Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury.

BACKGROUND: Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology. METHODS: In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS RESULTS: Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP >or= 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained 128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained CONCLUSIONS: Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.

Penetrating injuries of the thorax and abdomen: Type of medical-care institution and case fatality

The purpose of this study was to determine, for penetrating injuries (gunshot, stab) of the chest/abdomen, the impact on fatality of treatment in trauma centers and shock trauma units compared with general hospitals. Medical records of all cases of penetrating injury limited to chest/abdomen and admitted to and discharged from 7 study facilities in Baltimore city 1979-1980 (n = 581) were studied: 4 general hospitals (n = 241), 2 area-wide trauma centers (n = 298), and a shock trauma unit (n = 42). Emergency center and transferred cases were not studied. Anatomical injury severity, measured by modified Injury Severity Score (mISS), was a significant prognostic factor for death, as were cardiovascular shock (SBP $\le$ 70), injury type (gunshot vs stab), and ambulance/helicopter (vs other) transport. All deaths occurred in cases with two or more prognostic factors. Unadjusted relative risks of death compared with general hospitals were 4.3 (95% confidence interval = 2.2, 8.4) for shock trauma and 0.8 (0.4, 1.7) for trauma centers. Controlling for prognostic factors by logistic regression resulted in these relative risks: shock trauma 4.0 (0.7, 22.2), and trauma centers 0.8 (0.2, 3.2). Factors significantly associated with increased risk had the following relative risks by multiple logistic regression: SBP $\le$ 70 (RR = 40.7 (11.0, 148.7)), highest mISS (42 (7.7, 227)), gunshot (8.4 (2.1, 32.6)), and ambulance/helicopter transport (17.2 (1.3, 228.1)). Controlling for age, race, and gender did not alter results significantly. Actual deaths compared with deaths predicted from a multivariable model of general-hospital cases showed 3.7 more than predicted deaths in shock trauma (SMR = 1.6 (0.8, 2.9)) and 0.7 more than predicted deaths in area-wide trauma centers (SMR = 1.05 (0.6, 1.7)). Selection bias due to exclusion of transfers and emergency center cases, and residual confounding due to insufficient injury information, may account for persistence of adjusted high case fatality in shock trauma. Studying all cases prospectively, including emergency center and transferred cases, is needed. ^

Subacute neural stem cell therapy for traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) frequently results in devastating and prolonged morbidity. Cellular therapy is a burgeoning field of experimental treatment that has shown promise in the management of many diseases, including TBI. Previous work suggests that certain stem and progenitor cell populations migrate to sites of inflammation and improve functional outcome in rodents after neural injury. Unfortunately, recent study has revealed potential limitations of acute and intravenous stem cell therapy. We studied subacute, direct intracerebral neural stem and progenitor cell (NSC) therapy for TBI. MATERIALS AND METHODS: The NSCs were characterized by flow cytometry and placed (400,000 cells in 50 muL 1x phosphate-buffered saline) into and around the direct injury area, using stereotactic guidance, of female Sprague Dawley rats 1 wk after undergoing a controlled cortical impact injury. Immunohistochemistry was used to identify cells located in the brain at 48 h and 2 wk after administration. Motor function was assessed using the neurological severity score, foot fault, rotarod, and beam balance. Cognitive function was assessed using the Morris water maze learning paradigm. Repeated measures analysis of variance with post-hoc analysis were used to determine significance at P < 0.05. RESULTS: Immunohistochemistry analysis revealed that 1.4-1.9% of infused cells remained in the neural tissue at 48 h and 2 wk post placement. Nearly all cells were located along injection tracks at 48 h. At 2 wk some cell dispersion was apparent. Rotarod motor testing revealed significant increases in maximal speed among NSC-treated rats compared with saline controls at d 4 (36.4 versus 27.1 rpm, P < 0.05) and 5 (35.8 versus 28.9 rpm, P < 0.05). All other motor and cognitive evaluations were not significantly different compared to controls. CONCLUSIONS: Placement of NSCs led to the cells incorporating and remaining in the tissues 2 wk after placement. Motor function tests revealed improvements in the ability to run on a rotating rod; however, other motor and cognitive functions were not significantly improved by NSC therapy. Further examination of a dose response and optimization of placement strategy may improve long-term cell survival and maximize functional recovery.

Quantitative MRI of spinal cord injury in a rat model: Correlative studies

Serial quantitative and correlative studies of experimental spinal cord injury (SCI) in rats were conducted using three-dimensional magnetic resonance imaging (MRI). Correlative measures included morphological histopathology, neurobehavioral measures of functional deficit, and biochemical assays for N-acetyl-aspartate (NAA), lactate, pyruvate, and ATP. A spinal cord injury device was characterized and provided a reproducible injury severity. Injuries were moderate and consistent to within $\pm$20% (standard deviation). For MRI, a three-dimensional implementation of the single spin-echo FATE (Fast optimum angle, short TE) pulse sequence was used for rapid acquisition, with a 128 x 128 x 32 (x,y,z) matrix size and a 0.21 x 0.21 x 1.5 mm resolution. These serial studies revealed a bimodal characteristic in the evolution in MRI pathology with time. Early and late phases of SCI pathology were clearly visualized in $T\sb2$-weighted MRI, and these corresponded to specific histopathological changes in the spinal cord. Centralized hypointense MRI regions correlated with evidence of hemorrhagic and necrotic tissue, while surrounding hyperintense regions represented edema or myelomalacia. Unexpectedly, $T\sb2$-weighted MRI pathology contrast at 24 hours after injury appeared to subside before peaking at 72 hours after injury. This change is likely attributable to ongoing secondary injury processes, which may alter local $T\sb2$ values or reduce the natural anisotropy of the spinal cord. MRI, functional, and histological measures all indicated that 72 hours after injury was the temporal maximum for quantitative measures of spinal cord pathology. Thereafter, significant improvement was seen only in neurobehavioral scores. Significant correlations were found between quantitated MRI pathology and histopathology. Also, NAA and lactate levels correlated with behavioral measures of the level of function deficit. Asymmetric (rostral/caudal) changes in NAA and lactate due to injury indicate that rostral and caudal segments from the injury site are affected differently by the injury. These studies indicate that volumetric quantitation of MRI pathology from $T\sb2$-weighted images may play an important role in early prediction of neurologic deficit and spinal cord pathology. The loss of $T\sb2$ contrast at 24 hours suggests MR may be able to detect certain delayed mechanisms of secondary injury which are not resolved by histopathology or other radiological modalities. Furthermore, in vivo proton magnetic resonance spectroscopy (MRS) studies of SCI may provide a valuable addition source of information about changes in regional spinal cord lactate and NAA levels, which are indicative of local metabolic and pathological changes. ^

Trauma care capacity and performance in Texas: Regional comparisons

Objective. The study reviewed one year of Texas hospital discharge data and Trauma Registry data for the 22 trauma services regions in Texas to identify regional variations in capacity, process of care and clinical outcomes for trauma patients, and analyze the statistical associations among capacity, process of care, and outcomes. ^ Methods. Cross sectional study design covering one year of state-wide Texas data. Indicators of trauma capacity, trauma care processes, and clinical outcomes were defined and data were collected on each indicator. Descriptive analyses were conducted of regional variations in trauma capacity, process of care, and clinical outcomes at all trauma centers, at Level I and II trauma centers and at Level III and IV trauma centers. Multilevel regression models were performed to test the relations among trauma capacity, process of care, and outcome measures at all trauma centers, at Level I and II trauma centers and at Level III and IV trauma centers while controlling for confounders such as age, gender, race/ethnicity, injury severity, level of trauma centers and urbanization. ^ Results. Significant regional variation was found among the 22 trauma services regions across Texas in trauma capacity, process of care, and clinical outcomes. The regional trauma bed rate, the average staffed bed per 100,000 varied significantly by trauma service region. Pre-hospital trauma care processes were significantly variable by region---EMS time, transfer time, and triage. Clinical outcomes including mortality, hospital and intensive care unit length of stay, and hospital charges also varied significantly by region. In multilevel regression analysis, the average trauma bed rate was significantly related to trauma care processes including ambulance delivery time, transfer time, and triage after controlling for age, gender, race/ethnicity, injury severity, level of trauma centers, and urbanization at all trauma centers. Transfer time only among processes of care was significant with the average trauma bed rate by region at Level III and IV. Also trauma mortality only among outcomes measures was significantly associated with the average trauma bed rate by region at all trauma centers. Hospital charges only among outcomes measures were statistically related to trauma bed rate at Level I and II trauma centers. The effect of confounders on processes and outcomes such as age, gender, race/ethnicity, injury severity, and urbanization was found significantly variable by level of trauma centers. ^ Conclusions. Regional variation in trauma capacity, process, and outcomes in Texas was extensive. Trauma capacity, age, gender, race/ethnicity, injury severity, level of trauma centers and urbanization were significantly associated with trauma process and clinical outcomes depending on level of trauma centers. ^ Key words: regionalized trauma systems, trauma capacity, pre-hospital trauma care, process, trauma outcomes, trauma performance, evaluation measures, regional variations ^

A descriptive and exploratory analysis of occupational injuries at a chemical manufacturing facility

A retrospective study of 1353 occupational injuries occurring at a chemical manufacturing facility in Houston, Texas from January, 1982 through May, 1988 was performed to investigate the etiology of the occupational injury process. Injury incidence rates were calculated for various sub-populations of workers to determine differences in the risk of injury for various groups. Linear modeling techniques were used to determine the association between certain collected independent variables and severity of an injury event. Finally, two sub-groups of the worker population, shiftworkers and injury recidivists, were examined. An injury recidivist as defined is any worker experiencing one or more injury per year. Overall, female shiftworkers evidenced the highest average injury incidence rate compared to all other worker groups analyzed. Although the female shiftworkers were younger and less experienced, the etiology of their increased risk of injury remains unclear, although the rigors of performing shiftwork itself or ergonomic factors are suspect. In general, females were injured more frequently than males, but they did not incur more severe injuries. For all workers, many injuries were caused by erroneous or foregone training, and risk taking behaviors. Injuries of these types are avoidable. The distribution of injuries by severity level was bimodal; either injuries were of minor or major severity with only a small number of cases falling in between. Of the variables collected, only the type of injury incurred and the worker's titlecode were statistically significantly associated with injury severity. Shiftworkers did not sustain more severe injuries than other worker groups. Injury to shiftworkers varied as a 24-hour pattern; the greatest number occurred between 1200-1230 hours, (p = 0.002) by Cosinor analysis. Recidivists made up 3.3% of the population (23 males and 10 females), yet suffered 17.8% of the injuries. Although past research suggests that injury recidivism is a random statistical event, analysis of the data by logistic regression implicates gender, area worked, age and job titlecode as being statistically significantly related to injury recidivism at this facility. ^

Clostridium difficile infection (CDI): Clinical outcomes associated with concomitant non-CDI antibiotic use

This research examined the relationship between concomitant non-CDI antibiotic use and complications arising due to Clostridium difficile infection. To observe the hypothesized association, 160 total CDI patients between the ages of 50-90 were selected, 80 exposed to concomitant antibiotics and 80 unexposed. Samples were matched based upon their age and Horn's index, a severity score for underlying illness. Patients were de-identified by a third party, and analyzed retrospectively for differences between the two groups. In addition, patients exposed to broad spectrum antibiotics at the time of CDI treatment were further studied to demonstrate whether antibiotics had any effect on CDI complications. Between the two groups, the outcomes of interest (recurrent CDI, refractory CDI, mortality, ICU stay, and length of hospitalization) were not associated with concomitant antibiotic use at the time of CDI therapy. However, within the exposed population, certain classes of antibiotics such as cephalosporin, antifungals, and tetracyclines were more common in patients compared to other types of therapy. In addition, days of therapy provided evidence that sustained use of antibiotics affected CDI (p = 0.08), although a more robust sample size and additional study would be needed. Finally, refractory CDI was found to be potentially overestimated within the exposed population due to the possibility of antibiotic-associated diarrhea.^

Effect of Acute Administration of Angiopoietin-1 in Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging and Neurobehavioral Studies

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI. In these studies, angiopoietin-1 (Ang1), an agent known to reduce vascular permeability, was hypothesized to attenuate the severity of secondary injuries of SCI. Using longitudinal magnetic resonance imaging (MRI) studies (dynamic contrast-enhanced [DCE]-MRI for quantification of BSCB permeability, highresolution anatomical MRI for calculation of lesion size, and diffusion tensor imaging for assessment of axonal integrity), the acute, subacute, and chronic effects of Ang1 administration after SCI were evaluated. Neurobehavioral assessments were also performed. These non-invasive techniques have applicability to the monitoring of therapies in patients with SCI. In the acute phase of injury, Ang1 was found to reduce BSCB permeability and improve neuromotor recovery. Dynamic contrast-enhanced MRI revealed a persistent compromise of the BSCB up to two months post-injury. In the subacute phase of injury, Ang1’s effect on reducing BSCB permeability was maintained and it was found to transiently reduce axonal integrity. The SCI lesion burden was assessed with an objective method that compared favorably with segmentations from human raters. In the chronic phase of injury, Ang1 resulted in maintained reduction in BSCB permeability, a decrease in lesion size, and improved axonal integrity. Finally, longitudinal correlations among data from the MRI modalities and neurobehavioral assays were evaluated. Locomotor recovery was negatively correlated with lesion size in the Ang1 cohort and positively correlated with diffusion measures in the vehicle cohort. In summary, the results demonstrate a possible role for Ang1 in mitigating the secondary pathologies of SCI during the acute and chronic phases of injury.

Effect of VEGF treatment on the blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced magnetic resonance imaging.

Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

The association of internet use and depression among spinal cord injury population

The purpose of this study was to exam the relationship between internet use and depression among a population of individuals who have sustained spinal cord injury. This was cross-sectional survey design conducted among spinal cord injury (SCI) patients in the Model Spinal Cord Injury System. We included a total of 1,011 SCI-patients who were interviewed face-to-face or by telephone interview over approximately a three year time period (2004–2006). All data were collected through a telephone survey which included the Patient Health Questionnaire-9 (PHQ-9) to assess depression. We examined various scales of this survey, included a reduced 3-item scale (items 1, 2 and 6) to avoid the presence of somatic symptoms among SCI patients from influencing classification of depression. The frequency of internet usage was grouped as daily/weekly/monthly/non user. Covariates examined as possible confounders included demographic characteristics, occupational status, educational level, injury type, daily function of living, pain level, self-perceived health status and satisfaction with life. We observed a negative association between the frequency of internet use and the level of depression. Daily use of internet was associated with lower PHQ-9 score and depression; however this association did not reach statistical significance after for the mentioned covariates. In conclusion, the factors related to lower depression in SCI patients who use the internet are complicated. Daily internet usage was associated with lower levels of depression. The accuracy of 3-item scale needs further validation and investigation. Further study of internet usage pattern in SCI patient is recommended. ^

Frequency, severity and distress of dialysis-related symptoms reported by patients on hemodialysis

Purpose. To determine which symptoms are the most reported, occur most frequently, have the greatest severity, and cause the most bother for hemodialysis (HD) patients and to determine if the symptoms experienced differ between the first (HD 1) and second (HD 2) treatments of the week. ^ Design. An observational, comparative design was used to determine participants' HD symptoms experience on HD 1 and HD 2, and the effect of the symptom experience on Quality of Life (QOL). One hundred subjects were recruited from five dialysis centers. ^ Methods. The adapted Dialysis Frequency, Severity and Symptom Burden Index (DFSSBI) and the Medical Outcomes Study Short Form 36 (MOS SF 36) were administered (N = 99) on HD 1 and the DFSSBI again on HD 2. Data were analyzed for significance among symptoms experience test scores in relation to HD 1 and HD 2, QOL, and gender and age. ^ Results. Of 31 symptoms assessed, respondents reported an average of 9.69 symptoms on HD 1 and 7.51 symptoms on HD 2. Overall, more symptoms were reported, and were more frequent, severe and bothersome on HD 1 when the level of metabolic waste is highest. The most reported symptoms included tiredness, dry skin, difficulty falling asleep, itching, numbness/tingling, difficulty staying asleep, decreased interest in sex, and bone/joint pain. Females scored consistently higher than males in the four symptom dimensions. The respondents reported about the same as the population norm (50) on the physical component summary score of the MOS SF 36 and higher than the norm (65.23) on the mental component summary score. ^ Conclusion. The study findings highlighted the fact that hemodialysis patients experience multiple symptoms that can be frequent, severe, and bothersome. Interventions should be developed and tested to reduce symptom burden and improve QOL. ^

SEVERE HEAD TRAUMA, EMERGENCY TRANSPORT, AND PATIENT OUTCOME

Trauma and severe head injuries are important issues because they are prevalent, because they occur predominantly in the young, and because variations in clinical management may matter. Trauma is the leading cause of death for those under age 40. The focus of this head injury study is to determine if variations in time from the scene of accident to a trauma center hospital makes a difference in patient outcomes.^ A trauma registry is maintained in the Houston-Galveston area and includes all patients admitted to any one of three trauma center hospitals with mild or severe head injuries. A study cohort, derived from the Registry, includes 254 severe head injury cases, for 1980, with a Glasgow Coma Score of 8 or less.^ Multiple influences relate to patient outcomes from severe head injury. Two primary variables and four confounding variables are identified, including time to emergency room, time to intubation, patient age, severity of injury, type of injury and mode of transport to the emergency room. Regression analysis, analysis of variance, and chi-square analysis were the principal statistical methods utilized.^ Analysis indicates that within an urban setting, with a four-hour time span, variations in time to emergency room do not provide any strong influence or predictive value to patient outcome. However, data are suggestive that at longer time periods there is a negative influence on outcomes. Age is influential only when the older group (55-64) is included. Mode of transport (helicopter or ambulance) did not indicate any significant difference in outcome.^ In a multivariate regression model, outcomes are influenced primarily by severity of injury and age which explain 36% (R('2)) of variance. Inclusion of time to emergency room, time to intubation, transport mode and type injury add only 4% (R('2)) additional contribution to explaining variation in patient outcome.^ The research concludes that since the group most at risk to head trauma is the young adult male involved in automobile/motorcycle accidents, more may be gained by modifying driving habits and other preventive measures. Continuous clinical and evaluative research are required to provide updated clinical wisdom in patient management and trauma treatment protocols. A National Institute of Trauma may be required to develop a national public policy and evaluate the many medical, behavioral and social changes required to cope with the country's number 3 killer and the primary killer of young adults.^

External validation study of a clinical prediction rule for ambulation outcomes after traumatic spinal cord injury

The main objective of this study was to determine the external validity of a clinical prediction rule developed by the European Multicenter Study on Human Spinal Cord Injury (EM-SCI) to predict the ambulation outcomes 12 months after traumatic spinal cord injury. Data from the North American Clinical Trials Network (NACTN) data registry with approximately 500 SCI cases were used for this validity study. The predictive accuracy of the EM-SCI prognostic model was evaluated using calibration and discrimination based on 231 NACTN cases. The area under the receiver-operating-characteristics curve (ROC) curve was 0.927 (95% CI 0.894 – 0.959) for the EM-SCI model when applied to NACTN population. This is lower than the AUC of 0.956 (95% CI 0.936 – 0.976) reported for the EM-SCI population, but suggests that the EM-SCI clinical prediction rule distinguished well between those patients in the NACTN population who were able to achieve independent ambulation and those who did not achieve independent ambulation. The calibration curve suggests that higher the prediction score is, the better the probability of walking with the best prediction for AIS D patients. In conclusion, the EM-SCI clinical prediction rule was determined to be generalizable to the adult NACTN SCI population.^