Skiers and snowboarders have improved short-term outcomes with immediate fixation of tibial plateau fractures.

BACKGROUND: Tibial plateau fractures (TPFs) are frequently associated with motor vehicle accidents, auto-pedestrian crashes and falls. However, hospitals near ski resorts commonly treat TPF resulting from skiing. The soft tissue envelope and original mechanism of injury are important determinants in the decision to proceed with immediate or delayed fixation of the fracture. Our objective was to assess whether immediate (≤24 hours) versus delayed (>24 hours) open reduction internal fixation (ORIF) affected in-hospital outcomes among snow sport participants. METHODS: This was a retrospective study of patients with isolated TPF who were injured while skiing or snowboarding and treated at a Level III Trauma Center that serves four major ski resorts between 2010 and 2013. Clinical characteristics and in-hospital outcomes were obtained from an existing trauma database. Imaging was reviewed to classify the fracture as high (Schatzker IV-VI) or low (Schatzker I-III) energy. Differences in clinical characteristics and outcomes between immediate and delayed ORIF patients were analyzed with χ2 and Wilcoxon two-sample tests. These analyses were also performed in the high-energy and low-energy fracture populations. RESULTS: ORIF was performed on 119 snow sport patients, 93 (78%) immediately. Patients had a median age of 49 years (range 19-70) and were predominantly male (66%). Forty percent sustained a high-energy TPF. No differences were observed between the demographic characteristics, injury severity, Schatzker scores or time from injury to hospital arrival for patients treated immediately versus delayed treatment. Compared with delayed fixation, patients treated immediately had less compartment syndrome (3% vs 27%), needed fewer fasciotomies (6% vs 31%) and had a shorter length of stay (3 vs 6.5 days), p<0.05 for all. These results persisted in the stratified analysis of high-energy fracture patients. DISCUSSION: Treating patients immediately led to more favorable in-hospital outcomes compared with delayed treatment, even among the patients with a high-energy fracture. LEVEL OF EVIDENCE: Level IV, Therapeutic/Care Management.

The epidemiology, prognosis, and trends of severe traumatic brain injury with presenting Glasgow Coma Scale of 3.

PURPOSE: To characterize trends and prognosis of severe traumatic brain injury (TBI). METHODS: This 5-year multicenter retrospective study included patients with TBI and Glasgow Coma Scale of 3. We analyzed demographic and clinical characteristics and mortality using Pearson χ2 tests, Cochran-Armitage trend tests, and stepwise logistic regression. Analyses were stratified by vehicular and fall etiologies; other etiologies were excluded (24%). RESULTS: Included were 481 patients. Fall-related injuries increased 58% (P=.001) but vehicular etiology did not change (P=.63). The characteristics of the populations changed over time; with falls, the population became older and increasingly presented with normal vital signs, whereas with vehicular etiology, the population became younger, with more alcohol-related injury (P<.05 for all). Mortality from falls increased substantially from 25% to 63% (P<.001), whereas death from vehicular injures remained statistically unchanged but with a downward trend (50%-38%, P=.28). Predictors of mortality included injury severity and age at least 65 years for both groups. Additional variables that were prognostic were abnormal vital signs and subdural hematoma for vehicular injuries, and sex for fall injuries. CONCLUSIONS: The epidemiology of severe TBI is changing. These epidemiologic data may be used for management and resource decisions, monitoring, and directing injury prevention measures.

Hypotensive Resuscitation among Trauma Patients.

Hemorrhagic shock is a principal cause of death among trauma patients within the first 24 hours after injury. Optimal fluid resuscitation strategies have been examined for nearly a century, more recently with several randomized controlled trials. Hypotensive resuscitation, also called permissive hypotension, is a resuscitation strategy that uses limited fluids and blood products during the early stages of treatment for hemorrhagic shock. A lower-than-normal blood pressure is maintained until operative control of the bleeding can occur. The randomized controlled trials examining restricted fluid resuscitation have demonstrated that aggressive fluid resuscitation in the prehospital and hospital setting leads to more complications than hypotensive resuscitation, with disparate findings on the survival benefit. Since the populations studied in each randomized controlled trial are slightly different, as is the timing of intervention and targeted vitals, there is still a need for a large, multicenter trial that can examine the benefit of hypotensive resuscitation in both blunt and penetrating trauma patients.

Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury.

There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 µC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome.

The low molecular weight fraction of human serum albumin upregulates production of 15d-PGJ2 in Peripheral Blood Mononuclear Cells.

Activation of the innate immune system involves a series of events designed to counteract the initial insult followed by the clearance of debris and promotion of healing. Aberrant regulation can lead to systemic inflammatory response syndrome, multiple organ failure, and chronic inflammation. A better understanding of the innate immune response may help manage complications while allowing for proper immune progression. In this study, the ability of several classes of anti-inflammatory drugs to affect LPS-induced cytokine and prostaglandin release from peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were cultured in the presence of dexamethasone (DEX), ibuprofen (IBU), and the low molecular weight fraction of 5% albumin (LMWF5A) followed by stimulation with LPS. After 24 h, TNFα, PGE2, and 15d-PGJ2 release was determined by ELISA. Distinct immunomodulation patterns emerged following LPS stimulation of PBMC in the presence of said compounds. DEX, a steroid with strong immunosuppressive properties, reduced TNFα, PGE2, and 15d-PGJ2 release. IBU caused significant reduction in prostaglandin release while TNFα release was unchanged. An emerging biologic with known anti-inflammatory properties, LMWF5A, significantly reduced TNFα release while enhancing PGE2 and 15d-PGJ2 release. Incubating LMWF5A together with IBU negated this observed increased prostaglandin release without affecting the suppression of TNFα release. Additionally, LMWF5A caused an increase in COX-2 transcription and translation. LMWF5A exhibited a unique immune modulation pattern in PBMC, disparate from steroid or NSAID administration. This enhancement of prostaglandin release (specifically 15d-PGJ2), in conjunction with a decrease in TNFα release, suggests a switch that favors resolution and decreased inflammation.

Aggressive operative neurosurgical management in patients with extra-axial mass lesion and Glasgow Coma Scale of 3 is associated with survival benefit: A propensity matched analysis.

INTRODUCTION: Prognosis in patients with traumatic brain injury (TBI) and Glasgow Coma Scale (GCS) score of 3 is poor, raising concern regarding the utility of aggressive operative neurosurgical management. Our purpose was to describe outcomes in a propensity matched population with TBI and GCS3 treated with operative neurosurgical procedures of craniotomy or craniectomy (CRANI). METHODS: We conducted a five-year, multicenter retrospective cohort study of patients with an ED GCS 3 and a positive head CT identified by ICD-9CM diagnosis codes. Two populations were examined: (1) patients with extra-axial mass lesion (subdural or epidural haematoma), (2) patients without mass lesion (subarachnoid and intraparenchymal haemorrhage including contusion, other intracerebral haemorrhage or intracranial injury including diffuse axonal injury). In patients with extra-axial mass lesion, propensity score techniques were used to match patients 1:1 by CRANI, and the following outcomes were analysed with conditional logistic regression: survival, favourable hospital disposition to home or rehabilitation, and development of complications. RESULTS: There were 541 patients with TBI and GCS3; 19% had a CRANI, 83% were initiated within 4h. In those with mass lesion, 27% (91/338) had a CRANI; after matching, a significant survival benefit was observed with CRANI vs. without CRANI (65% vs. 34% survival, OR: 3.9 (1.6-10.5) p<0.001). There was borderline increased odds of favourable disposition (43% vs. 26%, OR: 2.4 (0.99-6.3, p=0.052) with CRANI vs. without CRANI, and no difference in developing a complication (58% vs. 48%, OR: 1.5 (0.7-3.4), p=0.30). CONCLUSIONS: Survival was achieved in 65% of patients that underwent surgical intervention for subdural and epidural haematoma, despite a presenting GCS of 3. These results demonstrate prompt operative neurosurgical management of mass lesion is warranted for selected patients with a GCS of 3, contributing to a significant 4-fold survival benefit. In the absence of mass lesion the effect of immediate neurosurgery on outcomes is inconclusive.

Anti-Inflammatory Activity in the Low Molecular Weight Fraction of Commercial Human Serum Albumin (LMWF5A).

The innate immune system is increasingly being recognized as a critical component in osteoarthritis (OA) pathophysiology. An ex vivo immunoassay utilizing human peripheral blood mononuclear cells (PBMC) was developed in order to assess the OA anti-inflammatory properties of the low molecular weight fraction (<5 kDa) of commercial human serum albumin (LMWF5A). PBMC from various donors were pre-incubated with LMWF5A before LPS stimulation. TNFα release was measured by ELISA in supernatants after an overnight incubation. A ≥ 30% decrease in TNFα release was observed. This anti-inflammatory effect is potentially useful in assessing potency of LMWF5A for the treatment of OA.

Does diabetes type increase the odds of venous thromboembolism following traumatic injury?

BACKGROUND: Venous thromboembolism (VTE) remains a clinically significant complication after trauma even though screening and prophylaxis strategies for at-risk patients have substantially reduced incidence. Our study sought to determine if diabetes, a condition that promotes thrombi formation, is associated with developing a VTE in trauma patients. METHODS: The registries of 2 level I and a level II trauma centers were retrospectively reviewed for consecutively admitted trauma patients over a 6-year period. Demographics, VTE risk factors, injury characteristics, and VTE incidence were univariately compared between patients with insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), and no diabetes. Stepwise logistic regression was performed to identify independent predictors of VTE; results were further stratified by age (<65 and ≥65 years) and presented as adjusted ORs (AOR). RESULTS: Of the 26 934 total patients, 779 (2.9%) had IDDM, 2052 (7.6%) had NIDDM, and the remaining 89.5% were without diabetes. VTE incidence was 3.6%, 2.4%, and 2.2%, in IDDM, NIDDM, and non-diabetes, respectively (p=0.02). After adjustment for established and significant risk factors, neither IDDM (AOR=1.43, 95% CI 0.95 to 2.15, p=0.09) nor NIDDM (AOR=1.03, 95% CI 0.75 to 1.40, p=0.88) was associated with increased odds of developing a VTE. Patients ≥65 years developed VTE more frequently than those <65 years (2.5% vs 2.1%, p=0.04). Among patients <65 years, IDDM was significantly predictive of VTE (AOR=1.86, 95% CI 1.01-3.41, p=0.045), but NIDDM was not. For patients ≥65 years, neither type of diabetes was predictive of VTE. CONCLUSIONS: VTE incidence was ∼2 times higher among injured patients <65 years with IDDM versus no diabetes. Overall, we did not find an increased risk of VTE in patients with any diabetes. Additional studies are needed before a recommendation on VTE screening or prophylaxis in IDDM can be made. LEVEL OF EVIDENCE: Level III, therapeutic/care management.

Cerebral salt wasting after traumatic brain injury: a review of the literature.

Electrolyte imbalances are common among patients with traumatic brain injury (TBI). Cerebral salt wasting (CSW) is an electrolyte imbalance characterized by hyponatremia and hypovolemia. Differentiating the syndrome of inappropriate antidiuretic hormone and CSW remains difficult and the pathophysiological mechanisms underlying CSW are unclear. Our intent was to review the literature on CSW within the TBI population, in order to report the incidence and timing of CSW after TBI, examine outcomes, and summarize the biochemical changes in patients who developed CSW. We searched MEDLINE through 2014, hand-reviewed citations, and searched abstracts from the American Association for the Surgery of Trauma (2003-2014). Publications were included if they were conducted within a TBI population, presented original data, and diagnosed CSW. Publications were excluded if they were review articles, discussed hyponatremia but did not differentiate the etiology causing hyponatremia, or presented cases with chronic disease. Fifteen of the 47 publications reviewed met the selection criteria; nine (60%) were case reports, five (33%) were prospective and 1 (7%) was a retrospective study. Incidence of CSW varied between 0.8 - 34.6%. The populations studied were heterogeneous and the criteria used to define hyponatremia and CSW varied. Though believed to play a role in the development of CSW, increased levels of natriuretic peptides in patients diagnosed with CSW were not consistently reported. These findings reinforce the elusiveness of the CSW diagnosis and the need for strict and consistent diagnostic criteria.

Sepsis, oxidative stress, and hypoxia: Are there clues to better treatment?

Sepsis is a clinical syndrome characterized by systemic inflammation, usually in response to infection. The signs and symptoms are very similar to Systemic Inflammatory Response Syndrome (SIRS), which typically occur consequent to trauma and auto-immune diseases. Common treatments of sepsis include administration of antibiotics and oxygen. Oxygen is administered due to ischemia in tissues, which results in the production of free radicals. Poor utilization of oxygen by the mitochondrial electron transport chain can increase oxidative stress during ischemia and exacerbate the severity and outcome in septic patients. This course of treatment virtually mimics the conditions seen in ischemia-reperfusion disorders. Therefore, this review proposes that the mechanism of free radical production seen in sepsis and SIRS is identical to the oxidative stress seen in ischemia-reperfusion injury. Specifically, this is due to a biochemical mechanism within the mitochondria where the oxidation of succinate to fumarate by succinate dehydrogenase (complex II) is reversed in sepsis (hypoxia), leading to succinate accumulation. Oxygen administration (equivalent to reperfusion) rapidly oxidizes the accumulated succinate, leading to the generation of large amounts of superoxide radical and other free radical species. Organ damage possibly leading to multi-organ failure could result from this oxidative burst seen in sepsis and SIRS. Accordingly, we postulate that temporal administration with anti-oxidants targeting the mitochondria and/or succinate dehydrogenase inhibitors could be beneficial in sepsis and SIRS patients.

The epidemiology of do-not-resuscitate orders in patients with trauma: a community level one trauma center observational experience.

BACKGROUND: Do-Not-Resuscitate (DNR) orders in patients with traumatic injury are insufficiently described. The objective is to describe the epidemiology and outcomes of DNR orders in trauma patients. METHODS: We included all adults with trauma to a community Level I Trauma Center over 6 years (2008-2013). We used chi-square, Wilcoxon rank-sum, and multivariate stepwise logistic regression tests to characterize DNR (established in-house vs. pre-existing), describe predictors of establishing an in-house DNR, timing of an in-house DNR (early [within 1 day] vs late), and outcomes (death, ICU stay, major complications). RESULTS: Included were 10,053 patients with trauma, of which 1523 had a DNR order in place (15%); 715 (7%) had a pre-existing DNR and 808 (8%) had a DNR established in-house. Increases were observed over time in both the proportions of patients with DNRs established in-house (p = 0.008) and age ≥65 (p < 0.001). Over 90% of patients with an in-house DNR were ≥65 years. The following covariates were independently associated with establishing a DNR in-house: age ≥65, severe neurologic deficit (GCS 3-8), fall mechanism of injury, ED tachycardia, female gender, and comorbidities (p < 0.05 for all). Age ≥65, female gender, non-surgical service admission and transfers-in were associated with a DNR established early (p < 0.05 for all). As expected, mortality was greater in patients with DNR than those without (22% vs. 1%), as was the development of a major complication (8% vs. 5%), while ICU admission was similar (19% vs. 17%). Poor outcomes were greatest in patients with DNR orders executed later in the hospital stay. CONCLUSIONS: Our analysis of a broad cohort of patients with traumatic injury establishes the relationship between DNR and patient characteristics and outcomes. At 15%, DNR orders are prevalent in our general trauma population, particularly in patients ≥65 years, and are placed early after arrival. Established prognostic factors, including age and physiologic severity, were determinants for in-house DNR orders. These data may improve physician predictions of outcomes with DNR and help inform patient preferences, particularly in an environment with increasing use of DNR and increasing age of patients with trauma.

The effect of age on Glasgow Coma Scale score in patients with traumatic brain injury.

IMPORTANCE: The Glasgow Coma Scale (GCS) is used frequently to define the extent of neurologic injury in patients with a traumatic brain injury (TBI). Whether age affects the predictive ability of the GCS for severity of TBI (determined by the Abbreviated Injury Scale [AIS] score) remains unknown. OBJECTIVE: To investigate the effect of age on the association between the GCS and anatomic TBI severity. DESIGN, SETTING, AND PARTICIPANTS: We examined all patients with a TBI, defined by diagnostic codes 850 to 854 from the International Classification of Diseases, Ninth Revision, Clinical Modification, who were admitted to 2 level I trauma centers from January 1, 2008, through December 31, 2012. EXPOSURES: We compared elderly (≥65 years) and younger (18-64 years) adults with TBI. MAIN OUTCOMES AND MEASURES: We examined differences by age in GCS category (defined by emergency department GCS as severe [3-8], moderate [9-12], or mild [13-15]) at each level of TBI severity (head AIS score, 1 [minor] to 5 [critical]). Cochran-Armitage χ² trend tests and stepwise multivariate linear and logistic regression models were used. RESULTS: During the study period, 6710 patients had a TBI (aged <65 years, 73.17%). Significant differences in GCS category by age occurred at each AIS score (P ≤ .01 for all). In particular, among patients with an AIS score of 5, most of the elderly patients (56.33%) had a mild neurologic deficit (GCS score, 13-15), whereas most of the younger patients (63.28%) had a severe neurologic deficit (GCS score, 3-8). After adjustment, the younger adults had increased odds of presenting with a severe neurologic deficit (GCS score, 3-8) at each of the following AIS scores: 1, 4.2 (95% CI, 1.0-17.6; P = .05); 2, 2.0 (1.0-3.7; P = .04); 3, 2.0 (1.2-3.5; P = .01); 4, 4.6 (2.8-7.5; P < .001); and 5, 3.1 (2.1-4.6; P < .001). The interaction between age and GCS for anatomic TBI severity remained significant after adjustment (estimate, -0.11; P = .005). CONCLUSIONS AND RELEVANCE: Age affects the relationship between the GCS score and anatomic TBI severity. Elderly TBI patients have better GCS scores than younger TBI patients with similar TBI severity. These findings have implications for TBI outcomes research and for protocols and research selection criteria that use the GCS.

A rapid, real-time quantitative polymerase chain reaction test for the identification of pathogens in bronchoalveolar lavage samples.

BACKGROUND: Standard bacteriologic culture techniques offer results within 2 days to 3 days, precluding a focused and timely antibiotic therapy in ventilated trauma patients. Our laboratory developed a real-time quantitative polymerase chain reaction (qPCR) test that can detect 25 different bacteria and fungi and methicillin resistance and offers results within 3 hours. The objective of this study was to compare the qPCR method to standard culture techniques. METHODS: This was a prospective observational cohort study at a Level I trauma center from 2009 to 2012. Adult trauma patients on ventilation, receiving at least one bronchoalveolar lavage (BAL) with culture results were eligible for inclusion. DNA was isolated from the BAL samples and analyzed in 96-well plates using qPCR. Student's t tests were used to examine differences in mean qPCR cycle counts. Sensitivities, specificities, negative predictive values, and positive predictive values were calculated for the qPCR primer sets. RESULTS: There were 28 BALs in the study. The qPCR method detected a total of 165 organisms, and culture methods found 54. The qPCR test had an overall sensitivity of 85%, specificity of 74%, negative predictive value of 98%, and positive predictive value of 27%. Those organisms that were only identified through qPCR had significantly less DNA than those identified through both qPCR and quantitative culture (28.8 vs. 23.3, p < 0.001). Concurrent antibiotic therapy was found to decrease the qPCR specificity in some primer sets, and methicillin resistance was only found in BAL samples that were concurrent with antibiotics. CONCLUSION: The qPCR method shows promising initial diagnostic value. Many of the organisms not identified by quantitative culture had late cycle calls, suggesting that they might have been in quantities too low to result in culture identification. Once refined, our qPCR method has the potential to identify pathogens faster and earlier than standard quantitative culture methods, allowing for targeted antibiotic therapy within 3 hours. LEVEL OF EVIDENCE: Diagnostic test, level II.

The relationship between patient volume and mortality in American trauma centres: a systematic review of the evidence.

OBJECTIVE: To synthesise published and unpublished findings examining the relationship between institutional trauma centre volume or trauma patient volume per surgeon and mortality. BACKGROUND: Evidence on the relationship between patient volume and survival in trauma patients is inconclusive in the literature and remains controversial. METHODS: A literature search was performed to identify studies published between 1976 and 2013 via MEDLINE (Pubmed) and the Cumulative Index to Nursing and Allied Health Literature (EbscoHost) as well as footnote chasing. Abstracts from appropriate conferences and ProQuest Dissertations and Theses were also searched. Inclusion criteria required studies to be original research published in English that examined the relationship between mortality and either institutional or per surgeon volume in American trauma centres. We employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement checklist and flowchart. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the quality of the evidence. RESULTS: Of 1392 studies reviewed, 19 studies met defined inclusion criteria; all studies were retrospective. The definition of volume was heterogeneous across the studies. Patient population and analysis methods also varied across the studies. Sixteen studies (84%) examined the relationship between institutional trauma centre volume and mortality. Of the 16 studies, 12 examined the volume of severely injured patients and eight examined overall trauma patient volume. High institutional volume was associated with at least somewhat improved mortality in ten of 16 studies (63%); however, nearly half of these studies found only some subpopulations experienced benefits. In the remaining six studies, volume was not associated with any benefits. Four studies (25%) analysed the impact of surgeon volume on mortality. High volume per surgeon was associated with improved mortality in only one of four studies (25%). CONCLUSIONS: The studies were extremely heterogeneous, thus definitive conclusions cannot be drawn regarding optimal volume before a clear advantage in survival is observed. A prospective study defining volume as a continuous variable is warranted to support current admission criteria for American trauma patients.

Dipeptidyl peptidase IV activity in commercial solutions of human serum albumin.

Due to the heterogeneous nature of commercial human serum albumin (cHSA), other components, such as the protease dipeptidyl peptidase IV (DPP-IV), possibly contribute to the therapeutic effect of cHSA. Here, we provide evidence for the first time that DPP-IV activity contributes to the formation of aspartate-alanine diketopiperazine (DA-DKP), a known immunomodulatory molecule from the N terminus of human albumin. cHSA was assayed for DPP-IV activity using a specific DPP-IV substrate and inhibitor. DPP-IV activity was assayed at 37 and 60°C because cHSA solutions are pasteurized at 60°C. DPP-IV activity in cHSA was compared with other sources of albumin such as a recombinant albumin (rHSA). In addition, the production of DA-DKP was measured by negative electrospray ionization/liquid chromatography mass spectrometry (ESI(-)/LCMS). Significant levels of DPP-IV activity were present in cHSA. This activity was abolished using a specific DPP-IV inhibitor. Fully 70 to 80% DPP-IV activity remained at 60°C compared with the 37°C incubate. No DPP-IV activity was present in rHSA, suggesting that DPP-IV activity is present only in HSA produced using the Cohn fractionation process. The formation of DA-DKP at 60°C was observed with the DPP-IV inhibitor significantly decreasing this formation. DPP-IV activity in cHSA results in the production of DA-DKP, which could account for some of the clinical effects of cHSA.

Unintentional discontinuation of statins may increase mortality after traumatic brain injury in elderly patients: a preliminary observation.

BACKGROUND: The abrupt discontinuation of statin therapy has been suggested as being deleterious to patient outcomes. Although pre-injury statin (PIS) therapy has been shown to have a protective effect in elderly trauma patients, no study has examined how this population is affected by its abrupt discontinuation. This study examined the effects of in-hospital statin discontinuation on patient outcomes in elderly traumatic brain injury (TBI) patients. METHODS: This was a multicenter, retrospective cohort study on consecutively admitted elderly (≥ 55) PIS patients who were diagnosed with a blunt TBI and who had a hospital length of stay (LOS) ≥ 3 days. Patients who received an in-hospital statin within 48 hours of admission were considered continued, and patients who never received an in-hospital statin were considered discontinued. Differences in in-hospital mortality, having at least one complication, and LOS > 1 week were examined between those who continued and discontinued PIS. RESULTS: Of 93 PIS patients, 46 continued and 15 discontinued statin therapy. The two groups were equivalent vis-a-vis demographic and clinical characteristics. Those who discontinued statin therapy had a 4-fold higher mortality rate than those who continued (n = 4, 27% vs. n = 3, 7%, P = 0.055). Statin discontinuation did not have a higher complication rate, compared to statin continuation (n = 3, 20% vs. n = 7, 15%, P = 0.70), and no difference was seen in the proportion with a hospital LOS > 1 week (P > 0.99). CONCLUSIONS: Though our study is not definitive, it does suggest that the abrupt, unintended discontinuation of statin therapy is associated with increased mortality in the elderly TBI population. Continuing in-hospital statin therapy in PIS users may be an important factor in the prevention of in-hospital mortality in this elderly TBI population.

Biphasic effect of danazol on human vascular endothelial cell permeability and f-actin cytoskeleton dynamics.

Breakdown of endothelial barrier function is a hallmark event across a variety of pathologies such as inflammation, cancer, and diabetes. It has also been appreciated that steroid hormones impart direct biological activity on endothelial cells at many levels. The purpose of this investigation was to explore the effect of the androgen-like steroid, danazol, on endothelial cell barrier function in vitro. Primary human endothelial cells exposed to 0.01-50 µM danazol were evaluated for changes in permeability. We found that danazol altered endothelial permeability in a biphasic manner in which nanomolar concentrations enhance barrier function while micromolar concentrations are detrimental. Monitoring of trans-endothelial electrical resistance demonstrated that these barrier enhancing effects were rapid (within 5 min) and lasted for over 24h. Analysis of intracellular f-actin organization showed that barrier enhancement also correlated with the formation of a submembranous cortical actin ring. Conversely, at higher danazol concentrations, contractile cell phenotypes were observed, represented by stress fiber formation. Competitive binding studies performed using steroid hormone receptor antagonists proved that this activity is the result of androgen and estrogen receptor ligation. These findings suggest that low dose danazol may provide a therapeutic window for diseases involving vascular leakage.

A 5-year review of a trauma-trained hospitalist program for trauma patients: A matched cohort study.

BACKGROUND: Level I trauma centers have requirements on the percentage of trauma patients admitted to either a trauma surgeon or surgical subspecialist; however, surgical resources are in steady decline. Therefore, a trauma system might better utilize its surgical resources if trained hospitalists admitted a larger percentage of mild to moderately injured trauma patients. The objective of this report is to provide a 5-year evaluation of a trauma medical service (TMED) at treating mild to moderately injured trauma patients. METHODS: Adult trauma patients consecutively admitted to a Level I trauma center between January 2006 and December 2010 were analyzed. Patients admitted to trauma surgical services were matched 1:1 to those admitted to TMED, via propensity scores. Paired t tests examined differences in hospital duration of stay (DOS), and exact conditional logistic regression examined differences in the odds of having a delayed diagnosis, developing a complication, and dying. RESULTS: Of 1,202 TMED patients, 494 were matched; matched TMED patients had similar patient outcomes to nonmatched TMED patients. There were no differences between study groups in the mean hospital DOS, the proportion having a delayed diagnosis, or in the odds of dying in the hospital (P > .05 for all). The TMED group had a nominally higher complication rate (P = .12) owing to a higher rate of urinary tract infections. CONCLUSION: Since its inception, the TMED service has successfully and safely treated mild to moderately injured trauma patients, and decreased the dependency on trauma surgical services. Trauma centers might utilize declining surgical services more efficiently with the addition of trauma medical hospitalists.

Interrupted pharmocologic thromboprophylaxis increases venous thromboembolism in traumatic brain injury.

BACKGROUND: Pharmacologic thromboprophylaxis (PTP) is frequently withheld, begun late, or interrupted in patients with traumatic brain injury (TBI). The purpose of this study was to analyze whether late or interrupted PTP increases the risk of venous thromboembolism (VTE) after TBI. METHODS: We retrospectively studied patients with blunt TBI and stable head computed tomography (CT) scans who were admitted to two Level I trauma centers. PTP use was analyzed as an independent risk factor for VTE using separate logistic regression models for each definition of PTP use: (1) administration of PTP; (2) timing of PTP (early [<72 hours] vs. late [≥72 hours]); and (3) continuous versus interrupted use of PTP. RESULTS: Four hundred eighty patients with TBI were identified. VTE occurred in 15 patients (3.13%). VTE developed in six patients despite early PTP (5.56%), four patients with late PTP (2.72%), and five with no PTP (2.22%). Neither administration of PTP nor timing of PTP was independent predictor of developing a VTE (PTP vs. none: odds ratio [OR]=0.36, p=0.18; early PTP vs. late PTP: OR=2.00, p=0.41). PTP was administered continuously in 188 patients (73.7%). Patients with interrupted PTP had a significant increased odds of developing VTE compared with patients with continuous PTP (OR=7.07, p=0.04). Walking before discharge significantly decreased the odds of developing a VTE (OR=0.19, p=0.02). CONCLUSIONS: Interrupted administration of PTP in patients with TBI is associated with significantly increased risk of VTE. These findings underscore the importance of continuous PTP administration, and every effort should be made to avoid interruption if possible.

Injury severity and serum amyloid A correlate with plasma oxidation-reduction potential in multi-trauma patients: a retrospective analysis.

BACKGROUND: In critical injury, the occurrence of increased oxidative stress or a reduced antioxidant status has been observed. The purpose of this study was to correlate the degree of oxidative stress, by measuring the oxidation-reduction potential (ORP) of plasma in the critically injured, with injury severity and serum amyloid A (SAA) levels. METHODS: A total of 140 subjects were included in this retrospective study comprising 3 groups: healthy volunteers (N = 21), mild to moderate trauma (ISS < 16, N = 41), and severe trauma (ISS >or= 16, N = 78). For the trauma groups, plasma was collected on an almost daily basis during the course of hospitalization. ORP analysis was performed using a microelectrode, and ORP maxima were recorded for the trauma groups. SAA, a sensitive marker of inflammation in critical injury, was measured by liquid chromatography/mass spectrometry. RESULTS: ORP maxima were reached on day 3 (+/- 0.4 SEM) and day 5 (+/- 0.5 SEM) for the ISS < 16 and ISS >or= 16 groups, respectively. ORP maxima were significantly higher in the ISS < 16 (-14.5 mV +/- 2.5 SEM) and ISS >or= 16 groups (-1.1 mV +/- 2.3 SEM) compared to controls (-34.2 mV +/- 2.6 SEM). Also, ORP maxima were significantly different between the trauma groups. SAA was significantly elevated in the ISS >or= 16 group on the ORP maxima day compared to controls and the ISS < 16 group. CONCLUSION: The results suggest the presence of an oxidative environment in the plasma of the critically injured as measured by ORP. More importantly, ORP can differentiate the degree of oxidative stress based on the severity of the trauma and degree of inflammation.