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Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients. Observational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A \"Brainstem Responses Assessment Sedation Score\" (BRASS) was generated. Two distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80] respectively). In this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.

PurposeWe aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care.MethodsWe conducted a prospective multicenter international cohort study (2017–2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score ≤ 13), a cerebrospinal fluid pleocytosis ≥ 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint.ResultsAmong 599 patients enrolled, 589 (98.3%) completed the 3-month follow-up and were included. Overall, 591 etiologies were identified in those patients which were categorized into five groups: acute bacterial meningitis (n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38, 6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6–54.6%) had a poor functional outcome, including 152 deaths (25.8%). Variables independently associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI 1.22–2.51), immunodepression (OR 1.98, 95% CI 1.27–3.08), time between hospital and ICU admission > 1 day (OR 2.02, 95% CI 1.44–2.99), a motor component on the GCS ≤ 3 (OR 2.23, 95% CI 1.49–3.45), hemiparesis/hemiplegia (OR 2.48, 95% CI 1.47–4.18), respiratory failure (OR 1.76, 95% CI 1.05–2.94), and cardiovascular failure (OR 1.72, 95% CI 1.07–2.75). In contrast, administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37–0.78) and acyclovir (OR 0.55, 95% CI 0.38–0.80) on ICU admission were protective.ConclusionMeningoencephalitis is a severe neurologic syndrome associated with high mortality and disability rates at 3 months. Actionable factors for which improvement could be made include time from hospital to ICU admission, early antimicrobial therapy, and detection of respiratory and cardiovascular complications at admission.

Sepsis is associated with increased mortality, delirium and long-term cognitive impairment in intensive care unit (ICU) patients. Electroencephalogram (EEG) abnormalities occurring at the acute stage of sepsis may correlate with severity of brain dysfunction. Predictive value of early standard EEG abnormalities for mortality in ICU septic patients remains to be assessed. In this prospective, single center, observational study, standard EEG was performed, analyzed and classified according to both Synek and Young EEG scales, in consecutive patients acutely admitted in ICU for sepsis. Delirium, coma and the level of sedation were assessed at the time of EEG recording; and duration of sedation, occurrence of in-ICU delirium or death were assessed during follow-up. Adjusted analyses were carried out using multiple logistic regression. One hundred ten patients were included, mean age 63.8 (±18.1) years, median SAPS-II score 38 (29-55). At the time of EEG recording, 46 patients (42%) were sedated and 22 (20%) suffered from delirium. Overall, 54 patients (49%) developed delirium, of which 32 (29%) in the days after EEG recording. 23 (21%) patients died in the ICU. Absence of EEG reactivity was observed in 27 patients (25%), periodic discharges (PDs) in 21 (19%) and electrographic seizures (ESZ) in 17 (15%). ICU mortality was independently associated with a delta-predominant background (OR: 3.36; 95% CI [1.08 to 10.4]), absence of EEG reactivity (OR: 4.44; 95% CI [1.37-14.3], PDs (OR: 3.24; 95% CI [1.03 to 10.2]), Synek grade ≥ 3 (OR: 5.35; 95% CI [1.66-17.2]) and Young grade > 1 (OR: 3.44; 95% CI [1.09-10.8]) after adjustment to Simplified Acute Physiology Score (SAPS-II) at admission and level of sedation. Delirium at the time of EEG was associated with ESZ in non-sedated patients (32% vs 10%, p = 0.037); with Synek grade ≥ 3 (36% vs 7%, p< 0.05) and Young grade > 1 (36% vs 17%, p< 0.001). Occurrence of delirium in the days after EEG was associated with a delta-predominant background (48% vs 15%, p = 0.001); absence of reactivity (39% vs 10%, p = 0.003), Synek grade ≥ 3 (42% vs 17%, p = 0.001) and Young grade >1 (58% vs 17%, p = 0.0001). In this prospective cohort of 110 septic ICU patients, early standard EEG was significantly disturbed. Absence of EEG reactivity, a delta-predominant background, PDs, Synek grade ≥ 3 and Young grade > 1 at day 1 to 3 following admission were independent predictors of ICU mortality and were associated with occurence of delirium. ESZ and PDs, found in about 20% of our patients. Their prevalence could have been higher, with a still higher predictive value, if they had been diagnosed more thoroughly using continuous EEG.

To identify early predictors of recovery from mild carbon monoxide poisoning, and to search for qualitative interactions between subsets of patients and treatment effects. Inception cohort study from a 4-year, randomised, controlled trial, which compared normobaric oxygen therapy to the combination of normobaric plus hyperbaric oxygen therapy in 307 patients. Study was conducted at a hyperbaric oxygen therapy referral centre. Victims of unintentional, non-fire-related, domestic, carbon monoxide intoxication were evaluated if the time elapsed from end of exposure to hospital admission was less than 12 h, the carboxyhaemoglobin level was greater than or equal to 10% or 5% for smoker or non-smoker, respectively, and if they did not suffer a loss of consciousness. One course of hyperbaric oxygen therapy or 6-h normobaric oxygen therapy was given. The main outcome measure was status at the 1-month recovery. Of the 307 evaluated patients, 206 (67%, 95%CI: 62%-72%) had recovered at 1 month. None of the patients died or suffered severe sequelae. Apathy and headaches were the main moderate sequelae. The multivariate analysis selected dizziness before admission (OR=1.92, [1.17-3.15], p=0.010) and headaches upon hospital admission (OR=2.14, [1.09-4.17], p=0.026) as jointly associated with persistent neurological symptoms. No significant crossover interaction between each combination of these two predictors and treatment effects was observed. At 1 month after mild carbon monoxide intoxication, victims who presented with dizziness before hospital admission or headaches upon admission have an increased risk of minor persistent neurological symptoms, but almost all patients could resume their former occupation.

Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis (MG). In 22 patients we compared the validity and interobserver reliability of two scoring methods commonly used as main endpoints in clinical trials, i.e., the Myasthenic Muscle Score (MMS) ranging from 0 to 100 (normal) and the Quantified Myasthenia Gravis Strength Score (QMGSS) ranging from 0 (normal) to 39. Each score is correlated more with functional scale and less with the patient's self-evaluation. Using intraclass correlation we found strong agreement between observers for both the MMS (r = 0.906) and the QMGSS (r = 0.905). The correlation between MMS and QGMSS was high (r = 0.87). The reliability of neither score depended on any specific item, since the removal of individual items did not significantly alter the intraclass correlation coefficient (ranging from 0.86 to 0.93).

Leathery pocket (LP) and fruitlet core rot (FCR) of pineapple (Ananas comosus L.) caused by Penicillium funiculosum Thom. and/or Fusarium moniliforme Sheld cause significant damage in all production areas, resulting in a major economic impact that affects both the fresh fruit market and the processing sector. The detection of Penicillium and Fusarium in the two main areas of pineapple production in Reunion Island, and representing a large range of climatic conditions, indicated that these fungi responsible for FCR and LP diseases were present throughout the pineapple cycle, whatever the climatic conditions. The proportion of fruits naturally infected by these pathogens was not related to climatic conditions during the infection period, suggesting that the inoculum level was not limiting. As these diseases cannot be reliably controlled, due in particular to the role of climatic conditions, an important research goal is to predict periods of higher disease risk using a model based on weather data. Taking advantage of the great diversity of environments on the tropical island of Reunion (Indian Ocean), we were able to establish a link between a pluviothermic index (PTi: ratio between total rainfall and the average temperature over the fruit development stages), and LP or FCR incidence. Disease incidence was modelled as a function of the pluviothermic index via a Weibull model. The most accurate model was obtained during the open heart to harvest stage. Lastly, the model output can be used by pineapple production stakeholders in farm management strategies and to adapt fruit grading before marketing.