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Background Standardized methods to measure and describe Crohn disease strictures at CT enterography are needed to guide clinical decision making and for use in therapeutic studies. Purpose To assess the reliability of CT enterography features to describe Crohn disease strictures and their correlation with stricture severity. Materials and Methods A retrospective study was conducted in 43 adult patients with symptomatic terminal ileal Crohn disease strictures who underwent standard-of-care CT enterography at a tertiary care center at the Cleveland Clinic between January 2008 and August 2016. After training on standardized definitions, four abdominal radiologists blinded to all patient information assessed imaging features (seven continuous measurements and nine observations) of the most distal ileal stricture in two separate sessions (separated by ≥2 weeks) in random order. Features with an interrater intraclass correlation coefficient (ICC) of 0.41 or greater (ie, moderate reliability or better) were considered reliable. Univariable and multivariable linear regression analysis identified reliable features associated with a visual analog scale of overall stricture severity. Significant reliable features were assessed as components of a CT enterography-based model to quantitate stricture severity. Results Examinations in 43 patients (mean age, 52 years ± 16 [SD]; 23 female) were evaluated. Five continuous measurements and six observations demonstrated at least moderate interrater reliability (interrater ICC range, 0.42 [95% CI: 0.25, 0.57] to 0.80 [95% CI: 0.67, 0.88]). Of these, 10 were univariably associated with stricture severity, and three continuous measurements-stricture length (interrater ICC, 0.64 [95% CI: 0.42, 0.81]), maximal associated small bowel dilation (interrater ICC, 0.80 [95% CI: 0.67, 0.88]), and maximal stricture wall thickness (interrater ICC, 0.50 [95% CI: 0.34, 0.62])-were independently associated (P value range, <.001 to .003) with stricture severity in a multivariable model. These three measurements were used to derive a well-calibrated (optimism-adjusted calibration slope = 1.00) quantitative model of stricture severity. Conclusion Standardized CT enterography measurements and observations can reliably describe terminal ileal Crohn disease strictures. Stricture length, maximal associated small bowel dilation, and maximal stricture wall thickness are correlated with stricture severity. © RSNA, 2024 Supplemental material is available for this article. See also the article by Rieder et al in this issue. See also the editorial by Galgano and Summerlin in this issue.
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Doença de Crohn , Tomografia Computadorizada por Raios X , Humanos , Doença de Crohn/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Reprodutibilidade dos Testes , Constrição Patológica/diagnóstico por imagem , Adulto , IdosoRESUMO
BACKGROUND. New biologic agents for Crohn disease (CD) create a need for noninvasive disease markers. DWI may assess bowel inflammation without contrast agents. OBJECTIVE. The purpose of this study was to evaluate ADC values for identifying bowel inflammation and therapeutic response in patients with CD treated with biologic therapy. METHODS. This study entailed post hoc analysis of prospective trial data. Analysis included 89 patients (median age, 37 years; 49 women, 40 men) with CD treated by biologic therapy who underwent MR enterography (MRE) at baseline and 46 weeks after therapy, from March 2013 to April 2021; 43 patients underwent ileocolonoscopy at both time points. Analysis was conducted at the level of small-bowel and colorectal segments (586 segments analyzed). MR index of activity (MaRIA) score and presence of endoscopic ulcers were determined at both time points. One observer measured bowel wall ADC. Diagnostic performance was evaluated. Dichotomous ADC assessments used a threshold of 1301 × 10-6 mm2/s based on initial ROC analysis; dichotomous MaRIA score assessments used a threshold of 11 (moderate to severe inflammation). A second observer repeated ADC measurements in 15 patients. RESULTS. At baseline, ADC had AUC of 0.92, sensitivity of 78.6%, specificity of 91.4%, and accuracy of 88.2% for detecting segments with MaRIA score 11 or greater. At baseline, AUC for detecting endoscopic ulcers was 0.96 for MaRIA score versus 0.87 for ADC (p < .001); sensitivity, specificity, and accuracy were 70.8%, 90.2%, and 85.1% for ADC and 86.2%, 96.2%, and 93.6% for MaRIA score. At follow-up, ADC had AUC of 0.87, sensitivity of 75.4%, specificity of 83.6%, and accuracy of 80.0% for detecting improvement in MaRIA score to less than 11. At follow-up, AUC for detecting endoscopic ulcer healing was 0.94 for MaRIA score versus 0.84 for ADC (p = .01); sensitivity, specificity, and accuracy were 70.7%, 95.8%, and 84.4% for ADC and 90.2%, 100.0%, and 95.6% for MaRIA score. Interobserver agreement for ADC, based on intraclass correlation coefficient, was 0.70 at baseline and 0.65 at follow-up. CONCLUSION. The findings do not support use of ADC rather than MaRIA scores for detecting biologic therapy response. CLINICAL IMPACT. ADC may have an adjunct role in assessing bowel inflammation in CD, but showed limited performance for detecting biologic therapy response.
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Doença de Crohn , Adulto , Feminino , Humanos , Masculino , Terapia Biológica , Imagem de Difusão por Ressonância Magnética/métodos , Inflamação , Imageamento por Ressonância Magnética , Estudos Prospectivos , Úlcera , Ensaios Clínicos como AssuntoRESUMO
OBJECTIVES: Patients with Crohn's disease (CD) require multiple assessments with magnetic resonance enterography (MRE) from a young age. Standard MRE protocols for CD include contrast-enhanced sequences. Gadolinium deposits in brain tissue suggest avoiding gadolinium could benefit patients with CD. This study aimed to compare the accuracy of the simplified Magnetic Resonance Index of Activity (sMaRIA) calculated with and without contrast-enhanced sequences in determining the response to biologic drugs in patients with CD. METHODS: This post hoc analysis of a prospective study included patients with CD with endoscopic ulceration in ≥ 1 intestinal segment starting biologic drug therapy. Two blinded radiologists used the sMaRIA to score images obtained at baseline and week 46 of treatment first using only unenhanced sequences (T2-sMaRIA) and 1 month later using both unenhanced and enhanced images (CE-sMaRIA). We calculated the rates of agreement between T2-sMaRIA, CE-sMaRIA, and ileocolonoscopy for different conceptualizations of therapeutic response. RESULTS: A total of 46 patients (median age, 36 years [IQR: 28-47]) were included. Agreement with ileocolonoscopy was similar for CE-sMaRIA and T2-sMaRIA in identifying ulcer healing (kappa = 0.74 [0.55-0.93] and 0.70 [0.5-0.9], respectively), treatment response (kappa = 0.53 [0.28-0.79] and 0.44 [0.17 - 0.71]), and remission (kappa = 0.48 [0.22-0.73] and 0.43 [0.17-0.69]). The standardized effect size was moderate for both CE-sMaRIA = 0.63 [0.41-0.85] p < 0.001 and T2-sMaRIA = 0.58 [0.36-0.80] p < 0.001. CONCLUSIONS: sMaRIA with and without contrast-enhanced images accurately classified the response according to different therapeutic endpoints determined by ileocolonoscopy. KEY POINTS: ⢠The simplified Magnetic Resonance Index of Activity is accurate for the assessment of Crohn's disease activity, severity, and therapeutic response, using four dichotomic components that can be evaluated without the need of using contrast-enhanced sequences, representing a practical and safety advantage, but concerns have been expressed as to whether the lack of contrast sequences may compromise precision. ⢠The simplified Magnetic Resonance Index of Activity can assess the response to biologic therapy in patients with Crohn's disease without the need for intravenous contrast agents obtaining comparable results without and with contrast-enhanced sequences. ⢠Avoiding intravenous contrast agents could reduce the duration of the MRE examination and its cost and would increase the acceptance and safety of MRE in clinical research in patients with Crohn's disease.
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Doença de Crohn , Adulto , Meios de Contraste/farmacologia , Doença de Crohn/diagnóstico , Gadolínio/farmacologia , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos ProspectivosRESUMO
The management of Crohn disease (CD) has entered a new era in which it is imperative to incorporate objective data and symptoms to plan the best therapeutic approach for each patient. Magnetic resonance (MR) imaging provides powerful objective insights into the disease process, and its high sensitivity and specificity for detecting inflammation make it essential for diagnosis and management. Growing evidence indicates that MR provides reliable and accurate information that enables detection of changes after treatment with biological drugs. This article provides an overview of currently established and emerging MR biomarkers for assessing response to treatment in patients with CD.
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Biomarcadores/análise , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/terapia , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Índice de Gravidade de DoençaRESUMO
Patients with Crohn's disease (CD) commonly develop bowel strictures, which may contain various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment approach, fibrotic strictures would require endoscopic balloon dilation or surgery. Cross-sectional imaging surpasses endoscopy for characterization of stenotic segments and potentially may contribute to the optimal clinical management of these patients. This short review aims to discuss the potentialities and limitations of cross-sectional imaging techniques for assessing bowel fibrosis in patients with CD.
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BACKGROUND: Identifying predictors of therapeutic response is the cornerstone of personalised medicine. AIM: To identify predictors of long-term healing of severe inflammatory lesions based on magnetic resonance enterography (MRE) findings in patients with Crohn's disease (CD) treated with tumour necrosis factor alpha (TNF-α) inhibitors. METHODS: This prospective longitudinal single-centre study included patients with clinically active CD requiring treatment with TNF-α inhibitors with at least one intestinal segment with a severe inflammatory lesion detected by MRE (segmental MaRIA ≥11). MRE data were obtained at baseline, and at weeks 14 and 46. The primary endpoint was healing of severe inflammatory lesions (MaRIA <11) in each segment. The secondary endpoint was healing of all severe inflammatory lesions on a per-patient analysis. RESULTS: We included 58 patients with 86 intestinal segments with severe inflammatory lesions. At week 46, healing of severe lesions was found in 51/86 (59.3%) segments, and complete healing of inflammatory lesions in all segments was found in 28/58 (48.6%) patients. Multivariable analysis found baseline-negative predictors of long-term healing of severe inflammation were ileal (as opposed to colonic) location (OR 0.00, [0.00-0.56] P = 0.002) and presence of creeping fat on MRE (OR 0.00 [0.00-0.57]; P = 0.001). Persistence of segmental MaRIA score >10.6 at week 14 was a negative predictor of healing at week 46 (OR 0.3 [0.04--0.38]; P < 0.001). CONCLUSION: In patients with CD, the absence of creeping fat detected at baseline MRE and location of severe inflammatory lesions are clinically relevant predictors of long-term healing of severe inflammation under treatment with TNF-α inhibitors.
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Anti-Inflamatórios/uso terapêutico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Intestinos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Fator de Necrose Tumoral alfa/imunologia , Adulto , Idoso , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Doença de Crohn/patologia , Feminino , Humanos , Íleo/diagnóstico por imagem , Íleo/efeitos dos fármacos , Íleo/patologia , Fatores Imunológicos/uso terapêutico , Intestinos/efeitos dos fármacos , Intestinos/patologia , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity [sMARIA], but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn's disease. METHODS: We prospectively included patients with active Crohn's disease and at least one segment with severe inflammation [ulcers] at ileocolonoscopy, who required treatment with biologic drugs. Patients were evaluated by both magnetic resonance enterography [MRE] and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy Crohn's Disease Index of Severity [CDEIS], considered the gold standard. RESULTS: Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIAâ ≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIAâ ≥2 for predicting the presence of ulcers at ileocolonoscopy [AUC 0.93]. In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level [sMARIAâ <2] with 89.5% sensitivity and 87.5% specificity. The sMARIA decreased significantly [pâ <0.001] in segments achieving endoscopic ulcer healing, but did not change [pâ =â 0.222] in segments with persistent ulceration. CONCLUSIONS: The sMARIA is accurate and reliable in quantifying disease activity and response to treatment in luminal Crohn's disease, without the need for gadolinium-enhanced sequences.
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Doença de Crohn , Inflamação , Imageamento por Ressonância Magnética/métodos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Produtos Biológicos/uso terapêutico , Colonoscopia/métodos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Feminino , Humanos , Imunidade Ativa/efeitos dos fármacos , Imunoterapia/métodos , Inflamação/diagnóstico por imagem , Inflamação/imunologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Gravidade do Paciente , Índice de Gravidade de DoençaRESUMO
Traditional corticosteroids represent a well-established and effective treatment for active ulcerative colitis (UC). However, the severity of their systemic side effects, led in recent years to look for new steroid molecules that could reduce them, maximizing the anti-inflammatory activity. Budesonide has been one of the most studied steroid compounds and it has been approved for the treatment of mild to moderate active Crohn's disease (CD). In order to extend the release until the distally located inflammation, budesonide has been coupled with a controlled delivery system, called Multi-Matrix system (MMX), already successfully tested with oral mesalazine for the treatment of distal UC. After in vitro and in vivo models, the efficacy of Budesonide-MMX has been investigated in active UC with a first small phase II study, and partially encouraging results. This article will review the evidences on the use of budesonide in inflammatory bowel diseases and will discuss the role of Budesonide-MMX in active UC nowadays.
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Budesonida/administração & dosagem , Budesonida/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Budesonida/farmacocinética , Humanos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS: Ten consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10 mg/day for 8 weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: Eight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8-14) and 3 (range 2-9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77-175) to 175 (range 85-220) (p<0.001). CONCLUSION: Eight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.