Search

Background: The care of patients with aneurysmal subarachnoid hemorrhage has evolved significantly with the advent of new diagnostic and therapeutic modalities. Although it is believed that these advances have contributed to improved outcomes, considerable uncertainty persists regarding key areas of management.Objective: To review selected controversies in the management of aneurysmal subarachnoid hemorrhage, with a special emphasis on endovascular vs. surgical techniques for securing aneurysms, the diagnosis and therapy of cerebral vasospasm, neuroprotection, antithrombotic and anticonvulsant agents, cerebral salt wasting, and myocardial dysfunction, and to suggest venues for further clinical investigation.Data Source: Search of MEDLINE and Cochrane databases and manual review of article bibliographies.Data Synthesis and Conclusions: Many aspects of care in patients with aneurysmal subarachnoid hemorrhage remain highly controversial and warrant further resolution with hypothesis-driven clinical or translational research. It is anticipated that the rigorous evaluation and implementation of such data will provide a basis for improvements in short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Coma is a medical emergency and may constitute a diagnostic and therapeutic challenge for the intensivist.Objective: To review currently available data on the etiology, diagnosis, and outcome of coma. To propose an evidence-based approach for the clinical management of the comatose patient.Data Source: Search of Medline and Cochrane databases; manual review of bibliographies from selected articles and monographs.Data Synthesis and Conclusions: Coma and other states of impaired consciousness are signs of extensive dysfunction or injury involving the brainstem, diencephalon, or cerebral cortex and are associated with a substantial risk of death and disability. Management of impaired consciousness includes prompt stabilization of vital physiologic functions to prevent secondary neurologic injury, etiological diagnosis, and the institution of brain-directed therapeutic or preventive measures. Neurologic prognosis is determined by the underlying etiology and may be predicted by the combination of clinical signs and electrophysiological tests. [ABSTRACT FROM AUTHOR]

Background: The pivotal role of inflammation and edema across the spectrum of central nervous system injury has driven extensive investigation into the therapeutic potential of glucocorticoids.Objective: To review the experimental and clinical data relating to the efficacy and adverse effects of glucocorticoids in conditions encountered in critical neurologic and neurosurgical illness.Data Source: Search of MEDLINE and Cochrane databases, manual review of article bibliographies.Data Synthesis and Conclusions: The efficacy of glucocorticoids is well established in ameliorating edema associated with brain tumors and in improving outcome in subsets of patients with bacterial meningitis. Despite frequently encouraging experimental results, clinical trials of glucocorticoids in ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury have not shown a definite therapeutic effect. The evidence supporting glucocorticoid therapy for spinal cord injury is controversial; however methylprednisolone continues to be widely employed in this setting. [ABSTRACT FROM AUTHOR]

Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that when mutated, is associated with lighter than black melanin coloration in animal models and oculocutaneous albinism in humans. Inspection of RNA-Seq reads identified a single nucleotide deletion that is predicted to change the coding frame, introduce a premature stop codon in exon 6 and yield a truncated Tyrp1 protein in copper individuals. Using CRISPR-Cas9 editing, we show that wildtype Tyrp1 crispants exhibit copper pigmentation, thus confirming Tyrp1 as the copper locus. Our results suggest that commercial and hobbyist axolotl populations may harbor useful mutants for biological research., (© 2024. The Author(s).)

Competing Interests: Dr. Stevens received funding from Ceribell and B-Secur. Dr. Azad disclosed that he does not have any potential conflicts of interest.

Background: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment., Methods: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question., Results: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed., Conclusions: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Intracranial pressure (ICP) is commonly monitored to guide treatment in patients with serious brain disorders such as traumatic brain injury and stroke. Established methods to assess ICP are resource intensive and highly invasive. We hypothesized that ICP waveforms can be computed noninvasively from three extracranial physiological waveforms routinely acquired in the Intensive Care Unit (ICU): arterial blood pressure (ABP), photoplethysmography (PPG), and electrocardiography (ECG). We evaluated over 600 h of high-frequency (125 Hz) simultaneously acquired ICP, ABP, ECG, and PPG waveform data in 10 patients admitted to the ICU with critical brain disorders. The data were segmented in non-overlapping 10-s windows, and ABP, ECG, and PPG waveforms were used to train deep learning (DL) models to re-create concurrent ICP. The predictive performance of six different DL models was evaluated in single- and multi-patient iterations. The mean average error (MAE) ± SD of the best-performing models was 1.34 ± 0.59 mmHg in the single-patient and 5.10 ± 0.11 mmHg in the multi-patient analysis. Ablation analysis was conducted to compare contributions from single physiologic sources and demonstrated statistically indistinguishable performances across the top DL models for each waveform (MAE±SD 6.33 ± 0.73, 6.65 ± 0.96, and 7.30 ± 1.28 mmHg, respectively, for ECG, PPG, and ABP; p = 0.42). Results support the preliminary feasibility and accuracy of DL-enabled continuous noninvasive ICP waveform computation using extracranial physiological waveforms. With refinement and further validation, this method could represent a safer and more accessible alternative to invasive ICP, enabling assessment and treatment in low-resource settings., 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 © 2024 Elsevier Ltd. All rights reserved.)

Purpose of Review: We selectively review emerging noninvasive neuromonitoring techniques and the evidence that supports their use in the ICU setting. The focus is on neuromonitoring research in patients with acute brain injury., Recent Findings: Noninvasive intracranial pressure evaluation with optic nerve sheath diameter measurements, transcranial Doppler waveform analysis, or skull mechanical extensometer waveform recordings have potential safety and resource-intensity advantages when compared to standard invasive monitors, however each of these techniques has limitations. Quantitative electroencephalography can be applied for detection of cerebral ischemia and states of covert consciousness. Near-infrared spectroscopy may be leveraged for cerebral oxygenation and autoregulation computation. Automated quantitative pupillometry and heart rate variability analysis have been shown to have diagnostic and/or prognostic significance in selected subtypes of acute brain injury. Finally, artificial intelligence is likely to transform interpretation and deployment of neuromonitoring paradigms individually and when integrated in multimodal paradigms., Summary: The ability to detect brain dysfunction and injury in critically ill patients is being enriched thanks to remarkable advances in neuromonitoring data acquisition and analysis. Studies are needed to validate the accuracy and reliability of these new approaches, and their feasibility and implementation within existing intensive care workflows., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with disorders of consciousness who are behaviorally unresponsive may demonstrate volitional brain responses to motor imagery or motor commands detectable on functional magnetic resonance imaging or electroencephalography. This state of cognitive motor dissociation (CMD) may have prognostic significance., Methods: The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of monthly online meetings between September 2021 and April 2023 to examine the science of CMD and identify key knowledge gaps and unmet needs., Results: The group identified major knowledge gaps in CMD research: (1) lack of information about patient experiences and caregiver accounts of CMD, (2) limited epidemiological data on CMD, (3) uncertainty about underlying mechanisms of CMD, (4) methodological variability that limits testing of CMD as a biomarker for prognostication and treatment trials, (5) educational gaps for health care personnel about the incidence and potential prognostic relevance of CMD, and (6) challenges related to identification of patients with CMD who may be able to communicate using brain-computer interfaces., Conclusions: To improve the management of patients with disorders of consciousness, research efforts should address these mechanistic, epidemiological, bioengineering, and educational gaps to enable large-scale implementation of CMD assessment in clinical practice., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: The use of arterial partial pressure of carbon dioxide (PaCO 2 ) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO 2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO 2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO 2 with in-hospital mortality., Methods: We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO 2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO 2  > 35 and to 45 mmHg; mild hypocapnia as 32-35 mmHg; severe hypocapnia as 26-31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg., Results: 1476 patients (65.9% male, mean age 52 ± 18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO 2 had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients., Conclusions: Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO 2 values were significantly associated with increased in-hospital mortality., (© 2024. The Author(s).)

Background: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC., Methods: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC., Results: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC., Conclusions: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Acute respiratory distress syndrome (ARDS) is an important pulmonary complication in brain-injured patients receiving invasive mechanical ventilation (IMV). We aimed to evaluate the incidence and association between ARDS and clinical outcomes in patients with different forms of acute brain injury requiring IMV in the intensive care unit (ICU). Methods: This was a preplanned secondary analysis of a prospective, multicenter, international cohort study (NCT03400904). We included brain-injured patients receiving IMV for ≥ 24 h. ARDS was the main exposure of interest and was identified during index ICU admission using the Berlin definition. We examined the incidence and adjusted association of ARDS with ICU mortality, ICU length of stay, duration of IMV, and extubation failure. Outcomes were evaluated using mixed-effect logistic regression and cause-specific Cox proportional hazards models. Results: 1492 patients from 67 hospitals and 16 countries were included in the analysis, of whom 137 individuals developed ARDS (9.2% of overall cohort). Across countries, the median ARDS incidence was 5.1% (interquartile range [IQR] 0-10; range 0-27.3). ARDS was associated with increased ICU mortality (adjusted odds ratio (OR) 2.66; 95% confidence interval [CI], 1.29-5.48), longer ICU length of stay (adjusted hazard ratio [HR] 0.59; 95% CI, 0.48-0.73), and longer duration of IMV (adjusted HR 0.54; 95% CI, 0.44-0.67). The association between ARDS and extubation failure approached statistical significance (adjusted HR 1.48; 95% CI 0.99-2.21). Higher ARDS severity was associated with incrementally longer ICU length of stay and longer cumulative duration of IMV. Findings remained robust in a sensitivity analysis evaluating the magnitude of unmeasured confounding. Conclusions: In this cohort of acutely brain-injured patients, the incidence of ARDS was similar to that reported in other mixed cohorts of critically ill patients. Development of ARDS was associated with worse outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Over the past 5 decades, advances in neuroimaging have yielded insights into the pathophysiologic mechanisms that cause disorders of consciousness (DoC) in patients with severe brain injuries. Structural, functional, metabolic, and perfusion imaging studies have revealed specific neuroanatomic regions, such as the brainstem tegmentum, thalamus, posterior cingulate cortex, medial prefrontal cortex, and occipital cortex, where lesions correlate with the current or future state of consciousness. Advanced imaging modalities, such as diffusion tensor imaging, resting-state functional magnetic resonance imaging (fMRI), and task-based fMRI, have been used to improve the accuracy of diagnosis and long-term prognosis, culminating in the endorsement of fMRI for the clinical evaluation of patients with DoC in the 2018 US (task-based fMRI) and 2020 European (task-based and resting-state fMRI) guidelines. As diverse neuroimaging techniques are increasingly used for patients with DoC in research and clinical settings, the need for a standardized approach to reporting results is clear. The success of future multicenter collaborations and international trials fundamentally depends on the implementation of a shared nomenclature and infrastructure., Methods: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened an international panel of DoC neuroimaging experts to propose common data elements (CDEs) for data collection and reporting in this field., Results: We report the recommendations of this CDE development panel and disseminate CDEs to be used in neuroimaging studies of patients with DoC., Conclusions: These CDEs will support progress in the field of DoC neuroimaging and facilitate international collaboration., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Introduction: There is little consensus and high heterogeneity on the optimal set of relevant clinical outcomes in research studies regarding extubation in neurocritical care patients with brain injury undergoing mechanical ventilation. The aims of this study are to: (1) develop a core outcome set (COS) and (2) reach consensus on a hierarchical composite endpoint for such studies., Methods and Analysis: The study will include a broadly representative, international panel of stakeholders with research and clinical expertise in this field and will involve four stages: (1) a scoping review to generate an initial list of outcomes represented in the literature, (2) an investigator meeting to review the outcomes for inclusion in the Delphi surveys, (3) four rounds of online Delphi consensus-building surveys and (4) online consensus meetings to finalise the COS and hierarchical composite endpoint., Ethics and Dissemination: This study received ethical approval from the French Society of Anesthesia and Critical Care Medicine Institutional Review Board (SFAR CERAR-IRB 00010254-2023-029). The study results will be disseminated through communication to stakeholders, publication in a peer-reviewed journal, and presentations at conferences., Trial Registration Number: This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) Initiative., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Existing methods to characterise the evolving condition of traumatic brain injury (TBI) patients in the intensive care unit (ICU) do not capture the context necessary for individualising treatment. Here, we integrate all heterogenous data stored in medical records (1166 pre-ICU and ICU variables) to model the individualised contribution of clinical course to 6-month functional outcome on the Glasgow Outcome Scale -Extended (GOSE). On a prospective cohort (n = 1550, 65 centres) of TBI patients, we train recurrent neural network models to map a token-embedded time series representation of all variables (including missing values) to an ordinal GOSE prognosis every 2 h. The full range of variables explains up to 52% (95% CI: 50-54%) of the ordinal variance in functional outcome. Up to 91% (95% CI: 90-91%) of this explanation is derived from pre-ICU and admission information (i.e., static variables). Information collected in the ICU (i.e., dynamic variables) increases explanation (by up to 5% [95% CI: 4-6%]), though not enough to counter poorer overall performance in longer-stay (>5.75 days) patients. Highest-contributing variables include physician-based prognoses, CT features, and markers of neurological function. Whilst static information currently accounts for the majority of functional outcome explanation after TBI, data-driven analysis highlights investigative avenues to improve the dynamic characterisation of longer-stay patients. Moreover, our modelling strategy proves useful for converting large patient records into interpretable time series with missing data integration and minimal processing., (© 2023. Springer Nature Limited.)

Background: Increased burnout and decreased professional fulfillment among intensive care physicians is partly due to intensive care unit (ICU) workload. Although the SARS-CoV-2 (COVID-19) pandemic increased ICU workload, it also may have increased feelings of personal fulfillment due to positive public perceptions of physicians caring for COVID patients. We surveyed critical care anesthesiologists to identify the effect of provider demographics, ICU workload, and COVID-19-related workload, on professional fulfillment and burnout., Methods: We performed an exploratory survey of 606 members of the Society of Critical Care Anesthesiologists (SOCCA) in January and February 2022. We used the Stanford Professional Fulfillment Index (PFI) to grade levels of professional fulfillment and markers of burnout (ie, work exhaustion and disengagement). Univariable and multivariable models were used to identify associations between provider demographics and practice characteristics and professional fulfillment and work exhaustion., Results: One hundred and seventy-five intensivists (29%) responded. A total of 65% were male and 49% were between 36 and 45 years old. The overall median PFI score-0 (none) to 24 (most professional fulfillment)-was 17 (IQR, 1-24), with a wide distribution of responses. In multivariable analysis, factors associated with higher professional fulfillment included age >45 years ( P =.004), ≤15 weeks full-time ICU coverage in 2020 ( P =.02), role as medical director ( P =.01), and nighttime home call with supervision of in-house ICU fellows ( P =.01)., Conclusions: Professional fulfillment and work exhaustion in this cross-sectional survey were associated with several demographic and practice characteristics but not COVID-19-related workload, suggesting that COVID-19 workload may not have either positive or negative perceptions on professional fulfillment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). The primary endpoint was reintubation during ICU admission. We used mixed-effects logistic regression models with patient-level covariates and random intercepts for hospital and country to evaluate the association between prophylactic (i.e., planned) HFNC or NIPPV and reintubation. Measurements and Main Results: 1,115 patients were included from 62 hospitals and 19 countries, of whom 267 received HFNC or NIPPV following extubation (23.9%). Compared with conventional oxygen therapy, neither prophylactic HFNC nor NIPPV was associated with decreased odds of reintubation (respectively, odds ratios of 0.97 [95% confidence interval, 0.54-1.73] and 0.63 [0.30-1.32]). Findings remained consistent in sensitivity analyses accounting for alternate adjustment procedures, missing data, shorter time frames of the primary endpoint, and competing risks precluding reintubation. In a Bayesian analysis using skeptical and data-driven priors, the probabilities of reduced reintubation ranged from 17% to 34% for HFNC and from 46% to 74% for NIPPV. Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).

Disorders of consciousness are complex conditions characterised by persistent loss of responsiveness due to brain injury. They present diagnostic challenges and limited options for treatment, and highlight the urgent need for a more thorough understanding of how human consciousness arises from coordinated neural activity. The increasing availability of multimodal neuroimaging data has given rise to a wide range of clinically- and scientifically-motivated modelling efforts, seeking to improve data-driven stratification of patients, to identify causal mechanisms for patient pathophysiology and loss of consciousness more broadly, and to develop simulations as a means of testing in silico potential treatment avenues to restore consciousness. As a dedicated Working Group of clinicians and neuroscientists of the international Curing Coma Campaign, here we provide our framework and vision to understand the diverse statistical and generative computational modelling approaches that are being employed in this fast-growing field. We identify the gaps that exist between the current state-of-the-art in statistical and biophysical computational modelling in human neuroscience, and the aspirational goal of a mature field of modelling disorders of consciousness; which might drive improved treatments and outcomes in the clinic. Finally, we make several recommendations for how the field as a whole can work together to address these challenges., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Brain-injured patients in a state of cognitive motor dissociation (CMD) exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, patients with CMD may seem clinically indistinguishable from those with a true disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state minus). Yet, by expanding the range of motor testing across limb, facial, and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state. We propose the term of clinical CMD to describe patients showing these slight but determined motor responses and exhibiting a characteristic akinetic motor behavior as opposed to a pyramidal motor system behavior. These patients may harbor hidden cognitive capabilities and significant potential for a good long-term outcome. Indeed, we envision CMD as ranging from complete (no motor response) to partial (subtle clinical motor response) forms, falling within a spectrum of progressively better motor output in patients with considerable cognitive capabilities. In addition to providing a decisional flowchart, we present this novel approach to classification as a graphical model that illustrates the range of clinical manifestations and recovery trajectories fundamentally differentiating true disorders of consciousness from the spectrum of CMD., (© 2023 American Academy of Neurology.)

We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. We found that although mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree. Young TEs, particularly long interspersed elements, drive increases in genome size, whereas DNA transposons are associated with smaller genomes. Mammals tend to accumulate only a few types of TEs at any given time, with one TE type dominating. We also found association between dietary habit and the presence of DNA transposon invasions. These detailed annotations will serve as a benchmark for future comparative TE analyses among placental mammals.

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes., Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS)., Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22)., Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation., (© 2023. The Author(s).)

Motor impairments are only one aspect of Parkinson's disease (PD), which also include cognitive and linguistic impairments. Speech-derived interpretable biomarkers may help clinicians diagnose PD at earlier stages and monitor the disorder's evolution over time. This study focuses on the multilingual evaluation of a composite array of biomarkers that facilitate PD evaluation from speech. Hypokinetic dysarthria, a motor speech disorder associated with PD, has been extensively analyzed in previously published studies on automatic PD evaluation, with a relative lack of inquiry into language and task variability. In this study, we explore certain acoustic, linguistic, and cognitive information encoded within the speech of several cohorts with PD. A total of 24 biomarkers were analyzed from American English, Italian, Castilian Spanish, Colombian Spanish, German, and Czech by conducting a statistical analysis to evaluate which biomarkers best differentiate people with PD from healthy participants. The study leverages conceptual robustness as a criterion in which a biomarker behaves the same, independent of the language. Hence, we propose a set of speech-based biomarkers that can effectively help evaluate PD while being language-independent. In short, the best acoustic and cognitive biomarkers permitting discrimination between experimental groups across languages were fundamental frequency standard deviation, pause time, pause percentage, silence duration, and speech rhythm standard deviation. Linguistic biomarkers representing the length of the narratives and the number of nouns and auxiliaries also provided discrimination between groups. Altogether, in addition to being significant, these biomarkers satisfied the robustness requirements., 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 Favaro, Moro-Velázquez, Butala, Motley, Cao, Stevens, Villalba and Dehak.)

Background: Delirium poses significant risks to patients, but countermeasures can be taken to mitigate negative outcomes. Accurately forecasting delirium in intensive care unit (ICU) patients could guide proactive intervention. Our primary objective was to predict ICU delirium by applying machine learning to clinical and physiologic data routinely collected in electronic health records., Methods: Two prediction models were trained and tested using a multicenter database (years of data collection 2014 to 2015), and externally validated on two single-center databases (2001 to 2012 and 2008 to 2019). The primary outcome variable was delirium defined as a positive Confusion Assessment Method for the ICU screen, or an Intensive Care Delirium Screening Checklist of 4 or greater. The first model, named "24-hour model," used data from the 24 h after ICU admission to predict delirium any time afterward. The second model designated "dynamic model," predicted the onset of delirium up to 12 h in advance. Model performance was compared with a widely cited reference model., Results: For the 24-h model, delirium was identified in 2,536 of 18,305 (13.9%), 768 of 5,299 (14.5%), and 5,955 of 36,194 (11.9%) of patient stays, respectively, in the development sample and two validation samples. For the 12-h lead time dynamic model, delirium was identified in 3,791 of 22,234 (17.0%), 994 of 6,166 (16.1%), and 5,955 of 28,440 (20.9%) patient stays, respectively. Mean area under the receiver operating characteristics curve (AUC) (95% CI) for the first 24-h model was 0.785 (0.769 to 0.801), significantly higher than the modified reference model with AUC of 0.730 (0.704 to 0.757). The dynamic model had a mean AUC of 0.845 (0.831 to 0.859) when predicting delirium 12 h in advance. Calibration was similar in both models (mean Brier Score [95% CI] 0.102 [0.097 to 0.108] and 0.111 [0.106 to 0.116]). Model discrimination and calibration were maintained when tested on the validation datasets., Conclusions: Machine learning models trained with routinely collected electronic health record data accurately predict ICU delirium, supporting dynamic time-sensitive forecasting., (Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Patients with traumatic brain injury (TBI) frequently require invasive mechanical ventilation and admission to an intensive care unit. Ventilation of patients with TBI poses unique clinical challenges, and careful attention is required to ensure that the ventilatory strategy (including selection of appropriate tidal volume, plateau pressure, and positive end-expiratory pressure) does not cause significant additional injury to the brain and lungs. Selection of ventilatory targets may be guided by principles of lung protection but with careful attention to relevant intracranial effects. In patients with TBI and concomitant acute respiratory distress syndrome (ARDS), adjunctive strategies include sedation optimization, neuromuscular blockade, recruitment maneuvers, prone positioning, and extracorporeal life support. However, these approaches have been largely extrapolated from studies in patients with ARDS and without brain injury, with limited data in patients with TBI. This narrative review will summarize the existing evidence for mechanical ventilation in patients with TBI. Relevant literature in patients with ARDS will be summarized, and where available, direct data in the TBI population will be reviewed. Next, practical strategies to optimize the delivery of mechanical ventilation and determine readiness for extubation will be reviewed. Finally, future directions for research in this evolving clinical domain will be presented, with considerations for the design of studies to address relevant knowledge gaps., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Despite the growing contributions of critical care anesthesiologists to clinical practice, research, and administrative leadership of intensive care units (ICUs), relatively little is known about the subspecialty-specific clinical practice environment. An understanding of contemporary clinical practice is essential to recognize the opportunities and challenges facing critical care anesthesia, optimize staffing patterns, assess sustainability and satisfaction, and strategically plan for future activity, scope, and training. This study surveyed intensivists who are members of the Society of Critical Care Anesthesiologists (SOCCA) to evaluate practice patterns of critical care anesthesiologists, including compensation, types of ICUs covered, models of overnight ICU coverage, and relationships between these factors. We hypothesized that variability in compensation and practice patterns would be observed between individuals., Methods: Board-certified critical care anesthesiologists practicing in the United States were identified using the SOCCA membership distribution list and invited to take a voluntary online survey between May and June 2021. Multiple-choice questions with both single- and multiple-select options were used for answers with categorical data, and adaptive questioning was used to clarify stem-based responses. Respondents were asked to describe practice patterns at their respective institutions and provide information about their demographics, salaries, effort in ICUs, as well as other activities., Results: A total of 490 participants were invited to take this survey, and 157 (response rate 32%) surveys were completed and analyzed. The majority of respondents were White (73%), male (69%), and younger than 50 years of age (82%). The cardiothoracic/cardiovascular ICU was the most common practice setting, with 69.5% of respondents reporting time working in this unit. Significant variability was observed in ICU practice patterns. Respondents reported spending an equal proportion of their time in clinical practice in the operating rooms and ICUs (median, 40%; interquartile range [IQR], 20%-50%), whereas a smaller proportion-primarily those who completed their training before 2009-reported administrative or research activities. Female respondents reported salaries that were $36,739 less than male respondents; however, this difference was not statistically different, and after adjusting for age and practice type, these differences were less pronounced (-$27,479.79; 95% confidence interval [CI], -$57,232.61 to $2273.03; P = .07)., Conclusions: These survey data provide a current snapshot of anesthesiology critical care clinical practice patterns in the United States. Our findings may inform decision-making around the initiation and expansion of critical care services and optimal staffing patterns, as well as provide a basis for further work that focuses on intensivist satisfaction and burnout., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Purpose: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation., Methods: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality., Results: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI 95 ) [0.71-0.87] and 0.71 CI 95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure)., Conclusions: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)