|
1
|
Issa IA, Issa T. Assessing endoscopic remission in small bowel Crohn's disease: Are markers enough? World J Gastrointest Endosc 2025; 17:106083. [DOI: 10.4253/wjge.v17.i4.106083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/23/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
Mucosal healing in Crohn’s disease (CD) has been established as a crucial target of treatment, leading to long term remission and decrease in complication rates. Endoscopy still serves as the gold standard for assessment, particularly in the small bowel where balloon or capsule enteroscopy is frequently needed. However, these modalities are often unavailable, expensive, and invasive, posing risks to patients. Consequently, the identification of accessible and reliable biomarkers, especially in small intestinal CD, remains a challenge. The study by Ohno et al, published in this issue, further illuminates this field. It confirms the potential role of fecal biomarker leucine-rich α2 glycoprotein (LRG) and validates findings from previous smaller trials. Comparing to other markers LRG showed a much higher predictive value for mucosal healing of the small bowel, making it a useful option for small intestinal CD follow up. In this editorial, we explore the optimal marker of inflammation or mucosal healing in CD, particularly in the small bowel. We provide an overview of available conventional biomarkers and introduce several novel biomarkers, including an update on emerging technologies and innovations.
Collapse
Affiliation(s)
- Iyad A Issa
- Department of Gastroenterology and Hepatology, Harley Street Medical Center, Abu Dhabi 41475, United Arab Emirates
| | - Taly Issa
- Medical School, University of Nicosia, Nicosia 24005, Lefkosía, Cyprus
| |
Collapse
|
|
2
|
Rautakorpi J, Kolehmainen S, Löyttyniemi E, Björkesten CGA, Arkkila P, Sipponen T, Salminen K. Switching to Subcutaneous Infliximab Maintenance Therapy Is Effective in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2025; 70:1457-1466. [PMID: 39946070 PMCID: PMC11972210 DOI: 10.1007/s10620-025-08876-5] [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: 11/26/2024] [Accepted: 01/15/2025] [Indexed: 04/06/2025]
Abstract
BACKGROUND Recent studies suggest that subcutaneous infliximab is effective and safe for treating patients with inflammatory bowel disease. Real-world studies with larger cohorts are needed to confirm the efficacy of subcutaneous treatment. AIMS The aim was to assess real-world treatment persistence, clinical outcomes, infliximab concentrations, and treatment safety after switching from intravenous to subcutaneous infliximab treatment with patients with inflammatory bowel disease. METHODS This retrospective register-based study included patients with inflammatory bowel disease who were in clinical remission and switched from intravenous infliximab maintenance therapy to subcutaneous infliximab in two tertiary centers. RESULTS A total of 274 patients (104 Crohn's disease and 170 ulcerative colitis) were included. After the switch, the treatment persistence at 12 months was 94.8% in patients with Crohn's disease and 88.8% in patients with ulcerative colitis. Only 11.3% (n = 31) of the patients discontinued the treatment during 79-week median follow-up. Compared to the baseline, no change occurred in clinical disease activity at the time points of 3, 6, and 12 months, based on the Harvey-Bradshaw Index or partial Mayo Score (p = 0.792 and p = 0.426, respectively). Infliximab median concentrations were higher (p < 0.0001) during subcutaneous treatment (16.75 µg/ml) compared to the intravenous treatment median trough levels before the switch (6.71 µg/ml). In total, 15.0% (n = 41) of the patients reported adverse events. CONCLUSION Switching to subcutaneous infliximab maintenance therapy was associated with high treatment persistence, a stable disease course, increased infliximab concentrations, and an acceptable safety profile.
Collapse
Affiliation(s)
- Jaakko Rautakorpi
- Abdominal Center - Department of Gastroenterology, University of Turku and Turku University Hospital, Turku, Finland.
- Faculty of Medicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.
| | - Sara Kolehmainen
- Abdominal Center - Department of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Eliisa Löyttyniemi
- Department of Biostatistics, University of Turku and Turku University Hospital, Turku, Finland
| | - Clas-Göran Af Björkesten
- Abdominal Center - Department of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Perttu Arkkila
- Abdominal Center - Department of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Taina Sipponen
- Abdominal Center - Department of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Kimmo Salminen
- Abdominal Center - Department of Gastroenterology, University of Turku and Turku University Hospital, Turku, Finland
| |
Collapse
|
|
3
|
Binsaleh AY, El-Haggar SM, Hegazy SK, Maher MM, Bahgat MM, Elmasry TA, Alrubia S, Alsegiani AS, Eldesoqui M, Bahaa MM. The adjunctive role of metformin in patients with mild to moderate ulcerative colitis: a randomized controlled study. Front Pharmacol 2025; 16:1507009. [PMID: 40191419 PMCID: PMC11969268 DOI: 10.3389/fphar.2025.1507009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 02/14/2025] [Indexed: 04/09/2025] Open
Abstract
Background Metformin, hypoglycemic medication, is recognized for its diverse properties and its capacity to influence the inflammatory pathways. Medications with anti-inflammatory and anti-oxidative characteristics have been demonstrated to be able to elicit and sustain remission in ulcerative colitis (UC), chronic inflammatory disorder of the bowel. Studies in both preclinical and clinical settings have looked into the several metabolic pathways via which metformin protects against UC. Aim To assess efficacy of metformin as adjunctive therapy in patients with mild to moderate UC. Methods This clinical research was double-blinded, randomized, controlled, and involved 60 patients with mild to moderate UC. The participants were randomly assigned to one of two groups (n = 30). The control group was given 1 g of mesalamine three times a day (t.i.d.) for a period of 6 months (mesalamine group). The metformin group was given 500 mg of metformin twice daily and 1 g of mesalamine t. i.d. For a period of 6 months. Patients with UC were assessed by a gastroenterologist using the disease activity index (DAI) both at the beginning of treatment and 6 months thereafter. To evaluate the drug's biological efficacy, measurements of fecal calprotectin, serum C-reactive protein (CRP), interleukin 10 (IL-10), and nitric oxide (NO) were taken both before and after treatment. Study outcomes Decrease in DAI and change in the level of measured serum and fecal markers. Results The metformin group displayed a statistical reduction in DAI (p = 0.0001), serum CRP (p = 0.019), NO (p = 0.04), and fecal calprotectin (p = 0.027), as well as a significant increase in IL-10 (p = 0.04) when compared to the mesalamine group. There was a significant direct correlation between DAI and calprotectin (p < 0.0001, r = 0.551), and between DAI and CRP (p < 0.0001, r = 0.794). There was a significant negative correlation between DAI and IL-10 (p = 0.0003, r = 0.371). Conclusion Metformin may be an effective adjunct drug in management of patients with mild to moderate UC by decreasing DAI and other inflammatory markers that were involved in the pathogenesis of UC. Clinical Trial Registration identifier NCT05553704.
Collapse
Affiliation(s)
- Ammena Y. Binsaleh
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Sahar M. El-Haggar
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, Egypt
| | - Sahar K. Hegazy
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, Egypt
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt
| | - Maha M. Maher
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Internal Medicine Department, Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Monir M. Bahgat
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Thanaa A. Elmasry
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Sinai University, Arish campus, Egypt
| | - Sarah Alrubia
- Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Amsha S. Alsegiani
- Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mamdouh Eldesoqui
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Mostafa M. Bahaa
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt
| |
Collapse
|
|
4
|
Rasmussen MH, Brodersen JB, Brasen CL, Madsen JS, Knudsen T, Kjeldsen J, Jensen MD. The diagnostic accuracy of plasma and serum calprotectin is inferior to C-reactive protein in patients with suspected Crohn's disease. Scand J Gastroenterol 2025; 60:235-242. [PMID: 39878038 DOI: 10.1080/00365521.2025.2459236] [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: 11/07/2024] [Revised: 12/19/2024] [Accepted: 01/21/2025] [Indexed: 01/31/2025]
Abstract
BACKGROUND AND AIMS Prior studies indicate that serum calprotectin (SC) and plasma calprotectin (PC) can be used as biomarkers in Crohn's disease (CD). The aim of this study was to investigate the diagnostic accuracy of SC and PC in patients with a clinical suspicion of CD. METHOD This biobank study included patients from a prospective, blinded, multicenter study examining minimally invasive modalities for diagnosing CD. Patients had a standardized work-up including ileocolonoscopy, pan-enteric capsule endoscopy, and blood samples within a 2-week period. Plasma and serum were stored at - 80 °C until further analysis. A routine C-reactive protein (CRP) was measured on the same day. Pan-endoscopy served as reference standard. RESULTS 126 patients entered the study, and 58 (46.0%) were diagnosed with CD. Patients with CD had a median PC of 0.37 mg/L (IQR 0.20-0.70) compared to 0.29 mg/L (IQR 0.16-0.41) in non-CD patients (p = 0.03). The median SC was 1.09 mg/L (IQR 0.80-1.80) and 0.93 mg/L (IQR 0.66-1.25), respectively (p = 0.01). Receiver operating characteristics curves showed an AUC of 0.63 (CI 0.53-0.73) for SC and 0.61 (CI 0.51-0.71) for PC for detection of CD, which was inferior to that of CRP (AUC = 0.76, CI 0.68-0.85) (p < 0.02). None of the biomarkers reflected the endoscopic severity of CD. CONCLUSION Although levels of PC and SC are elevated in patients with CD, diagnostic accuracies are inferior to CRP. SC and PC are not reliable as stand-alone blood-based biomarkers for diagnosing CD and selecting patients for endoscopy.
Collapse
Affiliation(s)
- M H Rasmussen
- Department of Internal Medicine, Section of Gastroenterology, Esbjerg Hospital - University Hospital of Southern Denmark, Esbjerg, Denmark
| | - J B Brodersen
- Department of Internal Medicine, Section of Gastroenterology, Esbjerg Hospital - University Hospital of Southern Denmark, Esbjerg, Denmark
- Department of Regional Health Research, University of Southern Denmark, Denmark
| | - C L Brasen
- Department of Clinical Biochemistry and Immunology, Lillebaelt Hospital - University Hospital of Southern Denmark, Vejle, Denmark
| | - J S Madsen
- Department of Regional Health Research, University of Southern Denmark, Denmark
- Department of Clinical Biochemistry and Immunology, Lillebaelt Hospital - University Hospital of Southern Denmark, Vejle, Denmark
| | - T Knudsen
- Department of Internal Medicine, Section of Gastroenterology, Esbjerg Hospital - University Hospital of Southern Denmark, Esbjerg, Denmark
- Department of Regional Health Research, University of Southern Denmark, Denmark
| | - J Kjeldsen
- Department of Medical Gastrointestinal Diseases, Odense University Hospital, Odense, Denmark
- Research Unit of Medical Gastroenterology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- OPEN Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark
| | - M D Jensen
- Department of Internal Medicine, Section of Gastroenterology, Esbjerg Hospital - University Hospital of Southern Denmark, Esbjerg, Denmark
- Department of Regional Health Research, University of Southern Denmark, Denmark
| |
Collapse
|
|
5
|
Ohno M, Nishida A, Otsuki A, Yokota Y, Imai T, Bamba S, Inatomi O. Leucine-rich alpha-2 glycoprotein as a superior biomarker to C-reactive protein for detecting small bowel lesions in Crohn's disease. World J Gastrointest Endosc 2025; 17:100793. [PMID: 39989852 PMCID: PMC11843037 DOI: 10.4253/wjge.v17.i2.100793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/06/2025] [Accepted: 01/18/2025] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Achievement of endoscopic healing (EH) is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis. Existing biomarkers, including C-reactive protein (CRP), have relatively low accuracy for predicting EH, especially in small intestinal lesions in Crohn's disease (CD); thus, noninvasive and more accurate biomarkers are required. Leucine-rich alpha-2 glycoprotein (LRG), a 50-kD protein, is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease. However, the usefulness of LRG in small intestinal lesions in CD remains inconclusive. AIM To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP. METHODS This study included 133 consecutive patients with CD who underwent balloon-assisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital (Otsu, Japan). We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG, CRP, albumin, and Harvey-Bradshaw index (HBI). Spearman's rank correlation coefficient and receiver operating characteristic analysis were performed. RESULTS Either active ileal or colonic lesions exhibited significant differences in LRG, CRP, albumin, and HBI compared with EH. CRP, albumin, and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon; however, LRG did not show a worse correlation (colon, r = 0.5218; ileum, r = 0.5602). Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4 μg/mL. Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG (95% confidence interval, 0.017-0.194; P = 0.024), whereas the two showed no significant difference in the colon. CONCLUSION LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.
Collapse
Affiliation(s)
- Masashi Ohno
- Department of Medicine, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| | - Atsushi Nishida
- Department of Medicine, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| | - Akinori Otsuki
- Department of Medicine, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| | - Yoshihiro Yokota
- Department of Medicine, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| | - Takayuki Imai
- Department of Medicine, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| | - Shigeki Bamba
- Department of Fundamental Nursing, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| | - Osamu Inatomi
- Department of Medicine, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan
| |
Collapse
|
|
6
|
Jaakkola T, Merras‐Salmio L, Nikkonen A, Kolho K. Long-term follow-up of children with Crohn's disease and small bowel mucosal lesions detected through video capsule endoscopy. J Pediatr Gastroenterol Nutr 2025; 80:124-132. [PMID: 39487088 PMCID: PMC11717392 DOI: 10.1002/jpn3.12397] [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: 03/09/2024] [Revised: 10/11/2024] [Accepted: 10/12/2024] [Indexed: 11/04/2024]
Abstract
OBJECTIVES We report disease outcomes of pediatric Crohn's disease (CD) affecting the proximal small bowel (SB) and detected through video capsule endoscopy (VCE). METHODS We undertook a retrospective review of CD patients with VCE performed under age 18 between 2003 and 2017 and having received any biologics. We identified patients from our institutional registry. RESULTS Eligible patients (n = 118) had their first VCE performed after a median of 0.1 years after diagnostic endoscopies at a median age of 12.2 years. The proximal SB disease group (Paris classification L4b inclusive) comprised 70 patients with extensive SB lesions in 81% and deep ulcers in 79%. Patients with Paris L1-3 disease with no findings in VCE or disease restricted to the terminal ileum comprised the control group. At first VCE, levels of albumin (34 vs. 37 g/L) and hemoglobin (117 vs. 127 g/L) were lower in SB patients (p < 0.02). After the first VCE, 68% were introduced to biologics, while 10% already received them. Follow-up VCE was performed after a median of 2.4 years (SB group n = 42; controls n = 21). Proximal SB findings had disappeared in 40% of SB patients, and extensive lesions and deep ulcers had decreased to 26% and 29%, respectively (p = 0.001). In the control group, one had progressed to proximal disease. During the clinical follow-up of a median of 4.7 years, one patient with SB underwent surgery for a jejunal stricture. CONCLUSIONS Proximal SB disease detected through capsule endoscopy abated in most patients with biological medication.
Collapse
Affiliation(s)
- Tytti Jaakkola
- Pediatric Gastroenterology Unit, Children's HospitalHelsinki University Hospital HUSHelsinkiFinland
- Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
| | - Laura Merras‐Salmio
- Pediatric Gastroenterology Unit, Children's HospitalHelsinki University Hospital HUSHelsinkiFinland
- Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
| | - Anne Nikkonen
- Pediatric Gastroenterology Unit, Children's HospitalHelsinki University Hospital HUSHelsinkiFinland
- Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
| | - Kaija‐Leena Kolho
- Pediatric Gastroenterology Unit, Children's HospitalHelsinki University Hospital HUSHelsinkiFinland
- Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
| |
Collapse
|
|
7
|
Cosier D, Lambert K, Charlton K, Batterham M, Little RD, Wu N, Tavakoli P, Ghaly S, Pipicella JL, Connor S, Leach S, Lemberg DA, Houshyar Y, Jayawardana T, Koentgen S, Hold GL. Dietary Patterns and Fibre Intake Are Associated with Disease Activity in Australian Adults with Inflammatory Bowel Disease: An Exploratory Dietary Pattern Analysis. Nutrients 2024; 16:4349. [PMID: 39770970 PMCID: PMC11677955 DOI: 10.3390/nu16244349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/10/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Few studies have explored the relationship between habitual dietary patterns and disease activity in people with Inflammatory Bowel Disease (IBD). This cross-sectional study explored the association between dietary patterns and clinical and objective markers of inflammation in adults from the Australian IBD Microbiome Study. METHODS Dietary patterns were derived using principal component analysis (PCA) of baseline food frequency questionnaire data. Food intake was quantified using 3-day food record data. Associations between dietary intake and both clinical disease activity index (CDAI) and faecal calprotectin (FCP) were analysed. RESULTS Participants included 412 adults (IBD = 223, Healthy controls (HC) = 189). Both cohorts consumed poor-quality diets with inadequate servings of most food groups compared to Australian reference standards. IBD participants without FCP inflammation had significantly higher fibre intake than those with moderate FCP. In the Crohn's Disease group, high adherence to 'High plant diversity' and 'Meat eaters' dietary patterns were associated with increased CDAI and FCP, respectively. In the combined IBD cohort, high adherence to a 'Vegan-style' dietary pattern was associated with increased FCP. CONCLUSIONS There is a need for dietary modifications among Australian adults, both with and without IBD, to improve dietary fibre intake and adherence to dietary guidelines. Dietary patterns characterised by a high intake of plant foods or meat products were both positively associated with indicators of active IBD. It is possible that some participants with active IBD were modifying their diet to try to manage their disease and reduce symptoms, contributing to the association between healthier dietary patterns and active disease. Further clinical and longitudinal studies are needed to expand upon the findings. This study offers a unique contribution by utilising FCP as an objective marker of intestinal inflammation and applying dietary pattern analysis to investigate the relationship between diet and inflammatory markers.
Collapse
Affiliation(s)
- Denelle Cosier
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Kelly Lambert
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Karen Charlton
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Marijka Batterham
- Statistical Consulting Centre, National Institute for Applied Statistical Research Australia, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Robert D. Little
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia
| | - Nan Wu
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sutherland Hospital, Sydney, NSW 2229, Australia
| | - Paris Tavakoli
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Simon Ghaly
- Department of Gastroenterology and Hepatology, St Vincent’s Hospital Sydney and St Vincent’s Clinical School, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Joseph L. Pipicella
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
- Crohn’s Colitis Cure, Sydney, NSW 2009, Australia
| | - Susan Connor
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Steven Leach
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
| | - Daniel A. Lemberg
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sydney Children’s Hospital, Sydney, NSW 2031, Australia
| | - Yashar Houshyar
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Thisun Jayawardana
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Sabrina Koentgen
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | | | - Georgina L. Hold
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| |
Collapse
|
|
8
|
Bartosik B, Kapeluszna K, Bartosik D, Chobot A, Ciszewska-Hołda P, Gawrylak-Dryja E, Klus A, Bułdak R, Brzoza Z. Chronic Spontaneous Urticaria-New Predictor on the Horizon? J Clin Med 2024; 13:6812. [PMID: 39597957 PMCID: PMC11594686 DOI: 10.3390/jcm13226812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/01/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
Chronic urticaria is one of the most common diseases in allergology and dermatology practice with unclear causes of occurrence. Background: Some studies emphasize the correlation between inflammation in chronic urticaria and disturbed intestinal microbiota. It raises the question about the role of some intestine-related substances in the pathogenesis of urticaria as well as their potential role as disease predictors. Calprotectin is an acute-phase protein with a well-established diagnostic position in the field of gastroenterology. There are some data on the relationship between this parameter and gut microbiota. The major aim of this preliminary study is to investigate whether calprotectin can be potentially taken into account as a disease course predictor in urticaria. Methods: We included in our study 54 chronic spontaneous urticaria (CSU) patients (of whom 26 manifested the symptoms of recurrent angioedema) and 29 patients allergic to Hymenoptera venom for the reference group (in these patients, before venom immunotherapy induction, full diagnostics is performed including intestinal problems). Disease activity in the CSU patients was assessed using the Urticaria Activity Score (UAS) and the disease control in this group was assessed with the Urticaria Control Test (UCT). Moreover, we analyzed fecal and serum calprotectin concentrations. Results: Positive correlation was found only between the values of serum calprotectin concentration and the control level of CSU symptoms with the lack of other relations. Conclusions: Our results do not supply unequivocal evidence for calprotectin as a potential marker of CSU course, though this concept, in the light of growing evidence for microbiota's role in urticaria, requires further research.
Collapse
Affiliation(s)
- Bartosz Bartosik
- Department of Internal Diseases, Allergology, Endocrinology and Gastroenterology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (B.B.); (K.K.); (D.B.)
| | - Katarzyna Kapeluszna
- Department of Internal Diseases, Allergology, Endocrinology and Gastroenterology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (B.B.); (K.K.); (D.B.)
| | - Dagmara Bartosik
- Department of Internal Diseases, Allergology, Endocrinology and Gastroenterology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (B.B.); (K.K.); (D.B.)
| | - Agata Chobot
- Department of Pediatrics, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (A.C.); (P.C.-H.)
| | - Paulina Ciszewska-Hołda
- Department of Pediatrics, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (A.C.); (P.C.-H.)
| | - Ewa Gawrylak-Dryja
- Department of Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (E.G.-D.); (A.K.); (R.B.)
| | - Anna Klus
- Department of Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (E.G.-D.); (A.K.); (R.B.)
| | - Rafał Bułdak
- Department of Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (E.G.-D.); (A.K.); (R.B.)
| | - Zenon Brzoza
- Department of Internal Diseases, Allergology, Endocrinology and Gastroenterology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland; (B.B.); (K.K.); (D.B.)
| |
Collapse
|
|
9
|
Kemp K, Samaan MA, Verma AM, Lobo AJ. Crohn's disease management: translating STRIDE-II for UK clinical practice. Therap Adv Gastroenterol 2024; 17:17562848241280885. [PMID: 39526077 PMCID: PMC11544685 DOI: 10.1177/17562848241280885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 08/19/2024] [Indexed: 11/16/2024] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice.
Collapse
Affiliation(s)
- Karen Kemp
- Department of Gastroenterology, Manchester Clinical Academic Centre, Manchester Royal Infirmary, University of Manchester, Oxford Road, Manchester M13 9WL, UK
| | - Mark A. Samaan
- Guy’s and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London, UK
| | - Ajay M. Verma
- Kettering General Hospital NHS Foundation Trust, Kettering, UK
| | - Alan J. Lobo
- Inflammatory Bowel Disease Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Broomhill, Sheffield, UK
| |
Collapse
|
|
10
|
Gu H, Wang Y, Wang Y, Ding L, Huan W, Yang Y, Fang F, Cui W. Global Bibliometric and Visualized Analysis of Research on Lactoferrin from 1978 to 2024. Mol Nutr Food Res 2024; 68:e2400379. [PMID: 39044343 DOI: 10.1002/mnfr.202400379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 07/02/2024] [Indexed: 07/25/2024]
Abstract
SCOPE Lactoferrin (LF) is an iron-bound protein with a molecular weight of about 80 kDa. LF has many biological functions such as antibacterial, antiviral, immunomodulatory, and anticancer. The purpose of this study is to explore the research trend of LF through bibliometric analysis. METHODS AND RESULTS The search is conducted in the Web of Science Core Collection database, and then the publications information of LF related literature is exported. Based on CiteSpace and VOSviewer software, countries, institutions, authors, journals, keywords, and so on are analyzed. Since 1987, a total of 9382 literature have been included, and the number of papers related to LF has increased year by year. These publications come mainly from 124 countries and 725 institutions. Of the 1256 authors analyzed, Valenti Piera is the one with the most publications. The burst strength of gut microbiota, antioxidant, nanoparticles, and in vitro digestion are 21.3, 15.63, 23.03, and 13.51, respectively. They represent the frontier of research in this field and are developing rapidly. CONCLUSION This study shows that LF has important research value. The study of LF nanoparticles and the effects of LF on the gut microbiota are an emerging field that helps to explore new research directions.
Collapse
Affiliation(s)
- Hong Gu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Yiming Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Yating Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Liyi Ding
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Wenru Huan
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Yuting Yang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Fang Fang
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| | - Weiwei Cui
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, China
| |
Collapse
|
|
11
|
Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| |
Collapse
|
|
12
|
Yzet C, Brazier F, Hautefeuille V, Richard N, Decrombecque C, Sarba R, Aygalenq P, Venezia F, Buisson A, Pichois R, Michaud A, Fumery M. Non-invasive evaluation of mucosal healing by intestinal ultrasound or fecal calprotectin is efficient in Crohn's disease: A cross-sectional study. Clin Res Hepatol Gastroenterol 2024; 48:102387. [PMID: 38810879 DOI: 10.1016/j.clinre.2024.102387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/26/2024] [Accepted: 05/27/2024] [Indexed: 05/31/2024]
Abstract
INTRODUCTION Endoscopy is still the gold, standard for assessing disease activity in Crohn's disease (CD). Its invasiveness, poor acceptability, and cost limit its use in the era of tight control and treat-to-target management. Fecal calprotectin (FC) and intestinal ultrasound (IUS) are non-invasive alternatives to colonoscopy to assess disease activity. We aimed to evaluate the performance of IUS and FC to assess mucosal healing in CD. METHODS All consecutive CD patients who underwent colonoscopy for mucosal healing assessment and IUS and/or FC within four weeks between September 2019 and April 2022 were included in a prospective cohort. The bowel-wall thickness (BWT) and color Doppler signal (CDS) were assessed for each segment. Endoscopic remission was defined by a CDEIS score < 3. RESULTS In total, 153 patients were included, of whom 122 showed endoscopic mucosal healing. Eighty-two (53.6 %) were female, the median was age 36 years (IQR, 28-46), and the median disease duration was 10 years (IQR, 4-19). The sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of a BWT < 3 mm to predict endoscopic mucosal healing were 56 %, 88 %, 95 %, and 36 %, respectively (patients misclassified as mucosal healing, 2.5 %). The best FC threshold (< 92.9 µg/g) provided similar results: 77 %, 89 %, 96 %, and 67 %, respectively (patients misclassified, 2.2 %). The association of an FC < 250 µg/g with a BWT < 3 mm and the absence of CDS increased the Sp and PPV: Se 58 %, Sp 95 %, PPV 97 %, VPN 43 %; patients misclassified, 1.3 %. CONCLUSION Noninvasive evaluation of mucosal healing by IUS or calprotectin efficiently identifies patients with CD who have achieved endoscopic mucosal healing.
Collapse
Affiliation(s)
- Clara Yzet
- Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France.
| | - Franck Brazier
- Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Vincent Hautefeuille
- Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Nicolas Richard
- Hepato-gastroenterology and Digestive Oncology, Rouen University Hospital, Rouen, France
| | - Catherine Decrombecque
- Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Ruxandra Sarba
- Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Philippe Aygalenq
- Gastro-entérologie et Hépatologie, Clinique du Palais, Grasse, France
| | - Franck Venezia
- Gastro-entérologie et Hépatologie, Clinique de Bercy, Charenton-le-Pont, France
| | - Anthony Buisson
- Gastroenterology Unit, Clermont Ferrand University Hospital, Clermont Ferrand, France
| | | | - Audrey Michaud
- Department of Biostatistics, Amiens University Hospital, Amiens, France
| | - Mathurin Fumery
- Hepato-gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| |
Collapse
|
|
13
|
Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines 2024; 12:1520. [PMID: 39062093 PMCID: PMC11274502 DOI: 10.3390/biomedicines12071520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/30/2024] [Accepted: 07/06/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.
Collapse
Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Dorotea Bozic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| |
Collapse
|
|
14
|
Pierre N, Huynh-Thu VA, Baiwir D, Vieujean S, Bequet E, Reenaers C, Van Kemseke C, Salée C, Massot C, Fléron M, Mazzucchelli G, Trzpiot L, Eppe G, De Pauw E, Louis E, Meuwis MA. Serum proteome signatures associated with ileal and colonic ulcers in Crohn's disease. J Proteomics 2024; 302:105199. [PMID: 38763457 DOI: 10.1016/j.jprot.2024.105199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/06/2024] [Accepted: 05/15/2024] [Indexed: 05/21/2024]
Abstract
At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.
Collapse
Affiliation(s)
- Nicolas Pierre
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium.
| | - Vân Anh Huynh-Thu
- Department of Electrical Engineering and Computer Science, University of Liege, Liege, Belgium
| | | | - Sophie Vieujean
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium; Hepato-Gastroenterology and Digestive Oncology Department, Liege University Hospital, Liege, Belgium
| | - Emeline Bequet
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Liege University Hospital, Liege, Belgium
| | - Catherine Reenaers
- Hepato-Gastroenterology and Digestive Oncology Department, Liege University Hospital, Liege, Belgium
| | - Catherine Van Kemseke
- Hepato-Gastroenterology and Digestive Oncology Department, Liege University Hospital, Liege, Belgium
| | - Catherine Salée
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium
| | - Charlotte Massot
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium
| | | | - Gabriel Mazzucchelli
- Laboratory of Mass Spectrometry, MolSys Research Unit, University of Liege, Liege, Belgium
| | - Lisette Trzpiot
- Laboratory of Mass Spectrometry, MolSys Research Unit, University of Liege, Liege, Belgium
| | - Gauthier Eppe
- Laboratory of Mass Spectrometry, MolSys Research Unit, University of Liege, Liege, Belgium
| | - Edwin De Pauw
- Laboratory of Mass Spectrometry, MolSys Research Unit, University of Liege, Liege, Belgium
| | - Edouard Louis
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium; Hepato-Gastroenterology and Digestive Oncology Department, Liege University Hospital, Liege, Belgium
| | - Marie-Alice Meuwis
- Laboratory of Translational Gastroenterology, GIGA-institute, University of Liege, Liege, Belgium; Hepato-Gastroenterology and Digestive Oncology Department, Liege University Hospital, Liege, Belgium
| |
Collapse
|
|
15
|
Wiley JW, Higgins GA. Epigenomics and the Brain-gut Axis: Impact of Adverse Childhood Experiences and Therapeutic Challenges. JOURNAL OF TRANSLATIONAL GASTROENTEROLOGY 2024; 2:125-130. [PMID: 40012740 PMCID: PMC11864786 DOI: 10.14218/jtg.2024.00017] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
The brain-gut axis represents a bidirectional communication network that integrates neural, hormonal, and immunological signaling between the central nervous system and the gastrointestinal tract. Adverse childhood experiences (ACEs) have increasingly been recognized for their profound impact on this axis, with implications for both mental and physical health outcomes. This mini-review explores the emerging field of epigenomics-specifically, how epigenetic modifications incurred by ACEs can influence the brain-gut axis and contribute to the pathophysiology of various disorders. We examine the evidence linking epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs to the modulation of gene expression involved in stress responses, neurodevelopment, and immune function-all of which intersect at the brain-gut axis. Additionally, we discuss the emerging potential of the gut microbiome as both a target and mediator of epigenetic changes, further influencing brain-gut communication in the context of ACEs. The methodological and therapeutic challenges posed by these insights are significant. The reversibility of epigenetic marks and the long-term consequences of early life stress require innovative and comprehensive approaches to intervention. This underscores the need for comprehensive strategies encompassing psychosocial, pharmacological, neuromodulation, and lifestyle interventions tailored to address ACEs' individualized and persistent effects. Future directions call for a multi-disciplinary approach and longitudinal studies to uncover the full extent of ACEs' impact on epigenetic regulation and the brain-gut axis, with the goal of developing targeted therapies to mitigate the long-lasting effects on health.
Collapse
Affiliation(s)
- John W. Wiley
- Department of Internal Medicine, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Gerald A. Higgins
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
| |
Collapse
|
|
16
|
Clough J, Colwill M, Poullis A, Pollok R, Patel K, Honap S. Biomarkers in inflammatory bowel disease: a practical guide. Therap Adv Gastroenterol 2024; 17:17562848241251600. [PMID: 38737913 PMCID: PMC11085009 DOI: 10.1177/17562848241251600] [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: 02/13/2024] [Accepted: 04/12/2024] [Indexed: 05/14/2024] Open
Abstract
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a costly condition in terms of morbidity and healthcare utilization, with an increasing prevalence now approaching 1% in the Western world. Endoscopic assessment of IBD remains the gold standard for diagnosis, evaluation of treatment response and determination of post-operative recurrence, but is expensive and invasive. Biomarkers can facilitate non-invasive disease assessment, with C-reactive protein and faecal calprotectin as the most widely available biomarkers in current clinical practice. This narrative review summarizes the evidence for their use in both UC and CD and offers practical guidance for healthcare providers taking into account the limitations of biomarker interpretation. We present evidence for the future use of novel biomarkers in IBD and discuss how biomarker discovery could deliver the goal of precision medicine in IBD.
Collapse
Affiliation(s)
- Jennie Clough
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Michael Colwill
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Andrew Poullis
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Richard Pollok
- St George’s University Hospital NHS Foundation Trust
- Institute of Infection and Immunity, St George’s University, London, UK
| | - Kamal Patel
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Sailish Honap
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
| |
Collapse
|
|
17
|
Schmidt ML, McCrady E, Lee A, Bowerbank T, Miller MR, Watson M, Dhandapani A, Woolfson JP, Zizzo AN, Bax K, Crowley E. Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic. J Pediatr Gastroenterol Nutr 2024; 78:790-799. [PMID: 38318970 DOI: 10.1002/jpn3.12150] [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: 06/18/2023] [Revised: 12/20/2023] [Accepted: 01/14/2024] [Indexed: 02/07/2024]
Abstract
OBJECTIVE Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 μg/g, hFC 595 vs. 47 μg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 μg/g, p = 0.003, hFC 57 vs. 40 μg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.
Collapse
Affiliation(s)
- Melanie L Schmidt
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
| | - Emma McCrady
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Angus Lee
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | | | - Michael R Miller
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
| | - Melanie Watson
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
| | - Ashok Dhandapani
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
| | - Jessica P Woolfson
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
| | - Andréanne N Zizzo
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
| | - Kevin Bax
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
| | - Eileen Crowley
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Department of Pediatrics, Division of Pediatric Gastroenterology & Hepatology, Children's Hospital of Western Ontario, London Health Sciences Center, London, Ontario, Canada
- Children's Health Research Institute, London, Ontario, Canada
- Lawson Health Research Institute, London, Ontario, Canada
| |
Collapse
|
|
18
|
Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
Collapse
Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| |
Collapse
|
|
19
|
Fang YH, Luo YY, Zhang RF, Cheng Q, Chen J. [Clinical characteristics and prognosis of children with perianal fistulizing Crohn's disease]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2024; 26:42-47. [PMID: 38269458 PMCID: PMC10817735 DOI: 10.7499/j.issn.1008-8830.2308119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 12/06/2023] [Indexed: 01/26/2024]
Abstract
OBJECTIVES To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD). METHODS A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis. RESULTS The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05). CONCLUSIONS There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.
Collapse
Affiliation(s)
- You-Hong Fang
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine/National Clinical Research Center for Child Health/National Children's Regional Medical Center, Hangzhou 310052, China (Chen J, . cn)
| | - You-You Luo
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine/National Clinical Research Center for Child Health/National Children's Regional Medical Center, Hangzhou 310052, China (Chen J, . cn)
| | | | - Qi Cheng
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine/National Clinical Research Center for Child Health/National Children's Regional Medical Center, Hangzhou 310052, China (Chen J, . cn)
| | - Jie Chen
- Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine/National Clinical Research Center for Child Health/National Children's Regional Medical Center, Hangzhou 310052, China (Chen J, . cn)
| |
Collapse
|
|
20
|
Kawamoto A, Takenaka K, Hibiya S, Kitazume Y, Shimizu H, Fujii T, Saito E, Ohtsuka K, Okamoto R. Combination of leucine-rich alpha-2 glycoprotein and fecal markers detect Crohn's disease activity confirmed by balloon-assisted enteroscopy. Intest Res 2024; 22:65-74. [PMID: 37939721 PMCID: PMC10850704 DOI: 10.5217/ir.2023.00092] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/13/2023] [Accepted: 10/05/2023] [Indexed: 11/10/2023] Open
Abstract
BACKGROUND/AIMS Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn's disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy. METHODS One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed. RESULTS Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse. CONCLUSIONS The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.
Collapse
Affiliation(s)
- Ami Kawamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Endoscopic Unit, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kento Takenaka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shuji Hibiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Endoscopic Unit, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yoshio Kitazume
- Department of Radiology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiromichi Shimizu
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Eiko Saito
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazuo Ohtsuka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Endoscopic Unit, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| |
Collapse
|
|
21
|
Fasulo E, D’Amico F, Osorio L, Allocca M, Fiorino G, Zilli A, Parigi TL, Danese S, Furfaro F. The Management of Postoperative Recurrence in Crohn's Disease. J Clin Med 2023; 13:119. [PMID: 38202126 PMCID: PMC10779955 DOI: 10.3390/jcm13010119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/20/2023] [Accepted: 12/23/2023] [Indexed: 01/12/2024] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease with different phenotypes of presentation, inflammatory, penetrating, or stricturing disease, that significantly impacts patient well-being and quality of life. Despite advances in medical therapy, surgery sometimes represents the only treatment to address complications, such as strictures, fistulas, or abscesses. Minimizing postoperative recurrence (POR) remains a major challenge for both clinicians and patients; consequently, various therapeutic strategies have been developed to prevent or delay POR. The current review outlines an updated overview of POR management. We focused on diagnostic assessment, which included endoscopic examination, biochemical analyses, and cross-sectional imaging techniques, all crucial tools used to accurately diagnose this condition. Additionally, we delved into the associated risk factors contributing to POR development. Furthermore, we examined recent advances in the prophylaxis and treatment of POR in CD.
Collapse
Affiliation(s)
- Ernesto Fasulo
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20089 Milan, Italy
| | - Laura Osorio
- Gastroenterologist Hospital Pablo Tobon Uribe, Medellín 050010, Colombia;
| | - Mariangela Allocca
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Gionata Fiorino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
- Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| |
Collapse
|
|
22
|
Kamalova AA, Garina GA, Valeeva IK, Gaifutdinova AR. Fecal calprotectin as a marker of inflammatory bowel diseases. ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII (RUSSIAN BULLETIN OF PERINATOLOGY AND PEDIATRICS) 2023; 68:138-143. [DOI: 10.21508/1027-4065-2023-68-5-138-143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Calprotectin is a calcium- and zinc-binding protein belonging to the S100 protein family. This protein is found mainly in the cytoplasm of neutrophils, and, to a lesser extent, in monocytes and macrophages, which can be found in any human organs, but mainly in blood, cerebrospinal fluid, feces, saliva, and synovial fluid. Calprotectin is an effective tool forthe differential diagnosis of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). There is a connection of fecal calprotectin (FC) with the endoscopic activity of IBD, however, the available literature shows significant differences in the sensitivity and specificity of FC for predicting the endoscopic activity of the disease. In addition, FC can be considered as a predictor of histological mucosal healing and as a marker for assessing the response to treatment, including surgical, but there is still no consensus on the threshold value of a biomarker for these purposes. Conflicting data are presented in reports on FC as a predictor of IBD recurrence. FC seems to be effective for detecting relapse, however, there is no specific threshold value, therefore, the marker cannot completely replace endoscopic examination methods. In addition, there is intraindividual variability in the concentration of FC in patients, depending on age, type of feeding in the first year of life, taking medications, which significantly complicates the interpretation of the results.
Collapse
|
|
23
|
Pierre N, Vieujean S, Peyrin-Biroulet L, Meuwis MA, Louis E. Defining Biological Remission in Crohn's Disease: Interest, Challenges and Future Directions. J Crohns Colitis 2023; 17:1698-1702. [PMID: 37208498 DOI: 10.1093/ecco-jcc/jjad086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Indexed: 05/21/2023]
Abstract
In Crohn's disease, the treat-to-target strategy has been greatly encouraged and has become a standard of care. In this context, defining the target [remission] constitutes a major stake and is fuelling the literature. Currently, clinical remission [symptom control] is no longer the only objective of treatments since it does not allow to closely control inflammation-induced tissue damage. The introduction of endoscopic remission as a therapeutic target clearly represented progress but this examination remains invasive, costly, not well accepted by patients and does not allow tight control of disease activity. More fundamentally, morphological techniques [e.g. endoscopy, histology, ultrasonography] are limited since they do not evaluate the biological activity of the disease but only its consequences. Besides, emerging evidence suggests that biological signs of disease activity could better guide treatment decisions than clinical parameters. In this context, we stress the necessity to define a novel treatment target: biological remission. Based on our previous work, we propose a conceptual definition of biological remission which goes beyond the classical normalization of inflammatory markers [C-reactive protein and faecal calprotectin]: absence of biological signs associated with the risk of short-term relapse and mid-/long-term relapse. The risk of short-term relapse seems essentially to be characterized by a persistent inflammatory state while the risk of mid-/long-term relapse implies a more heterogeneous biology. We discuss the value of our proposal [guiding treatment maintenance, escalation or de-escalation] but also the fact that its clinical implementation would require overcoming major challenges. Finally, future directions are proposed to better define biological remission.
Collapse
Affiliation(s)
- Nicolas Pierre
- Laboratory of Translational Gastroenterology, GIGA Institute, University of Liège, Liège, Belgium
| | - Sophie Vieujean
- Laboratory of Translational Gastroenterology, GIGA Institute, University of Liège, Liège, Belgium
- Departement of Hepato-Gastroenterology and Digestive Oncology, Liège University Hospital, Liège, Belgium
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Marie-Alice Meuwis
- Laboratory of Translational Gastroenterology, GIGA Institute, University of Liège, Liège, Belgium
- Departement of Hepato-Gastroenterology and Digestive Oncology, Liège University Hospital, Liège, Belgium
| | - Edouard Louis
- Laboratory of Translational Gastroenterology, GIGA Institute, University of Liège, Liège, Belgium
- Departement of Hepato-Gastroenterology and Digestive Oncology, Liège University Hospital, Liège, Belgium
| |
Collapse
|
|
24
|
Latorre Añó P, Torrente Sánchez J, Pérez Ibañez AA, Tenias Burillo JM, Moreno Sánchez NP, López-Serrano A, Moreno Osset E, Murado Pardo J, Paredes JM. Fecal immunochemical test for hemoglobin versus fecal calprotectin to monitor endoscopic activity in inflammatory bowel disease. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:553-558. [PMID: 37114398 DOI: 10.17235/reed.2023.9536/2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/29/2023]
Abstract
AIM endoscopy identifies inflammatory activity, however, it is an unpleasant test and is not always accessible. The aim of the study was to compare the usefulness of quantitative fecal immunochemical test (FIT) versus fecal calprotectin (FC) to determine endoscopic activity in patients with inflammatory bowel disease (IBD). METHODS cross-sectional prospective observational study. The stool samples were collected within three days before starting the preparation for the colonoscopy. We used the Mayo index for ulcerative colitis (UC) and the simplified endoscopic index for Crohn's disease (CD). Mucosal healing (MH) was defined as the score 0 points in each of the endoscopic indices. RESULTS eighty-four patients were included, 40 (47.6 %) with UC. In patients with IBD, FIT and FC showed a significant correlation with the presence of inflammatory activity/MH on endoscopy, with no statistically significant differences between the two receiver-operating characteristic (ROC) curves. Both tests improved their diagnostic performance when assessing patients with UC; the Spearman correlations between FIT and FC and endoscopic inflammatory activity were r = 0.6 (p = 0.0001) and r = 0.7 (p = 0.0001), respectively. In Crohn's disease, the diagnostic utility of both tests was lower. CONCLUSIONS FIT is an alternative to monitor endoscopic activity among ulcerative colitis patients. In Crohn's disease, more studies are needed to determine the role of fecal biomarkers.
Collapse
Affiliation(s)
| | - Jorge Torrente Sánchez
- Gastroenterología, Hospital Universitario Dr.PesHospital Universitario Dr. Pesetet, España
| | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Statie RC, Iordache S, Florescu LM, Gheonea IA, Sacerdoțianu VM, Ungureanu BS, Rogoveanu I, Gheonea DI, Ciurea T, Florescu DN. Assessment of Ileal Crohn's Disease Activity by Gastrointestinal Ultrasound and MR Enterography: A Pilot Study. Life (Basel) 2023; 13:1754. [PMID: 37629610 PMCID: PMC10455412 DOI: 10.3390/life13081754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/15/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
INTRODUCTION In some cases, there may be a discrepancy between the symptomatology alleged by Crohn's disease (CD) patients and the results of laboratory tests or imaging investigations. Ileocolonoscopy with biopsy is the primary investigation for diagnosing and monitoring CD patients. Cross-sectional imaging techniques such as CT or MR enterography (MRE) and intestinal ultrasonography (IUS) have been proposed as complementary methods to colonoscopy for a complete evaluation of this category of patients. This study aims to identify the role of IUS, contrast-enhanced ultrasound (CEUS) and MRE in evaluating ileal CD activity, using clinical severity scores (Crohn's disease activity index-CDAI, Harvey-Bradshaw index-HBI) and faecal calprotectin or C-reactive protein (CRP) levels as reference methods. MATERIALS AND METHODS A total of 44 adult patients with ileal CD confirmed using an ileocolonoscopy with biopsy and histopathological examination were assessed by IUS, CEUS and MRE. The evaluation of the disease activity based on the results obtained from the cross-sectional imaging tests was carried out by using some severity scores available in the literature. The sensitivity and specificity of IUS + CEUS and MRE for differentiating active from inactive forms of CD were determined using CDAI, HBI, faecal calprotectin and CRP as reference methods. The accuracy of the results was assessed by the receiver operating characteristics method. The Pearson correlation coefficient was used to determine the types of correlation. A p-value less than 0.05 suggested a statistically significant relationship. RESULTS Compared to CDAI, the best correlation was identified for Limberg score (r = 0.667, 95% confidence interval (CI) [0.46, 0.8], p < 0.001), followed by MaRIAs score (r = 0.614, 95% CI [0.39, 0.77], p < 0.001). A sensitivity of 93.33% and a specificity of 71.43% (AUC = 0.98) were demonstrated in the case of Limberg score for differentiating patients with active disease from those in remission and for MaRIAs score a sensitivity of 100.00% and a specificity of 57.14% (AUC = 0.97). Regarding HBI, the best correlation was observed for MaRIAs score (r = 0.594, 95% CI [0.36, 0.76], p < 0.001). Also, faecal calprotectin showed the best correlation with MaRIAs score (r = 0.697, 95% CI [0.46, 0.84], p < 0.001), but in the case of CRP, there was only a weak correlation for all evaluated scores. CONCLUSIONS Although magnetic resonance imaging does not appear to be superior to ultrasonography in terms of accuracy for differentiating active forms of CD from those in remission, the results of our study suggest that MRE associates a better correlation with clinical severity scores and faecal calprotectin levels compared to ultrasonography. More studies are needed to validate these results.
Collapse
Affiliation(s)
- Răzvan-Cristian Statie
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Sevastița Iordache
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Lucian Mihai Florescu
- Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ioana-Andreea Gheonea
- Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Victor-Mihai Sacerdoțianu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Bogdan Silviu Ungureanu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ion Rogoveanu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan-Ionuț Gheonea
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Tudorel Ciurea
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Nicolae Florescu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| |
Collapse
|
|
26
|
Pauwels RWM, Ten Bokkel Huinink S, van der Woude CJ, Doukas M, Oudijk L, de Vries AC. Early fecal calprotectin levels at week 8 may guide therapeutic decisions on Ustekinumab therapy in patients with Crohn's disease. Scand J Gastroenterol 2023; 58:980-987. [PMID: 36970968 DOI: 10.1080/00365521.2023.2194009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/12/2023] [Accepted: 03/19/2023] [Indexed: 05/16/2023]
Abstract
BACKGROUND Response evaluation after induction therapy with ustekinumab (UST) in Crohn's disease (CD) is important for decisions on maintenance therapy. We aimed to assess the potential of fecal calprotectin (FC) levels to predict endoscopic response at week 16. METHODS CD patients with FC >100 µg/g and endoscopic active disease (SES-CD> 2, Rutgeerts' score ≥ i2) at initiation of UST therapy were enrolled. FC was determined at weeks 0, 2, 4, 8 and 16 and patients underwent a colonoscopy at week 16. The primary outcome was an endoscopic response at week 16 (SES-CD score ≥50% decrease or a decrease of ≥1 points in Rutgeerts' score). The optimal cut-off levels of FC and change in FC to predict endoscopic response were determined using ROC statistics. RESULTS 59 CD patients were included. Endoscopic response was observed in 21/59 (36%) patients. The diagnostic accuracy for FC levels at week 8 to predict endoscopic response at week 16 showed a predictive value of 0.71. A decrease in FC levels ≥500 µg/g between baseline at week 8 indicates endoscopic response (PPV = 89%), whereas absence of any decrease indicates endoscopic non-response after induction (NPV = 81%). CONCLUSIONS Continuation of UST therapy without endoscopic response evaluation may be considered in patients with a decrease in FC levels of ≥500 µg/g at week 8. The decision on continuation of UST therapy or therapy optimization needs reconsideration in patients without a decrease of FC level. In all other patients, endoscopic response evaluation of induction therapy remains essential for therapeutic decisions.
Collapse
Affiliation(s)
- Renske W M Pauwels
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | | | | | - M Doukas
- Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - L Oudijk
- Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| |
Collapse
|
|
27
|
Kitazume Y, Takenaka K, Ohtsuka K, Ozawa Y, Kimura K, Watanabe R, Tsuchiya J, Fujii T, Nagahori M, Watanabe M, Tateishi U. Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn's Disease: Comparison with Balloon-assisted Enteroscopy Findings. Magn Reson Med Sci 2023; 22:325-334. [PMID: 35545505 PMCID: PMC10449560 DOI: 10.2463/mrms.mp.2021-0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 03/05/2022] [Indexed: 11/09/2022] Open
Abstract
PURPOSE To quantify bowel motility shown on cine MRI using the classical optical flow algorithm and compare it with balloon-assisted enteroscopy (BAE) findings in patients with Crohn's disease (CD). METHODS This retrospective study included 29 consecutive patients with CD who had undergone MR enterocolonography (MREC) and BAE between March and May 2017. We developed computer software to present motion vector magnitudes between consecutive cine MR images as bowel motility maps via a classical optical flow algorithm using the Horn-Schunck method. Cine MR images were acquired with a balanced steady-state free precession sequence in the coronal direction to capture small bowel motility. The small bowels were divided into three segments. In total, 63 bowel segments were assessed via BAE and MREC. Motility scores on the maps, simplified MR index of activity (sMaRIA), and MREC score derived from a 5-point MR classification were assessed independently by two radiologists and compared with the CD endoscopic index of severity (CDEIS). Correlations were assessed using Spearman's rank coefficient. The areas under the receiver-operating characteristic curve (AUCs) of motility score for differentiating CDEIS was calculated; a P value < 0.05 was considered statistically significant. RESULTS Motility score was negatively correlated with CDEIS (r = -0.59 [P < 0.001] and -0.54 [P < 0.001]), and the AUCs of motility scores for detecting CDEIS ≥ 3 were 88.2% and 78.6% for observers 1 and 2, respectively. There were no significant differences in the AUC for detecting CDEIS ≥ 3 and CDEIS ≥ 12 between motility and sMaRIA or MREC score. CONCLUSION The motility map was feasible for locally quantifying the bowel motility. In addition, the motility score on the map reflected the endoscopic inflammatory activity of each small bowel segment in patients with CD; hence, it could be used as a tool in objectively interpreting cine MREC to predict inflammatory activity in CD.
Collapse
Affiliation(s)
- Yoshio Kitazume
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kento Takenaka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazuo Ohtsuka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuo Ozawa
- Systems Laboratories Corporation, Yokohama, Kanagawa, Japan
| | - Koichiro Kimura
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryosuke Watanabe
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Junichi Tsuchiya
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masakazu Nagahori
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ukihide Tateishi
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| |
Collapse
|
|
28
|
Leftwich HK, Vargas-Robles D, Rojas-Correa M, Yap YR, Bhattarai S, Ward DV, Fujimori G, Forconi CS, Yeboah T, Carter A, Kastrinakis A, Asirwatham AM, Bucci V, Moormann AM, Maldonado-Contreras A. The microbiota of pregnant women with SARS-CoV-2 and their infants. MICROBIOME 2023; 11:141. [PMID: 37365606 DOI: 10.1186/s40168-023-01577-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 05/16/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Infants receive their first bacteria from their birthing parent. This newly acquired microbiome plays a pivotal role in developing a robust immune system, the cornerstone of long-term health. RESULTS We demonstrated that the gut, vaginal, and oral microbial diversity of pregnant women with SARS-CoV-2 infection is reduced, and women with early infections exhibit a different vaginal microbiota composition at the time of delivery compared to their healthy control counterparts. Accordingly, a low relative abundance of two Streptococcus sequence variants (SV) was predictive of infants born to pregnant women with SARS-CoV-2 infection. CONCLUSIONS Our data suggest that SARS-CoV-2 infections during pregnancy, particularly early infections, are associated with lasting changes in the microbiome of pregnant women, compromising the initial microbial seed of their infant. Our results highlight the importance of further exploring the impact of SARS-CoV-2 on the infant's microbiome-dependent immune programming. Video Abstract.
Collapse
Affiliation(s)
- Heidi K Leftwich
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Massachusetts Memorial Health, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Daniela Vargas-Robles
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Mayra Rojas-Correa
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Yan Rou Yap
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Shakti Bhattarai
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Doyle V Ward
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Gavin Fujimori
- Department of Medicine. Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Catherine S Forconi
- Department of Medicine. Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Tracy Yeboah
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Massachusetts Memorial Health, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Acara Carter
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Massachusetts Memorial Health, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Alyssa Kastrinakis
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Massachusetts Memorial Health, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Alison M Asirwatham
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Massachusetts Memorial Health, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Vanni Bucci
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Ann M Moormann
- Department of Medicine. Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Ana Maldonado-Contreras
- Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
| |
Collapse
|
|
29
|
Li J, Xu M, Qian W, Ling F, Chen Y, Li S, Cheng Y, Zhu L. Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn's disease. Front Physiol 2023; 14:1186665. [PMID: 37324392 PMCID: PMC10267473 DOI: 10.3389/fphys.2023.1186665] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 05/24/2023] [Indexed: 06/17/2023] Open
Abstract
Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45 μg/g. These values were 26.94, 66.77, and 327.22 μg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.
Collapse
|
|
30
|
Bohra A, Mohamed G, Vasudevan A, Lewis D, Van Langenberg DR, Segal JP. The Utility of Faecal Calprotectin, Lactoferrin and Other Faecal Biomarkers in Discriminating Endoscopic Activity in Crohn's Disease: A Systematic Review and Meta-Analysis. Biomedicines 2023; 11:1408. [PMID: 37239079 PMCID: PMC10216423 DOI: 10.3390/biomedicines11051408] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/01/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
INTRODUCTION Currently, faecal calprotectin (FC) is the predominate faecal biomarker utilised in clinical practice to monitor Crohn's disease (CD) activity. However, there are several potential faecal biomarkers described in the literature. We performed a meta-analysis to determine the accuracy of faecal biomarkers in discriminating endoscopic activity and mucosal healing in CD. METHODS We searched the medical literature using MEDLINE, EMBASE, and PubMed from 1978 to 8 August 2022. Descriptive statistics, including sensitivity, specificity of the primary studies, their positive and negative likelihood ratios, and their diagnostic odds ratio (DOR), were calculated. The methodological quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS) criteria. RESULTS The search found 2382 studies, of which 33 were included for analysis after screening. FC was found to have a pooled sensitivity and specificity, DOR, and negative predictive value (NPV) in discriminating active endoscopic disease (versus inactive) of 81%, 74%, 13.93, and 0.27, respectively. Faecal lactoferrin (FL) had a pooled sensitivity and specificity, DOR, and NPV in discriminating active endoscopic disease of 75%, 80%, 13.41, and 0.34, respectively. FC demonstrated a pooled sensitivity and specificity, DOR, and NPV of 88%, 72%, 18.17, and 0.19 in predicting mucosal healing. CONCLUSION FC remains an accurate faecal biomarker. Further evaluation of the utility of novel faecal biomarkers is needed.
Collapse
Affiliation(s)
- Anuj Bohra
- Department of Gastroenterology, Eastern Health, Box Hill, Melbourne, VIC 3128, Australia
- Department of Gastroenterology, Northern Health, Epping, Melbourne, VIC 3076, Australia
| | - Ghada Mohamed
- Department of Gastroenterology, Duke University Health System, Durham, NC 27710, USA
| | - Abhinav Vasudevan
- Department of Gastroenterology, Eastern Health, Box Hill, Melbourne, VIC 3128, Australia
| | - Diana Lewis
- Department of Gastroenterology, Northern Health, Epping, Melbourne, VIC 3076, Australia
- Northern Health Clinical School, University of Melbourne, Epping, Melbourne, VIC 3076, Australia
| | | | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Melbourne, VIC 3050, Australia
| |
Collapse
|
|
31
|
Del Hoyo J, Millán M, Garrido-Marín A, Aguas M. Are we ready for telemonitoring inflammatory bowel disease? A review of advances, enablers, and barriers. World J Gastroenterol 2023; 29:1139-1156. [PMID: 36926667 PMCID: PMC10011957 DOI: 10.3748/wjg.v29.i7.1139] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/02/2022] [Accepted: 02/09/2023] [Indexed: 02/21/2023] Open
Abstract
This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease (IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in PubMed, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through mHealth applications. Web systems demonstrated patients’ acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients´ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users´ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.
Collapse
Affiliation(s)
- Javier Del Hoyo
- Department of Gastroenterology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| | - Mónica Millán
- Department of Surgery, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| | - Alejandro Garrido-Marín
- Department of Gastroenterology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| | - Mariam Aguas
- Department of Gastroenterology, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
- Health Research Institute La Fe, La Fe University and Polytechnic Hospital, Valencia 46026, Spain
| |
Collapse
|
|
32
|
Leung T, Long M, Horst S, Afzali A, Sapir T, Fajardo K, De Felice K, Sandler R, Cross R. A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and Persistence With Inflammatory Bowel Disease Therapy (ASSIST Study): Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2022; 11:e40382. [PMID: 36520519 PMCID: PMC9801266 DOI: 10.2196/40382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract. Although adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor. Consequently, there is a critical need to develop interventions that monitor adherence in real time and identify reasons for nonadherence to support clinical teams in initiating effective interventions. Recently, electronic- and web-based platforms have been developed to monitor adherence and guide interventions. A novel remote therapy monitoring (RTM) technology, the Tappt digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient-reported outcomes and barriers to care, and process patient data through algorithms that trigger personalized digital and human touch points between clinical visits. Such a digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. OBJECTIVE We propose a 12-month multicenter randomized controlled trial to assess the effectiveness of the Tappt digital health system on adherence, clinical outcomes, and health care use among patients diagnosed with IBD starting a new oral or subcutaneous therapy. METHODS The digital health system intervention will provide automatic measurement of medication adherence via smart labels for pill bottles or injectors as well as a monitoring platform for providers. The system will prompt patients to complete a two-item assessment of symptoms monthly using the PRO-2 scales for UC and Crohn disease, from which increased symptoms will be alerted to providers. Participants will be randomized 2:1 to the intervention group or the control group, which will receive standard of care. All participants are required to complete questionnaires at baseline as well as at 12, 26, and 52 weeks. Assuming an adherence rate of 0.65 and 0.9 among control and intervention participants, respectively, we will need to enroll 123 participants: 82 (66.7%) in the intervention group and 41 (33.3%) controls. We will compare adherence as measured by the medication possession ratio, defined as the number of days of supply of medication obtained during the observation period out of the total number of days in the observation period, in participants using the RTM versus those receiving standard of care. We will also compare clinical outcomes and health care use in participants using the RTM versus those receiving standard of care. RESULTS We anticipate starting recruitment in December 2022. CONCLUSIONS Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little or no burden to the patient, record reliable data in real time, and provide actionable insights to the health care team. We anticipate the Tappt digital health system to improve the medication possession ratio, clinical outcomes, and health care use compared with standard of care. TRIAL REGISTRATION ClinicalTrials.gov NCT05316584; https://clinicaltrials.gov/ct2/show/NCT05316584. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) PRR1-10.2196/40382.
Collapse
Affiliation(s)
| | - Millie Long
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Sara Horst
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Anita Afzali
- Division of Gastroenterology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | | | | | - Kara De Felice
- Division of Gastroenterology, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Robert Sandler
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Raymond Cross
- Division of Gastroenterology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| |
Collapse
|
|
33
|
Higher serum infliximab concentrations during induction predict short-term endoscopic response in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2022; 34:1125-1131. [PMID: 36170681 DOI: 10.1097/meg.0000000000002431] [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] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Measuring of serum infliximab (IFX) induction concentrations might reduce primary non-response rates in inflammatory bowel diseases (IBD), but optimal target concentrations are unclear. We investigated whether IFX induction concentrations predict short-term endoscopic response at week 12 or treatment persistence at week 52. METHODS Sixty-nine IBD patients (Crohn's disease, n=24; ulcerative colitis, n=45) received standard IFX induction of 5 mg/kg bodyweight at weeks 0, 2, and 6. Responders continued maintenance therapy and underwent follow-up until week 52 or treatment discontinuation. We measured IFX concentrations at weeks 2, 6, and 12, and evaluated treatment response around week 12 with endoscopy or with clinical scores and fecal calprotectin. Using the receiver operating characteristic analysis, we determined optimal IFX concentration thresholds associated with treatment response. We further compared IFX induction concentrations between patients persisting on IFX at week 52 and patients discontinuing treatment due to insufficient response. RESULTS Responders (74%, 51 out of 69 patients) had significantly higher median IFX concentrations than non-responders at weeks 6 (25.06 vs. 19.68 µg/ml; P = 0.04) and 12 (18.03 vs. 10.02 µg/ml; P = 0.03), but not at week 2 (33.12 vs. 34.20 µg/ml; P = 0.97). Optimal IFX concentration thresholds for induction response were 21.33 and 5.13 µg/ml at weeks 6 and 12, respectively. Fifty-three patients continued IFX maintenance therapy until week 52. Induction concentrations failed to predict persistence on IFX therapy at week 52. CONCLUSION Higher IFX induction concentrations predict endoscopic short-term response. However, induction concentrations failed to predict long-term persistence on IFX treatment.
Collapse
|
|
34
|
Chen H, Li P, Chen J, Wang Y, Yu Q, Wu Y, Chen Y, Cai J. Peripheral blood mononuclear cell microRNAs are novel biomarkers for diagnosing and monitoring Crohn's disease. FASEB J 2022; 36:e22549. [PMID: 36165177 DOI: 10.1096/fj.202200452r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 08/07/2022] [Accepted: 09/02/2022] [Indexed: 11/11/2022]
Abstract
Crohn's disease is a recurrent, progressive, immune-mediated inflammatory disease and merely manifests non-specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT-PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR-582-5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606-0.796, p < .001). While PBMC miR-96-5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p < .001) and endoscopic activity (ρ = 0.512, p = .015). Furthermore, PBMC miR-96-5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609-0.844, p = .001) than C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR-582-5p may be further utilized as a diagnostic biomarker, while miR-96-5p may be a novel and valuable biomarker in monitoring disease activity.
Collapse
Affiliation(s)
- Hanwen Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Peiwei Li
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Jiamin Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Yufang Wang
- Department of Gastroenterology, The Third People's Hospital of Hangzhou, Hangzhou, P. R. China
| | - Qiao Yu
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Yihua Wu
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, P. R. China
| | - Yan Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Jianting Cai
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| |
Collapse
|
|
35
|
Romero-Mascarell C, Fernández-Esparrach G, Rodríguez-De Miguel C, Masamunt MC, Rodríguez S, Rimola J, Urpí M, Casanova GS, Ordás I, Ricart E, Caballol B, Fernández-Clotet A, Panés J, Llach J, González-Suárez B. Fecal Calprotectin for Small Bowel Crohn's Disease: Is It a Cutoff Issue? Diagnostics (Basel) 2022; 12:diagnostics12092226. [PMID: 36140627 PMCID: PMC9497577 DOI: 10.3390/diagnostics12092226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/03/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Fecal calprotectin (FC) correlates well with colonic inflammatory activity of Crohn’s disease (CD); data about relation of FC and small bowel (SB) lesions are still contradictory. The main aim was to analyze the relationship between FC levels and SB inflammatory activity in patients with established or suspected Crohn’s disease, assessed by small bowel capsule endoscopy (SBCE) or magnetic resonance enterography (MRE). (2) Methods: Two cohorts of patients were included: 1. Prospective data were collected from patients with established or suspected CD who underwent SBCE and FC (Cohort A); 2. A retrospective cohort of patients who underwent MRE and FC determination (Cohort B). Different cutoffs for FC were tested in both cohorts. (3) Results: 83 patients were included and 66 were finally analyzed. A total of 69.6% had SB lesions seen by SBCE (n = 25) or MRE (n = 21). FC mean levels were 605.74 + 607.07 μg/g (IQ range: 99.00−878.75), being significantly higher in patients with SB lesions compared to patients without lesions (735.91 + 639.70 μg/g (IQ range: 107.75−1366.25) vs. 306.35 + 395.26 μg/g (IQ range: 78.25−411.0), p < 0.005). For cohort A, 25 out of 35 patients had SB lesions and a significant correlation between Lewis Score and FC levels was achieved (R2: 0.34; p = 0.04). FC sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive values (NPV) for predicting SB lesions were 80%, 50%, 80%, and 50%, respectively, for FC > 100 µg/g. For cohort B, inflammatory SB activity, measured by MaRIA score, was detected in 21 out of 31 patients (67.7%). Patients with positive findings in MRE had significantly higher values of FC than those with no lesions (944.9 + 672.1 µg/g vs. 221 + 212.2 µg/g, p < 0.05). S, E, PPV, and NPV of FC were 89%, 50%, 77.2%, and 71.4% for FC levels > 100 µg/g. The higher sensitivity and specificity of the FC levels for the detection of SB lesions with SBCE and MRE was obtained for an FC cutoff >265 μg/g and >430 μg/g, respectively. (4) Conclusions: FC has a good correlation with the presence of SB lesions, assessed by SBCE and MRE, in patients with established or suspected Crohn’s disease. However, the ideal cutoff is here proven to be higher than previously reported. Multicenter and large prospective studies are needed in order to establish definitive FC cutoff levels.
Collapse
Affiliation(s)
- Cristina Romero-Mascarell
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Gloria Fernández-Esparrach
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
| | - Cristina Rodríguez-De Miguel
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Maria Carme Masamunt
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Sonia Rodríguez
- Department of Radiology, Centre de Diagnòstic per la Imatge (CDI), Hospital Clínic Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Jordi Rimola
- Department of Radiology, Centre de Diagnòstic per la Imatge (CDI), Hospital Clínic Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Miguel Urpí
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Gherzon Simon Casanova
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
| | - Ingrid Ordás
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Elena Ricart
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Berta Caballol
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Agnès Fernández-Clotet
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Julià Panés
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, ICMDiM, 08036 Barcelona, Spain
| | - Josep Llach
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
| | - Begoña González-Suárez
- Endoscopy Unit, Gastroenterology Department, ICMDiM, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Correspondence:
| |
Collapse
|
|
36
|
Liu D, Saikam V, Skrada KA, Merlin D, Iyer SS. Inflammatory bowel disease biomarkers. Med Res Rev 2022; 42:1856-1887. [PMID: 35603998 PMCID: PMC10321231 DOI: 10.1002/med.21893] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 11/16/2021] [Accepted: 05/05/2022] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease (IBD) is characterized as chronic inflammation in the gastrointestinal tract, which includes two main subtypes, Crohn's disease and ulcerative colitis. Endoscopy combined with biopsy is the most effective way to establish IBD diagnosis and disease management. Imaging techniques have also been developed to monitor IBD. Although effective, the methods are expensive and invasive, which leads to pain and discomfort. Alternative noninvasive biomarkers are being explored as tools for IBD prognosis and disease management. This review focuses on novel biomarkers that have emerged in recent years. These serological biomarkers and microRNAs could potentially be used for disease management in IBD, thereby decreasing patient discomfort and morbidity.
Collapse
Affiliation(s)
- Dandan Liu
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| | - Varma Saikam
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| | - Katie A Skrada
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| | - Didier Merlin
- 790 Petit Science Center, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA
- Atlanta Veterans Medical Center, Decatur, Georgia, USA
| | - Suri S Iyer
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| |
Collapse
|
|
37
|
Volkers AG, Appleton L, Gearry RB, Frampton CM, de Voogd FAE, Peters van Ton AM, Leach ST, Lemberg DA, Day AS. Fecal Calprotectin, Chitinase 3-Like-1, S100A12 and Osteoprotegerin as Markers of Disease Activity in Children with Crohn’s Disease. GASTROINTESTINAL DISORDERS 2022; 4:180-189. [DOI: 10.3390/gidisord4030017] [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] [Indexed: 10/10/2023] Open
Abstract
Fecal calprotectin (FC), chitinase 3-like-1 protein (CHI3L1), S100A12 and osteoprotegerin (OPG) are biomarkers of intestinal inflammation. This cross-sectional study aimed to evaluate these biomarkers in a cohort of children with Crohn’s disease (CD) and compare them with other measures of disease activity. Stool samples from children with CD were used to measure FC, CHI3L1, S100A12 and OPG by enzyme-linked immunosorbent assay. Serum inflammatory markers were measured and pediatric CD disease activity index (PCDAI) scores calculated. The simple endoscopic score for CD (SES-CD) was reported for a subgroup who underwent ileocolonoscopy corresponding with the stool samples. Sixty-five children were recruited. Children in clinical remission had lower FC and CHI3L1 levels than those with active disease (FC: 277 vs. 1648 µg/g, p = 0.012; CHI3L1: 23 vs. 227 ng/g, p = 0.013). FC levels differed between patients with clinically active or inactive isolated ileal CD. Although FC and CHI3L1 levels correlated strongly (r = 0.83), none of the fecal markers correlated well with serum markers. Only FC and OPG correlated with SES-CD scores (r = 0.57 and r = 0.48, respectively). In conclusion, FC correlated with both endoscopic and clinical disease activity and was the only biomarker that differentiated between active and inactive ileal CD. CHI3L1 also predicted clinical disease activity and correlated highly with FC. Further investigation of the role of CHI3L1 is required.
Collapse
|
|
38
|
Wu RY, Tandon P, Oh JS, Ambrosio L, Hotte N, Shah-Gandhi B, Madsen KL, Dieleman LA, Elahi S, Kroeker KI, Huang V. Urine and Serum Metabolomic Profiles Differ by Disease Activity in Pregnant Women With Inflammatory Bowel Diseases. GASTRO HEP ADVANCES 2022; 1:993-1005. [PMID: 39131249 PMCID: PMC11308627 DOI: 10.1016/j.gastha.2022.07.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 07/11/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Inflammatory bowel disease (IBD), inclusive of ulcerative colitis and Crohn's disease, are chronic inflammatory conditions that impact women of childbearing age. It has been previously shown that IBD is associated with altered metabolomic profiles, but whether metabolomic changes also affect pregnant patients with IBD is completely unknown. Methods This was a prospective cohort study comprised of 48 pregnant women with IBD who were followed throughout preconception and pregnancy. IBD disease activity was measured using biochemical markers C-reactive protein or fecal calprotectin using enzyme-linked immunosorbent assay and clinical disease activity using Harvey-Bradshaw Index or partial Mayo scores. Serum and urine samples were collected from preconception, trimester 1, and trimester 2 and analyzed using nuclear magnetic resonance spectroscopy combined with metabolomics set enrichment analysis. Results We identified a total of 24 urine metabolites and 17 serum metabolites which were altered by active disease across pregnancy. First trimester (T1) active disease-associated metabolites were enriched in "amino acid metabolism" and "fatty-acid β-oxidation." The leading urine metabolites at T1 were trimethyl-N-oxide (TMAO), succinic acid, and 3-hydroxy-2-methylbutyric acid, and leading serum metabolites were TMAO, glucose, and acetic acid. Multivariate modeling using serum TMAO, glucose, and acetic acid predicts T1 disease activity and correlated with mode of delivery and infant weights at delivery. Moreover, cross-time point modeling using metabolomes predicted future disease flare-up during pregnancy. Conclusion These results suggest select host metabolites may be able to discriminate and predict disease activity and are correlated with pregnancy outcomes at delivery. This warrants further validation of metabolomics to monitor IBD in pregnancy.
Collapse
Affiliation(s)
- Richard Y. Wu
- Department of Medicine, University of Toronto, Toronto, Canada
| | - Parul Tandon
- Division of Gastroenterology, Mount Sinai Hospital, Toronto, Canada
| | - Joyce S. Oh
- Division of Gastroenterology, Mount Sinai Hospital, Toronto, Canada
| | - Lindsy Ambrosio
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Naomi Hotte
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Binal Shah-Gandhi
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Karen L. Madsen
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | | | - Shokrollah Elahi
- Department of Dentistry, University of Alberta, Edmonton, Canada
- Department of Oncology, University of Alberta, Edmonton, Canada
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada
| | - Karen I. Kroeker
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| | - Vivian Huang
- Division of Gastroenterology, Mount Sinai Hospital, Toronto, Canada
- Division of Gastroenterology, University of Alberta, Edmonton, Canada
| |
Collapse
|
|
39
|
Mapping of etiologies of computed tomography-proven acute colitis: a prospective cohort study. Sci Rep 2022; 12:9730. [PMID: 35697847 PMCID: PMC9192641 DOI: 10.1038/s41598-022-13868-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 05/30/2022] [Indexed: 11/08/2022] Open
Abstract
Our objective was to describe the etiologies of acute colitis and to identify patients who require diagnostic endoscopy. Patients with symptoms of gastrointestinal infection and colonic inflammation on CT were prospectively included. Those immunosuppressed, with history of colorectal cancer or inflammatory bowel disease (IBD), were excluded. Microbiological analysis of the feces was performed using PCR assays BD-Max and FilmArray (GI panel,) and fecal cultures. Fecal calprotectin was determined. Patients with negative BD-Max underwent colonoscopy. One hundred and seventy-nine patients were included. BD-Max was positive in 93 patients (52%) and FilmArray in 108 patients (60.3%). Patients with infectious colitis (n = 103, 57.5%) were positive for Campylobacter spp. (n = 57, 55.3%), Escherichia coli spp. (n = 8, 7.8%), Clostridioides difficile (n = 23, 22.3%), Salmonella spp. (n = 9, 8.7%), viruses (n = 7, 6.8%), Shigella spp. (n = 6, 5.8%), Entamoeba histolytica (n = 2, 1.9%) and others (n = 4, 3.9%). Eighty-six patients underwent colonoscopy, which was compatible with ischemic colitis in 18 patients (10.1%) and IBD in 4 patients (2.2%). Fecal calprotectin was elevated in all patients, with a mean concentration of 1922.1 ± 2895.6 μg/g, and was the highest in patients with IBD (8511 ± 9438 μg/g, p < 0.001). After exclusion of patients with infectious etiology, a fecal calprotectin > 625 μg/g allowed identifying patients with IBD with an area under ROC curve of 85.1%. To conclude, computed tomography-proven colitis was of infectious etiology in 57.5% of patients. The main pathogens identified were Campylobacter spp. (55.3%), Clostridioides difficile (22.3%) and Salmonella spp. (8.7%). Ischemic colitis (10.1%) and IBD (2.2%) were seldom represented. No colorectal cancer was found.
Collapse
|
|
40
|
Abstract
Inflammatory bowel diseases (IBD), namely, Crohn's disease (CD) and ulcerative colitis (UC), are lifelong and incurable chronic inflammatory diseases affecting 6.8 million people worldwide. By 2030, the prevalence of IBD is estimated to reach 1% of the population in Western countries, and thus there is an urgent need to develop effective therapies to reduce the burden of this disease. Microbiome dysbiosis is at the heart of the IBD pathophysiology, and current research and development efforts for IBD treatments have been focused on gut microbiome regulation. Diet can shape the intestinal microbiome. Diet is also preferred over medication, is safe, and has been proven to be an effective strategy for the management of IBD. Therefore, although often overlooked, dietary interventions targeting the microbiome represent ideal treatments for IBD. Here, I summarize the latest research on diet as a treatment for IBD from infancy to adulthood, compile evidence of the mechanisms of action behind diet as treatment, and, lastly, provide insights into future research focusing on culturally tailored diets for ethnic minority groups with increased incidence of IBD yet underrepresented in nutrition research.
Collapse
Affiliation(s)
- Ana Maldonado-Contreras
- University of Massachusetts Chan Medical School, Department of Microbiology and Physiological Systems, Program of Microbiome Dynamics, Worcester, Massachusetts, USA
| |
Collapse
|
|
41
|
Shimizu H, Ebana R, Kudo T, Sato T, Hara T, Hosoi K, Usami M, Yoshida M, Takeuchi I, Nakase H, Iwama I, Arai K, Shimizu T. Both fecal calprotectin and fecal immunochemical tests are useful in children with inflammatory bowel disease. J Gastroenterol 2022; 57:344-356. [PMID: 35165800 DOI: 10.1007/s00535-022-01856-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 01/25/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Noninvasive biomarkers of intestinal inflammation can reduce the number of endoscopies in children with inflammatory bowel disease (IBD). This study aimed to prospectively investigate the usefulness of fecal calprotectin (FCP) and fecal immunochemical test (FIT) in pediatric IBD. METHODS Patients aged 6-17 years who underwent ileocolonoscopy for established or suspected IBD were eligible for this study. Fecal samples for FCP and FIT were collected before colonoscopy. RESULTS A total of 251 samples were analyzed: 88 from ulcerative colitis (UC), 74 from Crohn's disease (CD), 75 from healthy controls (HC), and 14 from children with functional gastrointestinal disorders and normal colonoscopy (NC). At IBD diagnosis, both FCP and FIT were significantly higher in the newly diagnosed UC/CD group than in the HC/NC group (P < 0.001). The optimal cutoffs of FCP and FIT to predict IBD diagnosis were 217 mg/kg and 87 ng/mL, respectively. Patients without mucosal healing (MH) showed higher FCP and FIT than those with MH in both UC and CD (P < 0.001). The FCP increased exponentially as the endoscopic activity score increased. The optimal cutoff values of FCP and FIT for predicting MH were 161 mg/kg and 106 ng/mL for UC and 367 mg/kg and 57 ng/mL for CD, respectively. FCP showed better specificity than the FIT. Patients with CD and normal ileocolonoscopy had elevated FCP during active small intestinal inflammation. CONCLUSIONS Both FCP and FIT correlate well with endoscopic activity in pediatric patients with IBD. The FCP is a superior marker for predicting MH.
Collapse
Affiliation(s)
- Hirotaka Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
| | - Ryo Ebana
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takuro Sato
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Tomoko Hara
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Kenji Hosoi
- Department of Pediatrics, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Masaaki Usami
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Masashi Yoshida
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Ichiro Takeuchi
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Minami 1-jo Nishi 16-chome, Chuo-ku, Sapporo, 060-8543, Japan
| | - Itaru Iwama
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuou-ku, Saitama, 330-8777, Japan
| | - Katsuhiro Arai
- Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| |
Collapse
|
|
42
|
Paredes JM, Ripollés T, Algarra Á, Diaz R, Moreno N, Latorre P, Martínez MJ, Llopis P, López A, Moreno-Osset E. Intestinal ultrasonography and fecal calprotectin for monitoring inflammation of ileal Crohn's disease: two complementary tests. Intest Res 2022; 20:361-369. [PMID: 35279969 PMCID: PMC9344237 DOI: 10.5217/ir.2021.00126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 12/25/2021] [Indexed: 11/18/2022] Open
Abstract
Background/Aims Tight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn’s disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD. Methods Patients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used. Results One hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P<0.001); the area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.70–0.88; P<0.001). The FC value that best reflected the activity in IUS was 100 μg/g with sensitivity, specificity, and positive and negative predictive values of 73.0%, 71.4%, 79.3% and 63.8%, respectively. There were no differences in FC concentration between patients with or without transmural complications. The addition of serum C-reactive protein to FC did not improve the ability to assess IUS activity. Conclusions FC has a significant correlation with IUS to monitor ileal CD activity. This correlation is weak and it does not allow assessing the presence of CD complications. Both tests should be used in conjunction for tight control of ileal CD. More studies on noninvasive tests in this location are needed.
Collapse
Affiliation(s)
- José María Paredes
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| | - Tomás Ripollés
- Department of Radiology, Doctor Peset University Hospital, Valencia, Spain
| | - Ángela Algarra
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| | - Rafael Diaz
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| | - Nadia Moreno
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| | - Patricia Latorre
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| | | | - Pilar Llopis
- Department of Pharmacy, Doctor Peset University Hospital, Valencia, Spain
| | - Antonio López
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| | - Eduardo Moreno-Osset
- Department of Digestive Medicine, Doctor Peset University Hospital, Valencia, Spain
| |
Collapse
|
|
43
|
Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | | |
Collapse
|
|
44
|
Bao C, Wu L, Wang D, Chen L, Jin X, Shi Y, Li G, Zhang J, Zeng X, Chen J, Liu H, Wu H. Acupuncture improves the symptoms, intestinal microbiota, and inflammation of patients with mild to moderate Crohn's disease: A randomized controlled trial. EClinicalMedicine 2022; 45:101300. [PMID: 35198926 PMCID: PMC8850329 DOI: 10.1016/j.eclinm.2022.101300] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 01/16/2022] [Accepted: 01/24/2022] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The efficacy and mechanisms of acupuncture for Crohn's disease (CD) are not well understood. We investigated its effects on symptoms, intestinal microbiota, and circulating inflammatory markers in CD patients. METHODS This 48-week, randomized, sham controlled, parallel-group clinical trial was performed at a tertiary outpatient clinic in China. From April 2015 to November 2019, 66 patients (mean age 40·4, 62·1% were male, all were Han Chinese) with mild to moderate active CD and unresponsive to drug treatment were enrolled and randomly assigned equally to an acupuncture group or a sham group. The treatment group received 3 sessions of acupuncture plus moxibustion per week for 12 weeks and a follow-up of 36 weeks. Clinicaltrials.gov: NCT02559037. FINDINGS At week 12, the clinical remission rate (the primary outcome) and clinical response rate of acupuncture group were significantly higher than that of sham group, with a difference of 42·4% (95% CI: 20·1%-64·0%) and 45·5% (95% CI: 24·0%-66·9%), respectively, both of which maintained at week 48. The acupuncture group had significantly lower CD activity index and C-reactive protein level at week 12, which maintained at 36-week follow-up. The CD endoscopic index of severity, histopathological score, and recurrence rate at week 48 were significantly lower in acupuncture group. The number of operational taxonomic unit of intestinal microbiota and relative abundance of Faecalibacterium prausnitzii and Roseburia faecis were increased. Plasma diamine oxidase, lipopolysaccharide, and Th1/Th17 related cytokines were decreased in 12-week after acupuncture. INTERPRETATION Acupuncture was effective in inducing and maintaining remission in patients with active CD, which was associated with increased abundance of intestinal anti-inflammatory bacteria, enhanced intestinal barrier, and regulation of circulating Th1/Th17-related cytokines. FUNDING National Key Basic Research Program of China (2015CB554500 and 2009CB522900), Shanghai Rising-Star Program (19QA1408100).
Collapse
Key Words
- Acupuncture
- Alternative therapy
- CD, Crohn's disease
- CDAI, Crohn's disease activity index
- CDEIS, Crohn's disease endoscopic index of severity
- CRP, C-reactive protein
- DAO, diamine oxidase
- Gut microbes
- HCs, healthy control subjects
- HS, histopathological score
- IBD, inflammatory bowel disease
- ITT, intention to treat
- Inflammatory bowel disease
- Intestinal barrier
- LEfSe, linear discriminant analysis effect size
- LPS, lipopolysaccharides
- OTU, operational taxonomic unit
- PP, per-protocol
- SCFAs, short chain fatty acids
Collapse
Affiliation(s)
- Chunhui Bao
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Luyi Wu
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Di Wang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Liming Chen
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Xiaoming Jin
- Department of Anatomy and Cell Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Yin Shi
- Outpatient Department, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
| | - Guona Li
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Jingzhi Zhang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Xiaoqing Zeng
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jianhua Chen
- Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Huirong Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
- Corresponding authors at: Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
| | - Huangan Wu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China
- Corresponding authors at: Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
| |
Collapse
|
|
45
|
Yu Y, Zhao H, Luo Y, Lou J, Chen J, Fang Y. Poor Concordance Between Clinical Activity and Endoscopic Severity in Pediatric Crohn's Disease: Before and After Induction Therapy. Dig Dis Sci 2022; 67:997-1006. [PMID: 33818661 DOI: 10.1007/s10620-021-06917-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 02/22/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES AND STUDY Endoscopic assessments of disease activity are important to diagnose and evaluate treatment responses in patients with Crohn's disease (CD). However, the invasiveness of endoscopy limits the application of this technique in routine examination. Thus, interest has been increasing in identifying noninvasive surrogate markers to predict endoscopic CD activity. METHODS We retrospectively analyzed pediatric patients with new-onset CD from January 2013 to December 2018 at Zhejiang University Affiliated Children's Hospital. The disease severity was scored according to the Crohn's Disease Endoscopic Index of Severity (CDEIS). Routine blood tests were determined individually. Clinical activity was assessed based on the Pediatric Crohn's Disease Activity Index (PCDAI). RESULTS A total of 91 patients with CD had undergone one or more ileocolonoscopies (n = 146), the mean CDEIS for all the pediatric patients with CD was 7.0 (95% CI 5.7-8.2), and the mean PCDAI was 20.9 (95% CI 18.3-23.5). Pearson's linear analysis of the CDEIS and PCDAI in pediatric patients with CD showed a moderate correlation (r = 0.508, P < 0.001). Weak correlations were found between the PCDAI and CDEIS at the first diagnosis (r = 0.408, P < 0.001) and after completing induction therapy (r = 0.286, P < 0.05). Routine blood tests also did not correlate well with the CDEIS. CONCLUSIONS This study identified weak correlations between the PCDAI and CDEIS in assessing pediatric patients with CD severity both at first diagnosis and after induction therapy. A comprehensive assessment of PCDAI, CDEIS and multiple laboratory factors should be performed at diagnosis and during the follow-up of patients with CD.
Collapse
Affiliation(s)
- Yu Yu
- Department of Gastroenterology, The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Binjiang District, Hangzhou City, 310051, Zhejiang Province, China
| | - Hong Zhao
- Department of Gastroenterology, The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Binjiang District, Hangzhou City, 310051, Zhejiang Province, China
| | - Youyou Luo
- Department of Gastroenterology, The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Binjiang District, Hangzhou City, 310051, Zhejiang Province, China
| | - Jingan Lou
- Department of Gastroenterology, The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Binjiang District, Hangzhou City, 310051, Zhejiang Province, China
| | - Jie Chen
- Department of Gastroenterology, The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Binjiang District, Hangzhou City, 310051, Zhejiang Province, China.
| | - Youhong Fang
- Department of Gastroenterology, The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, 3333 Bin Sheng Road, Binjiang District, Hangzhou City, 310051, Zhejiang Province, China
| |
Collapse
|
|
46
|
Gacesa R, Vich Vila A, Collij V, Mujagic Z, Kurilshikov A, Voskuil M, Festen E, Wijmenga C, Jonkers D, Dijkstra G, Fu J, Zhernakova A, Imhann F, Weersma R. A combination of fecal calprotectin and human beta-defensin 2 facilitates diagnosis and monitoring of inflammatory bowel disease. Gut Microbes 2021; 13:1943288. [PMID: 34313538 PMCID: PMC8317932 DOI: 10.1080/19490976.2021.1943288] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies.We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing.Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing-based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7).HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.
Collapse
Affiliation(s)
- R. Gacesa
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - A. Vich Vila
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - V. Collij
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - Z. Mujagic
- Maastricht University Medical Center, Division of Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - A. Kurilshikov
- University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - M.D. Voskuil
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - E.A.M. Festen
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - C. Wijmenga
- University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - D.M.A.E. Jonkers
- Maastricht University Medical Center, Division of Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - G. Dijkstra
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands
| | - J. Fu
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Pediatrics, Groningen, The Netherlands
| | - A. Zhernakova
- University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
| | - F. Imhann
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands,University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands,CONTACT F. Imhann University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands
| | - R.K. Weersma
- University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands
| |
Collapse
|
|
47
|
Vernia F, Viscido A, Di Ruscio M, Stefanelli G, Valvano M, Latella G. Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role? Digestion 2021; 102:833-844. [PMID: 34518458 DOI: 10.1159/000518419] [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] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
Collapse
Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit of IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Marco Valvano
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| |
Collapse
|
|
48
|
Moriichi K, Fujiya M, Okumura T. The endoscopic diagnosis of mucosal healing and deep remission in inflammatory bowel disease. Dig Endosc 2021; 33:1008-1023. [PMID: 33020947 DOI: 10.1111/den.13863] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022]
Abstract
The therapeutic goal in inflammatory bowel disease (IBD) patients has shifted from controlling the clinical activity alone to managing other associated problems. The concept of mucosal healing (MH) and deep remission (DR) are advocated and regarded as new therapeutic goals in IBD. However, the definition of MH still remains controversial. It is unclear whether or not the histological structures or functional factors should be included in the definition of DR in addition to clinical remission and MH. The classifications of white-light imaging (e.g. Mayo endoscopic subscore, UCEIS, CD Endoscopic Index of Severity, simple Endoscopic Score-CD) have been proposed and are now widely used to assess the severity as well as the MH of inflammation in IBD. In ulcerative colitis, magnifying chromoendoscopy has been shown to be useful to assess the MH of inflammation while other types of image-enhanced endoscopy, such as narrow-band imaging, have not. Endocytoscopy and confocal laser endomicroscopy (CLE) are also applied to assess the activity in IBD. These endoscopic procedures can estimate MH with more precision through observing the details of superficial structures, such as crypt openings. In addition, CLE can partially assess the mucosal function by detecting fluorescence leakage. Molecular imaging can possibly detect the molecules associated with inflammation, intestinal regeneration and differentiation, and various functions including the intestinal barrier and mucus secretion. These novel procedures may improve the diagnosis strategy of DR through the assessment of DR-associated factors such as the histological structures and functional factors in the near future.
Collapse
Affiliation(s)
- Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| |
Collapse
|
|
49
|
Pierre N, Salée C, Vieujean S, Bequet E, Merli AM, Siegmund B, Meuwis MA, Louis E. Review article: distinctions between ileal and colonic Crohn's disease: from physiology to pathology. Aliment Pharmacol Ther 2021; 54:779-791. [PMID: 34297423 DOI: 10.1111/apt.16536] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/15/2021] [Accepted: 07/05/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Ileal and colonic Crohn's disease seem to be two separate entities. AIMS To describe the main physiological distinctions between the small and the large intestine and to analyse the differences between ileal and colonic Crohn's disease. METHODS The relevant literature was critically examined and synthesised. RESULTS The small and large intestine have fundamental distinctions (anatomy, cellular populations, immune defence, microbiota). The differences between ileal and colonic Crohn's disease are highlighted by a heterogeneous body of evidence including clinical features (natural history of the disease, efficacy of treatments, and monitoring), epidemiological data (smoking status, age, gender) and biological data (genetics, microbiota, immunity, mesenteric fat). However, the contribution of these factors to disease location remains poorly understood. CONCLUSION The classification of ileal and colonic Crohn's disease as distinct subphenotypes is well supported by the literature. Understanding of these differences could be exploited to develop more individualised patient care.
Collapse
Affiliation(s)
- Nicolas Pierre
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium
| | - Catherine Salée
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium
| | - Sophie Vieujean
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Hepato-Gastroenterology and Digestive Oncology Department, Liège University Hospital, Liège, Belgium
| | - Emeline Bequet
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Liège University Hospital, Liège, Belgium
| | - Angela-Maria Merli
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium
| | - Britta Siegmund
- Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Marie-Alice Meuwis
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Hepato-Gastroenterology and Digestive Oncology Department, Liège University Hospital, Liège, Belgium
| | - Edouard Louis
- Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.,Hepato-Gastroenterology and Digestive Oncology Department, Liège University Hospital, Liège, Belgium
| |
Collapse
|
|
50
|
Wang Z, Verstockt B, Sabino J, Vermeire S, Ferrante M, Declerck P, Dreesen E. Population pharmacokinetic-pharmacodynamic model-based exploration of alternative ustekinumab dosage regimens for patients with Crohn's disease. Br J Clin Pharmacol 2021; 88:323-335. [PMID: 34197653 DOI: 10.1111/bcp.14971] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 06/01/2021] [Accepted: 06/21/2021] [Indexed: 12/22/2022] Open
Abstract
AIMS In the UNITI endoscopy sub-study, only 17.4% of patients with Crohn's disease (CD) on ustekinumab achieved endoscopic response and 10.9% of patients achieved endoscopic remission at week (w)44. We aimed to evaluate the impact of alternative ustekinumab dosage regimens on endoscopic outcomes based on population pharmacokinetic-pharmacodynamic (popPK-PD) modelling and simulation analysis. METHODS Real-world data were obtained from 83 patients with moderate-to-severe CD (95% biological-refractory) enrolled in a prospective cohort study receiving intravenous ustekinumab (~6 mg/kg) followed by every eight-week (q8w) subcutaneous maintenance therapy (90 mg). Three sequential models were developed: a two-compartment popPK model linking ustekinumab dose to ustekinumab exposure, an indirect response popPK-PD model describing the effect of ustekinumab exposure on fecal calprotectin (fCal), and a logistic regression outcome model linking fCal to endoscopic outcomes. RESULTS Ustekinumab clearance increased with decreasing serum albumin and increasing bodyweight. fCal decreased with increasing ustekinumab exposure. The probability of endoscopic response at w24 increased from 10.0% to 17.9% with fCal at w8 decreasing from 1800 μg/g to 694 μg/g (EC50 ). The probability of endoscopic remission at w24 increased from 2.1% to 10.0% with fCal at w8 decreasing from 1800 μg/g to 214 μg/g (EC50 ). Simulation-based comparison of q8w and q4w maintenance dosing regimens predicted 16.7% and 22.2% endoscopic response rates, respectively. Endoscopic remission rates were estimated to be 4.2% on q8w dosing and 6.7% on q4w dosing. CONCLUSIONS The developed models can guide clinical trial design and support model-informed dose optimization (stratified or individualized dosing) to improve endoscopic outcomes.
Collapse
Affiliation(s)
- Zhigang Wang
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - João Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Paul Declerck
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Erwin Dreesen
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.,Department of Pharmacy, Uppsala University, Uppsala, Sweden
| |
Collapse
|