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Zhou J, Chen B, Wang Z, Liu L, OuYang H, Luo Y, Zhang W, Liu C, Zhan M, Duan J, Li C, Jiang N, You J, Zhao H. Diagnostic interval of inflammatory bowel disease in Chinese children and its relationship with growth parameters: a retrospective study. Front Pediatr 2025; 13:1465694. [PMID: 39974294 PMCID: PMC11835845 DOI: 10.3389/fped.2025.1465694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 01/13/2025] [Indexed: 02/21/2025] Open
Abstract
Background Delayed diagnosis of inflammatory bowel disease (IBD) is common in Europe and North America, with limited research in Asia. We aimed to investigate factors influencing delayed diagnosis of IBD in Chinese children and the impact of delayed diagnosis on growth. Methods This was a retrospective study. Clinical data on children with IBD were collected through electronic medical records. The diagnostic interval includes the time from symptom onset to hospital admission and admission to diagnosis. Diagnostic delay was defined as the upper quartile of the time interval from the first symptom to the diagnosis of IBD. For the effect on growth indicators, the length of follow-up was at least 3 months from diagnosis. Results This study included 222 children with IBD, predominantly with Crohn's disease (86.0%). Approximately one-quarter of children require more than 366 days to be diagnosed with IBD, primarily due to the extended interval between the onset of initial symptoms and hospital admission. Multivariate logistic regression models showed that fever was associated with a prolonged time interval from first symptom onset to admission and the odds ratio (OR) was 0.45 [95% confidence interval (CI) 0.22-0.94]. Age and bloody stools were associated with prolonged intervals from admission to diagnosis, with ORs of 0.84 (95% CI 0.77-0.92) and 0.36 (95% CI 0.14-0.94), respectively. Delayed diagnosis was associated with height at first admission and follow-up. Children with a delayed diagnosis had a 5.87-fold higher chance of growth retardation upon initial admission compared to children without a delayed diagnosis (95% CI 1.59-24.05). After 15.7 months of follow-up, this elevated risk remained (OR 3.28, 95% CI 1.00-10.50). Conclusion Delayed diagnosis is common in Chinese children with IBD and is associated with persistent height impairment.
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Affiliation(s)
- Juan Zhou
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - BinRong Chen
- The School of Pediatrics, Hengyang Medical School, University of South China (Hunan Children’s Hospital), Changsha, Hunan, China
| | - ZhiCheng Wang
- The School of Pediatrics, Hengyang Medical School, University of South China (Hunan Children’s Hospital), Changsha, Hunan, China
| | - Li Liu
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - HongJuan OuYang
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - YanHong Luo
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - WenTing Zhang
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - ChenXi Liu
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - MeiZheng Zhan
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - JiaQi Duan
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - CanLin Li
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - Na Jiang
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - JieYu You
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
| | - HongMei Zhao
- Department of Gastroenterology and Nutrition, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, Hunan, China
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Gargallo-Puyuelo CJ, Ricart E, Iglesias E, de Francisco R, Gisbert JP, Taxonera C, Mañosa M, Aguas Peris M, Navarrete-Muñoz EM, Sanahuja A, Guardiola J, Mesonero F, Rivero Tirado M, Barrio J, Vera Mendoza I, de Castro Parga L, García-Planella E, Calvet X, Martín Arranz MD, García S, Sicilia B, Carpio D, Domenech E, Gomollón F. Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA. Clin Gastroenterol Hepatol 2024; 22:2280-2290. [PMID: 38782172 DOI: 10.1016/j.cgh.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 05/12/2024] [Accepted: 05/15/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND & AIMS The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. METHODS We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales registry. Data extraction was conducted in July 2021. RESULTS A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17-40 y) (relative risk ratio, 1.45; 95% CI, 1.31-1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38-1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14-1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07-1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38-1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79-0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70-0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71-0.82), and complications (odds ratio, 0.73; 95% CI, 0.66-0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26-1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66-0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67-0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55-0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69-0.88). CONCLUSIONS There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.
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Affiliation(s)
- Carla J Gargallo-Puyuelo
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain; University of Zaragoza, School of Medicine, Zaragoza, Spain.
| | - Elena Ricart
- Gastroenterology Department, Hospital Clínic Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en RED (CIBEREHD), Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Eva Iglesias
- Gastroenterology Department, Hospital Reina Sofía, Cordoba, Spain
| | - Ruth de Francisco
- Gastroenterology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en RED (CIBEREHD), Madrid, Spain; Gastroenterology Department, Hospital Universitario de La Princesa, Madrid, Spain; Instituto de Investigación Sanitaria Princesa, Madrid, Spain; Universidad Autónoma de Madrid, Madrid, Spain
| | - Carlos Taxonera
- Gastroenterology Department, Hospital Clínico San Carlos, Madrid, Spain
| | - Miriam Mañosa
- Centro de Investigación Biomédica en RED (CIBEREHD), Madrid, Spain; Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mariam Aguas Peris
- Gastroenterology Department, Hospital Uniersitari i Politècnic La fe, València, Spain
| | - Eva María Navarrete-Muñoz
- Occupational Therapy Research Group (InTeO: Investigación en Terapia Ocupacional), Miguel Hernández University, Alicante, Spain; Institute for Health and Biomedical Research (ISABIAL: Instituto de InvestigaciónSanitaria y Biomédica de Alicante -FISABIO Foundation: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana), Alicante, Spain
| | - Ana Sanahuja
- Gastroenterology Department, Hospital Universitario Clínico de Valencia, Valencia, Spain
| | - Jordi Guardiola
- Gastroenterology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | - Francisco Mesonero
- Gastroenterology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Montserrat Rivero Tirado
- Gastroenterology Department, Hospital Universitario Marqués de Valdecilla e IDIVAL, Santander, Spain
| | - Jesús Barrio
- Gastroenterology Department, Hospital Rio Hortega, Valladolid, Spain
| | - Isabel Vera Mendoza
- Gastroenterology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | | | | | - Xavier Calvet
- Centro de Investigación Biomédica en RED (CIBEREHD), Madrid, Spain; Gastroenterology Department, Hospital Universitario Parc Taulí, Sabadel, Spain
| | - María Dolores Martín Arranz
- Gastroenterology Department, La Paz Hospital Universitario, Madrid, Spain; School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
| | - Santiago García
- Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain; Gastroenterology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Beatriz Sicilia
- Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Daniel Carpio
- Gastroenterology Department, Complexo Hospitalario de Pontevedra, Pontevedra, Spain
| | - Eugeni Domenech
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Fernando Gomollón
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain; University of Zaragoza, School of Medicine, Zaragoza, Spain
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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Wang Q, Chen F, Peng Y, Yi X, He Y, Shi Y. Research Progress of Interleukin-27 in Inflammatory Bowel Disease. Inflamm Bowel Dis 2024; 30:303-310. [PMID: 37540894 DOI: 10.1093/ibd/izad153] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Indexed: 08/06/2023]
Abstract
Inflammatory bowel disease (IBD) can be identified as an inflammatory disorder in the intestine, being characterized by maladjusted immune responses and chronic inflammation of the intestinal tract. However, as the etiology and pathogenesis are still unclear, more effective therapeutic approaches are needed. Recent studies have discovered a new cytokine, interleukin-27 (IL-27), which belongs to the superfamily of IL-6 and IL-12, demonstrating multiple functions in many infectious diseases, autoimmune diseases, and cancers. Interleukin-27 is mainly produced by antigen presentation cells (APCs) such as dendritic cells and mononuclear macrophages, playing a dual regulatory role in immunological response. Therefore, this updated review aims to summarize the new progress of the regulatory role of IL-27 in IBD and focus more on the interaction between IL-27 and immune cells, hoping to provide more evidence for the potential IBD treatment mediated by IL-27.
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Affiliation(s)
- Qing Wang
- Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Feifan Chen
- Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Yingqiu Peng
- Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Xuanyu Yi
- Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Yu He
- Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Yuan Shi
- Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
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Klemenak M, Zupan M, Riznik P, Krencnik T, Dolinsek J. Evolving Landscape of Paediatric Inflammatory Bowel Disease: Insights from a Decade-Long Study in North-East Slovenia on Incidence, Management, Diagnostic Delays, and Early Biologic Intervention. Diagnostics (Basel) 2024; 14:188. [PMID: 38248065 PMCID: PMC10813920 DOI: 10.3390/diagnostics14020188] [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: 12/15/2023] [Revised: 01/10/2024] [Accepted: 01/11/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND In the past decade, significant progress has been achieved in the care of children with inflammatory bowel disease (IBD). Our study concentrated on assessing the incidence and management of IBD in children in North-Eastern Slovenia over a 10-year period. METHODS Medical data from children and adolescents diagnosed with IBD in North-Eastern Slovenia (2014-2023) was analysed. Disease incidence and management of children were assessed. Findings were compared between two periods (2014-2019 and 2020-2023, coinciding with the COVID-19 pandemic). RESULTS 87 patients (median age 15.5 year; 50.6% male) with IBD (43.7% Crohn's disease (CD)), diagnosed between 2014 and 2023 were included. Extraintestinal manifestations were more common in CD than ulcerative colitis (UC) (15.8% vs. 2.4%, p < 0.05). Median delay from symptom onset to diagnosis was 2 months, lower in UC than CD (NS). Mean annual IBD incidence per 100,000 children aged 0 to 19 years was 6.4 (95% CI 4.4-8.3), slightly lower for CD than UC (2.8/100,000 vs. 3.1/100,000). In the second period, IBD incidence significantly rose (9.1 vs. 4.6, p < 0.05). During this period, 53% of CD patients transitioned to biological treatment within three months of diagnosis. CONCLUSION IBD incidence rose among children in North-Eastern Slovenia over the past decade. Additionally, more children with CD underwent biological therapy in the second period.
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Affiliation(s)
- Martina Klemenak
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
| | - Manca Zupan
- Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
| | - Petra Riznik
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
| | - Tomaz Krencnik
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
| | - Jernej Dolinsek
- Department of Gastroenterology, Hepatology and Nutrition, Pediatric Clinic, University Medical Centre Maribor, 2000 Maribor, Slovenia (J.D.)
- Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
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Martinelli M, Fedele F, Romano C, Aloi M, Lionetti P, Alvisi P, Arrigo S, Bosa L, Bramuzzo M, D'Arcangelo G, Dipasquale V, Felici E, Fuoti M, Gatti S, Graziano F, Illiceto MT, Labriola F, Norsa L, Pastore M, Scarallo L, Strisciuglio C, Zuin G, Miele E, Staiano A. Disease course of ulcerative proctitis in children: A population-based study on behalf of the SIGENP IBD Group. Dig Liver Dis 2024; 56:70-76. [PMID: 37481430 DOI: 10.1016/j.dld.2023.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/19/2023] [Accepted: 07/10/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND The natural history of ulcerative proctitis (UP) has been poorly investigated in children. AIMS We aimed to compare the disease course of children with UP at diagnosis to the other locations and to identify extension predictors. METHODS This was a multicenter, observational study carried out from data prospectively entered in the SIGENP-IBD-Registry. Children with ulcerative colitis (UC) diagnosis and at least 1-year follow-up were included. On the basis of Paris classification UP patients were identified and compared with the other locations. RESULTS 872 children were enrolled (median age at diagnosis: 11.2 years; M/F: 426/446), of whom 78 (9%) with UP. Kaplan-Meier analysis demonstrated increased cumulative probabilities of disease extension in the E1 group [1 year: 20.3%; 5 years: 52.7%; 10 years: 72.4%] compared to E3 group [1 year: 8.5%; 5 years: 24.9% and 10 years: 60.1%, p=0.001]. No differences were observed comparing E1 and E2 groups [p=0.4]. Cumulative probabilities of surgery at 1, 5 and 10 years were 1.3, 2.8 and 2.8% in the E1 group and 2.5, 8 and 12.8% in the E2-E3-E4 group, respectively (p=0.1). Cox regression analysis demonstrated that PUCAI>35 at diagnosis was associated with endoscopic extension (HR=4.9; CI 95% 1.5-15.2, p=0.006). CONCLUSIONS UP is associated with similar short and long-term outcomes compared to other locations.
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Affiliation(s)
- Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini, 5, Naples 80131, Italy
| | - Flora Fedele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini, 5, Naples 80131, Italy
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, University of Messina, Messina, Italy
| | - Marina Aloi
- Women's and Children's Health Department, Pediatric Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | | | - Patrizia Alvisi
- Pediatric Gastroenterology Unit, Maggiore Hospital, Bologna, Italy
| | - Serena Arrigo
- Pediatric Gastroenterology and Endoscopy Unit, Institute 'Giannina Gaslini', Genoa, Italy
| | - Luca Bosa
- Department of Women's and Children's Health, Unit of Pediatric Gastroenterology Digestive Endoscopy, Hepatology and Care of the Child With Liver Transplantation, Padua, Italy
| | - Matteo Bramuzzo
- Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy
| | - Giulia D'Arcangelo
- Women's and Children's Health Department, Pediatric Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, University of Messina, Messina, Italy
| | - Enrico Felici
- Pediatric and Pediatric Emergency Unit, "Umberto Bosio" Center for Digestive Diseases, The Children Hospital, AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy
| | - Maurizio Fuoti
- Pediatric Gastroenterology and GI Endoscopy, University Department of Pediatrics, Children's Hospital, Spedali Civili, Brescia, Italy
| | - Simona Gatti
- Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy
| | | | - Maria Teresa Illiceto
- Santo Spirito Hospital, Pediatric Gastroenterology and Endoscopic Unit- Department of Pediatrics, Pescara, Italy
| | - Flavio Labriola
- Pediatric Gastroenterology Unit, Maggiore Hospital, Bologna, Italy
| | - Lorenzo Norsa
- Paediatric Hepatology Gastroenterology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Maria Pastore
- Fondazione IRCCS Casa Sollievo della Sofferenza, Division of Pediatrics, San Giovanni Rotondo, Italy
| | - Luca Scarallo
- University of Florence-Meyer Hospital, Florence, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giovanna Zuin
- Department of Pediatrics, University of Milano-Bicocca, Foundation MBBM/San Gerardo Hospital, Monza, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini, 5, Naples 80131, Italy.
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini, 5, Naples 80131, Italy
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Green Z, Beattie RM, Ashton JJ. Recent developments in the assessment and management of inflammatory bowel disease in childhood: a narrative review. Transl Pediatr 2023; 12:1853-1874. [PMID: 37969128 PMCID: PMC10644027 DOI: 10.21037/tp-23-210] [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: 03/28/2023] [Accepted: 09/15/2023] [Indexed: 11/17/2023] Open
Abstract
Background and Objective The landscape of paediatric inflammatory bowel disease (pIBD) continues to evolve in an era of increasing incidence. There have been rapid developments in understanding, as we begin to perceive IBD as a spectrum of conditions, alongside advancements in monitoring and treatment. The objective of this article was to provide an overview of recent advances and challenges in the management of pIBD, with a focus on sustainable healthcare, personalised therapy, genomics, new drugs and avenues for future optimisation. Methods We present a narrative review that synthesises and summarises recent research (2017-2022) related to pIBD. We undertook a structured search of the literature (PubMed and Medline) and additional articles were identified through manual searches of reference lists. Evidence tables were compiled for disease outcomes. Key Content and Findings In this review we outline current practice, integrating clinical guidelines and contemporary research. We discuss initial investigations (including suggested threshold for paediatric faecal calprotectin), specialist investigations for disease monitoring [with reference to video capsule endoscopy (VCE) and therapeutic drug levels] and outline new and established treatment options. Biomarkers and genomic testing are examined as important tools for individualising care and identifying potential therapeutic targets, including for top-down therapy. Despite these advances, significant challenges remain, including the need for further research to understand the mechanisms of disease and the translation of these advances into real-world improvements in practice. Conclusions Recent advances in understanding of the pathogenesis of pIBD, alongside genomic and pharmacological developments have added more tools to the armamentarium for the treatment of these conditions and highlighted ongoing areas of research need.
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Affiliation(s)
- Zachary Green
- Department of Paediatric Gastroenterology, Southampton Children’s Hospital, Southampton, UK
- Department of Paediatric Gastroenterology, Noah’s Ark Children’s Hospital for Wales, Cardiff, UK
| | - Robert Mark Beattie
- Department of Paediatric Gastroenterology, Southampton Children’s Hospital, Southampton, UK
| | - James J. Ashton
- Department of Paediatric Gastroenterology, Southampton Children’s Hospital, Southampton, UK
- Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK
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Blum L, Jarach CM, Ellen ME. Perceptions of shared decision making in gastroenterology and inflammatory bowel disease: A qualitative analysis. PATIENT EDUCATION AND COUNSELING 2023; 115:107877. [PMID: 37437510 DOI: 10.1016/j.pec.2023.107877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 06/25/2023] [Accepted: 06/27/2023] [Indexed: 07/14/2023]
Abstract
OBJECTIVE Shared decision-making (SDM) is the partnership and discussion between clinicians and patients to make an appropriate decision based on scientific evidence and patient preferences. Many benefits are associated with SDM; however, little is known about its awareness or use by inflammatory bowel disease (IBD) clinicians in gastroenterology departments across Israel. This study aims to identify barriers and facilitators in implementing SDM as standard practice to achieve optimal disease management and personalized care for patients with IBD. METHODS Sixteen semi-structured interviews were conducted with IBD clinicians across Israel to identify the barriers and facilitators for SDM use. An interview guide was developed, based on the systematic approach of the Theoretical Domain Framework (TDF). Interview transcripts were coded into theoretical domains to identify factors that may impact SDM. RESULTS Sixteen gastroenterologists from nine different hospitals were interviewed. Common TDF domains that presented as barriers were: knowledge, skills, social/professional role and identity, environmental context and resources, and reinforcement. Most participants had never heard the precise term "shared decision making" and lacked formal training on SDM. CONCLUSION This study identified key barriers and facilitators to SDM in IBD clinics across Israel. Main barriers of SDM include limited or nonexistent training; clinicians were unaware of SDM guidelines or techniques. The main facilitators of SDM were clinicians' social and professional role and identity and their beliefs about the influence of IBD and/or CD. PRACTICE IMPLICATIONS These influencing factors and TDF domains identified provide a basis for developing future interventions to improve the implementation of SDM within IBD management.
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Affiliation(s)
- Livnat Blum
- Department of Health Policy and Management, Guilford Glazer Faculty of Business and Management and Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.
| | - Carlotta Micaela Jarach
- Laboratory of Lifestyle Research, Department of Medical Epidemiology, Mario Negri Institute of Pharmacological Research, IRCCS, Italy.
| | - Moriah E Ellen
- Department of Health Policy and Management, Guilford Glazer Faculty of Business and Management and Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel; Institute of Health Policy Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Canada; Israel Implementation Science and Policy Engagement Centre, Ben-Gurion University of the Negev, Israel.
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9
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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10
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Vernon-Roberts A, Day AS. Promoting early testing and appropriate referral to reduce diagnostic delay for children with suspected inflammatory bowel disease, a narrative review. Transl Pediatr 2023; 12:1416-1430. [PMID: 37575896 PMCID: PMC10416131 DOI: 10.21037/tp-23-35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 06/13/2023] [Indexed: 08/15/2023] Open
Abstract
BACKGROUND AND OBJECTIVE When a child with chronic gastrointestinal (GI) symptoms presents to a primary care physician or general paediatrician, the clinician is challenged with differentiating between functional or organic disease. When there is a high suspicion of inflammatory bowel disease (IBD), rapid referral to a paediatric gastroenterologist for assessment and treatment will help protect against the sequelae of a delayed diagnosis for a child. However, this must be balanced against the need for ensuring appropriate referrals and avoiding invasive diagnostic testing for those with non-organic aetiology. The objective of this narrative review was to present evidence on specific presenting symptoms, testing, and risk factors of paediatric IBD that may aid the identification of children requiring timely referral for specialist care, thereby reducing the chance of a delayed diagnosis. METHODS Literature databases (Medline, Embase) were searched using terms specific to the population studied, and topic specific terms relating to each section of the review. Year limits were set for 2010-2022. Included papers were limited to original research, with meta-analyses considered where of benefit. KEY CONTENT AND FINDINGS Children often present with non-specific GI symptoms that may be associated with a delayed diagnosis for those with subsequent IBD. Symptoms such as rectal bleeding or weight loss may indicate the need for rapid referral. However, non-specific symptoms necessitate testing strategies to differentiate between those with possible IBD and non-organic conditions. Definitive laboratory testing for IBD is not yet available. This review outlines those metrics that should be considered and monitored, then utilised to make a comprehensive referral to tertiary care for specialist paediatric gastroenterology review. Summaries are provided relating to presenting symptoms, extra-intestinal manifestations (EIMs), and alarm symptoms in order to highlight those reported most frequently. The diagnostic accuracy and importance of interpreting faecal calprotectin (FC) levels, in conjunction with additional measures, are also outlined. CONCLUSIONS Diagnostic testing to effectively identify children with IBD without the need for endoscopy is not yet available. Primary care physicians and general paediatricians must, therefore, rely on interpreting a combination of symptoms, laboratory parameters, and risk factors to assess the need for specialist referral and diagnosis.
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11
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Jo SY, Bang KS. Clinical characteristics and nursing diagnoses of pediatric patients hospitalized with inflammatory bowel disease: a single-center retrospective study in South Korea. CHILD HEALTH NURSING RESEARCH 2023; 29:218-228. [PMID: 37554089 PMCID: PMC10415836 DOI: 10.4094/chnr.2023.29.3.218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/17/2023] [Accepted: 06/26/2023] [Indexed: 08/10/2023] Open
Abstract
PURPOSE This study aimed to identify clinical characteristics of South Korean pediatric inflammatory bowel disease (IBD) in a children's hospital over the past 5 years, with a specific focus on comparing the features observed between Crohn's disease (CD) and ulcerative colitis (UC). Additionally, it aimed to examine the nursing diagnoses given to patients. METHODS This retrospective study analyzed the medical records of Korean pediatric patients under 18 years of age who were diagnosed with IBD and hospitalized at a children's hospital in Seoul, South Korea, from January 2017 to December 2021. RESULTS The number of pediatric patients diagnosed with IBD steadily increased. This finding was particularly prominent for CD patients, the majority of whom were male. Pediatric patients with CD had significantly higher rates of abdominal pain and perianal lesions, while pediatric patients with UC had a higher rate of bloody stool. Laboratory findings indicated that CD patients had higher levels of inflammatory markers and lower albumin levels than UC patients. The nursing diagnoses given during hospitalization mostly related to safety and protection, physical comfort, and gastrointestinal function. CONCLUSION This study provides insights into Korean pediatric IBD patients, enabling early detection and the development of nursing intervention strategies. From a comprehensive perspective, nursing care should not only address patients' physical needs but also their psychosocial needs.
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Affiliation(s)
- Sung-Yoon Jo
- Graduate Student, College of Nursing, Seoul National University, Seoul, Korea
| | - Kyung-Sook Bang
- Professor, College of Nursing · The Research Institute of Nursing Science, Seoul National University, Seoul, Korea
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12
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Bhangale N, Desai D, Abraham P, Gupta T, Dhoble P, Joshi A. A prospective study of inflammatory bowel disease phenotypes in extremes of age and comparison with adults. Indian J Gastroenterol 2023; 42:404-410. [PMID: 37261623 DOI: 10.1007/s12664-023-01360-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 02/09/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND AND AIMS Pediatric and elderly inflammatory bowel disease (IBD) are less explored, often in retrospective studies. The pediatric group has a more extensive and aggressive disease phenotype requiring aggressive treatments, whereas the elderly group may have less aggressive diseases. METHODS We prospectively compared disease characteristics of a single center cohort of IBD patients (pediatric age ≤ 16 years; adults 17 to 59 years; and elderly ≥ 60 years) seen between September 2018 and November 2019 with at least six months of follow-up. RESULTS Total 266 IBD patients (137 males) included 47 pediatric, 175 adults and 44 elderly patients. Among ulcerative colitis (UC) patients, pancolitis was more common in the pediatric group (p = 0.018), while the elderly group had more indolent behaviors and infrequent extraintestinal manifestations (p = 0.005). Among patients with Crohn's disease (CD), the pediatric group had more often colonic diseases (p = 0.02) and the elderly, ileal diseases (p = 0.04). The disease behavior was similar in the three age groups. Perianal disease was least common in elderly CD patients (p = 0.03). There was no treatment difference among different age groups in UC. In CD, pediatric patients needed biologics more frequently (p = 0.005), while elderly CD patients less frequently required steroids, biologics, immunosuppressants and surgery (p < 0.05). CONCLUSIONS We noted differences compared to western literature such as colonic location in pediatric CD and ileal location in elderly CD. Perianal disease was less frequent in the elderly CD group. There was no difference in treatment in the three age groups in UC, while there were no inter-age-group disease behavioral differences for UC and CD.
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Affiliation(s)
- Nikhil Bhangale
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India
| | - Devendra Desai
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India.
| | - Philip Abraham
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India
| | - Tarun Gupta
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India
| | - Pavan Dhoble
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India
| | - Anand Joshi
- Division of Gastroenterology, P D Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, 400 016, India
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Vanhelst J, Béghin L, Drumez E, Djeddi-Dine D, Tuck D, Coopman S, Gottrand F, Ley D. Validation of the IMPACT-III Questionnaire in French Children With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2023; 76:e71-e76. [PMID: 36735394 DOI: 10.1097/mpg.0000000000003716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES This study assessed the reliability and validity of the IMPACT-III questionnaire, a health-related quality of life (HRQoL) instrument, in French children with inflammatory bowel disease (IBD). METHODS Eighty-four children and adolescents (45 boys, aged 14.3 ± 2.7 years) were included in a validation study of the IMPACT-III questionnaire. Patients completed 2 questionnaires for measuring HRQoL: the IMPACT-III and the Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL). Internal consistency was assessed using Cronbach α. Factor analysis was performed on data from the IMPACT-III to help construct domains. Concurrent validity was assessed by calculating Spearman correlation coefficients. RESULTS Cronbach α for the PedsQL total score was good (0.89). The most robust factor solution was a 3-domain structure: (a) Concerns, (b) Body Image and Physical Condition, and (c) Symptoms and Socializing. All domains had good reliability (0.674-0.863). Only 2 items had to be removed. Discriminant validity was demonstrated by significant differences ( P < 0.001) in median IMPACT-III scores between inactive and active disease for the total score (83.3 vs 72.0), and for Concerns ( P < 0.002) and Symptoms and Socializing ( P < 0.001). CONCLUSIONS These results suggest that IMPACT-III appears to be a useful instrument for measuring HRQoL in French children with IBD.
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Affiliation(s)
- Jérémy Vanhelst
- From the Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Centre of Research in Epidemiology and Statistics - University of Paris Cité (CRESS), Bobigny, France
- Univ. Lille, INSERM, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000 Lille, France
| | - Laurent Béghin
- Univ. Lille, INSERM, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000 Lille, France
- Univ. Lille, INSERM, CHU Lille, CIC 1403 - Clinical Investigation Center, Lille, 59000 Lille, France
| | - Elodie Drumez
- Univ. Lille, CHU Lille, ULR 2694 - METRICS: Evaluation des technologies de santé et des pratiques médicales, 59000 Lille, France
- the Department of Biostatistics, CHU Lille, F-59000 Lille, France
| | - Djamal Djeddi-Dine
- the Department of Pediatrics, Amiens University Hospital and University of Amiens, Amiens, France
| | - Dominique Tuck
- Univ. Lille, INSERM, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000 Lille, France
- the CHU Lille, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000 Lille, France
| | - Stéphanie Coopman
- the CHU Lille, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000 Lille, France
| | - Frédéric Gottrand
- Univ. Lille, INSERM, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000 Lille, France
- the CHU Lille, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000 Lille, France
| | - Delphine Ley
- Univ. Lille, INSERM, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000 Lille, France
- the CHU Lille, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000 Lille, France
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14
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Vernon-Roberts A, Aluzaite K, Khalilipour B, Day AS. Systematic Review of Diagnostic Delay for Children With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2023; 76:304-312. [PMID: 36730088 DOI: 10.1097/mpg.0000000000003670] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVES Pediatric inflammatory bowel disease (IBD) is a complex inflammatory condition of the gut. Diagnosing IBD involves distinct longitudinal periods from first symptoms to primary care assessment, tertiary care referral, and then endoscopic confirmation. The term diagnostic delay (DD) is used if these periods are prolonged. The aim of this review was to amalgamate DD data for children with IBD, and identify factors associated with prolonged DD. METHODS Six health literature databases were searched (December 2020). Inclusion criteria for papers were children diagnosed with IBD before the age of 18 years, DD central tendency data, and to report a central tendency of their DD data, cohort >10 children. For analysis, all data were weighted by cohort sample size. RESULTS Searches identified 236 papers, and 26 were included in the final analysis with a pooled cohort of 7030 children. The overall DD periods were IBD 4.5 months [Interquartile range (IQR) 3.6-8.7 months], Crohn disease (CD) 5 months (IQR 4-7.2 months), and ulcerative colitis/indeterminate colitis/IBD-unclassified (UC/IC/IBDU) 3 months (IQR 2.2-4.9 months). The difference between subtypes was significant ( P < 0.001), with shorter DD for UC/IC/IBDU than CD ( P < 0.001) and IBD ( P < 0.001). DD periods were longer for CD than IBD ( P < 0.001). DD decreased over time for IBD ( P < 0.001) and UC ( P < 0.001) but the trend suggested an increase for CD ( P 0.069). CONCLUSIONS This data can be used to benchmark DD for children with IBD. Individual centers could determine whether improvements to awareness or infrastructure may reduce DD in order to minimize the risk of poor outcomes.
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Affiliation(s)
| | - Kristina Aluzaite
- the Department of Medicine, University of Otago, Dunedin, New Zealand
| | | | - Andrew S Day
- From the Department of Pediatrics, University of Otago, Christchurch, New Zealand
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15
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Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn's disease but not Ulcerative Colitis: a prospective cohort study. Hepatol Int 2023; 17:202-214. [PMID: 36194337 PMCID: PMC9895026 DOI: 10.1007/s12072-022-10424-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/15/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive. METHODS A total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006-2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations. RESULTS With a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants' circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD. CONCLUSIONS Individuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.
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Cohen NA, Kliper E, Zamstein N, Ziv-Baran T, Waterman M, Hodik G, Tov AB, Kariv R. Trends in Biochemical Parameters, Healthcare Resource and Medication Use in the 5 Years Preceding IBD Diagnosis: A Health Maintenance Organization Cohort Study. Dig Dis Sci 2023; 68:414-422. [PMID: 36221010 DOI: 10.1007/s10620-022-07714-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/29/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis. METHODS This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years. RESULTS This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p < 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p < 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC. CONCLUSIONS Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.
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Affiliation(s)
- Nathaniel A Cohen
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel.
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel.
| | | | | | - Tomer Ziv-Baran
- School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Matti Waterman
- Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel
- Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Gabriel Hodik
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amir Ben Tov
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Revital Kariv
- Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 6 Weizmann Street, Tel Aviv, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel
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Salguero MV, Deplewski D, Gokhale R, Wroblewski K, Sentongo T, Jan A, Kirschner BS. Growth After Menarche in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2023; 76:183-190. [PMID: 36705699 PMCID: PMC9889107 DOI: 10.1097/mpg.0000000000003667] [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] [Indexed: 01/28/2023]
Abstract
OBJECTIVES Growth impairment in pediatric patients with pediatric onset inflammatory bowel disease (IBD) is multifactorial. Reports on the effect of age at menarche on adult stature in this population are limited. This study investigated the impact of age at menarche, disease-associated factors, and mid-parental height on growth from menarche to final height (FHt) in pediatric patients with Crohn disease (CD) and ulcerative colitis (UC) and IBD unclassified (IBD-U). METHODS Subjects were enrolled from a prospectively maintained pediatric IBD database when IBD preceded menarche and dates of menarche and FHt measurements were recorded. RESULTS One hundred forty-six patients: CD 112 and UC 30/IBD-U 4. Mean age (years) at diagnosis (10.9 vs 10.1), menarche (14.4 vs 14.0), and FHt (19.6 vs 19.7). CD and UC/IBD-U patients showed significant association between Chronological age (CA) at menarche and FHt (cm, P < 0.001) but not FHt z score (FHt-Z) < -1.0 (P = 0.42). FHt-Z < -2.0 occurred in only 5 patients. Growth impairment (FHt-Z < -1.0) was associated with surgery before menarche (P = 0.03), jejunal disease (P = 0.003), low mid-parental height z score (MPH-Z) (P < 0.001), hospitalization for CD (P = 0.03) but not UC, recurrent corticosteroid, or anti-tumor necrosis factor alpha (anti-TNFα) therapy. CONCLUSIONS Early age of menarche was associated with greater potential for linear growth to FHt but not FHt-Z (P < 0.05). Surgery before menarche, jejunal disease, hospitalization for CD, low MPH, and weight z score were associated with FHt-Z < -1.0.
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Affiliation(s)
- Maria V. Salguero
- Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, IL 60637, USA
| | - Dianne Deplewski
- Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, IL 60637, USA
| | - Ranjana Gokhale
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Comer Children’s Hospital, Chicago, IL 60637, USA
| | - Kristen Wroblewski
- Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA
| | - Timothy Sentongo
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Comer Children’s Hospital, Chicago, IL 60637, USA
| | - Aseel Jan
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Comer Children’s Hospital, Chicago, IL 60637, USA
| | - Barbara S. Kirschner
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Comer Children’s Hospital, Chicago, IL 60637, USA
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Sun J, Fang F, Olén O, Song M, Halfvarson J, Roelstraete B, Khalili H, Ludvigsson JF. Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden. PLoS Med 2023; 20:e1004185. [PMID: 36821532 PMCID: PMC9949679 DOI: 10.1371/journal.pmed.1004185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 01/24/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. METHODS AND FINDINGS In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD. CONCLUSIONS Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD.
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Affiliation(s)
- Jiangwei Sun
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Fang Fang
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ola Olén
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden.,Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.,Broad Institute of MIT and Harvard, Cambridge Massachusetts, United States of America
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.,Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, United States of America
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Huang J, Walters TD. Growth Impairment in Pediatric Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:151-172. [DOI: 10.1007/978-3-031-14744-9_12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
OBJECTIVES Perianal fistulas are among the most severe complications of Crohn disease, but limited data regarding their outcomes are available in children. Our objective was to determine predictors of perianal fistula healing among pediatric patients newly diagnosed with Crohn disease. METHODS This single-center retrospective study followed patients with perianal fistulas at Crohn disease diagnosis until fistula healing. Time to healing was analyzed using Cox proportional hazard regression models considering relevant covariates including patient demographics, disease characteristics, medical therapies [no anti-tumor necrosis factor (TNF)α therapy, anti-TNFα therapy ±therapeutic drug monitoring], and perianal surgical procedures including fistulotomy, fistulectomy, removal of perianal lesions, seton placement, and incision and drainage. RESULTS Of 485 patients identified, 107 (22%) had a perianal fistula at Crohn disease diagnosis. Multivariate analysis identified that perianal fistulotomy, fistulectomy, and lesion removal [hazard ratio (HR) 0.46; P = 0.028], non-White race (HR 0.30, P < 0.01), and male sex (HR 0.42; P = 0.02) were associated with delayed fistula healing. Faster fistula healing was associated with treatment with anti-TNFα with therapeutic drug monitoring (HR 1.78, P = 0.009). There were no other differences in healing by treatment. CONCLUSIONS Fistulotomy, fistulectomy, and perianal lesion removal as well as non-White race were associated with delayed fistula healing. Anti-TNFα therapy was associated with faster fistula healing when combined with therapeutic drug monitoring, compared to all other medical treatment groups, including anti-TNFα therapy without therapeutic drug monitoring.
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21
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Diagnostic Delay in Pediatric Inflammatory Bowel Disease: A Systematic Review. Dig Dis Sci 2022; 67:5444-5454. [PMID: 35288834 DOI: 10.1007/s10620-022-07452-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/14/2022] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Delays in diagnosing pediatric inflammatory bowel disease (IBD) are common, but the extent of this delay remains unclear due to variations in reported time-periods between studies. The objectives of this systematic review were to examine the extent of diagnostic delay in pediatric IBD and examine any association between specific characteristics and length of diagnostic delay. METHODS We identified studies from several medical bibliographical databases (EMBASE, Medline and CINAHL) from their inception to April 2021. Studies examining pediatric cohorts (< 18 years old) defined as having a diagnosis of Crohn's Disease (CD), ulcerative colitis (UC), or by the more general definition of IBD, and reporting a median time-period between the onset of symptoms and a final diagnosis (diagnostic delay) were included. Two reviewers selected each study, extracted data, and assessed their quality using the Newcastle-Ottawa scale. Narrative synthesis was then used to examine the extent of overall diagnostic delay and delay associated with specific sample characteristics. RESULTS Of the 10,119 studies initially identified, 24 were included in the review. The overall median diagnostic delay range was 2-10.4 months for IBD, 2.0-18.0 months for UC and 4.0-24.0 months for CD. However, for approximately two thirds of UC (68.8%) and CD (66.7%) studies, delay ranged from 2.0-3.0 and 4.0-6.3 months, respectively. A longer delay was significantly associated with several sample characteristics; however, these were too infrequently examined to draw robust conclusion on their role. CONCLUSION Children continue to wait several months for a final diagnosis of IBD, and those with CD experience longer delay than those with UC. The role of specific characteristics on delay needs further exploration.
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22
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Brown SC, Whelan K, Frampton C, Wall CL, Gearry RB, Day AS. Food-Related Quality of Life in Children and Adolescents With Crohn's Disease. Inflamm Bowel Dis 2022; 28:1838-1843. [PMID: 35166341 PMCID: PMC9713495 DOI: 10.1093/ibd/izac010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Food-related quality of life (FRQoL) encompasses the psychosocial elements of eating and drinking. The FRQoL of children and adolescents with inflammatory bowel disease has not yet been assessed. This study aimed to evaluate the utility of the validated FR-Qol-29 instrument in children with Crohn's disease (CD). METHODS Children diagnosed with CD, a shared home environment healthy sibling, and healthy control subjects 6 to 17 years of age were recruited to this single-center, prospective, cross-sectional study. Children or their parent or guardian completed the FR-QoL-29 instrument. Internal consistency was assessed by completing Cronbach's α. Construct validity was established by correlating the CD FR-QoL-29 sum scores with the Physician Global Assessment and Pediatric Crohn Disease Activity Index scores. The discriminant validity was analyzed using a 1-way analysis of variance, and a Spearman's correlation coefficient test was completed to identify any correlations associated with FRQoL. RESULTS Sixty children or their parent or guardian completed the FR-QoL-29 instrument (10 children in each subgroup). The internal consistency was excellent (Cronbach's α = 0.938). The mean FR-QoL-29 sum scores were 94.3 ± 27.6 for CD, 107.6 ± 20 for siblings, and 113.7 ± 13.8 for control subjects (P = .005). Those with higher disease activity had worse FRQoL (Physician Global Assessment P = .021 and Pediatric Crohn Disease Activity Index P = .004). Inflammatory bowel disease FR-QoL-29 sum scores correlated with weight (P = .027), height (P = .035), body mass index (P = .023), and age (P = .015). CONCLUSIONS FRQoL is impaired in children with CD. Healthy siblings also have poorer FRQoL than control subjects. Several clinical factors are associated with poorer FRQoL in children with CD including age and level of nutritional risk (weight, height, and body mass index). Further research is required validate these findings and to develop strategies for the prevention or treatment of impaired FRQoL in children with CD.
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Affiliation(s)
- Stephanie C Brown
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Kevin Whelan
- Department of Nutritional Sciences, King’s College London, London, United Kingdom
| | - Chris Frampton
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Catherine L Wall
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Richard B Gearry
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
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Vanhelst J, Beghin L, Coopman S, Labreuche J, Djeddi D, Gottrand F, Turck D, Ley D. Physical fitness in children and adolescents with inflammatory bowel disease: protocol for a case-control study. BMJ Open 2022; 12:e063403. [PMID: 36220315 PMCID: PMC9557790 DOI: 10.1136/bmjopen-2022-063403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract, associated with adverse health consequences that may adversely influence physical activity and body composition in youth. These effects may lead to changes in physical fitness, which is positively associated with health-related outcomes. The aim is to assess health-related physical fitness levels in paediatric patients with IBD and to compare these levels with those in healthy matched controls. METHODS AND ANALYSIS This trial is a bicentric case-control study. Fifty paediatric patients with IBD and 50 matched healthy controls will be recruited (1:1), and physical fitness levels (cardiorespiratory fitness, muscular strength, speed/agility and flexibility) will be assessed. The primary outcome is cardiorespiratory fitness, which will be compared between children and adolescents with IBD and healthy controls matched for age, sex and body mass index class. We will assess whether the two groups differ with respect to other physical fitness components and cardiovascular risk in adulthood according to sex-specific cut-offs for a healthy cardiorespiratory fitness level in adolescents. We will identify relationships between physical fitness and characteristics of IBD, quality of life and daily physical activity. ETHICS AND DISSEMINATION This study was approved by the Research Ethics Committee (Comité de Protection des Personnes, Centre-Ouest I, Tours, France; No 2019-A02651-56) and was declared to the Commission Nationale de l'Informatique et des Libertés. All procedures will be performed according to the ethical standards of the 1975 Declaration of Helsinki, as revised in 2008, and the European Union's Guidelines for Good Clinical Practice. Written informed consent will be obtained from the youths and their parents. Research findings will be disseminated in peer-reviewed journals and scientific meetings, as well as in social media and IBD family support groups. TRIAL REGISTRATION NUMBER NCT04647578.
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Affiliation(s)
- Jérémy Vanhelst
- Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Centre of Research in Epidemiology and Statistics - University of Paris Cité (CRESS), Bobigny, France
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France
| | - Laurent Beghin
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France
| | - Stéphanie Coopman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, F-59000, Lille, France
| | - Julien Labreuche
- Univ. Lille, CHU Lille, EA 2694 - Public Health: epidemiology and quality of care, F-59000, Lille, France
| | - Djamal Djeddi
- Department of Paediatrics, Amiens University Hospital and University of Amiens, Amiens, France
| | - Frédéric Gottrand
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, F-59000, Lille, France
| | - Dominique Turck
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, F-59000, Lille, France
| | - Delphine Ley
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France
- Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Lille University Jeanne de Flandre Children's Hospital, F-59000, Lille, France
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Progression to Anti-TNF Treatment in Very Early Onset Inflammatory Bowel Disease Patients. J Pediatr Gastroenterol Nutr 2022; 75:473-479. [PMID: 35815885 DOI: 10.1097/mpg.0000000000003551] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Limited data are currently available regarding anti-tumor necrosis factor (TNF) use and outcomes in very early onset inflammatory bowel disease (VEOIBD) patients. We aimed to assess the long-term outcomes and time to progression to anti-TNF treatment in VEOIBD patients. METHODS We retrospectively reviewed IBD patients diagnosed under 6 years of age, between January 2005 and December 2019, from the British-Columbia (BC) Pediatric IBD database. Demographic data, disease characteristics, disease location and severity were documented. Data on anti-TNF treatment at initiation and during follow up including type of biologic, dosing, and response were collected. Kaplan-Meier curves were used to assess the number of years to progression to anti-TNF treatment and the parameters influencing commencement. RESULTS Eighty-nine patients with VEOIBD were diagnosed during the study period. Median age at diagnosis was 3.8 years [interquartile range (IQR) 2.6-5.1], 45.3% had Crohn disease (CD) and 62.8% were males. Median duration of follow up was 6.39 years (IQR 3.71-10.55). Anti-TNF treatment was started on 39.5% of patients and 7.0% underwent surgery. Rapid progression to biologic treatment was associated with Perianal fistulizing disease or stricturing disease in CD patients ( P = 0.026, P = 0.033, respectively), and disease severity ( P = 0.017) in ulcerative colitis(UC) patients. The median dose of infliximab at 1 year was 10 mg/kg (IQR 7.5-11) and a median dose interval of 4.5 weeks (IQR 4-6). Clinical remission was reported in 61.8% of patients on their first biologic agent. CONCLUSIONS The response rate was higher than previously reported and might be due to higher infliximab dosing with shorter infusion intervals than standard dosing.
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25
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Kuloglu Z, Çetin F, Urgancı N, Önal Z, Sarı S, Yüksekkaya H, Çaltepe G, Kutluk G, Dumlupinar E. Nutritional characteristic of children with inflammatory bowel disease in the nationwide inflammatory bowel disease registry from the Mediterranean region. Eur J Clin Nutr 2022; 76:1289-1296. [PMID: 35173290 DOI: 10.1038/s41430-022-01094-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 01/11/2022] [Accepted: 01/26/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND/OBJECTIVES We analyzed the nationwide pediatric inflammatory bowel disease (PIBD) registry (1998-2016), to evaluate the nutritional status at the time of diagnosis. SUBJECTS/METHODS Nine types of nutritional status by the combination of weight-for-length (<2 years)/body mass index (>2 years) and length/height-for-age with three categories (<-2, -2 to 2, and >2 SD) were described. Malnutrition was defined by WHO criteria. Univariate and multivariate regression analysis was used to identify risk factors for malnutrition. RESULTS In total, 824 IBD patients (498 Ulcerative colitis (UC); 289 Crohn's Disease (CD); 37 Indeterminate Colitis (IC); 412 male; the median age 12.5 years) were eligible. The prevalence of eutrophy, wasting/thinness, stunting, overweight, tall stature, concurrent wasting/thinness and stunting, tall stature with overweight, tall stature with wasting/thinness, and short stature with overweight were 67.4%, 14.9%, 6.6%, 3.1%, 3.2%, 3.3%, 1.1%, 0.4%, and 0.1%, respectively. The prevalence of malnutrition was 32.7%, indicating a higher prevalence in CD (p < 0.001). Incidence of overweight was less common in the CD than UC and IC (p < 0.001). Multivariate analysis revealed that age of onset (>10 years), prepubertal stage, severe disease activity, perianal involvement, and high C reactive protein level were independently associated with malnutrition in pediatric IBD. CONCLUSION We showed the frequency of nutritional impairment in PIBD. The percentage of overweight subjects was lower than the other studies. The age of onset, disease activity, CRP level, perianal involvement, and pubertal stage were associated with a higher risk for developing malnutrition. Our results also confirmed that CD patients are particularly vulnerable to nutritional impairment. CLINICAL TRIAL NUMBER ClinicalTrials.gov Identifier: NCT04457518.
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Affiliation(s)
- Zarife Kuloglu
- School of Medicine, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Ankara University, Ankara, Turkey.
| | - Funda Çetin
- Faculty of Medicine, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Ege University, İzmir, Turkey
| | - Nafiye Urgancı
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, Turkey
| | - Zerrin Önal
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Bakırköy Dr. Sadi Konuk Research and Training Center, İstanbul, Turkey
| | - Sinan Sarı
- Faculty of Medicine, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Gazi University University, Ankara, Turkey
| | - Hasan Yüksekkaya
- Meram Faculty of Medicine, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Necmettin Erbakan University, Konya, Turkey
| | - Gönül Çaltepe
- Faculty of Medicine, Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Ondokuz Mayıs University, Samsun, Turkey
| | - Günsel Kutluk
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Bakırköy Dr. Sadi Konuk Research and Training Center, İstanbul, Turkey
| | - Ebru Dumlupinar
- School of Medicine, Department of Biostatistics, Ankara University , Ankara, Turkey
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The Role of Magnetic Resonance Enterography in Crohn’s Disease: A Review of Recent Literature. Diagnostics (Basel) 2022; 12:diagnostics12051236. [PMID: 35626391 PMCID: PMC9140029 DOI: 10.3390/diagnostics12051236] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/06/2022] [Accepted: 05/13/2022] [Indexed: 11/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) is the term used to identify a form of chronic inflammation of the gastrointestinal tract that primarily contemplates two major entities: ulcerative colitis (UC) and Crohn’s disease (CD). The classic signs are abdominal pain and diarrhoea that correlate with the localization of gastro-enteric disease, although in this pathology extraintestinal symptoms may coexist. The diagnosis of CD relies on a synergistic combination of clinical, laboratory (stool and biochemical), cross-sectional imaging evaluation, as well as endoscopic and histologic assessments. The purpose of this paper is to prove the role of imaging in the diagnosis and follow-up of patients with CD with particular focus on recent innovations of magnetic resonance enterography (MRE) as a pivotal diagnostic tool, analysing the MRE study protocol and imaging features during the various phases of disease activity and its complications.
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Huang JG, Wong YKY, Chew KS, Tanpowpong P, Calixto Mercado KS, Reodica A, Rajindrajith S, Chang KC, Ni YH, Treepongkaruna S, Lee WS, Aw MM. Epidemiological characteristics of Asian children with inflammatory bowel disease at diagnosis: Insights from an Asian-Pacific multi-centre registry network. World J Gastroenterol 2022; 28:1830-1844. [PMID: 35633913 PMCID: PMC9099197 DOI: 10.3748/wjg.v28.i17.1830] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 01/03/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There remains a dearth of Asian epidemiological literature for paediatric inflammatory bowel disease (PIBD). AIM To describe the presenting features of PIBD from 7 Asia-Pacific pediatric gastroenterology centers via a central standardised electronic data platform. METHODS Clinical, endoscopic and radiologic data at diagnosis from the registry were extracted between 1st January 1995 to 31st December 2019. Disease phenotypic characteristics were classified as per the Paris classification system. RESULTS There was a distinct rise in new PIBD cases: Nearly half (48.6%) of the cohort was diagnosed in the most recent 5 years (2015-2019). The ratio of Crohn's disease (CD):Ulcerative colitis (UC):IBD-Unclassified was 55.9%:38.3%:5.8%. The mean age was 9.07 years with a high proportion of very early onset IBD (VEO-IBD) (29.3%) and EO-IBD (52.7%). An over-representation of the Indian/South Asian ethnic group was observed which accounted for 37.0% of the overall Singapore/Malaysia subcohort (6.8%-9.0% Indians in census). Indian/South Asian CD patients were also most likely to present with symptomatic perianal disease (P = 0.003). CD patients presented with significantly more constitutional symptoms (fever, anorexia, malaise/fatigue and muscle-wasting) than UC and higher inflammatory indices (higher C-reactive protein and lower albumin levels). CONCLUSION We observed a high incidence of VEO-IBD and an over-representation of the Indian ethnicity. South Asian CD patients were more likely to have symptomatic perianal disease.
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Affiliation(s)
- James Guoxian Huang
- Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore
- Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Yoko Kin Yoke Wong
- Epidemiology, Singapore Clinical Research Institute, Singapore 138669, Singapore
| | - Kee Seang Chew
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur 50603, Malaysia
| | - Pornthep Tanpowpong
- Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | | | - Almida Reodica
- Department of Pediatrics, The Medical City, Manila 0900, Philippines
| | - Shaman Rajindrajith
- Department of Pediatrics, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka
| | - Kai-Chi Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei 100229, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei 100229, Taiwan
| | - Suporn Treepongkaruna
- Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Way-Seah Lee
- Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur 50603, Malaysia
| | - Marion Margaret Aw
- Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore
- Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
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Wang S, Bai M, Shu Q, Liu Z, Shao Y, Xu K, Xiong X, Liu H, Li Y. Modulating Effect of Paeonol on Piglets With Ulcerative Colitis. Front Nutr 2022; 9:846684. [PMID: 35495936 PMCID: PMC9045399 DOI: 10.3389/fnut.2022.846684] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Piglet enteritis is a major problem that needs to be solved urgently in modern pig production. Paeonol (Pae) has been used as a novel treatment option due to its good medicinal value. This study purported to elucidate the regulatory mechanism of Pae on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in weaned piglets. A total of 36 crossbred (Duroc × Landrace × Yorkshire) weaned piglets were stochastically split into six groups: the control group, DSS group, 0.2% Pae group, 0.4% Pae group, 0.8% Pae group, and mesalazine group. The control and DSS groups were fed with a basic diet, the three Pae and mesalazine groups were fed with 0.2, 0.4, 0.8%, and 2 g mesalazine per kilogram of basic diet throughout the study. On the 15th day of the test period, the control group was gavaged with 10 ml of normal saline, while the remaining five groups were gavaged with 10 ml 5% DSS solution for 13 days. The study lasted for 27 days. The results showed that the 0.8% Pae group significantly increased the average daily feed intake (ADFI) and Occludin mRNA expression in the colon of piglets (P < 0.05). The 0.2% Pae group markedly increased the average daily gain (ADG) and zonula occludens-1 (ZO-1) mRNA expression (P < 0.05). In the 0.2% and 0.4% Pae groups, the feed-to-gain ratio (F/G) was significantly reduced and the mRNA expression levels of Caspase-8, respectively, markedly enhanced the mRNA expression levels of transforming growth factor-β (TGF-β) and interleukins-4 (IL-4) (P < 0.05). In the 0.8% Pae group, the relative abundance of Campilobacterota was significantly reduced (P < 0.05). In the 0.4% Pae group, the relative abundance of Firmicutes was notably increased (P < 0.05). In the 0.2 and 0.8% Pae groups, the relative abundance of Prevotella was markedly increased (P < 0.05). In the 0.2% Pae group, the contents of propionic acid, butyric acid, and valerate acid were markedly higher (P < 0.05). Thus, it is speculated that Pae may regulate the balance of anti-inflammatory/pro-inflammatory factors, improve intestinal tight junction expression, reduce apoptosis, and improve intestinal microflora structure and growth performance of piglets, thereby restoring intestinal barrier function and alleviating DSS-induced UC in piglets.
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Affiliation(s)
- Shanshan Wang
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, China
| | - Miaomiao Bai
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Key Laboratory of Agro-ecological Processes in Subtropical Region; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Qingyan Shu
- Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences (CAS), Beijing, China
| | - Zhengan Liu
- Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences (CAS), Beijing, China
| | - Yirui Shao
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Key Laboratory of Agro-ecological Processes in Subtropical Region; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Kang Xu
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Key Laboratory of Agro-ecological Processes in Subtropical Region; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Xia Xiong
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Key Laboratory of Agro-ecological Processes in Subtropical Region; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Hongnan Liu
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Key Laboratory of Agro-ecological Processes in Subtropical Region; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Yao Li
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, China
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Chen A, Stein R, Baldassano RN, Huang J. Learning Longitudinal Patterns and Subtypes of Pediatric Crohn Disease Treated With Infliximab via Trajectory Cluster Analysis. J Pediatr Gastroenterol Nutr 2022; 74:383-388. [PMID: 34908016 PMCID: PMC8885908 DOI: 10.1097/mpg.0000000000003370] [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] [Indexed: 12/10/2022]
Abstract
BACKGROUND The objective of this study is to identify subgroups of pediatric Crohn disease (CD) who had differential responses to the infliximab treatment through trajectory cluster analysis of disease activity using data from electronic health records. METHODS We conducted a retrospective study of 295 pediatric patients with CD who had been treated with infliximab for a minimum of one year at the Center for Inflammatory Bowel Disease at The Children's Hospital of Philadelphia between January 2010 and December 2017. The evolution of disease was described, and subgroups of patients were identified using trajectory analysis of longitudinal data of C-reactive protein (CRP). We compared patient characteristics, biomarker for disease activity, and long-term surgical outcomes across subgroups. Cox regression models were used to evaluate the added value of the subgroup classification to baseline phenotype and location in prediction of long-term surgical outcomes. RESULTS We identified three subgroups of patients with differential relapse-and-remission profiles (n = 33, 65 and 197 from subgroup 1 to 3), which represented patients with a higher risk of infliximab non-response, with infliximab response but with occasional disease flares, and patients with long-term response. Patients with the best treatment response had a significantly lower frequency of complicated disease phenotypes (P = 0.01), including perianal involvement (P = 0.05), lower baseline CRP (P < 0.01) and calprotectin (P = 0.01), and lowest risk of IBD-related gastrointestinal surgery within 10 years of starting treatment (P < 0.01). CONCLUSIONS Readily available longitudinal data from electronic health records can be leveraged to provide deeper characterization of treatment response in pediatric CD.
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Affiliation(s)
- Andrew Chen
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | - Ronen Stein
- Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
| | - Robert N. Baldassano
- Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
| | - Jing Huang
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
- Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA
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30
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Guo W, Chen S, Li C, Xu J, Wang L. Application of Disulfiram and its Metabolites in Treatment of Inflammatory Disorders. Front Pharmacol 2022; 12:795078. [PMID: 35185542 PMCID: PMC8848744 DOI: 10.3389/fphar.2021.795078] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 12/17/2021] [Indexed: 12/27/2022] Open
Abstract
Disulfiram has been used clinically for decades as an anti-alcoholic drug. Recently, several studies have demonstrated the anti-inflammatory effects of disulfiram and its metabolism, which can alleviate the progression of inflammation in vivo and in vitro. In the current study, we summarize the anti-inflammatory mechanisms of disulfiram and its metabolism, including inhibition of pyroptosis by either covalently modifying gasdermin D or inactivating nod-like receptor protein 3 inflammasome, dual effects of intracellular reactive oxygen species production, and inhibition of angiogenesis. Furthermore, we review the potential application of disulfiram and its metabolism in treatment of inflammatory disorders, such as inflammatory bowel disease, inflammatory injury of kidney and liver, type 2 diabetes mellitus, sepsis, uveitis, and osteoarthritis.
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Affiliation(s)
- Wenyi Guo
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shihong Chen
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chengqing Li
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jianwei Xu
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lei Wang
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Shandong University, China
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31
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Sulkanen E, Repo M, Huhtala H, Hiltunen P, Kurppa K. Impact of diagnostic delay to the clinical presentation and associated factors in pediatric inflammatory bowel disease: a retrospective study. BMC Gastroenterol 2021; 21:364. [PMID: 34620103 PMCID: PMC8495911 DOI: 10.1186/s12876-021-01938-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 09/20/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Undelayed diagnosis is thought to be a major determinant for good prognosis in pediatric inflammatory bowel disease (PIBD). However, factors predicting diagnostic delay and the consequences of this remain poorly defined. We investigated these issues in a well-defined cohort of PIBD patients. METHODS Comprehensive electronic data were collected from 136 PIBD patients retrospectively. Diagnostic delay was further classified into < 6 and ≥ 6 months, and < 12 and ≥ 12 months. Logistic regression was used to calculate whether the delay was associated with clinical features and/or risk of complications and co-morbidities at diagnosis. RESULTS The median age of patients was 12.4 years and 43.4% were females. Altogether 35.5% had Crohn´s disease (CD), 59.1% ulcerative colitis (UC) and 6.6% IBD undefined (IBD-U). The median delay before diagnosis was 5.0 months in all, 6.6 months in CD, 4.1 months in UC, and 9.8 months in IBD-U (UC vs. CD, p = 0.010). In all but IBD-U most of the delay occurred before tertiary center referral. Abdominal pain predicted a delay > 6 months in all PIBD (OR 2.07, 95% CI 1.00-4.31) and in UC patients (3.15, 1.14-8.7), while bloody stools predicted a shorter delay in all PIBD (0.28, 0.14-0.59) patients and in CD (0.10, 0.03-0.41) patients. A delay > 6 months was associated with a higher frequency of complications (2.28, 1.01-5.19). CONCLUSIONS Delay occurred mostly before specialist consultation, was longer in children presenting with abdominal pain and in CD and was associated with risk of complications. These findings emphasize the roles of active case-finding and prompt diagnostic evaluations.
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Affiliation(s)
- Emmiina Sulkanen
- Tampere Center for Child Health Research, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Marleena Repo
- Tampere Center for Child Health Research, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Pauliina Hiltunen
- Tampere Center for Child Health Research, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Kalle Kurppa
- Tampere Center for Child Health Research, Tampere University, Arvo Ylpön katu 34, 33520, Tampere, Finland. .,Department of Pediatrics, Tampere University Hospital, Tampere, Finland. .,Department of Pediatrics, Seinäjoki University Hospital, Seinäjoki, Finland. .,University Consortium of Seinäjoki, Seinäjoki, Finland.
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Vanhelst J, Béghin L, Turck D, Labreuche J, Coopman S, Gottrand F, Ley D. Daily physical activity patterns in children and adolescents with inflammatory bowel disease. Pediatr Res 2021; 90:847-852. [PMID: 33469176 DOI: 10.1038/s41390-020-01313-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/14/2020] [Accepted: 11/19/2020] [Indexed: 01/30/2023]
Abstract
BACKGROUND The aim of this study was to assess PA patterns among children and adolescents with inflammatory bowel disease (IBD). METHODS Sixty participants with IBD (42 Crohn's disease [CD], 10 ulcerative colitis [UC], and 8 IBD-unclassified [IBD-U], 30 male patients) in remission (n = 45) or with mild disease (n = 15) were compared with 60 healthy age- and sex-matched controls. Each participant wore a triaxial accelerometer during 4 consecutive days for objective daily PA quantification. RESULTS Overall, there was no significant difference in daily PA patterns between patients with IBD and healthy controls, with 31.7% of patients with IBD and 38.3% of healthy controls fulfilling the recommendation of 60 min of moderate-to-vigorous physical activity (MVPA) daily (NS). Male patients with IBD spent significantly less time in MVPA compared with matched healthy controls (mean difference, 16.2 min day-1; p < 0.05). No difference was observed for female patients with IBD. No difference in sedentary pattern between male patients with IBD and controls was found. CONCLUSIONS Children and adolescents with inactive or mildly active IBD have similar PA patterns compared with healthy controls, except for male patients who have reduced moderate-to-vigorous PA. By far, most patients with IBD do not fulfill the MVPA recommendations for health benefits. IMPACT There is few data on PA patterns in pediatric patients with IBD. Methodological issues to assess PA limit the strengths of these studies. Pediatric IBD patients with inactive or mildly active IBD have similar physical activity patterns compared with healthy controls, except for male patients who have reduced moderate-to-vigorous PA. Most patients with IBD do not fulfill the MVPA recommendations for health benefits.
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Affiliation(s)
- Jérémy Vanhelst
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France. .,CIC 1403 - Clinical Investigation Center, CHU Lille, 59000, Lille, France.
| | - Laurent Béghin
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,CIC 1403 - Clinical Investigation Center, CHU Lille, 59000, Lille, France
| | - Dominique Turck
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
| | - Julien Labreuche
- Univ. Lille, CHU Lille, ULR 2694 - METRICS: Evaluation des technologies de santé et des pratiques médicales, 59000, Lille, France
| | - Stéphanie Coopman
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
| | - Frédéric Gottrand
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
| | - Delphine Ley
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.,Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital, 59000, Lille, France
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Goddard GR, Lim IIP, Cheng YC, Velazco CS, Jenkins T, Rosen NG, Kotagal M, Garrison AP, Falcone R, Rymeski B, Frischer JS. A child presents with perianal symptoms - how often is this Crohn's disease? J Pediatr Surg 2021; 56:1618-1622. [PMID: 33280851 DOI: 10.1016/j.jpedsurg.2020.11.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 11/05/2020] [Accepted: 11/14/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND The cumulative incidence and predictors of future diagnosis of Crohn's disease (CD) following presentation with perianal symptoms, such as anorectal abscess, fistula or fissure, is unknown. METHODS A 5-year retrospective review of children presenting with perianal symptoms without prior CD diagnosis was performed. Institutional cumulative incidence of CD was calculated to determine the risk of CD presenting with perianal symptoms. RESULTS 1140 children presented for evaluation of an anorectal abscess (n = 232), fistula (n = 49), or fissure (n = 859). Thirty-five were later diagnosed with CD, resulting in an incidence of 3%. Prognostic indicators of future CD diagnosis included increased age per every additional year (RR 1.19, 95% CI: 1.14-1.25, p < 0.001), male sex (RR 2.12, 95% CI 1.07-4.22, p = 0.024), or perianal fistula (RR 4.67, 95% CI 2.26-9.67, p = 0.022). Among those diagnosed with CD, 57% experienced and had a documented history of a CD-associated symptom prior to perianal symptom onset. Absence of symptoms resulted in delayed diagnosis (43 vs 3 days, p < 0.02). CONCLUSION Of children presenting with a perianal symptom, three percent will eventually be diagnosed with CD. At highest risk (35%) were males aged 10 years or older with a perianal fistula; which should prompt expeditious workup.
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Affiliation(s)
- Gillian R Goddard
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Irene Isabel P Lim
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States.
| | - Yu-Chia Cheng
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Cristine S Velazco
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Todd Jenkins
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Nelson G Rosen
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Meera Kotagal
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Aaron P Garrison
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Richard Falcone
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Beth Rymeski
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
| | - Jason S Frischer
- Colorectal Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States
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Steell L, Gray SR, Russell RK, MacDonald J, Seenan JP, Wong SC, Gaya DR. Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease. Nutrients 2021; 13:nu13082899. [PMID: 34445056 PMCID: PMC8398806 DOI: 10.3390/nu13082899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/18/2021] [Accepted: 08/20/2021] [Indexed: 12/11/2022] Open
Abstract
Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn’s disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.
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Affiliation(s)
- Lewis Steell
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK; (L.S.); (S.R.G.)
| | - Stuart R. Gray
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK; (L.S.); (S.R.G.)
| | - Richard K. Russell
- Department of Paediatric Gastroenterology, Royal Hospital for Sick Children, Edinburgh EH16 4TJ, UK;
| | - Jonathan MacDonald
- Department of Gastroenterology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; (J.M.); (J.P.S.)
| | - John Paul Seenan
- Department of Gastroenterology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; (J.M.); (J.P.S.)
| | - Sze Choong Wong
- Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow G51 4TF, UK;
| | - Daniel R. Gaya
- Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK
- Correspondence:
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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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Sun Y, Zhang Z, Zheng CQ, Sang LX. Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review. World J Gastroenterol 2021; 27:2963-2978. [PMID: 34168401 PMCID: PMC8192286 DOI: 10.3748/wjg.v27.i22.2963] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/10/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.
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Affiliation(s)
- Yan Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Zhe Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Chang-Qing Zheng
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
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Wong K, Isaac DM, Wine E. Growth Delay in Inflammatory Bowel Diseases: Significance, Causes, and Management. Dig Dis Sci 2021; 66:954-964. [PMID: 33433805 DOI: 10.1007/s10620-020-06759-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/02/2020] [Indexed: 12/16/2022]
Abstract
Growth delay with height and weight impairment is a common feature of pediatric inflammatory bowel diseases (PIBD). Up to 2/3 of Crohn Disease patients have impaired weight at diagnosis, and up to 1/3 have impaired height. Ulcerative colitis usually manifests earlier with less impaired growth, though patients can be affected. Ultimately, growth delay, if not corrected, can reduce final adult height. Weight loss, reduced bone mass, and pubertal delay are also concerns associated with growth delay in newly diagnosed PIBD patients. The mechanisms for growth delay in IBD are multifactorial and include reduced nutrient intake, poor absorption, increased fecal losses, as well as direct effects from inflammation and treatment modalities. Management of growth delay requires optimal disease control. Exclusive enteral nutrition (EEN), biologic therapy, and corticosteroids are the primary induction strategies used in PIBD, and both EEN and biologics positively impact growth and bone development. Beyond adequate disease control, growth delay and pubertal delay require a multidisciplinary approach, dependent on diligent monitoring and identification, nutritional rehabilitation, and involvement of endocrinology and psychiatry services as needed. Pitfalls that clinicians may encounter when managing growth delay include refeeding syndrome, obesity (even in the setting of malnutrition), and restrictive diets. Although treatment of PIBD has improved substantially in the last several decades with the era of biologic therapies and EEN, there is still much to be learned about growth delay in PIBD in order to improve outcomes.
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Affiliation(s)
- Kerry Wong
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Edmonton Clinic Health Academy, University of Alberta, Stollery Children's Hospital, Room 4-577, 11405 87th Avenue NW, Edmonton, AB, T6G 1C9, Canada
| | - Daniela Migliarese Isaac
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Edmonton Pediatric IBD Clinic (EPIC), Edmonton Clinic Health Academy, University of Alberta, Stollery Children's Hospital, Room 4-577, 11405 87th Avenue NW, Edmonton, AB, T6G 1C9, Canada
| | - Eytan Wine
- Division of Pediatric Gastroenterology and Nutrition, Departments of Pediatrics and Physiology, Edmonton Pediatric IBD Clinic (EPIC), Edmonton Clinic Health Academy, University of Alberta, Stollery Children's Hospital, Room 4-577, 11405 87th Avenue NW, Edmonton, AB, T6G 1C9, Canada.
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Jin HY, Lim JS, Lee Y, Choi Y, Oh SH, Kim KM, Yoo HW, Choi JH. Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease. BMC Pediatr 2021; 21:35. [PMID: 33446154 PMCID: PMC7807425 DOI: 10.1186/s12887-021-02496-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 01/07/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Endocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents. METHODS This study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3 [25(OH)D3] levels, and BMD were reviewed retrospectively. RESULTS Short stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3 level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below - 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased. CONCLUSIONS Vitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.
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Affiliation(s)
- Hye-Young Jin
- Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Jae-Sang Lim
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Yena Lee
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Yunha Choi
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Seak-Hee Oh
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Kyung-Mo Kim
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Han-Wook Yoo
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Jin-Ho Choi
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea.
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Whole Transcription Profile of Responders to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease. Pharmaceutics 2021; 13:pharmaceutics13010077. [PMID: 33429950 PMCID: PMC7830359 DOI: 10.3390/pharmaceutics13010077] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/31/2020] [Accepted: 01/06/2021] [Indexed: 12/16/2022] Open
Abstract
Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
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Ashton JJ, Green Z, Young A, Borca F, Coelho T, Batra A, Afzal NA, Ennis S, Johnson MJ, Beattie RM. Growth failure is rare in a contemporary cohort of paediatric inflammatory bowel disease patients. Acta Paediatr 2021; 110:326-334. [PMID: 32485032 DOI: 10.1111/apa.15383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/15/2020] [Accepted: 05/27/2020] [Indexed: 11/28/2022]
Abstract
AIM We assessed growth in a paediatric inflammatory bowel disease (PIBD) cohort. METHODS Paediatric inflammatory bowel disease patients were eligible if they were diagnosed at Southampton Children's Hospital from 2011 to 2018. Weight and height standard deviation scores (SDS) were retrieved. Mean SDS values, SDS change and anti-TNF status were analysed at diagnosis and during follow-up. RESULTS Four hundred and ninety patients were included, 313 with Crohn's disease (CD). CD patients presented with mean height SDS -0.13, -0.1 at 1-year, -0.11 at 2-years and -0.03 at 5 years, reflecting preserved linear growth. There was no significant height-SDS change from diagnosis to 5-year follow-up, +0.12, 95%-CI: 0.48 to -0.24. Mean weight-SDS at diagnosis was -0.39, driven by CD patients (-0.65). Mean weight-SDS approached 0 after 1 year and remained at the 50th centile throughout follow-up. Growth in ulcerative colitis was maintained. In multivariable regression males had worse height growth from diagnosis to transition (P = .036). Anti-TNF treatment (P = .013) and surgical resection (P = .005) were also associated with poorer linear growth. Patients treated with anti-TNF therapy had lower height-SDS compared to those never treated with anti-TNF at 1 year (-0.2 vs -0.01, P = .22), 2-years (-0.27 vs -0.01, P = .07) and 5 years (-0.21 vs 0.25, P = .051). CONCLUSION Height was generally maintained in Crohn's disease, and impaired linear growth was rare in this cohort.
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Affiliation(s)
- James J. Ashton
- Department of Paediatric Gastroenterology Southampton Children's Hospital Southampton UK
- Department of Human Genetics and Genomic Medicine University of Southampton Southampton UK
| | - Zachary Green
- Department of Paediatric Gastroenterology Southampton Children's Hospital Southampton UK
| | - Aneurin Young
- NIHR Southampton Biomedical Research Centre University Hospital Southampton Southampton UK
- Department of Neonatal Medicine, Southampton Children's Hospital University Hospital Southampton NHS Foundation Trust Southampton UK
| | - Florina Borca
- NIHR Southampton Biomedical Research Centre University Hospital Southampton Southampton UK
| | - Tracy Coelho
- Department of Paediatric Gastroenterology Southampton Children's Hospital Southampton UK
| | - Akshay Batra
- Department of Paediatric Gastroenterology Southampton Children's Hospital Southampton UK
| | - Nadeem A. Afzal
- Department of Paediatric Gastroenterology Southampton Children's Hospital Southampton UK
| | - Sarah Ennis
- Department of Human Genetics and Genomic Medicine University of Southampton Southampton UK
| | - Mark J. Johnson
- NIHR Southampton Biomedical Research Centre University Hospital Southampton Southampton UK
- Department of Neonatal Medicine, Southampton Children's Hospital University Hospital Southampton NHS Foundation Trust Southampton UK
| | - R. Mark Beattie
- Department of Paediatric Gastroenterology Southampton Children's Hospital Southampton UK
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Stawerska R, Kolasa-Kicińska M, Kolejwa M, Smyczyńska J, Hilczer M, Czkwianianc E, Lewiński A. Frequency of oligosymptomatic gastrointestinal tract diseases and its relation to insulin-like growth factor I in idiopathic (non-GH-deficient) short stature children. Arch Med Sci 2021; 17:1663-1671. [PMID: 34900047 PMCID: PMC8641490 DOI: 10.5114/aoms.2020.93809] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 12/22/2018] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION There is a discussion about growth hormone therapy in idiopathic short stature (ISS) children. To diagnose ISS, it is necessary to exclude other diseases; gastrointestinal tract diseases (GIDs) are among them. However, GID symptoms may be scarce. The aim of the study was to evaluate the frequency of unexpected oligosymptomatic GIDs in ISS and assess their influence on auxological parameters and insulin-like growth factor I (IGF-I) concentration. MATERIAL AND METHODS The analysis included 101 children with ISS and 95 controls. All patients were tested for celiac disease (CD), inflammatory bowel disease (IBD), lactose malabsorption (LM), cystic fibrosis (CF), Helicobacter pylori (HP) and Ascaris sp. (Asc) infections, as well as Candida albicans (Calb) colonization, by applying simple blood and stool tests and gastrofiberoscopy. RESULTS In 75.2% of short children, one or more than one GIDs listed above were diagnosed, with the highest frequency of: Calb (46.5%), LM (33.7%), HP (24.7%) and/or Asc (21.8%). The incidence of GIDs was significantly higher than in the control group. The GID frequency increases with the age of children. In most ISS children, the IGF-I SDS was below -1.0 and it was the lowest in children with HP (p < 0.05). CONCLUSIONS High frequency of unexpected oligosymptomatic GIDs in children diagnosed with ISS indicates the need to search for gastrointestinal (GI) causes in each case of short stature in children. The pathomechanisms responsible for short stature in these cases may vary, although it seems that reduced production of IGF-I plays an important role.
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Affiliation(s)
- Renata Stawerska
- Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
- Department of Pediatric Endocrinology, Medical University of Lodz, Lodz, Poland
| | - Marzena Kolasa-Kicińska
- Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
| | - Michał Kolejwa
- Department of Gastroenterology, Allergology and Pediatrics, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
| | - Joanna Smyczyńska
- Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
| | - Maciej Hilczer
- Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
| | - Elżbieta Czkwianianc
- Department of Gastroenterology, Allergology and Pediatrics, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
| | - Andrzej Lewiński
- Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
- Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland
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Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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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. IBD phenotype at diagnosis, and early disease-course in pediatric patients in Croatia: data from the Croatian national registry. Pediatr Res 2020; 88:950-956. [PMID: 32193518 DOI: 10.1038/s41390-020-0853-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 02/28/2020] [Accepted: 03/04/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND Pediatric inflammatory bowel disease (IBD) presents with extensive phenotype. The aim of this study was to determine the phenotype of pediatric IBD patients in Croatia at diagnosis and follow-up. METHODS Children were prospectively recruited into Croatian IBD national registry. Data on diagnostic evaluation, therapy and 1-year follow-up were collected. RESULTS A total of 51 newly diagnosed patients were recruited (19 Crohn's disease (CD), 28 ulcerative colitis (UC) and 4 IBD-unclassified (IBD-U)). Most common location in CD was ileocolonic disease (52.6%), and pancolitis in UC (53.6%). The recommended complete diagnostic algorithm was performed only in 29.4% of patients. First-line therapy used in CD was exclusive enteral nutrition for remission induction (84.2%) and azathioprine for maintenance (73.7%). In patients with UC, aminosalicylates were the most common drug used (89.3%). By the end of the first year 41.2% of CD and 53.9% of UC patients had one or more relapses and required treatment escalation. CONCLUSION Our data confirm extensive intestinal involvement in pediatric IBD and relatively high relapse rate during the first year of follow-up. More effort should be invested on the national level to implement more stringent adherence to the current European guidelines. IMPACT The key message of our article is that pediatric IBD in Croatia shows extensive intestinal involvement with high relapse rates in first year of follow-up. It is the first cohort study reporting on the phenotype of pediatric IBD in Croatia, but also investigates adherence to diagnostic and therapeutic European guidelines which is not commonly reported. The study is national based, thus having the greatest impact on Croatian health care,stressing out that more effort should be invested on the national level to implement more stringent adherence to the current European guidelines.
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Affiliation(s)
| | - Iva Hojsak
- Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia. .,University of Zagreb School of Medicine, Zagreb, Croatia. .,School of Medicine, University J. J. Strossmayer, Osijek, Croatia.
| | - Ivana Trivić
- Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia
| | - Sara Sila
- Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia
| | - Pero Hrabač
- Department of Medical Statistics, Epidemiology, and Medical Informatics, "Andrija Štampar" School of Public Health, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Vlatka Konjik
- Department of Pediatric Gastroenterology, Hepatology, Pulmonology, Allergology and Immunology, University Hospital Osijek, Osijek, Croatia
| | - Irena Senečić-Čala
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, University Hospital Center Zagreb, Zagreb, Croatia
| | - Goran Palčevski
- Department of Nephrology, Gastroenterology, Endocrinology and Metabolism Diseases, Clinical Hospital Center Rijeka, Rijeka, Croatia
| | - Ranka Despot
- Department for Pediatric Diseases, University Hospital Center Split, Split, Croatia
| | - Orjena Žaja
- Department of Gastroenterology, Hepatology, Eating Disorders, Neurology with Epileptology and Hematology, University Hospital Sisters of Mercy, Zagreb, Croatia
| | - Sanja Kolaček
- Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
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CisarÒ F, Pizzol A, Rigazio C, Calvo PL. Fecal calprotectin in the pediatric population: a 2020 update. Minerva Pediatr 2020; 72:514-522. [PMID: 32731735 DOI: 10.23736/s0026-4946.20.06002-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Calprotectin is a calcium and zinc-binding protein, formed by a hetero complex of S100A8 and S100A9 proteins, which belong to the S-100 protein family consisting in more than 20 different proteins with a tissue-specific expression pattern. This protein is secreted extracellularly from stimulated neutrophils or released by cell disruption or death. The presence of calprotectin in feces quantitatively relates to neutrophil migration toward the gastrointestinal (GI) tract; thus, it represents a useful marker of intestinal inflammation. Fecal calprotectin (FC) has been proven largely useful for determining the inflammatory origin of GI symptoms differentiating between organic and non-organic diseases. Indeed, increased FC levels are also seen in gastroenteritis, microscopic colitis, polyps, malignancies and cystic fibrosis. To date, there are many evidences regarding usefulness in the detection of fecal calprotectin for the management of gastrointestinal disorders, both in children and adults but, especially in the pediatric population, still clear indications for its use are lacking. Its incorporation in primary care reduces the risk of missing an organic disease and facilitates the indication for expensive and invasive investigations as colonoscopy. We herein review and discuss the last evidence on the usefulness of FC in children, with its current indications and future prospective.
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Affiliation(s)
- Fabio CisarÒ
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy -
| | - Antonio Pizzol
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy
| | - Caterina Rigazio
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy
| | - Pier L Calvo
- Unit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza, Turin, Italy
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Gupta N, Liu C, King E, Sylvester F, Lee D, Boyle B, Trauernicht A, Chen S, Colletti R, Ali SA, Al-Nimr A, Ayers TD, Baron HI, Beasley GL, Benkov KJ, Cabrera JM, Cho-Dorado ME, Dancel LD, Di Palma JS, Dorsey JM, Gulati AS, Hellmann JA, Higuchi LM, Hoffenberg E, Israel EJ, Jester TW, Kiparissi F, Konikoff MR, Leibowitz I, Maheshwari A, Moulton DE, Moses J, Ogunmola NA, Palmadottir JG, Pandey A, Pappa HM, Pashankar DS, Pasternak BA, Patel AS, Quiros JA, Rountree CB, Samson CM, Sandberg KC, Schoen B, Steiner SJ, Stephens MC, Sudel B, Sullivan JS, Suskind DL, Tomer G, Tung J, Verstraete SG. Continued Statural Growth in Older Adolescents and Young Adults With Crohn's Disease and Ulcerative Colitis Beyond the Time of Expected Growth Plate Closure. Inflamm Bowel Dis 2020; 26:1880-1889. [PMID: 31968095 DOI: 10.1093/ibd/izz334] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cessation of statural growth occurs with radiographic closure of the growth plates, radiographically defined as bone age (BA) 15 years in females and 17 in males. METHODS We determined the frequency of continued growth and compared the total height gain beyond the time of expected growth plate closure and the chronological age at achievement of final adult height in Crohn's disease (CD) vs ulcerative colitis (UC) and described height velocity curves in inflammatory bowel disease (IBD) compared with children in the National Health and Nutrition Examination Survey (NHANES). We identified all females older than chronological age (CA) 15 years and males older than CA 17 years with CD or UC in the ImproveCareNow registry who had height documented at ≥3 visits ≥6 months apart. RESULTS Three thousand seven patients (48% female; 76% CD) qualified. Of these patients, 80% manifested continued growth, more commonly in CD (81%) than UC (75%; P = 0.0002) and in females with CD (83%) than males with CD (79%; P = 0.012). Median height gain was greater in males with CD (1.6 cm) than in males with UC (1.3 cm; P = 0.0004), and in females with CD (1.8 cm) than in females with UC (1.5 cm; P = 0.025). Height velocity curves were shifted to the right in patients with IBD vs NHANES. CONCLUSIONS Pediatric patients with IBD frequently continue to grow beyond the time of expected growth plate closure. Unexpectedly, a high proportion of patients with UC exhibited continued growth, indicating delayed BA is also common in UC. Growth, a dynamic marker of disease status, requires continued monitoring even after patients transition from pediatric to adult care.
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Affiliation(s)
- Neera Gupta
- Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
| | - Chunyan Liu
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Eileen King
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Francisco Sylvester
- Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Dale Lee
- Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA
| | - Brendan Boyle
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Anna Trauernicht
- Division of Pediatric Gastroenterology, Boys Town National Research Hospital, Boys Town, NE, USA
| | - Shiran Chen
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Richard Colletti
- Department of Pediatrics, University of Vermont College of Medicine, Burlington, VT, USA
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Amaro F, Chiarelli F. Growth and Puberty in Children with Inflammatory Bowel Diseases. Biomedicines 2020; 8:biomedicines8110458. [PMID: 33138015 PMCID: PMC7692295 DOI: 10.3390/biomedicines8110458] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/27/2020] [Accepted: 10/28/2020] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are gastrointestinal tract pathologies of unknown etiology; they have an alternating trend, with active and silent phases. IBD are classified in two main forms: ulcerative colitis (UC) and Crohn’s disease (CD). Both have chronic and recurrent course, gastrointestinal symptoms, and extraintestinal manifestations. The altered immune response role seems to be important both in UC and CD. In the majority of cases, CD begins with abdominal pain, diarrhea, decrease in appetite, and weight loss; there can be also perianal fistulas, rhagades, and perianal recurrent abscesses. In addition, retarded growth and delayed puberty can precede the development of the disease or can even be predominant at onset. Growth retardation is found in 40% of IBD patients, but the underlying mechanism of this and other extra-intestinal manifestations are partially known: the main hypotheses are represented by malnutrition and inflammatory response during the active phase of the disease. The increased level of pro-inflammatory cytokines can influence growth, but also the onset of puberty and its progression. In addition, it could be essential to clarify the role and the possible effects of all the currently used treatments concerning growth failure and delayed puberty.
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Mazhar F, Battini V, Pozzi M, Invernizzi E, Mosini G, Gringeri M, Capuano A, Scavone C, Radice S, Clementi E, Carnovale C. Changes in Anthropometric Parameters After Anti-TNFα Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. BioDrugs 2020; 34:649-668. [PMID: 32940873 PMCID: PMC7519901 DOI: 10.1007/s40259-020-00444-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Tumour necrosis factor (TNF)-α inhibitors have been widely used for the treatment of moderate-to-severe inflammatory bowel disease (IBD). TNFα also plays an important role in the regulation of weight homeostasis and metabolism and has been linked to variations in anthropometric responses. This relationship in patients with IBD has yet to be determined. OBJECTIVES Our objective was to evaluate the effects of TNFα inhibitors on changes in anthropometric measures in both adults and children with IBD through a systematic review and meta-analysis. METHODS Multiple database searches identified studies involving children and adults with IBD and treated with TNFα inhibitors and reporting at least one primary outcome measure. Where possible, data were combined for meta-analysis. The primary outcomes included weight, body mass index (BMI), waist circumference, height, height/velocity, and fat and lean mass. Secondary outcomes included surrogate markers of disease activity. A random-effects model was used to estimate the standardised mean difference (SMD). RESULTS In total, 23 cohort studies (total 1167 participants) met the inclusion criteria. Meta-analysis was performed on 13 of these studies. In children, 6-29.3 months of anti-TNFα therapy had a small but statistically significant effect on weight (SMD 0.31; 95% confidence interval [CI] 0.12-0.49; P = 0.001) with a mean gain in z score of 0.30 (standard error [SE] 0.12). In adults, 2-22.4 months of treatment had a moderate effect on BMI (SMD 0.72; 95% CI 0.17-1.26; P = 0.010; mean gain 1.23 kg/m2; SE 0.21). A small but statistically significant increase in BMI z score was found in children (SMD 0.28; 95% CI 0.03-0.53; P = 0.026; mean change 0.31 ± standard deviation [SD] 0.14) after 12-29.3 months of therapy. A meta-analysis of four studies found a negligible but statistically significant increase in height (SMD 0.16; 95% CI 0.06-0.26; P = 0.002; mean change 0.17 z score [SE 0.05]). A negligible effect on fat mass (SMD 0.24; 95% CI -0.19-0.66; P = 0.272) was found in a meta-analysis of five studies. Of note, despite the high heterogeneity among the studies that addressed the issue, these results were also consistently supported by findings from studies not included in the meta-analysis and reviewed in the systematic review. Unfortunately, a lack of data meant we were unable to perform moderator analysis on observed heterogeneity. CONCLUSION Anti-TNFα treatment appears to be associated with an increase in body weight, BMI, and other anthropometric parameters. Given the differing courses of IBD between children and adults, this association should be considered before initiating biologics for undernourished, overweight, and obese patients. Registration: PROSPERO registration number CRD42020163079.
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Affiliation(s)
- Faizan Mazhar
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
| | - Vera Battini
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
| | - Marco Pozzi
- Scientific Institute, IRCCS E. Medea, Bosisio Parini, LC, Italy
| | - Elena Invernizzi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
| | - Giulia Mosini
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
| | - Michele Gringeri
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
| | - Annalisa Capuano
- Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138, Naples, Italy
| | - Cristina Scavone
- Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, 80138, Naples, Italy
| | - Sonia Radice
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy.
| | - Emilio Clementi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
- Scientific Institute, IRCCS E. Medea, Bosisio Parini, LC, Italy
| | - Carla Carnovale
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan, Italy
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Ricciuto A, Mack DR, Huynh HQ, Jacobson K, Otley AR, deBruyn J, El-Matary W, Deslandres C, Sherlock ME, Critch JN, Bax K, Jantchou P, Seidman EG, Carman N, Rashid M, Muise A, Wine E, Carroll MW, Lawrence S, Van Limbergen J, Benchimol EI, Walters TD, Griffiths AM, Church PC. Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease. J Crohns Colitis 2020; 15:419-431. [PMID: 32978629 PMCID: PMC7944510 DOI: 10.1093/ecco-jcc/jjaa197] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. METHODS We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. RESULTS Overall (64% Crohn's disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. CONCLUSIONS Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. PODCAST This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
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Affiliation(s)
- Amanda Ricciuto
- SickKids Hospital, University of Toronto, Toronto, ON, Canada,Corresponding author: Amanda Ricciuto, MD, PhD, FRCPC, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8. Tel.: 416-813-7654; fax: 416-813-6531; email
| | - David R Mack
- Children’s Hospital of Eastern Ontario [CHEO], Inflammatory Bowel Disease Centre, Ottawa, ON, Canada
| | - Hien Q Huynh
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | | | | | - Jennifer deBruyn
- Alberta Children’s Hospital, University of Calgary, Calgary, AB, Canada
| | - Wael El-Matary
- Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | | | | | - Jeffrey N Critch
- Janeway Children’s Health and Rehabilitation Centre, St. John’s, NL, Canada
| | - Kevin Bax
- Children’s Hospital of Western Ontario, London, ON, Canada
| | | | | | - Nicholas Carman
- Children’s Hospital of Eastern Ontario [CHEO], Inflammatory Bowel Disease Centre, Ottawa, ON, Canada
| | | | - Aleixo Muise
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - Eytan Wine
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | - Matthew W Carroll
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | | | | | - Eric I Benchimol
- Children’s Hospital of Eastern Ontario [CHEO], Inflammatory Bowel Disease Centre, Ottawa, ON, Canada,CHEO Research Institute, Ottawa, ON, Canada,Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada,ICES uOttawa, Ottawa, ON, Canada
| | | | | | - Peter C Church
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
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49
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Roberts SE, Thorne K, Thapar N, Broekaert I, Benninga MA, Dolinsek J, Mas E, Miele E, Orel R, Pienar C, Ribes-Koninckx C, Thomson M, Tzivinikos C, Morrison-Rees S, John A, Williams JG. A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe. J Crohns Colitis 2020; 14:1119-1148. [PMID: 32115645 DOI: 10.1093/ecco-jcc/jjaa037] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states. METHODS We undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018. RESULTS Incidence rates for both paediatric Crohn's disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30. CONCLUSIONS The incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north-south than an east-west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.
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Affiliation(s)
- S E Roberts
- Medical School, Swansea University, Swansea, Wales, UK
| | - K Thorne
- Medical School, Swansea University, Swansea, Wales, UK
| | - N Thapar
- Neurogastroenterology and Motility Unit, Department of Gastroenterology, Great Ormond Street Hospital, London, UK
- Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, UK
- Prince Abdullah Ben Khalid Celiac Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| | - I Broekaert
- Department of Paediatrics, University Children's Hospital, University of Cologne, Cologne, Germany
| | - M A Benninga
- Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, The Netherlands
| | - J Dolinsek
- Department of Pediatrics, University Medical Center Maribor, Maribor, Slovenia
| | - E Mas
- Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires, du Métabolisme, Hôpital des Enfants, CHU de Toulouse, Toulouse, France
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France
| | - E Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples 'Federico II', Naples, Italy
| | - R Orel
- Department of Gastroenterology, Hepatology and Nutrition, Children's Hospital, University Medical Centre, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - C Pienar
- Department of Pediatrics, 'Victor Babes' University of Medicine and Pharmacy, Timisoara, Romania
| | - C Ribes-Koninckx
- Department of Paediatric Gastroenterology, Hepatology & Nutrition, La FE University Hospital, Valencia, Spain
| | - M Thomson
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
| | - C Tzivinikos
- Department of Paediatric Gastroenterology, Al Jalila Children's Specialty Hospital, Dubai, UAE
| | | | - A John
- Medical School, Swansea University, Swansea, Wales, UK
| | - J G Williams
- Medical School, Swansea University, Swansea, Wales, UK
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50
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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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