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)

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

Machine Learning for Predicting Pulmonary Graft Dysfunction After Double-Lung Transplantation: A Single-Center Study Using Donor, Recipient, and Intraoperative Variables

Grade 3 primary graft dysfunction at 72 h (PGD3-T72) is a severe complication following lung transplantation. We aimed to develop an intraoperative machine-learning tool to predict PGD3-T72. We retrospectively analyzed perioperative data from 477 patients who underwent double-lung transplantation at a single center between 2012 and 2019. Data were structured into nine chronological steps, and supervised machine-learning models (XGBoost and logistic regression) were trained to predict PGD3-T72, with hyperparameters optimized via grid search and cross-validation. PGD3-T72 occurred in 83 patients (17.3%). XGBoost outperformed logistic regression, achieving peak performance at second graft implantation with an AUROC of 0.84 IQR: 0.065, p < 0.001, with a sensitivity of 0.81 and a specificity of 0.68. The top predictors included extracorporeal membrane oxygenation (ECMO) use, blood lactate levels, PaO2/FiO2 ratio, and total lung capacity mismatch. Subgroup analyses confirmed robustness across ECMO and non-ECMO cohorts. PGD3-T72 can be reliably predicted intraoperatively, offering potential for early intervention

Excitation and Deexcitation of Benzene

This chapter contains sections titled: - Introduction; - The Nature of the Lower Excited States of Benzene; - Transitions Between Lower Energy States; - Excited State Geometry; - The Influence of the Environment on Electronic States; - The S1 ↔ S0 Radiative Transition; - The S1 ↔ Triplet Radiationless Transition; - The S1 → S0 Radiationless Transition; - The T1 → S0 Phosphorescence Transition; - The T1 → S0 Radiationless Transition; - Transitions from Higher (n > 1) Excited States; - Relevant Photochemical Reactions of Excited States of Benzene; - Benzene Excimer; - Conclusioninfo:eu-repo/semantics/publishedVersio

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Prise en charge du vertige positionnel paroxystique bénin chez l'adulte en médecine générale : thèse présentée pour le diplôme d'État de docteur en médecine, diplôme d'État, médecine générale

Médecine généraleIntroduction: Le vertige positionnel paroxystique bénin (VPPB) représente la cause la plus fréquente de vertige. Il est important pour le médecin généraliste de savoir bien diagnostiquer le vertige positionnel paroxystique bénin, d’essayer d’exclure tout autre diagnostic différentiel et de prendre en charge le VPPB. Matériels et méthodes: Il s’agit d’une revue de la littérature sur les dernières connaissances scientifiques concernant le vertige positionnel paroxystique bénin. Résultats: Le VPPB est fortement suspecté dans le cas d’un vertige rotatoire, bref, déclénché par certains changements de position de la tête et se répétant plusieurs fois par jour. Le diagnostic de VPPB du canal semi-circulaire postérieur est confirmé par la manoeuvre de Dix-Hallpike qui met en évidence un nystagmus torsionnel vertical battant vers le haut et l’oreille affectée. Son traitement consiste dans la manoeuvre d’Epley ou de Semont. Le VPPB du canal semi-circulaire latéral est confirmé par le test positionnel rotatoire couché déclenchant un nystagmus horizontal soit géotropique, soit agéotropique. Son traitement consisterait dans les manoeuvres rotatoire de Barbecue ou de Gufoni. Le diagnostic du VPPB du canal semicirculaire antérieur est difficile. Il faudra en premier lieu exclure une lésion centrale face au nystagmus battant verticalement vers le bas, déclenché à la manoeuvre de Dix-Hallpike. Son traitement est peu validé ; à priori les manoeuvres utiles seraient celles de Yacovino ou d’Epley ou d’Epley modifiée. Chaque symptôme neurologique ou ORL supplémentaire doit faire suspecter une atteinte différente du VPPB. Aucun examen complémentaire n'est recommandé dans le diagnostic du VPPB. De même, aucun traitement médicamenteux n'a fait sa preuve d'efficacité dans la prise en charge du VPPB. Discussion: Le VPPB du canal semi-circulaire postérieur est le VPPB le plus fréquent et le mieux étudié, son diagnostic et sa prise en charge sont codifiés. Par contre, le diagnostic du VPPB du canal semi-circulaire latéral, ainsi que du VPPB du canal semi-circulaire antérieur est souvent plus difficile et la prise en charge est moins étudiée. Le VPPB est une pathologie de découverte assez récente, qui nécessite encore à être explorée et précisée plus en détails. Conclusion: Le diagnostic du VPPB se pose en fonction d'un vertige rotatoire, bref et déclenché par certains changements de position de la tête et d'une manoeuvre diagnostique déclenchant un nystagmus caractéristique du canal semi-circulaire atteint. Il faudra toujours essayer d’exclure des lésions plus graves, si le patient présente des symptômes neurologiques ou ORL associés. Le traitement du VPPB consiste dans la manoeuvre de repositionnement des canalithes, adaptée au canal semi-circulaire affect