ASSESSMENT OF ABNORMAL SKELETAL MUSCLE PERFUSION BY CONTRAST-ENHANCED ULTRASOUND WITH PARAMETRIC IMAGING IN RATS AFTER SEVERE INJURY, HEMORRHAGIC SHOCK, AND WHOLE BLOOD RESUSCITATION.

ABSTRACT: Background: After severe injury, optical measures of microvascular blood flow (MBF) decrease and do not normalize with resuscitation to normal blood pressure. These changes are associated with organ dysfunction, coagulopathy, and death. However, the pathophysiology is not well understood. Several possible pathways could also contribute to the development of trauma-induced coagulopathy (TIC). A small-animal model of trauma-related MBF derangement that persists after resuscitation and includes TIC would facilitate further study. Parametric contrast-enhanced ultrasound (CEUS) is particularly advantageous in this setting, because it noninvasively assesses MBF in large, deep vascular beds. We sought to develop such a model, measuring MBF with CEUS. Methods: Sixteen male Sprague-Dawley rats were anesthetized, ventilated, and cannulated. Rats were subjected to either no injury (sham group) or a standardized polytrauma and pressure-targeted arterial catheter hemorrhage with subsequent whole blood resuscitation (trauma group). At prespecified time points, CEUS measurements of uninjured quadriceps muscle, viscoelastic blood clot strength, and complete blood counts were taken. Results: After resuscitation, blood pressure normalized, but MBF decreased and remained low for the rest of the protocol. This was primarily driven by a decrease in blood volume with a relative sparing of blood velocity. Viscoelastic blood clot strength and platelet count also decreased and remained low throughout the protocol. Conclusion: We present a rat model of MBF derangement in uninjured skeletal muscle and coagulopathy after polytrauma that persists after resuscitation with whole blood to normal macrohemodynamics. Parametric CEUS analysis shows that this change is primarily due to microvascular obstruction. This platform can be used to develop a deeper understanding of this important process.

A novel melanocortin fusion protein inhibits fibrinogen oxidation and degradation during trauma-induced coagulopathy.

Immune cell inflammation is implicated in the pathophysiology of acute trauma-induced coagulopathy (TIC). We hypothesized that leukocyte inflammation contributes to TIC through the oxidation and proteolysis of fibrinogen. To test this hypothesis, antioxidants and a novel anti-inflammatory melanocortin fusion protein (AQB-565) were used to study the effects of interleukin-6 (IL-6)-stimulated human leukocytes on fibrinogen using single-cell imaging flow cytometry and multiplex fluorescent western blotting. We also studied the effects of AQB-565 on fibrinogen using an in vivo rat trauma model of native TIC. IL-6 induced cellular inflammation and mitochondrial superoxide production in human monocytes, causing fibrinogen oxidation and degradation in vitro. Antioxidants suppressing mitochondrial superoxide reduced oxidative stress and inflammation and protected fibrinogen. AQB-565 decreased inflammation, inhibited mitochondrial superoxide, and protected fibrinogen in vitro. Trauma with hemorrhagic shock increased IL-6 and other proinflammatory cytokines and chemokines, selectively oxidized and degraded fibrinogen, and induced TIC in rats in vivo. AQB-565, given at the onset of hemorrhage, blocked inflammation, protected fibrinogen from oxidation and degradation, and prevented TIC. Leukocyte activation contributes to TIC through the oxidation and degradation of fibrinogen, which involves mitochondrial superoxide and cellular inflammation. Suppression of inflammation by activation of melanocortin pathways may be a novel approach for the prevention and treatment of TIC.

Slow Intravenous Infusion of a Novel Damage Control Cocktail Decreases Blood Loss in a Pig Polytrauma Model.

BACKGROUND: Our objective was to optimize a novel damage control resuscitation (DCR) cocktail composed of hydroxyethyl starch, vasopressin, and fibrinogen concentrate for the polytraumatized casualty. We hypothesized that slow intravenous infusion of the DCR cocktail in a pig polytrauma model would decrease internal hemorrhage and improve survival compared with bolus administration. METHODS: We induced polytrauma, including traumatic brain injury (TBI), femoral fracture, hemorrhagic shock, and free bleeding from aortic tear injury, in 18 farm pigs. The DCR cocktail consisted of 6% hydroxyethyl starch in Ringer's lactate solution (14mL/kg), vasopressin (0.8U/kg), and fibrinogen concentrate (100mg/kg) in a total fluid volume of 20mL/kg that was either divided in half and given as two boluses separated by 30 minutes as control or given as a continuous slow infusion over 60 minutes. Nine animals were studied per group and monitored for up to 3 hours. Outcomes included internal blood loss, survival, hemodynamics, lactate concentration, and organ blood flow obtained by colored microsphere injection. RESULTS: Mean internal blood loss was significantly decreased by 11.1mL/kg with infusion compared with the bolus group (p = .038). Survival to 3 hours was 80% with infusion and 40% with bolus, which was not statistically different (Kaplan Meier log-rank test, p = .17). Overall blood pressure was increased (p < .001), and blood lactate concentration was decreased (p < .001) with infusion compared with bolus. There were no differences in organ blood flow (p > .09). CONCLUSION: Controlled infusion of a novel DCR cocktail decreased hemorrhage and improved resuscitation in this polytrauma model compared with bolus. The rate of infusion of intravenous fluids should be considered as an important aspect of DCR.

Left Ventricular Function in the Initial Period After Severe Traumatic Brain Injury in Swine.

BACKGROUND: Cardiac dysfunction is common in the days after severe traumatic brain injury (TBI) and may contribute to hypotension episodes, leading to worse outcomes. Little is known about cardiac function in the minutes and hours immediately following TBI. By using fluid percussion TBI in a swine model, we aimed to characterize the immediate post injury cardiac function. METHODS: Intubated, anesthetized immature (25.8 ± 1.5 kg) female swine were subjected to severe fluid percussion TBI (4.2 ± 0.2 atm). Beginning at 45 min, simulating hospital arrival, all animals were resuscitated with normal saline (NS), mannitol, and phenylephrine as needed to maintain a cerebral perfusion pressure more than 60 mm Hg and intracranial pressure (ICP) less than 20 mm Hg. Primary outcomes of cardiac function were cardiac output measured by thermodilution and transesophageal echo measurements of cardiac function recorded at prespecified time points and tested for trends over time using linear regression with spline at the time of resuscitation onset. Secondary outcomes included hemodynamic measurements, ICP, and cerebral perfusion pressure. RESULTS: Eighteen animals were included. Post-TBI hemodynamic changes demonstrated an early decrease in mean arterial pressure and cerebral perfusion pressure with a corresponding increase in heart rate and ICP. Immediately after injury, there was a significant decrease in both left atrial area and tissue Doppler imaging e' of the LV lateral wall. In addition, there was a simultaneous increase in LV end diastolic diameter and increase in E/e' ratio of the lateral mitral annulus. All other transesophageal echo measurements demonstrated no significant changes throughout the duration of the experiment. CONCLUSIONS: Traumatic brain injury is associated with cardiac dysfunction and increased mortality, however there is still a limited understanding of the hemodynamic and echocardiographic response associated with TBI. In this study we demonstrate the hemodynamic and echocardiographic changes in the early stages of TBI in swine. The authors hope that these results may help better understanding on the management of patients with severe head injury.

Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress.

Critical illness leads to rapid fibrinogen consumption, hyperfibrinolysis, and coagulopathy that exacerbates bleeding and increases mortality. Immune cell activation and inflammation are associated with coagulopathy after injury but play an undetermined role. We performed high dimensional immunophenotyping and single-cell imaging flow cytometry to investigate for a pathophysiological mechanism governing the effects of leukocyte-associated inflammation on fibrinogen function. Fibrinogen was oxidized early, followed by its degradation after 3 hours of lipopolysaccharides (LPS)-induced sterile inflammation in a rat model in vivo. Fibrinogen incubated with human leukocytes activated by TNFα was similarly oxidized, and later proteolyzed after 3 hours in vitro. TNFα induced mitochondrial superoxide generation from neutrophils and monocytes, myeloperoxidase (MPO)-derived reactive oxygen species (ROS) from neutrophils, and nitric oxide from lymphocytes and monocytes. Inhibition of mitochondrial superoxide prevented oxidative modification and proteolysis of fibrinogen, whereas inhibition of MPO attenuated only fibrinogen proteolysis. Quenching of both mitochondrial superoxide and MPO-derived ROS prevented coagulopathy better than tranexamic acid. Collectively, these findings indicate that neutrophil and monocyte mitochondrial superoxide generation can rapidly oxidize fibrinogen as a priming step for fibrinogen proteolysis and coagulopathy during inflammation.

A Multifunctional, Low-Volume Resuscitation Cocktail Improves Vital Organ Blood Flow and Hemostasis in a Pig Model of Polytrauma with Traumatic Brain Injury.

The resuscitation of polytrauma with hemorrhagic shock and traumatic brain injury (TBI) is a balance between permissive hypotension and maintaining vital organ perfusion. There is no current optimal solution. This study tested whether a multifunctional resuscitation cocktail supporting hemostasis and perfusion could mitigate blood loss while improving vital organ blood flow during prolonged limited resuscitation. Anesthetized Yorkshire swine were subjected to fluid percussion TBI, femur fracture, catheter hemorrhage, and aortic tear. Fluid resuscitation was started when lactate concentration reached 3-4 mmol/L. Animals were randomized to one of five groups. All groups received hydroxyethyl starch solution and vasopressin. Low- and high-dose fibrinogen (FBG) groups additionally received 100 and 200 mg/kg FBG, respectively. A third group received TXA and low-dose FBG. Two control groups received albumin, with one also including TXA. Animals were monitored for up to 6 h. Blood loss was decreased and vital organ blood flow was improved with low- and high-dose fibrinogen compared to albumin controls, but survival was not improved. There was no additional benefit of high- vs. low-dose FBG on blood loss or survival. TXA alone decreased blood loss but had no effect on survival, and combining TXA with FBG provided no additional benefit. Pooled analysis of all groups containing fibrinogen vs. albumin controls found improved survival, decreased blood loss, and improved vital organ blood flow with fibrinogen delivery. In conclusion, a low-volume resuscitation cocktail consisting of hydroxyethyl starch, vasopressin, and fibrinogen concentrate improved outcomes compare to controls during limited resuscitation of polytrauma.

Plasma proteomic profile associated with platelet dysfunction after trauma.

BACKGROUND: Coagulopathic bleeding is a major cause of mortality after trauma, and platelet dysfunction contributes to this problem. The causes of platelet dysfunction are relatively unknown, but a great deal can be learned from the plasma environment about the possible pathways involved. OBJECTIVE: Describe the changes in plasma proteomic profile associated with platelet dysfunction after trauma. METHODS: Citrated blood was collected from severely injured trauma patients at the time of their arrival to the Emergency Department. Samples were collected from 110 patients, and a subset of twenty-four patients was identified by a preserved (n = 12) or severely impaired (n = 12) platelet aggregation response to five different agonists. Untargeted proteomics was performed by nanoflow liquid chromatography tandem mass spectrometry. Protein abundance levels for each patient were normalized to total protein concentration to control for hemodilution by crystalloid fluid infusion prior to blood draw. RESULTS: Patients with platelet dysfunction were more severely injured but otherwise demographically similar to those with retained platelet function. Of 232 proteins detected, twelve were significantly different between groups. These proteins fall into several broad categories related to platelet function, including microvascular obstruction with platelet activation, immune activation, and protease activation. CONCLUSIONS: This observational study provides a description of the change in proteomic profile associated with platelet dysfunction after trauma and identifies twelve proteins with the most profound changes. The pathways involving these proteins are salient targets for immediate investigation to better understand platelet dysfunction after trauma and identify targets for intervention.

Lessons learned from COVID-19 outbreak in a skilled nursing facility, Washington State.

Long-term care facilities have been identified as a local epicenter of disease among populations vulnerable to coronavirus disease 2019 (COVID-19). A skilled nursing facility in Washington State was the first major site of COVID-19 infections in the United States. Many lessons were learned during the events surrounding this outbreak, including how to develop, and the importance of, a coordinated response between emergency medical services and local area hospitals. As these events came early in the U.S. pandemic, unfortunately, disease spread and mortality was high. However, these events also resulted in rapid mobilization of the regional response to the COVID-19 pandemic. Understanding the events surrounding this outbreak demonstrate some of the challenges involved in responding to acute infectious illnesses within these unique environments and associated vulnerable populations.

Developing Emergency Medicine Leaders: The AACEM/SAEM Chair Development Program at 5 Years.

The Association of Academic Chairs of Emergency Medicine Chair Development Program (CDP) was started in 2014 to provide emergency medicine (EM) chairs and leaders who aspired to become academic chairs with EM-specific leadership training. Each class participated in a 1-year program, with five sessions taught primarily by EM leaders. Data from the first 5 years of the CDP are provided. A total of 81 participants completed the program (16% women). Twenty participants who were not chairs at entry have become EM chairs. Ratings of the CDP based on a survey of participants with a 94% response rate were very favorable. The CDP has been a popular and successful vehicle to increase leadership skills and prepare EM leaders for academic chair positions.

Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

INTRODUCTION: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. MATERIALS AND METHODS: We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. RESULTS: Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. CONCLUSION: In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage.

Hemorrhage is the leading cause of preventable death in trauma, and hemorrhage from noncompressible junctional anatomic sites is particularly difficult to control. The current standard is QuikClot Combat Gauze packing, which requires 3 min of compression. We have created a novel dressing with calcium carbonate microparticles that can disperse and self-propel upstream against flowing blood. We loaded these microparticles with thrombin and tranexamic acid and tested their efficacy in a swine arterial bleeding model without wound compression. Anesthetized immature female swine received 5 mm femoral arteriotomies to induce severe junctional hemorrhage. Wounds were packed with kaolin-based QuikClot Combat Gauze (KG), propelled thrombin-microparticles with protonated tranexamic acid (PTG), or a non-propelling formulation of the same thrombin-microparticles with non-protonated tranexamic acid (NPTG). Wounds were not compressed after packing. Each animal then received one 15 mL/kg bolus of hydroxyethyl starch solution followed by Lactated Ringer as needed for hypotension (maximum: 100 mL/kg) for up to 3 h. Survival was improved with PTG (3-h survival: 8/8, 100%) compared with KG (3/8, 37.5%) and NPTG (2/8, 25%) (P <0.01). PTG animals maintained lower serum lactate and higher hemoglobin concentrations than NPTG (P <0.05) suggesting PTG decreased severity of subsequent hemorrhagic shock. However, total blood loss, Lactated Ringer infusion volumes, and mean arterial pressures of surviving animals were not different between groups (P >0.05). Thus, in this swine model of junctional arterial hemorrhage, gauze with self-propelled, prothrombotic microparticles improved survival and 2 indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds.

Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury.

Victims of trauma often develop impaired blood clot formation (coagulopathy) that contributes to bleeding and mortality. Fibrin polymerization is one critical component of clot formation that can be impacted by post-translational oxidative modifications of fibrinogen after exposure to oxidants. In vitro evidence suggests that Aα-C domain methionine sulfoxide formation, in particular, can induce conformational changes that prevent lateral aggregation of fibrin protofibrils during polymerization. We used mass spectrometry of plasma from trauma patients to find that fibrinogen Aα-C domain methionine sulfoxide content was selectively-increased in patients with coagulopathy vs. those without coagulopathy. This evidence supports a novel linkage between oxidative stress, coagulopathy, and bleeding after injury.

Survey of Ebola Preparedness in Washington State Emergency Departments.

OBJECTIVE: The 2014 Ebola virus disease (EVD) outbreak in West Africa remains the most deadly in history. Emergency departments (EDs) are more likely to come into contact with potential EVD patients. It is important for EDs to be prepared to care for suspected EVD patients. Our objective was to understand the perceived challenges experienced by Washington State ED medical directors in EVD preparedness. METHODS: An anonymous, electronic survey was sent to a convenience sample of ED medical directors across Washington State between November and February of 2014-2015. The perceived challenges of and attitudes toward EVD preparations were assessed and reported as stratified proportions. RESULTS: Of 85 medical directors contacted, 59 responses (69%) were received. This included EDs with annual patient volumes of 60,000 (12 hospitals, 20%). Among the perceived challenges in EVD preparations were spatial modifications (eg, building an anteroom for donning and doffing of personal protective equipment) and waste management planning. Ninety-five percent of respondents moderately or strongly agreed that it is important to have a predesignated hospital to care for EVD patients. CONCLUSIONS: Washington State ED medical directors have faced significant challenges in ensuring their EDs are prepared to safely care for suspected EVD patients. Attitudes toward EVD preparations are mixed. Varying levels of perceived importance may represent an additional barrier to statewide EVD preparedness. (Disaster Med Public Health Preparedness. 2016;10:662-668).

Effects of rapid wound sealing on survival and blood loss in a swine model of lethal junctional arterial hemorrhage.

BACKGROUND: Hemostatic gauzes, which must be packed into wounds and compressed for several minutes, may be of limited use for noncompressible wounds in junctional anatomic locations. Rapid mechanical wound sealing is an alternative approach that seals the wound at the skin, allowing internal clot formation. We evaluate wound sealing for junctional hemorrhage control using a hemostatic clamp (iTClamp). METHODS: Severe junctional hemorrhage was induced in anesthetized immature female swine using a 5-mm femoral arteriotomy. After 30 seconds of free bleeding, animals were randomized to one of seven hemostatic interventions: no intervention (control), direct compression for 3 minutes (compression), plain gauze packing (packing), mechanical wound seal (seal), plain gauze packing + wound seal (packing + seal), plain gauze packing + compression (packing + compression), or hemostatic gauze packing (Combat Gauze) + compression (HS-packing + compression). All animals then received one 15-mL/kg bolus of Hextend, followed by lactated Ringer's solution for hypotension up to 100 mL/kg. Animals were monitored for 3 hours. RESULTS: Survival was similar between control (3-hour survival, 0%) and compression (0%, Kaplan-Meier survival analysis and log-rank test [KM-LR], p = 1.0) but marginally improved with packing (12.5%, KM-LR, p < 0.001). Survival improved with seal (62.5%) versus control (KM-LR, p < 0.001) and with packing + seal (100%) versus packing alone (KM-LR, p < 0.001). Survival was similar between packing + compression (87.5%), HS-packing + compression (62.5%), and packing + seal (100%) (KM-LR, p ≥ 0.05). Total hemorrhage volume was decreased for seal versus control (p < 0.001) and for packing + seal versus packing (p < 0.001). Hemorrhage was similar among packing + compression, HS-packing + compression, seal, and packing + seal (analysis of variance p ≥ 0.05). Application times (mean [SD]) were significantly faster with packing + seal (125.8 [56.2] seconds) than packing + compression (236.6 [7.2] seconds) and HS-packing + compression (223.0 [6.8] seconds) (analysis of variance, all p < 0.001). CONCLUSION: In this preclinical junctional hemorrhage model, rapid wound sealing improved survival and decreased hemorrhage in both packed and unpacked wounds and performed comparably with standard-of-care hemostatic bandages. Rapidly sealing junctional wounds may be a viable alternative to wound compression.

Coparenting breastfeeding support and exclusive breastfeeding: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a coparenting intervention on exclusive breastfeeding among primiparous mothers and fathers. METHODS: A randomized controlled trial was conducted in a large teaching hospital in Toronto, Canada. Couples were randomized to receive either usual care (n = 107) or a coparenting breastfeeding support intervention (n = 107). Follow-up of exclusive breastfeeding and diverse secondary outcomes was conducted at 6 and 12 weeks postpartum. RESULTS: Significantly more mothers in the intervention group than in the control group continued to breastfeed at 12 weeks postpartum (96.2% vs 87.6%, P = .02). Although proportionately more mothers in the intervention group were exclusively breastfeeding at 6 and 12 weeks, these differences were not significant. Fathers in the intervention group had a significantly greater increase in breastfeeding self-efficacy scores from baseline to 6 weeks postpartum compared with fathers in the control group (P = .03). In addition, significantly more mothers in the intervention group than in the control group reported that their partners provided them with breastfeeding help in the first 6 weeks (71% vs 52%, P = .02) and that they were satisfied with their partners' involvement with breastfeeding (89% vs 78.1%, P = .04). Mothers in the intervention group were also more satisfied with the breastfeeding information they received (81% vs 62.5%, P < .001). CONCLUSIONS: The significant improvements in breastfeeding duration, paternal breastfeeding self-efficacy, and maternal perceptions of paternal involvement and assistance with breastfeeding suggest that a coparenting intervention involving fathers warrants additional investigation.

Fibrinogen concentrate improves survival during limited resuscitation of uncontrolled hemorrhagic shock in a Swine model.

The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4-mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (n = 7 per group) were then randomized to receive (i) no fluid resuscitation (neg control) or (ii) limited resuscitation in the form of two boluses of 10 mL/kg of 6% hydroxyethyl starch solution given 30 min apart (HEX group), or (iii) the same fluid regimen with one dose of 120-mg/kg fibrinogen concentrate given with the first hydroxyethyl starch bolus (FBG). Animals were then observed for a total of 6 h with aortic repair and aggressive resuscitation with shed blood taking place at 3 h. Survival to 6 h was significantly increased with FBG (7/8, 86%) versus HEX (2/7, 29%) and neg control (0/7, 0%) (FBG vs. HEX, Kaplan-Meier log-rank P = 0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4 mL/kg per minute) when compared with FBG (0.1 mg/kg per minute, P = 0.047) and neg control (0.1 mL/kg per minute, P = 0.041). Systemic and cerebral hemodynamics also showed improvement with FBG versus HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock.

Fluid resuscitation of uncontrolled hemorrhage using a hemoglobin-based oxygen carrier: effect of traumatic brain injury.

Animal models of combined traumatic brain injury (TBI) and hemorrhagic shock (HS) suggest a benefit of hemoglobin-based oxygen carrier (HBOC)-based resuscitation, but their use remains controversial, and little is known of the specific effects of TBI and high-pressure (large arterial injury) bleeding on resuscitation. We examine the effect of TBI and aortic tear injury on low-volume HBOC resuscitation in a swine polytrauma model and hypothesize that HBOC-based resuscitation will improve survival in the setting of aortic tear regardless of the presence of TBI. Anesthetized swine subjected to HS with aortic tear with or without fluid percussion TBI underwent equivalent limited resuscitation with HBOC, lactated Ringer's solution, or HBOC + nitroglycerine (vasoattenuated HBOC) and were observed for 6 h. There was no independent effect of TBI on survival time after adjustment for fluid type, and there was no interaction between TBI and resuscitation fluid type. However, total catheter hemorrhage volume required to reach target shock blood pressure was less with TBI (14.0 mL · kg(-1) [confidence interval, 12.4-15.6 mL · kg(-1)]) versus HS only (21.0 mL · kg(-1) [confidence interval, 19.5-22.5 mL · kg(-1)]), with equivalent lactate accumulation. Traumatic brain injury did not affect survival in this polytrauma model, but less hemorrhage was required in the presence of TBI to achieve an equivalent degree of shock suggesting globally impaired cardiovascular response to hemorrhage in the presence of TBI. There was also no benefit of HBOC-based fluid resuscitation over lactated Ringer's solution, contrary to models using liver injury as the source of hemorrhage, considering wound location is of paramount importance when choosing resuscitation strategy.

Cognitive impairment and its relation to imaging measures in multiple sclerosis: a study using a computerized battery.

BACKGROUND AND PURPOSE: Cognitive impairment (CI) is an important component of multiple sclerosis (MS) disability. A complex biological interplay between white matter (WM) and gray matter (GM) disease likely sustains CI. This study aims to address this issue by exploring the association between the extent of normal WM and GM disease and CI. METHODS: Cognitive function of 24 MS patients and 24 healthy volunteers (HVs) was studied using the Automated Neuropsychological Assessment Metrics (ANAM) battery. WM focal lesions and normal appearing WM (NAWM) volume in patients, cortical thickness (CTh) and deep GM structure volumes in both patients and HVs were measured by high field strength (3.0-Tesla; 3T) imaging. RESULTS: An analysis of covariance showed that patients performed worse than HVs on Code Substitution Delayed Memory (P = .04) and Procedural Reaction Time (P = .05) indicative of reduced performance in memory, cognitive flexibility, and processing speed. A summary score (Index of Cognitive Efficiency) indicating global test battery performance was also lower for the patient group (P = .04). Significant associations, as determined by the Spearman rank correlation tests, were noted between each of these 3 cognitive scores and measures of NAWM volume [CDD-TP1(r = .609; P = .0035), PRO-TP1 (r = .456; P = .029) and ICE (r = .489; P = .0129)], CTh (r = .5; P ≤ .05) and volume of subcortical normal appearing GM (NAGM) structures (r = .4; P≤ .04), but not WM lesions. CONCLUSIONS: Both NAWM and NAGM volumes are related to CI in MS. The results highlight once again the urgent need to develop pharmacological strategies protecting patients from widespread neurodegeneration as possible preventive strategies of CI development.

Discrimination of ADHD and reading disability in adults using the D-KEFS.

Attention deficit/hyperactivity disorder (ADHD) is posited to be the result of a deficit in executive functions (EFs). The presence of EF deficits in adults with ADHD is not consistent, and EF deficits are not unique to ADHD, thus adding a level of complexity to differential diagnoses. The current study used three measures of EF to discriminate between college-level adults diagnosed with ADHD and reading disability (RD). The RD group performed below ADHD on all EF tasks and logistic regression analyses demonstrated poor sensitivity and adequate specificity of the EF measures to categorize the clinical groups. Results suggest that clinicians should be cognizant of the limitations of measures of EF in the differential diagnosis of ADHD.