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Giordano A, Pérez-Martínez I, Gisbert JP, Ricart E, Martín-Arranz MD, Mesonero F, De Castro Parga ML, Rivero M, Iglesias E, Fernández-Prada S, Calafat M, Arroyo Villarino MT, Ángel de Jorge Turrión M, Hernandez-Camba A, Lidón RV, Carpio D, Brunet E, Moranta FR, García LA, Cuquerella JT, Bermejo F, Madero L, Esteve M, González-Muñoza C, Martínez-Montiel P, Huguet JM, Pérez Calle JL, Rodríguez-Lago I, Ausín MS, Lorente Poyatos RH, García-Bosch O, Marín GS, Taxonera C, Ponferrada-Diaz Á, Acosta MBD, Bujanda L, Serra RB, Ramos L, Vera I, Abizanda ES, Piqueras M, Gómez CS, García-Sepulcre MF, Arregui MV, Murillo NR, LLaó J, Lucendo AJ, Marín-Jiménez I, Camps-Aler B, Villafranca CM, Ceballos D, Ver Y, Fernández-Salazar LI, Alcaín G, Valldosera G, Andrés PR, Martínez-Flores C, Coronel AF, Ginard D, García L, Gómez IB, Argüelles-Arias F, Miyashiro EI, De la Piscina PR, Villalba LH, Notari PA, de Jesús Martínez-Pérez T, Fernández H, Gilabert P, Rosas CM, Nos P, Gil JL, Navas López VM, Muñoz F, Diz-Lois Palomares MT, Lucio AS, Merino O, Nicolás de Prado I, Leal C, Martín de Carpi J, Sánchez LB, Arce NM, Frago S, Mateu BB, Domènech E, Planella EG. Ileal Predominance in Crohn's Disease Is Associated With Increased Intestinal Surgery and Biological Therapy Use, With Lower Treatment Persistence. Am J Gastroenterol 2025; 120:194-203. [PMID: 39745305 DOI: 10.14309/ajg.0000000000003207] [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] [Received: 06/07/2024] [Accepted: 10/22/2024] [Indexed: 02/02/2025]
Abstract
INTRODUCTION Crohn's disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns. METHODS We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry. A univariate Cox regression analysis assessed the association of disease location with biologic use and persistence (with treatment discontinuation as a failure event), as well as the use of intestinal resections. A multivariate model was constructed to evaluate the independent association of disease location with therapeutic patterns, controlling for potential confounders such as sex, age at inclusion and diagnosis, disease duration and behavior, previous surgery or biological therapy, extraintestinal manifestations, and perianal disease. RESULTS The study included 17,292 patients with a median follow-up period of 6 years (interquartile range 2-10 years). Ileocolonic location was associated with a higher biologic use than colonic location (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.22-1.38) and ileal disease (HR 1.21, 95% CI 1.16-1.27), independently predicting biologic use (P < 0.001). Ileal location was associated with a lower biologic persistence than ileocolonic location (HR 1.14, 95% CI 1.07-1.21) and colonic disease (HR 1.10, 95% CI 1.01-1.20), independently predicting biologic persistence (P = 0.019). Ileal disease was associated with a higher likelihood of intestinal resections than colonic (HR 2.82, 95% CI 2.45-3.25) and ileocolonic location (HR 1.13, 95% CI 1.05-1.22), independently predicting the use of surgery (P < 0.001). DISCUSSION CD location with ileal predominance is associated with a distinct therapeutic pattern, including higher biologic use, lower treatment persistence, and increased rates of intestinal resections.
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Affiliation(s)
- Antonio Giordano
- IBD Unit, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Isabel Pérez-Martínez
- Gastroenterology Department, Hospital Universitario Central de Asturias, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Javier P Gisbert
- Gastroenterology Department. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain
| | - Elena Ricart
- Gastroenterology Department. Hospital Clínic, Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). Centro de Investigación Biomédica en RED (CIBEREHD), Madrid, Spain
| | - María Dolores Martín-Arranz
- Gastroenterology Department, Hospital Universiario La Paz and Instituto de Investigación Sanitaria La Paz (IdiPaz), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Francisco Mesonero
- Gastroenterology Department. Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | - Montserrat Rivero
- Gastroenterology Department, Hospital Universitario Marqués de Valdecilla e IDIVAL, Santander, Spain
| | - Eva Iglesias
- Gastroenterology Department, Hospital Reina Sofía, Córdoba, Spain
| | | | - Margalida Calafat
- Gastroenterology Department. Hospital Universitari Germans Trias i Pujol, Badalona. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - María Teresa Arroyo Villarino
- Gastroenterology Department, Hospital Clínico Lozano Blesa, Zaragoza. Instituto de investigación sanitaria de Aragón (IIS). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Alejandro Hernandez-Camba
- Gastroenterology Department, Hospital Universitario Nuestra Sra. de la Candelaria, Santa Cruz de Tenerife, Spain
| | - Raquel Vicente Lidón
- Gastroenterology Department, Hospital Universitario Miguel Servet, Instituto de investigación sanitaria de Aragón (IIS), Zaragoza, Spain
| | - Daniel Carpio
- Gastroenterology Department, Complexo Hospitlario Universitario de Pontevedra, Pontevedra, Spain
| | - Eduard Brunet
- Gastroenterology Department. Parc Taulí, Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí. Departament de Medicina. Universitat Autònoma de Barcelona. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Lara Arias García
- Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Joan Tosca Cuquerella
- Gastroenterology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Fernando Bermejo
- Gastroenterology Department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
| | - Lucía Madero
- Gastroenterology Department, Hospital General Universitario Dr Balmis e ISABIAL, Alicante. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Maria Esteve
- Gastroenterology Department. Hospital Universitari Mútua Terrassa. University of Barcelona. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Carlos González-Muñoza
- IBD Unit, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | | | - Jose M Huguet
- Gastroenterology Department, Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Iago Rodríguez-Lago
- Gastroenterology Department, Hospital de Galdakao, Biobizkaia Health Research Institute, Vizcaya, Spain
| | - Mónica Sierra Ausín
- Gastroenterology Department, Complejo Asistencial Universitario de León, León, Spain
| | - Rufo H Lorente Poyatos
- Gastroenterology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - Orlando García-Bosch
- Gastroenterology Department, Hospital Moisès Broggi, Sant Joan Despí, Barcelona, Spain
| | - Gerard Surís Marín
- Gastroenterology Department. Hospital del Mar, Barcelona. IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
| | - Carlos Taxonera
- Inflammatory Bowel Disease Unit, Gastroenterology Department, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain
| | | | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Luis Bujanda
- Gastroenterology Department. Biodonostia Health Research Institute. Universidad del País Vasco (UPV/EHU), San Sebastián. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Rosa Blat Serra
- Gastroenterology Department, Hospital Dr. Josep Trueta, Girona, Spain
| | - Laura Ramos
- Gastroenterology Department. Hospital Universitario de Canarias, La Laguna, Spain
| | - Isabel Vera
- Gastroenterology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - Eva Sesé Abizanda
- Gastroenterology Department, Hospital Universitario Arnau de Vilanova, Lleida, Spain
| | - Marta Piqueras
- Gastroenterology Department, Consorci Sanitari de Terrassa, Terrassa, Spain
| | - Cristina Sánchez Gómez
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Ourence, Spain
| | | | | | | | - Jordina LLaó
- Gastroenterology Department, Althaia Xarxa Assistencial Universitaria de Manresa, Manresa, Spain
| | - Alfredo J Lucendo
- Gastroenterology Department, Hospital General de Tomelloso. Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Ignacio Marín-Jiménez
- Gastroenterology Department, IiSGM, Hospital Gregorio Marañón; Medicine Faculty, Complutense University, Madrid, Spain
| | - Blau Camps-Aler
- Gastroenterology Department, Hospital General de Granollers, Granollers, Spain
| | | | - Daniel Ceballos
- Gastroenterology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain
| | - Yolanda Ver
- Gastroenterology Department, Hospital San Jorge, Huesca, Spain
| | | | - Guillermo Alcaín
- Gastroenterology Department, Hospital Virgen de la Victoria, Málaga, Spain
| | - Gemma Valldosera
- Gastroenterology Department, Hospital Joan XXIII, Tarragona, Spain
| | | | - Carlos Martínez-Flores
- Gastroenterology Department, Hospital General La Mancha Centro, Alcázar de San Juan, Spain
| | | | - Daniel Ginard
- Gastroenterology Department, Hospital Son Espases, Palma de Mallorca, Spain
| | - Laura García
- Gastroenterology Department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain
| | - Isabel Blázquez Gómez
- Gastroenterology Department, Hospital Universitario de Torrejón, Universidad Francisco de Vitoria, Torrejón, Spain
| | - Federico Argüelles-Arias
- Gastroenterology Department, Hospital Universitario Virgen Macarena, Universidad de Sevilla (Facultad de Medicina), Sevilla, Spain
| | | | | | | | | | | | | | - Pau Gilabert
- Gastroenterology Department, Hospital de Viladecans, Viladecans, Spain
| | | | - Pilar Nos
- Gastroenterology Department, Hospital Universitari i Politècnic La Fe, València, Spain
| | - Jesús Legido Gil
- Gastroenterology Department, Complejo Asistencial de Segovia, Segovia, Spain
| | - Víctor Manuel Navas López
- Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Fernando Muñoz
- Gastroenterology Department, Hospital Universitario de Salmanca, Salamanca, Spain
| | | | | | - Olga Merino
- Gastroenterology Department, Hospital de Cruces, Bilbao, Spain
| | | | - Carles Leal
- Gastroenterology Department, Consorci Hospitalari de Vic, Universitat de Vic-UCC, Barcelona, Spain
| | | | | | | | - Santiago Frago
- Gastroenterology Department, Hospital de Santa Bárgara, Soria, Spain
| | - Belén Botella Mateu
- Gastroenterology Department, Hospital Universitario Infanta Cristina, Parla, Spain
| | - Eugeni Domènech
- Gastroenterology Department. Hospital Universitari Germans Trias i Pujol, Badalona. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Esther Garcia Planella
- IBD Unit, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
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Sands BE, Panés J, Feagan BG, Zhang H, Vetter ML, Mathias SD, Huang KHG, Johanns J, Germinaro M, Sahoo A, Terry NA, Han C. Qualitative and Psychometric Evaluation of 29-Item Patient-Reported Outcomes Measurement Information System® to Assess General Health-Related Quality of Life in Patients With Moderately to Severely Active Inflammatory Bowel Disease. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2024; 27:1225-1234. [PMID: 38843977 DOI: 10.1016/j.jval.2024.05.019] [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: 11/27/2023] [Revised: 04/22/2024] [Accepted: 05/15/2024] [Indexed: 07/01/2024]
Abstract
OBJECTIVES To evaluate content validity and psychometric properties of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) to determine its suitability in inflammatory bowel disease (IBD) clinical trials. METHODS Content validity of PROMIS-29 was evaluated using qualitative interviews, including concept elicitation and cognitive debriefing, among patients living with Crohn's disease (Crohn's disease n = 20) or ulcerative colitis (UC, n = 19). PROMIS-29 validity, reliability, and responsiveness were assessed using data from phase II clinical trials of Crohn's disease (N = 360) and UC (N = 518). RESULTS Common (≥74%) symptoms reported in qualitative interviews were increased stool frequency, fatigue, abdominal pain/cramping, blood/mucus in stool, bowel urgency, and diarrhea. Disease impact aligned with PROMIS-29 content (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles/activities). Cognitive debriefing indicated that PROMIS-29 instructions were easily understood, items were relevant, and the recall period was appropriate. Psychometric evaluations demonstrated that PROMIS-29 scores indicating worse symptoms/functioning were associated with lower health-related quality of life and greater disease activity and severity. PROMIS-29 domain scores correlated (rs ≥ 0.40) with IBD Questionnaire domains and EuroQol-5-Dimension-5-Level dimensions measuring similar concepts. Test-retest reliability among patients with stable disease was moderate-to-excellent (0.64-0.94) for nearly all domains in all studies. PROMIS-29 was responsive to change in disease status from baseline to week 12. Thresholds for clinically meaningful improvement ranged from ≥3 to ≥8, depending on domain. CONCLUSIONS PROMIS-29 is valid, reliable, and responsive for assessing general health-related quality of life and treatment response in IBD clinical trials.
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Affiliation(s)
- Bruce E Sands
- Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Julian Panés
- Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Brian G Feagan
- Western University and Alimentiv Inc, London, ON, Canada
| | - Hongyan Zhang
- Janssen Research and Development, LLC, Spring House, PA, USA
| | - Marion L Vetter
- Janssen Research and Development, LLC, Spring House, PA, USA
| | | | | | - Jewel Johanns
- Janssen Research and Development, LLC, Spring House, PA, USA
| | | | - Aparna Sahoo
- Janssen Research and Development, LLC, Spring House, PA, USA
| | - Natalie A Terry
- Janssen Research and Development, LLC, Spring House, PA, USA
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Zhang W, McCartney F, Xu Y, Michalowski CB, Domingues I, Kambale EK, Moreels TG, Guilbaud L, Chen C, Marotti V, Brayden DJ, Beloqui A. An in situ bioadhesive foam as a large intestinal delivery platform for antibody fragment to treat inflammatory bowel disease. J Control Release 2024; 374:254-266. [PMID: 39151828 DOI: 10.1016/j.jconrel.2024.08.023] [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: 05/16/2024] [Revised: 07/22/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024]
Abstract
Biologics have been widely used as injectables in the treatment of inflammatory bowel disease (IBD). Different local treatment attempts have been developed in recent years. However, maintaining systemic levels of biologics is still crucial for achieving colitis remission. An equilibrium between systemic and local concentrations of biologics is therefore essential for treatment of colitis. Current formulations struggle to create optimal balance between drug concentrations in plasma and the colonic wall. Addressing this challenge, we developed a rectally delivered in situ foam that generates CO2via a reaction between potassium bicarbonate (PB) and citric acid (CA) without the aid of an external device. An anti-TNF-α antibody fragment (Fab) was loaded into the foam formulation, which promoted prolonged colon retention and improved Fab distribution up to proximal colon following rectal administration to mice. In addition, we observed increased plasma Fab concentrations in mice receiving the rectal Fab foam compared to a Fab solution. In a non-everted rat gut ex vivo model, a single exposure to the CO2-containing foam improved macromolecule transepithelial flux across colonic tissue by over ten-fold. Foam efficacy for Fab was investigated in a range of colitis mouse models, from acute to chronic. This non-invasive formulation platform demonstrates potential to overcome existing limitations in delivering biologics to inflamed colonic tissue.
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Affiliation(s)
- Wunan Zhang
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Fiona McCartney
- University College Dublin School of Veterinary Medicine and Conway Institute, Belfield, Dublin D4, Ireland
| | - Yining Xu
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Cécilia Bohns Michalowski
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Inês Domingues
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Espoir K Kambale
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Tom G Moreels
- UCLouvain, Université Catholique de Louvain, Institute of Experimental and Clinical Research, Laboratory of Hepato-Gastroenterology, 1200 Brussels, Belgium
| | - Léo Guilbaud
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Cheng Chen
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Valentina Marotti
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - David J Brayden
- University College Dublin School of Veterinary Medicine and Conway Institute, Belfield, Dublin D4, Ireland
| | - Ana Beloqui
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium; WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium.
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Zhang C, Zheng C, Zhang Z, Yan X, Xu J, Gu C, Nie F. Quantitative analysis of contrast-enhanced ultrasound and superb microvascular imaging for the evaluation of disease activity in inflammatory bowel disease. Clin Hemorheol Microcirc 2024; 87:451-464. [PMID: 38788062 DOI: 10.3233/ch-242114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2024]
Abstract
OBJECTIVE To evaluate the effectiveness of conventional US (ultrasound), SMI (superb microvascular imaging), and CEUS (contrast-enhanced ultrasound) features for the assessment of the activity of inflammatory bowel disease. METHODS Conventional US, CEUS and SMI features of 76 patients were retrospectively analyzed. Patients were categorized into two groups: active group (n = 57) and inactive group (n = 19), with endoscopic results as reference standard. Results in the active group and inactive group were compared using an independent t-test, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve (ROC) analysis. Cut-off values were determined using ROC analysis, and sensitivity and specificity were calculated. US quantitative and TIC-based quantitative parameters were analyzed, and each patient was scored based on the parameters that are statistically significant and immediately available in the clinic to evaluate the diagnostic ability of conventional US, SMI, and CEUS features for active IBD patients. RESULTS Qualitative parameters such as CEUS enhancement pattern I/II, LimbergIII/IV, and lost bowel stratification were reliable indicators of active patients. Quantitative parameters such as bowel thickness and VI of mSMI were reliable indicators of active patients. Patients scored based on these statistically significant parameters with a score ≥3, were highly suspected to be active patients. For TIC-based quantitative parameters, PE, WiAUC, WoAUC, WiWoAUC, WiR, WiPI, and WoR were statistically significant in the differentiation of active IBD from inactive IBD. CONCLUSIONS Conventional US, SMI, and CEUS features may help in the differentiation of active IBD from inactive IBD and have potential application value in the choice of treatment options.
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Affiliation(s)
- Chi Zhang
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
| | - Chunyao Zheng
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
| | - Zhiqi Zhang
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
| | - Xueliang Yan
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
| | - Jianhua Xu
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
| | - Changyan Gu
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
| | - Fang Nie
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
- Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, China
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Elzayat H, Malik T, Al-Awadhi H, Taha M, Elghazali G, Al-Marzooq F. Deciphering salivary microbiome signature in Crohn's disease patients with different factors contributing to dysbiosis. Sci Rep 2023; 13:19198. [PMID: 37932491 PMCID: PMC10628307 DOI: 10.1038/s41598-023-46714-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 11/03/2023] [Indexed: 11/08/2023] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease. An imbalanced microbiome (dysbiosis) can predispose to many diseases including CD. The role of oral dysbiosis in CD is poorly understood. We aimed to explore microbiome signature and dysbiosis of the salivary microbiome in CD patients, and correlate microbiota changes to the level of inflammation. Saliva samples were collected from healthy controls (HC) and CD patients (n = 40 per group). Salivary microbiome was analyzed by sequencing the entire 16S rRNA gene. Inflammatory biomarkers (C-reactive protein and calprotectin) were measured and correlated with microbiome diversity. Five dominant species were significantly enriched in CD, namely Veillonella dispar, Megasphaera stantonii, Prevotella jejuni, Dolosigranulum pigrum and Lactobacillus backii. Oral health had a significant impact on the microbiome since various significant features were cariogenic as Streptococcus mutans or periopathogenic such as Fusobacterium periodonticum. Furthermore, disease activity, duration and frequency of relapses impacted the oral microbiota. Treatment with monoclonal antibodies led to the emergence of a unique species called Simonsiella muelleri. Combining immunomodulatory agents with monoclonal antibodies significantly increased multiple pathogenic species such as Salmonella enterica, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Loss of diversity in CD was shown by multiple diversity indices. There was a significant negative correlation between gut inflammatory biomarkers (particularly calprotectin) and α-diversity, suggesting more inflammation associated with diversity loss in CD. Salivary dysbiosis was evident in CD patients, with unique microbiota signatures and perturbed species that can serve as disease biomarkers or potential targets for microbiota modulation. The interplay of various factors collectively contributed to dysbiosis, although each factor probably had a unique effect on the microbiome. The emergence of pathogenic bacteria in the oral cavity of CD patients is alarming since they can disturb gut homeostasis and induce inflammation by swallowing, or hematogenous spread of microbiota, their metabolites, or generated inflammatory mediators.
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Affiliation(s)
- Hala Elzayat
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE
| | - Talha Malik
- Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, UAE
| | - Haifa Al-Awadhi
- Department of Pediatric Gastroenterology, Tawam Hospital, Al Ain, UAE
| | - Mazen Taha
- Department of Internal Medicine, Tawam Hospital, Al Ain, UAE
| | - Gehad Elghazali
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE
- Department of Immunology, Sheikh Khalifa Medical City, Union71-Purehealth, Abu Dhabi, UAE
| | - Farah Al-Marzooq
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, UAE.
- Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, UAE.
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Cockburn E, Kamal S, Chan A, Rao V, Liu T, Huang JY, Segal JP. Crohn's disease: an update. Clin Med (Lond) 2023; 23:549-557. [PMID: 38065612 PMCID: PMC11298500 DOI: 10.7861/clinmed.2023-0493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.
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Affiliation(s)
| | | | - Andrea Chan
- Royal Melbourne Hospital, Melbourne, Australia
| | | | - Tianwei Liu
- Royal Melbourne Hospital, Melbourne, Australia
| | | | - Jonathan P Segal
- Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
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7
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Nakase H, Esaki M, Hirai F, Kobayashi T, Matsuoka K, Matsuura M, Naganuma M, Saruta M, Tsuchiya K, Uchino M, Watanabe K, Hisamatsu T. Treatment escalation and de-escalation decisions in Crohn's disease: Delphi consensus recommendations from Japan, 2021. J Gastroenterol 2023; 58:313-345. [PMID: 36773075 PMCID: PMC10050046 DOI: 10.1007/s00535-023-01958-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/08/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. METHODS PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. RESULTS Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. CONCLUSIONS These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.
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Affiliation(s)
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-Ku, Sapporo, Hokkaido 060-8543 Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Motoi Uchino
- Division of Inflammatory Bowel Disease, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Kenji Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-Shi, Tokyo, 181-8611 Japan
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8
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Kawamura T, Yamamura T, Nakamura M, Maeda K, Sawada T, Ishikawa E, Iida T, Mizutani Y, Ishikawa T, Kakushima N, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M. Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease. Inflamm Bowel Dis 2023; 29:245-253. [PMID: 35436345 DOI: 10.1093/ibd/izac076] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. METHODS Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. RESULTS Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. CONCLUSIONS Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.
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Affiliation(s)
- Tatsuya Kawamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Keiko Maeda
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Tsunaki Sawada
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Naomi Kakushima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
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9
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Sands BE, Irving PM, Hoops T, Izanec JL, Gao LL, Gasink C, Greenspan A, Allez M, Danese S, Hanauer SB, Jairath V, Kuehbacher T, Lewis JD, Loftus EV, Mihaly E, Panaccione R, Scherl E, Shchukina OB, Sandborn WJ. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet 2022; 399:2200-2211. [PMID: 35691323 DOI: 10.1016/s0140-6736(22)00688-2] [Citation(s) in RCA: 142] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/31/2022] [Accepted: 04/05/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease. METHODS We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220-450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41. FINDINGS Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in the occurrence of the primary endpoint; at week 52, 124 (65%) of 191 patients in the ustekinumab group versus 119 (61%) of 195 in the adalimumab group were in clinical remission (between-group difference 4%, 95% CI -6 to 14; p=0·42). Safety for both groups was consistent with previous reports. Serious infections were reported in four (2%) of 191 patients in the ustekinumab group and five (3%) of 195 in the adalimumab group. No deaths occurred through week 52 of the study. INTERPRETATION Both ustekinumab and adalimumab monotherapies were highly effective in this population of biologic-naive patients, with no difference in the primary outcome between the drugs. FUNDING Janssen Scientific Affairs.
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Affiliation(s)
- Bruce E Sands
- Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Peter M Irving
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK; School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Timothy Hoops
- Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, USA
| | | | | | | | | | - Matthieu Allez
- Gastroenterology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM U1160, Université de Paris, Paris, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy
| | - Stephen B Hanauer
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, University Hospital, London, ON, Canada; Division of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Tanja Kuehbacher
- Department of Internal Medicine, Gastroenterology, Diabetology, Hemato-Oncology, and Palliative Medicine, Medius Clinic Nuertingen, Nürtingen, Germany
| | - James D Lewis
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Emese Mihaly
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
| | - Remo Panaccione
- Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - Ellen Scherl
- Weill Department of Medicine, New York Presbyterian Hospital Weill Cornell Medicine, New York, NY, USA
| | - Oksana B Shchukina
- Division The City Center for IBD Diagnosis and Treatment, Saint Petersburg State Budgetary Health Institution, City Clinical Hospital 31, Saint Petersburg, Russia
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
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Is Ustekinumab Effective in Refractory Crohn's Disease of the Pouch and Chronic Pouchitis? A Systematic Review. Dig Dis Sci 2022; 67:1948-1955. [PMID: 34097166 DOI: 10.1007/s10620-021-07002-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 04/14/2021] [Indexed: 12/12/2022]
Abstract
Crohn's disease (CD) of the pouch and chronic pouchitis represent the most common long-term complications of total proctocolectomy and ileal pouch anal anastomosis (IPAA) for refractory ulcerative colitis (UC). These conditions are treated with multiple agents, including antibiotics, immunomodulators, and biologics. Among the latter, ustekinumab is approved for both CD and UC. We performed a systematic review to evaluate the efficacy of this anti-IL12/23 in CD of the pouch and chronic refractory pouchitis. Pubmed, Embase, Ovid, and the Cochrane Controlled Trials Register were searched to identify studies published until August 2020 investigating the use of ustekinumab for these conditions. Eighty-six eligible patients with IPAA-51 with CD of the pouch, 35 with chronic pouchitis-were identified from 2 retrospective studies and 5 case reports. Reported clinical response to ustekinumab was 63 and 85% in chronic pouchitis and CD of the pouch after 4-12 and 4-16 weeks, respectively. Clinical remission was reported in 10% of patients with chronic pouchitis and 27% of patients with CD of the pouch after 8-52 and 4-52 weeks of treatment, respectively. Endoscopic response was reported in 60% and 67% of patients with chronic pouchitis and CD of the pouch after 24-32 and 8-24 weeks of treatment respectively. Small sample sizes and large heterogeneity of therapy protocols/outcome definitions were significant studies limitations. In conclusion, there is a limited and inconclusive body of evidence suggesting that ustekinumab may be a therapeutic option for patients with chronic pouchitis and CD of the pouch refractory to other therapies.
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11
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Khashper A, Shwartz D, Taragin BH, Shalmon T. Splenic size as a marker for active inflammation in Crohn's disease. Clin Imaging 2022; 84:164-167. [DOI: 10.1016/j.clinimag.2022.02.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 02/11/2022] [Accepted: 02/12/2022] [Indexed: 11/03/2022]
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12
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Comparison of Magnetic Resonance Enterography Global Score (MEGS) with indices of Crohn's disease activity in South Asian population. Abdom Radiol (NY) 2022; 47:547-553. [PMID: 34958408 DOI: 10.1007/s00261-021-03381-5] [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: 09/17/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE Assessment of disease activity in Crohn's helps predict important clinical outcomes. Among the various modalities available to assess disease activity, magnetic resonance enterography (MRE) is considered a safe and reliable imaging option. Various MRE-based scoring systems have been developed to measure disease activity, one of which being the MRE global score (MEGS). We aimed to correlate MEGS with some of the important indices of Crohn's disease activity. METHODOLOGY Crohn's disease patients referred for MRE were included in the study. Along with demographic profile and relevant investigations, MRE parameters related to MEGS were also assessed. RESULT A total of 47 patients were recruited for the study. Their median age was 34 years (range 18-68 years), and male:female ratio was 16:31. There was modest positive correlation between MEGS and faecal calprotectin (r = 0.3, p = 0.04), CRP level (r = 0.34, p = 0.02) and Harvey Bradshaw index (r = 0.3, p = 0.043), respectively. However, there was strong correlation between segmental MEGS and Simple Endoscopic Score in those with terminal ileal disease (r = 0.81, p < 0.001). Mural thickness was the only MRE parameter that correlated with active disease (OR - 1.35, 95% CI 1.01, 1.81, p = 0.041) on multivariate analysis. There was moderate inter-observer agreement (Lin's r = 0.78, p < 0.001). CONCLUSION MEGS showed modest correlation with indices of Crohn's disease activity which corroborates the complementary role of MRE in management of such patients.
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13
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Moriichi K, Fujiya M, Okumura T. The endoscopic diagnosis of mucosal healing and deep remission in inflammatory bowel disease. Dig Endosc 2021; 33:1008-1023. [PMID: 33020947 DOI: 10.1111/den.13863] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022]
Abstract
The therapeutic goal in inflammatory bowel disease (IBD) patients has shifted from controlling the clinical activity alone to managing other associated problems. The concept of mucosal healing (MH) and deep remission (DR) are advocated and regarded as new therapeutic goals in IBD. However, the definition of MH still remains controversial. It is unclear whether or not the histological structures or functional factors should be included in the definition of DR in addition to clinical remission and MH. The classifications of white-light imaging (e.g. Mayo endoscopic subscore, UCEIS, CD Endoscopic Index of Severity, simple Endoscopic Score-CD) have been proposed and are now widely used to assess the severity as well as the MH of inflammation in IBD. In ulcerative colitis, magnifying chromoendoscopy has been shown to be useful to assess the MH of inflammation while other types of image-enhanced endoscopy, such as narrow-band imaging, have not. Endocytoscopy and confocal laser endomicroscopy (CLE) are also applied to assess the activity in IBD. These endoscopic procedures can estimate MH with more precision through observing the details of superficial structures, such as crypt openings. In addition, CLE can partially assess the mucosal function by detecting fluorescence leakage. Molecular imaging can possibly detect the molecules associated with inflammation, intestinal regeneration and differentiation, and various functions including the intestinal barrier and mucus secretion. These novel procedures may improve the diagnosis strategy of DR through the assessment of DR-associated factors such as the histological structures and functional factors in the near future.
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Affiliation(s)
- Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan
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14
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Sorrentino D, Nguyen VQ, Love K. Fecal Lactoferrin Predicts Primary Nonresponse to Biologic Agents in Inflammatory Bowel Disease. Dig Dis 2021; 39:626-633. [PMID: 33631768 PMCID: PMC8686729 DOI: 10.1159/000515432] [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: 12/07/2020] [Accepted: 02/22/2021] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Fecal lactoferrin (FL) is a timely and accurate marker of inflammation in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to verify whether FL can predict primary nonresponse (PNR) to biologic agents during induction. METHODS Retrospective outcome review in 27 patients (13 with CD and 14 with UC) tested for baseline FL and retested within a week after the first and second induction doses. Clinical/biochemical outcomes were evaluated at end of induction and at follow-up (3-24 months). RESULTS Compared to baseline, changes of the Harvey-Bradshaw (CD) and Partial Mayo Scoring (UC) indices at end of induction separated responders (18/27 or 67%) from nonresponders (9/17 or 33%). In all patients, the initial FL value at induction decreased compared to baseline, continuing to decrease after the following dose in clinical responders while bouncing back in the others. Models targeting the 2 consecutively decreased FL values or the second FL value compared to baseline or the second FL value compared to the first were able to accurately predict response at end of induction. Follow-up assessment confirmed clinical remission in initial responders (with FL values reduced on the average by 94 ± 10% compared to baseline). CONCLUSIONS In CD and UC patients during induction with biologic agents, early FL measurements accurately separate clinical responders from those experiencing PNR. The method described here offers several potential advantages over other strategies to assess and manage these patients.
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Affiliation(s)
- Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA,Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy,*Dario Sorrentino,
| | - Vu Q. Nguyen
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - Kim Love
- K.R. Love Quantitative Consulting and Collaboration, Athens, Georgia, USA
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15
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Sorrentino D, Gray JM. Timely Monitoring of Inflammation by Fecal Lactoferrin Rapidly Predicts Therapeutic Response in Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1237-1247. [PMID: 33501943 PMCID: PMC8314109 DOI: 10.1093/ibd/izaa348] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Fecal lactoferrin (FL) levels may mirror drug-induced changes in inflammation in ulcerative colitis and Crohn disease in a timely way and could be used to assess loss of response (LOR) to biologics. METHODS This study is a retrospective outcome review in 61 patients on adalimumab, infliximab, or vedolizumab managed in our center and followed for 6 to 24 months. Patients were 1) in clinical remission or 2) were experiencing possible LOR. RESULTS For group 1, in 71% of 31 patients, FL slowly increased during the therapeutic interval (R2 = 0.769; P < 0.001), thus reflecting increasing inflammation as drug concentrations decreased. In the remaining patients, FL was undetectable throughout the therapeutic interval because of a stronger suppression of inflammation. For group 2, in 30 patients negative for infections, FL levels measured 1 to 3 days after infusion/injection compared to preadministration values either increased (nonresponders)-in these patients the medication was switched to another class; partially decreased (partial responders)-the therapeutic interval was shortened; or were normal throughout (responders)-causes for symptoms unrelated to disease activity were found for all. After FL-based management, 3-month standardized clinical scores were normalized in both partial responders (0.58 ± 0.21 vs 0.13 ± 0.09; P < 0.001) and nonresponders (0.81 ± 0.17 vs 0.12 ± 0.08; P < 0.001), and FL levels dropped by up to 99%. CONCLUSIONS Levels of FL reflect drug-induced changes in mucosal inflammation in a timely way, thus enabling rapid assessment of therapeutic response in patients with ulcerative colitis and with Crohn disease. In patients with suspected LOR, FL levels before and after infusion/injection accurately separated responders, partial responders, and nonresponders. The strategy proposed here is simple, accurate, and easily applicable to clinical practice.
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Affiliation(s)
- Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
- Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy
| | - James M Gray
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
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16
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Lactoferrin and Its Detection Methods: A Review. Nutrients 2021; 13:nu13082492. [PMID: 34444652 PMCID: PMC8398339 DOI: 10.3390/nu13082492] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/12/2021] [Accepted: 07/19/2021] [Indexed: 12/17/2022] Open
Abstract
Lactoferrin (LF) is one of the major functional proteins in maintaining human health due to its antioxidant, antibacterial, antiviral, and anti-inflammatory activities. Abnormal levels of LF in the human body are related to some serious diseases, such as inflammatory bowel disease, Alzheimer’s disease and dry eye disease. Recent studies indicate that LF can be used as a biomarker for diagnosis of these diseases. Many methods have been developed to detect the level of LF. In this review, the biofunctions of LF and its potential to work as a biomarker are introduced. In addition, the current methods of detecting lactoferrin have been presented and discussed. We hope that this review will inspire efforts in the development of new sensing systems for LF detection.
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17
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Normalization of C-Reactive Protein Predicts Better Outcome in Patients With Crohn's Disease With Mucosal Healing and Deep Remission. Clin Transl Gastroenterol 2021; 11:e00135. [PMID: 32463625 PMCID: PMC7145028 DOI: 10.14309/ctg.0000000000000135] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Therapeutic targets for Crohn's disease (CD) have evolved from clinical and biological remission to mucosal healing (MH) and deep remission (DR). MH is defined as disappearance of ulceration, whereas DR is defined as a combination of clinical remission and MH. Limited data are available regarding differences in long-term outcomes of these patients reaching these targets. We thus aimed to evaluate patients' long-term clinical outcomes using different composite remission parameters.
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18
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Ishida N, Miyazu T, Suzuki T, Tamura S, Tani S, Yamade M, Hamaya Y, Iwaizumi M, Osawa S, Furuta T, Sugimoto K. Evaluation of the modified Crohn's disease activity index in patients with Crohn disease with enterostomy: A single-center observational study. Medicine (Baltimore) 2021; 100:e24717. [PMID: 33578614 PMCID: PMC10545123 DOI: 10.1097/md.0000000000024717] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 01/20/2021] [Accepted: 01/21/2021] [Indexed: 10/22/2022] Open
Abstract
ABSTRACT Although the Crohn's Disease Activity Index (CDAI) is often used to evaluate the disease activity in Crohn's disease (CD), the number of liquid or soft stools cannot be precisely evaluated, and thus accurate scores cannot be calculated, in patients with enterostomy. Therefore, we created the modified CDAI (mCDAI), without the defecation frequency item from the CDAI, and examined its usefulness.Study participants comprised 9 patients with CD with enterostomy and 20 patients with CD without enterostomy. Correlations between the mCDAI and serum albumin (Alb) levels or C-reactive protein (CRP) levels were examined using regression analysis. Additionally, regression analyses were conducted in patients with CD without enterostomy to determine the Alb and CRP levels corresponding to the CDAI at its cutoff value for remission status (150). The obtained values were applied to the mCDAI regression equations to determine the equivalent mCDAI cutoff value.mCDAI and Alb levels were significantly negatively correlated (P < .0001). The mCDAI had a significant positive correlation with the CRP level and erythrocyte sedimentation rate (P = .0061 and P = .0133, respectively). From the regression analysis of patients with CD without enterostomy, the Alb and CRP levels equivalent to a CDAI of 150 were 3.85 g/dL and 0.62 mg/dL, respectively. When applying these values to the mCDAI regression formulas, the values of 113.8 and 115.2, respectively, were obtained. Thus, the cutoff value of the mCDAI indicating disease activity was estimated as 115.The mCDAI fully reflects the nutritional status and inflammatory response, and is convenient and useful for assessing disease activity over time, in patients with CD with enterostomy. A mCDAI score ≥ 115 indicates disease activity.
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Affiliation(s)
| | | | | | | | - Shinya Tani
- Department of Endoscopic and Photodynamic Medicine
| | | | | | | | | | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
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19
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Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 44:87-95. [PMID: 32680729 DOI: 10.1016/j.gastrohep.2020.04.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 03/12/2020] [Accepted: 04/06/2020] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Proper management of the inflammatory process in Crohn's disease (CD) results in lower rates of complications. The objective of this study was to investigate the performance of isolated and combined use of fecal calprotectin (FC) and serum levels of C-reactive protein (CRP) as markers of inflammatory activity in CD and the possibility of their use as a therapeutic target. PATIENTS AND METHODS Patients with CD and indication for colonoscopy were prospectively enrolled in the study and allocated according to the presence or absence of endoscopic inflammatory activity. The correlation between FC and CRP levels and the Simplified Endoscopic Score of Crohn's Disease (SES-CD) was performed, and the accuracy of these markers was evaluated for the diagnosis of inflammatory activity, when used alone or in series. RESULTS Eighty colonoscopies were performed in patients with CD. The FC cut-off value of 155μg/g showed high sensitivity (96%) and accuracy (78%) for the diagnosis of endoscopic activity. For CRP, the value of 6.7mg/L demonstrated sensitivity of 75% and specificity of 67%. The sequential usage of these markers (FC+CRP) showed greater specificity (82%) when compared to the use of these markers alone. Depending on the probability of inflammatory activity, different scenarios were used to evaluate the performance of these markers and an algorithm is proposed. DISCUSSION Combined analysis of FC and CRP, when performed consecutively, allows decisions to be made with a high degree of certainty and even eliminates the need for colonoscopy in many situations.
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20
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Strictures in Crohn's Disease: From Pathophysiology to Treatment. Dig Dis Sci 2020; 65:1904-1916. [PMID: 32279173 DOI: 10.1007/s10620-020-06227-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 03/19/2020] [Indexed: 12/16/2022]
Abstract
Despite recent advances aimed to treat transmural inflammation in Crohn's disease (CD) patients, the progression to a structuring behavior still represents an issue for clinicians. As inflammation becomes chronic and severe, the attempt to repair damaged tissue can result in an excessive production of extracellular matrix components and deposition of connective tissue, thus favoring the formation of strictures. No specific and accurate clinical predictors or diagnostic tools for intestinal fibrosis exist, and to date, no genetic or serological marker is in routine clinical use. Therefore, intestinal fibrosis is usually diagnosed when it becomes clinically evident and strictures have already occurred. Anti-fibrotic agents such as tranilast, peroxisome proliferator-activated receptor gamma agonists, rho kinase inhibitors, and especially mesenchymal stem cell therapy have provided interesting results, but most of the evidence has been derived from studies performed in vitro. Therefore, current therapy of fibrotic strictures relies mainly on endoscopic and surgical procedures. Although its long-term outcomes may be debated, endoscopic balloon dilation appears to be the safest and most effective approach to treat appropriately selected strictures. The use of endoscopic stricturotomy is currently limited by the expertise needed to perform it and by the few data available in the literature. Some good results have been achieved by the positioning of self-expandable metal stents (SEMS). However, there is no concordance regarding the type of stent to use and for how long it should be left in place. The development of new specific SEMS may lead to better outcomes and to an increased use of this alternative in CD-related strictures.
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21
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Nardone OM, Shivaji UN, Ferruzza V, Ghosh S, Iacucci M. Soluble Blood Markers of Mucosal Healing in Inflammatory Bowel Disease: The Future of Noninvasive Monitoring. Inflamm Bowel Dis 2020; 26:961-969. [PMID: 31587036 DOI: 10.1093/ibd/izz226] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Indexed: 12/13/2022]
Abstract
The traditional management of inflammatory bowel disease (IBD) based on symptom control is not considered valid anymore by most specialists in this field, and a new paradigm called "treat to target" has been introduced. This is based on the assessment of disease activity using objective measures. The identification of noninvasive biomarkers is crucial to diagnosis and monitor IBD because frequent endoscopic examinations are costly and uncomfortable for the patient. In this review, we focus on blood markers that may be able to assess mucosal healing (MH) in IBD and recent advances in this area. Introduction of commercial panel to predict MH opens the way for further developments so that colonoscopy or fecal markers may be avoided in some patients. This may also permit frequent monitoring for therapeutic response and achieve MH. It is a challenging area of research to identify a panel of biomarkers that may reflect inflammation and healing to serve as a surrogate of MH.
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Affiliation(s)
- Olga Maria Nardone
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK
| | - Uday Nagesh Shivaji
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK
| | - Vittoria Ferruzza
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK
| | - Subrata Ghosh
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK.,University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK.,NIHR Biomedical Research Centre, University of Birmingham and University Hospitals NHS Foundation Trust Birmingham, UK.,Department of Gastroenterology and Hepatology, University of Calgary, Alberta, Canada
| | - Marietta Iacucci
- Institute of Translational Medicine and Institute of Immunology and Immunotherapy, University of Birmingham, UK.,University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK.,NIHR Biomedical Research Centre, University of Birmingham and University Hospitals NHS Foundation Trust Birmingham, UK.,Department of Gastroenterology and Hepatology, University of Calgary, Alberta, Canada
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22
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Wang WG, Lu WZ, Yang CM, Yu KQ, He HB. Modified Van Assche magnetic resonance imaging-based score for assessing the clinical status of anal fistulas. Medicine (Baltimore) 2020; 99:e20075. [PMID: 32384475 PMCID: PMC7440082 DOI: 10.1097/md.0000000000020075] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The modified Van Assche magnetic resonance imaging (MRI)-based score is a feasible system to assess the clinical status of anal fistulas in Crohn disease. In this study, we evaluated this score's association with clinical status in patients with anal fistulas (AFs).We included all patients with AF who underwent contrast-enhanced pelvic MRI and surgery between January 2011 and December 2016. The score was evaluated retrospectively preoperatively and 1, 3, and 6 months postoperatively. Univariate and multivariate analyses of the risk factors for AF recurrence were also performed.We retrospectively analyzed data for 104 patients. Twelve (11.5%) patients developed AF recurrence. We classified patients' preoperative clinical status into three grades: 52 (50.0%) grade A, 31 (29.8%) grade B, and 21 (20.2%) grade C. The preoperative MRI-based score was significantly correlated with patients' preoperative clinical status grade (Pearson correlation: 0.547; P < .001). The 3 preoperative clinical status grades showed significant (F = 23.303, P < .001) tendencies for associations with lower respective MRI-based scores. The incidence of AF recurrence decreased with the MRI-based score to 1-month postoperatively, then gradually increased (F = 60.863, P = .000). Long duration of disease, prior interventions, and high MRI-based score were independent risk factors for AF recurrence.The MRI-based score objectively assessed the clinical status and disease activity of patients with AFs, with a high score being associated with severe clinical status and long recovery time.
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Affiliation(s)
- Wei-Guo Wang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University
| | - Wen-Zhu Lu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University
| | - Chun-Mei Yang
- Department of Integrated Traditional Chinese and Western Medicine, Cheng Du Shang Jin Nan Fu Hospital, Chengdu, Sichuan Province, China
| | - Ke-Qiang Yu
- Department of Integrated Traditional Chinese and Western Medicine, Cheng Du Shang Jin Nan Fu Hospital, Chengdu, Sichuan Province, China
| | - Hong-Bo He
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University
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23
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Cantarelli BCF, de Oliveira RS, Alves AMA, Ribeiro BJ, Velloni F, D'Ippolito G. Evaluating inflammatory activity in Crohn's disease by cross-sectional imaging techniques. Radiol Bras 2020; 53:38-46. [PMID: 32313336 PMCID: PMC7159043 DOI: 10.1590/0100-3984.2018.0096] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The evaluation of inflammatory bowel activity in patients with Crohn’s disease has traditionally been a challenge, mainly because of the difficulty in gaining endoscopic access to the small bowel. Historically, barium-based contrast studies were the only option for the evaluation of inflammatory activity in Crohn’s disease. They were gradually replaced by cross-sectional imaging techniques, computed tomography enterography (CTE) and magnetic resonance enterography (MRE) now being the modalities of choice for such evaluations. Those two imaging methods have provided important information regarding intestinal wall involvement and extra-intestinal manifestations of Crohn’s disease, not only assessing lesion characteristics and complications but also quantifying inflammatory bowel activity. The objective of this article is to review the main technical aspects of CTE and MRE, together with their indications, contraindications, and limitations, as well as the CTE and MRE imaging characteristics of inflammatory activity in Crohn’s disease.
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Affiliation(s)
| | | | - Aldo Maurici Araújo Alves
- Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Bruno Jucá Ribeiro
- Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Fernanda Velloni
- Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil.,Diagnósticos da América S/A, Barueri, SP, Brazil
| | - Giuseppe D'Ippolito
- Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
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24
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E Penna FGC, Rosa RM, da Cunha PFS, de Souza SCS, de Abreu Ferrari MDL. Faecal calprotectin is the biomarker that best distinguishes remission from different degrees of endoscopic activity in Crohn's disease. BMC Gastroenterol 2020; 20:35. [PMID: 32054445 PMCID: PMC7020548 DOI: 10.1186/s12876-020-1183-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 02/05/2020] [Indexed: 12/14/2022] Open
Abstract
Background Effective control of the inflammatory process in Crohn’s disease (CD) is reflected in intestinal mucosal healing. The performances of faecal calprotectin (fcal), clinical and serologic parameters in the inflammatory activity evaluation and their correlation to the simple endoscopic score (SES-CD) are the goals of this study. Methods Patients with CD referred for ileocolonoscopy were prospectively included and distributed according to the degree of endoscopic inflammatory activity into remission, mild activity, and moderate to severe activity groups. The different degrees of endoscopic activity were correlated with the following indexes: Crohn’s disease activity index (CDAI), fCal, serum C-reactive protein (CRP), and haemogram. The control group comprised individuals without known intestinal disease who were referred for colorectal cancer screening. Results Eighty colonoscopies were performed in patients with CD and 21 in the control group. The control group had a lower median fCal (59.7 mcg/g) than patients with CD (683 mcg/g, p < 0.001). A moderate Spearman correlation occurred between SES-CD and CRP (r = 0.525), fCal (r = 0.450), and CDAI (r = 0.407), while a weak correlation was found with the platelet count (r = 0.257). Only fCal distinguished patients in remission from those with mild activity (236.6 mcg/g × 654.9 mcg/g, p = 0.014) or moderate to severe activity (236.6 mcg/g × 1128 mcg/g, p < 0.001). An fCal cut-off of 155 mcg/g was sensitive (96%) and accurate (78%) for the diagnosis of endoscopic activity. Conclusions fCal provides greater diagnostic accuracy than the other activity markers for endoscopic activity of patients with CD, moderate correlation to SES-CD, and a capacity to discriminate patients in remission from those with mild or moderate to severe activity.
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Affiliation(s)
- Francisco Guilherme Cancela E Penna
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 110, second floor. Bairro: Santa Efigênia, Belo Horizonte, Minas Gerais, CEP: 30130-100, Brazil.
| | - Rodrigo Macedo Rosa
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 110, second floor. Bairro: Santa Efigênia, Belo Horizonte, Minas Gerais, CEP: 30130-100, Brazil
| | - Pedro Ferrari Sales da Cunha
- Medical student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 190. Bairro: Santa Efigênia, Belo Horizonte, Minas Gerais, CEP: 30130-100, Brazil
| | - Stella Cristina Silva de Souza
- Medical student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 190. Bairro: Santa Efigênia, Belo Horizonte, Minas Gerais, CEP: 30130-100, Brazil
| | - Maria de Lourdes de Abreu Ferrari
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena 190. Bairro: Santa Efigênia, Belo Horizonte, Minas Gerais, CEP: 30130-100, Brazil
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25
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Rubio MG, Amo-Mensah K, Gray JM, Nguyen VQ, Nakat S, Grider D, Love K, Boone JH, Sorrentino D. Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease. World J Gastrointest Pathophysiol 2019; 10:54-63. [PMID: 31911845 PMCID: PMC6940564 DOI: 10.4291/wjgp.v10.i5.54] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 12/12/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin (FC) and fecal lactoferrin (FL) in monitoring inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC). However, their correlation to endoscopic scores, disease severity and affected intestinal surface has not been extensively investigated.
AIM To correlate FL, and for comparison white blood cell (WBC) and C-reactive protein (CRP), with endoscopic scores, disease extent and location in CD and UC.
METHODS Retrospective analysis in 188 patients who had FL, CRP and WBC determined within 30 d of endoscopy. Disease location, disease extent (number of intestinal segments involved), disease severity (determined by endoscopic scores), timing of FL testing in relation to colonoscopy, as well as the use of effective fast acting medications (steroids and biologics) between colonoscopy and FL measurement, were recorded.
RESULTS In 131 CD and 57 UC patients, both CRP and FL - but not WBC - distinguished disease severity (inactive, mild, moderate, severe). In patients receiving fast-acting (steroids or biologics) treatment in between FL and colonoscopy, FL showed a higher correlation to endoscopic scores when tested before vs after the procedure (r = 0.596, P < 0.001, vs r = 0.285, P = 0.15 for the Simple Endoscopic Score for CD; and r = 0.402, P = 0.01 vs r = 0.054 P = 0.84 for Disease Activity Index). Finally, FL was significantly correlated with the diseased mucosal surface (colon-ileocolon > small bowel) and the number of inflamed colon segments.
CONCLUSION FL and CRP separated disease severity categories with FL showing lower discriminating P-values. FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure – this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels. FL can accurately and timely characterize intestinal inflammation in IBD.
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Affiliation(s)
- Marrieth G Rubio
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Kofi Amo-Mensah
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - James M Gray
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Vu Q Nguyen
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Sam Nakat
- Department of Radiology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
| | - Douglas Grider
- Department of Basic Science Education; Virginia Tech Carilion School of Medicine and Dominion Pathology Associates, Roanoke, VA 24016, United States
| | - Kim Love
- K. R. Love Quantitative Consulting and Collaboration, Athens, GA 30605, United States
| | - James H Boone
- Research and Development, TECHLAB Inc, Blacksburg, VA 24060, United States
| | - Dario Sorrentino
- IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
- Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine 33100, Italy
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26
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Straksyte V, Kiudelis G, Gineikiene I, Janciauskas D, Basevicius A, Lukosevicius S, Kupcinskas L. Lemann Index for Assessment of Crohn's Disease: Correlation with the Quality of Life, Endoscopic Disease Activity, Magnetic Resonance Index of Activity and C- Reactive Protein. Open Med (Wars) 2019; 14:785-791. [PMID: 31737782 PMCID: PMC6843552 DOI: 10.1515/med-2019-0092] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 09/03/2019] [Indexed: 02/06/2023] Open
Abstract
AIM Crohn's disease (CD) is characterized by continuing inflammation and progressive gut damage. Despite many scoring indices of CD, there is a lack of more global assessment tools for the evaluation of the total disease impact on the gut. METHODS Fift y-three adult patients with proven CD underwent magnetic resonance enterocolonography (MR-EC), colonoscopy, and clinical activity assessment, including CRP. Quality of life was assessed using IBDQ. MR-EC was used to evaluate the Magnetic Resonance Index of Activity (MaRIA- global (G)) and the Lemann Index (LI). The CD Endoscopic Index of Severity (CDEIS) was used to score the endoscopic activity of the disease. RESULTS A signifi cant correlation between the LI and IBDQ was found (r=-0.812, P<0.01). LI and MaRIA-G correlated moderately, while the LI did not correlate significantly with CRP and CDEIS. For the detection of endoscopically active CD, MaRIA-G was more sensitive and specific (83.3%; 73.3%) compared to the LI (66.7%; 60.0%). There was a moderate correlation between CRP and MaRIA-G, as well as CRP and CDEIS (r=0.496; r=0.527,<0.01). CONCLUSION A signifi cant negative correlation between the LI and quality of life, measured by IBDQ, was found in our study, suggesting that the LI could resemble more global features of the disease, besides inflammatory activity of the gut.
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Affiliation(s)
- Vestina Straksyte
- Department of Radiology, Lithuanian University of Health Sciences, Eivenių str. 2, Kaunas, Lithuania
| | - Gediminas Kiudelis
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Irina Gineikiene
- Department of Radiology, Lithuanian University of Health Sciences, Eivenių str. 2, Kaunas, Lithuania
| | - Dainius Janciauskas
- Department of Pathological Anatomy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Algidas Basevicius
- Department of Radiology, Lithuanian University of Health Sciences, Eivenių str. 2, Kaunas, Lithuania
| | - Saulius Lukosevicius
- Department of Radiology, Lithuanian University of Health Sciences, Eivenių str. 2, Kaunas, Lithuania
| | - Limas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
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27
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Impaired nutritional status in outpatients in remission or with active Crohn's disease – classified by objective endoscopic and imaging assessments. Clin Nutr ESPEN 2019; 33:60-65. [DOI: 10.1016/j.clnesp.2019.07.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 03/15/2019] [Accepted: 07/16/2019] [Indexed: 12/15/2022]
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28
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Abstract
PURPOSE OF REVIEW Crohn's disease management has changed significantly with increasing use of biologics. We review the recent literature on the clinical management of Crohn's disease and new approaches in selecting and optimizing therapy. RECENT FINDINGS Recent studies have addressed the efficacy of proactive anti-TNFα trough level monitoring, the efficacy of biosimilars, and the efficacy and immunogenicity of newer biologics including anti-integrin therapy and anti-IL12/23 therapy. Optimizing anti-TNFα therapy according to trough concentrations correlates with improved remission rates. Patients can be switched from the reference drug to a biosimilar, or vice versa, without a measurable change in efficacy, safety, or immunogenicity. Immunomodulators are effective in decreasing immunogenicity and boosting anti-TNFα drug level. The anti-integrin and anti-IL12/23 therapies are effective as induction and maintenance therapy with low immunogenicity and excellent safety profiles. Patients at high risk for post-operative recurrence should be started on a biologic therapy within 4 weeks post-op. Multiple biologic therapies are currently available for treatment of Crohn's disease including anti-TNFα therapy, anti-integrin therapy, and anti-IL12/23 therapy. The choice of first-line therapy should be based on individual risk-benefit analysis, route of administration, and patient preference. Patient with inadequate response should have their trough level checked and therapy optimized. Therapeutic prophylaxis for post-operative recurrence should be based on patient's risk factors for recurrence.
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Affiliation(s)
- Thomas X Lu
- Section of Gastroenterology, Hepatology and Nutrition, Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, 60637, USA
| | - Russell D Cohen
- Section of Gastroenterology, Hepatology and Nutrition, Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, 60637, USA.
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29
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Sturm A, Maaser C, Calabrese E, Annese V, Fiorino G, Kucharzik T, Vavricka SR, Verstockt B, van Rheenen P, Tolan D, Taylor SA, Rimola J, Rieder F, Limdi JK, Laghi A, Krustiņš E, Kotze PG, Kopylov U, Katsanos K, Halligan S, Gordon H, González Lama Y, Ellul P, Eliakim R, Castiglione F, Burisch J, Borralho Nunes P, Bettenworth D, Baumgart DC, Stoker J. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principles and technical aspects. J Crohns Colitis 2019; 13:273-284. [PMID: 30137278 DOI: 10.1093/ecco-jcc/jjy114] [Citation(s) in RCA: 258] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Andreas Sturm
- Department of Gastroenterology, DRK Kliniken Berlin I Westend, Berlin, Germany
| | - Christian Maaser
- Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Emma Calabrese
- Department of Systems Medicine, University of Rome, Tor Vergata, Italy
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic & American Hospital, Dubai, UAE
| | - Gionata Fiorino
- Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | | | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven and CHROMETA - Translational Research in Gastrointestinal Disorders, KU Leuven, Belgium
| | - Patrick van Rheenen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, University Medical Center Groningen, Groningen, The Netherlands
| | - Damian Tolan
- Clinical Radiology, St James's University Hospital, Leeds, UK
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Jordi Rimola
- Department of Radiology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester; Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
| | - Andrea Laghi
- Department of Clinical and Surgical Translational Medicine, Sapienza - University of Rome, Rome, Italy
| | - Eduards Krustiņš
- Department of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Riga, Latvia
| | - Paulo G Kotze
- Colorectal Surgery Unit, Catholic University of Paraná PUCPR, Curitiba, Brazil
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Steve Halligan
- Centre for Medical Imaging, University College London, London, UK
| | - Hannah Gordon
- Section of Gastroenterology & Hepatology, Royal London Hospital, London, UK
| | - Yago González Lama
- Department of Gastroenterology, University Hospital Puerta De Hierro, Majadahonda Madrid, Spain
| | - Pierre Ellul
- Department of Medicine, Mater Dei Hospital, Msida, Malta
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Fabiana Castiglione
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
| | - Paula Borralho Nunes
- Department of Anatomic Pathology, Hospital Cuf Descobertas; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Daniel C Baumgart
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Academic Medical Center AMC, University of Amsterdam, Amsterdam, The Netherlands
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Zawadka-Kunikowska M, Słomko J, Kłopocka M, Liebert A, Tafil-Klawe M, Klawe JJ, Newton JL, Zalewski P. Cardiac and autonomic function in patients with Crohn's disease during remission. Adv Med Sci 2018; 63:334-340. [PMID: 30053718 DOI: 10.1016/j.advms.2018.04.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 01/25/2018] [Accepted: 04/26/2018] [Indexed: 01/01/2023]
Abstract
PURPOSE The aim of the study was to assess cardiac and autonomic function in patients with Crohn's disease and explore their relation to disease duration using cardiovascular reflex tests. MATERIALS AND METHODS Cardiovascular parameters, baroreflex sensitivity, spectral-indices of short-term heart rate variability and blood pressure variability were compared between patients with Crohn's disease in remission (n = 30) and a control group (n = 29). Cardiac autonomic function was assessed during response to standing (tilt) and deep breathing test (expiration/inspiration ratio-E/I). Aortic pulse wave velocity, aortic augmentation index and central systolic blood pressure were measured oscillometrically. RESULTS At rest, Crohn's disease patients had significantly higher systolic (p = 0.03) and diastolic (p = 0.03) blood pressure, total peripheral resistance index (p = 0.003), sympathetic-parasympathetic ratio (p = 0.033) and lower baroreceptor effectiveness (p = 0.047), myocardial variables (stroke index; p = 0.03, cardiac index; p = 0.025, Heather index; p = 0.039, left ventricular ejection time; p = 0.038), as compared to controls. Orthostatic response to the tilt test in the Crohn's disease group and the control group was similar, no intergroup differences were observed for E/I ratio and autonomic parameters. In Crohn's disease patients, disease duration was negatively associated with baroreflex sensitivity and positively correlated with normalised high frequency heart rate variability, sympathetic-parasympathetic ratio at rest and post-tilt changes in Δsystolic blood pressure, p < 0.05. The control group had significantly lower central systolic blood pressure (p = 0.043) compared to Crohn's disease patients. CONCLUSIONS Crohn's disease patients in remission have preserved cardiac and autonomic function in response to cardiovascular reflex tests with a shift in cardiovascular autonomic regulation towards sympathetic predominate in the rest position.
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Padoan A, D’Incà R, Scapellato ML, De Bastiani R, Caccaro R, Mescoli C, Moz S, Bozzato D, Zambon CF, Lorenzon G, Rugge M, Plebani M, Basso D. Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability. ACTA ACUST UNITED AC 2018; 56:1926-1935. [DOI: 10.1515/cclm-2018-0134] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 04/03/2018] [Indexed: 12/12/2022]
Abstract
Abstract
Background:
The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting.
Methods:
Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry.
Results:
A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older (≥65 years) subjects (ROC area: 0.584; 95% CI: 0.399–0.769). Among the young, assays have different optimal thresholds (120 μg/g for ELISA, 50 μg/g for CLIA and 100 μg/g for turbidimetry).
Conclusions:
We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV.
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Affiliation(s)
- Andrea Padoan
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Renata D’Incà
- Division of Gastroenterology , University Hospital , Padova , Italy
| | - Maria Luisa Scapellato
- Department of Cardiologic, Thoracic and Vascular Sciences , Preventive Medicine and Risk Assessment Unit , University Hospital of Padova , Padova , Italy
| | - Rudi De Bastiani
- Italian Association for Gastroenterology in Primary Care (GICA-CP) , Feltre , Italy
| | - Roberta Caccaro
- Division of Gastroenterology , University Hospital , Padova , Italy
| | - Claudia Mescoli
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Stefania Moz
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Dania Bozzato
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | | | - Greta Lorenzon
- Division of Gastroenterology , University Hospital , Padova , Italy
| | - Massimo Rugge
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Mario Plebani
- Department of Medicine – DIMED , University of Padova , Padova , Italy
| | - Daniela Basso
- Department of Medicine – DIMED , University of Padova , Padova , Italy
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Sandborn WJ, Abreu MT, Dubinsky MC. A Noninvasive Method to Assess Mucosal Healing in Patients* With Crohn's Disease. Gastroenterol Hepatol (N Y) 2018; 14:1-12. [PMID: 29991933 PMCID: PMC6018319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Ongoing inflammation in the gastrointestinal tract and loss of the mucosal barrier are key components of Crohn's disease. Current treatment paradigms, including treat-to-target, are based on improvement of both clinical and endoscopic symptoms. Endoscopy is an essential tool for the evaluation of mucosal healing, but patients may be reluctant to undergo repeated procedures. Surrogate markers of inflammation, such as C-reactive protein and fecal calprotectin, are being used, yet they have several limitations in the assessment of mucosal healing. A new strategy, known as the Monitr test, assesses mucosal healing status by evaluating serum levels of 13 biomarkers in patients with Crohn's disease. The 13 biomarkers are associated with cell adhesion, inflammation, angiogenesis, extracellular matrix remodeling, cell proliferation and repair, and immune cell recruitment. Monitr testing yields a mucosal healing index score that reflects disease severity. Validation of the test showed an overall accuracy of 90%, with a negative predictive value of 92% and a positive predictive value of 87% for identifying patients with endoscopic evidence of Crohn's disease. Use of this noninvasive test may aid in the monitoring and management of patients with Crohn's disease, while potentially reducing the need for repeated endoscopy.
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Affiliation(s)
- William J Sandborn
- Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Director, UCSD IBD Center University of California San Diego University of California San Diego Health System La Jolla, California
| | - Maria T Abreu
- Director, Crohn's and Colitis Center Professor of Medicine, Microbiology, and Immunology University of Miami Miller School of Medicine Miami, Florida
| | - Marla C Dubinsky
- Professor of Pediatrics Chief, Pediatric Gastroenterology and Hepatology and Nutrition Co-Director, Susan and Leonard Feinstein IBD Clinical Center Icahn School of Medicine at Mount Sinai New York, New York
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Fomin VV, Ternovoy SK, Makhov VM, Isaykina MA, Dzhenzhera NA, Turko TV, Ugryumova LN, Babenko OV. Ultrasound examination with contrast in the diagnosis of inflammatory bowel disease. The results of the pilot study. TERAPEVT ARKH 2018; 90:53-58. [DOI: 10.26442/terarkh201890253-58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Aim. Assessment of diagnostic significance of informativeness and security of ultrasonography with contrast enhancement drug SonoVue in the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). Materials and methods. The pilot conducted a prospective study which involved 15 patients with inflammatory bowel disease (IBD). All patients gave written consent to participate in the study and processing of personal data. The study included adult patients with an established diagnosis of UC and CD, with proven clinical activity of the disease. Activity was evaluated based on clinical and laboratory data on the scale of best (CDAI >150) for patients with CD and on a scale of Trulove-Witts (2-3 stage) and the Mayo index (DAI) for patients with UC. All the patients underwent colonoscopy with biopsy, ultrasound examination of abdominal cavity organs with the study of the vascularization of the intestinal wall (color Doppler, power Doppler, contrast study). Results. The use of contrast showed additional features in the instrumental evaluation of activity of inflammatory process, identification of complications and assessment of prognosis. Conclusion. The results of ultrasound of the bowel with contrast can be used to assess the activity and stage of disease in patients with UC or CD.
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Correlation of 18F-FDG PET/MRE Metrics with Inflammatory Biomarkers in Patients with Crohn's Disease: A Pilot Study. CONTRAST MEDIA & MOLECULAR IMAGING 2017; 2017:7167292. [PMID: 29097934 PMCID: PMC5625758 DOI: 10.1155/2017/7167292] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 08/03/2017] [Indexed: 12/22/2022]
Abstract
Background To investigate the association between 18F-FDG (Fluorodeoxyglucose) PET (positron emission tomography)/MRE (magnetic resonance enterography) metrics with the inflammatory biomarkers fecal calprotectin and C-reactive protein (CRP) in patients with Crohn's disease (CD). Methods This prospective pilot study was institutional review board (IRB) approved with informed consent obtained. Consecutive CD patients were referred to 18F-FDG PET/MRE. Patients in whom colonoscopy was performed and CRP and fecal calprotectin levels were measured were included. CRP and fecal calprotectin were regarded as positive for inflammation if they were greater than 0.5 mg/dl and 150 mcg/g, respectively. Correlation of quantitative variables was performed using the Pearson's correlation coefficient. Receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was calculated to evaluate the accuracy of PET and MRE metrics in determining the presence of inflammation evaluated by calprotectin and CRP levels. Results Analysis of 21 patients (16 women and 5 men, 43 ± 18 years) was performed. Magnetic resonance index of activity (MaRIA) score had an AUC of 0.63 associated with fecal calprotectin and CRP. Adding apparent diffusion coefficient (ADC) and metabolic inflammatory volume (MIV) to MaRIA score resulted in an AUC of 0.92 with a cutoff value of 447 resulting in 83% and 100% sensitivity and specificity, respectively. Conclusion The addition of ADC and MIV to the MaRIA score increases the accuracy for discrimination of disease activity in patients with CD. Trial registration number is 2015062.
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Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol: Longitudinal Data from a 7-Year Study in Crohn's Disease. Inflamm Bowel Dis 2017; 23:1047-1056. [PMID: 28410341 DOI: 10.1097/mib.0000000000001100] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. METHODS PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. RESULTS Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. CONCLUSIONS This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.
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Small-bowel mucosal healing assessment by capsule endoscopy as a predictor of long-term clinical remission in patients with Crohn's disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2017; 29:844-848. [PMID: 28410352 DOI: 10.1097/meg.0000000000000881] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Capsule endoscopy (CE) may be used for the evaluation and follow-up of patients with Crohn's disease. CE scores correspond to the degree of mucosal inflammation, a major therapeutic target. The aim of this meta-analysis and systematic review was to determine whether mucosal healing assessment by CE may serve as a predictor of clinical remission in patients with Crohn's disease. To identify observational or controlled English-language full-text studies assessing mucosal healing by CE in patients with Crohn's disease up to 30 September 2016, we searched PubMed, Embase, Central, Medline, and Scopus using the key words 'mucosal healing' and 'capsule endoscopy'. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios and 95% confidence intervals were calculated. Five observational studies including 142 patients from five countries fulfilled the inclusion criteria. No publication bias was found by funnel plot. The mucosal healing CE score was found to be significantly associated with improved outcome after a follow-up of 12 weeks to 24 months, with an odds ratio of 11.06 (95% confidence interval: 3.74-32.73, P<0.001). The degree of heterogeneity among the studies was small (Q=2.014, d.f.[Q]=3, P=0.569 and I=0). Endoscopy scores may play a role in the long-term prognostic evaluation of patients with Crohn's disease. Our results may be accepted as proof of concept, but larger studies are needed to corroborate these findings.
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Wei SC, Chang TA, Chao TH, Chen JS, Chou JW, Chou YH, Chuang CH, Hsu WH, Huang TY, Hsu TC, Lin CC, Lin HH, Lin JK, Lin WC, Ni YH, Shieh MJ, Shih IL, Shun CT, Tsang YM, Wang CY, Wang HY, Weng MT, Wu DC, Wu WC, Yen HH, Wong JM. Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease. Intest Res 2017; 15:285-310. [PMID: 28670226 PMCID: PMC5478754 DOI: 10.5217/ir.2017.15.3.285] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 05/02/2017] [Accepted: 05/02/2017] [Indexed: 12/12/2022] Open
Abstract
Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.
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Affiliation(s)
- Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ting-An Chang
- Department of Pathology, Taipei City Hospital Renai Branch, Taipei, Taiwan
| | - Te-Hsin Chao
- Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jinn-Shiun Chen
- Division of Colorectal Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Jen-Wei Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Hsin Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, National Yang-Ming University, Taipei, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wei-Chen Lin
- Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - I-Lun Shih
- Department of Medical Imaging, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yuk-Ming Tsang
- Division of Medical Imaging, Department of Radiology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.,MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.,MacKay Medical College, New Taipei City, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wen-Chieh Wu
- Division of Gastroenterology, Department of Medicine, Taipei City Hospital Renai Branch, Taipei, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Gordon M. 5-Aminosalicylates to maintain remission in Crohn’s disease: Interpreting conflicting systematic review evidence. World J Gastrointest Pharmacol Ther 2017; 8:99-102. [PMID: 28533918 PMCID: PMC5421116 DOI: 10.4292/wjgpt.v8.i2.99] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/15/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
5-Aminosalicylates are a class of anti-inflammatory agents that have been used for decades in inflammatory bowel disease. Whilst they are first line for induction and an option for maintenance of remission in ulcerative colitis, the picture in Crohn’s disease is variable. For maintenance of remission, key Cochrane systematic reviews have found conflicting results between the medical and surgical induced contexts. In this piece, the possible reasons for this are considered. It is proposed that clinicians should consider 5-aminosalicylates agents an option to maintain remission post-surgery. Future primary research is needed in the medical induced remission setting which considers the length of remission on enrolment and endoscopic or histological disease scores. Additionally, secondary research to rank the various treatment options in the post-surgical setting could be achieved through the use of network meta-analysis and will guide policy makers in the future.
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Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps. J Perinatol 2016; 36:862-9. [PMID: 27388941 PMCID: PMC5045760 DOI: 10.1038/jp.2016.105] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 03/30/2016] [Accepted: 04/05/2016] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Neonates with necrotizing enterocolitis (NEC) have higher calprotectin levels in stool than do healthy neonates. However, it is not known whether high stool calprotectin at the onset of bowel symptoms identifies neonates who truly have NEC vs other bowel disorders. STUDY DESIGN Neonates were eligible for this study when an x-ray was ordered to 'rule-out NEC'. Stool calprotectin was quantified at that time and in a follow-up stool. Each episode was later categorized as NEC or not NEC. The location of calprotectin in the bowel was determined by immunohistochemistry. RESULTS Neonates with NEC had higher initial and follow-up stool calprotectin levels than did neonates without NEC. Calprotectin in bowel from neonates with NEC was within neutrophil extracellular traps (NETs). CONCLUSION At the onset of signs concerning for NEC, fecal calprotectin is likely to be higher in neonates with NEC. Calprotectin in their stools is exported from neutrophils via NETs.
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Eder P, Korybalska K, Lykowska-Szuber L, Krela-Kazmierczak I, Stawczyk-Eder K, Klimczak K, Szymczak A, Linke K, Witowski J. Association of serum VEGF with clinical response to anti-TNFα therapy for Crohn's disease. Cytokine 2016; 76:288-293. [PMID: 26481259 DOI: 10.1016/j.cyto.2015.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 09/04/2015] [Accepted: 09/30/2015] [Indexed: 12/17/2022]
Abstract
Down-regulation of immune-mediated angiogenesis seems to be an important mechanism in anti-tumor necrosis factor α (anti-TNFα) therapy for Crohn's disease (CD). However, it remains to be established whether the baseline pro-angiogenic activity as reflected by the level of vascular endothelial growth factor (VEGF) could be of predictive value for successful clinical outcome of such treatment. Here, the levels of serum VEGF and other crucial angiogenesis-regulating peptides were assessed before and after induction anti-TNFα therapy in CD patients, and in age- and sex-matched healthy controls. Clinical, endoscopic, and biochemical activity of CD was estimated in parallel. CD patients were divided into two subgroups, depending on baseline VEGF levels: a "low-VEGF" subgroup with VEGF levels similar to those detected in healthy people, and a "high-VEGF" subgroup with VEGF levels significantly increased. VEGF levels were found to significantly correlate with CD clinical activity. Compared to the "low-VEGF" subgroup, the reduction in CD clinical activity as assessed by Crohn's Disease Activity Index was significantly greater in "high-VEGF" patients both in absolute numbers, and as a percentage of pre-treatment values. Accordingly, the fraction of patients who did not respond adequately to treatment was significantly greater in the "low-VEGF" group. These data indicate that VEGF may serve as an additional marker of CD activity and that baseline VEGF levels can be helpful in predicting the efficacy of anti-TNFα therapy.
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Affiliation(s)
- Piotr Eder
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland.
| | - Katarzyna Korybalska
- Department of Pathophysiology, Poznan University of Medical Sciences, 8 Rokietnicka St., 60-806 Poznan, Poland
| | - Liliana Lykowska-Szuber
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland
| | - Iwona Krela-Kazmierczak
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland
| | - Kamila Stawczyk-Eder
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland
| | - Katarzyna Klimczak
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland
| | - Aleksandra Szymczak
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland
| | - Krzysztof Linke
- Department of Gastroenterology, Human Nutrition and Internal Diseases, Poznan University of Medical Sciences, Heliodor Swiecicki Hospital, 49 Przybyszewskiego St., 60-355 Poznan, Poland
| | - Janusz Witowski
- Department of Pathophysiology, Poznan University of Medical Sciences, 8 Rokietnicka St., 60-806 Poznan, Poland
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Zhu C, Ma X, Xue L, Xu J, Li Q, Wang Y, Zhang J. Small intestine contrast ultrasonography for the detection and assessment of Crohn disease: A meta-analysis. Medicine (Baltimore) 2016; 95:e4235. [PMID: 27495028 PMCID: PMC4979782 DOI: 10.1097/md.0000000000004235] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Crohn disease (CD) is a chronic relapsing disease. Imaging modalities are essential for the diagnosis and assessment of CD. Small intestine contrast ultrasonography (SICUS) is a well-tolerated, noninvasive and radiation-free modality and has shown potential in CD assessment. We aimed at evaluating the diagnostic accuracy of SICUS in the detection and assessment of small-bowel lesions and complications in CD. METHODS We searched PubMed database for relevant studies published before April 24, 2016. We integrated the true positive, false positive, false negative, and true negative into the pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. Forest plots were to represent the pooled results of all studies. RESULTS Thirteen articles were finally considered eligible. The pooled sensitivity and specificity of SICUS in detecting small-bowel lesions were 0.883 (95% confidence interval (CI) 0.847-0.913) and 0.861 (95% CI 0.828-0.890), respectively. The pooled diagnostic odds ratio was 39.123 (95% CI 20.014-76.476) and the area under the curve of summary receiver operating characteristic was 0.9273 (standard error: 0.0152). In subgroup analyses, SICUS represented fine sensitivity and specificity in proximal and distal small intestine lesion, as well as in CD-related complications such as stricture, dilation, abscess, and fistula. CONCLUSION SICUS is accurate enough to make a complete assessment about the location, extent, number, and almost all kinds of complications in CD small-bowel lesions.
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Affiliation(s)
- Chenjing Zhu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital
| | - Xuelei Ma
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital
- Correspondence: Xuelei Ma, West China Hospital, No. 37, Guoxue Alley, 610041 Chengdu, P.R. China (e-mail: )
| | - Luqi Xue
- West China School of Medicine, Sichuan University, Chengdu
| | - Jing Xu
- West China School of Medicine, Sichuan University, Chengdu
| | - Qingfang Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital
| | - Yun Wang
- Gansu Province Wuwei Cancer Hospital, P.R. China
| | - Jing Zhang
- West China School of Medicine, Sichuan University, Chengdu
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Masselli G, Mastroiacovo I, De Marco E, Francione G, Casciani E, Polettini E, Gualdi G. Current tecniques and new perpectives research of magnetic resonance enterography in pediatric Crohn's disease. World J Radiol 2016; 8:668-82. [PMID: 27551337 PMCID: PMC4965351 DOI: 10.4329/wjr.v8.i7.668] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2015] [Revised: 03/24/2016] [Accepted: 04/07/2016] [Indexed: 02/06/2023] Open
Abstract
Crohn's disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past two decades. The endoscopy with biopsy is generally considered the diagnostic reference standard, this combination can evaluates only the mucosa, not inflammation or fibrosis in the mucosa. Actually, the only modalities that can visualize submucosal tissues throughout the small bowel are the computed tomography (CT) enterography (CTE) with the magnetic resonance enterography (MRE). CT generally is highly utilized, but there is growing concern over ionizing radiation and cancer risk; it is a very important aspect to keep in consideration in pediatric patients. In contrast to CTE, MRE does not subject patients to ionizing radiation and can be used to detect detailed morphologic information and functional data of bowel disease, to monitor the effects of medical therapy more accurately, to detect residual active disease even in patients showing apparent clinical resolution and to guide treatment more accurately.
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Kyriakidi KS, Tsianos VE, Karvounis E, Christodoulou DK, Katsanos KH, Tsianos EV. Neutrophil anti-neutrophil cytoplasmic autoantibody proteins: bactericidal increasing protein, lactoferrin, cathepsin, and elastase as serological markers of inflammatory bowel and other diseases. Ann Gastroenterol 2016; 29:258-67. [PMID: 27366026 PMCID: PMC4923811 DOI: 10.20524/aog.2016.0028] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Accepted: 02/26/2016] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract comprising Crohn's disease and ulcerative colitis. Although the pathogenesis of the disease is not clearly defined yet, environmental, genetic and other factors contribute to the onset of the disease. Apart from the clinical and histopathological findings, several serological biomarkers are also employed to detect IBD. One of the most thoroughly studied biomarker is anti-neutrophil cytoplasmic autoantibody (ANCA). We herein provide an overview of the current knowledge on the use of ANCA and certain ANCA proteins, such as bactericidal increasing protein, lactoferrin, cathepsin G and elastase, as serological markers for IBD and other diseases.
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Affiliation(s)
- Kallirroi S. Kyriakidi
- Research Laboratory of Immunology (Kallirroi S. Kyriakidi, Vasileios E. Tsianos, Evaggelos Karvounis), Ioannina, Greece
| | - Vasileios E. Tsianos
- Research Laboratory of Immunology (Kallirroi S. Kyriakidi, Vasileios E. Tsianos, Evaggelos Karvounis), Ioannina, Greece
| | - Evaggelos Karvounis
- Research Laboratory of Immunology (Kallirroi S. Kyriakidi, Vasileios E. Tsianos, Evaggelos Karvounis), Ioannina, Greece
| | | | - Konstantinos H. Katsanos
- Division of Gastroenterology (Dimitrios K. Christodoulou, Konstantinos H. Katsanos), Ioannina, Greece
| | - Epameinondas V. Tsianos
- Faculty of Medicine, School of Health Sciences (Epameinondas V. Tsianos), University of Ioannina, Ioannina, Greece
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Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound. AJR Am J Roentgenol 2016; 206:64-73. [PMID: 26700336 DOI: 10.2214/ajr.15.14506] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. MATERIALS AND METHODS One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. RESULTS Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global assessment as the reference standard: using 18.2 dB to differentiate mild versus moderate activity yielded sensitivity of 89.2% and specificity of 90.9% and using 22.9 dB to differentiate moderate versus severe activity yielded sensitivity of 89.5% and specificity of 83.1%. CONCLUSION Quantitative CEUS parameters integrated into inflammatory assessments with ultrasound reduce indeterminate results and improve disease activity level determinations.
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Miot J, Smith S, Bhimsan N. Resource use and cost of care with biologicals in Crohn's disease in South Africa: a retrospective analysis from a payer perspective. Int J Clin Pharm 2016; 38:880-7. [PMID: 27118462 DOI: 10.1007/s11096-016-0304-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 04/13/2016] [Indexed: 12/30/2022]
Abstract
Background Crohn's disease is a relapsing remitting inflammatory disease of the gastrointestinal tract. Treatment may require expensive biological therapy in severe patients. Affordability of the high cost anti-TNF-α agents has raised concern although evidence suggests cost-offsets can be achieved. There is little information on the resource utilisation of Crohn's patients in low and middle income countries. Objective The objective of this study is to investigate the resource utilisation and costs associated with biologicals treatment of Crohn's disease. Setting The setting for this study is in private healthcare in South Africa from a payer perspective. Method A retrospective longitudinal analysis of an administrative claims database from a large private healthcare insurer of patients who had at least 1 year claims exposure prior to starting biologicals and 2 years follow-up thereafter. Resource utilisation and costs including total Crohn's costs, hospital admissions and surgery, out of hospital costs, biologicals and chronic medicines were analysed. Main outcome measure The primary objective was to compare the change in resource utilisation and costs for Crohn's related conditions before and after starting biological treatment. Results A cohort of 72 patients was identified with a 35% (p = 0.005) reduction in Crohn's related costs (excluding the cost of biologicals) from ZAR 55,925 (U$5369) 1 year before compared to ZAR 36,293 (U$3484) 2 years after starting biological medicines. However, inclusion of the cost of biologicals more than doubled the total costs to ZAR 150,915 (±91,642) U$14,488 (±8798) in Year 2. Significant reductions in out-of hospital Crohn's related spend was also observed. Conclusions A reduction in healthcare costs is seen following starting biologicals in patients with moderate to severe Crohn's disease. However, the high cost of biological therapy outweighs any possible savings achieved in other areas of healthcare utilisation.
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Affiliation(s)
- Jacqui Miot
- Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of Witwatersrand, 7 York Road, Parktown, Johannesburg, 2196, South Africa. .,Clinical Policy Unit, Discovery Health, Sandton, South Africa.
| | - Susan Smith
- Clinical Policy Unit, Discovery Health, Sandton, South Africa
| | - Niri Bhimsan
- Clinical Policy Unit, Discovery Health, Sandton, South Africa
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Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn's Disease. Gastroenterol Res Pract 2016; 2016:7896478. [PMID: 26997952 PMCID: PMC4779516 DOI: 10.1155/2016/7896478] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 01/26/2016] [Accepted: 01/28/2016] [Indexed: 12/23/2022] Open
Abstract
Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD).
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Teruel C, Garrido E, Mesonero F. Diagnosis and management of functional symptoms in inflammatory bowel disease in remission. World J Gastrointest Pharmacol Ther 2016; 7:78-90. [PMID: 26855814 PMCID: PMC4734957 DOI: 10.4292/wjgpt.v7.i1.78] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/03/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) patients in remission may suffer from gastrointestinal symptoms that resemble irritable bowel syndrome (IBS). Knowledge on this issue has increased considerably in the last decade, and it is our intention to review and summarize it in the present work. We describe a problematic that comprises physiopathological uncertainties, diagnostic difficulties, as IBS-like symptoms are very similar to those produced by an inflammatory flare, and the necessity of appropriate management of these patients, who, although in remission, have impaired quality of life. Ultimately, from almost a philosophical point of view, the presence of IBS-like symptoms in IBD patients in remission supposes a challenge to the traditional functional-organic dichotomy, suggesting the need for a change of paradigm.
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Bettenworth D, Nowacki TM, Cordes F, Buerke B, Lenze F. Assessment of stricturing Crohn's disease: Current clinical practice and future avenues. World J Gastroenterol 2016; 22:1008-1016. [PMID: 26811643 PMCID: PMC4716016 DOI: 10.3748/wjg.v22.i3.1008] [Citation(s) in RCA: 36] [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: 07/01/2015] [Revised: 08/27/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
Crohn’s disease (CD) is a chronic remittent idiopathic disease. Although the early phase of the disease is commonly characterized by inflammation-driven symptoms, such as diarrhea, the frequency of fibrostenotic complications in patients with CD increases over the long-term course of the disease. This review presents the current diagnostic options for assessing CD-associated strictures. In addition to the endoscopic evaluation of CD strictures, this review summarizes the currently available imaging modalities, including ultrasound and cross-sectional imaging techniques. In addition to stricture detection, differentiating between the primarily inflammatory strictures and the predominantly fibrotic ones is essential for selecting the appropriate treatment strategy (anti-inflammatory medical treatment vs endoscopical or surgical approaches). Therefore, recent imaging advances, such as contrast-enhanced ultrasound and ultrasound elastography, contribute to the development of non-invasive non-radiating imaging of CD-associated strictures. Finally, novel magnetic resonance imaging techniques, such as diffusion-weighted, motility and magnetization transfer imaging, as well as 18F-FDG PET/CT, molecular imaging approaches and biomarkers, are critically reviewed with regard to their potential role in assessing stricturing CD.
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Oliveira AM, Cardoso FS, Rodrigues CG, Santos L, Martins A, de Deus JR, Reis J. Can Red Cell Distribution Width Be Used as a Marker of Crohn's Disease Activity? GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 23:6-12. [PMID: 28868424 PMCID: PMC5579976 DOI: 10.1016/j.jpge.2015.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 10/11/2015] [Indexed: 12/22/2022]
Abstract
Introduction Recently, it has been suggested an association between red cell distribution width (RDW) and Crohn's disease activity index (CDAI), but its use is not yet performed in daily clinical practice. Objectives To determine whether RDW can be used as a marker of Crohn's disease (CD) activity. Methods This was a cross-sectional study including patients with CD, observed consecutively in an outpatient setting between January 1st and September 30th 2013. Blood cell indices, erythrocyte sedimentation rate (ESR), and C-reactive protein were measured. CD activity was determined by CDAI (active disease if CDAI ≥ 150). Associations were analyzed using logistic regression (SPSS version 20). Results 119 patients (56% female) were included in the study with a mean age of 47 years (SD 15.2). Twenty patients (17%) had active disease. The median RDW was 14.0 (13–15). There was an association between RDW and disease activity (p = 0.044). After adjustment for age and gender, this association remained consistent (OR 1.20, 95% CI 1.03–1.39, p = 0.016). It was also found that the association between RDW and disease activity was independent of hemoglobin and ESR (OR 1.36, 95% CI 1.08–1.72, p = 0.01) and of biologic therapy (OR 1.19, 95% CI 1.03–1.37, p = 0.017). A RDW cutoff of 16% had a specificity and negative predictive value for CDAI ≥ 150 of 88% and 86%, respectively. Conclusion In this study, RDW proved to be an independent and relatively specific marker of CD activity. These results may contribute to the implementation of this simple parameter, in clinical practice, aiming to help therapeutic decisions.
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Affiliation(s)
- Ana Maria Oliveira
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | - Filipe Sousa Cardoso
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | | | - Liliana Santos
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | - Alexandra Martins
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | - João Ramos de Deus
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
| | - Jorge Reis
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
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Intestinal healing after anti-TNF induction therapy predicts long-term response to one-year treatment in patients with ileocolonic Crohn's disease naive to anti-TNF agents. GASTROENTEROLOGY REVIEW 2015; 11:187-193. [PMID: 27713781 PMCID: PMC5047962 DOI: 10.5114/pg.2015.55185] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 06/14/2014] [Indexed: 12/21/2022]
Abstract
Introduction Objective assessment of Crohn’s disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD. Aim To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment. Material and methods Twenty-six patients with ileocolonic CD were enrolled into the study. In this group a parallel assessment of disease activity was estimated before and after induction doses of anti-TNF antibodies with ileocolonoscopy and MRE by using appropriate scores. Subsequently the patients were treated until 12 months and then followed-up. The associations between intestinal healing (assessed in MRE and endoscopy), and mucosal and transmural healing with long-term results of 1-year anti-TNF therapy were analysed statistically. Results The median time of follow-up was 29 months (interquartile range – IQR: 14–46). Intestinal healing was significantly associated with favourable therapeutic outcomes (p = 0.02) and had 75% (IQR: 35–97%) sensitivity and 72% (IQR: 46–90%) specificity in predicting long-term remission. Other parameters were not useful (transmural healing) or their usefulness was of borderline significance (mucosal healing). Conclusions Dynamic assessment of intestinal healing is an accurate method in predicting long-term outcomes in CD patients responding to 1-year anti-TNF therapy.
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