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BACKGROUND: Diagnosing paediatric Crohn's disease (CD) based on histology can present challenges. We evaluate the histological spectrum of treatment-naïve biopsies from children with CD and assess these findings' diagnostic and predictive value. METHODS: Three cohorts were identified: (1) 137 patients with CD, (2) 116 patients with ulcerative colitis (UC) and (3) 50 patients without inflammatory bowel disease. Biopsies from the gastrointestinal (GI) tract were re-examined for signs of active and chronic inflammation, including lymphocyte-pattern oesophagitis, focal enhancing gastritis and indicators of chronicity. Additionally, granulomas and microgranulomas (defined as clusters of 4-9 epithelioid histiocytes) were evaluated. RESULTS: Lymphocyte-pattern oesophagitis was observed in 15% of patients (n=20). Moderate-to-severe diffuse gastritis was noted in 50.4% of patients (n=68), while focal enhancing gastritis was identified in 11.1% (n=15). In terminal ileal biopsies, 46.1% exhibited activity and 5.3% showed features of chronicity. Active colitis was present in 73% of patients (n=100), with chronic colitis seen in 11.7% (n=16). Granulomas and microgranulomas were observed in 31.4% (43/137) and 48.9% (67/137) of patients, respectively. Notably, 30.7% (42/137) of patients with microgranulomas were without granulomas. Previously undetected microgranulomas were found in 20 of 27 cases. 2.5% of patients with UC and none of the control cohort showed microgranulomas. Lymphocyte-pattern oesophagitis was associated with an increased need for anti-tumor necrosis factor (TNF) therapy (p=0.007). CONCLUSIONS: GI microgranulomas, often overlooked, are specific to CD in the proper clinical context. Oesophageal lymphocytosis may predict a need for more aggressive treatment. The study brings to light under-recognised aspects of CD's histological diagnosis, including the oversight of microgranulomas, the high prevalence of diffuse gastritis and low prevalence of focal enhancing gastritis, the frequent absence of terminal ileitis and the infrequent occurrence of chronic colitis.
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BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.
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Metotrexato , Inhibidores del Factor de Necrosis Tumoral , Niño , Humanos , Femenino , Adolescente , Masculino , Metotrexato/efectos adversos , Adalimumab/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Infliximab/efectos adversos , Factor de Necrosis Tumoral alfa , Resultado del TratamientoRESUMEN
BACKGROUND: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic. METHODS: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation. RESULTS: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8-3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC ( P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date. CONCLUSIONS: Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.
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Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Adolescente , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/uso terapéutico , Adalimumab/uso terapéutico , Factores Biológicos , Productos Biológicos/uso terapéuticoRESUMEN
OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients. METHODS: This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition. RESULTS: Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered. CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.
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Clostridioides difficile , Infecciones por Clostridium , Adulto , Humanos , Niño , Adolescente , Trasplante de Microbiota Fecal/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia , Infecciones por Clostridium/terapiaRESUMEN
Purpose: The aim of this study was to explore potential correlation of the MR imaging features and clinical characteristics with formation of perianal abscess in children with Crohn's perianal fistulas (CPF). Methods: From 2010 to 2020, pediatric patients with CPF diagnosis on their first pelvic MRI were identified retrospectively. All patients were divided into two groups based on the presence or absence of perianal abscess. Baseline clinical and MRI characteristics were recorded for each patient. All the statistical calculations were performed using R (version 3.6.3). Results: A total of 60 patients [F:M 17:43, median age 14 years (IQR 10-15), ranging 3-18 years] were included in this study. Forty-four abscesses were identified in 36/60 children (mean volume 3 ± 8.6â ml, median 0.3â ml). In 24/60 patients with perianal disease, no abscess was detected on the MRI. Ten patients (28%) showed perianal abscess on pelvic MRI at the initial diagnosis. The rate of active disease on colonoscopy (visible ulcerations/aphthous ulcers) was similar in both groups (95% vs. 94%). With regards to disease location, the majority of patients (40/60, 66.6%) in both groups had ileocolonic CD. All patients without abscess had a single perianal fistula (n = 24; 3 simple and 21 complex fistulae), however, patients with perianal abscess tended to have >1 fistulous tracts (n = 50 fistulas; all complex, 27 single, 10 double and 1 triple). Intersphincteric fistula was the most common fistula type in both groups (79% and 66%, p = 0.1). The total length of fistula (3.8 ± 1.7 vs. 2.8 ± 0.8â cm, p = 0.006) and presence of multiple external openings (n = 25 vs. 7, p = 0.019) were significantly higher in patients with abscesses, and fistula length >3.3â cm showed 80% specificity and 83% PPV for the presence of perianal abscess. Fistulas were symptomatic (pain, bleeding or drainage) at similar rates in both groups (68% and 70%, p = 0.1). Conclusion: Pediatric patients with CPF who develop perianal abscess have a distinct imaging phenotype defined by longer fistula length (>3.3â cm), multiple skin openings and multiple fistulous tracts (≥2) on MRI. Patients who have these features but does not have an abscess on imaging may merit more aggressive treatment (and close monitoring) to prevent the development of an abscess.
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INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.
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Colitis Ulcerosa , Enfermedad de Crohn , Complejo de Antígeno L1 de Leucocito , Adolescente , Teorema de Bayes , Niño , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/dietoterapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/dietoterapia , Dieta , Heces/química , Humanos , Inflamación/complicaciones , Inflamación/dietoterapia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/dietoterapia , Complejo de Antígeno L1 de Leucocito/análisis , Medicina de PrecisiónRESUMEN
INTRODUCTION: Granulomas are a pathologic hallmark of Crohn disease (CD) although they are found in only a subset of patients. Well-formed granulomas are associated with an aggressive phenotype although it is unknown if microgranulomas confer a similar phenotype. This study sought to define the incidence of microgranulomas in pediatric CD and compare the clinical course with cases with granulomas and those without granulomatous inflammation. METHODS: We performed a single-center, retrospective study of pediatric CD patients who had at least 3âyears of follow-up. initial diagnostic biopsies were systematically re-examined by a gastrointestinal pathologist. A priori definitions of granuloma (10+ histiocytes) and microgranuloma (4-9 histiocytes) were used. Disease outcomes of hospitalization, development of complicated disease behavior, perianal disease, and the use of anti-tumor necrosis factor (anti-TNF) therapy were assessed by Kaplan-Meier survival plots. RESULTS: This study included 138 subjects with an average follow-up of 4.6âyears. Granulomas were seen in 38 of 138 subjects (27.5%) and an additional 38 subjects (27.5%) had at least 1 microgranuloma (in the absence of granulomas). Escalation to anti-TNF therapy was higher in CD with granulomas (Pâ =â0.001) and microgranulomas (Pâ =â0.0001) compared with those without granulomatous inflammation. CONCLUSIONS: A significant subset of pediatric CD patients have microgranulomas (in the absence of well-defined granulomas). Children with CD who have microgranulomas are escalated to anti-TNF therapy more frequently than those without granulomatous inflammation (and at a similar rate to those with granulomas). Pathologists should have a low threshold to report microgranulomas as they may help to predict disease behavior.
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Enfermedad de Crohn , Niño , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Granuloma/etiología , Granuloma/patología , Humanos , Inflamación/complicaciones , Necrosis , Estudios Retrospectivos , Inhibidores del Factor de Necrosis TumoralRESUMEN
BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. CONCLUSIONS: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.
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Clostridioides difficile , Infecciones por Clostridium , Enfermedades Inflamatorias del Intestino , Adulto , Niño , Enfermedad Crónica , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/efectos adversos , Heces , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/terapia , Recurrencia , Resultado del TratamientoRESUMEN
OBJECTIVES: Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established. METHODS: This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined. RESULTS: Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30âng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (Pâ=â0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, Pâ=â0.034). CONCLUSIONS: Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.
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Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Adalimumab/uso terapéutico , Niño , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa , Vitamina DRESUMEN
OBJECTIVES: Endoscopic mucosal improvement is the gold standard for assessing treatment efficacy in clinical trials of Crohn's disease. Current endoscopic indices are not routinely used in clinical practice. The lack of endoscopic information in large clinical registries limits their use for research. A quick, easy, and accurate method is needed for assessing mucosal improvement for clinicians in real-world practice. We developed and tested a novel simplified endoscopic mucosal assessment for Crohn's disease (SEMA-CD). METHODS: We developed a 5-point scale for ranking endoscopic severity of ileum and colon based on Simple Endoscopic Score for Crohn's disease (SES-CD). Central readers were trained to perform SES-CD and SEMA-CD. Pediatric patients with Crohn's disease undergoing colonoscopy were enrolled. Video recordings of colonoscopies were de-identified and randomly assigned to blinded central readers. The SES-CD and SEMA-CD were scored for each video. The SES-CD was considered the validated standard for comparison. Correlation was assessed with Spearman rho, inter- and intrarater reliability with kappa statistics. RESULTS: Fifty-seven colonoscopies were read a total of 212 times. Correlation between SEMA-CD and SES-CD was strong (rho = 0.98, P < 0.0001). Inter-rater reliability for SEMA-CD was 0.80, and intrarater reliability was 0.83. Central readers rated SEMA-CD as easier than SES-CD. CONCLUSION: The SEMA-CD accurately and reproducibly correlates with the standard SES-CD. Central readers viewed SEMA-CD as easier than SES-CD. Use of SEMA-CD in practice should enable collecting mucosal improvement information in large populations of patients. This will improve the quality of research that can be conducted in clinical registries. External validation is needed.
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Enfermedad de Crohn , Niño , Colon/fisiopatología , Colonoscopía/métodos , Enfermedad de Crohn/diagnóstico , Humanos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.
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Clostridioides difficile , Infecciones por Clostridium , Niño , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Heces , Humanos , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Advancing the understanding of inflammatory bowel disease (IBD) pathogenesis has been facilitated by mechanistic studies that require human intestinal tissue. Enrolling pediatric subjects into these studies improves our knowledge of IBD in this underserved population. Given the additional research protections granted to children, institutional review boards (IRBs) must weigh the benefit of obtaining research biopsies against perceived risks. Although obtaining clinical biopsies from children is generally considered safe, there are only limited data on the safety of obtaining research biopsies in children.1-6.
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Colitis , Enfermedades Inflamatorias del Intestino , Biopsia , Niño , Endoscopía , Humanos , Mucosa IntestinalRESUMEN
BACKGROUND: MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. PURPOSE: To determine whether MRE imaging features are associated with clinical recurrence. STUDY TYPE: Retrospective. POPULATIONS: Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. FIELD STRENGTH/SEQUENCE: 1.5T including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T1 -weighted gradient recalled echo sequences. ASSESSMENT: MREs were reviewed by three radiologists independently for mural thickening, T2 -weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. STATISTICAL TESTS: Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. RESULTS: Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T2 -weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). DATA CONCLUSION: MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;50:1955-1963.
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Medios de Contraste , Enfermedad de Crohn/diagnóstico por imagen , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Niño , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Gadolinio DTPA , Tracto Gastrointestinal/diagnóstico por imagen , Humanos , Masculino , Meglumina , Compuestos Organometálicos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: C-reactive protein (CRP) is a serum marker that is used to measure disease activity in Crohn's disease (CD). However, a subset of CD patients have normal CRP during flares. In rheumatoid arthritis and lupus, genetic variants can restrict CRP elevations during flares. This study sought to determine if common CRP genetic variants affect CRP values during active CD. METHODS: Subjects with CD who participated in the Partners HealthCare BioBank were genotyped for 5 common CRP genetic variants (rs2794520, rs3122012, rs3093077, rs2808635, and rs1800947). Medical records were reviewed to determine disease activity and the highest CRP value during active CD. CRP values during active infection or malignancy at the time of the test were excluded. CRP values were compared by genotype using the Mann-Whitney test. RESULTS: The study included 199 subjects with active CD (21 to 86 years of age). Subjects with the rs2794520 TT genotype had a lower CRP than subjects with the CC genotype (58.3 mg/L vs 28.4 mg/L, P = 0.008). Subjects with the rs1800947 CG genotype had a lower CRP than those with the CC genotype (54.3 mg/L vs 22.4 mg/L, P < 0.0001); 41.6% of TT subjects had a normal CRP compared with 24.1% of CT subjects and 16.5% of CC subjects (P = 0.041). CONCLUSIONS: This study demonstrates that rs2794520 and rs1800947 are associated with a restriction of CRP elevations during active CD. While CRP is typically a reliable biomarker in CD, there is a subset of CD patients with a genetically determined restriction of CRP in whom other disease markers should be utilized.
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Proteína C-Reactiva/genética , Enfermedad de Crohn/sangre , Variación Genética/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad de Crohn/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Brote de los Síntomas , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC. METHODS: Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001). RESULTS: 457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5). CONCLUSIONS: Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.
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Colitis Ulcerosa , Mesalamina , Polimorfismo de Nucleótido Simple , Sialiltransferasas/genética , Adulto , Transporte Biológico Activo/efectos de los fármacos , Transporte Biológico Activo/genética , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Femenino , Humanos , Masculino , Mesalamina/administración & dosificación , Mesalamina/farmacocinética , Persona de Mediana Edad , Pruebas de Farmacogenómica , Sialiltransferasas/metabolismoRESUMEN
Inflammatory bowel diseases (IBD) are chronic autoimmune conditions of the gut affecting both pediatric and adult patients. Medical therapy is often successful at inducing and maintaining remission and preventing disease complications. The mainstays of treatment are medications and other therapies that reduce inflammation and suppress the overactive immune system. Here we review current medical therapies for pediatric IBD, discuss future therapeutics, and present current treatment goals and approaches.
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Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/terapia , Dietoterapia , Nutrición Enteral , Inmunosupresores/uso terapéutico , Niño , Terapia Combinada , HumanosRESUMEN
Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.
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Cuidados Posteriores/métodos , Enfermedad de Crohn/cirugía , Cuidados Posoperatorios/métodos , Prevención Secundaria/métodos , Niño , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/etiología , Enfermedad de Crohn/prevención & control , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Humanos , Recurrencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/métodos , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Adulto , Anciano , Niño , Trasplante de Microbiota Fecal/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Resultado del Tratamiento , Adulto JovenAsunto(s)
Hidrocefalia/diagnóstico , Vómitos/etiología , Análisis Químico de la Sangre , Diagnóstico Diferencial , Diarrea/etiología , Femenino , Cabeza/diagnóstico por imagen , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/cirugía , Lactante , Hipertensión Intracraneal/complicaciones , Imagen por Resonancia Magnética , Errores Innatos del Metabolismo/diagnóstico , Recurrencia , VentriculostomíaRESUMEN
BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. METHODS: We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above. RESULTS: Overall, 180 patients aged 7-95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. CONCLUSIONS: We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.