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Xu L, Xiao T, Xu L, Zou B, Yao W. Bulk and single-cell RNA sequencing reveal the roles of neutrophils in pediatric Crohn's disease. Pediatr Res 2025:10.1038/s41390-025-03961-x. [PMID: 40121337 DOI: 10.1038/s41390-025-03961-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/28/2025] [Accepted: 02/13/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Pediatric Crohn's disease (CD) is a chronic inflammatory bowel disorder that poses significant health risks to children. Although the precise etiology of CD remains elusive, further exploration is needed to identify diagnostic biomarkers and therapeutic targets. METHODS This study utilized single-cell and bulk RNA sequencing data derived from ileal and colonic biopsy samples to explore the molecular mechanisms and cell types associated with CD, as well as to pinpoint potential biomarkers and therapeutic targets. RESULTS The results revealed a more pronounced alteration in both the quantity and functional state of neutrophils in the CD cohort compared to those with ulcerative colitis and healthy controls. Neutrophils were present in higher proportions in the CD group, primarily in an activated state, potentially correlating with the presence of deep ulcerations and inflammatory histopathological features. Additionally, neutrophil interactions with other cell types were markedly enhanced in the CD group, making neutrophils the dominant participants in cell-to-cell communications. Further analysis indicated a shift in neutrophil phenotype from pro-inflammatory and antimicrobial to tissue-repairing, which may contribute to the progression and exacerbation of CD. CONCLUSION IL1B, ICAM1, CXCL1, and CXCL9, primarily expressed in neutrophils, were potential biomarkers for CD. Neutrophils might be considered a potential target for pediatric CD. IMPACT STATEMENT This study demonstrated that patients with CD exhibited a greater proportion of activated neutrophils, with enhanced interactions between neutrophils and all other cell types, resulting in neutrophils contributing the most cell-cell interactions within the CD gut. Neutrophils in the CD gut transition from a pro-inflammatory and antibacterial phenotype to one that promotes tissue healing, potentially influencing the progression and exacerbation of CD. Neutrophils represent a promising therapeutic target in pediatric CD. Hub genes associated with CD, including IL1B, ICAM1, CXCL1, and CXCL9, are predominantly expressed in neutrophils, positioning them as promising diagnostic biomarkers for CD.
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Affiliation(s)
- Lei Xu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ting Xiao
- Department of Ultrasonography, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ling Xu
- Department of Nursing, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Biao Zou
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Wei Yao
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Mahurkar‐Joshi S, Thompson M, Villarruel E, Lewis JD, Lin LD, Farid M, Nayeb‐Hashemi H, Storage T, Weiss GA, Limketkai BN, Sauk JS, Mayer EA, Chang L. Genome-Wide DNA Methylation Identifies Potential Disease-Specific Biomarkers and Pathophysiologic Mechanisms in Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Celiac Disease. Neurogastroenterol Motil 2025; 37:e14980. [PMID: 39673136 PMCID: PMC11748828 DOI: 10.1111/nmo.14980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND AND AIMS Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease (CeD) present with similar gastrointestinal (GI) symptoms. DNA methylation-based biomarkers have not been investigated as diagnostic biomarkers to classify these disorders. We aimed to study DNA methylation profiles of IBS, IBD, CeD, and healthy controls (HC), develop machine learning-based classifiers, and identify associated gene ontology (GO) terms. METHODS Genome-wide DNA methylation of peripheral blood mononuclear cells from 315 patients with IBS, IBD, CeD, and HC was measured using Illumina's 450K or EPIC arrays. A methylation dataset on 304 IBD and HC samples was used for external validation. Differential methylation was measured using general linear models. Classifiers were developed using penalized generalized linear models using double cross-validation controlling for confounders. Functional enrichment was assessed using GO. RESULTS Three hundred and fifteen participants (148 IBS, 47 IBD, 34 CeD, and 86 HC) had DNA methylation data. IBS-IBD and IBD-CeD showed the highest number of differentially methylated CpG sites followed by IBD-HC, CeD-HC, and IBS-HC. IBS-associated genes were enriched in cell adhesion and neuronal pathways, while IBD- and CeD-associated markers were enriched in inflammation and MHC class II pathways, respectively (p < 0.05). Classification performances assessed using area under the receiver operating characteristic curves (AUC) for IBS-IBD, IBS-CeD, and IBD-CeD were 0.80 (95% CI = 0.7-0.87, p = 6.75E-10), 0.78 (95% CI = 0.68-0.86, p = 4.57E-10), and 0.73 (95% CI = 0.62-0.83, p = 0.03), respectively. The performance of IBD-HC was successfully validated using external data (AUC = 0.74 [95% CI = 68-0.80, p < 0.001]). CONCLUSIONS Blood-based DNA methylation biomarkers can potentially distinguish chronic GI disorders that present with similar symptoms. GO suggested functional significance of the classifiers in disease-specific pathology.
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Affiliation(s)
- Swapna Mahurkar‐Joshi
- G. Oppenheimer Center for the Neurobiology of Stress and ResilienceLos AngelesCaliforniaUSA
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Mike Thompson
- Systems BiologyCentre for Genomic RegulationBarcelonaSpain
| | | | - James D. Lewis
- Division of Gastroenterology and HepatologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUSA
| | - Lisa D. Lin
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Mary Farid
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Hamed Nayeb‐Hashemi
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Tina Storage
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Guy A. Weiss
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
- UCLA Celiac Disease ProgramLos AngelesCaliforniaUSA
| | - Berkeley N. Limketkai
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Jenny S. Sauk
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Emeran A. Mayer
- G. Oppenheimer Center for the Neurobiology of Stress and ResilienceLos AngelesCaliforniaUSA
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Lin Chang
- G. Oppenheimer Center for the Neurobiology of Stress and ResilienceLos AngelesCaliforniaUSA
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
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Umar N, Harvey P, Adderley NJ, Haroon S, Trudgill N. The Time to Inflammatory Bowel Disease Diagnosis for Patients Presenting with Abdominal Symptoms in Primary Care and its Association with Emergency Hospital Admissions and Surgery: A Retrospective Cohort Study. Inflamm Bowel Dis 2025; 31:140-150. [PMID: 38563769 DOI: 10.1093/ibd/izae057] [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: 10/20/2023] [Indexed: 04/04/2024]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes. METHODS A retrospective cohort study using English primary care data from January 1, 2010, to December 31, 2019, linked to hospital admission data was undertaken. Patients were followed from the first IBD-related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models, respectively. RESULTS Of 28 092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn's disease (CD). The median age was 43 (interquartile range, 30-58) years and 51.9% were female. Median time to diagnosis was 15.6 (interquartile range, 4.3-28.1) months. Factors associated with more than a year to diagnosis included female sex (adjusted risk ratio [aRR], 1.23; 95% CI, 1.21-1.26), older age (aRR, 1.05; 95% CI, 1.01-1.10; comparing >70 years of age with 18-30 years of age), obesity (aRR, 1.03; 95% CI, 1.00-1.06), smoking (aRR, 1.05; 95% CI, 1.02-1.08), CD compared with UC (aRR, 1.13; 95% CI, 1.11-1.16), and a fecal calprotectin over 500 μg/g (aRR, 0.89; 95% CI, 0.82-0.95). The highest quartile of time to diagnosis compared with the lowest was associated with IBD-related emergency admissions (incidence rate ratio, 1.06; 95% CI, 1.01-1.11). CONCLUSION Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn's disease. More IBD-related emergency admissions were observed in patients with a prolonged time to diagnosis.
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Affiliation(s)
- Nosheen Umar
- Department of Gastroenterology, Sandwell and West Birmingham NHS Trust, West Bromwich, United Kingdom
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Phil Harvey
- Gastroenterology Department, Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom
| | - Nicola J Adderley
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
- National Institute for Health and Care Research Birmingham Biomedical Research Centre, Birmingham, United Kingdom
| | - Shamil Haroon
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Nigel Trudgill
- Department of Gastroenterology, Sandwell and West Birmingham NHS Trust, West Bromwich, United Kingdom
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
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Souaid C, Fares E, Primard P, Macaigne G, El Hajj W, Nahon S. A review investigating delays in Crohn's disease diagnosis. Clin Res Hepatol Gastroenterol 2025; 49:102500. [PMID: 39551466 DOI: 10.1016/j.clinre.2024.102500] [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: 10/27/2024] [Accepted: 11/14/2024] [Indexed: 11/19/2024]
Abstract
Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract where early diagnosis and timely, appropriate management are essential to prevent severe complications and reduce the need for surgery. This review sought to investigate factors contributing to diagnostic delays in CD, which typically ranged from 5 to 16 months. Delays were often due to nonspecific symptoms that could be mistaken for irritable bowel syndrome (IBS) and were influenced by various factors including age, education level, smoking, NSAID use, and disease characteristics like isolated ileal involvement. Healthcare system disparities also played a significant role, with delays varying by access to care. The review highlighted that delayed diagnosis was linked to worse disease outcomes, such as increased severity and complications, and underscored the importance of early intervention combined with timely management. Strategies to mitigate delays included implementing red flag tools, using inflammatory biomarkers like fecal calprotectin, and enhancing public and healthcare provider awareness. Addressing these factors and improving referral pathways and healthcare system efficiencies were crucial for enhancing early diagnosis and patient outcomes.
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Affiliation(s)
- Christophe Souaid
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Eddy Fares
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Paul Primard
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Gilles Macaigne
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Weam El Hajj
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France
| | - Stephane Nahon
- Gastroenterology Unit, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, France.
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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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Ferraro S, Cappello E, Bartolini C, Convertino I, Bertani L, Lucenteforte E, Costa F, Paoletti O, Giometto S, Gini R, Tuccori M. Potential missed diagnoses of Crohn's disease in tertiary care: impact on drug utilization and healthcare facilities use. Eur J Gastroenterol Hepatol 2023; 35:1263-1269. [PMID: 37724478 DOI: 10.1097/meg.0000000000002642] [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] [Indexed: 09/20/2023]
Abstract
BACKGROUND A missed diagnosis of Crohn's disease (CD) can delay treatment initiation with consequences on disease course. AIMS To measure the possible impact of missed diagnoses on drug utilization and access to healthcare facilities in a real-world cohort of CD patients. METHODS This retrospective observational study has been conducted on the regional administrative databases of Tuscany (Italy). We included patients with a first record of CD diagnosis between 06/11/2011 and 06/30/2016. Possible missed diagnosis (exposure) was defined by hospital presentation for gastrointestinal symptoms consistent with CD diagnosis that occurred in the 7-60 months preceding CD diagnosis. We compared exposed and non-exposed patients by assessing time-free from biologic drugs and from Emergency Department (ED) or hospital access. Hazard ratio (HR) was calculated using Cox models. RESULTS Among 3342 CD patients, 584 (17.5%) had a possible missed diagnosis. A risk of being treated with biologic drugs [adjusted HR (aHR): 2.17, 95% CI: 1.75-2.71] and of access to ED or hospitalization (aHR: 1.59, 95% CI: 1.44-1.75) was observed in patients with a possible missed diagnosis as compared to those without. CONCLUSION Tertiary care caregivers should be trained in the identification of early CD symptoms, to timely identify CD diagnosis and optimize pharmacological treatment and disease management.
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Affiliation(s)
- Sara Ferraro
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa
| | - Emiliano Cappello
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa
| | - Claudia Bartolini
- Osservatorio di Epidemiologia, Agenzia Regionale di Sanità della Toscana, Firenze
| | - Irma Convertino
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa
| | - Lorenzo Bertani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa
| | - Ersilia Lucenteforte
- Unit of Medical Statistics, Department of Clinical and Experimental Medicine, University of Pisa
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, Pisa University Hospital
| | - Olga Paoletti
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa
| | - Sabrina Giometto
- Unit of Medical Statistics, Department of Clinical and Experimental Medicine, University of Pisa
| | - Rosa Gini
- Osservatorio di Epidemiologia, Agenzia Regionale di Sanità della Toscana, Firenze
| | - Marco Tuccori
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, Pisa
- Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy
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Xie J, Chen M, Wang W, Shao R. Factors associated with delayed diagnosis of Crohn's disease: A systematic review and meta-analysis. Heliyon 2023; 9:e20863. [PMID: 37860523 PMCID: PMC10582495 DOI: 10.1016/j.heliyon.2023.e20863] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 09/27/2023] [Accepted: 10/09/2023] [Indexed: 10/21/2023] Open
Abstract
Background Delayed diagnosis is a major barrier to the effective management of Crohn's disease (CD). Several studies have investigated factors responsible for delays in diagnosis, but no meta-analyses have systematically assessed the impact of these factors. Aim To assess the impact of various factors on the delayed diagnosis of CD. Methods PubMed, EMBASE, and Web of Science databases were searched to identify observational studies published before April 2022 that assessed factors associated with delays in CD diagnosis. Further, we excluded review articles, case reports, or commentaries without original data. We pooled effect siee distinct samples. The assessment of study quality was performed utilizing the Newcastle-Ottawa Scale, while the presence of between-study heterogeneity was investigated. For a visual appraisal of potential publication bias, a funnel plot was employed. The study protocol was registered with PROSPERO, CRD42022322251. Results A total of 18 studies were included in the paper, covering 13 countries. The study sample consisted of 9669 cases. Ileal CD (OR = 1.46, 95 % CI = 1.21-1.76), smoking at the time of diagnosis (OR = 1.19, 95 % CI = 1.02-1.38), and use of NSAIDs (OR = 1.34, 95 % CI = 1.04-1.72) were significantly associated with a delay in CD diagnosis. However, no significant associations were observed between diagnostic delay and sex, age, endoscopic ileocolonoscopy, or diarrhea. Funnel plot analysis, indicating potential risks of publication bias, suggested the existence of unpublished or unreported study findings. Conclusion The findings suggest that ileal CD, use of NSAIDs, and smoking are risk factors for the delayed diagnosis of CD. Enhancing education of patients and primary care providers about these factors is warranted.
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Affiliation(s)
| | | | - Wenrui Wang
- The Research Center of National Drug Policy & Ecosystem, China Pharmaceutical University, Nanjing, 211198, China
| | - Rong Shao
- The Research Center of National Drug Policy & Ecosystem, China Pharmaceutical University, Nanjing, 211198, China
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Scott FI, Ehrlich O, Wood D, Viator C, Rains C, DiMartino L, McArdle J, Adams G, Barkoff L, Caudle J, Cheng J, Kinnucan J, Persley K, Sariego J, Shah S, Heller C, Rubin DT. Creation of an Inflammatory Bowel Disease Referral Pathway for Identifying Patients Who Would Benefit From Inflammatory Bowel Disease Specialist Consultation. Inflamm Bowel Dis 2023; 29:1177-1190. [PMID: 36271884 PMCID: PMC10393070 DOI: 10.1093/ibd/izac216] [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: 03/18/2022] [Indexed: 08/03/2023]
Abstract
BACKGROUND Recommendations regarding signs and symptoms that should prompt referral of patients with inflammatory bowel disease (IBD) to an IBD specialist for a consultation could serve to improve the quality of care for these patients. Our aim was to develop a consult care pathway consisting of clinical features related to IBD that should prompt appropriate consultation. METHODS A scoping literature review was performed to identify clinical features that should prompt consultation with an IBD specialist. A panel of 11 experts was convened over 4 meetings to develop a consult care pathway using the RAND/UCLA Appropriateness Method. Items identified via scoping review were ranked and were divided into major and minor criteria. Additionally, a literature and panel review was conducted assessing potential barriers and facilitators to implementing the consult care pathway. RESULTS Of 43 features assessed, 13 were included in the care pathway as major criteria and 15 were included as minor criteria. Experts agreed that stratification into major criteria and minor criteria was appropriate and that 1 major or 2 or more minor criteria should be required to consider consultation. The greatest barrier to implementation was considered to be organizational resource allocation, while endorsements by national gastroenterology and general medicine societies were considered to be the strongest facilitator. CONCLUSIONS This novel referral care pathway identifies key criteria that could be used to triage patients with IBD who would benefit from IBD specialist consultation. Future research will be required to validate these findings and assess the impact of implementing this pathway in routine IBD-related care.
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Affiliation(s)
- Frank I Scott
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | | | - Dallas Wood
- RTI International, Research Triangle Park, NC, USA
| | | | - Carrie Rains
- RTI International, Research Triangle Park, NC, USA
| | | | - Jill McArdle
- RTI International, Research Triangle Park, NC, USA
| | | | | | - Jennifer Caudle
- Department of Family Medicine, Rowan University School of Osteopathic Medicine, Sewell, NJ, USA
| | | | - Jami Kinnucan
- Section of Gastroenterology and Hepatology Mayo Clinic, Jacksonville, FL, USA
| | | | - Jennifer Sariego
- Penn Medicine At Home, University of Pennsylvania Health System, Bala Cynwd, PA, USA
| | - Samir Shah
- Division of Gastroenterology, Brown University, Providence, RI, USA
| | | | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
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9
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Jayasooriya N, Baillie S, Blackwell J, Bottle A, Petersen I, Creese H, Saxena S, Pollok RC. Systematic review with meta-analysis: Time to diagnosis and the impact of delayed diagnosis on clinical outcomes in inflammatory bowel disease. Aliment Pharmacol Ther 2023; 57:635-652. [PMID: 36627691 DOI: 10.1111/apt.17370] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/29/2022] [Accepted: 12/10/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND The impact of diagnostic delay on the clinical course of inflammatory bowel disease (IBD) remains uncertain. AIM To perform a systematic review of time to diagnosis and the impact of delayed diagnosis on clinical outcomes in Crohn's disease (CD) and ulcerative colitis (UC). METHODS We searched EMBASE and Medline from inception to 30th November 2022 for studies reporting diagnostic interval, from symptom onset to IBD diagnosis. We calculated the median, interquartile range (IQR) and pooled weighted median, of median diagnostic intervals of eligible studies. We defined delayed diagnosis as individuals above the 75th centile of longest time to diagnosis in each study. Using random effects meta-analysis, we pooled odds ratios (ORs) with 95% confidence intervals (CI) for studies reporting clinical outcomes, according to delayed diagnosis. RESULTS One hundred and one studies representing 112,194 patients with IBD (CD = 59,359; UC = 52,835) met inclusion criteria. The median of median times to diagnosis was 8.0 (IQR: 5.0-15.2) and 3.7 months (IQR: 2.0-6.7) in CD and UC, respectively. In high-income countries, this was 6.2 (IQR: 5.0-12.3) and 3.2 months (IQR: 2.2-5.3), compared with 11.7 (IQR: 8.3-18.0) and 7.8 months (IQR: 5.2-21.8) in low-middle-income, countries, for CD and UC respectively. The pooled weighted median was 7.0 (95% CI: 3.0-26.4) and 4.6 (95% CI: 1.0-96.0) months, for CD and UC respectively. Eleven studies, representing 6164 patients (CD = 4858; UC = 1306), were included in the meta-analysis that examined the impact of diagnostic delay on clinical outcomes. In CD, delayed diagnosis was associated with higher odds of stricturing (OR = 1.88; CI: 1.35-2.62), penetrating disease (OR = 1.64; CI: 1.21-2.20) and intestinal surgery (OR = 2.24; CI: 1.57-3.19). In UC, delayed diagnosis was associated with higher odds of colectomy (OR = 4.13; CI: 1.04-16.40). CONCLUSION Delayed diagnosis is associated with disease progression in CD, and intestinal surgery in both CD and UC. Strategies are needed to achieve earlier diagnosis of IBD.
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Affiliation(s)
- Nishani Jayasooriya
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Samantha Baillie
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Jonathan Blackwell
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
| | - Alex Bottle
- School of Public Health, Imperial College London, London, UK
| | - Irene Petersen
- Department of Primary Care and Population Health, University College London, London, UK
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Hanna Creese
- School of Public Health, Imperial College London, London, UK
| | - Sonia Saxena
- School of Public Health, Imperial College London, London, UK
| | - Richard C Pollok
- Department of Gastroenterology, St George's Healthcare NHS Trust, St George's University, London, UK
- Institute of Infection and Immunity, St George's University, London, UK
- School of Public Health, Imperial College London, London, UK
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Sung KY, Zhang B, Wang HE, Bai YM, Tsai SJ, Su TP, Chen TJ, Hou MC, Lu CL, Wang YP, Chen MH. Schizophrenia and risk of new-onset inflammatory bowel disease: a nationwide longitudinal study. Aliment Pharmacol Ther 2022; 55:1192-1201. [PMID: 35261051 DOI: 10.1111/apt.16856] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/16/2021] [Accepted: 02/16/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with increasing global prevalence. The risk of IBD in patients with schizophrenia remains unclear. We aim to investigate the risk of new-onset IBD in patients with schizophrenia compared with matched controls. METHODS We conducted a retrospective, population-based cohort study utilising patient data from the Taiwan National Health Insurance Research Database collected between January 1, 2001, and December 31, 2011. Patients diagnosed with schizophrenia by board-certified psychiatrists without prior diagnosis of IBD were enrolled and matched to controls in 1:4 fashion by age, sex, residence, income level and medical comorbidities. Adjusted hazard ratios (HRs) for new-onset IBD and sub-analyses were determined using Cox regression analysis with adjustments. RESULTS Among 116 164 patients with schizophrenia and 464 656 matched controls, overall incidence of IBD among patients was significantly higher (1.14% vs. 0.25%). Average age of IBD diagnosis was 46.82 among patients with schizophrenia, versus 55.30 among controls. The HR of developing IBD among patients was 3.28, with a 95% confidence interval (95% CI) 2.49-4.33. IBD risk was higher among patients with psychiatric admissions more than once per year (HR 7.99, 95% CI 5.25-12.15) compared to those hospitalised less frequently (HR 2.72, 95% CI 2.03-3.66). CONCLUSIONS This population-based cohort study demonstrates a significant association between schizophrenia and subsequent IBD development. Patients with schizophrenia develop IBD at a younger age, and the risk increases with inadequately controlled schizophrenia. Physician vigilance and awareness of this correlation will improve IBD diagnosis and management among this vulnerable patient population.
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Affiliation(s)
- Kuan-Yi Sung
- Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Bing Zhang
- Department of Medicine, Division of Gastrointestinal and Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Hohui E Wang
- Department of Psychiatry, University of California San Francisco, San Francisco, California, USA
| | - Ya-Mei Bai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tung-Ping Su
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Departments of Psychiatry and Medicine, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Tzeng-Ji Chen
- Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Hospital and Health Care Administration, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Liang Lu
- Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Brain Science, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yen-Po Wang
- Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Brain Science, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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11
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Holmes H, McMaster J, Davies H, Vaines V, Turvill J. Evaluation of the Cost-Utility of the York Faecal Calprotectin Care Pathway. Expert Rev Pharmacoecon Outcomes Res 2022; 22:521-528. [DOI: 10.1080/14737167.2020.1751613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
| | | | | | - Victoria Vaines
- Yorkshire and Humber Academic Health Science Network, Wakefield, UK
| | - James Turvill
- Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York, UK
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12
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Turvill JL, Turnock D, Cottingham D, Haritakis M, Jeffery L, Girdwood A, Hearfield T, Mitchell A, Keding A. The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer. Br J Gen Pract 2021; 71:e643-e651. [PMID: 33798091 PMCID: PMC8279659 DOI: 10.3399/bjgp.2020.1098] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/24/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme. AIM To determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC. DESIGN AND SETTING Patients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation. METHOD The diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results. RESULTS In total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively. CONCLUSION FIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.
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Affiliation(s)
- James L Turvill
- Department of Gastroenterology, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Daniel Turnock
- Department of Gastroenterology, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Dan Cottingham
- Macmillan GP Cancer and End of Life lead, Vale of York Clinical Commissioning Group, West Offices Station Rise, York
| | - Monica Haritakis
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Laura Jeffery
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Annabelle Girdwood
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Tom Hearfield
- Department of Research and Development, York and Scarborough Teaching Hospitals NHS Foundation Trust, York
| | - Alex Mitchell
- Department of Health Sciences, Faculty of Sciences, University of York, York
| | - Ada Keding
- Department of Health Sciences, Faculty of Sciences, University of York, York
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13
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Halligan S, Boone D, Archer L, Ahmad T, Bloom S, Rodriguez-Justo M, Taylor SA, Mallett S. Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review. Health Technol Assess 2021; 25:1-66. [PMID: 34225839 DOI: 10.3310/hta25450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Identification of biomarkers that predict severe Crohn's disease is an urgent unmet research need, but existing research is piecemeal and haphazard. OBJECTIVE To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn's disease. DESIGN This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). DATA SOURCES PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. REVIEW METHODS Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn's disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. RESULTS In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). LIMITATIONS Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as 'high' in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. CONCLUSIONS Research for individual biomarkers to predict severe Crohn's disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. FUTURE WORK We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable. STUDY REGISTRATION This study is registered as PROSPERO CRD42016029363. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 45. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Steve Halligan
- Centre for Medical Imaging, University College London, London, UK
| | - Darren Boone
- Centre for Medical Imaging, University College London, London, UK
| | - Lucinda Archer
- Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK
| | - Tariq Ahmad
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Stuart Bloom
- Department of Gastroenterology, University College Hospital, London, UK
| | | | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Sue Mallett
- Centre for Medical Imaging, University College London, London, UK
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14
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Agrawal M, Spencer EA, Colombel JF, Ungaro RC. Approach to the Management of Recently Diagnosed Inflammatory Bowel Disease Patients: A User's Guide for Adult and Pediatric Gastroenterologists. Gastroenterology 2021; 161:47-65. [PMID: 33940007 PMCID: PMC8640961 DOI: 10.1053/j.gastro.2021.04.063] [Citation(s) in RCA: 144] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 03/29/2021] [Accepted: 04/27/2021] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn's disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.
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Affiliation(s)
- Manasi Agrawal
- The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Elizabeth A. Spencer
- The Division of Pediatric Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jean-Frederic Colombel
- The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ryan C. Ungaro
- The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
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15
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Chen BX, Han ZM, Zhou Q, Liu HB, Xu PC, Zhi FC. Efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn's disease. Scand J Gastroenterol 2021; 56:812-819. [PMID: 33962533 DOI: 10.1080/00365521.2021.1922748] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES The efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn's disease (CD) has not been well studied. We aimed to evaluate the efficacy of infliximab in these patients. MATERIALS AND METHODS This was a retrospective study of all consecutive treatment-naïve patients with newly diagnosed CD with small bowel stricture who started regular infliximab therapy in Nanfang Hospital between January 2015 and December 2019. An effective infliximab therapy was defined as infliximab continuation without the use of steroids, new biologics, endoscopic interventions or intestinal surgery. RESULTS Seventy-nine patients were included. After a median 38 months follow-up, an effective infliximab therapy was achieved in 37 patients. Long diagnostic delay (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.19-0.78; p= .008), pre-stenotic dilatation (HR 0.17, 95%CI 0.09-0.35; p < .001), long segmental stricture (HR 0.20, 95%CI 0.10-0.41; p < .001), and penetrating disease (HR 0.22, 95%CI 0.10-0.49; p < .001) were negatively correlated with an effective infliximab therapy. CONCLUSIONS Infliximab is effective in nearly 50% of treatment-naïve patients with CD with small bowel stricture, and an effective therapy is more likely to be achieved in patients without long diagnostic delay, pre-stenotic dilatation, long segmental stricture or penetrating disease.
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Affiliation(s)
- Bing-Xia Chen
- Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
| | - Ze-Min Han
- Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
| | - Qian Zhou
- Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
| | - Hong-Bin Liu
- Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
| | - Pei-Chun Xu
- Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
| | - Fa-Chao Zhi
- Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China
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16
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Zhu M, Feng Q, Xu X, Qiao Y, Cui Z, Yan Y, Ran Z. Efficacy of early intervention on the bowel damage and intestinal surgery of Crohn's disease, based on the Lémann index. BMC Gastroenterol 2020; 20:421. [PMID: 33308166 PMCID: PMC7733289 DOI: 10.1186/s12876-020-01575-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 12/07/2020] [Indexed: 01/12/2023] Open
Abstract
Background Clinicians aim to prevent progression of Crohn’s disease (CD); however, many patients require surgical resection because of cumulative bowel damage. The aim of this study was to evaluate the impact of early intervention on bowel damage in patients with CD using the Lémann Index and to identify bowel resection predictors.
Methods We analyzed consecutive patients with CD retrospectively. The Lémann Index was determined at the point of inclusion and at follow-up termination. The Paris definition was used to subdivide patients into early and late CD groups. Results We included 154 patients, comprising 70 with early CD and 84 with late CD. After follow-up for 17.0 months, more patients experienced a decrease in the Lémann Index (61.4% vs. 42.9%), and fewer patients showed an increase in the Lémann Index (20% vs. 35.7%) in the early compared with the late CD group. Infliximab and other therapies reversed bowel damage to a greater extent in early CD patients than in late CD patients. Twenty-two patients underwent intestinal surgery, involving 5 patients in the early CD group and 17 patients in the late CD group. Three independent predictors of bowel resection were identified: baseline Lémann index ≥ 8.99, disease behavior B1, and history of intestinal surgery. Conclusions Early intervention within 18 months after CD diagnosis could reverse bowel damage and decrease short-term intestinal resection. Patients with CD with a history of intestinal surgery, and/or a Lémann index > 8.99 should be treated aggressively and monitored carefully to prevent progressive bowel damage.
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Affiliation(s)
- Mingming Zhu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Qi Feng
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xitao Xu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yuqi Qiao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Zhe Cui
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yunqi Yan
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
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17
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Lin SN, Zheng DP, Qiu Y, Zhang SH, He Y, Chen BL, Zeng ZR, Mao R, Chen MH. Classifying Crohn's disease into colon-involving versus non-colon-involving groups is a better predictor of clinical outcomes than the Montreal classification. Therap Adv Gastroenterol 2020; 13:1756284820968732. [PMID: 33329758 PMCID: PMC7720347 DOI: 10.1177/1756284820968732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 10/01/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND A suitable disease classification is essential for individualized therapy in patients with Crohn's disease (CD). Although a potential mechanistic classification of colon-involving and non-colon-involving disease was suggested by recent genetic and microbiota studies, the clinical implication has seldom been investigated. We aimed to explore the association of this colonic-based classification with clinical outcomes in patients with CD compared with the Montreal classification. METHODS This was a retrospective study of CD patients from a tertiary referral center. Patients were categorized into colon-involving and non-colon-involving disease, and according to the Montreal classification. Clinico-demographic data, medications, and surgeries were compared between the two classifications. The primary outcome was the need for major abdominal surgery. RESULTS Of 934 patients, those with colonic involvement had an earlier median (interquartile range) age of onset [23.0 (17.0-30.0) versus 26.0 (19.0-35.0) years, p = 0.001], higher frequency of perianal lesions (31.2% versus 14.5%, p < 0.001) and extraintestinal manifestations (21.8% versus 14.5%, p = 0.010), but lower frequency of stricture (B2) (16.3% versus 24.0%, p = 0.005), than those with non-colon-involving disease. Colon-involving disease was a protective factor against major abdominal surgery [hazard ratio, 0.689; 95% confidence interval (CI), 0.481-0.985; p = 0.041]. However, patients with colon-involving CD were more prone to steroids [odds ratio (OR), 1.793; 95% CI, 1.206-2.666; p = 0.004] and azathioprine/6-mercaptopurine (AZA/6-MP) treatment (OR, 1.732; 95% CI, 1.103-2.719; p = 0.017) than were patients with non-colon-involving disease. The Montreal classification was not predictive of surgery or steroids and AZA/6-MP treatment. CONCLUSION This study supports the rationale for disease classification based on the involvement of colon. This new classification of CD is a better predictor of clinical outcomes than the Montreal classification.
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Affiliation(s)
- Si-Nan Lin
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Dan-Ping Zheng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Sheng-Hong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Yao He
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Bai-Li Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Zhi-Rong Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, Guangdong, P.R. China
| | - Min-Hu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, P.R. China
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18
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Fiorino G, Bonovas S, Gilardi D, Di Sabatino A, Allocca M, Furfaro F, Roda G, Lenti MV, Aronico N, Mengoli C, Angeli E, Gaffuri N, Peyrin-Biroulet L, Danese S. Validation of the Red Flags Index for Early Diagnosis of Crohn's Disease: A Prospective Observational IG-IBD Study Among General Practitioners. J Crohns Colitis 2020; 14:1777-1779. [PMID: 32990721 DOI: 10.1093/ecco-jcc/jjaa111] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Diagnostic delay >12 months is frequent in Crohn's disease [CD]. Recently, the International Organization for Inflammatory Bowel Disease [IO-IBD] developed a tool to identify early CD and reduce diagnostic delay. Subjects with an index ≥8 are more likely to have suspected CD (odds ratio [OR] 205, p <0.0001). We aimed to validate this questionnaire at the community level in patients seen by the general practitioners [GPs] in two large areas of Lombardy, Italy. METHODS Consecutive adult patients referring to the GP were screened. The GPs administered the Red Flags [RF] questionnaire to the eligible patients. All patients were referred to the nearest participating centre to confirm or exclude the diagnosis of CD. Sensitivity, specificity, and positive and negative predictive values [PPV, NPV] of the RF index [RFI] were calculated. Patients lost to follow-up after the first gastroenterological visit were analysed using a non-responder imputation, assuming they were negative for CD diagnosis. RESULTS From November 2016 to November 2019, 112 patients were included. A total of 66 subjects [59%] completed the study after the first gastroenterological visit. The prevalence of CD was 3.6% in the study population [4/112]. The RF index had 50% sensitivity, 58% specificity, 4% PPV, and 97% NPV. A combined diagnostic strategy with faecal calprotectin [FC] [RFI ≥8 and/or FC >250 ng/g] resulted in significantly improved accuracy: sensitivity 100% [29-100%], specificity 72% [55-85%], PPV = 21% [5-51%], NPV = 100% [88-100%]. CONCLUSIONS The RF Index combined with FC is a valid tool to identify patients with high probability of having CD at early stage.
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Affiliation(s)
- Gionata Fiorino
- Humanitas University, Biomedical Sciences, Pieve Emanuele, Italy
| | - Stefanos Bonovas
- Humanitas University, Biomedical Sciences, Pieve Emanuele, Italy
| | - Daniela Gilardi
- Humanitas Clinical and Research Center - IRCCS, IBD Center, Department of Gastroenterology, Rozzano, Italy
| | - Antonio Di Sabatino
- IRCCS San Matteo Hospital Hospital Foundation University of Pavia, First Department of Internal Medicine, Pavia, Italy
| | | | - Federica Furfaro
- Humanitas Clinical and Research Center - IRCCS, IBD Center, Department of Gastroenterology, Rozzano, Italy
| | - Giulia Roda
- Humanitas Clinical and Research Center - IRCCS, IBD Center, Department of Gastroenterology, Rozzano, Italy
| | - Marco V Lenti
- IRCCS San Matteo Hospital Hospital Foundation University of Pavia, First Department of Internal Medicine, Pavia, Italy
| | - Nicola Aronico
- IRCCS San Matteo Hospital Hospital Foundation University of Pavia, First Department of Internal Medicine, Pavia, Italy
| | - Caterina Mengoli
- IRCCS San Matteo Hospital Hospital Foundation University of Pavia, First Department of Internal Medicine, Pavia, Italy
| | - Enzo Angeli
- Humanitas Gavazzeni, Radiology, Bergamo, Italy
| | - Nicola Gaffuri
- Humanitas Gavazzeni, Gastroenterology and Endoscopy, Bergamo, Italy
| | | | - Silvio Danese
- Humanitas University, Biomedical Sciences, Pieve Emanuele, Italy
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19
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Ricciuto A, Mack DR, Huynh HQ, Jacobson K, Otley AR, deBruyn J, El-Matary W, Deslandres C, Sherlock ME, Critch JN, Bax K, Jantchou P, Seidman EG, Carman N, Rashid M, Muise A, Wine E, Carroll MW, Lawrence S, Van Limbergen J, Benchimol EI, Walters TD, Griffiths AM, Church PC. Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease. J Crohns Colitis 2020; 15:419-431. [PMID: 32978629 PMCID: PMC7944510 DOI: 10.1093/ecco-jcc/jjaa197] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. METHODS We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. RESULTS Overall (64% Crohn's disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. CONCLUSIONS Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. PODCAST This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
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Affiliation(s)
- Amanda Ricciuto
- SickKids Hospital, University of Toronto, Toronto, ON, Canada,Corresponding author: Amanda Ricciuto, MD, PhD, FRCPC, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8. Tel.: 416-813-7654; fax: 416-813-6531; email
| | - David R Mack
- Children’s Hospital of Eastern Ontario [CHEO], Inflammatory Bowel Disease Centre, Ottawa, ON, Canada
| | - Hien Q Huynh
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | | | | | - Jennifer deBruyn
- Alberta Children’s Hospital, University of Calgary, Calgary, AB, Canada
| | - Wael El-Matary
- Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | | | | | - Jeffrey N Critch
- Janeway Children’s Health and Rehabilitation Centre, St. John’s, NL, Canada
| | - Kevin Bax
- Children’s Hospital of Western Ontario, London, ON, Canada
| | | | | | - Nicholas Carman
- Children’s Hospital of Eastern Ontario [CHEO], Inflammatory Bowel Disease Centre, Ottawa, ON, Canada
| | | | - Aleixo Muise
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - Eytan Wine
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | - Matthew W Carroll
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | | | | | - Eric I Benchimol
- Children’s Hospital of Eastern Ontario [CHEO], Inflammatory Bowel Disease Centre, Ottawa, ON, Canada,CHEO Research Institute, Ottawa, ON, Canada,Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada,ICES uOttawa, Ottawa, ON, Canada
| | | | | | - Peter C Church
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
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20
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Atia O, Shosberger A, Focht G, Ledder O, Lev-Tzion R, Navon D, Assa A, Yerushalmi B, Shaoul R, Shouval DS, Bar-Gil Shitrit A, Koslowsky B, Dotan I, Kariv R, Lavon E, Turner D. Development and Validation of the IBD-REFER Criteria: Early Referral for Suspected Inflammatory Bowel Diseases in Adults and Children. CROHN'S & COLITIS 360 2020; 2:otaa027. [PMID: 36777296 PMCID: PMC9802171 DOI: 10.1093/crocol/otaa027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Indexed: 11/14/2022] Open
Abstract
Background Early treatment of inflammatory bowel disease (IBD) is associated with positive outcomes but a significant diagnostic delay has been reported in most countries. Aim We aimed to develop and validate IBD-REFER criteria, intended for primary care physicians, to screen patients at risk for IBD. Methods A Delphi group of 10 experts generated a list of symptoms associated with the onset of IBD, supplemented by a review of the literature. The list was reduced in an iterative process and graded based on importance. For data-driven statistical formatting, the charts of 200 IBD (100 children, 100 adults) and 100 non-IBD controls but with gastrointestinal symptoms were reviewed. The IBD-REFER items were scored for each subject, as well as the contending Red Flag criteria from the International Organization for the Study of IBD. External validation was performed on additionally enrolled cohorts of 100 IBD patients and 50 controls. Results The Delphi process retained 5 items as major criteria (≥1 item required for early referral) and 11 as minor (≥2 items required). Following the removal of uninformative items and further formatting in the data-driven stage, 10 core items were retained: 3 as major and 7 as minor. In the external validation, the final IBD-REFER criteria had a sensitivity/specificity of 98%/96% in adults and 96%/96% in children, significantly higher than achieved by the Red Flag criteria (71%/84% and 60%/88%, respectively; P < 0.001). Conclusion The IBD-REFER criteria may guide the selection of patients for expedited gastrointestinal investigation.
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Affiliation(s)
- Ohad Atia
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Adi Shosberger
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Gili Focht
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Oren Ledder
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Raffi Lev-Tzion
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Dan Navon
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Amit Assa
- Schneider Children's Hospital, Petach Tikva, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Baruch Yerushalmi
- Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ron Shaoul
- Pediatric Gastroenterology Institute, Ruth Children’s Hospital, Rambam Medical Center, Haifa, Israel
| | - Dror S Shouval
- Pediatric Gastroenterology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Benjamin Koslowsky
- Digestive diseases institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Revital Kariv
- Health Division, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Eitan Lavon
- Health Division, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel,Address correspondence to: Dan Turner MD, PhD, P.O.B 3235, Shmuel Bait, 12, Jerusalem 91031, Israel ()
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21
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Krishna M, Britto S, Qian J, Ihekweazu F, Rodriguez JR, Kellermayer R. Diagnostic delay and colectomy risk in pediatric ulcerative colitis. J Pediatr Surg 2020; 55:403-405. [PMID: 30992148 DOI: 10.1016/j.jpedsurg.2019.03.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 02/22/2019] [Accepted: 03/19/2019] [Indexed: 01/29/2023]
Abstract
BACKGROUND/PURPOSE Diagnostic delay or time to diagnosis, and its relationship with colectomy risk has been studied in adult Inflammatory Bowel Disease (IBD), but rarely in pediatric IBD (PIBD), especially pediatric ulcerative colitis (P-UC), which often has a more severe course than adult UC. This study compared the relationship between diagnostic delay and colectomy in P-UC. METHODS The medical records of P-UC patients, ages <18 years, diagnosed at Texas Children's Hospital from 2012 to 2018 were examined. We identified 106 P-UC patients, where the onset of symptoms of IBD (i.e. fever, diarrhea, blood in stool, weight loss, abdominal pain) could be clearly identified. RESULTS Twenty (20 = 18.9%) patients progressed to colectomy, and 86 did not. There was no significant difference in diagnostic delay between the patients undergoing colectomy with UC (C-UC) and those with no colectomy (NC-UC) (p = 0.2192). The median (C-UC = 7.1 weeks; NC-UC = 11.9 weeks) and mean (C-UC = 16.5 weeks±4.7; NC-UC = 20.1 ± 2.6) diagnostic delay actually tended to be shorter in C-UC compared to NC-UC. Fecal calprotectin levels were significantly higher (p = 0.0228) in C-UC than NC-UC patients at diagnosis. CONCLUSIONS Shorter time to diagnosis may reflect disease severity at the time of disease onset and also a more aggressive subsequent course of P-UC. The significantly higher level of fecal calprotectin in the C-UC patients at diagnosis provided biologic/biochemical support for our conclusion. LEVELS OF EVIDENCE Prognosis study, Level III evidence.
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Affiliation(s)
- Mahesh Krishna
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX; Wiess School of Natural Sciences, Rice University, Houston, TX, USA
| | - Savini Britto
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX
| | - Justin Qian
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX
| | - Faith Ihekweazu
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX
| | - Jose Ruben Rodriguez
- Texas Children's Hospital, Baylor College of Medicine, Houston, TX; The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX
| | - Richard Kellermayer
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Houston, TX; USDA/ARS Children's Nutrition Research Center, Texas Children's Hospital, Houston, TX.
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22
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Yao JY, Jiang Y, Ke J, Lu Y, Hu J, Zhi M. Development of a prognostic model for one-year surgery risk in Crohn’s disease patients: A retrospective study. World J Gastroenterol 2020; 26:524-534. [PMID: 32089628 PMCID: PMC7015715 DOI: 10.3748/wjg.v26.i5.524] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/06/2020] [Accepted: 01/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Accelerated therapeutic treatment should be considered in patients with progressive Crohn’s disease (CD) to prevent complications as well as surgery. Therefore, screening for risk factors and predicting the need for early surgery are of great importance in clinical practice.
AIM To establish a model to predict CD-related early surgery.
METHODS This was a retrospective study collecting data from CD patients diagnosed at our inflammatory bowel disease center from January 1, 2012 to December 31, 2016. All data were randomly stratified into a training set and a testing set at a ratio of 8:2. Multivariable logistic regression analysis was conducted with receiver operating characteristic curves constructed and areas under the curve calculated. This model was further validated with calibration and discrimination estimated. A nomogram was finally developed.
RESULTS A total of 1002 eligible patients were enrolled with a mean follow-up period of 53.54 ± 13.10 mo. In total, 24.25% of patients received intestinal surgery within 1 year after diagnosis due to complications or disease relapse. Disease behavior (B2: OR [odds ratio] = 6.693, P < 0.001; B3: OR = 14.405, P < 0.001), smoking (OR = 4.135, P < 0.001), body mass index (OR = 0.873, P < 0.001) and C-reactive protein (OR = 1.022, P = 0.001) at diagnosis, previous perianal (OR = 9.483, P < 0.001) or intestinal surgery (OR = 8.887, P < 0.001), maximum bowel wall thickness (OR = 1.965, P < 0.001), use of biologics (OR = 0.264, P < 0.001), and exclusive enteral nutrition (OR = 0.089, P < 0.001) were identified as independent significant factors associated with early intestinal surgery. A prognostic model was established and further validated. The receiver operating characteristic curves and calculated areas under the curves (94.7%) confirmed an ideal predictive ability of this model with a sensitivity of 75.92% and specificity of 95.81%. A nomogram was developed to simplify the use of the predictive model in clinical practice.
CONCLUSION This prognostic model can effectively predict 1-year risk of CD-related intestinal surgery, which will assist in screening progressive CD patients and tailoring therapeutic management.
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Affiliation(s)
- Jia-Yin Yao
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Yi Jiang
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Jia Ke
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Yi Lu
- Department of Anesthesiology, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510130, Guangdong Province, China
| | - Jun Hu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
| | - Min Zhi
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, Guangdong Province, China
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23
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Grob L, Bluemel S, Biedermann L, Fournier N, Rossel JB, Vavricka SR, Zeitz J, Rogler G, Stallmach A, Scharl M. Effect of distance to specialist care for the diagnosis and disease outcome of inflammatory bowel disease in the Swiss inflammatory bowel disease cohort study. Therap Adv Gastroenterol 2020; 13:1756284819895217. [PMID: 32047533 PMCID: PMC6984432 DOI: 10.1177/1756284819895217] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 11/20/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) needs early interventions and an individual specialist-patient relationship. Distance from a tertiary IBD center might affect patient's disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). METHODS Patient's home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity: <10 km (group 1); 10-35 km (group 2); >35 km (group 3). RESULTS Our study included in total 408 IBD patients [234 Crohn's disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1: 28 years; G2: 21 years, G3: 26 years, p < 0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p < 0.01). The occurrence of IBD-related surgeries did not differ between groups. CONCLUSIONS Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland.
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Affiliation(s)
| | | | - Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolas Fournier
- Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Jean-Benoit Rossel
- Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Stephan R. Vavricka
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Jonas Zeitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland Center of Gastroenterology, Clinic Hirslanden Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Andreas Stallmach
- Department of Internal Medicine IV, University Hospital Jena, Jena, Germany
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24
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Schoepfer A, Santos J, Fournier N, Schibli S, Spalinger J, Vavricka S, Safroneeva E, Aslan N, Rogler G, Braegger C, Nydegger A. Systematic Analysis of the Impact of Diagnostic Delay on Bowel Damage in Paediatric Versus Adult Onset Crohn's Disease. J Crohns Colitis 2019; 13:1334-1342. [PMID: 31002741 DOI: 10.1093/ecco-jcc/jjz065] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Length of diagnostic delay is associated with bowel strictures and intestinal surgery in adult patients with Crohn's disease [CD]. Here we assessed whether diagnostic delay similarly impacts on the natural history of paediatric CD patients. METHODS Data from the Swiss IBD Cohort Study were analysed. Frequency of CD-related complications [bowel stenosis, perianal fistula, internal fistula, any fistula, resection surgery, fistula/abscess surgery, any complication] at diagnosis and in the long term [up to 30 years after CD diagnosis] was compared between paediatric patients [diagnosed <18 years] and adult patients [diagnosed ≥18 years] using multivariate Cox proportional hazard regression modelling. RESULTS From 2006 to 2016, 387 paediatric and 1163 adult CD patients were included. Median [interquartile range: IQR] diagnostic delay was 3 [1-9] for the paediatric and 6 [1-24] months for the adult group, respectively. Adult onset CD patients presented at diagnosis more frequently with bowel stenosis [p <0.001] and bowel surgery [p <0.001] compared with paediatric CD patients. In the long term, length of diagnostic delay was significantly associated with bowel stenosis [p = 0.001], internal fistula [p = 0.038], and any complication [p = 0.024] in the adult onset CD population. No significant association between length of diagnostic delay and CD-related outcomes in the long term was observed in the paediatric population. CONCLUSIONS Adult CD patients have longer diagnostic delay compared with paediatric CD patients and present at diagnosis more often with bowel stenosis and surgery. Length of diagnostic delay was found to be predictive for CD-related complications only in the adult but not in the paediatric CD population.
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Affiliation(s)
- Alain Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois [CHUV] and University of Lausanne, Lausanne, Switzerland
| | - Jessica Santos
- Division of Paediatric Gastroenterology, Centre Hospitalier Universitaire Vaudois [CHUV] and University of Lausanne, Lausanne, Switzerland
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine [IUMSP], Lausanne University Hospital, Lausanne, Switzerland
| | - Susanne Schibli
- Division of Paediatric Gastroenterology, Children's Hospital LUKS, Lucerne, Switzerland
| | - Johannes Spalinger
- Division of Paediatric Gastroenterology, Children's Hospital LUKS, Lucerne, Switzerland.,Division of Gastroenterology, University Children's Hospital of Bern, Bern, Switzerland
| | - Stephan Vavricka
- Center for Gastroenterology and Hepatology, Zurich, Switzerland.,Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Nurullah Aslan
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois [CHUV] and University of Lausanne, Lausanne, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Christian Braegger
- Division of Gastroenterology and Nutrition, University Children's Hospital Zurich, Zurich, Switzerland
| | - Andreas Nydegger
- Division of Paediatric Gastroenterology, Centre Hospitalier Universitaire Vaudois [CHUV] and University of Lausanne, Lausanne, Switzerland
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25
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Kinnucan J, Binion D, Cross R, Evans E, Harlen K, Matarese L, Mullins A, O'Neal B, Reiss M, Scott FI, Weaver A, Rosenberg J. Inflammatory Bowel Disease Care Referral Pathway. Gastroenterology 2019; 157:242-254.e6. [PMID: 30980795 DOI: 10.1053/j.gastro.2019.03.064] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 02/12/2019] [Accepted: 03/10/2019] [Indexed: 12/20/2022]
Affiliation(s)
| | - David Binion
- University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Raymond Cross
- University of Maryland School of Medicine, Baltimore, Maryland; Digestive Health Center, University of Maryland Medical Center, Baltimore, Maryland
| | - Elisabeth Evans
- Univeristy of California-San Diego IBD Center, San Diego, California
| | - Kevin Harlen
- Capital Digestive Care, Silver Spring, Maryland; Digestive Health Physicians Association, Silver Spring, Maryland
| | - Laura Matarese
- Brody School of Medicine, East Carolina University, Greenville, North Carolina
| | - Amy Mullins
- American Academy of Family Physicians, Washington, DC
| | - Bud O'Neal
- Our Lady of the Lake, Baton Rouge, Louisiana; Louisiana State University, Baton Rouge, Louisiana
| | - Marci Reiss
- IBD Support Foundation, Los Angeles, California; University of Southern California, Los Angeles, California
| | - Frank I Scott
- IBD Specialist, University of Colorado School of Medicine, Aurora, Colorado
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26
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Loy L, Roda G, Fiorino G, Allocca M, Furfaro F, Argollo M, Peyrin-Biroulet L, Danese S. Detection and management of early stage inflammatory bowel disease: an update for clinicians. Expert Rev Gastroenterol Hepatol 2019; 13:547-555. [PMID: 31007098 DOI: 10.1080/17474124.2019.1605291] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, are lifetime chronic and progressive disorders of poorly known etiology. Over the past few decades, new therapeutic approaches, including early and more aggressive intervention with immunomodulators and biological agents have offered the possibility of a favorable modification in the natural history of inflammatory bowel diseases. Area covered: Here, we review the literature about the effectiveness of early detection and intervention in adult inflammatory bowel diseases patients. Expert commentary: Detecting and managing early stages of inflammatory bowel diseases represents an effective strategy to avoid disease progression in selected patients. Primary care physicians may play a key role in attaining these outcomes by recognizing the signs and symptoms early and making timely referrals. Moreover, early therapeutic intervention with complete disease control may allow dose reduction or even treatment withdrawal in the maintenance phase, reducing side effects, costs, and also improving quality of life.
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Affiliation(s)
- Laura Loy
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy
| | - Giulia Roda
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy
| | - Gionata Fiorino
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy
| | - Mariangela Allocca
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy
| | - Federica Furfaro
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy
| | - Marjorie Argollo
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy
| | - Laurent Peyrin-Biroulet
- b Department of Hepato-Gastroenterology and Inserm U954 , University Hospital of Nancy, Lorraine University , Vandoeuvre-lès-Nancy , France
| | - Silvio Danese
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Rozzano, Milan , Italy.,c Department of Biomedical Sciences , Humanitas Rozzano , Milan , Italy
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27
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Kang HS, Koo JS, Lee KM, Kim DB, Lee JM, Kim YJ, Yoon H, Jang HJ. Two-year delay in ulcerative colitis diagnosis is associated with anti-tumor necrosis factor alpha use. World J Gastroenterol 2019; 25:989-1001. [PMID: 30833804 PMCID: PMC6397722 DOI: 10.3748/wjg.v25.i8.989] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 01/30/2019] [Accepted: 02/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is an uncommon inflammatory bowel disease (IBD). However, its incidence has recently increased in South Korea. Moreover, UC diagnoses are frequently delayed, and the relationship between diagnostic delay and UC prognosis has not been extensively studied in South Korean patients.
AIM To identify meaningful diagnostic delay affecting UC prognosis and to evaluate risk factors associated with diagnostic delay in South Korean patients.
METHODS Medical records of 718 patients with UC who visited the outpatient clinic of six university hospitals in South Korea were reviewed; 167 cases were excluded because the first symptom date was unknown. We evaluated the relationship between the prognosis and a diagnostic delay of 3, 6, 12, 18, and 24 mo by comparing the prognostic factors [anti-tumor necrosis factor (TNF)-α use, admission history due to acute flare-ups, frequent admission due to flare-ups, surgery associated with UC, and the clinical remission state at the latest follow-up] at each diagnostic interval.
RESULTS The mean diagnostic interval was 223.3 ± 483.2 d (median, 69 d; 75th percentile, 195 d). Among the prognostic factors, anti-TNFα use was significantly increased after a diagnostic delay of 24 mo. Clinical risk factors predictive of a 24-mo diagnostic delay were age < 60 years at diagnosis [odd ratio (OR) = 14.778, 95% confidence interval (CI): 1.731-126.121], smoking history (OR = 2.688, 95%CI: 1.239-5.747, P = 0.012), and misdiagnosis of hemorrhoids (OR = 11.066, 95%CI: 3.596-34.053). Anti-TNFα use was associated with extensive UC at diagnosis (OR = 3.768, 95%CI: 1.860-7.632) and 24-mo diagnostic delay (OR = 2.599, 95%CI: 1.006-4.916).
CONCLUSION A diagnostic delay > 24 mo was associated with increased anti-TNFα use. Age < 60 years at diagnosis, smoking history, and misdiagnosis of hemorrhoids were risk factors for delayed diagnosis.
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Affiliation(s)
- Ho Suk Kang
- Department of Internal Medicine, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, South Korea
| | - Ja Seol Koo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, South Korea
| | - Kang Moon Lee
- Department of Internal Medicine, The Catholic University of Korea, St. Vincent’s Hospital, Suwon 16247, South Korea
| | - Dae Bum Kim
- Department of Internal Medicine, The Catholic University of Korea, St. Vincent’s Hospital, Suwon 16247, South Korea
| | - Ji Min Lee
- Department of Internal Medicine, The Catholic University of Korea, St. Vincent’s Hospital, Suwon 16247, South Korea
| | - Yoon Jae Kim
- Department of Gastroenterology, Gachon Graduate School of Medicine Gil Medical Center, Incheon 21565, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, South Korea
| | - Hyun Joo Jang
- Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong 18450, South Korea
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Novacek G, Gröchenig HP, Haas T, Wenzl H, Steiner P, Koch R, Feichtenschlager T, Eckhardt G, Mayer A, Kirchgatterer A, Ludwiczek O, Platzer R, Papay P, Gartner J, Fuchssteiner H, Miehsler W, Peters PG, Reicht G, Vogelsang H, Dejaco C, Waldhör T. Diagnostic delay in patients with inflammatory bowel disease in Austria. Wien Klin Wochenschr 2019; 131:104-112. [PMID: 30715607 DOI: 10.1007/s00508-019-1451-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 01/12/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Delayed diagnosis seems to be common in inflammatory bowel diseases (IBD). The study was carried out to investigate the diagnostic delay and associated risk factors in Austrian IBD patients. METHODS In a multicenter cross-sectional study adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded medical and socioeconomic characteristics. The study outcome was diagnostic delay defined as the period from symptom onset to diagnosis of IBD. RESULTS A total of 1286 patients (Crohn's disease 830, ulcerative colitis 435, inflammatory bowel disease unclassified 21; females 651) with a median age of 40 years (interquartile range 31-52 years) and a median disease duration of 10 years (4-18 years) were analyzed. The median diagnostic delay was 6 months (2-23 months) in Crohn's disease and 3 months (1-10 months) in ulcerative colitis (p < 0.001). In the multivariable regression analysis Crohn's disease, greater age at diagnosis and a high educational level (compared to middle degree level) were independently associated with longer diagnostic delay. CONCLUSION The diagnostic delay was longer in Crohn's disease than in ulcerative colitis patients and was associated with greater age at diagnosis and a higher educational level.
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Affiliation(s)
- Gottfried Novacek
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Hans Peter Gröchenig
- Department of Internal Medicine, Brothers of St. John of God Hospital, St. Veit an der Glan, Spitalgasse 26, 9300, St. Veit an der Glan, Austria
| | - Thomas Haas
- Darmpraxis Salzburg, Bayernstraße 17, 5020, Salzburg, Austria
| | - Heimo Wenzl
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 2, 8036, Graz, Austria
| | - Pius Steiner
- Department of Internal Medicine I, Wels-Grieskirchen Hospital, Grieskirchnerstraße 42, 4600, Wels, Austria
| | - Robert Koch
- Department of Internal Medicine I, Medical University of Innsbruck, Christoph-Probst-Platz 1, Innrain 52, 6020, Innsbruck, Austria
| | - Thomas Feichtenschlager
- Department of Internal Medicine IV, Rudolfstiftung Hospital, Juchgasse 25, 1030, Vienna, Austria
| | - Gerald Eckhardt
- Department of Internal Medicine, Oberpullendorf Hospital, Spitalstraße 32, 7350, Oberpullendorf, Austria
| | - Andreas Mayer
- Department of Internal Medicine II, Universitätsklinikum St. Pölten, Dunant-Platz 1, 3100, St. Pölten, Austria
| | - Andreas Kirchgatterer
- Department of Internal Medicine V, Wels-Grieskirchen Hospital, Wagnleithnerstraße 27, 4710, Grieskirchen, Austria
| | - Othmar Ludwiczek
- Department of Internal Medicine, Hall in Tirol Hospital, Milserstraße 10, 6060, Hall in Tirol, Austria
| | - Reingard Platzer
- Department of Internal Medicine I, Wiener Neustadt Hospital, Corvinusring 3-5, 2700, Wiener Neustadt, Austria
| | - Pavol Papay
- Department of Internal Medicine, Franziskus Hospital, Nikolsdorfergasse 32, 1050, Vienna, Austria
| | - Johanna Gartner
- Department of Internal Medicine, Hanusch Hospital, Heinrich-Collin-Straße 30, 1140, Vienna, Austria
| | - Harry Fuchssteiner
- Department of Internal Medicine IV, Elisabethinen Hospital, Fadingerstraße 1, 4020, Linz, Austria
| | - Wolfgang Miehsler
- Department of Internal Medicine, Brothers of St. John of God Hospital, Kajetanerplatz 1, 5010, Salzburg, Austria
| | - Paul-Gerhard Peters
- Department of Internal Medicine, Feldkirch Hospital, Carinagasse 47, 6800, Feldkirch, Austria
| | - Gerhard Reicht
- Department of Internal Medicine II, Brothers of St. John of God Hospital, Marschallgasse 12, 8020, Graz, Austria
| | - Harald Vogelsang
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Clemens Dejaco
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Thomas Waldhör
- Department of Epidemiology, Center for Public Health, Medical University of Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria
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El Mouzan MI, AlSaleem BI, Hasosah MY, Al-Hussaini AA, Al Anazi AH, Saadah OI, Al Sarkhy AA, Al Mofarreh MA, Assiri AA. Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia. Saudi J Gastroenterol 2019; 25:257-261. [PMID: 30971589 PMCID: PMC6714469 DOI: 10.4103/sjg.sjg_457_18] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIM Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children. PATIENTS AND METHODS This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis. RESULTS There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75th percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC. CONCLUSIONS Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.
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Affiliation(s)
- Mohammad I. El Mouzan
- Department of Pediatrics, Division of Gastroenterology and Head, Pediatric IBD Research Group, King Saud University, Riyadh, Kingdom of Saudi Arabia,Address for correspondence: Prof. Mohammad I. El Mouzan, Department of Pediatrics, College of Medicine, King Saud University, Riyadh - 11461, Kingdom of Saudi Arabia. E-mail:
| | - Badr I. AlSaleem
- Division of Gastroenterology, The Children Hospital, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Mohammed Y. Hasosah
- Department of Pediatrics, Division of Gastroenterology, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | - Abdulrahman A. Al-Hussaini
- Division of Gastroenterology, The Children Hospital, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Aziz H. Al Anazi
- Department of Pediatrics, Division of Gastroenterology, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | - Omar I. Saadah
- Department of Pediatrics, Faculty of Medicine and Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Ahmed A. Al Sarkhy
- Department of Pediatrics, Division of Gastroenterology, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | | | - Asaad A. Assiri
- Department of Pediatrics, Division of Gastroenterology and Prince Abdullah Bin Khalid Celiac Disease Research Chair, King Saud University, Riyadh, Kingdom of Saudi Arabia
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30
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Evolution in clinical presentation of inflammatory bowel disease over time at diagnosis: a multicenter cohort study. Eur J Gastroenterol Hepatol 2018; 30:1125-1129. [PMID: 30004906 DOI: 10.1097/meg.0000000000001201] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Delayed diagnosis of inflammatory bowel disease (IBD) has become a major issue, particularly in terms of the presence of nonspecific and heterogeneous clinical signs. This study aimed to identify changes over time in the epidemiological characteristics and clinical presentation of IBD in a French cohort. PATIENTS AND METHODS Sociodemographic data from patients at three French hospitals (age, sex, country of origin, smoking habits) and characteristics of IBD [diagnostic delay, phenotype, location, first symptoms, first test suggesting diagnosis (endoscopy, imaging examination)] were collected in a computerized database (Focus_MICI). Four diagnostic time periods were assessed: <2000, 2000-2004, 2005-2009, and >2009. RESULTS Among the 926 patients analyzed, 638 (<2000, n=181; 2000-2004, n=104; 2005-2009, n=147; >2009, n=206) had Crohn's disease (CD) and 288 (<2000, n=54; 2000-2004, n=39; 2005-2009, n=80; >2009, n=115) had ulcerative colitis (UC). For CD, statistically significant differences over time were observed for (a) the first revealing disease symptom [more frequent abdominal pain vs. chronic diarrhea (P<0.001)], (b) first investigation suggestive of diagnosis [more frequent computed tomography vs. colonoscopy (P<0.001)], and (c) CD behavior [more frequent inflammatory vs. stricturing/penetrating forms (P<0.001)]. No significant differences over time were observed for UC variables. CONCLUSION In this large multicenter cohort study clinical diagnostic presentation of CD has changed over time. By contrast, there were no changes in the UC clinical presentation.
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31
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Jung D, Lee S, Jeong I, Oh SH, Kim KM. Short-Term Outcome of Infliximab Therapy in Pediatric Crohn's Disease: A Single-Center Experience. Pediatr Gastroenterol Hepatol Nutr 2017; 20:236-243. [PMID: 29302505 PMCID: PMC5750378 DOI: 10.5223/pghn.2017.20.4.236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 10/01/2017] [Accepted: 10/24/2017] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Studies on the efficacy of infliximab (IFX) in a large population of pediatric patients with Crohn's disease (CD) are limited, and prognostic factors are not well-known. The aim of this study was to evaluate outcomes of IFX in pediatric patients with CD and to identify factors associated with poor prognosis. METHODS We retrospectively analyzed medical data of 594 pediatric patients with CD between 1987 and 2013 in a tertiary center. Of these, 156 children treated with IFX were enrolled and were followed up for at least a year with intact data. Outcomes of induction and maintenance, classified as failure or clinical response, were evaluated on the tenth and 54th week of IFX therapy. RESULTS We treated 156 pediatric patients with CD with IFX, and the median duration of IFX therapy was 47 months. For IFX induction therapy, 134 (85.9%) patients experienced clinical response on the 10th week. Among the 134 patients who showed response to induction, 111 (82.8%) patients maintained the clinical response on the 54th week. In multivariate analysis, low hematocrit (p=0.046) at the time of IFX initiation was associated with the failure of IFX induction. For IFX maintenance therapy, longer duration from the initial diagnosis to IFX therapy (p=0.017) was associated with maintenance failure on the 54th week. CONCLUSION We have shown the acceptable outcomes of IFX in a large cohort of pediatric CD patients in Korea. Hematocrit and early introduction of IFX may be prognostic factors for the outcomes of IFX.
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Affiliation(s)
- Dai Jung
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Sunghee Lee
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Insook Jeong
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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32
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Kopylov U, Koulaouzidis A, Klang E, Carter D, Ben-Horin S, Eliakim R. Monitoring of small bowel Crohn's disease. Expert Rev Gastroenterol Hepatol 2017; 11:1047-1058. [PMID: 28737951 DOI: 10.1080/17474124.2017.1359541] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In recent years, the therapeutic paradigm in Crohn's disease has shifted from a mere symptom-oriented approach, to aiming to healing of the underlying inflammation and prevention of long-term structural complications. Such 'treat-to-target' approach may allow for a more stable disease course with less hospitalizations, lower requirement for surgery and improved quality of life. In Crohn's disease, the small bowel is affected in the majority of patients; frequently, Crohn's involves only the small bowel, which remains inaccessible to conventional ileocolonoscopic techniques. Thus, non-invasive monitoring techniques are crucial for accurate disease assessment. Areas covered: This review addresses the indications and clinical implications of non-invasive small bowel monitoring modalities (magnetic resonance enterography, intestinal ultrasound, capsule endoscopy) in the assessment and management of Crohn's disease. Expert commentary: This review addresses the limitations of the current knowledge and future areas of research, including the possible utilization of transmural healing as an imaging target and the need to establish clear quantitative target values to guide treatment by imaging findings in Crohn's disease.
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Affiliation(s)
- Uri Kopylov
- a Department of Gastroenterology, Sheba Medical Center, Tel Hashomer and Sackler Medical School , Tel Aviv University , Tel-Aviv , Israel
| | - Anastasios Koulaouzidis
- b Centre for Liver & Digestive Disorders , The Royal Infirmary of Edinburgh , Edinburgh , UK
| | - Eyal Klang
- c Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer and Sackler Medical School , Tel Aviv University , Tel-Aviv , Israel
| | - Dan Carter
- a Department of Gastroenterology, Sheba Medical Center, Tel Hashomer and Sackler Medical School , Tel Aviv University , Tel-Aviv , Israel
| | - Shomron Ben-Horin
- a Department of Gastroenterology, Sheba Medical Center, Tel Hashomer and Sackler Medical School , Tel Aviv University , Tel-Aviv , Israel
| | - Rami Eliakim
- a Department of Gastroenterology, Sheba Medical Center, Tel Hashomer and Sackler Medical School , Tel Aviv University , Tel-Aviv , Israel
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33
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Hong Z, Ren J, Li Y, Wang G, Gu G, Wu X, Ren H, Li J. Delayed Diagnosis is Associated with Early and Emergency Need for First Crohn's Disease-Related Intestinal Surgery. Med Sci Monit 2017; 23:4841-4846. [PMID: 28991890 PMCID: PMC5644456 DOI: 10.12659/msm.904238] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Increasing evidence suggests that delayed diagnosis in Crohn's disease is associated with a complicated disease course. The aim of this study was to explore the association between delayed diagnosis and the timing of the first Crohn's disease-related intestinal surgery. MATERIAL AND METHODS A retrospective study included 215 Crohn's disease patients with previous surgical history in the Department of General Surgery of Jinling Hospital, China, between January 2013 and March 2016. Data were collected on demographics, clinical characteristics, medication history, and operation history. RESULTS The time from the first appearance of Crohn's disease-related symptoms to the first intestinal surgery in the delayed diagnosis group was obviously shorter than in the non-delayed diagnosis group (26.4±28.7 months vs. 42.6±58.4 months, respectively, p=0.032). Patients in the delayed diagnosis group tended to receive more ileal resections (47.8% vs. 26.4%, respectively, p=0.002) and less ileocecal resections (22.4% vs. 37.2%, respectively, p=0.032). More patients in the delayed diagnosis group received the first Crohn's disease-related intestinal surgery as an emergency one (20.9% vs. 4.7%, respectively, p=0.001). CONCLUSIONS Delayed diagnosis is associated with early and emergency need for the first Crohn's disease-related intestinal surgery.
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Affiliation(s)
- Zhiwu Hong
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Jianan Ren
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Yuan Li
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Gefei Wang
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Guosheng Gu
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Xiuwen Wu
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Huajian Ren
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
| | - Jieshou Li
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China (mainland)
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Cantoro L, Di Sabatino A, Papi C, Margagnoni G, Ardizzone S, Giuffrida P, Giannarelli D, Massari A, Monterubbianesi R, Lenti MV, Corazza GR, Kohn A. The Time Course of Diagnostic Delay in Inflammatory Bowel Disease Over the Last Sixty Years: An Italian Multicentre Study. J Crohns Colitis 2017; 11:975-980. [PMID: 28333328 DOI: 10.1093/ecco-jcc/jjx041] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 03/16/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] patients are still under-diagnosed or diagnosed with serious delay. We examined whether diagnostic delay [DD] in IBD has changed over the last 60 years, and explored the risk factors of longer DD. METHODS In total, 3392 IBD patients recorded in the registry of four IBD Italian centres were divided according to the year of diagnosis into a historical cohort [HC: 1955-84] and modern cohort [MC: 1985-2014]. DD, i.e. time lapse between onset of symptoms indicative of IBD and definitive diagnosis, was divided into four sub-periods [0-6, 7-12, 13-24, >24 months], which were correlated with age and disease location/behaviour at diagnosis. RESULTS Median DD in IBD was 3.0 months, it was significantly [P < 0.0001] higher in Crohn's disease [CD] [7.1 months] than in ulcerative colitis [UC] [2.0 months], and did not differ either between the HC and the MC or over the last three decades. However, the proportion of patients with a DD>24 months was significantly [P < 0.0001] higher in the HC [26.0%] than in the MC [18.2%], and the same trend was evident over the last three decades [1985-94: 19.9%; 1995-2004: 16.4%; 2005-14: 13.9%; P = 0.04]. At logistic regression analysis, age at diagnosis >40 years (CD: odds ratio 1.73, 95% confidence interval [CI] 1.31-2.28, P < 0.0001; UC: 1.41, 95% CI 1.02-1.96, P = 0.04) and complicated disease at CD diagnosis [1.39, 95% CI 1.06-1.82, P = 0.02] were independently associated with a DD>24 months. CONCLUSIONS DD duration has not changed over the last 60 years in Italy, but the number of IBD patients with a longer DD significantly decreased. Older age at diagnosis and a complicated disease at CD diagnosis are risk factors for longer DD.
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Affiliation(s)
- Laura Cantoro
- IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy
| | - Antonio Di Sabatino
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | | | - Sandro Ardizzone
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Italy
| | - Paolo Giuffrida
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Diana Giannarelli
- Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy
| | - Alessandro Massari
- Gastroenterology Unit, Department of Biomedical and Clinical Sciences, Luigi Sacco University Hospital, Italy
| | | | - Marco Vincenzo Lenti
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Gino Roberto Corazza
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Anna Kohn
- IBD Unit, San Camillo-Forlanini Hospital, Rome, Italy
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Kopylov U, Eliakim R. The Lemann Index-A Glance Through the Window of Opportunity? J Crohns Colitis 2017; 11:261-262. [PMID: 27797923 DOI: 10.1093/ecco-jcc/jjw195] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 10/26/2016] [Indexed: 02/08/2023]
Affiliation(s)
- Uri Kopylov
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Rami Eliakim
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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Colombel JF, Narula N, Peyrin-Biroulet L. Management Strategies to Improve Outcomes of Patients With Inflammatory Bowel Diseases. Gastroenterology 2017; 152:351-361.e5. [PMID: 27720840 DOI: 10.1053/j.gastro.2016.09.046] [Citation(s) in RCA: 208] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 09/07/2016] [Accepted: 09/16/2016] [Indexed: 12/12/2022]
Abstract
Strategies for management of inflammatory bowel diseases are shifting from simple control of symptoms toward full control of these diseases (clinical and endoscopic remission), with the final aim of blocking their progression and preventing bowel damage and disability. New goals have been proposed for treatment, such as treat to target and tight control based on therapeutic monitoring and early intervention. For patients who achieve clinical remission, there is often interest in discontinuation of therapy due to safety or economic concerns. We review the evidence supporting these emerging paradigms, the reasons that early effective treatment can alter progression of inflammatory bowel diseases, the importance of examining objective signs of inflammation, and the safety of reducing treatment dosage. We also discuss recent findings regarding personalization of care, including factors that predict patient outcomes and response to therapies, as well as preventative strategies.
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Affiliation(s)
| | - Neeraj Narula
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Laurent Peyrin-Biroulet
- Institut National de la Santé et de la Recherche Médicale U954 and Department of Gastroenterology, Nancy University Hospital, Lorraine University, France
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Fiorino G, Danese S. Diagnostic Delay in Crohn's Disease: Time for Red Flags. Dig Dis Sci 2016; 61:3097-3098. [PMID: 27638835 DOI: 10.1007/s10620-016-4298-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 08/31/2016] [Indexed: 12/19/2022]
Affiliation(s)
- Gionata Fiorino
- Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy. .,Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089, Rozzano, Milan, Italy.
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