI 1.11 to 1.81), UC-related hospitalisation (aHR=1.36, 95% CI 1.06 to 1.95) and colectomy (aHR=1.54, 95% CI 1.01 to 2.34). For CD, consultation intensity in the year before diagnosis was associated with CD-related hospitalisation (aHR=1.19, 95% CI 1.12 to 1.28) and intestinal surgery (aHR=1.13, 95% CI 1.03 to 1.23); for UC, it was associated with corticosteroid use (aHR=1.08, 95% CI 1.04 to 1.13), corticosteroid dependency (aHR=1.05, 95% CI 1.00 to 1.11), and UC-related hospitalisation (aHR=1.12, 95% CI 1.03 to 1.21). For CD, time to diagnosis was associated with risk of CD-related hospitalisation (aHR=1.03, 95% CI 1.01 to 1.68); for UC, it was associated with reduced risk of UC-related hospitalisation (aHR=0.83, 95% CI 0.70 to 0.98) and colectomy (aHR=0.59, 95% CI 0.43 to 0.80). CONCLUSION Electronic records contain valuable information about patterns of healthcare use that can be used to expedite timely diagnosis and identify aggressive forms of IBD.
Collapse
Affiliation(s)
- Nishani Jayasooriya
- Institute for Infection and Immunity, St George's University of London, London, UK
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Sonia Saxena
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Jonathan Blackwell
- Edinburgh Inflammatory Bowel Disease, Western General Hospital, Edinburgh, UK
| | - Alex Bottle
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Hanna Creese
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
| | - Irene Petersen
- Research Department of Primary Care and Population Health, University College London, London, UK
| | - Richard C G Pollok
- Institute for Infection and Immunity, St George's University of London, London, UK
- Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| |
Collapse
|
|
14
|
Dold L, Kalthoff S, Frank L, Zhou T, Esser P, Lutz P, Strassburg CP, Spengler U, Langhans B. STAT activation in regulatory CD4 + T cells of patients with primary sclerosing cholangitis. Immun Inflamm Dis 2024; 12:e1248. [PMID: 38607233 PMCID: PMC11010953 DOI: 10.1002/iid3.1248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/25/2024] [Accepted: 03/31/2024] [Indexed: 04/13/2024] Open
Abstract
INTRODUCTION Regulatory CD4+ T cells (Tregs) are pivotal for inhibition of autoimmunity. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology where contribution of Tregs is still unclear. Activation of the JAK-STAT pathway critically modifies functions of Tregs. In PSC, we studied activation of STAT proteins and Treg functions in response to cytokines. METHODS In 51 patients with PSC, 10 disease controls (chronic replicative hepatitis C), and 36 healthy controls we analyzed frequencies of Foxp3+CD25+CD127lowCD4+ Tregs, their expression of ectonucleotidase CD39, and cytokine-induced phosphorylation of STAT1, 3, 5, and 6 using phospho-flow cytometry. In parallel, we measured cytokines IFN-gamma, interleukin (IL)-6, IL-2, and IL-4 in serum via bead-based immunoassays. RESULTS In patients with PSC, ex vivo frequencies of peripheral Tregs and their expression of CD39 were significantly reduced (p < .05 each). Furthermore, serum levels of IFN-gamma, IL-6, IL-2, and IL-4 were markedly higher in PSC (p < .05 each). Unlike activation of STAT1, STAT5, and STAT6, IL-6 induced increased phosphorylation of STAT3 in Tregs of PSC-patients (p = .0434). Finally, STAT3 activation in Tregs correlated with leukocyte counts. CONCLUSIONS In PSC, we observed enhanced STAT3 responsiveness of CD4+ Tregs together with reduced CD39 expression probably reflecting inflammatory activity of the disease.
Collapse
Affiliation(s)
- Leona Dold
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
- German Center for Infection Research (DZIF)Partner Site Cologne‐BonnBonnGermany
| | - Sandra Kalthoff
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
| | - Leonie Frank
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
| | - Taotao Zhou
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
| | - Pia Esser
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
| | - Philipp Lutz
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
| | | | - Ulrich Spengler
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
| | - Bettina Langhans
- Department of Internal Medicine IUniversity Hospital of BonnBonnGermany
- German Center for Infection Research (DZIF)Partner Site Cologne‐BonnBonnGermany
| |
Collapse
|
|
15
|
Amadu M, Soldera J. Duodenal Crohn's disease: Case report and systematic review. World J Methodol 2024; 14:88619. [PMID: 38577197 PMCID: PMC10989410 DOI: 10.5662/wjm.v14.i1.88619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 12/16/2023] [Accepted: 01/18/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease, including ulcerative colitis, microscopic colitis, and Crohn's disease (CD), has a global impact. This review focuses on duodenal CD (DCD), a rare subtype affecting the duodenum. DCD's rarity and asymptomatic nature create diagnostic challenges, impacting prognosis and patient well-being. Delayed diagnosis can worsen DCD outcomes. AIM To report a rare case of DCD and to discuss the diagnostic challenges and its implications on prognosis. METHODS A systematic literature search, following the PRISMA statement, was conducted. Relevant studies were identified and analysed using specific Medical Subject Terms (MeSH) from PubMed/MEDLINE, American Journal of Gastroenterology, and the University of South Wales database. Data collection included information from radiology scans, endoscopy procedures, biopsies, and histopathology results. RESULTS The review considered 8 case reports and 1 observational study, involving 44 participants diagnosed with DCD, some of whom developed complications due to delayed diagnosis. Various diagnostic methods were employed, as there is no gold standard workup for DCD. Radiology scans [magnetic resonance imaging (MRI), computed tomography (CT), and upper gastrointestinal X-ray], endoscopy procedures (colonoscopy and esophagogastroduodenoscopy), biopsies, and clinical suspicions were utilized. CONCLUSION This review discusses DCD diagnosis challenges and the roles of CT, MRI, and fluoroscopy. It notes their limitations and compares findings with endoscopy and histopathology studies. Further research is needed to improve diagnosis, emphasizing scan interpretation, endoscopy procedures, and biopsies, especially in high-risk patients during routine endoscopy.
Collapse
Affiliation(s)
- Muniratu Amadu
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
| | - Jonathan Soldera
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
| |
Collapse
|
|
16
|
Vega P, Huguet JM, Gómez E, Rubio S, Suarez P, Vera MI, Paredes JM, Hernández-Camba A, Plaza R, Mañosa M, Pajares R, Sicilia B, Madero L, Kolterer S, Leitner C, Heatta-Speicher T, Michelena N, Santos de Lamadrid R, Dignass A, Gomollón F. IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management. Dig Dis Sci 2024; 69:749-765. [PMID: 38217680 PMCID: PMC10960747 DOI: 10.1007/s10620-023-08220-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 10/10/2023] [Indexed: 01/15/2024]
Abstract
BACKGROUND Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.
Collapse
Affiliation(s)
- P Vega
- Complejo Hospitalario Universitario de Ourense, Orense, Spain
| | - J M Huguet
- Hospital General Universitario de Valencia, Valencia, Spain
| | - E Gómez
- Hospital Universitario Juan Ramon Jimenez, Huelva, Spain
| | - S Rubio
- Hospital Universitario de Navarra, Pamplona, Spain
| | - P Suarez
- Complejo Asistencial Universitario de León, León, Spain
| | - M I Vera
- Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - J M Paredes
- Hospital Universitario Dr. Peset, Valencia, Spain
| | - A Hernández-Camba
- Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - R Plaza
- Hospital Universitario Infanta Leonor, Madrid, Spain
| | - M Mañosa
- HHospital Universitario Germans Trias i Pujol, Barcelona, Spain
- CIBERehd, Madrid, Spain
| | - R Pajares
- Hospital Universitario Infanta Sofía, Madrid, Spain
| | - B Sicilia
- Hospital Universitario de Burgos, Burgos, Spain
| | - L Madero
- Servicio de Medicina Digestiva, Hospital General de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | | | | | | | | | | | - A Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt am Main, Germany
| | - F Gomollón
- Hospital Clínico Universitario Lozano Blesa, IIS Aragón, Avda. San Juan Bosco, 15, 50009, Zaragoza, Spain.
| |
Collapse
|
|
17
|
Caenepeel C, Falony G, Machiels K, Verstockt B, Goncalves PJ, Ferrante M, Sabino J, Raes J, Vieira-Silva S, Vermeire S. Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease. Gastroenterology 2024; 166:483-495. [PMID: 38096956 DOI: 10.1053/j.gastro.2023.11.304] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/13/2023] [Accepted: 11/25/2023] [Indexed: 01/09/2024]
Abstract
BACKGROUND & AIMS Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.
Collapse
Affiliation(s)
- Clara Caenepeel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Gwen Falony
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Kathleen Machiels
- Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Pfizer Biopharmaceuticals, Brussels, Belgium
| | - Bram Verstockt
- Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Pedro J Goncalves
- Machine Learning in Science, Excellence Cluster "Machine Learning," Tübingen University, Tübingen, Germany
| | - Marc Ferrante
- Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - João Sabino
- Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Jeroen Raes
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium; Center for Microbiology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium
| | - Sara Vieira-Silva
- Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany
| | - Séverine Vermeire
- Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
| |
Collapse
|
|
18
|
Chen J, Chen H, Huang Y, Xie H, Li S, Wang C. Serum food specific IgG antibodies are associated with small bowel inflammation in patients with Crohn's disease. Eur J Clin Nutr 2024; 78:48-53. [PMID: 37726342 DOI: 10.1038/s41430-023-01343-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 09/04/2023] [Accepted: 09/08/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND/AIMS Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn's disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients. METHODS We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score. RESULTS Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively). CONCLUSION Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.
Collapse
Affiliation(s)
- Jintong Chen
- Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, China
- Department of Gastroenterology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Huaning Chen
- Department of Rheumatology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yanni Huang
- Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, China
- Department of Gastroenterology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Hongchai Xie
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China
| | - Silin Li
- Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Chengdang Wang
- Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
- Fujian Clinical Research Center for Liver and Intestinal Diseases, Fuzhou, China.
- Department of Gastroenterology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
| |
Collapse
|
|
19
|
Balestrieri P, Ribolsi M, Cimini P, Alvaro G, Zobel BB, Tullio A, Cicala M. Wall Thickness Ratio-A New Magnetic Resonance Parameter-Is Associated With the Outcome of Biological Therapy in Patients With Ileal and Ileocolonic Crohn's Disease. J Clin Gastroenterol 2024; 58:64-70. [PMID: 36730458 DOI: 10.1097/mcg.0000000000001809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 10/20/2022] [Indexed: 02/04/2023]
Abstract
GOALS The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD). BACKGROUND Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH. MATERIALS AND METHODS Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0. RESULTS A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response. CONCLUSION WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.
Collapse
Affiliation(s)
| | | | - Paola Cimini
- Diagnostic Imaging, Campus Bio Medico University of Rome, Roma, Italy
| | - Giuseppe Alvaro
- Diagnostic Imaging, Campus Bio Medico University of Rome, Roma, Italy
| | - Bruno B Zobel
- Diagnostic Imaging, Campus Bio Medico University of Rome, Roma, Italy
| | | | | |
Collapse
|
|
20
|
Fukushima S, Katsurada T, Nishida M, Omotehara S, Sakurai K, Yamanashi K, Onishi R, Sakamoto N. Effectiveness of transabdominal ultrasonography in predicting clinical relapse of Crohn's disease. Intest Res 2024; 22:82-91. [PMID: 38326999 PMCID: PMC10850700 DOI: 10.5217/ir.2023.00093] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 10/22/2023] [Accepted: 10/22/2023] [Indexed: 02/09/2024] Open
Abstract
BACKGROUND/AIMS Transabdominal ultrasonography (US) helps evaluate Crohn's disease (CD) activity. We investigated whether the US could predict subsequent adverse outcomes for patients with CD in clinical remission. METHODS This single-center retrospective study included patients with CD in clinical remission who underwent US between April 2011 and April 2021, focusing on the predictability of subsequent adverse outcomes within 5 years. We used the US-CD, which was calculated using multiple US findings. Predictive variables were assessed using Cox proportional hazards regression analysis, and the predictive value was evaluated using receiver operating characteristic curves. RESULTS Seventy-three patients were included. During a median follow-up of 1,441 days (range, 41-1,825 days), 16.4% (12/73) experienced clinical relapse, 9.6% (7/73) required endoscopic balloon dilation (EBD), 58.9% (43/73) required enhanced treatment, and 20.5% (15/73) underwent surgery. In the multivariate analysis, US-CD was significantly associated with clinical relapse (P= 0.038) and the need for enhanced treatment (P= 0.005). The area under the receiver operating characteristic curve for predicting clinical relapse and the need for EBD was 0.77 and 0.81, respectively, with US-CD (cutoff value = 11), and that for requiring enhanced treatment was 0.74 with US-CD (cutoff value = 6). Patients with US-CD ≥ 11 demonstrated a significantly higher occurrence of clinical relapse (P= 0.001) and EBD (P= 0.002) within 5 years. Patients with US-CD ≥ 6 experienced a significantly higher likelihood of requiring enhanced treatment (P< 0.001) within 5 years. CONCLUSIONS High US-CD is associated with subsequent adverse outcomes in patients with CD.
Collapse
Affiliation(s)
- Shinya Fukushima
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Takehiko Katsurada
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Mutsumi Nishida
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Satomi Omotehara
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
- Diagnostic Center for Sonography, Hokkaido University Hospital, Sapporo, Japan
| | - Kensuke Sakurai
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Kana Yamanashi
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Reizo Onishi
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| |
Collapse
|
|
21
|
Sipeki N, Kovats PJ, Deutschmann C, Schierack P, Roggenbuck D, Papp M. Location-based prediction model for Crohn's disease regarding a novel serological marker, anti-chitinase 3-like 1 autoantibodies. World J Gastroenterol 2023; 29:5728-5750. [PMID: 38075846 PMCID: PMC10701337 DOI: 10.3748/wjg.v29.i42.5728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 10/03/2023] [Accepted: 11/02/2023] [Indexed: 11/13/2023] Open
Abstract
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease (IBD) is thought to play an important role in the onset or manifestation of IBD, as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defense of the intestinal epithelium. Under normal conditions, IgA contributes to the elimination of microbes, but in connection with the loss of tolerance to chitinase 3-like 1 (CHI3L1) in IBD, IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear. AIM To determine the predictive potential of Ig subtypes of a novel serological marker, anti-CHI3L1 autoantibodies (aCHI3L1) in determining the disease phenotype, therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients. METHODS Sera of 257 Crohn's disease (CD) and 180 ulcerative colitis (UC) patients from a tertiary IBD referral center of Hungary (Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen) were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1, along with 86 healthy controls (HCONT). RESULTS The IgA type was more prevalent in CD than in UC (29.2% vs 11.1%) or HCONT (2.83%; P < 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT (39.3% and 32.8% vs 4.65%, respectively; P < 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (P < 0.0001 and P = 0.038, respectively) in patients with CD. Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity (57.1% vs 36.0%, P = 0.009). IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group (46.9% vs 25.7%, P = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis, positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations. CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD. The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
Collapse
Affiliation(s)
- Nora Sipeki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
| | - Patricia Julianna Kovats
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
- Kálmán Laki Doctoral School, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
| | - Claudia Deutschmann
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
| | - Peter Schierack
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
- Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
| | - Dirk Roggenbuck
- Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
- Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg 01968, Germany
- Medipan GmbH & GA Generic Assays GmbH, Dahlewitz-Berlin 15827, Germany
| | - Maria Papp
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hungary
| |
Collapse
|
|
22
|
Kumar P, Vuyyuru SK, Das P, Kante B, Ranjan MK, Thomas DM, Mundhra S, Sahu P, Venigalla PM, Jain S, Goyal S, Golla R, Virmani S, Singh MK, Sachdeva K, Sharma R, Dash NR, Makharia G, Kedia S, Ahuja V. Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring. Intest Res 2023; 21:460-470. [PMID: 36926698 PMCID: PMC10626021 DOI: 10.5217/ir.2022.00128] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/03/2023] [Accepted: 01/09/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND/AIMS Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). METHODS Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. RESULTS One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. CONCLUSIONS Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.
Collapse
Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer K. Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - David Mathew Thomas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Pratap Mouli Venigalla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Goyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Shubi Virmani
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh K. Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Karan Sachdeva
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Nihar Ranjan Dash
- Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
23
|
Tang W, Xie G, Li J, Tan W, Yi R, Yang L, Zhang L, Deng J, Zhang Y, Li K. Body composition parameters correlate with the endoscopic severity in Crohn's disease patients treated with infliximab. Front Nutr 2023; 10:1251448. [PMID: 37674885 PMCID: PMC10478258 DOI: 10.3389/fnut.2023.1251448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 08/07/2023] [Indexed: 09/08/2023] Open
Abstract
Background The disease activity status and behavior of Crohn's disease (CD) can reflect the severity of the disease, and changes in body composition are common in CD patients. Aims The aim of this study was to investigate the relationship between body composition parameters and disease severity in CD patients treated with infliximab (IFX). Methods Patients with CD assessed with the simple endoscopic score (SES-CD) and were treated with IFX were retrospectively collected, and body composition parameters at the level of the 3rd lumbar vertebrae were calculated from computed tomography (CT) scans of the patients. The correlation of patients' body composition parameters with disease activity status and disease behavior was analyzed, and the diagnostic value of the relevant parameters was assessed using receiver operating characteristic (ROC) curves. Results A total of 106 patients were included in this study. There were significant differences in the subcutaneous adiposity index (SAI) (p = 0.010), the visceral adiposity index (VAI) (p < 0.001), the skeletal muscle mass index (SMI) (p < 0.001), and decreased skeletal muscle mass (p < 0.001) among patients with different activity status. After Spearman and multivariate regression analysis, SAI (p = 0.006 and p = 0.001), VAI (p < 0.001 and p < 0.001), and SMI (p < 0.001and p = 0.007) were identified as independent correlates of disease activity status (both disease activity and moderate-to-severe activity), with disease activity status independently positively correlated with SAI and SMI and independently negatively correlated with VAI. In determining the disease activity and moderate-to-severe activity status, SMI performed best relative to SAI and VAI, with areas under the ROC curve of 0.865 and 0.801, respectively. SAI (p = 0.015), SMI (p = 0.011) and decreased skeletal muscle mass (p = 0.027) were significantly different between different disease behavior groups (inflammatory disease behavior group, complex disease behavior group) but were not independent correlates (p > 0.05). Conclusion Body composition parameters of CD patients treated with IFX correlate with the endoscopic disease severity, and SMI can be used as a reliable indicator of disease activity status.
Collapse
Affiliation(s)
- Wuli Tang
- Chongqing Medical University, Chongqing, China
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China
- Chongqing School, University of Chinese Academy of Science, Chongqing, China
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Gang Xie
- Department of Radiology, The Third People’s Hospital of Chengdu, Chengdu, China
| | - Junlin Li
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Wei Tan
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, China
| | - Rongqi Yi
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Ling Yang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Lingqin Zhang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Jiaxing Deng
- Department of General Medicine, Chongqing General Hospital, Chongqing, China
| | - Yue Zhang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Kang Li
- Chongqing Medical University, Chongqing, China
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China
- Chongqing School, University of Chinese Academy of Science, Chongqing, China
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| |
Collapse
|
|
24
|
Dold L, Frank L, Lutz P, Kaczmarek DJ, Krämer B, Nattermann J, Weismüller TJ, Branchi V, Toma M, Gonzalez-Carmona M, Strassburg CP, Spengler U, Langhans B. IL-6-Dependent STAT3 Activation and Induction of Proinflammatory Cytokines in Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2023; 14:e00603. [PMID: 37256725 PMCID: PMC10461951 DOI: 10.14309/ctg.0000000000000603] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 05/04/2023] [Indexed: 06/02/2023] Open
Abstract
INTRODUCTION Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with periductal inflammation and fibrosis. Genetic studies suggest inflammatory cytokines and IL-6-dependent activation of transcription factor STAT3 as pivotal steps in PSC pathogenesis. However, details of inflammatory regulation remain unclear. METHODS We recruited 50 patients with PSC (36 with inflammatory bowel disease, 14 without inflammatory bowel disease), 12 patients with autoimmune hepatitis, and 36 healthy controls to measure cytokines in the serum, bile, and immune cell supernatant using bead-based immunoassays and flow cytometry and immunohistochemistry to analyze phosphorylation of STATs in immune cells. Finally, we analyzed cytokines and STAT3 phosphorylation of T cells in the presence of JAK1/2 inhibitors. RESULTS In PSC, IL-6 specifically triggered phosphorylation of STAT3 in CD4 + T cells and lead to enhanced production of interferon (IFN) gamma and interleukin (IL)-17A. Phospho-STAT3-positive CD4 + T cells correlated with systemic inflammation (C-reactive protein serum levels). Combination of immunohistology and flow cytometry indicated that phospho-STAT3-positive cells were enriched in the peribiliary liver stroma and represented CD4 + T cells with prominent production of IFN gamma and IL-17A. JAK1/2 inhibitors blocked STAT3 phosphorylation and production of IFN gamma and IL-6, whereas IL-17A was apparently resistant to this inhibition. DISCUSSION Our results demonstrate systemic and local activation of the IL-6/STAT3 pathway in PSC. Resistance of IL-17A to STAT3-targeted inhibition points to a more complex immune dysregulation beyond STAT3 activation.
Collapse
Affiliation(s)
- Leona Dold
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
- German Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Bonn, Germany;
| | - Leonie Frank
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
| | - Philipp Lutz
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
| | | | - Benjamin Krämer
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
- German Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Bonn, Germany;
| | - Tobias J. Weismüller
- Department of Internal Medicine - Gastroenterology and Oncology, Vivantes Humboldt Hospital, Berlin, Germany;
| | - Vittorio Branchi
- Department of General, Abdominal, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany;
| | - Marieta Toma
- Institute of Pathology, University Hospital Bonn, Bonn, Germany.
| | | | | | - Ulrich Spengler
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
| | - Bettina Langhans
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany;
- German Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Bonn, Germany;
| |
Collapse
|
|
25
|
Hu J, Wu J, Zhang P, Hu N, Mei Q, Wu X, Han W. Evaluation of symptomatic small bowel stricture in Crohn's disease by double-balloon endoscopy. BMC Gastroenterol 2023; 23:247. [PMID: 37475007 PMCID: PMC10360240 DOI: 10.1186/s12876-023-02839-8] [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: 10/26/2022] [Accepted: 05/30/2023] [Indexed: 07/22/2023] Open
Abstract
PURPOSE To assess the efficacy of double-balloon endoscopy (DBE) for the detection of small-bowel strictures in Crohn's disease (CD). METHODS This tertiary-referral hospital cohort study was conducted between January 2018 and May 2022. CD patients with symptoms of small-bowel stricture were enrolled sequentially. All of the patients were subjected to both computed tomography enterography (CTE) and DBE, and their symptoms of stricture were assessed using the Crohn's Disease Obstructive Score (CDOS). The diagnostic yield of DBE was compared to that of CTE, and the relationship between the DBE findings and CDOS was investigated. The factors influencing the DBE diagnosis were examined using Cox regression analysis. RESULTS This study included 165 CD patients. The CDOS scores were higher in 95 patients and lower in 70 patients. DBE detected 92.7% (153/165) and CTE detected 85.5% (141/165) of the strictures. The DBE diagnostic yields were 94.7% (90/95) in the high CDOS patients and 91.4% (64/70) in the low CDOS patients (P = 0.13). Patients with a history of abdominal surgery and abscess had a lower diagnosis rate in the multivariate analysis. CONCLUSION DBE has been demonstrated to be an efficient diagnostic method for detecting small bowel strictures in CD patients. Additionally, there was no difference in the diagnostic yields between patients with low and high obstructive scores.
Collapse
Affiliation(s)
- Jing Hu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, People's Republic of China
| | - Juan Wu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, People's Republic of China
| | - Peipei Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, People's Republic of China
| | - Naizhong Hu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, People's Republic of China
| | - Qiao Mei
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, People's Republic of China
| | - Xingwang Wu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China
| | - Wei Han
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, People's Republic of China.
| |
Collapse
|
|
26
|
Boulagnon-Rombi C, Marchal A, Lirsac M, Svrcek M. [Inflammatory bowel diseases: Scoring and pathological reports optimization]. Ann Pathol 2023:S0242-6498(23)00083-4. [PMID: 37059601 DOI: 10.1016/j.annpat.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/13/2023] [Accepted: 03/26/2023] [Indexed: 04/16/2023]
Abstract
The two main forms of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). Both diseases have inflammatory flare-ups that alternate with periods of remission. The pathologist may examine biopsies of the digestive tract from IBD patients in different contexts: at the time of the initial diagnosis, in the event of a disease flare-up in order to differentiate a flare of the disease from another cause, particularly an infectious one, and during the long term follow-up of the disease in order to detect the occurrence of dysplastic lesions. Pathologists are increasingly involved in the evaluation of inflammatory activity during the follow-up of IBD patients. The therapeutic management of IBD has evolved significantly and the emergence of new treatments allows a global approach targeting endoscopic mucosal healing. However, mucosal healing is not always correlated with histological healing. Numerous studies have shown the value of histological evaluation during follow-up. A higher score for histological activity in ulcerative colitis predicts a higher likelihood of neoplasia. Histological activity is a better predictor than endoscopic inflammation of the risk. In UC, histological remission may be a long-term therapeutic goal but its role in CD remains unclear. Different scores have been developed to quantify the inflammatory activity of IBD patients and the response to treatment. The aim of this review is to present the main activity scores used in the follow-up of IBD, their interest, their evaluation and their limitations.
Collapse
Affiliation(s)
- Camille Boulagnon-Rombi
- Service de pathologie, CHU de Reims, 51092 Reims, France; CNRS, MEDyC UMR 7369, université de Reims Champagne Ardenne, 51097 Reims, France.
| | - Aude Marchal
- Émile-Gallé groupe, centre de pathologie, Nancy, France
| | | | - Magali Svrcek
- Université de la Sorbonne, Paris, France; Service d'anatomie et cytologie pathologiques, Sorbonne université, hôpital Saint-Antoine, AP-HP, Paris, France
| |
Collapse
|
|
27
|
Vitali R, Palone F, Armuzzi A, Fulci V, Negroni A, Carissimi C, Cucchiara S, Stronati L. Proteomic Analysis Identifies Three Reliable Biomarkers of Intestinal Inflammation in the Stools of Patients With Inflammatory Bowel Disease. J Crohns Colitis 2023; 17:92-102. [PMID: 36040453 DOI: 10.1093/ecco-jcc/jjac110] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Faecal biomarkers have emerged as important tools in managing of inflammatory bowel disease [IBD], which includes Crohn's disease [CD] and ulcerative colitis [UC]. AIM To identify new biomarkers of gut inflammation in the stools of IBD patients using a proteomic approach. METHODS Proteomic analysis of stools was performed in patients with both active CD and CD in remission and in controls by 2-DIGE and MALDI-TOF/TOF MS. An ELISA was used to confirm results in a second cohort of IBD patients and controls. RESULTS 2-DIGE analysis detected 70 spots in the stools of patients with active CD or patients in remission CD and in controls. MALDI-TOF/TOF MS analysis identified 21 proteins with Chymotrypsin C, Gelsolin and Rho GDP-dissociation inhibitor 2 [RhoGDI2] best correlating with the levels of intestinal inflammation. Results were confirmed in a second cohort of IBD patients and controls [57 CD, 60 UC, 31 controls]. The identified faecal markers significantly correlated with the severity of intestinal inflammation in IBD patients [SES-CD in CD, Mayo endoscopic subscore in UC] [CD; Chymotrypsin-C: r = 0.64, p < 0.001; Gelsolin: r = 0.82, p < 0.001; RhoGDI2: r = 0.64, p < 0.001; UC; Chymotrypsin-C: r = 0.76, p < 0.001; Gelsolin: r = 0.75, p < 0.001; RhoGDI2: r = 0.63, p < 0.001]. Moreover, ROC analysis showed that Gelsolin [p < 0.0002] and RhoGDI2 [p < 0.0001] in CD, and RhoGDI2 [p = 0.0004] in UC, have higher sensitivity and specificity than faecal calprotectin in discriminating between patients and controls. CONCLUSIONS We show for the first time that 2-DIGE is a reliable method to detect proteins in human stools. Three novel faecal biomarkers of gut inflammation have been identified that display good specificity and sensitivity for identifying IBD and significantly correlate with IBD severity.
Collapse
Affiliation(s)
- Roberta Vitali
- Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy
| | - Francesca Palone
- Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Valerio Fulci
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Anna Negroni
- Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy
| | - Claudia Carissimi
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Salvatore Cucchiara
- Department of Maternal and Child Health, Sapienza University of Rome, Rome, Italy
| | - Laura Stronati
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
28
|
Regueiro M, Hunter T, Lukanova R, Shan M, Wild R, Knight H, Bannikoppa P, Naegeli AN. Burden of Fatigue Among Patients with Ulcerative Colitis and Crohn's Disease: Results from a Global Survey of Patients and Gastroenterologists. Adv Ther 2023; 40:474-488. [PMID: 36370288 PMCID: PMC9898407 DOI: 10.1007/s12325-022-02364-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 10/18/2022] [Indexed: 11/13/2022]
Abstract
INTRODUCTION To assess the prevalence of fatigue and its association with disease activity and patient-reported outcomes among patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS Data from a cross-sectional survey conducted with gastroenterologists and their consulting adult patients with UC or CD were analyzed. Data were collected via gastroenterologist-completed patient record forms and patient-self completion forms. Patient demographics, clinical characteristics, disease activity and medication use were reported by the gastroenterologist, while current symptoms (fatigue, rectal urgency, abdominal pain, sleep disturbance), work productivity and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) were reported by the patient. Logistic regression models were used to identify measures associated with fatigue and expressed as odds ratio (OR) with 95% confidence interval. p < 0.05 was considered statistically significant. RESULTS A total of 1057 patients with UC and 1228 patients with CD were included in this analysis. Fatigue was reported in 22.6% of UC and 26.0% of patients with CD. Higher proportion of patients with UC and fatigue had moderate/severe disease activity (p = 0.0001), had a higher Mayo score (5.0 vs. 4.0, p < 0.0001) and were unemployed (5.6% vs. 3.9%, p = 0.0149) compared to those without fatigue. In patients with CD reporting fatigue, a higher proportion were female (55.9% vs. 48.2%, p = 0.0193), were unemployed (5.8% vs. 4.9%, p = 0.0069), had moderate/severe disease (p < 0.0001) and had a higher mean Crohn's Disease Activity Index score (145.0 vs. 96.2, p < 0.0001) than patients without fatigue. Patients with UC and fatigue had higher mean level of pain (p < 0.0001) and sleep disturbance (p < 0.0001), whereas patients with CD and fatigue had lower SIBDQ scores (p < 0.0001) and greater work impairment (p = 0.0015) than patients without fatigue. Abdominal pain (OR: 2.01, p = 0.001) and use of immunomodulators (OR: 1.69, p = 0.006) increased the odds of having fatigue in patients with UC. In patients with CD, abdominal pain (OR: 2.29, p < 0.001) and use of biologics or biosimilars (OR: 2.02, p = 0.003) increased the odds of having fatigue. CONCLUSION Fatigue is a common symptom among patients with UC or CD that is associated with higher levels of disease activity and decreased work productivity and is driven by various factors. A multidisciplinary approach may be needed to manage fatigue.
Collapse
Affiliation(s)
| | - Theresa Hunter
- Eli Lilly and Company, 893 S. Delaware Street, Indianapolis, IN, 46225, USA.
| | | | - Mingyang Shan
- Eli Lilly and Company, 893 S. Delaware Street, Indianapolis, IN 46225 USA
| | | | | | | | - April N. Naegeli
- Eli Lilly and Company, 893 S. Delaware Street, Indianapolis, IN 46225 USA
| |
Collapse
|
|
29
|
An Obscure Presence of Gastroduodenal Involvement in a Newly Diagnosed Ileocolic Crohn’s Disease Patient. Case Rep Gastrointest Med 2022; 2022:2200438. [DOI: 10.1155/2022/2200438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 11/13/2022] [Accepted: 11/18/2022] [Indexed: 12/28/2022] Open
Abstract
Whereas typical Crohn’s disease is confined to the terminal ileum and presents with abdominal pain and diarrhea, gastroduodenal manifestations of Crohn’s disease are rare, with often asymptomatic patient presentations and inconclusive diagnostic testing. It is, however, a more severe form of Crohn’s disease and thus warrants treatment with steroids and biologics much earlier than its ileocolonic counterpart. We present the case of a young, otherwise healthy, male with newly diagnosed ileocolonic Crohn’s disease with concurrent gastroduodenal involvement that initially failed management with biologic agents. We discuss the clinical manifestations and often obscure pathology of gastroduodenal Crohn’s disease and highlight the necessity of performing a concurrent esophagogastroduodenoscopic evaluation on newly diagnosed ileocolonic Crohn’s disease to assess the presence of upper gastrointestinal involvement.
Collapse
|
|
30
|
Fernández-Clotet A, Panés J, Ricart E, Castro-Poceiro J, Masamunt MC, Rodríguez S, Caballol B, Ordás I, Rimola J. Predictors of bowel damage in the long-term progression of Crohn’s disease. World J Clin Cases 2022; 10:12208-12220. [PMID: 36483818 PMCID: PMC9724529 DOI: 10.12998/wjcc.v10.i33.12208] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/06/2022] [Accepted: 10/31/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Crohn’s disease (CD) is a chronic inflammatory bowel disorder that progresses to bowel damage (BD) over time. An image-based index, the Lémann index (LI), has been developed to measure cumulative BD.
AIM To characterize the long-term progression of BD in CD based on changes in the LI and to determine risk factors for long-term progression.
METHODS This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as a gold standard and who had a follow-up of at least 5 years were re-evaluated after 5-12 years.
RESULTS Seventy-two patients were included. LI increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%), and decreased in 25 patients (34.7%). The small bowel score and surgery subscale significantly increased (P = 0.002 and P = 0.001, respectively), whereas the fistulizing subscale significantly decreased (P = 0.001). Baseline parameters associated with BD progression were ileal location (P = 0.026), CD phenotype [stricturing, fistulizing, or both (P = 0.007, P = 0.006, and P = 0.035, respectively)], disease duration > 10 years (P = 0.019), and baseline LI stricturing score (P = 0.049). No correlation was observed between BD progression and baseline clinical activity, biological markers, or severity of endoscopic lesions.
CONCLUSION BD, as assessed by the LI, progressed in half of the patients with CD over a period of 5-12 years. The main determinants of BD progression were ileal location, stricturing/fistulizing phenotype, and disease duration.
Collapse
Affiliation(s)
- Agnes Fernández-Clotet
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Julian Panés
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Elena Ricart
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Jesús Castro-Poceiro
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Maria Carme Masamunt
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Sonia Rodríguez
- Department of Radiology, Hospital Clinic, Barcelona 08036, Spain
| | - Berta Caballol
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Ingrid Ordás
- Department of Gastroenterology, Hospital Clinic, Barcelona 08036, Spain
- Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
| | - Jordi Rimola
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid 28029, Spain
- Department of Radiology, Hospital Clinic, Barcelona 08036, Spain
| |
Collapse
|
|
31
|
Sun A, Li W, Shang S. Association of polymorphisms in the
IL‐10
promoter region with Crohn's disease. J Clin Lab Anal 2022; 36:e24780. [DOI: 10.1002/jcla.24780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 11/22/2022] Open
Affiliation(s)
- Anna Sun
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center For Child Health Hangzhou China
| | - Wei Li
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center For Child Health Hangzhou China
| | - Shiqiang Shang
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center For Child Health Hangzhou China
| |
Collapse
|
|
32
|
Serial Changes in Body Composition and the Association with Disease Activity during Treatment in Patients with Crohn's Disease. Diagnostics (Basel) 2022; 12:diagnostics12112804. [PMID: 36428862 PMCID: PMC9689369 DOI: 10.3390/diagnostics12112804] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/08/2022] [Accepted: 11/09/2022] [Indexed: 11/18/2022] Open
Abstract
Objectives: To analyze serial changes in body composition and investigate the association between body composition changes and disease activity changes in patients with Crohn’s disease (CD). Methods: Seventy-one patients with CD who had been treated and followed-up at our institution were included. Two to four computed tomography images were acquired at baseline, and the 2−5-year, 5−8-year, and last follow-ups were selected per patient for body composition and disease activity analyses. Visceral fat area (VFA), skeletal muscle index (SMI; skeletal muscle area/height2), and subcutaneous fat area (SFA) were assessed using an artificial-intelligence-driven fully automated method. Disease activity was assessed using a modified computed tomography scoring system and the Simple Endoscopic Score for Crohn’s Disease. The associations between body composition, disease activity, and remission were investigated. Results: The mean age was 29.83 ± 11.27 years; most patients were men (48/71, 67.6%); and the median follow-up was 144 (12−264) months. Overall, VFA and SFA gradually increased, while SMI decreased during the follow-up. Sarcopenia was associated with the female sex, higher disease activities at baseline (p = 0.01) and the last follow-up (p = 0.001). SMI and SFA inversely correlated with the disease activity, i.e., the more severe the disease activity, the lower the SMI and SFA (p < 0.05). SMI at the last follow-up was the only significant predictor of remission (OR = 1.21, 95% confidence interval: 1.03−1.42, p = 0.021). Conclusion: SMI decreased while VFA and SFA increased during the treatment follow-up in patients with CD. Sarcopenia was associated with higher disease activity, and SMI and SFA inversely correlated with disease activity. SMI at the last follow-up was the significant factor for remission.
Collapse
|
|
33
|
Wang S, Miao S, Qiu X, Wu J, Wang Y. Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease. Medicine (Baltimore) 2022; 101:e31163. [PMID: 36281159 PMCID: PMC9592269 DOI: 10.1097/md.0000000000031163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn's disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.
Collapse
Affiliation(s)
- Shengnan Wang
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Shijian Miao
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Xiaoxia Qiu
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Jie Wu
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Yuhuan Wang
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
- * Correspondence: Yuhuan Wang, Department of gastroenterology in Children’s hospital of Fudan University, Wanyuan Road 399, Minhang District, Shanghai (e-mail: )
| |
Collapse
|
|
34
|
Kumar P, Vuyyuru SK, Kante B, Kedia S, Sahu P, Ranjan MK, Mundhra S, Golla R, Kumar M, Virmani S, Gupta A, Yadav N, Makharia G, Ahuja V. Efficacy and safety of biosimilar versus originator infliximab in patients with inflammatory bowel disease: A real-world cohort analysis. Indian J Gastroenterol 2022; 41:446-455. [PMID: 36378484 DOI: 10.1007/s12664-022-01252-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 02/01/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD). METHODS Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up. RESULTS In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar. CONCLUSIONS Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD.
Collapse
Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Bhaskar Kante
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Sandeep Mundhra
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Rithvik Golla
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Mukesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Shubi Virmani
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Anvita Gupta
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Nidhi Yadav
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.
| |
Collapse
|
|
35
|
Agraib LM, Yamani MI, Tayyem R, Abu-Sneineh AT, Rayyan YM. Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study. Clin Nutr ESPEN 2022; 51:83-91. [DOI: 10.1016/j.clnesp.2022.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/03/2022] [Accepted: 08/14/2022] [Indexed: 11/30/2022]
|
|
36
|
Yang H, Zhou R, Bai X, Guo M, Ruan G, Wang L, Qian J. Trend and Geographic Variation in Incidence and Prevalence of Inflammatory Bowel Disease in Regions Across China: A Nationwide Employee Study Between 2013 and 2016. Front Med (Lausanne) 2022; 9:900251. [PMID: 35957856 PMCID: PMC9357923 DOI: 10.3389/fmed.2022.900251] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
Background Incidence and prevalence rates and trends of inflammatory bowel disease (IBD) in China remain largely unknown. Objective This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in China between 2013 and 2016. Methods We conducted a population-based analysis using data from the National Urban Employee Basic Medical Insurance database. Patients with at least three claims of IBD diagnosis were identified. A Joinpoint regression model was used to analyze the annual percent change (APC) of the age-standardized incidence and prevalence. Results The age-standardized prevalence of Crohn's disease (CD) increased from 1.59/100,000 in 2013 to 3.39/100,000 (p < 0.05) in 2016, and that of ulcerative colitis (UC) increased from 8.72/100,000 to 17.24/100,000 (p < 0.05) during the period, with a UC/CD ratio of 5.09 in 2016. The age-standardized incidence of CD varied between 0.82/100,000 and 0.97/100,000 (p = 0.9), whereas that of UC slightly increased from 4.54/100,000 to 4.85/100,000 (p = 0.7). The eastern region of China had the highest incidence and prevalence, and the western region had the lowest rates, in both UC and CD, showing an east-to-west gradient. Conclusion The incidence and prevalence of IBD in most urban regions in China had an emerging trend over the study period, and an east-to-west gradient was observed, which indicated a greater burden in eastern China. Efforts to improve prevention strategies and promote awareness of IBD are needed, particularly in young men who are at higher risk for CD.
Collapse
Affiliation(s)
- Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runing Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
- Li Wang
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Jiaming Qian
| |
Collapse
|
|
37
|
Molecular characterization and antibiotic resistance of Clostridioides difficile in patients with inflammatory bowel disease from two hospitals in China. J Glob Antimicrob Resist 2022; 30:252-258. [PMID: 35764214 DOI: 10.1016/j.jgar.2022.06.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 05/27/2022] [Accepted: 06/16/2022] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE Patients with inflammatory bowel disease (IBD) are susceptible to Clostridioides difficile infection (CDI), resulting in poor outcomes and recurrence; therefore, the molecular characterization of C. difficle in IBD patients in China needs further investigation. METHODS C. difficile strains were isolated and identified from fecal samples of adult and pediatric IBD patients. Toxigenic strains were typed using multilocus sequence typing (MLST) and whole genomic sequencing (WGS) to construct the phylogenetic tree. Susceptibility to 10 antimicrobials was evaluated using the E-test. RESULTS Among the 838 IBD patients, 82 toxigenic C. difficile were identified, which comprised 46 from adults and 36 children. 90.2% (74/82) of the isolates were positive for both toxin A and toxin B genes (A+B+), while the remaining 9.8% were negative for toxin A gene, but positive for toxin B gene (A-B+). These toxigenic strains were susceptible to metronidazole and vancomycin, but highly resistant to clindamycin, erythromycin, and fluoroquinolones. All moxifloxacin-resistant isolates had mutations resulting in an amino acid substitution in gryA (T82I). The dominant types were ST-35 (20.7%), ST-2 (17.1%), ST-54 (13.4%), and ST-3 (13.4%) in all patients. CONCLUSION The incidence and molecular epidemiology of C. difficile infection in adult IBD patients resembled CDI in the general inpatient population. A higher antibiotic resistance rate was identified among the C. difficile isolates obtained from pediatric IBD patients than adult patients, and few STs accounted for most multidrug-resistant strains. However, the molecular genetic features of the same ST-type between these two groups remains highly correlated.
Collapse
|
|
38
|
Circulating Exosomal miR-144-3p from Crohn’s Disease Patients Inhibits Human Umbilical Vein Endothelial Cell Function by Targeting FN1. DISEASE MARKERS 2022; 2022:8219557. [PMID: 35692876 PMCID: PMC9184168 DOI: 10.1155/2022/8219557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 04/20/2022] [Indexed: 11/20/2022]
Abstract
Background Crohn's disease (CD) is a chronic nonspecific inflammatory disease with unknown pathogenesis and vascular changes associated with the progression of CD. Many studies have shown that miRNAs participate in the development of CD. However, the effect of miRNAs in circulating exosomes on vascular endothelial cells in CD has not been investigated. Our study is aimed at identifying the differential miRNAs in circulating exosomes in CD and exploring their potential roles in human umbilical vein endothelial cells (HUVECs). Methods In our study, exosomes were extracted from circulating blood to identify differential miRNAs. After in vitro transfection of HUVECs with miR-144-3p mimics and inhibitors and the corresponding controls, cell counting kit-8, wound healing, Transwell migration, and tube formation assays were performed to study the viability, migration, and angiogenesis of HUVECs. Furthermore, bioinformatics analysis was used to predict miRNA targets. Western blotting was used to determine protein expression. In addition, exogenous supplementation with the fibronectin 1 (FN1) protein rescued the effects of miR-144-3p on changes in cell function in vitro. Results miR-144-3p was significantly increased in circulating exosomes of patients with CD compared with those in the control group. The promotion or inhibition of miR-144-3p correspondingly abolished or accelerated cell viability, migration, and angiogenesis. FN1 is a significant target of miR-144-3p, and exogenous FN1 administration improved the function of HUVECs in vitro. Conclusions Circulating exosomal miR-144-3p from patients with active CD contributes to vascular endothelial dysfunction by affecting the gene expression of FN1. These findings suggested that circulating exosomal miR-144-3p could be a potential biological marker for CD.
Collapse
|
|
39
|
Bai X, Zhang H, Ruan G, Lv H, Li Y, Li J, Tan B, Zheng W, Jin M, Xu H, Yang H, Qian J. Long-term Disease Behavior and Surgical Intervention Analysis in Hospitalized Patients With Crohn's Disease in China: A Retrospective Cohort Study. Inflamm Bowel Dis 2022; 28:S35-S41. [PMID: 34894147 DOI: 10.1093/ibd/izab295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND There is lack of real-world data for disease behavior and surgery of Crohn's disease (CD) from large-scale Chinese cohorts. METHODS Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression of B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected. RESULTS Overall, 504 patients were included. Two hundred thirty-one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least 1 CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery. CONCLUSIONS This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase.
Collapse
Affiliation(s)
- Xiaoyin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Huimin Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hong Lv
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Weiyang Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Meng Jin
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hui Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
|
40
|
Kumar P, Vuyyuru SK, Kante B, Sahu P, Goyal S, Madhu D, Jain S, Ranjan MK, Mundhra S, Golla R, Singh M, Virmani S, Gupta A, Yadav N, Kalaivani M, Sharma R, Das P, Makharia G, Kedia S, Ahuja V. Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region. Aliment Pharmacol Ther 2022; 55:1431-1440. [PMID: 35229906 DOI: 10.1111/apt.16839] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/10/2022] [Accepted: 02/07/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. AIM We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. METHODS We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. RESULTS One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5 ± 13.4 years, 60% males, median follow-up duration after anti-TNF: 33 months [interquartile range: 23-57 months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p < 0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p = 0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. CONCLUSION The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.
Collapse
Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Sandeep Goyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Deepak Madhu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Sandeep Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Mukesh Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Shubi Virmani
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Anvita Gupta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Nidhi Yadav
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Mani Kalaivani
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| |
Collapse
|
|
41
|
Hanzel J, Ma C, Jairath V, Sedano R, Shackelton LM, D'Haens GR, Sandborn WJ, Feagan BG. Design of Clinical Trials for Mild to Moderate Crohn's Disease. Gastroenterology 2022; 162:1800-1814.e1. [PMID: 35240140 DOI: 10.1053/j.gastro.2022.02.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/21/2022] [Accepted: 02/18/2022] [Indexed: 12/02/2022]
Affiliation(s)
- Jurij Hanzel
- Department of Gastroenterology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Alimentiv Inc, London, Ontario, Canada; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Academic Medical Centre, Amsterdam, the Netherlands
| | - Christopher Ma
- Alimentiv Inc, London, Ontario, Canada; Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Services, University of Calgary, Calgary, Alberta, Canada
| | - Vipul Jairath
- Alimentiv Inc, London, Ontario, Canada; Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | | | - Rocio Sedano
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Alimentiv Inc., London, Ontario, Canada
| | | | - Geert R D'Haens
- Alimentiv Inc., London, Ontario, Canada; Department of Gastroenterology and Hepatology, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism Research Institute, University of Amsterdam, Amsterdam, The Netherlands
| | - William J Sandborn
- Alimentiv Inc., London, Ontario, Canada; Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Brian G Feagan
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Alimentiv Inc., London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| |
Collapse
|
|
42
|
Nardone OM, Calabrese G, Testa A, Caiazzo A, Fierro G, Rispo A, Castiglione F. The Impact of Intestinal Ultrasound on the Management of Inflammatory Bowel Disease: From Established Facts Toward New Horizons. Front Med (Lausanne) 2022; 9:898092. [PMID: 35677820 PMCID: PMC9167952 DOI: 10.3389/fmed.2022.898092] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 04/25/2022] [Indexed: 11/15/2022] Open
Abstract
Intestinal ultrasound (IUS) plays a crucial role as a non-invasive and accurate tool to diagnose and assess inflammatory bowel disease (IBD). The rationale for using IUS in Crohn’s disease (CD), a transmural disease, is widely acknowledged. While the use of IUS in ulcerative colitis (UC), a mucosal disease, is often underestimated, but, recently, it is increasingly expanding. In the context of a treat-to-target approach, the role of IUS is shifting toward a monitoring tool for predicting response to therapy. Hence, adjusting therapeutic strategies based on IUS response could reduce the burden related to endoscopy and speed the decision process with the ultimate goal to alter the natural course of IBD. Assessment of bowel wall thickness (BWT) is the most reliable IUS measure. However, the development of validated and reproducible sonographic scores to measure disease activity and the identification of parameters of therapeutic response remain relevant issues to implement the daily adoption of IUS in clinical practice. Accordingly, this review focuses on the current literature investigating the impact of IUS on CD with emphasis on the concept of transmural healing (TH) and the main related advantages. We further explore new insights on the role of IUS in UC and its clinical implications.
Collapse
Affiliation(s)
- Olga Maria Nardone
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Giulio Calabrese
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Anna Testa
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Anna Caiazzo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Giuseppe Fierro
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Antonio Rispo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Fabiana Castiglione
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
- *Correspondence: Fabiana Castiglione,
| |
Collapse
|
|
43
|
Thomsen SB, Ungaro RC, Allin KH, Elmahdi R, Poulsen G, Andersson M, Colombel JF, Jess T. Impact of thiopurine discontinuation at anti-tumour necrosis factor initiation in inflammatory bowel disease treatment: a nationwide Danish cohort study. Aliment Pharmacol Ther 2022; 55:1128-1138. [PMID: 35080036 DOI: 10.1111/apt.16777] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/27/2021] [Accepted: 01/08/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Escalation to anti-tumour necrosis factor (anti-TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing thiopurine at escalation is unclear. AIM To assess the impact of discontinuing versus continuing thiopurine therapy at anti-TNF initiation. METHODS We used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti-TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti-TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD-related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS Of the 10,352 anti-TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti-TNF. After anti-TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti-TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10-1.36), particularly for IBD-related hospitalization (aHR: 1.14; 95% CI: 1.00-1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13-1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02-1.34) and UC (aHR: 1.32; 95% CI: 1.12-1.55). CONCLUSIONS In a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti-TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.
Collapse
Affiliation(s)
- Sandra Bohn Thomsen
- Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, Denmark
| | - Ryan C Ungaro
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Kristine H Allin
- Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, Denmark
| | - Rahma Elmahdi
- Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, Denmark
| | - Gry Poulsen
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Mikael Andersson
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Tine Jess
- Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease, Aalborg University, Copenhagen, Denmark.,Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
| |
Collapse
|
|
44
|
Schaefer M, Laurent V, Grandmougin A, Vuitton L, Bourreille A, Luc A, Clerc-Urmes I, Orry X, Frampas E, De Billy M, Pouillon L, Le Berre C, Gay C, Meyer J, Baumann C, Peyrin-Biroulet L. A Magnetic Resonance Imaging Index to Predict Crohn's Disease Postoperative Recurrence: The MONITOR Index. Clin Gastroenterol Hepatol 2022; 20:e1040-e1049. [PMID: 34216820 DOI: 10.1016/j.cgh.2021.06.035] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/01/2021] [Accepted: 06/25/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). METHODS Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. RESULTS Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. CONCLUSIONS The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.
Collapse
Affiliation(s)
- Marion Schaefer
- Department of Hepatogastroenterology, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Valérie Laurent
- Central Department of Radiology, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Aurélie Grandmougin
- Central Department of Radiology, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Lucine Vuitton
- Department of Gastroenterology, Besançon University Hospital, Besancon
| | | | - Amandine Luc
- Unit of Methodology, Data Management and Statistic, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Isabelle Clerc-Urmes
- Unit of Methodology, Data Management and Statistic, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Xavier Orry
- Central Department of Radiology, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Eric Frampas
- Department of Radiology, Nantes University Hospital, Nantes
| | | | - Lieven Pouillon
- Department of Hepatogastroenterology, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | | | - Claire Gay
- Department of Gastroenterology, Besançon University Hospital, Besancon
| | - Jeremy Meyer
- Department of Radiology, Nantes University Hospital, Nantes
| | - Cédric Baumann
- Unit of Methodology, Data Management and Statistic, Nancy University Hospital, Vandoeuvre-lès-Nancy
| | - Laurent Peyrin-Biroulet
- Department of Hepatogastroenterology, Nancy University Hospital, Vandoeuvre-lès-Nancy; INSERM U1256, Nutrition-Génétique et Exposition aux Risques Environnementaux, Faculté de Médecine, Université de Lorraine, Vandoeuvre-les-Nancy, France.
| |
Collapse
|
|
45
|
Hyun HK, Yu J, Kang EA, Park J, Park SJ, Park JJ, Kim TI, Kim WH, Cheon JH. Radiology plus ileocolonoscopy versus radiology alone in Crohn's disease: prognosis prediction and mutual agreement. Korean J Intern Med 2022; 37:567-578. [PMID: 34695881 PMCID: PMC9082435 DOI: 10.3904/kjim.2021.233] [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: 05/14/2021] [Revised: 07/30/2021] [Accepted: 08/17/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND/AIMS The optimal tools for monitoring Crohn's disease (CD) are controversial. We compared radiology plus ileocolonoscopy and radiology alone in terms of prognosis prediction and evaluated the agreement between radiologic and ileocolonoscopic findings in patients with CD. METHODS Patients with CD who were followed up with computed tomography enterography (CTE) or magnetic resonance enterography (MRE) alone or CTE or MRE plus ileocolonoscopy were retrospectively recruited. Time to relapse was investigated to evaluate the difference in prognosis using the log-rank and Cox regression tests, and the agreement between radiologic and ileocolonoscopic findings was determined using a kappa value. RESULTS A total of 501 patients with CD in clinical remission who underwent CTE or MRE and/or ileocolonoscopy were analyzed. Of these, 372 (74.3%) patients underwent CTE or MRE alone and 129 (25.7%) patients underwent CTE or MRE plus ileocolonoscopy. The cumulative maintenance rate of clinical remission between the two groups was not significantly different (p = 0.526, log-rank test). In multivariate analysis, age <40 years (hazard ratio [HR], 2.756; 95% confidence interval [CI], 1.263 to 6.013) and a history of steroid use (HR, 2.212; 95% CI, 1.258 to 3.577) were found to independently predict an increased risk for clinical relapse in patients with CD in clinical remission. Radiologic and ileocolonoscopic findings had a moderate degree of agreement (κ = 0.401, -0.094 to 0.142). The comparison of agreement between radiologic and ileocolonoscopic findings was the highest in the anastomotic site (κ = 0.749, -0.168 to 0.377). CONCLUSION Radiology plus ileocolonoscopy was not superior to radiology alone in predicting the prognosis of CD.
Collapse
Affiliation(s)
- Hye Kyung Hyun
- Department of Gastroenterology and Institute of Gastroenterology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin,
Korea
| | - Jongwook Yu
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Eun Ae Kang
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Jihye Park
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Soo Jung Park
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Jae Jun Park
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Tae Il Kim
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Won Ho Kim
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Jae Hee Cheon
- Department of Gastroenterology and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| |
Collapse
|
|
46
|
Xia H, Li S, He Y, Ren Q, Qin S. Long non-coding RNA ANRIL serves as a potential marker of disease risk, inflammation, and disease activity of pediatric inflammatory bowel disease. Clin Res Hepatol Gastroenterol 2022; 46:101895. [PMID: 35227955 DOI: 10.1016/j.clinre.2022.101895] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 02/10/2022] [Accepted: 02/15/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Long non-coding antisense RNAs in the INK4 locus (lnc-ANRIL) have been reported to be involved in inflammation and immunity. However, few studies have reported its clinical application in pediatric inflammatory bowel disease (IBD). Therefore, we conducted this study to investigate the correlation between lnc-ANRIL expression and disease risk, inflammation, and activity in pediatric IBD patients. METHODS Pediatric patients with Crohn's disease (CD; n = 40), ulcerative colitis (UC; n = 40), and controls (n = 20) were recruited. For all pediatric IBD patients, lnc-ANRIL expression in peripheral blood mononuclear cells and serum inflammatory cytokine levels were measured by RT-qPCR and ELISA, respectively. For the controls, lnc-ANRIL expression was also measured. RESULTS Lnc-ANRIL levels were lower in CD (P = 0.002) and UC (P = 0.001) patients compared with the controls; negatively correlated with C-reactive protein levels (P<0.01), erythrocyte sedimentation rate (P<0.01), disease activity (P<0.05), and severity (P<0.05) in CD and UC patients; and inversely associated with tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17, and IL-23 levels in both CD and UC patients (all P<0.01). Further subgroup analyses revealed that the association between lnc-ANRIL and inflammatory cytokines and disease activity was more remarkable in pediatric patients with moderate or severe IBD. CONCLUSION Lnc-ANRIL may serve as a potential marker for evaluating disease risk and monitoring disease activity in pediatric IBD patients.
Collapse
Affiliation(s)
- Hong Xia
- Department of Pediatrics, Xingtai People's Hospital, Xingtai, China
| | - Shaofei Li
- Department of Gastroenterology, Minmetals Hanxing Staff General Hospital, Handan, China.
| | - Yuanyuan He
- Department of Pediatrics, Xingtai People's Hospital, Xingtai, China
| | - Qingguo Ren
- Department of Pediatrics, Xingtai People's Hospital, Xingtai, China
| | - Simei Qin
- Department of Pediatrics, The Second Affiliated Hospital of Baotou Medical College, Baotou, China
| |
Collapse
|
|
47
|
Kante B, Sahu P, Kedia S, Vuyyuru SK, Soni K, Singhal M, Sharma R, Makharia G, Ahuja V. Efficacy and tolerability of hyperbaric oxygen therapy in small bowel stricturing Crohn's disease: a pilot study. Intest Res 2022; 20:231-239. [PMID: 35124954 PMCID: PMC9081995 DOI: 10.5217/ir.2021.00056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/14/2021] [Accepted: 06/30/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND/AIMS Existing therapeutic options for complicated Crohn's disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD. METHODS This pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5-2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months. RESULTS Fourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3-20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03). CONCLUSIONS HBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment.
Collapse
Affiliation(s)
- Bhaskar Kante
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer K. Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Kapil Soni
- Department of Anesthesia, All India Institute of Medical Sciences, New Delhi, India
| | - Maneesh Singhal
- Department of Plastic Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
48
|
Abo El Ela A, Meuli N, Hruz P, Burri E. Faecal calprotectin increases the diagnostic yield in patients with suspected small bowel disease - a multicenter retrospective cohort study. Swiss Med Wkly 2022; 153:40050. [PMID: 37096776 DOI: 10.57187/smw.2023.40050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2023] Open
Abstract
AIM OF THE STUDY Diagnosing small bowel pathology is challenging, and the diagnostic yield of small bowel capsule endoscopy is highly variable. Faecal calprotectin is a non-invasive intestinal inflammation marker that could be used as a selection tool to identify patients who might benefit from small bowel capsule endoscopy and increase its diagnostic yield. This study aimed to investigate the value of faecal calprotectin in detecting small bowel lesions in an unselected patient population. METHODS We performed a retrospective analysis of consecutive patients who underwent small bowel capsule endoscopy at the University Hospital Basel and the University Medical Clinic Cantonal Hospital Baselland, Switzerland, between 2010 and 2018. Patients without faecal calprotectin testing were excluded from the analysis. The primary endpoint was the presence of a clinically significant small bowel finding. RESULTS Patients with positive faecal calprotectin results were more likely to have small bowel findings (66.7% vs 39.4%; P = 0.007). The optimal faecal calprotectin cut-off to identify clinically significant small bowel lesions was 63 μg/g with 78.3% (95% confidence interval: 66.7-87.9) sensitivity, 47.9% (33.3-62.8) specificity, 1.50 (1.1-2.0) positive and 0.45 (0.3-0.8) negative likelihood ratios, 68.4% (61.6-74.4) positive and 60.5% (47.3-72.4) negative predictive values, and 65.0% overall accuracy. Faecal calprotectin performed best in patients with suspected inflammatory bowel disease, with 66.7% (48.2-82.0) sensitivity, 70.6% (44.0-89.7) specificity, 2.27 (1.0-4.9) positive and 0.47 (0.3-0.8) negative likelihood ratios, 81.5% (67.0-90.5) positive and 54.5% (39.7-68.6) negative predictive values, and 71.4% overall accuracy. CONCLUSION Faecal calprotectin testing increases the diagnostic yield of small bowel capsule endoscopy and may help identify patients at risk of small bowel disease.
Collapse
Affiliation(s)
- Aisha Abo El Ela
- Gastroenterology and Hepatology, University Medical Clinic, Kantonsspital Baselland, Liestal, Switzerland
- Universitäres Bauchzentrum Basel, Clarunis, Basel, Switzerland
| | - Nina Meuli
- Gastroenterology and Hepatology, University Medical Clinic, Kantonsspital Baselland, Liestal, Switzerland
| | - Petr Hruz
- Gastroenterology and Hepatology, University Medical Clinic, Kantonsspital Baselland, Liestal, Switzerland
| | - Emanuel Burri
- Gastroenterology and Hepatology, University Medical Clinic, Kantonsspital Baselland, Liestal, Switzerland
| |
Collapse
|
|
49
|
Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, Li G, Zhang J, Zeng X, Chen J, Liu H, Wu H. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial. EClinicalMedicine 2022; 45:101300. [PMID: 35198926 PMCID: PMC8850329 DOI: 10.1016/j.eclinm.2022.101300] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 01/16/2022] [Accepted: 01/24/2022] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The efficacy and mechanisms of acupuncture for Crohn's disease (CD) are not well understood. We investigated its effects on symptoms, intestinal microbiota, and circulating inflammatory markers in CD patients. METHODS This 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks. Clinicaltrials.gov: NCT02559037. FINDINGS At week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture. INTERPRETATION Acupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines. FUNDING National Key Basic Research Program of China (2015CB554500 and 2009CB522900), Shanghai Rising-Star Program (19QA1408100).
Collapse
Key Words
- Acupuncture
- Alternative therapy
- CD, Crohn's disease
- CDAI, Crohn's disease activity index
- CDEIS, Crohn's disease endoscopic index of severity
- CRP, C-reactive protein
- DAO, diamine oxidase
- Gut microbes
- HCs, healthy control subjects
- HS, histopathological score
- IBD, inflammatory bowel disease
- ITT, intention to treat
- Inflammatory bowel disease
- Intestinal barrier
- LEfSe, linear discriminant analysis effect size
- LPS, lipopolysaccharides
- OTU, operational taxonomic unit
- PP, per-protocol
- SCFAs, short chain fatty acids
Collapse
Affiliation(s)
- Chunhui Bao
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Luyi Wu
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Di Wang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Liming Chen
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Xiaoming Jin
- Department of Anatomy and Cell Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Yin Shi
- Outpatient Department, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Guona Li
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Jingzhi Zhang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Xiaoqing Zeng
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jianhua Chen
- Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Huirong Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
- Corresponding authors at: Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
| | - Huangan Wu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
- Corresponding authors at: Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
| |
Collapse
|
|
50
|
Medical Treatment of Intestinal Crohn's disease. SEMINARS IN COLON AND RECTAL SURGERY 2022. [DOI: 10.1016/j.scrs.2022.100862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|