Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia.

BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. METHODS: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. RESULTS: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. CONCLUSIONS: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia

Diagnosis and Management of Esophageal Injuries: A Western Trauma Association Critical Decisions Algorithm

ABSTRACT: This is a recommended management algorithm from the Western Trauma Association addressing the diagnostic evaluation and management of esophageal injuries in adult patients. Because there is a paucity of published prospective randomized clinical trials that have generated Class I data, the recommendations herein are based primarily on published observational studies and expert opinion of Western Trauma Association members. The algorithms and accompanying comments represent a safe and sensible approach that can be followed at most trauma centers. We recognize that there will be patient, personnel, institutional, and situational factors that may warrant or require deviation from the recommended algorithm. We encourage institutions to use this guideline to formulate their own local protocols. The algorithm contains letters at decision points; the corresponding paragraphs in the text elaborate on the thought process and cite pertinent literature. The annotated algorithm is intended to (a) serve as a quick bedside reference for clinicians; (b) foster more detailed patient care protocols that will allow for prospective data collection and analysis to identify best practices; and (c) generate research projects to answer specific questions concerning decision making in the management of adults with esophageal injuries

Whole Blood Resuscitation and Association with Survival in Injured Patients with an Elevated Probability of Mortality.

BACKGROUND: Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation. STUDY DESIGN: A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors. RESULTS: A total of 1,051 patients in hemorrhagic shock met all enrollment criteria. The cohort was severely injured with \u3e70% of patients requiring massive transfusion. After propensity adjustment, no significant 4-hour mortality difference across LTOWB and component patients was found (relative risk [RR] 0.90, 95% CI 0.59 to 1.39, p = 0.64). Similarly, no adjusted mortality differences were demonstrated at 24 hours or 28 days for the enrolled cohort. When patients with an elevated prehospital probability of mortality were analyzed, LTOWB resuscitation was independently associated with a 48% lower risk of 4-hour mortality (relative risk [RR] 0.52, 95% CI 0.32 to 0.87, p = 0.01) and a 30% lower risk of 28-day mortality (RR 0.70, 95% CI 0.51 to 0.96, p = 0.03). CONCLUSIONS: Early LTOWB resuscitation is safe but not independently associated with survival for the overall enrolled population. When patients were selected with an elevated probability of mortality based on prehospital injury characteristics, LTOWB was independently associated with a lower risk of mortality starting at 4 hours after arrival through 28 days after injury

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection

Background: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. Methods: Five hundred eighteen patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated. Patients were stratified by obese (BMI ≥30) versus non-obese (BMI≥30) status. Descriptive comparisons were performed using Chi-square test, Fisher exact test, or Wilcoxon rank-sum tests as appropriate. Multivariable logistic regression using a priori selected variables was performed to assess the independent association between obesity and treatment failure in patients with IAI. Results: Overall, 198 (38.3%) of patients were obese (BMI ≥30) versus 319 (61.7%) who were non-obese. Mean antibiotic d and total hospital d were similar between both groups. Unadjusted outcomes of surgical site infection (9.1% vs. 6.9%, p?=?0.36), recurrent intra-abdominal infection (16.2% vs. 13.8, p?=?0.46), death (1.0% vs. 0.9%, p?=?1.0), and a composite of all complications (25.3% vs. 19.8%, p?=?0.14) were also similar between both groups. After controlling for appropriate demographics, comorbidities, severity of illness, treatment group, and duration of antimicrobial therapy, obesity was not independently associated with treatment failure (c-statistic: 0.64). Conclusions: Obesity is not associated with antimicrobial treatment failure among patients with IAI. These results suggest that obesity may not independently influence the need for longer duration of antimicrobial therapy in treatment of IAI versus non-obese patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140219/1/sur.2015.213.pd

Hemoperitoneum Score Helps Determine Need for Therapeutic Laparotomy

Purpose: Sonography provides a fast, portable, and noninvasive method for patient assessment. However, the benefit of providing real-time ultrasound (US) imaging and fluid quantification shortly after patient arrival has not been explored. The objective of this study was to prospectively validate a US hemoperitoneum scoring system developed at our institution and determine whether sonography can predict a therapeutic operation. Methods: For 12 months, prospective data on all patients undergoing a trauma sonogram were recorded. All sonograms positive for free fluid were given a hemoperitoneum score. The US score was compared with initial systolic blood pressure and base deficit to assess the ability of sonography to predict a therapeutic laparotomy. Results: Forty of 46 patients (87%) with a US score > 3 required a therapeutic laparotomy. Forty-six of 54 patients with a US score < 3 (85%) did not need operative intervention. The sensitivity of sonography was 83% compared with 28% and 49% for systolic blood pressure and base deficit, respectively, in determining the need for therapeutic operation. Conclusion: We conclude that the majority of patients with a score > 3 will need surgery. The US hemoperitoneum scoring system was a better predictor of a therapeutic laparotomy than initial blood pressure and/or base deficit

Role of the Gulf Stream and Kuroshio–Oyashio systems in large-scale atmosphere–ocean interaction : a review

Author Posting. © American Meteorological Society, 2010. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 23 (2010): 3249-3281, doi:10.1175/2010JCLI3343.1.Ocean–atmosphere interaction over the Northern Hemisphere western boundary current (WBC) regions (i.e., the Gulf Stream, Kuroshio, Oyashio, and their extensions) is reviewed with an emphasis on their role in basin-scale climate variability. SST anomalies exhibit considerable variance on interannual to decadal time scales in these regions. Low-frequency SST variability is primarily driven by basin-scale wind stress curl variability via the oceanic Rossby wave adjustment of the gyre-scale circulation that modulates the latitude and strength of the WBC-related oceanic fronts. Rectification of the variability by mesoscale eddies, reemergence of the anomalies from the preceding winter, and tropical remote forcing also play important roles in driving and maintaining the low-frequency variability in these regions. In the Gulf Stream region, interaction with the deep western boundary current also likely influences the low-frequency variability. Surface heat fluxes damp the low-frequency SST anomalies over the WBC regions; thus, heat fluxes originate with heat anomalies in the ocean and have the potential to drive the overlying atmospheric circulation. While recent observational studies demonstrate a local atmospheric boundary layer response to WBC changes, the latter’s influence on the large-scale atmospheric circulation is still unclear. Nevertheless, heat and moisture fluxes from the WBCs into the atmosphere influence the mean state of the atmospheric circulation, including anchoring the latitude of the storm tracks to the WBCs. Furthermore, many climate models suggest that the large-scale atmospheric response to SST anomalies driven by ocean dynamics in WBC regions can be important in generating decadal climate variability. As a step toward bridging climate model results and observations, the degree of realism of the WBC in current climate model simulations is assessed. Finally, outstanding issues concerning ocean–atmosphere interaction in WBC regions and its impact on climate variability are discussed.Funding for LT was provided by the NASA-sponsored Ocean Surface Topography Science Team, under Contract 1267196 with the University of Washington, administered by the Jet Propulsion Laboratory. HN was supported in part by the Grant-in-Aid 18204044 by the Japan Society for Promotion for Science (JSPS) and the Global Environment Research Fund (S-5) of the Japanese Ministry of Environment. YK was supported by the Kerr Endowed Fund and Penzance Endowed Fund

Advances in burn care

This article reviews and critiques new developments in the critical care of burn patients. The practice of restrictive transfusion is slowly gaining traction. Abdominal compartment syndrome is associated with resuscitation volumes of 300 ml/kg per 24 h, and percutaneous decompression may be a treatment option. Adrenal insufficiency is common, but whom and when to treat are unclear. Imaging or noninvasive monitoring may confirm renal perfusion before urine output, and the concept of permissive hypovolemia should be explored. There is progress in the laboratory in smoke inhalation and myocardial depression, but no human translation. Antibiotic pharmacokinetics in large burns are unpredictable, and so aminoglycosides (measurable concentrations) are not obsolete. Selective digestive decontamination remains controversial. Nutritional predictions by formula are inaccurate. Oxandrolone is safe and effective in promoting anabolism in large burns. Deep venous thrombosis prophylaxis remains guided only by expert opinion. Females fare worse than male patients after burns. The application of the scientific method to burn care is improving slowly. Randomized controlled trials are becoming more common. There is a need for translation of excellent animal work to the human arena