Abstract Objectives To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. Methods Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. Results Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n= 18) had been exposed to cow's milk-based formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milk-based formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. Conclusions In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance.

Abstract Objectives: To describe the management, to compare treatment at initial referral vs. during specialized follow-up, and to describe outcomes of children with functional constipation (FC) referred to a Brazilian tertiary care center. Methods: Retrospective study, including children (4–18 years) with FC followed at a single center from 2006 to 2019. Demographics, treatments, time of follow-up, and outcomes were analyzed. The management of FC followed an institutional protocol. Results: 104 patients were identified, 79 were eligible and included in the analysis: 59% male, mean age at referral was 6.4 years, and mean duration of symptoms was 4.4 years. There were significant changes in the therapy(ies) used at the time of referral compared to during follow-up, with a noticeable increase in the frequency of the use of polyethylene glycol, enemas, magnesium hydroxide, and bisacodyl; 5.1% received trans-anal irrigation, and 3.8% underwent surgery. Outcomes were favorable in more than half of the cases: 31% improved; 19.5% had complete resolution and 2.5% were transferred back to primary care. Symptoms remained unchanged in 30.4%, and no patients experienced worsening of symptoms. The mean duration of follow-up was 2.8 years. When comparing patients with favorable vs. unfavorable outcomes, the authors did not identify significant differences in gender, age, therapies used, duration of symptoms, or length of follow-up. Conclusions: Children with FC are often referred to specialized care not receiving optimal therapy. Many patients whose FC was labeled “refractory” may be treated successfully with a well-established plan of care, and do not truly present intractable constipation.

RESUMO Contexto A dor abdominal crônica (DAC) pode acarretar importante morbidade. A última edição dos Critérios de Roma (Roma IV) permite o diagnóstico de distúrbios gastrointestinais funcionais (DGIFs) de acordo com critérios baseados em sintomas; no entanto, esses pacientes continuam a apresentar atraso no diagnóstico e a serem submetidos a diferentes intervenções antes do estabelecimento de um diagnóstico. Objetivo Caracterizar a etiologia, características clínicas e intervenções de crianças com DAC que não são mantidas na atenção primária e que foram encaminhadas ao nosso hospital universitário de nível terciário, no Brasil. Métodos Estudo retrospectivo descritivo de crianças e adolescentes (com idade igual ou inferior a 20 anos) encaminhados a nossa instituição, entre janeiro/2013 e dezembro/2018, por DAC e que preenchiam os critérios para DGIFs conforme o consenso de Roma IV. Resultados Trezentos e vinte e oito pacientes com DAC foram triados, 67,9% (223 pacientes) preencheram os critérios para DGIFs e foram analisados. Sessenta por cento do sexo feminino, com idade média de 8,3 anos. A duração média dos sintomas no encaminhamento era de 2,8 anos. Os escores z médios de estatura para idade e peso para idade foram -0,08±1,87 e -0,38±1,62, respectivamente. Dor abdominal funcional sem outra especificação foi o diagnóstico mais comum (70,4%). Antes do diagnóstico de DGIFs, múltiplas intervenções farmacológicas foram descritas, enquanto depois, a base da terapia foi a educação, passar segurança à família e intervenções dietéticas. Trinta e dois por cento dos pacientes apresentaram resolução dos sintomas e receberam alta do acompanhamento especializado. Conclusão Mesmo no nível terciário, as desordens gastrointestinais funcionais ainda constituem a etiologia mais comum da DAC, particularmente a dor abdominal funcional não especificada. Apesar da duração longa dos sintomas, alta do serviço especializados foi possível em aproximadamente um terço dos casos.

ABSTRACT Background Chronic abdominal pain (CAP) carries a significant burden of disease. The last edition of the Rome Criteria (Rome IV) allows the diagnosis of functional gastrointestinal disorders (FGIDs) according to symptoms-based criteria; however, patients continue to experience a delay in their diagnosis and to be submitted to different interventions before the establishment of a positive diagnosis. Objective We aimed to characterize etiology, clinical features, and interventions in a pediatric cohort of patients with CAP secondary to FGIDs, who were referred to our tertiary care university-affiliated hospital, in Brazil. Methods A retrospective descriptive study of children and adolescents (aged 20 years and younger) referred to our institution, from January/2013 to December/2018, for CAP, and who fulfilled criteria for FGIDs classified according to Rome IV criteria. Results Three hundred twenty-eight patients with CAP were screened, of which 67.9% (223 patients) fulfilled the criteria for FGIDs and were included in the study. Sixty percent were female, with a mean age of 8.3 years. At the time of referral, the mean duration of symptoms was 2.8 years. Length/height for age and weight for age mean z-scores were -0.08±1.87 and -0.38±1.62, respectively. Functional abdominal pain not otherwise specified was overall the most common diagnosis (70.4%). Before establishing the diagnosis of FGIDs, multiple pharmacological interventions were described, while after, the mainstay of therapy was education/reassurance and dietary interventions. Thirty-two percent of patients did not further require specialized follow-up. Conclusion Even at the tertiary care level, FGIDs were still the most common etiology of chronic abdominal pain, particularly functional abdominal pain not otherwise specified. Despite the relatively long duration of symptoms at referral, cessation of specialized care follow-up was possible in approximately a third of the cases.

RESUMO Objetivo: Relatar os casos de duas pacientes com doença inflamatória intestinal de início muito precoce (em inglês VEOIBD) secundária a mutações do receptor de interleucina 10 (IL-10R), explorar dados de imunofenotipagem e perfil de citocinas plasmáticas nesses casos em comparação com indivíduos saudáveis e descrever o fenótipo de mutações IL-10/IL-10R com base em uma revisão da literatura. Descrição do caso: Duas lactentes do sexo feminino foram encaminhadas ao nosso centro terciário, ambas com dez meses no momento do encaminhamento, com doença colônica e perianal grave, bem como desnutrição significativa, tendo uma resposta limitada aos agentes de terapia usuais de doença inflamatória intestinal (DII). No primeiro caso, o sequenciamento completo do exoma revelou mutação homozigótica (c. 537G>A/p.T179T) no exon 4 do gene IL-10RA, enquanto no segundo caso heterozigosidade composta foi identificada também no gene IL-10RA [chr11: 117.859.199 - variante A>G/p.Tyr57Cys e chr11: 117.860.335 - variante G>T/ p.Val123Leu]. Ambas as pacientes foram submetidas a Transplante de Células-Tronco Hematopoiéticas. A investigação imunológica das pacientes revelou aumento dos níveis plasmáticos de IL-10 e aumento da IgA. Comentários: Nossos relatos de casos descrevem novos achados no perfil de citocinas plasmáticas na deficiência de IL-10R, e relatamos o fenótipo grave da deficiência de IL-10/IL-10R que deve ser reconhecido pelos médicos.

ABSTRACT Objective: To report two patients with very-early-onset inflammatory bowel disease (VEOIBD) secondary to interleukin-10 receptor (IL-10R) mutations, explore immunophenotyping data and plasma cytokine profile on these cases compared to healthy controls, and describe the phenotype of IL-10/IL-10R mutations based on a literature review. Case description: We report on two female infants referred to our tertiary center at the age of ten months, with severe colonic and perianal disease, as well as significant malnutrition, who had shown limited response to usual inflammatory bowel disease (IBD) therapy agents. In the first case, whole-exome sequencing (WES) revealed a homozygous (c.537G>A/p.T179T) mutation in exon 4 of the IL-10RA gene, while in the second patient, compound heterozygosity was identified, also in the IL-10RA gene (chr11:117.859.199 variant A>G/p.Tyr57Cys and chr11: 117.860.335 variant G>T/p.Val123Leu). Both patients underwent hematopoietic cell transplantation (HCT). Immunological work-up of these patients revealed increased IL-10 plasma levels and increased IgA. Comments: Our case reports disclose novel findings on plasma cytokine profile in IL-10R deficiency, and we describe the severe phenotype of IL-10/IL-10R deficiency that should be recognized by physicians.

ABSTRACT Background: Approximately 25% of patients with inflammatory bowel disease (IBD) develop the disease during childhood or adolescence and treatment aims to control active symptoms and prevent long-term complications. The management of Crohn’s disease (CD) and ulcerative colitis (UC) can be especially challenging in children and adolescents, related to particularities that may affect growth, development, and puberty. Objective: This consensus aims to provide guidance on the most effective medical and surgical management of pediatric patients with CD or UC. Methods: Experts in Pediatric IBD representing Brazilian gastroenterologists (Brazilian Organization for Crohn’s Disease and Colitis [GEDIIB]) developed this consensus. A rapid review was performed to support the recommendations/statements. Medical and surgical recommendations were structured and mapped according to the disease type, disease activity, and indications and contraindications for medical and surgical treatment. After structuring the statements, the modified Delphi Panel methodology was used to conduct the voting. The process took place in three rounds: two using a personalized and anonymous online voting platform and one face-to-face. Whenever participants did not agree with a specific recommendation, an option to explain why was offered to enable free-text responses and provide the opportunity for the experts to elaborate or explain disagreement. The consensus of recommendations in each round was accepted when reached ≥80% agreement. Results and conclusion: The recommendations are presented according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/ patient monitoring after initial treatment, follow-up/ patient monitoring after initial treatment. Surgical recommendations were grouped according to disease type and recommended surgery. The target audience for this consensus was general practitioners, gastroenterologists, and surgeons interested in the treatment and management of pediatric CD and UC. Additionally, the consensus aimed to support the decision-making of health insurance companies, regulatory agencies, and health institutional leaders and/or administrators.

RESUMO Contexto: Aproximadamente 25% dos pacientes desenvolvem doença inflamatória intestinal (DII) durante a infância ou adolescência, e o tratamento visa controlar os sintomas ativos e prevenir complicações a longo prazo. O tratamento da doença de Crohn (DC) e retocolite ulcerativa (RCU) pode ser especialmente desafiador em crianças e adolescentes, relacionado a particularidades que podem afetar o crescimento, o desenvolvimento e a puberdade. Objetivo: Este consenso visa fornecer orientações sobre o tratamento clínico e cirúrgico mais eficaz de pacientes pediátricos com DC ou RCU. Métodos: Gastroenterologistas brasileiros especialistas em DII Pediátrico membro da Organização Brasileira para Doença de Crohn e Colite (GEDIIB) desenvolveram este consenso. Uma revisão rápida foi realizada para apoiar as recomendações/declarações. As recomendações médicas e cirúrgicas foram estruturadas e mapeadas de acordo com o tipo de doença, atividade da doença e indicações e contraindicações para tratamento médico e cirúrgico. Após a estruturação das declarações, foi utilizada a metodologia modificada do Painel Delphi para conduzir a votação. O processo ocorreu em três rodadas: duas por meio de uma plataforma de votação online personalizada e anônima e uma presencial. Sempre que os participantes não concordavam com a recomendação específica, uma opção para explicar o motivo era oferecida para permitir respostas em texto livre e dar a oportunidade para os especialistas elaborarem ou explicarem a discordância. O consenso das recomendações em cada rodada foi aceito quando houve concordância ≥80%. Resultados e conclusão: As recomendações são apresentadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, acompanhamento/monitoramento do paciente após tratamento. As recomendações cirúrgicas foram agrupadas de acordo com o tipo de doença e cirurgia recomendada. O público-alvo deste consenso foram clínicos gerais, gastroenterologistas e cirurgiões interessados no tratamento e manejo da RCU e DC pediátrica. Além disso, o consenso visava apoiar a tomada de decisão das operadoras de planos de saúde, agências reguladoras e líderes e/ou administradores de instituições de saúde.

RESUMO CONTEXTO: A colangite esclerosante primária (CEP) é uma doença hepatobiliar rara, cuja etiologia ainda não está totalmente elucidada. Dada a raridade do CEP na infância, até a recente publicação de uma colaboração multicêntrica internacional, mesmo dados sobre suas características e história natural eram escassos. A colelitíase sintomática não foi relatada anteriormente como a apresentação inicial de CEP na infância. OBJETIVO: O objetivo deste estudo foi o diagnóstico de CEP após a apresentação inicial incomum com colelitíase sintomática, que seguiu um curso clínico atípico que não poderia ser explicado apenas pela colelitíase. Também foi realizada uma revisão da literatura. MÉTODOS: Foi realizada uma revisão retrospectiva dos prontuários de três pacientes, que foram diagnosticados e/ou acompanhados no Hospital das Clínicas da Universidade Estadual de Campinas - São Paulo / Brasil, entre 2014 e 2020. Os dados analisados incluíram sexo, idade de apresentação, história médica pregressa, achados de imagem, resultados laboratoriais, avaliação endoscópica, resposta à terapia médica e acompanhamento. RESULTADOS: A idade no momento da apresentação da colelitíase variou de 10 a 12 anos. Em dois dos casos relatados, um início mais subagudo dos sintomas precedeu o episódio de colelitíase. Dois pacientes foram tratados com colecistectomia, não seguida de qualquer complicação cirúrgica, e um paciente foi tratado de forma conservadora. Biópsia hepática percutânea foi realizada em todos os três casos, mostrando achados histológicos compatíveis com CEP. Doença inflamatória intestinal associada não foi observada em nenhum dos pacientes. Os pacientes foram acompanhados por um tempo médio de 3,4 anos. CONCLUSÃO: CEP e colelitíase são raras na população pediátrica. Este estudo relata a colelitíase sintomática como uma apresentação de CEP e levanta a importância da suspeita de doença hepatobiliar subjacente em crianças com colelitíase sem quaisquer fatores predisponentes conhecidos e/ou que seguem um curso clínico atípico.

ABSTRACT BACKGROUND: Primary sclerosing cholangitis (PSC) is a rare hepatobiliary disorder, whose etiology remains not fully elucidated. Given how rare PSC is in childhood, until the recent publication of a multicenter international collaboration, even data on its characteristics and natural history were scarce. Symptomatic cholelithiasis has not been previously reported as the presentation of PSC. OBJECTIVE: The aim of this study was the diagnosis of PSC following the initial unusual presentation with symptomatic cholelithiasis, that followed an atypical clinical course that could not be explained by cholelithiasis alone. A literature review was also conducted. METHODS: We conducted a retrospective chart review of three patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/ Brazil, between 2014 and 2020. Data analyzed included gender, age of presentation, past medical history, imaging findings, laboratory results, endoscopic evaluation, response to medical therapy and follow-up. RESULTS: Age at time of presentation with cholelithiasis varied from 10 to 12 years. In two of the cases reported, a more subacute onset of symptoms preceded the episode of cholelithiasis. Two patients were managed with cholecystectomy, not followed by any surgical complications, one patient was managed conservatively. Percutaneous liver biopsy was performed in all three cases, showing histological findings compatible with PSC. Associated inflammatory bowel disease (IBD) was not seen in any of the patients. The patients have been followed for a mean time of 3.4 years. CONCLUSION: PSC and cholelithiasis are both rare in the pediatric population. This study reports on symptomatic cholelithiasis as a presentation of PSC and raises the importance of suspecting an underlying hepatobiliary disorder in children with cholelithiasis without any known predisposing factors and/or that follow an atypical clinical course for cholelithiasis alone.

RESUMO CONTEXTO Glicogenose (GSD) tipo 1b é uma doença multissistêmica em que complicações imunológicas e infecciosas estão presentes, além das manifestações metabólicas bem conhecidas da GSD. O tratamento com fator estimulador de colônias de granulócitos (G-CSF) é frequentemente indicado no tratamento da neutropenia e doença inflamatória intestinal. OBJETIVO Relatar sobre a dados demográficos, genótipo, apresentação clínica, manejo e complicações de pacientes pediátricos com GSD tipo 1b (GSD 1b), com atenção especial às complicações relacionadas ao sistema imunológico. MÉTODOS Série de casos retrospectiva de sete pacientes com GSD 1b diagnosticados e acompanhados em um hospital universitário terciário no Brasil, de julho/2000 a julho/2016. RESULTADOS A idade média no encaminhamento foi de 14 meses. O diagnóstico de GSD 1b foi baseado em achados clínicos e laboratoriais e apoiado por estudos genéticos em cinco casos. Todos os pacientes apresentaram neutropenia, tratada com G-CSF - especificamente Filgrastim. As hospitalizações por infecções foram frequentes. Dois pacientes desenvolveram doença inflamatória intestinal. Seis pacientes permanecem vivos, um morreu aos 14 anos e 9 meses de idade. A média de idade ao final do acompanhamento foi de 11,5 anos. A adesão ao tratamento foi sub-ótima: má adesão aos medicamentos, amido e manejo dietético de GSD foram documentados, e consultas ambulatoriais foram frequentemente perdidas. CONCLUSÃO O manejo da GSD 1b é um desafio, não apenas pela natureza crônica e multissistêmica desta doença, mas também pelas demandas adicionais relacionadas a restrições dietéticas, uso de múltiplos medicamentos e a necessidade de consultas de acompanhamento frequentes; no Brasil, isso ainda é dificultado em um cenário em que frequentemente atendemos pacientes com situação socioeconômica desfavorável e com oferta irregular de medicamentos no sistema público de saúde.

ABSTRACT BACKGROUND Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.

RESUMO CONTEXTO: A síndrome de Peutz-Jeghers (SPJ) é uma doença autossômica dominante rara, causada por deleções no cromossomo 19p33.3/gene LKB1/STK11. Essas mutações inativam uma serina/treonina quinase e predispõem à carcinogênese. Na SPJ, podem ser encontrados tumores do trato gastrointestinal, testicular, pulmonar, de mama, de pâncreas, de útero e de ovários. OBJETIVO: Avaliar dados demográficos, apresentação clínica e complicações de pacientes pediátricos que se apresentam com SPJ, além de apresentar e discutir o manejo no contexto de recursos limitados. MÉTODOS: Realizamos uma revisão retrospectiva de prontuários de uma coorte de seis pacientes, diagnosticados e/ou acompanhados no Hospital das Clínicas da Universidade de Campinas - São Paulo, Brasil, entre 2000 e 2018. Os dados analisados incluíram sexo, idade de apresentação, idade do diagnóstico, história familiar, complicações da SPJ. RESULTADOS: Idade média de diagnóstico de 6,7 anos, com tempo médio de seguimento de 8,1 anos. A pigmentação mucocutânea estava universalmente presente. Metade dos pacientes tinha um histórico familiar conhecido no momento do diagnóstico. Intussuscepção intestinal foi observada em quatro dos seis pacientes durante o período de acompanhamento, sendo que em três ocorreram vários episódios em diferentes múltiplas localizações. A investigação ativa de irmãos e pais do caso-índice levou ao diagnóstico de três parentes de primeiro grau na presente série de casos. CONCLUSÃO: Nesta primeira série de casos brasileiros de SPJ pediátrica, relatamos um amplo espectro de manifestações e complicações da SPJ. Em um contexto de recursos limitados, apesar das limitações para a vigilância de complicações, a frequência relativa de complicações não foi maior do que o relatado historicamente.

ABSTRACT BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare, autosomal dominant disease, caused by deletions in the chromosome 19p33.3/ gene LKB1/STK11. These mutations inactivate a serine/threonine kinase and predispose to carcinogenesis. In PJS, tumors of the gastrointestinal, testicles, pulmonary, breast, pancreas, uterus and ovaries can be found. OBJECTIVE: To evaluate demographics, clinical presentation and complication/outcomes of pediatric patients presenting with Peutz-Jeghers syndrome (PJS), as well as to present and discuss management in the context of limited resources. METHODS: We conducted a retrospective chart review of a cohort of six patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/Brazil, between 2000 and 2018. Data analyzed included gender, age of presentation, age of diagnosis, family history, PJS complications. RESULTS: Median age of diagnosis of 6.7 years, with a mean time of follow-up of 8.1 years. Mucocutaneous pigmentation was universally present. Half of the patients had a known family history at the time of diagnosis. On follow up, intestinal intussusception was documented in four out of six patients, in most (three), in different locations and in multiple occasions. The active investigation of siblings and parents of the index case led to the diagnosis of three first-degree relatives in the present case series. CONCLUSION: In this first pediatric PJS Brazilian case series, we report a wide spectrum of PJS manifestations and complications. In a resource limited scenario, despite limitations for the surveillance of complications, the relative frequency of complications was not higher than historically reported.

Purpose To ensure patient safety and surgical efficiency, much emphasis has been placed on the training of laparoscopic skills using virtual reality simulators. The purpose of this study was to determine whether laparoscopic skills can be objectively quantified by measuring specific skill parameters during training in a virtual reality surgical simulator (VRSS). Materials and Methods Ten medical students (with no laparoscopic experience) and ten urology residents (PGY3-5 with limited laparoscopic experience) were recruited to participate in a ten-week training course in basic laparoscopic skills (camera, cutting, peg transfer and clipping skills) on a VRSS. Data were collected from the training sessions. The time that individuals took to complete each task and the errors that they made were analyzed independently. Results The mean time that individuals took to complete tasks was significantly different between the groups (p < 0.05), with the residents being faster than the medical students. The residents' group also completed the tasks with fewer errors. The majority of the subjects in both groups exhibited a significant improvement in their task completion time and error rate. Conclusion The findings in this study demonstrate that laparoscopic skills can be objectively measured in a VRSS based on quantified skill parameters, including the time spent to complete skill tasks and the associated error rate. We conclude that a VRSS is a feasible tool for training and assessing basic laparoscopic skills.