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1.
Artigo em Inglês | MEDLINE | ID: mdl-38723980

RESUMO

BACKGROUND & AIMS: Biologic therapies may effectively treat Crohn's disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation have not been well-characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD. METHODS: Pediatric patients with CD at 7 U.S. centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease. RESULTS: Of 823 patients included (median age, 13.0 years; 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). Twenty-six percent used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. Twenty-nine percent discontinued their first biologic after median 793 days because of inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 µg/mL. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation. CONCLUSIONS: Most children with CD are treated with biologics; 25%-37% discontinue biologics, resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation.

2.
J Pediatr Gastroenterol Nutr ; 78(5): 1135-1142, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38558411

RESUMO

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.


Assuntos
Doença de Crohn , Nutrição Enteral , Microbioma Gastrointestinal , Humanos , Doença de Crohn/terapia , Doença de Crohn/dietoterapia , Nutrição Enteral/métodos , Projetos Piloto , Feminino , Masculino , Adolescente , Estudos Prospectivos , Criança , Fezes/microbiologia , Indução de Remissão/métodos , Alimentos Formulados , Resultado do Tratamento , Complexo Antígeno L1 Leucocitário/análise
3.
Gastroenterology ; 161(3): 837-852.e9, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34052278

RESUMO

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.


Assuntos
Doença de Crohn/dietoterapia , Dieta Mediterrânea , Carboidratos da Dieta/administração & dosagem , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Pesquisa Comparativa da Efetividade , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/microbiologia , Dieta Mediterrânea/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Mediadores da Inflamação/sangue , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
4.
Am J Gastroenterol ; 117(6): 902-917, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35442220

RESUMO

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.


Assuntos
Colite Ulcerativa , Doença de Crohn , Complexo Antígeno L1 Leucocitário , Adolescente , Teorema de Bayes , Criança , Colite Ulcerativa/complicações , Colite Ulcerativa/dietoterapia , Doença de Crohn/complicações , Doença de Crohn/dietoterapia , Dieta , Fezes/química , Humanos , Inflamação/complicações , Inflamação/dietoterapia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/dietoterapia , Complexo Antígeno L1 Leucocitário/análise , Medicina de Precisão
5.
Clin Gastroenterol Hepatol ; 18(3): 612-619.e1, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31009795

RESUMO

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.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Criança , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Fezes , Humanos , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
J Pediatr Gastroenterol Nutr ; 71(6): 749-754, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32910089

RESUMO

OBJECTIVES: Although abdominal pain is a hallmark symptom of pediatric inflammatory bowel disease (IBD), limited research has examined pain during the first year after diagnosis. The purpose of the present study is to examine prevalence, predictors, and impact of abdominal pain during the 12 months after pediatric IBD diagnosis using data from the ImproveCareNow (ICN) Network. PATIENTS AND METHODS: Participants consisted of 13,875 youth (age 8-18 years, 44% female, 81% Caucasian) with IBD (65% Crohn's disease; 27% ulcerative colitis, 8% indeterminate colitis) enrolled in the ICN Network with data from clinic visits during the first year after diagnosis (1-22 visits; mean = 3.7). Multivariable mixed effects logistic regression models were conducted to analyze the presence versus the absence of abdominal pain, activity limitations, and decrements in well-being. RESULTS: The percentage of youth reporting abdominal pain decreased significantly during the first year after diagnosis and yet a sizeable group reported continued pain at 12 months (55.9% at diagnosis; 34.0% at 12 months). Multivariable analyses revealed that greater time since diagnosis (odds ratio [OR] = 0.98, P < 0.001), higher disease severity (OR = 11.84, P < 0.001), presence of psychosocial risk factors (OR = 2.33, P = 0.036), and female sex (OR = 1.90, P < 0.010) were significant correlates of continuing abdominal pain. Abdominal pain was significantly associated with decrements in well-being (OR = 5.11, P < 0.001) as well as limitations in activity (OR = 9.31, P < 0.001), over and above the influence of disease severity. CONCLUSIONS: Abdominal pain is prevalent and impactful, even when controlling for disease activity, during the first year after pediatric IBD diagnosis. Results from the present study can inform screening and tailored pain management intervention efforts in pediatric IBD.


Assuntos
Dor Abdominal , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Dor Abdominal/diagnóstico , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , Adolescente , Criança , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Índice de Gravidade de Doença
7.
Anaerobe ; 57: 1-3, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826445

RESUMO

Clostridium difficile (C. difficile) is an important nosocomial pathogen in adults and children. Roughly 4-5% of non hospitalized healthy adults carry the organism in their intestinal flora while adults in long term care facilities have asymptomatic carriage rates estimated at 20-50%. C. difficile colonization results in a spectrum of clinical conditions from asymptomatic carrier state to fulminant colitis. Changes in the fecal microbiome are central in the development of C. difficile colonization and disease pathogenesis. C. difficile infection has been shown to be associated with reduced biodiversity of the gut microbiome and intestinal dysbiosis. With the importance of the intestinal microbiota in development of CDI and with the known impact of diet on the intestinal microbiota, we report the first known case of C. difficile colonization/recurrence successful treated by dietary modification.


Assuntos
Portador Sadio/terapia , Infecções por Clostridium/terapia , Dietoterapia/métodos , Adolescente , Criança , Clostridioides difficile/isolamento & purificação , Feminino , Humanos , Masculino , Resultado do Tratamento
8.
J Clin Gastroenterol ; 52(2): 155-163, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28030510

RESUMO

GOAL: To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD). BACKGROUND: IBD is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Diet is a potential therapeutic option for IBD based on the hypothesis that changing the fecal dysbiosis could decrease intestinal inflammation. STUDY: Pediatric patients with mild to moderate IBD defined by pediatric Crohn's disease activity index (PCDAI 10-45) or pediatric ulcerative colitis activity index (PUCAI 10-65) were enrolled into a prospective study of the SCD. Patients started SCD with follow-up evaluations at 2, 4, 8, and 12 weeks. PCDAI/PUCAI, laboratory studies were assessed. RESULTS: Twelve patients, ages 10 to 17 years, were enrolled. Mean PCDAI decreased from 28.1±8.8 to 4.6±10.3 at 12 weeks. Mean PUCAI decreased from 28.3±23.1 to 6.7±11.6 at 12 weeks. Dietary therapy was ineffective for 2 patients while 2 individuals were unable to maintain the diet. Mean C-reactive protein decreased from 24.1±22.3 to 7.1±0.4 mg/L at 12 weeks in Seattle Cohort (nL<8.0 mg/L) and decreased from 20.7±10.9 to 4.8±4.5 mg/L at 12 weeks in Atlanta Cohort (nL<4.9 mg/L). Stool microbiome analysis showed a distinctive dysbiosis for each individual in most prediet microbiomes with significant changes in microbial composition after dietary change. CONCLUSIONS: SCD therapy in IBD is associated with clinical and laboratory improvements as well as concomitant changes in the fecal microbiome. Further prospective studies are required to fully assess the safety and efficacy of dietary therapy in patients with IBD.


Assuntos
Colite Ulcerativa/dietoterapia , Doença de Crohn/dietoterapia , Disbiose/dietoterapia , Fezes/microbiologia , Adolescente , Proteína C-Reativa/metabolismo , Criança , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Carboidratos da Dieta/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo
9.
Curr Opin Pediatr ; 30(5): 671-676, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30004946

RESUMO

PURPOSE OF REVIEW: Nutritional interventions play a central role in the treatment and management of inflammatory bowel disease (IBD) in children. Although malnutrition is a common presenting sign of IBD, nutritional interventions have focused not only on correction of the malnourished state but also on treatment of the primary disease. RECENT FINDINGS: Exclusive enteral nutrition (EEN) has been the primary therapy utilized in pediatric IBD specifically, Crohn's disease. This intervention provides total calories from formula meeting complete macronutrient and micronutrient needs for a patient. EEN has been shown to improve growth and correct micronutrient deficiencies as well as improve comorbid conditions like osteopenia and anemia. EEN has also been shown to be equally as efficacious as steroids in inducing remission with better mucosal healing. SUMMARY: EEN is a primary therapy in IBD. Both the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition consider EEN as first line therapy for inducing remission in Crohn's disease.


Assuntos
Doença de Crohn/reabilitação , Nutrição Enteral , Microbioma Gastrointestinal/imunologia , Indução de Remissão/métodos , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Doença de Crohn/imunologia , Doença de Crohn/fisiopatologia , Nutrição Enteral/métodos , Medicina Baseada em Evidências , Humanos
10.
Dig Dis Sci ; 63(10): 2722-2728, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29862484

RESUMO

OBJECTIVE: Certain food additives may promote the pathogenesis of Crohn's disease (CD), but thus far the evaluation of food additive exposures in humans has been limited. The objective of this study was to quantify food additive exposures in children with CD. METHODS: In a trial for bone health in CD, children were followed over 24 months with evaluation of disease characteristics, dietary intake, and body composition. At baseline, participants completed three 24-h dietary recalls. Foods were categorized, and the ingredient list for each item was evaluated for the presence of select food additives: polysorbate-80, carboxymethylcellulose, xanthan gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposures to these food additives was described for study participants and for food categories. RESULTS: At study baseline, 138 participants, mean age 14.2 ± 2.8 years, 95% having inactive or mild disease, were enrolled and dietary recalls were collected. A total of 1325 unique foods were recorded. Mean exposures per day for xanthan gum was 0.96 ± 0.72, carrageenan 0.58 ± 0.63, maltodextrin 0.95 ± 0.77, and soy lecithin 0.90 ± 0.74. The other additives had less than 0.1 exposures per day. For the 8 examined food additives, participants were exposed to a mean (SD) of 3.6 ± 2.1 total additives per recall day and a mean (SD) of 2.4 ± 1.0 different additives per day. CONCLUSION: Children with CD frequently consume food additives, and the impact on disease course needs further study.


Assuntos
Doença de Crohn , Dieta/efeitos adversos , Aditivos Alimentares/classificação , Análise de Alimentos , Adolescente , Composição Corporal , Densidade Óssea , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Feminino , Aditivos Alimentares/efeitos adversos , Aditivos Alimentares/química , Análise de Alimentos/métodos , Análise de Alimentos/estatística & dados numéricos , Humanos , Masculino , Gravidade do Paciente , Estudos Retrospectivos , Fatores de Risco , Estatística como Assunto , Estados Unidos
11.
J Pediatr Gastroenterol Nutr ; 65(5): 533-538, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28825603

RESUMO

INTRODUCTION: The specific carbohydrate diet (SCD) is an exclusion diet used as a therapy in inflammatory bowel disease. The aim of this study was to evaluate the nutritional adequacy of the SCD. METHODS: Prospective dietary data for 12 weeks were analyzed for pediatric patients on the SCD. Intake of 20 key nutrients was compared to dietary recommended intake levels and nutrient intake data from similarly aged children from The National Health and Nutrition Examination Survey National Youth Fitness Survey in 2012. RESULTS: Nine patients enrolled, with 8 patients completing the study. Six of 8 individuals completing the study had gained weight, 1 individual had weight loss, and 1 had no change in weight. Energy intake was significantly greater than 100% of the recommended daily allowance (RDA)/adequate intake for 64% of daily intakes completed for this study. The majority of participants' daily intakes met or exceeded the RDA for vitamins B2, B3, B5, B6, B7, B12, C, A, and E. One hundred percent of participants' intakes were below the RDA for vitamin D. Seventy-five percent of daily intakes were less than the RDA for calcium. The upper limit was met or exceeded for magnesium in 42% of daily intakes. Average vitamin A intake was significantly greater than the upper limit (P = 0.01). CONCLUSIONS: Nutrient intake of pediatric inflammatory bowel disease patients on the SCD was adequate when compared with a healthy peer reference population, but adequacy was variable when compared with the dietary recommended intakes. Close monitoring with a multidisciplinary team for patients using the SCD as an alternative or adjunct therapy is recommend to ensure positive outcomes for overall patient health.


Assuntos
Colite Ulcerativa/dietoterapia , Doença de Crohn/dietoterapia , Dieta com Restrição de Carboidratos , Estado Nutricional , Adolescente , Estudos de Casos e Controles , Criança , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Inquéritos sobre Dietas , Ingestão de Energia , Feminino , Seguimentos , Humanos , Masculino , Avaliação Nutricional , Estudos Prospectivos , Recomendações Nutricionais , Resultado do Tratamento , Aumento de Peso , Redução de Peso
12.
J Pediatr Gastroenterol Nutr ; 65(3): 289-292, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28825776

RESUMO

Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of "illegal foods") were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ±â€Š3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 µg/g, median 201, range 65-312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.


Assuntos
Colo/patologia , Doença de Crohn/dietoterapia , Dieta com Restrição de Carboidratos/métodos , Íleo/patologia , Mucosa Intestinal/patologia , Adolescente , Criança , Colo/diagnóstico por imagem , Colonoscopia , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Feminino , Seguimentos , Humanos , Íleo/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Resultado do Tratamento
13.
Dig Dis Sci ; 62(8): 2196-2200, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28551707

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract caused by a dysregulated immune response to the fecal microbiota. Very early-onset inflammatory bowel disease (VEO-IBD) refers to a subgroup of pediatric patients with IBD diagnosed before 6 years of age. This subgroup is often characterized by increased severity, aggressive progression, strong family history of IBD, and often poor response to conventional treatments. Nutritional therapies have been utilized to treat IBD, but their role in VEO-IBD is unclear. Disease behavior in VEO-IBD is often different from disease in adolescents and adults, as it is often restricted to the colon and refractory to standard medical therapies. Up to 25% of VEO-IBD patients have an identified underlying immunodeficiency, which may impact response to therapy. While specific mutations in interleukin 10 (IL-10), the IL-10 receptor (IL-10R), and mutations in NCF2, XIAP, LRBA, and TTC7 have been identified in VEO-IBD, polymorphisms in these genes are also associated with increased risk of developing IBD in adolescence or adulthood. We describe two cases in which infants presenting with VEO-IBD achieved clinical remission using exclusive enteral nutrition, a formula-based diet which has been shown to induce remission in older children with active Crohn's disease.


Assuntos
Nutrição Enteral/métodos , Alimentos Formulados , Doenças Inflamatórias Intestinais/dietoterapia , Indução de Remissão/métodos , Idade de Início , Sedimentação Sanguínea , Humanos , Lactente , Doenças Inflamatórias Intestinais/sangue , Masculino , Resultado do Tratamento
14.
Hepatology ; 61(1): 268-74, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25163551

RESUMO

UNLABELLED: Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated five patients (one male, four females) from four families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form, of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and posttreatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction, and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1,000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients. CONCLUSION: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects.


Assuntos
Aciltransferases/deficiência , Colagogos e Coleréticos/uso terapêutico , Ácido Glicocólico/uso terapêutico , Erros Inatos do Metabolismo/tratamento farmacológico , Aciltransferases/genética , Adolescente , Ácidos e Sais Biliares/metabolismo , Criança , Desenvolvimento Infantil , Pré-Escolar , Ergocalciferóis/sangue , Feminino , Humanos , Lactente , Masculino , Erros Inatos do Metabolismo/sangue , Tocoferóis/sangue
15.
J Pediatr Gastroenterol Nutr ; 63(3): 348-51, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26854655

RESUMO

OBJECTIVES: We describe the use of ustekinumab for 4 patients with pediatric Crohn disease treated at the Seattle Children's Hospital Inflammatory Bowel Disease Center. METHODS: A retrospective chart review was done to identify patients' clinical data, disease phenotype, treatment history, and laboratory and growth parameters before treatment with ustekinumab and at last follow-up. Adverse events while on ustekinumab were also recorded. RESULTS: Four adolescent patients with Crohn disease at our center received ustekinumab. All had previously received corticosteroids, methotrexate, azathioprine/6-mercaptopurine, and both infliximab and adalimumab. Patients had varying disease phenotypes. Ages at ustekinumab initiation were 12, 13, 16, and 17 years. Weight ranged from 40.5 to 57.8 kg, mean 49.5 kg. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy because of continued symptoms and disease complications and required multiple hospitalizations. CONCLUSIONS: Ustekinumab was used in 4 children with pediatric Crohn disease with 2 of 4 patients showing clinical response (1 with persistently elevated C-reactive protein). A prospective study is needed to define its efficacy, safety, and placement in managing pediatric Crohn disease in the future.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Doença de Crohn/tratamento farmacológico , Ustekinumab/administração & dosagem , Adolescente , Proteína C-Reativa/análise , Criança , Humanos , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
J Pediatr Gastroenterol Nutr ; 62(5): 728-33, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26465789

RESUMO

OBJECTIVES: Medically intractable pediatric ulcerative colitis can lead to colectomy after which patients commonly receive an ileoanal pouch. Postoperative complications are more common in patients with Crohn disease, a diagnosis that may be rendered after the colectomy specimen is examined. Because most children are likely to be exposed to medications before colectomy, we sought to examine whether such exposure influences the distribution of the inflammation within the resected colon and therefore potentially raise questions about the diagnosis accuracy. METHODS: We conducted a retrospective cohort study of 32 pediatric ulcerative colitis cases undergoing colectomy from 2007 to 2014 for clinical data and precolectomy treatment history. The resected colon histology was reviewed independently by 2 blinded pathologists. The acute/active inflammation was scored using the modified Riley score for 3 colonic segments (proximal, transverse, and distal colon) for each patient. Linear mixed-effects models were used to evaluate possible association between acute/active inflammation scores at various sites and medication use. RESULTS: Twelve cases (38%) showed decreasing acute inflammation score distally to proximally, 8 (25%) had increasing scores, and 12 cases showed no change. Patients were most commonly exposed to corticosteroids, followed by anti-tumor necrosis factor antibodies. There was no statistically or clinically significant change in the histologic scores across the colonic segments of the resected colon in association with exposure to any specific medication or combination of medications, sex, age at diagnosis and surgery, or duration of disease. CONCLUSIONS: Precolectomy therapy does not seem to influence the distribution of inflammation within the resected colon.


Assuntos
Colite Ulcerativa/cirurgia , Cuidados Pré-Operatórios , Adolescente , Anti-Inflamatórios/administração & dosagem , Criança , Pré-Escolar , Estudos de Coortes , Colectomia/métodos , Colite Ulcerativa/patologia , Bases de Dados Factuais , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Imunossupressores/administração & dosagem , Lactente , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
17.
Dig Dis Sci ; 61(11): 3255-3260, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27638834

RESUMO

BACKGROUND: Recent studies suggest that dietary therapy may be effective for patients with inflammatory bowel disease (IBD), but limited published data exist on the usage and efficacy of dietary therapy. AIM: To evaluate the perspective of IBD patients using the specific carbohydrate diet (SCD). METHODS: An anonymous online survey was conducted using REDCap, a Web-based survey tool. Survey links were sent to known Web sites as well as support groups in an attempt to characterize patient utilization of the SCD and perception of efficacy of the SCD. RESULTS: There were 417 respondents of the online survey on the SCD with IBD. Mean age for individuals on the SCD was 34.9 ± 16.4 years. Seventy percent were female. Forty-seven percent had Crohn's disease, 43 % had ulcerative colitis, and 10 % had indeterminate colitis. Individuals perceived clinical improvement on the SCD. Four percent reported clinical remission prior to the SCD, while 33 % reported remission at 2 months after initiation of the SCD, and 42 % at both 6 and 12 months. For those reporting clinical remission, 13 % reported time to achieve remission of less than 2 weeks, 17 % reported 2 weeks to a month, 36 % reported 1-3 months, and 34 % reported greater than 3 months. For individuals who reported reaching remission, 47 % of individuals reported associated improvement in abnormal laboratory values. CONCLUSIONS: The SCD is utilized by many patients as a primary and adjunct therapy for IBD. Most patients perceive clinical benefit to use of the SCD.


Assuntos
Colite Ulcerativa/dietoterapia , Doença de Crohn/dietoterapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Carboidratos da Dieta , Feminino , Humanos , Lactente , Doenças Inflamatórias Intestinais/dietoterapia , Masculino , Pessoa de Meia-Idade , Percepção , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
18.
J Pediatr Gastroenterol Nutr ; 60(1): 27-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25162366

RESUMO

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease of the large intestine, is characterized by a dysregulated immune reaction. UC is associated with fecal dysbiosis. Human and animal studies support the fact that the gastrointestinal microbiome may trigger the intestinal immune response, resulting in UC. Fecal microbial transplantation (FMT), by changing the gastrointestinal microbiome of patients with UC, may be a therapeutic option. METHODS: Four patients with moderate symptoms defined by the Pediatric Ulcerative Colitis Activity Index were enrolled in a prospective, open-label study of FMT via nasogastric tube in pediatric UC (US Food and Drug Administration IND 14942). After the donor and patient evaluation, patients received FMT with follow-up evaluations at 2, 6, and 12 weeks after transplantation. Study subjects were maintained on their pretransplant medications. The Pediatric Ulcerative Colitis Activity Index score, C-reactive protein, and stool calprotectin were completed during each study visit. RESULTS: Four patients with UC were enrolled (all boys). Ages ranged from 13 to 16 years. Patients tolerated FMT without adverse effects. None of the patients clinically improved with FMT, nor were there any significant changes in stool calprotectin or laboratory values, including C-reactive protein, albumin, and hematocrit. Three individuals received additional standard medical therapies before the end of the study. CONCLUSIONS: This study, although showing that single-dose FMT via nasogastric tube is well tolerated in active pediatric UC, did not show any clinical or laboratory benefit.


Assuntos
Colite Ulcerativa/terapia , Microbiota , Terapias em Estudo , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Colite Ulcerativa/fisiopatologia , Terapia Combinada/efeitos adversos , Seleção do Doador , Fezes/microbiologia , Seguimentos , Hospitais Pediátricos , Humanos , Imunossupressores/uso terapêutico , Intubação Gastrointestinal , Masculino , Ambulatório Hospitalar , Probióticos/uso terapêutico , Índice de Gravidade de Doença , Terapias em Estudo/efeitos adversos , Washington
19.
J Pediatr Gastroenterol Nutr ; 60(1): 23-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25162365

RESUMO

Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.


Assuntos
Clostridioides difficile/isolamento & purificação , Enterocolite Pseudomembranosa/terapia , Microbiota , Terapias em Estudo , Criança , Pré-Escolar , Clostridioides difficile/crescimento & desenvolvimento , Clostridioides difficile/imunologia , Comorbidade , Seleção do Doador , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/imunologia , Enterocolite Pseudomembranosa/microbiologia , Fezes/microbiologia , Feminino , Seguimentos , Hospitais Pediátricos , Humanos , Hospedeiro Imunocomprometido , Intubação Gastrointestinal , Masculino , Recidiva , Estudos Retrospectivos , Terapias em Estudo/efeitos adversos , Washington/epidemiologia
20.
Gastroenterology ; 144(5): 945-955.e6; quiz e14-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23415802

RESUMO

BACKGROUND & AIMS: The final step in bile acid synthesis involves conjugation with glycine and taurine, which promotes a high intraluminal micellar concentration to facilitate lipid absorption. We investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some with growth failure or transient neonatal cholestatic hepatitis. METHODS: We identified the genetic defect that causes this disorder using mass spectrometry analysis of urine, bile, and serum samples and sequence analysis of the genes encoding bile acid-CoA:amino acid N-acyltransferase (BAAT) and bile acid-CoA ligase (SLC27A5). RESULTS: Levels of urinary bile acids were increased (432 ± 248 µmol/L) and predominantly excreted in unconjugated forms (79.4% ± 3.9%) and as sulfates and glucuronides. Glycine or taurine conjugates were absent in the urine, bile, and serum. Unconjugated bile acids accounted for 95.7% ± 5.8% of the bile acids in duodenal bile, with cholic acid accounting for 82.4% ± 5.5% of the total. Duodenal bile acid concentrations were 12.1 ± 5.9 mmol/L, which is too low for efficient lipid absorption. The biochemical profile was consistent with defective bile acid amidation. Molecular analysis of BAAT confirmed 4 different homozygous mutations in 8 patients tested. CONCLUSIONS: Based on a study of 10 pediatric patients, genetic defects that disrupt bile acid amidation cause fat-soluble vitamin deficiency and growth failure, indicating the importance of bile acid conjugation in lipid absorption. Some patients developed liver disease with features of a cholangiopathy. These findings indicate that patients with idiopathic neonatal cholestasis or later onset of unexplained fat-soluble vitamin deficiency should be screened for defects in bile acid conjugation.


Assuntos
Deficiência de Vitaminas/genética , Ácidos e Sais Biliares/metabolismo , Coenzima A Ligases/genética , DNA/genética , Predisposição Genética para Doença , Mutação de Sentido Incorreto , Aciltransferases/genética , Aciltransferases/metabolismo , Deficiência de Vitaminas/metabolismo , Deficiência de Vitaminas/patologia , Biópsia , Criança , Pré-Escolar , Coenzima A Ligases/metabolismo , Análise Mutacional de DNA , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Feminino , Homozigoto , Humanos , Lactente , Fígado/patologia , Masculino , Espectrometria de Massas
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