Search

Background: MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH., Purpose: To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES)., Study Type: Prospective., Subjects: 28 control subjects (age: 35.9 ± 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 ± 11.3 years)., Field Strength/sequence: 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES., Assessment: We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls., Statistical Tests: Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant., Results: HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 ± 0.60 vs 2.51 ± 0.55, P < 0.01) and Glx (8.69 ± 1.23 vs 7.72 ± 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 ± 0.35 vs 1.22 ± 0.28, P = 0.65) levels showing no significant difference., Data Conclusion: Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Corticosteroids are prescribed for refractory headache in patients with spontaneous subarachnoid hemorrhage (SAH) despite limited supporting evidence. We hypothesized that a short course of corticosteroids would reduce pain., Methods: We reviewed all patients who received corticosteroids for refractory headache following spontaneous SAH within our institutional database. Pain was measured by a numeric rating scale (NRS) every 2 h. The primary outcome was maximum daily NRS score; secondary outcomes were the mean daily NRS score and daily opioid consumption. Propensity scores were developed using potential predictors of corticosteroid use, including age, sex, pretreatment 24-h pain burden, and the number of analgesics being used to control pain. Inverse probability treatment weighting (IPTW) was used to balance baseline covariate distributions between patients receiving corticosteroids and control patients. Generalized estimating equations were used to analyze longitudinal NRS scores and oral morphine equivalents based on the weighted cohort., Results: A total of 213 patients were included. The mean age was 55 (SD 13) years, and 141 of 213 (66%) were female. Of 213 patients, 195 (92%) had a low clinical grade (i.e., Hunt-Hess grades 1-3). Seventy patients were prescribed corticosteroids on postbleed day 5 (SD 3.3) on average, with an average of 26 (SD 10) mg of dexamethasone over 48 h. Patients receiving corticosteroids and controls were well balanced on baseline predictors of treatment status. After IPTW, we found that corticosteroid therapy reduced the daily maximum pain NRS score by 0.59 (SE = 0.39, p = 0.12), 0.96 (SE = 0.42, p = 0.02), and 0.91 (SE = 0.46, p = 0.048) on days 1-3, respectively, after adjusting for control effects. The mean daily pain NRS score and daily opioid use were nonsignificantly reduced in the 3 days following corticosteroid initiation after adjusting for control effects., Conclusions: Short-term corticosteroids only slightly reduced maximum pain severity after spontaneous SAH. Other analgesic strategies are required to manage refractory pain in this population., Competing Interests: Conflicts of interest The authors report no conflict of interest.Ethical Approval/Informed ConsentInstitutional review board approval was waved given the retrospective nature of the study., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Importance: Fever is associated with worse outcomes in patients with stroke, but whether preventing fever improves outcomes is unclear., Objective: To determine whether fever prevention after acute vascular brain injury is achievable and impacts functional outcome., Design, Setting, and Participants: Open-label randomized clinical trial with blinded outcome assessment that enrolled 686 of 1176 planned critically ill patients with stroke at 43 intensive care units in 7 countries from March 2017 to April 2021 (last date of follow-up was May 12, 2022)., Intervention: Patients randomized to fever prevention (n = 339) were targeted to 37.0 °C for 14 days or intensive care unit discharge using an automated surface temperature management device. Standard care patients (n = 338) received standardized tiered fever treatment on occurrence of temperature of 38 °C or greater., Main Outcomes and Measures: Primary outcome was daily mean fever burden: the area under the temperature curve above 37.9 °C (total fever burden) divided by the total number of hours in the acute phase, multiplied by 24 hours (°C-hour). The principal secondary outcome was 3-month functional recovery by shift analysis of the 6-category modified Rankin Scale, which is scored from 0 (no symptoms) to 6 (death). Major adverse events included death, pneumonia, sepsis, and malignant cerebral edema., Results: Enrollment was stopped after a planned interim analysis demonstrated futility of the principal secondary end point. In total, 686 patients were enrolled, and 9 were consented but not randomized, leaving a primary analysis population of 677 patients (254 ischemic stroke, 223 intracerebral hemorrhage, 200 subarachnoid hemorrhage; 345 were female [51%]; median age, 62 years) with 433 (64%) completing the study through 12 months. Daily mean (SD) fever burden was significantly lower in the fever prevention group (0.37 [1.0] °C-hour; range, 0.0-8.0 °C-hour) compared with the standard care group (0.73 [1.1] °C-hour; range, 0.0-10.3 °C-hour) (difference, -0.35 [95% CI, -0.51 to -0.20]; P < .001). Between-group differences for the primary outcome by stroke subtype were -0.10 (95% CI, -0.35 to 0.15) for ischemic stroke, -0.50 (95% CI, -0.78 to -0.22) for intracerebral hemorrhage, and -0.52 (95% CI, -0.81 to -0.23) for subarachnoid hemorrhage (all P < .001 by Wilcoxon rank-sum test). There was no significant difference in functional recovery at 3 months (median modified Rankin Scale score, 4.0 vs 4.0, respectively; odds ratio for a favorable shift in functional outcome, 1.09 [95% CI, 0.81 to 1.46]; P = .54). Major adverse events occurred in 82.2% of participants in the fever prevention group vs 75.9% in the standard care group, including 33.8% vs 34.5% for infections, 14.5% vs 14.0% for cardiac disorders, and 24.5% vs 20.5% for respiratory disorders., Conclusions and Relevance: In patients with acute vascular brain injury, preventive normothermia using an automated surface temperature management device effectively reduced fever burden but did not improve functional outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT02996266.

Objective: Comatose survivors of cardiac arrest (CA) pose a complex challenge for physicians reliant on imperfect studies to determine the extent of neurologic injury. Clinically available imaging is frequently relied upon despite limited sensitivity. We conducted a prospective pilot study comparing diffusion kurtosis imaging (DKI)-MRI and somatosensory evoked potentials (SSEPs) in comatose survivors of CA to investigate the benefit of utilizing higher diffusion b-values to enhance prediction of arousal recovery., Methods: Survivors of CA admitted from June 2015 through November 2019 with DKI-MRI and SSEPs were evaluated. Advanced diffusion metrics differentiating present or absent SSEPs were analyzed using whole-brain voxelwise nonparametric permutation inference with threshold-free cluster enhancement., Results: Twenty survivors of CA were included, mean age 52, 45% female and out-of-hospital arrests accounting for 75% of cases. Baseline characteristics and examination findings were not statistically different between groups at admission or 48 h after achieving normothermia. A decrease in mean diffusivity (MD) and increase in mean kurtosis (MK) was demonstrated in subjects without arousal recovery potential, most prominently in the posterior mesial temporal, parietal and occipital lobes., Conclusion: DKI-MRI may improve early arousal recovery prediction during the immediate phase of post-CA care, especially where SSEPs are unavailable or unreliable.

Objective: Laser interstitial thermal therapy (LITT) is an emerging tool for treating a variety of focal brain lesions, including recurrent high-grade glioma (HGG). While the efficacy and uses of LITT have been well studied, the impact of this treatment on patient functional outcomes has not been analyzed in detail. This study sought to better define the role of LITT in treating patients with recurrent HGG, examining which patients exhibit good functional outcomes after LITT, and to determine risk factors for worsening neurological function., Methods: The medical records of patients treated with LITT for recurrent HGG at a single tertiary care center were retrospectively reviewed. Functional status was assessed using the Karnofsky Performance Scale (KPS). Demographic, clinical, and radiological data were examined for associations with change in KPS score assessed 4-6 weeks following surgery., Results: Forty-seven patients were included in the study with histopathologically confirmed recurrent HGG. The mean age was 57 years, and 21 (45%) patients were female. The pre-LITT KPS scores were as follows: 100 in 4 (9%) patients, 90 in 15 (32%) patients, 80 in 10 (21%) patients, 70 in 13 (28%) patients, and 60 in 5 (11%) patients. Overall, 59% of patients showed a stable or improved KPS score after undergoing LITT. Tumor volume was the sole predictor of decreased KPS score after LITT. Notably, tumor location including eloquent location, preoperative KPS score, and other comorbidities were not independently associated with change in functional status., Conclusions: The majority of patients undergoing LITT for recurrent HGG had a favorable functional outcome at the initial follow-up visit. The treated tumor volume was inversely and independently associated with post-LITT functional outcome. This information may help guide patient selection and treatment optimization in the setting of LITT-based approaches for recurrent HGG.

Background: Patients with severe stroke are at high risk of secondary neurologic decline (ND) from the development of malignant cerebral edema (MCE). However, early infarcts are hard to diagnose on conventional head computed tomography (CT). We hypothesize that high-energy (190 keV) virtual monochromatic imaging (VMI) from dual-energy CT (DECT) imaging enables earlier detection of ND from MCE., Methods: Consecutive patients with severe stroke with National Institute of Health Stroke Scale (NIHSS) scores > 15 and DECT within 10 h of mechanical thrombectomy from May 2020 to March 2022 were included. We excluded patients with parenchymal hematoma type 2 transformation. Retrospective analysis of clinical and novel variables included the VMI Alberta Stroke Program Early CT Score (ASPECTS), total iodine content, and VMI infarct volume. The primary outcome was secondary ND, defined using a composite outcome variable of clinical worsening (increase in NIHSS score ≥ 4 or decrease in Glasgow Coma Scale score > 2) or malignant radiographical edema (midline shift ≥ 5 mm at the level of the septum pellucidum). Fisher's exact test and Wilcoxon's test were used for univariate analysis. Logistic regression was used to develop prediction models for categorical outcomes., Results: Eighty-four patients with severe stroke with a median age of 67.5 (interquartile range [IQR] 57-78) years and an NIHSS score of 22 (IQR 18-25) were included. Twenty-nine patients had ND. The VMI ASPECTS, total iodine content, and VMI infarct volume were associated with ND. The VMI ASPECTS, VMI infarct volume, and total iodine content were predictors of ND after adjusting for age, sex, initial NIHSS score, and tissue plasminogen activator administration, with areas under the receiver operating characteristic curve (AUROC) of 0.691 (95% confidence interval [CI] 0.572-0.810), 0.877 (95% CI 0.800-0.954), and 0.845 (95% CI 0.750-0.940). By including all three predictors, the model achieved an AUROC of 0.903 (95% CI 0.84-0.97) and was cross-validated by the leave one out method, with an AUROC of 0.827., Conclusions: The VMI ASPECTS and VMI infarct volume from DECT are superior to the conventional CT ASPECTS and are novel predictors for secondary ND due to MCE after severe stroke. Clinical trial registration ClinicalTrials.gov identifier: NCT04189471., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Paroxysmal Sympathetic Hyperactivity (PSH) occurs with high prevalence among critically ill Traumatic Brain Injury (TBI) patients and is associated with worse outcomes. The PSH-Assessment Measure (PSH-AM) consists of a Clinical Features Scale (CFS) and a Diagnosis Likelihood Tool (DLT), intended to quantify the severity of sympathetically-mediated symptoms and likelihood that they are due to PSH, respectively, on a daily basis. Here, we aim to identify and explore the value of dynamic trends in the evolution of sympathetic hyperactivity following acute TBI using elements of the PSH-AM., Methods: We performed an observational cohort study of 221 acute critically ill TBI patients for whom daily PSH-AM scores were calculated over the first 14 days of hospitalization. A principled group-based trajectory modeling approach using unsupervised K-means clustering was used to identify distinct patterns of CFS evolution within the cohort. We also evaluated the relationships between trajectory group membership and PSH diagnosis, as well as PSH DLT score, hospital discharge GCS, ICU and hospital length of stay, duration of mechanical ventilation, and mortality. Baseline clinical and demographic features predictive of trajectory group membership were analyzed using univariate screening and multivariate multinomial logistic regression., Results: We identified four distinct trajectory groups. Trajectory group membership was significantly associated with clinical outcomes including PSH diagnosis and DLT score, ICU length of stay, and duration of mechanical ventilation. Baseline features independently predictive of trajectory group membership included age and post-resuscitation motor GCS., Conclusions: This study adds to the sparse research characterizing the heterogeneous temporal trends of sympathetic nervous system activation during the acute phase following TBI. This may open avenues for early identification of at-risk patients to receive tailored interventions to limit secondary brain injury associated with autonomic dysfunction and thereby improve TBI patient outcomes.

Introduction: Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery., Methods: In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis., Results: Our key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information., Conclusion: ePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes., Competing Interests: EW’s institution has received research funding from the AASM Foundation, Department of Defense, Merck, NIH/NIA, ResMed, the ResMed Foundation, and the SRS Foundation. EW has served as a scientific consultant to Axsome Therapeutics, DayZz, Ensodata, Eisai, Idorsia, Merck, Nox Health, Primasun, Purdue, and ResMed and is an equity shareholder in WellTap. 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhuo, Raghavan, Li, Roys, Njonkou Tchoquessi, Chen, Wickwire, Parikh, Schwartzbauer, Grattan, Wang, Gullapalli and Badjatia.)

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort., Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury., Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months., Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed., Level of Evidence: IV., Trial Registration Number: NCT02119182., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and β-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume., (© 2024. The Author(s).)

Objectives: Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans after brain injury. The Coma Recovery Scale-Revised (CRS-R) is a sensitive measure of consciousness validated in the rehabilitation phase of care. We tested the feasibility, safety, and impact of CRS-R-guided rehabilitation in the ICU for patients with DoC after acute hemorrhagic stroke., Design: Retrospective cohort study., Setting: This single-center study was conducted in the neurocritical care unit at the University of Maryland Medical Center., Patients: We analyzed records from consecutive patients with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), who underwent serial CRS-R assessments during ICU admission from April 1, 2018, to December 31, 2021, where CRS-R less than 8 is vegetative state/unresponsive wakefulness syndrome (VS/UWS); CRS-R greater than or equal to 8 is a minimally conscious state (MCS)., Interventions: None., Measurements and Main Results: Outcomes included adverse events during CRS-R evaluations and associations between CRS-R and discharge disposition, therapy-based function, and mobility. We examined the utility of CRS-R compared with other therapist clinical assessment tools in predicting discharge disposition. Seventy-six patients (22 SAH, 54 ICH, median age = 59, 50% female) underwent 276 CRS-R sessions without adverse events. Discharge to acute rehabilitation occurred in 4.4% versus 41.9% of patients with a final CRS-R less than 8 and CRS-R greater than or equal to 8, respectively (odds ratio [OR] 13.4; 95% CI, 2.7-66.1; p < 0.001). Patients with MCS on final CRS-R completed more therapy sessions during hospitalization and had improved mobility and functional performance. Compared with other therapy assessment tools, the CRS-R had the best performance in predicting discharge disposition (area under the curve: 0.83; 95% CI, 0.72-0.94; p < 0.0001)., Conclusions: Early neurorehabilitation guided by CRS-R appears to be feasible and safe in the ICU following hemorrhagic stroke complicated by DoC and may enhance access to inpatient rehabilitation, with the potential for lasting benefit on recovery. Further research is needed to assess generalizability and understand the impact on long-term outcomes., Competing Interests: Drs. Woodward, Ahmed, Edlow, Braun, and Parikh received support for article research from the National Institutes of Health. Dr. Woodward’s institution received funding from the Institute for Clinical and Translational Research (ICTR) (5TL1TR003100-04). Dr. Morris received funding from the National Institute of Neurological Disorders and Stroke (1R01NS131606); he disclosed he serves on the editorial board of Neurology. Dr. Ciryam’s institution received funding from GEn1E Lifesciences, the Henry M. Jackson Foundation, and the Passano Foundation. Dr. Braun’s institution received funding from the National Center for Medical Rehabilitation Research (R03) and the National Institutes on Aging; they disclosed they are a University of Maryland Rehabilitation Institute–Medical Executive Committee member. Dr. Parihk received funding from the University of Maryland Baltimore, the ICTR, the National Center for Advancing Translational Sciences (1UL1TR003098), and the Korean Neurocritical Care Society. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Background: Paroxysmal sympathetic hyperactivity (PSH) occurs in a subset of patients with traumatic brain injury (TBI) and is associated with worse outcomes. Sepsis is also associated with worse outcomes after TBI and shares several physiologic features with PSH, potentially creating diagnostic confusion and suboptimal management of each. This is the first study to directly investigate the interaction between PSH and infection using robust diagnostic criteria., Methods: We performed a retrospective cohort study of patients with TBI admitted to a level I trauma center intensive care unit with hospital length of stay of at least 2 weeks. From January 2016 to July 2018, 77 patients diagnosed with PSH were 1:1 matched by age and Glasgow Coma Scale to 77 patients without PSH. Trauma infectious diseases subspecialists prospectively documented assessments corroborating diagnoses of infection. Extracted data including incidence, timing, classification, and anatomical source of infections were compared according to PSH diagnosis. We also evaluated daily PSH clinical feature severity scores and systemic inflammatory response syndrome (SIRS) criteria and compared values for patients with and without confirmed infection, stratified by PSH diagnosis., Results: During the first 2 weeks of hospitalization, there were no differences in rates of suspected (62%) nor confirmed (48%) infection between patients with PSH and controls. Specific treatments for PSH were initiated on median hospital day 7 and for confirmed infections on median hospital day 8. SIRS criteria could identify infection only in patients who were not diagnosed with PSH., Conclusions: In the presence of brain injury-induced autonomic nervous system dysregulation, the initiation and continuation of antimicrobial therapy is a challenging clinical decision, as standard physiologic markers of sepsis do not distinguish infected from noninfected patients with PSH, and these entities often present around the same time. Clinicians should be aware that PSH is a potential driver of SIRS, and familiarity with its diagnostic criteria as proposed by the PSH assessment measure is important. Management by a multidisciplinary team attentive to these issues may reduce rates of inappropriate antibiotic usage and misdiagnoses., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009-2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3-8), 223 (3.7%) moderate TBI (GCS 9-12), and 5913 (88.5%) mild TBI (GCS 13-15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation., (© 2024. The Author(s).)

Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders., Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI., Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023., Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI])., Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury., Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI)., Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

The perivascular space (PVS) is important to brain waste clearance and brain metabolic homeostasis. Enlarged PVS (ePVS) becomes visible on magnetic resonance imaging (MRI) and is best appreciated on T2-weighted (T2w) images. However, quantification of ePVS is challenging because standard-of-care T1-weighted (T1w) and T2w images are often obtained via two-dimensional (2D) acquisition, whereas accurate quantification of ePVS normally requires high-resolution volumetric three-dimensional (3D) T1w and T2w images. The purpose of this study was to investigate the use of a deep-learning-based super-resolution (SR) technique to improve ePVS quantification from 2D T2w images for application in patients with traumatic brain injury (TBI). We prospectively recruited 26 volunteers (age: 31 ± 12 years, 12 male/14 female) where both 2D T2w and 3D T2w images were acquired along with 3D T1w images to validate the ePVS quantification using SR T2w images. We then applied the SR method to retrospectively acquired 2D T2w images in 41 patients with chronic TBI (age: 41 ± 16 years, 32 male/9 female). ePVS volumes were automatically quantified within the whole-brain white matter and major brain lobes (temporal, parietal, frontal, occipital) in all subjects. Pittsburgh Sleep Quality Index (PSQI) scores were obtained on all patients with TBI. Compared with the silver standard (3D T2w), in the validation study, the SR T2w provided similar whole-brain white matter ePVS volume (r = 0.98, p  < 0.0001), and similar age-related ePVS burden increase (r = 0.80, p  < 0.0001). In the patient study, patients with TBI with poor sleep showed a higher age-related ePVS burden increase than those with good sleep. Sleep status is a significant interaction factor in the whole brain ( p  = 0.047) and the frontal lobe ( p  = 0.027). We demonstrate that images produced by SR of 2D T2w images can be automatically analyzed to produce results comparable to those obtained by 3D T2 volumes. Reliable age-related ePVS burden across the whole-brain white matter was observed in all subjects. Poor sleep, affecting the glymphatic function, may contribute to the accelerated increase of ePVS burden following TBI.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population., Competing Interests: 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., (© 2024 The Authors.)

Background: Clinicians working in intensive care units (ICUs) are immersed in a cacophony of alarms and a relentless onslaught of data. Within this frenetic environment, clinicians make high-stakes decisions using many data sources and are often oversaturated with information of varying quality. Traditional bedside monitors only depict static vital signs data, and these data are not easily viewable remotely. Clinicians must rely on separate nursing charts-handwritten or electric-to review physiological patterns, including signs of potential clinical deterioration. An automated physiological data viewer has been developed to provide at-a-glance summaries and to assist with prioritizing care for multiple patients who are critically ill., Objective: This study aims to evaluate a novel vital signs viewer system in a level 1 trauma center by subjectively assessing the viewer's utility in a high-volume ICU setting., Methods: ICU attendings were surveyed during morning rounds. Physicians were asked to conduct rounds normally, using data reported from nurse charts and briefs from fellows to inform their clinical decisions. After the physician finished their assessment and plan for the patient, they were asked to complete a questionnaire. Following completion of the questionnaire, the viewer was presented to ICU physicians on a tablet personal computer that displayed the patient's physiologic data (ie, shock index, blood pressure, heart rate, temperature, respiratory rate, and pulse oximetry), summarized for up to 72 hours. After examining the viewer, ICU physicians completed a postview questionnaire. In both questionnaires, the physicians were asked questions regarding the patient's stability, status, and need for a higher or lower level of care. A hierarchical clustering analysis was used to group participating ICU physicians and assess their general reception of the viewer., Results: A total of 908 anonymous surveys were collected from 28 ICU physicians from February 2015 to June 2017. Regarding physicians' perception of whether the viewer enhanced the ability to assess multiple patients in the ICU, 5% (45/908) strongly agreed, 56.6% (514/908) agreed, 35.3% (321/908) were neutral, 2.9% (26/908) disagreed, and 0.2% (2/908) strongly disagreed., Conclusions: Morning rounds in a trauma center ICU are conducted in a busy environment with many data sources. This study demonstrates that organized physiologic data and visual assessment can improve situation awareness, assist clinicians with recognizing changes in patient status, and prioritize care., (©Shiming Yang, Samuel Galvagno, Neeraj Badjatia, Deborah Stein, William Teeter, Thomas Scalea, Stacy Shackelford, Raymond Fang, Catriona Miller, Peter Hu, VS viewer study group. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 05.01.2024.)

Mild traumatic brain injury (mTBI) accounts for 70-90% of all TBI cases. Lipid metabolites have important roles in plasma membrane biogenesis, function, and cell signaling. As TBI can compromise plasma membrane integrity and alter brain cell function, we sought to identify circulating phospholipid alterations after mTBI, and determine if these changes were associated with clinical outcomes. Patients with mTBI (Glasgow Coma Score [GCS] ≥13 and loss of consciousness <30 min) were recruited. A total of 84 mTBI subjects were enrolled after admission to a level I trauma center, with the majority having evidence of traumatic intracranial hemorrhage on brain computed tomography (CT). Plasma samples were collected within 24 h of injury with 32 mTBI subjects returning at 3 months after injury for a second plasma sample to be collected. Thirty-five healthy volunteers were enrolled as controls and had a one-time blood draw. Lipid metabolomics was performed on plasma samples from each subject. Fold change of selected lipid metabolites was determined. Multivariable regression models were created to test associations between lipid metabolites and discharge and 6-month Glasgow Outcomes Scale-Extended (GOSE) outcomes (dichotomized between "good" [GOSE ≥7] and "bad" [GOSE ≤6] functional outcomes). Plasma levels of 31 lipid metabolites were significantly associated with discharge GOSE using univariate models; three of these metabolites were significantly increased, while 14 were significantly decreased in subjects with good outcomes compared with subjects with poor outcomes. In multivariable logistic regression models, higher circulating levels of the lysophospholipids (LPL) 1-linoleoyl-glycerophosphocholine (GPC) (18:2), 1-linoleoyl-GPE (18:2), and 1-linolenoyl-GPC (18:3) were associated with both good discharge GOSE (odds ratio [OR] 12.2 [95% CI 3.35, 58.3], p  = 5.23 × 10 -4 ; OR 9.43 [95% CI 2.87, 39.6], p  = 7.26 × 10 -4 ; and OR 5.26 [95% CI 1.99, 16.7], p  = 2.04 × 10 -3 , respectively) and 6-month (OR 4.67 [95% CI 1.49, 17.7], p  = 0.013; OR 2.93 [95% CI 1.11, 8.87], p  = 0.039; and OR 2.57 [95% CI 1.08, 7.11], p  = 0.046, respectively). Compared with healthy volunteers, circulating levels of these three LPLs were decreased early after injury and had normalized by 3 months after injury. Logistic regression models to predict functional outcomes were created by adding each of the described three LPLs to a baseline model that included age and sex. Including 1-linoleoyl-GPC (18:2) (8.20% improvement, p  = 0.009), 1-linoleoyl-GPE (18:2) (8.85% improvement, p  = 0.021), or 1-linolenoyl-GPC (18:3) (7.68% improvement, p =  0.012), significantly improved the area under the curve (AUC) for predicting discharge outcomes compared with the baseline model. Models including 1-linoleoyl-GPC (18:2) significantly improved AUC for predicting 6-month outcomes (9.35% improvement, p  = 0.034). Models including principal components derived from 25 LPLs significantly improved AUC for prediction of 6-month outcomes (16.0% improvement, p =  0.020). Our results demonstrate that higher plasma levels of LPLs (1-linoleoyl-GPC, 1-linoleoyl-GPE, and 1-linolenoyl-GPC) after mTBI are associated with better functional outcomes at discharge and 6 months after injury. This class of phospholipids may represent a potential therapeutic target.

Importance: Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known., Objective: To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers., Design, Setting, and Participants: This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023., Exposures: Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury., Main Outcomes and Measures: Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test)., Results: The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups)., Conclusions and Relevance: In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Background: Shivering is a common adverse effect of achieving and maintaining normothermia in neurocritical care patients. We compared the burden of shivering and shivering-related interventions between a novel transnasal temperature-modulating device (tnTMD) and surface cooling temperature-modulating devices (sTMDs) during the first 24 h of targeted normothermia in mechanically ventilated febrile neurocritical care patients., Methods: This is a case-control study controlling for factors that impact shiver burden: age, sex, body surface area. All patients underwent transnasal cooling (CoolStat, KeyTech, Inc.) as part of an ongoing multicenter clinical trial (NCT03360656). Patients undergoing treatment with sTMDs were selected from consecutively treated patients during the same time period. Data collected included the following: core body temperature (every 2 h), bedside shivering assessment scale (BSAS) score (every 2 h), and administration of antishivering medication for a BSAS score > 1. Time to normothermia (≤ 37.5 °C), as well as temperature burden > 37.5 °C (°C × h), were compared between groups using Student's t-test for mean differences. The proportion of patients requiring interventions, as well as the number of interventions per patient, was compared using the χ 2 test. Significance was determined based on a p value < 0.05., Results: There were 10 tnTMD patients and 30 sTMD patients included in the analysis (mean age: 62 ± 4, 30% women, body surface area = 1.97 ± 0.25). There were no differences between groups in temperature at cooling initiation (tnTMD: 38.5 ± 0.2 °C vs. sTMD: 38.7 ± 0.5 °C, p = 0.3), time to ≤ 37.5 °C (tnTMD: 1.8 ± 1.5 h vs. sTMD: 2.9 ± 1.4 h, p = 0.1), or temperature burden > 37.5 (tnTMD: - 0.4 ± 1.13 °C × h vs. sTMD median [IQR]: - 0.57 ± 0.58 °C × h, p = 0.67). The number of tnTMD patients who received pharmacologic shivering interventions was lower than the number of controls (20 vs. 67%, p = 0.01). tnTMD patients also had fewer shivering interventions per patient (0 [range: 0-3] vs. 4 [range: 0-23], p < 0.001)., Conclusions: A transnasal cooling approach achieved similar time to normothermia and temperature burden with less shivering than surface cooling. This approach may be a feasible option to consider for mechanically ventilated febrile neurocritical care patients., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: The implementation of multimodality monitoring in the clinical management of patients with disorders of consciousness (DoC) results in physiological measurements that can be collected in a continuous and regular fashion or even at waveform resolution. Such data are considered part of the "Big Data" available in intensive care units and are potentially suitable for health care-focused artificial intelligence research. Despite the richness in content of the physiological measurements, and the clinical implications shown by derived metrics based on those measurements, they have been largely neglected from previous attempts in harmonizing data collection and standardizing reporting of results as part of common data elements (CDEs) efforts. CDEs aim to provide a framework for unifying data in clinical research and help in implementing a systematic approach that can facilitate reliable comparison of results from clinical studies in DoC as well in international research collaborations., Methods: To address this need, the Neurocritical Care Society's Curing Coma Campaign convened a multidisciplinary panel of DoC "Physiology and Big Data" experts to propose 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 physiologic and big data studies of patients with DoC., Conclusions: These CDEs will support progress in the field of DoC physiologic and big data and facilitate international collaboration., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objectives: To describe the factors affecting critical care capacity and how critical care organizations (CCOs) within academic centers in the U.S. flow-size critical care resources under normal operations, strain, and surge conditions., Data Sources: PubMed, federal agency and American Hospital Association reports, and previous CCO survey results were reviewed., Study Selection: Studies and reports of critical care bed capacity and utilization within CCOs and in the United States were selected., Data Extraction: The Academic Leaders in the Critical Care Medicine Task Force established regular conference calls to reach a consensus on the approach of CCOs to "flow-sizing" critical care services., Data Synthesis: The approach of CCOs to "flow-sizing" critical care is outlined. The vertical (relation to institutional resources, e.g., space allocation, equipment, personnel redistribution) and horizontal (interdepartmental, e.g., emergency department, operating room, inpatient floors) integration of critical care delivery (ICUs, rapid response) for healthcare organizations and the methods by which CCOs flow-size critical care during normal operations, strain, and surge conditions are described. The advantages, barriers, and recommendations for the rapid and efficient scaling of critical care operations via a CCO structure are explained. Comprehensive guidance and resources for the development of "flow-sizing" capability by a CCO within a healthcare organization are provided., Conclusions: We identified and summarized the fundamental principles affecting critical care capacity. The taskforce highlighted the advantages of the CCO governance model to achieve rapid and cost-effective "flow-sizing" of critical care services and provide recommendations and resources to facilitate this capability. The relevance of a comprehensive approach to "flow-sizing" has become particularly relevant in the wake of the latest COVID-19 pandemic. In light of the growing risks of another extreme epidemic, planning for adequate capacity to confront the next critical care crisis is urgent., Competing Interests: Dr. Halpern received funding from Werfen and Airstrip Technologies. Dr. Jacobi received funding from La Jolla Pharmaceuticals, Pfizer Hospital Products Division, AcelRx, Society of Critical Care Medicine LEAD and Glycemic Guidelines Co-Chair, BD Voices of Vascular Educational Advisor, Visante, Infusion Nurses Society, and Postgraduate Healthcare Education. Dr. Pastores’ institution received funding from Biomerieux, RevImmune, and Eisai/Global Coalition for Adaptive Research; he received funding from McGraw Hill. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Evidence for optimal analgesia following subarachnoid hemorrhage (SAH) is limited. Steroid therapy for pain refractory to standard regimens is common despite lack of evidence for its efficacy. We sought to determine if steroids reduced pain or utilization of other analgesics when given for refractory headache following SAH., Methods: We performed a retrospective within-subjects cohort study of SAH patients who received steroids for refractory headache. We compared daily pain scores, total daily opioid, and acetaminophen doses before, during, and after steroids. Repeated measures were analyzed with a multivariable general linear model and generalized estimating equations., Results: Included 52 patients treated with dexamethasone following SAH, of whom 11 received a second course, increasing total to 63 treatment epochs. Mean pain score on the first day of therapy was 7.92 (standard error of the mean [SEM] .37) and decreased to 6.68 (SEM .36) on the second day before quickly returning to baseline levels, 7.36 (SEM .33), following completion of treatment. Total daily analgesics mirrored this trend. Mean total opioid and acetaminophen doses on days one and two and two days after treatment were 47.83mg (SEM 6.22) and 1848mg (SEM 170.66), 34.24mg (SEM 5.12) and 1809mg (SEM 150.28), and 46.38mg (SEM 11.64) and 1833mg (SEM 174.23), respectively. Response to therapy was associated with older age, decreasing acetaminophen dosing, and longer duration of steroids. Hyperglycemia and sleep disturbance/delirium effected 28.6% and 55.6% of cases, respectively., Conclusion: Steroid therapy for refractory pain in SAH patients may have modest, transient effects in select patients., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Secondary neurologic decline (ND) after traumatic brain injury (TBI) is independently associated with outcome, but robust predictors of ND are lacking. In this retrospective analysis of consecutive isolated TBI admissions to the R. Adams Cowley Shock Trauma Center between November 2015 and June 2018, we aimed to develop a triage decision support tool to quantify risk for early ND. Three machine learning models based on clinical, physiologic, or combined characteristics from the first hour of hospital resuscitation were created. Among 905 TBI cases, 165 (18%) experienced one or more ND events (130 clinical, 51 neurosurgical, and 54 radiographic) within 48 h of presentation. In the prediction of ND, the clinical plus physiologic data model performed similarly to the physiologic only model, with concordance indices of 0.85 (0.824-0.877) and 0.84 (0.812-0.868), respectively. Both outperformed the clinical only model, which had a concordance index of 0.72 (0.688-0.759). This preliminary work suggests that a data-driven approach utilizing physiologic and basic clinical data from the first hour of resuscitation after TBI has the potential to serve as a decision support tool for clinicians seeking to identify patients at high or low risk for ND., (© 2023. The Author(s).)

Background and Purpose: Therapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation., Methods: An international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion., Results: These recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5°C) hypothermia was identified as the most promising treatment strategy., Conclusions: These recommendations provide a general outline for the use of TH after minimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population., Competing Interests: Author NB has received research funding from Becton Dickenson, Maryland Industrial Partnerships, Department of Defense. Author TB owns equity in a start-up investigating mechanisms of local cooling for ICH. Authors TB and CK are listed inventors in IP relating to cooling after ICH. 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. The reviewer BE declared a shared affiliation with the author PL to the handling editor at the time of review., (Copyright © 2022 Baker, Kellner, Colbourne, Rincon, Kollmar, Badjatia, Dangayach, Mocco, Selim, Lyden, Polderman and Mayer.)

Subtle and profound changes in autonomic nervous system (ANS) function affecting sympathetic and parasympathetic homeostasis occur as a result of critical illness. Changes in ANS function are particularly salient in neurocritical illness, when direct structural and functional perturbations to autonomic network pathways occur and may herald impending clinical deterioration or intervenable evolving mechanisms of secondary injury. Sympathetic and parasympathetic balance can be measured quantitatively at the bedside using multiple methods, most readily by extracting data from electrocardiographic or photoplethysmography waveforms. Work from our group and others has demonstrated that data-analytic techniques can identify quantitative physiologic changes that precede clinical detection of meaningful events, and therefore may provide an important window for time-sensitive therapies. Here, we review data-analytic approaches to measuring ANS dysfunction from routine bedside physiologic data streams and integrating this data into multimodal machine learning-based model development to better understand phenotypical expression of pathophysiologic mechanisms and perhaps even serve as early detection signals. Attention will be given to examples from our work in acute traumatic brain injury on detection and monitoring of paroxysmal sympathetic hyperactivity and prediction of neurologic deterioration, and in large hemispheric infarction on prediction of malignant cerebral edema. We also discuss future clinical applications and data-analytic challenges and future directions., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Mild (mTBI) traumatic brain injury (TBI) accounts for the majority of all TBI cases. Evidence has suggested that patients with mTBI can suffer from long-lasting cognitive deficits, persistent symptoms, and decreased quality of life. Sleep disorders are commonly observed after TBI, with the prevalence rate of sleep disturbances in persons with TBI being much higher than that in the general population. Poor sleep quality can impair cognitive functions in the general population. This effect of sleep disturbances may impede the recovery processes in the population with TBI. The objective of this study is to add to our understanding of the relationship between self-reported sleep problems and other post-concussion symptoms and look at the association between early sleep problems and long-term outcomes in mTBI. Post-concussion symptoms, neurocognitive functions, level of global outcomes, and rating of satisfaction of life were assessed in 64 patients with mTBI. The results revealed that the presence of sleep disturbances co-occur with an increased level of overall post-concussion symptoms at the subacute stage of mTBI, particularly with symptoms including poor concentration, memory problems, and irritability. In addition, sleep disturbance at the subacute stage is associated with persistent poor concentration and memory problems, as well as worse neurocognitive function, slower overall recovery, and lower satisfactory of life at the long term. Our findings suggest that sleep disturbance can be a prognostic factor of long-term outcomes after mTBI. Early interventions to improve sleep quality can have potential benefits to facilitate the recovery process from mTBI., Competing Interests: No competing financial interests exist., (© Shiyu Tang et al., 2022; Published by Mary Ann Liebert, Inc.)

Objective: To determine the incidence of and assess risk factors for repetitive traumatic brain injury (TBI) among older adults in the United States., Design: Retrospective cohort study., Setting: Administrative claims data obtained from the Centers for Medicare & Medicaid Services' Chronic Conditions Data Warehouse., Participants: Individuals 65 years or older and diagnosed with TBI between July 2008 and September 2012 drawn from a 5% random sample of US Medicare beneficiaries., Main Measures: Repetitive TBI was identified as a second TBI occurring at least 90 days after the first occurrence of TBI following an 18-month TBI-free period. We identified factors associated with repetitive TBI using a log-binomial model., Results: A total of 38 064 older Medicare beneficiaries experienced a TBI. Of these, 4562 (12%) beneficiaries sustained at least one subsequent TBI over up to 5 years of follow-up. The unadjusted incidence rate of repetitive TBI was 3022 (95% CI, 2935-3111) per 100 000 person-years. Epilepsy was the strongest predictor of repetitive TBI (relative risk [RR] = 1.44; 95% CI, 1.25-1.56), followed by Alzheimer disease and related dementias (RR = 1.32; 95% CI 1.20-1.45), and depression (RR = 1.30; 95% CI, 1.21-1.38)., Conclusions: Injury prevention and fall-reduction interventions could be targeted to identify groups of older adults at an increased risk of repetitive head injury. Future work should focus on injury-reduction initiatives to reduce the risk of repetitive TBI as well as assessment of outcomes related to repetitive TBI., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute cervical spinal cord injury (ACSCI) is commonly complicated by spinal shock, resulting in hemodynamic instability characterized by bradycardia and hypotension that can have fatal consequences. Current guidelines recommend the use of intravenous beta and dopamine agonists, such as norepinephrine and dopamine, respectively. We sought to determine whether enteral albuterol would be a safe and feasible treatment for bradycardia without an increase in the occurrence of known side effects of albuterol in patients with ACSCI., Methods: A retrospective review of patients with ACSCI admitted to an intensive care unit at a level I trauma center and treated with enteral albuterol was conducted. Patients were excluded for the following reasons: pure beta blocker use prior to injury, concurrent use of pacemaker, age of less than 18 years, or age more than 75 years. As part of the standard of care, all patients underwent mean arterial pressure (MAP) augmentation to reach a goal of greater than 85 mm Hg during the first 7 days post injury. All eligible patient charts were reviewed for demographic characteristics, daily minimum and maximum heart rate and MAP, and concomitant vasoactive medication use. Bradycardia and tachycardia were defined as heart rate less than 60 beats per minute (bpm) and greater than 100 bpm, respectively. Factors found to be associated with bradycardia on univariate analysis were entered into a multivariable generalized estimating equation analysis to determine factors independently associated with bradycardia during the study period., Results: There were 58 patients with cervical ASCI (age 45 ± 18 years, 76% men) admitted between January 1, 2016, and December 31, 2017, that met the study criteria. The mean time to initiation of albuterol was 1.5 ± 1.7 days post injury, with a duration of 9.3 ± 4.5 days and a mean daily dosage of 7.8 ± 4.5 mg. Bradycardia was observed in 136 of 766 patient days (17%). There were a few episodes of hyperglycemia (1%) and tachycardia (3%), but no episodes of hypokalemia. In a multivariable analysis, female sex (P = 0.006) and American Spinal Cord Injury Association grade A, B, or C (P < 0.001) were associated with a higher risk of developing bradycardia, whereas dosage of albuterol (P = 0.009) and norepinephrine use (P = 0.008) were associated with a lower risk of developing bradycardia., Conclusions: Albuterol administration in ASCI is a safe and feasible treatment for bradycardia, given that no significant side effects, such as hyperglycemia, hypokalemia, or tachycardia, were observed. The administration of enteral albuterol was well tolerated and, in a dose-dependent manner, associated with a lower occurrence of bradycardia. Further prospective trials for the use of enteral albuterol after SCI are warranted., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

When detected at single-base-pair resolution, the genome-wide location, occupancy level, and structural organization of DNA-binding proteins provide mechanistic insights into genome regulation. Here we use ChIP-exo to provide a near-base-pair resolution view of the epigenomic organization of the Escherichia coli transcription machinery and nucleoid structural proteins at the time when cells are growing exponentially and upon rapid reprogramming (acute heat shock). We examined the site specificity of three sigma factors (RpoD/σ 70 , RpoH/σ 32 , and RpoN/σ 54 ), RNA polymerase (RNAP or RpoA, -B, -C), and two nucleoid proteins (Fis and IHF). We suggest that DNA shape at the flanks of cognate motifs helps drive site specificity. We find that although RNAP and sigma factors occupy active cognate promoters, RpoH and RpoN can occupy quiescent promoters without the presence of RNAP. Thus, promoter-bound sigma factors can be triggered to recruit RNAP by a mechanism that is distinct from an obligatory cycle of free sigma binding RNAP followed by promoter binding. These findings add new dimensions to how sigma factors achieve promoter specificity through DNA sequence and shape, and further define mechanistic steps in regulated genome-wide assembly of RNAP at promoters in E. coli ., (© 2022 John et al.; Published by Cold Spring Harbor Laboratory Press.)

Objectives: Results from previous ex-vivo continuous renal replacement therapy (CRRT) models have successfully demonstrated similar extraction coefficients (EC) identified from in-vivo clinical trials. The objectives of this study are to develop an ex-vivo in-vivo correlation (EVIVC) model to predict drug clearance for commonly used antiepileptics and to evaluate similarity in drug extraction across different CRRT modalities to extrapolate dosing recommendations., Methods: Levetiracetam, lacosamide, and phenytoin CRRT clearance was evaluated using the Prismaflex CRRT system and M150 hemodiafilters using an albumin containing normal saline (ALB-NS) vehicle with 3 different albumin concentrations (2 g/dL, 3 g/dL, and 4 g/dL) and a human plasma vehicle at 3 different effluent flow rates (1 L/hr, 2 L/hr, and 3 L/hr). Blood and effluent/dialysate concentrations were collected after circuit priming. ECs were calculated for each drug, modality, vehicle, and experimental arm combination., Results: The calculated average EC for levetiracetam and lacosamide was approximated to the fraction unbound from plasma protein. Human plasma and ALB-NS vehicles demonstrated adequate prediction of in-vivo CRRT clearance. Geometric mean ratios indicated similarity in extraction coefficients when comparing between hemofiltration and hemodiafiltration modalities and between filtration and dialysis modalities at effluent flow rates ≤ 2L/hr. Evaluation of phenytoin provided inconsistent findings with regards to extraction coefficient similarity across different CRRT modalities., Conclusion: The findings indicate that an ex-vivo study can be used as a surrogate to predict in-vivo levetiracetam and lacosamide clearance in patients receiving CRRT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To assess trainees' performance in managing a patient with post-cardiac arrest complicated by status epilepticus., Methods: In this prospective, observational, single-center simulation-based study, trainees ranging from sub interns to critical care fellows evaluated and managed a post cardiac arrest patient, complicated by status epilepticus. Critical action items were developed by a modified Delphi approach based on American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurological Life Support protocols. The primary outcome measure was the critical action item sum score. We sought validity evidence to support our findings by including attending neurocritical care physicians and comparing performance across four levels of training., Results: Forty-nine participants completed the simulation. The mean sum of critical actions completed by trainees was 10/21 (49%). Eleven (22%) trainees verbalized a differential diagnosis for the arrest. Thirty-two (65%) reviewed the electrocardiogram, recognized it as abnormal, and consulted cardiology. Forty trainees (81%) independently decided to start temperature management, but only 20 (41%) insisted on it when asked to reconsider. There was an effect of level of training on critical action checklist sum scores (novice mean score [standard deviation (SD)] = 4.8(1.8) vs. intermediate mean score (SD) = 10.4(2.1) vs. advanced mean score (D) = 11.6(3.0) vs. expert mean score (SD) = 14.7(2.2))., Conclusions: High-fidelity manikin-based simulation holds promise as an assessment tool in the performance of post-cardiac arrest care., Competing Interests: 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., (© 2022 The Authors.)

Background: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment., Methods: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention., Results: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th-75th interquartile range 22.5-30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4)., Conclusions: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Science continues to search for a neuroprotective drug therapy to improve outcomes after cardiac arrest (CA). The use of glibenclamide (GBC) has shown promise in preclinical studies, but its effects on neuroprognostication tools are not well understood. We aimed to investigate the effect of GBC on somatosensory evoked potential (SSEP) waveform recovery post CA and how this relates to the early prediction of functional outcome, with close attention to arousal and somatosensory recovery, in a rodent model of CA., Methods: Sixteen male Wistar rats were subjected to 8-min asphyxia CA and assigned to GBC treatment (n = 8) or control (n = 8) groups. GBC was administered as a loading dose of 10 μg/kg intraperitoneally 10 min after the return of spontaneous circulation, followed by a maintenance dosage of 1.6 μg/kg every 8 h for 24 h. SSEPs were recorded from baseline until 150 min following CA. Coma recovery, arousal, and brainstem function, measured by subsets of the neurological deficit score (NDS), were compared between both groups. SSEP N10 amplitudes were compared between the two groups at 30, 60, 90, and 120 min post CA., Results: Rats treated with GBC had higher sub-NDS scores post CA, with improved arousal and brainstem function recovery (P = 0.007). Both groups showed a gradual improvement of SSEP N10 amplitude over time, from 30 to 120 min post CA. Rats treated with GBC showed significantly better SSEP recovery at every time point (P < 0.001 for 30, 60, and 90 min; P = 0.003 for 120 min). In the GBC group, the N10 amplitude recovered to baseline by 120 min post CA. Quantified Cresyl violet staining revealed a significantly greater percentage of damage in the control group compared with the GBC treatment group (P = 0.004)., Conclusions: Glibenclamide improves coma recovery, arousal, and brainstem function after CA with decreased number of ischemic neurons in a rat model. GBC improves SSEP recovery post CA, with N10 amplitude reaching the baseline value by 120 min, suggesting early electrophysiologic recovery with this treatment. This medication warrants further exploration as a potential drug therapy to improve functional outcomes in patients after CA., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis., Methods: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported., Results: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert., Conclusions: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Targeted temperature management (TTM) directly impacts energy expenditure via temperature modulation and shivering associated with temperature modulating devices. We hypothesized that resting energy expenditure (REE) can be accurately estimated utilizing data obtained from a surface gel pad temperature modulating device (TMD) and demographic factors. Baseline demographic data, along with concurrent temperature, sedation, and shivering data, and indirect calorimetry (IDC) were collected from patients undergoing TTM. The data from the IDC and temperature modulation device (TMD) were synchronized and averaged over 60-second intervals to provide simultaneous comparisons. Heat transfer (calories) was calculated from the TMD by an equation that assessed water temperature from the TMD to the patient, water temperature returning to the TMD, water flow rates, and device mode. A linear regression model was used to determine factors associated with REE as measured by IDC. A difference in the mean between REE and estimated REE was used to assess accuracy. There were 48 assessments conducted in 40 subjects [mean (standard deviation)] age: 58 (14) years, 60% female, body surface area (BSA): 2.0 ± 0.3 who underwent simultaneous assessments. Target temperature was 36-37°C in 75%, with a median Bedside Shivering Assessment Score of 0 (range 0-2). Factors associated with REE on multivariable linear regression included older age ( p  < 0.001), male sex ( p  = 0.004), higher BSA ( p  < 0.001), higher patient temperature ( p  < 0.001), and lower heat transfer ( p  = 0.003). Adjusted prediction coefficients from this model were then tested against REE by a Bland-Altman analysis. The difference between difference in resting energy estimation (REEdiff) and measured REE by IDC was 6.2 calories/min (REEdiff: 95% confidence interval: -14.1 calories, 26.5 calories, p  = 0.5). We believe that the heat transfer data from the TMD coupled with clinical characteristics of patients can be utilized to calculate the REE for every minute of TTM. These data can be utilized to mitigate the consequences of shivering and malnutrition during TTM.

Background: Malignant cerebral edema (MCE) and intracranial hemorrhage (ICH) are associated with poor neurological outcomes despite revascularization after mechanical thrombectomy (MT). The factors associated with the development of MCE and ICH after MT are not well understood., Objective: To determine periprocedural factors associated with MCE, ICH, and poor functional outcome., Methods: We retrospectively analyzed anterior cerebral circulation large vessel occlusion cases that underwent MT from 2012 to 2019 at a single Comprehensive Stroke Center. Multivariate logistic regression analyses were performed to determine significant predictors of MCE, ICH, and poor functional outcome (modified Rankin Scale, 3-6) at 90 d., Results: Four hundred patients were included. Significant independent predictors of MCE after MT included initial stress glucose ratio (iSGR) (odds ratio [OR], 14.26; 95% CI, 3.82-53.26; P < .001), National Institutes of Health Stroke Scale (NIHSS) (OR, 1.10; 95% CI, 1.03-1.18; P = .008), internal carotid artery compared with M1 or M2 occlusion, and absence of successful revascularization (OR, 0.16; 95% CI, 0.06-0.44; P < .001). Significant independent predictors of poor functional outcome included MCE (OR, 7.47; 95% CI, 2.20-25.37; P = .001), iSGR (OR, 5.15; 95% CI, 1.82-14.53; P = .002), ICH (OR, 4.77; 95% CI, 1.20-18.69; P = .024), NIHSS (OR, 1.10; 95% CI, 1.05-1.16; P < .001), age (OR, 1.04; 95% CI, 1.03-1.07; P < .001), and thrombolysis in cerebral infarction 2C/3 recanalization (OR, 0.12; 95% CI, 0.05-0.29; P < .001)., Conclusion: Elevated iSGR significantly increases the risk of MCE and ICH and is an independent predictor of poor functional outcome. Thrombolysis in cerebral infarction 2C/3 revascularization is associated with reduced risk of MCE, ICH, and poor functional outcome. Whether stress hyperglycemia represents a modifiable risk factor is uncertain, and further investigation is warranted., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of Congress of Neurological Surgeons.)

Objectives: The Society of Critical Care Medicine convened its Academic Leaders in Critical Care Medicine taskforce on February 22, 2016, during the 45th Critical Care Congress to develop a series of consensus papers with toolkits for advancing critical care organizations in North America. The goal of this article is to propose a framework based on the expert opinions of critical care organization leaders and their responses to a survey, for current and future critical care organizations, and their leadership in the health system to design and implement successful regionalization for critical care in their regions., Data Sources and Study Selection: Members of the workgroup convened monthly via teleconference with the following objectives: to 1) develop and analyze a regionalization survey tool for 23 identified critical care organizations in the United States, 2) assemble relevant medical literature accessed using Medline search, 3) use a consensus of expert opinions to propose the framework, and 4) create groups to write the subsections and assemble the final product., Data Extraction and Synthesis: The most prevalent challenges for regionalization in critical care organizations remain a lack of a strong central authority to regulate and manage the system as well as a lack of necessary infrastructure, as described more than a decade ago. We provide a framework and outline a nontechnical approach that the health system and their critical care medicine leadership can adopt after considering their own structure, complexity, business operations, culture, and the relationships among their individual hospitals. Transforming the current state of regionalization into a coordinated, accountable system requires a critical assessment of administrative and clinical challenges and barriers. Systems thinking, business planning and control, and essential infrastructure development are critical for assisting critical care organizations., Conclusions: Under the value-based paradigm, the goals are operational efficiency and patient outcomes. Health systems that can align strategy and operations to assist the referral hospitals with implementing regionalization will be better positioned to regionalize critical care effectively., Competing Interests: Dr. Galvagno’s institution received funding from the Department of Defense; he received funding from Northwest Anesthesia Seminars and from expert defense for medicolegal work. Dr. Jacobi received funding from Visante, Merck, Pfizer, American Society of Health System Pharmacists, and a Pharmacy Continuing Education group. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background Variation exists in outcomes following out-of-hospital cardiac arrest (OHCA), but whether racial and ethnic disparities exist in post-arrest provision of targeted temperature management (TTM) is unknown. Methods and Results We performed a retrospective analysis of a prospectively collected cohort of patients who survived to admission following OHCA from the Cardiac Arrest Registry to Enhance Survival, whose catchment area represents ~50% of the United States from 2013-2019. Our primary exposure was race/ethnicity and primary outcome was utilization of TTM. We built a mixed-effects model with both state of arrest and admitting hospital modeled as random intercepts to account for clustering. Among 96,695 patients (24.6% Black, 8.0% Hispanic/Latino, 63.4% White), a smaller percentage of Hispanic/Latino patients received TTM than Black or White patients (37.5% vs. 45.0 % vs 43.3%, P < .001) following OHCA. In the mixed-effects model, Black patients (Odds Ratio [OR] 1.153, 95% Confidence Interval [CI] 1.102-1.207, P < .001) and Hispanic/Latino patients (OR 1.086, 95% CI 1.017-1.159, P < .001) were slightly more likely to receive TTM compared to White patients, perhaps due to worse admission neurological status. We did find community level disparity as Hispanic/Latino-serving hospitals (defined as the top decile of hospitals that cared for the highest proportion of Hispanic/Latino patients) provided less TTM (OR 0.587, 95% CI 0.474 to 0.742, P < .001). Conclusions Reassuringly, we did not find evidence of intrahospital or interpersonal racial or ethnic disparity in the provision of TTM. However, we did find inter-hospital, community level disparity. Hispanic/Latino-serving hospitals provided less guideline-recommended TTM after OHCA.

Background and Objectives: Multidisciplinary acute stroke teams improve acute ischemic stroke management but may hinder trainees' education, which in turn may contribute to poorer outcomes in community hospitals on graduation. Our goal was to assess graduate neurology trainee performance independently of a multidisciplinary stroke team in the management of acute ischemic stroke, tissue plasminogen activator (tPA)-related hemorrhage, and cerebral herniation syndrome., Methods: In this prospective, observational, single-center simulation-based study, participants (subinterns to attending physicians) managed a patient with acute ischemic stroke followed by tPA-related hemorrhagic conversion leading to cerebral herniation. Critical actions were developed by a modified Delphi approach based on relevant American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurologic Life Support protocols. The primary outcome measure was graduate neurology trainees' critical action item sum score. We sought validity evidence to support our findings by comparing performance across 4 levels of training., Results: Fifty-three trainees (including 31 graduate neurology trainees) and 5 attending physicians completed the simulation. The mean sum of critical actions completed by graduate neurology trainees was 15 of 22 (68%). Ninety percent of graduate neurology trainees properly administered tPA; 84% immediately stopped tPA infusion after patient deterioration; but only 55% reversed tPA according to guidelines. There was a moderately strong effect of level of training on critical action sum score (level 1 mean [SD] score 7.2 [2.8] vs level 2 mean [SD] score 12.3 [2.6] vs level 3 mean [SD] score 13.3 [2.2] vs level 4 mean [SD] score 16.3 [2.4], p < 0.001, R 2 = 0.54)., Discussion: Graduate neurology trainees reassuringly perform well in initial management of acute ischemic stroke but frequently make errors in the treatment of hemorrhagic transformation after thrombolysis, suggesting the need for more education surrounding this low-frequency, high-acuity event. High-fidelity simulation holds promise as an assessment tool for acute stroke management performance., (© 2021 American Academy of Neurology.)