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Fennessy A, Doyle M, Boland A, Bourke R, O'Connor A. Four-strain probiotic exerts a positive effect on irritable bowel syndrome symptoms occurring in inflammatory bowel diseases in absence of inflammation (train-IBD trial). World J Gastrointest Pharmacol Ther 2025; 16:101268. [DOI: 10.4292/wjgpt.v16.i2.101268] [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: 09/09/2024] [Revised: 01/16/2025] [Accepted: 04/25/2025] [Indexed: 06/03/2025] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) symptoms are common in patients with inflammatory bowel disease (IBD), with systematic review reporting an overall pooled prevalence of 35-39% in patients with clinical remission. This subset of patients reports a reduced quality of life and increased anxiety and depression. A multi-strain probiotic (Symprove™, Symprove Ltd, Farnham, United Kingdom) has been shown to improve overall symptom severity in patients with IBS and is associated with decreased intestinal inflammation in patients with ulcerative colitis (UC), but not in Crohn’s disease (CD).
AIM To ascertain whether this multi-strain probiotic would be effective in an IBS/IBD overlap population.
METHODS The treatment of symptoms in the absence of inflammation in inflammatory bowel diseases trial was a randomized, double-blind, placebo-controlled trial of a four-strain probiotic Symprove, containing Lactobacillus rhamnosus NCIMB 30174, Lactobacillus plantarum NCIMB 30173, Lactobacillus acidophilus NCIMB 30175 and Enterococcus faecium NCIMB 30176. The duration of the study was 3 months, at the end of which IBS-Symptom Severity Score (IBS-SSS) was repeated. Primary Endpoint was a 100-point reduction in IBS-SSS.
RESULTS 61 participants were randomized into the intention-to-treat analysis. 45% of patients receiving the active agent achieved the endpoint compared to 33% of those receiving placebo (P = 0.42). In UC, 50% of patients receiving placebo achieved the endpoint compared to 44% of those receiving the active agent (P = 1.00). In CD 45% of those receiving the active agent achieved the endpoint compared to 29% of those receiving placebo (P = 0.34). The mean change in IBS-SSS for patients receiving placebo was a reduction of 61 points, compared to a reduction in 90 points for patients receiving active agent (P = 0.31). There was no difference between the groups with regard to IBD outcomes.
CONCLUSION Probiotics may represent a safe and effective means of addressing the unmet clinical need for symptom relief in patients with overlapping IBS and IBD, especially in those with CD.
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Affiliation(s)
- Anne Fennessy
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24NR0A, Ireland
| | - Micheal Doyle
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24NR0A, Ireland
| | - Anna Boland
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24NR0A, Ireland
| | - Rachel Bourke
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24NR0A, Ireland
| | - Anthony O'Connor
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24NR0A, Ireland
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Cenni S, Colucci A, Salomone S, Pacella D, Casertano M, Buono P, Martinelli M, Miele E, Staiano A, Strisciuglio C. The prevalence of constipation in children with new diagnosis of inflammatory bowel disease: A retrospective study. J Pediatr Gastroenterol Nutr 2025; 80:799-806. [PMID: 39935294 DOI: 10.1002/jpn3.70005] [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: 09/25/2023] [Revised: 12/05/2024] [Accepted: 01/10/2025] [Indexed: 02/13/2025]
Abstract
OBJECTIVES Functional constipation (FC) is a common problem in childhood and the first-line therapy is macrogol. The role of FC in the onset of inflammatory bowel disease (IBD) is poorly understood. Our main aim was to investigate the prevalence of FC in children before the diagnosis of IBD. METHODS This is a cross-sectional observational study in pediatric IBD-patients. We collected data on demographics, clinical and endoscopic characteristics at IBD diagnosis, and on the presence of FC and its treatment before IBD diagnosis. RESULTS A total of 238 children with IBD, 104 (44%) with Crohn disease (CD), 130 (56%) with ulcerative colitis (UC) and 4 (0.016%) with IBD Unclassified (IBD-U) were enrolled. The mean age was 174 ± 47 months, 56% were male. Forty-seven out of 238 (19.7%) had a FC history before the IBD diagnosis and 31 out of these 47 patients (65%) received macrogol therapy. In the FC group, we found a delay in the diagnosis of IBD compared to the group with no FC [median (interquartile range [IQR]): 5 months (2.5-9.5) and 2 months (0-4), respectively, p ≤ 0.001]. The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively). CONCLUSION In conclusion our study highlighted a prevalence of constipation in pediatric IBD patients at diagnosis of 19.7%, which must be taken into account to avoid diagnostic delay and which is associated with limited extent of disease in UC pediatric patients.
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Affiliation(s)
- Sabrina Cenni
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Antonio Colucci
- Department of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Simona Salomone
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy
| | - Daniela Pacella
- Department of Public Health, University of Naples "Federico II", Naples, Italy
| | - Marianna Casertano
- Department of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pietro Buono
- Directorate general of health, Campania Region, Naples, Italy
| | - Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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Zhao Q, Shao M, Ma L, Zhou R. Insights into Modeling Inflammatory Bowel Disease from Stem Cell Derived Intestinal Organoids. Stem Cell Rev Rep 2025:10.1007/s12015-025-10887-8. [PMID: 40299197 DOI: 10.1007/s12015-025-10887-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2025] [Indexed: 04/30/2025]
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial, immune-mediated condition marked by chronic gastrointestinal inflammation. This condition significantly impairs patients' quality of life and represents a major public health challenge globally. Pathogenesis of IBD arises from complex interplay among genetic predisposition, environmental factors, immune dysregulation, and microbial dysbiosis. Although significant strides have been made in unraveling these mechanisms, existing therapeutic options remain inadequate in addressing the full spectrum of clinical needs, underscoring the urgent demand for innovative strategies. Regenerative medicine has emerged as a promising frontier, offering novel tools for therapeutic development. We briefly consolidated current knowledge on IBD pathogenesis and treatments, emphasized the pivotal potential of human intestinal organoids (including adult stem cell-derived organoids and pluripotent stem cell- derived organoids) as a robust platform for mechanistic studies and treatment exploration. Leveraging this technology, we aim to advance personalized and next-generation therapies for IBD.
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Affiliation(s)
- Qi Zhao
- The Affiliated Wenling Hospital of Wenzhou Medical University (The First People's Hospital of Wenling), Taizhou, Zhejiang Province, China
| | - Miaoli Shao
- The Affiliated Wenling Hospital of Wenzhou Medical University (The First People's Hospital of Wenling), Taizhou, Zhejiang Province, China
| | - Lisha Ma
- The Affiliated Wenling Hospital of Wenzhou Medical University (The First People's Hospital of Wenling), Taizhou, Zhejiang Province, China
| | - Renfang Zhou
- The Affiliated Wenling Hospital of Wenzhou Medical University (The First People's Hospital of Wenling), Taizhou, Zhejiang Province, China.
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4
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Bakhshaie J, Smit T, Bradford A, Lackner JM, Zvolensky MJ. Gastrointestinal-specific anxiety as a transdiagnostic mechanism involved in persons with irritable bowel syndrome who smoke. J Health Psychol 2025:13591053251333950. [PMID: 40265221 DOI: 10.1177/13591053251333950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that imposes significant life impairment. Smoking is an addictive and potentially exacerbating behavior that may be important to IBS, but the psychological factors linking IBS and smoking remain underexplored. This study aims to investigate gastrointestinal-specific anxiety (GI-specific anxiety) in relation to smoking processes among adults with IBS who smoke. The sample consisted of 263 adults who met the criteria for IBS and reported smoking at least 5 cigarettes per day for the past year (Mean age = 44.1 years, SD = 12.71, 52.1% female). Hierarchical regression results indicated that higher GI-specific anxiety was statistically significantly associated with greater perceived barriers for smoking cessation, increased negative affect reduction smoking expectancies, and stronger urges to smoke for relief of negative affect. The present investigation found that GI-specific anxiety is an important construct informing smoking among individuals with IBS. Future research considerations are explored.
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Affiliation(s)
- Jafar Bakhshaie
- Harvard Medical School, Massachusetts General Hospital, USA
- University of Houston, USA
- Baylor College of Medicine, USA
| | | | | | | | - Michael J Zvolensky
- University of Houston, USA
- The University of Texas MD Anderson Cancer Center, USA
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Saleh AA, Waghela R, Amini S, Moskow J, Irani M, Fan C, Glassner K, Abraham BP. A Guide to De-escalation of Combination Therapy in Inflammatory Bowel Disease: A Retrospective Cohort Study. CROHN'S & COLITIS 360 2025; 7:otaf026. [PMID: 40321837 PMCID: PMC12048838 DOI: 10.1093/crocol/otaf026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Indexed: 05/08/2025] Open
Abstract
Background Advanced combination therapy with biologics and small molecules has seen more widespread implementation for inflammatory bowel disease (IBD). However, there is a paucity of data available to guide the successful de-escalation of combination therapy following the achievement of disease remission. Therefore, we pursued this retrospective study to evaluate our center's approach to de-escalation of these patients. Methods IBD patients undergoing de-escalation of combination biologic therapy from May 2017 to March 2023 with a follow-up visit were included. The need for re-escalation, steroid therapy, and hospitalization at follow-up was compared between the de-escalation method, adherence, patient demographics, disease characteristics, and measures of disease activity. Results Fifty IBD patients underwent de-escalation, with a median age of 35.7 years. All 50 patients had a follow-up visit within a median of 168 (111) days. Patients were divided into two groups with 12 (24%) patients requiring re-escalation of therapy and 38 (76%) able to maintain or further de-escalate. Of those that required re-escalation, 3 (25%) required the use of systemic steroids and none required hospitalization for IBD. Non-adherence to the de-escalation plan significantly correlated with the need for re-escalation (P < .001). Conclusions Patient adherence and the number of prior failed biologic therapies were identified as potential risk factors for re-escalation. The type of agent being de-escalated (biologic or Janus kinase inhibitors [JAKi] did not correlate with the need for re-escalation).
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Affiliation(s)
- Adam A Saleh
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Rajdeepsingh Waghela
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Shayan Amini
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Joshua Moskow
- Texas A&M College of Engineering Medicine, Houston, TX, USA
| | - Malcom Irani
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Christopher Fan
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Kerri Glassner
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
| | - Bincy P Abraham
- Houston Methodist Hospital, Underwood Center for Digestive Diseases, Fondren Inflammatory Bowel Disease Center, Houston, TX, USA
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Wespi N, Vavricka S, Brand S, Aepli P, Burri E, Misselwitz B, Seibold F, Hruz P, Peyrin‐Biroulet L, Schoepfer A, Biedermann L, Sokollik C, Rogler G, Greuter T. Fecal urgency and incontinence in inflammatory bowel disease perceived by physician and patient: Results from the Swiss fecal urgency survey. United European Gastroenterol J 2025; 13:392-401. [PMID: 39246002 PMCID: PMC11999039 DOI: 10.1002/ueg2.12657] [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: 05/09/2024] [Accepted: 08/06/2024] [Indexed: 09/10/2024] Open
Abstract
INTRODUCTION Although increasingly appreciated, little is known about the prevalence of fecal urgency, fecal incontinence and differences between patients' and physicians' perception in inflammatory bowel disease (IBD). METHODS We performed an online patient and physician survey to evaluate the assessment, prevalence and impact of fecal urgency and incontinence in IBD. RESULTS A total of 593 patients (44.0% ulcerative colitis (UC), 53.5% Crohn's disease (CD), 2.2% indeterminate colitis, 2 not specified) completed the survey (65.8% females, mean age 47.1 years). Fecal urgency was often reported (UC: 98.5%, CD: 96.2%) and was prevalent even during remission (UC: 65.9%, CD: 68.5%). Fecal urgency considerably impacted daily activities (visual analog scale [VAS] 5, IQR 3-8). Yet, 22.8% of patients have never discussed fecal urgency with their physicians. Fecal incontinence was experienced by 44.7% of patients and 7.9% on a weekly basis. Diapers/pads were required at least once a month in 20.4% of patients. However, 29.7% of patients never talked with their physician about fecal incontinence. UC was an independent predictor for the presence of moderate-severe fecal urgency (OR 1.65, 95% CI 1.13-2.41) and fecal incontinence (OR 1.77, 95% CI 1.22-2.59). All physicians claimed to regularly inquire about fecal urgency and incontinence. However, the impact of these symptoms on daily activities was overestimated compared with the patient feedback (median VAS 8 vs. 5, p = 0.0113, and 9 vs. 5, p = 0.0187). CONCLUSIONS Fecal urgency and incontinence are burdensome symptoms in IBD, with a similar prevalence in UC and CD. A mismatch was found between the physician and patient perception. These symptoms should be addressed during outpatient visits.
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Affiliation(s)
- Nadia Wespi
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Stephan Vavricka
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Stephan Brand
- Division of Gastroenterology and HepatologyCantonal Hospital St. GallenSt. GallenSwitzerland
| | - Patrick Aepli
- Division of Gastroenterology and HepatologyCantonal Hospital LucerneLucerneSwitzerland
| | - Emanuel Burri
- Division of Gastroenterology and HepatologyUniversity Medical ClinicCantonal Hospital BasellandLiestalSwitzerland
| | - Benjamin Misselwitz
- Department of Visceral Surgery and MedicineBern University HospitalUniversity of BernBernSwitzerland
| | | | - Petr Hruz
- Division of Gastroenterology and HepatologyClarunisUniversity Hospital BaselBaselSwitzerland
| | - Laurent Peyrin‐Biroulet
- Department of GastroenterologyINFINY InstituteFHU‐CUREINSERM NGERENancy University HospitalVandœuvre‐lès‐NancyFrance
- Groupe Hospitalier privé Ambroise Paré ‐ HartmannParis IBD CenterNeuilly‐sur‐SeineFrance
- Division of Gastroenterology and HepatologyMcGill University Health CentreMontrealQuebecCanada
| | - Alain Schoepfer
- Division of Gastroenterology and HepatologyCHUV University Hospital Lausanne and University of Lausanne UNILLausanneSwitzerland
| | - Luc Biedermann
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Christiane Sokollik
- Pediatric Gastroenterology, Hepatology and NutritionChildren's HospitalBern University HospitalUniversity of BernBernSwitzerland
| | - Gerhard Rogler
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Thomas Greuter
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
- Division of Gastroenterology and HepatologyCHUV University Hospital Lausanne and University of Lausanne UNILLausanneSwitzerland
- Division of Gastroenterology and HepatologyGZO—Zurich Regional Health CenterWetzikonSwitzerland
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7
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Florio M, Crudele L, Sallustio F, Moschetta A, Cariello M, Gadaleta RM. Disentangling the nutrition-microbiota liaison in inflammatory bowel disease. Mol Aspects Med 2025; 102:101349. [PMID: 39922085 DOI: 10.1016/j.mam.2025.101349] [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: 06/05/2024] [Revised: 10/24/2024] [Accepted: 01/24/2025] [Indexed: 02/10/2025]
Abstract
Inflammatory Bowel Disease (IBD) is a set of chronic intestinal inflammatory disorders affecting the gastrointestinal (GI) tract. Beside compromised intestinal barrier function and immune hyperactivation, a common IBD feature is dysbiosis, characterized by a reduction of some strains of Firmicutes, Bacteroidetes, Actinobacteria and an increase in Proteobacteria and pathobionts. Emerging evidence points to diet and nutrition-dependent gut microbiota (GM) modulation, as etiopathogenetic factors and adjuvant therapies in IBD. Currently, no nutritional regimen shows universal efficacy, and advice are controversial, especially those involving restrictive diets potentially resulting in malnutrition. This review provides an overview of the role of macronutrients, dietary protocols and GM modulation in IBD patients. A Western-like diet contributes to an aberrant mucosal immune response to commensal bacteria and impairment of the intestinal barrier integrity, thereby triggering intestinal inflammation. Conversely, a Mediterranean nutritional pattern appears to be one of the most beneficial dietetic regimens able to restore the host intestinal physiology, by promoting eubiosis and preserving the intestinal barrier and immune function, which in turn create a virtuous cycle improving patient adherence to the pattern. Further clinical studies are warranted, to corroborate current IBD nutritional guidelines, and develop more accurate models to move forward precision nutrition and ameliorate patients' quality of life.
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Affiliation(s)
- Marilina Florio
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Lucilla Crudele
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124, Bari, Italy; INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie D'Oro 305, 00136, Rome, Italy
| | - Fabio Sallustio
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Piazza Giulio Cesare n. 11, 70124, Bari, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124, Bari, Italy; INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie D'Oro 305, 00136, Rome, Italy.
| | - Marica Cariello
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124, Bari, Italy; INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie D'Oro 305, 00136, Rome, Italy.
| | - Raffaella M Gadaleta
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124, Bari, Italy; INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie D'Oro 305, 00136, Rome, Italy.
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Jeong ES, Jung HK, Choi E, Yun K, Lee A, Kim YS. Characterization of post-inflammatory irritable bowel syndrome animal model following acute colitis recovery. Sci Rep 2025; 15:8512. [PMID: 40075091 PMCID: PMC11904205 DOI: 10.1038/s41598-025-88981-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent disorder with an unclear pathophysiology. This study aimed to investigate the features of dextran sulfate sodium (DSS)-induced low-grade inflammation using murine models of acute severe colitis (acute model) and chronic mild repeated colitis (chronic model), with potential implications for IBS research. The acute model was induced with 3% DSS for 5 days, followed by a 12-week recovery period. The chronic model involved administration of 0.5% DSS for 5 days, followed by a 5-day resting period, repeated thrice. We conducted comparative analyses to assess inflammation severity, intestinal motility, permeability, visceral hypersensitivity, and microbiome composition. In the acute model, mild leukocyte infiltration was observed, colonic transit time shortened at 12 weeks (P < 0.001), occludin expression decreased (P = 0.041), inflammatory cytokines, and transient receptor potential vanilloid 1 was upregulated in colonic mucosa (P < 0.050). In the chronic model, only mild inflammatory changes were noted. Microbiota analysis in the acute model revealed differences in microbial abundance and compositions (P = 0.001). The acute model demonstrated low-grade inflammation that caused gut dysmotility, altered permeability, and increased visceral hypersensitivity with notable microbial composition changes, potentially relevant to IBS phenotypes.
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Affiliation(s)
- Eui Sun Jeong
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
| | - Euno Choi
- Department of Pathology, College of Medicine, Ewha Womans University, Seoul, Korea
| | | | - Ayoung Lee
- Department of Internal Medicine, College of Medicine, Korea University, Ansan, Gyeonggi-do, Korea
| | - Yong Sung Kim
- Digestive Disease Research Institute, College of Medicine, Wonkwang University, Iksan, Jeonlabuk-do, Korea
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Golob J, Rao K, Berinstein JA, Singh P, Chey WD, Owyang C, Kamada N, Higgins PDR, Young V, Bishu S, Lee AA. Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways. Inflamm Bowel Dis 2025; 31:763-776. [PMID: 39541261 PMCID: PMC11879174 DOI: 10.1093/ibd/izae238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S. METHODS We performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls. RESULTS Thirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S. DISCUSSION Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.
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Affiliation(s)
- Jonathan Golob
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Krishna Rao
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Jeffrey A Berinstein
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Prashant Singh
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - William D Chey
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Chung Owyang
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Nobuhiko Kamada
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Peter D R Higgins
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Vincent Young
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
| | - Shrinivas Bishu
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Allen A Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
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Vieujean S, Jairath V, Peyrin-Biroulet L, Dubinsky M, Iacucci M, Magro F, Danese S. Understanding the therapeutic toolkit for inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2025:10.1038/s41575-024-01035-7. [PMID: 39891014 DOI: 10.1038/s41575-024-01035-7] [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] [Accepted: 12/19/2024] [Indexed: 02/03/2025]
Abstract
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician-patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice.
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Vandœuvre-lès-Nancy, France
| | - Vipul Jairath
- Division of Gastroenterology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, CHRU Nancy, Vandœuvre-lès-Nancy, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Marla Dubinsky
- Department of Paediatrics, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Fernando Magro
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy.
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11
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Isoldi S, Mallardo S, Quitadamo P, Leter B, Cucchiara S. Review on Advances in Pediatric Endoscopy in the Management of Inflammatory Bowel Disease. Curr Pediatr Rev 2025; 21:154-165. [PMID: 38265388 DOI: 10.2174/0115733963268547231128101929] [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: 06/22/2023] [Revised: 08/26/2023] [Accepted: 10/19/2023] [Indexed: 01/25/2024]
Abstract
Over the past decades, an increased importance has been given to gastrointestinal (GI) endoscopy in the management of children with inflammatory bowel diseases (IBD), considering that mucosal healing has been recognized as the optimal endpoint in the treat-to-target paradigm. The recent advances in technology and anesthesia have facilitated the comprehensive evaluation of the GI tract. In this review, we will discuss the role of ileocolonoscopy, upper GI endoscopy, and device-assisted enteroscopy in the work-up and management of pediatric Crohn's disease (CD) and ulcerative colitis, with particular attention on non-invasive endoscopic techniques, such as wireless capsule endoscopy. We will also analyze the most commonly used endoscopic scoring systems, including small bowel scoring systems and endoscopic recurrence grading of neo-terminal ileum CD. Moreover, we will focus on the endoscopic management of complications, such as strictures, that commonly require surgery. Lastly, we will discuss cancer surveillance in children with IBD, with particular consideration of the role of high-definition endoscopic equipment and chromoendoscopy in dysplasia detection rates.
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Affiliation(s)
- Sara Isoldi
- Pediatric Gastroenterology and Hepatology Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy
- Maternal and Child Health Department, Santa Maria Goretti Hospital, Sapienza-University of Rome, Latina, Italy
| | - Saverio Mallardo
- Maternal and Child Health Department, Santa Maria Goretti Hospital, Sapienza-University of Rome, Latina, Italy
| | - Paolo Quitadamo
- Pediatric Gastroenterology and Hepatology Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - Beatrice Leter
- Department of Women's and Children's Health, Sapienza University of Rome, Rome, Italy
| | - Salvatore Cucchiara
- Department of Women's and Children's Health, Sapienza University of Rome, Rome, Italy
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12
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Goodoory VC, Riggott C, Khasawneh M, Black CJ, Ford AC. Validating Simple Modifications to the Rome IV Criteria for the Diagnosis of Irritable Bowel Syndrome in Secondary Care. Aliment Pharmacol Ther 2025; 61:354-362. [PMID: 39466700 DOI: 10.1111/apt.18363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 10/30/2024]
Abstract
BACKGROUND The Rome IV criteria for irritable bowel syndrome (IBS) may be too restrictive for clinical practice and research. AIMS To validate the Rome IV criteria and study the diagnostic performance of simple modifications to them. METHODS We collected symptom data from consecutive adults with suspected IBS seen in a single clinic. We used a reference standard to confirm IBS (presence of lower abdominal pain associated with altered stool form or frequency; no evidence of organic gastrointestinal disease after limited investigation). We applied Rome IV criteria, but also two modifications. First, we re-incorporated abdominal discomfort but kept symptom frequency required for both abdominal pain and discomfort to at least 1 day per week. Second, we included only abdominal pain but relaxed symptom frequency back to 3 days per month. We calculated sensitivity, specificity and positive and negative likelihood ratios (LRs), with 95% confidence intervals (CIs), for each diagnostic criterion. RESULTS We recruited 170 patients (76.5% female, mean age 37.9 years). Sensitivity and specificity of the Rome IV criteria were 82.1% and 85.1%, respectively; positive and negative LRs were 5.51 (95% CI 2.95-11.3) and 0.21 (95% CI 0.14-0.31), respectively. Modifying the criteria by relaxing the frequency of abdominal pain to 3 days per month led to the best performance [sensitivity 90.2%, specificity 85.1%, positive LR 6.06 (95% CI 3.25-12.2), and negative LR 0.11 (95% CI 0.07-0.19)]. CONCLUSIONS The Rome IV criteria performed well in diagnosing IBS. A simple modification relaxing the required frequency of abdominal pain improved their performance.
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Affiliation(s)
- Vivek C Goodoory
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Christy Riggott
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Mais Khasawneh
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute for Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute for Medical Research at St. James's, University of Leeds, Leeds, UK
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Barros LL, Leite G, Morales W, Barlow GM, de Azevedo MFC, de Sousa Carlos A, Damião AOMC, Pimentel M, Farias AQ. Anti-CdtB and anti-vinculin antibodies to diagnose irritable bowel syndrome in inflammatory bowel disease patients. BMC Gastroenterol 2024; 24:448. [PMID: 39627697 PMCID: PMC11613581 DOI: 10.1186/s12876-024-03509-z] [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] [Received: 08/08/2023] [Accepted: 11/12/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Despite adequate treatment, a subgroup of patients with inflammatory bowel disease (IBD), including Crohn`s disease and ulcerative colitis, have persistent gastrointestinal symptoms that are not always related to mucosal damage. Recently, two autoantibodies, anti-CdtB and anti-vinculin, were validated as post-infectious IBS (PI-IBS) markers, however there is limited evidence of its diagnostic role in IBD population. METHODS Patients with more than 3 bowel movements/day and indication of colonoscopy were enrolled. Samples were collected at the time of colonoscopy for assessment of serum levels of anti-CdtB and anti-vinculin antibodies. RESULTS A total of 160 subjects were included in 4 groups: active IBD (n = 44); quiescent IBD and chronic diarrhea IBD-IBS (n = 25); predominant-diarrhea IBS (n = 45) and controls (n = 46). The mean value of the optical density for anti-CdtB was 1.2 ± 0.65 in group 1, 1.27 ± 0.64 in group 2, 1.49 ± 0.47 in the group 3 and 1.6 ± 0.68 in group 4, p = 0.012. For anti-vinculin, optical densities were: 1.34 ± 0.78 in group 1, 1.46 ± 0.92 in group 2, 1.31 ± 0.79 in group 3 and 1.41 ± 0.86 for controls (p = 0.875). Using a cut-off of 1.56 for anti-CdtB, the positivity between groups was n = 10 (22.7%) in group 1, n = 9 (34.6%) in group 2, 19 (43.2%) in group 3, 21 (45.7%) in group 4 (p = 0.106). The positivity of anti-vinculin using a cut-off of 1.6 was n = 18 (40.9%) in group 1, n = 11 (42.3%), n = 15 (34.1%), n = 22 (47.8%) (p = 0.622). CONCLUSIONS Our findings show that anti-CdtB and anti-vinculin could not identify IBD-IBS patients or discriminate IBS-D from healthy controls.
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Affiliation(s)
- Luisa Leite Barros
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Av. Dr. Eneas C Aguiar 255, Sao Paulo-SP, 9117, Brazil
| | - Gabriela Leite
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Walter Morales
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Gillian M Barlow
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | | - Alexandre de Sousa Carlos
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Av. Dr. Eneas C Aguiar 255, Sao Paulo-SP, 9117, Brazil
| | | | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Alberto Queiroz Farias
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Av. Dr. Eneas C Aguiar 255, Sao Paulo-SP, 9117, Brazil.
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Klemm N, Moosavi S. Chronic Abdominal Pain in Patients with Inflammatory Bowel Disease in Remission: A Continuing Challenge for Clinicians. Dig Dis Sci 2024; 69:4336-4346. [PMID: 39537891 DOI: 10.1007/s10620-024-08716-y] [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: 06/06/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic condition that includes ulcerative colitis and Crohn's disease. It is characterized by a relapsing and remitting pattern that negatively impacts quality of life (QoL). Current goals of treatment involve symptomatic, biochemical, and endoscopic remission in a treat-to-target approach. Despite effective treatment and remission of IBD, many patients report frequent and isolated abdominal pain. A wide range of etiologies exist, including surgery-related, infections, pelvic conditions, immune-related, and systemic illnesses. Disorders of the gut-brain interaction (DGBI), frequently characterized by abdominal pain, are increasingly recognized in IBD patients, including those with quiescent disease. Various mechanisms are involved and numerous non-pharmacologic and pharmacologic therapies have been proposed. Hereby, we outline the pertinent findings of the literature on management of chronic abdominal pain, focusing on quiescent IBD.
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Affiliation(s)
- Natasha Klemm
- Department of Gastroenterology, University of British Columbia, Vancouver, V5Z 1M9, Canada.
| | - Sarvee Moosavi
- Neurogastroenterology & GI Motility, Department of Gastroenterology, University of British Columbia, Vancouver, Canada
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15
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Peropat F, Abbas MI, Perez ME, Yu EL, Leiby A. Yoga in Pediatric Gastroenterology. Curr Gastroenterol Rep 2024; 26:335-341. [PMID: 39134867 PMCID: PMC11496368 DOI: 10.1007/s11894-024-00941-9] [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] [Accepted: 07/24/2024] [Indexed: 09/07/2024]
Abstract
PURPOSE OF REVIEW Pediatric use of yoga as an integrative medicine modality has increased in prevalence over the last several decades. In this article, we review the available evidence for yoga in pediatric gastrointestinal disorders. RECENT FINDINGS Evidence supports that in many pediatric disorders of gut brain interaction (DGBI), including irritable bowel syndrome, functional abdominal pain and functional dyspepsia, yoga decreases pain intensity and frequency and increases school attendance. Yoga has been shown to improve health-related quality of life and improve stress management as an effective adjunct to standard medical therapy in pediatric inflammatory bowel disease (IBD). Further studies are needed regarding optimal frequency, duration of practice and evaluation of the impact on IBD disease activity measures. Yoga may benefit pediatric gastroenterology patients with DGBIs and IBD through improving quality of life and reducing pain. Future yoga studies could investigate biomarkers and continued research will help integrate this modality into routine pediatric gastroenterology care.
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Affiliation(s)
- Francis Peropat
- Atlantic Children's Health-Goryeb Children's Hospital, Morristown, NJ, USA
| | - Mazen I Abbas
- Kapi'olani Medical Center for Women and Children, Pediatric Gastroenterology, Honolulu, HI, USA
| | - Maria E Perez
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Ann and Robert H. Lurie Children's Hospital, Chicago, IL, USA
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Elizabeth L Yu
- Division of Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital, San Diego, CA, USA
- Department of Pediatrics, University of California, San Diego, CA, USA
| | - Alycia Leiby
- Atlantic Children's Health-Goryeb Children's Hospital, Pediatric Gastroenterology and Nutrition, Morristown, NJ, USA.
- Department of Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
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16
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Salwen-Deremer JK, Westvold SJ, Siegel CA, Smith MT. The Bidirectional Relationship Between Sleep and Pain in Crohn's Disease: A Daily Diary Study. Inflamm Bowel Dis 2024:izae265. [PMID: 39536319 DOI: 10.1093/ibd/izae265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Pain is common in Crohn's disease (CD) even after endoscopic healing is achieved. Depression, sleep disturbances, fatigue, and worry about pain impact the pain experience. There is a bidirectional relationship between sleep and pain, though it has received minimal attention in CD. Herein, we sought to comprehensively assess this relationship in CD using daily diaries. METHOD Patients with active symptoms of insomnia and CD were recruited as part of an ongoing clinical trial. Participants completed 14-day diaries on sleep patterns and CD symptoms. Temporal associations between sleep and pain were assessed using cross-lagged path analysis and controlled for age, sex, and menstrual cycle. RESULTS Overall, 26 participants completed 14-day diaries. All assessed aspects of sleep continuity disturbance were associated with worse next-day abdominal pain (Ps < 0.01). When assessed microlongitudinally, sleep onset latency predicted next-day pain (P = 0.07) and vice versa (P = 0.03). Similarly, nightly awakenings predicted next day pain (P = 0.02) and vice versa (P = 0.04). Sleep efficiency (P = 0.003), sleep quality (P < 0.001), and total sleep time (P = 0.04) predicted next-day pain whereas models with pain as the predictor were not significant. CONCLUSIONS Sleep continuity and abdominal pain are closely related, with sleep efficiency, total sleep time, and sleep quality potentially driving next-day abdominal pain. As interventions for pain in IBD are limited, it may be important to capitalize on the impact of sleep disturbances on pain to optimize overall wellbeing in people with CD.
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Affiliation(s)
- Jessica K Salwen-Deremer
- Department of Psychiatry, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA
- Center for Digestive Health, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA
| | - Sarah J Westvold
- General Internal Medicine, Yale School of Medicine, 333 Cedar St, New Haven, CT 06510, USA
| | - Corey A Siegel
- Center for Digestive Health, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA
| | - Michael T Smith
- Department of Psychology and Behavioral Sciences, Johns Hopkins School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA
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Olson JL, Palumbo A, Desjardins C, Wicks C, Bhopa S, Cheyne K, D'Silva A, Graff LA, Narula N, Rodrigues DM, Fernandes A, Marshall DA, Moayyedi P, Presseau J. Perspectives on the sustained engagement with digital health tools: protocol for a qualitative interview study among people living with Inflammatory Bowel Disease or irritable bowel syndrome. BMJ Open 2024; 14:e089220. [PMID: 39521469 PMCID: PMC11551993 DOI: 10.1136/bmjopen-2024-089220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 08/28/2024] [Indexed: 11/16/2024] Open
Abstract
INTRODUCTION Digital health tools can be beneficial in the care of patients with chronic conditions and have the potential for widespread impact as readily scalable and cost-effective health interventions. However, benefits are often contingent on users sustaining their engagement with these tools over time. Sustained engagement with digital health tools can be challenging, and high rates of attrition from digital interventions are common. Inflammatory Bowel Disease (IBD) and irritable bowel syndrome (IBS) are prominent gastrointestinal conditions resulting in significant burdens for individuals and society. Emerging evidence suggests digital health tools can be beneficial for IBD and IBS management; however, it is not clear what barriers and enablers are experienced by people living with these conditions to sustaining their engagement with these tools, when necessary. Such knowledge could inform the tailoring of new and existing digital health tools to the needs of people living with IBD and/or IBS. This study will seek to identify the barriers and enablers of sustained engagement with digital health tools among adults living with IBD and/or IBS. METHODS AND ANALYSIS We will conduct semistructured interviews with a purposive sample of approximately 30 adults (>18 years) who (a) reside in Canada, (b) self-report that they have been diagnosed with IBD and/or IBS, (c) have ever used a digital health tool (ie, any application/platform) to manage their condition and (d) are capable of providing informed consent. Interviews will be audio and video recorded and transcribed verbatim. Data will be coded deductively and barriers and enablers to sustained engagement will be categorised in accordance with the Theoretical Domains Framework. Data analysis will be verified by a patient research partner. ETHICS AND DISSEMINATION The study has been approved by the Ottawa Health Science Network Research Ethics Board. The findings will inform the codevelopment of strategies to overcome modifiable barriers and leverage identified enablers of sustained engagement with digital health tools for IBD and IBS care. These strategies can inform the design of new, or modifications to existing, digital health tools for IBD and IBS care where sustained engagement is desirable. Strategies will be compiled into a guidebook and disseminated via the Inflammation, Microbiome and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects (IMAGINE) Strategy for Patient Oriented Research chronic disease network in Canada.
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Affiliation(s)
- Jenny L Olson
- Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Amelia Palumbo
- Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Chloé Desjardins
- Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Chantel Wicks
- IMAGINE Network, McMaster University, Hamilton, Ontario, Canada
| | - Shania Bhopa
- Global Health Program, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
| | - Kelsey Cheyne
- Canadian Digestive Health Foundation, Oakville, Ontario, Canada
| | - Adrijana D'Silva
- Department of Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Lesley A Graff
- Department of Clinical Health Psychology, University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada
| | - Neeraj Narula
- Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Ontario, Canada
| | - David M Rodrigues
- Division of Gastroenterology, Queen's University School of Medicine, Kingston, Ontario, Canada
| | - Aida Fernandes
- IMAGINE Network, McMaster University, Hamilton, Ontario, Canada
| | - Deborah A Marshall
- IMAGINE Network, McMaster University, Hamilton, Ontario, Canada
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Paul Moayyedi
- IMAGINE Network, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Institute, McMaster University, Hamilton, Ontario, Canada
| | - Justin Presseau
- Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health and Department of Psychology, University of Ottawa, Ottawa, Ontario, Canada
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18
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Luo Z, Huang C, Chen J, Chen Y, Yang H, Wu Q, Lu F, Zhang TE. Potential diagnostic markers and therapeutic targets for non-alcoholic fatty liver disease and ulcerative colitis based on bioinformatics analysis and machine learning. Front Med (Lausanne) 2024; 11:1323859. [PMID: 39568749 PMCID: PMC11576177 DOI: 10.3389/fmed.2024.1323859] [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] [Received: 11/07/2023] [Accepted: 10/21/2024] [Indexed: 11/22/2024] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) and ulcerative colitis (UC) are two common health issues that have gained significant global attention. Previous studies have suggested a possible connection between NAFLD and UC, but the underlying pathophysiology remains unclear. This study investigates common genes, underlying pathogenesis mechanisms, identification of diagnostic markers applicable to both conditions, and exploration of potential therapeutic targets shared by NAFLD and UC. Methods We obtained datasets for NAFLD and UC from the GEO database. The DEGs in the GSE89632 dataset of the NAFLD and GSE87466 of the UC dataset were analyzed. WGCNA, a powerful tool for identifying modules of highly correlated genes, was employed for both datasets. The DEGs of NAFLD and UC and the modular genes were then intersected to obtain shared genes. Functional enrichment analysis was conducted on these shared genes. Next, we utilize the STRING database to establish a PPI network. To enhance visualization, we employ Cytoscape software. Subsequently, the Cytohubba algorithm within Cytoscape was used to identify central genes. Diagnostic biomarkers were initially screened using LASSO regression and SVM methods. The diagnostic value of ROC curve analysis was assessed to detect diagnostic genes in both training and validation sets for NAFLD and UC. A nomogram was also developed to evaluate diagnostic efficacy. Additionally, we used the CIBERSORT algorithm to explore immune infiltration patterns in both NAFLD and UC samples. Finally, we investigated the correlation between hub gene expression, diagnostic gene expression, and immune infiltration levels. Results We identified 34 shared genes that were found to be associated with both NAFLD and UC. These genes were subjected to enrichment analysis, which revealed significant enrichment in several pathways, including the IL-17 signaling pathway, Rheumatoid arthritis, and Chagas disease. One optimal candidate gene was selected through LASSO regression and SVM: CCL2. The ROC curve confirmed the presence of CCL2 in both the NAFLD and UC training sets and other validation sets. This finding was further validated using a nomogram in the validation set. Additionally, the expression levels of CCL2 for NAFLD and UC showed a significant correlation with immune cell infiltration. Conclusion This study identified a gene (CCL2) as a biomarker for NAFLD and UC, which may actively participate in the progression of NAFLD and UC. This discovery holds significant implications for understanding the progression of these diseases and potentially developing more effective diagnostic and treatment strategies.
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Affiliation(s)
- Zheng Luo
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cong Huang
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Biology Laboratory for TCM Viscera-Manifestation Research of Sichuan University, Chinese Medical Center of Chengdu University of TCM, Chengdu, China
| | - Jilan Chen
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Biology Laboratory for TCM Viscera-Manifestation Research of Sichuan University, Chinese Medical Center of Chengdu University of TCM, Chengdu, China
| | - Yunhui Chen
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hongya Yang
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiaofeng Wu
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fating Lu
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Tian E Zhang
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Biology Laboratory for TCM Viscera-Manifestation Research of Sichuan University, Chinese Medical Center of Chengdu University of TCM, Chengdu, China
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Hybelius J, Kosic A, Salomonsson S, Wachtler C, Wallert J, Nordin S, Axelsson E. Measurement Properties of the Patient Health Questionnaire-15 and Somatic Symptom Scale-8: A Systematic Review and Meta-Analysis. JAMA Netw Open 2024; 7:e2446603. [PMID: 39565620 PMCID: PMC11579800 DOI: 10.1001/jamanetworkopen.2024.46603] [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: 04/30/2024] [Accepted: 10/01/2024] [Indexed: 11/21/2024] Open
Abstract
Importance The subjective experience of somatic symptoms is a key concern throughout the health care system. Valid and clinically useful instruments are needed. Objective To evaluate the measurement properties of 2 widespread patient-reported outcomes: the Patient Health Questionnaire-15 (PHQ-15) and Somatic Symptom Scale-8 (SSS-8). Data Sources Medline, PsycINFO, and Web of Science were last searched February 1, 2024. Study Selection English-language studies reporting estimates pertaining to factor analysis, taxometric analysis, internal consistency, construct validity, mean scores in relevant groups, cutoffs, areas under the receiver operating characteristic curves (AUROCs), minimal clinically important difference, test-retest reliability, or sensitivity to change. Data Extraction and Synthesis Search hits were reviewed by independent raters. Cronbach α, Pearson r, means, and between-group effect sizes indicative of sensitivity to change were pooled in random-effects meta-analysis. Study quality was assessed using 3 instruments. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 reporting guideline. Main Outcomes and Measures Comprehensive overview of evidence pertaining to the measurement properties of the PHQ-15 and SSS-8. Results A total of 305 studies with 361 243 participants were included. Most concerned routine care (178 studies) and the general population (27 studies). In factor analyses, both scales reflected a combination of domain-specific factors (cardiopulmonary, fatigue, gastrointestinal, pain) and a general symptom burden factor. The pooled PHQ-15 α was 0.81 (95% CI, 0.80-0.82), but with low item-total correlations for items concerning menstrual problems, fainting spells, and sexual problems (item-total correlations <0.40), and the SSS-8 α was 0.80 (0.77-0.83). Pooled correlations with other measures of somatic symptom burden were 0.71 (95% CI, 0.64-0.78) for the PHQ-15 and 0.82 (95% CI, 0.72-0.92) for the SSS-8. Reported AUROCs for identification of somatoform disorders ranged from 0.63 (95% CI, 0.50-0.76) to 0.79 (95% CI, 0.73-0.85) for the PHQ-15 and from 0.71 (95% CI, 0.66-0.77) to 0.73 (95% CI, 0.69-0.76) for the SSS-8. The minimal clinically important difference on both scales was 3 points. Test-retest reliability could not be pooled and was inconsistent for the PHQ-15 (PHQ-15: r = 0.65-0.93; ICC, 0.87; SSS-8: r = 0.996, ICC = 0.89). The PHQ-15 showed tentative sensitivity to change (g = 0.32; 95% CI, 0.08-0.56), but data for the SSS-8 were lacking. Conclusions and Relevance In this systematic review and meta-analysis, findings supported use of the PHQ-15 and SSS-8 for the assessment of symptom burden, but users should be aware of the complex, multifactorial structures of these scales. More evidence is needed concerning longitudinal measurement properties.
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Affiliation(s)
- Jonna Hybelius
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
- Liljeholmen University Primary Health Care Centre, Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden
| | - Amanda Kosic
- School of Law, Psychology and Social Work, Örebro University, Örebro, Sweden
| | - Sigrid Salomonsson
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Caroline Wachtler
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
- Liljeholmen University Primary Health Care Centre, Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden
| | - John Wallert
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Steven Nordin
- Department of Psychology, Umeå University, Umeå, Sweden
| | - Erland Axelsson
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
- Liljeholmen University Primary Health Care Centre, Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden
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Bai B, Yin H, Wang H, Liu F, Liang Y, Liu A, Guo L, Ma H, Geng Q. The combined effects of depression or anxiety with high-sensitivity C-reactive protein in predicting the prognosis of coronary heart disease patients. BMC Psychiatry 2024; 24:717. [PMID: 39438827 PMCID: PMC11515698 DOI: 10.1186/s12888-024-06158-4] [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: 10/23/2023] [Accepted: 10/08/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Depression, anxiety and high-sensitivity C-reactive protein (hs-CRP) are individually associated with poor prognosis in patients with coronary heart disease (CHD). However, the combined effects of depression with inflammation or anxiety with inflammation on the prognosis have been rarely explored. METHODS This prospective cohort study included 414 patients diagnosed with CHD. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression and anxiety. A score ≥ 5 points was defined as elevated depression or anxiety. High hs-CRP was defined as ≥ 3 mg/L. Follow-up was performed 2 years after the patients were discharged. The clinical results included noncardiac readmission, cardiac readmission, major cardiovascular events (MACEs), and composite events. The composite events included noncardiac readmission and MACEs. The Cox proportional hazard regression model was used to analyze the prognostic risk. RESULTS After full adjustment, patients with elevated depression and high hs-CRP had a higher risk in predicting noncardiac readmission (hazard ratio (HR) = 3.87, 95% confidence interval (CI) = 1.10-9.02, p = 0.002) and composite events (HR = 1.93, 95% CI = 1.13-3.30, p = 0.016) than those with high hs-CRP alone. For the anxiety and hs-CRP group, high hs-CRP alone predicted a higher risk of noncardiac readmission (HR = 3.32, 95% CI = 1.57-7.03, p = 0.002) and composite events (HR = 1.75, 95% CI = 1.12-2.76, p = 0.015) than references. Elevated anxiety had no significant effects on all the endpoints. Furthermore, we didn't find interactions between depression and hs-CRP or anxiety and hs-CRP. CONCLUSION In patients with CHD, elevated depression with high hs-CRP was found to be significant in predicting the risk of noncardiac readmission and composite events. Early diagnosis and treatment of depression with inflammation are necessary in CHD patients.
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Affiliation(s)
- Bingqing Bai
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, P. R. China
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China
| | - Han Yin
- Shenzhen People's Hospital, Jinan University, Shenzhen, 518020, Guangdong, P. R. China
| | - Haochen Wang
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China
| | - Fengyao Liu
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China
- School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, P. R. China
| | - Yanting Liang
- Shenzhen People's Hospital, Jinan University, Shenzhen, 518020, Guangdong, P. R. China
| | - Anbang Liu
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China
| | - Lan Guo
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China
| | - Huan Ma
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China.
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, Guangdong, China.
| | - Qingshan Geng
- Department of Cardiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, Guangdong, P. R. China.
- School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, P. R. China.
- Shenzhen People's Hospital, Jinan University, Shenzhen, 518020, Guangdong, P. R. China.
- Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, Guangdong, China.
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McFarlin BK, Deemer SE, Bridgeman EA. Oral Spore-Based Probiotic Supplementation Alters Post-Prandial Expression of mRNA Associated with Gastrointestinal Health. Biomedicines 2024; 12:2386. [PMID: 39457699 PMCID: PMC11504401 DOI: 10.3390/biomedicines12102386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 10/14/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Unregulated post-prandial dietary endotoxemia may accumulate over time and underlie the development of chronic disease (e.g., leaky gut, inflammatory bowel disease, etc.), for which oral probiotic supplementation may be a prophylactic. The purpose of this study was to determine if 45 d of oral spore-based probiotic supplementation altered gastrointestinal-associated mRNA expression following a high-fat meal. Methods: A subset of apparently healthy individuals from a larger study who had dietary endotoxemia at baseline completed 45 d of supplementation with either a placebo (rice flour; n = 10) or spore-based probiotic (Megasporebiotic™; Novonesis, Kongens Lyngby, Denmark; Bacillus indicus (HU36™), Bacillus subtilis (HU58™), Bacillus coagulans (SC208™), and Bacillus licheniformis (SL-307), and Bacillus clausii (SC109™); n = 10). Venous blood was collected in Paxgene RNA tubes prior to (PRE), 3 h, and 5 h after consumption of a high-fat meal (85% of the daily fat RDA and 65% of the daily calorie needs). Total RNA was analyzed for 579 mRNAs of interest (Nanostring nCounter Sprint; Seattle, WA, USA). After normalization to housekeeping controls and calculation of differential expression relative to PRE and controlled for FDR, 15 mRNAs were determined to be significantly changed at either 3 h and/or 5 h post-prandial in the probiotic group but not in the placebo group. Results: Significant mRNA expressions were associated with gastrointestinal tract barrier function (four mRNAs: BATF3, CCR6, CXCR6, and PDCD2), gastrointestinal immunity (four mRNAs: CLEC5A, IL7, CARD9, and FCER1G), or future IBD risk (seven mRNAs: PD-L1, CSF1R, FAS, BID, FADD, GATA3, and KIR3DL). Conclusions: Collectively, the present findings may support the notion that post-prandial immune response to eating is enhanced following 45 d of probiotic supplementation.
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Affiliation(s)
- Brian K. McFarlin
- Applied Physiology Laboratory, University of North Texas, Denton, TX 76205, USA; (S.E.D.); (E.A.B.)
- Department of Biological Sciences, University of North Texas, Denton, TX 76205, USA
| | - Sarah E. Deemer
- Applied Physiology Laboratory, University of North Texas, Denton, TX 76205, USA; (S.E.D.); (E.A.B.)
| | - Elizabeth A. Bridgeman
- Applied Physiology Laboratory, University of North Texas, Denton, TX 76205, USA; (S.E.D.); (E.A.B.)
- Department of Biological Sciences, University of North Texas, Denton, TX 76205, USA
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22
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Monfort-Ferré D, Boronat-Toscano A, Sánchez-Herrero JF, Caro A, Menacho M, Vañó-Segarra I, Martí M, Espina B, Pluvinet R, Cabrinety L, Abadia C, Ejarque M, Nuñez-Roa C, Maymo-Masip E, Sumoy L, Vendrell J, Fernández-Veledo S, Serena C. Genome-wide DNA Methylome and Transcriptome Profiling Reveals Key Genes Involved in the Dysregulation of Adipose Stem Cells in Crohn's Disease. J Crohns Colitis 2024; 18:1644-1659. [PMID: 38747506 DOI: 10.1093/ecco-jcc/jjae072] [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: 10/25/2023] [Revised: 04/18/2024] [Accepted: 05/13/2024] [Indexed: 10/17/2024]
Abstract
BACKGROUND AND AIMS Crohn's disease [CD] is characterised by the expansion of mesenteric adipose tissue [MAT], named creeping fat [CF], which seems to be directly related to disease activity. Adipose-stem cells [ASCs] isolated from the CF of patients with CD are extremely pro-inflammatory, which persists during disease remission. We hypothesised that the dysfunctional ASCs in CD accumulate epigenetic modifications triggered by the inflammatory environment, that could serve as molecular markers. METHODS Genome-wide DNA methylome and transcriptome profiling were performed in ASCs isolated from MAT biopsies of patients with active and inactive disease and from non-Crohn's disease patients [non-CD]. A validation cohort was used to test the main candidate genes via quantitative polymerase chain reaction in other fat depots and immune cells. RESULTS We found differences in DNA methylation and gene expression between ASCs isolated from patients with CD and from non-CD subjects, but we found no differences related to disease activity. Pathway enrichment analysis revealed that oxidative stress and immune response were significantly enriched in active CD, and integration analysis identified MAB21L2, a cell fate-determining gene, as the most affected gene in CD. Validation analysis confirmed the elevated gene expression of MAB21L2 in MAT and in adipose tissue macrophages in active CD. We also found a strong association between expression of the calcium channel subunit gene CACNA1H and disease remission, as CACNA1H expression was higher in ASCs and MAT from patients with inactive CD, and correlates negatively with C-reactive protein in peripheral blood mononuclear cells. CONCLUSION We identified a potential gene signature of CD in ASCs obtained from MAT. Integration analysis highlighted two novel genes demonstrating a negative correlation between promoter DNA methylation and transcription: one linked to ASCs in CD [MAB21L2] and the other [CACNA1H] related to disease remission.
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Affiliation(s)
- Diandra Monfort-Ferré
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
| | - Albert Boronat-Toscano
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
| | | | - Aleidis Caro
- Unitat de Cirurgia Colorectal, Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain
| | - Margarita Menacho
- Servei de Digestiu, Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain
| | - Irene Vañó-Segarra
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
| | - Marc Martí
- Unitat de Cirurgia Colorectal, Servei de Cirurgia General, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Beatriz Espina
- Unitat de Cirurgia Colorectal, Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain
| | - Raquel Pluvinet
- Genòmica d'Alt Contingut i Bioinformàtica, Institut d'Investigació Germans Trias i Pujol, Badalona, Spain
- Unitat de Genòmica, Josep Carreras Leukaemia Research Institute, Badalona, Spain
| | - Lidia Cabrinety
- Servei de Digestiu, Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain
| | - Carme Abadia
- Servei de Digestiu, Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Tarragona, Spain
| | - Miriam Ejarque
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
| | - Cati Nuñez-Roa
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
| | - Elsa Maymo-Masip
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud, Carlos III, Madrid, Spain
| | - Lauro Sumoy
- Genòmica d'Alt Contingut i Bioinformàtica, Institut d'Investigació Germans Trias i Pujol, Badalona, Spain
| | - Joan Vendrell
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud, Carlos III, Madrid, Spain
| | - Sonia Fernández-Veledo
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud, Carlos III, Madrid, Spain
| | - Carolina Serena
- Hospital Universitari Joan XXIII, Institut d´Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain
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Riggott C, Fairbrass KM, Selinger CP, Gracie DJ, Ford AC. Impact of Opioid Use on the Natural History of Inflammatory Bowel Disease: Prospective Longitudinal Follow-up Study. Inflamm Bowel Dis 2024; 30:1724-1731. [PMID: 37929997 DOI: 10.1093/ibd/izad256] [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: 07/06/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND Opioid use is increasingly prevalent amongst patients with inflammatory bowel disease (IBD), but whether opioids have deleterious effects, or their use is merely linked with more severe disease, is unclear. We conducted a longitudinal follow-up study examining this issue. METHODS Data on demographics, gastrointestinal and psychological symptoms, quality of life, and opioid use were recorded at baseline. Data on healthcare use and adverse disease outcomes were obtained from a review of electronic medical records at 12 months. Characteristics at baseline of those using opioids and those who were not were compared, in addition to occurrence of flare, prescription of glucocorticosteroids, treatment escalation, hospitalization, or intestinal resection during the 12 months of follow-up. RESULTS Of 1029 eligible participants, 116 (11.3%) were taking opioids at baseline. Medium (odds ratio [OR], 4.67; 95% confidence interval [CI], 1.61-13.6) or high (OR, 8.03; 95% CI, 2.21-29.2) levels of somatoform symptom-reporting and use of antidepressants (OR, 2.54; 95% CI, 1.34-4.84) or glucocorticosteroids (OR, 6.63; 95% CI, 2.26-19.5; P < .01 for all analyses) were independently associated with opioid use. Following multivariate analysis, opioid users were significantly more likely to undergo intestinal resection (hazard ratio, 7.09; 95% CI, 1.63 to 30.9; P = .009), particularly when codeine or dihydrocodeine were excluded (hazard ratio, 42.9; 95% CI, 3.36 to 548; P = .004). CONCLUSIONS Opioid use in IBD is associated with psychological comorbidity and increased risk of intestinal resection, particularly in stronger formulations. Future studies should stratify the risk of individual opioids, so that robust prescribing algorithms can be developed and assess whether addressing psychological factors in routine IBD care could be an effective opioid avoidance strategy.
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Affiliation(s)
- Christy Riggott
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Keeley M Fairbrass
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Christian P Selinger
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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24
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Gordon M, Sinopoulou V, Mardare R, Abdulshafea M, Grafton-Clarke C, Vasiliou J. Patients' and health professionals' research priorities for chronic pain associated with inflammatory bowel disease: a co-produced sequential mixed methods Delphi consensus study. BMJ Open Gastroenterol 2024; 11:e001483. [PMID: 39266019 PMCID: PMC11404265 DOI: 10.1136/bmjgast-2024-001483] [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: 06/04/2024] [Accepted: 08/21/2024] [Indexed: 09/14/2024] Open
Abstract
OBJECTIVE Chronic pain in inflammatory bowel disease (IBD) is common and detrimental to quality of life. Recent Cochrane reviews identified a multitude of randomised controlled trial interventions, but the certainty of the findings is low or very low. We set out to reach a patient and professional co-produced Delphi consensus on treatment priorities, key outcomes and propose a model for understanding our findings. METHODS An online survey was co-produced with Crohn's and Colitis UK and sent to patients and healthcare professionals in two phases, for prioritisation of treatments and outcome measures. Phase three consisted of four online group interviews, where patients and healthcare professionals discussed the rationale of their choices. Transcripts were combined with the free text data from the Delphi surveys and analysed through a three-phase qualitative technique. RESULTS The phase 1 survey was completed by 128 participants (73 patients, 3 carers and 53 health professionals). Diet was the top priority for both patients (n=26/73, 36.1%) and healthcare professionals (n=29/52, 56.9%). Phase 2 was completed by 68 participants. FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, stress management therapy and relaxation therapy were the top three consensus priorities. Phase 3 group interviews were attended by 13 patients and 5 healthcare professionals. Key themes included: The patient as an individual, beliefs and experiences, disease activity influencing therapy choice, accessibility barriers and quality of life. CONCLUSION Low FODMAP diet, followed by psychological therapies were the highest-rated research priorities for healthcare professionals and patients. Funding bodies and researchers should consider these findings, alongside the model for understanding our findings, when making research decisions.
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Affiliation(s)
- Morris Gordon
- University of Central Lancashire, Preston, UK
- Blackpool Victoria Hospital, Blackpool, UK
| | | | - Roxana Mardare
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, London, UK
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Golob J, Rao K, Berinstein JA, Singh P, Chey WD, Owyang C, Kamada N, Higgins PDR, Young V, Bishu S, Lee AA. Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.09.08.24313266. [PMID: 39314983 PMCID: PMC11419226 DOI: 10.1101/2024.09.08.24313266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
Introduction Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with ( qCD+S ) vs. without persistent GI symptoms ( qCD-S ). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur-metabolic pathways in qCD+S. Methods We performed a multi-center observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level <150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD ( aCD ) and non-IBD diarrhea-predominant irritable bowel syndrome ( IBS-D ) were included as controls. Results Thirty-nine patients with qCD+S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD+S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD+S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD+S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H 2 S signaling. Multi-omic integration demonstrated that enriched microbes in qCD+S were associated with important sulfur-metabolic pathways. Bacterial sulfur-metabolic genes, including CTH , isfD , sarD , and asrC , were dysregulated in qCD+S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting presence of qCD+S. Discussion Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD+S, which implicate H 2 S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H 2 S pathways results in improved quality of life in qCD+S. Key Messages What is Already Known Even in the absence of inflammation, persistent gastrointestinal symptoms are common in Crohn's disease.The microbiome is altered in quiescent Crohn's disease patients with persistent symptoms, but the functional significance of these changes is unknown. What is New Here Sulfur metabolites and sulfur metabolic pathways were enriched in stool in quiescent Crohn's disease patients with persistent symptoms.Multi-omic integration showed enriched microbes were associated with important sulfur metabolic pathways in quiescent Crohn's disease patients with persistent symptoms. How Can This Study Help Patient Care Strategies to decrease sulfidogenic microbes and associated sulfur metabolic pathways could represent a novel strategy to improve quality of life in quiescent Crohn's disease with persistent GI symptoms.
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Rajindrajith S, Boey CCM, Devanarayana NM, Niriella MA, Thapar N, Benninga MA. Navigating through 65 years of insights: lessons learned on functional abdominal pain in children. Eur J Pediatr 2024; 183:3689-3703. [PMID: 38972964 DOI: 10.1007/s00431-024-05667-4] [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: 03/21/2024] [Revised: 06/21/2024] [Accepted: 06/24/2024] [Indexed: 07/09/2024]
Abstract
In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.
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Affiliation(s)
- Shaman Rajindrajith
- Department of Pediatrics, Faculty of Medicine, University of Colombo, Colombo 8, 00800, Western Province, Sri Lanka.
| | - Christopher Chiong-Meng Boey
- Department of Paediatrics, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
- Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lampur, Malaysia
| | | | | | - Nikhil Thapar
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - Marc Alexander Benninga
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Burdine LK, Rakowsky S, Grossberg L, Rabinowitz L, Cheifetz AS, Ballou S. Irritable Bowel Syndrome/Inflammatory Bowel Disease Overlap: Less Common Than We Think. GASTRO HEP ADVANCES 2024; 3:1135-1137. [PMID: 39555317 PMCID: PMC11564024 DOI: 10.1016/j.gastha.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 08/06/2024] [Indexed: 11/19/2024]
Affiliation(s)
- Lauren K. Burdine
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | | | - Laurie Grossberg
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Loren Rabinowitz
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Adam S. Cheifetz
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Sarah Ballou
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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28
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Huisman D, Fernhout F, Moxham F, Norton C, Bannister K, Moss-Morris R. Managing patients' reports of abdominal pain and irritable bowel syndrome-like symptoms during quiescent inflammatory bowel disease: a role for shared sensemaking. Br J Pain 2024; 18:325-336. [PMID: 39092211 PMCID: PMC11289903 DOI: 10.1177/20494637241230807] [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] [Indexed: 08/04/2024] Open
Abstract
Background Patients with inflammatory bowel disease (IBD) are often faced with distressing and confusing abdominal pain during remission. Some people respond adversely to healthcare professionals' (HCPs) suggestions that this pain and related symptoms are due to secondary irritable bowel syndrome (IBS). Exploring how HCPs view, manage, and explain pain during quiescent disease may provide insights into how communication can be improved to increase understanding and mitigate negative responses. Methods In-depth semi-structured interviews were conducted with 12 IBD-nurses (n = 4) and gastroenterologists (n = 8) working in the United Kingdom or the Netherlands. Reflexive thematic analysis was used to analyse interviews. Results Findings suggest that HCPs pay relatively little attention to pain when there is no underlying pathology and prefer to concentrate on objectifiable causes of symptoms and treating disease activity (Theme 1: Focus on disease activity, not pain and associated symptoms). Explanations of abdominal pain and IBS-like symptoms during remission were not standardised (Theme 2: Idiosyncratic and uncertain explanations for pain during remission). Processes of shared decision-making were outlined and shared sensemaking was reported as a strategy to enhance acceptance of IBS explanations (Theme 3: Shared decision making versus shared sensemaking). Conclusion Future work should focus on establishing how pain during remission may be best defined, when to diagnose IBS in the context of IBD, and how to explain both to patients. The formulation of standardised explanations is recommended as they might help HCPs to adopt practices of shared sensemaking and shared decision-making. Explanations should be adaptable to specific symptom presentations and different health literacy levels.
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Affiliation(s)
- Danielle Huisman
- Health Psychology Section, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Felice Fernhout
- Health Psychology Section, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Faye Moxham
- Health Psychology Section, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Christine Norton
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King’s College London, London, UK
| | - Kirsty Bannister
- Central Modulation of Pain, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Rona Moss-Morris
- Health Psychology Section, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Barnes A, Mukherjee S, Andrews JM, Spizzo P, Mountifield R. Active Inflammatory Bowel Disease Is Associated with Short Sleep Duration via Objective Measures. Dig Dis Sci 2024; 69:2937-2943. [PMID: 38842741 PMCID: PMC11341642 DOI: 10.1007/s10620-024-08485-8] [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: 02/19/2024] [Accepted: 05/07/2024] [Indexed: 06/07/2024]
Abstract
INTRODUCTION Poor sleep quality has been associated with inflammatory bowel disease (IBD) activity, although studies incorporating actigraphy suggest that the perception of sleep differs rather than objective difference in sleep quality. Short sleep duration has been associated with increased pro-inflammatory cytokines that have been implicated in the pathogenesis of IBD. METHODS An observational study incorporated home-based polysomnography that was conducted within twelve weeks of an objective assessment of IBD activity such as calprotectin, colonoscopy, or MRI. Participants completed a survey on subjective measures of sleep quality, clinical IBD activity, depression, and anxiety. Polysomnography results were normalized by standardized results for a healthy population matched by gender and age. RESULTS Twenty participants were included in the final analysis. Those with objective evidence of active IBD had shorter stage 2 sleep duration, leading to shorter NREM sleep and total sleep time. Sleep latency was also longer in those with active IBD, leading to worse sleep efficiency-despite no difference in time available for sleep between the two groups. These changes persisted after normalization of polysomnography results by health population age and gender matched norms. Depression scores correlated with sleep latency and stage 2 sleep duration and were associated with objectively active IBD. CONCLUSIONS Objectively confirmed active IBD was associated with shorter sleep duration. Observed sleep changes may, in part, relate to coexistent depression. Further research should consider the utility of changes in sleep duration and quality as a means of longitudinally assessing objective IBD activity.
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Affiliation(s)
- Alex Barnes
- Department of Gastroenterology, Flinders Medical Centre, Southern Adelaide Local Health Network (SALHN), Flinders Drive, Bedford Park, SA, 5042, Australia.
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.
| | - Sutapa Mukherjee
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
- Department of Respiratory and Sleep Medicine, Flinders Medical Centre, Southern Adelaide Local Health Network (SALHN), Bedford Park, SA, Australia
| | - Jane M Andrews
- Inflammatory Bowel Disease Service, Department of Gastroenterology and Hepatology, (CAHLN) Royal Adelaide Hospital, Adelaide, SA, Australia
- Faculty of Health & Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - Paul Spizzo
- Department of Gastroenterology, Flinders Medical Centre, Southern Adelaide Local Health Network (SALHN), Flinders Drive, Bedford Park, SA, 5042, Australia
| | - Réme Mountifield
- Department of Gastroenterology, Flinders Medical Centre, Southern Adelaide Local Health Network (SALHN), Flinders Drive, Bedford Park, SA, 5042, Australia
- College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
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Varma S, Sullivan K, DiCarlo J, Coromilas A, Staller K, Dougan M. The Development of Persistent Gastrointestinal Symptoms in Patients With Melanoma Who Have Had an Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity. Clin Transl Gastroenterol 2024; 15:e00746. [PMID: 38995215 PMCID: PMC11346846 DOI: 10.14309/ctg.0000000000000746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/27/2024] [Indexed: 07/13/2024] Open
Abstract
INTRODUCTION Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE. METHODS This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms. RESULTS One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23). DISCUSSION In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors.
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Affiliation(s)
- Sanskriti Varma
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital, Center for Neurointestinal Health, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Keri Sullivan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Jamie DiCarlo
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Alexandra Coromilas
- Department of Dermatology, NewYork-Presbyterian Hospital, Columbia University Irving Medical Center, New York City, New York, USA
| | - Kyle Staller
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital, Center for Neurointestinal Health, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Michael Dougan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Cicerone C, D’Amico F, Allocca M, Zilli A, Parigi TL, Danese S, Furfaro F. A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities. Diagnostics (Basel) 2024; 14:1530. [PMID: 39061667 PMCID: PMC11275644 DOI: 10.3390/diagnostics14141530] [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: 06/04/2024] [Revised: 07/12/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.
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Affiliation(s)
- Clelia Cicerone
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
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Truyens M, Lernout H, De Vos M, Laukens D, Lobaton T. Unraveling the fatigue puzzle: insights into the pathogenesis and management of IBD-related fatigue including the role of the gut-brain axis. Front Med (Lausanne) 2024; 11:1424926. [PMID: 39021817 PMCID: PMC11252009 DOI: 10.3389/fmed.2024.1424926] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 06/17/2024] [Indexed: 07/20/2024] Open
Abstract
A significant percentage of patients with an inflammatory bowel disease (IBD) encounter fatigue which can profoundly diminish patients' quality of life, particularly during periods of disease remission when gastrointestinal symptoms have receded. Various contributing risk factors have been identified including active inflammation, anemia, psychological, lifestyle and drug-related factors. While addressing these risk factors has been suggested as the initial approach to managing fatigue, a considerable number of patients still experience persisting symptoms, the primary causes of which remain incompletely understood. Recent insights suggest that dysfunction of the gut-brain axis may play a pathogenic role. This review provides an overview of established risk factors for fatigue, alongside emerging perspectives on the role of the gut-brain axis, and potential treatment strategies.
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Affiliation(s)
- Marie Truyens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Hannah Lernout
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium
| | - Martine De Vos
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Debby Laukens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium
- Ghent Gut Inflammation Group (GGIG), Ghent University, Ghent, Belgium
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
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34
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Hidayat AA, Waskito LA, Sugihartono T, Aftab H, Rezkitha YAA, Vilaichone RK, Miftahussurur M. Diagnostic strategy of irritable bowel syndrome: a low- and middle-income country perspective. Intest Res 2024; 22:286-296. [PMID: 38528371 PMCID: PMC11309822 DOI: 10.5217/ir.2023.00199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/06/2024] [Accepted: 02/15/2024] [Indexed: 03/27/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder associated with substantial impairment which considerably burdens healthcare systems worldwide. Research on IBS has largely been conducted in high-income countries posing barriers to the application of diagnostic strategies in low- and middle-income countries (LMICs) due to differences in disease characteristics, healthcare resources, and socioeconomic factors. This review discusses the diagnostic issues associated with LMICs. We present a concise overview of the relevant approaches and propose a diagnostic strategy based on the latest evidence. A positive diagnostic strategy that relies on appropriate symptom-based criteria is crucial within the diagnostic framework. A combination of complete blood count, fecal occult blood test, and complete stool test may reliably identify individuals with suspected IBS who are more likely to have organic diseases, thus justifying the necessity for a colonoscopy. Eventually, we developed a diagnostic algorithm based on a limited setting perspective that summarizes the available evidence and may be applied in LMICs.
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Affiliation(s)
- Amal Arifi Hidayat
- Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Langgeng Agung Waskito
- Department of Physiology and Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Titong Sugihartono
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Hafeza Aftab
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh
| | - Yudith Annisa Ayu Rezkitha
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Department of Internal Medicine, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Ratha-korn Vilaichone
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University, Pathumthani, Thailand
| | - Muhammad Miftahussurur
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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Hawker P, Zhang L, Liu L. Mas-related G protein-coupled receptors in gastrointestinal dysfunction and inflammatory bowel disease: A review. Br J Pharmacol 2024; 181:2197-2211. [PMID: 36787888 DOI: 10.1111/bph.16059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/25/2022] [Accepted: 02/04/2023] [Indexed: 02/16/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic debilitating condition, hallmarked by persistent inflammation of the gastrointestinal tract. Despite recent advances in clinical treatments, the aetiology of IBD is unknown, and a large proportion of patients are refractory to pharmacotherapy. Understanding IBD immunopathogenesis is crucial to discern the cause of IBD and optimise treatments. Mas-related G protein-coupled receptors (Mrgprs) are a family of approximately 50 G protein-coupled receptors that were first identified over 20 years ago. Originally known for their expression in skin nociceptors and their role in transmitting the sensation of itch in the periphery, new reports have described the presence of Mrgprs in the gastrointestinal tract. In this review, we consider the impact of these findings and assess the evidence that suggests that Mrgprs may be involved in the disrupted homeostatic processes that contribute to gastrointestinal disorders and IBD. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein-Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc.
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Affiliation(s)
- Patrick Hawker
- School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
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36
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Löwe B, Toussaint A, Rosmalen JGM, Huang WL, Burton C, Weigel A, Levenson JL, Henningsen P. Persistent physical symptoms: definition, genesis, and management. Lancet 2024; 403:2649-2662. [PMID: 38879263 DOI: 10.1016/s0140-6736(24)00623-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 01/30/2024] [Accepted: 03/22/2024] [Indexed: 08/29/2024]
Abstract
Persistent physical symptoms (synonymous with persistent somatic symptoms) is an umbrella term for distressing somatic complaints that last several months or more, regardless of their cause. These symptoms are associated with substantial disability and represent a major burden for patients, health-care professionals, and society. Persistent physical symptoms can follow infections, injuries, medical diseases, stressful life events, or arise de novo. As symptoms persist, their link to clearly identifiable pathophysiology often weakens, making diagnosis and treatment challenging. Multiple biological and psychosocial risk factors and mechanisms contribute to the persistence of somatic symptoms, including persistent inflammation; epigenetic profiles; immune, metabolic and microbiome dysregulation; early adverse life experiences; depression; illness-related anxiety; dysfunctional symptom expectations; symptom focusing; symptom learning; and avoidance behaviours, with many factors being common across symptoms and diagnoses. Basic care consists of addressing underlying pathophysiology and using person-centred communication techniques with validation, appropriate reassurance, and biopsychosocial explanation. If basic care is insufficient, targeted psychological and pharmacological interventions can be beneficial. A better understanding of the multifactorial persistence of somatic symptoms should lead to more specific, personalised, and mechanism-based treatment, and a reduction in the stigma patients commonly face.
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Affiliation(s)
- Bernd Löwe
- Department of Psychosomatic Medicine and Psychotherapy, Centre for Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
| | - Anne Toussaint
- Department of Psychosomatic Medicine and Psychotherapy, Centre for Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Judith G M Rosmalen
- Department of Psychiatry, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands; Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
| | - Wei-Lieh Huang
- Department of Psychiatry, National Taiwan University Hospital Yunlin Branch, Douliu City, Taiwan; Department of Psychiatry, College of Medicine, National Taiwan University, Taipei City, Taiwan
| | - Christopher Burton
- School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Angelika Weigel
- Department of Psychosomatic Medicine and Psychotherapy, Centre for Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - James L Levenson
- Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Peter Henningsen
- Department of Psychosomatic Medicine and Psychotherapy, Technical University Munich, Munich, Germany
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AWARE-IBD Diagnostic Delay Working Group. Sources of diagnostic delay for people with Crohn's disease and ulcerative colitis: Qualitative research study. PLoS One 2024; 19:e0301672. [PMID: 38857292 PMCID: PMC11164383 DOI: 10.1371/journal.pone.0301672] [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: 09/12/2023] [Accepted: 03/20/2024] [Indexed: 06/12/2024] Open
Abstract
OBJECTIVE An improved understanding of the causes and experience of diagnostic delay in Inflammatory Bowel Disease (IBD). METHODS Framework analysis of semi-structured interviews with 20 adults with IBD. RESULTS Participants' prior knowledge of normal bowel function/IBD was limited. Symptoms were sometimes misattributed to mild/transient conditions or normalised until intolerable. Family pressures, work, education, mistrust of doctors, fear and embarrassment could exacerbate delays. Poor availability of face-to-face appointments deterred people from seeing a GP. Patients feared that by the time they got to see their GP, their symptoms would have resolved. Patients instead self-managed symptoms, but often regretted not seeking help earlier. Limited time in consultations, language barriers, embarrassment, and delays in test results subsequently delayed specialist referrals. GPs misattributed symptoms to other conditions due to atypical or non-specific presentations, leading to reduced trust in health systems. Patients complained of poor communication, delays in accessing test results, appointments, and onward referrals-all associated with clinical deterioration. GPs were sometimes unable to 'fast-track' patients into specialist care. Consultations and endoscopies were often difficult experiences for patients, especially for non-English speakers who are also less likely to receive information on mental health support and the practicalities of living with IBD. CONCLUSIONS The framework analysis demonstrates delay in the diagnosis of IBD at each stage of the patient journey. RECOMMENDATIONS Greater awareness of IBD amongst the general population would facilitate presentation to healthcare services through symptom recognition by individuals and community advice. Greater awareness in primary care would help ensure IBD is included in differential diagnosis. In secondary care, greater attention to the wider needs of patients is needed-beyond diagnosis and treatment. All clinicians should consider atypical presentations and the fluctuating nature of IBD. Diagnostic overshadowing is a significant risk-where other diagnoses are already in play the risk of delay is considerable.
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Affiliation(s)
- AWARE-IBD Diagnostic Delay Working Group
- Sheffield CTRU, University of Sheffield, Regent Court, Sheffield, United Kingdom
- The Medical School, The University of Sheffield, Sheffield, United Kingdom
- Academic Unit of Medical Education, The Medical School, The University of Sheffield, Sheffield, United Kingdom
- Sheffield Inflammatory Bowel Disease Centre, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
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Jiang C, Godoy-Brewer G, Rodriguez A, Graff E, Quintero MA, Leavitt J, Lopez J, Goldberg DS, Damas OM, Whelan K, Abreu MT. Food-Related Quality of Life Is Impaired in Latinx and Non-Latinx Patients With Inflammatory Bowel Disease. GASTRO HEP ADVANCES 2024; 3:773-782. [PMID: 39280907 PMCID: PMC11401539 DOI: 10.1016/j.gastha.2024.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/21/2024] [Indexed: 09/18/2024]
Abstract
Background and Aims Anxiety over food choices and symptoms related to food consumption diminish quality of life (QoL) in inflammatory bowel disease (IBD) patients. However, the specific factors that impact QoL among IBD patients remain unclear. In this study, we analyzed the relationships of demographic and disease factors with food-related QoL (FRQoL) in a large, diverse US cohort of IBD patients. Methods In this cross-sectional analysis of 1108 IBD patients aged ≥18 years, we measured FRQoL with the 29-item Food-Related Quality of Life Questionnaire (FR-QoL-29) and disease activity with the Harvey-Bradshaw index in Crohn's disease (CD) patients or the Simple Clinical Colitis Activity Index in ulcerative colitis (UC) patients. Latinx immigrants completed a Spanish translation of the FR-QoL-29. A subset of patients had colonoscopy and inflammatory marker data available. We used univariate, multivariate, and subgroup analyses to examine the factors that influence FRQoL. Results In our cohort, 55% of IBD patients self-identified as Latinx. Latinx and non-Latinx patients had similar FR-QoL-29 scores. Female patients had significantly lower FRQoL than male patients (P = .001). Increasing age and IBD duration correlated with higher FRQoL (P < .0001). In UC patients, higher Simple Clinical Colitis Activity Index scores (P < .0001), higher Mayo scores (P = .0009), and longer disease duration (P = .03) predicted significantly lower FRQoL. Disease activity and FRQoL were not significantly related in CD patients. Conclusion This is the largest study to date to examine FRQoL in American IBD patients, and the first to include Latinx patients. Disease-related factors had a greater impact on FRQoL than ethnicity. Clinical and endoscopic disease activity had a more detrimental impact on FRQoL in UC than in CD. Diet intervention studies are needed to alleviate symptoms and improve FRQoL in the IBD population.
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Affiliation(s)
- Chunsu Jiang
- Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida
| | - Gala Godoy-Brewer
- Department of Internal Medicine, University of Miami, Miami, Florida
| | - Andres Rodriguez
- Department of Internal Medicine, University of Miami, Miami, Florida
| | - Erica Graff
- Department of Internal Medicine, University of Miami, Miami, Florida
| | | | | | | | - David S Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida
| | - Oriana M Damas
- Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida
| | - Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, UK
| | - Maria T Abreu
- Division of Digestive Health and Liver Diseases, University of Miami, Miami, Florida
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Nieva C, Pryor J, Williams GM, Hoedt EC, Burns GL, Eslick GD, Talley NJ, Duncanson K, Keely S. The Impact of Dietary Interventions on the Microbiota in Inflammatory Bowel Disease: A Systematic Review. J Crohns Colitis 2024; 18:920-942. [PMID: 38102104 PMCID: PMC11147801 DOI: 10.1093/ecco-jcc/jjad204] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/12/2023] [Accepted: 12/09/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND AND AIMS Diet plays an integral role in the modulation of the intestinal environment, with the potential to be modified for management of individuals with inflammatory bowel disease [IBD]. It has been hypothesised that poor 'Western-style' dietary patterns select for a microbiota that drives IBD inflammation and, that through dietary intervention, a healthy microbiota may be restored. This study aimed to systematically review the literature and assess current available evidence regarding the influence of diet on the intestinal microbiota composition in IBD patients, and how this may affect disease activity. METHODS MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library were searched from January 2013 to June 2023, to identify studies investigating diet and microbiota in IBD. RESULTS Thirteen primary studies met the inclusion criteria and were selected for narrative synthesis. Reported associations between diet and microbiota in IBD were conflicting due to the considerable degree of heterogeneity between studies. Nine intervention studies trialled specific diets and did not demonstrate significant shifts in the diversity and abundance of intestinal microbial communities or improvement in disease outcomes. The remaining four cross-sectional studies did not find a specific microbial signature associated with habitual dietary patterns in IBD patients. CONCLUSIONS Diet modulates the gut microbiota, and this may have implications for IBD; however, the body of evidence does not currently support clear dietary patterns or food constituents that are associated with a specific microbiota profile or disease marker in IBD patients. Further research is required with a focus on robust and consistent methodology to achieve improved identification of associations.
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Affiliation(s)
- Cheenie Nieva
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Jennifer Pryor
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Georgina M Williams
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Emily C Hoedt
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Grace L Burns
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Guy D Eslick
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Nicholas J Talley
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Kerith Duncanson
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Simon Keely
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
- National Health and Medical Research Council [NHMRC], Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
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Ahmed M, Pu A, Jencks K, Bishu S, Higgins P, Chey WD, Rao K, Lee A. Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease. Neurogastroenterol Motil 2024; 36:e14809. [PMID: 38651743 PMCID: PMC11806413 DOI: 10.1111/nmo.14809] [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: 09/30/2023] [Revised: 04/04/2024] [Accepted: 04/14/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 μg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.
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Affiliation(s)
- Mehwish Ahmed
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Autumn Pu
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Kara Jencks
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Shrinivas Bishu
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Peter Higgins
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - William D. Chey
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Krishna Rao
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan, USA
| | - Allen Lee
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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Sauer P, Luft VC, Dall'Alba V. Patients with Inflammatory Bowel Disease who regularly consume fruits and vegetables present lower prevalence of disease activation: A cross-sectional study. Clin Nutr ESPEN 2024; 61:420-426. [PMID: 38777464 DOI: 10.1016/j.clnesp.2024.04.010] [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: 11/10/2023] [Revised: 04/11/2024] [Accepted: 04/15/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Exclusion diets are common practices among individuals with Inflammatory Bowel Disease (IBD). Reports that certain foods trigger or worsen symptoms are recurrent but lack evidence. The aim of the study was to identify which foods were most frequently avoided by patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) and whether the consumption of any food group was associated with disease activity. METHODS Cross-sectional study with adult patients seen at an outpatient clinic in a tertiary public hospital. Dietary intake and eating habits were accessed through questionnaires administered via telephone interview. Disease activity and symptoms were assessed using the Harvey-Bradshaw Index (IHB) for CD and the Lichtiger Index (LI) for UC. Poisson regression with a robust variance estimator was used to estimate prevalence ratios. Analyzes were performed using SPSS - Statistical Package for the Social Sciences. RESULTS The study included 145 patients. Of these, 69.7% avoided certain foods, with citrus fruits and raw vegetables among the most avoided (16.8% and 13.8%, respectively). Regular consumption of fruits (PR = 0.56; CI 95% 0.32-0.97; p = 0.042) and vegetables (PR = 0.56; CI 95% 0.32-0.98; p = 0.045) was associated with a 44% lower prevalence of the active phase of the disease, compared to those who do not consume these foods, adjusted for age, sex and type of disease. Other food items did not present significant associations in the adjusted model. CONCLUSIONS Fruit and vegetable intake appears to have a protective role in the recurrence of IBD. Excluding foods is a common practice, even among patients in remission, and this should be combated as it can lead to nutritional losses. It is important to reinforce with patients the benefits of a varied and less restrictive diet.
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Affiliation(s)
- Patrícia Sauer
- Graduate Program in Gastroenterology and Hepatology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Nutrition Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
| | - Vivian Cristine Luft
- Nutrition Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Graduate Program in Food, Nutrition and Health, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Graduate Program in Epidemiology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Valesca Dall'Alba
- Graduate Program in Gastroenterology and Hepatology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Nutrition Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Graduate Program in Food, Nutrition and Health, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
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Mitrev N, Kariyawasam V. Treatment endpoints in ulcerative colitis: Does one size fit all? World J Gastrointest Pharmacol Ther 2024; 15:91591. [PMID: 38764502 PMCID: PMC11099350 DOI: 10.4292/wjgpt.v15.i2.91591] [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: 12/31/2023] [Revised: 02/28/2024] [Accepted: 04/10/2024] [Indexed: 04/24/2024] Open
Abstract
A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician's subjective assessment of symptoms. However, choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy. The treatment endpoints for ulcerative colitis (UC), recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) consensus have changed somewhat over time. The latest STRIDE-II consensus advises immediate (clinical response), intermediate (clinical remission and biochemical normalisation) and long-term treatment (endoscopic healing, absence of disability and normalisation of health-related quality of life, as well as normal growth in children) endpoints in UC. However, achieving deeper levels of remission, such as histologic normalisation or healing of the gut barrier function, may further improve outcomes among UC patients. Generally, all medical therapy should seek to improve short- and long-term mortality and morbidity. Hence treatment endpoints should be chosen based on their ability to predict for improvement in short- and long-term mortality and morbidity. Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient. In addition, changing therapy that has achieved partial response may lead to worse outcomes, with failure to recapture response on treatment reversion. Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians, or may have strong opinions re certain therapies. Potential benefits and harms of therapies, incremental benefits of achieving deeper levels of remission, as well as uncertainties of the same, need to be discussed with individual patients, and a treatment endpoint agreed upon with the clinician. Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission, such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.
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Affiliation(s)
- Nikola Mitrev
- Department of Gastroenterology, Blacktown Hospital, Blacktown 2148, NSW, Australia
- Blacktown/Mt Druitt Clinical School, University of Western Sydney, Blacktown 2148, NSW, Australia
- Department of Gastroenterology, Wollongong Hospital, Loftus St, Wollongong 2500, NSW, Australia
| | - Viraj Kariyawasam
- Department of Gastroenterology, Blacktown Hospital, Blacktown 2148, NSW, Australia
- Blacktown/Mt Druitt Clinical School, University of Western Sydney, Blacktown 2148, NSW, Australia
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Hassan SA, Kapur N, Sheikh F, Fahad A, Jamal S. Disease clearance in ulcerative colitis: A new therapeutic target for the future. World J Gastroenterol 2024; 30:1801-1809. [PMID: 38659483 PMCID: PMC11036494 DOI: 10.3748/wjg.v30.i13.1801] [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: 01/06/2024] [Revised: 02/16/2024] [Accepted: 03/19/2024] [Indexed: 04/03/2024] Open
Abstract
Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression. This has fueled the identification of molecular targets, resulting in a rapidly expanding therapeutic armamentarium. Subsequently, management strategies have evolved from symptomatic resolution to well-defined objective endpoints, including clinical remission, endoscopic remission and mucosal healing. While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications, studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures. Current recommendations lack consideration of histological healing. The simultaneous achievement of clinical, endoscopic, and histologic remission has not been fully investigated. This has laid the groundwork for a novel therapeutic outcome termed disease clearance (DC). This article summarizes the concept of DC and its current evidence.
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Affiliation(s)
- Syed Adeel Hassan
- Division of Digestive Disease and Nutrition, University of Kentucky, Lexington, KY 40536, United States
| | - Neeraj Kapur
- Division of Digestive Disease and Nutrition, University of Kentucky, Lexington, KY 40536, United States
| | - Fahad Sheikh
- Department of Pathology and Laboratory Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY 10461, United States
| | - Anam Fahad
- Division of Primary Care, Essen Healthcare, New York, NY 10457, United States
| | - Somia Jamal
- Department of Internal Medicine, Karachi Medical and Dental College, Karachi 74700, Sindh, Pakistan
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Khasawneh M, Shaikh FA, Ng CE, Black CJ, Goodoory VC, Ford AC. Utility of irritable bowel syndrome subtypes and most troublesome symptom in predicting disease impact and burden. Neurogastroenterol Motil 2024; 36:e14756. [PMID: 38321517 DOI: 10.1111/nmo.14756] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 01/20/2024] [Accepted: 01/23/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND Little is known about the characteristics of individuals with irritable bowel syndrome (IBS) according to stool subtype or the most troublesome symptom reported by the individual, or whether these are useful in predicting the impact of IBS. METHODS We collected demographic, gastrointestinal, and psychological symptoms, healthcare usage and direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV-defined IBS. KEY RESULTS We recruited 752 people with Rome IV IBS. Individuals with IBS-D reported a poorer disease-specific quality of life than those with IBS-C or IBS-M (mean (SD) IBS-QOL 45.3 (23.0) for IBS-D, vs. 52.3 (19.9) for IBS-C, vs. 49.4 (22.0) for IBS-M, p = 0.005). Mean (SD) IBS-QOL scores were also lower amongst those who reported diarrhea (44.8 (22.3)) or urgency (44.6 (22.3)) as their most troublesome symptom, compared with those reporting abdominal pain (52.2 (22.9)), constipation (49.5 (21.8)), or abdominal bloating or distension (50.4 (21.3)). However, there were no differences in mean EQ-5D scores, IBS severity, levels of anxiety, depression, somatoform symptom-reporting, or gastrointestinal symptom-specific anxiety. Direct healthcare costs of IBS were similar across all subtypes and all most troublesome symptom groups, although some differences in work productivity and social leisure activities were detected. CONCLUSIONS AND INFERENCES There appears to be limited variation in the characteristics of individuals with Rome IV IBS based on both stool subtypes and most troublesome symptom reported, suggesting that gastrointestinal symptoms alone have limited ability to predict disease impact and burden.
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Affiliation(s)
- Mais Khasawneh
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Fahad Ali Shaikh
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Cho Ee Ng
- County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Christopher J Black
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Vivek C Goodoory
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
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Zhou S, Sun Q, Gao N, Hu Z, Jia J, Song J, Xu G, Dong A, Xia W, Wu J. The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study. Can J Gastroenterol Hepatol 2024; 2024:1266139. [PMID: 38529201 PMCID: PMC10963109 DOI: 10.1155/2024/1266139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 02/03/2024] [Accepted: 03/10/2024] [Indexed: 03/27/2024] Open
Abstract
Background While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn's disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10-8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Results Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03-1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03-1.11; (p < 0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03-1.25; p=0.01). Conclusions The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD.
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Affiliation(s)
- Shu Zhou
- Hangzhou Ninth People's Hospital, Hangzhou, China
| | - Qi Sun
- Hangzhou Ninth People's Hospital, Hangzhou, China
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China
| | - Ning Gao
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Zekai Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China
| | - Junjun Jia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China
| | | | - Guocong Xu
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Aiqiang Dong
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Weiliang Xia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, China
| | - Jiafeng Wu
- Hangzhou Ninth People's Hospital, Hangzhou, China
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Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W, Narula N. Predicting Endoscopic Improvement in Ulcerative Colitis Using the Ulcerative Colitis Severity Index. Inflamm Bowel Dis 2024; 30:370-381. [PMID: 37116893 DOI: 10.1093/ibd/izad074] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Indexed: 04/30/2023]
Abstract
INTRODUCTION We developed and internally validated a prognostic scoring index for ulcerative colitis (UC) patients that includes baseline patient-reported outcomes (PROs), biomarkers, endoscopy, and histology for achieving 1-year endoscopic improvement (EI). METHODS This post hoc analysis included 644 patients treated with ustekinumab induction therapy. Data were randomly split to obtain a 70% training and 30% testing cohort. Multivariate analyses assessed baseline variables and those with P < .05 were assigned weights based on their relative prognostic value from logistic regression modeling for predicting 1-year EI (Mayo endoscopic score ≤1). A cutoff was obtained by calculating the maximum Youden index and validated in the testing cohort. RESULTS Prior biologic failure, albumin <40 g/L, C-reactive protein >5 mg/L, Mayo stool frequency subscore, endoscopic erosions/ulcerations, and chronic histologic structural/architectural changes demonstrated significant associations with 1-year EI and were included in the final model. The Ulcerative Colitis Severity Index (UCSI) had acceptable discriminative ability for 1-year EI in the training (area under the curve [AUC], 0.78; 95% confidence interval, 0.70-0.86) and testing cohort (AUC, 0.76; 95% CI, 0.68-0.85). Compared with the UCSI, the Mayo Clinic score demonstrated poor accuracy (AUC, 0.49; 95% CI, 0.40-0.58) for predicting 1-year EI (P = .0006). The UCSI predicted 1-year endoscopic healing (Mayo endoscopic score = 0), clinical remission (total Mayo Clinic score ≤2 and no subscore >1), partial Mayo score remission <2, and 2-item Patient-Reported Outcome score (Mayo stool frequency and rectal bleeding subscore = 0) with significantly greater accuracy compared with the Mayo Clinic score. DISCUSSION The UCSI is an internally validated prognostic scoring tool that accurately predicts 1-year EI at baseline among moderate-to-severe UC patients initiating therapy. Further validation with additional datasets is needed.
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Affiliation(s)
- Emily C L Wong
- Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton ON, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, IL, USA
| | - John K Marshall
- Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton ON, Canada
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Neeraj Narula
- Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton ON, Canada
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Barberio B, Fairbrass KM, Gracie DJ, Ford AC. Natural history and impact of irritable bowel syndrome-type symptoms in inflammatory bowel disease during 12 months of longitudinal follow-up. Neurogastroenterol Motil 2024; 36:e14713. [PMID: 37994228 DOI: 10.1111/nmo.14713] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 10/15/2023] [Accepted: 11/06/2023] [Indexed: 11/24/2023]
Abstract
BACKGROUND Little is known about the natural history and impact of irritable bowel syndrome (IBS)-type symptoms on psychological health and quality of life in inflammatory bowel disease (IBD). We aimed to address this in a 12-month longitudinal follow-up study of secondary care patients. METHODS We collected demographic, Rome III IBS-type symptom, psychological, and quality of life data, with questionnaires at 3-month intervals, over 12 months of follow-up in patients with IBD in clinical remission at baseline. We assessed the natural history of Rome III IBS-type symptoms over the 12 months of the study and compared psychological and quality of life data between those reporting Rome III IBS-type symptoms at each of the points of follow-up with those not reporting such symptoms. KEY RESULTS Among 206 patients with IBD in clinical remission at baseline (104 [50.5%] women, mean age 56.9 years [range 18-83 years], 79 [38.3%] Crohn's disease), 33 (16.0%) reported Rome III IBS-type symptoms at baseline and 72 (35.0%) reported Rome III IBS-type symptoms at one or more time points. Among the 33 patients with Rome III IBS-type symptoms at baseline, symptoms resolved in 6 (18.2%) patients, were present throughout in 6 (18.2%) patients, and fluctuated in the remaining 21 (63.6%) patients. Among the 39 patients with new onset of Rome III IBS-type symptoms after baseline, 24 (65.1%) had symptoms at one point in time only, 10 (25.6%) at two points, four (10.3%) at three points, and one (2.6%) at four points. At each point in time, reporting IBS-type symptoms was associated with significantly higher anxiety, depression, or somatoform symptom-reporting scores, and/or lower quality of life scores. CONCLUSIONS & INFERENCES In this 12-month follow-up study, one-third of patients with IBD reported presence of Rome III IBS-type symptoms at any point in time. Reporting such symptoms was associated with significant impacts on psychological health and/or quality of life.
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Affiliation(s)
- Brigida Barberio
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University Hospital of Padova, Padova, Italy
| | - Keeley M Fairbrass
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research, St. James's, University of Leeds, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research, St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research, St. James's, University of Leeds, Leeds, UK
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Kim YJ, Lee SG, Lee JS, Choi YJ, Son CG. Comparative characteristics of fatigue in irritable bowel syndrome and inflammatory bowel disease: A systematic review and meta-analysis. J Psychosom Res 2024; 177:111589. [PMID: 38199049 DOI: 10.1016/j.jpsychores.2024.111589] [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: 10/24/2023] [Revised: 12/30/2023] [Accepted: 01/04/2024] [Indexed: 01/12/2024]
Abstract
OBJECTIVE Fatigue is a common symptom in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to distinguish fatigue characteristics in IBS and IBD, two functional and organic disorders. METHODS We systematically searched the PubMed and Cochrane Library databases from inception to June 30, 2023, and conducted a meta-analysis to generate precise estimates and 95% confidence intervals. The analyses were stratified by fatigue type, severity, sex, disease phase, and comorbidities, and study quality was assessed using Newcastle-Ottawa Scale (NOS). RESULTS Our analysis included 74 data (13 IBS, 31 CD, 30 UC) encompassing 16,689 participants (6484 males, 7402 females, and 2803 unknown). Overall, fatigue prevalence trended higher in IBS (54.5% [95%CI, 44.5-64.6]), followed by CD (49.8% [95%CI, 44.0-55.5]) and UC (43.6% [95%CI, 38.5-48.7]). This pattern persisted across sub-analyses, including general fatigue (63.4% vs. 51.3% vs. 45.3%) and moderate to severe fatigue (73.8% vs. 59.5% vs. 52.7%) for IBS, CD, and UC, respectively. Female predominance was observed in all three diseases (odds ratio: 1.5 in IBS and CD, 1.8 in UC). Fatigue prevalence significantly varied between disease phases (active vs. remission) in CD (61.3% vs. 36.3%) and UC (53.8% vs. 32.6%). Anemia, anxiety/depression, and/or IBS-like symptoms also contributed to fatigue in CD and UC. CONCLUSIONS This study is the first extensive comparison of fatigue prevalence and features in IBS, CD, and UC. The findings offer valuable insights for treatment and management, aiding our understanding of functional and organic diseases.
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Affiliation(s)
- Yeon-Jae Kim
- Korean Medical College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon 34520, Republic of Korea
| | - Seul-Gi Lee
- Korean Medical College of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon 34520, Republic of Korea
| | - Jin-Seok Lee
- Research Center for CFS/ME, Daejeon Oriental Hospital of Daejeon University, 176 Daedeokdae-ro, Seo-gu, Daejeon 35235, Republic of Korea
| | - Yu-Jin Choi
- Research Center for CFS/ME, Daejeon Oriental Hospital of Daejeon University, 176 Daedeokdae-ro, Seo-gu, Daejeon 35235, Republic of Korea
| | - Chang-Gue Son
- Research Center for CFS/ME, Daejeon Oriental Hospital of Daejeon University, 176 Daedeokdae-ro, Seo-gu, Daejeon 35235, Republic of Korea; Institute of Bioscience and Integrative Medicine, Daejeon University, 62 Daehak-ro, Dong-gu, Daejeon 34520, Republic of Korea.
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Kazyulin A, Goncharenko A, Pavleeva E, Lyubozhnova I, Kalyagin I. Understanding similarities and differences of irritable bowel syndrome and conditions with IBS-like symptoms. RUSSIAN JOURNAL OF EVIDENCE-BASED GASTROENTEROLOGY 2024; 13:66. [DOI: 10.17116/dokgastro20241301166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Khasawneh M, Craig OF, Gracie DJ, Black CJ, Ford AC. A Diagnosis of Irritable Bowel Syndrome Using Rome IV Criteria and Limited Investigations is Durable in Secondary Care. Clin Gastroenterol Hepatol 2023; 21:3397-3404.e1. [PMID: 37302448 DOI: 10.1016/j.cgh.2023.05.022] [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: 02/21/2023] [Revised: 03/30/2023] [Accepted: 05/22/2023] [Indexed: 06/13/2023]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a positive diagnosis, made using symptom-based criteria and limited, judicious, investigation. However, this may lead to uncertainty on the part of clinicians regarding potential for a missed diagnosis of organic gastrointestinal disease. Few studies have examined durability of a diagnosis of IBS, and none have used the current gold standard to diagnose IBS, the Rome IV criteria. METHODS We collected complete symptom data from 373 well-characterized adults meeting Rome IV criteria for IBS referred to a single UK clinic between September 2016 and March 2020. All patients underwent relatively standardized work-up to exclude relevant organic disease before diagnosis. We followed these individuals up to December 2022, assessing rates of rereferral, reinvestigation, and missed organic gastrointestinal disease. RESULTS During a mean follow-up of 4.2 years per patient (total follow-up in all patients, 1565 years), 62 (16.6%) patients were rereferred. Of these, 35 (56.5%) were rereferred for IBS and 27 (43.5%) for other gastrointestinal symptoms. Among the 35 rereferred with IBS this was caused by a change in symptoms in only 5 (14.3%). Reinvestigation was undertaken in 21 (60.0%) of 35 rereferred with IBS and 22 (81.5%) of 27 rereferred with other symptoms (P = .12). Only 4 (9.3% of those reinvestigated and 1.1% of the entire cohort) new cases of relevant organic disease, which may have been responsible for IBS symptoms at baseline, were identified (1 case of chronic calcific pancreatitis among those rereferred with IBS and 1 case each of inflammatory bowel disease-unclassified, moderate bile acid diarrhea, and small bowel obstruction among those rereferred with other gastrointestinal symptoms). CONCLUSIONS Despite rereferral for gastrointestinal symptoms among 1 in 6 patients overall, with almost 10% rereferred with ongoing IBS symptoms, and substantial reinvestigation rates, missed organic gastrointestinal disease occurred in only 1%. A diagnosis of Rome IV IBS after limited investigation is safe and durable.
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Affiliation(s)
- Mais Khasawneh
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Orla F Craig
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute for Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute for Medical Research at St. James's, University of Leeds, Leeds, United Kingdom.
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