Actualización en fibrosis quística: diabetes relacionada a fibrosis quística en la era de los moduladores del regulador de transmembrana de fibrosis quística (CFTR) / Update on cystic fibrosis/cystic fibrosis related diabete in the era of transmembrane regulator in cystic fibrosis (CFTR)

Las disglicemias, objetivadas en el test de tolerancia a la glucosa de 2 horas y en el monitoreo continuo de glicemia, son el factor de riesgo principal para el desarrollo de la diabetes relacionada a fibrosis quística (FQ) (DRFQ), la que constituiría la etapa final de un continuo de alteraciones del metabolismo de la glucosa en los pacientes con FQ. Estas disglicemias se deben tanto al daño directo de las células de los islotes pancreáticos productores de insulina, como al aumento de la resistencia a la insulina asociada al estado inflamatorio sistémico de la FQ. El uso cada vez más precoz de los moduladores del CFTR debiera contribuir a evitar el desarrollo de DRFQ y sus complicaciones. La siguiente revisión se enfoca en los efectos de los moduladores del CFTR en la tolerancia a la glucosa en pacientes con FQ.

Dysglycemia, observed in the 2-hour glucose tolerance test and in the continuous monitoring of glycemia, are the main risk factor for the development of diabetes related to cystic fibrosis (CF), which constitutes the final stage of a continuum of impaired glucose metabolism in people with CF. These dysglycemias are due both to direct damage to insulin-producing pancreatic islet cells, and to increased insulin resistance associated with the systemic inflammatory state of CF. The increasingly early use of CFTR modulators should help prevent the development of CRFD and its complications. The following review focuses on the effects of regulador de transmembrana de fibrosis quística (CFTR) modulators on glucose tolerance in people with CF.

Approach and anesthetic management for kidney transplantation in a patient with bilateral lung transplantation: case report

Abstract Lung transplantation is the last resort for end-stage lung disease treatment. Due to increased survival, lung recipients present an increased likelihood to be submitted to anesthesia and surgery. This case report describes a 23-year-old female patient with history of lung transplantation for cystic fibrosis, with multiple complications, and chronic kidney disease, and who underwent kidney transplantation under general anesthesia. Understanding the pathophysiology and changes related to immunosuppressive therapy is essential to anesthetic technique planning and safety, and for perioperative management. The success of both anesthesia and surgery requires a qualified multidisciplinary team due to the rarity of the clinical scenario and high incidence of associated morbidity and mortality.

Predictive factors for premature birth and respiratory exacerbation in pregnancies of women with cystic fibrosis

Abstract Objective: In this present study, the authors evaluated the predictive factors for adverse maternal-fetal outcomes in pregnancies of women with cystic fibrosis (CF). Patients were followed up by a referral center for adults in southern Brazil. Methods: This is a retrospective cohort study that used data from electronic medical records regarding pregnancies of women diagnosed with CF. Results: The study included 39 pregnancies related to 20 different women. The main adverse outcomes were high prevalence rates of premature birth (38.5%) and maternal respiratory exacerbation (84.6%). Lower body mass index (BMI) values (< 20.8) and younger ages of CF diagnosis increased the risk of premature birth. The presence of methicillin-resistant and absence of methicillin-sensitive Staphylococcus aureus, as well as a younger age of diagnosis, increased the risk of maternal respiratory exacerbation during pregnancy. Conclusions: Conception in women with CF is often associated with maternal and fetal complications. Continuous monitoring by a multidisciplinary team should emphasize appropriate nutritional status, investigation of bacterial colonization, and immediate attention to respiratory exacerbations.

Brazilian Guidelines for Nutrition in Cystic Fibrosis

ABSTRACT Objective To develop a scientific consensus on nutrition in cystic fibrosis. Methods Sixteen coordinators elaborated relevant questions on nutritional therapy in cystic fibrosis, which were divided into six sections: nutritional assessment, nutritional recommendations, nutritional intervention, dietary counseling, special situations and enzyme replacement, and gastrointestinal manifestations. Two to three specialists in the field were responsible for each section and obtaining answers formulated based on standardized bibliographic searches. The available literature was searched in the PubMed®/MEDLINE database, after training and standardization of search strategies, to write the best level of evidence for the questions elaborated. Issues related to disagreement were discussed until a consensus was reached among specialists, based on the current scientific literature. Results Forty-two questions were prepared and objectively answered, resulting in a consensus of nutritional therapy in cystic fibrosis. Conclusion This work enabled establishing a scientific consensus for nutritional treatment of cystic fibrosis patients.

Diabetes de inicio precoz en pacientes con fibrosis quística, a propósito de 3 casos / Early-onset diabetes in patients with cystic fibrosis, about 3 cases

INTRODUCCIÓN. La diabetes es la complicación extrapulmonar más frecuente en adultos con fibrosis quística. Existen escasas publicaciones de diabetes relacionada a la fibrosis quística en preescolares a nivel mundial. En Chile se desconoce su prevalencia. MÉTODO. Reportamos una serie de tres casos de niños con fibrosis quística (FQ) y diagnóstico de diabetes a muy temprana edad. RESULTADOS. Caso 1: Niño de 8 años, con diagnóstico de fibrosis quística a los 3 meses de vida por test de sudor y estudio genético p.Phe508del /-. Presenta hiperglicemia no cetósica desde los 6 meses de edad, con colonización traqueal de Staphylococcus Aureus (SA) y Pseudomona Aeruginosa (PA) y debut de diabetes a los 2 años 1 mes. Caso 2: Niño de 16 años, a los 7 meses de vida se diagnostica FQ por test de sudor y estudio genético p.Phe508del /-. Presenta colonización traqueal por SA y múltiples infecciones por PA. A los 5 años 7 meses se diagnostica diabetes presentando cetosis al debut. Caso 3: Niño de 13 años, con diagnóstico de FQ a los 7 meses de vida mediante test de sudor y estudio genético p.Phe508del/-. Presenta colonización traqueal por SA y múltiples infecciones por PA, se realiza diagnóstico de diabetes a los 2 años 7 meses de edad. DISCUSIÓN: La diabetes asociada a fibrosis quística es una complicación frecuente en adultos con fibrosis quística, pero puede presentarse desde edades tempranas. Se debe tener alto nivel de sospecha para el diagnóstico oportuno y óptimo manejo.

INTRODUCTION: Diabetes is the most common extra pulmonary complication in adults with cystic fibrosis (CF). There are few reports of diabetes related to (CF) in preschool children worldwide. Prevalence in Chile is unknown. MÉTODO: We report ta serie of three cases of children with CF and diagnosis of diabetes at an early age. Case 1: Boy 8 year old, CF diagnosed at the age of 3 months by sweat test and genetic study p.Phe508del/-. He presented non-ketotic hyperglycemia since he was 6 months old, with tracheal colonization of Staphylococcus Aureus (SA) and Pseudomona Aeruginosa (PA) , and diagnosis of diabetes at the age of 2 years 1 month. Case 2: Boy patient, 16 years old, with diagnosis of CF at the of age 7 months by sweat test and genetic study p.Phe508del/-. He presents tracheal colonization by SA and multiple PA infections. At the age 5 years 7 months, diabetes is diagnosed, presenting ketosis at the beginning. Case 3: Boy 13 years diagnosed with CF at the age of 7 months, presented sweat test and genetic study p.Phe508del/-. He presents tracheal colonization by SA and multiple infections. DISCUSSION: CF related diabetes is common in adults with cystic fibrosis, but it can be diagnosed in early childhood. A high level of suspicious is required for a proper and timely diagnosis

SARS-CoV-2 infection in a pediatric patient with cystic fibrosis / Infección por SARS-CoV-2 en un paciente pediátrico con fibrosis quística

Abstract Background: Cystic fibrosis (CF) is a potentially mortal disease characterized by a chronic pulmonary disease with persistent airway infection. Children with this disease are more susceptible to respiratory infections due to the limitation in mucociliary transport and anatomical disruption of the bronchial tree. SARS-CoV-2 causes COVID-19, a respiratory illness related to exacerbations of chronic pulmonary pathologies in children, such as CF and asthma. There are not enough case reports on pediatric patients with SARS-CoV-2 infection and CF, for which we share our experience. Case report: A 22-month-old male patient diagnosed with CF presented in the hospital with cough, fever, and increased respiratory work. The patient received supplemental oxygen and antibiotic and antiviral therapy. Positive results for type B influenza and RT-PCR (reverse transcription-polymerase chain reaction) for SARS-CoV-2 were obtained. Due to the persistence of respiratory difficulty, high-flow therapy was initiated, with a good response. After an episode of hypoxemia, bradycardia, and increased respiratory work secondary to accumulated secretions, orotracheal intubation and invasive mechanical ventilation were performed. The patient evolved with clinical and gasometric improvement. After 10 days of in-hospital antibiotic management with adequate clinical evolution, the patient was discharged to complete oral treatment and home isolation. Conclusions: We present a case of chronic respiratory disease and SARS-CoV-2 infection with severity criteria in a pediatric patient. The evolution was favorable with timely support management and antibiotic therapy in a third-level hospital.

Resumen Introducción: La fibrosis quística es una afección potencialmente mortal caracterizada por enfermedad pulmonar crónica con infección persistente de las vías aéreas. Los niños con esta enfermedad son más susceptibles a infecciones respiratorias debido a la limitación en el transporte mucociliar y la distorsión anatómica del árbol bronquial. El SARS-CoV-2 (coronavirus tipo 2 del síndrome agudo respiratorio grave) es el virus causante de la COVID-19, enfermedad respiratoria que puede estar relacionada con exacerbaciones de patologías pulmonares crónicas en niños, como la fibrosis quística y el asma. No hay suficientes reportes de casos de pacientes pediátricos con infección por SARS-CoV-2 y fibrosis quística, por lo cual se comparte la presente experiencia. Caso clínico: Paciente de sexo masculino de 22 meses de edad con diagnóstico de fibrosis quística que presentó tos, fiebre y aumento en el trabajo respiratorio. A su ingreso se inició manejo con oxígeno suplementario y tratamiento antibiótico y antiviral. Se obtuvo prueba positiva para influenza tipo B y para SARS-CoV-2 por RT-PCR (reacción en cadena de la polimerasa de transcriptasa inversa). Ante un episodio de hipoxemia, bradicardia y mayor trabajo respiratorio, requirió intubación orotraqueal y ventilación mecánica invasiva. El paciente evolucionó con mejoría clínica y gasométrica. Después de 10 días de manejo antibiótico intrahospitalario, con adecuada evolución clínica, egresó para completar tratamiento por vía oral y aislamiento en casa. Conclusiones: Se presenta el caso de un paciente pediátrico con enfermedad respiratoria crónica de base e infección por SARS-CoV-2 con criterios de gravedad. El paciente evolucionó favorablemente con el manejo de soporte oportuno y terapia de antibióticos en un hospital de tercer nivel.

Clinical outcomes of cystic fibrosis patients with hemoptysis treated with bronchial artery embolization / Desfechos clínicos de pacientes com fibrose cística e hemoptise tratada por meio de embolização arterial brônquica

ABSTRACT Objective: Massive hemoptysis is one of the most serious complications in patients with cystic fibrosis (CF). This study aimed to evaluate the hemoptysis-free period following bronchial and non-bronchial artery embolization (BAE/non-BAE) in CF patients and to investigate predictors of recurrent bleeding and mortality by any cause. Methods: This was a retrospective cohort study of CF patients ≥ 16 years of age undergoing BAE/non-BAE for hemoptysis between 2000 and 2017. Results: We analyzed 39 hemoptysis episodes treated with BAE/non-BAE in 17 CF patients. Hemoptysis recurrence rate was 56.4%. Of the sample as a whole, 3 (17.6%) were hemoptysis-free during the study period, 2 (11.8%) underwent lung transplantation, and 3 (17.6%) died. The median hemoptysis-free period was 17 months. The median hemoptysis-free period was longer in patients with chronic infection with Pseudomonas aeruginosa (31 months; 95% CI: 0.00-68.5) than in those without that type of infection (4 months; 95% CI: 1.8-6.2; p = 0.017). However, this association was considered weak, and its clinical significance was uncertain due to the small number of patients without that infection. Conclusions: BAE appears to be effective in the treatment of hemoptysis in patients with CF.

RESUMO Objetivo: A hemoptise maciça é uma das complicações mais graves em pacientes com fibrose cística (FC). O objetivo deste estudo foi avaliar o período livre de hemoptise após a embolização arterial brônquica/não brônquica (EAB/não EAB) em pacientes com FC e investigar preditores de sangramento recorrente e mortalidade por qualquer causa. Métodos: Trata-se de um estudo retrospectivo de coorte de pacientes com FC com idade ≥ 16 anos submetidos a EAB/não EAB para o tratamento de hemoptise entre 2000 e 2017. Resultados: Foram analisados 39 episódios de hemoptise tratada por meio de EAB/não EAB em 17 pacientes com FC. A taxa de recidiva da hemoptise foi de 56,4%. Do total de pacientes, 3 (17,6%) permaneceram sem hemoptise durante o estudo, 2 (11,8%) foram submetidos a transplante de pulmão e 3 (17,6%) morreram. A mediana do período sem hemoptise foi de 17 meses. A mediana do período sem hemoptise foi maior em pacientes com infecção crônica por Pseudomonas aeruginosa (31 meses; IC95%: 0,00-68,5) do que naqueles sem esse tipo de infecção (4 meses; IC95%: 1,8-6,2; p = 0,017). No entanto, essa associação foi considerada fraca, e sua importância clínica foi considerada incerta em virtude do pequeno número de pacientes sem essa infecção. Conclusões: A EAB parece ser eficaz no tratamento de hemoptise em pacientes com FC.

Diabetes relacionada con la fibrosis quística / Cystic fibrosis-related diabetes

Los avances en el campo de la fibrosis quística han aumentado la esperanza de vida de estos pacientes, por lo que cada vez es más prevalente la Diabetes Relacionada con la Fibrosis Quística (DRFQ) y sus complicaciones. La DRFQ se asocia a mayor morbimortalidad, deterioro de la función pulmonar y del estado nutricional. Por lo mismo, el manejo óptimo de esta patología depende de un diagnóstico precoz, tratamiento individualizado y vigilancia de las complicaciones diabéticas. El screening de DRFQ debe realizarse anualmente a partir de los 10 años, mediante una Prueba de Tolerancia a la Glucosa Oral (PTGO), lo cual permite el diagnóstico. El manejo de esta patología tiene por objetivo estabilizar y mejorar la función pulmonar y el estado nutricional y metabólico de los pacientes. Actualmente, la insulina es el tratamiento farmacológico de elección para controlar la hiperglicemia y el esquema de uso debe ser individualizado para cada persona. En caso de enfermedades agudas pueden existir mayores requerimientos de insulina. Además, se deben tener consideraciones especiales en cuanto a la dieta y la insuficiencia pancreática exocrina que presentan estos pacientes. Para la vigilancia de complicaciones microvasculares se debe realizar una monitorización anual a partir de los 5 años desde el diagnóstico de DRFQ. Debido a la complejidad de estos pacientes, para alcanzar el mejor cuidado posible se necesita un enfoque multidisciplinario con distintos profesionales de la salud coordinados, incluyendo en la toma de decisiones al paciente y su familia.

Advances made in the field of cystic fibrosis have increased the life expectancy of these patients, which is why Cystic Fibrosis-Related Diabetes (CFRD) and its complications are becoming more and more prevalent. CFRD is associated with increased morbidity and mortality, lower lung function and inadequate weight maintenance. Therefore, the optimal management of this pathology depends on an early diagnosis, individualized treatment and monitoring of diabetic complications. For CFRD, routine screening with an Oral Glucose Tolerance Test (OGTT) should be carried out yearly from the age of 10, which allows to diagnose it. The treatment goals in CFRD are to stabilize and improve lung function and obtain adequate weight gain. Currently, insulin is the pharmacological treatment of choice to control hyperglycemia and the insulin regimen must be personalized for each person. In acute illnesses, there may be higher insulin requirements. In addition, special considerations must be taken regarding diet and exocrine pancreatic insufficiency that these patients present. For the surveillance of microvascular complications, annual monitoring should be carried out 5 years after the diagnosis of CFRD. Due to the complexity of these patients, in order to achieve the best possible care, a multidisciplinary approach is needed with different coordinated health professionals, including the patients and their family in the decision-making process.

Prevalencia de aspergilosis broncopulmonar alérgica en niños con fibrosis quística / Prevalence of bronchopulmonary aspergillosis in children with cystic fibrosis

La aspergilosis broncopulmonar alérgica (ABPA) es una reacción de hipersensibilidad secundaria al Aspergillus fumigatus (Af) que complica la evolución en fibrosis quística (FQ). Existen pocos estudios pediátricos de su prevalencia publicados en el mundo y en Chile se desconoce. El objetivo de este trabajo fue estimar la prevalencia de ABPA en niños con FQ en un hospital de referencia, explorar factores de riesgo y describir los criterios diagnósticos, tratamiento y evolución. Se incluyeron retrospectivamente los niños con FQ atendidos en un hospital terciario en Santiago de Chile (Hospital Roberto del Río) entre los años 2011 a 2019, se identificaron aquellos con diagnóstico de ABPA. Se registraron criterios diagnósticos según la Cystic Fibrosis Foundation, presencia de factores de riesgo, tratamientos recibidos y efectos adversos. De 65 pacientes con FQ atendidos en este período, la prevalencia de ABPA fue del 12%. El promedio de edad al diagnóstico fue ± 11 años (5-17 años), predominando la edad adolescente y el género masculino. El 50% cumplieron con los criterios clásicos, el 87,5% usaron antibióticos y el 62,5% corticoides inhalados. La respuesta favorable al tratamiento inicial con corticoides y antifúngico vía oral fue 62,5%, con una exacerbación al momento del estudio. El 25% se comportaron como refractario y el 12,5% respondieron a tratamiento con pulsos de metilprednisolona. El 37,5% presentaron eventos adversos relacionados a corticoides. La prevalencia de ABPA observada es comparable a las series publicadas. Se necesitan trabajos prospectivos para conocer la prevalencia nacional y su tendencia a lo largo de los años, identificando factores de riesgo.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity response to Aspergillus fumigatus (Af) and worsens outcome in children with cystic fibrosis (CF). Its prevalence varies in the literature, but we do not know it in Chile. The aim of the study was to know the prevalence of ABPA in children with CF and to describe risk factors, diagnostic criteria, treatment and outcome. We included all patients with CF seen in a tertiary hospital in Santiago, Chile (Hospital Roberto del Río), between 2011 and 2019; ABPA cases (CF Foundation diagnostic criteria) were identified for the estimation of the prevalence. Risk factors, diagnostic criteria and treatment were recorded, as proposed by the Cystic Fibrosis Foundation. A total of 65 patients with CF were identified in the study period, with a prevalence of 12% (8 cases). Mean age at diagnosis ± 11 years (5-17), more frequent in adolescence and male. CF Foundation criteria diagnostic were identified in 50% of cases, with high frequency of antibiotic use (87,5%) and inhaled steroids (62,5%). Positive oral steroids and antifungal treatment response was 62,5%. Refractary response was 25% and 12,5% needed intravenous metilprednisolone pulses. A 37,5% of cases presented adverse effects to steroids. Prevalence of ABPA is comparable to literature. A prospective study is needed to identified national prevalence and trends, identifying risks factors.

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.

Prevalence of constipation in cystic fibrosis patients: a systematic review of observational studies / Prevalência de constipação em pacientes com fibrose cística: uma revisão sistemática de estudos observacionais

Abstract Objective: To systematically revise the literature in search of data about the prevalence of constipation in patients with cystic fibrosis according to the publications in this field, which partly refer to guidelines defined in 2010 by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Sources: Systematic review selecting articles based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, including Cystic Fibrosis patients of all ages. Sources of information were selected to identify the articles without period limitation: CADTH - Canadian Agency for Drugs and Technologies in Health, CINAHL Complete, Clinical Trials US NIH, Cochrane Library, Embase, MEDLINE via Ovid, Scopus, Web Of Science, PubMed, SciELO, MEDLINE and LILACS , Health Systems Evidence, PDQ Evidence, CRD Canadian Agency for Drugs and Technologies in Health, INAHTA - International Network of Agencies for Health Technology Assessment, and PEDro. Findings: The prevalence of constipation was reported in eight observational studies. Only two studies assessed the frequency of constipation as a primary objective; in the others, constipation was quoted along with the prevalence of the spectrum of gastrointestinal manifestations. Altogether, the publications included 2,018 patients, the reported prevalence varied from 10% to 57%. Only two of the six articles published after 2010 followed the definition recommended by the European Society. Conclusions: Constipation is a frequent but still insufficiently assessed complaint of Cystic Fibrosis patients. The use of diverse diagnostic criteria restricts comparison and epidemiological conclusions, future studies should compulsorily apply the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition definition.

Resumo Objetivo Revisar sistematicamente a literatura em busca de dados sobre a prevalência de constipação em pacientes com fibrose cística (FC), de acordo com as publicações nesse campo, que se referem parcialmente às diretrizes definidas pela European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN, 2010). Fontes de dados Revisão sistemática, selecionaram-se artigos com base no Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), incluindo todos os pacientes com FC de todas as faixas etárias. As fontes de informação foram selecionadas para identificar os artigos sem limitação de período para a pesquisa: CADTH (Canadian Agency for Drugs and Technologies in Health), CINAHL Complete, Clinical Trials US NIH, Cochrane Library, Embase, Medline via Ovid, Scopus, Web of Science, PubMed, SciELO, Medline e Lilacs por meio da Biblioteca Virtual em Saúde (BVS), Health Systems Evidence, PDQ Evidence, CRD (Canadian Agency for Drugs and Technologies in Health), INAHTA (International Network of Agencies for Health Technology Assessment) e PEDRO. Achados A prevalência de constipação em pacientes com FC foi relatada em oito estudos observacionais. Apenas dois estudos avaliaram a frequência de constipação como objetivo primário; nos outros, a constipação foi citada juntamente com a prevalência do espectro de manifestações gastrointestinais. No total, as publicações incluíram 2.018 pacientes e a prevalência relatada variou amplamente, de 10 a 57%. Apenas dois dos seis artigos publicados após 2010 seguiram a definição recomendada pela ESPGHAN. Conclusões A constipação é uma queixa frequente, mas ainda insuficientemente avaliada, dos pacientes com FC. O uso de diversos critérios diagnósticos restringe as comparações e declarações epidemiológicas, de modo que futuros estudos deveriam aplicar a definição ESPGHAN de maneira compulsória.

Burkholderia cepacia complex: 11 years of surveillance in patients with Cystic Fibrosis in Posadas, Argentina

Abstract Cystic fibrosis patients with Burkholderia cepacia complex pulmonary infections have high morbidity and mortality. Worldwide, this disease is undergoing substantial epidemiological changes. Advances in the diagnosis and treatment have conditioned an increase in child sur-vival as well as in the proportion of affected adults. In order to know our reality, we refer to an epidemiological study in 64 CF patients during 11 years of surveillance, focusing on infections caused by Burkholderia species. Conventional and automated phenotypic tests, restriction fragment length polymorphism-recA, recA gene sequencing, and matrix-assisted laser desorp-tion ionization-time of flight (MALDI-TOF) mass spectrometry were applied. Bacterial isolates were also tested for antimicrobial susceptibility patterns. The prevalence of Burkholderia cepacia complex was 9.4%. Based on recA gene sequencing, the most common species identified were Burkholderia cenocepacia (67.3%) and Burkholderia vietnamiensis (20.3%). Ceftazidime and meropenem were the most active, inhibiting 53% and 46% of isolates, respectively. This report represents the first systematic study of Burkholderia infections in our CF population since beginning of monitoring and treatment and highlights the importance of continued longitudinal studies.

Resumen Los pacientes con fibrosis quística (FQ) con infecciones pulmonares causadas por especies del complejo Burkholderia cepacia tienen una alta morbimortalidad. En todo el mundo, esta enfermedad está experimentando cambios epidemiológicos sustanciales. Los avances en el diagnóstico y el tratamiento han condicionado un aumento en la supervivencia infantil, así como en la proporción de adultos afectados. Para conocer nuestra realidad, nos referimos a un estudio epidemiológico en 64 pacientes con FQ durante 11 años de vigilancia, focalizando las infecciones causadas por especies del género Burkholderia. Se aplicaron pruebas fenotípicas convencionales y automatizadas, polimorfismo de longitud de fragmentos de restricción-recA, secuenciación del gen recA y espectrometría de masa MALDI-TOF. Los aislados bacterianos también se analizaron para determinar los patrones de susceptibilidad antimicrobiana. La prevalencia de complejo B. cepacia fue del 9,4%. Con base en la secuenciación del gen recA, las especies más comunes identificadas fueron Burkholderia cenocepacia (67,3%) y Burkholderia vietnamiensis (20,3%). Ceftazidima y meropenem fueron los antibióticos más activos e inhibieron el 53 y el 46% de los aislamientos, respectivamente. Este informe representa el primer estudio sistemático de las infecciones por Burkholderia en nuestra población desde el comienzo de la monitorización y el tratamiento, y resalta la importancia de continuar los estudios de vigilancia longitudinales.

Effectiveness of a multistep Pseudomonas aeruginosa eradication treatment protocol in children with cystic fibrosis in Brazil / Efetividade de um protocolo de tratamento de erradicação em fases de Pseudomonas aeruginosa em crianças com fibrose cística no Brasil

ABSTRACT Objective: Although various strategies have been proposed for eradicating Pseudomonas aeruginosa in patients with cystic fibrosis (CF), only a few employ multistep treatment in children colonized by that pathogen for the first time. The aim of this study was to describe the effectiveness of a three-phase eradication protocol, initiated after the first isolation of P. aeruginosa, in children with CF in Brazil. Methods: This was a retrospective real-life study in which we reviewed the medical records of pediatric CF patients in whom the eradication protocol was applied between June of 2004 and December of 2012. The three-phase protocol was guided by positive cultures for P. aeruginosa in airway secretions, and the treatment consisted of inhaled colistimethate and oral ciprofloxacin. Success rates were assessed after each phase, as well as cumulatively. Results: During the study period, 47 episodes of P. aeruginosa colonization, in 29 patients, were eligible for eradication. Among the 29 patients, the median age was 2.7 years, 17 (59%) were male, and 19 (65%) had at least one F508del allele. All 29 patients completed the first phase of the protocol, whereas only 12 and 6 completed the second and third phases, respectively. Success rates for eradication in the three treatment phases were 58.6% (95% CI: 40.7-74.5), 50.0% (95% CI: 25.4-74.6), and 66.7% (95% CI: 30.0-90.3), respectively. The cumulative success rate was 93.1% (95% CI: 78.0-98.1). Treatment failure in all three phases occurred in only 2 patients. Conclusions: In this sample of patients, the multistep eradication protocol was effective and had a high success rate.

RESUMO Objetivo: Embora várias estratégias de erradicação de Pseudomonas aeruginosa tenham sido propostas para pacientes com fibrose cística (FC), apenas algumas usaram um tratamento em fases e incluíram crianças na primeira colonização por esse patógeno. O objetivo deste estudo foi descrever a eficácia de um protocolo de erradicação em três fases em crianças com FC a partir do primeiro isolamento de P. aeruginosa no Brasil. Métodos: Estudo retrospectivo de vida real que avaliou prontuários de pacientes pediátricos com FC submetidos ao protocolo de erradicação entre junho de 2004 e dezembro de 2012. O protocolo em três fases foi orientado pela cultura positiva para P. aeruginosa de secreções das vias aéreas, utilizando-se colistimetato inalatório e ciprofloxacina oral no tratamento. As taxas de sucesso após cada fase e a de sucesso acumulado foram avaliadas. Resultados: Durante o período do estudo, 47 episódios de colonização por P. aeruginosa, em 29 pacientes, foram elegíveis para erradicação. Todos os 29 pacientes foram submetidos à primeira fase do protocolo (mediana de idade de 2,7 anos, 17 pacientes (59%) do sexo masculino e 19 (65%) com pelo menos um alelo F508del), sendo que 12 e 6 pacientes foram submetidos a segunda e terceira fases, respectivamente. As taxas de sucesso de erradicação nas três fases de tratamento foram de 58,6% (IC95%: 40,7-74,5), 50,0% (IC95%: 25,4-74,6) e 66,7% (IC95%: 30,0-90,3), respectivamente. A taxa de sucesso acumulado foi de 93,1% (IC95%: 78,0-98,1). Apenas 2 pacientes apresentaram falha do tratamento de erradicação. Conclusões: O primeiro isolamento de P. aeruginosa ocorreu em crianças de baixa idade. O protocolo de erradicação em fases foi efetivo com alta taxa de sucesso.

Prevalence of hepatic steatosis among children and adolescents with cystic fibrosis and its association with nutritional status / Prevalência de esteatose hepática em crianças e adolescentes com fibrose cística e associação com o estado nutricional

ABSTRACT Objective: To determine the prevalence of hepatic steatosis (HS) in children and adolescents with cystic fibrosis (CF) and associate it with nutritional status. Methods: Cross-sectional study with children and adolescents with CF diagnosis. Weight and height were used to calculate the body mass index (BMI) and subsequent classification of the nutritional status. The midarm circumference (MAC), triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC) were used to evaluate body composition. Abdominal ultrasonography was performed for diagnosis of HS. The statistical tests used were Student's t test, Mann-Whitney test and chi-square test with significance level of 5%. Results: 50 patients with CF were evaluated, 18 (36%) were diagnosed with HS (Group A) and 32 (64%) without HS (Group B). The mean age of Group A was 13,2±4,9 years old and Group B 11,7±4,9; for BMI, the value for Group A was 18,0±4,1 and Group B was 15,7±3,8; the TSF of Group A was 8,4±3,5 mm and Group B was 7,0±2,5 mm. For these variables, there was no significant difference between the groups. The mean of MAC and MAMC differed significantly between the groups, being higher in the HS group, with p values of 0,047 and 0,043. Conclusions: The frequency of HS in patients with CF is high and it is not related to malnutrition, according to the parameters of BMI, TSF and MAMC. The values of MAC and MAMC indicated a greater reserve of muscle mass in patients with HS.

RESUMO Objetivo: Determinar a prevalência de esteatose hepática (EH) em crianças e adolescentes com fibrose cística (FC) e associá-la com o estado nutricional. Métodos: Estudo transversal com crianças e adolescentes com diagnóstico de FC. Foram aferidos o peso e a altura para o cálculo do índice de massa corpórea (IMC) e classificação do estado nutricional. A circunferência do braço (CB), a dobra cutânea tricipital (DCT) e a circunferência muscular do braço (CMB) foram empregadas para avaliação da composição corporal. A ultrassonografia abdominal foi realizada para o diagnóstico de EH. Os testes estatísticos empregados foram o teste t de Student, o teste de Mann-Whitney e o teste do qui-quadrado, com nível de significância de 5%. Resultados: Dos 50 pacientes avaliados, 18 (36%) apresentaram EH (Grupo A) e 32 (64%) não (Grupo B). Para as médias de idade (Grupo A: 13,3±5,0 anos; e Grupo B: 11,7±5,0 anos), IMC (Grupo A: 18,0±4,1; e Grupo B: 15,7±3,8) e DCT (Grupo A: 8,4±3,5 mm; e Grupo B: 7,0±2,5 mm), não houve diferença significativa entre os grupos. A média da CB e da CMB diferiram significativamente entre os grupos, sendo mais elevada no grupo com EH, com valores p respectivos de 0,047 e 0,043. Conclusões: É alta a frequência de EH em pacientes com FC e ela não está relacionada com a desnutrição, segundo os parâmetros de IMC, DCT e CMB. Os valores de CB e CMB indicaram maior reserva de massa muscular nos pacientes com EH.

Desarrollo y evaluación de una base de datos in house para la identificación rápida de Burkholderia contaminons por EM MALDI-TOF / Development and evaluation of an in-house database for quick identification of Burkholderia contaminans by MALDI-TOF MS

La espectrometría de masas (EM) (matrix assisted laser desorption ionization-time of flight) MALDI-TOF demostró ser una herramienta robusta para la identificación de numerosos grupos taxonómicos. No obstante, presenta limitaciones. Una ventaja clave de la técnica es la flexibilidad para la incorporación de espectros proteicos de microorganismos ausentes en la base de datos comercial. Dada la prevalencia de Burkholderia contaminans en los pacientes fibroquísticos en Argentina, y a que en ellos es crucial el diagnóstico microbiológico rápido y confiable, la EM MALDI-TOF surge como una herramienta estratégica. El objetivo del trabajo fue desarrollar una base de datos adicional con espectros peptídicos de aislamientos de referencia de B. contaminans. La misma demostró ser exitosa para la identificación del 97% de los aislamientos analizados. Por lo cual la EM MALDI-TOF con la base de datos extendida resultó ser una herramienta útil para la identificación y diferenciación de otras especies relacionadas a B. contaminans.

MALDI-TOF (matrix assisted laser desorption ionization-time of flight) mass spectrometry (MS) proved to be a robust tool for the identification of numerous taxonomic groups. However, it has limitations. A key advantage of this technique is the flexibility for the incorporation of protein profiles of microorganisms not included in the commercial database. Due to the prevalence of Burkholderia contaminans in fibrocystic patients in Argentina and the fact that rapid and reliable microbiological diagnosis is crucial in them, MALDI-TOF MS emerges as a strategic tool. The aim of this work was to develop an additional database with peptide spectra of reference isolates of B. contaminans. This database demonstrated to be successful for the identification of 97% of the isolates analyzed. Therefore, MALDI-TOF MS with the extended database was a useful tool for the identification and differentiation of other related species to B. contaminans.

Factibilidad de la bipartición hepática derecha-izquierda in situ en el trasplante Hepático / Feasibility of in situ full-right full-left split liver transplantation

Debido a la falta de órganos para trasplantes se han desarrollado diferentes alternativas quirúrgicas, como la bipartición hepática (BH) y los trasplantes hepáticos con donantes vivos. En la BH clásica, de la división de un hígado de donante cadavérico se obtienen dos injertos, uno correspondiente a los segmentos 2-3 y otro a los segmentos 1, 4-8. Para poder utilizar los injertos de una BH, en pacientes adultos, se puede realizar una BH derecha/izquierda típica, donde se obtienen un injerto derecho (segmentos 5-8) y otro izquierdo (segmentos 1-4). La BH se puede realizar en el momento de la ablación (BH in situ) o en la cirugía de banco (BH ex situ). En este trabajo informamos el primer caso de BH in situ derecha/izquierda típica de la Argentina, resaltando los detalles de la cirugía del donante y del receptor.

Due to the shortage of organs for transplantation, different surgical alternatives have been developed, as split liver transplantation (SLT) and living-donor liver transplantation. In classical SLT, the liver of a cadaveric donor is divided and two allografts are obtained, one corresponding to segments 2-3 and the other to segments 1, 4-8. In order to produce two grafts from one liver for two adult recipients, splitting of the liver can create a right graft including segments 5-8 and a left graft with segments 1-4. Splitting of the liver can be performed during procurement (in situ) or on the bench (ex situ). The aim of our study is to describe the first case of in situ full-right full-left split liver transplantation, with focus on donor and recipient surgery.

Fibrosis quística del adulto y cirugía laparoscópica / Cystic fibrosis in the adult and laparoscopic surgery

Introducción: La fibrosis quística es una enfermedad genética que constituye causa frecuente de neumopatía crónica grave en adultos jóvenes. Se asocia a cirrosis de vías biliares y cálculos vesiculares, por lo que el anestesiólogo debe estar familiarizado con las características clínicas de la enfermedad a fin de disminuir el índice de complicaciones perioperatorias que pueden presentarse. Objetivo: Presentar las características clínicas y la conducta perioperatoria en una paciente con diagnóstico de fibrosis quística anunciada para colecistectomía videolaparoscópica. Caso clínico: Paciente femenina de 19 años de edad, raza negra, con múltiples infecciones respiratorias durante la infancia, que se diagnosticó como caso nuevo de fibrosis quística y durante los estudios se observó litiasis vesicular sintomática por lo que se anunció para colecistectomía videolaparoscópica. Se describe la evaluación y preparación preoperatoria, así como la conducta anestésica intraoperatoria. Conclusiones: Los resultados anestésicos dependen de la atención a una enfermedad compleja que afecta a múltiples órganos y el control estrecho y el tratamiento oportuno de la enfermedad pulmonar previa(AU)

Introduction: Cystic fibrosis is a genetic disease that is a frequent cause of severe chronic lung disease in young adults. It is associated with biliary tract cirrhosis and gallstones, a reason why the anesthesiologist must be familiar with the clinical characteristics of the disease in order to reduce the rate of perioperative complications that may occur. Objective: To present the clinical characteristics and perioperative behavior in a patient diagnosed with cystic fibrosis announced for videolaparoscopic cholecystectomy. Clinical case: Female patient of 19 years of age, black race, with multiple respiratory infections during childhood, who was diagnosed as a new case of cystic fibrosis. During the studies, symptomatic vesicular lithiasis was observed, that's why the patient what was announced for videolaparoscopic cholecystectomy. The evaluation and preoperative preparation, as well as the intraoperative anesthetic behavior are described. Conclusions: Anesthetic outcomes depend on the attention to a complex disease that affects multiple organs and the close control and timely treatment of previous lung disease(AU)

Neutropenia asociada al uso de cefepime en pacientes pediátricos con fibrosis quística / Neutropenia associated with the use of cefepime in pediatric patients with cystic fibrosis

Resumen Las exacerbaciones pulmonares de causa infecciosa son una de las mayores complicaciones en los pacientes con fibrosis quística (FQ). Estas se asocian a un progresivo aumento en la morbilidad y mortalidad. El tratamiento antimicrobiano se realiza dependiendo del microorganismo aislado. Con frecuencia se utilizan antimicrobianos β-lactámicos, los cuales no están exentos de reacciones adversas. A continuación, se describen dos casos de neutropenia tras el uso prolongado de cefepime en pacientes con FQ.

Pulmonary exacerbations of infectious cause are one of the major complications in patients with cystic fibrosis (CF). These are associated with a progressive increase in morbidity and mortality. The treatment depending on the isolated microorganism. The β-lactam antibiotics are generally used which are not exempt from adverse reactions. Next, two report of neutropenia cases are described after prolonged use of cefepime in CF patients.