ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

Cinacalcet sustainedly prevents pancreatitis in a child with a compound heterozygous SPINK1/AP2S1 mutation.

Familial hypocalciuric hypercalcemia is an autosomal dominant genetic disorder characterized by hypercalcemia associated with inappropriate hypocalciuria and normal parathyroid hormone levels. Acute recurrent pancreatitis (ARP) is rare in children. Predisposing factors include hypercalcemia and mutations in the serine protease inhibitor Kazal-type 1 (SPINK1) gene. The disease carries a heavy morbidity and preventive treatment options are scant. Here, we report a child with a novel genetic/metabolic form of ARP associated with compound heterozygous SPINK1/AP2S1 (adaptor protein-2 σ1-subunit) mutations, recurrence of which was completely abrogated for 6 years by cinacalcet treatment.

The Belgian national registry on chronic pancreatitis: A prospective multi-centre study covering more than 800 patients in one year.

BACKGROUND/OBJECTIVES: The epidemiology, natural history, complications, and therapeutic management of chronic pancreatitis (CP) are not well described at the national level. This multi-centre prospective observational study involving eight Belgian hospitals aimed to improve the understanding of these aspects of CP in Belgium. METHODS: All patients with a diagnosis of CP based on imaging were eligible for this study. Data were gathered regarding epidemiology, etiology, CP complications, and treatment modalities. RESULTS: A total of 809 patients were included between 1/9/2014 and 31/8/2015. Most patients (794) were adults ≥16-years old, 74% were male, the median age at symptom onset was 47 (38-57) years, the median disease duration was 7 (3-13) years, and the median Izbicki pain score (IPS) was 96 (0-195). The main etiological risk factors according to the TIGAR-O classification were alcohol and tobacco (67%). Current drinkers had lower body mass index (BMI) (21.4 kg/m2 vs 24.1 kg/m2), higher IPS (110 vs 56), and longer inability to work than non-drinkers. Current smokers had lower BMI (21.5 kg/m2 vs 25 kg/m2) and higher IPS (120 vs 30) than non-smokers. Endocrine insufficiency and/or clinical steatorrhea was recorded in 41% and 36% of patients, respectively. The highest IPS was reported in patients with ongoing endotherapy (166 vs 50 for patients who completed endoscopy). CONCLUSION: This multicentric study on CP patients showed that current alcohol drinking and smoking are associated with pain and malnutrition. Pain scores were higher in patients with ongoing endotherapy, independently of surgery.

[Influence of chest physiotherapy on gastro-œsophageal reflux in children]. / Influence de la kinésithérapie respiratoire sur le reflux gastro-œsophagien chez l'enfant.

INTRODUCTION: Chest physiotherapy is regularly prescribed for children, particularly in cystic fibrosis. Gastro-oesophageal reflux is common in this disease and is associated with certain chest physiotherapy manoeuvres. AIM OF THE STUDY: To evaluate the influence of two chest physiotherapy techniques on gastro-oesophageal reflux in children. MATERIAL AND METHOD: Twenty-nine children were investigated by routine pHmetry. During the examination, they performed two chest physiotherapy manoeuvres in a seated position for 10 minutes each with a 5 minutes rest between them. The two manoeuvres used were a slow expiration technique (ELPr) and positive expiratory pressure (PEP). It was a prospective study and the order of manoeuvres was randomised. The pH traces were analysed blindly when all the studies had been completed. RESULTS: In the sample, 21% of children had gastro-oesophageal reflux during the physiotherapy session. No relationship was found between reflux during physiotherapy and pathological reflux (P=0.411) nor the physiotherapy technique used (P=0.219). CONCLUSION: The use of these two chest physiotherapy techniques in children in a seated position can produce gastro-oesophageal reflux.

Cerebrospinal fluid compartmental pharmacokinetics of amikacin in neonates.

To describe and investigate the covariate effects of cerebrospinal fluid (CSF) amikacin pharmacokinetics in neonates, CSF samples were prospectively collected from neonates in whom amikacin had been initiated before a diagnostic lumbar puncture was performed. CSF analysis (amikacin concentration, white blood count [WBC], glucose content, and protein concentration) and amikacin therapeutic drug monitoring results (peak and trough concentrations) in serum were recorded. Correlations (Spearman rank) between the CSF amikacin concentration and the CSF WBC and glucose and protein concentration were investigated. There were 44 CSF amikacin concentrations and 83 serum samples available from 43 neonates (mean postmenstrual age, 36 weeks [range, 26 to 41 weeks]; mean weight, 2.43 kg [range, 0.87 to 3.86 kg]). The median time interval between initiation of amikacin administration and CSF sampling was 25 h (range, 2.5 to 93.7 h). The median amikacin concentration in the CSF was 1.08 mg/liter (range, 0.34 to 2.65 mg/liter), and the mean trough and peak amikacin concentrations in serum were 3.8 +/- 2.5 mg/liter and 35.7 +/- 5.9 mg/liter, respectively. A correlation between CSF amikacin and CSF protein contents (P < 0.01, r = 0.41, 95% confidence interval = 0.13 to 0.63) but not between CSF WBC and CSF glucose was documented. A two-compartment (central and CSF) linear disposition model was used to estimate population pharmacokinetics. The half time for equilibration (T(eq)) between serum and CSF compartments was used as a measure of blood-brain barrier permeability. The T(eq) was 7.58 h (coefficient of variation [CV] = 49.1%) with a partition coefficient of 0.103 (CV = 26.4%). There was no relationship between the T(eq) and CSF WBC, CSF glucose content, or CSF protein content.