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1.
Am J Physiol Endocrinol Metab ; 326(5): E626-E639, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38536037

RESUMO

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.


Assuntos
Metabolismo Energético , Estradiol , Hormônio Foliculoestimulante , Ovariectomia , Ratos Wistar , Animais , Feminino , Metabolismo Energético/efeitos dos fármacos , Ratos , Hormônio Foliculoestimulante/metabolismo , Estradiol/farmacologia , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38615728

RESUMO

BACKGROUND & AIMS: Celiac disease (CD) mass screening remains controversial in part because of a paucity of data to support its benefit. The Autoimmunity Screening for Kids study is a mass screening study for pediatric CD and type 1 diabetes in Colorado. METHODS: This study prospectively follows up children ages 1 to 17 years who screened positive for tissue transglutaminase IgA autoantibodies in the Autoimmunity Screening for Kids study subsequently referred for diagnostic evaluation. Children diagnosed with CD by biopsy or serologic criteria were included in this study. Evaluation at baseline and 12 month follow-up evaluation included demographics, laboratory studies, symptoms, health-related quality of life, anxiety/depression, and gluten-free diet adherence. Paired Student t test, chi-square, and Wilcoxon sign rank tests compared baseline and follow-up data. For symptom scores, odds of improvement were assessed. RESULTS: Of the 52 children with CD enrolled, 42 children completed 12-month follow-up evaluation. On the symptom questionnaire completed at diagnostic evaluation, 38 of 42 children reported 1 or more symptoms. CD mean symptom severity and frequency scores improved from baseline to follow-up evaluation (P < .001). Reported health-related quality of life scores improved among caregivers (P = .002). There was no significant change in reported anxiety or depression. Iron deficiency without anemia was common at baseline (21 of 24 children; 87.5%) and normalized at follow-up evaluation (11 of 21 children; 52.3%). Twenty-six of 28 families reported good or excellent gluten-free diet adherence. CONCLUSIONS: This novel study of children with CD identified through a mass screening program demonstrated improvement in symptoms, quality of life, and iron deficiency after 1 year follow-up evaluation. This demonstrates that there may be benefit to CD mass screening.

3.
Am J Gastroenterol ; 119(7): 1298-1308, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38174865

RESUMO

INTRODUCTION: Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories. METHODS: The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis. RESULTS: We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63). DISCUSSION: Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications.


Assuntos
Duodenite , Eosinofilia , Gastrite , Humanos , Masculino , Criança , Feminino , Eosinofilia/epidemiologia , Gastrite/epidemiologia , Gastrite/complicações , Gastrite/patologia , Duodenite/epidemiologia , Duodenite/patologia , Adolescente , Pré-Escolar , Enterite/epidemiologia , Enterite/complicações , Enterite/diagnóstico , Recidiva , Estudos Retrospectivos , Endoscopia Gastrointestinal
4.
J Pediatr ; 275: 114221, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39097266

RESUMO

OBJECTIVE: To describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multicenter cohort, given that data supporting its use in pediatric PAH are sparse. STUDY DESIGN: We report a multicenter, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: before selexipag, 3-12 months after selexipag, and >12 months follow-up. RESULTS: Eighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. The median starting and final doses were 4.7 and 28.5 µg/kg/dose twice daily, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53; P = .034) with a lower average mean pulmonary artery pressure (46 vs 39 mm Hg; P = NS), and oxygen consumption (maximal oxygen consumption during cardiopulmonary exercise testing [VO2 max] 27.8 mL/kg/min vs 30.9 mL/kg/min; P = NS). Transition patients demonstrated stable mean pulmonary artery pressure (47 mm Hg vs 45 mm Hg; P = NS) and a lower mean indexed pulmonary vascular resistance (10.9 Wood units∗m2 vs 8.2 Wood units∗m2; P = NS) but late functional worsening in some with VO2 max decreased at follow-up (26.0 mL/kg/min vs 19.5 mL/kg/min). Side effects were noted in 40% of the cohort, but prompted discontinuation in only 2%. CONCLUSIONS: In a large, multicenter cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring.

5.
J Pediatr Gastroenterol Nutr ; 78(2): 381-385, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38374574

RESUMO

Transnasal endoscopy (TNE) with virtual reality (VR) distraction allows for unsedated pediatric upper endoscopy. Understanding the pediatric population that is successful with TNE is imperative for patient selection and experience. We developed a "TNEase Score" to assess patient tolerance from the physician's assessment. The aim of this study was to identify factors that influence patient's acceptance and tolerability of sedation-free TNE in pediatric patients undergoing the procedure. From March 2020 to April 2021, 110 TNEs were performed on subjects 5-22 years of age. The overall completion rate was 98.1%. Of these subjects, 66 subjects (60%) were graded by the gastroenterologist as TNEase Score 1 (with ease); 27 subjects (25%) were graded as TNEase Score 2 (minimal complaints); nine subjects (8%) were graded as TNEase score 3 (moderate complaints, required frequent reassurance); six subjects were graded as TNEase Score 4 (significant complaints and resistance); two subjects (2%) were graded as TNEase Score 5 (procedure terminated). Feasibility of TNE was significantly related to age, height, and whether the patient had undergone previous TNE. Thus, young age, shorter height, and first time TNE were significant predictors of higher TNEase score or difficulty tolerating TNE. Factors examined that did not predict higher TNEase score included gender, junior versus senior endoscopist, past medical history of anxiety, autism, attention-deficit/hyperactivity disorder (ADHD), or history of using a nasal spray at home. "TNEase score" allowed grading of the subject's experience and the majority of patients tolerated TNE with minimal complaints.


Assuntos
Endoscopia Gastrointestinal , Satisfação do Paciente , Humanos , Criança , Endoscopia Gastrointestinal/métodos , Boca , Sedação Consciente , Endoscopia do Sistema Digestório/métodos
6.
J Pediatr Orthop ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39282710

RESUMO

PURPOSE: Hip subluxation and dislocation are known problems for children with spinal muscular atrophy (SMA). Medical complexity of these children typically results in absence of monitoring and intervention for pathologic hips. Patterns of hip migration and acetabular morphology in SMA have not been described. This study examines the natural progression of hip instability across all types of SMA in a pediatric population. METHODS: Following institutional review board approval, a retrospective chart review of all children with SMA at our institution was performed. All x-rays taken before the age of 18 years containing adequate projections of the pelvis were measured for Reimer migration index (MI), acetabular depth ratio (ADR), and acetabular index (AI). Demographics and clinical data were collected including use of nusinersen, ambulatory status, contractures, and hip pain. Linear mixed effects model was fit to serial MI measures of individual hips with fixed effects consisting of SMA type, age at x-ray, and their interaction. ADR and AI measures were similarly modeled following conversion of raw values to z-scores based on the model developed by Novais et al Slope indicated rate of measure change as a function of age. RESULTS: Forty-five children (22 males) with SMA types 1 to 3 were included in this retrospective study. Six children were classified as type 1, 25 were type 2, and 14 were type 3. The interaction of age by SMA type was statistically significant (P=0.01), indicating a difference in the rate of hip subluxation between the 3 SMA types as measured by MI. By age 4, MI values were different from one another across all 3 groups (P<0.01). ADR decreased with age across all SMA types. The slopes of ADR regression lines were negative and statistically significant between the 3 groups (P=0.002). AI values were higher for all types of SMA, which is the opposite of expected in normal hips. CONCLUSIONS: Hip subluxation occurs across all SMA types, most rapidly in SMA type 1. Regression lines of ADR and AI compared with those seen in unaffected populations suggest hips in children with SMA demonstrate a difference in morphology of the acetabulum and do not follow normal adaptive remodeling. As treatments advance and the population of SMA patients becomes more mobile, there is an increased need to monitor hip instability in children with SMA, thus making orthopaedic management an important consideration.

7.
J Pediatr Gastroenterol Nutr ; 76(6): 786-792, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306502

RESUMO

OBJECTIVE: To evaluate the impact of type and dose of swallowed topical steroids (STS) and concurrent steroid therapy on the development and resolution of adrenal insufficiency (AI) in pediatric eosinophilic esophagitis (EoE). METHODS: We performed a retrospective case-control study of pediatric EoE subjects in a single tertiary care center, who were treated with STS for at least 3 months and diagnosed with AI based on a peak stimulated cortisol level of <18 µg/dL (500 nmol/L). Steroid forms and doses, and endoscopy data were collected at the time of AI diagnosis and AI resolution or the last known evaluation. Steroid formulations were converted to a fluticasone-equivalent dose for analysis. RESULTS: Thirty-two EoE subjects with AI were identified, and 20 had AI resolution, including 12 who remained on lower dose STS. Eight of the 32 patients were also treated with extended-release budesonide (ER budesonide), which resulted in a 7-fold higher total daily steroid dose, and thus were analyzed separately. When the 24 cases that were not on ER budesonide were compared to the 81 controls, no difference was found in the STS dose nor total daily steroid dose, although the inhaled steroid dose had marginal significance. Peak eosinophil counts tended to increase when STS doses were decreased, except in subjects on ER budesonide at AI diagnosis. CONCLUSION: Altering the total daily steroid regimen can lead to resolution of AI in patients with EoE, though this may come at the expense of disease control.


Assuntos
Insuficiência Adrenal , Esofagite Eosinofílica , Humanos , Criança , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/diagnóstico , Estudos Retrospectivos , Estudos de Casos e Controles , Redução da Medicação , Budesonida/uso terapêutico , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/induzido quimicamente , Esteroides/uso terapêutico
8.
J Pediatr Gastroenterol Nutr ; 77(4): 532-535, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37438889

RESUMO

Although swallowed topical steroids are effective in inducing histological remission in eosinophilic esophagitis (EoE), their efficacy is limited by treatment nonadherence. In this study, we objectively measured adherence rates to swallowed topical steroids in adolescents with EoE over the course of 8 weeks and analyzed the association between adherence rate, disease and demographic features, symptom severity, and medication-taking habit strength. We found that approximately 20% of adolescents with EoE were over-dosing on their medications. After excluding these patients, mean adherence rate was 67.0% (±19.4%) and median adherence rate was 63% (interquartile range 53%-88%). Adherence was not associated with demographic features, disease history, symptom severity, or quality of life but was associated with habit strength (Pearson r = 0.48, P = 0.04). These findings suggest that habit strength may serve as a potential target for interventions aimed at improving adherence in adolescents with EoE.


Assuntos
Esofagite Eosinofílica , Humanos , Adolescente , Esofagite Eosinofílica/diagnóstico , Fluticasona/uso terapêutico , Qualidade de Vida , Esteroides/uso terapêutico , Administração Oral
9.
Adv Neonatal Care ; 23(1): 81-92, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35670723

RESUMO

BACKGROUND: Benefits of mother's own milk (MOM) for infants in neonatal intensive care units (NICUs) are well known. Many mothers provide for their infant's feedings during their entire hospitalization while others are unable. Knowledge is limited about which infant and maternal factors may contribute most to cessation of MOM feedings. PURPOSE: Study aims were to (1) identify which maternal and infant risk factors or combination of factors are associated with cessation of provision of MOM during hospitalization, (2) develop a lactation risk tool to identify neonatal intensive care unit infants at higher risk of not receiving MOM during hospitalization, and (3) identify when infants stop receiving MOM during hospitalization. METHODS: A data set of 797 infants admitted into a level IV neonatal intensive care unit before 7 days of age, whose mothers chose to provide MOM, was created from analysis of data from the Children's Hospital Neonatal Database. Maternal and infant factors of 701 dyads who received MOM at discharge were compared with 87 dyads who discontinued use of MOM by discharge using χ 2 , t tests, and Wilcoxon rank tests. Logistic regression was used to build a risk-scoring model. RESULTS: The probability of cessation of MOM increased significantly with the number of maternal-infant risk factors. A Risk Calculator was developed to identify dyads at higher risk for cessation of MOM by discharge. IMPLICATIONS FOR PRACTICE: Identifying mothers at risk for cessation of MOM can enable the healthcare team to provide optimal lactation management and outcomes. IMPLICATIONS FOR RESEARCH: Although the Risk Calculator has potential to identify dyads at risk of early MOM cessation, further research is needed to validate these results.


Assuntos
Unidades de Terapia Intensiva Neonatal , Mães , Recém-Nascido , Lactente , Feminino , Criança , Humanos , Leite Humano , Aleitamento Materno/métodos , Lactação , Recém-Nascido de muito Baixo Peso
10.
J Allergy Clin Immunol ; 150(3): 649-656.e5, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35405206

RESUMO

BACKGROUND: Esophageal remodeling is a factor in disease progression and symptom severity for patients with eosinophilic esophagitis (EoE). Remodeling can begin early in children, resulting in stricture and food impaction. Detection of esophageal remodeling often depends on endoscopy and is appreciated only in its later stages. OBJECTIVE: We sought to determine whether luminal eosinophil-associated and remodeling proteins captured by the esophageal string test (EST) correlate with measures of esophageal remodeling and biomarkers of the epithelial-mesenchymal transition (EMT). METHODS: Patients with EoE (7-18 years old) were enrolled from 2 pediatric hospitals. Participants performed the EST and underwent endoscopy. Histology, distensibility measured by endoluminal functional lumen imaging probe, and symptoms were assessed. Protein quantitation by ELISA was performed on mucosal biopsy and EST samples. Tissue sections were evaluated for EMT. Outcome measures were summarized, and Spearman ρ was used to assess bivariate correlations. RESULTS: Forty patients (68% male) were enrolled (mean age, 12.5 years). Twenty-four (60%) had active disease (≥15 eosinophils per high-power field). EST-captured eotaxin-3, major basic protein 1, EDN, eosinophil peroxidase, and Charcot-Leyden crystal protein/galectin-10 showed significant correlations with peak eosinophils per high-power field (ρ 0.53-0.68, P < .001). Luminal proteins positively correlated with endoscopic features and markers of EMT, and negatively with esophageal distensibility. Periostin was captured by the EST and correlated with eosinophil density, basal zone hyperplasia, endoscopic appearance, and markers of EMT. CONCLUSION: Luminal markers of esophageal remodeling in addition to biomarkers of eosinophilic inflammation correlate with epithelial and functional remodeling in EoE.


Assuntos
Esofagite Eosinofílica , Adolescente , Biomarcadores/metabolismo , Criança , Enterite , Eosinofilia , Esofagite Eosinofílica/patologia , Eosinófilos/patologia , Feminino , Gastrite , Humanos , Inflamação/patologia , Masculino
11.
Clin Gastroenterol Hepatol ; 20(4): 766-775.e4, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34062314

RESUMO

BACKGROUND & AIMS: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and peak esophageal eosinophils per high-power field (eos/hpf). METHODS: Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens. Patients were stratified based on dilation status as absent, performed 1 year or less before endoscopy, and performed more than 1 year before endoscopy. Assessments included Spearman correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. RESULTS: Among 100 patients (n = 61 males; median age, 37 y), 15 and 40 patients underwent dilation 1 year or less and more than 1 year before index endoscopy, respectively. In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ = 0.49; P < .001); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002). In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ = -0.38; P = .157 for ≤1 y and ρ = 0.02; P = .883 >1 y); for a 10-eos/hpf increase, the predicted EEsAI changed by -1.64 (P = .183) and 0.78 (P = .494), respectively. Dilation modified the association between symptoms and eos/hpf (P = .005 and P = .187 for interaction terms of eos/hpf and dilation 1 or less years before and more than 1 year before index endoscopy, respectively). CONCLUSIONS: In nondilated EoE adults, eos/hpf correlate modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than 1 year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up evaluation.


Assuntos
Esofagite Eosinofílica , Adulto , Dilatação , Endoscopia Gastrointestinal , Esofagite Eosinofílica/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos
12.
J Pediatr Gastroenterol Nutr ; 75(5): 666-674, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35897136

RESUMO

OBJECTIVES: While dietary changes are recommended to treat pediatric non-alcoholic fatty liver disease (NAFLD), the role of specific nutrients in disease progression is unclear. The objective of this study is to (1) assess the macronutrient and micronutrient intake in adolescents with liver biopsy proven NAFLD [with and without non-alcoholic steatohepatitis (NASH)] and lean controls; (2) determine nutritional predictors of disease severity amongst these groups. METHODS: Adolescents with biopsy-proven NAFLD and lean controls completed the Harvard Food Frequency Questionnaire. RESULTS: Twenty-eight NAFLD and 15 lean controls were studied. NAFLD with (n = 20) and without NASH (n = 8) had similar total calorie, protein, fat, and carbohydrate intake. Subjects with NASH had higher total sugar (122.3 ± 48.3 vs 83.1 ± 38.8 g), glucose (24.3 ± 9.3 vs 15.2 ± 7.5 g), sucrose (42.3 ± 16.9 vs 28.8 ± 11.7 g), and fructose (29.4 ± 12.5 vs 18.1 ± 8.0 g) intake than those with NAFLD but without NASH ( P < 0.05). Both NAFLD groups had similar micronutrient intake. Alanine aminotransferase (ALT) correlated with total caloric intake ( ρ = 0.4; P = 0.04). Total carbohydrate calories correlated with a higher NAS summary score ( ρ = 0.38; P = 0.04) and lobular inflammation ( ρ = 0.50; P = 0.007). Percent calories from added sugar and glucose correlated with worsening NAS summary score ( ρ = 0.44, P = 0.02; ρ = 0.48, P = 0.009) and lobular inflammation ( ρ = 0.51, P = 0.006; ρ = 0.53, P = 0.004). Percent calories from fructose correlated with lobular inflammation ( ρ = 0.56; P = 0.002). Total daily calories, protein, fat, carbohydrate, and micronutrient intake were similar between NAFLD and lean controls. CONCLUSIONS: NASH patients consume similar total calories, protein, and fat as those without NASH, but have significantly higher sugar intake. NAFLD and lean children, however, have similar macro/micronutrient intake. Histologic disease severity correlates with total carbohydrate and added sugar intake, supporting a role for simple sugar intake in NAFLD progression.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Adolescente , Criança , Hepatopatia Gordurosa não Alcoólica/patologia , Frutose , Índice de Gravidade de Doença , Carboidratos da Dieta , Ingestão de Alimentos , Nutrientes , Inflamação/complicações , Glucose , Fígado/patologia
13.
J Pediatr Gastroenterol Nutr ; 75(6): 737-742, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122373

RESUMO

OBJECTIVES: Celiac disease (CeD) autoimmunity and coexisting inflammatory bowel disease (IBD) present a diagnostic dilemma. Our aims were to describe the phenotype of children with IBD and CeD seropositivity and evaluate provider confidence for diagnosing CeD in this population. METHODS: We performed a single-center retrospective cohort study of subjects ≤18 years old with IBD and CeD seropositivity between 2006 and 2020. Subjects were considered to have IBD-CeD if they met CeD diagnosis by serology and histology per North American Society For Pediatric Gastroenterology, Hepatology and Nutrition guidelines and if providers suspected CeD as evaluated by a survey. The IBD-only cohort included seropositive participants that did not meet criteria for CeD. Demographic, histologic, gross endoscopic, and laboratory features were compared using Fisher exact test. RESULTS: Of 475 children with IBD, 8 had concomitant CeD, 5 had tissue transglutaminase (tTG) immunoglobulin A (IgA) > 10x upper limit of normal (ULN, P = 0.006), and 8 had villous atrophy (VA, P = 0.003) when compared with 17 seropositive participants with IBD-only. No children with IBD-CeD had esophageal eosinophilia, duodenal cryptitis, duodenal ulceration, or fecal calprotectin >250 µg/g. Factors that contributed to provider uncertainty for diagnosing CeD in IBD included the absence of VA and intraepithelial lymphocytes, the presence of neutrophilic and eosinophilic duodenitis, diffuse ulceration, elevated inflammatory markers, and immunosuppression therapy. CONCLUSIONS: Diagnosing CeD in children with IBD continues to be challenging. Although high titers of tTG IgA and VA increased provider confidence for diagnosing CeD in IBD, development of evidence-based guidelines are needed. They should better assess the importance of features atypical of concomitant CeD that contribute to uncertainty.


Assuntos
Doença Celíaca , Doenças Inflamatórias Intestinais , Humanos , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Estudos Retrospectivos , Duodeno/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Autoanticorpos , Imunoglobulina A , Transglutaminases
14.
J Pediatr Gastroenterol Nutr ; 75(2): 181-185, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35641896

RESUMO

Mental health is a growing concern in pediatric celiac disease (CD). This study utilized the Revised Children's Anxiety and Depression Scale (RCADS) to investigate anxiety and depression symptom rates. Participants were children ages 8 to 17 years (M = 11.7, SD = 2.7; N = 175) with biopsy-proven CD (Median = 1.1 years post-diagnosis, IQR = 0-4) categorized into groups based on the child's age, caregiver or child respondent, presence or absence of comorbidities, and gluten-free diet duration. Self-reported RCADS scores showed 39% of children having clinically significant concerns for anxiety or depression ( P < 0.0001) but only 7% of caregiver-proxy RCADS scores indicated significant concerns for the child's anxiety and 14% for the child's depression. Rates of child-reported anxiety and depression symptoms were significantly higher for those without medical comorbidities than those with ( P = 0.04). Therefore, screening for mental health concerns, particularly anxiety and depression, should be routinely performed in pediatric patients with CD.


Assuntos
Doença Celíaca , Depressão , Adolescente , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Doença Celíaca/complicações , Doença Celíaca/psicologia , Criança , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Humanos , Escalas de Graduação Psiquiátrica
15.
Int J Obes (Lond) ; 45(9): 2074-2082, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34127805

RESUMO

BACKGROUND/OBJECTIVES: Individuals successful at weight loss maintenance engage in high amounts of physical activity (PA). Understanding how and when weight loss maintainers accumulate PA within a day and across the week may inform PA promotion strategies and recommendations for weight management. METHODS: We compared patterns of PA in a cohort of weight loss maintainers (WLM, n = 28, maintaining ≥13.6 kg weight loss for ≥1 year, BMI 23.6 ± 2.3 kg/m2), controls without obesity (NC, n = 30, BMI similar to current BMI of WLM, BMI 22.8 ± 1.9 kg/m2), and controls with overweight/obesity (OC, n = 26, BMI similar to pre-weight loss BMI of WLM, 33.6 ± 5.1 kg/m2). PA was assessed during 7 consecutive days using the activPALTM activity monitor. The following variables were quantified; sleep duration, sedentary time (SED), light-intensity PA (LPA), moderate-to-vigorous intensity PA (MVPA), and steps. Data were examined to determine differences in patterns of PA across the week and across the day using mixed effect models. RESULTS: Across the week, WLM engaged in ≥60 min of MVPA on 73% of days, significantly more than OC (36%, p < 0.001) and similar to NC (59%, p = 0.10). Across the day, WLM accumulated more MVPA in the morning (i.e., within 3 h of waking) compared to both NC and OC (p < 0.01). WLM engaged in significantly more MVPA accumulated in bouts ≥10 min compared to NC and OC (p < 0.05). Specifically, WLM engaged in more MVPA accumulated in bouts of ≥60 min compared to NC and OC (p < 0.05). CONCLUSIONS: WLM engage in high amounts of MVPA (≥60 min/d) on more days of the week, accumulate more MVPA in sustained bouts, and accumulate more MVPA in the morning compared to controls. Future research should investigate if these distinct patterns of PA help to promote weight loss maintenance.


Assuntos
Exercício Físico/psicologia , Fatores de Tempo , Programas de Redução de Peso/normas , Adulto , Análise de Variância , Índice de Massa Corporal , Colorado/epidemiologia , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/terapia , Programas de Redução de Peso/métodos , Programas de Redução de Peso/estatística & dados numéricos
16.
Liver Transpl ; 27(6): 808-817, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33621376

RESUMO

Little is known about the impact of sarcopenia (reduced muscle mass and function) in pediatric chronic liver disease. We compared psoas muscle surface area (PMSA), measured at the 4th lumbar vertebrae, in children listed for liver transplantation (LT) to that of healthy controls and studied the impact of sarcopenia on transplant-associated outcomes. The effect of PMSA (raw value and z score) on survival was studied using multivariable proportional hazards, whereas the impact of PMSA on other transplant-associated outcomes was assessed by multivariable linear or logistic regression. The correlation of PMSA with anthropometric values and markers of disease severity was studied using Spearman's rank-order correlation. Mean PMSA was significantly lower in LT candidates (n = 57, 699.4 ± 591.9 mm2 [mean ± SD]) than controls (n = 53, 1052.9 ± 960.7 mm2 ; P = 0.02). For LT candidates, there was an increased risk of death (either while on the waiting list or following transplantation) with lower PMSA (hazard ratio [HR], 1.6 per 100 mm2 [P = 0.03]; 95% confidence interval [CI], 1.1-2.8), amounting to a 4.9 times higher risk of death for every 1 unit decrease in PMSA z score (HR, 4.9 [P = 0.05], 95% CI, 1.2-34.5), adjusting for age and sex. PMSA did not correlate with posttransplant length of intubation, hospital length of stay, or perioperative complications. PMSA also did not correlate with calculated (r = 0.10, P = 0.60) or appealed Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (r = 0.10, P = 0.69). Pediatric LT candidates have a significant reduction in muscle compared with controls. LT candidates with lower PMSA experience significant increases in mortality. As such, sarcopenia may provide a novel indicator of disease severity in children with chronic liver disease.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Sarcopenia , Criança , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Sarcopenia/complicações , Sarcopenia/diagnóstico , Índice de Gravidade de Doença , Listas de Espera
17.
J Pediatr ; 235: 246-252.e1, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33811869

RESUMO

OBJECTIVE: To measure adherence rates to swallowed topical steroids in children with eosinophilic esophagitis (EoE), describe factors related to adherence, and determine the association between adherence, symptoms, perceived disease severity, and quality of life in children with EoE. STUDY DESIGN: Subjects in this cross-sectional study of 117 children between 5 and 18 years old with EoE completed the Pediatric Eosinophilic Esophagitis Symptoms Score V2.0 (PEESS), Pediatric Quality of Life Inventory Eosinophilic Esophagitis Module (PedsQL EoE), a Medication-Taking Checklist (MTC), and a demographics questionnaire. Adherence rate was calculated based on reported number of missed doses/prescribed doses in the last week. Parent-reported measures were used for children aged 5-12 years and self-report was used for children aged 13-18 years. RESULTS: Adolescents had lower adherence rates than younger children (76.2 ± 24.5% vs 88.6 ± 16.7%, P = .002). Adherence rates were not associated with disease history, PEESS, or PedsQL EoE scores but instead correlated with MTC scores (Pearson r of 0.65, P < .001 for child-report and Pearson r of 0.74, P < .001 for parent-report). Symptomatology was associated with worse quality of life (PEESS Frequency: r = -0.7, P < .001; PEESS Severity: r = -0.71, P < .001 for children 5-12 years old; PEESS Frequency: r = -0.61, P < .001; PEESS Severity: r = -.5, P < .001 for adolescents). CONCLUSIONS: Unrelated to their clinical history, demographic factors, symptoms, and quality of life, adolescents with EoE have lower medication adherence rates. The MTC may serve as a clinical tool to discuss adherence and provide targeted educational counseling regarding adherence interventions.


Assuntos
Esofagite Eosinofílica/psicologia , Adesão à Medicação/estatística & dados numéricos , Qualidade de Vida , Índice de Gravidade de Doença , Administração Oral , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Esofagite Eosinofílica/tratamento farmacológico , Humanos , Esteroides/administração & dosagem , Inquéritos e Questionários
18.
J Nutr ; 151(12): 3628-3636, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34510212

RESUMO

BACKGROUND: Angelman syndrome (AS) patients often respond to low glycemic index therapy to manage refractory seizures. These diets significantly affect quality of life and are challenging to implement. These formulations may have benefits in AS even in the absence of biomarkers suggesting ketosis. OBJECTIVES: We aimed to compare an exogenous medical food ketone formulation (KF) with placebo for the dietary management of AS. METHODS: This randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in an academic center from 15 November, 2018 to 6 January, 2020. Thirteen participants with molecularly confirmed AS aged 4-11 y met the criteria and completed the 16-wk study. The study consisted of four 4-wk phases: a baseline phase, a blinded KF or placebo phase, a washout phase, and the crossover phase with alternate blinded KF or placebo. Primary outcomes were safety and tolerability rated by retention in the study and adherence to the formulation. Additional secondary outcomes of safety in this nonverbal population included blood chemistry, gastrointestinal health, seizure burden, cortical irritability, cognition, mobility, sleep, and developmental staging. RESULTS: Data were compared between the baseline, KF, and placebo epochs. One participant exited the trial owing to difficulty consuming the formulation. Adverse events included an increase in cholesterol in 1 subject when consuming KF and a decrease in albumin in 1 subject when consuming placebo. Stool consistency improved with KF consumption, from 6.04 ± 1.61 at baseline and 6.35 ± 1.55 during placebo to 4.54 ± 1.19 during KF (P = 0.0027). Electroencephalograph trends showed a decrease in Δ frequency power during the KF arm and event-related potentials suggested a change in the frontal memory response. Vineland-3 showed improved fine motor skills in the KF arm. CONCLUSIONS: The exogenous KF appears safe. More data are needed to determine the utility of exogenous ketones as a nutritional approach in children with AS.This trial was registered at clinicaltrials.gov as NCT03644693.


Assuntos
Síndrome de Angelman , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Cetonas , Qualidade de Vida , Convulsões , Resultado do Tratamento
19.
Echocardiography ; 38(4): 641-645, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33682205

RESUMO

BACKGROUND: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. METHODS: Six hundred and ninety-eight healthy children (ages 0-18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor-independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA)-based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). RESULTS: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV was 0.99, 0.99, and 0.99, respectively. The ICC for interobserver variability for EDV, ESV, and SV was 0.98, 0.94, and 0.98, respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). CONCLUSIONS: We report pediatric z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.


Assuntos
Ecocardiografia Tridimensional , Pediatria , Adolescente , Criança , Pré-Escolar , Ventrículos do Coração/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Reprodutibilidade dos Testes , Volume Sistólico , Função Ventricular Esquerda
20.
Dis Esophagus ; 34(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33993222

RESUMO

Esophageal food impactions (EFI) are associated with esophageal pathology, most commonly eosinophilic esophagitis (EoE). Obtaining biopsies provides opportunity for diagnosis, which is important since treatment of EoE decreases the risk for future EFI. Outpatient follow-up rates remain suboptimal and outcomes of patients without timely follow-up are unknown. We aimed to identify the factors associated with pediatric subspecialty follow-up post-EFI and to determine the symptom burden in patients without follow-up. We performed a retrospective review of patients presenting with EFI at a tertiary children's hospital between 2010 and 2018. Patients without subspecialty follow-up within 1 year of EFI were included in a prospective telephone survey investigating the barriers to care, outcomes, and symptoms. Clinical characteristics were compared between groups. Multivariate analysis was used to control for multiple variables. There were 127 EFI identified in 123 individuals (73% male, mean age: 12.2 years). Esophageal biopsies were collected in 76% of cases, and 49% of patients had follow-up. Individuals with follow-up were more likely (P ≤ 0.05) to have had biopsies. In a multivariate analysis, written recommendation for follow-up (Odds Ratio: 6.9 [2.4-19.5], P = 0.001) as well as atopic history and identified stricture were associated with a higher likelihood of follow-up. Those without follow-up had subsequent stricture (35%), dilation (44%), or EFI (39%), and 55% (12/22) described ongoing esophageal symptoms. Identification of treatable findings at time of EFI and ongoing symptom burden after EFI support an imperative for follow-up after EFI. Clear recommendations are a modifiable factor that may improve follow-up in this population.


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Estenose Esofágica , Criança , Transtornos de Deglutição/etiologia , Esofagite Eosinofílica/complicações , Estenose Esofágica/etiologia , Feminino , Seguimentos , Alimentos , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos
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