Axonal injury after TBI can be reliably quantified using plasma NfL, which predicts long-term functional outcomes and progressive neurodegeneration.

Reduced quantitative PLR correlates with postanoxic brain injury and, when compared to standard multimodal assessment, is highly accurate in predicting long-term prognosis after CA. This is the first prognostication study to show the value of automated pupillometry using a blinded approach to minimize self-fulfilling prophecy. Ann Neurol 2017;81:804-810.

This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

Adaptive metabolic response to injury includes the utilization of alternative energy substrates -such as ketone bodies (KB) -to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n ¼ 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and b-hydroxybutyrate). Nutrition -from fasting vs. stable nutrition state -was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] mmol/L vs. 13.1 [6.5-64.3] mmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] mmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p ¼ 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.

Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients.

Objectives: To examine neurophysiologic predictors and outcomes of patients with late awakening following cardiac arrest. Design: Observational cohort study. Setting: Academic ICU. Patients: Adult comatose cardiac arrest patients treated with targeted temperature management and sedation. Interventions: None. Measurement and Main Results: Time to awakening was calculated starting from initial sedation stop following targeted temperature management and rewarming (median 34 hr from ICU admission). Two-hundred twenty-eight of 402 patients (57%) awoke: late awakening (> 48 hr from sedation stop; median time to awakening 5 days [range, 3–23 d]) was observed in 78 subjects (34%). When considering single neurophysiologic tests, late awakening was associated with a higher proportion of discontinuous electroencephalography (21% vs 6% of early awakeners), absent motor and brainstem responses (38% vs 11%; 23 vs 4%, respectively), and serum neuron specific enolase greater than 33 ng/mL (23% vs 8%; all p < 0.01): no patient had greater than 2 unfavorable tests. By multivariable analysis—adjusting for cardiac arrest duration, Sequential Organ Failure Assessment score, and type of sedation—discontinuous electroencephalography and absent neurologic responses were independently associated with late awakening. Late awakening was more frequent with midazolam (58% vs 45%) and was associated with higher rates of delirium (62% vs 39%) and unfavorable 3-months outcome (27% vs 12%; all p = 0.005). Conclusions: Late awakening is frequent after cardiac arrest, despite early unfavorable neurophysiologic signs and is associated with greater neurologic complications. Limiting benzodiazepines during targeted temperature management may accelerate awakening. Postcardiac arrest patients with late awakening had a high rate of favorable outcome, thereby supporting prognostication strategies relying on multiple rather than single tests and that allow sufficient time for outcome prediction.

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Purpose:The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes.Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization.Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (V T ) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH 2 0, plateau pressure was 20 cmH 2 0 (IQR = 17-23), driving pressure was 12 cmH 2 0 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was