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Contrast-enhanced ultrasound (CEUS) is a versatile imaging modality that improves the diagnostic potential of conventional ultrasound. It allows for portable imaging at the bedside. In this paper, we illustrate how CEUS can be used in evaluating several focal lesions in the pediatric population, including liver hemangioma, telangiectasias, splenic hamartomas, and bladder lesions. We describe the ultrasound findings and contrast enhancement patterns associated with these lesions. Findings are correlated with MRI, CT, and/or pathology when available. This paper demonstrates the value of CEUS in improving characterization of many focal lesions in the pediatric population. CONCLUSION: CEUS is a valuable bedside technique for use in the pediatric population to evaluate focal lesions in various organs, and will allow for safe, more efficient diagnostic imaging. What is Known: ⢠CEUS offers many advantages over CT and MRI and is underutilized in the United States. ⢠It is only FDA approved for vesicoureteral reflux and liver in the pediatric population. However, off label uses are well described. What is New: ⢠This pictorial essay describes ultrasound findings and contrast enhancement patterns associated with liver hemangioma, liver telangiectasia, splenic hamartoma, hemorrhagic ovarian cyst, urachal remnant, spinning top urethras, and kaposiform hemangioendothelioma. ⢠We demonstrate the utility of CEUS in expanding the diagnostic potential of conventional ultrasound.
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Abdome/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Pelve/diagnóstico por imagem , Ultrassonografia/métodos , Abdome/patologia , Criança , Pré-Escolar , Meios de Contraste , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pescoço/patologia , Pelve/patologia , Baço/diagnóstico por imagem , Baço/patologia , Tomografia Computadorizada por Raios X/métodos , Sistema Urogenital/diagnóstico por imagem , Sistema Urogenital/patologia , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/patologiaRESUMO
Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.
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Terapia Biológica , Clostridioides difficile , Infecções por Clostridium/terapia , Fezes/microbiologia , Crescimento , Intestinos/microbiologia , Microbiota , Bacteroides/crescimento & desenvolvimento , Pré-Escolar , Clostridioides difficile/crescimento & desenvolvimento , Infecções por Clostridium/microbiologia , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
[This corrects the article DOI: 10.1016/j.conctc.2023.101144.].
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Purpose: Crohn's disease (CD) is a chronic, idiopathic bowel disorder that can progress to partial or complete bowel obstruction. At present, there are no reliable diagnostic tests that can readily distinguish between acute inflammatory, purely fibrotic and mixed inflammatory and fibrotic. Our aim is to study the utility of contrast enhanced ultrasound (CEUS) in combination with shear wave elastography (SWE) to differentiate fibrotic from inflammatory strictures in children with obstructive CD of the terminal ileum. Methods: Twenty-five (19 male) children between 2016-2021 with CD of the terminal ileum were recruited into the study. Among these patients, 22 had CEUS kinetic measurements of tissue perfusion, including wash-in slope (dB/sec), peak intensity (dB), time to peak intensity (sec), area under the curve (AUC) (dB sec), and SWE. In total, 11 patients required surgery due to bowel obstruction. Histopathologic analysis was performed by a pathologist who was blinded to the CEUS and SWE test results. Results: Patients that underwent surgical resection had significantly higher mean area under the curve on CEUS compared to patients responsive to medical therapy (p=0.03). The AUC also correlated with the degree of hypertrophy and the percent fibrosis of the muscularis propria, as determined by histopathologic grading (p<0.01). There was no difference in the mean elastography measurements between these two patient groups. Conclusion: CEUS is a useful radiological technique that can help identify pediatric patients with medically refractory obstructive fibrotic strictures of the terminal ileum that should be considered for early surgical resection.
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Background: A previous phase 3 trial of prucalopride in pediatric patients (6 months-18 years old) with functional constipation (FC) demonstrated no efficacy versus placebo. We designed an additional phase 3 trial to further assess the efficacy, long-term safety and tolerability of prucalopride in children and adolescents. Methods: This multicenter trial (ClinicalTrials.gov identifier: NCT04759833; EudraCT number: 2022-003221-22) comprises a 12-week, randomized, double-blind, placebo-controlled phase, followed by a 36-week, double-blind, safety extension phase. Approximately 240 toilet-trained patients aged 3-17 years will be randomized 1:1:1 to receive low- (0.04 mg/kg) or high-dose (0.08 mg/kg) prucalopride, or placebo once daily. Fifteen non-toilet-trained patients ≥6 months old with FC will be included in an exploratory efficacy and safety analysis. Discussion: The efficacy endpoints used in this study will differ from those used in adults and in the previous pediatric phase 3 trial; they have been adapted to be more suitable for a wider age range of pediatric patients. Both study phases will be longer than in the previous pediatric study, providing a longer time period in which to assess the efficacy and safety of prucalopride. Study participants will be identified using the modified Rome IV criteria for FC, instead of the Rome III criteria, and non-toilet-trained patients will be included, which will broaden the population of pediatric patients assessed. Patients will undergo fecal disimpaction before randomization and undergo standardized continuous behavioral therapy throughout the trial. This pediatric study of prucalopride will aim to demonstrate the efficacy and long-term safety of this treatment.
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Percutaneous endoscopic gastrostomy (PEG) is a relatively safe and minimally invasive surgical method for providing enteral access in children. In pediatrics, the indications for PEG placement frequently include malnutrition or failure to thrive, as well as oropharyngeal dysphagia, especially in children with neurological impairment (NI). The risk for postoperative complications is low. However, among children with NI, gastroesophageal reflux disease (GERD) may necessitate fundoplication prior to gastrostomy tube placement. Preoperative pH probe testing has not been shown to be an effective screening tool prior to PEG placement among patients with GERD. Laparoscopic gastrostomy tube insertion was introduced in pediatric patients in an attempt to decrease complications associated with PEG. Although outcomes were reported to be similar to or better than PEG alone, future comparative studies are needed to better define the optimal patient demographic for this technique.
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Refluxo Gastroesofágico/etiologia , Gastrostomia/efeitos adversos , Criança , Nutrição Enteral/métodos , Insuficiência de Crescimento/cirurgia , Gastroscopia , Humanos , Lactente , Desnutrição/prevenção & controle , Desnutrição/cirurgiaRESUMO
Specific antimicrobial antibodies present in the sera of patients with inflammatory bowel disease (IBD) have been proven to be valuable serological biomarkers for diagnosis/prognosis of the disease. Herein we describe the use of a whole Escherichia coli proteome microarray as a novel high throughput proteomics approach to screen and identify new serological biomarkers for IBD. Each protein array, which contains 4,256 E. coli K12 proteins, was screened using individual serum from healthy controls (n = 39) and clinically well characterized patients with IBD (66 Crohn disease (CD) and 29 ulcerative colitis (UC)). Proteins that could be recognized by serum antibodies were visualized and quantified using Cy3-labeled goat anti-human antibodies. Surprisingly significance analysis of microarrays identified a total of 417 E. coli proteins that were differentially recognized by serum antibodies between healthy controls and CD or UC. Among those, 169 proteins were identified as highly immunogenic in healthy controls, 186 proteins were identified as highly immunogenic in CD, and only 19 were identified as highly immunogenic in UC. Using a supervised learning algorithm (k-top scoring pairs), we identified two sets of serum antibodies that were novel biomarkers for specifically distinguishing CD from healthy controls (accuracy, 86 +/- 4%; p < 0.01) and CD from UC (accuracy, 80 +/- 2%; p < 0.01), respectively. The Set 1 antibodies recognized three pairs of E. coli proteins: Era versus YbaN, YhgN versus FocA, and GabT versus YcdG, and the Set 2 antibodies recognized YidX versus FrvX. The specificity and sensitivity of Set 1 antibodies were 81 +/- 5 and 89 +/- 3%, respectively, whereas those of Set 2 antibodies were 84 +/- 1 and 70 +/- 6%, respectively. Serum antibodies identified for distinguishing healthy controls versus UC were only marginal because their accuracy, specificity, and sensitivity were 66 +/- 5, 69 +/- 5, and 61 +/- 7%, respectively (p < 0.04). Taken together, we identified novel sets of serological biomarkers for diagnosis of CD versus healthy control and CD versus UC.
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Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Proteínas de Escherichia coli/imunologia , Doenças Inflamatórias Intestinais/sangue , Proteômica/métodos , Adulto , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/microbiologia , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/microbiologia , Escherichia coli/imunologia , Escherichia coli/metabolismo , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/análise , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Análise em Microsséries , Proteômica/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Antitumor necrosis factor (anti-TNF) therapy has proven efficacy in the induction and maintenance of remission in children with Crohn's disease (CD). With the increased use of these medications, several adverse events have been associated, including the emergence of neurologic side effects. While demyelinating conditions and neuropathy associated with anti-TNF therapy have been reported in adults, seizures have been anecdotally described in case reports. We describe a case of an adolescent boy who experienced an infliximab-associated seizure during an infusion and the potential role that medication antibody levels may have played in this adverse event.
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BACKGROUND AND OBJECTIVES: Factors predicting outcome after percutaneous endoscopic gastrostomy (PEG) in large pediatric cohorts are not well defined. We hypothesized that definable preoperative clinical factors predict the need for further intervention to provide enteral access after PEG. Our aim was to identify factors associated with PEG outcome. MATERIALS AND METHODS: A retrospective review of 760 (407 boys and 353 girls) patients was performed after PEG at the Johns Hopkins Children's Center from 1994 to 2005. Logistic or multiple linear regression was used to analyze indication; diagnosis; age; prematurity; neurological impairment; weight-for-age z scores; modified barium swallow; postoperative complications; need for fundoplication (FP), gastrojejunal tube, or jejunostomy; and length of hospital stay. RESULTS: The median age was 1 year (range 0-26 years). The most common indications given for PEG were failure to thrive (n = 373) and dysphagia (n = 27). Postoperative FP, gastrojejunal tube, or jejunostomy were performed in 66 (10%), 24 (4%), and 9 (1%) patients, respectively. Preoperative report indicated that dysphagia and direct aspiration on modified barium swallow was strongly associated with patients undergoing FP after PEG, 10.6% of patients (P = 0.008, odds ratio 2.4) and 11.2% of patients (P = 0.013, odds ratio 2.8), respectively. Younger preoperative age was also associated with the need for FP (P = 0.0006; median age of 5.8 vs 14 months). Patients with preoperative dysphagia had a longer median length of hospital stay: 8 versus 3 days (P < 0.00001). Patients with neurological impairment demonstrated greater weight gain than neurologically normal patients after PEG (P = 0.04). Minor postoperative complications (most commonly wound infection) were observed in 4% (27/747) of children before hospital discharge from PEG and in 20% of children (138/682) after discharge. There were only 2 major complications (gastric separation and gastrocolonic fistula.). There were no fatalities. CONCLUSIONS: Preoperative diagnosis, indication, prematurity, and neurological impairment did not influence postoperative complications.
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Nutrição Enteral/métodos , Gastroscopia/métodos , Gastrostomia/métodos , Complicações Pós-Operatórias , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Transtornos de Deglutição/terapia , Insuficiência de Crescimento/terapia , Feminino , Fundoplicatura , Humanos , Lactente , Intubação Gastrointestinal , Jejunostomia , Masculino , Doenças do Sistema Nervoso , Complicações Pós-Operatórias/epidemiologia , Prevalência , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento , Aumento de Peso , Adulto JovemRESUMO
BACKGROUND: Bowel preparation in children can be challenging. AIM: To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid (SPMC) bowel preparation in children. METHODS: Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ½ dose × 2, SPMC 1 dose × 2, or polyethylene glycol (PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders (rating of 'excellent' or 'good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ½ dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was 'very easy' or 'easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG. CONCLUSION: SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.
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Óxido de Magnésio , Compostos Organometálicos , Catárticos/efeitos adversos , Criança , Citratos/efeitos adversos , Ácido Cítrico/efeitos adversos , Colonoscopia , Humanos , Óxido de Magnésio/efeitos adversos , Compostos Organometálicos/efeitos adversos , Picolinas , Polietilenoglicóis/efeitos adversosRESUMO
Characterizing inflammation and fibrosis in Crohn's disease (CD) is necessary to guide clinical management, but distinguishing the two remains challenging. Novel ultrasound (US) techniques: contrast-enhanced US (CEUS) and shear wave elastography (SWE) offer great potential in evaluating disease activity in pediatric patients. Three patients ages 16 to 20 with known CD underwent CEUS and SWE to characterize bowel wall inflammation and fibrosis. Magnetic resonance enterography, endoscopy, or surgical pathology findings are also described when available. The patients' disease activity included acute inflammation, chronic inflammation with stricture formation, and a fibrotic surgical anastomosis without inflammation. CEUS was useful in determining the degree of inflammation, and SWE identified bowel wall fibrosis. Used together these techniques allow for better characterization of the degree of fibrosis and inflammation in bowel strictures. With further validation CEUS and SWE may allow for improved characterization of bowel strictures and disease flares in pediatric patients suffering from CD.
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Androgen therapy has proven efficacy in treating patients with bone marrow failure who are not candidates for bone marrow transplantation. Herein, we report on a case of colonic angioectasia secondary to oxymetholone use in an adolescent patient with Hoyeraal-Hreidarsson syndrome (HHS). A 13-year-old Caucasian male with HHS characterized by cerebellar hypoplasia, developmental delay, microcephaly, esophageal strictures and myelodysplasia presented with severe hematochezia from colonic angioectasia secondary to long-term oxymetholone therapy. These vascular lesions resolved spontaneously once this anabolic steroid was discontinued. While androgen therapy is often recommended for certain anemias and myelodysplastic syndromes, clinicians should be aware of the potential complication in developing these perceived uncommon colonic angioectasias. Moreover, pediatric gastroenterologists should familiarize themselves in identifying these vascular lesions by colonoscopy, especially among the high risk groups on long-term anabolic steroid therapy.
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OBJECTIVES: To assess the prevalence of adherence to prescribed medications in children with Crohn disease and to identify possible factors associated with nonadherence. PATIENTS AND METHODS: This was a cross-sectional study of 51 pediatric patients with Crohn disease who were prescribed maintenance therapy with a thiopurine immunomodulator (6-mercaptopurine or azathioprine) and/or mesalamine during a 180-day period. Medication adherence rates were calculated from a validated formula using pharmacy records, and nonadherence was defined as a refill rate of <80% of the prescribed medication. Seventy-five percent of patients were prescribed thiopurine immunomodulators and 86% were prescribed mesalamine. RESULTS: The prevalence of nonadherence was 50% for the thiopurine immunomodulators and 66% for mesalamine. The mean number of emergency department visits for patients adherent to mesalamine was significantly greater than the nonadherent group (P < 0.0008). Having an emergency department visit increased the chances of a patient being adherent to mesalamine therapy by >9-fold (odds ratio, 9.6; 95% confidence interval, 1.87-52.17). The mean number of total health care visits was significantly greater for patients adherent to mesalamine (6.1 +/- 0.8) compared with those who were not adherent (3.0 +/- 0.4) (P < 0.001). CONCLUSIONS: These findings suggest that nonadherence to thiopurine immunomodulator or mesalamine therapy in pediatric patients with Crohn disease is common. Having a health care visit was associated with being adherent.
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Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Mercaptopurina/uso terapêutico , Mesalamina/uso terapêutico , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adolescente , Adulto , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Doença de Crohn/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , PrevalênciaRESUMO
BACKGROUND: The purpose of this study is to develop patient-reported (PRO) and observer-reported (ObsRO) outcome measures of ulcerative colitis (UC) signs/symptoms in children aged 5-17 with mild/moderate UC. The daily ulcerative colitis signs and symptoms scale (DUCS) was developed in two phases. Phase I involved concept elicitation interviews with patients and healthcare providers, review of website posts and item generation. Phase II involved cognitive debriefing and assessment of usability and feasibility of the eDiaries. Participants were recruited from five US clinical sites, a research recruitment agency, and internet advertising. Thematic and content analysis was performed to identify concepts from Phase I. The Phase II cognitive debriefing interviews were analyzed iteratively to identify problems with clarity and relevance of eDiary content. The US Food and Drug Administration (FDA) also reviewed and provided feedback on the eDiaries. RESULTS: Phase I included 32 participants (22 remission; 10 active disease). Phase II included 38 participants (22 remission; 16 active disease). A core set of seven signs and symptoms emerged that were reported by at least 30% of the patients interviewed: abdominal pain, blood in stool, frequent stools, diarrhea, stool urgency, nighttime stools, and tiredness. Participant input influenced changes such as refinement of item wording, revision of graphics, and selection of response scales. Revisions suggested by FDA included simplifying the response scale and adding questions to capture symptoms during sleeping hours. CONCLUSIONS: The findings of instrument development suggest that the DUCS PRO and ObsRO eDiaries are content-valid instruments for capturing the daily signs and symptoms of pediatric patients with mild to moderate UC in a clinical trial setting.
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Colite Ulcerativa/diagnóstico , Pesquisa Qualitativa , Adolescente , Criança , Cognição , Demografia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Indeterminate colitis (IC) is a subgroup of inflammatory bowel disease (IBD) that cannot be characterized as either ulcerative colitis (UC) or Crohn's disease (CD). Our aims are to determine the prevalence of IC in our pediatric patient population and to describe its clinical presentation, natural history,and disease distribution. METHODS: We performed a retrospective database analysis of all children diagnosed with IBD at the Johns Hopkins Children's IBD Center between 1996 and 2001. Patient demographics, including age, sex, and age at disease onset, were tallied. Disease distribution was identified on the basis of a review of all endoscopic, colonoscopic, histopathological, and radiological records. All of the patients were followed up clinically to determine the extent of disease progression on the basis of the initial diagnosis of IC. RESULTS: Among 250 children registered in the database, 127 (50.8%) had a diagnosis of CD, 49 (19.6%) had UC, and 74(29.6%) had IC. Patients with IC had a significantly younger mean +/- SEM age (9.53 +/- 4.8 years) at diagnosis compared with patients with CD (12.4 +/- 3.8 years; P < 0.001) but not compared with patients with UC (7.41 +/- 3.5 years). Among the patients with IC, 59 (79.7%) had a pancolitis at diagnosis, and the remaining 15 had left-sided disease that progressed to a pancolitis within a mean of 6 years. Twenty-five patients (33.7%) with an initial diagnosis of IC were reclassified to either CD or UC after a median follow-up of 1.9 years (range 0.6-4.5 years). Forty-nine patients (66.2%) maintained their diagnosis of IC after a mean follow-up of 7 years (SEM 2.5 years). CONCLUSIONS: IC is a distinct pediatric subgroup of IBD with a prevalence that is higher than that observed in adults. Children with IC have an early age of disease onset and a disease that rapidly progresses to pancolitis. Longitudinal studies are needed to determine the clinical implications of this pediatric IBD subgroup.
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Colite Ulcerativa/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Colite Ulcerativa/diagnóstico , Colonoscopia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Prevalência , Prognóstico , Estudos Retrospectivos , Estados Unidos/epidemiologiaAssuntos
Neoplasias do Colo/terapia , Hemangioma/terapia , Síndrome de Klippel-Trenaunay-Weber/complicações , Escleroterapia , Criança , Neoplasias do Colo/complicações , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Hemangioma/complicações , Humanos , Masculino , RecidivaAssuntos
Adenocarcinoma , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Adenocarcinoma/genética , Adolescente , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa , Humanos , Proteína 1 Homóloga a MutL/genéticaRESUMO
BACKGROUND: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). AIM: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. METHODS: Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. RESULTS: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. CONCLUSION: Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Mesalamina/administração & dosagem , Adolescente , Ácidos Aminossalicílicos/metabolismo , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacocinética , Área Sob a Curva , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mesalamina/efeitos adversos , Mesalamina/farmacocinéticaRESUMO
Although uncommon, diffuse jejunoilietis is one of the most difficult areas in Crohn's disease (CD) to treat. Although the exact frequency is unknown, most gastroenterologists believe that its prevalence has been underestimated and that it may have an increased incidence among children and young adolescents. The clinical importance of this clinical disease phenotype is the impact diffuse small bowel disease is expected to have on a child's growth and development. Moreover, patients with jejunoileitis are more likely to experience complications, including fistulization, and most commonly, intestinal obstruction. The associated morbidity and frequent need for surgical intervention renders these patients at risk for intestinal insufficiency. Although stricturoplasty has reduced the incidence of short bowel syndrome, most patients with proximal small bowel CD still require repeated surgical intervention. Jejunoileitis represents a distinct clinical phenotype within the heterogenous family of disease phenotypes considered as CD. Whether a specific genotype will be found to associate with jejunoileitis remains to be determined. Through the development of novel diagnostic techniques, including gadolinium enhanced magnetic resonance imaging (GMRI), enteroscopy, and capsule endoscopy, the mean age at diagnosis is expected to decrease. Coupled with an increase in clinical suspicion, early diagnosis may allow physicians to consider implementing aggressive immunomodulatory therapy. Future studies are needed to determine if the early detection and use of immune modulators in patients with proximal small bowel disease will improve overall quality of life and decrease the risk of nutritional and surgical comorbidity.
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Doença de Crohn , Enterite , Ileíte , Doenças do Jejuno , Adolescente , Criança , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Doença de Crohn/terapia , Diagnóstico por Imagem/métodos , Endoscopia Gastrointestinal/métodos , Enterite/diagnóstico , Enterite/terapia , Humanos , Ileíte/diagnóstico , Ileíte/terapia , Doenças do Jejuno/diagnóstico , Doenças do Jejuno/terapia , FenótipoRESUMO
BACKGROUND: The effects of infliximab, a tumor necrosis factor-alpha (TNF-alpha) antibody, have been well established in adult patients with inflammatory and fistulizing Crohn's disease. This study evaluates short- and long-term efficacy of infliximab in children with ulcerative colitis. METHODS: All pediatric patients with ulcerative colitis who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. RESULTS: Twelve pediatric patients with ulcerative colitis received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 long-term responders. Patients receiving 6-mercaptopurine had a better response to infliximab. CONCLUSION: Infliximab should be considered in the treatment of children with symptoms of acute moderate to severe ulcerative colitis.