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BACKGROUND AND AIMS: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD. METHODS: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 U.S. sites from 2019-2022. Parents/guardians reported race, ethnicity, time between symptom onset and diagnosis, and other social determinants of health. Through bivariate and multivariable analyses using generalized estimating equations we evaluated associations between these factors and diagnosis time defined as ≤60 days, 61-180 days, 181-365 days and >365 days. RESULTS: We enrolled 869 participants (mean age at diagnosis 13.1 years, 52% male, 57% Crohn's disease (CD), 34% ulcerative colitis (UC), 8% Hispanic, 30% non-White). Overall, the mean time to diagnosis was 265.9 days. After adjustment, factors associated with longer diagnosis time included CD vs. UC (OR 2.6, 95% CI 1.9-3.5), 2 or more other health conditions (OR 1.7, 95% CI 1.1-2.7), and longer travel time to clinic [(> 1 hour (OR 1.7, 95% CI 1.2-2.4), > 2 hours (OR 1.8, 95% CI 1.2-2.9) each vs<30 minute]. There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust. CONCLUSIONS: Consistent with prior literature, diagnostic delay is longer for CD than UC. Reassuringly, time to diagnosis is equitable across racioethnic groups. New models of diagnostic care are needed for communities affected by longer travel times.
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OBJECTIVES: Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. METHODS: We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. RESULTS: Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. CONCLUSIONS: UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.
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Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Fármacos Gastrointestinales , Ustekinumab , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Ustekinumab/uso terapéutico , Femenino , Masculino , Niño , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adolescente , Fármacos Gastrointestinales/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Inducción de Remisión/métodos , Puntaje de Propensión , Sistema de RegistrosRESUMEN
BACKGROUND: Pouchitis is the most frequent complication following restorative proctocolectomy and ileal pouch anal anastomosis (RP-IPAA) in patients with Ulcerative colitis (UC). Pediatric data on nutritional status during RP-IPAA and in patients with pouchitis are limited. AIMS: We aimed to delineate nutritional changes in children undergoing 2-stage and 3-stage surgeries and to evaluate the association between nutrition and the development of recurrent or chronic pouchitis. METHODS: This single-center retrospective study involved 46 children with UC who underwent a RP-IPAA. Data were collected at each surgical stage and for up to 2-year post-ileostomy takedown. We used Wilcoxon matched-pairs signed-rank test to evaluate the differences in nutritional markers across surgical stages and logistic regression to identify the factors associated with recurrent or chronic pouchitis. RESULTS: Twenty patients (43.5%) developed recurrent or chronic pouchitis. Children who underwent a 3-stage procedure had improvements in albumin, hematocrit, and body mass index (BMI)-for-age Z-scores (p < 0.01) between the first two stages. A positive trend in BMI-for-age Z-scores (p = 0.08) was identified in children with 2-stage procedures. All patients showed sustained nutritional improvement during the follow-up period. Among patients who underwent 3-stage surgeries, BMI worsened by 0.8 standard deviations (SDs) (p = 0.24) between the initial stages in those who developed recurrent or chronic pouchitis and improved by 1.1 SDs (p = 0.04) in those who did not. CONCLUSIONS: Early improvement in BMI-for-age Z-scores following the initial stage was associated with lower rates of recurrent or chronic pouchitis. Larger prospective studies are needed to validate these findings.
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Colitis Ulcerosa , Reservoritis , Proctocolectomía Restauradora , Humanos , Niño , Reservoritis/etiología , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/complicaciones , Estudios Retrospectivos , Estado Nutricional , Proctocolectomía Restauradora/efectos adversos , Colectomía/efectos adversosRESUMEN
Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.
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Enfermedades Inflamatorias del Intestino/complicaciones , Ensayos Clínicos como Asunto , Oftalmopatías/etiología , Humanos , Enfermedades Reumáticas/etiología , Enfermedades de la Piel/etiologíaRESUMEN
INTRODUCTION: Ustekinumab (UST), a human monoclonal antibody against interleukin-12 and 23, is approved to treat adult patients with psoriasis or Crohn disease (CD). Outcomes data for off-label use in pediatric patients with CD are limited. AIM: We conducted a retrospective cohort study to analyze the long-term efficacy of UST, including dose adjustments, in the treatment of pediatric patients with medically refractory CD. Adverse events were documented. METHODS: We identified 40 pediatric patients with CD treated with UST between January 1, 2016 and December 31, 2019. Electronic medical records were reviewed for demographics, Paris Classification, significant comorbidities, previous CD therapy, adverse events after initiation, and surveillance markers at the time of their first dose and most recent clinic visit. A validated abbreviated pediatric CD activity index (aPCDAI) was used to assess response to therapy. RESULTS: Thirty-eight pediatric patients with CD, including 34.2% with stricturing or penetrating disease, were analyzed after initiation of treatment with UST. Median age at diagnosis of CD was 12.5âyears, and median age at UST induction was 17.2âyears. No patients were anti-TNF-naive, and 34.2% were previously exposed to 2 or more anti-TNF agents. At time of last follow-up, 84.2% of patients remained on UST for a median duration on UST of 62.1âweeks, and 60.5% achieved clinical remission. Patients had significant improvement in aPCDAI scores, clinical remission rates, albumin, and hematocrit, and 89.5% of patients had no significant adverse events. Similar results were observed among those who required dose adjustment, including 61.1% achieving clinical remission, and among those with perianal disease, including 38.5% achieving clinical remission. CONCLUSIONS: Our data suggest that, within our cohort of pediatric patients with CD, UST has long-term efficacy with no observed safety concerns. Dose adjustment may be helpful in achieving clinical remission.
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Enfermedad de Crohn , Ustekinumab , Adulto , Anticuerpos Monoclonales , Niño , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral , Ustekinumab/uso terapéuticoRESUMEN
ABSTRACT: Transgender and gender nonconforming (TGNC) individuals have a different gender identity than the sex they were assigned at birth. Despite an increase in provider awareness of TGNC health over the past decade, no original research or societal guidelines exist on TGNC patients with inflammatory bowel disease (IBD). We review TGNC IBD cases in the University of California, San Francisco (UCSF) Pediatric IBD Program and in the literature. We then provide some recommendations for the provision of high-quality care to the TGNC IBD population, divided into 3 categories: medications, anatomy, and mental health.
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Enfermedades Inflamatorias del Intestino , Personas Transgénero , Adolescente , Femenino , Identidad de Género , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Adulto JovenRESUMEN
OBJECTIVES: We examined the fecal virome and bacterial community composition of children with Crohn disease (CD), ulcerative colitis (UC), and healthy controls to test the hypothesis that unique patterns of viral organisms and/or presence of bacterial pathogens may be identified that could contribute to the pathogenesis of pediatric inflammatory bowel disease (IBD). METHODS: Fecal samples from 24 children (mean 12.2 years) with CD (nâ=â7) or UC (nâ=â5) and similar aged controls (nâ=â12) were processed to determine individual viromes. Viral sequences were identified through translated protein sequence similarity search. Bacterial microbiota were determined by sequencing of the V4 region of the 16S rRNA gene. RESULTS: Only a few human viruses were detected, so virome analyses focused on bacterial viruses. The relative abundance of Caudovirales was greater than that of Microviridae phages in both IBD and healthy controls. Caudovirales phages were more abundant in CD (mean 80.8%) than UC (48.8%) (Pâ=â0.05) but not controls. The richness of viral strains in Microviridae but not Caudovirales was higher in controls than CD (Pâ=â0.05) but not UC cases. No other measure of phage abundance, richness, or Shannon diversity showed significant difference between the 2 IBD and control groups. Bacterial microbiota analysis revealed that IBD diagnosis, albumin, hemoglobin, erythrocyte sedimentation rate, and probiotic supplementation correlated to the composition of gut bacterial microbiota. CONCLUSIONS: Minor patterns in gut virome and bacterial community composition distinguish pediatric IBD patients from healthy controls. Probiotics are associated with bacterial microbiota composition. These exploratory results need confirmation in larger studies.
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Colitis Ulcerosa/microbiología , Enfermedad de Crohn/microbiología , Heces/microbiología , Microbioma Gastrointestinal/genética , Genoma Viral , Adolescente , Bacteriófagos/aislamiento & purificación , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Probióticos/uso terapéutico , ARN Ribosómico 16S , Tropismo Viral , Virus/genéticaRESUMEN
Goal: The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population. Background: IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals. Clinical IBD trials now underway target S1PR1, a receptor for the pro-inflammatory sphingolipid S1P. However, circulating and tissue sphingolipid levels and S1P-related gene expression have not been characterized in pediatric IBD. Methods: Pediatric IBD patients and controls were recruited in a four-site study. Patients received a clinical score using PUCAI or PCDAI evaluation. Colon biopsies were collected during endoscopy. Gene expression was measured by qRT-PCR. Plasma and gut tissue sphingolipids were measured by LC-MS/MS. Results: Genes of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, and S1PR4) were significantly upregulated in colon biopsies of IBD patients with moderate/severe symptoms compared with controls or patients in remission. Tissue ceramide, dihydroceramide, and ceramide-1-phosphate (C1P) levels were significantly elevated in IBD patients compared with controls. Conclusions: A signature of elevated S1P-related gene expression in colon tissues of pediatric IBD patients correlates with active disease and normalizes in remission. Biopsied gut tissue from symptomatic IBD patients contains high levels of pro-apoptotic and pro-inflammatory sphingolipids. A combined analysis of gut tissue sphingolipid profiles with this S1P-related gene signature may be useful for monitoring response to conventional therapy.
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Colon/metabolismo , Expresión Génica , Enfermedades Inflamatorias del Intestino/metabolismo , Lisofosfolípidos/metabolismo , Esfingosina/análogos & derivados , Adolescente , Animales , Estudios de Casos y Controles , Ceramidas/metabolismo , Niño , Preescolar , Cromatografía Liquida , Colon/patología , Femenino , Humanos , Lactante , Enfermedades Inflamatorias del Intestino/genética , Lisofosfolípidos/genética , Masculino , Proyectos Piloto , Transducción de Señal , Esfingosina/genética , Esfingosina/metabolismo , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
BACKGROUND: Bisphenol-A (BPA) is a ubiquitous chemical and recognized endocrine disruptor associated with obesity and related disorders. We explored the association between BPA levels and suspected non-alcoholic fatty liver disease (NAFLD). METHODS: Unweighted analyses were used to study the relationship between urinary BPA levels and suspected NAFLD (alanine aminotransferase (ALT). > 30 U/L, body mass index (BMI) Z-score > 1.064 and evidence of insulin resistance) using National Health and Nutrition Examination Survey (NHANES) data (2003-2010) on 12-19 year olds. Unweighted and weighted analyses were used to evaluate the risk with only elevated ALT. RESULTS: We included 944 adolescents with urinary BPA and fasting laboratory tests from a total of 7168 adolescents. Risk of suspected NAFLD was increased in the second quartile of BPA levels (1.4-2.7 ng/mL) when compared to the first (< 1.4 ng/mL) (Odds Ratio (OR) 4.23, 95% Confidence Interval (CI) 1.44-12.41). The ORs for the third and second quartiles were positive but did not reach statistical significance. The association was stronger in Hispanics (n = 344) with BPA levels in the second (OR 6.12, 95% C.I. 1.62-23.15) quartile and when limiting the analyses to overweight/obese adolescents (n = 332), in the second (OR 5.56, 95% C.I. 1.28-24.06) and fourth BPA quartiles (OR 6.85, 95% C.I. 1.02-46.22) compared to the first quartile. BPA levels were not associated with ALT elevation. CONCLUSIONS: The risk of suspected NAFLD is increased in participants in higher quartiles of BPA exposure, particularly in those of Hispanic ethnicity. Further studies are required to fully understand the potential role of BPA in non-alcoholic fatty liver disease.
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Compuestos de Bencidrilo/orina , Disruptores Endocrinos/orina , Contaminantes Ambientales/orina , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Fenoles/orina , Adolescente , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Encuestas Nutricionales , Prevalencia , Factores de Riesgo , Estados Unidos/epidemiología , Estados Unidos/etnologíaRESUMEN
OBJECTIVE: To assess whether individual obesity risk factors, present during gestation, and the first 6 months of life, can be combined into a simple prognostic model that has the ability to accurately predict childhood obesity at age 5 years in a high-risk cohort. STUDY DESIGN: A total of 201 Latina women were recruited during pregnancy, and their infants followed longitudinally. Ten risk factors for childhood obesity were included in an initial logistic model; a second reduced model was created via stepwise deletion (confirmed with nonparametric conditional random forest classifier), after which 5 risk factors remained. From each model, an obesity risk equation was derived, and an obesity risk score was generated for each patient. Derived algorithms were assessed using discrimination, calibration, and via predictive statistics. RESULTS: Of the 166 children followed through age 5 years, 56 (32%) met criteria for childhood obesity. Discrimination accuracy for both derivation models was excellent, and after optimism-corrected bootstrapping, both models showed meaningful clinical performance. Both models were adequately calibrated, showed strong sensitivity and negative predictive value at conservatively set obesity risk thresholds, and displayed excellent specificity among those classified as highest risk. Birth weight z-score and change in weight-for-age z-score between birth and 6 months were the risk factors with the strongest contribution to the obesity risk score. CONCLUSIONS: Obesity risk algorithms are reliable in their prediction of childhood obesity and have the potential to be integrated into the electronic medical record. These models could provide a filter for directing early prevention resources to children with high obesity risk but should be evaluated in a larger external dataset.
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Obesidad Infantil/etiología , Adulto , Peso al Nacer , Niño , Preescolar , Femenino , Hispánicos o Latinos , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Estudios Longitudinales , Masculino , Embarazo , Factores de Riesgo , Población Urbana , Aumento de PesoRESUMEN
OBJECTIVES: The aim of the study was to investigate the value of microscopic findings in the classification of pediatric Crohn disease (CD) by determining whether classification of disease changes significantly with inclusion of histologic findings. METHODS: Sixty patients were randomly selected from a cohort of patients studied at the Pediatric Inflammatory Bowel Disease Clinic at the University of California, San Francisco Benioff Children's Hospital. Two physicians independently reviewed the electronic health records of the included patients to determine the Paris classification for each patient by adhering to present guidelines and then by including microscopic findings. RESULTS: Macroscopic and combined disease location classifications were discordant in 34 (56.6%), with no statistically significant differences between groups. Interobserver agreement was higher in the combined classification (κ = 0.73, 95% confidence interval 0.65-0.82) as opposed to when classification was limited to macroscopic findings (κ = 0.53, 95% confidence interval 0.40-0.58). When evaluating the proximal upper gastrointestinal tract (Paris L4a), the interobserver agreement was better in macroscopic compared with the combined classification. CONCLUSIONS: Disease extent classifications differed significantly when comparing isolated macroscopic findings (Paris classification) with the combined scheme that included microscopy. Further studies are needed to determine which scheme provides more accurate representation of disease extent.
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Enfermedad de Crohn/clasificación , Intestinos/patología , Fenotipo , Tracto Gastrointestinal Superior/patología , California , Niño , Enfermedad de Crohn/patología , Femenino , Humanos , Masculino , Microscopía/métodos , ParisRESUMEN
Breastfeeding has been found to have a protective effect on subsequent development of obesity in childhood, particularly in white, non-Hispanic populations. The protective effect of nursing for more than 12 months in children of Latina women is less clear, which may be due to differences in levels of acculturation in previously studied populations. We evaluated the association between breastfeeding for 12 months or more and risk for obesity in a cohort of children of recently immigrated relatively unacculturated Latina mothers. Maternal characteristics at birth, including length of stay in the United States, breastfeeding habits at 4-6 weeks of age, 6 months, and 1 year, and anthropometric measurements were obtained for a cohort of 196 children participating in a prospective study. At 1 year of age 39.0% of infants were being breastfed. Being breastfed at 1 year of age was associated with a decreased risk of obesity in both univariate (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.21-0.83) and multivariate models (OR 0.39, 95% CI 0.02-0.93) adjusting for maternal BMI, marital status, education level, country of origin, age, years of living in the United States, and child's birth weight at 3 years of age, regardless of mother's acculturation status using length of stay in the United States as a proxy for acculturation. The association with breastfeeding persisted at 4 years of age as a protective factor for obesity (OR 0.29, 95% CI 0.11-0.80). Breastfeeding for longer than 12 months provides a significant protective effect on the development of obesity in early childhood in a cohort of children of high-risk recently immigrated Latina women in San Francisco who were relatively unacculturated to the United States.