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1
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Yamanaka-Takaichi M, Nadalian S, Loftus EV, Ehman EC, Todd A, Grimaldo AB, Yalon M, Matchett CL, Patel NB, Isaq NA, Raffals LE, Wetter DA, Murphree DH, Cima RR, Dozois EJ, Goldfarb N, Tizhoosh HR, Alavi A. Differentiating clinical characteristics of perianal inflammatory bowel disease from perianal hidradenitis suppurativa. Int J Dermatol 2025; 64:520-530. [PMID: 39306801 DOI: 10.1111/ijd.17498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 08/12/2024] [Accepted: 09/07/2024] [Indexed: 02/21/2025]
Abstract
BACKGROUND Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas. METHODS We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD. RESULTS A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife-cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral. CONCLUSIONS The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome.
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Affiliation(s)
| | - Soheila Nadalian
- Laboratory for Knowledge Inference in Medical Image Analysis, University of Waterloo, Waterloo, ON, Canada
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Eric C Ehman
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Austin Todd
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA
| | - Anna B Grimaldo
- Mayo Clinic Alix School of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Mariana Yalon
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Caroline L Matchett
- Division of Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Nisha B Patel
- Division of Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Nasro A Isaq
- Department of Dermatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - David A Wetter
- Department of Dermatology, Mayo Clinic, Rochester, MN, USA
| | | | - Robert R Cima
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
| | - Eric J Dozois
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
| | - Noah Goldfarb
- Department of Dermatology, University of Minnesota Physicians, Minneapolis, MN, USA
| | - Hamid R Tizhoosh
- Kimia lab, Department of Artificial Intelligence and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Afsaneh Alavi
- Department of Dermatology, Mayo Clinic, Rochester, MN, USA
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2
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Herrlinger KR, Stange EF. [New treatment targets for inflammatory bowel disease?]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2025; 66:55-63. [PMID: 39714486 DOI: 10.1007/s00108-024-01826-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/27/2024] [Indexed: 12/24/2024]
Abstract
The classic therapeutic goals of chronic inflammatory bowel disease (IBD) are, on the one hand, clinical remission and, on the other, the prevention of disease progression. The introduction of additional "targets" such as normalization of laboratory inflammation values, endoscopic and, possibly, histological mucosal healing and transmural parameters (ultrasound, magnetic resonance imaging and computed tomography) is intended to improve prognosis. A good response to therapy is usually (also) evident from these targets, although the obligatory change in medication in order to improve the prognosis if the additional treatment goals are not achieved is not evidence-based. In the case of Crohn's disease and ulcerative colitis, individual and, if possible, personalized medicine should continue to be provided instead of strict target specifications.
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Affiliation(s)
| | - E F Stange
- Innere Medizin I, Universitätsklinikum Tübingen, Otfried-Müller-Straße 10, 72076, Tübingen, Deutschland.
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Aguas Peris M, Del Hoyo Francisco J, Nos Mateu P, Echarri Piudo A, Calvo Moya M, Gros B, Martín-Arranz MD, Monte Boquet E, Inglán Agustín S, Valdivia Martínez A, Correcher M, Barreiro-de Acosta M, Mañosa Ciria M, Rodriguez-Moranta F, Zabana Y, Gutiérrez Casbas A. Position statement of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis on the use of Telemedicine in Inflammatory Bowel Disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2024:502320. [PMID: 39672505 DOI: 10.1016/j.gastrohep.2024.502320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 12/08/2024] [Indexed: 12/15/2024]
Abstract
Inflammatory Bowel Disease (IBD) is a chronic digestive condition that requires continuous monitoring by healthcare professionals to determine appropriate therapy and manage short- and long-term complications. Telemedicine has become an essential approach for managing chronic conditions such as IBD, improving care accessibility and continuity, decreasing hospitalization rates, and optimizing patient follow-up. It enables rapid treatment adjustments and encourages patient self-management. Additionally, it reduces the burden on the healthcare system by decreasing unnecessary in-person visits and provides real-time support, thereby improving quality of life and clinical outcomes. The objective of this position statement by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) is to establish recommendations for the use of telemedicine in its different modalities (teleconsulting, telemonitoring, mobile applications and telepharmacy) for patients with IBD and address the legal, ethical, and technical aspects necessary for its proper implementation.
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Affiliation(s)
- Mariam Aguas Peris
- Servicio Aparato Digestivo, Hospital Universitario y Politécnico La Fe, Instituto de Investigación Sanitaria La Fe (IISLaFe), Valencia, España.
| | - Javier Del Hoyo Francisco
- Servicio Aparato Digestivo, Hospital Universitario y Politécnico La Fe, Instituto de Investigación Sanitaria La Fe (IISLaFe), Valencia, España
| | - Pilar Nos Mateu
- Servicio Aparato Digestivo, Hospital Universitario y Politécnico La Fe, Instituto de Investigación Sanitaria La Fe (IISLaFe), Valencia, España
| | - Ana Echarri Piudo
- Servicio Aparato Digestivo, Complejo Hospitalario Universitario Ferrol, A Coruña, España
| | - Marta Calvo Moya
- Servicio Aparato Digestivo, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, España
| | - Beatriz Gros
- Servicio Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España; Instituto Maimónides de Investigación Biomédica (IMIBIC), Universidad de Córdoba, Córdoba, España; Centro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas, CIBEREHD, Madrid, España
| | - María Dolores Martín-Arranz
- Servicio Aparato Digestivo, Hospital Universitario La Paz, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid, España
| | - Emilio Monte Boquet
- Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Valencia, España
| | | | | | - Marisa Correcher
- Departamento Sistemas de Información, Hospital Universitario y Politécnico La Fe, Valencia, España
| | | | - Miriam Mañosa Ciria
- Servicio Aparato Digestivo, Hospital Universitario Germans Trias i Pujol de Badalona, CIBERehd, Barcelona, España
| | | | - Yamile Zabana
- Servicio Aparato Digestivo, Hospital Universitario Mútua Terrassa, Barcelona, España
| | - Ana Gutiérrez Casbas
- Servicio Aparato Digestivo, Hospital General Universitario Dr. Balmis e ISABIAL, CIBERehd, Alicante, España
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Srinivasan AR. Treat to target in Crohn's disease: A practical guide for clinicians. World J Gastroenterol 2024; 30:50-69. [PMID: 38293329 PMCID: PMC10823901 DOI: 10.3748/wjg.v30.i1.50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/23/2023] [Accepted: 12/21/2023] [Indexed: 01/06/2024] Open
Abstract
A treat-to-target (T2T) approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)-II guidelines specify short, intermediate, and long-term treatment goals, documenting specific treatment targets to be achieved at each of these timepoints. Scheduled appraisal of Crohn's disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified. Consensus treatment targets in Crohn's disease comprise combination clinical and patient-reported outcome remission, in conjunction with biomarker normalisation and endoscopic healing. Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing, clinicians must consider that this may not always be appropriate, acceptable, or achievable in all patients. This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets. The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques, particularly intestinal ultrasound, holds great promise; as do emerging treatment targets such as transmural healing. Two randomised clinical trials, namely, CALM and STARDUST, have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn's disease. Findings from these studies reflect that patient subgroups and Crohn's disease characteristics likely to benefit most from a T2T approach, remain to be clarified. Moreover, outside of clinical trials, data pertaining to the real-world effectiveness of a T2T approach remains scare, highlighting the need for pragmatic real-world studies. Despite the obvious promise of a T2T approach, a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake. This highlights the need to describe strategies, processes, and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice. Hence, this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn's disease.
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Affiliation(s)
- Ashish R Srinivasan
- Department of Gastroenterology, Austin Health, Victoria, Melbourne 3083, Australia
- Department of Gastroenterology, Eastern Health, Victoria, Melbourne 3128, Australia
- Department of Medicine, University of Melbourne, Victoria, Melbourne 3052, Australia
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Yoshida Y, Fujioka S, Moriyama T, Umeno J, Kawasaki K, Fuyuno Y, Matsuno Y, Ihara Y, Torisu T, Kitazono T. Disease Flares Following COVID-19 Vaccination in Patients with Inflammatory Bowel Disease. Intern Med 2023; 62:3579-3584. [PMID: 37779068 PMCID: PMC10781543 DOI: 10.2169/internalmedicine.2335-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 08/15/2023] [Indexed: 10/03/2023] Open
Abstract
Objective Flares of inflammatory bowel disease (IBD) can occur infrequently after vaccination for coronavirus disease 2019 (COVID-19), although the details of this phenomenon are poorly understood. To clarify the possibility of an unfavorable response in patients with IBD, we investigated IBD-related symptoms during the COVID-19 vaccination. Methods Between October 2021 and February 2022, we obtained the COVID-19 vaccination status of 411 IBD patients who were being treated at our institution. The disease course of IBD after vaccination was investigated in 188 patients with ulcerative colitis (UC) and 119 patients with Crohn's disease (CD) who had received at least one dose of the vaccine during the clinical remission phase. The baseline characteristics before vaccination were compared between the patients with UC with or without disease flares. Results During the 30-day follow-up period, eight patients with UC (4.3%) and one patient with CD (0.8%) experienced disease flares following vaccination. Disease flares occurred after the first vaccination in six patients and after the second vaccination in three patients. As for the timing of onset of disease flares, eight events (88.9%) occurred within one week of vaccination. Two patients required hospitalization, and one patient with CD required surgery for an intra-abdominal abscess. The baseline characteristics did not significantly differ between patients with UC who experienced flares and those who did not. Conclusion IBD flares following COVID-19 vaccination are rare and vaccination should therefore be recommended for patients with IBD. However, the possibility of disease flares should be considered for approximately one week after each vaccination, especially in patients with UC.
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Affiliation(s)
- Yuichiro Yoshida
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Shin Fujioka
- Department of Endoscopic Diagnostics and Therapeutics, Kyushu University Hospital, Japan
| | | | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Keisuke Kawasaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yuta Fuyuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yuichi Matsuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yutaro Ihara
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
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6
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Herrlinger KR, Stange EF. To STRIDE or not to STRIDE: a critique of "treat to target" in Crohn´s disease. Expert Rev Gastroenterol Hepatol 2023; 17:1205-1219. [PMID: 38131269 DOI: 10.1080/17474124.2023.2296564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023]
Abstract
INTRODUCTION The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease. AREAS COVERED We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn´s disease.' EXPERT OPINION All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.
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Affiliation(s)
| | - Eduard F Stange
- Innere Medizin I, UniversitätsklinikTübingen, Tübingen, Germany
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7
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Narula N, Wong ECL, Aruljothy A, Dulai PS, Colombel JF, Marshall JK, Ferrante M, Reinisch W. Baseline Patient-reported Symptoms Less Predictive Than MM-SES-CD for Endoscopic Remission in Crohn's Disease. J Clin Gastroenterol 2023; 57:913-919. [PMID: 36227009 DOI: 10.1097/mcg.0000000000001774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 09/04/2022] [Indexed: 12/10/2022]
Abstract
BACKGROUND This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn's disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (ER). METHODS This post hoc analysis of 2 clinical trials of infliximab in CD included 601 patients and evaluated baseline PRS variables (abdominal pain, stool frequency, and general well-being) as measured by the Crohn's disease activity index and their association with 6-month clinical remission (CR) (Crohn's Disease Activity Index<150), corticosteroid-free CR, and week 26/54 ER (absence of mucosal ulceration). Logistic regression models assessed the relationships between PRS and outcomes of interest. Receiver operating characteristic curve analyses compared the sensitivity and specificity of the different baseline PRS compared with baseline endoscopic scores for achievement of ER at weeks 26 and 54. RESULTS No difference was found comparing patients with higher baseline PRS to those with lower PRS in achieving 6-month CR, 6-month corticosteroid-free CR, or week 26/54 ER. Modified multiplier of the SES-CD (MM-SES-CD) at baseline demonstrated a significant ability to predict week 54 ER (area under the curve, 0.71; 95% CI 0.65-0.78; P =0.017). CONCLUSIONS Baseline PRS in CD is not prognostic of clinical or endoscopic response. In contrast, active endoscopic disease as measured by the MM-SES-CD, more accurately predicts endoscopic outcomes. Endoscopic scores such as the MM-SES-CD may be considered for selection criteria and as a primary outcome of interest in CD trials, with PRS as a co-primary or secondary endpoint.
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Affiliation(s)
- Neeraj Narula
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Emily C L Wong
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Achuthan Aruljothy
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, IL
| | | | - John K Marshall
- Division of Gastroenterology, Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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8
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Hu X, Li J, Sun Y, Wu D, Zhao T, Ma M, Chen J, Wang M, Hou S. Combined use of CDAI and blood indices for assessing endoscopic activity in ileocolic Crohn's disease. BMC Gastroenterol 2023; 23:337. [PMID: 37770845 PMCID: PMC10540500 DOI: 10.1186/s12876-023-02968-0] [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: 03/29/2023] [Accepted: 09/21/2023] [Indexed: 09/30/2023] Open
Abstract
BACKGROUND Mucosal healing has become the primary treatment target for patients with Crohn's disease (CD). We aimed to develop a noninvasive and convenient tool to evaluate the endoscopic activity in patients with ileocolic CD. METHODS A retrospective multicenter study including 300 CD patients (training, 210 patients; test, 90 patients) was conducted at two tertiary referral centers. Independent risk factors associated with endoscopic activity were explored, which were then combined into a comprehensive index. The predictive performance was evaluated with the area under receiver operating characteristic curve (ROC). Cohen's Kappa was adopted to examine the consistency between each indicator and endoscopic activity. RESULTS A total of 210 CD patients were recruited in the training cohort. We found that Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP) and platelet-to-lymphocyte percentage ratio (PLpR) were independently associated with endoscopic activity. Additionally, the comprehensive index generated from the above three indices achieved good discrimination and performed better than CDAI in AUC (0.849 vs. 0.769, P < 0.05). This was further well demonstrated by the external test cohort, which showed good discrimination (AUC: 0.84, 95% CI: 0.744-0.936). Intra-individual comparison revealed the comprehensive index to be superior in the prediction of endoscopic activity. In the subgroup analysis, the AUC of comprehensive index was significantly higher than CDAI especially in inflammatory phenotype (0.824 vs. 0.751, P < 0.05). CONCLUSION Combining CDAI, CRP and PLpR significantly improved the accuracy for predicting endoscopic activity in ileocolic CD, which can help better monitor an endoscopic flare.
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Affiliation(s)
- Xiaolin Hu
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China
- Medical College of Yangzhou University, Jiangsu, China
| | - Jiajia Li
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China
| | - Yunyun Sun
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China
| | - Dacheng Wu
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China
| | - Tiantian Zhao
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China
- Medical College of Yangzhou University, Jiangsu, China
| | - Maofeng Ma
- Medical College of Yangzhou University, Jiangsu, China
| | - Jie Chen
- Department of Gastroenterology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225009, Jiangsu, China.
| | - Mei Wang
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China.
| | - Sicong Hou
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, 225009, Jiangsu, China.
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Wilkens R, Dolinger M, Burisch J, Maaser C. Point-of-Care Testing and Home Testing: Pragmatic Considerations for Widespread Incorporation of Stool Tests, Serum Tests, and Intestinal Ultrasound. Gastroenterology 2022; 162:1476-1492. [PMID: 34995530 DOI: 10.1053/j.gastro.2021.10.052] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 10/13/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022]
Abstract
Breaking through the biologic therapy efficacy plateau for inflammatory bowel disease requires the strategic development of personalized biomarkers in the tight control model. After risk stratification early in the disease course, targeted serial monitoring consistently to assess clinical outcomes in response to therapy allows for quick therapeutic adjustments before bowel damage can occur. Point-of-care intestinal ultrasound performed by the treating gastroenterologist is an accurate cross- sectional biomarker that monitors intestinal inflammation in real-time, enhances patient care, and increases shared understanding to help achieve common treatment goals. Combining intestinal ultrasound during a clinic visit with existing serum and stool biomarkers in a home testing setup with electronic health monitoring allows for an optimized, patient-centered personalized treatment algorithm that may improve treatment outcomes. Here, we review the current state, pragmatic considerations, and future implications of point-of-care testing and home testing for noninvasive inflammatory bowel disease monitoring in the tight control model.
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Affiliation(s)
- Rune Wilkens
- Gastrounit, Division of Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Copenhagen, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Denmark; Digestive Disease Center, Copenhagen University Hospital - Bispebjerg & Frederiksberg, Copenhagen, Denmark.
| | - Michael Dolinger
- Susan and Leonard Feinstein Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Johan Burisch
- Gastrounit, Division of Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Copenhagen, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University of Copenhagen, Hvidovre Hospital, Denmark
| | - Christian Maaser
- Inflammatory Bowel Disease Outpatient Unit, Department of Geriatric Medicine, University Teaching Hospital Lueneburg, Lueneburg, Germany
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10
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Stascheit F, Hotter B, Klose S, Meisel C, Meisel A, Klehmet J. Calprotectin in Chronic Inflammatory Demyelinating Polyneuropathy and Variants-A Potential Novel Biomarker of Disease Activity. Front Neurol 2021; 12:723009. [PMID: 34589050 PMCID: PMC8473624 DOI: 10.3389/fneur.2021.723009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 08/12/2021] [Indexed: 12/04/2022] Open
Abstract
Background: In chronic inflammatory demyelinating polyneuropathy (CIDP), there is an urgent need for biomarkers to monitor ongoing disease activity. Serum calprotectin (CLP) induces signaling pathways involved in inflammatory processes and has been shown to correlate with markers of disease activity in other autoimmune disorders. Thus, we wanted to study the potential value of CLP in comparison to serum neurofilament light chain (sNfl) to monitor disease activity. Materials and Methods: Sera from 63 typical and atypical CIDP and 6 MMN patients with varying degrees of disease activity were analyzed in comparison with 40 healthy controls (HC) in a cross-sectional design. Association of CLP and sNfl levels with socio-demographics, disease duration, CIDP disease activity scale (CDAS), and impairment status [medical research council-sum score (MRC-SS), the inflammatory neuropathy cause and treatment disability score (INCAT-DS), grip strength, and maximum walking distance], patient-reported outcome (PRO) parameters [SF-36 questionnaire, Beck's depression index (BDI), and fatigue severity scale (FSS)], as well as treatment regime were investigated using uni- and multivariate analysis. Results: CLP and sNfl levels were significantly higher in all CIDP patients compared to HC (p = 0.0009). Multivariate analysis adjusted for age and gender revealed that CLP acts as an independent predictor for CIDP and MMN. CLP was significantly associated with active disease course according to CDAS and correlated with MRC-SS, whereas sNfl correlated with parameters of disease impairment. There was no correlation with PRO, except for sNfl and the mental health composite score. Subgroup analysis revealed no differences between typical CIDP and atypical variants. Conclusions: CLP was elevated in CIDP and variants and was associated with active disease course, whereas sNfl shows further potential as biomarker of axonal degeneration. Thus, CLP might be a suitable additive biomarker for measurement of ongoing inflammation, which is greatly needed to guide better patient care in CIDP.
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Affiliation(s)
- Frauke Stascheit
- Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.,NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Benjamin Hotter
- Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.,NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Sarah Klose
- NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Christian Meisel
- Department of Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.,Department of Immunology, Labor Berlin, Charité Vivantes GmbH, Berlin, Germany
| | - Andreas Meisel
- Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.,NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,German Myasthenia Gravis Society (Deutsche Myasthenie Gesellschaft, DMG), Bremen, Germany
| | - Juliane Klehmet
- NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,Department of Neurology, Jüdisches Krankenhaus Berlin, Berlin, Germany
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11
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Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, Bettenworth D, Sandborn WJ, Sands BE, Reinisch W, Schölmerich J, Bemelman W, Danese S, Mary JY, Rubin D, Colombel JF, Peyrin-Biroulet L, Dotan I, Abreu MT, Dignass A. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021; 160:1570-1583. [PMID: 33359090 DOI: 10.1053/j.gastro.2020.12.031] [Citation(s) in RCA: 1412] [Impact Index Per Article: 353.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 10/21/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. METHODS Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale. RESULTS In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth. CONCLUSIONS STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Jerusalem, Israel.
| | | | - Ayanna Lewis
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Ferdinando D'Amico
- Humanitas Clinical and Research Center - IRCCS, Rozzano and Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy
| | - Jasbir Dhaliwal
- Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio
| | | | - Dominik Bettenworth
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Bruce E Sands
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Walter Reinisch
- Medical University of Vienna, Department of Internal Medicine III, Division Gastroenterology and Hepatology, Vienna, Austria
| | | | - Willem Bemelman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Locatie AMC, the Netherlands
| | - Silvio Danese
- Humanitas Clinical and Research Center - IRCCS, Rozzano and Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy
| | - Jean Yves Mary
- Inserm UMR1153 CRESS, équipe ECSTRRA, Université de Paris, Paris, France
| | - David Rubin
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, Illinois
| | - Jean-Frederic Colombel
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt/Main, Germany.
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12
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Reinisch W, Panaccione R, Bossuyt P, Baert F, Armuzzi A, Hébuterne X, Travis S, Danese S, Sandborn WJ, Schreiber S, Berg S, Zhou Q, Kligys K, Neimark E, Suleiman AA, D’Haens G, Colombel JF. Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study. Inflamm Bowel Dis 2020; 26:1562-1571. [PMID: 32105310 PMCID: PMC7500520 DOI: 10.1093/ibd/izaa025] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. METHODS The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or ≥5 mg/L and FC <250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. RESULTS The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 µg/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 µg/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization. CONCLUSION This post hoc analysis of CALM demonstrated that a cutoff of FC <250 µg/g is a useful surrogate marker for mucosal healing in CD.
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Affiliation(s)
- Walter Reinisch
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Remo Panaccione
- Inflammatory Bowel Disease Unit, Department of Medicine, University of Calgary, AB, Canada
| | | | | | - Alessandro Armuzzi
- Presidio Columbus, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Xavier Hébuterne
- Inflammatory Bowel Disease Center, University of Nice-Sophia Antipolis, CHU of Nice, Nice, France
| | - Simon Travis
- Translational Gastroenterology Unit, National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - William J Sandborn
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Stefan Schreiber
- Department of Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Sofie Berg
- Global Medical Affairs, AbbVie AB, Solna, Sweden
| | | | | | - Ezequiel Neimark
- Research and Development, Gastroenterology/Immunology, AbbVie Inc., Worcester, MA, USA
| | - Ahmed A Suleiman
- Clinical Pharmacology and Pharmacometrics, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen am Rhein, Germany
| | | | - Jean-Frederic Colombel
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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13
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Laserna-Mendieta EJ, Lucendo AJ. Faecal calprotectin in inflammatory bowel diseases: a review focused on meta-analyses and routine usage limitations. Clin Chem Lab Med 2020; 57:1295-1307. [PMID: 30785706 DOI: 10.1515/cclm-2018-1063] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022]
Abstract
A growing body of evidence has been published about the usefulness of measuring calprotectin in faecal samples (FCAL) in inflammatory bowel disease (IBD) assessment, including diagnosis, monitoring of disease activity and relapse prediction. Several systematic reviews with meta-analyses compiling studies for each particular clinical setting have been carried out in recent years. Most of these were focused on the use of FCAL in IBD diagnosis and showed a relevant role for this marker in selecting patients with gastrointestinal symptoms who would not need a further examination by endoscopy. Although a lesser number of meta-analyses have been performed on the use of FCAL as a surrogate marker of disease activity, a close correlation between FCAL and endoscopic activity of IBD has been shown. With respect to the predictive capacity of FCAL for IBD relapse, a single meta-analysis published indicates that this role is more limited. Furthermore, FCAL thresholds vary considerably depending on the clinical setting and, what is more concerning, among different commercially available assays due to a lack of FCAL concentration interchangeability. Here, we summarise recent publications about the role and limitations of FCAL in IBD, with a special focus on meta-analyses, and give an overview of alternative faecal biomarkers.
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Affiliation(s)
- Emilio J Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Clinical Laboratory, Hospital General de Villarrobledo, Villarrobledo, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Biomedical Research Network Centre for Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
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14
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Zittan E, Gralnek IM, Berns MS. The New Proactive Approach and Precision Medicine in Crohn's Disease. Biomedicines 2020; 8:biomedicines8070193. [PMID: 32635316 PMCID: PMC7400127 DOI: 10.3390/biomedicines8070193] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 06/23/2020] [Accepted: 06/28/2020] [Indexed: 12/11/2022] Open
Abstract
The proactive approach to Crohn's disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.
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Affiliation(s)
- Eran Zittan
- Ellen and Pinchas Mamber Institute of Gastroenterology and Liver Diseases, IBD unit, Emek Medical Center, Afula 1834111, Israel;
- Correspondence:
| | - Ian M. Gralnek
- Ellen and Pinchas Mamber Institute of Gastroenterology and Liver Diseases, IBD unit, Emek Medical Center, Afula 1834111, Israel;
- Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa 31096, Israel;
| | - Marc S. Berns
- Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa 31096, Israel;
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15
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Brand EC, Elias SG, Minderhoud IM, van der Veen JJ, Baert FJ, Laharie D, Bossuyt P, Bouhnik Y, Buisson A, Lambrecht G, Louis E, Pariente B, Pierik MJ, van der Woude CJ, D'Haens GRAM, Vermeire S, Oldenburg B. Systematic Review and External Validation of Prediction Models Based on Symptoms and Biomarkers for Identifying Endoscopic Activity in Crohn's Disease. Clin Gastroenterol Hepatol 2020; 18:1704-1718. [PMID: 31881273 DOI: 10.1016/j.cgh.2019.12.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 12/02/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Endoscopic healing, an important target of treatment for Crohn's disease (CD), requires ileocolonoscopy, which is costly and burdensome. We investigated whether published noninvasive models (based on symptoms and biomarkers) to evaluate CD activity have sufficient accuracy to replace ileocolonoscopy. METHODS We performed a systematic review of published noninvasive diagnostic models to evaluate CD activity that used endoscopic features of activity (endoscopic activity) or healing as the reference standard. We externally validated these models for the outcome endoscopic activity (CD endoscopic index of severity scores, ≥3) using data from the a randomized controlled trial investigating tailored treatment with infliximab for active luminal Crohn's disease (TAILORIX) study (346 ileocolonoscopies in 155 patients) and the Utrecht Activity Index (UAI) study (93 ileocolonoscopies in 82 patients). We calculated the area under the receiver operating characteristic curves (AUROCs) for the models using data from these studies, and compared the performance of these models against measurements of fecal calprotectin (FC) and C-reactive protein (CRP). RESULTS We screened 5303 articles and identified 27 models (from 21 studies) for our analysis. Seven models could be validated externally; in the TAILORIX data set, these models identified patients with endoscopic activity with AUROC values ranging from 0.61 (95% CI, 0.51-0.70) to 0.81 (95% CI, 0.76-0.86). In this data set, the AUROC value for FC concentration was 0.79 (95% CI, 0.74-0.85) and the AUROC value for CRP level was 0.72 (95% CI, 0.66-0.77). The AUROC values for the validation in the UAI data set were similar. In the TAILORIX and/or UAI data set, 4 of the 7 models, as well as the FC and CRP assays, were able to identify patients with endoscopic activity with positive predictive values of 90% or more. Two of the 7 models (but not the FC or CRP values) identified patients without endoscopic activity with a negative predictive value (NPV) of 90% or more, leading to correct prediction of endoscopic healing in 3.2% to 11.3% of all patients. For example, applying the Herranz-Bachiller model (1 of 7 models) at a NPV of 92.1% and a positive predictive value of 91.9% correctly identified 35.7% of all patients in whom ileocolonoscopy could be avoided for expected endoscopic activity or healing but incorrectly identified 3.2% of all patients. Most ileocolonoscopies (66.5% in TAILORIX and 72.6% in the UAI of all ileocolonoscopies) could be avoided correctly based on concentrations of FC of 100 μg/g or less and 250 μg/g or higher. However, using this range of FC concentrations to identify patients who do not require ileocolonoscopy caused 18.7% of all patients in the TAILORIX cohort and 19.8% of all patients in the UAI cohort to be predicted incorrectly to have endoscopic activity or healing. CONCLUSIONS In a systematic review and external validation of noninvasive models to identify patients with endoscopic activity of CD, we found only 2 of 7 models evaluated to have NPVs of 90% or more, however, leading to correctly predicted EH in only a small proportion of patients. Ileocolonoscopy therefore remains the mainstay to evaluate CD mucosal disease activity and healing.
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Affiliation(s)
- Eelco C Brand
- Department of Gastroenterology and Hepatology, Utrecht, The Netherlands; Center for Translational Immunology, Utrecht, The Netherlands
| | - Sjoerd G Elias
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Itta M Minderhoud
- Department of Gastroenterology and Hepatology, Tergooi Hospitals, Blaricum/Hilversum, The Netherland
| | | | - Filip J Baert
- Department of Gastroenterology, AZ Delta, Roeselare, Belgium
| | - David Laharie
- Service d'Hépato-gastroentérologie et Oncologie Digestive, Hôpital Haut-Lévêque, Bordeaux, France
| | - Peter Bossuyt
- Inflammatory Bowel Disease Clinic, Imelda General Hospital, Bonheiden, Belgium
| | - Yoram Bouhnik
- Department of Gastroenterology, Beaujon Hospital, Assistance publique - Hôpitaux de Paris (APHP), Paris Diderot University, Clichy, France
| | - Anthony Buisson
- Department of Gastroenterology, Estaing University Hospital, Clermont-Ferrand, France
| | - Guy Lambrecht
- Department of Gastroenterology, Algemeen Ziekenhuis (AZ), Damiaan, Oostende, Belgium
| | - Edouard Louis
- Department of Gastroenterology, Liège University Hospital Centre Hospitalier Universitaire (CHU), Liège, Belgium
| | - Benjamin Pariente
- Department of Gastroenterology, Huriez Hospital, Lille 2 University, Lille, France
| | - Marieke J Pierik
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - C Janneke van der Woude
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Geert R A M D'Haens
- Department of Gastroenterology, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Bas Oldenburg
- Department of Gastroenterology and Hepatology, Utrecht, The Netherlands.
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16
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Correlation of Patient-Reported Outcome (PRO-2) with Endoscopic and Histological Features in Ulcerative Colitis and Crohn's Disease Patients. Gastroenterol Res Pract 2020; 2020:2065383. [PMID: 32328091 PMCID: PMC7154964 DOI: 10.1155/2020/2065383] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/01/2020] [Accepted: 03/23/2020] [Indexed: 12/11/2022] Open
Abstract
Methods A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn's disease. Histopathological activity was assessed using a validated numeric scoring system. Results We included 159 patients (63 Crohn's disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn's disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn's disease (rs = −0.67; rs = −0.72), while positive correlation was found in ulcerative colitis (rs = 0.84; rs = 0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn's disease.
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17
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Syed S, Al-Boni M, Khan MN, Sadiq K, Iqbal NT, Moskaluk CA, Kelly P, Amadi B, Ali SA, Moore SR, Brown DE. Assessment of Machine Learning Detection of Environmental Enteropathy and Celiac Disease in Children. JAMA Netw Open 2019; 2:e195822. [PMID: 31199451 PMCID: PMC6575155 DOI: 10.1001/jamanetworkopen.2019.5822] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 04/30/2019] [Indexed: 12/16/2022] Open
Abstract
Importance Duodenal biopsies from children with enteropathies associated with undernutrition, such as environmental enteropathy (EE) and celiac disease (CD), display significant histopathological overlap. Objective To develop a convolutional neural network (CNN) to enhance the detection of pathologic morphological features in diseased vs healthy duodenal tissue. Design, Setting, and Participants In this prospective diagnostic study, a CNN consisting of 4 convolutions, 1 fully connected layer, and 1 softmax layer was trained on duodenal biopsy images. Data were provided by 3 sites: Aga Khan University Hospital, Karachi, Pakistan; University Teaching Hospital, Lusaka, Zambia; and University of Virginia, Charlottesville. Duodenal biopsy slides from 102 children (10 with EE from Aga Khan University Hospital, 16 with EE from University Teaching Hospital, 34 with CD from University of Virginia, and 42 with no disease from University of Virginia) were converted into 3118 images. The CNN was designed and analyzed at the University of Virginia. The data were collected, prepared, and analyzed between November 2017 and February 2018. Main Outcomes and Measures Classification accuracy of the CNN per image and per case and incorrect classification rate identified by aggregated 10-fold cross-validation confusion/error matrices of CNN models. Results Overall, 102 children participated in this study, with a median (interquartile range) age of 31.0 (20.3-75.5) months and a roughly equal sex distribution, with 53 boys (51.9%). The model demonstrated 93.4% case-detection accuracy and had a false-negative rate of 2.4%. Confusion metrics indicated most incorrect classifications were between patients with CD and healthy patients. Feature map activations were visualized and learned distinctive patterns, including microlevel features in duodenal tissues, such as alterations in secretory cell populations. Conclusions and Relevance A machine learning-based histopathological analysis model demonstrating 93.4% classification accuracy was developed for identifying and differentiating between duodenal biopsies from children with EE and CD. The combination of the CNN with a deconvolutional network enabled feature recognition and highlighted secretory cells' role in the model's ability to differentiate between these histologically similar diseases.
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Affiliation(s)
- Sana Syed
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Virginia, Charlottesville
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Mohammad Al-Boni
- Systems and Information Engineering, University of Virginia, Charlottesville
| | - Marium N. Khan
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Virginia, Charlottesville
| | - Kamran Sadiq
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Najeeha T. Iqbal
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | | | - Paul Kelly
- Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Beatrice Amadi
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
| | - S. Asad Ali
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Sean R. Moore
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Virginia, Charlottesville
| | - Donald E. Brown
- Data Science Institute, University of Virginia, Charlottesville
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18
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Ma C, Battat R, Parker CE, Khanna R, Jairath V, Feagan BG. Update on C-reactive protein and fecal calprotectin: are they accurate measures of disease activity in Crohn's disease? Expert Rev Gastroenterol Hepatol 2019; 13:319-330. [PMID: 30791776 DOI: 10.1080/17474124.2019.1563481] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
'Treat-to-target' paradigms in Crohn's disease (CD) directed at suppressing intestinal inflammation require accurate and reliable measures of disease activity. Although endoscopy has traditionally been considered a gold standard, cost, complexity, resource limitations, and invasiveness are important limitations. Hence, substantial interest exists for non-invasive serum and fecal biomarkers, namely C-reactive protein (CRP) and fecal calprotectin (FC), in the diagnosis, monitoring, and treatment of CD. Areas covered: We review the evidence for using serum CRP and FC in distinguishing patients with CD from those with irritable bowel syndrome, categorizing disease activity among patients with an established diagnosis of CD, predicting the likelihood of treatment response, identifying asymptomatic patients in medically or surgically induced remission who are at risk for disease relapse, and as treatment targets. Expert commentary: Accurate interpretation of CRP and FC is dependent on several factors including the clinical context, the performance characteristics of the assay, the specified test cut-offs, and the pre-test probability of disease. Emerging evidence indicates that CRP and FC are valuable adjuncts for the management of CD in specific circumstances described in this review.
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Affiliation(s)
- Christopher Ma
- a Division of Gastroenterology and Hepatology , University of Calgary , Calgary , Alberta , Canada.,b Robarts Clinical Trials Inc ., London , Ontario , Canada
| | - Robert Battat
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,c Division of Gastroenterology , University of California San Diego , La Jolla , CA , USA
| | | | - Reena Khanna
- d Department of Medicine , Western University , London , Ontario , Canada
| | - Vipul Jairath
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
| | - Brian Gordon Feagan
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
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