No description available.

Cardiac-specific troponins (Tns) are sensitive and specific markers of myocardial injury that have been shown to be predictive of outcomes in many cardiac and noncardiac conditions. We sought to determine whether normal cardiac Tn concentrations obtained during the first 24 hours following blunt chest trauma would predict good cardiac outcomes. A PubMed/MEDLINE search was performed to identify prospective studies in patients with blunt chest trauma in which serial cardiac TnT or TnI values were measured within 24 hours of admission and clinical outcomes assessed. Ten studies qualified for review. Studies that used the lower reference limit of Tn as the cutoff for cardiac injury showed 100% negative predictive value (NPV) for developing cardiac complications, whereas studies using higher Tn cutoffs showed wider variation in NPV (50%-98%). Cardiac Tn measured within 24 hours using the lower reference limit (LRL) as the cutoff appears to have excellent NPV for clinically significant adverse cardiac events. This could allow for early discharge after a 24-hour observation period in otherwise uncomplicated blunt chest trauma patients and avoid the need for more expensive cardiac imaging and additional resource utilization.

Patients with a brain injury must overcome a central neurological insult and a systematic metabolic response. The systematic response includes hypermetabolism, hypercatabolism, altered vascular permeability, increased hormone and cytokine release, altered gastric emptying, altered mineral metabolism and altered immune status. This response may initiate mechanisms which lead to secondary brain injury and may adversely affect the function of other organs. Last two decades have improved our knowledge of pathophysiology in patients with primary and secondary brain injury including traumatic contusions. In a moment of injury, primary brain injury which is traumatic contusion can not be therapeutically prevented it can only have a preventive effect. Secondary brain injury can be therapeutically affected although both types of injuries have common pathophysiological signs of disturbed metabolism on cells and subcellular level. Research methods based on molecular biology opens a new zone of research reaction of central neurological system for trauma or ischemia with effort to get involved immediately at the beginning of developing adverse pathophysiological cascade leading to a death of neurotic cell. The brain contusion is a primary centre of brain injury with anatomic changes which can be graphically proved. In...

Patients with a brain injury must overcome a central neurological insult and a systematic metabolic response. The systematic response includes hypermetabolism, hypercatabolism, altered vascular permeability, increased hormone and cytokine release, altered gastric emptying, altered mineral metabolism and altered immune status. This response may initiate mechanisms which lead to secondary brain injury and may adversely affect the function of other organs. Last two decades have improved our knowledge of pathophysiology in patients with primary and secondary brain injury including traumatic contusions. In a moment of injury, primary brain injury which is traumatic contusion can not be therapeutically prevented it can only have a preventive effect. Secondary brain injury can be therapeutically affected although both types of injuries have common pathophysiological signs of disturbed metabolism on cells and subcellular level. Research methods based on molecular biology opens a new zone of research reaction of central neurological system for trauma or ischemia with effort to get involved immediately at the beginning of developing adverse pathophysiological cascade leading to a death of neurotic cell. The brain contusion is a primary centre of brain injury with anatomic changes which can be graphically proved. In...

Older individuals sustaining traumatic brain injury (TBI) experience a much higher incidence of morbidity and mortality. This age-related exacerbated response to neurological insult has been demonstrated experimentally in aged animals, which can serve as a model to combat this devastating clinical problem. The reasons for this worse initial response are unknown but may be related to age-related changes in mitochondrial respiration. Evidence is shown that mitochondrial dysfunction occurs early following traumatic brain injury (TBI), persists long after the initial insult, and is severitydependent. Synaptic and extrasynaptic mitochondrial fractions display distinct respiration capacities, stressing the importance to analyze these fractions separately. Sprague- Dawley and Fischer 344 rats, two commonly used strains used in TBI and aging research, were found to show very similar respiration profiles, indicating respiration data are not strain dependent. Neither synaptic nor extrasynaptic mitochondrial respiration significantly declined with age in naïve animals. Only the synaptic fraction displayed significant age-related increases in oxidative damage, measured by 3-nitrotyrosine (3- NT), 4-hydroxynonenal (4-HNE), and protein carbonyls (PC). Alterations in respiration with age appear to be more subtle than previously thought. Subtle declines in respiration and elevated levels of oxidative damage may not to be sufficient to produce detectable deficits until the system is challenged. Following TBI, synaptic mitochondria exhibit dysfunction that increased significantly with age at injury, evident in lower respiratory control ratio (RCR) values and declines in ATP production rates. Furthermore, synaptic mitochondria displayed increased levels of oxidative damage with age and injury, while extrasynaptic mitochondria only displayed significant elevations following the insult. Age-related synaptic mitochondrial dysfunction following TBI may contribute to an exacerbated response in the elderly population.

Traumatic brain injury (TBI) is a prevalent CNS neurodegenerative condition that results in lasting neurological dysfunction, including potentially debilitating cognitive impairments. Despite the advancements in understanding the complex damage that can culminate in cellular dysfunction and loss, no therapeutic treatment has been effective in clinical trials, highlighting that new approaches are desperately needed. A therapy that limits cell death while simultaneously promoting reparative mechanisms, including post-traumatic neurogenesis, in the injured brain may have maximum effectiveness in improving recovery of function after TBI. Insulin-like growth factor-1 (IGF-1) is a potent growth factor that has previously been shown to promote recovery of function after TBI, but no studies have evaluated the efficacy of IGF-1 to promote cell survival and modulate neurogenesis following brain injury. Systemic infusion of IGF-1 resulted in undetectable levels of IGF-1 in the brain, but did promote increased cortical activation of Akt, a pro-survival downstream mediator of IGF-1 signaling, in mice subjected to controlled cortical impact (CCI), a well-established model of contusion TBI. However, systemic infusion of IGF-1 did not promote recovery of motor function in mice after CCI. A one week central infusion of IGF-1 elevated brain levels of IGF-1, increased Akt activation and improved motor and cognitive function after CCI. Central infusion of IGF-1 also significantly increased immature neuron density at 7 d post-injury for a range of doses and when administered with a clinically relevant delayed onset of 6 hr post-injury. To mitigate potential side effects of central infusion, an alternative conditional astrocyte-specific IGF-1 overexpressing mouse model was utilized to evaluate the efficacy of IGF-1 to promote post-traumatic neurogenesis. Overexpression of IGF-1 did not protect against acute immature neuron loss, but did increase immature neuron density above uninjured levels at 10 d post-injury. The increase in immature neuron density appeared to be driven by enhanced neuronal differentiation. In wildtype mice, immature neurons exhibited injury-induced reductions in dendritic arbor complexity following severe CCI, a previously unknown pathological phenomenon. Overexpression of IGF-1 in brain-injured mice promoted the restoration of dendritic arbor complexity to the dendritic morphology observed in uninjured mice. Together, these findings provide strong evidence that treatment with IGF-1 promotes the recovery of neurobehavioral function and enhances post-traumatic neurogenesis in a mouse model of contusion TBI.

In order to describe the trend, characteristics, and cost of occupational injuries that occurred in industrial settings across the United States between 1998 and 2009, a cross sectional analysis based on hospital discharge data was conducted. The National Inpatient Sample (NIS) data from the Healthcare and Cost Utilization Project (HCUP)(1) was used. Identification of relevant injuries from the sample was performed using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) code E849.3 (industrial place and premises)(8). A total of 307,586 (weighted) patients with industrial related injuries were discharged from hospitals in the United States during the period 1998-2009. They were largely male (81.8% vs. 16.6% female) and made up of 48.6% Non-Hispanic Whites, 18.2% Hispanic, and 6.2% Non-Hispanic Black. Two-thirds of patients were within the [25-54] years age group, broken down as 20.4%, 24.8% and 22.1% in the 25-34, 35-44, and 45-54 years age group respectively. Persons in the ≥65 age group also represented a sizable proportion at 7.3%. The patients were mostly admitted from an Emergency Department (61.2%), followed by routine/standard admissions (22.2%). While they were for the most part discharged home (81.7%), 7.2% were released to a home care facility, 7.9% to another type of facility, and 0.7% died during their stay in the hospital. As for the geographical distribution, 38.9% were admitted in the West, 24.6% in the South, 19.5% in the Midwest, and 17% in the Northeast United States. Furthermore, 88.6% were admitted in a hospital in urban settings vs. 11.2% in rural settings. The common injury sites were lower and upper extremities (52.6%), multiple locations (14.2%), trunk (9.3%), and head (8.9%). Of all admissions, 48.4% involved fractures, followed by open wounds (25.7%), internal crush injuries (19.4%), and superficial contusions (10.1%). "Foreign Body Entering through Orifice" (0.5%) and poisoning (2.3%) scored the lowest, while burns (5.8%), dislocations (3.9%), and crushing (5%) were noted as well. The mean length of stay was 4.09 days (95% CI 3.92 - 4.22), while the 95th percentile was ≤13 days. When analyzed by injury site, persons with multiple injuries stayed the longest, averaging 6.21 days (95% CI 5.85 - 6.57) while those with injuries at extremities stayed the shortest, 3.53 days (95% CI 3.42 - 3.65). Patients admitted for burns stayed 7.21 days on average (95% CI 6.52 - 7.9) while those with sprain/strain injuries (2.87 days, 95% CI 2.71 - 3.02) and poisoning (2.92 days, 95% CI 2.69 - 3.16) stayed the shortest. Overall, the mean cost of care (crude 2001-2009) was $10,153 per admission. Viewed from the injury site angle, the "multiple" category was the most costly at $17,518 and "extremity" the lowest ($8,269). Diagnostics of "Foreign Body Entering through Orifice" were the most expensive, costing on average ($17,036), closely followed by "burns" ($16,495), while "poisoning" was the least costly, with a mean cost of $6,077. Using Joinpoint regression modeling, we found an overall annual percentage rate change (APC) decrease (-1.73%) over the course of the study. While this improvement was noted in most study sub-segments, it was reversed for women (1.53%), government insurance (Medicare/Medicaid) recipients (7.72%), and older workers (9.16%). The results also revealed a high annual percentage rate (APC) decrease for Hispanics (-9.65%) for the period 1998-2004, jumping to (-18.65%) from 2007 to 2009. A similar pattern with two models was noted for the younger [18-24] age group where the annual percentage rate decreased constantly by (-2.08%) during the period 1998-2007 and drastically jumped to (-18.34%) from 2007 to 2009. In conclusion, a comprehensive trend analysis of industry-related occupational injuries recorded nationwide within the United States as presented in this study is useful to policy makers in formulating targeted strategies and allocation of resources as needed to address disparities found at various levels. Disparities found in trends observed from a gender angle calls for action to reverse the positive rate recorded for females (1.53%) when compared to males (-2.74%). Similarly, there is a call for action to address the age demographic disparity for older worker, the "≥65" age group exhibiting an alarming rate of occupational injuries (9.16%), bucking an across-the-board general negative trend.

No description available.

Motor vehicle crash (MVC) and its associated injuries remain a major public health problem world wide. In 2005 alone there were 6 million police-reported crashes in the United States resulting in 2.5 million injuries and 46,000 fatalities. The thorax is second only to the head in terms of frequency of injury following MVC, and pulmonary contusion (PC) is the most common intra-thoracic soft tissue injury sustained as a result of blunt chest trauma. The goal of this dissertation research is to mitigate this commonly-sustained and potentially life threatening injury. We have taken a computational approach to solving this problem by developing a predictive injury metric for PC using finite element analysis (FEA). The dissertation begins with an epidemiological examination of the crash modes, vehicles, and patient demographics most commonly associated with PC. This study was conducted using real world crash data from the Crash Injury Research and Engineering Network (CIREN) database and data from government-sponsored vehicle crash tests. The CIREN data showed that a substantial portion of the crashes resulting in PC were lateral impacts (48%). Analysis of the thoracic loading of dummy occupants in lateral crash tests resulted in mean values of medial-lateral chest compression and deflection velocity of 25.3 ± 2.6 % and 4.6 ± 0.42 m·s-1 respectively. These data provided quantified loading conditions associated with crash-induced PC and a framework for the remaining research studies, which were focused on blunt impact experiments examining the relationship between insult and outcome in a living model of this injury. A combined experimental and computational approach was used to develop injury metrics for PC. The animal model selected for this research was the Sprague-Dawley male rat. In the remaining studies that comprise this dissertation, an outcome measure of the inflammatory response in the lung parenchyma was correlated with a mechanical analog calculated via a finite element model of the lung. For all studies, a precise and instrumented electronic piston was used to apply prescribed insults directly to the lungs of the subjects. In the first set of experiments, contusion volume was calculated from MicroPET (Micro Positron Emission Tomography) scans and normalized on the basis of liver uptake of 18F-FDG. The subjects were scanned at 24 hours, 7 days, and 28 days (15 scans), and the contused volume was measured. A tentative criteria based on first principal strain in the parenchyma between 9 and 36% was established. In subsequent experiments Computed Tomography was used to acquire volumetric contusion data. The second set of experiments introduced two important aspects of this dissertation; a semi-automated algorithm for CT segmentation and a technique to match the spatial distribution of contusion within the lung to finite element analysis results. The results of this study indicated that the product of first principal strain and strain rate is the most appropriate output variable upon which to base an injury metric for PC. Digital analysis of histology from study subjects that underwent CT scanning prior to sacrifice was conducted and showed good agreement between CT and histology. A final set of experiments was conducted to synthesize the techniques developed in previous studies to determine an injury metric for PC. A concurrent optimization technique was applied to the FEA model to match force vs. deflection traces from four distinct impact cohorts. The resulting predictive injury metrics for PC were exceeding 94.5 sec-1, first principal strain exceeding 0.284 (true strain, dimensionless), and first principal strain rate exceeding 470 sec-1. The method used in this dissertation and the resulting injury metrics for PC are based on quantified inflammatory response observed in a living model, specifically in the organ of interest. This injury metric improves upon current thoracic injury criteria that rely on gross measures of chest loading such as acceleration, or deflection, and are not specific to a particular injury. We anticipate that the findings of this work will lead to more data-driven improvements to vehicular safety systems and ultimately diminish the instance of PC and mitigate its severity. / Ph. D.

Les impacts non transfixiants sur les gilets pare-balles sont responsables de lésions non pénétrantes potentiellement létales, regroupées sous le terme d’effets arrière (Behind Armor Blunt Trauma : BABT). De telles lésions fermées se retrouvent également lors d’impacts thoraciques de projectiles d’Armes à Létalité Réduite cinétiques (ALRc). Afin d’améliorer le pouvoir protecteur des protections balistiques et de mieux maitriser le pouvoir vulnérant des ALRc, il est nécessaire de définir un critère lésionnel permettant de prédire l’importance des lésions en cas de traumatisme thoracique fermé de type balistique. Ce critère se doit d’être bien corrélé à la gravité du traumatisme, et de pouvoir être facilement transposable à l’ensemble des systèmes d’évaluation des protections balistiques et des ALRc. La gravité du traumatisme a été définie ici par le volume de la contusion pulmonaire. L’utilisation de cette valeur nécessitait le recours au modèle animal. Or, nous avons démontré que le thorax du modèle porcin n’offrait pas le même comportement biomécanique lors de l’impact que le thorax de l’adulte jeune. Nous avons donc développé un critère, l’impulsion de pression intrathoracique maximale (PImax), basé sur la mesure de la pression intrathoracique lors de l’impact, et donc indépendant du comportement biomécanique de la paroi thoracique vis-à-vis de ses effets sur le poumon. Ce critère très bien corrélé avec le volume de la contusion pulmonaire, quelque soit le type d’impact thoracique balistique (ALRc ou BABT), a l’avantage de pouvoir être transposable aux autres moyens d’évaluations balistiques tels que les modèles numériques ou mécaniques de thorax, afin de s’affranchir de l’expérimentation animale / When non-penetrating, impacts on bulletproof jackets can lead to potentially lethal blunt injuries known as behind armor blunt trauma (BABT). Impacts of less lethal kinetic weapons (LLKW) can also lead to such injuries. To both improve the protection capabilities of the BPJ and better comprehend the ounding potential of the LLKW, we need to design a wounding criterion to predict the injury severity of ballistic blunt thoracic trauma. In one hand, this criterion has to be well correlated with the severity of the injuries, and in the other hand, it has to be easily used with all the LLKW and BPJ assessment systems in use. First, we defined the pulmonary contusion volume as the severity of the injuries. Studying the pulmonary contusion involves the use of animal experiments. But we demonstrated that the biomechanics of the chest wall are different in animals and young adults. Then, we developed the maximum pressure impulse criterion (PImax). As it is based on the intrathoracic pressure measure during the blunt impact, it is independent from the chest wall behavior. This criterion can be used with the other assessment tools as the numerical simulation mechanical chest surrogates. This can help to reduce the use of animal experiments, which is more and more expensive, heavy and questionable on the ethical aspect