Tratamiento de reposición enzimática en la insuficiencia pancreática exocrina asociada a la fibrosis quística. Grupo de trabajo de Fibrosis Quística de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPHGAN) / Enzyme replacement treatment in exocrine pancreatic insufficiency associated with cystic fibrosis. Cystic fibrosis Working group of the Latin American Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPHGAN)

La fibrosis quística (FQ) es un trastorno hereditario, de las glándulas de secreción exocrina, considerada la causa más frecuente de insuficiencia pancreática exocrina (IPE) en la infancia. Esta revisión resume el panorama del tratamiento de reposición enzimática en la IPE asociada a la FQ, las formulaciones disponibles, su dosificación y modo de administración, así como las limitaciones y desafíos actuales y las posibles áreas del desarrollo futuro

Cystic fibrosis (CF) is an inherited disorder of the exocrine secretion glands, considered the most frequent cause of exocrine pancreatic insufficiency (EPI) in childhood. This review summarizes the landscape of enzyme replacement therapy in PEI associated with CF, the available formulations, their dosage and mode of administration, as well as the current limitations and challenges and potential areas for future development.

Pancreatitis crónica: análisis de factores de progresión de la enfermedad / Chronic pancreatitis: analysis of disease progression factors

BACKGROUND: Alcohol and tobacco are important risk factors for chronic pancreatitis (CP). AIM: To analyze the effect of etiological factors such as tobacco and alcohol and pancreatic enzyme replacement therapy (PERT) in the progression of CP. MATERIAL AND METHODS: Patients with a diagnosis of CP were recruited and grouped according to variables such as tobacco, alcohol and PERT. They were followed for 18 months. Subsequently, different variables and analytical parameters involved in the progression of the disease were analyzed. RESULTS: A total of 50 patients diagnosed with CP were included. Of these, 28 patients underwent PERT, 39 were smokers and 33 were alcohol users. Compared with patients without PERT, those with PERT had a higher proportion of diabetes (64 and 32%, respectively), had a higher need for endoscopic treatment (25 and 0%, respectively) and a normal body mass index (71 and 27.3%, respectively. The smokers had higher calcium levels and increased lymphocytosis and leukocytosis. The alcohol consumption group had a higher mean age (p = 0.04) CONCLUSIONS: PERT may improve the nutritional status but does not reduce the need for endoscopic or surgical treatment. Smoking and alcohol consumption favored the progression of CP. Also, smoking induced a pro-inflammatory state.

Factores clínicos asociados a complicaciones pulmonares y extrapulmonares en pacientes con fibrosis quística. Un estudio observacional de centro único / Clinical factors associated with pulmonary and extrapulmonary complications in patients with cystic fibrosis. A single-center observational study

Introducción: La fibrosis quística (FQ), afecta el epitelio exocrino, formando una mucosidad espesa que obstruye los conductos de los diferentes órganos, siendo el pulmón y páncreas los más afectados. El objetivo del presente estudio fue determinar la asociación entre los factores clínicos y las complicaciones, así como la supervivencia de pacientes con FQ atendidos en un centro de referencia pediátrica en México. Métodos: El presente estudio observacional, longitudinal, fue realizado en el Instituto Nacional de Pediatría en México, de abril del 2012, a abril del 2022. Con una muestra no probabilística ingresaron al estudio niños con fibrosis quística. Las variables fueron: demográficas, complicaciones pulmonares, extrapulmonares y mortalidad. Se realiza la asociación con chi-cuadrado y la supervivencia con Kaplan-Meir. Resultados: Se analizan 71 pacientes, lactantes menores 41 casos (62%), pre-escolares 12 casos (16.9%). Fueron 40 hom-bres (56.3%). 57 casos (80.3%) tuvieron exacerbación infecciosa, 11 casos (15.5%) aspergi-losis broncopulmonar, 9 casos (12.7%) con hipertensión pulmonar, 5 casos (7%) con neumotórax, 12 casos (16.9%) con ventilación mecánica, 70 casos (98.5) con insuficiencia pancreática, 10 casos (14%) con enfermedad hepatobiliar. Hubo asociación de complica-ciones extrapulmonares con el fenotipo F508. La supervivencia global fue de 150 meses. En pacientes con ventilación mecánica invasiva la supervivencia fue de 55 meses (P<0.001), en pacientes con ventilación mecánica no invasiva fue de 106 meses (P<0.001), en pacientes con neumotórax fue de 25 meses P<0.001, en pacientes con aspergilosis bronco-pulmonar alérgica fue de 125 meses P<0.01. Conclusión: la mayor compli-cación extrapulmonar de pa-cientes con FQ es la insuficien-cia pancreática. La presencia de neumotórax disminuye la supervivencia.

Introduction: Cystic fibrosis (CF) affects the exocrine epithelium, forming a thick mucus that obstructs the ducts of the different organs, with the lungs and pancreas being the most affected. This study aimed to determine the association between clinical factors and complications, as well as the survival of CF patients treated at a pediatric reference center in Mexico. Methods: This observational, longitudinal study was conducted at the National Institute of Pediatrics in Mexico from April 2012 to April 2022. Children with cystic fibrosis were entered into the study with a nonprobabilistic sample. The variables were demographic, pulmonary and extrapulmonary complications and mortality. The association was made with chi-square and survival with Kaplan- Meir. Results: Seventy-one patients were analyzed, including 41 infants (62%) and 12 preschoolers (16.9%). There were 40 men (56.3%). Fifty-seven cases (80.3%) had an infectious exacerbation, 11 cases (15.5%) had allergic bronchopulmonary aspergillosis, 9 cases (12.7%) had pulmonary hypertension, 5 cases (7%) had pneumothorax, 12 cases (16.9%) had mechanical ventilation, 70 cases (98.5%) had pancreatic insufficiency, and 10 cases (14%) had hepatobiliary disease. There was an association of extrapulmonary complications with the F508 phenotype. Overall survival was 150 months. In patients with invasive mechanical ventilation, survival was 55 months (P<0.001); in patients with noninvasive mechanical ventilation, it was 106 months (P<0.001); in patients with pneumothorax, it was 25 months (P<0.001); and in patients with allergic bronchopulmonary aspergillosis, it was 125 months (P<0.01). Conclusion: The most significant extrapulmonary complication in CF patients is pancreatic insufficiency. The presence of pneumothorax markedly decreases survival.

Evaluación de la técnica de conteo de grasas y ajuste de enzimas pancreáticas en un grupo de pacientes con insuficiencia pancreática secundaria a fibrosis quística con seguimiento en un hospital de alta complejidad / Evaluation of the fat counting technique and pancreatic enzyme adjustment in a group of patients with pancreatic insufficiency secondary to cystic fibrosis followed-up in a tertiary-level hospital

Objetivo: evaluar la efectividad de la técnica de conteo de grasas y ajuste de enzimas pancreáticas en un grupo de pacientes con insuficiencia pancreática secundaria a fibrosis quística (FQ). Materiales y métodos: En un grupo de pacientes con FQ, sin otra patología asociada, mayores de 1 año, con >10 000 UKD (unidades por kilo por día) de lipasa; se realizó educación y aplicación de técnica de conteo de grasas con ajuste enzimático, solicitando Van de Kamer y registro alimentario de 5 días durante la recolección de la muestra con un intervalo de 3 meses entre ambas determinaciones. Se evaluó la efectividad de la misma y las dosis de enzimas utilizadas mediante el porcentaje de excreción grasa (PEG), así como las variaciones en la cantidad de enzimas utilizadas y la ganancia de peso. Los datos se registraron en RED Cap (Research Electronic Data Capture) y se analizaron mediante Stata 12. Resultados: De un total de 21 pacientes, 16 completaron la intervención. El 50% presentó un índice de masa corporal (IMC) mayor del Plo 25 antes y después, un 87% alcanzó adecuación calórica mayor del 120% de la ingestas diarias recomendadas (RDA) al final, logrando un aumento promedio de z score de peso de 0,28 con una media inicial de 17 kg y final de 18,2 kg. En cuanto a la media del requerimiento enzimático fue de 14 800 UKD antes y 10 145 UKD después (z=0,002), asimismo el porcentaje de excreción grasa (PEG) tuvo una disminución del 38% (p=0,1705). Conclusiones: La implementación de la técnica de conteo de grasas y ajuste enzimático, podría ser una estrategia válida para aquellos pacientes con FQ que tienen dosis altas de enzimas e inadecuada ganancia de peso (AU)

Objective: To evaluate the effectiveness of the fat counting technique and pancreatic enzyme adjustment in a group of patients with pancreatic insufficiency secondary to cystic fibrosis (CF). Materials and methods: A group of patients with CF without other associated diseases, older than 1 year of age, lipase dose >10 000 UKD (units per kilo per day), received education on the fat counting technique with enzyme adjustment followed by its implementation of the intervention. Van de Kamer was requested and a 5-day food record was kept during the sample collection with an interval of 3 months between both measurements. The effectiveness of the technique and the enzyme doses used were evaluated based on the percentage of fat excretion (PFE), as well as the variations in the amount of enzymes used and weight gain. Data were recorded in RED Cap (Research Electronic Data Capture) and analyzed using Stata 12. Results: Of a total of 21 patients, 16 completed the intervention. Fifty percent had a body mass index (BMI) greater than Plo 25 before and after the intervention; 87% had achieved a caloric increase greater than 120% of the recommended daily intake (RDA) at the end of the study and an average increase in weight z score of 0.28 with an initial mean of 17 kg and a final mean of 18.2 kg. Mean enzyme requirement was 14 800 UKD before and 10 145 UKD after the intervention (z=0.002). PFE decreased by 38% (p=0.1705). Conclusions: The implementation of the technique of fat counting and enzyme adjustment may be a valid strategy for CF patients with high enzyme doses and inadequate weight gain. (AU)

Eurytrema coelomaticum infection: correlation between parasite burden and impairment of pancreatic exocrine enzyme secretion / Eurytrema coelomaticum: correlação entre carga parasitária e insuficiência pancreática exócrina

Eurytrema coelomaticum is a trematode reported in the pancreatic ducts of ruminants. It is conjectured that may cause disorders in the pancreas, as well as digestive and metabolic processes dependent on them. This study, determined if there is an impairment of exocrine pancreatic function, and correlated it with parasite burden. Pancreas, blood, and fecal samples were collected from 119 bovines at a abattoir. Stool samples were subjected to the gelatin and x-ray film digestion tests (to detect the presence of trypsin in feces). Using blood samples, the following biochemical tests were performed: amylase, lipase, glucose, fructosamine, cholesterol, triglycerides, total protein, albumin, and globulins. Analyses were correlated with pancreatic parasite burden. Cattle with a high parasitic load presented higher incidence of negative tests in both gelatin digestion and x-ray film digestion tests (P < 0.001) when compared to non-parasitized animals and those with a low parasitic load. Changes in those tests only occurred if the parasitemia was moderate or severe. The activity of the amylase and lipase enzymes was significantly higher in animals with low parasitemia (P < 0.05), compared to non-parasitized animals and with a high parasitic burden. In this study, in cases of high parasitemia, negative results were observed in both gelatin and x-ray film in the feces digestion tests. However, the low infection of E. coelomaticum, higher levels of serum amylase and lipase that also indicated loss of pancreatic exocrine functions were reported.

Eurytrema coelomaticum, um trematódeo de ductos pancreáticos de ruminantes. Conjectura-se que possa ocasionar transtornos nas funções pancreáticas, mais especificamente nos processos digestivos e metabólicos dependentes destas. Neste estudo, o objetivo foi determinar se há comprometimento da função pancreática exócrina, correlacionado-a a carga parasitária. Foram utilizados pâncreas e respectivas amostras de sangue e fezes de 119 bovinos. As amostras de fezes foram submetidas aos testes de digestão da gelatina em tubo e digestão de filme radiográfico, ambos para detecção de tripsina nas fezes. Foram realizados os seguintes exames bioquímicos em amostras de sangue: amilase, lipase, glicemia, frutosamina, colesterol, triglicerídeos, proteínas totais, albumina e globulinas. Após isto, as análises bioquímicas foram correlacionadas com a quantidade numérica de parasitas encontrados no pâncreas (post-mortem). Houve maior quantidade de testes negativos (digestão do filme radiográfico e prova de digestão da gelatina) nos animais com alta carga parasitária (P < 0.001), quando comparados aos animais não parasitados e com baixa carga parasitária. Portanto, os exames supracitados se alteram somente se a quantidade de parasitas for moderada ou severa. As atividades das enzimas amilase e lipase foram significativamente maiores nos animais que apresentavam baixa parasitemia (P < 0.05), em comparação com os animais com alta carga parasitária e não parasitados. Conclui-se que em quadros de alta parasitemia há alteração significativa nos testes de digestão nas fezes, e que em quadros de baixa parasitemia há alterações significativas nos valores de amilase e lipase séricas, ambos comprovando alterações pancreáticas importantes, de acordo com o quadro de parasitemia.

Comparação de custos da terapia de reposição enzimática empírica com terapia guiada por diagnóstico laboratorial da insuficiência pancreática / Costs comparison of empirical enzymatic replacement therapy with laboratory diagnosis guided therapy of pancreatic insufficiency

Introdução: a fibrose cística, também conhecida como mucoviscidose, é uma doença genética cujas manifestações resultam da disfunção do gene cystic fibrosis transmembrane conductorance regulator. Cerca de 85% dos indivíduos com essa doença desenvolvem insuficiência pancreática exógena. Objetivo: comparar os custos da terapia de reposição enzimática empírica com a terapia de reposição enzimática empírica guiada pelo teste da elastase fecal, em indivíduos com fibrose cística, acompanhados em um centro de referência para assistência à doença. Metodologia: realizou-se um estudo descritivo e comparativo, que incluiu indivíduos de 0 a 21 anos, com fibrose cística. Coletaram-se dados referentes ao período de janeiro de 2016 a fevereiro de 2020, com registros clínicos, demográficos e laboratoriais. Inicialmente, com base em critérios clínicos, os participantes foram classificados como suficientes pancreáticos ou insuficientes pancreáticos. Após o resultado da dosagem da elastase fecal, o diagnóstico do status pancreático foi reavaliado. Realizouse a estimativa dos custos do teste da elas tase fecal por participante e da terapia por reposição enzimática empírica da insuficiência pancreática em indivíduos que, posteriormente, foram diagnostica dos como suficientes pancreáticos. Resultados: incluíram-se 50 participantes, com média de idade de 9,4 anos, sendo 52% do sexo masculino. Após o resultado da dosagem da elastase fecal, 7 participantes considerados insuficientes pancreáticos e foram reclassificados como suficientes pancreáticos. No período estudado, a economia média estimada, por participante suficiente pancreático, com a suspensão das enzimas, após resultado da elastase fecal, foi de R$ 6.770,13. Conclusão: a terapia de reposição enzimática empírica no tratamento da insuficiência pancreática pode levar a custos desnecessários. A medida de dosagem da elastase fecal contribui para decisão mais objetiva da avaliação da função pancreática.

Introduction: Cystic fibrosis, also known as mucoviscidosis, is a genetic disorder whose manifestations result from dysfunction of the cystic fibrosis transmembrane conductance regulator gene. About 85% of individuals with this disease develop exogenous pancreatic insufficiency. Objetivo: to compare the costs of empirical enzyme replacement therapy with fecal elastase test-guided empirical enzyme replacement therapy in individuals with cystic fibrosis followed up at a referral center for disease care. Methodology: a descriptive and comparative study was carried out, which included individuals aged 0 to 21 years, with cystic fibrosis. Data for the period from January 2016 to February 2020 were collected, with clinical, demographic and laboratory records. Initially, based on clinical criteria, participants were classified as pancreatic sufficient or pancreatic insufficient. After the result of the fecal elastase measurement, the diagnosis of pancreatic status was reassessed. Estimates were made of the costs of the fecal elastase test per participant and of the empiric enzyme replacement therapy for pancreatic insufficiency in individuals who were later diagnosed as pancreatic sufficient. Results: fifty participants were included, with a mean age of 9.4 years, 52% male. After the result of the fecal elastase measurement, 7 participants considered as pancreatic insufficient were reclassified as pancreatic sufficient. In the period studied, the estimated mean savings, per sufficient pancreatic participant, with the suspension of enzymes, after the result of fecal elastase, was R$ 6,770.13. Conclusion: empirical enzyme replacement therapy in the treatment of pancreatic insufficiency can lead to unnecessary costs. The measurement of fecal elastase dosage contributes to a more objective decision on the assessment of pancreatic function.

Distal intestinal obstruction syndrome: a diagnostic and therapeutic challenge in cystic fibrosis / Síndrome da obstruc¸ão intestinal distal: um desafio diagnóstico e terapêutico na fibrose cística

Abstract Objective: To evaluate the demographics, genotype, and clinical presentation of pediatric patients presenting with distal intestinal obstruction syndrome (DIOS), and factors associated with DIOS recurrence. Methods: Case series of ten patients (median age 13.2 years), followed-up in a reference center, retrospectively assessed. Data analyzed included age, gender, cystic fibrosis genotype, meconium ileus at birth, hydration status, pulmonary exacerbation, Pseudomonas aeruginosa colonization, pancreatic insufficiency (PI), body mass index (BMI) at the episodes, clinical manifestations of DIOS, imaging studies performed, acute management of DIOS, maintenance therapy, and recurrence on follow-up. Results: All patients had two positive sweat chloride tests, and nine of ten also had genotype study. The most common genotype identified was homozygosis for the delta F508 mutation. In seven cases, a previous history of meconium ileus was reported. All patients had pancreatic insufficiency. Diagnosis of DIOS was based on clinical and imaging findings. Of the total number of episodes, 85% were successfully managed with oral osmotic laxatives and/or rectal therapy (glycerin enema or saline irrigation). Recurrence was observed in five of ten patients. Conclusion In this first report of pediatric DIOS in South America, the presence of two risk factors for DIOS occurrence was universal: pancreatic insufficiency and severe genotype. Medical history of meconium ileus at birth was present in most patients, as well as in the subgroup with DIOS recurrence. The diagnosis relied mainly on the clinical presentation and on abdominal imaging. The practices in the management of episodes varied, likely reflecting changes in the management of this syndrome throughout time.

Resumo Objetivo: Avaliar os dados demográficos, o genótipo e o quadro clínico de pacientes pediátricos que apresentam síndrome da obstrução intestinal distal (DIOS) e os fatores associados à recidiva da DIOS. Métodos: Casuística de 10 pacientes (média de 13,2 anos) monitorados em um centro de referência e avaliados de forma retroativa. Os dados analisados incluíram idade, sexo, genótipo da fibrose cística, íleo meconial no nascimento, estado de hidratação, exacerbação pulmonar, colonização por Pseudomonas aeruginosa, insuficiência pancreática (IP), IMC nos episódios, manifestações clínicas da DIOS, estudos de diagnóstico por imagem realizados, manejo agudo da DIOS, terapia de manutenção e recidiva no acompanhamento. Resultados: Todos os pacientes apresentaram dois exames de cloreto no suor positivos e 09/10 também apresentaram estudo do genótipo. O genótipo mais comum identificado foi a homozigose da mutação delta F508. Em sete casos foi mencionado um histórico de íleo meconial. Todos os pacientes apresentaram insuficiência pancreática. O diagnóstico da DIOS teve como base achados clínicos e de imagem; 85% do número total de episódios foram tratados com sucesso com laxantes osmóticos orais e/ou terapia retal (enema de glicerina ou irrigação salina). A recidiva foi observada em 5 de 10 pacientes. Conclusão: Neste primeiro relatório da DIOS pediátrica na América do Sul, a presença de dois fatores de risco na ocorrência da DIOS foi universal: insuficiência pancreática e genótipo associado a doença grave. O histórico de íleo meconial no nascimento esteve presente na maioria dos pacientes, bem como no subgrupo com recidiva da DIOS. O diagnóstico dependeu principalmente do quadro clínico e do diagnóstico por imagem abdominal. As práticas de manejo de episódios variaram, provavelmente refletiram as mudanças no tratamento dessa síndrome ao longo do tempo.

Clinical features and gene mutations of children with Shwachman-Diamond syndrome and malignant myeloid transformation / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome (SDS) and malignant myeloid transformation.@*METHODS@#Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation, and their clinical features and genetic mutations were analyzed.@*RESULTS@#Of the 11 children with SDS, 9 (82%) presented with refractory cytopenia of childhood (RCC), 1 (9%) had myelodysplastic syndrome with excess blasts (MDS-EB), and 1 (9%) had acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). The median age of onset of malignant myeloid transformation was 48 months (ranged 7 months to 14 years). Of the 11 children, 45% had abnormalities in the hematological system alone. Mutations of the SBDS gene were detected in all 11 children, among whom 5 (45%) had c.258+2T>C homozygous mutation and 3 (27%) had c.184A>T+c.258+2T>C compound heterozygous mutation. The new mutations of the SBDS gene, c.634_635insAACATACCTGT+c.637_638delGA and c.8T>C, were rated as "pathogenic" and "possibly pathogenic" respectively. The 3-year predicted overall survival rates of children transformed to RCC and MDS-EB/AML-MRC were 100% and 0% respectively (P=0.001).@*CONCLUSIONS@#SDS children may have hematological system symptoms as the only manifestation, which needs to be taken seriously in clinical practice. The type of malignant transformation is associated with prognosis.

Clinical features, diagnosis, and treatment of Chinese children with Shwachman-Diamond syndrome / 中国当代儿科杂志

In order to clearly define the features of Shwachman-Diamond syndrome (SDS) in Chinese children, this article analyzes and summarizes the epidemiology, clinical features, and key points in the diagnosis and treatment of SDS in Chinese children with review of the clinical data of 27 children with SDS from related articles published previously. A comparative analysis was made between the Chinese and international data related to childhood SDS. The results showed a male/female ratio of about 2:1 in the Chinese children with SDS, with an age of onset of <1 month to 5 years (median 1 month) and an age of 3 months to 12 years (median 12 months) at the time of confirmed diagnosis. Reductions in peripheral blood cells due to myelopoiesis inhibition were observed in all 27 children with SDS, among whom 93% had neutropenia. Chronic diarrhea (85%), liver damage (78%), and short stature (83%) were the three main clinical features of SDS. Supplementation of pancreatin and component blood transfusion may temporarily alleviate the disease, while allogeneic hematopoietic stem cell transplantation is still an effective radical treatment. The comparative analysis of the Chinese and oversea data showed that compared with those in the European and American countries, the children with SDS in China had significantly higher incidence rates of chronic diarrhea, reductions in peripheral blood cells (three lineages), and liver damage, and there were also differences in the type of mutant genes.

Relação entre genótipo e insuficiência pancreática em crianças e adolescentes com fibrose cística de um centro de referência no Brasil / Relationship between genotype and pancreatic insufficiency in children and adolescents with cystic fibrosis in a referral center in Brazil

Introdução: fibrose cística (FC) é uma doença genética que culmina em alterações na proteína transmembrana CFTR, resultando na produção de muco mais espesso em diversos órgãos, destacando-se os tratos respiratório e digestório. A insuficiência pancreática (IP) acomete até 95% dos pacientes com FC. Objetivos: determinar a frequência de IP através da dosagem de elastase fecal-1 (EF-1) e compará-la com o genótipo de pacientes com FC assistidos em um centro de referência. Metodologia: foi realizado um estudo transversal, incluindo-se pacientes com FC de 0 a 20 anos. Após a inclusão dos sujeitos à pesquisa, foi realizada consulta ao prontuário para a obtenção de dados clinicos e demograficos e amostras de fezes foram obtidas para dosagem da (EF-1). Os pacientes foram submetidos à análise molecular das mutações por métodos convencionais, através da extração do DNA em sangue periférico. Quando duas mutações patológicas não foram identificadas, o sequenciamento de nova geração com utilização da plataforma Illumina HiSeq foi realizado em amostras da mucosa oral. Resultados: foram incluídos 31 pacientes, 17 (54,8%) do sexo feminino, mediana de idade de 10 anos, e apenas um paciente foi classificado como branco. Vinte e dois (70,9%) pacientes apresentaram dosagem de EF-1 inferior a 200 µg/g, compatível com o diagnóstico de IP. Destes, 21 (95,4%) apresentaram dosagem de EF-1 menor ou igual a 15µg/g, caracteristica de IP grave. Todos os pacientes com IP apresentavam duas mutações de classes I a III. Conclusão: a IP foi identificada em 70% dos pacientes, ocorrendo em todos os pacientes com duas mutações de classe I-III.

Introduction: cystic fibrosis (CF) is a genetic disease that culminates in alterations in the CFTR transmembrane protein, resulting in the production of thicker mucus in various organs, especially the respiratory and digestive tract. Pancreatic insufficiency (PI) affects up to 95% of CF patients. Objectives: To determine the frequency of PI by measuring fecal elastase-1 (FE-1) and comparing it with the genotype of CF patients assisted at a referral Center. Methodology: a cross-sectional study was conducted, including patients with CF from 0 to 20 years. After the inclusion of the subjects to the research, medical records were consulted to obtain clinical and demographic data and stool samples were obtained for the measurement of (FE-1). Patients were submitted to molecular analysis of mutations by conventional methods by DNA extraction in peripheral blood. When two pathological mutations were not identified, next-generation sequencing using the Illumina HiSeq platform was performed on oral mucosa samples. Results: thirty one patients were included, 17 (54.8%) female, median age 10 years, and only one patient was classified as white. Twenty-two (70.9%) patients had an FE-1 dosage of less than 200 µg / g, compatible with the diagnosis of pancreatic insufficiency (PI). Of these, 21 (95,4%) had an EF-1 dosage less than or equal to 15µg / g, characteristic of severe PI. All patients with two mutations class I to III were PI. Conclusion: PI was identified in 70% of patients, occurring in all patients with class I-III mutations.

Hepatobiliary disease in children and adolescents with cystic fibrosis / Doença hepatobiliar em crianças e adolescentes com fibrose cística

Abstract Objectives: The aims of the study were to determine the frequency of hepatobiliary disease in patients with cystic fibrosis and to describe the sociodemographic, clinical, and laboratory profile of these patients. Methods: This was a retrospective, descriptive, and analytical study of 55 patients diagnosed with cystic fibrosis, aged between 3 months and 21 years, followed-up from January 2008 to June 2016 in a referral center. Medical records were consulted and sociodemographic, clinical and laboratory data, including hepatobiliary alterations, imaging studies, genetic studies, liver biopsies, and upper digestive endoscopies were registered. Results: Hepatobiliary disease was diagnosed in 16.4% of the patients and occurred as an initial manifestation of cystic fibrosis in 55.6% of these cases. The diagnosis of hepatopathy occurred before or concomitantly with the diagnosis of cystic fibrosis in 88.9% of the children. All patients with hepatobiliary disease were considered non-white, with a predominance of females (77.8%) and median (IQR) of 54 (27-91) months. Compared with the group without hepatobiliary disease, children with liver disease had a higher frequency of severe mutations identified in the CFTR gene (77.8% vs. 39.6%, p = 0.033) and severe pancreatic insufficiency (88.9% vs. 31.6%, p = 0.007). Conclusion: The frequency of hepatobiliary disease was high, with a very early diagnosis of the disease and its complications in the studied series. A statistical association was observed between the occurrence of hepatobiliary disease and the presence of pancreatic insufficiency and severe mutations in the CFTR gene. It is emphasized that cystic fibrosis is an important differential diagnosis of liver diseases in childhood.

Resumo Objetivos: Os objetivos do estudo foram determinar a frequência da doença hepatobiliar em pacientes com fibrose cística e descrever o perfil sociodemográfico, clínico e laboratorial destes. Métodos: Estudo retrospectivo, descritivo e analítico de 55 pacientes com diagnóstico de fibrose cística, entre três meses e 21 anos, acompanhados de janeiro de 2008 a junho de 2016 em um centro de referência. Foi realizada consulta aos prontuários médicos, registrando-se os dados sociodemográficos, clínicos e laboratoriais, incluindo-se alterações hepatobiliares, exames de imagem, estudos genéticos, biópsias hepáticas e endoscopias digestivas altas. Resultados: A doença hepatobiliar foi diagnosticada em 16,4% dos pacientes e ocorreu como manifestação inicial da fibrose cística em 55,6% destes casos. O diagnóstico da hepatopatia ocorreu antes ou concomitante ao diagnóstico da fibrose cística em 88,9% das crianças. Todos os pacientes com doença hepatobiliar foram considerados não brancos, havendo predominância do sexo feminino (77,8%) e mediana (I.I.Q) de idade de 54 (27-91) meses. Em comparação com o grupo sem doença hepatobiliar, as crianças com hepatopatia tiveram maior frequência de mutações graves no gene CFTR identificadas (77,8% vs 39,6%; p = 0,033) e de insuficiência pancreática grave (88,9% vs 31,6%; p = 0,007). Conclusão: A frequência de doença hepatobiliar foi elevada, observando-se um diagnóstico muito precoce da mesma e de suas complicações na casuística estudada. Houve associação estatística entre a ocorrência de doença hepatobiliar e a presença de insuficiência pancreática e de mutações graves do gene CFTR. Enfatiza-se que a fibrose cística represente um importante diagnóstico diferencial de hepatopatias na infância.

Fatty acid profile in erythrocytes associated with serum cytokines in pediatric cystic fibrosis patients / Perfil de ácidos graxos nos eritrócitos associados com citocinas séricas em pacientes pediátricos com Fibrose Cística

ABSTRACT Objective To analyze erythrocyte fatty acid composition and its association with serum cytokine levels in pediatric cystic fibrosis patients. Methods A cross-sectional study was performed at a reference center in Rio de Janeiro, Brazil. We have included all pediatric patients aged 5-19 years with confirmed cystic fibrosis diagnosis. Erythrocyte fatty acid composition and serum cytokine (TNF-α, IL-1β, IL-6 and IL-8) and C-reactive protein levels were measured. The cut-off point to determine essential fatty acids deficiency was the linoleic acid concentration of <21%. Results Twenty-six children (<10 years old) and thirty-one adolescents were studied. Most patients were female and heterozygous for DF508 mutation and suffered from exocrine pancreatic insufficiency. Both children and adolescents had lower linoleic acid concentration (<21%). TNF-α was the only pro-inflammatory marker whose levels were increased; the increase was greater in children. An association between fatty acid composition in erythrocytes and cytokines IL-1β and IL-6 was observed (p<0.05). Conclusion The pediatric cystic fibrosis patients studied presented a deficiency of essential fatty acids, and an association between fatty acid profile in erythrocytes and serum pro-inflammatory cytokines was observed. These findings highlight the importance of this type of assessment that may open new possibilities for studying pathophysiology and treating cystic fibrosis patients, such as the dietary supplementation with n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids). However, further longitudinal studies are needed for better clarification of the imbalance in lipid metabolism and inflammation in cystic fibrosis

RESUMO Objetivo Analisar a composição dos ácidos graxos nos eritrócitos e sua associação com os níveis séricos de citocinas em pacientes pediátricos com fibrose cística. Métodos Estudo transversal, realizado em um centro de referência no Rio de Janeiro/Brasil. Foram incluídos todos os pacientes pediátricos com diagnóstico confirmado de fibrose cística, entre cinco e 19 anos de idade. Foram analisadas a composição de ácidos graxos nos eritrócitos, as citocinas séricas (TNFα, IL-1, IL-6 e IL-8) e a proteína C reativa. O ponto de corte para determinar a deficiência de ácidos graxos essenciais foi a concentração de ácido linoleico <21%. Resultados Foram estudadas 26 crianças (<10 anos) e 31 adolescentes, sendo a maioria do sexo feminino, heterozigoto para a mutação DF508 e com insuficiência pancreática exócrina. Nas crianças e nos adolescentes as concentrações de ácido graxo linoleico eram baixas (<21%). O TNF-α foi o único marcador pró-inflamatório cujas concentrações estavam aumentadas, principalmente nas crianças. Uma associação entre a composição de ácidos graxos nos eritrócitos e as citocinas IL-1β e IL-6 foi observada (p<0,05). Conclusão Os pacientes pediátricos estudados apresentaram deficiência de ácidos graxos essenciais e foi observada associação entre o perfil de ácidos graxos nos eritrócitos com as citocinas pró-inflamatórias séricas. Os achados destacam a importância deste tipo de avaliação sobre a fisiopatologia e o tratamento de pacientes com fibrose cística, como a suplementação com ácidos graxos n-3 (eicosapentaenoico e docosahexaenoico). No entanto são necessários mais estudos longitudinais no esclarecimento entre o desequilíbrio do metabolismo lipídico e a inflamação na fibrose cística.

Cystic Fibrosis: Clinical Phenotypes in Children and Adolescents / 대한소아소화기영양학회지

PURPOSE: The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis. METHODS: A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations. RESULTS: Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02). CONCLUSION: The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.

Insuficiência pancreática exócrina em cão - Relato de caso / Exocrine pancreatic insufficiency in a dog ­ Case report / Insuficiencia pancreática exócrina en perro- Relato de caso

A insuficiência pancreática exócrina é uma incapacidade na secreção de enzimas digestivas decorrentes da diminuição do tecido acinar do pâncreas acarretando uma má digestão e absorção. O presente trabalho relata o caso de uma cadela SRD de um ano e meio com histórico de emagrecimento, esteatorréia, burburinhos e polifagia que foi diagnostica com insuficiência pancreática exócrina após teste de imunorreatividade da tripsina. O tratamento instituído com suplementação de enzimas pancreáticas foi eficiente no controle e evolução da doença.(AU)

Exocrine pancreatic insufficiency is the inability to secrete digestive enzymes due to the decrease in the acinar tissue of the pancreas leading to poor digestion and absorption. This work is a case report of a 1.5-years' old mongrel bitch with a history of weight loss, steatorrhea, rumbling sounds and polyphagia that was diagnosed with exocrine pancreatic insufficiency after a trypsin immunoreactivity test. The pancreatic enzyme supplementation was efficient in controlling the evolution of the disease.(AU)

La insuficiencia pancreática exocrina es una incapacidad en la secreción de enzimas digestivas derivadas de la disminución del tejido acinar del páncreas, acarreando mala digestión y absorción. El presente trabajo relata el caso de una perra SRD de un año y medio con historial de adelgazamiento, esteatorrea, burbujas y polifagia que fue diagnosticada con insuficiencia pancreática exocrina después de la prueba de inmune reactividad de la tripsina. El tratamiento instituido con suplementación de enzimas pancreáticas fue eficiente en el control y evolución de la enfermedad.(AU)

Displasia Torácica Asfixiante o Síndrome de Jeune / Asphyxiating Thoracic Dysplasia or Jeune Syndrome

El Síndrome de Jeune es una distrofia esquelética rara, caracterizada por costillas cortas y alteraciones en extremidades y pelvis. La dificultad respiratoria viene determinada por el grado de estrechez torácica, más tar-díamente pueden aparecer insuficiencia pancreática o renal. Se presenta el caso de un lactante de 7 meses que acudió al Hospital Vicente Corral Moscoso por neumonía sin respuesta al tratamiento en hospital cantonal;a su ingreso presenta insuficiencia respiratoria y llama la atención un tóraxcilíndrico, marcadamente estrecho y alargado además de micromelia y polidactilia. Se administró soporte ventilatorio y antibióticos teniendo una evolución favorable durante hospitalización.

Jeune Syndrome is a rare skeletal dystrophy, characterized by short ribsand alterations in limbs and pelvis. The respiratory distress is determinedby the degree of thoracic stricture, and later, pancreatic or renal insufficiencymay occur. A case of a 7-months-old infant who came to the Vicente Corral Moscoso Hospital for pneumonia without treatment response in the cantonal hospital was presented. When the patient arrives he presentsa respiratory insufficiency and it calls the attention a cylindrical thorax,markedly narrow and elongated in addition of micromelia and polydactyly.A respiratory support and antibiotics were given during hospitalization having a favorable evolution.

Controversias sobre el rastreo de los niveles séricos de vitamina D y su suplementación / Controversies about serum vitamin D levels screening and its supplementation

Si bien los niveles bajos de vitamina D se han asociado con varios resultados de interés en salud, aún resulta motivo de controversia qué significa un nivel bajo, cual es la utilidad de su suplementación y cuales son sus potenciales efectos adversos. En ese contexto, se realizó en el Servicio de Medicina Familiar y Comunitaria del Hospital Italiano un taller de discusión denominado "Actividad ECCO" (Evidencia Científica en la Clínica Cotidiana) en la que fueron presentados los resulta-dos de estudios identificados que hubieran comparado el uso de vitamina D (con o sin suplementación de calcio) ver-sus placebo, con el objetivo de discutir cuál es la evidencia actual para el rastreo de deficiencia de vitamina D y para, eventualmente, recomendar o no su suplementación. Este artículo resume la evidencia identificada y las conclusiones consensuadas en dicha actividad. (AU)

Although low levels of vitamin D have been associated with several health outcomes, it is controversial what a low level means, the usefulness of its supplementation and its potential adverse effects. In this context, a workshop called "ECCO Activity" (Scientific Evidence in the Daily Clinic) was held in the Family and Community Medicine Division of Hospital Italiano de Buenos Aires, where the results of identified studies that compared the use of vitamin D (with or without calcium supplementation) versus placebo, with the aim of discussing what is the current evidence for screening of vitamin D deficiency and to, eventually, recommend or not its supplementation. This article summarizes the identified evidence and the agreed conclusions in that activity. (AU)

Comparing the enzyme replacement therapy cost in post pancreatectomy patients due to pancreatic tumor and chronic pancreatitis

ABSTRACT Background - Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. Objective - The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Methods - Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, P<0.05 was considered statistically significant. Results - The annual cost of the treatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. Conclusion - There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

RESUMO Contexto - Dentre as complicações pós-operatórias tardias da pancreatectomia estão as insuficiências pancreáticas exócrina e endócrina. O reconhecimento da presença de insuficiência pancreática exócrina impõe, como tratamento padrão, a reposição de enzimas pancreáticas. Pacientes portadores de pancreatite crônica, com dor clinicamente intratável ou com alguma complicação com indicação de tratamento cirúrgico, podem vir a apresentar insuficiência pancreática exócrina ou ter essa condição agravada requerendo adequação de dose de enzimas pancreáticas. Objetivo - O objetivo deste estudo é comparar a dose necessária de enzima pancreática e o custo do tratamento de reposição enzimática em pacientes pancreatectomizados, com e sem pancreatite crônica. Métodos - Estudo transversal observacional. No primeiro semestre de 2015 pacientes acompanhados no ambulatório de Cirurgia do Aparelho Digestivo do HC-FMUSP, submetidos a pancreatectomia há pelo menos 6 meses e em terapia de reposição enzimática foram incluídos nessa casuística. O estudo foi aprovado pelo Comitê de Ética. Os pacientes foram divididos em dois grupos, de acordo com a presença ou ausência de pancreatite crônica prévia à cirurgia pancreática. Para este estudo, P<0,05 foi considerado como estatisticamente significante. Resultados - O custo anual do tratamento foi R$ 2150,51 ± 729,39; R$ 2118,18 ± 731,02 em pacientes sem pancreatite crônica e R$ 2217,74 ± 736,30 em pacientes com pancreatite crônica. Conclusão - Não houve diferença estatisticamente significante no custo do tratamento de reposição enzimática entre pacientes pancreatectomizados com ou sem pancreatite crônica prévia à indicação cirúrgica.

Pain Control, Nutritional and Emotional Support / 대한췌담도학회지

Pancreatic cancer is one of the most lethal malignancies. Despite the availability of newer and better antineoplastic combinations, the 5-year survival rate for all stages of pancreatic cancer remains only 6%. Palliative care represents an important aspect of care in patient with pancreatic cancer. Thus, optimal palliation of symptoms to maximize remaining quality of life is of primary importance to most patients. This review discusses highlights the most significant problems faced when caring for patients with advanced pancreatic cancer. Common problems include pain, pancreatic insufficiency, anorexia-cachexia and depression. To provide optimal and meaningful supportive care for patients with advanced pancreatic cancer is complex and requires ongoing close monitoring of the physical and emotional aspects of the patient. Prompt management of the many symptoms and problems associated with pancreatic cancer is essential to minimize distress and improve quality of life for patients with this fatal disease. Recognizing end-of-life concerns and patient preferences during the dying process helps clinicians find ways to alleviate suffering for patients and families.

Two Cases of Shwachman-Diamond Syndrome in Adolescents Confirmed by Genetic Analysis

No abstract available.