Pronostic du coma après lésion cérébrale aiguë chez l'homme

Contexte: L'ensemble des phénomènes aigus suivant un arrêt cardio-respiratoire (ACR) est décrit sous le nom de maladie de post-réanimation (MPR) (post-resuscitation disease). Celle- ci est la conséquence du syndrome de reperfusion et est caractérisée par une réponse inflammatoire systémique intense, d'allure septique. La procalcitonine (PCT) est un marqueur aigu de la réponse inflammatoire systémique, qui a été beaucoup étudiée aux soins intensifs (SI) dans le contexte du sepsis, et constitue un outil diagnostic et pronostique important. Toutefois la PCT n'est pas un marqueur spécifique pour le sepsis mais peut également augmenter lors de réponse inflammatoire systémique d'origine non infectieuse. Objectifs: 1) Evaluer s'il existe une corrélation entre la valeur plasmatique de PCT et la MPR ; 2) examiner la relation entre le taux au pic de PCT et le pronostic des patients avec coma post-ACR ; 3) comparer la valeur pronostique de la PCT à celle d'un marqueur pronostic connu du coma post-anoxique tel que la neuron specific enolase (NSE). Méthodologie: Analyse d'une base de données prospective comprenant des patients admis aux SI du centre hospitalier universitaire vaudoise (CHUV) entre décembre 2009 et juillet 2011 en raison d'un ACR et traités par hypothermie thérapeutique (33 - 34 °C pendant 24h), selon notre protocole standard de prise en charge. La concentration plasmatique de PCT est mesurée à 24-72h après ACR, la valeur maximale (PCTmax) étant incluse dans l'analyse. La durée de l'arrêt circulatoire et le score de SOFA (Sequential Organ Failure Assessment) sont utilisés pour quantifier la sévérité de la MPR. Le pronostic est composé de la mortalité hospitalière, ainsi que la mortalité et la récupération neurologique à trois mois, mesurée avec le score de « Cerebral Performance Categories » (CPC), dichotomisé en bonne récupération (CPC 1 = pas de handicap ; CPC 2 = handicap modéré) et mauvaise récupération (CPC 3 = handicap sévère ; CPC 4 = état végétatif ; CPC 5 = décès). Résultats: 68 patients consécutifs (âge médian 65 ans, durée médiane totale de l'arrêt circulatoire [time to ROSC] 20.5 min) ont été étudiés. La PCTmax corrélait avec la durée de l'arrêt circulatoire (p = 0.001) ainsi qu'avec les scores de SOFA à l'admission et aux jours 1 et 2 (p<0.001 pour les trois associations). Une association significative a été observée entre la PCTmax et la survie hospitalière (médiane 3.9 [écart interquartile (EI) 1.0 - 16.8] chez les non-survivants vs. 1.4 [EI 0.6 - 6.2] ng/ml chez les survivants, p=0.032) et à trois mois (médiane 3.8 ([EI 1.0 - 15.6] vs. 1.4 [EI 0.5 - 6.0] ng/ml, p=0.034). La PCTmax était aussi plus basse chez les patients avec bonne récupération neurologique à trois mois (p=0.064). En comparaison avec la NSEmax, la PCTmax avait une valeur prédictive supérieure pour la sévérité de la maladie de post-réanimation et inférieure pour le pronostic. Conclusions: La valeur plasmatique maximale de PCT corrèle avec la sévérité de la MPR et est associé à la mortalité et à l'état neurologique à trois mois après coma post-anoxique. Ces données suggèrent que la PCT peut être un marqueur utile dans la prise en charge des patients comateux après ACR et hypothermie thérapeutique. Des études à plus large échelle sont en cours pour confirmer ces résultats.

Chromosomal number aberrations and transformation in adult mouse retinal stem cells in vitro.

PURPOSE: The potential of stem cells (SCs) as a source for cell-based therapy on a wide range of degenerative diseases and damaged tissues such as retinal degeneration has been recognized. Generation of a high number of retinal stem cells (RSCs) in vitro would thus be beneficial for transplantation in the retina. However, as cells in prolonged cultivation may be unstable and thus have a risk of transformation, it is important to assess the stability of these cells. METHODS: Chromosomal aberrations were analyzed in mouse RSC lines isolated from adult and from postnatal day (PN)1 mouse retinas. Moreover, selected cell lines were tested for anchorage-dependent proliferation, and SCs were transplanted into immunocompromised mice to assess the possibility of transformation. RESULTS: Marked aneuploidy occurred in all adult cell lines, albeit to different degrees, and neonatal RSCs were the most stable and displayed a normal karyotype until at least passage 9. Of interest, the level of aneuploidy of adult RSCs did not necessarily correlate with cell transformation. Only the adult RSC lines passaged for longer periods and with a higher dilution ratio underwent transformation. Furthermore, we identified several cell cycle proteins that might support the continuous proliferation and transformation of the cells. CONCLUSIONS: Adult RSCs rapidly accumulated severe chromosomal aberrations during cultivation, which led to cell transformation in some cell lines. The culture condition plays an important role in supporting the selection and growth of transformed cells.

Progression of auditory discrimination based on neural decoding predicts awakening from coma.

Auditory evoked potentials are informative of intact cortical functions of comatose patients. The integrity of auditory functions evaluated using mismatch negativity paradigms has been associated with their chances of survival. However, because auditory discrimination is assessed at various delays after coma onset, it is still unclear whether this impairment depends on the time of the recording. We hypothesized that impairment in auditory discrimination capabilities is indicative of coma progression, rather than of the comatose state itself and that rudimentary auditory discrimination remains intact during acute stages of coma. We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and five healthy, age-matched controls. Using a mismatch negativity paradigm, we performed two electroencephalography recordings with a standard 19-channel clinical montage: the first within 24 h after coma onset and under mild therapeutic hypothermia, and the second after 1 day and under normothermic conditions. We analysed electroencephalography responses based on a multivariate decoding algorithm that automatically quantifies neural discrimination at the single patient level. Results showed high average decoding accuracy in discriminating sounds both for control subjects and comatose patients. Importantly, accurate decoding was largely independent of patients' chance of survival. However, the progression of auditory discrimination between the first and second recordings was informative of a patient's chance of survival. A deterioration of auditory discrimination was observed in all non-survivors (equivalent to 100% positive predictive value for survivors). We show, for the first time, evidence of intact auditory processing even in comatose patients who do not survive and that progression of sound discrimination over time is informative of a patient's chance of survival. Tracking auditory discrimination in comatose patients could provide new insight to the chance of awakening in a quantitative and automatic fashion during early stages of coma.

“Searching for the ghost of Tom Joad”: resurrecting Steinbeck’s gaze

This dissertation involves a close reading of Springsteen’s lyrics in relation to the thematic concerns of the Tom Joad album. Enquiring into the sometimes multiple levels of significance that these lyrics can be seen to express, in order to show the manner in which Springsteen mirrors the broader thematic concerns of Steinbeck’s The Grapes of Wrath’ s novel but also adapts and reinterprets these themes for his own time. In this sense, I will try to underline the ways in which, for Springsteen’s vision of his country in the 1990’s, the presence of troublesome issues from decades before is one that can, in certain ways, still be seen, felt and experienced. It is in this manner that the ghost of Tom Joad is summoned

Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.

The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years.

BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are considered important predictors of outcome after traumatic brain injury. We investigated the predictive value of the GCS in a large group of patients whose computerised multimodal bedside monitoring data had been collected over the previous 10 years. METHODS: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.

Utilização da Escala de Coma de Glasgow e Escala de Coma de Jouvet para avaliação do nível de consciência

A Escala de Coma de Glasgow (ECGl) e a Escala de Coma de Jouvet (ECJ), são duas escalas usadas na avaliação da consciência em nosso meio. A análise e o uso dessas duas escalas têm indicado que elas se complementam, sendo a ECGl mais sensível à mudanças nos rebaixamentos mais intensos da consciência e a ECJ nos estados mais próximos do normal. O presente estudo teve como objetivo comparar os resultados obtidos na avaliação do nível de consciência no uso dessas duas escalas. A comparação foi realizada num estudo prospectivo com 48 pacientes maiores de 18 anos internados em três unidades gerais de terapia intensiva de diferentes hospitais privados do Município de São Paulo. As avaliações foram realizadas pelos pesquisadores diariamente, sendo as duas escalas aplicadas seqüencialmente uma à outra no tempo de aproximadamente 5 minutos. Cada uma das escalas foi aplicada em 106 avaliações realizadas e os resultados mostraram uma diferença estatisticamente significativa entre a ECGl e a ECJ na indicação de alteração de nível de consciência. Em 37,74% das avaliações realizadas com a ECJ houve indicação de alteração do nível de consciência, enquanto que na ECGl a alteração era apontada em apenas 23,58% das avaliações. Outra observação importante no uso de ambas escalas, foi que em indivíduos com escores na ECGl entre 9 e 11, a indicação de alteração de nível de consciência foi mais acentuada pela ECGl e naquelas com escores na ECGl entre 12 e 15 a ECJ indicou mais acentuada alteração de nível de consciência. No uso da ECGl houve aplicação do não testável (NT) em 20% das avaliações realizadas, não ocorrendo inviabilidade de aplicação de indicadores na ECJ. Entretanto, acredita-se que condições específicas do grupo estudado favoreceram esse resultado, assim como, características específicas de grupos de pacientes podem favorecer o uso de diferentes escalas para avaliação de nível de consciência. A escolha final entre escalas desse tipo deve considerar as características peculiares e condições da clientela a ser avaliada e não preferências individuais ou de departamentos de serviços de saúde.

Analytical expressions for the flame front speed in the downward combustion of thin solid fuels and comparison to experiments

We derive analytical expressions for the propagation speed of downward combustion fronts of thin solid fuels with a background flow initially at rest. The classical combustion model for thin solid fuels that consists of five coupled reaction-convection-diffusion equations is here reduced into a single equation with the gas temperature as the single variable. For doing so we apply a two-zone combustion model that divides the system into a preheating region and a pyrolyzing region. The speed of the combustion front is obtained after matching the temperature and its derivative at the location that separates both regions.We also derive a simplified version of this analytical expression expected to be valid for a wide range of cases. Flame front velocities predicted by our analyticalexpressions agree well with experimental data found in the literature for a large variety of cases and substantially improve the results obtained from a previous well-known analytical expression

Temporal variability and trends of the downward solar radiation over Europe during the 20th century, with regional focus in the dimming/brightening phenomena on the Iberian Peninsula

Proyecto de investigación elaborado a partir de una estancia en el Institute for Atmospheric and Climate Science, a Alemanya, entre 2010 y 2012. La radiación solar que alcanza la superficie terrestre es un factor clave entre los procesos que controlan el clima de la Tierra, dado el papel que desempeñan en el balance energético y el ciclo hidrológico. Establecer su contribución al cambio climático reciente supone una gran dificultad debido a la complejidad de los procesos implicados, la gran cantidad de información requerida, y la incertidumbre de las bases de datos disponibles en la actualidad. Así, el objetivo principal del proyecto ha consistido en generar una base de datos de insolación incluyendo las series más largas (desde finales del siglo XIX) disponibles en toda Europa. Esta base de datos complementa para nuestro continente el Global Energy Balance Archive (GEBA) que mantiene y gestiona el grupo que ha acogido al receptor de la ayuda postdoctoral, y permite extender espacial (especialmente en países del sur de Europa) y temporalmente las series climáticas disponibles de mediciones de irradiancia solar. Como la insolación es un proxy de la irradiancia solar, el proyecto actual también ha tratado de calibrar de forma exhaustiva ambas variables, a fin de generar una nueva base de datos reconstruida de esta segunda variable que esté disponible desde finales del siglo XIX en Europa. Un segundo objetivo del proyecto ha consistido en continuar trabajando a escala de mayor detalle sobre la Península Ibérica, con el fin de proporcionar una mejor comprensión del fenómeno del “global dimming/brightening” y su impacto en el ciclo hidrológico y balance energético. Finalmente, un tercer objetivo del presente proyecto postdoctoral ha consistido en continuar estudiando los posibles ciclos semanales a gran escala de diferentes variables climáticas, línea de investigación de interés para la detección de posibles efectos de los aerosoles antrópicos en el clima a escalas temporales breves, y consecuentemente estrechamente vinculado al fenómeno del “global dimming/brightening”.

Estratégias de ensino-aprendizagem na enfermagem: análise pela Escala de Coma de Glasgow

Usando como tema a Escala de Coma de Glasgow (ECGl), este estudo objetivou analisar e verificar a retenção do conhecimento frente às estratégias de ensino-aprendizagem e autoaprendizado oferecidas, e verificar o grau de conhecimento adquirido neste processo e a possível associação entre ser ou não aluno que trabalha na enfermagem. Estudo descritivo de abordagem quantitativa. Participaram 62 alunos regularmente matriculados no primeiro semestre do 4º ano de enfermagem. As estratégias de ensino-aprendizagem utilizadas foram: aula expositiva com diapositivos e videoteipe e texto-base. Dos participantes, 41,9% eram trabalhadores na enfermagem; 61,3% informaram ter cuidado de pacientes com alteração do nível de consciência, com predomínio no grupo em que trabalha. Houve incremento estatisticamente significante no percentual de acerto após a aula expositiva e o videoteipe, não havendo alteração no resultado após o autoaprendizado. Não houve diferença no grau de conhecimento adquirido entre os grupos.

Investigating Gaze of Children with ASD in Naturalistic Settings.

BACKGROUND: Visual behavior is known to be atypical in Autism Spectrum Disorders (ASD). Monitor-based eye-tracking studies have measured several of these atypicalities in individuals with Autism. While atypical behaviors are known to be accentuated during natural interactions, few studies have been made on gaze behavior in natural interactions. In this study we focused on i) whether the findings done in laboratory settings are also visible in a naturalistic interaction; ii) whether new atypical elements appear when studying visual behavior across the whole field of view. METHODOLOGY/PRINCIPAL FINDINGS: Ten children with ASD and ten typically developing children participated in a dyadic interaction with an experimenter administering items from the Early Social Communication Scale (ESCS). The children wore a novel head-mounted eye-tracker, measuring gaze direction and presence of faces across the child's field of view. The analysis of gaze episodes to faces revealed that children with ASD looked significantly less and for shorter lapses of time at the experimenter. The analysis of gaze patterns across the child's field of view revealed that children with ASD looked downwards and made more extensive use of their lateral field of view when exploring the environment. CONCLUSIONS/SIGNIFICANCE: The data gathered in naturalistic settings confirm findings previously obtained only in monitor-based studies. Moreover, the study allowed to observe a generalized strategy of lateral gaze in children with ASD when they were looking at the objects in their environment.

Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.

PURPOSE: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents. MATERIALS AND METHODS: Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured. RESULTS: After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection. CONCLUSION: Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

Well-being and the frailty process in later life: an evaluation of the effectiveness of downward social comparison

This article, which is based on a longitudinal study conducted with a cohort ofoctogenarians, examines downward social comparison and its effectiveness as an adjustment mechanism during the frailty process. First of all, a paradoxical stability of subjective well-being is to be observed: it remains stable over five years notwithstanding the general decline in health. Next, an analysis based on individual health trajectories reveals that downward social comparison is associated with the maintenance of a stable level of well-being, whereas, when it is not associated with well-being, the latter tends to vary.

Recognition and political accommodation: from regionalism to secessionism. The Catalan case

Having lived through a bloody civil war in the 1930s followed by four decades of General Franco’s dictatorship, the Spanish state carried out a transition to a democratic system at the end of the 1970s. The 1978 Constitution was the legal outcome of this transition process. Among other things, it established a territorial model – the so-called “Estado de las Autonomías” (State of Autonomous Communities) – which was designed to satisfy the historical demands for recognition and self-government of, above all, the citizens and institutions of Catalonia and the Basque Country .In recent years support for independence has increased in Catalonia. Different indicators show that pro-independence demands are endorsed by a majority of its citizens, as well as by most of the political parties and organizations that represent its civil society. This is a new phenomenon. Those in favour of independence had been in the minority throughout the 20th century. Nowadays, however, demands of a pro-autonomy and pro-federalist nature, which until recently had been dominant, have gradually lost public support in favour of demands for self-determination and secession. This paper analyses the massive increase in support for secession in Catalonia during the early years of the 21st century. After describing the different theories of secession in plurinational liberal democracies (section 1), we analyse Catalonia’s political evolution over the past decade focusing on the shortcomings with regard to constitutional recognition and accommodation displayed by the Spanish political system. The latter have been exacerbated by the reform process of Catalonia’s Statute of Autonomy (2006) and the subsequent judgement of Spain’s Constitutional Court regarding the aforementioned Statute (2010) (section 2). Finally, we present our conclusions by linking the Catalan case with theories of secession applied to plurinational contexts