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Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain.

ABSTRACT: Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the thalamus and frontoparietal network are consistent findings. We test the hypothesis that global reductions of background synaptic activity in DOCs will associate with changes in the pattern of metabolic activity in the central thalamus and globus pallidus. We compared 32 [(18)F]fluorodeoxyglucose PETs obtained from severely brain-injured patients (BIs) and 10 normal volunteers (NVs). We defined components of the anterior forebrain mesocircuit on high-resolution T1-MRI (ventral, associative, and sensorimotor striatum; globus pallidus; central thalamus and noncentral thalamus). Metabolic profiles for BI and NV demonstrated distinct changes in the pattern of uptake: ventral and association striatum (but not sensorimotor) were significantly reduced relative to global mean uptake after BI; a relative increase in globus pallidus metabolism was evident in BI subjects who also showed a relative reduction of metabolism in the central thalamus. The reversal of globus pallidus and central thalamus profiles across BIs and NVs supports the mesocircuit hypothesis that broad functional (or anatomic) deafferentation may combine to reduce central thalamus activity and release globus pallidus activity in DOCs. In addition, BI subjects showed broad frontoparietal metabolic down-regulation consistent with prior studies supporting the link between central thalamic/pallidal metabolism and down-regulation of the frontoparietal network. Recovery of left hemisphere frontoparietal metabolic activity was further associated with command following.

SUBMITTER: Fridman EA

PROVIDER: S-EPMC4035959 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBone marrow (BM) dysfunction is common in severely injured trauma patients, resulting from elevated catecholamines and plasma granulocyte colony-stimulating factor (G-CSF) as well as prolonged mobilization of hematopoietic progenitor cells (HPCs). We have previously shown that propranolol (β-blocker [BB]) reduces HPC mobilization in a rodent model of injury and hemorrhagic shock. We hypothesize that BB would prevent BM dysfunction in humans following severe injury.MethodsForty-five severely injured trauma patients were studied in a prospective, randomized pilot trial. Twenty-five patients received BB, and 20 served as untreated controls. The dose of propranolol was adjusted to decrease the heart rate by 10% to 20% from baseline. Blood was analyzed for the presence of HPC (blast-forming unit erythroid cells [BFU-E] and colony-forming unit erythroid cells) and G-CSF. Demographic data, Injury Severity Score (ISS), hemoglobin, reticulocyte number, and outcome data were obtained.ResultsThe mean age of the study population was 33 years; 87% were male, with a mean ISS of 29. There is a significant increase in BFU-E in peripheral blood immediately following traumatic injury, and this mobilization persists for 30 days. The use of BB significantly decreases BFU-E and colony-forming unit erythroid cells at all time points. G-CSF is significantly elevated in both groups on admission; the use of BB decreases G-CSF levels by 51% as compared with 37% for controls. The average hemoglobin is nearly 1 g higher on the day of discharge with propranolol treatment (BB, 9.9 ± 0.4 g/dL vs. no BB, 9.1 ± 0.6 g/dL).ConclusionFollowing severe trauma, early treatment with propranolol following resuscitation is safe. The use of propranolol blunts early tachycardia, reduces HPC mobilization, and results in a faster return to baseline of the G-CSF peak seen after injury. There is also a trend toward faster recovery and resolution of anemia. Propranolol may be the first therapeutic agent to show improved BM function after severe injury.Level of evidenceTherapeutic study, level III.

Project description:BackgroundUnderstanding the changes in characteristics of patients who visited trauma centres during the coronavirus disease 2019 (COVID-19) pandemic is important to facilitate aneffective response. This retrospective study was conducted to analyse differences in the characteristics and outcomes of patients who visited our trauma centre between pre-COVID-19 and COVID-19 eras.MethodsMedical data of trauma patients enrolled in the Korean trauma database from 1 January 2018 to 31 August 2021 were collected. The number of trauma centre visits, patient characteristics, factors associated with in-hospital intervention, and outcomes werecompared between patients in the two time periods. Propensity score matching was performed to analyse the outcomes in patients with similar characteristics and severitybetween patients in the two time periods.ResultsThe number of emergency department (ED) trauma service visits reduced in the COVID-19 era. Based on the mean age, the patients were older in the COVID-19 era. Abbreviated injury scale (AIS) 1, AIS3, AIS5, and injury severity score (ISS) were higher in the COVID-19 era. The proportion of motor vehicle collisions decreased, whereas falls increased during the COVID-19 era. Ambulance transportation, admission to the general ward, and time from injury to ED visit significantly increased. Patient outcomes, such as hospital length of stay (LOS), intensive care unit (ICU) LOS, and duration of mechanical ventilation improved, while injury severity worsened during the COVID-19 era. After adjusting for patient characteristics and severity, similar findings were observed.ConclusionThe small reduction in the number of trauma patients and visits by patients who hadhigher ISS during the COVID-19 pandemic highlights the importance of maintaining trauma service capacity and capability during the pandemic. A nationwide or nationalmulticentre study will be more meaningful to examine the impact of the COVID-19 outbreak on the changes in trauma patterns, volume, and patient outcomes.

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Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain.

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