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Edwards TS, Ho SSC, Brown SC, Appleton L, Smith BR, Borichevsky GM, Swaminathan A, Frampton CMA, Gearry RB, Kettle AJ, Day AS. Fecal Myeloperoxidase Levels Reflect Disease Activity in Children With Crohn's Disease. Inflamm Bowel Dis 2025; 31:800-811. [PMID: 39527499 PMCID: PMC11879223 DOI: 10.1093/ibd/izae262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Crohn's disease (CD) is a major form of inflammatory bowel disease (IBD) which has relapsing and remitting symptoms. Better ways to detect and monitor active disease are required for early diagnosis and optimal outcomes. We assessed fecal myeloperoxidase (fMPO), a neutrophil-derived enzyme that produces hypochlorous acid, as a marker of disease activity in children with CD. METHODS This observational study assessed myeloperoxidase (MPO) levels in fecal samples from children aged <17 years with CD (51 with active or 42 inactive disease) measured by enzyme-linked immunosorbent assay (ELISA) and compared to controls (35 healthy siblings and 15 unrelated well children). Results were correlated with fecal calprotectin, serum C-reactive protein, urinary glutathione sulfonamide (a biomarker of hypochlorous acid), and disease activity scores. Differences between groups were assessed by analysis of variance. Receiver-operating-characteristic curves were used to assess how biomarkers predicted disease and disease activity. RESULTS Fecal myeloperoxidase activity and fMPO protein correlated with fecal calprotectin (r = 0.78, P < .0001, and r = 0.81, P < .0001, respectively). Fecal myeloperoxidase activity and protein levels were significantly higher (P ≤ .0001) in individuals with active disease compared to healthy sibling controls, unrelated well children, and those with inactive disease. A 9.7 µg/g fMPO protein cutoff distinguished inactive from active disease (sensitivity = 75%, specificity = 76%). Urinary GSA was elevated in children with active disease (P < .0001) and correlated with fMPO protein (r = 0.43, P = .0002) in a subset of 72 children with IBD and controls. CONCLUSIONS Fecal myeloperoxidase may be superior to fCal at reflecting disease severity in children with CD and produces the damaging oxidant hypochlorous acid during active inflammation.
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Affiliation(s)
- Teagan S Edwards
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Shaun S C Ho
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
- Department of Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
- Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
| | - Stephanie C Brown
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Laura Appleton
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Briana R Smith
- Department of Pathology and Biomedical Sciences, Mātai Hāora—Centre for Redox Biology and Medicine, University of Otago, Christchurch, New Zealand
| | - Grace M Borichevsky
- Department of Pathology and Biomedical Sciences, Mātai Hāora—Centre for Redox Biology and Medicine, University of Otago, Christchurch, New Zealand
| | | | | | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Anthony J Kettle
- Department of Pathology and Biomedical Sciences, Mātai Hāora—Centre for Redox Biology and Medicine, University of Otago, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
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Zhang H, Shen Y, Cao B, Zheng X, Zhao D, Hu J, Wu X. A Nomogram Based on Laboratory Data, Inflammatory Bowel Disease Questionnaire and CT Enterography for Activity Evaluation in Crohn's Disease. J Inflamm Res 2025; 18:183-194. [PMID: 39802507 PMCID: PMC11720638 DOI: 10.2147/jir.s491043] [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: 09/06/2024] [Accepted: 12/31/2024] [Indexed: 01/16/2025] Open
Abstract
Background Accurately assessing the activity of Crohn's disease (CD) is crucial for determining prognosis and guiding treatment strategies for CD patients. Objective This study aimed to develop and validate a nomogram for assessing CD activity. Methods The semi-automatic segmentation method and PyRadiomics software were employed to segment and extract radiomics features from the spectral CT enterography images of lesions in 107 CD patients. The radiomic score (rad-score) was calculated using the radiomic signature formula. Multivariate logistic regression analysis identified the independent risk factors of erythrocyte sedimentation rate, fecal calprotectin, and Inflammatory Bowel Disease Questionnaire (IBDQ), and a nomogram was constructed in combination with rad-score. The nomogram underwent evaluation and testing in the training set (n = 84) and validation set (n = 23), respectively. Results The discrimination performance of the combined (AUC 0.877) was marginally superior to that of IBDQ + clinical (AUC 0.854). However, there was no significant difference in AUC between the two models in the validation set (P = 0.206). IBDQ + clinical outperformed clinical (AUC 0.808), clinical outperformed IBDQ (AUC 0.746), and IBDQ outperformed radiomic signature (AUC 0.688). Significant differences in AUC were observed between the two models (radiomic signature vs clinical, P = 0.026; radiomic signature vs IBDQ + clinical, P = 0.011; radiomic signature vs combined, P = 0.008; in the validation set). Conclusion The nomogram, combined with laboratory data, IBDQ and rad-score, presents an accurate and reliable method for assessing CD activity. Clinical Impact The nomogram enhances the potential for personalized treatment plans and better disease management, making it a valuable tool for clinical practice.
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Affiliation(s)
- Han Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China
| | - Yi Shen
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China
| | - Bo Cao
- Department of Radiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, People’s Republic of China
| | - Xiaomin Zheng
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China
| | - Dehan Zhao
- Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, 230022, People’s Republic of China
| | - Jing Hu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China
| | - Xingwang Wu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China
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Kim H, Kim YZ, Kim SY, Choe YH, Kim MJ. Risk factors affecting relapse after discontinuation of biologics in children with Crohn's disease who maintained deep remission. Front Pediatr 2024; 12:1479619. [PMID: 39435384 PMCID: PMC11491326 DOI: 10.3389/fped.2024.1479619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 09/24/2024] [Indexed: 10/23/2024] Open
Abstract
Objectives Biologics are important therapeutic agents for pediatric Crohn's disease. Discontinuation of biologics is known to increase the relapse rate up to 71.4% in these patients; however, their long-term use increases the risk of opportunistic infections and causes economic burden and psychological fatigue. Therefore, taking a drug holiday is meaningful, even if the biologics cannot be completely discontinued. This study aimed to analyze the risk factors affecting relapse after discontinuation of biologics in children with Crohn's disease. Methods We retrospectively reviewed the data of 435 children with Crohn's disease who visited a single health center between March 2013 and March 2021. Subsequently, we analyzed data from the patients who discontinued biologics after deep remission. Results Among the enrolled patients, 388 were followed up for ≥2 years, and of these, 357 were administered biologics. A total of 103 patients discontinued biologics after deep remission, subsequently 31 maintained remission and 72 relapsed. The shorter the duration of biologic treatment (odds ratio of 0.444, P = 0.029), the higher the ESR (odds ratio of 1.294, P = 0.009) and fecal calprotectin (odds ratio of 1.010, P = 0.032), and the less histological remission at the time of discontinuation of biologics (odds ratio of 0.119, P = 0.026), the greater the risk of relapse after discontinuation of biologics. Conclusions We identified factors associated with relapse after discontinuation of biologics. The results suggest that biologics can be discontinued in the absence of these factors after deep remission. However, because the relapse rate may increase after the discontinuation of biologics, close monitoring is important, and if necessary, re-administration of biologics should be actively considered.
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Affiliation(s)
| | | | | | | | - Mi Jin Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Demase K, Ward MG. Mimics of inflammatory bowel disease: commonly encountered differentials of an uncommon condition. Med J Aust 2024; 221:136-139. [PMID: 38951130 DOI: 10.5694/mja2.52372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 03/18/2024] [Indexed: 07/03/2024]
Affiliation(s)
| | - Mark G Ward
- Alfred Health, Melbourne, VIC
- Monash University, Melbourne, VIC
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Chen Y, Chen L, Huang S, Yang L, Wang L, Yang F, Huang J, Ding X. Predicting novel biomarkers for early diagnosis and dynamic severity monitoring of human ulcerative colitis. Front Genet 2024; 15:1429482. [PMID: 39144720 PMCID: PMC11321978 DOI: 10.3389/fgene.2024.1429482] [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: 05/08/2024] [Accepted: 07/18/2024] [Indexed: 08/16/2024] Open
Abstract
Background Ulcerative colitis is an emerging global health concern that poses a significant threat to human health and can progress to colorectal cancer if not diagnosed and treated promptly. Currently, the biomarkers used clinically for diagnosis and dynamic severity monitoring lack disease specificity. Methods Mouse models induced with 2%, 2.5%, and 3% DSS were utilized to simulate human UC with varying severities of inflammation. Transcriptome sequencing technology was employed to identify differentially expressed genes (DEGs) between the control group and each treatment group. Functional enrichment analysis of the KEGG database was performed for shared DEGs among the three treatment groups. DEGs that were significantly and strongly correlated with DSS concentrations were identified using Spearman correlation analysis. Human homologous genes of the interested DEGs were searched in the HomoloGene database, and their regulation patterns in UC patients were validated using the GSE224758 dataset. These genes were then submitted to the DisGeNET database to identify their known associations with human diseases. Online tools, including SignalP 6.0 and DeepTMHMM 1.0, were used to predict signal peptides and transmembrane helices in the amino acid sequences of human genes homologous to the DEGs of interest. Results A total of 1,230, 995, and 2,214 DEGs were identified in the 2%, 2.5%, and 3% DSS-induced groups, respectively, with 668 DEGs common across all three groups. These shared DEGs were primarily associated with signaling transport, pathogenesis, and immune response. Through extensive screening, LGI2 and PRSS22 were identified as potentially novel biomarkers with higher specificity and ease of detection for the early diagnosis and dynamic severity monitoring of human UC, respectively. Conclusion We have identified two potentially novel biomarkers, LGI2 and PRSS22, which are easy of detection and more specific for human UC. These findings provide new insights into the accurate diagnosis and dynamic monitoring of this persistent disease.
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Affiliation(s)
- Yu Chen
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Li Chen
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Sheng Huang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Li Yang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Li Wang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Feiyun Yang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Jinxiu Huang
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
| | - Xiuliang Ding
- Animal Nutrition Institute, Chongqing Academy of Animal Science, Chongqing, China
- Institute of Nutrition and Feed, National Center of Technology Innovation for Pigs, Chongqing, China
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Wiley JW, Higgins GA. Epigenomics and the Brain-gut Axis: Impact of Adverse Childhood Experiences and Therapeutic Challenges. JOURNAL OF TRANSLATIONAL GASTROENTEROLOGY 2024; 2:125-130. [PMID: 40012740 PMCID: PMC11864786 DOI: 10.14218/jtg.2024.00017] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
The brain-gut axis represents a bidirectional communication network that integrates neural, hormonal, and immunological signaling between the central nervous system and the gastrointestinal tract. Adverse childhood experiences (ACEs) have increasingly been recognized for their profound impact on this axis, with implications for both mental and physical health outcomes. This mini-review explores the emerging field of epigenomics-specifically, how epigenetic modifications incurred by ACEs can influence the brain-gut axis and contribute to the pathophysiology of various disorders. We examine the evidence linking epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs to the modulation of gene expression involved in stress responses, neurodevelopment, and immune function-all of which intersect at the brain-gut axis. Additionally, we discuss the emerging potential of the gut microbiome as both a target and mediator of epigenetic changes, further influencing brain-gut communication in the context of ACEs. The methodological and therapeutic challenges posed by these insights are significant. The reversibility of epigenetic marks and the long-term consequences of early life stress require innovative and comprehensive approaches to intervention. This underscores the need for comprehensive strategies encompassing psychosocial, pharmacological, neuromodulation, and lifestyle interventions tailored to address ACEs' individualized and persistent effects. Future directions call for a multi-disciplinary approach and longitudinal studies to uncover the full extent of ACEs' impact on epigenetic regulation and the brain-gut axis, with the goal of developing targeted therapies to mitigate the long-lasting effects on health.
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Affiliation(s)
- John W. Wiley
- Department of Internal Medicine, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Gerald A. Higgins
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
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Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
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Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
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Clinton JW, Cross RK. Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions. Clin Exp Gastroenterol 2023; 16:249-276. [PMID: 38111516 PMCID: PMC10726957 DOI: 10.2147/ceg.s360248] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023] Open
Abstract
Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.
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Affiliation(s)
- Joseph William Clinton
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond Keith Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
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Hameed NAA, Shaker OG, Hasona NA. LINC00641/miR-378a and Their Cross-Talk with TNF-α/IFN-γ as Potential Biomarkers in Ulcerative Colitis and Crohn's Diseases. J Interferon Cytokine Res 2023; 43:531-537. [PMID: 37956249 DOI: 10.1089/jir.2023.0097] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2023] Open
Abstract
The most well-known forms of inflammatory bowel disease (IBD) that affect the entire gastrointestinal tract are ulcerative colitis (UC) and Crohn's disease (CD). The serum profile of inflammatory biomarkers and noncoding RNA and their role in the propagation of the inflammatory process remains controversial. Thus, this study was designed to examine the relationship between hematological profile, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), and the expression of LINC00641 and miR-378a in individuals with IBDs. In addition, we elucidated the correlation between the expression of LINC00641 and miR-378a and the biochemical variables analyzed. This retrospective study analyzed 94 unrelated participants. Group I included healthy controls, Group II consisted of participants diagnosed with UC, and Group III consisted of participants diagnosed with CD. Patients with IBDs experienced significant elevations in CRP, total leukocyte count, platelets, erythrocyte sedimentation rate, TNF-α, and INF-γ. However, participants with IBD had lower hemoglobin and albumin levels than healthy control participants. Moreover, the expression levels of LINC00641 and miR-378a were elevated in participants with IBD, with a significant difference between participants with IBD and healthy controls. The most striking observation was a clear association between serum LINC00641 and miR-378a levels and the biochemical variables assessed. This study demonstrated a positive correlation between the expression of LINC00641/miR-378a and TNF-α in patients with UC and CD patients. This study suggests that LINC00641 and miR-378a are prospective biomarkers and noninvasive screening tools for IBDs, which may help predict the progression of complications.
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Affiliation(s)
- Nour A Abdel Hameed
- Biochemistry Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
| | - Olfat G Shaker
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nabil A Hasona
- Biochemistry Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
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Janker L, Schuster D, Bortel P, Hagn G, Meier-Menches SM, Mohr T, Mader JC, Slany A, Bileck A, Brunmair J, Madl C, Unger L, Hennlich B, Weitmayr B, Del Favero G, Pils D, Pukrop T, Pfisterer N, Feichtenschlager T, Gerner C. Multiomics-empowered Deep Phenotyping of Ulcerative Colitis Identifies Biomarker Signatures Reporting Functional Remission States. J Crohns Colitis 2023; 17:1514-1527. [PMID: 36961872 PMCID: PMC10588787 DOI: 10.1093/ecco-jcc/jjad052] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Indexed: 03/25/2023]
Abstract
INTRODUCTION Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights into disease processes and characteristic features of remission states. METHODS UC pathomechanisms were assessed by proteome profiling of human tissue specimens, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multiomics analyses comprising proteins, metabolites, and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission, in comparison with healthy controls. RESULTS Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B and T cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. Whereas pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells, and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission several, but not all, molecular candidate biomarker levels recovered back to normal. CONCLUSION The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission, but apparently persist as disease-associated molecular signatures. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms, potentially supporting the assessment of disease and remission states in UC patients.
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Affiliation(s)
- Lukas Janker
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Dina Schuster
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Patricia Bortel
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Gerhard Hagn
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Samuel M Meier-Menches
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
- Joint Metabolome Facility, University of Vienna, Vienna, Austria
| | - Thomas Mohr
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
- Joint Metabolome Facility, University of Vienna, Vienna, Austria
| | - Johanna C Mader
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Astrid Slany
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Andrea Bileck
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
- Joint Metabolome Facility, University of Vienna, Vienna, Austria
| | - Julia Brunmair
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Christian Madl
- Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria
| | - Lukas Unger
- Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Barbara Hennlich
- Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria
| | - Barbara Weitmayr
- Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria
| | - Giorgia Del Favero
- Core Facility Multimodal Imaging, Faculty of Chemistry, University of Vienna, Vienna, Austria
| | - Dietmar Pils
- Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria
| | - Tobias Pukrop
- Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Nikolaus Pfisterer
- Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria
| | | | - Christopher Gerner
- Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
- Joint Metabolome Facility, University of Vienna, Vienna, Austria
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Jo SY, Bang KS. Clinical characteristics and nursing diagnoses of pediatric patients hospitalized with inflammatory bowel disease: a single-center retrospective study in South Korea. CHILD HEALTH NURSING RESEARCH 2023; 29:218-228. [PMID: 37554089 PMCID: PMC10415836 DOI: 10.4094/chnr.2023.29.3.218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/17/2023] [Accepted: 06/26/2023] [Indexed: 08/10/2023] Open
Abstract
PURPOSE This study aimed to identify clinical characteristics of South Korean pediatric inflammatory bowel disease (IBD) in a children's hospital over the past 5 years, with a specific focus on comparing the features observed between Crohn's disease (CD) and ulcerative colitis (UC). Additionally, it aimed to examine the nursing diagnoses given to patients. METHODS This retrospective study analyzed the medical records of Korean pediatric patients under 18 years of age who were diagnosed with IBD and hospitalized at a children's hospital in Seoul, South Korea, from January 2017 to December 2021. RESULTS The number of pediatric patients diagnosed with IBD steadily increased. This finding was particularly prominent for CD patients, the majority of whom were male. Pediatric patients with CD had significantly higher rates of abdominal pain and perianal lesions, while pediatric patients with UC had a higher rate of bloody stool. Laboratory findings indicated that CD patients had higher levels of inflammatory markers and lower albumin levels than UC patients. The nursing diagnoses given during hospitalization mostly related to safety and protection, physical comfort, and gastrointestinal function. CONCLUSION This study provides insights into Korean pediatric IBD patients, enabling early detection and the development of nursing intervention strategies. From a comprehensive perspective, nursing care should not only address patients' physical needs but also their psychosocial needs.
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Affiliation(s)
- Sung-Yoon Jo
- Graduate Student, College of Nursing, Seoul National University, Seoul, Korea
| | - Kyung-Sook Bang
- Professor, College of Nursing · The Research Institute of Nursing Science, Seoul National University, Seoul, Korea
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Padoan A, Musso G, Contran N, Basso D. Inflammation, Autoinflammation and Autoimmunity in Inflammatory Bowel Diseases. Curr Issues Mol Biol 2023; 45:5534-5557. [PMID: 37504266 PMCID: PMC10378236 DOI: 10.3390/cimb45070350] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 07/29/2023] Open
Abstract
In this review, the role of innate and adaptive immunity in the pathogenesis of inflammatory bowel diseases (IBD) is reported. In IBD, an altered innate immunity is often found, with increased Th17 and decreased Treg cells infiltrating the intestinal mucosa. An associated increase in inflammatory cytokines, such as IL-1 and TNF-α, and a decrease in anti-inflammatory cytokines, such as IL-10, concur in favoring the persistent inflammation of the gut mucosa. Autoinflammation is highlighted with insights in the role of inflammasomes, which activation by exogenous or endogenous triggers might be favored by mutations of NOD and NLRP proteins. Autoimmunity mechanisms also take place in IBD pathogenesis and in this context of a persistent immune stimulation by bacterial antigens and antigens derived from intestinal cells degradation, the adaptive immune response takes place and results in antibodies and autoantibodies production, a frequent finding in these diseases. Inflammation, autoinflammation and autoimmunity concur in altering the mucus layer and enhancing intestinal permeability, which sustains the vicious cycle of further mucosal inflammation.
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Affiliation(s)
- Andrea Padoan
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Giulia Musso
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Nicole Contran
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
| | - Daniela Basso
- Department of Medicine-DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
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13
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Isolated Terminal Ileitis in Children. J Pediatr Gastroenterol Nutr 2023; 76:338-342. [PMID: 36729703 DOI: 10.1097/mpg.0000000000003679] [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: 02/03/2023]
Abstract
Isolated terminal ileitis in adults is a well described entity that rarely progresses to Crohn disease (CD), and pediatric literature on this topic is very limited. We describe the prevalence, clinical, endoscopic, histologic, and radiological features, along with long-term outcome of isolated terminal ileitis in our institution. We reviewed charts of 956 children who underwent colonoscopy from 2013 to 2017. Thirty-three children had isolated histologically-defined terminal ileitis. Seventeen children were diagnosed with CD and 16 children had idiopathic terminal ileitis. Children with CD had higher prevalence of abnormal C-reactive protein levels, severe inflammation, and radiological evidence of bowel wall thickening compared with children with idiopathic ileitis. Children with idiopathic ileitis did not develop CD over a follow-up period of 83 months. In contrast to adults, CD is common in children with isolated terminal ileitis and those with idiopathic ileitis do well over long-term.
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Lee WS, Arai K, Alex G, Treepongkaruna S, Kim KM, Choong CL, Mercado KC, Darma A, Srivastava A, Aw MM. Management and monitoring of pediatric inflammatory bowel disease in the Asia-Pacific region: A position paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group: Surgical management, disease monitoring, and special considerations. J Gastroenterol Hepatol 2022; 38:510-522. [PMID: 36508314 DOI: 10.1111/jgh.16084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/11/2022] [Accepted: 11/29/2022] [Indexed: 01/15/2023]
Abstract
Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia-Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia-Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia-Pacific region.
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Affiliation(s)
- Way Seah Lee
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.,Department of Population Medicine, Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, 59100, Kajang, Selangor, Malaysia
| | - Katsuhiro Arai
- Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan
| | - George Alex
- Department of Gastroenterology and Nutrition, Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Suporn Treepongkaruna
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chee Liang Choong
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - Karen Calixto Mercado
- Makati Medical Center and The Medical City, Philippine Society for Pediatric Gastroenterology, Hepatology and Nutrition, Manila, Philippines
| | - Andy Darma
- Department of Child Health, Dr. Soetomo General Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Anshu Srivastava
- Department of Paediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Marion M Aw
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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15
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Chen X, Ning J, Li Q, Kuang W, Jiang H, Qin S. Prediction of acute pancreatitis complications using routine blood parameters during early admission. Immun Inflamm Dis 2022; 10:e747. [PMID: 36444624 PMCID: PMC9695081 DOI: 10.1002/iid3.747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/16/2022] [Accepted: 11/06/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND There have been many reports on biomarkers for predicting the severity of acute pancreatitis (AP), but few studies on biomarkers for predicting complications; some simple and inexpensive indicators, in particular, are worth exploring. METHODS We retrospectively collected clinical data of 809 AP patients, including medical history and results of routine blood tests, and grouped them according to the occurrence of complications. Differences in clinical characteristics between groups with and without complications were compared using t-test or χ2 test. Receiver operating curve (ROC) and area under the curve were calculated to evaluate the ability of predicting the occurrence of complications for the routine blood parameters with statistical differences. Then, through univariate and multivariate analyses, independent risk factors closely associated with complications were identified. Finally, we built a three-parameter prediction system and evaluated its ability to predict AP complications. RESULTS Compared with the group without complications, the patients in the complication group had higher white blood cells, neutrophils, C-reactive protein, and erythrocyte sedimentation rate (ESR), and lower red blood cells and hemoglobin (Hb) (all p < .05), and most of them had severe pancreatitis. In addition, pseudocysts were more common in patients with alcoholic etiology, recurrence, low BMI, and high platelet (PLT) and plateletocrit. Acute respiratory failure was more common in patients with first onset and high mean PLT volume (MPV). Sepsis was more common in patients with lipogenic etiology, high MPV, and low lymphocytes. Infectious pancreatic necrosis was more common in patients with alcoholic etiology. Acute renal failure was more common in patients with monocytes and high MPV and low PLT. Multivariate analysis showed that PLT and ESR were risk factors for pseudocyst development. The ROC showed that the combination of Hb, PLT and ESR had a significantly higher predictive ability for pseudocyst than the single parameter. CONCLUSION Routine blood parameters can be used to predict the complications of AP. A predictive model combining ESR, PLT, and Hb may be an effective tool for identifying pseudocysts in AP patients.
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Affiliation(s)
- Xiubing Chen
- Department of GastroenterologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Jing Ning
- Department of GastroenterologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Qing Li
- Department of GastroenterologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Wenxi Kuang
- Department of GastroenterologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Haixing Jiang
- Department of GastroenterologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
| | - Shanyu Qin
- Department of GastroenterologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
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16
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Park S, Kang B, Kim S, Choi S, Suh HR, Kim ES, Park JH, Kim MJ, Choe YH, Lee YJ, Park JH, Ryoo E, Koh H, Choe BH. Comparison between Pediatric Crohn's Disease and Ulcerative Colitis at Diagnosis in Korea: Results from a Multicenter, Registry-Based, Inception Cohort Study. Gut Liver 2022; 16:921-929. [PMID: 36059091 PMCID: PMC9668495 DOI: 10.5009/gnl210488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/01/2021] [Accepted: 12/21/2021] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND/AIMS We aimed to compare the differences in pediatric Crohn's disease (CD) and ulcerative colitis (UC) at diagnosis in Korea. METHODS This was a multicenter, registry-based, inception cohort study conducted at five centers in Korea between 2013 and 2017. Baseline demographics, clinical characteristics, and results from laboratory, endoscopic, radiologic examinations were compared between pediatric CD and UC patients who were <19 years old at diagnosis. RESULTS A total 307 patients were included (227 CD [73.9%] and 80 UC [26.1%]). The male to female ratio was 2.49:1 for CD, and 1.49:1 for UC (p=0.019). Median age at diagnosis was 14.4 years (interquartile range, 12.4 to 16.2) for CD, and 14.4 years (interquartile range, 11.7 to 16.5) for UC (p=0.962). Hematochezia was the only dominant symptom in UC patients compared to CD patients (86.2% vs 30.8%, p<0.001). White blood cell counts, platelet counts, erythrocyte sedimentation rate, and C-reactive protein levels were significantly higher, and serum albumin level was significantly lower in CD patients than in UC patient. Anti-Saccharomyces cerevisiae antibody was positive in 44.5% and 16.2% of CD and UC patients, respectively (p<0.001), and antineutrophil cytoplasmic antibody was positive in 15.0% and 58.8% of CD and UC patients, respectively (p<0.001). Terminal ileal involvement was prominent in CD, while rectal involvement was more prominent in UC. Small bowel involvement and perianal perforating diseases were also more prominent in CD. CONCLUSIONS This is the first a multicenter study in Korea to compare the differences between pediatric CD and UC at diagnosis in Korea. A large-scale, national study is expected to better clarify these findings in the future.
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Affiliation(s)
- Sowon Park
- Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ben Kang
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Seung Kim
- Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sujin Choi
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyo Rim Suh
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Eun Sil Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hyung Park
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi Jin Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yon Ho Choe
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yeoun Joo Lee
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
| | - Jae Hong Park
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
| | - Eell Ryoo
- Department of Pediatrics, Gachon University College of Medicine, Incheon, Korea
| | - Hong Koh
- Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung-Ho Choe
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
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17
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Sherlock ME, Zachos M, Issenman RM, Mulder DJ. Clinical and Laboratory Characteristics Are Associated With Biologic Therapy Use in Pediatric Inflammatory Bowel Disease: A Retrospective Cohort Study. J Can Assoc Gastroenterol 2021; 4:e92-e100. [PMID: 34617006 PMCID: PMC8489526 DOI: 10.1093/jcag/gwaa033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 09/15/2020] [Indexed: 12/18/2022] Open
Abstract
Background Biologic agents are a highly useful class of medications for treating inflammatory bowel disease (IBD). Limited evidence exists to guide initiation of biologic therapy, especially in pediatric patients. It is unclear if disease severity is connected to biologic response. We hypothesized that the clinical, biochemical and radiographic characteristics of pediatric IBD at diagnosis were associated with subsequent initiation of biologic therapy. Methods We performed a retrospective analysis of the charts of all pediatric patients diagnosed with IBD at our centre over 14 years. Kaplan–Meier curves evaluated patient characteristics at diagnosis with time to initiation of biologic therapy. A Cox proportional hazards model was used for multivariate characteristic analysis. Results A total of 198 patients were included, 57.6% had Crohn’s disease, 27.8% had ulcerative colitis and 14.6% had IBD type unclassified. Mean follow-up time was 47.8 months. About 55.5% of the patients received a biologic medication, the mean time to biologic initiation was 21.5 months. Earlier initiation of biologic therapy was frequently associated with older age, higher disease activity index and lower serum albumin. Conclusions Older pediatric patients with more severely active disease and lower serum albumin levels at the time of IBD diagnosis were more likely to initiate biologic therapy when considering biologic initiation, even many years after diagnosis. Identification of these characteristics may help inform decisions to initiate biologic therapy earlier in the IBD disease course.
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Affiliation(s)
- Mary E Sherlock
- Department of Pediatrics, Division of Pediatric Gastroenterology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Mary Zachos
- Department of Pediatrics, Division of Pediatric Gastroenterology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Robert M Issenman
- Department of Pediatrics, Division of Pediatric Gastroenterology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Daniel J Mulder
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada
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18
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Affiliation(s)
- Nathan S Rubalcava
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Mott Children's Hospital, 1540 East Hospital Drive SPC 4217, Ann Arbor, MI 48109 - 4217, USA
| | - Samir K Gadepalli
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Mott Children's Hospital, 1540 East Hospital Drive SPC 4217, Ann Arbor, MI 48109 - 4217, USA; Susan B. Meister Child Health Evaluation and Research Center, Michigan Medicine, Ann Arbor, MI 48109, USA.
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19
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El Megeed KHA, Saleh SAB, Mohamed AE, Alphonse Anwar C. Predictors of surgical intervention in patients with inflammatory bowel disease (two-center study). THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2021. [DOI: 10.1186/s43162-021-00050-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Sixty percent of Crohn’s disease (CD) patients require intestinal resection, and 20% of ulcerative colitis (UC) patients undergo proctocolectomy for medically refractory disease. Scarcity of literature about predictors for surgical intervention in inflammatory bowel disease (IBD) encouraged the conduction of this study to assess risk factors for surgical intervention in IBD patients.
Results
This cohort study included 80 Egyptian inflammatory bowel disease patients recruited from two medical centers. Patients were classified into two groups, 40 patients each, according to their need for surgical intervention to control inflammatory bowel disease. The two groups were compared regarding age of onset, type and location of disease, smoking, extraintestinal manifestations, perianal disease, granuloma, severity scores, stool calprotectin, complete blood count, erythrocyte sedimentation rate, C-reactive protein, and serum albumin at diagnosis for Crohn’s disease patients.
Twelve ulcerative colitis and 28 Crohn’s disease patients required surgical intervention in the form of total colectomy (30%), fistulectomy (32.5%), resection anastomosis (17.5%) or abscess drainage (20%). Perianal disease, smoking, and disease severity scores showed high significant differences (P value < 0.001); disease type and presence of granuloma showed statistically significant difference (P value < 0.05) between both groups. But, patient age at onset, location of the disease or extraintestinal manifestation had no statistical significance (P value > 0.5). Surgical interventions were more likely to be needed in patients with higher stool calprotectin level, C-reactive protein, erythrocyte sedimentation rate, and lower serum albumin for Crohn’s disease patients (P value < 0.001 for each).
Conclusion
Smoking, perianal disease, higher severity scores, stool calprotectin, C-reactive protein, and erythrocyte sedimentation rate levels are predictors of surgical treatment.
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20
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Marques JG, Shokry E, Frivolt K, Werkstetter KJ, Brückner A, Schwerd T, Koletzko S, Koletzko B. Metabolomic Signatures in Pediatric Crohn's Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study. SLAS Technol 2021; 26:165-177. [PMID: 33207993 PMCID: PMC7985853 DOI: 10.1177/2472630320969147] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 09/29/2020] [Accepted: 10/06/2020] [Indexed: 12/22/2022]
Abstract
Little is known about the metabolic response of pediatric Crohn's disease (CD) patients to partial enteral nutrition (PEN) therapy and the impact of disease activity and inflammation. We analyzed plasma samples from a nonrandomized controlled intervention study investigating the effect of partial enteral nutrition (PEN) on bone health and growth throughout one year with untargeted metabolomics using high-performance liquid chromatography (HPLC) coupled with high-resolution mass spectrometry (HRMS). Thirty-four paired samples from two time points (baseline and 12 months) were analyzed. Patients (median age: 13.9 years, range: 7-18.9 years, 44% females) were in remission or had mild disease activity. The intervention group received a casein-based formula for 12 months, providing ~25% of estimated daily energy requirements. Sparse partial least squares discriminant analysis (splsda) was applied for group discrimination and identifying sources of variation to identify the impact of PEN. We also investigated the correlation of metabolites with inflammation markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. After 12 months, our results show substantial difference between PEN and non-PEN groups in the metabolome of CD patients in remission or with mild disease activity. Inflammatory markers were associated with individual compounds and chemical classes such as isoprenoids and phospholipids. Identified compounds comprise metabolites produced by human or bacterial metabolism, as well as xenobiotics recognized as flavoring agents and environmental contaminants and their biotransformation products. Further longitudinal studies that also include patients with higher disease activity are warranted to evaluate the suitability of these metabolic biomarkers for predicting disease activity.
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Affiliation(s)
- Jair Gonzalez Marques
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Engy Shokry
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Klara Frivolt
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
- Department of Paediatrics, Comenius University Medical School, Bratislava, Slovakia
| | - Katharina Julia Werkstetter
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Annecarin Brückner
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Tobias Schwerd
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Sibylle Koletzko
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
- Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Berthold Koletzko
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
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21
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Xiong Y, Mizuno T, Colman R, Hyams J, Noe JD, Boyle B, Tsai YT, Dong M, Jackson K, Punt N, Rosen MJ, Denson LA, Vinks AA, Minar P. Real-World Infliximab Pharmacokinetic Study Informs an Electronic Health Record-Embedded Dashboard to Guide Precision Dosing in Children with Crohn's Disease. Clin Pharmacol Ther 2021; 109:1639-1647. [PMID: 33354765 DOI: 10.1002/cpt.2148] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 11/27/2020] [Indexed: 12/20/2022]
Abstract
Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn's disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic. In a multicenter observational study, 671 peak and trough infliximab concentrations from 78 patients with CD were analyzed with a drug-tolerant assay (Esoterix; LabCorp, Calabasas, CA). Individual area under the curve (AUC) estimates were generated as a measure of drug exposure over time. Population PK modeling (nonlinear mixed-effect modeling) identified serum albumin, antibody to infliximab, erythrocyte sedimentation rate (ESR), and neutrophil CD64 as biomarkers for drug clearance. Week 14 and week 52 biochemical remitters (fecal calprotectin < 250 µg/g) had higher infliximab exposure (AUC) throughout induction. The optimal infliximab AUC target during induction for week 14 biochemical remission was 79,348 µg*h/mL (area under the receiver operating characteristic curve (AUROC) 0.77, [0.63-0.90], 85.7% sensitive, and 64.3% specific) with those exceeding the AUC target more likely to achieve a surgery-free week 52 biochemical remission (OR 4.3, [1.2-14.6]). Pretreatment predictors for subtherapeutic week 14 AUC included neutrophil CD64 > 6 (OR 4.5, [1.4-17.8]), ESR > 30 mm/h (OR 3.8, [1.4-11]), age < 10 years old (OR 4.2, [1.2-20]), and weight < 30 kg (OR 6.6, [2.1-25]). We created a decision-support PK dashboard with an iterative process and embedded the modeling program within the electronic health record. Model-informed precision dosing guided by real-world PKs is now available at the bedside in real-time.
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Affiliation(s)
- Ye Xiong
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Tomoyuki Mizuno
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Ruben Colman
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Jeffrey Hyams
- Connecticut Children's Medical Center, Hartford, Connecticut, USA
| | - Joshua D Noe
- Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | | | - Yi-Ting Tsai
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Min Dong
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Kimberly Jackson
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | | | - Michael J Rosen
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Lee A Denson
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Alexander A Vinks
- Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Phillip Minar
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
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22
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Rodrigues BL, Mazzaro MC, Nagasako CK, Ayrizono MDLS, Fagundes JJ, Leal RF. Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores. World J Gastrointest Endosc 2020; 12:504-520. [PMID: 33362904 PMCID: PMC7739141 DOI: 10.4253/wjge.v12.i12.504] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/06/2020] [Accepted: 11/05/2020] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.
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Affiliation(s)
- Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Márcia Carolina Mazzaro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Cristiane Kibune Nagasako
- Department of Gastroenterology, Gastrocenter, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - João José Fagundes
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
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Martín-Masot R, Navas-López VM. Inflammatory bowel disease's association with growth retardation even before presenting digestive symptoms. Minerva Pediatr (Torino) 2020; 74:224-225. [PMID: 33274904 DOI: 10.23736/s2724-5276.20.06063-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Rafael Martín-Masot
- Unit of Pediatric Gastroenterology and Nutrition, Regional University Hospital of Málaga, Málaga, Spain
| | - Víctor M Navas-López
- Unit of Pediatric Gastroenterology and Nutrition, Regional University Hospital of Málaga, Málaga, Spain -
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Gunji N, Katakura K, Abe K, Kawashima K, Fujiwara T, Onizawa M, Takahashi A, Ohira H. Upregulation of complement C1q reflects mucosal regeneration in a mouse model of colitis. Med Mol Morphol 2020; 54:87-94. [PMID: 33029672 DOI: 10.1007/s00795-020-00266-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 09/18/2020] [Indexed: 12/22/2022]
Abstract
Confirming mucosal healing is important in inflammatory bowel disease treatment. Complement C1q-mediated Wnt signaling activation has recently been suggested to mediate tissue repair and mucosal regeneration. We investigated the involvement of complement C1q and Wnt signaling in intestinal mucosal regeneration using a murine colitis model. The colitis model was established by providing C57BL/6J mice with 4% dextran sodium sulfate (DSS) for 1 week (inflammation phase) followed by regular water for 2 weeks (recovery phase). After 3 weeks, we investigated the relationship between C1q in serum and colonic tissue during the inflammation and recovery phases. We assessed Wnt signaling activity by evaluating β-catenin expression in mouse intestinal tissue. Serum C1q levels were elevated during the recovery phase. C1q-specific staining indicated high C1q expression in pathological intestinal tissue during the inflammation and recovery phases. C1q mRNA and protein expression was increased during both phases. Interestingly, C1q-expressing cells were consistent with macrophages (F4/80-positive cells). Moreover, the expression of β-catenin increased in the colonic tissues during the recovery phase of DSS-induced colitis but decreased during the inflammation phase of DSS-induced colitis. C1q expression may mediate Wnt signaling activity and intestinal epithelial regeneration.
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Affiliation(s)
- Naohiko Gunji
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Kyoko Katakura
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.
| | - Kazumasa Kawashima
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Tatsuo Fujiwara
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Michio Onizawa
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Atsushi Takahashi
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan
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D'Arcangelo G, Aloi M. Treat-to-Target in Pediatric Inflammatory Bowel Disease: What Does the Evidence Say? Paediatr Drugs 2020; 22:463-472. [PMID: 32572841 DOI: 10.1007/s40272-020-00406-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The traditional management of inflammatory bowel disease, based on treatment intensification guided by clinical activity alone, has been revised in the last 10 years and a treat-to-target approach has been proposed and is currently under evaluation as a disease-modifying strategy. Treat-to-target focuses on objective and scheduled measures to monitor intestinal damage, with consequent therapeutic adjustments in case of failure to achieve pre-defined targets. Identification of targets has been set out by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) committee in 2015. Mucosal healing is universally accepted as the main target both in Crohn's disease and ulcerative colitis, given its proven association with better long-term outcomes than clinical remission alone. Equally important is to ensure patients' clinical remission and improve patient-reported outcomes. Transmural healing (for Crohn's disease) and histological remission (for ulcerative colitis), listed as adjunctive targets, are likely to become primary targets in the near future. The ultimate goal of this approach is to modify the natural history of inflammatory bowel diseases by trying to block bowel damage progression, with interventions in the pre-clinical stage. In this review, we will discuss the current recommended therapeutic targets, as well as those that are considered adjunctive targets, with a focus on the limited pediatric literature available. Prospective long-term trials are warranted in order to identify the most appropriate target for the pediatric population and its specific issues. Identification of reliable predictors of disease course, outcome, and response to treatment will help to individually adapt each step of this monitoring algorithm and consequent therapeutic decision.
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Affiliation(s)
- Giulia D'Arcangelo
- Department of Women's and Children's Health, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Marina Aloi
- Department of Women's and Children's Health, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
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Chen P, Zhou G, Lin J, Li L, Zeng Z, Chen M, Zhang S. Serum Biomarkers for Inflammatory Bowel Disease. Front Med (Lausanne) 2020; 7:123. [PMID: 32391365 PMCID: PMC7188783 DOI: 10.3389/fmed.2020.00123] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/20/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. Aims: To review the available data on serological biomarkers for IBD. Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
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Affiliation(s)
- Peng Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Gaoshi Zhou
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingxia Lin
- Division of Blood Transfusion, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Li
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhirong Zeng
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shenghong Zhang
- Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Hauer AC. Labordiagnostik bei chronisch‑entzündlichen Darmerkrankungen. Monatsschr Kinderheilkd 2020. [DOI: 10.1007/s00112-020-00853-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ZusammenfassungDie Labordiagnostik hat sowohl im empfohlenen initialen „work up“ bei Verdacht auf eine chronisch entzündliche Darmerkrankung (CED) wie auch für das Monitoring des Krankheitsverlaufs und des Therapieansprechens einen klar umrissenen Stellenwert: Mithilfe der „Basislaborparameter“ wie z. B. Blutkörperchensenkungsgeschwindigkeit (BSG) können krankheitsspezifische Aktivitätsindizes erstellt werden, und neue serologische Marker (u. a. ANCA [„antineutrophil cytoplasmic antibodies“], ASCA [„anti-saccharomyces cerevisiaeantibodies“]) dienen der ergänzenden Differenzierung der CED-Entitäten. Derzeit dürfte das Stuhl-Calprotectin – als am weitreichendsten untersuchter fäkaler Inflammationsmarker – v. a. aufgrund der hohen Sensitivität initial und zur Einschätzung der Krankheitsaktivität der relativ beste Surrogatmarker sein. Nach wie vor ist aber die endoskopisch-histopathologische Evaluierung nicht nur für die Diagnose unabdingbar, sondern auch bezüglich des erklärten Therapieziels des „mucosal healing“, also im Rahmen der präzisen Verlaufsdokumentation. Der Entwicklung weniger invasiver „Biomarker“, die möglichst gut mit dem Schleimhautbefund korrelieren, kommt besondere Bedeutung zu, um die derzeit oft noch notwendige invasive Reevaluierung verringern zu helfen. Wie die Wertigkeit sowohl in der Routine etablierter, aber auch neuer, teils experimentell angewandter serologischer, fäkaler und funktioneller Laborparameter bzw. -tests einzuschätzen ist, und welche diagnostischen Methoden in Erprobung sind, wird im vorliegenden Beitrag erläutert.
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Agrawal M, Colombel JF. Treat-to-Target in Inflammatory Bowel Diseases, What Is the Target and How Do We Treat? Gastrointest Endosc Clin N Am 2019; 29:421-436. [PMID: 31078245 DOI: 10.1016/j.giec.2019.02.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Inflammatory bowel diseases, including Crohn disease (CD) and ulcerative colitis (UC), are chronic, progressive, immune-mediated inflammatory diseases of the gastrointestinal tract. Early therapy using a treat-to-target (T2T) approach, which implies identification of a pre-defined target, followed by optimization of therapy and regular monitoring until the goal is achieved is critical in preventing adverse long-term outcomes. In this review, the authors discuss the T2T guidance developed by the Selecting Therapeutic Targets in Inflammatory Bowel Disease committee, new evidence published on the role of various targets in CD and UC, as well as the real-world applicability of T2T."
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Affiliation(s)
- Manasi Agrawal
- Division of Gastroenterology, Lenox Hill Hospital, Northwell Health, 100 East 77th Street, New York, NY 10075, USA.
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1428 Madison Avenue, New York, NY 10029, USA
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Abstract
OBJECTIVES In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program proposed shifting the therapeutic focus on ulcerative colitis (UC) toward altering the natural history of the disease course by regularly monitoring objective measurements of disease activity and tailoring treatment accordingly. The therapeutic paradigm shift was well received in the research community and is often cited. However, new evidence on optimal UC treatment targets continues to accumulate since the time of the STRIDE guidelines. This systematic review summarizes the evidence accrued since the STRIDE UC recommendations, discusses the barriers for adoption of treat-to-target approaches in clinical practice in UC, and suggests directions for future research. METHODS We systematically reviewed MEDLINE for studies from the time of the STRIDE systematic review up to March 31, 2018, that assessed the potential treatment targets identified by the STRIDE recommendations. RESULTS Each potential treatment target literature search returned > 200 articles, which were then reviewed by 2 independent investigators for relevant studies. Selected studies of clinical factors, patient-reported outcomes, endoscopy, histology, imaging, and biomarkers and implications on treatment targets are summarized. CONCLUSIONS It appears that the relative weight given to different therapeutic targets in the development and improvement of UC treatments could be optimized, with an increased emphasis on endoscopic and histological targets over clinical or symptomatic targets. For this evolution to occur, however, new research has to demonstrate that the treat-to-target approach will deliver on the promise of better long-term outcomes compared with current approaches.
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Foster AJ, Smyth M, Lakhani A, Jung B, Brant RF, Jacobson K. Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn’s disease patients. World J Gastroenterol 2019; 25:1266-1277. [PMID: 30886509 PMCID: PMC6421242 DOI: 10.3748/wjg.v25.i10.1266] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Asymptomatic children with Crohn’s disease (CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.
AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.
METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn’s Disease Activity Index, C-reactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.
RESULTS 53 children were included and eighteen patients (34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median (interquartile range), relapse 723 μg/g (283-1758) vs 244 μg/g (61-627), P = 0.02]. Fecal calprotectin levels > 250 μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo (area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).
CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.
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Affiliation(s)
- Alice Jane Foster
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Matthew Smyth
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Alam Lakhani
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Benjamin Jung
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
| | - Rollin F Brant
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Kevan Jacobson
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Department of Cellular and Physiological Sciences, Faculty of Medicine, Vancouver, BC V6T 1Z3, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
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Chen JM, He LW, Yan T, Guo XF, Hu PJ, Peng JS, Cheng WJ, Li LL, He Q. Oral exclusive enteral nutrition induces mucosal and transmural healing in patients with Crohn's disease. Gastroenterol Rep (Oxf) 2019; 7:176-184. [PMID: 31217981 PMCID: PMC6573804 DOI: 10.1093/gastro/goy050] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/16/2018] [Accepted: 12/05/2018] [Indexed: 12/21/2022] Open
Abstract
Background and aims Mucosal healing is regarded as a clinical endpoint of Crohn’s disease (CD), and transmural healing is correlated to the concept of deep remission. Current therapies to induce mucosal and transmural healing in CD are not satisfactory. Exclusive enteral nutrition (EEN) is underestimated therapy and its value has not been fully evaluated. Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients. Methods This was a prospective, single-center, open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University. All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein, erythrocyte sedimentation rate, platelets, hemoglobin, body mass index, CD activity index, simple endoscopic score for CD and bowel sonography. Azathioprine was combined to prevent relapse. Results In this prospective observational study, 29 CD patients with an average age of 28.9 years were identified. After oral EEN treatment, 23 patients (79%) achieved complete mucosal healing, and the mean time to reach mucosal healing was 123 days (ranged from 50 to 212 days). Although only five patients (17%) achieved transmural healing, a significant reduction was observed in bowel-wall thickness (9.41 ± 3.06 vs 4.97 ± 1.76 mm, P < 0.001) and a significant improvement was observed in complications (including fistulas, abscess, ascites, stricture) assessed by bowel sonography (all P < 0.05). Conclusions Oral EEN therapy is highly effective for inducing mucosal healing in CD patients. Both CD patients at active stage and those at clinical remission show excellent clinical response to oral EEN.
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Affiliation(s)
- Jia-Min Chen
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Li-Wen He
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Ting Yan
- Department of Clinical Nutrition, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Xue-Feng Guo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Pin-Jin Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Jun-Sheng Peng
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Wen-Jie Cheng
- Department of Medical Ultrasound, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Ling-Ling Li
- Department of Clinical Nutrition, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
| | - Qing He
- Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China.,Department of Clinical Nutrition, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal Hospital), Guangzhou, Guangdong, China
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Kwapisz L, Gregor J, Chande N, Yan B, Ponich T, Mosli M. The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease. Scand J Gastroenterol 2017; 52:846-850. [PMID: 28423962 DOI: 10.1080/00365521.2017.1315740] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. METHODS Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. RESULTS A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p < .0001). For the remaining patients who at baseline did not have inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. CONCLUSIONS Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.
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Affiliation(s)
- Lukasz Kwapisz
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Jamie Gregor
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Nilesh Chande
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Brian Yan
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Terry Ponich
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Mahmoud Mosli
- b Department of Medicine, Division of Gastroenterology , King Abdulaziz University , Jeddah , Saudi Arabia
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