Alternativa terapéutica para mejorar la calidad de vida en pacientes con fibrosis quística y discinesia ciliar primaria / Therapeutic alternative to improve quality of life in patients with cystic fibrosis and primary ciliary dyskinesia

Objective: To evaluate the clinical response of patients with cystic fibrosis and primary ciliary dyskinesia after endoscopic sinus surgery at the Dr. Robert Reid Cabral Children's Hospital from September 2021 to February 2022. Methods: An ambispective, cross-sectional, observational case series study was conducted, where the study population was made up of patients with cystic fibrosis and primary ciliary dyskinesia at the Dr. Robert Reid Cabral children's hospital during the study period. Inclusion criteria: Patients older than 6 years with a confirmed diagnosis of cystic fibrosis and primary ciliary dyskinesia (Genetic test with 2 homozygous mutations, positives electrolytes in sweat), severe respiratory symptoms of CRS that did not improve with conventional treatment and underwent endoscopic surgery for sinuses. Results: Of a total of 41 patients, only 10 met the inclusion criteria, the most prevalent age range was 14 to 18 years. Both CF and PCD patients decreased the frequency of CRS symptoms. After ENC, there were discrete changes in lung function, and only patients with severe to moderate disease increased % of FEV1. Most of the patients did not require admission after surgery. The most common germ found in nasopharyngeal and sputum cultures in preoperative patients was Pseudomonas aeruginosa in 86%; after ESS there was a significant increase in MRSA colonization in both CF and PCD patients. More than 50% of postoperative patients improved their quality of life, so endoscopic sinus surgery is effective in this population in the treatment of chronic rhinosinusitis.

Objetivo: Evaluar la respuesta clínica de los pacientes con fibrosis quística y discinesia ciliar primaria posterior a la cirugía endoscópica de senos paranasales en el Hospital Infantil Dr. Robert Reid Cabral en el período septiembre 2021 a febrero 2022. Métodos: Se realizó un estudio observacional tipo serie de casos, de corte transversal y ambispectivo, donde la población estudiada estuvo conformada por los pacientes con fibrosis quística y discinesia ciliar primaria del hospital infantil Dr. Robert Reid Cabral en el período de estudio. Criterios de inclusión: Pacientes mayores de 6 años con diagnóstico confirmado de fibrosis quística y discinesia ciliar primaria (Prueba genética con 2 mutaciones homocigotas, electrolitos en sudor positivos), síntomas respiratorios severos de RSC que no mejoraron con tratamiento convencional y sometidos a la cirugía endoscópica de senos paranasales. Resultados: De un total de 41 pacientes, sólo 10 cumplieron con los criterios de inclusión, el rango de edad más prevalente fue de 14 a 18 años. Tanto los pacientes con FQ como los de DCP disminuyeron la frecuencia de los síntomas de RSC. Posterior a la CEN hubo cambios discretos en la función pulmonar, y sólo los pacientes con enfermedad grave a moderada aumentaron el % de FEV1. La mayoría de los pacientes no ameritaron ingresos posterior a la cirugía. El germen más común encontrado en los cultivos nasofaríngeo y esputo en los pacientes preoperatorios fue la Pseudomonas aeruginosa en el 86%, luego de la CEN hubo un aumento significativo de la colonización por MRSA tanto en los pacientes con FQ como en los de DCP. Más del 50% de los pacientes postquirúrgicos mejoraron su calidad de vida, por lo que la cirugía endoscópica de senos paranasales es efectiva en dicha población en el tratamiento de la rinosinusitis crónica.

Cystic fibrosis: when neonatal screening is unsatisfactory for early diagnosis / Fibrose cística: quando a triagem neonatal é insatisfatória para o diagnóstico precoce

Abstract Introduction: cystic fibrosis newborn screening must enable its earlier diagnosis, which may enhance outcomes. This study was a series case of delayed-diagnosis children submitted to cystic fibrosis newborn screening. Description: fourteen children were included; eight (57.1%) were due to false-negative screening, while six (42.9%) were due to processing errors. Two samples collected after 30 days of life were incorrectly classified as negative, and four infants with a positive test could not be located due to screening processing errors. Cystic fibrosis diagnosis was confirmed at a median (IQR) age of 5.3 (4.2-7.4) months. Poor nutritional status was the most prevalent clinical sign at diagnosis, being present in 78.6% of infants. The mean (SD) weight-for-length and length-for-age Z-scores were -3.46 (0.84) and -3.99 (1.16), respectively. Half of the children had Pseudo-Bartter syndrome, and 42.9% had breathing difficulties. Twelve children (85.7%) required hospitalization, with a median (IQR) length of stay of 17.0 (11.5-26.5) days. Discussion: newborn screening had some faults, from incorrect collections to inefficient active search. Early identification of these children in which screening was unsatisfactory is essential, emphasizing the importance and efforts to not miss them. In the case of a failed test, healthcare professionals must be prepared to recognize the main symptoms and signs of the disease.

Resumo Introdução: a triagem neonatal para fibrose cística deve contribuir para diagnóstico precoce e melhor prognóstico da doença. O estudo é uma série de casos com lactentes submetidos à triagem, porém com diagnóstico tardio da doença. Descrição: quatorze crianças foram incluídas; oito (57,1%) com triagem falso-negativo e seis (42,9%) com erros processuais na triagem neonatal. Duas amostras foram coletadas tardiamente, sendo incorretamente classificadas como negativas e quatro lactentes com triagem positiva não foram localizados, por erros na busca ativa. Confirmou-se o diagnóstico da fibrose cística com idade mediana (IIQ) de 5,3 (4,2-7,4) meses. O Comprometimento nutricional precoce foi o sinal clínico mais prevalente ao diagnóstico, presente em 78,6% das crianças. Os Z escores médios (SD) do peso para altura e altura para idade foram -3,46 (0,84) e -3,99 (1,16), respectivamente. Metade das crianças teve síndrome de Pseudo-Bartter e 42,9% dificuldade respiratória. Doze crianças (85,7%) precisaram hospitalização com tempo mediano de permanência de 17 dias. Discussão: a triagem neonatal para fibrose cística apresentou falhas, desde testes falso-negativos, coletas incorretas, até problemas com a busca ativa. Entretanto, o diagnóstico ágil é essencial e os profissionais de saúde devem reconhecer os sintomas e sinais precoces da doença, mesmo quando a triagem neonatal não for satisfatória.

Effect of Baihe Yuzi Prescription on CFTR， AQP， and ZIP Ion Channels and Oxidative Stress in Epididymis of Oligoasthenozoospermia Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Baihe Yuzi prescription （BYP） on the cystic fibrosis transmembrane conductance regulator （CFTR）， aquaporin （AQP）， zinc/iron-regulated transporter-like protein （ZIP） and local oxidative stress in epididymis of oligoasthenozoospermia （OAS） rats， and to explore the mechanism of its intervention in OAS. MethodAfter 35 rats were acclimatized for 1 week， 7 rats were randomly selected as the normal group， and the remaining 28 rats were given tripterygium glycosides （TG） 30 mg·kg-1. After 4 weeks of modeling， they were randomly divided into 4 groups： model group， BYP low-dose group （LBYP）， BYP high-dose group （HBYP） and levocarnitine group， with 7 rats in each group. The rats in the normal group and model group were given normal saline at the same dosage. The levocarnitine group rats were given L-carnitine oral liquid （100 mg·kg-1） by gavage. The LBYP group rats were given BYP 6.3 g·kg-1， and the HBYP group rats were given BYP 12.6 g·kg-1 by gavage once a day for consecutive 4 weeks. After the end of the intervention， sperm count and motility of all rats were detected， the histopathological structure of epididymis was observed by hematoxylin-eosin （HE） staining， and the expressions of CFTR， AQP9， AQP3， ZIP8， ZIP12 and other proteins were detected by Western blot. The contents of α-glycosidase （α-GC）， sialic acid （SA）， carnitine， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Total zinc content was measured using an inductively coupled plasma mass spectrometer. Free zinc ion content was detected by zinc ion probes. ResultCompared with those in the normal group， the sperm count and motility of rats were decreased and the epididymal structure was disordered in the model group. The contents of α-GC and carnitine were decreased in epididymis （P<0.05）. MDA levels were increased， while SOD， GSH-Px and zinc levels were decreased （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were down-regulated， and AQP3 expression was up-regulated. The expression of ZIP8 in the cauda epididymis was up-regulated （P<0.05）. Compared with the model group， BYP can significantly improve the sperm count and motility， the epididymal structure of OAS rats and the levels of α-GC and carnitine （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were up-regulated， while the expressions of ZIP8 in the cauda epididymis and AQP3 in the head of the epididymis were decreased （P<0.05）. The SOD and GSH-Px levels and total zinc content in epididymis were increased， and the MDA levels were decreased （P<0.05）. ConclusionBYP may improve the sperm quality and repair epididymal tissue structure and function of OAS rats， by regulating the expressions of CFTR， AQP3， and ZIP12 ion channels and local antioxidant mechanism.

Impact of COVID-19 social distancing recommendations on pulmonary function, nutritional status, and morbidity in patients with cystic fibrosis / Impacto das recomendações de distanciamento social por COVID-19 sobre a função pulmonar, estado nutricional e morbidade em pacientes com fibrose cística

ABSTRACT Objective: To evaluate the impact of COVID-19 social distancing recommendations on nutritional status, pulmonary function, and morbidity in patients with cystic fibrosis (CF). Methods: A retrospective cohort study including patients older than six years with a diagnosis of CF was performed. Demographic and clinical data, anthropometric measurements, pulmonary function, days of antibiotic use, and length of hospital stay were recorded. Variables were recorded at three time points relative to the baseline for implementation of social distancing measures: T-1 (14 months before implementation), T0 (baseline), and T1 (14 months after implementation). Delta (Δ) was calculated for each period: Δ1 (pre-pandemic T0-T-1) and Δ2 (pandemic T1-T0). Results: The study included 25 patients, with a mean age of 11.7±4.3 years. The mean forced expiratory volume in the first second (FEV1) was 85.6±23.6%, and body mass index (BMI) was 17.5±3.0 kg/m2. When comparing the two periods (Δ1 and Δ2), there was a significant increase in the FEV1/forced vital capacity (FVC) ratio (p=0.013) and in the forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) (p=0.037) in the pandemic period. There was also a significant reduction (p=0.005) in the use of antibiotics in the pandemic period compared with the pre-pandemic period. The Δ1 and Δ2 values did not differ significantly for BMI, FEV1, or length of hospital stay. Conclusions: COVID-19 social distancing recommendations had a positive impact (decrease) on morbidity (use of antibiotics) and small airway obstruction (FEF25-75%) in patients with CF.

RESUMO Objetivo: Avaliar o impacto das recomendações de medidas de distanciamento social por COVID-19 sobre estado nutricional, função pulmonar e morbidade em pacientes com fibrose cística (FC). Métodos: Estudo de coorte, retrospectivo, que incluiu pacientes com diagnóstico de FC e idade superior a seis anos. Foram registrados os dados demográficos, antropométricos, clínicos, de função pulmonar e o total de dias de uso de antibiótico e de hospitalizações. As variáveis foram registradas em três momentos relativos ao início das recomendações de distanciamento social: T-1 (14 meses antes), T0 (início das recomendações) e T1 (14 meses depois). Foram calculados deltas (Δ) para cada um dos períodos: Δ1 (pré-pandemia T0-T-1) e Δ2 (pandemia T1-T0). Resultados: Vinte e cinco pacientes, com média de idade de 11,7±4,3 anos, sendo 76% homozigotos para Δf508 e 28% colonizados por Pseudomonas aeruginosa, foram incluídos. A média do volume expiratório forçado no primeiro segundo (VEF1) foi de 85,6±23,6 (% do previsto) e o índice de massa corporal (IMC) foi de 17,5±3,0 kg/m2. Ao compararmos os períodos (Δ1 e Δ2), houve aumento significativo do VEF1/CVF (p=0,013) e do FEF25-75% (p=0,037) no período das recomendações de distanciamento. Também se observou redução significativa (p=0,005) do uso de antibióticos no período da pandemia em comparação ao período anterior a ela. Não houve diferenças significativas nos deltas para o IMC, VEF1 e dias de hospitalização. Conclusões: As recomendações de distanciamento social por COVID-19 tiveram impacto positivo (redução) sobre a morbidade (uso de antibióticos) e a obstrução de vias aéreas de menor calibre (FEF25-75%) em pacientes com FC.

Evolución clínico funcional de pacientes con fibrosis quística tratados con lumacaftor/ivacaftor en un centro pediátrico. Serie de casos / Clinical and functional course of patients with cystic fibrosis treated with lumacaftor/ivacaftor at a children's hospital. A case series

Los moduladores de la proteína reguladora transmembrana de fibrosis quística (CFTR) tratan el defecto de esta proteína. El objetivo es describir la evolución de niños con fibrosis quística tratados con lumacaftor/ivacaftor. Se trata de una serie de 13 pacientes de 6 a 18 años con ≥ 6 meses de tratamiento. Se analizaron el volumen espiratorio forzado en el primer segundo (VEF1), puntaje Z del índice de masa corporal (IMC), antibioticoterapia/año, antes del tratamiento y durante 24 meses posteriores. A los 12 meses (9/13) y 24 meses (5/13), la mediana de cambio del porcentaje del predicho VEF1 (ppVEF1) fue de 0,5 pp [-2-12] y 15 pp [8,7-15,2], y del puntaje Z de IMC de 0,32 puntos [-0,2-0,5] y 1,23 puntos [0,3-1,6]. El primer año (11/13) la mediana de días de uso de antibiótico disminuyó de 57 a 28 (oral) y de 27 a 0 (intravenoso). Dos niños evidenciaron eventos adversos asociados.

Cystic fibrosis transmembrane regulator (CFTR) modulators treat defective CFTR protein. Our objective is to describe the course of children with cystic fibrosis treated with lumacaftor/ivacaftor. This is a case series of 13 patients aged 6 to 18 years with ≥ 6 months of treatment. Forced expiratory volume in the first second (FEV1), body mass index (BMI) Z-score, antibiotic therapy/year, before treatment and for 24 months after treatment were analyzed. At 12 months (9/13) and 24 months (5/13), the median change in the percent predicted FEV1 (ppFEV1) was 0.5 pp (-2­12) and 15 pp (8.7­15.2) and the BMI Z-score was 0.32 points (-0.2­0.5) and 1.23 points (0.3­1.6). In the first year, in 11/13 patients, the median number of days of antibiotic use decreased from 57 to 28 (oral) and from 27 to 0 (intravenous). Two children had associated adverse events.

Programa de actividades físico-terapéuticas para educandos con fibrosis quística

La investigación se realizó en el municipio Jiguaní, provincia de Granma, Cuba. Se inició, a partir de la limitada atención que reciben los educandos fibroquísticos en el contexto escolar; pues, en el sistema educativo cubano no hay evidencias de programas de actividades físico-terapéuticas que orienten la prescripción de ejercicios físicos y tengan en cuenta las posibilidades, potencialidades y necesidades de estos niños. La investigación tiene como objetivo elaborar un programa de actividades físico-terapéuticas, caracterizado por un enfoque integral físico-educativo que mejore la condición física orientada a la salud de educandos con fibrosis quística. Para su desarrollo, se efectuó un estudio correlacional, con diseño pre-experimental en el período comprendido entre septiembre 2019 y junio 2021. Se emplearon métodos teóricos, empíricos y estadístico-matemáticos, así como técnicas de investigación, entre ellos: analítico-sintético, hipotético-deductivo, sistémico estructural-funcional, revisión documental, observación estructurada, criterio de expertos, entrevista, triangulación metodológica y estadística descriptiva e inferencial. A partir de un muestreo intencional, se seleccionaron cuatro educandos con manifestaciones clínicas de las vías respiratorias, baja autoestima y escasa condición física, que representan el total de la población, para el 100 %, con una edad promedio de nueve años. En los resultados del experimento, mediante los indicadores evaluados con la implementación del programa de actividades físico-terapéuticas, se observaron cambios significativos en el 100 % de la muestra, con ello mejoró la condición física orientada a la salud en educandos con fibrosis quística.

A pesquisa foi realizada no município de Jiguaní, província de Granma, Cuba. Ela foi iniciada devido à atenção limitada que os alunos fibrocísticos recebem no contexto escolar, uma vez que no sistema educacional cubano não há evidências de programas de atividades físico-terapêuticas que orientem a prescrição de exercícios físicos e levem em conta as possibilidades, o potencial e as necessidades dessas crianças. O objetivo desta pesquisa é elaborar um programa de atividades físico-terapêuticas, caracterizado por um enfoque físico-educacional integral que melhore a condição física orientada para a saúde dos alunos com fibrose cística. Para seu desenvolvimento, foi realizado um estudo correlacional, com um desenho pré-experimental no período entre setembro de 2019 e junho de 2021. Foram utilizados métodos teóricos, empíricos e estatístico-matemáticos, bem como técnicas de pesquisa, incluindo: analítico-sintético, hipotético-dedutivo, estrutural-funcional sistêmico, revisão documental, observação estruturada, julgamento de especialistas, entrevista, triangulação metodológica e estatística descritiva e inferencial. A partir de uma amostragem intencional, foram selecionados quatro alunos com manifestações clínicas do trato respiratório, baixa autoestima e condição física ruim, representando 100% da população total, com idade média de nove anos. Nos resultados do experimento, por meio dos indicadores avaliados com a implementação do programa de atividades físico-terapêuticas, foram observadas mudanças significativas em 100% da amostra, melhorando assim a condição física voltada para a saúde dos alunos com fibrose cística.

The research was carried out in the Jiguaní municipality, Granma province, Cuba. It began, from the limited attention that fibrocystic students receive in the school context due to in the Cuban educational system there is no evidence of physical-therapeutic activity programs that guide the prescription of physical exercises and take into account the possibilities, potentialities and needs of these children. The objective of the research is to develop a program of physical-therapeutic activities, characterized by a comprehensive physical -educational approach that improves the health-oriented physical condition of students with cystic fibrosis. For its development, a correlational study was carried out, with a pre-experimental design in the period between September 2019 and June 2021. Theoretical, empirical and statistical-mathematical methods were used, as well as research techniques, including: analytical-synthetic, hypothetical-deductive, structural-functional systemic, documentary review, structured observation, expert judgment, interview, methodological triangulation and descriptive and inferential statistics. From an intentional sampling, four students with clinical manifestations of the respiratory tract, low self-esteem and poor physical condition were selected, representing the total population, for 100 %, with an average age of nine years. In the results of the experiment, through the indicators evaluated with the implementation of the program of physical-therapeutic activities, significant changes were observed in 100 % of the sample, thereby improving the health-oriented physical condition in students with cystic fibrosis.

Enfermedad hepática en la fibrosis quística pediátrica. Una revisión de los conocimientos actuales / Cystic fibrosis liver disease in children ­ A review of our current understanding

La fibrosis quística, la segunda enfermedad genética más frecuente, es el resultado de una proteína de canal mutada, la CFTR, que secreta iones de cloro que fluidifican las secreciones. La esperanza de vida en los pacientes ha aumentado en años recientes gracias a mejoras en el tratamiento. No obstante, las complicaciones hepáticas son la tercera causa de muerte y la comprensión de su fisiopatología es aún deficiente. Se considera que la obstrucción biliar secundaria a la presencia de secreciones espesas conduce a la cirrosis. Sin embargo, el ácido ursodesoxicólico no ha modificado la historia natural. Además, la presencia de hipertensión portal en ausencia de cirrosis no puede ser explicada. Se ha propuesto el rol de la CFTR como modulador de tolerancia inmune, que explica la presencia de una inflamación portal persistente que culmina en fibrosis. El eje intestino-hígado tendría un rol importante en la presentación y la progresión de esta enfermedad

Cystic fibrosis is the second most common genetic disease in infancy. It is the result of a mutated channel protein, the CFTR, which secretes chloride ions, fluidifying secretions. Recent improvements in the treatment have increased life expectancy in these patients. Nevertheless, liver involvement remains the third cause of death. Unfortunately, our understating of the physiopathology is still deficient. Biliary obstruction secondary to the presence of thick secretions is considered to lead to cirrhosis. However, treatment with ursodeoxycolic acid has not changed the natural history. Furthermore, the presence of portal hypertension in the absence of cirrhosis cannot be explained. Recently, the role of CFTR as modulator of immune tolerance has been proposed, which could explain the presence of a persistent portal inflammation leading to fibrosis, and the gut-liver axis would also have a role in disease presentation and progression.

La fibrosis quística en niños en el Ecuador / Cystic fibrosis in children in Ecuador

Objetivo: analizar la fibrosis quística en niños en el Ecuador. Metodología: Revisión sistemática de 21 publicaciones relacionadas al tema, específicamente 13 articulos de investigación en contexto ecuatoriano. Resultados y conclusión: En el Ecuador la incidencia de la enfermedad es de 1 por cada 11.110 habitantes y cada año nacen aproximadamente 23 niños con esta afección, teniéndose en cuenta las mutaciones en el CFTR, entorpecen el diagnóstico molecular, así como se ha estudiado un caso pediátrico de FQ con complicaciones en pancreatitis, siendo esto inusual en la población infantil, siendo considerable proseguir con investigaciones conducentes a tener una mejor referencia científica de la FQ en el Ecuador.

Objective: to analyze cystic fibrosis in children in Ecuador. Methodology: Systematic review of 21 publications related to the subject, specifically 13 research articles in the Ecuadorian context. Results and conclusion: In Ecuador the incidence of the disease is 1 for every 11,110 inhabitants and each year approximately 23 children are born with this condition, taking into account CFTR mutations, which hinder molecular diagnosis, as well as a study pediatric case of CF with complications in pancreatitis, this being unusual in the child population, it is important to continue with research leading to a better scientific reference of CF in Ecuador.

Transición en las enfermedades crónicas gastrointestinales. Del cuidado pediátrico al del adulto / Transition in chronic gastrointestinal diseases. From pediatric to adult care

Los avances tecnológicos y del conocimiento hicieron que un mayor número de pacientes con enfermedad crónica gastrointestinal pasen de ser atendidos por el pediatra al control por los médicos de adultos durante una de las etapas más vulnerables de la vida: la adolescencia. El Grupo de Trabajo de Transición del Comité de Gastroenterología de la Sociedad Argentina de Pediatría realizó una búsqueda de literatura exhaustiva y convocó a especialistas referentes del país, con el objeto de unificar los criterios basados en la evidencia y la experiencia. De esta manera, se proponen una serie de recomendaciones para todo el equipo de salud (pediatra, gastroenterólogo infantil, nutricionista, gastroenterólogo de adultos, psicólogo, enfermería), incluso para pacientes y familias, que faciliten el proceso de transición y optimicen el seguimiento, el control, la prevención de complicaciones y la calidad de vida de los pacientes con enfermedades crónicas gastrointestinales

Technological advances and the globalization of knowledge have led to a considerable increase in the number of patients with chronic gastrointestinal disease who transition from pediatric to adult care during one of the most vulnerable life stages: adolescence. The Transition Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría conducted an exhaustive literature search and summoned leading specialists in the most frequent chronic pathologies from all over the country to unify criteria based on evidence and experience. As a result, a series of recommendations are proposed for the whole health team (pediatrician, pediatric gastroenterologist, nutritionist, adult gastroenterologist, psychologist, and nurse) including patients and families, to facilitate the transition process, optimize follow-up, prevent complications, and improve the quality of life of patients with chronic gastrointestinal diseases.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis

Abstract Objective To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. Methods An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. Results A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. Conclusions The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

Use of Methylene Blue to Treat Vasoplegia Syndrome in Cystic Fibrosis Patients Undergoing Lung Transplantation: A Case Series

Background: Several studies have demonstrated the utility of methylene blue (MB) to treat vasoplegic syndrome (VS), but some have cautioned against its routine use in lung transplantation with only two cases described in prominent literature. Cystic fibrosis patients commonly have chronic infections which predispose them to a systemic inflammatory syndrome-like vasoplegic response during lung transplantation. We present 13 cystic fibrosis patients who underwent lung transplantation and received MB for vasoplegic syndrome while on cardiopulmonary bypass, with or without inhaled pulmonary vasodilator therapy. Methods: Single?center, retrospective, case series analysis of cystic fibrosis patients who underwent lung transplant and received MB for vasoplegia. We defined the primary outcome as 30-day mortality, and secondary outcomes as primary graft failure, 1-year mortality, postoperative complications, and hemodynamic response to MB. Results: MB was associated with a significant increase in mean arterial pressure (MAP) (P < 0.001) in all patients, and 84.6% (11/13) of the patients had either a decrease or no change in vasopressor requirement. No patients developed acute primary graft dysfunction and there was 100% 30?day and 1?year survival. One patient required Extracorporeal membrane oxygenation (ECMO) for hypoxemia and 69% (9/13) of the patients had evidence of postoperative right ventricular dysfunction, but no patients required a right ventricular assist device. Conclusion: This case series demonstrates the effectiveness of MB in treating vasoplegia in cystic fibrosis patients during lung transplantation, without evidence of primary graft dysfunction, 30?day or 1?year mortality. The safety of MB regarding hypoxemia and increased pulmonary vascular resistance requires further investigation.

Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil

Abstract Objective: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. Methods: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. Results: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. Conclusions: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

Systematic review on fecal calprotectin in cystic fibrosis

Abstract Objectives: Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF), a multi-systemic genetic disease caused by alterations to the CFTR gene. Manifestations of the disease favor a systemic inflammation not limited to the respiratory tract, therefore, calprotectin is a non-invasive and effective diagnostic method. The aim of the study was to perform a systematic review of the literature with a qualitative synthesis of studies. Sources: The articles were selected from PubMed, Web of Science, Scielo and Lilacs. Summary of the findings: Nine studies were selected for that qualitative synthesis, one was a randomized clinical trial, and eight were case-control or cohort designs. Most studies have indicated that calprotectin is a marker of systemic inflammation in CF and not just intestinal inflammation. Calprotectin is an aid in monitoring inflammatory bowel conditions in patients with cystic fibrosis. Conclusion: Further studies should be conducted to investigate the role of this marker in the systemic inflammation of CF.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis / Uso de elexacaftor + tezacaftor + ivacaftor em indivíduos com fibrose cística com pelo menos um alelo F508del: revisão sistemática e meta-análise

ABSTRACT Objective: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. Methods: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, −0.16; 95% CI, −0.28 to −0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, −0.03; 95% CI, −0.08 to 0.01), and none of the studies reported deaths. Conclusions: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

RESUMO Objetivo: Avaliar o efeito do tratamento com a combinação de três moduladores da proteína cystic fibrosis transmembrane conductance regulator (CFTR, reguladora de condutância transmembrana em fibrose cística) - elexacaftor + tezacaftor + ivacaftor (ETI) - sobre desfechos clínicos importantes em indivíduos com fibrose cística. Métodos: Revisão sistemática e meta-análise de ensaios clínicos randomizados que compararam o uso de ETI em indivíduos com fibrose cística com pelo menos um alelo F508del com o uso de placebo ou de um comparador ativo como outras combinações de moduladores da CFTR. O estudo foi realizado seguindo as recomendações Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e a metodologia Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO). Foram realizadas buscas nos seguintes bancos de dados: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov, desde a sua criação até 26 de dezembro de 2022. O risco de viés foi avaliado por meio da ferramenta de risco de viés da Cochrane, e a qualidade das evidências foi determinada com base no sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: Foram identificados 54 estudos na busca primária. Destes, 6 preencheram os critérios de inclusão e foram analisados (1.127 pacientes: 577 pacientes intervenção e 550 pacientes controle). A meta-análise revelou que o uso de ETI aumentou o VEF1 em porcentagem do previsto [diferença de risco (DR): +10,47%; IC95%: 6,88-14,06], reduziu o número de exacerbações pulmonares agudas (DR: −0,16; IC95%: −0,28 a −0,04) e melhorou a qualidade de vida (DR: +14,93; IC95%: 9,98-19,89) e o IMC (DR: +1,07 kg/m2; IC95%: 0,90-1,25). Os eventos adversos não diferiram entre os grupos (DR: −0,03; IC95%: −0,08 a 0,01), e nenhum dos estudos relatou óbitos. Conclusões: Nossos achados demonstram que o tratamento com ETI melhora substancialmente os desfechos clinicamente significativos centrados no paciente.

Supervivencia en pacientes con fibrosis quística / Survival in Patients with Cystic Fibrosis

Introducción: La fibrosis quística ha dejado de ser una enfermedad pediátrica para ser una enfermedad crónica del adulto. Existen múltiples factores que condicionan la supervivencia de estos enfermos. Objetivo: Determinar la sobrevida de pacientes pediátricos con fibrosis quística hospitalizados en un centro especializado. Métodos: Estudio retrospectivo de cohorte cuyo universo lo conformaron 27 pacientes incluidos en el Registro Provincial de Fibrosis Quística de Granma, 2003-2018. Se analizaron variables: edad actual y sexo, variante genética, presencia de gérmenes, formas clínicas, y supervivencia a partir del diagnóstico y tratamiento. Se utilizó el método de Kaplan-Meier y Log-Rank Test, para un nivel de significación de 95 por ciento. Resultados: El 40,7 por ciento de los pacientes declaró tener actualmente más de 15 años, predominó el sexo masculino (63 por ciento), y la mutación F508 del en su variante genética heterocigótica (44,4 por ciento). El promedio de supervivencia resultó en 21,4 años, no existieron diferencias significativas según sexo, formas clínicas y tipos de gérmenes. Conclusiones: Los pacientes con fibrosis quística en Granma, Cuba mostraron un promedio de supervivencia de 21,4 años, inferior a lo documentado en países desarrollados. El Estado cubano garantiza recursos para la atención de estos pacientes, a pesar de las dificultades económicas del país(AU)

Introduction: Cystic fibrosis is no longer a pediatric disease but a chronic adult disease. There are multiple factors that condition the survival of these patients. Objective: To determine the survival of pediatric patients with cystic fibrosis hospitalized in a specialized center. Methods: Retrospective cohort study whose universe consisted of 27 patients included in the Granma provincial cystic fibrosis registry, 2003-2018. Variables were analyzed: current age and gender, genetic variant, presence of germs, clinical forms and survival after diagnosis and treatment. The Kaplan-Meier method and Log-Rank Test were used, for a significance level of 95 percent. Results: 40.7 percent of patients are currently over 15 years of age, male sex predominates (63 percent) and the F508del mutation in its heterozygous genetic variant (44.4 percent). The average survival is 21.4 years, there were no significant differences according to gender, clinical forms and types of germs. Conclusions: The average survival rate of patients with cystic fibrosis in Granma, Cuba, is 21.4 years, lower than that documented in developed countries. The Cuban State guarantees resources for the care of these patients, despite the country's economic difficulties(AU)

Repercussões Clínicas da Gameterapia no Manejo do Indivíduo com Fibrose Cística / Clinical repercussions of game therapy in the management of individuals with cystic fibrosis

Introdução: A gameterapia (GT) tem sido utilizada como método para estimular a prática de atividade física em indivíduos com fibrose cística (FC), podendo proporcionar melhora no sistema cardiorrespiratório e na adesão ao tratamento. Objetivo: analisar as repercussões clínicas da gameterapia no manejo de pacientes com FC. Métodos:Conduziu-se uma revisão sistemática de literatura nas seguintes bases de dados: PubMed, Embase, Scopus e MEDLINE via Ovid, utilizando-se os descritores:"Cystic fibrosis","video games" e seus cognatos, por meio da qual se incluíram estudos que descrevessem as repercussões do uso da GT em indivíduos com FC. Resultados: Foram identificados 293 estudos, sendo 7 selecionados ao final. Em 6 estudos, a frequência cardíaca alcançada durante a GT apresentou-se dentro dos padrões recomendados para treinamento. A avaliação do consumo máximo de oxigênio (VO2máx) foi realizada em 3 publicações, e este parâmetro apresentou níveis mais elevados em comparação ao identificado no teste de caminhada de seis minutos. Os consoles mais utilizados foram Nintendo Wii TM e Xbox 360 ™ e a intensidade na realização dos exercícios com a GT esteve entre moderada e intensa. A adesão dos indivíduos quanto a esse recurso também foi verificada, e a GT apresentou-se mais aceitável que outros e foi considerada lúdica. Conclusão: a GT se mostra uma intervenção capaz de gerar respostas fisiológicas que correspondem às necessidades de treinamento, além de maior adesão e satisfação dos indivíduos com FC em sua realização (AU),

Game therapy (GT) has been used as a method to encourage the practice of physical activity in individuals with cystic fibrosis (CF), which may provide improvement in the cardiorespiratory system and treatment adherence. Objective: analyze the clinical repercussions of game therapy in the management of patients with CF. Methods: A systematic review of the literature was carried out in the following databases: PubMed, Embase, Scopus and MEDLINE via Ovid, using the descriptors: "Cystic fibrosis", "video games" and their cognates, through which they included Studies describing the repercussions of the use of GT in individuals with CF were sought. Results: 293 studies were identified, seven of which were selected at the end. In six studies, the heart rate reached during the TG was within the recommended standards for training. The assessment of maximum oxygen consumption (VO2max) was performed in three publications, and this parameter showed higher levels compared to that identified in the six-minute walk test. The most used consoles were Nintendo WiiTM and Xbox 360™and the intensity in carrying out the exercises with the TG was moderate and intense. The individuals' adherence to this resource was also verified, and the GT was more acceptable than others and was considered playful. Conclusion: TG proves to be an intervention capable of generating physiological responses that correspond to training needs and greater adherence and satisfaction of individuals with CF in its performance (AU).

How the speech-language pathologist interacts with cystic fibrosis patients? a scoping review / Qual a relação da fonoaudiologia com a fibrose cística? uma revisão de escopo / ¿Cuál es la relación entre la logopedia y la fibrosis quís- tica? una revisión del alcance

Objective: The review describes the changes related to sleep-breathing disorders, com- munication and feeding processes in subjects with CF, through a scoping review. Meth- ods: A scoping review based on the PRISMA protocol was carried out in Pubmed, Lilacs and Scopus databases, to investigate the possibility of including SLP in the treatment of patients with CF. The inclusion criteria included studies that addressed communication and eating processes and disorders related to CF. Studies with a sample that presented other comorbidities that would justify the worsening of the condition, or secondary stud- ies, were excluded. There was no time or language delimitation. Results: The search found 1566 works, 27 Lilacs, 1009 Pubmed and 530 Scopus, by analysis of titles, abstract and reading in full. A total of 30 articles were selected for inclusion, 2 Lilacs, 22 Pubmed and 6 Scopus, all related to Speech-Language Pathology. Conclusion: It was observed that there is a poor sleep quality due to nocturnal desaturation, mild and moderate obstructive apnea. In studies related to hearing, individuals had sensorineural hearing loss. Speech-Language Pathology is of paramount importance in monitoring these sub- jects.

Objetivo: Descrever alterações relacionadas aos processos de distúrbios respiratórios do sono, comunicação e alimentação em sujeitos com FC, por meio de uma scoping review. Métodos: Foi realizada uma scoping review nas bases de dados Pubmed, Lilacs e Scopus, para investigar a possibilidade de incluir o fonoaudiólogo no tratamento de pacientes com FC, utilizando o checklist PRISMA. Os critérios de inclusão incluíram estudos que abor- dassem processos de comunicação e alimentação e distúrbios relacionados à FC. Foram excluídos estudos com amostra que apresentasse outras comorbidades que justificassem o agravamento do quadro, ou estudos secundários. Não houve delimitação de tempo ou idioma. Resultados: A busca encontrou 1566 trabalhos, sendo 27 Lilacs, 1009 Pubmed e 530 Scopus, por meio de análise de títulos, resumo e leitura na íntegra. Foram seleciona- dos para inclusão 30 artigos, sendo 2 Lilacs, 22 Pubmed e 6 Scopus, todos relacionados à Fonoaudiologia. Conclusão: Observou-se que há má qualidade do sono devido à dessa- turação noturna, apneia obstrutiva leve e moderada. Em estudos relacionados à audição, os indivíduos apresentaram perda auditiva neurossensorial. A Fonoaudiologia é de suma importância no acompanhamento desses sujeitos.

Objetivo: Describir las alteraciones relacionadas con los procesos de trastornos respira- torios del sueño, comunicación y alimentación en sujetos con FQ, a través de una revisión de alcance. Métodos: Se realizó una revisión de alcance en las bases de datos Pubmed, Lilacs y Scopus, para investigar la posibilidad de incluir al logopeda en el tratamiento de pacientes con FQ, utilizando la lista de verificación PRISMA. Los criterios de inclusión incluyeron estudios que abordaran los procesos de comunicación y alimentación y los trastornos relacionados con la FQ. Se excluyeron los estudios con una muestra que pre- sentaba otras comorbilidades que justificasen el empeoramiento del cuadro, o estudios secundarios. No había delimitación de tiempo ni de idioma. Resultados: La búsqueda en- contró 1566 trabajos, de los cuales 27 fueron Lilacs, 1009 Pubmed y 530 Scopus, me- diante análisis de títulos, resúmenes y lectura completa. Se seleccionaron 30 artículos para inclusión, 2 Lilacs, 22 Pubmed y 6 Scopus, todos relacionados con Logopedia. Con- clusión: Se observó que existe mala calidad del sueño por desaturación nocturna, apnea obstructiva leve y moderada. En estudios relacionados con la audición, los individuos tenían pérdida auditiva neurosensorial. La logopedia es de suma importancia en el segui- miento de estos sujetos.

Role of mucociliary clearance system in respiratory diseases / 中南大学学报(医学版)

Mucociliary clearance system is the primary innate defense mechanism of the lung. It plays a vital role in protecting airways from microbes and irritants infection. Mucociliary clearance system, which is mediated by the actions of airway and submucosal gland epithelial cells, plays a critical role in a multilayered defense system via secreting fluids, electrolytes, antimicrobial and anti-inflammatory proteins, and mucus onto airway surfaces. Changes in environment, drugs or diseases can lead to mucus overproduction and cilia dysfunction, which in turn decrease the rate of mucociliary clearance and enhance mucus gathering. The dysfunction of mucociliary clearance system often occurs in several respiratory diseases, such as primary ciliary dysfunction, cystic fibrosis, asthma and chronic obstructive pulmonary disease, which are characterized by goblet cell metaplasia, submucosal gland cell hypertrophy, mucus hypersecretion, cilia adhesion, lodging and loss, and airway obstruction.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Patient care in cystic fibrosis centers: a real-world analysis in Brazil / Assistência ao paciente em centros de fibrose cística: análise do mundo real no Brasil

ABSTRACT Objective: To analyze the characteristics of cystic fibrosis (CF) care centers (CFCCs) in Brazil. Methods: A questionnaire was sent to the coordinators of all 51 registered CFCCs between May and September of 2021. Results: The response rate was 100%. Southeastern Brazil is the region where most of the CFCCs in the country are located (21 centers; 41%), followed by the southern and northeastern regions (11 centers each; 21.5%), the central-western region (6; 12%), and the northern region (2; 4%). A total of 4,371 patients with CF were cared for in Brazil during the study period, ranging from 7 to 240 patients per center (mean, 86 patients/center; median, 75 patients/center); 2,197 patients (50%) were cared for in centers in the southeastern region of the country, particularly in the state of São Paulo (33%), the remaining patients being treated in southern Brazil (1,014 patients, 23%), northeastern Brazil (665 patients, 15%), central-western Brazil (354 patients, 8%), and northern Brazil (141 patients, 4%). Overall, 47 centers (92%) reported having an incomplete multidisciplinary team; 4 (8%) lacked essential team members; 6 (12%) lacked a physical therapist; 5 (10%) lacked a dietitian; 17 (33%) lacked outpatient nursing care; 13 (25%) lacked outpatient social work services; 14 (27%) lacked a psychologist; and 32 (63%) lacked a clinical pharmacist. Seven CFCCs (14%) in the northern and northeastern regions of Brazil reported that the quality of newborn screening for CF was poor. All centers reported having difficulties in accessing CF medications. Conclusions: Brazilian CFCCs experience multiple problems, including inadequate staffing, infrastructure, testing, and medication supply. There is an urgent need to regulate the implementation of CF referral centers and an appropriate network structure for the diagnosis and follow-up of CF patients using optimal treatment recommendations.

RESUMO Objetivo: Analisar as características dos centros de tratamento de fibrose cística (CTFC) no Brasil. Métodos: Entre maio e setembro de 2021, um questionário foi enviado aos coordenadores de todos os 51 CTFC registrados. Resultados: A taxa de resposta foi de 100%. O Sudeste do Brasil é a região onde está a maioria dos CTFC do país (21 centros; 41%), seguida pelas regiões Sul e Nordeste (11 centros cada; 21,5%), Centro-Oeste (6; 12%) e Norte (2; 4%). No total, 4.371 pacientes com fibrose cística (FC) foram atendidos no Brasil durante o período do estudo, variando de 7 a 240 pacientes por centro (média de 86 pacientes/centro; mediana de 75 pacientes/centro); 2.197 pacientes (50%) foram atendidos em centros da região Sudeste, particularmente no estado de São Paulo (33%), e os demais receberam atendimento nas regiões Sul (1.014 pacientes, 23%), Nordeste (665 pacientes, 15%), Centro-Oeste (354 pacientes, 8%) e Norte (141 pacientes, 4%). Do total de CTFC, 47 (92%) relataram que a equipe multidisciplinar estava incompleta; em 4 centros (8%), as equipes multidisciplinares careciam de membros essenciais; 6 centros (12%) careciam de fisioterapeuta; 5 (10%) careciam de dietista; 17 (33%) careciam de cuidados ambulatoriais de enfermagem; 13 (25%) careciam de serviços ambulatoriais de assistência social; 14 (27%) careciam de psicólogo e 32 (63%) careciam de farmacêutico clínico. Sete CTFC (14%) nas regiões Norte e Nordeste relataram que a qualidade da triagem neonatal de FC era ruim. Todos os centros relataram dificuldades de acesso a medicamentos para FC. Conclusões: Os CTFC brasileiros enfrentam múltiplos problemas: pessoal inadequado, infraestrutura inadequada, testes inadequados e fornecimento inadequado de medicamentos. Há uma necessidade urgente de regulamentar a implantação de centros de referência em FC e de uma rede adequada para o diagnóstico e acompanhamento de pacientes com FC com base nas recomendações para o tratamento ideal da doença.