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Inoue S, Ito K, Zaha K, Yoshida Y, Sekinaka Y, Kawamura Y. Usefulness of Fecal Calprotectin Measurement in a Pediatric Patient with Crohn's Disease. Fukushima J Med Sci 2025; 71:57-61. [PMID: 39662938 PMCID: PMC11799666 DOI: 10.5387/fms.23-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 07/30/2024] [Indexed: 12/13/2024] Open
Abstract
Acute pancreatitis in children in Japan is often caused by an anatomical abnormality of the pancreatic and bile duct, resulting in fever, abdominal pain, vomiting, diarrhea, and other symptoms. Crohn's disease, however, is a chronic granulomatous inflammatory bowel disease with ulcerative lesions of the intestinal tract of unknown cause that occurs mainly in young people, with symptoms similar to those of acute pancreatitis. We report a case of acute pancreatitis diagnosed in a patient not only with incomplete fusion of the pancreatic duct but also with Crohn's disease. A 14-year-old girl, healthy by nature, presented to our hospital with complaints of abdominal pain and diarrhea. She was initially diagnosed as having acute pancreatitis due to incomplete pancreas divisum. However, a high level of fecal calprotectin led to endoscopic examination, which resulted in the diagnosis of Crohn's disease. Fecal calprotectin can be useful in the diagnosis of inflammatory bowel disease associated with acute pancreatitis in children. Although the relationship between inflammatory bowel disease and acute pancreatitis has not yet been clarified, we suggest that in the present case, acute pancreatitis may have manifested as a complication of Crohn's disease and an underlying case of incomplete pancreas divisum.
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Affiliation(s)
- Shota Inoue
- Department of Pediatrics, Japan Self Defense Forces Central Hospital
| | - Kana Ito
- Department of Pediatrics, Japan Self Defense Forces Central Hospital
| | - Kiyotaka Zaha
- Department of Pediatrics, Japan Self Defense Forces Central Hospital
| | - Yusuke Yoshida
- Department of Pediatrics, Japan Self Defense Forces Central Hospital
| | - Yujin Sekinaka
- Department of Pediatrics, Japan Self Defense Forces Central Hospital
| | - Yoichi Kawamura
- Department of Pediatrics, Japan Self Defense Forces Central Hospital
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Lorenc-Góra J, Waniczek D, Czuba ZP, Kryj M, Lorenc Z, Muc-Wierzgoń M. Assessment of the Utility of Selected Inflammatory Markers in Correlation with Magnetic Resonance Enterography (MRE) Findings in the Diagnosis of Crohn's Disease. Biomolecules 2025; 15:116. [PMID: 39858510 PMCID: PMC11763748 DOI: 10.3390/biom15010116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 12/31/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Crohn's Disease (CD) is a chronic inflammatory bowel disease affecting the gastrointestinal tract. The search continues for new markers for assessing the activity of CD. Among them, pro-inflammatory and anti-inflammatory cytokines appear promising. We performed the analysis of cytokine concentrations in blood serum using the Bio-Plex Multiplex system (Bio-Rad), and their correlations with radiological parameters were assessed by magnetic resonance enterography (MRE), and fecal calprotectin levels were measured quantitatively by ELISA and clinical evaluation according to the Crohn's Disease Activity Index (CDAI). Our study found that measuring cytokine serum concentrations can be a valuable tool in the diagnosis and treatment of CD. Positive correlations were reported between contrast enhancement on DCE-MRE and the concentrations of PDGF-BB and RANTES. Also, a positive correlation was found between the delayed-phase of DCE and IL-10 concentration, a strong negative correlation between the delayed-phase of DCE and IL-12 concentration, and a strong positive correlation between the delayed-phase of DCE and RANTES concentrations. A strong positive correlation was also observed between the thickness of the intestinal wall on T2-weighted images and RANTES concentration. Therefore, concentrations of PDGF-BB, RANTES, IL-10 and IL-12 are promising markers of CD activity. The study also demonstrated significant correlations between the severity of disease activity assessed by the CDAI and the concentrations of IL-5, IL-8 and IL-9, as well as positive correlations between the levels of fecal calprotectin and the concentrations of IL-1RA and VEGF. Therefore, the levels of IL-5, IL-8, IL-9, VEGF and IL-1RA may be useful markers in the diagnosis and clinical assessment of disease activity.
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Affiliation(s)
- Justyna Lorenc-Góra
- Department of Imaging Diagnostics, St Barbara Regional Specialist Hospital No 5, 41-214 Sosnowiec, Poland
- Department of Imaging Diagnostics, Katowice Oncology Centre, 40-074 Katowice, Poland
| | - Dariusz Waniczek
- Department of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, Poland; (D.W.)
| | - Zenon P. Czuba
- Department of Microbiology and Immunology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Mariusz Kryj
- Department of Oncological Surgery, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Katowice, Poland; (D.W.)
| | - Zbigniew Lorenc
- Department of General and Colorectal Surgery and Multiple Trauma, St Barbara Regional Specialist Hospital No 5, Medical University of Silesia, 40-055 Katowice, Poland
| | - Małgorzata Muc-Wierzgoń
- Department of Internal Diseases Propaedeutics and Emergency Medicine, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Piekarska 18, 44-902 Bytom, Poland
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Zheng J, Zheng D, Fan Z, Li L, Chen R, Zhang S. Developing and Externally Validating a Simple Index Based on the Nonlinear Relationship of Fecal Calprotectin and Long-Term Outcomes in Ulcerative Colitis. J Inflamm Res 2024; 17:11247-11256. [PMID: 39717662 PMCID: PMC11665438 DOI: 10.2147/jir.s497655] [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: 09/24/2024] [Accepted: 12/14/2024] [Indexed: 12/25/2024] Open
Abstract
Background The possible nonlinear association with therapeutic outcomes in ulcerative colitis may contribute to the inconclusive cutoff values of fecal calprotectin (FC). We aimed to explore the nonlinear association between FC levels and long-term therapeutic outcomes in patients with ulcerative colitis and establish a clinically applicable FC index. Methods We included patients treated with vedolizumab or adalimumab from the VARSITY (n=661) and GEMINI 1 (n=620) studies as discovery and validation cohorts, respectively. The primary outcome was endoscopic remission at week 52 (Mayo Endoscopic Score 0). Restricted cubic splines were used to model nonlinearity between FC and long-term outcomes. Cutoff values were determined using piecewise regression to establish the FC index. Multivariable logistic regression and receiver operating characteristic curve analyses were performed to assess its predictive value. Results A nonlinear approximate enantiomorphic "J-shaped" association was observed between post-induction FC levels and long-term outcomes. Cutoff values of 180, 500, and 1300 μg/g were selected to construct the FC index; a higher index was significantly associated with a poorer outcome (P for trend <0.05). Furthermore, the FC index had an area under the receiver operating characteristic curve of 0.7095 [95% CI: 0.6621-0.7569], 0.6856 [95% CI: 0.6427-0.7284], 0.7527 [95% CI: 0.7084-0,7971], and 0.7630 [95% CI: 0.7110-0.8150] in predicting long-term endoscopic remission, clinical remission, histological remission, and disease clearance, respectively, approximately comparable to continuous FC, and superior to dichotomous FC. Conclusion The FC index is a promising indicator of therapeutic outcomes and may guide clinicians' therapeutic decisions.
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Affiliation(s)
- Jieqi Zheng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Danping Zheng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Zinan Fan
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Li Li
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Rirong Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Shenghong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
- Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-Sen University, Nanning, People’s Republic of China
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Nagata M, Inage E, Yamada H, Kudo T, Toriumi S, Sakaguchi K, Tanaka Y, Jimbo K, Ohtsuka Y, Shimizu T. Efficacy of sequential fecal-marker examination for evaluating gastrointestinal inflammation in solid food protein-induced enterocolitis syndrome. Allergol Int 2024; 73:556-562. [PMID: 38749792 DOI: 10.1016/j.alit.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/19/2024] [Accepted: 04/24/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES. METHODS This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course. RESULTS The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p < 0.01). The median FHb, FLf, and FCp ratios were 3.25, 9.09, and 9.79 in the FPIES group and 1.08, 1.29, and 1.49 in the control group, respectively. In the remission group, several patients had fluctuating fecal markers despite negative OFC, and one patient was diagnosed with FPIES by OFC with increased load. Receiver operating characteristic curve analyses revealed high diagnostic performance for each fecal marker in FPIES. CONCLUSIONS Sequential fecal marker examination proved valuable in diagnosing Solid-FPIES and evaluating the degree of gastrointestinal inflammation.
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Affiliation(s)
- Masumi Nagata
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Pediatrics, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan.
| | - Eisuke Inage
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hiromichi Yamada
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takahiro Kudo
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Shun Toriumi
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Keita Sakaguchi
- Department of Pediatrics, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan
| | - Yuko Tanaka
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Pediatrics, Tokyo Rinkai Hospital, Tokyo, Japan
| | - Keisuke Jimbo
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yoshikazu Ohtsuka
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Nestler J, Syrjä P, Kilpinen S, Moniz CA, Spillmann T, Hanifeh M, Heilmann RM. Duodenal and colonic mucosal S100A8/A9 (calprotectin) expression is increased and correlates with the severity of select histologic lesions in dogs with chronic inflammatory enteropathy. BMC Vet Res 2024; 20:393. [PMID: 39238011 PMCID: PMC11378391 DOI: 10.1186/s12917-024-04256-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 08/29/2024] [Indexed: 09/07/2024] Open
Abstract
BACKGROUND Calprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE. RESULTS Mucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P < 0.05). Higher mucosal calprotectin levels in the duodenum and across all segments correlated with lower serum albumin concentrations (both P < 0.05); duodenal mucosal calprotectin concentrations were more than sixfold higher in hypoalbuminemic dogs (median: 1441 µg/g, n = 4) than normoalbuminemic dogs (median: 227 µg/g, n = 40). There was no significant association of mucosal calprotectin levels with CIBDAI scores or individual clinical outcomes. CONCLUSIONS These results show that duodenal and colonic mucosal calprotectin concentrations are increased in dogs with CIE, providing further supporting evidence for the diagnostic potential of fecal calprotectin (presumably reflecting mucosal) concentrations and in dogs with CIE. Further longitudinal research is needed to assess changes in mucosal calprotectin concentrations with clinical response to treatment vs. mucosal disease remission and to determine the clinical utility of fecal calprotectin concentrations to diagnose and monitor dogs with CIE in clinical practice.
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Affiliation(s)
- Jasmin Nestler
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Pernilla Syrjä
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Susanne Kilpinen
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | | | - Thomas Spillmann
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Mohsen Hanifeh
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Romy M Heilmann
- Department for Small Animals, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany.
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Danese S, Fiorino G, Vicaut E, Paridaens K, Ugur A, Clark B, Vanasek T, Stepek D, D'Amico F, West R, Gilissen LPL, Wisniewska Jarosinka M, Drobinski P, Fronik G, Fic M, Walczak M, Kowalski M, Korczowski B, Wiatr M, Peyrin-Biroulet L. Clinical Trial: A Pragmatic Randomised Controlled Study to Assess the Effectiveness of Two Patient Management Strategies in Mild to Moderate Ulcerative Colitis-The OPTIMISE Study. J Clin Med 2024; 13:5147. [PMID: 39274360 PMCID: PMC11395821 DOI: 10.3390/jcm13175147] [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: 07/24/2024] [Revised: 08/15/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2-6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02-0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07-0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results.
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Affiliation(s)
- Silvio Danese
- Department of Gastroenterology and Digestive Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Eric Vicaut
- Clinical Trial Unit, Hospital Lariboisière APHP, 75010 Paris, France
| | | | - Asiya Ugur
- Ferring Pharmaceuticals A/S, 2770 Kastrup, Denmark
| | - Brian Clark
- Ferring Pharmaceuticals A/S, 2770 Kastrup, Denmark
| | - Tomas Vanasek
- Hepato-Gastroenterologie HK, s.r.o., 50012 Hradec Králové, Czech Republic
| | - David Stepek
- Internal Department, Military Hospital Brno, 61500 Brno, Czech Republic
| | - Ferdinando D'Amico
- Department of Gastroenterology and Digestive Endoscopy, San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Rachel West
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands
| | - Lennard P L Gilissen
- Department of Gastroenterology and Hepatology, Catharina Hospital Eindhoven, 5623 EJ Eindhoven, The Netherlands
| | | | - Piotr Drobinski
- Centrum Medyczne Lukamed in Chojnice, 89-600 Chojnice, Poland
| | - Grzegorz Fronik
- Melita Medical-Centrum Proktologii, Onkologii i Chorób Jelit, 50-449 Wrocław, Poland
| | - Mirosław Fic
- Polish Society of Gastroenterology, 58-521 Jezów Sudecki, Poland
| | - Michał Walczak
- Institute of Human Genetics, Polish Academy of Sciences, 61-772 Poznan, Poland
| | - Maciej Kowalski
- Department of Gastroenterology, Centrum Diagnostyczno-Lecznicze Barska, 87-806 Włocławek, Poland
| | - Bartosz Korczowski
- Institute of Medical Sciences, Medical College, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Michal Wiatr
- Ośrodek Badań Klinicznych CLINSANTE S.C. Ewa Galczak-Nowak Małgorzata Trzaska, Chałubińskiego, 85-004 Bydgoszcz, Poland
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, 54000 Vandoeuvre-lès-Nancy, France
- Department of Gastroenterology, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- INFINY Institute, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, 54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré-Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
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Sataranatarajan K, Adhikari S, Nguyen N, Narasimhan M, Balani J, Muthukumar A. Performance Evaluation of Open Channel Buhlmann Fecal Calprotectin Turbo Assay on Abbott Alinity C Analyzer. Diagnostics (Basel) 2024; 14:1744. [PMID: 39202232 PMCID: PMC11353904 DOI: 10.3390/diagnostics14161744] [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: 07/01/2024] [Revised: 07/28/2024] [Accepted: 08/06/2024] [Indexed: 09/03/2024] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal (GI) tract. Fecal calprotectin (fCAL) is a noninvasive laboratory test used in the diagnosis and monitoring of IBDs such as Crohn's disease and ulcerative colitis. The fCAL send-out test that our facility has been offering so far uses an ELISA-based method. In the current study, we sought to validate the performance of a Buhlmann fCAL turbo assay in an automated Abbott Alinity C analyzer (AFCAL) in our core laboratory. Five-day imprecision studies showed good performance for both within-run (5.3%) and between-day (2.5%) measurements. The reportable range was verified as 30-20,000 µg/g. Deming regression and Bland-Altman analysis indicated a strong correlation of r = 0.99 with a low, acceptable bias of 1.8% for AFCAL relative to the predicate Buhlmann fCAL ELISA results. AFCAL's clinical performance was determined retrospectively in 62 patients with ICD codes for IBD. Overall, the implementation of AFCAL in our routine clinical testing has improved our turnaround time, reduced the cost per test, and significantly increased our clinician satisfaction.
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Affiliation(s)
| | - Shishir Adhikari
- Core Laboratory, Clements University Hospital, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (S.A.); (N.N.)
| | - Ngoc Nguyen
- Core Laboratory, Clements University Hospital, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (S.A.); (N.N.)
| | - Madhusudhanan Narasimhan
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (K.S.); (M.N.); (J.B.)
| | - Jyoti Balani
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (K.S.); (M.N.); (J.B.)
| | - Alagarraju Muthukumar
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (K.S.); (M.N.); (J.B.)
- Core Laboratory, Clements University Hospital, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (S.A.); (N.N.)
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8
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Meng Q, Ning J, Lu J, Zhang J, Zu M, Zhang J, Han X, Zheng H, Gong Y, Hao X, Xiong Y, Gu F, Han W, Fu W, Wang J, Ding S. Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100a8/9 expression. J Genet Genomics 2024; 51:811-823. [PMID: 38575111 DOI: 10.1016/j.jgg.2024.03.009] [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: 03/26/2024] [Revised: 03/28/2024] [Accepted: 03/28/2024] [Indexed: 04/06/2024]
Abstract
The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis (UC), and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development. Here, we find that the IL-17 receptor subunit, CMTM4, is reduced in UC patients and dextran sulfate sodium (DSS)-induced colitis. The deletion of CMTM4 (Cmtm4-/-) in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type, and the gut microbiome significantly changes in composition. The causal role of the gut microbiome is confirmed with a cohousing experiment. We further identify that S100a8/9 is significantly up-regulated in Cmtm4-/- colitis, with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency. CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway, further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis. Taken together, the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis, suppression of S100a8/9, and prevention of colitis development. Our study further shows CMTM4 as a crucial innate immunity component, confirming its important role in UC development and providing insights into potential targets for the development of future therapies.
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Affiliation(s)
- Qiao Meng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Jing Ning
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Jingjing Lu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China
| | - Jing Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Ming Zu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Jing Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Xiurui Han
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Huiling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Yueqing Gong
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Xinyu Hao
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Ying Xiong
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Fang Gu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China
| | - Wenling Han
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, NHC Key Laboratory of Medical Immunology (Peking University), Beijing 100191, China; Peking University Center for Human Disease Genomics, Beijing 100191, China
| | - Weiwei Fu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China.
| | - Jun Wang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
| | - Shigang Ding
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases (BZ0371), Beijing 100191, China.
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9
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Edwards TS, Day AS. The role of fecal biomarkers in individuals with inflammatory bowel disease. Expert Rev Mol Diagn 2024; 24:497-508. [PMID: 38995110 DOI: 10.1080/14737159.2024.2375224] [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: 02/02/2024] [Accepted: 06/28/2024] [Indexed: 07/13/2024]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and Ulcerative Colitis (UC), is a relapsing and remitting condition. Noninvasive biomarkers have an increasingly important role in the diagnosis of IBD and in the prediction of future disease course in individuals with IBD. Strategies for the management of IBD increasingly rely upon close monitoring of gastrointestinal inflammation. AREAS COVERED This review provides an update on the current understanding of established and novel stool-based biomarkers in the diagnosis and management of IBD. It also highlights key gaps, identifies limitations, and advantages of current markers, and examines aspects that require further study and analysis. EXPERT OPINION Current noninvasive inflammatory markers play an important role in the diagnosis and management of IBD; however, limitations exist. Future work is required to further characterize and validate current and novel markers of inflammation. In addition, it is essential to better understand the roles and characteristics of noninvasive markers to enable the appropriate selection to accurately determine the condition of the intestinal mucosa.
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Affiliation(s)
- Teagan S Edwards
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
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10
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Saviano A, Schettino A, Iaccarino N, Mansour AA, Begum J, Marigliano N, Raucci F, Romano F, Riccardi G, Mitidieri E, d'Emmanuele di Villa Bianca R, Bello I, Panza E, Smimmo M, Vellecco V, Rimmer P, Cheesbrough J, Zhi Z, Iqbal TH, Pieretti S, D'Amore VM, Marinelli L, La Pietra V, Sorrentino R, Costa L, Caso F, Scarpa R, Cirino G, Randazzo A, Bucci M, McGettrick HM, Iqbal AJ, Maione F. A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease. J Autoimmun 2024; 144:103181. [PMID: 38522129 DOI: 10.1016/j.jaut.2024.103181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 02/05/2024] [Accepted: 02/10/2024] [Indexed: 03/26/2024]
Abstract
Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.
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Affiliation(s)
- Anella Saviano
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Anna Schettino
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Nunzia Iaccarino
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Adel Abo Mansour
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Jenefa Begum
- Institute of Cardiovascular Sciences (ICVS), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK
| | - Noemi Marigliano
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Federica Raucci
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Francesca Romano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Gelsomina Riccardi
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Emma Mitidieri
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | | | - Ivana Bello
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Elisabetta Panza
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Martina Smimmo
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Valentina Vellecco
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Peter Rimmer
- Institute of Cardiovascular Sciences (ICVS), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK; Department of Gastroenterology, Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jonathan Cheesbrough
- Institute of Cardiovascular Sciences (ICVS), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK; Department of Gastroenterology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Zhaogong Zhi
- Institute of Cardiovascular Sciences (ICVS), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK
| | - Tariq H Iqbal
- Department of Gastroenterology, Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Microbiology and Infection (IMI), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2WB, UK
| | - Stefano Pieretti
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy
| | - Vincenzo Maria D'Amore
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Luciana Marinelli
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Valeria La Pietra
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Raffaella Sorrentino
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Luisa Costa
- Rheumatology Research Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, via S. Pansini 5, 80131, Naples, Italy
| | - Francesco Caso
- Rheumatology Research Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, via S. Pansini 5, 80131, Naples, Italy
| | - Raffaele Scarpa
- Rheumatology Research Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, via S. Pansini 5, 80131, Naples, Italy
| | - Giuseppe Cirino
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Antonio Randazzo
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Mariarosaria Bucci
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy
| | - Helen Michelle McGettrick
- Institute of Inflammation and Ageing (IIA), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2WB, UK
| | - Asif Jilani Iqbal
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy; Institute of Cardiovascular Sciences (ICVS), College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
| | - Francesco Maione
- ImmunoPharmaLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy.
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11
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Sbeit W, Maamoun B, Azzam S, Shahin A, Carmiel-Haggai M, Khoury T. Ascites fluid calprotectin level is highly accurate in diagnosing spontaneous bacterial peritonitis: a preliminary proof of concept prospective study. Clin Exp Med 2024; 24:25. [PMID: 38281236 PMCID: PMC10822801 DOI: 10.1007/s10238-023-01257-0] [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: 10/19/2023] [Accepted: 12/15/2023] [Indexed: 01/30/2024]
Abstract
Ascites is the most common complication of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is a common complication of ascites. The diagnosis is made by an ascitic fluid polymorphonuclear (PMN) cell count of ≥ 250/mm3. However, no other diagnostic test is present for the diagnosis of SBP. The aim of the study present study is to assess the diagnostic yield of ascitic calprotectin in SBP, and to explore whether it can predict disease stage. We performed a single center proof-of-concept prospective study including all patients with cirrhosis and ascites who underwent paracentesis. Overall, 31 patients were included in the study. Eight patients had SBP vs. 23 patients without SBP. Ascitic calprotectin level was 77.4 ± 86.5 μg/mL in the SBP group, as compared to 16.1 ± 5.6 μg/mL in the non-SBP group (P = 0.001). An ascitic calprotectin cut-off value of > 21 μg/mL was associated with sensitivity and specificity of 85.7% and 89.5%, respectively, with ROC of 0.947 (95% CI 0.783 to 0.997, P < 0.0001). Notably, ascitic calprotectin did not had a prognostic value in cirrhosis stage and prognosis. Ascitic calprotectin was highly accurate in the diagnosis of SBP. It can be a serve as adjunct for indefinite cases of SBP.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Basheer Maamoun
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Subhi Azzam
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Amir Shahin
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Michal Carmiel-Haggai
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
- Liver Unit, Galilee Medical Center, Nahariya, Israel
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel.
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel.
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12
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Fantini MC, Loddo E, Petrillo AD, Onali S. Telemedicine in inflammatory bowel disease from its origin to the post pandemic golden age: A narrative review. Dig Liver Dis 2024; 56:1-6. [PMID: 37330279 DOI: 10.1016/j.dld.2023.05.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/19/2023]
Abstract
Inflammatory bowel disease (IBD), a chronic intestinal inflammatory disorder encompassing ulcerative colitis and Crohn's disease can be disabling and often requires lifelong treatment and follow-up. Digital health technologies and distance-management tools are less costly alternatives for IBD management and clinical monitoring. This review discusses how telephone/videoconference appointments enable treatment optimization from an early disease stage, provide complementary value-based patient care and educational resources, and allow consistent follow-up with a high standard of care. Replacing/supplementing traditional clinical consultations with telemedicine reduces healthcare utilization costs and the need for in-person consultations. The COVID-19 pandemic has accelerated the evolution of telemedicine in IBD, with several studies conducted since 2020 reporting high levels of patient satisfaction. Home-based injectable formulations coupled with telemedicine may become permanently embedded in healthcare systems in the post-pandemic period. While telemedicine consultations are well-accepted by many patients with IBD, they do not suit all patients or are not preferred (e.g., by elderly who do not have the means or ability to understand the associated technology). Ultimately, use of telemedicine should be decided by the patient and careful consideration is required to ensure that the patient is willing and capable of a successful remote visit.
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Affiliation(s)
- Massimo Claudio Fantini
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; Azienda Ospedaliero-Universitaria (AOU) di Cagliari, Cagliari, Italy.
| | - Erica Loddo
- Azienda Ospedaliero-Universitaria (AOU) di Cagliari, Cagliari, Italy
| | - Amalia Di Petrillo
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Sara Onali
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; Azienda Ospedaliero-Universitaria (AOU) di Cagliari, Cagliari, Italy
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13
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Dajti E, Frazzoni L, Iascone V, Secco M, Vestito A, Fuccio L, Eusebi LH, Fusaroli P, Rizzello F, Calabrese C, Gionchetti P, Bazzoli F, Zagari RM. Systematic review with meta-analysis: Diagnostic performance of faecal calprotectin in distinguishing inflammatory bowel disease from irritable bowel syndrome in adults. Aliment Pharmacol Ther 2023; 58:1120-1131. [PMID: 37823411 DOI: 10.1111/apt.17754] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/29/2023] [Accepted: 09/25/2023] [Indexed: 10/13/2023]
Abstract
BACKGROUND Symptoms of inflammatory bowel disease (IBD) often overlap with those of irritable bowel syndrome (IBS). AIM To evaluate the diagnostic performance of faecal calprotectin in distinguishing patients with IBD from those with IBS METHODS: We searched MEDLINE, Embase, Scopus, and Cochrane Library databases up to 1 January 2023. Studies were included if they assessed the diagnostic performance of faecal calprotectin in distinguishing IBD from IBS (defined according to the Rome criteria) using colonoscopy with histology or radiology as reference standard in adults. We calculated summary sensitivity and specificity and their 95% confidence intervals (CI) using a random-effect bivariate model. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies II. RESULTS We included 17 studies with a total of 1956 patients. The summary sensitivity was 85.8% (95% CI: 78.3-91), and the specificity was 91.7% (95% CI: 84.5-95.7). At a prevalence of IBD of 1%, the negative predictive value was 99.8%, while the positive predictive value was only 9%. Subgroup analyses showed a higher sensitivity in Western than in Eastern countries (88% vs 73%) and at a cut-off of ≤50 μg/g than at >50 μg/g (87% vs. 79%), with similar estimates of specificity. All studies were at "high" or "unclear" risk of bias. CONCLUSIONS Faecal calprotectin is a reliable test in distinguishing patients with IBD from those with IBS. Faecal calprotectin seems to have a better sensitivity in Western countries and at a cut-off of ≤50 μg/g.
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Affiliation(s)
- Elton Dajti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Leonardo Frazzoni
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Veronica Iascone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Secco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Amanda Vestito
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
- Gastro-Esophageal Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Lorenzo Fuccio
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Leonardo Henry Eusebi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Pietro Fusaroli
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
- Gastroenterology Unit, Hospital of Imola, Imola, Italy
| | - Fernando Rizzello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IBD Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Carlo Calabrese
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IBD Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IBD Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
| | - Franco Bazzoli
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Rocco Maurizio Zagari
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Gastro-Esophageal Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, S. Orsola Hospital, Bologna, Italy
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14
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Ogihara R, Kurumi H, Kanda T, Yashima K, Isomoto H, Yamaguchi N. Serum Activin A Is a Novel Biomarker of Endoscopic Activity in Ulcerative Colitis. Gastroenterology Res 2023; 16:334-341. [PMID: 38186584 PMCID: PMC10769608 DOI: 10.14740/gr1677] [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: 10/10/2023] [Accepted: 11/16/2023] [Indexed: 01/09/2024] Open
Abstract
Background Endoscopic healing (EH) is the long-term therapeutic goal for ulcerative colitis (UC). Since repeated colonoscopies are inconvenient and invasive, a surrogate biomarker for endoscopic activity is needed. Activin A is one of the transforming growth factor-β superfamily of proteins and has been shown to be associated with intestinal inflammation. Methods This single-center observational study included 27 Japanese patients with UC in clinical remission who underwent colonoscopy and blood sampling. We investigated the correlations between laboratory parameters, including serum activin A levels, and endoscopic activity, classified by the Mayo endoscopic subscore (MES) in these patients. Results This study included 15 males and 12 females. The median age was 44.0 years. In terms of endoscopic activity, five patients were diagnosed with MES 0, 14 patients with MES 1, seven patients with MES 2, and one patient with MES 3. The median serum activin level was 134.8 pg/mL (interquartile range (IQR), 105.3 - 188.1). Serum activin A levels were significantly correlated with the MES (Spearman's rank correlation coefficient r = 0.591, P = 0.001), which was better than that of C-reactive protein (CRP) (r = 0.487, P = 0.010). In the comparison between the EH group (MES 0) and non-EH group (MES 1-3), patients without EH had significantly higher serum activin A levels (Mann-Whitney U test, P = 0.047). A cutoff value of 133.6 pg/mL indicated non-EH with a sensitivity and specificity of 0.682 and 1.000, respectively. The area under the curve (AUC) of serum activin A for detecting non-EH was 0.791 (95% confidence interval (CI), 0.618 - 0.964), while that of CRP was 0.723 (95% CI, 0.504 - 0.941). Conclusions The serum activin A level is a potential novel biomarker of endoscopic activity in UC.
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Affiliation(s)
- Ryohei Ogihara
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Hiroki Kurumi
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Tsutomu Kanda
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Kazuo Yashima
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Japan
| | - Naoyuki Yamaguchi
- Department of Endoscopy, Nagasaki University Hospital, Nagasaki, Japan
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15
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Gaikwad U, Bhargava A, Jindal A, Padhy GK, Das P, Jagzape T, Lalwani A, Dash D. Faecal calprotectin as an inflammatory biomarker to distinguish between bacterial and viral causes of childhood diarrhoea in Indian settings. Indian J Med Microbiol 2023; 46:100459. [PMID: 37945132 DOI: 10.1016/j.ijmmb.2023.100459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 07/19/2023] [Accepted: 08/03/2023] [Indexed: 11/12/2023]
Abstract
OBJECTIVES The purpose of this study was to determine the value of faecal calprotectin (f-CP) in distinguishing between bacterial and viral aetiologies of infective diarrhoea in children attending a tertiary care hospital in Central India. METHODS Stool samples from children aged 3 months to 10 years who had acute or persistent diarrhoea were processed for microscopy, bacterial culture, and viral antigen detection (Rotavirus and Norovirus). The remaining samples, as well as stool samples from 20 healthy controls, were tested for f-CP using the enzyme linked immunosorbent assay. RESULTS Among 48 patients, 21 (43.7%) had bacterial diarrhoea, 14 (29.2%) had viral diarrhoea, and 13 (27.1%) had an unidentified aetiology. The median f-CP values were significantly (p = 0.004) higher in children with bacterial diarrhoea (75.2 μg/g; IQR-18.75-239.15) than in children with viral diarrhoea (75.2 μg/g; IQR-123.5-1987.5). Bacterial aetiology could be reliably predicted at the optimum f-CP concentrations of >541 μg/g and >238.4 μg/g in children aged 1 and 1-4 years, with an area under the curve of 0.767 and 0.867, respectively, using receiver-operator characteristic analysis. CONCLUSIONS Faecal calprotectin could reliably distinguish between bacterial and viral aetiologies of diarrhoea in children aged up to four years, but at relatively higher age-specified cut off values.
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Affiliation(s)
- Ujjwala Gaikwad
- Department of Microbiology, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099, India.
| | - Anudita Bhargava
- Department of Microbiology, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099, India.
| | - Atul Jindal
- Department of Paediatrics, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099 , India.
| | - Gouri Kumari Padhy
- Department of Community and Family Medicine, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099, India.
| | - Padma Das
- Department of Microbiology, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099, India.
| | - Tushar Jagzape
- Department of Paediatrics, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099 , India.
| | - Akash Lalwani
- Department of Pediatrics and Neonatology Pt. Jawahar Lal Nehru Memorial Medical College, Jail Road, Raipur, 492001, India.
| | - Debabrata Dash
- Department of Microbiology, All India Institute of Medical Sciences Raipur, Tatibandh, G E Road, Raipur, 492099, India.
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16
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Kapel N, Ouni H, Benahmed NA, Barbot-Trystram L. Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseases. Clin Transl Gastroenterol 2023; 14:e00617. [PMID: 37440723 PMCID: PMC10522095 DOI: 10.14309/ctg.0000000000000617] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 06/13/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Calprotectin is a heterodimeric calcium- and zinc-binding protein mainly derived from the cytoplasm of neutrophils that has direct antimicrobial functions and a role in the regulation of the innate immune response. It can be found in various biological compartments, in particular, the stool, with concentrations related to the level of mucosal inflammation. The measurement of fecal calprotectin has thus been recognized as a useful surrogate marker to distinguish patients with inflammatory bowel disease from those with irritable bowel syndrome. Moreover, it allows the monitoring of intestinal inflammation with a high negative predictive value, making it possible to exclude the diagnosis of inflammatory bowel disease for symptomatic patients. It also shows high sensitivity for the identification of patients requiring additional examinations for diagnosis, such as colonoscopy, and the evaluation of therapeutic responses, providing evidence of relapse or mucosal healing, which can lead to the intensification or reduction of treatment. As calprotectin levels are a measure of mucosal inflammation, high fecal concentrations are also found in other diseases with an inflammatory component, such as infectious enteritis or colorectal cancer. Interpretation of the concentration must therefore always take into account the clinical history and symptoms specific to each patient.
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Affiliation(s)
- Nathalie Kapel
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
- INSERM UMR-S1139, Faculté de Pharmacie, Université de Paris Cité, Paris, France
| | - Hamza Ouni
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Nacer Adam Benahmed
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Laurence Barbot-Trystram
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
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17
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Wirthgen E, Weber F, Kubickova-Weber L, Schiller B, Schiller S, Radke M, Däbritz J. Identifying predictors of clinical outcomes using the projection-predictive feature selection-a proof of concept on the example of Crohn's disease. Front Pediatr 2023; 11:1170563. [PMID: 37576142 PMCID: PMC10420065 DOI: 10.3389/fped.2023.1170563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/11/2023] [Indexed: 08/15/2023] Open
Abstract
Objectives Several clinical disease activity indices (DAIs) have been developed to noninvasively assess mucosal healing in pediatric Crohn's disease (CD). However, their clinical application can be complex. Therefore, we present a new way to identify the most informative biomarkers for mucosal inflammation from current markers in use and, based on this, how to obtain an easy-to-use DAI for clinical practice. A further aim of our proof-of-concept study is to demonstrate how the performance of such a new DAI can be compared to that of existing DAIs. Methods The data of two independent study cohorts, with 167 visits from 109 children and adolescents with CD, were evaluated retrospectively. A variable selection based on a Bayesian ordinal regression model was applied to select clinical or standard laboratory parameters as predictors, using an endoscopic outcome. The predictive performance of the resulting model was compared to that of existing pediatric DAIs. Results With our proof-of-concept dataset, the resulting model included C-reactive protein (CRP) and fecal calprotectin (FC) as predictors. In general, our model performed better than the existing DAIs. To show how our Bayesian approach can be applied in practice, we developed a web application for predicting disease activity for a new CD patient or visit. Conclusions Our work serves as a proof-of-concept, showing that the statistical methods used here can identify biomarkers relevant for the prediction of a clinical outcome. In our case, a small number of biomarkers is sufficient, which, together with the web interface, facilitates the clinical application. However, the retrospective nature of our study, the rather small amount of data, and the lack of an external validation cohort do not allow us to consider our results as the establishment of a novel DAI for pediatric CD. This needs to be done with the help of a prospective study with more data and an external validation cohort in the future.
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Affiliation(s)
- Elisa Wirthgen
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany
| | - Frank Weber
- Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany
| | | | - Benjamin Schiller
- Department of Pediatrics, Pediatric Gastroenterology, Rostock University Medical Center, Rostock, Germany
| | - Sarah Schiller
- Department of Pediatrics, Pediatric Gastroenterology, Rostock University Medical Center, Rostock, Germany
| | - Michael Radke
- Department of Pediatrics, Pediatric Gastroenterology, Rostock University Medical Center, Rostock, Germany
| | - Jan Däbritz
- Department of Pediatrics, Rostock University Medical Center, Rostock, Germany
- Department of Pediatrics, Pediatric Gastroenterology, Rostock University Medical Center, Rostock, Germany
- Department of Pediatrics, Greifswald University Medical Center, Greifswald, Germany
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18
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Carretero C, Bojorquez A, Eliakim R, Lazaridis N. Updates in the diagnosis and management of small-bowel Crohn's disease. Best Pract Res Clin Gastroenterol 2023; 64-65:101855. [PMID: 37652654 DOI: 10.1016/j.bpg.2023.101855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 07/06/2023] [Accepted: 08/01/2023] [Indexed: 09/02/2023]
Affiliation(s)
- Cristina Carretero
- Gastroenterology Department, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IDISNA), Clínica Universidad de Navarra. Pio XII 36, 31004, Pamplona, Spain.
| | - Alejandro Bojorquez
- Gastroenterology Department, Clínica Universidad de Navarra, Clínica Universidad de Navarra. Pio XII 36, 31004, Pamplona, Spain.
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tek-Aviv, Israel.
| | - Nikolaos Lazaridis
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London, United Kingdom; Saint Luke's Hospital, Small Bowel Service, Agias Sofias 18, 54622, Thessaloniki, Greece.
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19
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Wang Z, Yuan H, Zhu X, Wang J, Xiu W, Chen Y, Zhang G, Fu J, Peng K, Li A, Liu D, Huang X, He C, Lu F. Fecal calprotectin as an intestinal inflammation marker is elevated in glaucoma. Biomark Med 2023; 17:465-473. [PMID: 37656013 DOI: 10.2217/bmm-2023-0352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023] Open
Abstract
Objective: The aim of this study was to investigate the potential association between glaucoma and fecal calprotectin. Methods: A total of 144 glaucomatous patients and 66 healthy controls were enlisted for this study. The fecal calprotectin was assessed using enzyme-linked immunosorbent assay. Results: The median fecal calprotectin levels were significantly elevated in glaucoma (73.67 vs 41.97 μg/g; p < 0.001), primary angle-closure glaucoma (76.85 μg/g; p < 0.001) and primary open-angle glaucoma (69.29 μg/g; p = 0.016) groups compared with controls. A notable proportion of the glaucoma (24%; p < 0.001), primary angle-closure glaucoma (21%; p < 0.001) and primary open-angle glaucoma (24%; p < 0.001) subgroups exhibited highly abnormal fecal calprotectin levels (≥250 μg/g). Conclusion: Elevated fecal calprotectin might indicate potential intestinal inflammation in glaucoma.
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Affiliation(s)
- Zuo Wang
- Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science & Technology of China, Chengdu, China
| | - Hang Yuan
- Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China
| | - Xiong Zhu
- Department of Prenatal Diagnosis, Chengdu Women's & Children's Central Hospital, School of Medicine, University of Electronic Science & Technology of China, Chengdu, China
| | - Jinxia Wang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Wenbo Xiu
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Yang Chen
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Gao Zhang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Jing Fu
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Kun Peng
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - An Li
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Donghua Liu
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Xijing Huang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
| | - Chong He
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
- Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science & Technology of China, Chengdu, China
| | - Fang Lu
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
- Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science & Technology of China, Chengdu, China
- Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science & Technology of China, Chengdu, China
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20
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Kawashima K, Oshima N, Kishimoto K, Kataoka M, Fukunaga M, Kotani S, Sonoyama H, Oka A, Mishima Y, Kazumori H, Ishikawa N, Araki A, Ishihara S. Low Fecal Calprotectin Predicts Histological Healing in Patients with Ulcerative Colitis with Endoscopic Remission and Leads to Prolonged Clinical Remission. Inflamm Bowel Dis 2023; 29:359-366. [PMID: 35583193 DOI: 10.1093/ibd/izac095] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND Consensus regarding the cutoff value of fecal calprotectin (FC) for predicting histological healing (HH) in ulcerative colitis (UC) is lacking. This study aimed to determine an optimal FC cutoff value for predicting HH in patients with UC with clinical and endoscopic remission. Furthermore, FC's predictability for prolonged clinical remission (CR) was investigated. METHODS Patients with UC in clinical and endoscopic remission, defined as a partial Mayo score (PMS) ≤ 2 points and a Mayo endoscopic subscore 0-1, were prospectively enrolled. Biopsy samples were evaluated by Geboes score (GS), with HH defined as a GS < 2.0. Patients were followed for 2 years or until relapse, defined as a PMS > 2 or medication escalation. RESULTS Seventy-six patients with UC were included. The median FC value in patients with HH (n = 40) was 56.2 µg/g, significantly lower than that in those with histological activity (118.1 µg/g; P < .01). The area under the curve (AUC) in a receiver operating characteristic (ROC) curve analysis to predict HH for FC was 0.71 (95% confidence interval [CI], 0.59-0.83), with an optimal cutoff value of 82.7 µg/g (73% sensitivity; 64% specificity; P < .01). Of 74 patients observed for 2 years, 54 (73%) had prolonged CR. In the ROC curve analysis, the AUC to predict prolonged CR for FC was 0.79 (95% CI, 0.68-0.90), equivalent to that for HH (0.73; 95% CI, 0.64-0.86; P = .40). The optimal FC cutoff value to predict prolonged CR was 84.6 µg/g (72% sensitivity; 85% specificity; P < .01). CONCLUSIONS Fecal calprotectin < 82 µg/g predicts HH in patients with UC with clinical and endoscopic remission. Low FC leads to prolonged CR, equivalent to HH.
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Affiliation(s)
- Kousaku Kawashima
- Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Naoki Oshima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Kenichi Kishimoto
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Masatoshi Kataoka
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Mai Fukunaga
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Satoshi Kotani
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Hiroki Sonoyama
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Akihiko Oka
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Yoshiyuki Mishima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Hideaki Kazumori
- Division of Internal Medicine, Matsue Seikyo General Hospital, Matsue, Shimane, Japan
| | - Noriyoshi Ishikawa
- Department of Pathology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Asuka Araki
- Department of Pathology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
| | - Shunji Ishihara
- Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
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21
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Dulai PS, Feagan BG, Sands BE, Chen J, Lasch K, Lirio RA. Prognostic Value of Fecal Calprotectin to Inform Treat-to-Target Monitoring in Ulcerative Colitis. Clin Gastroenterol Hepatol 2023; 21:456-466.e7. [PMID: 35934286 DOI: 10.1016/j.cgh.2022.07.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 06/30/2022] [Accepted: 07/18/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND & AIMS We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic. METHODS This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization. RESULTS The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%-79%). However, a post-induction FCP concentration of ≤250 μg/g vs >250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78-5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83-6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77-8.14; Geboes grade: OR, 6.42; 95% CI, 4.02-10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130-0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389-0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline. CONCLUSIONS Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs >250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).
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Affiliation(s)
- Parambir S Dulai
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
| | - Brian G Feagan
- Robarts Clinical Trials, Western University, London, Ontario, Canada
| | - Bruce E Sands
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jingjing Chen
- Statistics and Quantitative Sciences, Takeda Development Center Americas, Inc, Cambridge, Massachusetts
| | - Karen Lasch
- US Medical Office, Takeda Pharmaceuticals U.S.A Inc., Lexington, Massachusetts
| | - Richard A Lirio
- Clinical Science, Takeda Development Center Americas, Inc., Cambridge, Massachusetts
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22
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Trends of fecal calprotectin levels and associations with early life experience in preterm infants. INTERDISCIPLINARY NURSING RESEARCH 2022; 1:36-42. [PMID: 36590866 PMCID: PMC9766919 DOI: 10.1097/nr9.0000000000000006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/23/2022] [Indexed: 12/03/2022]
Abstract
Background Preterm infants are at risk for severe infections due to their immature immune systems. Factors such as early life pain/stress experiences and feeding may influence immune activation and maturation of immune systems. However, the underlying mechanism remains unclear. Fecal calprotectin (FCP) is a noninvasive surrogate biomarker of mucosal inflammation in the gastrointestinal tract and has been used in detecting intestinal inflammation in specific pediatric gastrointestinal disorders. Objective To describe the longitudinal trajectory of FCP levels in preterm infants and investigate the contributing factors that are associated with FCP levels. Design A longitudinal study design was used. Settings Preterm infants were recruited from 2 neonatal intensive care units (NICU) of a children's medical center in the North-eastern US. Methods Preterm infants were followed during their first 4 weeks of NICU hospitalization. Stool samples were collected twice per week to quantify the FCP levels. Cumulative pain/stress experiences and feeding types were measured daily. A linear mixed-effect model was used to examine the associations between FCP levels and demographic and clinical characteristics, cumulative pain/stress, and feeding over time. Results Forty-nine preterm infants were included in the study. Infants' FCP levels varied largely with a mean of 268.7±261.3 µg/g and increased over time. Preterm infants experienced an average of 7.5±5.0 acute painful procedures and 15.3±20.8 hours of chronic painful procedures per day during their NICU stay. The mean percentage of mother's own milk increased from the first week (57.1±36.5%) to the fourth week (60.7±38.9%) after birth. Elevated FCP concentration was associated with acute and cumulative (chronic) pain/stress levels, mother's own milk, non-White race, and higher severity of illness score. Conclusions FCP levels were elevated in preterm infants with wide interindividual and intraindividual variations. Cumulative pain/stress during the NICU hospitalization, feeding, race, and health status may influence FCP concentrations in early life that may be associated with inflammatory gut processes.
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Wang S, Miao S, Qiu X, Wu J, Wang Y. Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease. Medicine (Baltimore) 2022; 101:e31163. [PMID: 36281159 PMCID: PMC9592269 DOI: 10.1097/md.0000000000031163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn's disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.
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Affiliation(s)
- Shengnan Wang
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Shijian Miao
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Xiaoxia Qiu
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Jie Wu
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
| | - Yuhuan Wang
- Department of Gastroenterology in Children’s hospital of Fudan University, Shanghai, China
- * Correspondence: Yuhuan Wang, Department of gastroenterology in Children’s hospital of Fudan University, Wanyuan Road 399, Minhang District, Shanghai (e-mail: )
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Falloon K, Cohen BL, Ottichilo R, Grove D, Rieder F, Qazi T. Biomarkers for the Evaluation of Pouch Inflammation: A Systematic Review. CROHN'S & COLITIS 360 2022; 4:otac043. [PMID: 36778511 PMCID: PMC9802421 DOI: 10.1093/crocol/otac043] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Indexed: 11/25/2022] Open
Abstract
Background Ileal pouch inflammation is a common problem following ileal pouch-anal anastomosis (IPAA). Despite its prevalence, diagnosis remains multimodal and requires endoscopy. The use of biomarkers in the prediction of and/or association with pouchitis has not been well characterized. We performed a systematic review to summarize the available evidence. Method A search of Ovid, MEDLINE, Cochrane Library, EMBASE, and Web of Science was conducted. Inclusion criteria included studies evaluating biomarkers for the evaluation and prediction of inflammation in patients with IPAA utilizing pouchoscopy as the gold standard. Exclusion criteria included studies on the role of the microbiome or genetic markers. Results A total of 28 studies, 5 case-control studies, and 23 observational cohort studies were identified. Fecal biomarkers were assessed in 23 studies, of which fecal calprotectin was the most commonly studied with sensitivities ranging from 57% to 92% and specificities from 19% to 92%. Six studies examined serum biomarkers. None of the serum biomarkers demonstrated a high sensitivity or specificity in association with pouch inflammation. Six studies described the longitudinal assessment of biomarkers. Of these studies, only three reported a predictive role of biomarkers in diagnosing endoscopic inflammation. Conclusions Biomarkers have emerged as a potential option to improve the management of pouchitis given the relative ease of sampling compared to pouchoscopy. Unfortunately, the evaluated biomarkers have not consistently demonstrated accuracy in predicting inflammation. Moreover, these biomarkers have not been reliably shown to be sensitive or specific in association with endoscopic pouch inflammation to merit their widespread use in clinical practice.
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Affiliation(s)
- Katherine Falloon
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Benjamin L Cohen
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Ronald Ottichilo
- Department of Inflammation and Immunity; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - David Grove
- Department of Inflammation and Immunity; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
- Department of Inflammation and Immunity; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Taha Qazi
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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New Faecal Calprotectin Assay by IDS: Validation and Comparison to DiaSorin Method. Diagnostics (Basel) 2022; 12:diagnostics12102338. [PMID: 36292026 PMCID: PMC9600005 DOI: 10.3390/diagnostics12102338] [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: 08/25/2022] [Revised: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The faecal calprotectin (FC) measurement is used for inflammatory bowel disease (IBD) diagnosis and follow-up. The aim of this study was to validate for the first time the new IDS FC extraction device and immunoassay kit, and to compare it with the DiaSorin test in patients with and without IBD. Methods: First, the precision of the IDS assay and its stability were assessed. Then, 379 stool extracts were analysed with the IDS kit on iSYS and compared with a DiaSorin Liaison XL assay. Results: The intra- and inter-assay CVs did not exceed 5%. The stool samples were stable up to 4 weeks at −20 °C. Lot-to-lot comparison showed a good correlation (Lot1 = 1.06 × Lot2 + 0.60; p > 0.05). The Passing and Bablok regression showed no significant deviation from linearity between the two methods (IDS = 1.06 × DiaSorin − 0.6; p > 0.05; concordance correlation coefficient = 0.93). According to the recommended cut-offs, the IDS assay identified more IBD and irritable bowel syndrome patients than DiaSorin, which had more borderline results (16 vs. 20%, respectively). Conclusions: The IDS faecal calprotectin had good analytical validation parameters. Compared to the DiaSorin method, it showed comparable results, but slightly outperformed it in the identification of more IBD patients and active disease.
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26
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Ishida N, Kaneko M, Asai Y, Miyazu T, Tamura S, Tani S, Yamade M, Iwaizumi M, Hamaya Y, Osawa S, Furuta T, Sugimoto K. Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study. BMC Gastroenterol 2022; 22:420. [PMID: 36109718 PMCID: PMC9476332 DOI: 10.1186/s12876-022-02502-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/13/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.
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Affiliation(s)
- Natsuki Ishida
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Masanao Kaneko
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Yusuke Asai
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Takahiro Miyazu
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Satoshi Tamura
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
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Hardis K, Johansen SB, Eriksen J, Damgaard K, Leutscher PDC, Jepsen S. Fecal calprotectin as a biomarker of intestinal inflammation in ICU patients with diarrhea - testing the pipette method against the collection pin and weighing methods. Scandinavian Journal of Clinical and Laboratory Investigation 2022; 82:504-507. [PMID: 35943415 DOI: 10.1080/00365513.2022.2107567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Fecal calprotectin is an established biomarker in inflammatory bowel disease, but its role in assessment of intestinal inflammation in ICU patients is yet to be explored. ICU patients tend to acquire diarrhea, which complicates the extraction of fecal calprotectin using a collection pin for stool sampling. Pipetting is an alternative sampling method. The aim of the study was to compare the collection pin method with the pipette method for measurement of fecal calprotectin in ICU patients with diarrhea. Stool samples were collected from fecal bags used in the patients and then analyzed for calprotectin using an extraction device and a piston pipette, respectively. In addition, a validation test for the pipette method of extraction was conducted on liquid stool samples. Eleven stool samples were collected from five randomly selected ICU patients. Calprotectin was detectable in all fecal samples. On average the collection pin measured 45% lower than the pipette method with a 95% confidence interval (30 - 59%). The coefficient of variation when using the pipette method was 13% in low calprotectin concentrations and 39% in high concentrations. In conclusion, the pipette method seems to be appropriate for measuring calprotectin in liquid feces, due to practicalities and a greater precision.
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Affiliation(s)
- Karoline Hardis
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Sarah B Johansen
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Janne Eriksen
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Kjeld Damgaard
- Department of Anesthesiology and Intensive Care, North Denmark Regional Hospital, Hjoerring, Denmark
| | | | - Soren Jepsen
- Department of Clinical Biochemistry, North Denmark Regional Hospital, Hjoerring, Denmark
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Screening for gastrointestinal and pancreatic diseases. Adv Clin Chem 2022; 108:129-153. [PMID: 35659059 DOI: 10.1016/bs.acc.2021.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Diagnosis of chronic gastrointestinal and pancreatic diseases is challenging because patients generally present with nonspecific symptoms, such as abdominal pain and chronic diarrhea, some of which can last for many years. Although stool assays are more sensitive than serum assays, the former has unique limitations that healthcare providers should be aware of. One algorithm to screen for chronic gastrointestinal and pancreatic issues is to perform stool testing to assess inflammatory, watery (osmotic) and malabsorptive conditions. This chapter will discuss several stool-based screening tests, the major disorders they screen for and clinical performance. Sections on assay and sample limitations are also included. Stool testing can provide valuable diagnostic, prognostic and treatment response information if both the laboratory and clinician understand the benefits and limitations of these assays.
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Güven B, İssi F, Sağ E, Buruk K, Çakır M. Impact of Fecal Calprotectin Measurement for Inflammatory Bowel Disease in Children with Alarm Symptoms. THE JOURNAL OF PEDIATRIC RESEARCH 2022; 9:126-131. [DOI: 10.4274/jpr.galenos.2021.99907] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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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.
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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
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Lin L, Wyness SP, Jensen R, Bird J, Norgyal T, Jensen G, Johnson LM. Comparison of Next-Generation Assays for Fecal Calprotectin vs the PhiCal Assay. Am J Clin Pathol 2022; 157:252-256. [PMID: 34390332 DOI: 10.1093/ajcp/aqab114] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/27/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES To compare the PhiCal assay (CALPRO), the first US Food and Drug Administration-approved assay for fecal calprotectin, to 4 next-generation assays. METHODS Stool samples from 50 patients were selected, and relevant clinical information was collected. Comparisons were performed using the PhiCal, fCAL turbo (BÜHLMANN), LIAISON Calprotectin (DiaSorin), QUANTA Lite Calprotectin ELISA (Inova Diagnostics), and Calprotectin Chemiluminescence ELISA (ALPCO) assays. RESULTS All 4 assays had acceptable agreement with PhiCal when qualitatively categorizing results. Within the PhiCal reportable range of 16 to 1,250 μg/g, the DiaSorin, Inova Diagnostics, and ALPCO assays had Spearman correlation coefficients of 0.98, 0.97, and 0.95 and positive biases of 17%, 20%, and 15%, respectively. The BÜHLMANN assay ran approximately 2-fold higher than the PhiCal assay but had a correlation coefficient of 0.98, with similar result categorization. CONCLUSIONS Our results demonstrate good comparison between PhiCal and 4 next-generation assays. Laboratories performing fecal calprotectin assays may have compelling reasons to adopt next-generation fecal calprotectin testing, such as greater automation, a decreased number of replicates needed per test, and the use of stool-extraction devices. These benefits could decrease turnaround times and lower costs. Although the results of the assays correlated, they are not standardized. Laboratories adopting the newer assays will need to further investigate their performance through validation studies.
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Affiliation(s)
- Leo Lin
- Department of Pathology, University of Utah, Salt Lake City, USA
- ARUP Laboratories, Salt Lake City, UT, USA
| | - Sara P Wyness
- ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA
| | | | | | | | - Gabrielle Jensen
- ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA
| | - Lisa M Johnson
- Department of Pathology, University of Utah, Salt Lake City, USA
- ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA
- ARUP Laboratories, Salt Lake City, UT, USA
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Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease. Life (Basel) 2021; 11:life11121375. [PMID: 34947906 PMCID: PMC8707558 DOI: 10.3390/life11121375] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 11/28/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Endoscopy is the gold standard to assess the condition of IBD. The problem with this procedure is that the burden and cost on the patient are high. Therefore, the identification of a reliable biomarker to replace endoscopy is desired. Biomarkers are used in various situations such as diagnosis of IBD, evaluation of disease activity, prediction of therapeutic effect, and prediction of relapse. C-reactive protein and fecal calprotectin have a lot of evidence as objective biomarkers of disease activity in IBD. The usefulness of the fecal immunochemical test, serum leucine-rich glycoprotein, and urinary prostaglandin E major metabolite have also been reported. Herein, we comprehensively review the usefulness and limitations of biomarkers that can be used in daily clinical practice regarding IBD. To date, no biomarker is sufficiently accurate to replace endoscopy; however, it is important to understand the characteristics of each biomarker and use the appropriate biomarker at the right time in daily clinical practice.
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Hsu CF, Huang CC, Liu TT, Yang UC, Liu CW, Huang SF, Yang YY, Huang YH, Hou MC, Lin HC. Deletion of intestinal SIRT1 exacerbated muscle wasting in cirrhotic mice by decreasing the intestinal concentration of short-chain fatty acids and inflammation. J Pharmacol Sci 2021; 147:376-385. [PMID: 34663520 DOI: 10.1016/j.jphs.2021.09.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/28/2021] [Accepted: 09/06/2021] [Indexed: 11/20/2022] Open
Abstract
Systemic sirtuin 1 (SIRT1) activation alleviates muscle wasting and improves muscle function by downregulation of myotropic and proteolytic markers. In this study, we evaluated the effects of the intestinal Sirt1 deletion on the dysregulated gutmuscle axis in cirrhotic mice. Cirrhosis-related muscle wasting was induced by common bile duct ligated (BDL) in either wild-type (WT) or intestine-specific Sirt1-deleted (Sirt1IEC-KO) mice, including WT-BDL, WT-sham, Sirt1IEC-KO-BDL and Sirt1IEC-KO-sham mice. Compared with WT-BDL mice, Sirt1IEC-KO-BDL mice showed worsened low lean mass, exacerbated muscle wasting, increased expression of myotropic markers, increased muscular protein degradation, and decreased expression of myogenic markers through aggravation of intestinal inflammation (as evidenced by increased fecal calprotectin/lipocalin-2 levels, increased intestinal macrophage infiltration, and increased intestinal TNFα/IL-6 levels), decrease in abundance of short-chain fatty acid (SCFA)-producing bacteria, decrease in levels of intestinal SCFAs (with anti-inflammatory effects), and downregulation of SCFA receptor GPR43. In biliary cirrhotic mice, a decrease in the abundance of SCFA-producing bacteria and an increase in the levels of intestinal/muscular inflammatory markers are involved in the pathogenesis of dysregulated gut-muscle axis-related muscle wasting, and intestinal deletion of Sirt1 exacerbated these changes.
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Affiliation(s)
- Chien-Fu Hsu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chia-Chang Huang
- Division of Clinical Skills Training Center, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tze-Tze Liu
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ueng-Cheng Yang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chih-Wei Liu
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shiang-Fen Huang
- Division of Infection, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ying-Ying Yang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Shirazinia R, Golabchifar AA, Fazeli MR. Efficacy of probiotics for managing infantile colic due to their anti-inflammatory properties: a meta-analysis and systematic review. Clin Exp Pediatr 2021; 64:642-651. [PMID: 33848417 PMCID: PMC8650819 DOI: 10.3345/cep.2020.01676] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 03/06/2021] [Accepted: 03/29/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Infantile colic (IC) is excessive crying in otherwise healthy children. Despite vast research efforts, its etiology remains unknown. PURPOSE Most treatments for IC carry various side effects. The collection of evidence may inform researchers of new strategies for the management and treatment of IC as well as new clues for understanding its pathogenesis. This review and meta-analysis aimed to evaluate the efficacy and possible mechanisms of probiotics for mananaging IC. METHODS Ten papers met the study inclusion and exclusion criteria, and the meta-analysis was conducted using Review Manager (RevMan) software and a random-effects model. RESULTS This meta-analysis revealed that probiotics are effective for treating infantile colic, while the review showed that this efficacy may be due to their anti-inflammatory effects. CONCLUSION Probiotics may be an important treatment option for managing infantile colic due to their anti-inflammatory properties.
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Affiliation(s)
- Reza Shirazinia
- Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Ali Akbar Golabchifar
- Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Mohammad Reza Fazeli
- Pharmaceutical Quality Assurance Research Center, The institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
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Coculture Strategy for Developing Lactobacillus paracasei PS23 Fermented Milk with Anti-Colitis Effect. Foods 2021; 10:foods10102337. [PMID: 34681392 PMCID: PMC8535234 DOI: 10.3390/foods10102337] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 09/25/2021] [Accepted: 09/28/2021] [Indexed: 12/27/2022] Open
Abstract
Few studies have documented the effects of fermented milk on intestinal colitis, which are mediated by regulating various microbial and inflammatory processes. Here, we investigated the effects of fermented milk with Lactobacillus paracasei PS23 on intestinal epithelial cells in vitro and dextran sulfate sodium (DSS)-induced colitis in vivo. As L. paracasei PS23 grew poorly in milk, a coculture strategy with yogurt culture was provided to produce fermented milk (FM). The results indicated that the coculture exhibited a symbiotic effect, contributing to the better microbial and physicochemical property of the fermented milk products. We further evaluated the anti-colitis effect of fermented milk with L. paracasei PS23 in vitro. Both PS23-fermented milk (PS23 FM) and its heat-killed counterpart (HK PS23 FM) could protect or reverse the increased epithelial permeability by strengthening the epithelial barrier function in vitro by increasing transepithelial electrical resistance (TEER). In vivo analysis of the regulation of intestinal physiology demonstrated that low-dose L. paracasei PS23-fermented ameliorated DSS-induced colitis, with a significant attenuation of the bleeding score and reduction of fecal calprotectin levels. This anti-colitis effect may be exerted by deactivating the inflammatory cascade and strengthening the tight junction through the modification of specific cecal bacteria and upregulation of short-chain fatty acids. Our findings can clarify the role of L. paracasei PS23 in FM products when cocultured with yogurt culture and can elucidate the mechanisms of the anti-colitis effect of L. paracasei PS23 FM, which may be considered for therapeutic intervention.
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Yang RX, Song WJ, Wu ZQ, Goyal H, Xu HG. Association of Serum Neuron-Specific Enolase and C-Reactive Protein With Disease Location and Endoscopic Inflammation Degree in Patients With Crohn's Disease. Front Med (Lausanne) 2021; 8:663920. [PMID: 34513858 PMCID: PMC8427157 DOI: 10.3389/fmed.2021.663920] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 07/26/2021] [Indexed: 12/22/2022] Open
Abstract
Objective: The objective of this study was to explore the association between serum markers neuron-specific enolase (NSE) and C-reactive protein (CRP) with intestinal lesion location and degree of inflammation in patients with Crohn's disease (CD). Design: The levels of serum NSE, CRP, and fecal calprotectin (FC) in patients with CD were analyzed retrospectively. The severity of inflammatory lesions in the intestinal wall was accessed using the Simple Endoscopic Score for Crohn's disease (SES-CD). Results: The levels of NSE in patients with CD were higher than those of healthy individuals (14.87 vs. 12.68 ng/ml, P < 0.001). The levels of CRP in patients with CD were higher than those of healthy individuals (12.30 vs. 3.40 mg/l, P < 0.001). The FC levels in patients with CD were higher than those of patients with non-inflammatory bowel disease (1,143.90 vs. 114.21 μg/g, P < 0.05). The levels of NSE in CD with ileal lesions and simultaneous ileal and colon lesions were significantly higher than those in patients with CD with colonic lesions. However, the CRP was higher in patients with colonic lesions than those with ileal lesions. The levels of NSE in patients with severe inflammation were higher than those in patients with moderate inflammation (15.95 vs. 13.89 ng/ml, P < 0.05). Similarly, the NSE levels in patients with CD with severe inflammation were higher than those in patients with CD with mild inflammation (15.95 vs. 13.53 ng/mL, P < 0.05). The levels of CRP in severe inflammation were higher than those in moderate inflammation (29.80 vs. 19.60 mg/l, P < 0.05). In addition, the CRP levels in severe inflammation were higher than those in mild inflammation (29.80 vs. 5.86 mg/l, P < 0.05). ROC curve analysis showed that when NSE was combined with CRP for distinguishing between patients with CD and those without CD, sensitivity increased to 80.41%, specificity increased to 74.66%, and a highest AUC was equal to 0.843. Conclusion: Our study shows that serum NSE and CRP can be used to assess the severity of CD as well as the location of intestinal involvement. Therefore, NSE and CRP could be used as the non-invasive tests in detecting the location and severity of disease in patients with CD in daily routine practice.
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Affiliation(s)
- Rui-Xia Yang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei-Juan Song
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhi-Qi Wu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hemant Goyal
- Department of Internal Medicine, Wright Center for Graduate Medical Education, Scranton, PA, United States
| | - Hua-Guo Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Chen F, Hu Y, Fan YH, Lv B. Clinical Value of Fecal Calprotectin in Predicting Mucosal Healing in Patients With Ulcerative Colitis. Front Med (Lausanne) 2021; 8:679264. [PMID: 34414201 PMCID: PMC8369158 DOI: 10.3389/fmed.2021.679264] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 06/07/2021] [Indexed: 11/13/2022] Open
Abstract
Aim: This study aimed to evaluate the clinical significance of fecal calprotectin (FC) in assessment of ulcerative colitis (UC) patients' endoscopic patterns and clinical manifestation. Methods: A total of 143 UC patients who received colonoscopy and 108 controls were included. After providing stool samples, patients underwent total colonoscopy. FC was measured by an enzyme-linked immunosorbent assay (ELISA). Clinical activity was based on the Mayo score. Endoscopic findings was scored by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Correlation analysis and receiver-operator characteristic (ROC) analysis were carried out to determine the significance of measurements. Results: The median (interquartile range, IQR) of FC levels was 211 (43–990) μg/g in UC and 87.5 (40.50~181) μg/g in the control group. Fecal calprotectin correlated significantly with both Mayo and UCEIS scores (Spearman's r 0.670 and 0.592, P < 0.01). With a cut-off value of 164 μg/g for fecal calprotectin concentration, the area under the curve (AUC) in receiver operator characteristic analysis was 0.830, sensitivity was 85.42%, specificity was 73.68%, positive predictive value (PPV) was 62.12%, and negative predictive value (NPV) was 9.10% in predicting clinical active disease. Similarly, the power of FC to predict mucosal healing (MH) was modest. With a cut-off value of 154.5 μg/g, the AUC was 0.839, sensitivity was 72.34%, and specificity was 85.71%. Conclusion: For evaluating the disease activity of UC, FC is a clinically relevant biomarker for both clinically active disease and MH in patients with UC. But the cut-off value still needs large and multicenter studies for confirmation.
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Affiliation(s)
- Fang Chen
- Department of Gastroenterology, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, China
| | - Yue Hu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Yi-Hong Fan
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Bin Lv
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Ueno N, Sugiyama Y, Kobayashi Y, Murakami Y, Iwama T, Sasaki T, Kunogi T, Takahashi K, Tanaka K, Ando K, Kashima S, Inaba Y, Moriichi K, Tanabe H, Taruishi M, Saitoh Y, Okumura T, Fujiya M. Fecal calprotectin is a useful biomarker for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis in ulcerative colitis patients: a prospective observation study. BMC Gastroenterol 2021; 21:316. [PMID: 34362299 PMCID: PMC8348877 DOI: 10.1186/s12876-021-01889-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 06/17/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. METHODS In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. RESULT Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. CONCLUSION We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.
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Affiliation(s)
- Nobuhiro Ueno
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan.
| | - Yuya Sugiyama
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Yu Kobayashi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Yuki Murakami
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Takuya Iwama
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Takahiro Sasaki
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Takehito Kunogi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Keitaro Takahashi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Kazuyuki Tanaka
- Asahikawa Kosei General Hospital, Asahikawa, Hokkaido, Japan
| | - Katsuyoshi Ando
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Shin Kashima
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Yuhei Inaba
- Asahikawa City Hospital, Asahikawa, Hokkaido, Japan
| | - Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Hiroki Tanabe
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | | | | | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
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The Role of Biomarkers in Surgery for Ulcerative Colitis: A Review. J Clin Med 2021; 10:jcm10153362. [PMID: 34362144 PMCID: PMC8348722 DOI: 10.3390/jcm10153362] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/25/2021] [Accepted: 07/28/2021] [Indexed: 12/19/2022] Open
Abstract
Ulcerative colitis (UC) is an inflammatory condition that generally affects the rectum and extends proximally into the colon in a continuous, distal-to-proximal pattern. Surgical resection (total proctocolectomy) is the only cure for UC and is often necessary in managing complicated or refractory disease. However, recent advances in biologically targeted therapies have resulted in improved disease control, and surgery is required in only a fraction of cases. This ever-increasing array of options for medical management has added complexity to surgical decision-making. In some circumstances, the added time required to ensure failure of medical therapy can delay colectomy in patients who will ultimately need it. Indeed, many patients with severe disease undergo trials of multiple medical therapies prior to considering surgery. In severe cases of UC, continued medical management has been associated with a delay to surgical intervention and higher rates of morbidity and mortality. Biomarkers represent a burgeoning field of research, particularly in inflammatory bowel disease and cancer. This review seeks to highlight the different possible settings for surgery in UC and the role various biomarkers might play in each.
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Eidet JR, Akopian M, Olstad OK, Jørstad ØK, Moe MC, Petrovski G, Pepaj M. The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis. J Ophthalmic Inflamm Infect 2021; 11:19. [PMID: 34212267 PMCID: PMC8249488 DOI: 10.1186/s12348-021-00249-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 05/28/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. METHODS Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. RESULTS Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. CONCLUSIONS The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.
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Affiliation(s)
- Jon Roger Eidet
- Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
| | - Maja Akopian
- Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Ole K Olstad
- Department of Medical Biochemistry, Blood Cell Research Group, Section for Research, Oslo University Hospital, Oslo, Norway
| | - Øystein Kalsnes Jørstad
- Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Morten C Moe
- Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Goran Petrovski
- Department of Ophthalmology, Center for Eye Research, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Milaim Pepaj
- Department of Medical Biochemistry, Hormone Laboratory, Oslo University Hospital, Oslo, Norway
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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.
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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
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Dal Pont GC, Belote BL, Lee A, Bortoluzzi C, Eyng C, Sevastiyanova M, Khadem A, Santin E, Farnell YZ, Gougoulias C, Kogut MH. Novel Models for Chronic Intestinal Inflammation in Chickens: Intestinal Inflammation Pattern and Biomarkers. Front Immunol 2021; 12:676628. [PMID: 34054868 PMCID: PMC8158159 DOI: 10.3389/fimmu.2021.676628] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 04/23/2021] [Indexed: 01/30/2023] Open
Abstract
For poultry producers, chronic low-grade intestinal inflammation has a negative impact on productivity by impairing nutrient absorption and allocation of nutrients for growth. Understanding the triggers of chronic intestinal inflammation and developing a non-invasive measurement is crucial to managing gut health in poultry. In this study, we developed two novel models of low-grade chronic intestinal inflammation in broiler chickens: a chemical model using dextran sodium sulfate (DSS) and a dietary model using a high non-starch polysaccharide diet (NSP). Further, we evaluated the potential of several proteins as biomarkers of gut inflammation. For these experiments, the chemical induction of inflammation consisted of two 5-day cycles of oral gavage of either 0.25mg DSS/ml or 0.35mg DSS/ml; whereas the NSP diet (30% rice bran) was fed throughout the experiment. At four times (14, 22, 28 and 36-d post-hatch), necropsies were performed to collect intestinal samples for histology, and feces and serum for biomarkers quantification. Neither DSS nor NSP treatments affected feed intake or livability. NSP-fed birds exhibited intestinal inflammation through 14-d, which stabilized by 36-d. On the other hand, the cyclic DSS-treatment produced inflammation throughout the entire experimental period. Histological examination of the intestine revealed that the inflammation induced by both models exhibited similar spatial and temporal patterns with the duodenum and jejunum affected early (at 14-d) whereas the ileum was compromised by 28-d. Calprotectin (CALP) was the only serum protein found to be increased due to inflammation. However, fecal CALP and Lipocalin-2 (LCN-2) concentrations were significantly greater in the induced inflammation groups at 28-d. This experiment demonstrated for the first time, two in vivo models of chronic gut inflammation in chickens, a DSS and a nutritional NSP protocols. Based on these models we observed that intestinal inflammation begins in the upper segments of small intestine and moved to the lower region over time. In the searching for a fecal biomarker for intestinal inflammation, LCN-2 showed promising results. More importantly, calprotectin has a great potential as a novel biomarker for poultry measured both in serum and feces.
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Affiliation(s)
- Gabriela C Dal Pont
- Department of Poultry Science, Texas A&M Agrilife Research, Texas A&M University, College Station, TX, United States.,Department of Veterinary Science, Federal University of Paraná, Curitiba, Brazil.,Department of Animal Science, Western Parana State University, Marechal C. Rondon, Brazil.,Innovad NV/SA, Essen, Belgium.,Southern Plains Agricultural Research Center, United States Department of Agriculture - Agricultural Research Service (USDA-ARS), College Station, TX, United States
| | - Bruna L Belote
- Department of Veterinary Science, Federal University of Paraná, Curitiba, Brazil
| | - Annah Lee
- Department of Poultry Science, Texas A&M Agrilife Research, Texas A&M University, College Station, TX, United States
| | - Cristiano Bortoluzzi
- Department of Poultry Science, Texas A&M Agrilife Research, Texas A&M University, College Station, TX, United States
| | - Cinthia Eyng
- Department of Animal Science, Western Parana State University, Marechal C. Rondon, Brazil
| | | | | | - Elizabeth Santin
- Department of Veterinary Science, Federal University of Paraná, Curitiba, Brazil
| | - Yuhua Z Farnell
- Department of Poultry Science, Texas A&M Agrilife Research, Texas A&M University, College Station, TX, United States
| | | | - Michael H Kogut
- Southern Plains Agricultural Research Center, United States Department of Agriculture - Agricultural Research Service (USDA-ARS), College Station, TX, United States
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Kan YM, Chu SY, Loo CK. Diagnostic accuracy of fecal calprotectin in predicting significant gastrointestinal diseases. JGH OPEN 2021; 5:647-652. [PMID: 34124380 PMCID: PMC8171161 DOI: 10.1002/jgh3.12548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/07/2021] [Accepted: 04/11/2021] [Indexed: 12/22/2022]
Abstract
Background and Aim It is often unreliable to triage patients for timely endoscopic investigations based on symptoms alone. We need an objective assessment to differentiate between organic gastrointestinal diseases and functional bowel symptoms. We evaluated the diagnostic accuracy of fecal calprotectin (FC) in predicting organic gastrointestinal diseases. Methods In a prospective observational study, consecutive patients referred for colonoscopy to the Department of Medicine and Geriatrics at the Kwong Wah Hospital in Hong Kong were recruited. Stool samples were collected within 24 h before colonoscopy. FC was measured by a commercial kit. Upper endoscopy investigations were then proceeded if normal colonoscopy but elevated FC. Results Two hundred and seventy out of 429 patients had FC above 50 μg/g. Eighty‐six out of 270 with elevated FC had significant colonoscopy pathological findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FC test for diagnosing a significant organic colonoscopy or upper endoscopy disease were 91.7, 55.6, 57.0, and 91.2%, respectively. The NPV of FC for colorectal cancer, high risk polyp, and colon inflammation were 98.7, 96.2, and 98.1%, respectively. The NPV of FC in the condition of altered bowel habit or abdominal pain in predicting colorectal cancer and inflammation were 93.8 and 100%, respectively. Conclusions FC is a reliable marker of ruling out organic bowel diseases. A single negative FC test could be used as a triage tool to prioritize the need and urgency of further investigation, particularly in the setting of altered bowel habits and abdominal pain.
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Affiliation(s)
- Yee Man Kan
- Department of Medicine and Geriatrics Kwong Wah Hospital Kowloon Hong Kong
| | - Sin Yan Chu
- Department of Pathology Kwong Wah Hospital Kowloon Hong Kong
| | - Ching Kong Loo
- Department of Medicine and Geriatrics Kwong Wah Hospital Kowloon Hong Kong
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The utility of faecal and urine biomarkers for small bowel diseases. Curr Opin Gastroenterol 2021; 37:284-294. [PMID: 33769381 DOI: 10.1097/mog.0000000000000730] [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
PURPOSE OF REVIEW Small bowel diseases pose a unique diagnostic and management challenge and often requires tertiary specialist referral. The use of biomarkers may provide a cheap, noninvasive tool to assess the small bowel in terms of diagnosis, offering a better way to triage referrals and select patients for early management. This review looks at the most recent evidence behind the use of several faecal and urine biomarkers for small bowel diseases. RECENT FINDINGS Faecal calprotectin shows the most promise, with evidence to support its role in predicting relapse postsurgery and monitoring treatment response in patients with Crohn's disease. A faecal calprotectin less than 50 μg/g may also be used as a cut-off to triage further investigation. Faecal lactoferrin also appears promising as a marker of small bowel inflammation. A positive faecal immunohistochemistry test precapsule may help to prioritize referrals for obscure bleeding. SUMMARY The use of biomarkers in the diagnosis and management of small bowel disease is still controversial and remains unclear. More studies are required to further develop their potential and before societal guidelines can be developed to direct their appropriate use in clinical practice.
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Hagan M, Hayee BH, Rodriguez-Mateos A. (Poly)phenols in Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Review. Molecules 2021; 26:1843. [PMID: 33805938 PMCID: PMC8036772 DOI: 10.3390/molecules26071843] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 03/22/2021] [Accepted: 03/23/2021] [Indexed: 12/12/2022] Open
Abstract
(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.
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Affiliation(s)
- Marilyn Hagan
- Department of Nutrition and Dietetics, Royal Papworth Hospital NHS Foundation Trust, Cambridge CB2 0AY, UK;
| | - Bu' Hussain Hayee
- Department of Gastroenterology, King’s College Hospital NHS Foundation Trust, London SE5 9RS, UK;
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
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Kim ES, Tarassishin L, Eisele C, Barre A, Nair N, Rendon A, Hawkins K, Debebe A, White S, Thjømøe A, Mørk E, Bento-Miranda M, Panchal H, Agrawal M, Patel A, Chen CL, Kornbluth A, George J, Legnani P, Maser E, Loudon H, Mella MT, Stone J, Dubinsky M, Sabino J, Torres J, Colombel JF, Peter I, Hu J. Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies. Gastroenterology 2021; 160:1118-1130.e3. [PMID: 33307026 DOI: 10.1053/j.gastro.2020.11.050] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/09/2020] [Accepted: 11/29/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.
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Affiliation(s)
- Eun Soo Kim
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Leonid Tarassishin
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Caroline Eisele
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Amelie Barre
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Cochin Hospital, Université de Paris, Paris, France
| | - Nilendra Nair
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Alexa Rendon
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Kelly Hawkins
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Anketse Debebe
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sierra White
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | - Mario Bento-Miranda
- Division of Gastroenterology, Hospital and University Center of Coimbra, Coimbra, Portugal
| | - Hinaben Panchal
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Manasi Agrawal
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Anish Patel
- Division of Gastroenterology, Brooke Army Medical Center, San Antonio, Texas
| | - Ching-Lynn Chen
- Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Asher Kornbluth
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - James George
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Peter Legnani
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Elana Maser
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Holly Loudon
- Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Maria-Teresa Mella
- Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joanne Stone
- Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Marla Dubinsky
- Department of Pediatric Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York
| | - João Sabino
- Department of Gastroenterology, University Hospitals of Leuven, Leuven, Belgium
| | - Joana Torres
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Jean-Frederic Colombel
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Inga Peter
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jianzhong Hu
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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Ye X, Wang Y, Wang HHX, Feng R, Ye Z, Han J, Li L, Zeng Z, Chen M, Zhang S. Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis. Therap Adv Gastroenterol 2021; 14:1756284821994741. [PMID: 33717211 PMCID: PMC7923968 DOI: 10.1177/1756284821994741] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 01/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions. METHODS Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn's and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves. RESULTS Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52-0.82], 0.77 (95% CI: 0.63-0.87), and 0.80 (95% CI: 0.76-0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71-0.81), 0.71 (95% CI: 0.62-0.78), and 0.79 (95% CI: 0.75-0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 versus 0.65). CONCLUSION FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100-200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.
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Affiliation(s)
- Xiaoqi Ye
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Ying Wang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Harry H. X. Wang
- School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong Province, PR China,General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Scotland, UK
| | - Rui Feng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Ziyin Ye
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Jing Han
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Li Li
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Zhirong Zeng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
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48
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Maalouly G, Hajal J, Noujeim C, Choueiry M, Nassereddine H, Smayra V, Saliba Y, Fares N. New insights in gut-liver axis in wild-type murine imiquimod-induced lupus. Lupus 2021; 30:926-936. [PMID: 33596715 DOI: 10.1177/0961203321995254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Intestinal and hepatic manifestations of lupus seem to be underestimated in comparison to other major organ lesions. Although recent data point to gut-liver axis involvement in lupus, gut permeability dysfunction and liver inflammation need to be more investigated. OBJECTIVE This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus. METHODS C57BL/6 mice were topically treated on their right ears with 1.25 mg of 5% imiquimod cream, three times per week for six weeks. Fecal calprotectin was collected at day 0, 22 and 45. Renal, liver and intestinal pathology, as well as inflammatory markers, intestinal tight junction proteins, and E. coli protein in liver were assessed at sacrifice. RESULTS At six weeks, lupus nephritis was confirmed on histopathology and NGAL and KIM-1 expression. Calprotectin rise started at day 22 and persists at day 45. Protein expression of Claudine, ZO-1 and occludin was significantly decreased. E. coli protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression. CONCLUSION This study is the first to demonstrate early fecal calprotectin increase and liver activation of TLR4- NFκB pathway in wild-type murine imiquimod-induced lupus.
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Affiliation(s)
- Georges Maalouly
- Faculty of Medicine, CHU Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Joelle Hajal
- Physiology and Pathophysiology Research Laboratory, Pole of Technology and Health, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Charbel Noujeim
- Physiology and Pathophysiology Research Laboratory, Pole of Technology and Health, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Michel Choueiry
- Physiology and Pathophysiology Research Laboratory, Pole of Technology and Health, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Hussein Nassereddine
- Faculty of Medicine, CHU Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Viviane Smayra
- Faculty of Medicine, CHU Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Youakim Saliba
- Physiology and Pathophysiology Research Laboratory, Pole of Technology and Health, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Nassim Fares
- Physiology and Pathophysiology Research Laboratory, Pole of Technology and Health, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
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49
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Neyrinck AM, Rodriguez J, Zhang Z, Seethaler B, Sánchez CR, Roumain M, Hiel S, Bindels LB, Cani PD, Paquot N, Cnop M, Nazare JA, Laville M, Muccioli GG, Bischoff SC, Walter J, Thissen JP, Delzenne NM. Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. Eur J Nutr 2021; 60:3159-3170. [PMID: 33544206 PMCID: PMC8354918 DOI: 10.1007/s00394-021-02484-5] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 01/08/2021] [Indexed: 02/07/2023]
Abstract
Purpose Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients. Methods Microbiota (16S rRNA sequencing), long- and short-chain fatty acids (LCFA, SCFA), bile acids, zonulin, and calprotectin were analyzed in fecal samples obtained from obese patients included in a randomized, placebo-controlled trial. Participants received either 16 g/d native inulin (prebiotic n = 12) versus maltodextrin (placebo n = 12), coupled to dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction. Results Both placebo and prebiotic interventions lowered energy and protein intake. A substantial increase in Bifidobacterium was detected after ITF treatment (q = 0.049) supporting our recent data obtained in a larger cohort. Interestingly, fecal calprotectin, a marker of gut inflammation, was reduced upon ITF treatment. Both prebiotic and placebo interventions increased the ratio of tauro-conjugated/free bile acids in feces. Prebiotic treatment did not significantly modify fecal SCFA content but it increased fecal rumenic acid, a conjugated linoleic acid (cis-9, trans-11 CLA) with immunomodulatory properties, that correlated notably to the expansion of Bifidobacterium (p = 0.031; r = 0.052). Conclusions Our study demonstrates that ITF-prebiotic intake during 3 months decreases a fecal marker of intestinal inflammation in obese patients. Our data point to a potential contribution of microbial lipid-derived metabolites in gastro-intestinal dysfunction related to obesity. ClinicalTrials.gov Identifier NCT03852069 (February 22, 2019 retrospectively, registered). Supplementary Information The online version contains supplementary material available at 10.1007/s00394-021-02484-5.
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Affiliation(s)
- Audrey M Neyrinck
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium
| | - Julie Rodriguez
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium
| | - Zhengxiao Zhang
- Department of Medicine, University of Alberta, Edmonton, Canada
| | - Benjamin Seethaler
- Institute of Nutritional Medicine, University of Hohenheim, Hohenheim, Germany
| | - Cándido Robles Sánchez
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium
| | - Martin Roumain
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Sophie Hiel
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium
| | - Laure B Bindels
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium
| | - Patrice D Cani
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium.,WELBIO- Walloon Excellence in Life Sciences and Biotechnology, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Nicolas Paquot
- Laboratory of Diabetology, Nutrition and Metabolic Disease, Université de Liège, Liège, Belgium
| | - Miriam Cnop
- ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.,Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Julie-Anne Nazare
- Rhône-Alpes Research Center for Human Nutrition, Université-Lyon, CarMeN Laboratory, Hospices Civils de Lyon, Lyon, France
| | - Martine Laville
- Rhône-Alpes Research Center for Human Nutrition, Université-Lyon, CarMeN Laboratory, Hospices Civils de Lyon, Lyon, France
| | - Giulio G Muccioli
- Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Hohenheim, Germany
| | - Jens Walter
- Department of Medicine, University of Alberta, Edmonton, Canada.,Department of Medicine, and School of Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Jean-Paul Thissen
- Pole of Endocrinology, Diabetes and Nutrition, Institut de Recherche Expérimentale et Clinique, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Nathalie M Delzenne
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, avenue E. Mounier box B1.73.11, B-1200, Brussels, Belgium.
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50
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Shelly CE, Filatava EJ, Thai J, Pados BF, Rostas SE, Yamamoto H, Fichorova R, Gregory KE. Elevated Intestinal Inflammation in Preterm Infants With Signs and Symptoms of Gastroesophageal Reflux Disease. Biol Res Nurs 2021; 23:524-532. [PMID: 33541135 DOI: 10.1177/1099800420987888] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVES Reflux is common in infancy; however, persistent signs and symptoms of gastrointestinal distress are often attributed to gastroesophageal reflux disease (GERD). In this pilot study, we aimed to characterize associations between signs and symptoms of suspected GERD and noninvasive markers of intestinal inflammation in preterm infants. METHODS We reviewed Electronic Medical Record (EMR) data to identify clinical signs and symptoms among case patients (n = 16). Controls (n = 16) were matched on gestational age. Univariate and multivariate regression analyses were used to compare fecal calprotectin and urinary intestinal fatty acid binding protein (I-FABP) levels between cases and controls. RESULTS We found no differences in baseline characteristics between cases and controls. In the multivariate regression analysis controlling for the proportion of mother's milk, cases had higher fecal calprotectin levels than controls, with no differences in I-FABP levels between cases and controls. CONCLUSION Our findings suggest that preterm infants with signs and symptoms of GERD have higher levels of intestinal inflammation as indicated by fecal calprotectin compared to their controls. Further studies are needed to evaluate the role of intestinal inflammation in signs and symptoms of gastrointestinal distress and whether fecal calprotectin might have predictive value in diagnosing GERD.
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Affiliation(s)
- Colleen E Shelly
- Department of Nursing, 1861Brigham and Women's Hospital, Boston, MA, USA
| | - Evgenia J Filatava
- Department of Pediatric Newborn Medicine, 1861Brigham and Women's Hospital, Boston, MA, USA
| | - Julie Thai
- 1811Harvard Medical School, Boston, MA, USA
| | - Britt F Pados
- 15712W.F. Connell School of Nursing, Boston College, MA, USA
| | - Sara E Rostas
- Department of Pediatric Newborn Medicine, 1861Brigham and Women's Hospital, Boston, MA, USA.,1811Harvard Medical School, Boston, MA, USA
| | - Hidemi Yamamoto
- 1811Harvard Medical School, Boston, MA, USA.,Department of Obstetrics, Gynecology and Reproductive Biology, 1861Brigham and Women's Hospital, Boston, MA, USA
| | - Raina Fichorova
- 1811Harvard Medical School, Boston, MA, USA.,Department of Obstetrics, Gynecology and Reproductive Biology, 1861Brigham and Women's Hospital, Boston, MA, USA
| | - Katherine E Gregory
- Department of Nursing, 1861Brigham and Women's Hospital, Boston, MA, USA.,Department of Pediatric Newborn Medicine, 1861Brigham and Women's Hospital, Boston, MA, USA.,1811Harvard Medical School, Boston, MA, USA
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