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  1. Article ; Online: Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study.

    Åkerlund, Cecilia A I / Holst, Anders / Bhattacharyay, Shubhayu / Stocchetti, Nino / Steyerberg, Ewout / Smielewski, Peter / Menon, David K / Ercole, Ari / Nelson, David W

    The Lancet. Neurology

    2023  Volume 23, Issue 1, Page(s) 71–80

    Abstract: Background: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur ... ...

    Abstract Background: Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU.
    Methods: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated.
    Findings: Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E ≤4) was improved.
    Interpretation: First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice.
    Funding: European Union 7th Framework program, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, and NeuroTrauma Sciences.
    MeSH term(s) Humans ; Biomarkers ; Brain Injuries, Traumatic/diagnosis ; Glial Fibrillary Acidic Protein ; Glucose ; Intensive Care Units ; Prospective Studies ; Ubiquitin Thiolesterase ; Adolescent ; Adult
    Chemical Substances Biomarkers ; Glial Fibrillary Acidic Protein ; Glucose (IY9XDZ35W2) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
    Language English
    Publishing date 2023-11-14
    Publishing country England
    Document type Observational Study ; Multicenter Study ; Journal Article
    ZDB-ID 2081241-3
    ISSN 1474-4465 ; 1474-4422
    ISSN (online) 1474-4465
    ISSN 1474-4422
    DOI 10.1016/S1474-4422(23)00358-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction: Accuracy of Manual Intracranial Pressure Recording Compared to a Computerized High-Resolution System: A CENTER-TBI Analysis.

    Zoerle, Tommaso / Birg, Tatiana / Carbonara, Marco / Smielewski, Peter / Placek, Michal M / Zanier, Elisa R / Åkerlund, Cecilia A I / Ortolano, Fabrizio / Stocchetti, Nino

    Neurocritical care

    2023  Volume 38, Issue 3, Page(s) 833–834

    Language English
    Publishing date 2023-04-14
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2381896-7
    ISSN 1556-0961 ; 1541-6933
    ISSN (online) 1556-0961
    ISSN 1541-6933
    DOI 10.1007/s12028-023-01722-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Accuracy of Manual Intracranial Pressure Recording Compared to a Computerized High-Resolution System: A CENTER-TBI Analysis.

    Zoerle, Tommaso / Birg, Tatiana / Carbonara, Marco / Smielewski, Peter / Placek, Michal M / Zanier, Elisa R / Åkerlund, Cecilia A I / Ortolano, Fabrizio / Stocchetti, Nino

    Neurocritical care

    2023  Volume 38, Issue 3, Page(s) 781–790

    Abstract: Background: Monitoring intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is crucial in the management of the patient with severe traumatic brain injury (TBI). In several institutions ICP and CPP are summarized hourly and entered manually ...

    Abstract Background: Monitoring intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is crucial in the management of the patient with severe traumatic brain injury (TBI). In several institutions ICP and CPP are summarized hourly and entered manually on bedside charts; these data have been used in large observational and interventional trials. However, ICP and CPP may change rapidly and frequently, so data recorded in medical charts might underestimate actual ICP and CPP shifts. The aim of this study was to evaluate the accuracy of manual data annotation for proper capturing of ICP and CPP. For this aim, we (1) compared end-hour ICP and CPP values manually recorded (MR) with values recorded continuously by computerized high-resolution (HR) systems and (2) analyzed whether MR ICP and MR CPP are reliable indicators of the burden of intracranial hypertension and low CPP.
    Methods: One hundred patients were included. First, we compared the MR data with the values stored in the computerized system during the first 7 days after admission. For this point-to-point analysis, we calculated the difference between end-hour MR and HR ICP and CPP. Then we analyzed the burden of high ICP (> 20 mm Hg) and low CPP (< 60 mm Hg) measured by the computerized system, in which continuous data were stored, compared with the pressure-time dose based on end-hour measurements.
    Results: The mean difference between MR and HR end-hour values was 0.02 mm Hg for ICP (SD 3.86 mm Hg) and 1.54 mm Hg for CPP (SD 8.81 mm Hg). ICP > 20 mm Hg and CPP < 60 mm Hg were not detected by MR in 1.6% and 5.8% of synchronized measurements, respectively. Analysis of the pathological ICP and CPP throughout the recording, however, indicated that calculations based on manual recording seriously underestimated the ICP and CPP burden (in 42% and 28% of patients, respectively).
    Conclusions: Manual entries fairly represent end-hour HR ICP and CPP. However, compared with a computerized system, they may prove inadequate, with a serious risk of underestimation of the ICP and CPP burden.
    MeSH term(s) Humans ; Brain Injuries ; Brain Injuries, Traumatic/diagnosis ; Cerebrovascular Circulation ; Hospitalization ; Intracranial Hypertension/diagnosis ; Intracranial Pressure
    Language English
    Publishing date 2023-03-15
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2381896-7
    ISSN 1556-0961 ; 1541-6933
    ISSN (online) 1556-0961
    ISSN 1541-6933
    DOI 10.1007/s12028-023-01697-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study.

    Åkerlund, Cecilia A I / Holst, Anders / Stocchetti, Nino / Steyerberg, Ewout W / Menon, David K / Ercole, Ari / Nelson, David W

    Critical care (London, England)

    2022  Volume 26, Issue 1, Page(s) 228

    Abstract: Background: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as 'mild', 'moderate' or 'severe' based on this fails to capture enormous heterogeneity in ... ...

    Abstract Background: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as 'mild', 'moderate' or 'severe' based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.
    Methods: We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.
    Results: Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with 'moderate' TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with 'severe' GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001).
    Conclusions: Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
    MeSH term(s) Brain Injuries, Traumatic/therapy ; Cluster Analysis ; Critical Care ; Glasgow Coma Scale ; Humans ; Prognosis
    Language English
    Publishing date 2022-07-27
    Publishing country England
    Document type Clinical Trial ; Journal Article
    ZDB-ID 2041406-7
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-022-04079-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The impact of sedative and vasopressor agents on cerebrovascular reactivity in severe traumatic brain injury.

    Froese, Logan / Hammarlund, Emma / Åkerlund, Cecilia A I / Tjerkaski, Jonathan / Hong, Erik / Lindblad, Caroline / Nelson, David W / Thelin, Eric P / Zeiler, Frederick A

    Intensive care medicine experimental

    2023  Volume 11, Issue 1, Page(s) 54

    Abstract: Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in ...

    Abstract Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics.
    Results: Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4-9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact.
    Conclusions: Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.
    Language English
    Publishing date 2023-08-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2740385-3
    ISSN 2197-425X
    ISSN 2197-425X
    DOI 10.1186/s40635-023-00524-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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