The gut-lung axis in the CFTR modulator era

The advent of CFTR modulators represents a turning point in the history of cystic fibrosis (CF) management, changing profoundly the disease’s clinical course by improving mucosal hydration. Assessing changes in airway and digestive tract microbiomes is of great interest to better understand the mechanisms and to predict disease evolution. Bacterial and fungal dysbiosis have been well documented in patients with CF; yet the impact of CFTR modulators on microbial communities has only been partially deciphered to date. In this review, we aim to summarize the current state of knowledge regarding the impact of CFTR modulators on both pulmonary and digestive microbiomes. Our analysis also covers the inter-organ connections between lung and gut communities, in order to highlight the gut-lung axis involvement in CF pathophysiology and its evolution in the era of novel modulators therapies

Nutritional impact of CFTR modulators in children with cystic fibrosis

BackgroundNutritional status is a major prognostic factor for breathing and the survival of patients with cystic fibrosis (CF). Since 2012, the development of CFTR modulators has considerably transformed the outcome of this disease. Indeed, both lung function and body mass index are improved by CFTR modulators, such as Lumacaftor/Ivacaftor. However, few data exist regarding the outcome of nutritional intakes under Lumacaftor/Ivacaftor.MethodsWe conducted a prospective single-center study in children with CF treated with Lumacaftor/Ivacaftor to evaluate their nutritional intake before and after treatmentResultsThirty-four children were included in this study, with a median age of 12.4 years [11.9; 14.7]. There was no significant improvement in weight, height or BMI. Patients' total energy intake was not significantly changed with Lumacaftor/Ivacaftor, while carbohydrate intakes decreased significantly. We found that blood levels of vitamin E and Selenium were significantly increased under Lumacaftor/Ivacaftor, without a significant increase in supplementation. In patients with a BMI Z-score < 0 at treatment initiation, there was a significant improvement in weight and BMI Z-score, while TEI and carbohydrate intakes were significantly lower.ConclusionWe showed that treatment with Lumacaftor/Ivacaftor improved the nutritional status of patients without necessarily being associated with an increase in nutritional intake. Although these data need to be confirmed in larger cohorts, they support the hypothesis that weight gain under modulators is multifactorial, and may be related to a decrease in energy expenditure or an improvement in absorption

The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. METHODS/DESIGN: We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na(+)) transport in response to the Na(+ )channel inhibitor amiloride, and CFTR-mediated chloride (Cl(-)) secretion in response to isoproterenol, a β-agonist in a Cl(- )free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. DISCUSSION: A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling

Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)

3D Imaging on heterogeneous surfaces on laterite drill core materials

The SOLSA project aims to construct an analytical expert system for on-line-on-mine-real-time mineralogical and geochemical analyses on sonic drilled cores. A profilometer is indispensable to obtain reliable and quantitative data from RGB and hyperspectral cameras, and to get 3D definition of close-to-surface objects such as rheology (grain shape, grain size, fractures and vein systems), material hardness and porosities. Optical properties of minerals can be analyzed by focusing on the reflectance. Preliminary analyses were performed with the commercial scan control profilometer MI-CRO-EPSILON equipped with a blue 405 nm laser on a conveyor belt (depth resolution: 10 μm; surface resolution: 30x30 μm2 (maximum resolution; 1m drill core/4 min). Drill core parts and rocks with 4 different surface roughness states: (1) sonic drilled, (2) diamond saw-cut, polished at (3) 6 mm and (4) 0.25 μm were measured (see also abstract Duée et al. this volume). The ΜICRO- EPSILON scanning does not detect such small differences of surface roughness states. Profilometer data can also be used to access rough mineralogical identification of some mineral groups like Fe-Mg silicates, quartz and feldspars). Drill core parts from a siliceous mineralized breccia and laterite with high and deep porosity and fractures were analyzed. The determination of holes’ convexity and fractures) is limited by the surface/depth ratio. Depending on end-user’s needs, parameters such as fracture densities and mineral content should be combined, and depth and surface resolutions should be optimized, to speed up “on-line-on-mine-real- time” mineral and chemical analyses in order to reach the target of about 80 m/day of drilled core

Efficient long-term open-access data archiving in mining industries

Efficient data collection, analysis and preservation are needed to accomplish adequate business decision making. Long-lasting and sustainable business operations, such as mining, add extra requirements to this process: data must be reliably preserved over periods that are longer than that of a typical software life-cycle. These concerns are of special importance for the combined on-line-on-mine-real-time expert system SOLSA (http://www.solsa-mining.eu/) that will produce data not only for immediate industrial utilization, but also for the possible scientific reuse. We thus applied the experience of scientific data publishing to provide efficient, reliable, long term archival data storage. Crystallography, a field covering one of the methods used in the SOLSA expert system, has long traditions of archiving and disseminating crystallographic data. To that end, the Crystallographic Interchange Framework (CIF, [1]) was developed and is maintained by the International Union of Crystallography (IUCr). This framework provides rich means for describing crystal structures and crystallographic experiments in an unambiguous, human- and machine- readable way, in a standard that is independent of the underlying data storage technology. The Crystallography Open Database (COD, [2]) has been successfully using the CIF framework to maintain its open-access crystallographic data collection for over a decade [3,4]. Since the CIF framework is extensible it is possible to use it for other branches of knowledge. The SOLSA system will generate data using different methods of material identification: XRF, XRD, Raman, IR and DRIFT spectroscopy. For XRD, the CIF is usable out-of-the-box, since we can rely on extensive data definition dictionaries (ontologies) developed by the IUCr and the crystallographic community. For spectroscopic techniques such dictionaries, to our best knowledge, do not exist; thus, the SOLSA team is developing CIF dictionaries for spectroscopic techniques to be used in the SOLSA expert system. All dictionaries will be published under liberal license and communities are encourage to join the development, reuse and extend the dictionaries where necessary. These dictionaries will enable access to open data generated by SOLSA by all interested parties. The use of the common CIF framework will ensure smooth data exchange among SOLSA partners and seamless data publication from the SOLSA project

Impact de la sévérité de l'insuffisance pancréatique exocrine chez les patients atteints de mucoviscidose suivis depuis 2002 en Aquitaine

INTRODUCTION : la gravité de la mucoviscidose est principalement due à l'évolution de la fonction pulmonaire, cependant un pronostic favorable est indissociable d'une bonne croissance staturo-pondérale. 85 % des patients présentent une insuffisance pancréatique externe qui peut être mesurée facilement par le dosage de l'EF-1. OBJECTIF : l'objectif principal de cette étude est de déterminer si le taux d'EF-1 (élastase fécale 1) peut être un facteur pronostic de la croissance staturo-pondérale des enfants. PATIENTS ET METHODES : cette étude rétrospective porte sur 69 enfants entre 6 mois et 8 ans suivis au CRCM d'Aquitaine depuis 2002. Le diagnostic de mucoviscidose a été confirmé par 2 tests de la sueur positifs ou 2 mutations retrouvées en biologie moléculaire. L'insuffisance pancréatique exocrine était définie pour des taux d'EF-1 inférieurs à 200 g/g (par la méthode monoclonale ELISA). La cohorte a été divisée en 4 groupes selon le taux d'EF-1 : 31/71 (43,6 %) avaient un taux d'EF-1 15 g/g) and they have earlier colonisation with S. aureus.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Resolution of linear viscoelastic equations in the frequency domain using real Helmholtz boundary integral equations

Boundary integral equations are well suitable for the analysis of seismic waves propagation in unbounded domains. Formulations in elastodynamics are well developed. In contrast, for the dynamic analysis of viscoelastic media, there are very seldom formulations by boundary integral equations. In this Note, we propose a new and simple formulation of time harmonic viscoelasticity with the Zener model, which reduces to classical elastodynamics if a compatibility condition is satisfied by boundary conditions. Intermediate variables which satisfy the classical elastodynamic equations are introduced. It makes it possible to utilize existing numerical tools of time harmonic elastodynamics