Focal Neurologic Deficit After Epidural Catheter Removal Leads to Meningioma Diagnosis.

We present an unusual case of a 60-year-old female who developed subtle, new-onset left upper and lower extremity weakness on day five of perioperative thoracic epidural placement. The onset of a focal neurological deficit after epidural placement usually raises suspicion for the presence of an epidural hematoma, abscess, or traumatic cord lesion. However, in this patient, brain imaging revealed a large, previously undiagnosed intracranial mass. Classically, the risk of mass-related intracranial pressure shifts leading to neurological changes is associated with spinal techniques, including diagnostic lumbar puncture, combined spinal-epidural catheter analgesia, and unintended dural puncture during epidural placement. However, based on this case and our summary of case reports in the literature, we determined that symptom onset associated with an intracranial mass may also arise after apparently uncomplicated epidural placement. Symptom onset in our case series ranged from six hours to ten days and was highly variable depending on tumor location, with reported signs and symptoms including headache, vision changes, focal deficits, or alterations of consciousness. Further studies are required to establish definitive causation between the epidural technique and changes in cerebrospinal fluid pressures leading to symptom onset. Though rare, this is a time-sensitive diagnosis that must be considered for any patient with unexplained neurological findings after neuraxial anesthesia.

Medical biofilms--nanotechnology approaches.

Biofilms are colonies of bacteria or fungi that adhere to a surface, protected by an extracellular polymer matrix composed of polysaccharides and extracellular DNA. They are highly complex and dynamic multicellular structures that resist traditional means of killing planktonic bacteria. Recent developments in nanotechnology provide novel approaches to preventing and dispersing biofilm infections, which are a leading cause of morbidity and mortality. Medical device infections are responsible for approximately 60% of hospital acquired infections. In the United States, the estimated cost of caring for healthcare-associated infections is approximately between $28 billion and $45 billion per year. In this review, we will discuss our current understanding of biofilm formation and degradation, its relevance to challenges in clinical practice, and new technological developments in nanotechnology that are designed to address these challenges.

Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.

Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The novel nanoprodrug contains a derivative of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen in an emulsion with the antioxidant α-tocopherol. The ibuprofen derivative, Ibu2TEG, contains a tetra ethylene glycol (TEG) spacer consisting of biodegradable ester bonds. The biodegradable ester bonds ensure that the prodrug molecules break down hydrolytically or enzymatically. The drug is labeled with the fluorescent reporter Cy5.5 using nonbiodegradable bonds to 1-octadecanethiol, allowing us to reliably track its accumulation in the brain after TBI. We delivered a moderate injury using a highly reproducible mouse model of closed-skull controlled cortical impact to the parietal region of the cortex, followed by an injection of the nanoprodrug at a dose of 0.2 mg per mouse. The blood brain barrier is known to exhibit increased permeability at the site of injury. We tested for accumulation of the fluorescent drug particles at the site of injury using confocal and bioluminescence imaging of whole brains and brain slices 36 hours after administration. We demonstrated that the drug does accumulate preferentially in the region of injured tissue, likely due to an enhanced permeability and retention (EPR) phenomenon. The use of a nanoprodrug approach to deliver therapeutics in TBI represents a promising potential therapeutic modality.

Insurance-and race-related disparities decrease in elderly trauma patients.

BACKGROUND: Little focus is on health care disparities in the elderly, a population largely covered by public insurance. We characterized insurance type and race in elderly trauma patients to determine if lack of insurance or minority status predict increased mortality. METHODS: The National Trauma Data Bank (version 7.0) was queried for all adult blunt trauma patients. We divided patients into two cohorts (15-64 or ≥ 65 years) based on age for universal Medicare eligibility. Our primary outcome measure was in-hospital mortality. Multiple logistic regression was used to control for confounding variables. RESULTS: A total of 541,471 patients met inclusion criteria. Among younger patients, the most common insurance type was private (41.0%), with 26.9% uninsured. In contrast, the most common insurance type among older patients was Medicare (64.6%), with 6.0% uninsured. Within the younger cohort, private insurance (adjusted odds ratio [AOR], 0.6; p < 0.01) and other insurance (AOR, 0.8; p < 0.01) predicted reduced mortality, while Medicare predicted similar mortality (AOR, 1.1; p = 0.18) compared with no insurance. Black race (AOR, 1.4; p < 0.01) and Hispanic ethnicity (AOR, 1.4; p < 0.01) predicted higher mortality compared with white race. Within the older cohort, no insurance predicted similar mortality as Medicare (AOR, 1.0; p = 0.43), private insurance (AOR, 1.0; p = 0.51), and other insurance (AOR, 1.0; p = 0.71). Hispanic ethnicity predicted increased mortality (AOR, 1.4; p < 0.01), while Asian race was protective (AOR, 0.7; p = 0.01) compared with white race. CONCLUSION: Elderly trauma patients present primarily with Medicare, while younger trauma patients are mostly privately insured; elderly patients are four times more likely to be insured. Disparities caused by lack of insurance and minority race are reduced in elderly trauma patients. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

ß-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, and inflammatory response after traumatic brain injury.

BACKGROUND: The purpose of this study was to evaluate how ß-adrenergic receptor inhibition after traumatic brain injury (TBI) alters changes in early cerebral glucose metabolism and motor performance, as well as cerebral cytokine and heat shock protein (HSP) expression. METHODS: Mouse cerebral glucose metabolism was measured by microPET fluorodeoxyglucose uptake and converted into standardized uptake values (SUV). Four groups of C57/Bl6 mice (wild type [WT]) were initially evaluated: sham or TBI, followed by tail vein injection of either saline or a nonselective ß-adrenergic receptor inhibitor (propranolol, 4 mg/kg). Then motor performance, cerebral cytokine, and HSP70 expression were studied at 12 hours and 24 hours after sham injury or TBI in WT mice treated with saline or propranolol and in ß1-adrenergic/ß2-adrenergic receptor knockout (BARKO) mice treated with saline. RESULTS: Cerebral glucose metabolism was significantly reduced after TBI (mean SUV TBI, 1.63 vs. sham 1.97, p < 0.01) and propranolol attenuated this reduction (mean SUV propranolol, 1.89 vs. saline 1.63, p < 0.01). Both propranolol and BARKO reduced motor deficits at 24 hours after injury, but only BARKO had an effect at 12 hours after injury. TBI WT mice treated with saline performed worse than propranolol mice at 24 hours after injury on rotarod (23 vs. 44 seconds, p < 0.01) and rearing (130 vs. 338 events, p = 0.01) results. At 24 hours after injury, sham BARKO and TBI BARKO mice were similar on rotarod (21 vs. 19 seconds, p = 0.53), ambulatory testing (2,891 vs. 2,274 events, p = 0.14), and rearing (129 vs. 64 events, p = 0.09) results. Interleukin 1ß expression was affected by BARKO and propranolol after TBI; attenuation of interleukin 6 and increased HSP70 expression were noted only with BARKO. CONCLUSION: ß-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, as well as cerebral cytokine and HSP expression after TBI.

Elevated systolic blood pressure after trauma: tolerated in the elderly.

BACKGROUND: We undertook the current study to determine the impact of elevated admission systolic blood pressure (SBP) on trauma patients without severe brain injury. MATERIALS AND METHODS: We conducted a retrospective review of the Los Angeles County Trauma System database to identify all patients with moderate to severe injuries (injury severity score >9) admitted between 2003 and 2008. Patients with head abbreviated injury score >3 were excluded. We divided the remaining patients into three age cohorts and conducted multivariate regression modeling at increasing SBP thresholds to identify independent predictors of mortality. RESULTS: A total of 23,931 patients met inclusion criteria. Overall mortality was 8.6% and it increased with age across the three groups. The admission SBP thresholds associated with significantly increased mortality in the young and middle-aged were >190 mm Hg (AOR 1.5, P = 0.04) and >180 mm Hg (AOR 1.5, P = 0.01), respectively. In the elderly, no admission SBP threshold was associated with significantly increased mortality. Interestingly, several elevated admission SBP thresholds were associated with significantly reduced mortality in the elderly (>150 mm Hg AOR 0.6, P < 0.01; >160 mm Hg AOR 0.6, P < 0.01; and >170 mm Hg AOR 0.7, P = 0.02). CONCLUSIONS: The admission SBP thresholds that predicted higher mortality for the young and middle-aged were >190 mm Hg and >180 mm Hg, respectively. Elderly trauma patients tolerated higher admission SBP than their younger counterparts and multiple elevated SBP thresholds were associated with significantly reduced mortality in the elderly.

Long-term effect of trauma splenectomy on blood glucose.

BACKGROUND: Increasing evidence suggests that the spleen harbors stem cells that act as precursors to insulin-producing pancreas cells. Additionally, small studies with short-term follow-up associate splenectomy with increased rates of diabetes mellitus. The purpose of this study was to analyze the long-term effect of trauma splenectomy on blood glucose. MATERIALS AND METHODS: Patients were included if a blood glucose level was measured more than 5 y after trauma splenectomy or laparotomy with bowel repair. Mean blood glucose level was then compared between the two groups. RESULTS: During the 10-y study period 61 patients underwent trauma splenectomy and 50 survived until discharge. In comparison, 229 patients underwent trauma laparotomy and bowel repair and 207 survived until discharge. Nine splenectomy patients compared with 12 control patients had, blood glucose measured at least 5 y after initial trauma. Mean follow-up period was not significantly different between groups (splenectomy 82.8 ± 17.6 mo versus control 96.0 ± 44.3 mo, P = 0.41). In the splenectomy cohort mean glucose level was significantly higher compared with the control (114 ± 34 mg/dL versus 90 ± 13 mg/dL, P = 0.04), as was the number of patients with recorded blood glucose level greater than 130 mg/dL (4 patient versus 0 patients P = 0.02). One new diagnosis of diabetes mellitus was noted only in the trauma splenectomy cohort. CONCLUSIONS: This small study suggests that trauma splenectomy may be associated with hyperglycemia at long-term follow-up.

Admission heart rate is a predictor of mortality.

BACKGROUND: The association between admission heart rate (AHR) and mortality after trauma can assist initial emergency department triage and resuscitation. In addition, increased AHR is often associated with sympathetic hyperactivity which may require targeted treatment. We determined whether AHR was a predictor for mortality in trauma patients. METHODS: The Los Angeles County Trauma System Database was queried for all injured patients admitted between 1998 and 2005 (n = 147,788). Traumatic brain injury (TBI) patients (head Abbreviated Injury Scale score ≥ 3) were excluded. Demographics were compared at various AHR subgroups (<50, 50-59, 60-69, 70-79, 80-89, 90-99, 100-109, and ≥ 110). Mortality was compared at various AHR ranges, and logistic regression was performed to determine significance. RESULTS: After exclusions, 103,799 trauma patients requiring admission were identified; overall mortality was 1.4%. AHR 80 to 89 demonstrated a statistically significant lower mortality (0.5%) compared with all other AHR ranges, except AHR 70 to 79 (0.6%). In trauma patients who required admission, AHR 70 to 79 and 80 to 89 were predictors of lower mortality. Mortality for 22,232 moderate to severely injured patients was 5.5% and AHR 80 to 89 demonstrated a statistically lower mortality (2.0%) than all other AHR ranges, except AHR 70 to 79 (1.9%). After moderate to severe trauma, AHR <60 and ≥ 100 were associated with significantly higher mortality. CONCLUSION: Mortality after trauma increases outside the AHR range of 70 to 89 beats per minute. AHR ranges previously considered "normal" were associated with significantly increased mortality. Prospective research is required to evaluate if resuscitation goals should target heart rate at the 70 to 89 range.

Gender influences outcomes in trauma patients with elevated systolic blood pressure.

BACKGROUND: This analysis explored the association between gender and systolic blood pressure (SBP) in trauma patients and then established how gender influenced outcomes in those with elevated SBP. METHODS: Demographics and outcomes were compared using the Los Angeles County Trauma System Database and multivariable modeling determined predictors for SBP, pneumonia, and mortality. RESULTS: Age and male sex were significant predictors for increased SBP, whereas the Injury Severity Score (ISS) ≥16 was a significant predictor for decreased SBP. In both male and female TBI patients, SBP ≥160 mmHg was associated with increased pneumonia (Adjusted odds ratio [AOR] = 1.74, P = .002 and AOR = 2.37, P = .046, respectively), whereas SBP ≥160 mmHg was a predictor for mortality only among male TBI patients (AOR = 1.48, P = .03). In non-TBI patients, SBP ≥160 mmHg was not a predictor for pneumonia or mortality in either sex. CONCLUSIONS: In this retrospective review of trauma registry data, men presented with higher SBP. In patients with TBI, regardless of gender, increased SBP was associated with increased pneumonia, and in men with TBI increased SBP was associated with increased mortality. The cause and relevance of these epidemiological findings require further investigation.

Mortality by decade in trauma patients with Glasgow Coma Scale 3.

The aim of this study was to assess how increasing age affects mortality in trauma patients with Glasgow Coma Scale (GCS) 3. The Los Angeles County Trauma System Database was queried for all patients aged 20 to 99 years admitted with GCS 3. Mortality was 41.8 per cent for the 3306 GCS 3 patients. Mortality in the youngest patients reviewed, those in the third decade, was 43.5 per cent. After logistic regression analysis, patients in the third decade had similar mortality rates to patients in the sixth (adjusted OR, 0.88; CI, 0.68 to 1.14; P = 0.33) and seventh decades (adjusted OR, 0.96; CI, 0.70 to 1.31; P = 0.79). A significantly lower mortality rate, however, was noted in the fifth decade (adjusted OR, 0.76; CI, 0.61 to 0.95; P = 0.02). Conversely, significantly higher mortality rates were noted in the eighth (adjusted OR, 1.93; CI, 1.38 to 2.71; P = 0.0001) and combined ninth/tenth decades (adjusted OR, 2.47; CI, 1.71 to 3.57; P < 0.0001). Given the high survival in trauma patients with GCS 3 as well as continued improvement in survival compared with historical controls, aggressive care is indicated for patients who present to the emergency department with GCS 3.

Elevated admission systolic blood pressure after blunt trauma predicts delayed pneumonia and mortality.

BACKGROUND: Although avoiding hypotension is a primary focus after trauma, elevated systolic blood pressure (SBP) is frequently disregarded. The purpose of this study was to determine the association between elevated admission SBP and delayed outcomes after trauma. METHODS: The Los Angeles County Trauma System Database was queried for all patients between 2003 and 2008 with blunt injuries who survived for at least 2 days after admission. Demographics and outcomes (pneumonia and mortality) were compared at various admission SBP subgroups (≥160 mm Hg, ≥170 mm Hg, ≥180 mm Hg, ≥190 mm Hg, ≥200 mm Hg, ≥210 mm Hg, and ≥220 mm Hg). Patients with moderate-to-severe traumatic brain injury (TBI), defined as head Abbreviated Injury Score ≥3, were then identified and compared with those without using multivariable logistic regression. RESULTS: Data accessed from 14,382 blunt trauma admissions identified 2,601 patients with moderate-to-severe TBI (TBI group) and 11,781 without moderate-to-severe TBI (non-TBI group) who were hospitalized ≥2 days. Overall mortality was 2.9%, 7.1% for TBI patients, and 1.9% for non-TBI patients. Overall pneumonia was 4.6%, 9.5% for TBI patients, and 3.6% for non-TBI patients. Regression modeling determined SBP ≥160 mm Hg was a significant predictor of mortality in TBI patients (adjusted odds ratio [AOR], 1.59; confidence interval [CI], 1.10-2.29; p = 0.03) and non-TBI patients (AOR, 1.47; CI, 1.14-1.90; p = 0.003). Similarly, SBP ≥160 mm Hg was a significant predictor for increased pneumonia in TBI patients (AOR, 1.79; CI, 1.30-2.46; p = 0.0004), compared with non-TBI patients (AOR, 1.28; CI, 0.97-1.69; p = 0.08). CONCLUSIONS: In blunt trauma patients with or without TBI, elevated admission SBP was associated with worse delayed outcomes. Prospective research is necessary to determine whether algorithms that manage elevated blood pressure after trauma, especially after TBI, affect mortality or pneumonia.

Diabetic patients with traumatic brain injury: insulin deficiency is associated with increased mortality.

BACKGROUND: Hyperglycemia after traumatic brain injury (TBI) is an independent predictor of mortality. Insulin deficiency, as opposed to elevated blood glucose, might be the reason for increased mortality. TBI patients with diabetes mellitus (DM) were analyzed to determine how insulin deficiency affects mortality after TBI. METHODS: NTDB version 7 was queried for patients with isolated moderate to severe TBI (head abbreviated injury score [AIS]≥3 with AIS≤3 for other body regions). Demographics and outcomes were compared between TBI patients with insulin-dependent DM (IDDM), noninsulin-dependent DM (NIDDM), and those without DM. Logistic regression analysis was used to investigate the relationship between mortality and DM. RESULTS: Overall, 51,585 patients with isolated moderate to severe TBI were analyzed. Mortality was 14.4% and 8.2% in patients with and without DM, respectively (p<0.0001). Although head AIS scores were similar, patients with DM had a statistically higher Glasgow coma scale (GCS) at presentation compared with patients without DM (GCS score 12.4 vs. GCS score 10.9; p<0.0001). After multivariable logistic regression analysis, DM was an independent predictor for mortality (odds ratio 1.5, confidence interval 1.29-1.74, p<0.0001). When comparing TBI patients with IDDM to NIDDM, mortality was 17.1% for IDDM and 13.0% for NIDDM (p=0.025). CONCLUSION: DM is a significant predictor for mortality after moderate to severe TBI. Insulin deficiency is a likely contributor to increased mortality after TBI as IDDM patients have higher mortality than NIDDM patients who have higher mortality than no-DM patients.

IL6 deficiency affects function after traumatic brain injury.

OBJECTIVE: Interleukin-6 (IL6) is a major inflammatory mediator and one of the first cytokines produced after traumatic brain injury (TBI). This study evaluates early behavioral changes and acute inflammation after TBI in IL6 knock-out mice using electromagnetic controlled cortical impact. METHODS: IL6 knock-out (KO) and C57BL/6 (WT) male mice were subjected to TBI or sham injury (n = 6 mice per group) using electromagnetic controlled cortical impact. Behavioral deficits were tested by standard performance tests. Brain IL1ß expression was measured by ELISA and HSP70 expression was measured by Western blot. RESULTS: After TBI, KO showed reduced performance on the neuroscreen compared with wild type (KO 3.2 ± 0.7 versus WT 4.7 ± 0.2 points, P = 0.007), less exploratory activity in the open field test (KO 1090.2 ± 1799.2 versus WT 5636.8 ± 1291.8 regions explored per hour, P = 0.003) less rearing behavior in the open field test (KO 36.4 ± 79.2 versus WT 346.5 ± 18.5 rearing per hour, P = 0.0006), reduced travel on the rotarod (KO 3.5 ± 4.0 versus WT 13.0 ± 4.0 cm, P = 0.0109), and reduced time balanced on the rotarod (KO 15.0 ± 11.5 versus WT 36.2 ± 5.9 s, P = 0.0109). After TBI, IL6 knock-out mice had significantly elevated IL1ß (KO 58.16 ± 17.54 versus WT 14.98 ± 8.33 pg/mL, P = 0.003 and nonsignificantly increased HSP70 levels (KO 0.93 ± 0.96 versus WT 0.68 ± 0.97, P = 0.77). CONCLUSION: IL6 deficiency after TBI is associated with poor behavior performance, and appears to affect expression of IL1ß and, possibly, HSP70.

Emergency department crystalloid resuscitation of 1.5 L or more is associated with increased mortality in elderly and nonelderly trauma patients.

BACKGROUND: Recent evidence suggests a survival advantage in trauma patients who receive controlled or hypotensive resuscitation volumes. This study examines the threshold crystalloid volume that is an independent risk factor for mortality after trauma. METHODS: This study analyzed prospectively collected data from a Level I Trauma Center between January 2000 and December 2008. Demographics and outcomes were compared in elderly (≥70 years) and nonelderly (<70 years) trauma patients who received crystalloid fluid in the emergency department (ED) to determine a threshold volume that was an independent predictor for mortality. RESULTS: A total of 3,137 patients who received crystalloid resuscitation in the ED were compared. Overall mortality was 5.2%. Mortality among the elderly population was 17.3% (41 deaths), whereas mortality in the nonelderly population was 4% (116 deaths). After multivariate logistic regression analysis, fluid volumes of 1.5 L or more were significantly associated with mortality in both elderly (odds ratio [OR]: 2.89, confidence interval [CI] [1.13-7.41], p=0.027) and nonelderly patients (OR: 2.09, CI [1.31-3.33], p=0.002). Fluid volumes up to 1 L were not associated with significantly increased mortality. At 3 L, mortality was especially pronounced in the elderly (OR: 8.61, CI [1.55-47.75] p=0.014), when compared with the nonelderly (OR=2.69, CI [1.53-4.73], p=0.0006). CONCLUSION: ED volume replacement of 1.5 L or more was an independent risk factor for mortality. High-volume resuscitations were associated with high-mortality particularly in the elderly trauma patient. Our finding supports the notion that excessive fluid resuscitation should be avoided in the ED and when required, operative intervention or intensive care admission should be considered.