Dysfonction énergétique cérébrale après traumatisme crânien sévère: prévalence et impact pronostique

Introduction : Le traumatisme crânien sévère est une pathologie fréquente pour laquelle il n’existe pas encore de traitement pharmacologique, la prise en charge étant basée sur un soutien limitant les agressions cérébrales secondaires. Le monitorage cérébral multimodal permet d’effectuer une prise en charge individualisée précoce visant à optimiser la perfusion/oxygénation cérébrales et contrôler les agresseurs secondaires d’origine systémique. La circulation cérébrale est monitorée par un capteur de pression intracrânienne (PIC), la perfusion/oxygénation par oxymétrie tissulaire cérébrale (PbtiO2). Le développement de la microdialyse cérébrale (CMD) permet une compréhension plus fine de la physiopathologie post-traumatique ainsi que des perturbations du métabolisme énergétique cellulaire grâce notamment à la mesure du rapport lactate/pyruvate (LPR) qui met en évidence un état de dysfonction énergétique non ischémique lié à une hyperglycolyse compensatoire et une dysfonction mitochondriale, rendant la phosphorylation oxydative impossible. Objectifs : Le but de ce travail est d’estimer la prévalence des épisodes de LPR élevé dans la phase aigüe post-traumatique, d’en déterminer l’étiologie ainsi que décrire l’impact pronostique et la récupération fonctionnelle des patients qui présentent un LPR élevé. Méthodologie : Cette étude de cohorte observationnelle a inclus des patients admis dans le Service de Médecine Intensive Adulte du CHUV suite à un traumatisme crânien sévère (échelle de Glasgow <9 avec lésions au CT-cérébral) ayant bénéficié d’un monitorage intracérébral multimodal incluant PIC, PbtiO2 et CMD pendant au moins 5 jours (n=108). A la phase aigüe (0-48h et 0-120h) après l’ admission, nous avons identifié les épisodes d’anomalies physiopathologiques selon des seuils définis (LPR>35 = dysfonction énergétique, PIC>20mmHg = hypertension intracrânienne, PbtiO2<20mmHg = hypoxie cérébrale), mesuré leur prévalence et durée, puis le pourcentage d’heures passé en zone pathologique. Nous avons ensuite examiné pour le LPR, la PIC et PbtiO2, l’impact de la charge pathologique sur le pronostic fonctionnel à 6 mois (Glasgow Outcome Score ; n= 83). Résultats : Les résultats principaux montrent que sur les 5 premiers jours de monitorage, la dysfonction énergétique cérébrale (LPR>35) est fréquente, s’observant chez plus de 80% des patients. Les épisodes de LPR élevé surviennent indépendamment d’une élévation de la PIC et de la PbtiO2, ce qui signifie qu’ils ne peuvent être diagnostiqués qu’avec la CMD. La dysfonction énergétique et l’hypoxie cérébrales sont associées à un pronostic défavorable. Après ajustement pour d’autres déterminants pronostiques (âge, score de Marshall, score Apache II), seule l’hypoxie cérébrale est significativement associée à un pronostic défavorable. Finalement, à aucun moment (0-48 h et 0-120h) l’hypertension intracrânienne n’est associée au pronostic neurologique à long terme. Conclusion : Le monitorage combiné du LPR et de la PbtiO2 permet d’identifier de nouveaux déterminants physiopathologiques tels que dysfonction énergétique et l’hypoxie cérébrale qui sont indépendantes du monitorage de la PIC et ont un impact significatif sur le pronostic à long terme. Il reste à déterminer si des stratégies thérapeutiques ciblées visant à normaliser le LPR pourraient améliorer la prise en charge et le pronostic après un traumatisme crânien sévère

Galois theory and commutators

We prove that the relative commutator with respect to a subvariety of a variety of Omega-groups introduced by the first author can be described in terms of categorical Galois theory. This extends the known correspondence between the Froehlich-Lue and the Janelidze-Kelly notions of central extension. As an example outside the context of Omega-groups we study the reflection of the category of loops to the category of groups where we obtain an interpretation of the associator as a relative commutator.Comment: 14 page

Early Glycemic Control in Critically Ill Emergency Department Patients: Pilot Trial

Objective: Glycemic control in the critically ill intensive care unit (ICU) patient has been shown to improve morbidity and mortality. We sought to investigate the effect of early glycemic control in critically ill emergency department (ED) patients in a small pilot trial.Methods: Adult non-trauma, non-pregnant ED patients presenting to a university tertiary referral center and identified as critically ill were eligible for enrollment on a convenience basis. Critical illness was determined upon assignment for ICU admission. Patients were randomized to either ED standard care or glycemic control. Glycemic control involved use of an insulin drip to maintain blood glucose levels between 80-140 mg/dL. Glycemic control continued until ED discharge. Standard patients were managed at ED attending physician discretion. We assessed severity of illness by calculation of APACHE II score. The primary endpoint was in-hospital mortality. Secondary endpoints included vasopressor requirement, hospital length of stay, and mechanical ventilation requirement.Results: Fifty patients were randomized, 24 to the glycemic group and 26 to the standard care cohort. Four of the 24 patients (17%) in the treatment arm did not receive insulin despite protocol requirements. While receiving insulin, three of 24 patients (13%) had an episode of hypoglycemia. By chance, the patients in the treatment group had a trend toward higher acuity by APACHE II scores. Patient mortality and morbidity were similar despite the acuity difference.Conclusion: There was no difference in morbidity and mortality between the two groups. The benefit of glycemic control may be subject to source of illness and to degree of glycemic control, or have no effect. Such questions bear future investigation. [West J Emerg Med. 2010; 11(1):20-23]

Structure Formation, Melting, and the Optical Properties of Gold/DNA Nanocomposites: Effects of Relaxation Time

We present a model for structure formation, melting, and optical properties of gold/DNA nanocomposites. These composites consist of a collection of gold nanoparticles (of radius 50 nm or less) which are bound together by links made up of DNA strands. In our structural model, the nanocomposite forms from a series of Monte Carlo steps, each involving reaction-limited cluster-cluster aggregation (RLCA) followed by dehybridization of the DNA links. These links form with a probability $p_{eff}$ which depends on temperature and particle radius $a$. The final structure depends on the number of monomers (i. e. gold nanoparticles) $N_m$, $T$, and the relaxation time. At low temperature, the model results in an RLCA cluster. But after a long enough relaxation time, the nanocomposite reduces to a compact, non-fractal cluster. We calculate the optical properties of the resulting aggregates using the Discrete Dipole Approximation. Despite the restructuring, the melting transition (as seen in the extinction coefficient at wavelength 520 nm) remains sharp, and the melting temperature $T_M$ increases with increasing $a$ as found in our previous percolation model. However, restructuring increases the corresponding link fraction at melting to a value well above the percolation threshold. Our calculated extinction cross section agrees qualitatively with experiments on gold/DNA composites. It also shows a characteristic ``rebound effect,'' resulting from incomplete relaxation, which has also been seen in some experiments. We discuss briefly how our results relate to a possible sol-gel transition in these aggregates.Comment: 12 pages, 10 figure

Influence of airway management strategy on "no-flow-time" during an "Advanced life support course" for intensive care nurses – A single rescuer resuscitation manikin study

<p>Abstract</p> <p>Background</p> <p>In 1999, the laryngeal tube (VBM Medizintechnik, Sulz, Germany) was introduced as a new supraglottic airway. It was designed to allow either spontaneous breathing or controlled ventilation during anaesthesia; additionally it may serve as an alternative to endotracheal intubation, or bag-mask ventilation during resuscitation. Several variations of this supraglottic airway exist. In our study, we compared ventilation with the laryngeal tube suction for single use (LTS-D) and a bag-mask device. One of the main points of the revised ERC 2005 guidelines is a low no-flow-time (NFT). The NFT is defined as the time during which no chest compression occurs. Traditionally during the first few minutes of resuscitation NFT is very high. We evaluated the hypothesis that utilization of the LTS-D could reduce the NFT compared to bag-mask ventilation (BMV) during simulated cardiac arrest in a single rescuer manikin study.</p> <p>Methods</p> <p>Participants were studied during a one day advanced life support (ALS) course. Two scenarios of arrhythmias requiring defibrillation were simulated in a manikin. One scenario required subjects to establish the airway with a LTS-D; alternatively, the second scenario required them to use BMV. The scenario duration was 430 seconds for the LTS-D scenario, and 420 seconds for the BMV scenario, respectively. Experienced ICU nurses were recruited as study subjects. Participants were randomly assigned to one of the two groups first (LTS-D and BMV) to establish the airway. Endpoints were the total NFT during the scenario, the successful airway management using the respective device, and participants' preference of one of the two strategies for airway management.</p> <p>Results</p> <p>Utilization of the LTS-D reduced NFT significantly (p < 0.01). Adherence to the time frame of ERC guidelines was 96% in the LTS-D group versus 30% in the BMV group. Two participants in the LTS-D group required more than one attempt to establish the LTS-D correctly. Once established, ventilation was effective in 100%. In a subjective evaluation all participants preferred the LTS-D over BMV to provide ventilation in a cardiac arrest scenario.</p> <p>Conclusion</p> <p>In our manikin study, NFT was reduced significantly when using LTS-D compared to BMV. During cardiac arrest, the LTS-D might be a good alternative to BMV for providing and maintaining a patent airway. For personnel not experienced in endotracheal intubation it seems to be a safe airway device in a manikin use.</p

Controlling Pandemic Flu: The Value of International Air Travel Restrictions

BACKGROUND: Planning for a possible influenza pandemic is an extremely high priority, as social and economic effects of an unmitigated pandemic would be devastating. Mathematical models can be used to explore different scenarios and provide insight into potential costs, benefits, and effectiveness of prevention and control strategies under consideration. METHODS AND FINDINGS: A stochastic, equation-based epidemic model is used to study global transmission of pandemic flu, including the effects of travel restrictions and vaccination. Economic costs of intervention are also considered. The distribution of First Passage Times (FPT) to the United States and the numbers of infected persons in metropolitan areas worldwide are studied assuming various times and locations of the initial outbreak. International air travel restrictions alone provide a small delay in FPT to the U.S. When other containment measures are applied at the source in conjunction with travel restrictions, delays could be much longer. If in addition, control measures are instituted worldwide, there is a significant reduction in cases worldwide and specifically in the U.S. However, if travel restrictions are not combined with other measures, local epidemic severity may increase, because restriction-induced delays can push local outbreaks into high epidemic season. The per annum cost to the U.S. economy of international and major domestic air passenger travel restrictions is minimal: on the order of 0.8% of Gross National Product. CONCLUSIONS: International air travel restrictions may provide a small but important delay in the spread of a pandemic, especially if other disease control measures are implemented during the afforded time. However, if other measures are not instituted, delays may worsen regional epidemics by pushing the outbreak into high epidemic season. This important interaction between policy and seasonality is only evident with a global-scale model. Since the benefit of travel restrictions can be substantial while their costs are minimal, dismissal of travel restrictions as an aid in dealing with a global pandemic seems premature

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis

A quasi-unit cell model for Al-Ni-Co Ideal Quasicrystal based on clusters with broken 10-fold symmetry

We present new evidence supporting the quasi-unit cell description of the $Al_{72}Ni_{20}Co_{8}$ decagonal quasicrystal which shows that the solid is composed of repeating, overlapping decagonal cluster columns with broken 10-fold symmetry. We propose an atomic model which gives a significantly improved fit to electron microscopy experiments compared to a previous proposal by us and to alternative proposals with 10-fold symmetric clusters.Comment: 4 pages, 4 eps figures, use epsfig.sty and revtex revised text and figure