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Pathological abdominal adhesions can cause bowel obstructions. A history of appendectomy (appy) increases patient rehospitalization risk directly related to adhesions. To potentially identify strategies for adhesion treatment, we characterized reactive ascites (rA) collected during appy or adhesiolysis for small bowel obstruction (SBO).This is a non-randomized, prospective observational study recruiting patients with non-perforated appendicitis or SBO from three Level 1 trauma centers in the United States. rA were analyzed via liquid chromatography-mass spectrometry (LC-MS) (n = 31), bead-based quantification cytokines and chemokines (n = 32) and soluble receptors (n = 30), and LC-MS metabolomics (n = 18).LC-MS showed that samples contained albumin, apolipoprotein A1, and transthyretin and that metabolites increased in SBO vs appy rA were biomarkers of oxidative stress. Multi-plex analyses showed levels of 17 cytokines/chemokines and 6 soluble receptors were significantly different in appy vs SBO rA. Top increased proteins in appy compared to SBO rA by 20.14-, 11.53-, and 8.18-fold were granulocyte-colony stimulating factor, C-X-C motif chemokine ligand 10, and interleukin-10, respectively.These data further define pro- and anti-inflammatory mediators and metabolites that may drive formation or perpetuate chronic abdominal adhesions. Future research is to further explore whether attenuation of these factors may decrease pathologic adhesion formation.

Background Dysregulation of transcription and cytokine expression has been implicated in the pathogenesis of a variety inflammatory diseases. The resulting imbalance between inflammatory and resolving transcriptional programs can cause an overabundance of pro-inflammatory, classically activated macrophage type 1 (M1) and/or helper T cell type 1 (Th1) products, such as IFNγ, TNFα, IL1-β, and IL12, that prevent immune switching to resolution and healing. The low molecular weight fraction of human serum albumin (LMWF5A) is a novel biologic drug that is currently under clinical investigation for the treatment of osteoarthritis and the hyper-inflammatory response associated with COVID-19. This study aims to elucidate transcriptional mechanisms of action involved with the ability of LMWF5A to reduce pro-inflammatory cytokine release. Methods ELISA arrays were used to identify cytokines and chemokines influenced by LMWF5A treatment of LPS-stimulated peripheral blood mononuclear cells (PBMC). The resulting profiles were analyzed by gene enrichment to gain mechanistic insight into the biologic processes and transcription factors (TFs) underlying the identified differentially expressed cytokines. DNA-binding ELISAs, luciferase reporter assays, and TNFα or IL-1β relative potency were then employed to confirm the involvement of enriched pathways and TFs. Results LMWF5A was found to significantly inhibit a distinct set of pro-inflammatory cytokines (TNFα, IL-1β, IL-12, CXCL9, CXCL10, and CXCL11) associated with pro-inflammatory M1/Th1 immune profiles. Gene enrichment analysis also suggests these cytokines are, in part, regulated by NF-κB and STAT transcription factors. Data from DNA-binding and reporter assays support this with LMWF5A inhibition of STAT1α DNA-binding activity as well as a reduction in overall NF-κB-driven luciferase expression. Experiments using antagonists specific for the immunomodulatory and NF-κB/STAT-repressing transcription factors, peroxisome proliferator-activated receptor (PPAR)γ and aryl hydrocarbon receptor (AhR), indicate these pathways are involved in the LMWF5A mechanisms of action by reducing LMWF5A drug potency as measured by TNFα and IL-1β release. Conclusion In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARγ and AhR. In addition, our data indicate that LMWF5A suppresses NF-κB and STAT1α pro-inflammatory pathways. This suggests that LMWF5A acts through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production.

BackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) is not widely adopted for pelvic fracture management. Western Trauma Association recommends REBOA for hemodynamically unstable pelvic fractures, whereas Eastern Association for the Surgery of Trauma and Advanced Trauma Life Support do not.MethodUtilizing a prospective cross-sectional survey, all 158 trauma medical directors at American College of Surgeons-verified Level I trauma centers were emailed survey invitations. The study aimed to determine the rate of REBOA use, REBOA indicators, and the treatment sequence of REBOA for hemodynamically unstable pelvic fractures.ResultsOf those invited, 25% (40/158) participated and 90% (36/40) completed the survey. Nearly half of trauma centers [42% (15/36)] use REBOA for pelvic fracture management. All participants included hemodynamic instability as an indicator for REBOA placement in pelvic fractures. In addition to hemodynamic instability, 29% (4/14) stated REBOA is used for patients who are ineligible for angioembolization, 14% (2/14) use REBOA when interventional radiology is unavailable, 7% (1/14) use REBOA for patients with a negative FAST. Fifty percent (7/14) responded that hemodynamically unstable pelvic fractures exclusively indicates REBOA placement. Hemodynamic instability for pelvic fractures was most commonly defined as systolic blood pressure of ConclusionsThere is little consensus on REBOA use for pelvic fractures at US Level I Trauma Centers, except that hemodynamically unstable pelvic fractures consistently indicated REBOA use.

Background Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions. Methods Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated. Results The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils. Conclusions Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.

OBJECTIVEA paucity of studies have examined neurosurgical interventions in the mild traumatic brain injury (mTBI) population with intracranial hemorrhage (ICH). Furthermore, it is not understood how the dimensions of an ICH relate to the risk of a neurosurgical intervention. These limitations contribute to a lack of treatment guidelines. Isolated subdural hematomas (iSDHs) are the most prevalent ICH in mTBI, carry the highest neurosurgical intervention rate, and account for an overwhelming majority of all neurosurgical interventions. Decision criteria in this population could benefit from understanding the risk of requiring neurosurgical intervention. The aim of this study was to quantify the risk of neurosurgical intervention based on the dimensions of an iSDH in the setting of mTBI.METHODSThis was a 3.5-year, retrospective observational cohort study at a Level I trauma center. All adult (≥ 18 years) trauma patients with mTBI and iSDH were included in the study. Maximum length and thickness (in mm) of acute SDHs, the presence of acute-on-chronic (AOC) SDH, mass effect, and other hemorrhage-related variables were double–data entered; discrepant results were adjudicated after a maximum of 4 reviews. Patients with coagulopathy, skull fractures, no acute hemorrhage, a non-SDH ICH, or who did not undergo imaging on admission were excluded. Tentorial SDHs were not measured. The primary outcome was neurosurgical intervention (craniotomy, burr holes, intracranial pressure monitor placement, shunt, ventriculostomy, or SDH evacuation). Multivariate stepwise logistic regression was used to identify significant covariates, to assess interactions, and to create the scoring system.RESULTSThere were a total of 176 patients included in our study: 28 patients did and 148 did not receive a neurosurgical intervention. There were no significant differences between neurosurgical intervention groups in 11 demographic and 22 comorbid variables. Patients with neurosurgical intervention had significantly longer and thicker SDHs than nonsurgical controls. Logistic regression identified thickness and AOC hemorrhage as being the most important variables in predicting neurosurgical intervention; SDH length was not. Risk of neurosurgical intervention was calculated based on the SDH thickness and presence of an AOC hemorrhage from a multivariable logistic regression model (area under the receiver operating characteristic curve 0.94, 95% CI 0.90–0.97; p < 0.001). With a decision point of 2.35% risk, we predicted neurosurgical intervention with 100% sensitivity, 100% negative predictive value, and 53% specificity.CONCLUSIONSThis is the first study to quantify the risk of neurosurgical intervention based on hemorrhage characteristics in patients with mTBI and iSDH. Once validated in a second population, these data can be used to inform the necessity of interhospital transfers and neurosurgical consultations.

Background: Catheter-based regional analgesia has been proposed as an alternative to systemic analgesia for patients with multiple rib fractures (MRF). This study sought to compare the efficacy of regional techniques for decreasing pain and improving clinical outcomes. Study design: This was a multi-institutional, retrospective cohort study of adult (≥18 years) patients admitted to four nonacademic trauma centers over two years (from 07/1/2014 to 06/30/2016). Study inclusion was MRF (≥3 fractures) with no other severe injuries. Two primary regional analgesia techniques were utilized and compared: continuous intercostal nerve blocks (CINB) and epidural (EPI) analgesia. The primary outcome, average pain scores on treatment, was examined using a repeated measures, linear regression mixed model. Secondary outcomes included hospital LOS, ICU LOS, ICU admission and hospital readmission, pulmonary complications, and incentive spirometry volumes during treatment, and were examined with univariate statistics. Results: There were 339 patients with isolated MRF; 85 (25%) required regional analgesia (CINB, n=41; EPI, n=44) and the remaining 75% received systemic analgesia only (IV, n=195; PO, n=59). There were demographic and clinical differences between regional analgesia and systemic analgesia groups; on the contrary, there were no demographic or clinical differences between the CINB and EPI groups. Adjusted pain scores were similar for the EPI and CINB groups (4.0 vs 4.4, p=0.49). Secondary outcomes were worse in the EPI group compared to the CINB group: less improvement in incentive spirometry volume (p=0.004), longer ICU LOS (p=0.03), longer hospital LOS (p

OBJECTIVEIsolated subdural hematomas (iSDHs) are one of the most common intracranial hemorrhage (ICH) types in the population with mild traumatic brain injury (mTBI; Glasgow Coma Scale score 13–15), account for 66%–75% of all neurosurgical procedures, and have one of the highest neurosurgical intervention rates. The objective of this study was to examine how quantitative hemorrhage characteristics of iSDHs in patients with mTBI at admission are associated with subsequent neurosurgical intervention.METHODSThis was a 3.5-year, retrospective observational cohort study at a Level I trauma center. All adult trauma patients with mTBI and iSDHs were included in the study. Maximum length and thickness (in mm) of acute SDHs, the presence of acute-on-chronic SDH, mass effect, and other hemorrhage-related variables were double–data entered; discrepant results were adjudicated after a maximum of 4 reviews. Patients with coagulopathy, skull fractures, no acute hemorrhage, a non-SDH ICH, or who did not undergo imaging on admission were excluded. The primary outcome was neurosurgical intervention (craniotomy, burr hole, catheter drainage of SDH, placement of intracranial pressure monitor, shunt, or ventriculostomy). Multivariate stepwise logistic regression was used to identify significant covariates and to assess interactions.RESULTSA total of 176 patients were included in our study: 28 patients did and 148 patients did not receive a neurosurgical intervention. Increasing head Abbreviated Injury Scale score was significantly associated with neurosurgical interventions. There was a strong correlation between the first 3 reviews on maximum hemorrhage length (R2 = 0.82) and maximum hemorrhage thickness (R2 = 0.80). The neurosurgical intervention group had a mean maximum SDH length and thickness that were 61 mm longer and 13 mm thicker than those of the nonneurosurgical intervention group (p < 0.001 for both). After adjusting for the presence of an acute-on-chronic hemorrhage, for every 1-mm increase in the thickness of an iSDH, the odds of a neurosurgical intervention increase by 32% (95% CI 1.16–1.50). There were no interventions for any SDH with a maximum thickness ≤ 5 mm on initial presenting scan.CONCLUSIONSThis is the first study to quantify the odds of a neurosurgical intervention based on hemorrhage characteristics in patients with an iSDH and mTBI. Once validated in a second population, these data can be used to better inform patients and families of the risk of future neurosurgical intervention, and to evaluate the necessity of interhospital transfers.

Introduction: As the COVID-19 pandemic spread, patient care guidelines were published and elective surgeries postponed. However, trauma admissions are not scheduled and cannot be postponed. There is a paucity of information available on continuing trauma care during the pandemic. The study purpose was to describe multicenter trauma care process changes made during the COVID-19 pandemic. Methods: This descriptive survey summarized the response to the COVID-19 pandemic at six Level I trauma centers. The survey was completed in 05/2020. Questions were asked about personal protective equipment, ventilators, intensive care unit (ICU) beds, and negative pressure rooms. Data were summarized as proportions. Results: The survey took an average of 5 days. Sixty-seven percent reused N-95 respirators; 50% sanitized them with 25% using ultraviolet light. One hospital (17%) had regional resources impacted. Thirty-three percent created ventilator allocation protocols. Most hospitals (83%) designated more beds to the ICU; 50% of hospitals designated an ICU for COVID-19 patients. COVID-19 patients were isolated in negative pressure rooms at all hospitals. Conclusions: In response to the COVID-19 pandemic, Level I trauma centers created processes to provide optimal trauma patient care and still protect providers. Other centers can use the processes described to continue care of trauma patients during the COVID-19 pandemic.

Background A common complication of viral pulmonary infections, such as in the ongoing COVID-19 pandemic, is a phenomenon described as a “cytokine storm”. While poorly defined, this hyperinflammatory response results in diffuse alveolar damage. The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic in development for osteoarthritis, demonstrates beneficial in vitro immunomodulatory effects complimentary to addressing inflammation, thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm. Presentation of the hypothesis A variety of human in vitro immune models indicate that LMWF5A reduces the production of pro-inflammatory cytokines implicated in cytokine storm associated with COVID-19. Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures. Testing the hypothesis A randomized controlled trial, to evaluate the safety and efficacy of nebulized LMWF5A in adults with Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 infection, was developed and is currently under review by the Food and Drug Administration. Implications of hypothesis If successful, this therapy may attenuate the cytokine storm observed in these patients and potentially reduce mortality, increase ventilation free days, improve oxygenation parameters and consequently lessen the burden on patients and the intensive care unit. Conclusions In conclusion, in vitro findings suggest that the immunomodulatory effects of LMWF5A make it a viable candidate for treating cytokine storm and restoring homeostasis to the immune response in COVID-19.

After a traumatic insult, macrophages can become activated leading to general inflammation at the site of injury. Activated macrophages are partially regulated by the aryl hydrocarbon receptor (AhR) which when activated suppresses inflammation by limiting the secretion of pro-inflammatory cytokines and promoting the over expression of immuno-modulatory mediators. This study aims to determine whether the low molecular weight fraction of 5% human serum albumin (LMWF5A) and N-acetyl kynurenine (NAK), an N-acetyl tryptophan (NAT) breakdown product in LMWF5A, can regulate inflammation by inhibiting macrophage activation through the AhR since kynurenine is a known AhR agonist. Using LCMS, we demonstrate that NAT is non-enzymatically degraded during accelerated aging of LMWF5A with high heat accelerating degradation. More importantly, NAK is a major degradation product found in LMWF5A. THP-1 monocytes were differentiated into macrophages using phorbol 12-myristate 13-acetate (PMA) and pre-treated with 2-fold dilutions of LMWF5A or synthetic NAK with or without an AhR antagonist (CH223191) prior to overnight stimulation with lipopolysaccharide (LPS). Treatment with LMWF5A caused a 50–70% decrease in IL-6 release throughout the dilution series. A dose-response inhibition of IL-6 release was observed for NAK with maximal inhibition (50%) seen at the highest NAK concentration. Finally, an AhR antagonist partially blocked the anti-inflammatory effect of LMWF5A while completely blocking the effect of NAK. A similar inhibitory effect was observed for CXCL-10, but the AhR antagonist was not effective suggesting additional mechanisms for CXCL-10 release. These preliminary findings suggest that LMWF5A and NAK partially promote the suppression of activated macrophages via the AhR receptor. Therefore, LMWF5A, which contains NAK, is potentially a useful therapeutic in medical conditions where inflammation is prevalent such as trauma, sepsis, and wound healing., Highlights • LMWF5A contains degradation products of N-acetyl tryptophan (NAT). • A major degradation product of NAT in LMWF5A is N-acetyl kynurenine (NAK). • LMWF5A and NAK decrease IL-6 and CXCL-10 release from activated macrophages. • AhR is partially involved in the mechanism of action for LMWF5A and NAK. • The anti-inflammatory properties of LMWF5A are also AhR-independent.

Within the first few hours of a traumatic brain injury, the activity of extracellular matrix degradative enzymes increases. As a result, the blood brain barrier becomes disrupted as secondary white matter injury increases. Anoikis, a form of apoptosis, results from cells detaching from the extracellular matrix leading to cell death. This “homelessness” (anoikis) of cells hinders recovery progression, exacerbating brain injury while disrupting synaptic plasticity and other central nervous system functions. Here, we discuss the current knowledge of molecular pathways and proteins involved in both the activation and inhibition of anoikis.

Objective: A few studies report comparable analgesic efficacy between low-dose ketamine and opioids such as morphine or fentanyl; however, limited research has explored the safety and effectiveness...

Colorado requires Level III and IV trauma centers to conduct a formal performance improvement program (PI), but provides limited support for program development. Trauma program managers and coordinators in rural facilities rarely have experience in the development or management of a PI program. As a result, rural trauma centers often face challenges in evaluating trauma outcomes adequately. Through a multidisciplinary outreach program, our Trauma System worked with a group of rural trauma centers to identify and define seven specific PI filters based on key program elements of rural trauma centers. This retrospective observational project sought to develop and examine these PI filters so as to enhance the review and evaluation of patient care. The project included 924 trauma patients from eight Level IV and one Level III trauma centers. Seven PI filters were retrospectively collected and analyzed by quarter in 2016: prehospital managed airway for patients with a Glasgow Coma Scale (GCS) score of less than 9; adherence to trauma team activation criteria; evidence of physician team leader presence within 20 min of activation; patient with a GCS score less than 9 in the emergency department (ED): intubated in less than 20 min; ED length of stay (LOS) less than 4 hr from patient arrival to transfer; adherence to admission criteria; documentation of GCS on arrival, discharge, or with change of status. There was a significantly increasing compliance trend toward appropriate documentation of GCS (p trend < .001) and a significantly decreasing compliance trend for ED LOS of less than 4 hr (p trend = .04). Moving forward, these data will be used to develop compliance thresholds, to identify areas for improvement, and create corrective action plans as necessary.

Despite the unique opportunity race car driving provides to study exercise in extreme conditions, the sport of racing is under-represented. A better understanding of how racing changes physiological measures combined with driver demographics may help reduce driver risks and expand the field of driver science. This study charted the changes in heart rate, body temperature, blood pressure, static oxidation reduction potential (sORP), and antioxidant capacity in drivers before and after racing (n=23). The interaction between racing and driver characteristics on physiological variables were evaluated. Heart rate, body temperature, and sORP were elevated after racing (P0.05). Elevated post-race sORP values were associated with higher pre-race systolic blood pressure and lower antioxidant capacity (P

We sought to determine occurrence, predictors, and prognosis of alcohol withdrawal syndrome and delirium tremens in patients with traumatic injury.Retrospective multicenter cohort study.Three U.S. trauma centers.Twenty-eight thousand one hundred one trauma patients admitted from 2010-2014.None.Measures included occurrence of alcohol withdrawal syndrome and delirium tremens, injury characteristics, risk factors for alcohol withdrawal syndrome, clinical outcomes, pharmacologic treatment for alcohol withdrawal syndrome, and Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) scores. Alcohol withdrawal syndrome severity was defined by CIWA-Ar score as minimal (10), moderate (10-20), and severe (20). Alcohol withdrawal syndrome developed in 0.88% (n = 246), including 12% minimal, 36% moderate, and 53% severe. Alcohol withdrawal syndrome progressed to delirium tremens in 11%. Before adjustment, alcohol withdrawal syndrome severity was associated with injury severity, hypokalemia, baseline CIWA-Ar score, and established alcohol withdrawal syndrome risk factors. Logistic regression identified the following predictors of delirium tremens: baseline CIWA-Ar score greater than or equal to 10 (odds ratio, 6.05; p = 0.02) and age greater than or equal to 55 (odds ratio, 3.24; p = 0.03). In patients with severe alcohol withdrawal syndrome, severe head injury also predicted progression to delirium tremens (odds ratio, 6.08; p = 0.01), and hypokalemia was borderline significant (odds ratio, 3.23; p = 0.07). Clinical outcomes of hospital length of stay, ICU length of stay, and alcohol withdrawal syndrome complications differed significantly by alcohol withdrawal syndrome severity and were worse with more severe manifestations of alcohol withdrawal syndrome. Mortality also significantly differed by alcohol withdrawal syndrome severity but was only greater in patients who progressed to delirium tremens (11.1%; p = 0.02); otherwise, there were no differences in mortality by severity (4%, 4%, and 0% by minimal, moderate, and severe alcohol withdrawal syndrome).Trauma patients with alcohol withdrawal syndrome experience a high occurrence of delirium tremens that is associated with significant mortality. These data demonstrate the predictive ability of baseline CIWA-Ar score, age, and severe head injury for developing delirium tremens.

Blunt cerebrovascular injuries (BCVIs) are associated with long-term neurological effects. The first-line treatment for BCVIs is antithrombotics, but consensus on the optimal choice and timing of treatment is lacking.This was a retrospective study on patients aged at least 18 years admitted to 6 level 1 trauma centers between 1/1/2014 and 12/31/2017 with grade 1-4 BCVI and treated with antithrombotics. Differences in treatment practices were examined across the 6 centers. The primary outcome was ischemic stroke, and secondary outcomes were related to bleeding complications: blood transfusion and intracranial hemorrhage (ICH). Treatment characteristics examined were time to diagnosis and first computerized tomography angiography, time of total treatment course, time on each antithrombotic (anticoagulants, antiplatelets, combination), time from hospital arrival to antithrombotic initiation, and treatment interruption, i.e., treatment halted for a surgical procedure and restarted postoperatively. Chi-square, Fisher exact, Spearman's rank-order correlation, Wilcoxon rank-sum, Kruskal-Wallis, and Cox proportional hazards models with time-varying covariates were used to evaluate associations with the outcomes.A total of 189 patients with BCVI were included. The median (IQR) time from arrival to antithrombotic initiation was 27 (8-61) hours, and 28% of patients had treatment interrupted. The ischemic stroke rate was 7.5% (n = 14), with most strokes (64%, n = 9) occurring between arrival and treatment initiation. Treatment interruption was associated with ischemic stroke (75% of patients with stroke had an interruption versus 24% of patients with no stroke; P.01). Time on anticoagulants was not associated with ischemic stroke (P = .78), transfusion (P = .43), or ICH (P = .96). Similarly, time on antiplatelets (P = .54, P = .65, P = .60) and time on combination therapy (P = .96, P = .38, P = .57) were not associated with these outcomes.The timing and consistency of antithrombotic administration are critical in preventing adverse outcomes in patients with BCVI. Most ischemic strokes in this study population occurred between arrival and antithrombotic initiation, representing events that may potentially be intervened upon by earlier treatment. Future studies should examine the safety of continuing treatment through surgical procedures.

BackgroundWe sought to identify predictors of splenic artery embolization (SAE) over observation for hemodynamically stable patients with blunt splenic injury (BSI), by Organ Injury Scale (OIS) grade.MethodsThis was a multi-institutional retrospective study of all adults (≥18) with BSI who were initially managed non-operatively between 2014 and 2016. Multivariate logistic regression analysis was used to identify predictors of SAE by OIS grade. Covariates included radiographic characteristics (presence/quantity of hemoperitoneum, blush, vascular injury), demographics (age, sex, cause), Injury Severity Score, vital signs, and hemoglobin values. We also examined outcomes of death, length of stay (LOS), intensive care unit (ICU) admission, blood products, and failed non-operative management (NOM).ResultsAmong 422 patients with stable BSI, 93 (22%) had SAE and 329 (78%) were observed. The rate of SAE increased by grade (pConclusionThese results strongly support SAE consideration for patients with stable grade IV and V BSI even if there are no other high-risk clinical or radiographic findings. For grades I–III, the identified predictors may help refine consideration for SAE.Level of evidenceLevel III, retrospective epidemiological study.

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.

Emergent ambulance transportation is associated with increased risk of collision, injury, and death for EMS professionals, patients, and the general public. Time saved using lights and siren (LS) is typically small, and often provides minimal clinical benefit. Our objective was to investigate the frequency of LS transports, describe the precision of the decision to employ LS to predict the need for a time critical hospital intervention (TCHI) within 15 minutes of hospital arrival, identify clinical predictors of a TCHI, and compare clinical outcomes in patients transported by Emergency Medical Services (EMS) with and without LS in a trauma-specific population. EMS patient care reports and trauma registry data were retrospectively reviewed for trauma patients consecutively transported from the field by three EMS agencies to three trauma centers within urban and suburban settings over a two-year period. TCHIs were collaboratively developed by the study team. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were utilized to report the precision of the decision to employ LS to predict the need of a TCHI. Univariate and multivariate analyses determined predictors of a TCHI and compared clinical outcomes. 2,091 patients were included in the study. Of the 19.8% of patients transported with LS, 22.9% received a TCHI. The most common TCHI was airway or respiratory procedures (87.2% of all TCHI's). The sensitivity and specificity of LS to predict the need for a TCHI was 87.2% (95% CI 79.4-92.8) and 84.0% (95% CI 82.2-85.5), respectively. PPV was 23.0% (95% CI 23.53-38.01); NPV was 99.2% (95% CI 98.6-99.6). LS was predictive for the need for a TCHI (p0.001), as was abnormal Glasgow Coma Score (p0.001), abnormal systolic blood pressure and age (p0.05 for all). Among patients that received a TCHI, over a third that were transported with LS (36.8%) expired, compared with two of 14 patients (14.3%) not transported LS. EMS professionals in this study demonstrated a high ability to discern which trauma patients did not require LS. Nevertheless, LS transport resulted in a TCHI less than one quarter of the time, suggesting an opportunity for further reduction of LS transports in trauma patients.

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 (

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.

Objective To outline differences in neurosurgical intervention (NI) rates between intracranial hemorrhage (ICH) types in mild traumatic brain injuries and help identify which ICH types are most likely to benefit from creation of predictive models for NI. Methods A multicenter retrospective study of adult patients spanning 3 years at 4 U.S. trauma centers was performed. Patients were included if they presented with mild traumatic brain injury (Glasgow Coma Scale score 13–15) with head CT scan positive for ICH. Patients were excluded for skull fractures, “unspecified hemorrhage,” or coagulopathy. Primary outcome was NI. Stepwise multivariable logistic regression models were built to analyze the independent association between ICH variables and outcome measures. Results The study comprised 1876 patients. NI rate was 6.7%. There was a significant difference in rate of NI by ICH type. Subdural hematomas had the highest rate of NI (15.5%) and accounted for 78% of all NIs. Isolated subarachnoid hemorrhages had the lowest, nonzero, NI rate (0.19%). Logistic regression models identified ICH type as the most influential independent variable when examining NI. A model predicting NI for isolated subarachnoid hemorrhages would require 26,928 patients, but a model predicting NI for isolated subdural hematomas would require only 328 patients. Conclusions This study highlighted disparate NI rates among ICH types in patients with mild traumatic brain injury and identified mild, isolated subdural hematomas as most appropriate for construction of predictive NI models. Increased health care efficiency will be driven by accurate understanding of risk, which can come only from accurate predictive models.

Purpose – The purpose of this paper is to describe an American healthcare organization's experience creating the first multi-facility trauma system managed by a private, nonprofit organization. Design/methodology/approach – A leadership structure was established to initiate the first steps of system development, followed by needs assessments that identified key components essential to creating the interconnected system. The key components were applied as a result of evidence-based system development. After system implementation, early benefits were explored. Findings – Data collection and research, prehospital support, system-wide quality improvement, rural outreach, communication, and system evaluation were identified as key components essential to creating an interconnected trauma system. The system currently connects 12 trauma centers throughout the state of Colorado while working within the parameters of an established statewide system. Early benefits included improved designation review results, the utilization of system-wide best practice protocols, a rich trauma registry, and closer relations with rural, out-of-network facilities. Practical implications – This study describes the process undertaken to implement a unique medical system that provides regionalized care and complements an existing statewide trauma system. The authors hope their experience may serve as a roadmap for healthcare professionals wishing to develop an integrated, patient-centered model of care. Originality/value – The development of this multi-facility trauma system within a private, not-for-profit healthcare organization is the first of its kind.

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.

Objectives To investigate whether implementing a geriatric resuscitation protocol that uses lactate-guided therapy with early trauma surgeon involvement is associated with lower mortality through the early recognition of occult hypoperfusion (OH). Design Prospective cohort study. Setting Level I trauma center. Participants All hemodynamically stable individuals with blunt trauma aged 65 and older admitted to the Level I trauma center from October 1, 2008, through December 31, 2011 (n = 1,998). Measurements Mortality over time (according to quarter) was analyzed using an adjusted logarithmic regression model stratified according to the presence of OH. OH was defined as lactate of 2.5 mM or greater. Results Overall mortality was 3.9% (n = 78). Admission venous lactate was collected in 73.5% of participants, of whom 20.5% had OH (n = 301). In participants with OH, a significant decrease in mortality was observed over time (adjusted coefficient of determination (R2) = 0.66, P = .002). A smaller yet significant decrease in mortality rates in participants with normal perfusion status was also observed (adjusted R2 = 0.55, P = .01). Conclusion Early identification and treatment of OH in elderly adults with trauma using venous lactate-guided therapy coupled with early trauma surgeon involvement was associated with significantly lower mortality. A protocol that uses lactate-guided therapy with early trauma surgeon involvement should be followed to improve the care of elderly adults with trauma.

This study describes the process undertaken by a private health care network to develop and implement an outreach program for rural level III to V trauma centers. The program provided individualized trauma program support to 18 rural out-of-network facilities. A case study and participant satisfaction survey demonstrate the experiences of rural trauma nurse coordinators working with the program. The Trauma Outreach Program presents a solution to enhance the effectiveness of regional trauma systems, lift the burden on rural facilities, and improve care for the injured patient.

Statin discontinuation has been investigated in a wide range of diseases and injuries, but there is a paucity of data in the older adult population with traumatic brain injury (TBI). The purpose of this study was to re-examine the extent to which early discontinuation of pre-injury statin (PIS) therapy increases the risk of poor patient outcomes in older adult patients suffering a TBI.This was a retrospective observational cohort study of adult trauma patients with a blunt TBI across three trauma centres over four years. Patients were excluded because of no PIS use, age55years, or a hospital length of stay (LOS) less than three days. Patients found to be intentionally discontinued from statin therapy within 48h of hospital admission for injury-related reasons were excluded. The primary and secondary outcomes were in-hospital mortality and a hospital LOS ≥1 week. Outcomes were analysed using logistic regression.There were 266 patients in the continuation group, and 131 in the discontinuation group. The statin discontinuation group had a significantly higher proportion of patients with a moderate or severe head injury, intubation in emergency department (ED), and disposition to the intensive care unit or operating room. Overall, 23 (6%) patients died while in the hospital. After adjusting for ED Glasgow coma scale, the odds of dying in the hospital were not significantly larger for patients having been discontinued from PIS, compared to those who were continued (OR=1.75, 95%CI=0.71-4.31, p=0.22). Among patients who received an in-hospital statin, the median (interquartile range) time between hospital admission and first administration of statin medication did not differ between patients who died and those who survived (22.8h [10.96-28.91] vs. 22.9h [11.67-39.80], p=0.94). There were no significant differences between study groups in the proportion of patients with a hospital length of stay1 week (continuation=29% vs. discontinuation=36%, p=0.19).We did not observe a significantly increased odds of in-hospital mortality following PIS discontinuation, compared to PIS continuation, in an older adult population with TBI. It remains to be seen whether statin discontinuation is a proxy variable for injury severity, or whether it exerts deleterious effects after 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 (

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.

Warfarin-related traumatic intracerebral hemorrhage (ICH) is often fatal, yet timely evaluation and treatment can improve outcomes. Our study describes the process of developing and implementing a protocol to guide the care of patients with traumatic brain injury (TBI) on preinjury warfarin developed by nurses across several service lines at our Level I trauma center over a 6-month period. Further, we evaluated its efficacy by examining records of adult patients with TBI on preinjury warfarin admitted 1 year before and after protocol implementation. Efficacy was defined as activation rates, receipt and time to head computed tomography (CT) scan and international normalization ratio (INR), and receipt and time to fresh frozen plasma (FFP) administration in patients with ICH with an INR more than 1.5, as per protocol. A subset analysis examined patients with and without an ICH. Outcomes were compared using univariate analyses. One hundred seventy-eight patients were included in the study; 90 (50.6%) were admitted before and 88 (49.4%) after implementation. After implementation, there were improvements in activation rates (34.4% vs. 65.9%; p < .001), the frequency of head CT scans (55.6% vs. 83.0%; p < .001), time to INR (24.0 min vs. 15.0 min; p < .05), and, for patients with ICH with an INR 1.5 or more, decreased time to FFP (157.0 vs. 90.5; p < .05). In conclusion, our protocol led to a more efficient process of care for patients with TBI on warfarin. We believe the implementation process, managed by a dedicated group of nurses across several service lines, substantially contributed to the success of the protocol.

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 24 h. 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.

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 [

Background: Pharmacologic thromboprophylaxis (PTP) may exacerbate intracranial hemorrhage (ICH) in patients with traumatic brain injury (TBI). We examined risk factors for hemorrhage progression in patients with blunt TBI and hypothesized that PTP would increase ICH progression in a subset of these patients. Methods: We retrospectively studied patients with TBI admitted to our level I trauma center during 19 months. Progression of hemorrhage was examined in two populations: patients with a stable initial follow-up (F/U) computed tomography (CT) and patients with hemorrhage progression on initial F/U CT. Risk factors potentially associated with hemorrhage progression were analyzed using logistic regression. Timing of PTP was defined two ways: exposed to PTP versus not exposed; early (

The abbreviated injury scale (AIS) was updated in 2005 from the AIS 1998 version. The purpose of this study is to describe the effects of this change on injury severity scoring and outcome measures.Analyses were performed on all trauma patients consecutively admitted over a 6-month period at two geographically separate Level I trauma centers. Injuries were manually double-coded according to the AIS 05 and the AIS 98. Changes in AIS, ISS, and new ISS (NISS) were analysed using paired t-tests. Apparent differences in outcome by ISS strata (16, 16-24,24) were compared for AIS 05 versus AIS 98 using the Wald-type statistic. Lastly, the percent of patients with a change in ISS strata are reported.There were 2250 patients included in the study. Nearly half (46.4%) of AIS codes changed, resulting in a different AIS score for 18.9% of all codes. The mean ISS was significantly lower using the AIS 05 (11.7) versus the AIS 98 (13.3, p0.001). Similarly, the mean NISS was significantly lower (16.3 versus 18.7, p0.001). In the ISS strata 16-24 an apparent increase in mortality, length of stay, and percent of patients not discharged home was observed for the AIS 05 versus AIS 98. Changes in outcome measures for this stratum were as follows (AIS 98 versus AIS 05): mortality, 4.3% versus 7.7% (p=0.002); hospital length of stay, 5.2 days versus 7.3 days (p0.001); percent of patients not discharged home, 39.2% versus 49.3% (p0.001). Finally, there was a 20.5% reduction in patients with an ISSor=16 and a 26.2% reduction in patients with an ISSor=25 using the AIS 05.The AIS revision had a significant impact on overall injury severity measures, clinical outcome measures, and percent of patients in each ISS strata. Therefore, the AIS revision affects the ability to directly compare data generated using AIS 05 and AIS 98 which has implications in trauma research, reimbursement and ACS accreditation.

Objective: To quantify the cumulative effective dose of radiation received during hospitalization after traumatic injury and to compare the computed tomography (CT) utilization practices for two time periods in patients with trauma. Design: A retrospective analysis of radiologic and medical data. Setting: A level I trauma center. Patients: Consecutively admitted adult patients with trauma with moderate to severe injuries (injury severity score >8), an intensive care unit (ICU) length of stay of one or more days, who were directly admitted and not transferred to another acute care center. Measurements and Main Results: CT examination means and utilization were compared for April through August, 2003 and April to August, 2007. Cumulative effective doses were calculated for the 2007 period, and patients with a high radiation dose (>100 mSv) were identified. One hundred sixty-five adult patients with trauma were included. An increase in mean CT examinations per patient was observed in the 2007 period compared with the 2003 period, overall (4.41 vs. 3.44, p = 0.002) and among subsets of patients. The overall increase remained significant after adjustment for patient demographics (p = 0.05). The mean cumulative effective dose per patient was 11.13 mSv in 2007; 9% of patients received a dose ≥100 mSv. Conclusions: Patients with trauma are at an increased risk of adverse effects from CT studies, because they receive high doses of radiation, and the number of CT examinations that patients receive is increasing with time. We recommend that risk of radiation be prospectively monitored and estimated by hospitals through the use of CT examination count per patient.

Background Aspartyl-alanyl- diketopiperazine (DA-DKP) is generated by cleavage and cyclization from the N-terminus of human albumin during the preparation of commercial serum albumin product. Antigen-stimulated human T lymphocytes produce significantly lower quantities of interferon-gamma and tumor necrosis factor-alpha after stimulation in vitro in the presence of DA-DKP. Methods T lymphocytes activated in the presence of DA-DKP were analyzed by pull-down western blot assay for the activation of the guanosine triphosphatase Rap1 and by quantitative immunoassay for the phosphorylated transcription factors ATF-2 (activating transcription factor-2) and c-jun, which regulate the production of interferon-gamma and tumor necrosis factor-alpha. Results Exposure of human T lymphocytes to DA-DKP resulted in increased levels of active Rap1 and decreased activation factors relevant to the T-cell receptor signal transduction pathway and subsequently, decreased phosphorylated ATF-2 and c-jun expression. Conclusion The cyclized N- terminal fragment of human serum albumin, DA-DKP, can modulate the inflammatory immune response through a molecular pathway implicated in T- lymphocyte anergy.

Currently, the rapid diagnosis of mesenteric ischemia is problematic because of the nonspecificity of most laboratory assays and the unreliability of physical examinations. The evaluation of the cobalt-albumin binding assay (CABA) as a diagnostic marker for short-term risk stratification of emergency department patients presenting with symptoms of intestinal ischemia is reported. This preliminary study includes patients scheduled for exploratory laparotomy with symptoms of ischemic bowel and/or bowel obstruction. Approximately 10 mL of blood was drawn from each patient 1 hour preoperatively into a serum separator gel tube. After 30 minutes of clotting time, serum was collected and frozen at -80 degrees C. The CABA test was performed on the samples by an investigator blinded to the patient's condition, and values were compared with the clinical and pathologic diagnosis of ischemic bowel postoperatively. CABA test values are reported as absorbance units (ABSU) at 470 nm. Of the 26 patients enrolled in the study, 12 were clinically diagnosed with intestinal ischemia. These patients had significantly higher CABA test values (0.52 ABSU +/- 0.04 SEM) than patients without intestinal ischemia (0.31 ABSU +/- 0.02 SEM, p = 0.00023). Only two false-positives and no false-negatives were recorded. This resulted in a sensitivity of 100% and a specificity of 85.7% for the CABA test for these particular samples. The CABA test could be a useful tool for clinicians in the risk stratification of intestinal ischemia.

Background We previously hypothesized that the N-terminus of human serum albumin (HSA) is altered during ischemic events, thus establishing the foundation for the cobalt–HSA binding assay phenomenon. In this investigation, we attempt to clarify the mode of action of the cobalt–HSA binding assay by direct observations of cobalt binding to HSA. Methods High pressure liquid chromatography coupled to positive electrospray ionization mass spectrometry (HPLC/MS) was used to study cobalt binding to HSA in the plasma of patients with and without evidence of myocardial ischemia. Results Strong binding of cobalt to the N-terminus of HSA occurs at pH > 7.0. No differences in cobalt binding to the N-terminus of HSA are observed in ischemic versus non-ischemic patients' plasma despite differences in the cobalt–HSA binding assay. Plasma free cysteine/cystine ratio appears to play a role in the quantitative response of the cobalt–HSA binding assay. Conclusions The main determinants of the cobalt–HSA binding assay mechanism of action include but are not limited to: the proportion of intact N-terminus of HSA, HSA concentration, plasma cysteine/cystine ratio, plasma pH, and the state of oxidation of cys34 of HSA. Assay improvements that consider and take these factors into account could lead to an improved cobalt–HSA binding assay with greater clinical utility.

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. Electronic supplementary material The online version of this article (doi:10.1186/s13049-015-0180-5) contains supplementary material, which is available to authorized users.

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.To investigate the effect of age on the association between the GCS and anatomic TBI severity.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.We compared elderly (≥65 years) and younger (18-64 years) adults with TBI.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.During the study period, 6710 patients had a TBI (aged65 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).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.

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.