Risk Factors for Admission and Prolonged Length of Stay in Pediatric Isolated Skull Fractures.

OBJECTIVES: This study aimed to assess management of pediatric isolated skull fracture (ISF) patients by determining frequency of admission and describing characteristics associated with patients admitted for observation compared with patients discharged directly from the emergency department (ED) and those requiring a prolonged hospitalization. METHODS: We evaluated children younger than 5 years who presented with ISF using the South Carolina Traumatic Brain Injury Surveillance and Registry System data from 2001 to 2011. Outcomes analyzed included discharged from ED, admitted for less than 24 hours, and admitted for more than 24 hours (prolonged hospitalization). Bivariate analyses and a polytomous logistic regression model identified factors associated with patient disposition. RESULTS: Five hundred twenty-seven patients met the study criteria (ED discharge = 283 [53%]; inpatient <24 hours = 156 [29%]; inpatient >24 hours = 88 [18%]). The mean length of stay for admissions was 1.9 (SD, 1.5) days. In the regression model, ED discharges had greater odds of presenting to levels 2 to 3 hospitals (level 2: odds ratio [OR], 6.16; 95% confidence interval [CI], 3.66-10.39; level 3: OR, 30.98; 95% CI, 10.92-87.91) and lower odds of a high poverty status (OR, 0.20; 95% CI, 0.10-0.40). Prolonged hospitalizations had greater odds of concomitant injuries (OR, 2.21; 95% CI, 1.12-4.36). CONCLUSIONS: Admission after ISF is high despite a low risk of deterioration. High-poverty patients presenting to high-acuity medical centers are more commonly admitted for observation. Only presence of concomitant injuries was clinically predictive of prolonged hospitalization. The ability to better stratify risk after pediatric ISF would help providers make more informed decisions regarding ED disposition.

Antimicrobial copper alloys decreased bacteria on stethoscope surfaces.

BACKGROUND: Stethoscopes may serve as vehicles for transmission of bacteria among patients. The aim of this study was to assess the efficacy of antimicrobial copper surfaces to reduce the bacterial concentration associated with stethoscope surfaces. METHODS: A structured prospective trial involving 21 health care providers was conducted at a pediatric emergency division (ED) (n = 14) and an adult medical intensive care unit located in tertiary care facilities (n = 7). Four surfaces common to a stethoscope and a facsimile instrument fabricated from U.S. Environmental Protection Agency-registered antimicrobial copper alloys (AMCus) were assessed for total aerobic colony counts (ACCs), methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and vancomycin-resistant enterococci for 90 days. RESULTS: The mean ACCs collectively recovered from all stethoscope surfaces fabricated from the AMCus were found to carry significantly lower concentrations of bacteria (pediatric ED, 11.7 vs 127.1 colony forming units [CFU]/cm2, P < .00001) than their control equivalents. This observation was independent of health care provider or infection control practices. Absence of recovery of bacteria from the AMCu surfaces (66.3%) was significantly higher (P < .00001) than the control surfaces (22.4%). The urethane rim common to the stethoscopes was the most heavily burdened surface; mean concentrations exceeded the health care-associated infection acquisition concentration (5 CFU/cm2) by at least 25×, supporting that the stethoscope warrants consideration in plans mitigating microbial cross-transmission during patient care. CONCLUSIONS: Stethoscope surfaces fabricated with AMCus were consistently found to harbor fewer bacteria.

Essential roles of neutral ceramidase and sphingosine in mitochondrial dysfunction due to traumatic brain injury.

In addition to immediate brain damage, traumatic brain injury (TBI) initiates a cascade of pathophysiological events producing secondary injury. The biochemical and cellular mechanisms that comprise secondary injury are not entirely understood. Herein, we report a substantial deregulation of cerebral sphingolipid metabolism in a mouse model of TBI. Sphingolipid profile analysis demonstrated increases in sphingomyelin species and sphingosine concurrently with up-regulation of intermediates of de novo sphingolipid biosynthesis in the brain. Investigation of intracellular sites of sphingosine accumulation revealed an elevation of sphingosine in mitochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingosine kinase 2 (SphK2). The lack of change in gene expression suggested that post-translational mechanisms are responsible for the shift in the activities of both enzymes. Immunoprecipitation studies revealed that SphK2 is complexed with NCDase and cytochrome oxidase (COX) subunit 1 in mitochondria and that brain injury hindered SphK2 association with the complex. Functional studies showed that sphingosine accumulation resulted in a decreased activity of COX, a rate-limiting enzyme of the mitochondrial electron transport chain. Knocking down NCDase reduced sphingosine accumulation in mitochondria and preserved COX activity after the brain injury. Also, NCDase knockdown improved brain function recovery and lessened brain contusion volume after trauma. These studies highlight a novel mechanism of secondary TBI involving a disturbance of sphingolipid-metabolizing enzymes in mitochondria and suggest a critical role for mitochondrial sphingosine in promoting brain injury after trauma.

Beneficial effect of a CXCR4 agonist in murine models of systemic inflammation.

The chemokine CXC receptor 4 (CXCR4) is activated by stromal cell-derived factor (SDF-1α). CXCR4 may be part of a lipopolysaccharide (LPS) sensing co-clustering complex that modulates TLR4 activation and evidence suggest that SDF-1α can activate anti-inflammatory signaling pathways and suppress inflammation. In the present study we examined the hypothesis that the SDF-1α peptide analog and CXCR4 agonist CTCE-0214 is anti-inflammatory in three distinct models of murine systemic inflammation. Our findings demonstrate that CTCE-0214 in vivo significantly suppressed plasma tumor necrosis factor alpha (TNF-α) increases in acute endotoxemia and following zymosan-induced multiple organ dysfunction syndrome (MODS). In both models, CTCE-0214 did not suppress plasma increases in the anti-inflammatory cytokine interleukin (IL)-10. CTCE-0214 improved survival without antibiotics in a model of severe sepsis induced by cecal ligation and puncture (CLP). CTCE-0214 also decreased plasma increases in IL-6 but not TNF-α and IL-10 in response to CLP-induced inflammation. We demonstrated in a moderately severe model of CLP (one puncture) that IL-6 levels at 24 h were similar to sham controls. However in severe CLP (two punctures) plasma IL-6 levels were markedly elevated. Plasma SDF-1α levels varied inversely with the plasma IL-6. In addition to the beneficial effect of CTCE-0214 in these models of systemic inflammation in vivo, we also demonstrated that the analog dose dependently suppressed LPS-induced IL-6 production in bone marrow-derived macrophages. CTCE-0214 therefore may be beneficial in controlling inflammation sepsis and systemic inflammatory syndromes.

Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: isoform specific regulation of inflammation.

Pro-inflammatory cytokines and chemokines play critical roles in autoimmune diseases including rheumatoid arthritis (RA). Recently, it has been reported that ß-arrestin 1 and 2 are involved in the regulation of inflammation. We hypothesized that ß-arrestin 1 and 2 play critical roles in murine models of RA. Using a collagen-induced arthritis (CIA) and a human TNFα transgenic (TNFtg) mouse model, we demonstrated that ß-arrestin 1 and 2 expression are significantly increased in joint tissue of CIA mice and TNFtg mice. In fibroblast-like synoviocytes (FLS) isolated from hind knee joint of CIA mice, we observed an increase of ß-arrestin 1 and 2 protein and mRNA levels in the early stage of arthritis. In FLS, low molecular weight hyaluronan (HA)-induced TNFα and IL-6 production was increased by overexpression of ß-arrestin 1 but decreased by overexpression of ß-arrestin 2 demonstrating isoform specific regulation. TNFα and HA induced an increase of ß-arrestin 1 and 2 expression in FLS, while high mobility group box (HMGB)-1 only stimulated ß-arrestin 1 expression. TNFα- or HA-induced ß-arrestin 2 expression was blocked by a p38 inhibitor. To examine the in vivo role of ß-arrestin 2 in the pathogenesis of arthritis, WT and ß-arrestin 2 KO mice were subjected to collagen antibody-induced arthritis (CAIA). ß-Arrestin 2 KO mice exhibited more severe arthritis in CAIA. Thus ß-arrestin 2 is anti-inflammatory in CAIA. These composite observations suggest that ß-arrestin 1 and 2 differentially regulate FLS inflammation and increased ß-arrestin 2 may reduce experimental arthritis severity.

Identification and risk-stratification of problem alcohol drinkers with minor trauma in the emergency department.

BACKGROUND: Brief alcohol intervention may improve outcomes for injury patients with hazardous drinking but is less effective with increased severity of alcohol involvement. This study evaluated a brief method for detecting problem drinking in minor trauma patients and differentiating hazardous drinkers from those with more severe alcohol problems. METHODS: Subjects included 60 minor trauma patients in an academic urban emergency department (ED) who had consumed any amount of alcohol in the prior month. Screening and risk stratification involved the use of a heavy-drinking-day screening item and the Rapid Alcohol Problems Screen (RAPS). We compared the heavy-drinking-day item to past-month alcohol use, as obtained by validated self-reporting methods, and measured the percentage of carbohydrate-deficient transferrin (%CDT) to assess the accuracy of self-reporting. The Alcohol Dependence Scale (ADS) was administered to gauge the severity of alcohol involvement and compared to the RAPS. RESULTS: Eighty percent of the subjects endorsed at least one heavy drinking day in the past year, and all patients who exceeded recommended weekly drinking limits endorsed at least one heavy drinking day. Among those with at least one heavy drinking day, 58% had a positive RAPS result. Persons with no heavy drinking days (n=12) had a median ADS of 0.5 (range 0 to 3). RAPS-negative persons with heavy drinking days (n=20) had a median ADS of 2 (range 0 to 8). RAPS-positive persons with heavy drinking days (n=28) had a median ADS of 8 (range 1 to 43). CONCLUSION: A heavy-drinking-day item is useful for detecting hazardous drinking patterns, and the RAPS is useful for differentiating more problematic drinkers who may benefit from referral from those more likely to respond to a brief intervention. This represents a time-sensitive approach for risk-stratifying non-abstinent injury patients prior to ED discharge.

Prevalence of problem drinking and characteristics of a single-question screen.

Hazardous drinking and alcohol use disorders (i.e, abuse and dependence) are common in Emergency Departments (EDs). This study examined 1) the prevalence of these conditions among ED patients and 2) characteristics of a single screening question (having consumed at least five drinks for males or four for females during a single day). Data from the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed. Logistic regression for clustered data was used to estimate the relative risk for past-year ED use associated with hazardous drinking, abuse, and dependence. Contingency tables were analyzed to estimate the sensitivity and specificity of the single-question screen for detecting these conditions. Hazardous drinking was not associated with ED utilization. Alcohol abuse was associated with a relative risk of 1.3 (95% confidence interval [CI] 1.1-1.5) and alcohol dependence with a relative risk of 1.9 (95% CI 1.6-2.2). For current drinkers, the single question screen was 0.96, 0.85, and 0.90 sensitive for hazardous drinking, alcohol abuse, and alcohol dependence, respectively. Individuals with a positive screen in the past year were considered at least hazardous drinkers, and specificity was 0.80, 0.64, and 0.65 for hazardous drinking, abuse, and dependence, respectively. Specificity was modestly increased in women. Most problem drinkers were hazardous drinkers, but only severe alcohol use disorders were particularly prevalent in the ED. The single heavy-drinking-day item appears sensitive for problem drinking. Positive tests must be followed by additional assessment to differentiate hazardous drinking from alcohol use disorders.

beta-Arrestin 2: a Negative Regulator of Inflammatory Responses in Polymorphonuclear Leukocytes.

Heterotrimeric Gi proteins have been previously implicated in signaling leading to inflammatory mediator production induced by bacterial lipopolysaccharide (LPS). beta-arrestins are ubiquitously expressed proteins that alter G-protein-coupled receptors signaling. beta-arrestin 2 plays a multifaceted role as a scaffold protein in regulating cellular inflammatory responses. Polymorphonuclear leukocytes (PMNs) activated by LPS induce inflammatory responses resulting in organ injury during sepsis. We hypothesized that beta-arrestin 2 is a critical modulator of inflammatory responses in PMNs. To examine the potential role of beta-arrestin 2 in LPS-induced cellular activation, we studied homozygous beta-arrestin 2 (-/-), heterozygous (+/-), and wildtype (+/+) mice. PMNs were stimulated with LPS for 16h. There was increased basal TNFalpha and IL-6 production in the beta-arrestin 2 (-/-) compared to both beta-arrestin 2 (+/-) and (+/+) cells. LPS failed to stimulate TNFalpha production in the beta-arrestin 2 (-/-) PMNs. However, LPS stimulated IL-6 production was increased in the beta-arrestin 2 (-/-) cells compared to (+/+) cells. In subsequent studies, peritoneal PMN recruitment was increased 81% in the beta-arrestin 2 (-/-) mice compared to (+/+) mice (p<0.05). beta-arrestin 2 deficiency resulted in an augmented expression of CD18 and CD62L (p<0.05). In subsequent studies, beta-arrestin 2 (-/-) and (+/+) mice were subjected to cecal ligation and puncture (CLP) and lung was collected and analyzed for myeloperoxidase activity (MPO) as index of PMNs infiltrate. CLP-induced MPO activity was significantly increased (p<0.05) in the beta-arrestin 2 (-/-) compared to (+/+) mice. These studies demonstrate that beta-arrestin 2 is a negative regulator of PMN activation and pulmomary leukosequestration in response to polymicrobial sepsis.