Mannose binding lectin deficiency attenuates neurobehavioral deficits following experimental traumatic brain injury

Introduction: Mannose binding lectin (MBL) is the activator of the lectin complement pathway. After cerebral ischemia it has been shown that MBL could be a mediator of secondary brain damage, in contrast after traumatic brain injury (TBI) there are data suggesting that it could be linked to neuroprotection. We tested the hypothesis that MBL is involved in the pathophysiology of TBI. We 1) characterized the temporal activation of MBL and 2) the effects of its inhibition in a model of experimental TBI. Methods: 1) Male C57/Bl6 mice were subjected to intraperitoneal anesthesia (Pentobarbital, 65 mg/kg) followed by the controlled cortical impact brain injury model of experimental TBI (injury parameters: velocity of 5 meter/second and 1 mm depth of deformation). MBL immunostaining was evaluated at various time points after TBI: 30 minutes, 1, 6, 12, 24, 48, 96 hours and 1 week using anti MBL-A and MBL-C antibodies (n=3). 2) The effects of MBL inhibition were evaluated by comparing functional and histologic outcomes in C57/Bl6 mice (WT) and in MBL knock-out (-/-) mice. Functional outcome was tested using the Composite Neuroscore and Beam Walk test weekly up to 4 weeks postinjury (n = 11). Histologic outcome was evaluated by calculating the contusion volume at 4 weeks postinjury (n = 6). Sham-operated mice received identical anesthesia without brain injury. Results: We observed a robust MBL positive immunostaining in the injured cerebral cortex starting at 30 minutes postinjury and up to 1 week, suggestive of an activation of this pathway following TBI. MBL was observed both at endothelial and tissue level. Consistently, injured WT and MBL (-/-) mice showed neurological motor deficits up to 4 weeks postinjury when compared to their sham controls. Notably, MBL (-/-) mice showed attenuated behavioral deficits when compared to their WT counterpart at 2-4 weeks postinjury (p < 0.01 for both Neuroscore and Beam Walk test). In contrast we observed similar contusion volumes at 4 weeks postinjury (WT = 15.6 \ub1 3.2 cm3 and MBL KO = 13.9 \ub1 3.2 cm3, p = 0.3). Conclusions: We observed that 1) MBL deposition and/or synthesis is increased following TBI; 2) MBL deficiency is associated with functional neuroprotection, suggesting that MBL modulation might be a potential therapeutic target after TBI

Chronic impact of traumatic brain injury on outcome and quality of life : a narrative review

Traditionally seen as a sudden, brutal event with short-term impairment, traumatic brain injury (TBI) may cause persistent, sometimes life-long, consequences. While mortality after TBI has been reduced, a high proportion of severe TBI survivors require prolonged rehabilitation and may suffer long-term physical, cognitive, and psychological disorders. Additionally, chronic consequences have been identified not only after severe TBI but also in a proportion of cases previously classified as moderate or mild. This burden affects the daily life of survivors and their families; it also has relevant social and economic costs. Outcome evaluation is difficult for several reasons: co-existing extra-cranial injuries (spinal cord damage, for instance) may affect independence and quality of life outside the pure TBI effects; scales may not capture subtle, but important, changes; co-operation from patients may be impossible in the most severe cases. Several instruments have been developed for capturing specific aspects, from generic health status to specific cognitive functions. Even simple instruments, however, have demonstrated variable inter-rater agreement. The possible links between structural traumatic brain damage and functional impairment have been explored both experimentally and in the clinical setting with advanced neuro-imaging techniques. We briefly report on some fundamental findings, which may also offer potential targets for future therapies. Better understanding of damage mechanisms and new approaches to neuroprotection-restoration may offer better outcomes for the millions of survivors of TBI

Comparison of the Full Outline of UnResponsiveness and Glasgow Liege Scale/Glasgow Coma Scale in an Intensive Care Unit Population.

peer reviewedBACKGROUND: The Full Outline of UnResponsiveness (FOUR) has been proposed as an alternative for the Glasgow Coma Scale (GCS)/Glasgow Liege Scale (GLS) in the evaluation of consciousness in severely brain-damaged patients. We compared the FOUR and GLS/GCS in intensive care unit patients who were admitted in a comatose state. METHODS: FOUR and GLS evaluations were performed in randomized order in 176 acutely (<1 month) brain-damaged patients. GLS scores were transformed in GCS scores by removing the GLS brainstem component. Inter-rater agreement was assessed in 20% of the studied population (N = 35). A logistic regression analysis adjusted for age, and etiology was performed to assess the link between the studied scores and the outcome 3 months after injury (N = 136). RESULTS: GLS/GCS verbal component was scored 1 in 146 patients, among these 131 were intubated. We found that the inter-rater reliability was good for the FOUR score, the GLS/GCS. FOUR, GLS/GCS total scores predicted functional outcome with and without adjustment for age and etiology. 71 patients were considered as being in a vegetative/unresponsive state based on the GLS/GCS. The FOUR score identified 8 of these 71 patients as being minimally conscious given that these patients showed visual pursuit. CONCLUSIONS: The FOUR score is a valid tool with good inter-rater reliability that is comparable to the GLS/GCS in predicting outcome. It offers the advantage to be performable in intubated patients and to identify non-verbal signs of consciousness by assessing visual pursuit, and hence minimal signs of consciousness (11% in this study), not assessed by GLS/GCS scales

Intracranial pressure dynamics in patients with acute brain damage

The time pattern of intracranial pressure (ICP) during pressure-volume index (PVI) tests was analyzed in 20 patients with severe acute brain damage by means of a simple mathematical model. In most cases, a satisfactory fitting between model response and patient data was achieved by adjusting only four parameters: the cerebrospinal fluid (CSF) outflow resistance, the intracranial elastance coefficient, and the gain and time constant of cerebral autoregulation. The correlation between the parameter estimates was also analyzed to elucidate the main mechanisms responsible for ICP changes in each patient. Starting from information on the estimated parameter values and their correlation, the patients were classified into two main classes: those with weak autoregulation (8 of 20 patients) and those with strong autoregulation (12 of 20 patients). In the first group of patients, ICP mainly reflects CSF circulation and passive cerebral blood volume changes. In the second group, ICP exhibits paradoxical responses attributable to active changes in cerebral blood volume. Moreover, in two patients of the second group, the time constant of autoregulation is significantly increased (>40 s). The correlation between the parameter estimates was significantly different in the two groups of patients, suggesting the existence of different mechanisms responsible for ICP changes. Moreover, analysis of the correlation between the parameter estimates might give information on the directions of parameter changes that have a greater impact on ICP

Consensus statement from the 2014 International Microdialysis Forum.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.We gratefully acknowledge financial support for participants as follows: P.J.H. - National Institute for Health Research (NIHR) Professorship and the NIHR Biomedical Research Centre, Cambridge; I.J. – Medical Research Council (G1002277 ID 98489); A. H. - Medical Research Council, Royal College of Surgeons of England; K.L.H.C. - NIHR Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); M.G.B. - Wellcome Trust Dept Health Healthcare Innovation Challenge Fund (HICF-0510-080); L. H. - The Swedish Research Council, VINNOVA and Uppsala Berzelii Technology Centre for Neurodiagnostics; S. M. - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; D.K.M. - NIHR Senior Investigator Award to D.K.M., NIHR Cambridge Biomedical Research Centre (Neuroscience Theme), FP7 Program of the European Union; M. O. - Swiss National Science Foundation and the Novartis Foundation for Biomedical Research; J.S. - Fondo de Investigación Sanitaria (Instituto de Salud Carlos III) (PI11/00700) co-financed by the European Regional Development; M.S. – NIHR University College London Hospitals Biomedical Research Centre; N. S. - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00134-015-3930-

Burnout in intensive care unit workers during the second wave of the covid-19 pandemic : A single center cross-sectional Italian study

The COVID-19 pandemic had a massive impact on the Italian healthcare systems, which became overwhelmed, leading to an increased risk of psychological pressure on ICU workers. The present study aimed to investigate the prevalence of distress (anxiety, depression and insomnia symptoms), burnout syndrome and resilience in healthcare workers during the COVID-19 pandemic and to detect potential factors associated with their psychological response. This cross-sectional, survey-based study enrolled 136 healthcare workers assisting COVID-19 patients in the new COVID19 ward (Intensive Care Unit), at Milano Fiera, Lombardy. Participants completed an online survey that comprised different validated and standardized questionnaires: Maslach Burnout Inventory (MBI), Resilience Scale for adults (RSA), Hospital Anxiety and Depression scale (HADS) and Insomnia Severity Index (ISI). Socio-demographic and work characteristics were also collected. Out of 136 ICU specialists, there were 84 nurses (62%) and 52 physicians (38%). Over half (60%) met the criteria for burnout, with nearly the same percentages among nurses and physicians. Nurses reported significantly higher scores of anxiety and insomnia levels. Forty-five percent of participants reported symptoms of depression (of whom 13.9% in the clinical range) and most of the staff showed moderate to high levels (82.4%) of resilience. The COVID-19 pandemic can have a significant impact on ICU staff. Effective interventions are needed to maintain healthcare professionals’ mental health and relieve burnout. Follow-up and tailored procedures should be provided to alleviate the psychological burden in the frontline staff at highest risk

Neuro-Link, a computer-assisted database for head injury in intensive care

Reliable information is vital for clinical trials, so we developed a database, for head trauma victims admitted to neuro-intensive care units (NICU). This database, first step in a sequential project, comprises 176 selected fields mainly focused on the early post-traumatic phase and has a user-friendly computerized interface. The software was tested for a trimester in 18 Italian neuro-intensive care units. The paper describes the main features of the database, the results of a three months' data collection test, its limitations and its potential improvements. A description of the database fields and a brief summary of the 282 patients included so far are also presented

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]