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1.
J Pediatr Gastroenterol Nutr ; 79(3): 738-745, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39073140

RESUMO

BACKGROUND: Therapeutic endoscopic procedures are increasingly necessary for children. Pediatric gastroenterologist training and experience with endoscopic hemostasis and other complex therapeutic endoscopy procedures are often limited. We evaluated the impact of the implementation of an advanced complex endoscopy (ACE) team, which provides 24/7 inpatient/outpatient back-up endoscopy support. METHODS: We analyzed hemostasis quality outcomes in the 2 years before implementation of ACE (2018-2020) versus the year following the implementation of ACE (2020-2021). We analyzed pediatric gastroenterology provider satisfaction and perspectives with a survey that was distributed to faculty, fellows, and advanced practice providers 1 month before implementation of ACE and again 12 months following ACE implementation. RESULTS: Endoscopy volume and outcome metrics for hemostasis procedures, including latency to endoscopy, need for reintervention, and administration/diversity of hemostatic therapy, including multimodal therapy, improved in the year following implementation of the ACE (p < 0.05 for each). Survey results demonstrated a positive impact on provider endoscopy experience and high utilization of ACE. Twenty-two percent of providers reported activating ACE in the prior month and 66% in the prior year. Most providers who activated ACE were very satisfied (85%) or satisfied (7.7%). Eighty-three percent noted ACE had a positive impact on inpatients, and 50% noted a positive impact on outpatient endoscopy. Provider anxiety with endoscopy diminished post-ACE implementation (62% vs. 28%). Respondents unanimously found ACE beneficial to patient care (100%). CONCLUSIONS: ACE implementation was associated with improved provider perspectives surrounding endoscopy and significant improvement in hemostasis quality parameters, escalation of hemostasis procedure volume, and broadening the range of hemostasis interventions.


Assuntos
Equipe de Assistência ao Paciente , Humanos , Criança , Gastroenterologia/normas , Endoscopia Gastrointestinal/métodos , Pediatria/normas , Pediatria/métodos , Hemorragia Gastrointestinal/terapia , Qualidade da Assistência à Saúde , Inquéritos e Questionários , Masculino , Feminino
2.
J Pediatr Gastroenterol Nutr ; 78(5): 1059-1068, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38533633

RESUMO

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.


Assuntos
Constipação Intestinal , Agonistas da Guanilil Ciclase C , Peptídeos , Humanos , Constipação Intestinal/tratamento farmacológico , Criança , Adolescente , Método Duplo-Cego , Feminino , Masculino , Peptídeos/uso terapêutico , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Resultado do Tratamento , Agonistas da Guanilil Ciclase C/uso terapêutico , Agonistas da Guanilil Ciclase C/administração & dosagem , Defecação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem
3.
J Pediatr Gastroenterol Nutr ; 79(1): 54-61, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38477410

RESUMO

OBJECTIVES: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD. METHODS: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ). RESULTS: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission. CONCLUSIONS: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.


Assuntos
Adalimumab , Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Doença de Crohn , Quimioterapia Combinada , Infliximab , Ustekinumab , Humanos , Criança , Estudos Retrospectivos , Masculino , Feminino , Adolescente , Pré-Escolar , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Seguimentos , Infliximab/uso terapêutico , Infliximab/administração & dosagem , Resultado do Tratamento , Ustekinumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Adalimumab/uso terapêutico , Adalimumab/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Lactente , Terapia Biológica/métodos , Fármacos Gastrointestinais/uso terapêutico , Indução de Remissão/métodos , Produtos Biológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Índice de Gravidade de Doença
4.
J Pediatr Gastroenterol Nutr ; 78(1): 77-84, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38291697

RESUMO

BACKGROUND: Clinical disease activity associated with inflammatory bowel disease (IBD) can place physical limitations on youths' activities of daily living. In turn, functional limitations potentially contribute to youths' heightened experience of IBD-induced intrusions on a wide range of routine and valued activities (i.e., illness intrusiveness), which can increase their risk for depressive symptoms. The present study examined the contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in youth with IBD. METHODS: Youth (N = 180) completed the Functional Disability Inventory (FDI), Illness Intrusiveness Scale-Child (IIS-C), and Children's Depression Inventory-2 (CDI-2). Physicians completed the Physicians Global Assessment of disease activity (PGA). RESULTS: Results revealed a mediating effect for functional disability in the association between disease activity and depressive symptoms (PGA → FDI → CDI-2); illness intrusiveness mediated the association between functional disability and depressive symptoms (i.e., FDI → IIS-C → CDI-2). Serial mediation revealed that clinical disease activity conferred an indirect effect on youth depressive symptoms through the sequential effects of functional disability and illness intrusiveness (i.e., PGA → FDI → IIS-C → CDI-2). CONCLUSIONS: Taken together, these findings indicate that youth who encounter more physical limitations as a function of clinical disease activity are more likely to experience an amplified sense of IBD-related intrusions on their ability to participate in meaningful activities. In turn, heightened illness intrusiveness increases the likelihood of depressive symptoms. Clinical interventions that help youth maintain adequate functional ability in the face of IBD disease activity and encourage involvement in positively valued activities could decrease the negative impact of IBD on youths' emotional adjustment.


Assuntos
Depressão , Doenças Inflamatórias Intestinais , Adolescente , Humanos , Criança , Depressão/etiologia , Depressão/diagnóstico , Atividades Cotidianas , Doenças Inflamatórias Intestinais/diagnóstico , Probabilidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-39233517

RESUMO

OBJECTIVES: To assess the relative frequency and associated factors of disorders of gut-brain interaction (DGBIs) in outpatient gastrointestinal (GI) clinics in young children of Latin America. METHODS: Cross-sectional study in 10 pediatric GI outpatient clinics (private and public) in five countries of Latin America (El Salvador, México, Colombia, Panamá, and Nicaragua). Parents of patients 1 month 4 years of age from outpatient clinics complete/d a diagnostic questionnaire for DGBIs per Rome IV criteria (QPGS-IV, Spanish version). We conducted descriptive analysis, two-sample t-tests and chi-square tests, univariate analyses, and logistic regression to evaluate risk factors. RESULTS: We collected data from 783 children. In total, 34.5% had a DGBI. Overall, functional constipation (FC) was the most common diagnosis (23.4%) in children of all ages (infants, 16.1%, 1-4-years-old, 32.7%). In infants, the second most common DGBI was regurgitation (6.6%) and in 1-4-years-old and cyclic vomiting syndrome (4.1%). The diagnosis of a DGBI was significantly associated with a family history of DGBIs (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.61-5.57, p = 0.0001). Patients who identified as black (OR 2.25, 95% CI 1.28-3.92, p = 0.0021) or mixed race (OR 1.76, 95% CI 1.25-2.48, p = 0.0006) were also significantly associated with a higher likelihood of DGBIs. CONCLUSIONS: DGBIs are a common diagnosis in pediatric GI clinics of Latin America. Overall, FC was the most common DGBI.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39243338

RESUMO

PURPOSE OF REVIEW: The integration of digital technology into medical practice is often thrust upon clinicians, with standards and routines developed long after initiation. Clinicians should endeavor towards a basic understanding even of emerging technologies so that they can direct its use. The intent of this review is to describe the current state of rapidly evolving generative artificial intelligence (GAI), and to explore both how pediatric gastroenterology practice may benefit as well as challenges that will be faced. RECENT FINDINGS: Although little research demonstrating the acceptance, practice, and outcomes associated with GAI in pediatric gastroenterology is published, there are relevant data adjacent to the specialty and overwhelming potential as professed in the media. Best practice guidelines are widely developed in academic publishing and resources to initiate and improve practical user skills are prevalent. Initial published evidence supports broad acceptance of the technology as part of medical practice by clinicians and patients, describes methods with which higher quality GAI can be developed, and identifies the potential for bias and disparities resulting from its use. GAI is broadly available as a digital tool for incorporation into medical practice and holds promise for improved quality and efficiency of care, but investigation into how GAI can best be used remains at an early stage despite rapid evolution of the technology.

7.
J Gastroenterol Hepatol ; 38(12): 2076-2082, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37658800

RESUMO

BACKGROUND AND AIM: The association between hypermobility spectrum disorders/hypermobile type Ehlers-Danlos syndrome (HDS/hEDS) and irritable bowel syndrome (IBS) is yet to be clarified. We aimed to assess this association in a national sample of adolescents. METHODS: A population-based cross-sectional study included 1 627 345 Israeli adolescents (58% male; mean age 17 years) who were medically assessed before compulsory military service during 1998-2020. Diagnoses of HSD/hEDS and IBS were confirmed by board-certified specialists. The prevalence and odds ratios (ORs) for IBS in adolescents with and without HSD/hEDS were computed. RESULTS: A total of 4686 adolescents (2553 male) with HSD/hEDS were identified, of whom 71 were diagnosed with IBS (prevalence = 1.5%). Of the 1 621 721 adolescents in the control group, 8751 were diagnosed with IBS (prevalence = 0.5%). Unadjusted logistic regression revealed a significant association between HSD/hEDS and IBS (OR = 2.16 [95% confidence interval, CI, 1.90-2.45]), which persisted in multivariable adjusted models (OR = 2.58 [95% CI, 2.02-3.24]), and in several sensitivity analyses. The association was evident in both male and female adolescents with ORs of 2.60 (95% CI, 1.87-3.49), and 2.46 (95% CI, 1.66-3.49), respectively. The association was accentuated in a sensitivity analysis accounting for other medical and psychiatric comorbidities. CONCLUSIONS: We found a significant association between HSD/hEDS and IBS in both male and female adolescents. Clinical awareness of the association can promote early diagnosis of IBS and appropriate multidisciplinary treatment. Further research is required to identify the common pathological pathways of the conditions and to develop new IBS treatment strategies for people with HSD/hEDS.


Assuntos
Síndrome de Ehlers-Danlos , Síndrome do Intestino Irritável , Instabilidade Articular , Humanos , Masculino , Feminino , Adolescente , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/etiologia , Estudos Transversais , Instabilidade Articular/diagnóstico , Instabilidade Articular/patologia , Síndrome de Ehlers-Danlos/diagnóstico
8.
Eur J Pediatr ; 181(3): 1213-1220, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34817672

RESUMO

Adequate follow-up in celiac disease is important to improve dietary compliance and treat disease-related symptoms and possible complications. However, data on the follow-up of celiac children is scarce. We aimed to assess current pediatric celiac follow-up practices across Europe. Pediatricians and pediatric gastroenterologists from 35 countries in Europe, Israel, Turkey, and Russia completed an anonymous survey which comprised a 52-item questionnaire developed by the ESPGHAN Special Interest Group on Celiac Disease. A total of 911 physicians, the majority of whom exclusively worked in pediatric care (83%) and academic institutions (60%), completed the questionnaire. Mean age and mean experience with celiac care were 48.7 years (± 10.6) and 15.7 years (± 9.9), respectively. The vast majority (≥ 92%) always assessed anthropometry, dietary adherence, and tissue-transglutaminase IgA-antibodies at every visit, with the first visit being between 3 and 6 months after diagnosis. Other parameters (% always tested) were as follows: complete blood count (60%), iron status (48%), liver enzymes (42%), thyroid function (38%), and vitamin D (26%). Quality of life was never assessed by 35% of the responding physicians. Transition to adult care was mostly completed via a written transition report (37%) or no formal transition at all (27%).Conclusions: Follow-up of celiac children and adolescents in Europe may be improved, especially regarding a more rational use of (laboratory) tests, dietary and QoL assessment, and transition to adult care. Evidence-based advice from international scientific societies is needed. What is Known: • Follow-up in celiac disease is important to treat disease-related symptoms, improve dietary compliance, and prevent possible complications. • There is a lack of consensus about the appropriate follow-up. What is New: • Almost all European physicians assess anthropometry, tissue-transglutaminase IgA-antibodies, and dietary adherence at every visit, but there are large variations in other follow-up aspects. • Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance, and quality of life together with transition programs to adult care.


Assuntos
Doença Celíaca , Qualidade de Vida , Adolescente , Adulto , Doença Celíaca/diagnóstico , Doença Celíaca/terapia , Criança , Dieta , Seguimentos , Humanos , Inquéritos e Questionários
9.
Dis Esophagus ; 36(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35796004

RESUMO

Esophageal strictures in children may cause dysphagia, choking during feeds, and failure to thrive. They can be treated by balloon dilatations, either under endoscopic or fluoroscopic guidance; there is no literature comparing the methods. Retrospective review of the medical records of children (0-18 years) who were treated with balloon dilatations between 2010 and 2020. The primary outcome was the number of dilatation sessions required until clinical success after 3 months. Secondary outcomes were long-term success at 12 months, and complications of bleeding and perforation. Forty-six patients underwent 174 dilatation sessions. Success rates in the endoscopy and fluoroscopy groups were similar: 62% versus 67% (p = 0.454) at 3 months and 57% versus 67% (p = 0.721) at 12 months. Complication rate was lower in the endoscopy group (0% vs. 15%, p < 0.001). Both endoscopic and radiologic-guided balloon dilatations were shown to be equally effective, but endoscopic guidance had fewer complications.


Assuntos
Estenose Esofágica , Humanos , Criança , Estenose Esofágica/diagnóstico por imagem , Estenose Esofágica/etiologia , Estenose Esofágica/terapia , Dilatação/efeitos adversos , Dilatação/métodos , Resultado do Tratamento , Endoscopia , Fluoroscopia/efeitos adversos , Estudos Retrospectivos
10.
Med Princ Pract ; 30(4): 311-319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33120396

RESUMO

Gastrointestinal tract symptoms such as abdominal pain, constipation, diarrhea, and fever are common reasons for which parents take children to the pediatrician. An increasing prevalence of chronic diseases of the gastrointestinal tract and a decrease in the median age of their onset indicate the need to search for new diagnostic methods for differentiating inflammatory bowel diseases (IBDs) from other gastrointestinal tract diseases. An example of a novel biomarker is fecal calprotectin (FC), which is considered a noninvasive and useful marker of intestinal inflammation. This review summarizes currently available information on the use of FC in the diagnosis and monitoring of IBD in children. Additionally, it attempts to determine the course of action depending on the concentration of FC. Application of FC determination within the framework of primary medical care can decrease the number of children unnecessarily referred either to endoscopic or radiologic examination. There is a double advantage of calprotectin screening; for patients, it reduces delays in diagnosis and unnecessary exposure to endoscopy, and for doctors, it reduces pressure on endoscopy testing and facilitates decision-making. We emphasize the role of FC as a noninvasive marker, primarily in patients with IBD, in monitoring disease activity, predicting relapse, monitoring therapy efficacy, and monitoring postoperative relapses.


Assuntos
Fezes/química , Doenças Inflamatórias Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Biomarcadores/análise , Criança , Gastroenterologia , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Pediatria , Valor Preditivo dos Testes , Sensibilidade e Especificidade
11.
Clin Gastroenterol Hepatol ; 18(1): 133-140.e1, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981008

RESUMO

BACKGROUND & AIMS: Mucosal healing (MH) has become a goal of therapy for Crohn's disease (CD), but frequent endoscopies are not feasible. We aimed to develop and validate a non-invasive index to assess mucosal inflammation in children with CD. METHODS: We collected data from the multi-center prospective ImageKids study, in which children with CD underwent ileocolonoscopy with magnetic resonance enterography. We investigated the association of pediatric CD activity index (PCDAI) items and laboratory test results with the simple endoscopic score for CD (SESCD). We used these data in a blended mathematical judgmental clinimetric approach to develop a weighted categorized index to identify children with CD who have MH, which we called the MINI index. We validated the index using data from 3 independent patient cohorts. The derivation and validation cohorts included 154 and 168 children, respectively (age 14.1 ± 2.5 years and 14.2 ± 3.9 years), of whom 16% and 36% had MH (defined as SESCD<3). RESULTS: In multivariable models, the stooling item of the PCDAI, erythrocyte sedimentation rate, and level of fecal calprotectin were associated with SESCD (all P < .05). We added data on level of C-reactive protein to develop the MINI index. MINI scores below 8 identified children with MH with 88% sensitivity and 85% specificity in the derivation cohort and with 84% sensitivity and 87% specificity in the validation cohorts. Ninety percent of the patients in the validation cohort with scores of 8 or more had active mucosal inflammation, yet 78% of patients with scores below 8 had MH. Scores below 6 increase the positive predictive value to 86%. CONCLUSIONS: We developed an index to non-invasively assess mucosal inflammation in children with CD. This index, identifies children with MH with high sensitivity and specificity. The added benefit of MINI over measurement of fecal calprotectin was small but significant, especially for patients with concentrations of fecal calprotectin from 100 to 599 µg/g. ClinicalTrials.gov no: NCT01881490.


Assuntos
Doença de Crohn/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mucosite/diagnóstico por imagem , Índice de Gravidade de Doença , Adolescente , Biomarcadores/análise , Criança , Colonoscopia , Doença de Crohn/complicações , Técnicas de Diagnóstico do Sistema Digestório , Fezes/química , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/análise , Masculino , Mucosite/etiologia , Sensibilidade e Especificidade , Cicatrização
13.
Am J Emerg Med ; 37(6): 1124-1127, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30876776

RESUMO

OBJECTIVE: There have been various interventions to reduce ED utilization. Little is known about the sustainability of outcomes of interventions to reduce ED overcrowding. We sought to investigate whether the outcomes from one of successful interventions to reduce ED utilization, specialist physician level reporting were sustained over time and how this practice change was sustained over time. METHOD: This study is a longitudinal analysis of the pre and post intervention ED utilization data collected on ED pediatric patients who were followed by pediatric gastroenterologists in an urban, academic hospital. The primary outcome was the mean rate of ED visits per 1000 office visits from January, 2013 to June, 2017 using a u control chart with three sigma limits. RESULTS: There were continuous leadership's support, physicians' engagement and communications among different members involved in the intervention. The rate of gastrointestinal (GI)-related ED visits after an intervention decreased by 54% from 4.89 to 2.23 during all hours and by 59% from 2.19 to 0.91 during office hours. DISCUSSION: Physician-level reporting reduced ED utilization over a four year period. The outcomes could be sustained over time with sustained leadership and physicians' engagement.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/tendências , Gastroenterologia/organização & administração , Pediatria/organização & administração , Planos de Incentivos Médicos , Centros Médicos Acadêmicos , Idoso , Boston , Serviço Hospitalar de Emergência/organização & administração , Gastroenterologistas , Humanos , Liderança , Estudos Longitudinais , Motivação , Responsabilidade Social
14.
J Pediatr ; 202: 186-193, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30029859

RESUMO

OBJECTIVES: To describe a case of Kawasaki disease with intestinal involvement and to analyze other published reports to define clinical characteristics, diagnostic issues, and therapeutic approaches of gastrointestinal involvement in Kawasaki disease. STUDY DESIGN: A computerized search without language restriction was conducted using PubMed and SCOPUS. An article was considered eligible for inclusion in the systematic review if it reported data on patient(s) with intestinal involvement in Kawasaki disease. Our case was also included in the analysis. RESULTS: Thirty-three articles reporting 48 cases of Kawasaki disease with intestinal involvement were considered. Fever, abdominal pain, and vomiting were the most frequent symptoms observed and typical Kawasaki disease signs and symptoms appeared after intestinal complaints in all cases. Plain radiographs, ultrasonography, and computed tomography showed pseudo-obstruction as the most frequent sign of gastrointestinal involvement; 25 patients underwent surgery. Cardiac involvement was documented in 21 cases. All but three patients received medical treatment with immunoglobulin intravenous or aspirin. The outcome was good in 28 patients; 7 patients showed persistence of coronary artery abnormalities; 1 patient developed cyanosis, and later, left hand and forefoot gangrene; 3 patients died. CONCLUSIONS: The diagnosis and treatment of Kawasaki disease might be delayed if intestinal symptoms appear before the characteristic clinical features of Kawasaki disease, thus, increasing the risk of cardiac complications. Furthermore, patients may undergo unnecessary invasive procedures. Pediatricians and pediatric surgeons, therefore, should consider Kawasaki disease among diagnoses in children with fever, abdominal symptoms, and radiologic findings of pseudo-obstruction.


Assuntos
Hospitalização , Imunoglobulinas Intravenosas/administração & dosagem , Enteropatias/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adolescente , Diagnóstico Diferencial , Febre/diagnóstico , Febre/etiologia , Testes Hematológicos/métodos , Hepatomegalia/diagnóstico , Hepatomegalia/diagnóstico por imagem , Humanos , Enteropatias/diagnóstico , Obstrução Intestinal/diagnóstico , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Esplenomegalia/diagnóstico , Esplenomegalia/diagnóstico por imagem
15.
Am J Physiol Gastrointest Liver Physiol ; 312(4): G327-G339, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28039159

RESUMO

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option.NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Metagenoma , Adolescente , Criança , Feminino , Humanos , Masculino , Irmãos , Adulto Jovem
16.
J Clin Immunol ; 37(1): 67-79, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27747465

RESUMO

PURPOSE: Pediatric inflammatory bowel disease (IBD) is a heterogeneous disorder caused by multiple factors. Although genetic and immunological analyses are required for a definitive diagnosis, no reports of a comprehensive genetic study of a Japanese population are available. METHODS: In total, 35 Japanese patients <16 years of age suffering from IBD, including 27 patients aged <6 years with very early-onset IBD, were enrolled in this multicenter study. Exome and targeted gene panel sequencing was performed for all patients. Mutations in genes responsible for primary immunodeficiency diseases (PID) and clinical and immunological parameters were evaluated according to disease type. RESULTS: We identified monogenic mutations in 5 of the 35 patients (14.3 %). We identified compound heterozygous and homozygous splice-site mutations in interleukin-10 receptor A (IL-10RA) in two patients, nonsense mutations in X-linked inhibitor of apoptosis protein (XIAP) in two patients, and a missense mutation in cytochrome b beta chain in one patient. Using assays for protein expression levels, IL-10 signaling, and cytokine production, we confirmed that the mutations resulted in loss of function. For each patient, genotype was significantly associated with clinical findings. We successfully treated a patient with a XIAP mutation by allogeneic cord blood hematopoietic stem cell transplantation, and his symptoms were ameliorated completely. CONCLUSIONS: Targeted sequencing and immunological analysis are useful for screening monogenic disorders and selecting curative therapies in pediatric patients with IBD. The genes responsible for PID are frequently involved in pediatric IBD and play critical roles in normal immune homeostasis in the gastrointestinal tract.


Assuntos
Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Imunidade/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Adolescente , Alelos , Criança , Pré-Escolar , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Padrões de Herança , Interleucina-10/genética , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-10/deficiência , Subunidade alfa de Receptor de Interleucina-10/genética , Subunidade alfa de Receptor de Interleucina-10/metabolismo , Japão , Masculino , Mutação , Fenótipo , Transdução de Sinais , Sequenciamento do Exoma , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/deficiência , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
18.
J Gastroenterol Hepatol ; 32(9): 1604-1610, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28142194

RESUMO

BACKGROUND AND AIM: In preceding studies, we identified that the myenteric plexus (MP) could be visualized with confocal laser endomicroscopy (CLE) by applying neural fluorescent probes lacking clinical safety profiling data from the submucosal side. In this study, we evaluated the technical feasibility of MP visualization using probe-based CLE (pCLE) from the serosal side with cresyl violet (CV), which has been used clinically for chromoendoscopy. METHODS: The dye affinity of CV for MP was first explored in an in vivo transgenic mouse model using neural crest derivatives labeled with green fluorescent protein. We also tested the feasibility of CV-assisted visualization of MP in human surgical specimens, wherein the tissue dying and pCLE observation were performed from the serosal side. In the human study, rate of MP visualization by pCLE was evaluated as the primary outcome. We also evaluated the sensitivity and specificity of MP visualization by pCLE, using pathological presence/absence of MP as the gold standard. RESULTS: We confirmed the dye affinity of CV to MP in all tested models. The MP appeared as brightly stained ladder-like structures with pCLE, and in the human study, MP was visualized in 12/14 (85.7%) samples, with 92.3% sensitivity and 100% specificity. In positive cases showing the ladder-like structure of MP by pCLE, the mean maximum and minimum widths of nerve strands were 54.3 (± 23.6) and 19.7 (± 6.0) µm, respectively. A ganglion was detected by pCLE in 10 cases (10/12, 83.3%). CONCLUSIONS: This study demonstrated the technical feasibility of visualizing the MP in real time by CV-assisted pCLE (UMIN-CTR number, UMIN000015056).


Assuntos
Microscopia Confocal/métodos , Plexo Mientérico/ultraestrutura , Adolescente , Animais , Benzoxazinas , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Corantes Fluorescentes , Proteínas de Fluorescência Verde , Humanos , Lactente , Masculino , Camundongos Transgênicos , Modelos Animais
19.
Curr Gastroenterol Rep ; 19(3): 13, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28365899

RESUMO

PURPOSE OF REVIEW: The Chicago classification was based on metrics derived from studies in asymptomatic adult subjects. Our objectives were to characterize esophageal motility disorders in children and to determine whether the spectrum of manometric findings is similar between the pediatric and adult populations. RECENT FINDINGS: Studies have suggested that the metrics utilized in manometric diagnosis depend on age, size, and manometric assembly. This would imply that a different set of metrics should be used for the pediatric population. There are no standardized and generally accepted metrics for use in the pediatric population, though there have been attempts to establish metrics specific to this population. Overall, we found that the distribution of esophageal motility disorders in children was like that described in adults using the Chicago classification. This analysis will serve as a prequel to follow-up studies exploring the individual metrics for variability among patients, with the objective of establishing novel metrics for the pediatric population.


Assuntos
Transtornos de Deglutição/etiologia , Transtornos da Motilidade Esofágica/complicações , Transtornos da Motilidade Esofágica/diagnóstico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Esôfago/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Manometria/métodos , Processamento de Sinais Assistido por Computador , Adulto Jovem
20.
Curr Gastroenterol Rep ; 19(7): 33, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28639091

RESUMO

PURPOSE OF REVIEW: The prevalence of feeding disorders in medically complex children is estimated to be as high as 80%. Enteral tube nutrition (ETN) is commonly used for nutritional support in children with feeding disorders. Adverse consequences of ETN include medical complications, psychosocial problems, and higher healthcare costs. We used a retrospective cohort controlled study design to compare outcomes of our outpatient multidisciplinary intensive feeding therapy (IFT) program to our traditional therapy (TT) of single-discipline, once weekly feeding therapy to reduce ETN dependence in medically complex young children. RECENT FINDINGS: Children in the IFT cohort experienced a median reduction in ETN dependence of 49% (34.5-58.5%) compared with a median reduction of 0% (0-25%) for TT (p > 0.0001). Almost half of the IFT cohort no longer required ETN by the conclusion of the 5-week program. Medically complex young children (median age 26 months) successfully reduce or eliminate ETN in an outpatient multidisciplinary intensive feeding program.


Assuntos
Assistência Ambulatorial/métodos , Nutrição Enteral/estatística & dados numéricos , Transtornos de Alimentação na Infância/terapia , Assistência Ambulatorial/estatística & dados numéricos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Equipe de Assistência ao Paciente , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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