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Hamdi W, Migowa A, Ferjani HL, Makhloufi CD, Makhlouf Y, Nasef SI, Ziade N, Baraliakos X, Brunner H, Hassan M, Libe T, Palalane E, Hassan W, Sobh A, Seri A, Mosad D, Lishan H, Taha Y, Gacem O, Hashed S, Furia FF, Slimani S, Scott C, Hadef D. Pediatric Society of the African League Against Rheumatism juvenile idiopathic arthritis recommendations for enthesitis-related arthritis and juvenile psoriatic arthritis. Clin Rheumatol 2025; 44:901-922. [PMID: 39893309 DOI: 10.1007/s10067-025-07334-x] [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: 12/12/2024] [Revised: 01/07/2025] [Accepted: 01/11/2025] [Indexed: 02/04/2025]
Abstract
The objective of this study is to develop evidence-based recommendations for the diagnosis and management of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in the African context. The recommendations for ERA and JPsA were combined into a single document. The steering committee and task force identified 15 key questions and formulated 35 research questions. A comprehensive literature review, utilizing Medline and a manual search for African local data, was conducted to gather evidence. Following this synthesis, the task force developed draft recommendations and engaged in a Delphi process with an expert panel, including 17 African and three international experts, to reach a consensus and ensure alignment with global standards. The final recommendations were assigned a level of evidence and subsequently approved by the task force members, the expert panel, and the PAFLAR Board. Fifteen recommendations on the diagnosis and management of ERA and JPsA were developed, covering the role of the pediatric rheumatologist in multiple aspects of disease management, including diagnosis, monitoring of disease and extra-articular manifestations, determining treatment strategies, and guiding interventions. The level of evidence supporting these recommendations was variable, leading to the identification of a research agenda to address African particularities and answer pending questions. The final recommendations achieved a high level of agreement, with consensus ranging from 90 to 100%. These recommendations represent an important achievement for pediatric rheumatology in Africa, being the first of their kind, tailored specifically to the region. Developed through a rigorous methodology and collaboration between international and African experts, they aim to standardize care and address the unique challenges faced in African setting.
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Affiliation(s)
- Wafa Hamdi
- Department of Rheumatology, Faculty of Medicine of Tunis, Kassab Institute, Tunis El Manar University, UR17SP04, Tunis, Tunisia.
| | - Angela Migowa
- Department of Pediatrics, Aga Khan University Medical College East Africa, Nairobi, P.O. Box 30270, Nairobi, 00100, Kenya
| | - Hanene Lassoued Ferjani
- Department of Rheumatology, Faculty of Medicine of Tunis, Kassab Institute, Tunis El Manar University, UR17SP04, Tunis, Tunisia
| | - Chafia Dahou Makhloufi
- Department of Rheumatology, Faculty of Medicine of Algiers, Med Lamine Debaghine University Hospital, Bab El Oued, BD Said Touati, Algiers, Algeria
| | - Yasmine Makhlouf
- Department of Rheumatology, Tunis El Manar University Faculty of Medicine of Tunis, Mongi Slim Hospital, Tunis, Tunisia
| | - Samah Ismail Nasef
- Department of Rheumatology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Nelly Ziade
- Rheumatology Department, Saint Joseph University and Hotel-Dieu De France, Beirut, Lebanon
| | | | - Hermine Brunner
- Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Mohammed Hassan
- Rheumatology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Temesgen Libe
- College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | | | - Waleed Hassan
- Rheumatology and Rehabilitation Department, Benha University, Banha, Egypt
| | - Ali Sobh
- Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, Mansoura, Egypt
| | - Ahmed Seri
- Clinical Immunology and Allergy Center, Royal Care International Hospital, Khartoum, Sudan
- Clinical Immunology and Allergy Department, Soba University Hospital, Al Khurtum, Sudan
| | - Doaa Mosad
- Department of Rheumatology and Rehabilitation, Mansoura University Hospitals, Mansoura University Faculty of Medicine, Mansoura, Egypt
| | - Hanna Lishan
- Rheumatology Unit, Department of Pediatrics and Child Health, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Yassmin Taha
- Pediatric Rheumatology Unit, Ahmed Gasim Children Hospital, Khartoum, Sudan
| | - Ourida Gacem
- Algiers Faculty of Medicine, Department of Pediatrics, El Biar Hospital Algiers, Algiers, Algeria
| | - Soad Hashed
- Tripoli Children's Hospital, University of Tripoli, Tripoli, Libya
| | - Francis Fredrick Furia
- School of Clinical Medicine, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania
| | | | - Christiaan Scott
- Pediatric Rheumatology, University of Ottawa, Ottawa, Ontario, Canada
- University of Cape Town, Cape Town, South Africa
| | - Djohra Hadef
- Department of Pediatrics, University Hospital Center of Batna Faculty of Medicine, Batna 2 University, Batna, Algeria
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Lee SH, Shin M, Kim SH, Kim SP, Yoon HJ, Park Y, Koh J, Oh SH, Ko JS, Moon JS, Kim KM. Prevalence of Inflammatory Bowel Disease Unclassified, as Estimated Using the Revised Porto Criteria, among Korean Pediatric Patients with Inflammatory Bowel Disease. Pediatr Gastroenterol Hepatol Nutr 2024; 27:206-214. [PMID: 39035400 PMCID: PMC11254648 DOI: 10.5223/pghn.2024.27.4.206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 05/06/2024] [Indexed: 07/23/2024] Open
Abstract
Purpose Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis. Methods We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes. Results Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively. Conclusion This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.
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Affiliation(s)
- Sung Hee Lee
- Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Minsoo Shin
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Seo Hee Kim
- Department of Pediatrics, Chonnam National University Children’s Hospital, Chonnam National University College of Medicine, Gwangju, Korea
| | - Seong Pyo Kim
- Interdisciplinary Program of Medical Informatics, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Jin Yoon
- Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Korea
| | - Yangsoon Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaemoon Koh
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Soo Moon
- Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea
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Kolho KL, Nikkonen A, Merras-Salmio L, Molander P. The need for surgery in pediatric patients with inflammatory bowel disease treated with biologicals. Int J Colorectal Dis 2024; 39:58. [PMID: 38661931 PMCID: PMC11045629 DOI: 10.1007/s00384-024-04634-7] [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] [Accepted: 04/19/2024] [Indexed: 04/26/2024]
Abstract
PURPOSE Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. METHODS This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. RESULTS A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18-36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. CONCLUSION Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics.
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Affiliation(s)
- Kaija-Leena Kolho
- Children's Hospital, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland.
| | - Anne Nikkonen
- Children's Hospital, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland
| | - Laura Merras-Salmio
- Children's Hospital, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland
| | - Pauliina Molander
- Abdominal Center, Gastroenterology, Helsinki University Hospital HUS and Helsinki University, Helsinki, Finland
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Du R, Chen S, Han C, He Z, Pei H, Yang Y. M1 intestinal macrophages-derived exosomes promote colitis progression and mucosal barrier injury. Aging (Albany NY) 2024; 16:5703-5710. [PMID: 38535999 PMCID: PMC11006457 DOI: 10.18632/aging.205672] [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: 09/28/2023] [Accepted: 12/07/2023] [Indexed: 04/06/2024]
Abstract
AIM This work aimed to investigate the role of M1 intestinal macrophages-derived exosomes (M1-Exo) in colitis and its mechanism. METHODS M1 polarization of intestinal macrophages was induced in vitro, and their exosomes were extracted and identified. Thereafter, the DSS-induced colitis mouse model was built. Each mouse was given intraperitoneal injection of exosomes, and then mouse weight and DAI were dynamically monitored. In addition, the levels of cytokines were detected by ELISA. After treatment with the TLR4 inhibitor Resatorvid, the effects of M1 macrophages-derived exosomes were observed. Besides, the mouse intestinal epithelial cells were cultured in vitro for observing function of M1-Exo. RESULTS M1-exo aggravated the colitis and tissue inflammation in mice, activated the TLR4 signal, and destroyed the mucosal barrier. But M0 macrophages-derived exosomes (M0-Exo) did not have the above effects. Resatorvid treatment antagonized the roles of M1-exo. Moreover, as confirmed by cellular experiments in vitro, M1-exo destroyed mucosal barrier. CONCLUSION M1-exo serve as the pro-inflammatory mediator, which can promote mouse colitis progression by activating TLR4 signal.
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Affiliation(s)
- Rui Du
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Sihan Chen
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Chenyang Han
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, China
| | - Zhongmei He
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Hongyan Pei
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
| | - Yang Yang
- Department of Cardiology, Shenyang Medical College Affiliated Second Hospital, Shenyang 314005, China
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Weidner J, Glauche I, Manuwald U, Kern I, Reinecke I, Bathelt F, Amin M, Dong F, Rothe U, Kugler J. Correlation of Socioeconomic and Environmental Factors With Incidence of Crohn Disease in Children and Adolescents: Systematic Review and Meta-Regression. JMIR Public Health Surveill 2024; 10:e48682. [PMID: 38526534 PMCID: PMC11002755 DOI: 10.2196/48682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 12/28/2023] [Accepted: 01/23/2024] [Indexed: 03/26/2024] Open
Abstract
BACKGROUND The worldwide incidence of Crohn disease (CD) in childhood and adolescence has an increasing trend, with significant differences between different geographic regions and individual countries. This includes an increase in the incidence of CD in countries and geographic regions where CD was not previously prevalent. In response to the increasing incidence, the pediatric care landscape is facing growing challenges. OBJECTIVE This systematic review and meta-analysis were undertaken to comprehensively delineate the incidence rates of CD in pediatric populations across different countries and to explore potential influencing factors. METHODS We performed a systematic review of PubMed and Embase (via Ovid) for studies from January 1, 1970, to December 31, 2019. In addition, a manual search was performed in relevant and previously published reviews. The results were evaluated quantitatively. For this purpose, random effects meta-analyses and meta-regressions were performed to investigate the overall incidence rate and possible factors influencing the incidence. RESULTS A qualitative synthesis of 74 studies was performed, with 72 studies included in the meta-analyses and 52 in the meta-regressions. The results of our meta-analysis showed significant heterogeneity between the individual studies, which cannot be explained by a sample effect alone. Our findings showed geographical differences in incidence rates, which increased with increasing distance from the equator, although no global temporal trend was apparent. The meta-regression analysis also identified geographic location, UV index, and Human Development Index as significant moderators associated with CD incidence. CONCLUSIONS Our results suggest that pediatric CD incidence has increased in many countries since 1970 but varies widely with geographic location, which may pose challenges to the respective health care systems. We identified geographic, environmental, and socioeconomic factors that contribute to the observed heterogeneity in incidence rates. These results can serve as a basis for future research. To this end, implementations of internationally standardized and interoperable registries combined with the dissemination of health data through federated networks based on a common data model, such as the Observational Medical Outcomes Partnership, would be beneficial. This would deepen the understanding of CD and promote evidence-based approaches to preventive and interventional strategies as well as inform public health policies aimed at addressing the increasing burden of CD in children and adolescents. TRIAL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42020168644; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168644. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR2-10.1136/bmjopen-2020-037669.
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Affiliation(s)
- Jens Weidner
- Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Ingmar Glauche
- Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Ulf Manuwald
- Faculty of Applied Social Sciences, University of Applied Sciences (FHD), Dresden, Germany
| | - Ivana Kern
- Institute and Policlinic for Occupational and Social Medicine, Department of Health Sciences/Public Health, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Ines Reinecke
- Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Franziska Bathelt
- Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
- Thiem-Research GmbH, Cottbus, Germany
| | - Makan Amin
- Institute and Policlinic for Occupational and Social Medicine, Department of Health Sciences/Public Health, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
- Department for Trauma Surgery and Orthopaedics, Park-Klinik Weissensee, Berlin, Germany
| | - Fan Dong
- Institute and Policlinic for Occupational and Social Medicine, Department of Health Sciences/Public Health, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
| | | | - Joachim Kugler
- Institute and Policlinic for Occupational and Social Medicine, Department of Health Sciences/Public Health, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany
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Stummer N, Feichtinger RG, Weghuber D, Kofler B, Schneider AM. Role of Hydrogen Sulfide in Inflammatory Bowel Disease. Antioxidants (Basel) 2023; 12:1570. [PMID: 37627565 PMCID: PMC10452036 DOI: 10.3390/antiox12081570] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/28/2023] [Accepted: 08/04/2023] [Indexed: 08/27/2023] Open
Abstract
Hydrogen sulfide (H2S), originally known as toxic gas, has now attracted attention as one of the gasotransmitters involved in many reactions in the human body. H2S has been assumed to play a role in the pathogenesis of many chronic diseases, of which the exact pathogenesis remains unknown. One of them is inflammatory bowel disease (IBD), a chronic intestinal disease subclassified as Crohn's disease (CD) and ulcerative colitis (UC). Any change in the amount of H2S seems to be linked to inflammation in this illness. These changes can be brought about by alterations in the microbiota, in the endogenous metabolism of H2S and in the diet. As both too little and too much H2S drive inflammation, a balanced level is needed for intestinal health. The aim of this review is to summarize the available literature published until June 2023 in order to provide an overview of the current knowledge of the connection between H2S and IBD.
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Affiliation(s)
- Nathalie Stummer
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
| | - René G. Feichtinger
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
| | - Daniel Weghuber
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
| | - Barbara Kofler
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
- Research Program for Receptor Biochemistry and Tumor Metabolism, Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Anna M. Schneider
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
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Bragg MA, Breaux WA, M’Koma AE. Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational and Transformational Risks Posed by Exogenous Free Hemoglobin Alpha Chain, A By-Product of Extravasated Erythrocyte Macrophage Erythrophagocytosis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1254. [PMID: 37476546 PMCID: PMC10358352 DOI: 10.3390/medicina59071254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 06/25/2023] [Accepted: 06/27/2023] [Indexed: 07/22/2023]
Abstract
Colonic inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn's colitis (CC). Patients with IBD are at increased risk for colitis-associated colorectal cancer (CACRC) compared to the general population. CACRC is preceded by IBD, characterized by highly heterogenous, pharmacologically incurable, pertinacious, worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the duration and severity of inflammation, which is influenced by the exogenous free hemoglobin alpha chain (HbαC), a byproduct of infiltrating immune cells; extravasated erythrocytes; and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS), which is exacerbated by decreased tissue antioxidant defenses. Mitigation of the Fenton Reaction via pharmaceutical therapy would attenuate ROS, promote apoptosis and DNAD repair, and subsequently prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin's clearance rate from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Further, deferoxamine's hydrophilic structure limits its ability to cross cell membranes. Finally, the effectiveness of flavonoids, natural herb antioxidants, is associated with the high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. The molecular immunopathogenesis pathways of CACRC herein reviewed are broadly still not well understood. Therefore, this timely review outlines the molecular and immunological basis of disease pathogenesis and pharmaceutical intervention as a protective measure for CACRC.
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Affiliation(s)
| | | | - Amosy E. M’Koma
- School of Medicine, Division of Biomedical Sciences, Meharry Medical College, Nashville, TN 37208, USA; (M.A.B.); (W.A.B.)
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Li W, Sheng Y, Wang J, Wu S, Han C. MicroRNA-9a-5p-NOX4 inhibits intestinal inflammatory injury by regulating the M1 polarization of intestinal macrophages. J Biochem Mol Toxicol 2023; 37:e23245. [PMID: 36281492 DOI: 10.1002/jbt.23245] [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: 06/29/2022] [Revised: 08/31/2022] [Accepted: 10/12/2022] [Indexed: 11/08/2022]
Abstract
We found that the expression of microRNA (miRNA)-9a-5p decreased in inflammatory bowel diseases (IBD; ulcerative colitis and Crohn's disease). Further, we revealed the effects and mechanisms of miRNA-9a-5p for regulating IBD progression. In C57BL/6N mice, IBD was induced with dextran sodium sulfate (DSS), and the effects of endogenous miRNA-9a-5p were mimicked/antagonized through intraperitoneal injection of miRNA-9a-5p agomir and antagomir. In animal experimentation, agomir could inhibit intestinal inflammation and tissue damage, and reduce the mucosal barrier permeability. Antagomir, on the other hand, could promote barrier damage, whose effect was associated with the M1 macrophage polarization. This study finds that miRNA-9a-5p targets NOX4 to suppress ROS production, which plays an important role in mucosal barrier damage in IBD.
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Affiliation(s)
- Wenyan Li
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Yongjia Sheng
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Jin Wang
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Shasha Wu
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Chenyang Han
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
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Muacevic A, Adler JR, Zambrana-Valenzuela R, Iglesias-Escabi IM, Arciniegas-Medina NJ. Development of Very-Early-Onset Inflammatory Bowel Disease After Multiple Early-Life Antibiotic Exposures: A Case Report and Literature Review. Cureus 2023; 15:e33813. [PMID: 36819429 PMCID: PMC9930002 DOI: 10.7759/cureus.33813] [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] [Accepted: 01/15/2023] [Indexed: 01/17/2023] Open
Abstract
The use of antibiotics has increased drastically over the last few decades. Many antibiotics can target the commensal microbiota and promote gut dysbiosis. These alterations contribute to disease onset and exacerbation. Although the etiology of inflammatory bowel disease (IBD) is mostly unknown, it involves a complex interaction among host genetics, microbiota, environmental factors, and aberrant immune responses. Studies have shown a relationship between very-early-onset inflammatory bowel disease (VEO-IBD) and microbiota alterations. The case discussed in this report endorses the current clinical evidence for this interaction. This is an anonymous record review with no identifiers involving a 23-month-old female patient who was brought to the emergency department by her parents due to persistent bloody diarrhea. Eight days before the presentation, she had experienced watery diarrhea that progressed to bloody stools. The patient had a history of acute otitis media, acute enteritis, and right-arm cutaneous abscess, for which she had received multiple antibiotic therapies. Strategies to manipulate the microbiome through diet, probiotics, antibiotics, or fecal microbiota transplantation (FMT) may be used therapeutically to modulate disease activity. A high index of clinical suspicion for VEO-IBD should be maintained for patients with a history of multiple, recurrent antibiotic use. We believe this case report will raise awareness about the issue of early anaerobic antibiotic exposure and help prevent its unnecessary use and, consequently, prevent gut microbiota dysbiosis that can lead to VEO-IBD. Also, our literature review will hopefully prompt clinicians to consider alternative therapeutic options for this patient population, such as rebuilding intestinal microbiota composition to improve VEO-IBD activity.
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Otley A, Day AS, Zachos M. Nutritional Management of Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:355-383. [DOI: 10.1007/978-3-031-14744-9_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Choe YJ, Han K, Shim JO. Treatment patterns of anti-tumour necrosis factor-alpha and prognosis of paediatric and adult-onset inflammatory bowel disease in Korea: a nationwide population-based study. Aliment Pharmacol Ther 2022; 56:980-988. [PMID: 35791668 DOI: 10.1111/apt.17125] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 03/28/2022] [Accepted: 06/23/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND The global prevalence of inflammatory bowel disease (IBD) is increasing. However, population-level data are scarce for Asian populations. AIMS To outline and compare paediatric and adult IBD incidence and prevalence data in Korea, describe prescription patterns, and analyse outcomes of anti-tumour necrosis factor (anti-TNF) use in a nationally representative cohort METHODS: IBD was identified based on the presence of Rare and Intractable Disease diagnosis codes for Crohn's disease (CD) and ulcerative colitis (UC). We calculated age-based prevalence and incidence, and examined prescription patterns. We used a Cox proportional hazard model to calculate the hazard ratio (HR) for undergoing surgery. RESULTS The prevalence of CD increased between 2006 and 2015, particularly among those aged 10-19 years (12.7-35.5 patients per 100,000 people). The use of anti-TNF agents increased from 3.2% to 22.9% in paediatric CD patients. Early use of an anti-TNF agent increased 25-fold in CD patients. Further, CD patients aged 0-14 years were most likely to undergo fistulectomy (HR, 2.63; 95% confidence interval [CI], 1.73-3.97). Children with UC had a higher risk of undergoing surgery (HR, 3.01; 95% CI, 1.33-6.83) than adults. Early use of an anti-TNF agent in CD patients was associated with lower odds of surgery than late-stage use. CONCLUSION The prevalence of IBD has increased over time, especially among paediatric patients. Given the magnitude of paediatric IBD disease burden, a multi-faceted approach is needed for early detection and vigilant monitoring to aim for better prognosis.
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Affiliation(s)
- Young June Choe
- Department of Pediatrics, Korea University Anam Hospital, Seoul, South Korea
| | - Kyoungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
| | - Jung Ok Shim
- Department of Pediatrics, Korea University Guro Hospital, Guro-Gu, South Korea.,Korea University College of Medicine, Seoul, South Korea
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12
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Han C, Sheng Y, Wang J, Zhou X, Li W, Zhang C, Guo L, Yang Y. NOX4 promotes mucosal barrier injury in inflammatory bowel disease by mediating macrophages M1 polarization through ROS. Int Immunopharmacol 2022; 104:108361. [PMID: 34949550 DOI: 10.1016/j.intimp.2021.108361] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 01/07/2023]
Abstract
NADPH oxidase 4 (NOX4) plays an important role in transporting electrons in the mitochondrial respiratory chain, which is also one major source of ROS. This study investigates the mechanism by which NOX4 promotes the M1 polarization of intestinal macrophages in inflammatory bowel disease (IBD) through ROS. Dextran sulfate sodium (DSS) was used to induce the inflammatory bowel disease (IBD) in wild-type (C57BL/6N, WT) and NOX4 knockout (C57BL/6N-NOX4em1cyagen, KO) mice. Body weights of mice were dynamically monitored and the disease active index (DAI) scores were assessed. H&E staining was performed to examine pathological changes, and immunohistochemical (IHC) staining was conducted to measure the expressions of TJ proteins (ZO-1, Occludin) and CD11c. Tissue ROS labeling was accomplished with ROS probe. More ucosal permeability was assessed by FITC-D. Tissue inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA), while the expressions of TJ proteins (ZO-1, Occludin) were measured through Western Blotting. After NOX4 inhibitor pretreatment of intestinal macrophages in vitro, polarization was induced by lipopolysaccharide (LPS) and IFN-γ, followed by determination of polarization degree. The polarized intestinal macrophages were co-cultured with Caco-2 cells, and their effect on the monolayer cell permeability was evaluated. DSS can induce the intestinal inflammation and mucosal barrier injury in mice. Besides, it can enhance the FITC-D permeability, reduce the TJ protein levels, and promote the CD11c and ROS expressions. In KO mice, intestinal inflammation was alleviated and barrier permeability was reduced. Moreover, the TJ protein levels were higher than those of WT mice, while the CD11c and ROS were down-regulated. In WT mice, the intestinal inflammation and barrier permeability could also be reduced after treatment with NOX4 inhibitor. Overexpression of NOX4 in intestinal macrophages could promote the macrophage M1 polarization while improving the barrier integrity of Caco-2 monolayer cells. NOX4 is capable of promoting M1 polarization of intestinal macrophages through ROS, thereby further aggravating the intestinal inflammation and mucosal barrier injury in IBD. NOX4 has potential as a novel therapeutic target for IBD.
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Affiliation(s)
- Chenyang Han
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
| | - Yongjia Sheng
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
| | - Jin Wang
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
| | - Xiaohong Zhou
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
| | - Wenyan Li
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
| | - Caiqun Zhang
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
| | - Li Guo
- Department of Center Laboratory, The Second Affiliated Hospital of Jiaxing University, China.
| | - Yi Yang
- Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 314001, China.
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13
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Adler J, Lee GJ, Singer AAM. Do Not Stop Anti-TNF Medications in Children With IBD When They Are Working. Inflamm Bowel Dis 2022; 28:322-324. [PMID: 33835170 DOI: 10.1093/ibd/izab047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Indexed: 12/09/2022]
Affiliation(s)
- Jeremy Adler
- Division of Pediatric Gastroenterology, C.S. Mott Children's Hospital, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.,Susan B. Meister Child Health Evaluation and Research Center, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Grace J Lee
- Division of Pediatric Gastroenterology, C.S. Mott Children's Hospital, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Andrew A M Singer
- Division of Pediatric Gastroenterology, C.S. Mott Children's Hospital, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
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14
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Abstract
New data suggest that incidence and prevalence of inflammatory bowel diseases [IBD] are still increasing worldwide, and approximately 0.2% of the European population suffer from IBD at the present time. Medical therapy and disease management have evolved significantly in recent decades, with an emphasis on tight objective monitoring of disease progression and a treat-to-target approach in Europe and also worldwide, aiming to prevent early bowel damage and disability. Surgery rate declined over time in Europe, with 10-30% of CD and 5-10% of UC patients requiring a surgery within 5 years. The health economic burden associated with IBD is high in Europe. Direct health care costs [approximately €3500 in CD and €2000 in UC per patient per year] have shifted from hospitalisation and surgery towards drug-related expenditures with the increasing use of biologic therapy and other novel agents, and substantial indirect costs arise from work productivity loss [approximately €1900 per patient yearly]. The aim of this paper is to provide an updated review of the burden of IBD in Europe by discussing current data on epidemiology, disease course, risk for surgery, hospitalisation, and mortality and cancer risks, as well as the economic aspects, patient disability, and work impairment, by discussing the latest population-based studies from the region.
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Affiliation(s)
- Mirabella Zhao
- Gastro Unit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Lóránt Gönczi
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Peter L Lakatos
- First Department of Medicine, Semmelweis University, Budapest, Hungary
- McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada
| | - Johan Burisch
- Gastro Unit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
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15
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MR enterography grading of pediatric ileocolonic Crohn disease activity based on a single bowel segment. Radiol Med 2021; 126:1396-1406. [PMID: 34414550 DOI: 10.1007/s11547-021-01409-w] [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: 01/12/2021] [Accepted: 08/04/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Ileocolonoscopy with histology has been considered the gold standard for Crohn disease (CD) diagnosis and monitoring. Over the last years, magnetic resonance enterography (MRE) has become more and more popular, representing a valid non-invasive technique. OBJECTIVE To propose a simplified MRE score, the pediatric CD magnetic resonance index (PCDMRI), based only on the most affected bowel segment, to grade active inflammation in children with CD. MATERIALS AND METHODS Two radiologists retrospectively evaluated MRE images of children with histopathology-proven CD. The PCDMRI was based on six mural and perimural variables assessed for the most affected bowel segment (chosen by visual inspection of the key bowel wall imaging findings associated with active inflammation), and five extramural per-examination features. Correlation analysis was performed between both the PCDMRI and the MRE global score (based on all the affected segments) and the pediatric clinical disease activity index (PCDAI), the simple endoscopic score for CD (SES-CD), serum C-reactive protein (CRP) and fecal calprotectin (fC). Inter-reader reproducibility of the scoring system was estimated. Agreement on disease location between MRE and ileocolonoscopy was evaluated. RESULTS The study involved 42 children for a total of 80 MRE. PCDMRI and global score positively correlated with PCDAI, SES-CD, CRP and fC. Inter-reader reproducibility was 91%. Agreement on disease location was substantial. CONCLUSION The PCDMRI and the global score resulted equally correlated with the PCDAI, suggesting a high impact of the most affected segment on symptoms. The PDCMRI may be a useful non-invasive tool for a rapid and reproducible grading of the disease activity in children with ileocolonic CD.
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16
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Liles E, Irving SA, Dandamudi P, Belongia EA, Daley MF, DeStefano F, Jackson LA, Jacobsen SJ, Kharbanda E, Klein NP, Weintraub E, Naleway AL. Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccination. Vaccine 2021; 39:3614-3620. [PMID: 34052066 DOI: 10.1016/j.vaccine.2021.05.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 04/15/2021] [Accepted: 05/11/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Recent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. METHODS Over a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. RESULTS Among 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19-2.65). CONCLUSIONS Data from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.
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Affiliation(s)
- Elizabeth Liles
- Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227, United States.
| | - Stephanie A Irving
- Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227, United States.
| | - Padma Dandamudi
- Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227, United States.
| | - Edward A Belongia
- Marshfield Clinic Research Institute, 1000 North Oak Avenue (ML2), Marshfield, WI 54449, United States.
| | - Matthew F Daley
- Kaiser Permanente of Colorado Institute for Health Research, 2550 South Parker Road, Suite 200, Aurora, CO 80014, United States.
| | - Frank DeStefano
- Immunization Safety Office, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS V18-4, Atlanta, GA 30333, United States.
| | - Lisa A Jackson
- Kaiser Permanente Washington Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101, United States.
| | - Steven J Jacobsen
- Department of Research and Evaluation, Kaiser Permanente Southern California, 100 South Los Robles Avenue, Pasadena, CA 91101, United States
| | - Elyse Kharbanda
- HealthPartners Institute for Education and Research, 8170 33(rd) Avenue South, MS 23301A, Bloomington, MN 55425, United States.
| | - Nicola P Klein
- Vaccine Study Center, Kaiser Permanente Division of Research, 1 Kaiser Plaza, 16(th) Floor, Oakland, CA 94612, United States.
| | - Eric Weintraub
- Immunization Safety Office, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS V18-4, Atlanta, GA 30333, United States.
| | - Allison L Naleway
- Kaiser Permanente Center for Health Research, 3800 North Interstate Avenue, Portland, OR 97227, United States.
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17
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Aloi M, Bramuzzo M, Norsa L, Arrigo S, Distante M, Miele E, Romano C, Giobbi C, Panceri R, Cucchiara S, Alvisi P. Disease Activity Patterns in the First 5 Years After Diagnosis in Children With Ulcerative Colitis: A Population-Based Study. J Crohns Colitis 2021; 15:367-374. [PMID: 33022055 DOI: 10.1093/ecco-jcc/jjaa203] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The aim of this study was to define clusters of activity in a population-based cohort during the first 5 years after diagnosis in children with ulcerative colitis [UC] and to identify early prognostic risk factors. METHODS All UC patients from the SIGENP IBD registry with a complete follow-up of at least 5 years were included. Active disease was defined every 6 months in the presence of at least one of the following: clinical activity [Paediatric Ulcerative Colitis Activity Index ≥ 35]; endoscopic activity [Mayo score ≥ 1]; faecal calprotectin > 250 µg/g; hospitalization; surgery; or treatment escalation. Formula-based clusters were generated based on four published questionnaire-based activity patterns in adults, plus one additional cluster. RESULTS In total, 226 patients were identified. Forty-two [19%] had moderate-severe chronically active disease, 31 [14%] chronic-intermittent, 75 [33%] quiescent, 54 [24%] active disease in the first 2 years after the diagnosis, then sustained remission, and 24 [11%] a remission in the first 2 years then an active disease. Mild disease onset along with a lower clinical severity not requiring the use of corticosteroids at 6 months were related to a quiescent disease course at the next follow-up (logistic model area under the curve 0.86 [95% confidence interval 0.78-0.94]; positive predictive value 67%; negative predictive value 70%). Eight per cent of patients needed surgery, none in the quiescent group [p = 0.04]. CONCLUSIONS More than one-third of children with UC present with a chronically active or intermittent course during the first 5 years of follow-up. A significant group of patients has active disease in the first 2 years and then sustained remission. Interestingly, after initial treatment, one-third of patients have well-controlled disease throughout.
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Affiliation(s)
- M Aloi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - M Bramuzzo
- Institute for Maternal and Child Health IRCCS 'Burlo Garofalo', Trieste, Italy
| | - L Norsa
- Pediatric Hepatology Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - S Arrigo
- Pediatric Gastroenterology Unit, Institute 'Giannina Gaslini', Genoa, Italy
| | - M Distante
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - E Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples 'Federico II', Naples, Italy
| | - C Romano
- Pediatric Gastroenterology and Endoscopy, University of Messina, Messina, Italy
| | - C Giobbi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - R Panceri
- Department of Pediatrics, University of Milano-Bicocca Fond., MBBM/Hosp., San Gerardo Monza, Italy
| | - S Cucchiara
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - P Alvisi
- Pediatric Department, Maggiore Hospital, Bologna, Italy
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18
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Räisänen L, Viljakainen H, Sarkkola C, Kolho KL. Perinatal risk factors for pediatric onset type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis, and inflammatory bowel diseases. Eur J Pediatr 2021; 180:2115-2123. [PMID: 33624160 PMCID: PMC8195774 DOI: 10.1007/s00431-021-03987-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 01/11/2021] [Accepted: 02/05/2021] [Indexed: 02/07/2023]
Abstract
Type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases with unknown risk factors. Using nationwide registers, we searched for their perinatal risk factors. Our study followed up 11,407 children (born 2000-2005) for a median of 16.6 years (from birth to 2018). Of them, 2.15% received primary diagnosis and 0.08% also secondary: 0.89% had DM, 0.60% had AIT, 0.48% had JIA, and 0.25% had IBD. The incidences per 100,000 children/year were 106.1 for DM, 46.0 for AIT, 55.0 for JIA, and 23.7 for IBD. There were more preterm births (< 37 weeks) among children with studied autoimmune diseases compared with the rest of the cohort (8.6% vs. 5.3%, p = 0.035). Among those born preterm, children with studied autoimmune diseases received more postnatal antibiotics compared with other preterm children in the cohort (47.6% vs. 27.7%, p = 0.046). Children with IBD were born to older mothers compared with those without studied diagnoses (33.0 vs 30.2, p = 0.004).Conclusion: Preterm birth was a shared risk factor for autoimmune diseases in our study, especially when combined with postnatal antibiotic treatments. High maternal age was associated with IBD. What is Known: • Type 1 diabetes (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases • It is unclear whether these diseases have shared risk factors, since there are no previous simultaneous epidemiological nor follow-up studies on them in one cohort What is New: • Preterm births were more common in children with DM, AIT, JIA, or IBD compared with other children in the cohort, and preterm children who developed these diseases recieved more postnatal antibiotics compared with other preterm children • High maternal age was associated with IBD.
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Affiliation(s)
- Laura Räisänen
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland. .,Folkhälsan Research Center, Helsinki, Finland.
| | - Heli Viljakainen
- grid.428673.c0000 0004 0409 6302Folkhälsan Research Center, Helsinki, Finland ,grid.7737.40000 0004 0410 2071Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Catharina Sarkkola
- grid.428673.c0000 0004 0409 6302Folkhälsan Research Center, Helsinki, Finland
| | - Kaija-Leena Kolho
- grid.502801.e0000 0001 2314 6254Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland ,grid.7737.40000 0004 0410 2071Faculty of Medicine and Children´s Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
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19
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Ivković L, Hojsak I, Trivić I, Sila S, Hrabač P, Konjik V, Senečić-Čala I, Palčevski G, Despot R, Žaja O, Kolaček S. Incidence and Geographical Variability of Pediatric Inflammatory Bowel Disease in Croatia: Data From the Croatian National Registry for Children With Inflammatory Bowel Disease. Clin Pediatr (Phila) 2020; 59:1182-1190. [PMID: 32674589 DOI: 10.1177/0009922820941202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The aim of this study was to determine the annual incidence and geographic distribution of pediatric inflammatory bowel disease (IBD) in Croatia. This is a prospective, cohort, multicenter observational study based on the data obtained from the Croatian national registry for children with IBD. Children and adolescents younger than 18 years diagnosed with IBD, in time period between June 1, 2016, and May 31, 2017, were recruited. In total, 51 new cases were identified; 19 Crohn's disease, 28 ulcerative colitis, and 8 IBD-unclassified. Male preponderance of all 3 types of the disease was noticed. The median age at diagnosis was 14.8 years. The calculated annual incidence of pediatric IBD per 100 000 persons per year was 7.05 (2.63 for Crohn's disease, 3.87 for ulcerative colitis, and 0.55 for IBD-unclassified). A north to south gradient was observed with almost 2 times higher incidence in the northern region of the country.
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Affiliation(s)
| | - Iva Hojsak
- Children's Hospital Zagreb, Zagreb, Croatia.,University of Zagreb, Zagreb, Croatia.,University J. J. Strossmayer, Osijek, Croatia
| | | | - Sara Sila
- Children's Hospital Zagreb, Zagreb, Croatia
| | | | | | | | | | - Ranka Despot
- University Hospital Center Split, Split, Croatia
| | - Orjena Žaja
- University Hospital Sisters of Mercy, Zagreb, Croatia
| | - Sanja Kolaček
- Children's Hospital Zagreb, Zagreb, Croatia.,University of Zagreb, Zagreb, Croatia
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20
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Strisciuglio C, Cenni S, Serra MR, Dolce P, Martinelli M, Staiano A, Miele E. Effectiveness of Mediterranean Diet's Adherence in children with Inflammatory Bowel Diseases. Nutrients 2020; 12:3206. [PMID: 33092159 PMCID: PMC7589768 DOI: 10.3390/nu12103206] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/02/2020] [Accepted: 10/07/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Nutritional support is very important in the treatment of Paediatric Inflammatory Bowel Disease (IBD). The role of the Mediterranean Diet (MD) has been understudied in children with IBD. The aims of this study were to assess the dietary intakes of IBD children in comparison with healthy controls (HCs), their adherence to MD; and the relationship between inflammation and dietary behaviors. METHODS Paediatric IBD patients in clinical remission and HCs were enrolled. The nutritional status and adherence to the Mediterranean Diet was evaluated through a 3-day food diary and the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED). RESULTS The analysis of food diaries showed a significantly higher kilocalorie intake in IBD patients compared to HCs (p = 0.012), an increase in carbohydrates (p = 0.015) and in protein intake (p = 0.024). Both IBD and HCs have an intermediate adherence to MD. The comparison between Crohn's disease (CD) and Ulcerative colitis (UC) patients showed significant difference in protein intake in CD patients (p = 0.047), as well as for vitamin D (p = 0.044) and iron intake (p = 0.023). Interestingly; in IBD patients we found a significant association between adherence to MD and a low level of fecal calprotectin (p = 0.027). CONCLUSION Children with IBD in remission have a sub-optimal food intake compared to HCs. MD seems to correlate to decreased intestinal inflammation.
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Affiliation(s)
- Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery, University of the Campania Luigi Vanvitelli, 81100 Naples, Italy;
| | - Sabrina Cenni
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy; (S.C.); (M.R.S.); (M.M.); (E.M.)
| | - Maria Rosaria Serra
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy; (S.C.); (M.R.S.); (M.M.); (E.M.)
| | - Pasquale Dolce
- Department of Public Health, University of Naples Federico II, 80131 Naples, Italy;
| | - Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy; (S.C.); (M.R.S.); (M.M.); (E.M.)
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy; (S.C.); (M.R.S.); (M.M.); (E.M.)
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy; (S.C.); (M.R.S.); (M.M.); (E.M.)
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21
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van Hoeve K, Vermeire S. Thiopurines in Pediatric Inflammatory Bowel Disease: Current and Future Place. Paediatr Drugs 2020; 22:449-461. [PMID: 32797366 DOI: 10.1007/s40272-020-00411-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Thiopurines have been widely used to maintain steroid-free remission in children with inflammatory bowel disease (IBD). However, within the expanding treatment armamentarium, the role of these non-selective immunomodulators has been questioned, especially in pediatric patients, who often present with a more aggressive disease course, which can impact growth and development. The less favorable safety but also inferior efficacy profile associated with thiopurines, in contrast to the newer biological therapies, has interfered with their use. The future place of thiopurines in the management of childhood IBD, therefore, needs revisiting. This review provides a practical overview on the historical and current use of thiopurines in pediatric IBD with specific attention for thiopurine S-methyltransferase testing and monitoring of thiopurine metabolite levels as an approach to improve outcomes. We also give a personal expert opinion on the future role of these drugs in childhood IBD.
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Affiliation(s)
- Karen van Hoeve
- Department of Pediatric Gastroenterology and Hepatology and Nutrition, University Hospitals Leuven, KU Leuven, Leuven, Belgium.,TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium. .,Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
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22
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Jenkinson PW, Plevris N, Siakavellas S, Lyons M, Arnott ID, Wilson D, Watson AJM, Jones GR, Lees CW. Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study. J Crohns Colitis 2020; 14:1241-1247. [PMID: 32840295 DOI: 10.1093/ecco-jcc/jjaa044] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.
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Affiliation(s)
- P W Jenkinson
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK.,Department of Surgery, Raigmore Hospital, Inverness, UK
| | - N Plevris
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | - S Siakavellas
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | - M Lyons
- School of Medicine, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
| | - I D Arnott
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | - D Wilson
- Department of Paediatric Gastroenterology, Royal Hospital for Sick Children, Edinburgh, UK
| | - A J M Watson
- Department of Surgery, Raigmore Hospital, Inverness, UK
| | - G-R Jones
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | - C W Lees
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
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23
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Ihekweazu FD, Fofanova T, Palacios R, Ajjarapu A, Karam L, Vogel AM, Rodriguez JR, Kellermayer R. Progression to colectomy in the era of biologics: A single center experience with pediatric ulcerative colitis. J Pediatr Surg 2020; 55:1815-1823. [PMID: 32087936 PMCID: PMC7396289 DOI: 10.1016/j.jpedsurg.2020.01.054] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 01/13/2020] [Accepted: 01/29/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND/PURPOSE Clinical outcomes in pediatric ulcerative colitis (UC) in the era of biologic agents are poorly defined. We aimed to describe risk factors for colectomy in pediatric UC in the era of infliximab therapy. METHODS We reviewed 217 pediatric patients at Texas Children's Hospital with newly diagnosed UC between 2003 and 2015; 117 had a minimum of 5 years of follow-up. Extent of disease at diagnosis, medication exposure, the presence of extraintestinal manifestations (EIMs), and need for surgery were noted. RESULTS Average length of follow up was 5.02 ± 2.27 years. Forty-two percent presented with pancolitis. Infliximab was used in 39%, immunomodulators in 65%, and steroids in 89% of patients. EIMs occurred in 24.9% of patients. The cumulative rate of colectomy was 12.9% at 5 years. Children presenting as E2 (Paris Classification) and children prescribed oral steroid monotherapy at diagnosis progressed to surgery faster than any other group. Of the children who received infliximab, females and children less than 5 years old were less likely to respond to therapy. CONCLUSIONS The natural course of pediatric UC remains aggressive despite the addition of infliximab to the standard of care and suggests a need for early aggressive clinical intervention. LEVEL-OF-EVIDENCE RATING Level IV.
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Affiliation(s)
- Faith D. Ihekweazu
- Department of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, MW1010, Houston, TX, 77030,Corresponding author at: Section of Pediatric Gastroenterology, Hepatology & Nutrition, Baylor College of Medicine, 1102 Bates St, FT 860.28, Houston, TX 77030-2399. Tel.: +1 832 824 3754 (Voice); fax: +1 832 825 3633, (F.D. Ihekweazu)
| | - Tatiana Fofanova
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, One Baylor Plaza, MS BCM385, Houston, TX 77030,Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030
| | - Ryan Palacios
- Department of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, MW1010, Houston, TX, 77030
| | - Avanthi Ajjarapu
- Department of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, MW1010, Houston, TX, 77030
| | - Lina Karam
- Department of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, MW1010, Houston, TX, 77030
| | - Adam M. Vogel
- Department of Pediatric Surgery, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, Houston, TX 77030
| | - J R Rodriguez
- Department of Pediatric Surgery, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, Houston, TX 77030
| | - Richard Kellermayer
- Department of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin St, MW1010, Houston, TX, 77030,USDA/ARS Children’s Nutrition Research Center, 1100 Bates Ave, Houston, TX, 77030
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24
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Qiu T, Li H, Sun T, Men P, Cui X, Liu C, Zhai S. Thalidomide as a treatment for inflammatory bowel disease in children and adolescents: A systematic review. J Clin Pharm Ther 2020; 45:1134-1142. [PMID: 32743898 DOI: 10.1111/jcpt.13196] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 05/06/2020] [Accepted: 05/14/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Tingting Qiu
- Department of Pharmacy Peking University Third Hospital Beijing China
- Institute for Drug Evaluation Peking University Health Science Center Beijing China
| | - Huibo Li
- Department of Pharmacy Peking University Third Hospital Beijing China
- Institute for Drug Evaluation Peking University Health Science Center Beijing China
| | - Tong Sun
- Department of Pharmacy Aviation General Hospital Beijing China
| | - Peng Men
- Department of Pharmacy Peking University Third Hospital Beijing China
- Institute for Drug Evaluation Peking University Health Science Center Beijing China
| | - Xiangli Cui
- Department of Pharmacy Beijing Friendship Hospital Capital Medical University Beijing China
| | - Cuiwen Liu
- Department of Pharmacy Peking University Third Hospital Beijing China
| | - Suodi Zhai
- Department of Pharmacy Peking University Third Hospital Beijing China
- Institute for Drug Evaluation Peking University Health Science Center Beijing China
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25
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Extraintestinal Manifestations Are Associated With Disease Severity in Pediatric Onset Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2020; 71:40-45. [PMID: 32187141 DOI: 10.1097/mpg.0000000000002707] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES The aim of this study was to investigate a possible association between extraintestinal manifestations (EIM) and a more severe disease course in pediatric onset inflammatory bowel disease (pIBD). METHODS This study compares the disease course of pIBD patients (IBD diagnosis <15 years of age) with and without EIM in a population-based cohort from Denmark. Patients diagnosed with pIBD between 1998 and 2008 were included in the study and followed until December 31, 2014. Data on phenotype, treatment, relapses, and the temporal relationship between IBD relapses and activity of EIM were collected at end of follow-up by manual revision of patient charts. RESULTS Of 333 pIBD patients, 14 (4.2%) had EIM at time of diagnosis and 47 (14.1%) developed EIM during follow-up. Median follow-up time was 9.6 years for patients with EIM and 8.8 years for patients without. In ulcerative colitis, EIM were associated with an increased risk of biological treatment and surgery (hazard ratio: 2.6; 95% confidence interval [CI]: 1.3-5.5, P = 0.008 and 2.9 [95% CI: 1.1-7.7, P = 0.03], respectively). In Crohn disease, EIM were associated with an increased relapse rate (1.3 [95% CI: 1.1-1.5], P = 0.001). Lastly, we found a positive temporal relationship between relapse of IBD and EIM activity. CONCLUSION The presence of EIM is associated with a more severe disease course in pIBD. This should be considered when deciding treatment options, as a more aggressive treatment approach could be warranted in patients with EIM. However, prospective studies are needed to fully evaluate this.
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26
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Long-term outcome of immunomodulator use in pediatric patients with inflammatory bowel disease. Dig Liver Dis 2020; 52:164-172. [PMID: 31640916 DOI: 10.1016/j.dld.2019.09.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 09/02/2019] [Accepted: 09/09/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES In the era where new biologicals are entering the market, the place of immunomodulators in the treatment of pediatric inflammatory bowel disease (IBD) needs to be reassessed. METHODS All children with Crohn's disease (CD) or ulcerative colitis (UC) followed at our center over the last 10 years were reviewed. Children who received conventional therapy (including 5-aminosalicylates, steroids, thiopurines and methotrexate) since diagnosis were included. Primary outcome was steroid-free clinical remission without need for rescue therapy (biologics or surgery) at 6 and 12 months after diagnosis and at last follow-up. Cox proportional hazard modelling was performed to determine variables at diagnosis associated with outcomes. RESULTS In total, 176 IBD patients (121 CD, 55 UC) were identified with a median follow-up of 4.6 [2.0-8.1] years. Remission rates were 79.6% at month 6, but decreased to 60.2% at month 12, and 31.8% at last follow-up. Higher CRP [1.006 (1.001-1.011)], lower albumin [1.050 (1.012-1.086)] and growth impairment [1.214 (1.014-1.373)] in CD patients and higher PUCAI score [1.038 (1.006-1.072)] and low iron [1.023 (1.003-1.043)] in UC patients were associated with treatment failure (all p < 0.05). CONCLUSION Only 32% pediatric IBD patients will remain free of biologics or surgery 5-years after diagnosis. Especially children with a high disease burden at diagnosis were more likely to fail conventional therapy.
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27
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Lund K, Larsen MD, Knudsen T, Kjeldsen J, Nielsen RG, Nørgård BM. The impact of anti-TNFα therapy on colectomy rates and corticosteroid treatment among 3001 paediatric and adolescent patients with ulcerative colitis-a nationwide study from 1995 to 2015. Aliment Pharmacol Ther 2019; 50:1077-1085. [PMID: 31579961 DOI: 10.1111/apt.15510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 06/07/2019] [Accepted: 08/29/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND The long-term effects of anti-TNFα therapy in ulcerative colitis are debatable. AIM To examine whether anti-TNFα therapy changed the colectomy proportion and reduced the use of corticosteroids. METHODS A nationwide cohort study among patients (age 0-20) diagnosed with ulcerative colitis through 1995-2015 from Danish health registries. We calculated the cumulative 5-year risk of colectomy after diagnosis and used a Cox regression model for comparison between a historical pre-anti-TNFα cohort 1 (1995-2003) and a cohort 2 for the era of anti-TNFα (2004-2015). Based on anti-TNFα users, defined as patients who had at least four anti-TNFα treatments within 4 months, we examined the subsequent need for corticosteroids. RESULTS We identified 3001 patients from 1995 to 2015. The 5-year cumulative proportion of colectomy in cohort 2 was 9.7% (95% confidence interval [CI] 8.4-11.1) and 12.3% (95% CI 10.4-14.6) in cohort 1. The adjusted 5-year hazard ratio (HR) was 0.76 (95% CI 0.60-0.96) for colectomy in cohort 2 compared to cohort 1. A total of 334 patients received anti-TNFα treatments, and 16.8% (56/334) were prescribed corticosteroids in the subsequent 3-month period. Corticosteroid treatment declined with follow-up after 6 and 12 months, 5.4% and 1.2%, respectively. CONCLUSION In patient's ≤20 years, the HR for colectomy within a period of 5 years from the time of diagnosis was reduced in the era of anti-TNFα compared to a historical cohort. In patients treated with anti-TNFα, prescriptions of corticosteroids were virtually ceased after 12 months.
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Affiliation(s)
- Ken Lund
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.,Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Michael Due Larsen
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.,Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Torben Knudsen
- Department of Medicine, Hospital of Southwest Jutland, Esbjerg, Denmark.,Institute for Regional Health Science, Center Southwest Jutland, University of Southern Denmark, Esbjerg, Denmark
| | - Jens Kjeldsen
- Department of Medical Gastroenterology S, Odense University Hospital, Odense, Denmark.,Research Unit of Medical Gastroenterology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Rasmus Gaardskjaer Nielsen
- Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.,Research Unit of Pediatric, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.,Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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28
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Tang WJ, Shi P, Zheng CF, Shi JR, Qiu XX, Wang SN, Huang Y. Special clinical characteristics and outcomes in Chinese pediatric patients with early-onset Crohn's disease. J Dig Dis 2019; 20:539-546. [PMID: 31347264 DOI: 10.1111/1751-2980.12803] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 07/13/2019] [Accepted: 07/23/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To study the clinical and nutritional characteristics of early-onset Crohn's disease (EO-CD) in China. METHODS Patients were defined as having EO-CD (age at diagnosis <10 y) or late-onset Crohn's disease (LO-CD; age at diagnosis of 10-17 y). Their characteristics, clinical, and nutritional data were collected at baseline and at each follow-up visit. Statistical analyses were used to compare differences in both groups. RESULTS From July 1993 to February 2017, of the 137 children enrolled, 68 (49.6%) had EO-CD and 69 (50.4%) had LO-CD. More patients with EO-CD than those with LO-CD presented with diarrhea, hematochezia, growth delay, anemia and skin disease, and had higher pediatric Crohn's disease activity index scores at diagnosis (all P < 0.05). Fewer patients with EO-CD achieved their first remission (42.6% vs 76.8%, P < 0.0001) during follow-up. Patients with EO-CD required a longer treatment time to reach remission (P = 0.0049) and had a higher mortality rate (P = 0.0133), as well as lower height and weight percentiles (P = 0.0200 and 0.0288, respectively), hemoglobin (P = 0.0185) and albumin levels (P = 0.0002), zinc (P = 0.0024) and iron (P = 0.0110) concentrations in blood at diagnosis. CONCLUSION The EO-CD group had worse clinical outcomes and nutritional status than the LO-CD group.
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Affiliation(s)
- Wen Juan Tang
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China
| | - Peng Shi
- Medical Statistics Department, Children's Hospital of Fudan University, Shanghai, China
| | - Cui Fang Zheng
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China
| | - Jie Ru Shi
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China
| | - Xiao Xia Qiu
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China
| | - Sheng Nan Wang
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children's Hospital of Fudan University, Shanghai, China
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29
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Sila S, Trivić I, Pavić AM, Niseteo T, Kolaček S, Hojsak I. Nutritional status and food intake in pediatric patients with inflammatory bowel disease at diagnosis significantly differs from healthy controls. Eur J Pediatr 2019; 178:1519-1527. [PMID: 31422462 DOI: 10.1007/s00431-019-03443-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 07/30/2019] [Accepted: 08/06/2019] [Indexed: 12/30/2022]
Abstract
Nutritional status and dietary intake in pediatric-onset inflammatory bowel disease are complex and need to be further explored. Therefore, we have assessed anthropometric measures, body composition, and dietary intake of newly diagnosed pediatric patients, and compared them with healthy controls. This was a prospective cross-sectional study including newly diagnosed patients with inflammatory bowel disease (n = 89) and healthy controls (n = 159). Mean energy intake was significantly lower in healthy controls compared to patients with ulcerative colitis, but not in patients with Crohn's disease. Intake of all macronutrients, dietary fiber, and calcium was significantly lower in patients with ulcerative colitis, whereas the only intake of animal protein, fruit, and calcium differed significantly in patients with Crohn's disease. There were no significant differences in the body fat percentage between patients with ulcerative colitis or Crohn's disease vs. controls; however, lean mass-for-age z-scores were significantly lower in patients with both diseases in comparison to controls.Conclusion: Food intake of newly diagnosed pediatric patients with inflammatory bowel disease significantly differed from healthy controls. Altered anthropometry and body composition are present already at the time of diagnosis. What is Known: • Children with inflammatory bowel disease suffer from malnutrition, especially children with Crohn's disease in whom linear growth failure often precedes gastrointestinal symptoms. What is New: • This study showed significantly lower intake of energy, macronutrients, and various micronutrients in patients with ulcerative colitis compared to healthy controls, while patients with Crohn's disease have a lower intake of fruits, calcium, and animal protein at diagnosis. • Altered body composition is present in both groups of patients at the time of diagnosis.
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Affiliation(s)
- Sara Sila
- Referral center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, 10000, Zagreb, Croatia
| | - Ivana Trivić
- Referral center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, 10000, Zagreb, Croatia
| | - Ana Močić Pavić
- Referral center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, 10000, Zagreb, Croatia
| | - Tena Niseteo
- Referral center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, 10000, Zagreb, Croatia
| | - Sanja Kolaček
- Referral center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, 10000, Zagreb, Croatia.,School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Iva Hojsak
- Referral center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Klaićeva 16, 10000, Zagreb, Croatia. .,School of Medicine, University of Zagreb, Zagreb, Croatia. .,School of Medicine Osijek, University J.J. Strossmayer, Osijek, Croatia.
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30
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Macaluso FS, Cavallaro F, Felice C, Mazza M, Armuzzi A, Gionchetti P, Vecchi M, Orlando A. Risk factors and timing for colectomy in chronically active refractory ulcerative colitis: A systematic review. Dig Liver Dis 2019; 51:613-620. [PMID: 30826279 DOI: 10.1016/j.dld.2019.01.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 01/20/2019] [Accepted: 01/21/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND In patients with chronic refractory ulcerative colitis (UC) the precise timing for indication to colectomy is unclear. AIMS We performed a systematic review of the literature on the risk factors for colectomy in patients with chronic refractory UC in the biologic era. METHODS PubMed Central/Medline and Embase were systemically searched for records published between January 2000 and December 2017. Current evidence was summarized and filtered by expert opinion. RESULTS 70 studies were included in the qualitative synthesis. Several factors were found to be associated with a higher or reduced risk for colectomy, including variables at baseline - such as progression from proctitis/left-sided to extensive colitis, extensive colitis at diagnosis, high baseline C Reactive Protein or erythrocyte sedimentation rate, male gender, and younger age at diagnosis - previous medical history, and factors arising during therapy with biologics, including the absence of clinical response after induction with infliximab or adalimumab, and the lack of mucosal healing during therapy with anti-TNFs. CONCLUSIONS Two main points may help physicians to decide when the surgical option may be considered in patients with chronic refractory UC: (1) a first risk stratification can be obtained by analyzing factors at baseline and medical history, including the previous exposure to anti-TNFs; (2) during therapy with biologics, the early assessment (after 12-16 weeks of treatment) of clinical and endoscopic response is a strong predictor of the subsequent risk of colectomy.
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Affiliation(s)
| | - Flaminia Cavallaro
- Gastroenterology & Digestive Endoscopy Unit, IRCCS Policlinico San Donato, Milano, Italy
| | - Carla Felice
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Marta Mazza
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Alessandro Armuzzi
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Organ Transplantation, University of Milan, Italy
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31
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Carlsen K, Hald M, Dubinsky MC, Keefer L, Wewer V. A Personalized eHealth Transition Concept for Adolescents With Inflammatory Bowel Disease: Design of Intervention. JMIR Pediatr Parent 2019; 2:e12258. [PMID: 31518331 PMCID: PMC6715343 DOI: 10.2196/12258] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 02/27/2019] [Accepted: 03/24/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Transfer from pediatric to adult care is a crucial period for adolescents with inflammatory bowel disease (IBD). OBJECTIVE Our aim was to develop a personalized transition-transfer concept including relevant tools in an established eHealth (electronic health) program. METHODS Required transition skills and validated patient-reported outcome measures (PROMs) were identified via bibliographic search and clinical experience and were implemented into an existing eHealth program. RESULTS The following skills were identified: disease knowledge, social life, disease management, and making well-informed, health-related decisions. The PROMs included the following: self-efficacy (the IBD Self-Efficacy Scale-Adolescents), resilience (the 10-item Connor-Davidson Resilience Scale), response to stress (the Child Self-Report Responses to Stress-IBD), and self-management and health care transition skills (the Self-Management and Transition to Adulthood with Treatment questionnaire). Starting at age 14, the patient will be offered a 1-hour annual transition consultation with an IBD-specialized nurse. The consultation will be based on the results of the PROMs and will focus on the patient's difficulties. Patients will complete the PROMs on the eHealth program at home, allowing nurses and patients to prepare for the meeting. Symptom scores and medication will be filled out on the eHealth program to support disease self-management. The consultation will be a topic-centered dialogue with practical exercises. During routine outpatient visits with the provider, parents will be left out of half of the consultation when the patient is 16 years old; at 17 years old, the parents will not be present. At the transfer consultation, the pediatric provider, the adult gastroenterologist, the pediatric nurse, the patient, and the parents will be present to ensure a proper transfer. CONCLUSIONS We have conducted a personalized eHealth transition concept consisting of basic elements that measure, train, and monitor the patients' transition readiness. The concept can be implemented and adjusted to local conditions.
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Affiliation(s)
- Katrine Carlsen
- Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark
| | - Mette Hald
- Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark
| | - Marla C Dubinsky
- Division of Pediatric Gastroenterology and Hepatology, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States
| | - Laurie Keefer
- Division of Gastroenterology, Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, United States
| | - Vibeke Wewer
- Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark
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32
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M'Koma AE. The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview. GASTROINTESTINAL DISORDERS 2019; 1:75-105. [PMID: 37577036 PMCID: PMC10416806 DOI: 10.3390/gidisord1010007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between genetic risk factors, the intestinal microbiota, urbanization, modernization, Westernization, the environmental influences and immune responses in the etiopathogenesis of inflammatory bowel disease in humans. Inflammatory bowel disease is an expensive multifactorial debilitating disease that affects thousands new people annually worldwide with no known etiology or cure. The conservative therapeutics focus on the established pathology where the immune dysfunction and gut injury have already happened but do not preclude or delay the progression. Inflammatory bowel disease is evolving globally and has become a global emergence disease. It is largely known to be a disease in industrial-urbanized societies attributed to modernization and Westernized lifestyle associated with environmental factors to genetically susceptible individuals with determined failure to process certain commensal antigens. In the developing nations, increasing incidence and prevalence of inflammatory bowel disease (IBD) has been associated with rapid urbanization, modernization and Westernization of the population. In summary, there are identified multiple associations to host exposures potentiating the landscape risk hazards of inflammatory bowel disease trigger, that include: Western life-style and diet, host genetics, altered innate and/or acquired/adaptive host immune responses, early-life microbiota exposure, change in microbiome symbiotic relationship (dysbiosis/dysbacteriosis), pollution, changing hygiene status, socioeconomic status and several other environmental factors have long-standing effects/influence tolerance. The ongoing multipronged robotic studies on gut microbiota composition disparate patterns between the rural vs. urban locations may help elucidate and better understand the contribution of microbiome disciplines/ecology and evolutionary biology in potentially protecting against the development of inflammatory bowel disease.
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Affiliation(s)
- Amosy E M'Koma
- Meharry Medical College School of Medicine, Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Nashville, TN 37208, USA
- Vanderbilt University School of Medicine, Department of Surgery, Colon and Rectal Surgery, Nashville, TN 37232, USA
- The American Society of Colon and Rectal Surgeons (ASCRS), Arlington Heights, IL 60005, USA
- The American Gastroenterological Association (AGA), Bethesda, MD 20814, USA
- Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, USA
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Kim J, Ye BD. Successful Transition from Pediatric to Adult Care in Inflammatory Bowel Disease: What is the Key? Pediatr Gastroenterol Hepatol Nutr 2019; 22:28-40. [PMID: 30671371 PMCID: PMC6333582 DOI: 10.5223/pghn.2019.22.1.28] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 11/27/2018] [Accepted: 11/28/2018] [Indexed: 12/13/2022] Open
Abstract
The incidence of pediatric-onset inflammatory bowel disease (IBD) is on the rise, accounting for up to 25% of IBD cases. Pediatric IBD often has extensive bowel involvement with aggressive and rapidly progressing behavior compared to adult IBD. Because IBD has a high morbidity rate and can have a lifelong impact, successful transition from pediatric to adult care is important to maintain the continuity of care. Furthermore, successful transition facilitates appropriate development and psychosocial well-being among patients, as well as comprehensive and harmonious healthcare delivery amongst stakeholders. However, there are various obstacles related to patients, family, providers, and organizations that interfere with successful transition. Successful transition requires a flexible and tailored plan that is made according to the patient's developmental abilities and situation. This plan should be established through periodic interviews with the patient and family and through close collaboration with other care providers. Through a stepwise approach to the transition process, patients' knowledge and self-management skills can be improved. After preparation for the transition is completed and the obstacles are overcome, patients can be gradually moved to adult care. Finally, successful transition can increase patients' adherence to therapy, maintain the appropriate health status, improve patients' self-management, and promote self-reliance among patients.
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Affiliation(s)
- Jeongseok Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Abstract
OBJECTIVES We examined the fecal virome and bacterial community composition of children with Crohn disease (CD), ulcerative colitis (UC), and healthy controls to test the hypothesis that unique patterns of viral organisms and/or presence of bacterial pathogens may be identified that could contribute to the pathogenesis of pediatric inflammatory bowel disease (IBD). METHODS Fecal samples from 24 children (mean 12.2 years) with CD (n = 7) or UC (n = 5) and similar aged controls (n = 12) were processed to determine individual viromes. Viral sequences were identified through translated protein sequence similarity search. Bacterial microbiota were determined by sequencing of the V4 region of the 16S rRNA gene. RESULTS Only a few human viruses were detected, so virome analyses focused on bacterial viruses. The relative abundance of Caudovirales was greater than that of Microviridae phages in both IBD and healthy controls. Caudovirales phages were more abundant in CD (mean 80.8%) than UC (48.8%) (P = 0.05) but not controls. The richness of viral strains in Microviridae but not Caudovirales was higher in controls than CD (P = 0.05) but not UC cases. No other measure of phage abundance, richness, or Shannon diversity showed significant difference between the 2 IBD and control groups. Bacterial microbiota analysis revealed that IBD diagnosis, albumin, hemoglobin, erythrocyte sedimentation rate, and probiotic supplementation correlated to the composition of gut bacterial microbiota. CONCLUSIONS Minor patterns in gut virome and bacterial community composition distinguish pediatric IBD patients from healthy controls. Probiotics are associated with bacterial microbiota composition. These exploratory results need confirmation in larger studies.
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Kim J, Ye BD. Successful transition from pediatric to adult care in inflammatory bowel disease: what is the key? Intest Res 2018; 17:24-35. [PMID: 30419636 PMCID: PMC6361010 DOI: 10.5217/ir.2018.00128] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Accepted: 10/07/2018] [Indexed: 12/13/2022] Open
Abstract
The incidence of pediatric-onset inflammatory bowel disease (IBD) is on the rise, accounting for up to 25% of IBD cases. Pediatric IBD often has extensive bowel involvement with aggressive and rapidly progressing behavior compared to adult IBD. Because IBD has a high morbidity rate and can have a lifelong impact, successful transition from pediatric to adult care is important to maintain the continuity of care. Furthermore, successful transition facilitates appropriate development and psychosocial well-being among patients, as well as comprehensive and harmonious healthcare delivery amongst stakeholders. However, there are various obstacles related to patients, family, providers, and organizations that interfere with successful transition. Successful transition requires a flexible and tailored plan that is made according to the patient’s developmental abilities and situation. This plan should be established through periodic interviews with the patient and family and through close collaboration with other care providers. Through a stepwise approach to the transition process, patients’ knowledge and self-management skills can be improved. After preparation for the transition is completed and the obstacles are overcome, patients can be gradually moved to adult care. Finally, successful transition can increase patients’ adherence to therapy, maintain the appropriate health status, improve patients’ self-management, and promote self-reliance among patients.
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Affiliation(s)
- Jeongseok Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Department of Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Change of treatment modalities over the last 10 years in pediatric patients with inflammatory bowel disease in Switzerland. Eur J Gastroenterol Hepatol 2018; 30:1159-1167. [PMID: 29985208 DOI: 10.1097/meg.0000000000001197] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM During the past decade, several new drugs were approved for the treatment of pediatric inflammatory bowel disease (IBD). We aimed to evaluate if and how pharmacologic treatment options for pediatric IBD in Switzerland have changed over time. PATIENTS AND METHODS Data from the pediatric Swiss IBD Cohort Study, a national prospective cohort study initiated in 2006, were analyzed. Patients were divided into two groups: patients with IBD diagnosis until 2009 (168 patients) and patients with IBD diagnosis in 2010 and after (210 patients). Both groups were analyzed regarding the past and the current therapies as well as need for surgery. RESULTS Overall, 378 pediatric patients with IBD were analyzed, of which 51.9% had Crohn's disease (CD) and 48.1% had ulcerative colitis/indeterminate colitis. Median age at diagnosis was 12 years. The majority (65.4%) of the patients with ulcerative colitis experienced pancolitis, whereas 45.4% of patients with CD presented with ileocolonic disease at diagnosis. A decreased use of corticosteroids in pediatric patients with CD can be found after 2010 (P=0.041). Use of 5-aminosalicylic acid for patients with CD was dramatically reduced after the year 2010 (33.5 vs. 67.7% after 6 years of disease). A significant shift toward earlier use of biologicals could be shown after 2010 (P<0.001). However, there was no significant decrease of surgery rate after 5 years of disease. CONCLUSION In the past decade, a significant earlier use of anti-tumor necrosis factor-α agents in pediatric patients with IBD was observed with steroid-sparing effect in patients with CD. However, this change was not associated with reduction of surgery.
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Diederen K, Krom H, Koole JCD, Benninga MA, Kindermann A. Diet and Anthropometrics of Children With Inflammatory Bowel Disease: A Comparison With the General Population. Inflamm Bowel Dis 2018; 24:1632-1640. [PMID: 29697827 DOI: 10.1093/ibd/izy027] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND There is a lack of knowledge regarding the diet of children with inflammatory bowel disease (IBD). Therefore, we investigated dietary intake in pediatric IBD compared to the general population and assessed anthropometrics and food avoidance. METHODS In this cross-sectional cohort study, patients younger than 18 years with IBD were included (2014-2017). Dietary intake (total energy, macro nutrients, food types) was assessed using a Food Frequency Questionnaire (FFQ) and compared with a matched reference population (n = 306). RESULTS There were 102 patients included (55% male, median age 15.0 years). Median height Z-score was -0.39 (interquartile range [IQR]: -1.17 to 0.26). Growth failure (height Z-scores<-1.64) was present in 11% of patients. Median BMI Z-score was 0.36 (IQR: -0.70 to 0.96). Acute malnutrition (weight-for-height Z-score<-2) was present in 3% of patients. Energy intake was lower in pediatric IBD compared to the reference population (mean kilojoule/day: 8286 vs 9794, P < 0.001). Protein intake did not differ, while fat intake was higher in pediatric IBD (mean gram/day: 101 vs 91, P < 0.001), with higher intake of vegetable oils/fats. Carbohydrate intake was lower in pediatric IBD (mean gram/day: 267 vs 305, P < 0.001), with lower intake of food types high in sugar. Food avoidance was reported in 53% of patients, with frequent avoidance of spicy (46%), high-fat food (30%), and dairy (30%). CONCLUSIONS The diet of children with IBD differs from the general pediatric population, with lower energy intake and high rates of food avoidance. Evaluation of the dietary intake alongside anthropometrics may be important to prevent nutrition deficiencies and promote health.
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Affiliation(s)
- Kay Diederen
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands
| | - Hilde Krom
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands
| | - Jeffrey C D Koole
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands
| | - Marc A Benninga
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands
| | - Angelika Kindermann
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands
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Sýkora J, Pomahačová R, Kreslová M, Cvalínová D, Štych P, Schwarz J. Current global trends in the incidence of pediatric-onset inflammatory bowel disease. World J Gastroenterol 2018; 24:2741-2763. [PMID: 29991879 PMCID: PMC6034144 DOI: 10.3748/wjg.v24.i25.2741] [Citation(s) in RCA: 259] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 06/01/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a comprehensive review and provide an up-to-date synopsis of the incidence and trends of inflammatory bowel disease (IBD). METHODS We systematically searched the MEDLINE (source PubMed), EMBASE and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (period: 1985-2018) to identify studies reporting population-based data on the incidence of pediatric-onset (< 19 years at diagnosis) IBD in full manuscripts. Two authors carried out screening and data extraction. Choropleth interactive maps and temporal trends were used to illustrate the international differences and incidences of and changes in IBD and subtypes. RESULTS In total, one hundred forty studies reporting data from 38 countries were considered in this review. The highest annual pediatric incidences of IBD were 23/100000 person-years in Europe, 15.2/100000 in North America, and 11.4/100000 in Asia/the Middle East and Oceania. The highest annual incidences of Crohn's disease (CD) were 13.9/100000 in North America and 12.3/100000 in Europe. The highest annual incidences of ulcerative colitis (UC) were 15.0/100000 in Europe and 10.6/100000 in North America. The highest annual incidences of IBD-unclassified (IBD-U) were 3.6/100000 in Europe and 2.1/100000 in North America. In the time-trend analyses, 67% of CD, 46% of UC and 11% of IBD-U studies reported an increasing incidence (P < 0.05). The risk of IBD is increasing among first-generation of migrant populations. CONCLUSION Globally, the incidence of IBD varies greatly by geographical areas. The steadily increasing incidence of pediatric IBD over time indicates its emergence as a global disease, suggesting that studies should investigate the environmental risk factors among pediatric cohorts.
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Affiliation(s)
- Josef Sýkora
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Pilsen 304 60, Czech Republic
| | - Renáta Pomahačová
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Pilsen 304 60, Czech Republic
| | - Marcela Kreslová
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Pilsen 304 60, Czech Republic
| | - Dominika Cvalínová
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Pilsen 304 60, Czech Republic
| | - Přemysl Štych
- Department of Applied Geoinformatics and Cartography, Charles University in Prague, Faculty of Science, Prague 128 43, Czech Republic
| | - Jan Schwarz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Charles University in Prague, Faculty of Medicine in Pilsen, Faculty Hospital, Pilsen 304 60, Czech Republic
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Rates and trends for inpatient surgeries in pediatric Crohn's disease in the United States from 2003 to 2012. J Pediatr Surg 2018; 53:1334-1338. [PMID: 29289343 DOI: 10.1016/j.jpedsurg.2017.11.060] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 11/15/2017] [Accepted: 11/26/2017] [Indexed: 11/21/2022]
Abstract
BACKGROUND Pediatric Crohn's disease (CD) is increasing in incidence globally. Trends in specific types of inpatient pediatric CD-related surgical procedures have not been widely reported. METHODS Patients ≤20 years of age with CD were identified in the Kids' Inpatient Database for 2003, 2006, 2009, and 2012. Bowel resection, stoma creation, and perianal or percutaneous drainage procedures were identified using ICD-9 procedure codes, and trends were identified. Logistic regression was used to identify factors associated with surgical intervention and trends. RESULTS Rates of overall bowel resection (including ileocolic resection, other small bowel resection, or other colon resection) did not change significantly over time. However, the odds of having a laparoscopic colon resection increased by 41% annually (p<0.001). Rates of subsequent ileostomy formation increased (odds ratio 1.09, p<0.001). Older age, male sex, fewer comorbidities, and treatment in large urban teaching hospitals were also associated with higher odds of undergoing bowel resection. CONCLUSIONS This study noted a stable rate of all types of bowel resections and increase in post resection ileostomy formation in US pediatric inpatients with CD from 2003-2012. Other rates of many CD-related procedures have remained stable. Further studies correlating the effects of biologic agents on surgical rates are warranted. TYPE OF STUDY Treatment Study LEVEL OF EVIDENCE: Level III.
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Martinelli M, Giugliano FP, Russo M, Giannetti E, Andreozzi M, Bruzzese D, Perrone L, Staiano A, Miraglia Del Giudice E, Miele E, Marzuillo P, Strisciuglio C. The Changing Face of Pediatric Ulcerative Colitis: A Population-based Cohort Study. J Pediatr Gastroenterol Nutr 2018; 66:903-908. [PMID: 29135823 DOI: 10.1097/mpg.0000000000001833] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The aims of this retrospective study were to describe ulcerative colitis (UC) phenotype at diagnosis and follow-up and to identify possible predictors of severe disease course. METHODS This was a retrospective, single-center study. We reviewed the charts of patients with UC diagnosed between 2 and 18 years at our referral center from January 2007 to January 2016. Laboratory and clinical features at diagnosis, such as disease extent, atypical phenotypes, extraintestinal manifestations, and therapies, and pattern changes during the follow-up, including relapse rate, disease extension, and the cumulative risk for colectomy were collected. RESULTS One hundred eleven patients were enrolled. Atypical phenotypes were identified at diagnosis in 55 out of 111 patients (49.5%). Extraintestinal manifestations were detected in 16 out of 111 (14.4%) at the diagnosis. During the follow-up 60 out of 111 (54%) patients needed to start azathioprine, 9 out of 111 (8.1%) patients started biologic therapy and 10 out of 111 (patients underwent surgery, resulting in a cumulative risk of 8% at 5 years and 16% at 10 years. Steroid refractoriness (hazard ratio: 13.9) and starting of biologic therapy (hazard ratio: 25.3) represented the best predictors for surgery. The cumulative probability of first relapse was 47% at 6 months and 63% at 1 year. Disease extension was reported in 21 out of 70 patients (30%). CONCLUSION Pediatric UC is associated with a severe phenotype and a high percentage of atypical features. Surgery rate seems to be decreased from early reports.
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Affiliation(s)
- Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Francesca P Giugliano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Marina Russo
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Eleonora Giannetti
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Marialuisa Andreozzi
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | | | - Laura Perrone
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, Naples, Italy
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | | | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Pierluigi Marzuillo
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, Naples, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery, Second University of Naples, Naples, Italy
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Abstract
OBJECTIVES The aim of the study was to evaluate clinical, endoscopic, radiologic, and histopathological features helpful in differentiating Crohn disease (CD) from intestinal tuberculosis (ITB) in children. METHODS Patients diagnosed to have CD or ITB based on standard recommended criteria were enrolled. Children with inflammatory bowel disease unclassified or suspected ITB or CD with incomplete work-up or lost to follow-up were excluded. The clinical and laboratory (radiology, endoscopy, and histology) details of children were analyzed. RESULTS Twenty cases of ITB (14 [3-17] years) and 23 of CD (11 [1-17] years) were enrolled. Presentation with chronic diarrhea (82% vs 40%; P = 0.006) and blood in stool (74% vs 10%; P = 0.001) favored CD, whereas subacute intestinal obstruction (20% vs 0%; P = 0.04) and ascites (30% vs 0%; P = 0.005) favored ITB. Presence of deep ulcers (61% vs 30%; P = 0.04), longitudinal ulcers (48% vs 15%; P = 0.02), involvement of multiple colonic segments (70% vs 35%; P = 0.02), left-sided colon (87% vs 40%; P = 0.003), extraintestinal manifestations (21.7% vs 0%; P = 0.02), and higher platelet count (3.9 vs 2.6 × 10/mm; P = 0.02) favored CD. Isolated ileocecal involvement (40% vs 8.7%; P = 0.03) was a feature of ITB. TB bacilli were demonstrated in 40% ITB cases (colon-6, ascites-1, abdominal lymph node-1). On multivariate analysis, presence of blood in stool (odds ratio: 37.5 [confidence interval: 3.85-365.72], P = 0.002) and left-sided colonic involvement (odds ratio: 16.2 [confidence interval: 1.63-161.98], P = 0.02) were independent predictors of CD. CONCLUSIONS Microbiologic confirmation of tuberculosis is possible in 40% ITB cases. Presence of blood in stool and left-sided colonic involvement are the most important features favoring CD.
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Yu YR, Rodriguez JR. Clinical presentation of Crohn's, ulcerative colitis, and indeterminate colitis: Symptoms, extraintestinal manifestations, and disease phenotypes. Semin Pediatr Surg 2017; 26:349-355. [PMID: 29126502 DOI: 10.1053/j.sempedsurg.2017.10.003] [Citation(s) in RCA: 227] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The incidence of inflammatory bowel disease (IBD) is rising with 25% of IBD diagnosed in children under 18 years of age. The clinical presentation of IBD in children is often vague leading to initial misdiagnosis as infectious colitis or irritable bowel syndrome. When IBD is identified, overlap in histologic and endoscopic features may lead to difficulty distinguishing Crohn's disease from ulcerative colitis, resulting in a higher frequency of the diagnosis indeterminate colitis or IBD unspecified. Recognizing the common and the atypical presentation of pediatric IBD and extraintestinal manifestations will aid in expeditious referral and early diagnosis. Activity severity scoring tools and more specific classification systems for pediatric IBD direct therapeutic algorithms and allow for improved longitudinal assessment since disease severity and location have been shown to be associated with outcome.
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Affiliation(s)
- Yangyang R Yu
- Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Houston, Texas
| | - J Ruben Rodriguez
- Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Houston, Texas.
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Amil-Dias J, Kolacek S, Turner D, Pærregaard A, Rintala R, Afzal NA, Karolewska-Bochenek K, Bronsky J, Chong S, Fell J, Hojsak I, Hugot JP, Koletzko S, Kumar D, Lazowska-Przeorek I, Lillehei C, Lionetti P, Martin-de-Carpi J, Pakarinen M, Ruemmele FM, Shaoul R, Spray C, Staiano A, Sugarman I, Wilson DC, Winter H, Kolho KL. Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr 2017; 64:818-835. [PMID: 28267075 DOI: 10.1097/mpg.0000000000001562] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
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Affiliation(s)
- Jorge Amil-Dias
- *Department of Pediatrics, Centro Hospitalar, S. João, Porto, Portugal †Children's Hospital Zagreb, Faculty of Medicine, Zagreb, Croatia ‡The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel §Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Denmark ||Pediatric Surgery, Children's Hospital, University of Helsinki, Helsinki, Finland ¶Department of Pediatric Gastroenterology, University Hospital Southampton, Southampton, UK #Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland **Department of Pediatrics, University Hospital Motol, Prague, Czech Republic ††Queen Mary's Hospital for Children, Epsom and St Helier NHS Trust, Surrey ‡‡Chelsea and Westminster Hospital, London, UK §§Paris-Diderot Sorbonne-Paris-Cité University and Robert Debré Hospital, Paris, France ||||Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians-University, Munich, Germany ¶¶St George's, University of London, London, UK ##Boston Children's Hospital and Harvard Medical School, Boston, MA ***Department NEUROFARBA, University of Florence - Meyer Hospital, Florence, Italy †††Unit for the Comprehensive Care of Pediatric Inflammatory Bowel Disease, Hospital Sant Joan de Déu, Barcelona, Spain ‡‡‡Department of Pediatric Gastroenterology, Necker Enfants Malades University Hospital, Sorbonne Paris Cité University, Paris Descartes University, Institut IMAGINE - INSERM U1163, Paris, France §§§Pediatric Gastroenterology Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel ||||||Department of Pediatric Gastroenterology, Bristol Royal Hospital for Children, Bristol, UK ¶¶¶Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy ###Department of Pediatric Surgery, Leeds Children's Hospital, Leeds General Infirmary, Leeds, UK ****Child Life and Health, University of Edinburgh, Scotland, UK ††††MassGeneral Hospital for Children, Harvard Medical School, Boston, MA ‡‡‡‡Children's Hospital, University of Helsinki, Helsinki, Finland
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Virta LJ, Saarinen MM, Kolho KL. Inflammatory Bowel Disease Incidence is on the Continuous Rise Among All Paediatric Patients Except for the Very Young: A Nationwide Registry-based Study on 28-Year Follow-up. J Crohns Colitis 2017; 11:150-156. [PMID: 27555642 DOI: 10.1093/ecco-jcc/jjw148] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 06/02/2016] [Accepted: 07/17/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS The burden of inflammatory bowel disease [IBD] in health care is high. We conducted research on the temporal changes in the incidence of paediatric IBD [PIBD] using nationwide registry-based data in Finland. METHODS All PIBD cases diagnosed at less than 20 years of age during 1987-2014 [in total, 5415 patients] were retrieved from a database documenting reimbursements for drug costs. Incidence rates were calculated by dividing the number of annual new PIBD cases by the size of the paediatric population at risk during each calendar year. Temporal trends in the incidences of PIBD and its subtypes, ulcerative colitis [UC] and Crohn's disease [CD], were estimated using Poisson regression analyses. RESULTS The mean annual incidence of PIBD increased from 7/100000 for the years 1987-1990 to 23/100000 for the years 2011-2014. The average rate of increase was 4.1% (95% confidence interval [CI]: 3.6-4.5) per annum. In the period 2000-2014, the increase rate in the annual incidence of UC [3.8%; 95% CI: 2.7-5.0], was steeper than for CD [2.5%; 95% CI: 1.0-3.8]. The most pronounced increase occurred in UC among adolescents aged 16-19 years [4.8%; 95% CI: 2.9-6.7]. For children less than 10 years of age, the rate of change remained low. Approximately 0.17% of the birth cohort for the years 1999-2000 was diagnosed with PIBD by the age of 14 years. CONCLUSION The incidence of PIBD is primarily increasing among adolescents, challenging the identification of the possible environmental triggers for the disease.
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Affiliation(s)
- Lauri J Virta
- Research Department, Social Insurance Institution of Finland, Turku, Finland
| | - Maiju M Saarinen
- Departments of Public Health and Child Neurology, University of Turku and Turku University Hospital, Turku, Finland
| | - Kaija-Leena Kolho
- Children's Hospital, Helsinki University Hospital and University of Helsinki, Finland
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Duricova D, Fumery M, Annese V, Lakatos PL, Peyrin-Biroulet L, Gower-Rousseau C. The natural history of Crohn's disease in children: a review of population-based studies. Eur J Gastroenterol Hepatol 2017; 29:125-134. [PMID: 27748673 DOI: 10.1097/meg.0000000000000761] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The incidence of Crohn's disease (CD) has been reported to increase. The aim of this review is to perform a comprehensive literature search of population-based studies focused on the natural history of paediatric-onset CD. A literature search of English and non-English language publications listed in the electronic database of MEDLINE (source PUBMED) and EMBASE from 1935 to 2016 was performed. Population-based studies or national cohorts reporting data on the short-term or long-term disease course of paediatric CD were included. Forty-nine paediatric and 15 nonpaediatric studies on CD have been identified. Up to one-third of children with inflammatory behaviour developed bowel complications more than 5 years after diagnosis. From 48 to 88% of children have experienced at least one corticosteroid course irrespective of the period of diagnosis and up to one-third became steroid dependent. Immunosuppressive preparations were used earlier and more frequently in newer than older cohorts (68 vs. 32% at 5 years) and more than one-third of children have received biological treatment early in the disease course. A decline in the surgery rate might be observed in more recent compared with older unselected populations. The relative risk of cancer in childhood-onset CD as well as the risk of death seem to have increased. Childhood-onset CD seems to be an aggressive phenotype of the disease. Compared with older cohorts, a trend towards decreasing surgical rate can be observed in newer cohorts paralleled by an increase in immunomodulator use and biologicals. Nevertheless, the causative role has yet to be investigated.
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Affiliation(s)
- Dana Duricova
- aIBD Clinical and Research Centre, ISCARE bInstitute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic cEPICOM, European Crohn & Colitis Organisation dGastroenterology Unit, EPIMAD Registry, Amiens University Hospital, University of Picardie Jules Verne, Amiens eGastroenterology Unit, Inserm U954, Nancy University and Hospital, Nancy fPublic Health, Epidemiology and Economic Health, EPIMAD Registry, Maison Régionale de la Recherche Clinique, Centre Hospitalier Universitaire Régional gLille Inflammation Research International Center LIRIC - UMR 995 Inserm/Université Lille 2/CHRU de Lille; Equipe IBD and Environmental factors: Epidemiology and Functional Analyses, Lille University, Lille, France hDepartment of Emergency, Unit of Gastroenterology, AOU Careggi, Florence, Italy iFirst Department of Medicine, Semmelweis University, Budapest, Hungary
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Otley AR, Day AS, Zachos M. Nutritional Management of Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2017:333-356. [DOI: 10.1007/978-3-319-49215-5_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Macaluso FS, Renna S, Orlando A, Cottone M. The biologics of ulcerative colitis. Expert Opin Biol Ther 2016; 17:175-184. [DOI: 10.1080/14712598.2017.1271871] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
| | - Sara Renna
- Di.Bi.M.I.S., Division of Internal Medicine, ‘Villa Sofia-Cervello’ Hospital, Palermo, Italy
| | - Ambrogio Orlando
- Di.Bi.M.I.S., Division of Internal Medicine, ‘Villa Sofia-Cervello’ Hospital, Palermo, Italy
| | - Mario Cottone
- Di.Bi.M.I.S., Division of Internal Medicine, ‘Villa Sofia-Cervello’ Hospital, Palermo, Italy
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Abstract
OBJECTIVES The respective role of disease activity and steroid therapy in growth impairment in paediatric-onset Crohn disease (CD) is still debated. Our aim was to investigate whether the growth pattern of children with CD was correlated with the inflammatory status during the disease course, regardless the cumulative duration of steroid therapy. METHODS One hundred and seven patients with a diagnosis of CD <17 years, followed during ≥2 years and for whom ≥2 height measures were available during follow-up, were identified between 1998 and 2010. Height, C-reactive protein (CRP), orosomucoid, and steroid therapy duration were collected at each visit. The relationship between the evolution of growth velocity and inflammatory status during follow-up was investigated using a linear mixed model with random coefficients. RESULTS Median age at diagnosis was 11.7 years (Q1-Q3: 9.8-13.5). Mean height for age (H/A) z score was 0.14 ± 1.29 at diagnosis and 0.05 ± 1.23 among the 75 patients who had reached their final height at maximal follow-up (median: 4.9 years; Q1-Q3: 3.8-6.4). Growth failure (H/A z score <-2) was present in 7 (8%) patients at diagnosis and 5 (5%) at maximal follow-up. Growth velocity was negatively correlated with the evolution of CRP (P < 0.0001) and orosomucoid (P < 0.0001) during follow-up. After adjustment for the cumulative duration of steroid therapy, these 2 correlations remained significant (CRP: P = 0.0008; orosomucoid: P < 0.0001). CONCLUSIONS Children with CD with uncontrolled inflammatory status have a lower growth velocity. The inflammatory status should be kept as close to normal as possible in paediatric-onset patients with CD to optimize their growth pattern.
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Abstract
BACKGROUND Data describing the incidence and the risk factors for surgical interventions in pediatric Crohn's disease (CD) is inconsistent. Our aim was to describe the rates of intestinal surgery and to identify associated risk factors in a large cohort of children with CD. METHODS Medical charts of 482 children with CD from the Schneider Pediatric Inflammatory Bowel Disease cohort who were diagnosed between 1981 and 2013 were carefully reviewed retrospectively. RESULTS Of 482 patients, 143 (29.7%) underwent intestinal surgery with a median follow-up time of 8.6 years (range, 1-30.5). Kaplan-Meier survival estimates of the cumulative probability of CD-related intestinal surgery were 14.2% at 5 years and 24.5% at 10 years from diagnosis. Of these, 14% needed more than one operation. Multivariate Cox models showed that isolated ileal disease (hazard ratio [HR] 2.39, P = 0.008), complicated behavior (penetrating or stricturing) (HR 2.44, P < 0.001) and higher severity indices, at diagnosis, including Harvey-Bradshaw (HR 1.06, P = 0.009) and short Pediatric Crohn's Disease Activity Index (HR 1.02, P = 0.001) were associated with increased risk for intestinal surgery. Age, gender, family history of CD, early introduction of immunomodulators, treatment with anti-tumor necrosis factor α, or diagnosis before the year 2000 did not affect the risk of bowel surgery. CONCLUSIONS Ileal location, complicated behavior, and higher disease activity indices at diagnosis are independent risk factors for bowel surgery, whereas anti-tumor necrosis factor α treatment and diagnosis during the "biological era" are not associated with diminished long-term surgical risk.
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Larsen L, Jensen MD, Larsen MD, Nielsen RG, Thorsgaard N, Vind I, Wildt S, Kjeldsen J. The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease. Clin Epidemiol 2016; 8:607-612. [PMID: 27822107 PMCID: PMC5094576 DOI: 10.2147/clep.s99478] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Aim The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. Study population The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn’s disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. Main variables The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician’s global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. Descriptive data Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200–1,300 new biological therapies are initiated each year in Danish patients with IBD. Conclusion The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk).
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Affiliation(s)
- Lone Larsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg
| | - Michael Dam Jensen
- Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Vejle
| | - Michael Due Larsen
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark
| | - Rasmus Gaardskær Nielsen
- Department of Paediatrics, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C
| | - Niels Thorsgaard
- Department of Internal Medicine, Section of Gastroenterology, Hospital Unit West, Herning
| | - Ida Vind
- Department of Gastroenterology, Copenhagen University Hospital, Hvidovre
| | - Signe Wildt
- Department of Medicine, Section of Gastroenterology, Køge Hospital, Køge
| | - Jens Kjeldsen
- Department of Medical Gastroenterology, Odense University Hospital, Odense C, Denmark
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