Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI.

BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.

The impact of cardiopulmonary resuscitation (CPR) training on schoolchildren and their CPR knowledge, attitudes toward CPR, and willingness to help others and to perform CPR: mixed methods research design.

BACKGROUND: The benefits of cardiopulmonary resuscitation training for schoolchildren are well known, but the appropriate age for introducing training is still being discussed. This is a very important issue, since out-of-hospital cardiac arrest is a major public health concern. The objective of this study was to investigate the effects of implemented cardiopulmonary resuscitation training on the knowledge of schoolchildren in the last three grades of Slovenian elementary schools and theirs willingness, attitudes, and intentions toward helping others and performing cardiopulmonary resuscitation. The experience of training instructors was also explored. METHODS: A mixed methods research design was employed, using a Separate Pre-Post Samples Design and focus groups. Research was conducted in 15 Slovenian public elementary schools offering cardiopulmonary resuscitation training. Focus groups included training instructors and developers. Data was collected with a structured questionnaire from April to June 2018 and analyzed using univariate and bivariate analyses. The three focus groups were convened in September and October 2018. Content analysis of the discussion transcriptions was conducted. The sample included 764 schoolchildren aged 12.5-14.5 years before cardiopulmonary resuscitation training and 566 schoolchildren after training. Three non-homogeneous focus groups included eight cardiopulmonary resuscitation instructors. RESULTS: Significant progress in cardiopulmonary resuscitation knowledge was noted after training implementation, with the greatest progress seen in the youngest age group (mean age 12.5). The greatest increase after training was seen for the variables Attitude toward helping others (p = 0.001) and Self-confidence (p = 0.001). Analysis of the focus groups yielded two themes: (a) the effects of cardiopulmonary resuscitation training on schoolchildren, and (b) the systemic responsibility of the school system and professional bodies. CONCLUSIONS: Significant progress in schoolchildren's cardiopulmonary resuscitation knowledge after training was established. Early introduction of training is recommended. Cardiopulmonary resuscitation knowledge raises awareness of the responsibility to help others and increases self-confidence to provide bystander cardiopulmonary resuscitation. It can be concluded that early cardiopulmonary resuscitation training for children is crucial. It should be a mandatory part of school curricula in those countries where cardiopulmonary resuscitation is not yet mandatory.

Idarucizumab for dabigatran reversal in daily clinical practice: A case series.

BACKGROUND: Real-life experience with idarucizumab, which reverses the anticoagulant effect of dabigatran, is currently limited. OBJECTIVE: To evaluate efficacy and safety of the clinical use of idarucizumab after its availability in Slovenia. METHODS: We analysed consecutive cases treated with idarucizumab in Slovenia from January to October 2016. The decision to reverse dabigatran with idarucizumab was made by the treating clinicians, as was the assessment of clinical outcomes and blood sampling/monitoring (activated partial thromboplastin time, thrombin time and diluted thrombin time) before and after use. RESULTS: Idarucizumab was used in 17 cases. One patient was treated with the antidote twice with an interval of 2 months between treatments. The indications for idarucizumab use were: emergency surgery (4/17), severe bleeding (11/17; seven with intracranial bleeding) and ischaemic stroke (2/17). During surgery, no excessive bleeding was reported. Five patients died due to cardiogenic, haemorrhagic or septic shock, intracranial bleeding or multiple organ failure. Among cases with laboratory data available, baseline coagulation tests were prolonged in 12/13 cases with bleeding or emergency surgery. After idarucizumab administration, normal coagulation parameters were confirmed in 10/11. However, re-occurrence of dabigatran effect was noted later in four patients with creatinine clearance less than 30 ml min, and one patient with persistent bleeding required retreatment with idarucizumab. CONCLUSION: Our first experiences with idarucizumab use in daily-care settings support a rapid and efficient decrease in the anticoagulant effect of dabigatran in emergency situations. Late re-occurrence of dabigatran effect was noted in a subset of patients with severe renal failure.

Huge variation in obtaining ethical permission for a non-interventional observational study in Europe.

BACKGROUND: Ethical approval (EA) must be obtained before medical research can start. We describe the differences in EA for an pseudonymous, non-interventional, observational European study. METHODS: Sixteen European national coordinators (NCs) of the international study on very old intensive care patients answered an online questionnaire concerning their experience getting EA. RESULTS: N = 8/16 of the NCs could apply at one single national ethical committee (EC), while the others had to apply to various regional ECs and/or individual hospital institutional research boards (IRBs). The time between applying for EA and the first decision varied between 7 days and 300 days. In 9/16 informed consent from the patient was not deemed necessary; in 7/16 informed consent was required from the patient or relatives. The upload of coded data to a central database required additional information in 14/16. In 4/16 the NCs had to ask separate approval to keep a subject identification code list to de-pseudonymize the patients if questions would occur. Only 2/16 of the NCs agreed that informed consent was necessary for this observational study. Overall, 6/16 of the NCs were satisfied with the entire process and 8/16 were (very) unsatisfied. 11/16 would welcome a European central EC that would judge observational studies for all European countries. DISCUSSION: Variations in the process and prolonged time needed to get EA for observational studies hampers inclusion of patients in some European countries. This might have a negative influence on the external validity. Further harmonization of ethical approval process across Europe is welcomed for low-risk observational studies. CONCLUSION: Getting ethical approval for low-risk, non-interventional, observational studies varies enormously across European countries.

Isoflurane rescue therapy for bronchospasm reduces intracranial pressure in a patient with traumatic brain injury.

PRIMARY OBJECTIVE: To assess the unusual use of a volatile anaesthetic for treatment of life-threatening bronchospasm in a patient with traumatic brain injury (TBI). RESEARCH DESIGN: Case report. METHODS AND PROCEDURES: This study presents a previously healthy 30-year-old man with severe TBI and bronchospasm-induced acute hypercapnia. He was treated with inhaled isoflurane in combination with monitoring of intracranial pressure (ICP) and regional cerebral blood flow (rCBF). RESULTS: Three-day-long isoflurane treatment resolved drug-refractory bronchospasm, decreased airway pressure and improved gas exchange, even at a low end-tidal concentration (0.3-0.5 vol%). Although rCBF was increased by 18 ml min(-1) 100 g(-1) during isoflurane treatment, there was a significant decrease in ICP (21 (SD = 3) mmHg, 9 (SD = 5) mmHg, 2 (SD = 3) mmHg; during pre-treatment, treatment and post-treatment, respectively; p < 0.001). Improved autoregulation due to lower partial pressure of carbon dioxide, restoration of carbon dioxide reactivity, isoflurane-induced regional differences in rCBF and improved microcirculation may have been responsible for the prompt and long-lasting normalization of ICP. The patient had no TBI-related disability at 6 months post-injury. CONCLUSIONS: Isoflurane at a low dose can be an effective and safe treatment option for drug-refractory bronchospasm in a patient with traumatic intracranial hypertension, provided that multimodality neuromonitoring is used.

A Model Predicting the 6-Month Disability of Patients With Traumatic Brain Injury to Assess the Quality of Care in Intensive Care Units: Results from the CREACTIVE Study.

Assessing quality of care is essential for improving the management of patients experiencing traumatic brain injury (TBI). This study aimed at devising a rigorous framework to evaluate the quality of TBI care provided by intensive care units (ICUs) and applying it to the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) consortium, which involved 83 ICUs from seven countries. The performance of the centers was assessed in terms of patients' outcomes, as measured by the 6-month Glasgow Outcome Scale-Extended (GOS-E). To account for the between-center differences in the characteristics of the admitted patients, we developed a multinomial logistic regression model estimating the probability of a four-level categorization of the GOS-E: good recovery (GR), moderate disability (MD), severe disability (SD), and death or vegetative state (D/VS). A total of 5928 patients admitted to the participating ICUs between March 2014 and March 2019 were analyzed. The model included 11 predictors and demonstrated good discrimination (area under the receiver operating characteristic [ROC] curve in the validation set for GR: 0.836, MD: 0.802, SD: 0.706, D/VS: 0.890) and calibration, both overall (Hosmer-Lemeshow test p value: 0.87) and in several subgroups, defined by prognostically relevant variables. The model was used as a benchmark for assessing quality of care by comparing the observed number of patients experiencing GR, MD, SD, and D/VS to the corresponding numbers expected in each category by the model, computing observed/expected (O/E) ratios. The four center-specific ratios were assembled with polar representations and used to provide a multidimensional assessment of the ICUs, overcoming the loss of information consequent to the traditional dichotomizations of the outcome in TBI research. The proposed framework can help in identifying strengths and weaknesses of current TBI care, triggering the changes that are necessary to improve patient outcomes.

The role of high-income countries in the establishment and development of modern critical care in low resource settings: A Slovenian model.

BACKGROUND: Critical care medicine is a young branch of medicine, of which the development was much faster in High Income Countries (HICs) than in Low Resources Settings (LRS). Slovenia, as one of the successor states of former Yugoslavia, passed the process of transition and joined the European Union successfully. On the contrary, Bosnia and Herzegovina (B&H) went through the extremely difficult process of transition (four years of civil war), which left a deep scar to the healthcare system, including critical care medicine. OBJECTIVE: To examine the impact of HICs on the development of critical care in LRS. METHOD: This review examined the process of growing up the first modern Medical Intensive Care Unit (MICU) in the Republic of Srpska. RESULTS: The five-year process of transferring critical care knowledge from Slovenia to the health care system of Republic of Srpska has contributed to the existence of modern and state of the art MICU with tremendous social effects. CONCLUSION: The model of using the impact of HICs for improving critical care in LRS can be extrapolated to other similar settings.

Investigating the characteristics and correlates of systemic inflammation after traumatic brain injury: the TBI-BraINFLAMM study.

INTRODUCTION: A significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI. METHODS AND ANALYSIS: TBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experimental medicine studies assessing the role and management of post-TBI systemic inflammation.

Comparative Effectiveness of Intracranial Pressure Monitoring on 6-Month Outcomes of Critically Ill Patients With Traumatic Brain Injury.

Importance: While the relationship between persistent elevations in intracranial pressure (ICP) and poorer outcomes is well established for patients with traumatic brain injury (TBI), there is no consensus on how ICP measurements should drive treatment choices, and the effectiveness of ICP monitoring remains unknown. Objective: To evaluate the effectiveness of ICP monitoring on short- and mid-term outcomes of patients with TBI. Design, Setting, and Participants: CREACTIVE was a prospective cohort study that started in March 2014 and lasted 5 years. More than 8000 patients with TBI were enrolled at 83 intensive care units (ICUs) from 7 countries who joined the CREACTIVE Consortium. Patients with TBI who met the Brain Trauma Foundation guidelines for ICP monitoring were selected for the current analyses, which were performed from January to November 2022. Exposure: Patients who underwent ICP monitoring within 2 days of injury (exposure group) were propensity score-matched to patients who were not monitored or who underwent monitoring 2 days after the injury (control group). Main Outcome and Measure: Functional disability at 6 months as indicated by Glasgow Outcome Scale-Extended (GOS-E) score. Results: A total of 1448 patients from 43 ICUs in Italy and Hungary were eligible for analysis. Of the patients satisfying the ICP-monitoring guidelines, 503 (34.7%) underwent ICP monitoring (median [IQR] age: 45 years [29-61 years]; 392 males [77.9%], 111 females [22.1%]) and 945 were not monitored (median [IQR] age: 66 years [48-78 years]; 656 males [69.4%], 289 females [30.6%]). After matching to balance the variables, worse 6-month recovery was observed for monitored patients compared with nonmonitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, respectively; P = .005). Monitored patients received medical therapies significantly more frequently. Conclusions and Relevance: In this cohort study, ICP monitoring was associated with poorer recovery and more frequent medical interventions with their relevant adverse effects. Optimizing the value of ICP monitoring for TBI requires further investigation on monitoring indications, clinical interventions, and management protocols.

Multiple indicators model of long-term mortality in traumatic brain injury.

OBJECTIVE: To examine the prognostic ability of protein S100B, neuron-specific enolase (NSE) and glial fibrillary acid protein (GFAP) for prediction of 1-year mortality in patients with traumatic brain injury (TBI) in relation to clinical and radiological characteristics of TBI. METHODS: Brain injury was quantified in 84 patients (Glasgow Coma Scale [GCS] ≤ 12) using clinical (GCS, pupils), radiological (computed tomography [CT] classification and individual CT characteristics) and biochemical (S100B, NSE and GFAP) data at admission and in the acute post-injury period. RESULTS: Initial and peak S100B, NSE and GFAP concentrations were higher in non-survivors (n = 26) than in survivors (p-value range: <0.001-0.018). Cox regression showed that GFAP and S100B concentration and the temporal profile of S100B were more powerful independent predictors of mortality than baseline clinical and radiological characteristics or clinical and radiological indicators of neurological deterioration. The prognostic models containing admission variables and those available during the subsequent clinical course showed the same discrimination ability (area under receiver characteristic curve 0.92), but the model based on variables available in the acute post-injury period calibrated better (p = 0.428). CONCLUSION: Mortality at 1-year post-TBI is accurately predicted by the combination of GFAP and S100B concentration and clinical and radiological characteristics at admission or in the acute post-injury period.

Basic Resuscitation Training for Third-Cycle Primary School Students: A Qualitative Research of Training Providers' Experiences.

The purpose of our research was to identify the experiences, obstacles, and self-reflective opinions regarding the qualifications of the training providers of cardiopulmonary resuscitation to third-cycle primary school students. The effectiveness and success of a training program in basic resuscitation procedures depend on the qualifications and knowledge of the training provider and the type of didactic materials used. The qualitative method was used with 3 non-homogenous focus groups. Training providers (n = 8) from primary health care participated. The selected text was analyzed using a thematic analysis. The focus groups were organized after the training conducted on basic resuscitation procedures to third-cycle primary school students in September and October 2018. Prior to conducting the research we gained approval by the Medical Ethics Committee. Twenty-five codes, 11 categories and 3 themes were designed: Obstacles that are present in conducting training on cardiopulmonary resuscitation, the effects of training on primary school students and the development of components of prosocial behavior, and systemic responsibility for the qualifications and knowledge of training providers. The research has found that training providers must have the skills and knowledge to motivate the participants of training sessions and encourage them to gain knowledge and skills on resuscitation. They should be familiar with various methods and forms of learning and use relevant teaching materials, so that they can conduct training sessions effectively. Activities are needed to implement minimal criteria for conducting training on resuscitation such as appropriately qualified providers that should follow the European Resuscitation Guidelines, an appropriate pedagogical approach employed by the providers, appropriate equipment and tools, content adjusted to the age of the primary school students, conducting training in small groups, revision of knowledge for training providers and primary school students.

Ventriculolumbar perfusion and inhalational anesthesia with sevoflurane in an accidental intrathecal injection of tranexamic acid: unreported treatment options.

BACKGROUND: Tranexamic acid (TXA) decreases hemorrhage-related mortality in trauma patients and is increasingly being used during obstetric and orthopedic surgeries. Inadvertent intrathecal injection of TXA is a rare, potentially lethal event leading to dose-dependent cardiotoxicity and neurotoxicity. TXA enhances neuronal excitation by antagonizing inhibitory γ-aminobutyric acid type A and glycine receptors. Until now, mechanistic-based pharmacological treatments targeting multiple central nervous system receptors have been advocated for use in such cases, with no data on intrathecal TXA elimination techniques. CASE PRESENTATION: A patient scheduled for hip surgery accidentally received 350 mg of intrathecal TXA instead of levobupivacaine. The clinical picture progressed from spinal segmental myoclonus to generalized convulsions and malignant arrhythmias. The treatment consisted of ventriculolumbar perfusion with normal saline at a rate of 50 mL/hour starting 5 hours after TXA administration and inhalational sedation with sevoflurane, in addition to drugs acting on multiple receptors at different central nervous system levels. Over 2 months the neurological status improved, although it was not complete. CONCLUSIONS: For the first time, the feasibility and possible clinical efficacy of combined treatment with ventriculolumbar perfusion and inhalational sedation with sevoflurane were demonstrated. A referral to a neurosurgical facility is recommended in patients with acute TXA-induced neurotoxicity and cardiotoxicity.

Successful Outcome of Inhalation Injury, Active SARS-CoV-2 Infection, and Concomitant Pneumonia in a Patient With 27% Full-Thickness Burn: A Case Report.

Burn injuries are a major cause of morbidity and mortality. Next to the inhalation injury, TBSA and age are strong predictors of mortality in burn victims. The novel coronavirus disease 2019 (COVID-19) pandemic is associated with a fatality rate of around 3.5%. We present a case of burn victim with full-thickness burn to face, scalp, both upper extremities (27% of TBSA), inhalation injury, and active severe acute respiratory syndrome coronavirus 2 infection with concomitant pneumonia. The inhalation injury in COVID-19 positive patient was severe. A bronchoscopy revealed a diffuse erythema of the trachea and both main bronchi, the whole bronchial tree up to the distal segments was covered with carbonaceous material which could not be removed. We decided to treat the inhalation injury according to the guidelines for burns and acute respiratory distress syndrome. Accordingly, the patient did not receive any antiviral drugs or corticosteroids. The reconstruction of a full-thickness scalp defect after burn presents a challenge in large size defects and in patients with comorbidities. Double layer Integra Dermal Regeneration Template (Integra LifeSciences, Plainsboro, New Jersey) was the reconstruction method of choice. The take of dermal template and split-thickness skin graft was 100% and good scalp contour was achieved. To our knowledge this is the first case report presenting a successful treatment outcome in a burn victim with inhalation injury, active severe acute respiratory syndrome coronavirus 2 infection, and concomitant pneumonia with full-thickness burn of 27% of TBSA.

Effects of Cardiopulmonary Resuscitation with Automated External Defibrillator Training among Schoolchildren in Slovenia: A Pre- and Post-test Cohort Study.

INTRODUCTION: A low proportion of bystanders in Slovenia are willing to provide resuscitation to people experiencing cardiac arrest. We measured knowledge acquired after cardiopulmonary resuscitation training among Slovenian children in the final three grades of primary school. METHODS: This pre- and post-test cohort study included 566 schoolchildren aged 12-15 years. From April to May 2018, we administered a 15-item questionnaire to children in 15 primary schools, to assess the effects of theoretical and practical cardiopulmonary resuscitation training on their knowledge of cardiopulmonary resuscitation at 1-2 months after training. Data were processed using univariate, bivariate, and multivariate analyses. RESULTS: A significantly greater level of post-training knowledge was noted in all three equally sized school grade groups (p=0.001). The youngest group (mean age 12.5 years) exhibited the greatest increase in knowledge, with test scores increasing by an average 2.65 (range 0-15) points. Age (p=0.001), body mass index (p=0.037), female sex (p=0.006), and previous resuscitation training (p=0.024) were significant independent predictors of pre-training knowledge level. Sex was the only predictor significantly influencing knowledge levels after training (p=0.002); girls scored up to 0.7 points higher than boys, both before and after training. CONCLUSIONS: Among Slovenian schoolchildren aged 12-15 years, a significantly improved level of theoretical knowledge was demonstrated after cardiopulmonary resuscitation training. The introduction of cardiopulmonary training may be most effective in children aged 12.5 years (seventh graders). Early, compulsory resuscitation training might reduce social barriers to performing resuscitation, which may eventually translate into better post-cardiac arrest outcomes.

Prognostic value of CT perfusion and permeability imaging in traumatic brain injury.

BACKGROUND: Currently established prognostic models in traumatic brain injury (TBI) include noncontrast computed tomography (CT) which is insensitive to early perfusion alterations associated with secondary brain injury. Perfusion CT (PCT) on the other hand offers insight into early perfusion abnormalities. We hypothesized that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model. METHODS: A prospective cohort study of consecutive 50 adult patients with head injury and Glasgow Coma Scale score of 12 or less was performed at a single Level 1 Trauma Centre. Perfusion CT was added to routine control CT 12 hours to 24 hours after admission. Region of interest analysis was performed in six major vascular territories on perfusion and permeability parametric maps. Glasgow Outcome Scale (GOS) was used 6 months later to categorize patients' functional outcomes to favorable (GOS score > 3) or unfavorable (GOS score ≤ 3). We defined core prognostic model, consisting of age, motor Glasgow Coma Scale score, pupillary reactivity, and CT Rotterdam Score. Next, we added perfusion and permeability data as predictors and compared updated models to the core model using cross-validated areas under the receiver operator curves (cv-AUC). RESULTS: Significant advantage over core model was shown by the model, containing both mean cerebral extravascular-extracellular volume per unit of tissue volume and cerebral blood volume of the least perfused arterial territory in addition to core predictors (cv-AUC, 0.75; 95% confidence interval, 0.51-0.84 vs. 0.6; 95% confidence interval, 0.37-0.74). CONCLUSION: The development of cerebral ischemia and traumatic cerebral edema constitutes the secondary brain injury and represents the target for therapeutic interventions. Our results suggest that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model in the setting of moderate and severe TBI. LEVEL OF EVIDENCE: Prognostic study, level III.

Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study.

Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients.

Hospitals with and without neurosurgery: a comparative study evaluating the outcome of patients with traumatic brain injury.

BACKGROUND: We leveraged the data of the international CREACTIVE consortium to investigate whether the outcome of traumatic brain injury (TBI) patients admitted to intensive care units (ICU) in hospitals without on-site neurosurgical capabilities (no-NSH) would differ had the same patients been admitted to ICUs in hospitals with neurosurgical capabilities (NSH). METHODS: The CREACTIVE observational study enrolled more than 8000 patients from 83 ICUs. Adult TBI patients admitted to no-NSH ICUs within 48 h of trauma were propensity-score matched 1:3 with patients admitted to NSH ICUs. The primary outcome was the 6-month extended Glasgow Outcome Scale (GOS-E), while secondary outcomes were ICU and hospital mortality. RESULTS: A total of 232 patients, less than 5% of the eligible cohort, were admitted to no-NSH ICUs. Each of them was matched to 3 NSH patients, leading to a study sample of 928 TBI patients where the no-NSH and NSH groups were well-balanced with respect to all of the variables included into the propensity score. Patients admitted to no-NSH ICUs experienced significantly higher ICU and in-hospital mortality. Compared to the matched NSH ICU admissions, their 6-month GOS-E scores showed a significantly higher prevalence of upper good recovery for cases with mild TBI and low expected mortality risk at admission, along with a progressively higher incidence of poor outcomes with increased TBI severity and mortality risk. CONCLUSIONS: In our study, centralization of TBI patients significantly impacted short- and long-term outcomes. For TBI patients admitted to no-NSH centers, our results suggest that the least critically ill can effectively be managed in centers without neurosurgical capabilities. Conversely, the most complex patients would benefit from being treated in high-volume, neuro-oriented ICUs.

Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury.

Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.

Transarterial embolization of the external carotid artery in the treatment of life-threatening haemorrhage following blunt maxillofacial trauma.

Background Severe bleeding after blunt maxillofacial trauma is a rare but life-threatening event. Non-responders to conventional treatment options with surgically inaccessible bleeding points can be treated by transarterial embolization (TAE) of the external carotid artery (ECA) or its branches. Case series on such embolizations are small; considering the relatively high incidence of maxillofacial trauma, the ECA TAE procedure has been hypothesized either underused or underreported. In addition, the literature on the ECA TAE using novel non-adhesive liquid embolization agents is remarkably scarce. Patients and methods PubMed review was performed to identify the ECA TAE literature in the context of blunt maxillofacial trauma. If available, the location of the ECA injury, the location of embolization, the chosen embolization agent, and efficacy and safety of the TAE were noted for each case. Survival prognostic factors were also reviewed. Additionally, we present an illustrative TAE case using a precipitating hydrophobic injectable liquid (PHIL) to safely and effectively control a massive bleeding originating bilaterally in the ECA territories. Results and conclusions Based on a review of 205 cases, the efficacy of TAE was 79.4-100%, while the rate of major complications was about 2-4%. Successful TAE haemostasis, Glasgow Coma Scale score ≥ 8 at presentation, injury severity score ≤ 32, shock index ≤ 1.1 before TAE and ≤ 0.8 after TAE were significantly correlated with higher survival rate. PHIL allowed for fast yet punctilious application, thus saving invaluable time in life-threatening situations while simultaneously diminishing the possibility of inadvertent injection into the ECA-internal carotid artery (ICA) anastomoses.