Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)

BACKGROUND: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition. METHODS: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099. FINDINGS: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04). INTERPRETATION: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition. FUNDING: La Roche-sur-Yon Departmental Hospital and French Ministry of Health

CVD OF TITANIUM CARBIDE AT MODERATE TEMPERATURE FROM TITANIUM SUBCHLORIDES

La formation in-situ des sous-halogénures de titane par réduction du tétrachlorure de titane par le titane métallique est utilisée conjointement avec du butane pour déposer des couches de carbure de titane à température modérée, de l'ordre de 850°C. La vitesse de dépôt, la composition en C/Ti et en chlore des revêtements ainsi que leur microdureté sont étudiées en fonction des paramètres expérimentaux, spécialement la composition initiale de la phase gazeuse. En les comparant aux résultats de calculs thermodynamiques, les variations de la vitesse de dépôt et de la composition du solide permettent de discuter l'influence de différentes limitations cinétiques du processus qui interviennent en fonction des conditions de dépôt. Dans tous les cas un grand écart à l'équilibre est observé. On montre que ces conditions de température de dépôt modérée et de sursaturation élevée conduisent à une structure à grains très fins. La microdureté des dépôts varie dans un large domaine. Des valeurs aussi faibles que 1000 kg.mm-2 sont obtenues quand la quantité de chlore incorporée est élevée. Dans les meilleures conditions de dépôt, les couches sont bien cristallisées avec une concentration en chlore faible et un rapport C/Ti proche de 1. Dans ce cas la taille des grains est particulièrement plus faible comparée à celle observée sur les couches déposées de façon classique à température plus élevée, comprise entre 1000 et 1050°C, la morphologie est très dense et la microdureté atteint des valeurs entre 4000 et 5000 kg.mm-2 sous une charge de 50g.The in-situ formation of the titanium subchlorides by the reduction of titanium tetrachloride by titanium metal is used together with butane to deposit titanium carbide layers at moderate temperature, in the order of 850°C. The deposition rate, the C/Ti composition of the coatings, the chlorine incorporation and the microhardness are studied as functions of the initial gaseous composition. When compared with the thermodynamical calculations, the variations of the deposition rate and the solid composition allow to discuss the influence of different kinetic limitations of the process which arise as a function of the deposition conditions. In any case a great departure from the equilibrium is observed. It is shown that these conditions of moderate temperature and supersaturation lead to a very fine-grained structure. The microhardness of the deposits varies in a large range. Values as low as 1000 kg.mm2 can be observed when the chlorine content is high. With the best deposition conditions, the deposits are well-crystallized with a low chlorine content and a C/Ti ratio approaching 1. In that case it is shown that the grain size is particularly lower than those observed in layers deposited at classical higher temperatures of 1000-1050°C, the morphology is very dense and the microhardness is in the range 4000-5000 kg.mm-2 under 50g load

ON THE OPTIMIZATION OF THE MICROSTRUCTURE AND THE ADHERENCE OF TiC/TiN COATINGS DEPOSITED AT MODERATE TEMPERATURE FOR MILLING APPLICATIONS

Titanium carbide and nitride coatings can be deposited at a moderate temperature of about 850°C, respectively from butane and nitrogen and a mixture of titanium chlorides containing high concentrations of the subchlorides which are generated in-situ by the prereduction of TiCl4 by Ti metal. Under optimized deposition conditions, a very hard titanium carbide with a polynucleated fine grained structure is obtained which is maintained inside the entire layer. However all conditions which lead to high microhardness do not allow the preservation of a good adherence with the cemented carbide substrate. The process was therefore optimized from a morphological, structural, and solid composition study and also from the point of view of microhardness and scratch test measurements. Titanium nitride deposition was also optimized from a composition, morphological and microhardness study but also in terms of surface roughness and friction coefficient. The value of this process which allows one both to obtain an improved bilayer coating and to maintain a high toughness of the substrate is demonstrated when compared to the performance of a classical TiC/TiN coating deposited at about 1000°C using the same severe conditions of a milling test

PURA-Related Developmental and Epileptic Encephalopathy

Background and ObjectivesPurine-rich element-binding protein A (PURA) gene encodes Pur-alpha, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients.MethodsData on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained.ResultsA cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations.DiscussionThe PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations