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Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.
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Adenocarcinoma , Pólipos Adenomatosos , Neoplasias Gástricas , Adenocarcinoma/patologia , Pólipos Adenomatosos/diagnóstico , Criança , Gastrectomia , Humanos , Masculino , Neoplasias Gástricas/patologiaRESUMO
Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.
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Doença Celíaca , Poluentes Ambientais , Bifenilos Policlorados , Doença Celíaca/induzido quimicamente , Doença Celíaca/epidemiologia , Doença Celíaca/genética , Criança , Diclorodifenil Dicloroetileno , Poluentes Ambientais/toxicidade , Feminino , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/toxicidade , Humanos , Masculino , Projetos PilotoRESUMO
BACKGROUND: The Accreditation Council for Graduate Medical Education has described 6 core competencies with which trainees should demonstrate proficiency. Using the Objective Structured Clinical Examination (OSCE), we aimed to assess 4 of these competencies among Pediatric Gastrointestinal (GI) fellows (PGs). METHODS: Eight first-year PGs from 6 medical centers in the New York area participated in a 4-station OSCE with trained standardized patient (SP) actors. The cases included an emergency department (ED) consult, or "ED Consult" for lower gastrointestinal bleeding; "Breaking Bad News" focusing on CF nutritional complications; "Second Opinion" for abdominal pain; "Transition of Care" for inflammatory bowel disease. At each station, attending faculty observed the encounters behind a 1-way mirror. SPs and faculties provided immediate feedback to the examined fellows. Previously validated OSCE checklists were used to assess performance. On completion, fellows attended debriefing sessions and completed surveys about the educational value. RESULTS: Median overall milestone competency scores were 6.9 (PC1), 4.8 (PC2), 5.9 (MK1), 5.7 (MK2), 6.4 (ICS1), 6.9 (Prof1), and 6.7 (Prof3). Overall, fellows score highest (7/9) on the inflammatory bowel disease "Transition of Care" case, found the "Breaking Bad News" Cystic Fibrosis OSCE to be the most challenging, and were most comfortable with the "ED Consult" OSCE, as a commonly encountered scenario. Overall, the fellows rated the educational value of the program highly. CONCLUSIONS: To our knowledge, although the OSCE has been validated in other medical fields, this is the first OSCE program developed for PGs fellows. These OSCEs have included Accreditation Council for Graduate Medical Education competencies, serving to assess fellows' skills in these areas while exposing them to challenging medical and psychosocial cases that they may not frequently encounter.
Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Gastroenterologia/educação , Pediatria/educação , Atitude do Pessoal de Saúde , Lista de Checagem , Competência Clínica/estatística & dados numéricos , Docentes de Medicina , Estudos de Viabilidade , Feedback Formativo , Humanos , New York , Simulação de Paciente , Projetos PilotoRESUMO
Celiac disease (CeD) and eosinophilic esophagitis (EoE) are immune-mediated disorders that can occur in the same patient. A retrospective study at a tertiary care hospital was conducted to determine the prevalence of EoE in a pediatric population with CeD and to compare characteristics of patients with both diseases to patients with CeD-only. Among the 148 patients with CeD identified in the study, 11 patients had both CeD and EoE (7.4%). Patients with both CeD and EoE had a higher absolute eosinophil count (per µL) at diagnosis compared to patients with CeD-only (454.1 ± 122.7 vs 231.9 ± 19.4, P = .003). In conclusion, there was a higher proportion of EoE in patients with CeD than would be expected in the general population, suggesting a potential pathophysiological overlap between the 2 diseases. An elevated peripheral absolute eosinophil count may help predict which patients with CeD may additionally have EoE.
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Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.
Assuntos
Diabetes Insípido/genética , Doenças do Sistema Endócrino/genética , Obesidade Mórbida/genética , Obesidade/genética , Pró-Proteína Convertase 1/deficiência , Pró-Proteína Convertases/genética , Alelos , Pré-Escolar , Diabetes Insípido/complicações , Diabetes Insípido/patologia , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/patologia , Heterozigoto , Humanos , Lactente , Mutação , Obesidade/complicações , Obesidade/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Osmorregulação/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 1/genéticaRESUMO
BACKGROUND: Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD. METHODS: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort. Children (aged 0-18 years) with IBD who had commenced vedolizumab were followed up at baseline and at 2, 6, and 14 weeks. Children were managed according to local prescribing practices without standardisation of dosing or criteria for escalation, but the study protocol suggested dosing of 177 mg/m2 body surface area (up to 300 mg maximum). The primary outcome was steroid-free and exclusive enteral nutrition-free remission at 14 weeks, analysed according to the intention-to-treat principle. Serum samples were taken for analysis of drug concentration and faecal calprotectin at baseline, and at 2, 6, and 14 weeks. Adverse events were recorded in real time and classified as severe or non-severe and related or unrelated to vedolizumab. This study is registered with ClinicalTrials.gov, NCT02862132. FINDINGS: Between May 19, 2016, and April 1, 2022, 142 children (76 [54%] girls and 66 [46%] boys; mean age 13·6 years [SD 3·6]) were enrolled. 65 (46%) children had Crohn's disease, 68 (48%) had ulcerative colitis, and nine (6%) had unclassified IBD (those with unclassified IBD were analysed with the ulcerative colitis group). 32 (42% [95% CI 30-54]) of 77 children with ulcerative colitis and 21 (32% [23-45]) of 65 children with Crohn's disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks. Median drug concentrations at week 14 were higher in children with ulcerative colitis than in those with Crohn's disease (11·5 µg/mL [IQR 5·5-18·1] vs 5·9 µg/mL [3·0-12·7]; p=0·006). In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 µg/mL at week 14 (area under the curve 0·69 [95% CI 0·41-0·98]), corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg. 32 (23%) of 142 children reported at least one adverse event, the most common were headache (five [4%]), myalgia (four [3%]), and fever (three [2%]). None of the adverse events were classified as severe, and only two (1%) patients discontinued treatment due to adverse events. INTERPRETATION: Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis. Vedolizumab should be considered in children when other approved drug interventions for IBD are unsuccessful. In children who weigh less than 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/m2) or weight (10 mg/kg). FUNDING: The European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Feminino , Humanos , Criança , Adolescente , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Estudos Prospectivos , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
BACKGROUND: Current treatments of eosinophilic esophagitis (EoE), including restrictive diets or glucocorticoids, provide only transient improvement. Proton pump inhibitor (PPI) use in EoE does not lead to histologic improvement; however, the long-term use of PPI on symptoms and prevention of complications has not been evaluated. OBJECTIVE: To evaluate the use of PPI as maintenance therapy in children with EoE. METHODS: Eosinophilic esophagitis was diagnosed based on initial endoscopic biopsies and persistent eosinophilic inflammation despite PPI therapy. Inclusion criteria included diagnosis of EoE and PPI use as primary maintenance treatment. Patients were excluded if they were treated with dietary or glucocorticoid therapy. Histologic evidence of inflammation as well as degree of subepithelial fibrosis at presentation was compared with most recent biopsies while receiving PPI therapy. RESULTS: Thirty-eight patients (30 males and 8 females; average age 6.7 ± 5.4 years) fulfilled inclusion criteria. Duration of follow-up was 3.0 ± 2.4 years. At presentation, vomiting was significantly more frequent in the younger patients, whereas dysphagia occurred more frequently in the older patients. At follow-up, 26 patients were asymptomatic, and the remaining 12 patients' symptoms were significantly improved. No complications of stricture or food impaction were seen. Significant eosinophilic inflammation persisted in 28 patients. No difference in degree of subepithelial fibrosis at diagnosis compared with most recent biopsies. The z-scores of the treated EoE patients significantly improved. CONCLUSION: Patients with EoE treated with PPIs show an improvement in symptoms and z-scores despite persistent eosinophilic inflammation. PPI treatment may be useful maintenance therapy in children with EoE.
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2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Esofagite Eosinofílica/tratamento farmacológico , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Criança , Pré-Escolar , Transtornos de Deglutição/tratamento farmacológico , Endoscopia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Lansoprazol , Masculino , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Resultado do Tratamento , Vômito/tratamento farmacológicoRESUMO
BACKGROUND AND AIMS: Increasing use of diagnostic radiography has led to concern about the malignant potential of ionizing radiation. We aimed to quantify the cumulative effective dose (CED) from diagnostic medical imaging in children with inflammatory bowel disease (IBD) and to identify which children are at greatest risk for high amounts of image-related radiation exposure. PATIENTS AND METHODS: A retrospective chart review of pediatric IBD patients seen between January 1 and May 30, 2008 was conducted. The effective dose of radiation received from all of the radiology tests performed during the course of each patient's treatment was estimated using typical effective doses and our institution's computed tomography dose index. A CED ≥50 mSv was considered high. RESULTS: Complete records were available for 257 of 372 screened subjects. One hundred seventy-one had Crohn disease (CD) and 86 had ulcerative colitis (UC). The mean CED was 17.56 ± 15.91 mSv and was greater for children with CD than for those with UC (20.5 ± 17.5 vs 11.7 ± 9.9 mSv, P < 0.0001). Fifteen children (5.8%) had a CED ≥50 mSv, including 14 of 171 (8.2%) with CD and 1 of 86 (1.2%) with UC (P = 0.02). In children with CD, factors associated with high CED per multivariate analysis were any IBD-related surgery (odds ratio 42, 95% confidence interval 8-223, P < 0.0001) and platelet count (odds ratio 16, 95% confidence interval 1.5-175, P = 0.02). CONCLUSIONS: Although all doses of ionizing radiation have some malignancy-inducing potential, a small but important percentage of children with IBD are exposed to particularly high doses of ionizing radiation from diagnostic tests and procedures. Physicians caring for such patients must seek to limit radiation exposure whenever possible to lessen the lifetime risk of malignancy.
Assuntos
Colite Ulcerativa/diagnóstico por imagem , Doença de Crohn/diagnóstico por imagem , Neoplasias Induzidas por Radiação/etiologia , Doses de Radiação , Tomografia Computadorizada por Raios X/efeitos adversos , Adolescente , Criança , Colite Ulcerativa/cirurgia , Doença de Crohn/cirurgia , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Análise Multivariada , Razão de Chances , Contagem de Plaquetas , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Altered gastrointestinal permeability in celiac disease (CD) is mediated by zonulin. The receptor for zonulin is expressed on podocytes. Therefore, we tested the effect of a gluten-free diet (GFD) on albuminuria in pediatric patients with newly diagnosed CD. METHODS: We performed a cohort study comparing urinary albumin (µg):creatinine (mg) ratio (ACR) in CD patients vs controls and in response to a GFD. RESULTS: Children with CD (n=46) had higher ACR compared to controls (n=21), 20.2±5.6 versus 8.4±1.1 µg/mg, P=0.16 and exceeded 30 µg/mg (microalbuminuria cut-off) in 7/46 cases. 17 patients had a follow-up assessment (interval 6.1±0.7 months) on a GFD. Baseline ACR was 20.7±5.2 that fell to 10.4±1.5 µg/mg, P=0.035. CONCLUSION: Children and adolescents with newly diagnosed CD have low-grade albuminuria that is numerically higher than controls and that declined after implementation of a GFD. CD may be associated with reversible defects in the glomerular barrier.
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BACKGROUND: Suicide risk screening is recommended in pediatric care. To date, no previous studies illustrate the implementation of suicide risk screening in pediatric subspecialty care, even though chronic medical conditions are associated with a higher risk of suicide. METHODS: A large multidivision pediatric ambulatory clinic implemented annual suicide risk screening. Patients ages 9-21 years participated in suicide risk screening using the Ask Suicide-Screening Questions during the project. A multidisciplinary team employed quality improvement methods and survey-research design methods to evaluate the feasibility and acceptability of the screening process for patients, families, and medical providers. RESULTS: During the quality improvement project period, 1,934 patients were offered screening; 1,301 (67.3%) patients completed screening; 82 patients (6.3% of 1,301 patients) screened positive. The monthly compliance rate held steady at 86% following several Plan-Do-Study-Act cycles of improvement. The survey results demonstrate that providers rated the suicide risk screening process positively; however, a subset of providers indicated that the screening process was out of their scope of practice or impeded their workflow. CONCLUSIONS: Suicide risk screening is feasible in pediatric specialty care and can identify at-risk patients. Continued efforts are needed to standardize suicide risk screening practices. Future directions include identifying factors associated with suicide risk in patients in pediatric subspecialty care settings.
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BACKGROUND: Poor weight gain and growth can be caused by many medical, nutritional, behavioral, and psychological factors. Crohn disease is one of the more common gastrointestinal etiologies associated with growth failure. The aim of this study is to determine the role of capsule endoscopy (CE) in the evaluation of older children and adolescents who were referred to a pediatric gastroenterology service for a chief complaint of unexplained growth failure. PATIENTS AND METHODS: We retrospectively reviewed the records of children with growth failure undergoing CE between August 2002 and November 2005. Height and weight (expressed as z scores) were recorded at least 6 months before study, at the time of the study, and at least 6 months post study. All of the patients had celiac disease and Crohn disease excluded using standard biochemical, radiologic, endoscopic, and histologic assessment. RESULTS: Seven children (4 males and 3 females) were included in the study-mean age 11.7+/-3.6 years. Indications for CE were growth failure associated with abdominal pain (3 patients), diarrhea and apthous ulcers (2 patients), delayed puberty (1 patient), or a family history of Crohn disease (1 patient). The mean z score for weight at the time of the study was 2.10+/-1.0 and for height was 1.50+/-0.7 All 7 children had normal small bowel series performed before the CE. All had both endoscopically and histologically normal esophagogastroduodenoscopy and colonoscopy. In 4 of 7 patients, multiple small bowel apthous ulcerations consistent with Crohn disease were identified by CE. All 4 patients who had abnormal CE were treated and started gaining weight. The mean z score for weight after 6 months of treatment was 1.35+/-1.2 and for height was 0.50+/-1.7. The mean z score for weight after treatment was significantly improved compared with the mean z score at diagnosis (P<0.05). CONCLUSIONS: In our study, 4 of the 7 older children and adolescents with unexplained growth failure and normal small bowel series were found to have Crohn disease involving the small intestine. In addition, we were able to show the improvement on the mean z score for weight after treatment of small bowel Crohn disease was instituted.
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Endoscopia por Cápsula/métodos , Doença de Crohn/diagnóstico , Transtornos do Crescimento/etiologia , Intestino Delgado/patologia , Adolescente , Criança , Doença de Crohn/complicações , Doença de Crohn/patologia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: Tumor necrosis factor (TNF)-alpha plays a role in the inflammatory process in Crohn disease, a disease with an apparent polygenic basis. We investigated whether polymorphisms in multiple genes involved in the lipopolysaccharide-TNF inflammatory pathway are independently associated with Crohn disease in the Jewish Ashkenazi population. Polymorphisms in CD14, Toll-like receptor 4 (TLR4), and TNF-alpha were studied. In addition, we investigated polymorphisms in the TNF-alpha converting enzyme (TACE) gene, which to date has not been studied for an association with Crohn disease. PATIENTS AND METHODS: To examine whether TLR4 Asp299Gly, CD14-260C/T, TNF-1031T/C, TNF-863C/A, TNF-857C/T, TACE-172C/T, and TACE-154C/A polymorphisms are associated with Crohn disease in the Ashkenazi Jewish population, we analyzed families with at least 1 child with Crohn disease for association with these mutations using a family-based association test (transmission disequilibrium test) for analysis. RESULTS: The allelic frequency in the patient population of TLR4 G allele was 8.0%, CD14 T allele was 51.3%, TNF-1031C was 18.8%, TNF-863A was 14.2%, TNF-857T was 25.2%, TACE172T was 20.7%, and TACE154A was 24.5%. The transmission disequilibrium test transmitted:untransmitted (T:U) result for TLR4G was T:U = 32:20, for CD14T was T:U = 103:88, for TNF-1031C was T:U = 48:56, for TNF-863A was T:U = 39:42, for TNF-857T was T:U = 63:62, for TACE-172C/T was T:U = 48:59, and for TACE-154C/A was T:U = 52:55. No statistically significant associations were observed. CONCLUSIONS: The transmission disequilibrium test did not demonstrate preferential transmission of these variants in Jewish Ashkenazi patients with Crohn disease. These results suggest that these polymorphisms in the TNF/lipopolysaccharide pathway play little or no role in susceptibility to Crohn disease in the Jewish Ashkenazi population.
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Doença de Crohn/genética , Judeus/genética , Desequilíbrio de Ligação/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adolescente , Idade de Início , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Receptores de Lipopolissacarídeos/genética , Lipopolissacarídeos , Masculino , Receptor 4 Toll-Like/genéticaRESUMO
AIM: Children with severe uncontrolled asthma (SUA) have a high burden of symptoms and increased frequency of asthma exacerbations. Reflux esophagitis and eosinophilic esophagitis are important co-morbid factors for SUA. Both are associated with the presence of eosinophils in esophageal mucosa. We hypothesized that esophageal eosinophils are frequently present and correlate with the presence of airway eosinophils in children with SUA. METHOD: We performed a retrospective analysis of a prospective database of children who underwent "triple endoscopy" (sleep laryngoscopy, bronchoscopy with bronchoalveolar lavage [BAL] and endobronchial biopsy [EBB], and esophagogastroduodenoscopy with esophageal biopsy [EsB]) at our Aerodigestive Center for evaluation of SUA. Children with known cystic fibrosis, primary ciliary dyskinesia, and aspiration-related lung disease were excluded. RESULT: Twenty-four children (21 males) ages 2-16 years were studied. Elevated BAL eosinophils were found in 10 (42%) patients, endobronchial eosinophils in 16 (67%); 7 (29%) had endobronchial eosinophils without elevated BAL eosinophils. Esophageal eosinophils were found in 11 (46%) patients. There was a correlation between the amount of eosinophils in BAL and EBB (R = 0.43, P = 0.05) airway eosinophils, defined as elevated BAL and/or EBB eosinophils, correlated with esophageal eosinophils (R = 0.41, P = 0.047). CONCLUSION: We concluded that airway and esophageal eosinophils are frequently present in children with SUA.
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Asma/complicações , Asma/metabolismo , Esofagite Eosinofílica/complicações , Eosinófilos/metabolismo , Mucosa Esofágica/metabolismo , Esofagite Péptica/complicações , Adolescente , Asma/diagnóstico , Biópsia , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar , Broncoscopia , Criança , Pré-Escolar , Endoscopia do Sistema Digestório , Feminino , Humanos , Laringoscopia , Masculino , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
In pediatric patients with chronic cough, respiratory culture techniques commonly yield negative results. Studies using culture-independent methods have found a high relative abundance of oral microbes in the lower airways, suggesting that the topographical continuity, and dynamics of the intraluminal contents of the aerodigestive system likely influence the lower airway microbiota. We hypothesize that in subjects with chronic cough, clinical diagnosis will correlate with distinct microbial signatures detected using culture-independent methods. STUDY DESIGN AND METHODS: We enrolled 36 pediatric subjects with chronic cough in a cross-sectional study. Subjects were categorized into four clinical groups: asthma, bacterial bronchitis, neurologically impaired-orally fed, and neurologically impaired enterally fed. Samples from the aerodigestive tract were obtained through bronchoscopy and upper endoscopy. 16S rRNA gene sequencing compared the microbiota from bronchoalveolar lavage (BAL), tracheal, supraglottic, esophageal, gastric, and duodenal samples. RESULTS: We observed that the lower airway microbiota of asthma subjects had higher α diversity as compared with the other groups. ß diversity analysis of BAL samples revealed significant differences between the groups. Among the taxonomic differences found, most differentially enriched taxa were upper airway organisms such as Rothia, Gemellaceae (u.g. or uncharacterized genus), and Granulicatella in asthma, Prevotella in bacterial bronchitis, and Veillonella in neurologically impaired orally fed subjects. Greater dissimilarity between the upper airway and lower airway microbiota was associated with increased neutrophilic airway inflammation. CONCLUSIONS: Distinct dysbiotic signatures can be identified in the lower airway microbiota of pediatric subjects with chronic cough that relates to the degree and type of inflammation.
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Líquido da Lavagem Broncoalveolar/microbiologia , Tosse/complicações , Tosse/diagnóstico , Disbiose/complicações , Disbiose/diagnóstico , Asma/complicações , Asma/microbiologia , Infecções Bacterianas/microbiologia , Bronquite/complicações , Bronquite/microbiologia , Lavagem Broncoalveolar , Broncoscopia , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Nutrição Enteral/efeitos adversos , Feminino , Humanos , Inflamação , Masculino , Microbiota , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/microbiologia , Estudos Prospectivos , RNA Ribossômico 16S/genética , Sistema Respiratório/microbiologiaRESUMO
BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
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Consenso , Disautonomia Familiar/epidemiologia , Transtornos Respiratórios/epidemiologia , Transtornos Respiratórios/terapia , Lavagem Broncoalveolar/métodos , Broncoscopia/métodos , Síndrome de Brugada/epidemiologia , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/fisiopatologia , Disautonomia Familiar/complicações , Disautonomia Familiar/mortalidade , Disautonomia Familiar/fisiopatologia , Prática Clínica Baseada em Evidências/métodos , Humanos , New York/epidemiologia , Pneumonia Aspirativa/diagnóstico por imagem , Pneumonia Aspirativa/fisiopatologia , Polissonografia/métodos , Estudos Prospectivos , Transtornos Respiratórios/diagnóstico por imagem , Transtornos Respiratórios/patologia , Testes de Função Respiratória/métodosRESUMO
BACKGROUND: The development of wireless capsule endoscopy (CE) provides a unique opportunity to visualize the entire small bowel in a minimally invasive manner. Studies in adult patients have demonstrated that the disposable capsule is well tolerated and highly effective, but few studies have been done in children. The aims of our study were to compare the diagnostic yield of CE and small bowel series in children being evaluated for possible small intestine disease and to determine the risk of developing an adverse event following capsule endoscopy. PATIENTS AND METHODS: We retrospectively reviewed the records of all children who underwent CE at 1 institution between August 2002 and July 2005. Results of CE were compared with those of small bowel radiographic studies when available. RESULTS: There were 46 CE studies from 45 patients, 28 male and 17 female, with a mean age of 14.9 +/- 3.6 years and mean weight of 49.7 +/- 17.5 kg. The indications for CE included unresponsive Crohn disease (n = 16), possible intestinal polyps (n = 11), unexplained iron deficiency anemia (n = 7), growth failure (n = 5), unresponsive ulcerative colitis (n = 3), persistent abdominal pain (n = 1), protein-losing enteropathy (n = 1), and allergic enteropathy with occult gastrointestinal bleeding (n = 1). Of the 46 CE studies, 41 were completed and 5 were incomplete studies. Based on the CE, 9 patients were newly diagnosed with Crohn disease, 9 patients with Crohn disease were newly diagnosed with small bowel involvement, 8 patients had upper intestinal polyps, 1 patient had findings consistent with Ménétrièr disease, and 1 had a duodenal ulcer. Thirty-three patients had small bowel series before CE: 24 studies were normal, 6 had abnormal thickening of the small bowel, 2 had polyps, and 1 patient had antral narrowing. All 9 patients with abnormal small bowel series had abnormal CE studies. Of the 24 patients with normal small bowel series, 20 had completed CE studies, and in 10 children, the study was abnormal. Nine of the 45 subjects had adverse events. Five patients had delayed passage from the stomach, with 2 needing endoscopic retrieval of the CE, and 4 had delayed passage from the small intestine (>5 days), with 2 requiring surgical removal, 1 responding to steroids, and the final patient requiring an ileocolic resection 2 months after the CE for an undiagnosed ileal stricture. The only significant association noted was that older patients were more likely to have intestinal retention. CONCLUSIONS: CE provides a valuable tool in the evaluation of pediatric patients for possible small bowel disease. However, the risk of developing complications appears to be greater in the pediatric population, with 20% of our patients having an adverse event.
Assuntos
Endoscopia por Cápsula , Gastroenteropatias/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: To determine whether children with celiac disease (CD) fail to show a response to hepatitis B virus (HBV) vaccine more frequently than children without CD. PATIENTS AND METHODS: This was a prospective study that compared the response to HBV, tetanus, rubella, and Haemophilus influenzae type b (Hib) vaccines between children with CD and age- and sex-matched control subjects. RESULTS: The study population included 26 patients with CD and 18 age- and sex-matched controls. All had received the full complement of childhood vaccinations. A significantly higher proportion of subjects in the CD group (14 of 26) failed to respond to HBV vaccine compared with controls (2 of 18; 53.9% vs 11.1%; P < 0.05). Patients with CD were 8.33 times more likely to test negative for hepatitis B surface antigen than control subjects (95% CI, 1.5-46.5). By contrast, all of the subjects in both groups tested positive for rubella antibodies; only 1 subject in the CD group tested negative for tetanus antibody versus none in the control group (3.9% vs 0%; P = 1.0). The percentage of subjects who tested negative for Hib antibodies was similar in the 2 groups (CD, 33.3%; control, 44.4%; P = 0.53). CONCLUSIONS: More than 50% of children with CD do not show a response to standard vaccination regimens for HBV. Given the large number of children with CD throughout the world, this observation suggests that there is a large HBV-susceptible population despite widespread vaccination. Current immunization strategies may need to be reassessed to protect this population and achieve the goal of universal protection.
Assuntos
Doença Celíaca/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Adolescente , Cápsulas Bacterianas , Doença Celíaca/sangue , Criança , Pré-Escolar , Feminino , Vacinas Anti-Haemophilus , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Masculino , Polissacarídeos Bacterianos , Estudos Prospectivos , Vacina contra Rubéola/imunologia , Toxina Tetânica/imunologiaRESUMO
OBJECTIVES: Infliximab, an anti-tumor necrosis factor (TNF) monoclonal antibody, might exert some of its long-term therapeutic effects in Crohn's disease (CD) by interacting directly with cells of the immune system such as monocytes and T lymphocytes via membrane TNF and by inducing apoptosis. Accordingly, the effects of inflix-imab on monocyte apoptosis and down-regulation of proinflammatory cytokines (reverse signaling) were assessed. METHODS: To assess apoptosis, monocytes from healthy individuals (controls) and CD patients were incubated in the presence or absence of infliximab or the apoptotic agent gliotoxin for 24 hours. Annexin V staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-FITC nick end labeling assay were used to measure early and late apoptosis. To measure the effects of infliximab on reverse signaling, monocytes from healthy individuals pretreated in vitro with infliximab were stimulated with lipopolysaccharide or staphylococcal enterotoxin A, and the induction of the proinflammatory cytokines, TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8 was measured by reverse transcription polymerase chain reaction. The effect of in vivo infliximab treatment of monocytes was similarly determined by comparing the responses of monocytes from CD patients before and immediately after infliximab infusion. RESULTS: Infliximab did not induce apoptosis of monocytes from either healthy individuals or CD patients but rather stabilized them. However, monocytes from healthy individuals treated with infliximab in vitro, or from CD patients infused with infliximab, produced significantly less TNF and other proinflammatory cytokines when stimulated with the bacterial products lipopolysaccharide and staphylococcal enterotoxin A. CONCLUSIONS: Apoptosis of monocytes is not responsible for the therapeutic effects of infliximab. However, some of the therapeutic effects of infliximab may be caused by its ability to down-regulate proinflammatory cytokines production by monocytes exposed to bacterial antigens.