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A letter to the editor is presented which discusses a case study of a 27-year-old man, who was admitted to undergo endovascular treatment for his right temporal arteriovenous malformation (AVM).

Background The aim of our study was to describe the anatomic relationships in internal jugular (IJV), subclavian (SCV), and femoral (FV) vein sites. Methods One hundred and forty-two children had a two-dimensional (2D) ultrasound (US) evaluation of IJV, SCV, and FV sites. They were enrolled according to their age: 0–1 month old (n=9), 1 month old to 2 yr old (n=61), 2–6 yr old (n=22), 6–12 yr old (n=32), and 12–18 yr old (n=18). Results We found about 7.7% variation for the IJV. The most common anatomic variations were a lateral (nine children) or anterior (nine children) position of the IJV to the carotid artery. Regardless of the age category, about 9.8% of the anatomic variations were found for the FV. The most common anatomic variation in our study was that the FV ran anteromedially to the femoral artery (17 children). Anatomic variation of the SCV, regardless of age category, was about 7.4%. The most common anatomic variation was the SCV, which ran medially (10 children) to the subclavian artery. Conclusions The relevant percentages of anatomic variations obtained for all these areas support at least a systematic US screening before attempting to obtain central venous access, ideally using a US-guided technique. [ABSTRACT FROM PUBLISHER]

The morbidity of aneurysmal subarachnoid hemorrhage (aSAH) remains high, particularly because of secondary cerebral lesions that significantly aggravate the primary lesions. The main type of secondary lesions is delayed cerebral ischemia (DCI), in which platelets (PLT) appear to play a key role. Mean platelet volume (MPV) is an indirect marker of platelet activation. We aimed to determine the individual trajectories of MPV over time in patients with and without DCI during the course of aSAH. This is a single-center, retrospective, longitudinal analysis of individual trajectories of MPV over time, in a cohort of aSAH patients included in the Prospective, Observational Registry of Patient with Subarachnoid Hemorrhage in Neurocritical Care Unit (ProReSHA). A mixed-effects linear regression model was used to compare the trajectories of MPV and MPV/PLT ratio between patients who developed a DCI and those who did not. A total of 3634 MPV values were collected in 587 patients. The analysis of MPV as a function of DCI occurrence showed a significant difference in the trajectory over time between patients with DCI and those without, with an estimate of 0.02 (95%CI 0.01, 0.04, p = 0.009). The analysis of the MPV/PLT ratio as a function of DCI occurrence and other covariates showed a significant difference in the trajectory over time only for patients with a modified Fisher score less than 3, with an estimate of -0.59 (95%CI: -0.94, -0.23, p = 0.001). The individual trajectories of MPV over time differ between patients with DCI and those without. However, MPV values vary greatly over time and between patients. Thus it does not appear as a reliable biomarker for stratifying patients based on their specific risk of developing DCI. ClinicalTrials.gov identifier: (NCT02890004), registered in August 2016., (© 2024. The Author(s).)

The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients. This study is based on the REA-IMMUNO-COVID cohort including 538 COVID-19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA-DR expression (mHLA-DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers' kinetics with mixed-effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA-DR value was associated with a lower risk of death. Predicted mHLA-DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA-DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID-19, decreased mHLA-DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders., (© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented., Results: To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30-6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09-4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72-13.57), p = 0.001)., Conclusions: By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches., (© 2024. The Author(s).)

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups., (© 2024. The Author(s).)

Background: Predicting the occurrence of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage is of interest to adjust the level of care. The VASOGRADE, a simple grading scale using admission World Federation of Neurosurgical Societies (WFNS) grading score and modified Fisher scale (mFS) on first CT scan, could help to select patients at risk of DCI. However, using data after initial resuscitation (initial complication treatment, aneurysm exclusion) may be more relevant., Methods: We calculated a post-resuscitation VASOGRADE (prVG) using WFNS grade and mFS after early brain injury treatment and aneurysm exclusion (or at day 3). Patients were categorized as green, yellow, or red., Results: Using our prospective observational registry, 566 patients were included in the study. Two hundred six (36.4%) were classified as green, 208 (36.7%) as yellow, and 152 (26.9%) as red, and DCI was experienced in 22 (10.7%), 67 (32.2%), and 45 (29.6%) cases respectively. Patients classified as yellow had higher risk of developing DCI (OR 3.94, 95% CI 2.35-6.83). Risk was slightly lower in red patients (OR 3.49, 95% CI 2.00-6.24). The AUC for prediction was higher with prVG (0.62, 95% CI 0.58-0.67) than with VASOGRADE (0.56, 95% CI 0.51-0.60) (p < 0.01)., Conclusion: By using simple clinical and radiological scale evaluated at subacute stage, prVG is more accurate to predict the occurrence of DCI., (© 2023. Fondazione Società Italiana di Neurologia.)

Fluctuations of consciousness and their rhythmicities have been rarely studied in patients with a disorder of consciousness after acute brain injuries. 24-h assessment of brain (EEG), behaviour (eye-opening), and circadian (clock-controlled hormones secretion from urine) functions was performed in acute brain-injured patients. The distribution, long-term predictability, and rhythmicity (circadian/ultradian) of various EEG features were compared with the initial clinical status, the functional outcome, and the circadian rhythmicities of behaviour and clock-controlled hormones. Here we show that more physiological and favourable patterns of fluctuations are associated with a higher 24 h predictability and sharp up-and-down shape of EEG switches, reminiscent of the Flip-Flop model of sleep. Multimodal rhythmic analysis shows that patients with simultaneous circadian rhythmicity for brain, behaviour, and hormones had a favourable outcome. Finally, both re-emerging EEG fluctuations and homogeneous 24-h cycles for EEG, eye-opening, and hormones appeared as surrogates for preserved functionality in brainstem and basal forebrain, which are key prognostic factors for later improvement. While the recovery of consciousness has previously been related to a high short-term complexity, we suggest in this exploratory study the importance of the high predictability of the 24 h long-term generation of brain rhythms and highlight the importance of circadian body-brain rhythms in awakening., (© 2023. The Author(s).)

Delayed cerebral ischemia (DCI) is a devastating complication of aneurysmal subarachnoid hemorrhage (ASAH) causing brain infarction and disability. Cerebral microdialysis (CMD) monitoring is a focal technique that may detect DCI-related neurochemical changes as an advance warning. We conducted retrospective analyses from 44 poor-grade ASAH patients and analyzed glucose, lactate, pyruvate, and glutamate concentrations in control patients without DCI (n = 19), and in patients with DCI whose CMD probe was located within (n = 17) or outside (n = 8) a new infarct. When monitored from within a lesion, DCI was preceded by a decrease in glucose and a surge in glutamate, accompanied by increases in lactate/pyruvate and lactate/glucose ratios whereas these parameters remained stable in control patients. When CMD monitoring was performed outside the lesion, the glutamate surge was absent, but glucose and L/G ratio were still significantly altered. Overall, glucose and L/G ratio were significant biomarkers of DCI (se96.0, spe73.7-68.4). Glucose and L/G predicted DCI 67 h before CT detection of a new infarct. The pathogenesis of DCI therefore induces early metabolic disturbances that can be detected by CMD as an advance warning. Glucose and L/G could provide a trigger for initiating further examination or therapy, earlier than when guided by other monitoring techniques., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Headache is the most common presenting symptom of spontaneous subarachnoid hemorrhage and managing this acute pain can be challenging. The aim of this study was to describe the course of headaches and factors associated with analgesic failure in patients with spontaneous subarachnoid hemorrhage., Methods: We conducted a prospective observational study in patients admitted to a neurocritical care unit (between April 2016 and March 2017) within 48 hours of spontaneous subarachnoid hemorrhage. Headache intensity was assessed using a Numerical Pain Rating Scale (NPRS) ranging from 0 to 10. Analgesic failure was defined as any day average NPRS score >3 after 72 hours of hospitalization despite analgesic treatment., Results: Sixty-three patients were included in the analysis. Thirty-six (56.25%) patients experienced at least 1 episode of severe headache (NPRS ≥7), and 40 (63.5%) patients still reported moderate to severe headache on the final day of the study (day 12). Forty-six (73.0%) patients required treatment with opioids and 37 (58.7%) experienced analgesic failure. Multivariable analysis showed that analgesic failure was associated with smoking history (odds ratio [OR]=4.31, 95% confidence interval [CI]: 1.23-17.07; P =0.027), subarachnoid blood load (OR=1.11, 95% CI: 1.01-1.24; P =0.032) and secondary complications, including rebleeding, hydrocephalus, delayed cerebral ischemia, hyponatremia, or death (OR=4.06, 95% CI: 1.17-15.77; P =0.032)., Conclusions: Headaches following spontaneous subarachnoid hemorrhage are severe and persist during hospitalization despite standard pain-reducing strategies. We identified risk factors for analgesic failure in this population., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: F13640 (a.k.a. befiradol, NLX-112) is a highly selective 5-HT 1A receptor ligand that was selected as a PET radiopharmaceutical-candidate based on animal studies. Due to its high efficacy agonist properties, [ 18 F]F13640 binds preferentially to functional 5-HT 1A receptors, which are coupled to intracellular G-proteins. Here, we characterize brain labeling of 5-HT 1A receptors by [ 18 F]F13640 in humans and describe a simplified model for its quantification., Methods: PET/CT and PET-MRI scans were conducted in a total of 13 healthy male volunteers (29 ± 9 years old), with arterial input functions (AIF) (n = 9) and test-retest protocol (n = 8). Several kinetic models were compared (one tissue compartment model, two-tissue compartment model, and Logan); two models with reference region were also evaluated: simplified reference tissue model (SRTM) and the logan reference model (LREF)., Results: [ 18 F]F13640 showed high uptake values in raphe nuclei and cortical regions. SRTM and LREF models showed a very high correlation with kinetic models using AIF. As concerns test-retest parameters and the prolonged binding kinetics of [ 18 F]F13640, better reproducibility, and reliability were found with the LREF method. Cerebellum white matter and frontal lobe white matter stand out as suitable reference regions., Conclusion: The favorable brain labeling and kinetic profile of [ 18 F]F13640, its high receptor specificity and its high efficacy agonist properties open new perspectives for studying functionally active 5-HT 1A receptors, unlike previous radiopharmaceuticals that act as antagonists. [ 18 F]F13640's kinetic properties allow injection outside of the PET scanner with delayed acquisitions, facilitating the design of innovative longitudinal protocols in neurology and psychiatry., Trial Registration: Trial Registration EudraCT 2017-002,722-21., (© 2023. The Author(s).)

Rationale: Nurse-to-nurse familiarity at work should strengthen the components of teamwork and enhance its efficiency. However, its impact on patient outcomes in critical care remains poorly investigated. Objectives: To explore the role of nurse-to-nurse familiarity on inpatient deaths during ICU stay. Methods: This was a retrospective observational study in eight adult academic ICUs between January 1, 2011 and December 31, 2016. Measurements and Main Results: Nurse-to-nurse familiarity was measured across day and night 12-hour daily shifts as the mean number of previous collaborations between each nursing team member during previous shifts within the given ICU (suboptimal if <50). Primary outcome was a shift with at least one inpatient death, excluding death of patients with a decision to forego life-sustaining therapy. A multiple modified Poisson regression was computed to identify the determinants of mortality per shift, taking into account ICU, patient characteristics, patient-to-nurse and patient-to-assistant nurse ratios, nurse experience length, and workload. A total of 43,479 patients were admitted, of whom 3,311 (8%) died. The adjusted model showed a lower risk of a shift with mortality when nurse-to-nurse familiarity increased in the shift (relative risk, 0.90; 95% confidence interval per 10 shifts, 0.82-0.98; P  = 0.012). Low nurse-to-nurse familiarity during the shift combined with suboptimal patient-to-nurse and patient-to-assistant nurse ratios (suboptimal if >2.5 and >4, respectively) were associated with increased risk of shift with mortality (relative risk, 1.84; 95% confidence interval, 1.15-2.96; P  < 0.001). Conclusions: Shifts with low nurse-to-nurse familiarity were associated with an increased risk of patient deaths.

Introduction: Behavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness., Methods: Hence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject's own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN ('SON effect', primary endpoint assessed by temporal clustering permutation tests)., Results: Patients were either coma ( n  = 38), unresponsive wakefulness syndrome (UWS, n  = 30) or minimally conscious state (MCS, n  = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a 'SON effect'. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients ( p  = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients ( p  = 0.013 for comparison between groups). Among the 72 survivors' patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome., Discussion: About 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferré, Heine, Naboulsi, Gobert, Beaudoin-Gobert, Dailler, Buffières, Corneyllie, Sarton, Riu, Luauté, Silva and Perrin.)

Background: A significant number of patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) are active smokers and are at risk of developing nicotine withdrawal symptoms (e.g., cravings, irritability, insomnia, headaches, etc.). This study aimed to evaluate the use of nicotine replacement therapy (NRT) regarding headache severity and analgesics consumption., Methods: A retrospective study was conducted using prospectively collected data from 2014 to 2019 in the neurointensive care unit of the Hospices Civils in Lyon, France. We performed a propensity score matching analysis. The covariables used were age, sex, initial World Federation of Neurosurgical Societies score, Hijdra sum score, and factors associated with pain following aSAH (history of chronic pain, anxiety, or depression). Smokers received NRT through a transdermal device. The primary end point was headache control. Secondary end points were mean numerical pain rating scale score and analgesics consumption., Results: One hundred and fifty-five patients were included among 523 patients hospitalized for aSAH. Fifty-one patients underwent nicotine substitution and were matched to 51 unsubstituted patients. The headache control rate was not different between the two groups (43.1% vs. 31.4%, p = 0.736). The mean numeric pain rating scale score in the substituted group was 2.2 (1.1-3.5) and 2.4 (1.6-3.1) in the unsubstituted group (p = 0.533). The analgesics consumption (acetaminophen, tramadol, and morphine) was the same in the two groups., Conclusions: The use of NRT in the acute phase of aSAH does not seem to have an impact on the intensity of headaches or analgesics consumption., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Early functional evaluation and prognosis of patients with disorders of consciousness is a major challenge that clinical assessments alone cannot solve. Objective measures of brain activity could help resolve this uncertainty. We used electroencephalogram at bedside to detect voluntary attention with a paradigm previously validated in healthy subjects., Methods: Using auditory-oddball sequences, our approach rests on detecting known attentional modulations of Event Related Potentials that reflect compliance with verbal instructions. Sixty-eight unresponsive patients were tested in their first year after coma onset (37 coma and 31 first year post-coma patients). Their evolution 6 months after the test was considered., Results: Fourteen of the 68 patients, showed a positive response. Nine were in a coma and 5 in a minimally conscious state (MCS). Except for one who died early, all responders evolved to exit-MCS within 6 months (93%), while 35 (65%) among non-responders only., Conclusions: Among those patients for whom the outcome is highly uncertain, 21% responded positively to this simple but cognitively demanding test. Strikingly, some coma patients were among responders., Significance: The proposed paradigm revealed cognitive-motor dissociation in some coma patients. This ability to sustain attention on demand predicted awakening within 6 months and represents an immediately useful information for relatives and caregivers., Competing Interests: Conflict of Interest Statement None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Immune responses affiliated with COVID-19 severity have been characterized and associated with deleterious outcomes. These approaches were mainly based on research tools not usable in routine clinical practice at the bedside. We observed that a multiplex transcriptomic panel prototype termed Immune Profiling Panel (IPP) could capture the dysregulation of immune responses of ICU COVID-19 patients at admission. Nine transcripts were associated with mortality in univariate analysis and this 9-mRNA signature remained significantly associated with mortality in a multivariate analysis that included age, SOFA and Charlson scores. Using a machine learning model with these 9 mRNA, we could predict the 28-day survival status with an Area Under the Receiver Operating Curve (AUROC) of 0.764. Interestingly, adding patients' age to the model resulted in increased performance to predict the 28-day mortality (AUROC reaching 0.839). This prototype IPP demonstrated that such a tool, upon clinical/analytical validation and clearance by regulatory agencies could be used in clinical routine settings to quickly identify patients with higher risk of death requiring thus early aggressive intensive care., Competing Interests: CT, VC, EC, KI, KB-P, EP, MBo, LK, SB, and J-FL are bioMérieux’s employees. EP, GM, and FV are co-inventors in patent applications covering the following markers: CX3CR1, CD127, IL10 and S100A9. bioFire – a bioMérieux company - holds patents on the technology. This does not alter the authors’ adherence to all the policies on sharing data and materials. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tardiveau, Monneret, Lukaszewicz, Cheynet, Cerrato, Imhoff, Peronnet, Bodinier, Kreitmann, Blein, Llitjos, Conti, Gossez, Buisson, Yonis, Cour, Argaud, Delignette, Wallet, Dailler, Monard, Brengel-Pesce, Venet and the RICO study group.)

Background and Purpose: To evaluate the accuracy of transcranial duplex sonography (TCS) for measuring the diameter of the third ventricle (DTV) and the brain midline shift (MLS), as compared to cerebral CT., Methods: Single-center retrospective study including 177 patients admitted to the neurological intensive care unit (NICU). We studied the correlation between TCS and CT measurements of DTV and MLS using a Bland-Altman analysis. The best threshold of DTV to diagnose acute hydrocephalus was evaluated with a receiver operating characteristic (ROC) analysis., Results: We analyzed 177 pairs of CT-TCS measurements for DTV and 165 for MLS. The mean time interval between CT and TCS was 87 ± 73 minutes. Median DTV measurement on CT was 4 ± 3 mm, and 5 ± 3 mm by TCS. Median MLS on CT was 2 ± 3 mm, and 2 ± 4 mm by TCS. The Pearson correlation coefficient (r 2 ) was .96 between TCS and CT measurements (p < .001). The Bland-Altman analysis found a proportional bias of 0.69 mm for the DTV with a limit of agreement ranging between -3.04 and 2.53 mm. For the MLS, the proportional bias was 0.23 mm with limits of agreements between -3.5 and 3.95. The area under the ROC curve was .97 for the detection of hydrocephalus by DTV on TCS, with a best threshold of 5.72 mm (Sensitivity [Se] = 92% Specificity [Sp] = 92.1%)., Conclusions: TCS seems to be a reliable and accurate bedside technique for measuring both DTV and MLS, which might allow detection of acute hydrocephalus among NICU patients., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019., Objective: To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France., Design: A retrospective study., Setting: Six ICUs in a single institution in Lyon, France., Patients: Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021., Main Outcomes and Measures: Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model., Results: COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement., Conclusion: After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Despite significant advances in the management of aneurysmal subarachnoid hemorrhage (SAH), morbidity and mortality remain devastating particularly for high-grade SAH. Poor functional outcome usually results from delayed cerebral ischemia (DCI). The pathogenesis of DCI during aneurysmal SAH has historically been attributed to cerebral vasospasm, but spreading depolarizations (SDs) are now considered to play a central role in DCI. During SAH, SDs may produce an inverse hemodynamic response leading to spreading ischemia. Several animal models have contributed to a better understanding of the pathogenesis of SDs during aneurysmal SAH and provided new therapeutic approaches including N-methyl-D-aspartate receptor antagonists and phosphodiesterase inhibitors. Herein we review the current knowledge in the field of SDs' pathogenesis and we detail the key experimental and clinical studies that have opened interesting new therapeutic approaches to prevent DCI in aneurysmal SAH., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: Brain injuries can cause systemic immunosuppression, which in turn can lead to infections that adversely affect the injured brain and worsen clinical outcomes. This study aimed to investigate whether systemic infection, such as ventilator-associated pneumonia (VAP), induce intracranial inflammation in patients with subarachnoid hemorrhage (SAH)., Methods: This prospective, observational study included 16 adults with SAH treated in the neuro-intensive care unit. Three paired cerebrospinal fluid samples (obtained from an external ventricular drain) and peripheral blood samples were obtained on days 1 to 3, 4 to 5, and 6 to 7 after SAH onset. Cell counts, cell phenotypes (monocyte HLA-DR, T regulatory cells, lymphocytes, and neutrophils), and inflammatory mediator levels were monitored., Results: Six patients developed VAP in the context of systemic immunosuppression demonstrated by a reduction in monocyte HLA-DR expression, lymphopenia, increased percentages of circulating T regulatory cells, and increased proportions of immature and immunosuppressive neutrophil subsets. During VAP, there was de novo recruitment of leukocytes into the cerebrospinal fluid, preferentially neutrophils, which exacerbated intracranial inflammation., Conclusions: VAP increased intracranial inflammatory responses in patients with SAH despite the occurrence of systemic immunosuppression. A better understanding of cell trafficking and their pleiotropic functions in brain injury is needed to define the optimal strategies for preventing infections in patients with SAH., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Haemodynamically unstable patients often require arterial and venous catheter insertion urgently. We hypothesised that ultrasound-guided arterial and venous catheterisation would reduce mechanical complications., Methods: We performed a prospective RCT, where patients requiring both urgent arterial and venous femoral catheterisation were randomised to either ultrasound-guided or landmark-guided catheterisation. Complications and characteristics of catheter insertion (procedure duration, number of punctures, and procedure success) were recorded at the time of insertion (immediate complications). Late complications were investigated by ultrasound examination performed between the third and seventh days after randomisation. Primary outcome was the proportion of patients with at least one mechanical complication (immediate or late), by intention-to-treat analysis. Secondary outcomes included success rate, procedure time, and number of punctures., Results: We analysed 136 subjects (102 [75%] male; age range: 27-62 yr) by intention to treat. The proportion of subjects with one or more complications was lower in 22/67 (33%) subjects undergoing ultrasound-guided catheterisation compared with landmark-guided catheterisation (40/69 [58%]; odds ratio: 0.35 [95% confidence interval: 0.18-0.71]; P=0.003). Ultrasound-guided catheterisation reduced both immediate (27%, compared with 51% in the landmark approach group; P=0.004) and late (10%, compared with 23% in the landmark approach group; P=0.047) complications. Ultrasound guidance also reduced the proportion of patients who developed deep vein thrombosis (4%, compared with 22% following landmark approach; P=0.012), and achieved a higher procedural success rate (96% vs 78%; P=0.004)., Conclusions: An ultrasound-guided approach reduced mechanical complications after urgent femoral arterial and venous catheterisation, while increasing procedural success., Clinical Trial Registration: NCT02820909., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting., Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission., Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020., Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission., Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale., Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions)., Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Delayed cerebral ischemia (DCI) is a poorly predictable complication occurring after aneurysmal subarachnoid hemorrhage (SAH) that can have dramatic functional consequences. Identifying the patients with the highest risk of DCI may help to institute more suitable monitoring and therapy. Early brain injuries and aneurysm-securing procedure complications could be regarded as confounding factors leading to severity misjudgment. After an early resuscitation phase, a subacute assessment may be more relevant to integrate the intrinsic SAH severity. A retrospective analysis was performed upon patients prospectively included in the registry of SAH patients between July 2015 to April 2020. The amount of cisternal and intraventricular blood were assessed semi-quantitatively on acute and subacute CT scans performed after early resuscitation. A clot clearance rate was calculated from their comparison. The primary endpoint was the occurrence of a DCI. A total of 349 patients were included in the study; 80 (22.9%) experienced DCI. In those patients, higher Fisher grades were observed on acute (p = 0.026) and subacute (p = 0.003) CT scans. On the subacute CT scan, patients who experienced DCI had a higher amount of blood, either at the cisternal (median Hijdra sum score: 11 vs 5, p < 0.001) or intraventricular (median Graeb score: 4 vs 2, p < 0.001) level. There was a negative linear relationship between the cisternal clot clearance rate and the risk of DCI. The assessment of the amount of subarachnoid blood and clot clearance following resuscitation after aneurysmal SAH can be useful for the prediction of neurological outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Early brain injuries (EBI) are one of the most important causes of morbidity and mortality after subarachnoid hemorrhage. At admission, a third of patients are unconscious (spontaneously or sedated) and EBI consequences are not evaluable. To date, it is unclear who will still be comatose (with severe EBI) and who will recover (with less severe EBI) once the aneurysm is treated and sedation withdrawn. The objective of the present study was to determine the diagnostic accuracy of S100B levels at hospital admission to identify patients with severe neurological consequences of EBI., Methods: Patients were consecutively included in this prospective blinded observational study. A motor component of the Glasgow coma score under 6 on day 3 was used to define patients with severe neurological consequences of EBI., Results: A total of 81 patients were included: 25 patients were unconscious at admission, 68 were treated by coiling. On day 3, 12 patients had severe consequences of EBI. A maximal S100B value between admission and day 1 had an area under the receiver operating characteristic curve (AUC) of 86.7% to predict severe EBI consequences. In patients with impaired consciousness at admission, the AUC was 88.2%., Conclusion: Early S100B seems to have a good diagnostic value to predict severe EBI. Before claiming the usefulness of S100B as a surrogate marker of EBI severity to start earlier multimodal monitoring, these results must be confirmed in an independent validation cohort.

Circadian rhythmicity (CR) is involved in the regulation of all integrated functions, from sleep-wake cycle regulation to metabolic function, mood and cognition. However, the interdependence of CR, cognition and consciousness has been poorly addressed. To clarify the state of CR in coma and to determine the chronological relationship between its recovery and consciousness after brain lesions, we conducted a longitudinal observational study investigating how the state of CR was chronologically related with the recovery of behavioural wakefulness, cognition and/or awareness. Among 16 acute comatose patients, we recruited two 37-year-old patients with a persistent disorder of consciousness, presenting diencephalic lesions caused by severe traumatic brain injuries. Two biological urinary markers of CR were explored every 2 hours during 24 hours (6-sulfatoxymelatonin, free cortisol) with a dedicated methodology to extract the endogenous component of rhythmicity (environmental light recording, near-constant-routine protocol, control of beta-blockers). They presented an initial absence of rhythmic secretions and a recovered CR 7-8 months later. This recovery was not associated with the restoration of behavioural wakefulness, but with an improvement of cognition and awareness (up to the minimally conscious state). MRI showed a lesion pattern compatible with the interruption of either the main hypothalamic-sympathetic pathway or the accessory habenular pathway. These results suggest that CR may be a prerequisite for coma recovery with a potential but still unproven favourable effect on brain function of the resorted circadian melatonin secretion and/or the functional recovery of the suprachiasmatic nucleus (SCN). Assessing circadian functions by urinary melatonin should be further explored as a biomarker of cognition reappearance and investigated to prognosticate functional recovery., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Secondary brain injuries, such as delayed cerebral infarction (DCI), are the leading causes of disability after subarachnoid hemorrhage (SAH). Detecting DCI may be challenging, especially for patients presenting an altered level of consciousness., Case Description: We describe herein the case of a patient who developed acute hemiplegia 4 days after SAH, with raised blood flow velocities on transcranial Doppler, compatible with vasospasm. Finally, full work-up, using computed tomography (CT) scan with perfusion CT and continuous electroencephalography, was consistent with nonconvulsive seizures., Conclusions: Multiple secondary complications (DCI, seizures, hydrocephalus) may occur after SAH but are clinically difficult to diagnose. A multimodal evaluation (transcranial Doppler, CT or magnetic resonance imaging, electroencephalography) is useful in order to detect and treat late complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: An efficient vascular access is mandatory for the proper conduction of therapeutic plasma exchanges (TPE). Peripheral and central venous catheters may be used, with respective advantages and limitations. In this study, vascular access devices (IV catheter, dialysis cannula, central venous catheter) and anatomic vein characteristics were evaluated., Method: From January to June 2016, 162 TPE in 29 patients were reviewed. Only TPE using centrifugation method (Spectra Optia apheresis system) were evaluated. Volume exchanged, procedure duration, mean flow rate, number of inlet, and return pressure pauses were recorded. Site, width, and depth of punctured veins were studied., Results: Median exchange volume planned was 3500 mL, and 152 (94%) procedures could be completed. Peripheral venous catheter was inserted in 103 (64%) cases (IV catheter: 61, dialysis cannulae: 42). Ultrasound guidance was used in 12 (11%) cases. Median procedure duration was shorter with central venous catheter (94 minutes), rather than dialysis cannula (133 minutes) or IV catheter (133 minutes). Median numbers of inlet pressure pauses were lower with central venous catheter (0) and dialysis cannulae (6), rather than IV catheter (10). There were no complications with peripheral venous access. There were no anatomic differences between catheterized veins with IV catheter or dialysis cannula., Conclusion: The use of peripheral venous access is possible in most of TPE, for emergency and during maintenance therapy. Dialysis cannulae are good compromise between classic IV catheters and central venous catheters, as it allows high flow rates, are easy to insert and associated with few complications., (© 2018 Wiley Periodicals, Inc.)

Objectives: Several studies have shown that bilateral abolition of somatosensory evoked potentials after a nontraumatic coma has 100% specificity for nonawakening with ethical consequences for active care withdrawal. We propose to evaluate the prognostic value of bilateral abolished cortical components of SEPs in severe vascular coma., Methods: A total of 144 comatose patients after subarachnoid haemorrhage were evaluated by multimodal evoked potentials (EPs); 7 patients presented a bilateral abolition of somatosensory and auditory EPs. Their prognosis value was interpreted with respect to brainstem auditory EPs, EEG, and structural imaging., Results: One patient emerged from vegetative state during follow-up; 6 patients did not return to consciousness. The main neurophysiological difference was a cortical reactivity to pain preserved in the patient who returned to consciousness. This patient had focal sub-cortical lesions, which could explain the abolition of primary cortical components by a bilateral deafferentation of somatosensory and auditory pathways., Conclusions: This is the first report of a favourable outcome after a multimodal abolition of primary cortex EPs in vascular coma. For the 3 cases of vascular coma with preserved brainstem function, EEG reactivity and cortical EPs were abolished by a diffuse ischaemia close to cerebral anoxia., Significance: The complementarity of EPs, EEG, and imaging must be emphasised if therapeutic limitations are considered to avoid over-interpretation of the prognosis value of EPs., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The latest French Guidelines for the management in the first 24hours of patients with severe traumatic brain injury (TBI) were published in 1998. Due to recent changes (intracerebral monitoring, cerebral perfusion pressure management, treatment of raised intracranial pressure), an update was required. Our objective has been to specify the significant developments since 1998. These guidelines were conducted by a group of experts for the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie et de réanimation [SFAR]) in partnership with the Association de neuro-anesthésie-réanimation de langue française (ANARLF), The French Society of Emergency Medicine (Société française de médecine d'urgence (SFMU), the Société française de neurochirurgie (SFN), the Groupe francophone de réanimation et d'urgences pédiatriques (GFRUP) and the Association des anesthésistes-réanimateurs pédiatriques d'expression française (ADARPEF). The method used to elaborate these guidelines was the Grade ® method. After two Delphi rounds, 32 recommendations were formally developed by the experts focusing on the evaluation the initial severity of traumatic brain injury, the modalities of prehospital management, imaging strategies, indications for neurosurgical interventions, sedation and analgesia, indications and modalities of cerebral monitoring, medical management of raised intracranial pressure, management of multiple trauma with severe traumatic brain injury, detection and prevention of post-traumatic epilepsia, biological homeostasis (osmolarity, glycaemia, adrenal axis) and paediatric specificities., (Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cerebral microdialysis could be useful to detect delayed cerebral ischemia in aneurysmal subarachnoid haemorrhage patients. The optimal location of the probes, however, remains controversial. Here, we determined the vascular territories with the highest infarct risk in relation to aneurysm location to define probe implantation guidelines. These guidelines were retrospectively validated by studying the likelihood of probe to fall in a secondary infarct area, and by analysing their influence to predict patient outcome. The vascular territories with highest risk of infarction were the anterior cerebral arteries for anterior communicating artery aneurysms and the ipsilateral middle cerebral artery for internal carotid artery, posterior communicating artery and middle cerebral artery aneurysms. When cerebral microdialysis probes had been implanted in these territories, 79% were located within an infarcted area versus 54% when they were implanted in other territories. Delayed cerebral ischemia was detected only when the probe was located within a brain area later affected by secondary infarction, which could justify the use of implantation guidelines. Moreover, individual patient outcomes could be predicted when probes were placed in the brain territories as suggested by this study. Thus, a precise probe placement algorithm can improve delayed cerebral ischemia detection sensitivity and allow for a better prediction concerning patient outcome.