Faecal calprotectin and rectal histological inflammatory markers in cystic fibrosis: a single-centre study.

OBJECTIVE: To analyse the association of faecal calprotectin with the genetic and clinical characteristics of paediatric patients with cystic fibrosis (PwCF). In a subset of these patients, we aimed to associate histological inflammatory features of rectal mucosa to faecal calprotectin levels. METHODS: In a prospective study, faecal calprotectin levels were collected in all 23 PwCF attending our paediatric centre, together with demographic and clinical data. Associations between faecal calprotectin and clinical features were determined. In 11 of these patients, endoscopic rectal biopsies were obtained and the association between faecal calprotectin and histological inflammatory markers was analysed. Statistical analyses included Spearman's correlation coefficient, Mann-Whitney U test and Fisher's exact test. Sensitivity and specificity was calculated. RESULTS: Median age of PwCF was 12 years, 19 had pancreatic insufficiency (PI) (19/23). Seventeen (17/23) had elevated faecal calprotectin, and the median value was 88 µg/g (IQR=178 µg/g). Higher faecal calprotectin levels were observed in the PI group (101 vs 30 µg/g, p=0.027). No significant correlation between elevated faecal calprotectin level and body mass index z-score was found. Five patients (22%) reported abdominal pain, three (13%) complained of diarrhoea and three (13%) had constipation, but these symptoms were not associated with elevated faecal calprotectin.Unspecific focal rectal inflammation was found in four patients (4/11). An association between rectal mucosa inflammation and elevated faecal calprotectin was found (p=0.015). Sensitivity was 100% and specificity was 86%. CONCLUSIONS: In our PwCF, elevated faecal calprotectin was frequent, particularly if PI, and it was not related to gastrointestinal symptoms or malnutrition. Elevated faecal calprotectin was present in patients with histological evidence of rectal inflammation. Faecal calprotectin may be an indicator of asymptomatic rectal inflammation in PwCF.

New drugs in cystic fibrosis: what has changed in the last decade?

Cystic fibrosis (CF), a life-limiting chronic disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, affects more than 90,000 people worldwide. Until recently, the only available treatments were directed to symptom control, but they failed to change the course of the disease. New drugs developed in the last decade have the potential to change the expression, function, and stability of CFTR protein, targeting the basic molecular defect. The authors seek to provide an update on the new drugs, with a special focus on the most promising clinical trials that have been carried out to date. These newly approved drugs that target specific CFTR mutations are mainly divided into two main groups of CFTR modulators: potentiators and correctors. New therapies have opened the door for potentially disease-modifying, personalized treatments for patients with CF.

Pediatric population with cystic fibrosis in the centre of Portugal: candidates for new therapies

Abstract Objectives: Cystic fibrosis (CF) is a severe autosomal recessive disease that results from mutations in a gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, a chloride channel. This study aims to characterize the clinical and genetic features of a cohort of pediatric people with CF (PwCF) in the center of Portugal and to determine which ones are candidates for the new drugs modulating the CFTR channel. Methods: A review of the demographic, genetic and clinical characteristics of PwCF undergoing follow-up at a CF reference center was carried out. Results: Twenty-three PwCF (12 male), with a median age of 12 years, were followed up. All patients carry the F508del mutation in at least one allele. Fifteen PwCF were F508del-homozygous, median BMI z-score was -0.13, all are pancreatic insufficient and median FEV1 value was 78.1%. These PwCF are eligible for dual therapy (lumacaftor/tezacaftor+ivacaftor) and for triple therapy (tezacaftor+ivacaftor+elexacaftor). PwCF with 711 +1G->T (n = 2), 2184insA (n = 1) mutations and a novel mutation c.3321dup (n = 1) have minimal function mutation and patients with a residual function mutation: R334W (n = 3) and P5L (n = 1) have a less severe phenotype. All these patients, because they also carry F508del mutation, are elegible to triple therapy. Conclusions: Genetic and molecular characterization of PwCF poses an important step not just for CF diagnosis and prognosis which is tightly correlated with the clinical phenotype, but also for the eligibility of CFTR modulator drugs.

Pediatric population with cystic fibrosis in the centre of Portugal: candidates for new therapies.

OBJECTIVES: Cystic fibrosis (CF) is a severe autosomal recessive disease that results from mutations in a gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, a chloride channel. This study aims to characterize the clinical and genetic features of a cohort of pediatric people with CF (PwCF) in the center of Portugal and to determine which ones are candidates for the new drugs modulating the CFTR channel. METHODS: A review of the demographic, genetic and clinical characteristics of PwCF undergoing follow-up at a CF reference center was carried out. RESULTS: Twenty-three PwCF (12 male), with a median age of 12 years, were followed up. All patients carry the F508del mutation in at least one allele. Fifteen PwCF were F508del-homozygous, median BMI z-score was -0.13, all are pancreatic insufficient and median FEV1 value was 78.1%. These PwCF are eligible for dual therapy (lumacaftor/tezacaftor+ivacaftor) and for triple therapy (tezacaftor+ivacaftor+elexacaftor). PwCF with 711 +1G->T (n = 2), 2184insA (n = 1) mutations and a novel mutation c.3321dup (n = 1) have minimal function mutation and patients with a residual function mutation: R334W (n = 3) and P5L (n = 1) have a less severe phenotype. All these patients, because they also carry F508del mutation, are elegible to triple therapy. CONCLUSIONS: Genetic and molecular characterization of PwCF poses an important step not just for CF diagnosis and prognosis which is tightly correlated with the clinical phenotype, but also for the eligibility of CFTR modulator drugs.

Secondary Hepatic Injury in Pediatric Intensive Care: Risk Factors and Prognostic Impact.

OBJECTIVES: The aim of this study was to assess the profile of secondary hepatic injury (SHI), to determine risk factors and to evaluate its impact on prognosis of pediatric intensive care patients. METHODS: An exploratory observational and retrospective study was conducted in a Pediatric Intensive Care Unit. Two groups were defined: with SHI [alanine aminotransferase (ALT) ≥100 IU/L or gamma glutamyl transpeptidase (GGT)≥100 IU/L or direct bilirubin ≥30 µmol/L] and without. SHI was divided into 3 patterns: cytolysis, cholestasis, and mixed. RESULTS: SHI occurred in 16.5%, cytolysis in 5%, cholestasis in 4%, and mixed pattern in 7%. Independent risk factors for SHI were: organ dysfunction score PELOD-2 in D1 in cytolysis (n = 28); total parenteral nutrition and Pediatric Index of Mortality 3 (PIM3) in cholestasis (n = 23); sepsis, oncologic comorbidities, PIM3, and respiratory dysfunction in mixed pattern (n = 37). The ALT was an independent risk factor and a good predictor of mortality (AUC = 0.865) with a cut-off of 137 IU/L. CONCLUSIONS: SHI was associated with worst prognostic. ALT may be useful for detecting patients at increased risk of death, probably being a surrogate marker of the illness severity, reflecting a secondary injury.

Cluster analysis of cognitive performance in a sample of patients with Parkinson's disease / "Análise de Cluster" do desempenho cognitivo em uma amostra de pacientes com doença de Parkinson

ABSTRACT Background: Cognitive impairment is a common feature of Parkinson's disease (PD). The diagnoses of mild cognitive impairment (MCI) in patients with PD implies an increased risk for later development of dementia, however, it is unclear whether a specific type of cognitive loss confers increased risk for faster cognitive decline. Objective: Determine whether it was possible to identify distinct cognitive phenotypes in a sample of patients with PD. Methods: A cross-sectional evaluation of 100 patients with PD recruited from a movement disorders clinic was conducted. The patients were evaluated using the simplified motor score of the UPDRS, the Hoehn and Yahr, Schwab and England, Geriatric Depression Scale, Pfeffer Functional Activities Questionnaire, Clinical Dementia Rating Scale, Mini-Mental State Examination, clock drawing test, digit span, word list battery of CERAD, Frontal Assessment Battery and verbal fluency test. We classified the patients as having normal cognition (PDNC), MCI (PDMCI) or dementia (PDD). Data were analyzed using the chi-square test, non-parametric statistics and cluster analysis. Results: There were 40 patients with PDD, 39 with PDMCI and 21 with PDNC. Patients with PDD were older, had longer disease duration, lower education and lower MMSE scores. Cluster analysis showed 3 general distinct cognitive profiles that represented a continuum from mild to severe impairment of cognition, without distinguishing specific cognitive profiles. Conclusion: Cognitive impairment in PD occurs progressively and heterogeneously in most patients. It is unclear whether the definition of the initial phenotype of cognitive loss can be used to establish the cognitive prognosis of patients.

RESUMO Embasamento: O comprometimento cognitivo é um problema comum da doença de Parkinson (DP). O diagnóstico de comprometimento cognitivo leve (CCL) em pacientes com DP implica em risco aumentado para o desenvolvimento posterior de demência, no entanto, não é claro se algum tipo específico de perda cognitiva confere risco para um declínio cognitivo mais rápido. Objetivo: Determinar se seria possível identificar fenótipos cognitivos em uma amostra de pacientes com DP. Métodos: Foi uma avaliação transversal de 100 pacientes com DP recrutados de uma clínica de distúrbios de movimento. Eles foram avaliados utilizando um escore motor simplificado da UPDRS, Hoehn e Yahr, Schwab e England, Escala de Depressão Geriátrica, Questionário de Atividades Funcionais de Pfeffer, Escala CDR, Mini-Exame do Estado Mental, desenho do relógio, extensão de dígitos, lista de palavras da bateria do CERAD, bateria de avaliação frontal e teste de fluência verbal. Nós classificamos os pacientes como tendo cognição normal (PDCN), CCL (PDCCL) ou demência (PDD). Os dados foram analisados por meio do teste do qui-quadrado, estatística não-paramétrica e análise de cluster. Resultados: Havia 40 pacientes com PDD, 39 com PDCCL e 21 com PDCN. Pacientes com PDD eram mais velhos, tinham maior tempo de doença, menor escolaridade e desempenho inferior no MEEM. A análise de cluster mostrou 3 perfis cognitivos distintos que representariam um continuo entre discreto a grave comprometimento da cognição, sem distinguir perfis cognitivos específicos. Conclusão: O comprometimento cognitivo na DP ocorre de forma progressiva e heterogênea na maioria dos pacientes. Não é claro se a definição do fenótipo inicial de perda cognitiva poderia ser utilizado para estabelecer o prognóstico cognitivo para o paciente.

[Multidimensional Strategy Regarding the Reduction of Central-Line Associated Infection in Pediatric Intensive Care]. / Estratégia Multidimensional na Redução de Infeção Associada a Cateter Venoso Central em Pediatria.

INTRODUCTION: To determine the central-line associated bloodstream infection rate after implementation of central venous catheter-care practice bundles and guidelines and to compare it with the previous central-line associated bloodstream infection rate. MATERIAL AND METHODS: A prospective, longitudinal, observational descriptive study with an exploratory component was performed in a Pediatric Intensive Care Unit during five months. The universe was composed of every child admitted to Pediatric Intensive Care Unit who inserted a central venous catheter. A comparative study with historical controls was performed to evaluate the result of the intervention (group 1 versus group 2). RESULTS: Seventy five children were included, with a median age of 23 months: 22 (29.3%) newborns; 28 (37.3%) with recent surgery and 32 (43.8%) with underlying illness. A total of 105 central venous catheter were inserted, the majority a single central venous catheter (69.3%), with a mean duration of 6.8 ± 6.7 days. The most common type of central venous catheter was the short-term, non-tunneled central venous catheter (45.7%), while the subclavian and brachial flexure veins were the most frequent insertion sites (both 25.7%). There were no cases of central-line associated bloodstream infection reported during this study. Comparing with historical controls (group 1), both groups were similar regarding age, gender, department of origin and place of central venous catheter insertion. In the current study (group 2), the median length of stay was higher, while the mean duration of central venous catheter (excluding peripherally inserted central line) was similar in both groups. There were no statistical differences regarding central venous catheter caliber and number of lumens. Fewer children admitted to Pediatric Intensive Care Unit had central venous catheter inserted in group 2, with no significant difference between single or multiple central venous catheter. DISCUSSION: After multidimensional strategy implementation there was no reported central-line associated bloodstream infection Conclusions: Efforts must be made to preserve the same degree of multidimensional prevention, in order to confirm the effective reduction of the central-line associated bloodstream infection rate and to allow its maintenance.

Introdução: Determinar a incidência de infeções da corrente sanguínea associadas ao uso de cateter venoso central, após reforço de medidas multidisciplinares de boa prática e a sua comparação com a taxa de incidência de infeções da corrente sanguínea associadas ao uso de cateter venoso central prévia. Material e Métodos: Estudo observacional descritivo, com colheita prospetiva de dados, durante cinco meses, após implementação de medidas multidisciplinares. Foram incluídas todas as crianças admitidas na unidade de Cuidados Intensivos Pediátricos, submetidas à colocação de cateter venoso central e foi efetuada comparação com controlos históricos.Resultados: Incluíram-se 75 doentes com idade mediana de 23 meses: 22 (29,3%) recém-nascidos, 28 (37,3%) submetidos a cirurgia e 32 (43,8%) com patologia subjacente. Foram colocados 105 cateteres venosos centrais, com tempo médio de permanência de 6,8 ± 6,7 dias. O tipo de cateter venoso central mais comum foi de curta duração (45,7%), sendo os locais de inserção mais frequentes a veia subclávia e da flexura braquial (ambos 25,7%). Não ocorreu nenhuma infeção da corrente sanguínea associada ao uso de cateter venoso central durante o período do estudo. Comparando com os controlos históricos, ambos os grupos eram semelhantes relativamente à idade, género, proveniência dos doentes e local de colocação de cateter venoso central. No estudo atual, a duração mediana de internamento foi superior, com tempo de permanência de cateter venoso central (excluindo epicutâneo-cava) semelhante. Não se verificou diferença em relação ao calibre e número de lumens do cateter venoso central utilizado. A percentagem de crianças que colocou cateter venoso central em relação ao total de crianças admitidas no serviço no mesmo período foi menor no estudo atual, não existindo diferença significativa entre colocação de cateter venoso central único ou múltiplo. Discussão: Após implementação da estratégia multidimensional não se registou nos Cuidados Intensivos Pediátricos ocorrência de infeções da corrente sanguínea associadas ao uso de cateter venoso central. Conclusões: Devem ser encetados esforços para preservar o mesmo grau de prevenção multidimensional, para que se confirme a redução efetiva da taxa de incidência de infeções da corrente sanguínea associadas ao uso de cateter venoso central.

Frontal assessment battery in a Brazilian sample of healthy controls: normative data / Bateria de avaliação frontal em uma amostra brasileira de controles saudáveis: dados normativos

OBJECTIVE: To show data on the performance of healthy subjects in the Frontal Assessment Battery (FAB), correlating with gender, age, education, and scores in the Mini-Mental State Examination (MMSE). METHODS: Two hundred and seventy-five healthy individuals with mean age of 66.4±10.6 years-old were evaluated. Mean total FAB scores were established according to the educational level. RESULTS: Mean total FAB scores according to the educational level were 10.9±2.3, for one to three years; 12.8±2.7, for four to seven years; 13.8±2.2, for eight to 11 years; and 15.3±2.3, for 12 or more years. Total FAB scores correlated significantly with education (r=0.47; p<0.0001) and MMSE scores (r=0.39; p<0.0001). No correlation emerged between FAB scores, age, and gender. CONCLUSION: In this group of healthy subjects, the Brazilian version of the FAB proved to be influenced by the education level, but not by age and gender.

OBJETIVO: Avaliar o desempenho de indivíduos brasileiros saudáveis na Bateria de Avaliação Frontal (FAB) correlacionado com gênero, idade, educação e escores do Exame do Mini-Mental (MMSE). MÉTODOS: Foram avaliados 275 controles saudáveis com média de idade de 66,4±10,6 anos. Os escores médios foram estabelecidos de acordo com o nível educacional. RESULTADOS: Os escores médios da FAB em relação ao nível educacional foram 10,9±2,3 para um a três anos; 12,8±2,7 para quatro a sete anos; 13,8±2,2 para oito a 11 anos e 15,3±2,3 para 12 ou mais anos. Os escores totais da FAB se correlacionaram significativamente com o nível educacional (r=0,47; p<0,0001) e com os escores do MMSE (r=0,39; p<0,0001). Não foram observadas correlações significativas entre os escores da FA, o gênero e a idade. CONCLUSÃO: Na presente amostra, a versão brasileira da FAB sofreu influência do nível de escolaridade, mas não da idade e do gênero.

[Post-traumatic meningitis in children: eleven years' analysis]. / Meningite bacteriana pós-traumática em idade pediátrica: análise de onze anos.

INTRODUCTION: Traumatic brain injury is a frequent reason for admission at pediatric emergency services. In severe cases, with basilar skull fracture, bacterial meningitis is a serious and potentially fatal complication to be considered. OBJECTIVE: To describe clinical and laboratory features, bacteriology and outcome of children with post-traumatic meningitis, and evaluate the proportion of meningitis in the population who suffered head trauma. METHODS AND MATERIALS: Retrospective review of medical records of children with this diagnosis admitted to a level 3 pediatric hospitals in the Central Region of Portugal, contextualized in the evaluation of the number of head injuries, fractures and cerebrospinal fluid leakages, during a 11-year period (January 1999 to December 2009). RESULTS: Four children were identified, corresponding to 0,7% of the children with skull fractures, 4,1% of children with basilar skull fractures and 13,8% of those with documented cerebrospinal fluid leakage. Three were boys, with a median age of 8 years (2-10 years). The median time between head trauma and meningitis was 1,1 years (3 days-3,4 years). In all cases a basilar skull fracture was identified and cerebrospinal fluid leakage documented. Two children required surgery. Streptococcus pneumonia was the pathogen identified in two cases with positive cerebrospinal fluid culture. One child died and other has post-traumatic peripheral facial palsy. CONCLUSIONS: Bacterial meningitis is a complication to be considered in head injury with basilar skull fracture, particularly when associated with cerebrospinal fluid leakage, even though the injury occurred several years earlier, and is usually a serious condition. One of our children died. Similar to what is described, S. pneumoniae was the most common bacteria, and this fact supports that children with head trauma and cerebrospinal fluid leakage should receive pneumococcal vaccine. The follow-up of these children requires constant vigilance and should include a multidisciplinary approach.

[Extended-spectrum ß-lactamase producing bacilli in a paediatric hospital]. / Bacilos gram negativos produtores de ß-lactamases de espectro expandido num hospital pediátrico.

BACKGROUND: Enterobacteriaceae are a common cause of invasive disease in children. The production of extended-spectrum ß-lactamase (ESBL) by these bacteria and consequent resistance to several antibiotics has increased. The paediatric data are scarce. AIMS: To identify children infected with ESBL-producing bacilli, determining their prevalence in health care related infection and community-acquired disease. To analyse demographic, clinical, laboratory, therapeutic and follow-up data. To identify potential risk factors for infection by ESBL-producing organisms. METHODOLOGY: A case-control study, conducted in a level III paediatric hospital, from July 2007 to December 2009. All patients were identified from the microbiology database. Children infected by ESBL-producing bacilli were compared with a group with infection by non-ESBL producers, selected in a systematic way, given the bacteria, product and date of isolation. Statistical data analysis was performed using SPSS® 17.1. RESULTS: The ESBL-producing phenotype was detected in 0.5% of Escherichia coli and 16.4% of Klebsiella spp identified. These bacteria were isolated in 23 children: 7 Escherichia coli (30.4%), 15 Klebsiella pneumoniae (65.2%) and 1 Klebsiella oxytoca (4.3%). The most common diagnosis was urinary tract infection (39%). Hospital admission was required in 70% of the cases versus 50% controls (p=0.141), with mean duration stay of 69 days for cases and 36 days for controls (p=0.235). The mean time between admission and infection was 32 days in both (p=0.978). Health care related infections were identified in 70% of cases versus 25% of controls (p=0.001). Infections due to ESBL producing organisms occurred in the community setting particularly in the last year of the study (n=4). The presence of chronic disease (p=0.022) and previous hospitalization (p=0.025), antibiotic use (p=0.008) and invasive ventilation (p=0.002) were more common in infection caused by ESBL-producing bacteria. Surgery (p=0.175) and the presence of a central venous catheter (p=0.189) were not risk factors. In a multivariate analysis, only prior invasive ventilation was an independent risk factor for infection by ESBL-producing bacteria (p=0.002, OR=7). CONCLUSIONS: The ESBL-producing phenotype was detected in 0.5% Escherichia coli and 16.4% Klebsiella spp identified; mainly in health care related infections. The presence of chronic disease and previous hospitalization, invasive ventilation and antibiotic intake were more common in infections caused by these bacteria. Prior invasive ventilation was an independent risk factor.

Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical characterization, and medical conditions.

The objective of this study was to estimate the prevalence of autistic spectrum disorder (ASD) and identify its clinical characterization, and medical conditions in a paediatric population in Portugal. A school survey was conducted in elementary schools, targeting 332,808 school-aged children in the mainland and 10,910 in the Azores islands. Referred children were directly assessed using the Diagnostic and Statistical Manual of Mental Disorders (4th edn), the Autism Diagnostic Interview-Revised, and the Childhood Autism Rating Scale. Clinical history and a laboratory investigation was performed. In parallel, a systematic multi-source search of children known to have autism was carried out in a restricted region. The global prevalence of ASD per 10,000 was 9.2 in mainland, and 15.6 in the Azores, with intriguing regional differences. A diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders.

Doença muscular inflamatória juvenil: relato de seis casos atendidos no Serviço de Reumatologia do HU-UFJF e revisão de literatura / Juvenile inflammatory myopathy: report of six patients seen at the Rheumatology Department at HU-UFJF and literature revision

A doença muscular inflamatória representa um grupo de desordens caracterizado por fraqueza muscular proximal, inflamação e lesão dos tecidos musculares. É a principal e a mais grave causa de miopatia até os 16 anos de idade, embora seja uma enfermidade rara. Uma dificuldade inerente ao seu diagnóstico é que não há limites clínicos precisos entre as diferentes síndromes que resultam em fraqueza muscular, assim como o fato de a maioria dessas entidades cursarem com manifestações sistêmicas diferentes (cutâneas, cardíacas, pulmonarese gastrintestinais) que podem confundir o seu diagnóstico correto. Relatamos seis casos de pacientes com diagnóstico realizado na infância, atendidos pelo Serviço de Reumatologia do Hospital Universitário da Universidade Federal de Juiz de Fora (HU-UFJF), no período de 1998 a 2004.

Inflammatory diseases of muscles are a heterogeneous group of disorders characterized by proximal muscle weakness and nonsuppurative inflammation of muscles. Idiopathic inflammatory myopathies are relatively rare diseases, but they are the most frequent and serious cause of myopathy in patients under 16 years. Clinical manifestations can occur in a variety of combinations or patterns, and no single feature is specific or diagnostic, making the correct differential diagnosis with other syndromes that result in skeletal muscle dysfunction a difficult task. We report six cases of patients diagnosed at childhood, seen at the rheumatology department at HU-UFJF.