Argon neuroprotection

Certain noble gases, though inert, exhibit remarkable biological properties. Notably, xenon and argon provide neuroprotection in animal models of central nervous system injury. In the previous issue of Critical Care, Loetscher and colleagues provided further evidence that argon may have therapeutic properties for neuronal toxicity by demonstrating protection against both traumatic and oxygen-glucose deprivation injury of organotypic hippocampal cultures in vitro. Their data are of interest as argon is more abundant, and therefore cheaper, than xenon (the latter of which is currently in clinical trials for perinatal hypoxic-ischemic brain injury; TOBYXe; NCT00934700). We eagerly await in vivo data to complement the promising in vitro data hailing argon neuroprotection.     

The impact of preinjury antithrombotic medication on hemostatic interventions in trauma patients

Purpose

The purpose of this study was to determine whether preinjury medication with antithrombotic agents was related to an increase in hemostatic interventions in patients with severe trauma without traumatic brain injury.

The role of prophylactic anticonvulsants in moderate to severe head injury

Background

Post-traumatic seizures cause secondary brain injury, contributing to morbidity and mortality after traumatic brain injury. Seizure activity may be undetectable if the patient is paralysed and ventilated.

Aims

The effect of prophylactic anticonvulsant therapy on the prevention of seizures after moderate to severe traumatic brain injury was studied.

Methods

A structured systematic literature review was performed.

Results

There may be a place for prophylactic anticonvulsants in the prophylaxis of early post-traumatic seizures.

Conclusion

Further randomised controlled trials are needed to firmly establish the benefits of prophylactic anticonvulsants.     

Propofol: neuroprotection in an in vitro model of traumatic brain injury

Introduction  

The anaesthetic agent propofol (2,6-diisopropylphenol) has been shown to be an effective neuroprotective agent in different in vitro models of brain injury induced by oxygen and glucose deprivation. We examined its neuroprotective properties in an in vitro model of traumatic brain injury.     

Infra-red thermometry: the reliability of tympanic and temporal artery readings for predicting brain temperature after severe traumatic brain injury

Introduction

Temperature measurement is important during routine neurocritical care especially as differences between brain and systemic temperatures have been observed. The purpose of the study was to determine if infra-red temporal artery thermometry provides a better estimate of brain temperature than tympanic membrane temperature for patients with severe traumatic brain injury.

Methods

Brain parenchyma, tympanic membrane and temporal artery temperatures were recorded every 15–30 min for five hours during the first seven days after admission.

Results

Twenty patients aged 17–76 years were recruited. Brain and tympanic membrane temperature differences ranged from -0.8 °C to 2.5 °C (mean 0.9 °C). Brain and temporal artery temperature differences ranged from -0.7 °C to 1.5 °C (mean 0.3 °C). Tympanic membrane temperature differed from brain temperature by an average of 0.58 °C more than temporal artery temperature measurements (95% CI 0.31 °C to 0.85 °C, P < 0.0001).

Conclusions

At temperatures within the normal to febrile range, temporal artery temperature is closer to brain temperature than is tympanic membrane temperature.     

Acute stress in patients with brain cancer during primary care

Purpose

This study investigated whether diagnosis and neurosurgical removal of a brain tumour induced Acute Stress Disorder (ASD) in adults. We also aimed to identify factors associated with the development of ASD in this specific patient group and setting.

Methods

Forty-seven consecutive patients with intracranial neoplasms completed a variety of self-report questionnaires and underwent a structured clinical interview (SCID) within the first 4?weeks after tumour detection on average 1?week after neurosurgical treatment. Moreover, the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), A1 and A2 criterion and thus the characteristics of the traumatic event were explored in detail.

Results

ASD symptoms were common. Twenty-three percent of the patients met stringent criteria of ASD and another 4% suffered from subsyndromal ASD. Predisposing factors previously reported in literature with the exception of previous trauma could not be identified in this study (e.g., sex, age, intelligence).

Conclusion

It has been critically discussed whether the diagnosis of ASD is appropriate in cancer patients due to the often future-related nature of cancer-related traumatic events. The diagnosis of ASD was justified in the vast majority of affected patients due to the specific, acute and past traumatic experiences in concordance with the DSM and International Statistical Classification of Diseases and Related Health Problems (ICD) trauma definitions. Thus, ASD is a common and relevant psychiatric comorbidity in patients with brain tumours. Our data highlight both the need for the routine psychological assessment as well as of psychosocial support in this early treatment phase.     

Traumatic aortic injury score (TRAINS): an easy and simple score for early detection of traumatic aortic injuries in major trauma patients with associated blunt chest trauma

Purpose

To develop a risk score based on physical examination and chest X-ray findings to rapidly identify major trauma patients at risk of acute traumatic aortic injury (ATAI).

Methods

A multicenter retrospective study was conducted with 640 major trauma patients with associated blunt chest trauma classified into ATAI (aortic injury) and NATAI (no aortic injury) groups. The score data set included 76 consecutive ATAI and 304 NATAI patients from a single center, whereas the validation data set included 52 consecutive ATAI and 208 NATAI patients from three independent institutions. Bivariate analysis identified variables potentially influencing the presentation of aortic injury. Confirmed variables by logistic regression were assigned a score according to their corresponding beta coefficient which was rounded to the closest integer value (1–4).

Results

Predictors of aortic injury included widened mediastinum, hypotension less than 90?mmHg, long bone fracture, pulmonary contusion, left scapula fracture, hemothorax, and pelvic fracture. Area under receiver operating characteristic curve was 0.96. In the score data set, sensitivity was 93.42?%, specificity 85.85?%, Youden’s index 0.79, positive likelihood ratio 6.60, and negative likelihood ratio 0.08. In the validation data set, sensitivity was 92.31?% and specificity 85.1?%.

Conclusions

Given the relative infrequency of traumatic aortic injury, which often leads to missed or delayed diagnosis, application of our score has the potential to draw necessary clinical attention to the possibility of aortic injury, thus providing the chance of a prompt specific diagnostic and therapeutic management.     

Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain

Purpose

Experimental evidence suggests that lactate is neuroprotective after acute brain injury; however, data in humans are lacking. We examined whether exogenous lactate supplementation improves cerebral energy metabolism in humans with traumatic brain injury (TBI).

Methods

We prospectively studied 15 consecutive patients with severe TBI monitored with cerebral microdialysis (CMD), brain tissue PO₂ (PbtO₂), and intracranial pressure (ICP). Intervention consisted of a 3-h intravenous infusion of hypertonic sodium lactate (aiming to increase systemic lactate to ca. 5 mmol/L), administered in the early phase following TBI. We examined the effect of sodium lactate on neurochemistry (CMD lactate, pyruvate, glucose, and glutamate), PbtO₂, and ICP.

Results

Treatment was started on average 33 ± 16 h after TBI. A mixed-effects multilevel regression model revealed that sodium lactate therapy was associated with a significant increase in CMD concentrations of lactate [coefficient 0.47 mmol/L, 95 % confidence interval (CI) 0.31–0.63 mmol/L], pyruvate [13.1 (8.78–17.4) μmol/L], and glucose [0.1 (0.04–0.16) mmol/L; all p < 0.01]. A concomitant reduction of CMD glutamate [?0.95 (?1.94 to 0.06) mmol/L, p = 0.06] and ICP [?0.86 (?1.47 to ?0.24) mmHg, p < 0.01] was also observed.

Conclusions

Exogenous supplemental lactate can be utilized aerobically as a preferential energy substrate by the injured human brain, with sparing of cerebral glucose. Increased availability of cerebral extracellular pyruvate and glucose, coupled with a reduction of brain glutamate and ICP, suggests that hypertonic lactate therapy has beneficial cerebral metabolic and hemodynamic effects after TBI.     

Soluble triggering receptor on myeloid cells-1 is expressed in the course of non-infectious inflammation after traumatic lung contusion: a prospective cohort study

Introduction

The triggering receptor expressed on myeloid cells-1 (TREM-1) is known to be expressed during bacterial infections. We investigated whether TREM-1 is also expressed in non-infectious inflammation following traumatic lung contusion.

Methods

In a study population of 45 adult patients with multiple trauma and lung contusion, we obtained bronchoalveolar lavage (BAL) (blind suctioning of 20 ml NaCl (0.9%) via jet catheter) and collected blood samples at two time points (16 hours and 40 hours) after trauma. Post hoc patients were assigned to one of four groups radiologically classified according to the severity of lung contusion based on the initial chest tomography. Concentration of soluble TREM-1 (sTREM-1) and bacterial growth were determined in the BAL. sTREM-1, IL-6, IL-10, lipopolysaccharide binding protein, procalcitonin, C-reactive protein and leukocyte count were assessed in blood samples. Pulmonary function was evaluated by the paO₂/FiO₂ ratio.

Results

Three patients were excluded due to positive bacterial growth in the initial BAL. In 42 patients the severity of lung contusion correlated with the levels of sTREM-1 16 hours and 40 hours after trauma. sTREM-1 levels were significantly (P < 0.01) elevated in patients with severe contusion (2,184 pg/ml (620 to 4,000 pg/ml)) in comparison with patients with mild (339 pg/ml (135 to 731 pg/ml)) or no (217 pg/ml (97 to 701 pg/ml)) contusion 40 hours following trauma. At both time points the paO₂/FiO₂ ratio correlated negatively with sTREM-1 levels (Spearman correlation coefficient = -0.446, P < 0.01).

Conclusions

sTREM-1 levels are elevated in the BAL of patients following pulmonary contusion. Furthermore, the levels of sTREM-1 in the BAL correlate well with both the severity of radiological pulmonary tissue damage and functional impairment of gas exchange (paO₂/FiO₂ ratio).     

Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice

Purpose

The aim of the present study was to develop short half-lived tools for in vitro and in vivo β-amyloid imaging in mice, for which no suitable PET tracers are available.

Procedures

Five ¹³N-labelled azo compounds (1–5) were synthesized using a three-step process using cyclotron-produced [¹³N]NO₃ ^?. Biodistribution studies were performed using positron emission tomography–computed tomography (PET–CT) on 20-month-old healthy, wild-type (WT) mice. In vivo and in vitro binding assays were performed using PET-CT and autoradiography, respectively, on 20-month-old healthy (WT) mice and transgenic (Tg2576) Alzheimer's disease model mice.

Results

¹³N-labelled azo compounds were prepared with decay corrected radiochemical yields in the range 27?±?4 % to 39?±?4 %. Biodistribution studies showed good blood–brain barrier penetration for compounds 1 and 3–5; good clearance data were also obtained for compounds 1–3 and 5. Compounds 2, 3 and 5 (but not 1) showed a significant uptake in β-amyloid-rich structures when assayed in in vitro autoradiographic studies. PET studies showed significant uptake of compounds 2 and 3 in the cortex of transgenic animals that exhibit β-amyloid deposits.

Conclusions

The results underscore the potential of compounds 2 and 3 as in vitro and in vivo markers for β-amyloid in animal models of Alzheimer's disease.     

Accessibility,accountability, affordability: healthcare policy in orthopedic trauma

Purpose of review

This review provides historical background on trauma care in the USA and summarizes contemporary trauma-related health policy issues. It is a primer for orthopedic surgeons who want to promote improvements in research, delivery, and cost reduction in trauma care.

Recent findings

As of 2010, funding for trauma research accounted for only 0.02% of all National Institutes of Health research funding. This is disproportionate to the societal burden of traumatic injury, which is the leading cause of death and disability among people aged 1 to 46 years in the USA. The diagnosis-related group model of hospital reimbursement penalizes level-I trauma centers, which typically treat the most severely injured patients. Treatment of traumatic injury at level-I and level-II trauma centers is associated with lower rates of major complications and death compared with treatment at non-trauma centers. Patient proximity to trauma centers has been positively correlated with survival after traumatic injury. Inadequate funding has been cited as a reason for recent closures of trauma centers.

Summary

Orthopedic surgeons have a responsibility to engage in efforts to improve the quality, accessibility, and affordability of trauma care. This can be done by advocating for greater funding for trauma research; choosing the most cost-effective, patient-appropriate orthopedic implants; supporting the implementation of a national trauma system; leading high-quality research of trauma patient outcomes; and advocating for greater accessibility to level-I trauma centers for underserved populations.

     

Pathogenic antibodies are active participants in spinal cord injury

The role of B cells and autoimmunity as contributing factors to poor neurological outcomes following spinal cord injury (SCI) is poorly understood. The study by Ankeny et al., in this issue of the JCI, identifies a new immunopathological mechanism arising after SCI in mice (see the related article beginning on page 2990). The study shows that B cells produce pathogenic antibodies that impair lesion repair, resulting in worse neurological outcome. This new understanding of SCI disease pathogenesis, if confirmed in humans, reveals potential avenues for the development of novel neuroprotective immunotherapies. Primary trauma to the CNS initiates a series of interrelated responses, including edema, excitotoxicity, and inflammation, that lead to secondary injury, resulting in further expansion of the initial lesion and additional loss of neurological function. The treatment of neuroinflammation in the context of both traumatic brain injury and spinal cord injury (SCI) still lacks a standard, universally accepted therapy that leads to improved neurological outcomes. There exists a clear, unmet medical need for an effective antiinflammatory treatment for the acute and chronic stages of traumatic brain injury and SCI arising in general civilian as well in injured military personnel populations. Currently, an important area of SCI research focuses on understanding the dual nature of post-SCI neuroinflammation. It can lead to increased damage to the neural tissue, yet it is an essential part of the wound healing process (1, 2). It is becoming increasingly clear that injury to the CNS results in alterations to the systemic immune system that in turn affect the competing pathogenic and wound healing processes evolving at the site of injury (3–5). The study reported by Ankeny et al. in this issue of the JCI (6) offers a new perspective on a poorly understood aspect of CNS inflammation in response to traumatic injury in mice, namely the impact of B cells and autoimmunity on neurological outcomes. This new understanding of SCI disease pathogenesis, if confirmed in humans, reveals avenues for the development of novel neuroprotective immunotherapies.     

Predictor of Isolated Trauma in Head: A New Simple Predictor for Survival of Isolated Traumatic Brain Injury

Background

Mortality prediction in patients with brain trauma during initial management in the emergency department (ED) is essential for creating the foundation for a better prognosis.

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

Introduction

Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress.

Methods

We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 μg, zinc 30 mg, vitamin C 1.1 g, and vitamin B₁ 100 mg) with a double-loading dose on days 1 and 2 or placebo.

Results

Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 ± 3.2 versus -4.2 ± 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).

Conclusion

The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.

Trials Registration

Clinical Trials.gov RCT Register: NCT00515736.     

Time-critical neurological emergencies: the unfulfilled role for point-of-care testing

Background

Neurological emergencies are common and frequently devastating. Every year, millions of Americans suffer an acute stroke, severe traumatic brain injury, subarachnoid hemorrhage, status epilepticus, or spinal cord injury severe enough to require medical intervention.

Aims

Full evaluation of the diseases in the acute setting often requires advanced diagnostics, and treatment frequently necessitates transfer to specialized centers. Delays in diagnosis and/or treatment may result in worsened outcomes; therefore, optimization of diagnostics is critical.

Methods

Point-of-care (POC) testing brings advanced diagnostics to the patient’s bedside in an effort to assist medical providers with real-time decisions based on real-time information. POC testing is usually associated with blood tests (blood glucose, troponin, etc.), but can involve imaging, medical devices, or adapting existing technologies for use outside of the hospital. Noticeably missing from the list of current point-of-care technologies are real-time bedside capabilities that address neurological emergencies.

Results

Unfortunately, the lack of these technologies may result in delayed identification of patients of these devastating conditions and contribute to less aggressive therapies than is seen with other disease processes. Development of time-dependent technologies appropriate for use with the neurologically ill patient are needed to improve therapies and outcomes.

Conclusion

POC-CENT is designed to support the development of novel ideas focused on improving diagnostic or prognostic capabilities for acute neurological emergencies. Eligible examples include biomarkers of traumatic brain injury, non-invasive measurements of intracranial pressure or cerebral vasospasm, and improved detection of pathological bacteria in suspected meningitis.     

Use of a Benzimidazole Derivative BF-188 in Fluorescence Multispectral Imaging for Selective Visualization of Tau Protein Fibrils in the Alzheimer’s Disease Brain

Purpose

Selective visualization of amyloid-β and tau protein deposits will help to understand the pathophysiology of Alzheimer’s disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique.

Procedures

Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [³H]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-β (Aβ) and tau fibrils.

Results

In AD brain sections, BF-188 clearly stained Aβ and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-β and tau fibrils with high affinity (K _i ?<?10 nM). In addition, BF-188 showed an excellent blood–brain barrier permeability in mice.

Conclusion

Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-β in the brain.     

FIBTEM provides early prediction of massive transfusion in trauma

Introduction

Prediction of massive transfusion (MT) among trauma patients is difficult in the early phase of trauma management. Whole-blood thromboelastometry (ROTEM^®) tests provide immediate information about the coagulation status of acute bleeding trauma patients. We investigated their value for early prediction of MT.

Methods

This retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score ≥16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM^® analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received ≥10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units).

Results

Of 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83).

Conclusions

FIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings.     

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

Background

Injuries represent a significant and growing public health concern in China. This Review was conducted to document the characteristics of injured patients presenting to the emergency department of Chinese hospitals and to assess of the nature of information collected and reported in published surveillance studies.

Methods

A systematic search of MEDLINE and China Academic Journals supplemented with a hand search of journals was performed. Studies published in the period 1997 to 2007 were included and research published in Chinese was the focus. Search terms included emergency, injury, medical care.

Results

Of the 268 studies identified, 13 were injury surveillance studies set in the emergency department. Nine were collaborative studies of which eight were prospective studies. Of the five single centre studies only one was of a prospective design. Transport, falls and industrial injuries were common mechanisms of injury. Study strengths were large patient sample sizes and for the collaborative studies a large number of participating hospitals. There was however limited use of internationally recognised injury classification and severity coding indices.

Conclusion

Despite the limited number of studies identified, the scope of each highlights the willingness and the capacity to conduct surveillance studies in the emergency department. This Review highlights the need for the adoption of standardized injury coding indices in the collection and reporting of patient health data. While high level injury surveillance systems focus on population-based priority setting, this Review demonstrates the need to establish an internationally comparable trauma registry that would permit monitoring of the trauma system and would by extension facilitate the optimal care of the injured patient through the development of informed quality assurance programs and the implementation of evidence-based health policy.     

Visco-induction et chondropathie post-traumatique du genou: existe-t-il des preuves fondamentales ?

Objective

A review of the clinical animal research on the use of intra-articular knee injections of hyaluronic acid (HA) to suggest the interest of clinical research of such injections for traumatic and orthopedic knee events in humans.

Methods

Systematic literature search of the PubMed database from 1966 to 2009 with the following keywords: hyaluronic acid, hyaluronan, and viscosupplementation combined with knee, injury, anterior cruciate ligament, meniscus, and arthroscopy Only articles published in English or French, containing an abstract and involving animal experiments, were searched.

Results

Fifteen randomized controlled studies describing HA injection in animals were selected: six related to meniscus injury, seven anterior cruciate ligament (ACL) injury, and two cartilage injury. Five studies demonstrated positive effects of intra-articular injection of HA for ACL injury, two a positive effect and four a moderate effect for meniscus injury, and two a negative effect for ACL injury.

Conclusion

Fundamental studies on animal models have demonstrated the positive effects of intra-articular injections of HA for post-traumatic knee injuries: improved healing process after a meniscal tear and/or protective role on articular cartilage after an ACL injury, but no positive effect on wound healing after a direct injury of articular cartilage. In humans, the injections of AH after arthroscopic partial meniscectomy, joint lavage, and/or surgical reconstruction of the ACL appear to be of interest. However, many questions remain about the indication, terms of use, and the benefit/ risk of HA injections in these post-traumatic situations.