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Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

Pupil dilation response (PDR) has been proposed as a physiological marker of conscious access to a stimulus or its attributes, such as novelty. In a previous study on healthy volunteers, we adapted the auditory “local global” paradigm and showed that violations of global regularity elicited a PDR. Notably without instructions, this global effect was present only in participants who could consciously report violations of global regularities. In the present study, we used a similar approach in 24 non-communicating patients affected with a Disorder of Consciousness (DoC) and compared PDR to ERPs regarding diagnostic and prognostic performance. At the group level, global effect could not be detected in DoC patients. At the individual level, the only patient with a PDR global effect was in a MCS and recovered consciousness at 6 months. Contrasting the most regular trials to the most irregular ones improved PDR’s diagnostic and prognostic power in DoC patients. Pupillometry is a promising tool but requires several methodological improvements to enhance the signal-to-noise ratio and make it more robust for probing consciousness and cognition in DoC patients.

The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20–29 to 80–89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.

Pupil dilation has been reliably identified as a physiological marker of consciously reportable mental effort. This classical finding raises the question of whether or not pupil dilation could be a specific somatic signature of conscious processing. In order to explore this possibility, we engaged healthy volunteers in the ‘local global’ auditory paradigm we previously designed to disentangle conscious from non-conscious processing of novelty. We discovered that consciously reported violations of global (inter-trials) regularity were associated with a pupil dilation effect both in an active counting task and in a passive attentive task. This pupil dilation effect was detectable both at the group-level and at the individual level. In contrast, unreported violations of this global regularity, as well as unreported violations of local (intra-trial) regularity that do not require conscious access, were not associated with a pupil dilation effect. We replicated these findings in a phonemic version of the ‘local global’. Taken together these results strongly suggest that pupil dilation is a somatic marker of conscious access in the auditory modality, and that it could therefore be used to easily probe conscious processing at the individual level without interfering with participant’s stream of consciousness by questioning him/her.

We report a fatal case of measles inclusion-body encephalitis occurring in a woman from Romania with AIDS. After an extensive but unsuccessful diagnostic evaluation, a pan-pathogen shotgun metagenomic approach revealed a measles virus infection. We identified no mutations previously associated with neurovirulence.

In the scope of its project on the assimilation and reproduction of experiments for the evaluation of stainless-steel nuclear data HARVEST-X, the LRS launches a pile-oscillation experimental program in the CROCUS reactor: BLOOM. For this program, an oscillator called POLLEN originally developed to be used as a vibrating absorber to compensate the fuel rods oscillator COLIBRI was reworked as a standalone pile-oscillator called. The oscillator operates with an arbitrary periodical shape, an amplitude of 1 m and a frequency ranging from the mHz to the Hz. An emphasis was put in the development of an interface for pseudo-square oscillations for BLOOM. This interface also allows independent adjustment of the ramping time and dwell time of the pseudo-square. The qualification of POLLEN was performed by video analysis of sinusoidal oscillations, using a 4K 30fps camera. With the current system, a precision of 0.2 mm was achieved during slow sinusoidal oscillation and a precision of 0.17 mm was obtained for pseudo square oscillations with a 500 g load. Whereas the results are satisfactory with respect to the current system and fulfill the requirement of the BLOOM program, it is planned to upgrade the system with the addition of a mechanical reference in the system. It is also in consideration to upgrade the acquisition card and controller to 16 bits systems to allow the use of POLLEN in setups where larger displacements are needed. The first in-core oscillation experiments are planned for early 2024.

Following recent health scandals in France, the French parliament adopted law n°2011-2012 to regulate ties between physicians and the pharmaceutical industry. The law also requires pharmaceutical companies to publicize financial and other benefits given to medical students. In this context, we administered a survey to medical students in France, in an effort to identify priorities for future education regarding conflicts of interest (COI). This web-based survey encompassed knowledge about, training on, personal exposure to, and opinions on COI among preclinical and clinical students as well as residents. Two thousand one hundred and one (2,101) students participated. Although most students (64.6%) believed that they are able to define what a COI is, they failed to correctly identify several situations as COI (receiving a gift, being offered a meal, being invited to a conference). Most students reported feeling inadequately educated about COI (85.2%). Compared to other class levels, residents were more exposed to pharmaceutical sales representatives. This exposure is highly associated to receipt of gifts (OR 14.51, 95% CI 11.67-18.05). Medical students were aware of potential bias induced by COI with respect to drug prescriptions and research, but felt personally immune towards COI. In our survey, personal research performed by students was more likely to be associated with perception of potential bias on prescription for self (but not for others) than attending a lecture on COI. Promulgating laws that regulate ties between physicians/students and the pharmaceutical industry is a mandatory first step. However, complementary strategies should be implemented within medical schools, in particular, specific training about COI in early medical education.

[...]determining the optimal timing for extubation is of major importance. Weaning according to a new definition (WIND) classification and criteria for considering a spontaneous breathing trial (SBT) in general ICU and in neurocritical ICU Weaning according to a new definition (WIND) classification Group “no weaning”: made of patients who never experienced any separation attempt Group 1 (short weaning): the first attempt resulted in a termination of the weaning process within 1 day (successful separation or early death) Group 2 (difficult weaning): the weaning was completed after more than 1 day but in less than 1 week after the first separation attempt (successful separation or death) Group 3 (prolonged weaning): the weaning was still not terminated 7 days after the first separation attempt (by successful separation or death) Group 3a prolonged weaning leading to a successful weaning after 7 days or more after the first attempt Group 3b prolonged weaning without success Criteria for considering SBT General ICU Resolution of the medical condition that led to MV Hemodynamic stability (BPM < 135/min, 90 < systolic arterial pressure < 160 mmHg with no need for vasopressors) Patient awake or easily aroused (RASS between 1 and − 2) and sedation stopped Patient able to cough effectively SpO2 > 90% with FIO2 < 40% or PaO2/FIO2 > 150 and PEEP < 8 cm H2O RR < 35/min pH > 7.35 Neurocritical ICU, especially GBS and MG patients Resolution of the medical condition that led to MV Hemodynamic stability (BPM < 135/min, 90 < systolic arterial pressure < 160 mmHg with no need for vasopressors) Patient awake or easily aroused (RASS between 1 and − 2) and sedation stopped Patient able to cough effectively Adequate secretion clearance (cough strength) SpO2 > 90% with FIO2 < 40% or PaO2/FIO2 > 150 and PEEP < 8 cm H2O RR < 35/min pH > 7.35 Normal blood gases Forced vital capacity (FVC) > 10 mL/kg (or 15 or improvement of more than 4 mL/kg) Maximal inspiratory pressure > − 20 cm H20 Maximal expiratory pressure > 40 cm H20 BPM beats per minute, FVC forced vital capacity, FIO2 inspired oxygen fraction, GBS Guillain–Barré syndrome, MG myasthenia gravis, MV mechanical ventilation, PaO2 partial oxygen arterial pressure, PEEP positive end-expiratory pressure, PSV pressure support ventilation, RASS Richmond assessment sedation scale, RR respiratory rate, SBT spontaneous breathing trial, SpO2 pulsed oxygen saturation Several questions arise when the weaning process begins: (1) which ventilation mode should be preferred to enable the respiratory muscles to both rest and not to waste? [9]; (2) when to start spontaneous breathing trials (SBT)?; (3) should positive pressure support (PSV) or T-piece trials be used for SBT?; (4) which respiratory parameters should be used to predict successful extubation?; and finally (5) is there any place for non-invasive mechanical ventilation (NIV) or high-flow nasal oxygenation to increase extubation success rate? The sample size was very limited, and it is not sure that GBS and MG behave exactly the same way. [...]studies should probably focus on a larger and more homogenous population. [...]this paper addresses weaning strategies of patients with neuromuscular diseases, which is a major issue in NICU.

Immune checkpoint inhibitors (ICI) widely improved the treatment of solid and hematologic malignancies. Yet, a remarkable proportion of patients receiving ICI develop immune related adverse events (irAEs) which are difficult to define as treatment-related. This underlines the need to develop a biomarker to guide irAE diagnosis. We developed a novel flow cytometry assay combining measurement of anti-PD-1 (programmed cell death protein-1) occupancy and evaluation of remaining PD-1 receptor availability with anti-IgG4 PE and anti-PD-1 BV421. We prospectively collected blood and biological fluids samples from patients treated by IgG4 anti-PD-1 therapy (nivolumab or pembrolizumab), with (n=18) or without (n=12) current irAE. We analyzed PD-1+ and IgG4+ staining pattern and MFI values of these parameters on CD4 and CD8 T cells, and IgG4+/PD-1+ MFI ratios are calculated. A higher mean fluorescence intensity IgG4+/PD-1+ ratio was measured on peripheral CD4+ T cells of irAE cases, when compared to controls (p=0.003). ICI-related toxicity is therefore associated with increased therapeutic antibody occupancy of PD-1 receptors on CD4+ T cells. Furthermore, in one case of ICI-related pneumonitis, binding of therapeutic antibody was stronger on lung CD4+ T cell than in blood. In another case of ICI-related encephalitis, the PD-1 receptor occupancy was total on CSF CD4 T cells, but only partial on peripherical CD4 T cells. Our results suggest that flow cytometry monitoring of ICI occupancy can be used in patients treated with monoclonal ICI to guide irAE diagnosis.