scholarly journals miR-142-3p Expression Is Predictive for Severe Traumatic Brain Injury (TBI) in Trauma Patients

2020 ◽  
Vol 21 (15) ◽  
pp. 5381
Author(s):  
Cora Rebecca Schindler ◽  
Mathias Woschek ◽  
Jan Tilmann Vollrath ◽  
Kerstin Kontradowitz ◽  
Thomas Lustenberger ◽  
...  

Background: Predictive biomarkers in biofluids are the most commonly used diagnostic method, but established markers in trauma diagnostics lack accuracy. This study investigates promising microRNAs (miRNA) released from affected tissue after severe trauma that have predictive values for the effects of the injury. Methods: A retrospective analysis of prospectively collected data and blood samples of n = 33 trauma patients (ISS ≥ 16) is provided. Levels of miR-9-5p, -124-3p, -142-3p, -219a-5p, -338-3p and -423-3p in severely injured patients (PT) without traumatic brain injury (TBI) or with severe TBI (PT + TBI) and patients with isolated TBI (isTBI) were measured within 6 h after trauma. Results: The highest miR-423-3p expression was detected in patients with severe isTBI, followed by patients with PT + TBI, and lowest levels were found in PT patients without TBI (2−∆∆Ct, p = 0.009). A positive correlation between miR-423-3p level and increasing AIShead (p = 0.001) and risk of mortality (RISC II, p = 0.062) in trauma patients (n = 33) was found. ROC analysis of miR-423-3p levels revealed them as statistically significant to predict the severity of brain injury in trauma patients (p = 0.006). miR-124-3p was only found in patients with severe TBI, miR-338-3p was shown in all trauma groups. miR-9-5p, miR-142-3p and miR-219a-5p could not be detected in any of the four groups. Conclusion: miR-423-3p expression is significantly elevated after isolated traumatic brain injury and predictable for severe TBI in the first hours after trauma. miR-423-3p could represent a promising new biomarker to identify severe isolated TBI.

2020 ◽  
Vol 9 (6) ◽  
pp. 1667 ◽  
Author(s):  
Cora Rebecca Schindler ◽  
Thomas Lustenberger ◽  
Mathias Woschek ◽  
Philipp Störmann ◽  
Dirk Henrich ◽  
...  

The inflammatory response plays an important role in the pathophysiology of multiple injuries. This study examines the effects of severe trauma and inflammatory response on markers of neuronal damage. A retrospective analysis of prospectively collected data in 445 trauma patients (Injury Severity Score (ISS) ≥ 16) is provided. Levels of neuronal biomarkers (calcium-binding Protein B (S100b), Enolase2 (NSE), glial fibrillary acidic protein (GFAP)) and Interleukins (IL-6, IL-10) in severely injured patients (with polytrauma (PT)) without traumatic brain injury (TBI) or with severe TBI (PT+TBI) and patients with isolated TBI (isTBI) were measured upon arrival until day 5. S100b, NSE, GFAP levels showed a time-dependent decrease in all cohorts. Their expression was higher after multiple injuries (p = 0.038) comparing isTBI. Positive correlation of marker level after concomitant TBI and isTBI (p = 0.001) was noted, while marker expression after PT appears to be independent. Highest levels of IL-6 and -10 were associated to PT und lowest to isTBI (p < 0.001). In all groups pro-inflammatory response (IL-6/-10 ratio) peaked on day 2 and at a lower level on day 4. Severe TBI modulates kinetic profile of inflammatory response by reducing interleukin expression following trauma. Potential markers for neuronal damage have a limited diagnostic value after severe trauma because undifferentiated increase.


2011 ◽  
Vol 04 (04) ◽  
pp. 409-420 ◽  
Author(s):  
BARBIRO-MICHAELY EFRAT ◽  
MANOR TAMAR ◽  
ROGATSKY GENNADY ◽  
MAYEVSKY AVRAHAM

The use of anesthetics is a well-known treatment for severely injured patients. In the present study we tested the pathophysiology of several levels of injury damage in a rat model and also tested the effect of Equithesin on brain vitality in these models. Traumatic Brain Injury (TBI) was induced using the fluid percussion injury model in four levels: mild, moderate and two levels of severe TBI. Brain real-time evaluation was performed by the multiparametric monitoring assembly (MPA) which enable cerebral blood flow (CBF) monitoring by laser Doppler flowmetry, mitochondrial NADH (Nicotinamide adenine dinucleotide) monitoring by the fluorometric technique, ionic homehostasis using special mini-electrodes, intracranial pressure (ICP) by the ICP camino device and needle electrodes for ECoG (Electrocorticogram) recording. Our results showed high correlation between the level of impact and the extent of changes in the physiological properties of the injury as indicated by the changes in all parameters monitored using the MPA device. Moreover, Equithesin improved CBF, ionic extracellular level and mitochondrial redox state following mild and moderate TBI while in severe TBI, Equithesin did not improve the metabolic state of the cerebral cortex, although it decreased the mortality rate from 66% to 20%, and following extra-severe TBI level, Equithesin did not improve survival rate. In conclusion it seems that Equithesin's protective effect exists under mild to moderate levels of injury and not in case of severe injuries.


Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 69 ◽  
Author(s):  
Nadine Kerr ◽  
Juan de Rivero Vaccari ◽  
Oliver Umland ◽  
M. Bullock ◽  
Gregory Conner ◽  
...  

Approximately 30% of traumatic brain injured patients suffer from acute lung injury or acute respiratory distress syndrome. Our previous work revealed that extracellular vesicle (EV)-mediated inflammasome signaling plays a crucial role in the pathophysiology of traumatic brain injury (TBI)-induced lung injury. Here, serum-derived EVs from severe TBI patients were analyzed for particle size, concentration, origin, and levels of the inflammasome component, an apoptosis-associated speck-like protein containing a caspase-recruiting domain (ASC). Serum ASC levels were analyzed from EV obtained from patients that presented lung injury after TBI and compared them to EV obtained from patients that did not show any signs of lung injury. EVs were co-cultured with lung human microvascular endothelial cells (HMVEC-L) to evaluate inflammasome activation and endothelial cell pyroptosis. TBI patients had a significant increase in the number of serum-derived EVs and levels of ASC. Severe TBI patients with lung injury had a significantly higher level of ASC in serum and serum-derived EVs compared to individuals without lung injury. Only EVs isolated from head trauma patients with gunshot wounds were of neural origin. Delivery of serum-derived EVs to HMVEC-L activated the inflammasome and resulted in endothelial cell pyroptosis. Thus, serum-derived EVs and inflammasome proteins play a critical role in the pathogenesis of TBI-induced lung injury, supporting activation of an EV-mediated neural-respiratory inflammasome axis in TBI-induced lung injury.


Author(s):  
P Scotti ◽  
J Troquet ◽  
C Seguin ◽  
B Lo ◽  
J Marcoux

Background: In the elderly population, use of antithrombotic therapy (AT), antiplatelets (AP – aspirin, clopidogrel) and/or anticoagulants (AC – warfarin, DoAC – Dabigatran, Rivaroxaban, Apixaban), to prevent thrombo-embolic events must be carefully weighed against the risk of intracranial hemorrhage (ICH) with trauma. We hypothesize that for all patients 65yro+ with head trauma, those on AT will be more likely to sustain a traumatic brain injury, ICH, and poorer outcomes. Methods: Data was collected from all head trauma patients 65yo+ presenting to our tertiary trauma center (level 1) over a 24-month period; age, gender, injury mechanism, medications, International Normalized Ratio, reversal therapy, Glasgow Coma Scale (GCS), ICH, surgery, Extended Glasgow Outcome Scale score (GOSE) and mortality. Results: 1365 patients were identified; 724 on AT (413 AP, 151 AC, 59 DoAC, 48 2AP, 38 AP+AC, 15 AP+DoAC) and 474 not (non-AT). When adjusted for covariates, AT patients were more likely to have ICH (p=0.0004), more invasive surgical interventions (p=0.0188), functional dependency (GOSE≤4; p<0.0001) and mortality (p<0.0001). Risk of mortality is notably high with 2AP (OR 5.74; p=0.0003) and AC+AP (OR 4.12; p=0.0118). Conclusions: Elderly trauma patients on AT, especially combination therapy, have higher risks of ICH and poorer outcomes compared to those who are not.


BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e040550
Author(s):  
Jean-Francois Payen ◽  
Marion Richard ◽  
Gilles Francony ◽  
Gérard Audibert ◽  
Emmanuel L Barbier ◽  
...  

IntroductionIntracranial hypertension is considered as an independent risk factor of mortality and neurological disabilities after severe traumatic brain injury (TBI). However, clinical studies have demonstrated that episodes of brain ischaemia/hypoxia are common despite normalisation of intracranial pressure (ICP). This study assesses the impact on neurological outcome of guiding therapeutic strategies based on the monitoring of both brain tissue oxygenation pressure (PbtO2) and ICP during the first 5 days following severe TBI.Methods and analysisMulticentre, open-labelled, randomised controlled superiority trial with two parallel groups in 300 patients with severe TBI. Intracerebral monitoring must be in place within the first 16 hours post-trauma. Patients are randomly assigned to the ICP group or to the ICP + PbtO2 group. The ICP group is managed according to the international guidelines to maintain ICP≤20 mm Hg. The ICP + PbtO2 group is managed to maintain PbtO2 ≥20 mm Hg in addition to the conventional optimisation of ICP. The primary outcome measure is the neurological status at 6 months as assessed using the extended Glasgow Outcome Scale. Secondary outcome measures include quality-of-life assessment, mortality rate, therapeutic intensity and incidence of critical events during the first 5 days. Analysis will be performed according to the intention-to-treat principle and full statistical analysis plan developed prior to database freeze.Ethics and disseminationThis study has been approved by the Institutional Review Board of Sud-Est V (14-CHUG-48) and from the National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament et des produits de santé) (141 435B-31). Results will be presented at scientific meetings and published in peer-reviewed publications.The study was registered with ClinTrials NCT02754063 on 28 April 2016 (pre-results).


2020 ◽  
Author(s):  
Simon Rauch ◽  
Matilde Marzolo ◽  
Tomas Dal Cappello ◽  
Mathias Ströhle ◽  
Peter Mair ◽  
...  

Abstract Background: Hypotension is associated with worse outcome in patients with traumatic brain injury (TBI) and maintaining a systolic blood pressure (SBP) ≥110 mmHg is recommended. The aim of this study was to assess the incidence of TBI in patients suffering multi-trauma in remote and mountainous areas; to describe associated factors, treatment and outcome compared to non-hypotensive patients with TBI and patients without TBI; and to evaluate pre-hospital variables to predict admission hypotension.Methods: Data from the International Alpine Trauma Registry including mountain multi-trauma patients (ISS≥16) collected between 2010 and 2019 were analysed. Patients were divided into three groups: 1) TBI with hypotension, 2) TBI without hypotension and 3) no TBI. TBI was defined as Abbreviated Injury Scale (AIS) of the head/neck ≥3 and hypotension as SBP <110 mmHg on hospital arrival.Results: A total of 287 patients were included. Fifty (17%) had TBI and hypotension, 92 (32%) suffered TBI without hypotension and 145 (51%) patients did not have TBI. Patients in group 1 were more severely injured (mean ISS 43.1±17.4 vs 33.3±15.3 vs 26.2±18.1 for group 1 vs 2 vs 3, respectively, p<0.001). Mean SBP on hospital arrival was 83.1±12.9 vs 132.5±19.4 vs 119.4±25.8 mmHg (p<0.001) despite patients in group 1 received more fluids. Patients in group 1 had higher INR, lower haemoglobin and lower base excess (p<0.001). The rate of hypothermia on hospital arrival was different between the groups (p=0.029). Patients in group 1 had the highest mortality (24% vs 10% vs 1%, p<0.001).Conclusion: Multi-trauma in the mountains goes along with severe TBI in almost 50%. One third of patients with TBI is hypotensive on hospital arrival and this is associated with a worse outcome. No single variable or set of variables easily obtainable at scene was able to predict admission hypotension in TBI patients.


2017 ◽  
Vol 83 (12) ◽  
pp. 1433-1437 ◽  
Author(s):  
Lia Aquino ◽  
Christopher Y. Kang ◽  
Megan Y. Harada ◽  
Ara Ko ◽  
Amy Do-nguyen ◽  
...  

Severe traumatic brain injury (TBI) is associated with increased risk for early clinical and sub-clinical seizures. The use of continuous electroencephalography (cEEG) monitoring after TBI allows for identification and treatment of seizures that may otherwise occur undetected. Benefits of “routine” cEEG after TBI remain controversial. We examined the rate of subclinical seizures identified by cEEG in TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma patients with moderate to severe TBI (head Abbreviated Injury Score ≥3) who received cEEG within seven days of admission between October 2011 and May 2015. Demographics, clinical data, injury severity, and costs were recorded. Clinical characteristics were compared between those with and without seizures as identified by cEEG. A total of 106 TBI patients with moderate to severe TBI received a cEEG during the study period. Most were male (74%) with a mean age of 55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of patients. Ninety-three per cent were on antiseizure prophylaxis at the time of cEEG. Patients who had subclinical seizures were significantly older than their counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were similar in both groups. Of all TBI patients who were monitored with cEEG, seizures were identified in only 3.8 per cent. Seizures were more likely to occur in older patients with severe head injury. Given the high cost of routine cEEG and the low incidence of subclinical seizures, we recommend cEEG monitoring only when clinically indicated.


Author(s):  
Simon Rauch ◽  
◽  
Matilde Marzolo ◽  
Tomas Dal Cappello ◽  
Mathias Ströhle ◽  
...  

Abstract Background Hypotension is associated with worse outcome in patients with traumatic brain injury (TBI) and maintaining a systolic blood pressure (SBP) ≥110 mmHg is recommended. The aim of this study was to assess the incidence of TBI in patients suffering multiple trauma in mountain areas; to describe associated factors, treatment and outcome compared to non-hypotensive patients with TBI and patients without TBI; and to evaluate pre-hospital variables to predict admission hypotension. Methods Data from the prospective International Alpine Trauma Registry including mountain multiple trauma patients (ISS ≥ 16) collected between 2010 and 2019 were analysed. Patients were divided into three groups: 1) TBI with hypotension, 2) TBI without hypotension and 3) no TBI. TBI was defined as Abbreviated Injury Scale (AIS) of the head/neck ≥3 and hypotension as SBP < 110 mmHg on hospital arrival. Results A total of 287 patients were included. Fifty (17%) had TBI and hypotension, 92 (32%) suffered TBI without hypotension and 145 (51%) patients did not have TBI. Patients in group 1 were more severely injured (mean ISS 43.1 ± 17.4 vs 33.3 ± 15.3 vs 26.2 ± 18.1 for group 1 vs 2 vs 3, respectively, p < 0.001). Mean SBP on hospital arrival was 83.1 ± 12.9 vs 132.5 ± 19.4 vs 119.4 ± 25.8 mmHg (p < 0.001) despite patients in group 1 received more fluids. Patients in group 1 had higher INR, lower haemoglobin and lower base excess (p < 0.001). More than one third of patients in group 1 and 2 were hypothermic (body temperature < 35 °C) on hospital arrival while the rate of admission hypothermia was low in patients without TBI (41% vs 35% vs 21%, for group 1 vs 2 vs 3, p = 0.029). The rate of hypothermia on hospital arrival was different between the groups (p = 0.029). Patients in group 1 had the highest mortality (24% vs 10% vs 1%, p < 0.001). Conclusion Multiple trauma in the mountains goes along with severe TBI in almost 50%. One third of patients with TBI is hypotensive on hospital arrival and this is associated with a worse outcome. No single variable or set of variables easily obtainable at scene was able to predict admission hypotension in TBI patients.


Author(s):  
Sarbjit Singh Chhiber ◽  
Adfer Gul ◽  
Sajad Arif ◽  
Abrar Ahad Wani ◽  
Altaf Umar Ramzan

AbstractDespite advances in research and improved neurological intensive care in recent years, the clinical outcome of severely head injured patients is still poor. Primary insult is followed by a complex cascade of molecular and biochemical events that lead to neuroinflammation, brain edema, and delayed neuronal death. No specific pharmacological therapy is currently available which prevents the development of secondary brain injuries, and most therapeutic strategies have failed in translation from bench to bedside. There are limitations of clinical and radiological methods in delineating the exact severity and prognosis of traumatic brain injury (TBI). A myriad complex biochemical markers are under investigation to delineate the extent of brain tissue damage and to independently predict the outcome, but a search for simple biomarker still eludes the research. Progesterone, a gonadal hormone and a neurosteroid, although controversial as a neuroprotective agent, may hold promise as a simple biochemical marker of the outcome in severe TBI.


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