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Background: The hyperglycemic state following trauma and surgery is related partially to insulin resistance (IR). The objective is to determine if critically ill surgical patients vary in their extent of IR and is IR associated with mortality. Methods: Prospective observational study in trauma and surgical intensive care units. There were 925 ventilated, critically ill surgical patients who were placed on an automated euglycemia protocol. A mathematic multiplier (M) employed by the protocol was used as a measure of IR. Outcome, phenotypic, laboratory, and treatment variables were analyzed. Results: 54,141 entries for glucose (mg/dl) and M were analyzed. Median glucose was 118mg/dL, with 45% of values between 80-110mg/dL, 81% between 80-150 mg/dL, and 0.2% less than 40 mg/ dL. M varied by 42 fold over the entire population, and by an average of 11-fold among individual patients. The median blood glucose was not different between groups (118 mg/dl for survivors and 118 mg/dl for non-survivors, P = 0.36). The median insulin dose and M were significantly higher in non-survivors (4.1 U/hr versus 3.4 U/hr, P = 0.005; 0.061 versus 0.058, P = 0.02). Conclusions: There was a large amount of variation in insulin resistance, as measured by an adapting multiplier, both across the population and within patients. In the setting of tight glucose control measures of glucose control (median blood glucose and percent in range) do not differentiate between patients who lived and died while measures of insulin resistance (median insulin dose and multiplier) do, suggesting that the insulin resistance is a better predictor of outcome. [ABSTRACT FROM AUTHOR]

Automated physiologic event detection and alerting is a challenging task in the ICU. Ideally care providers should be alerted only when events are clinically significant and there is opportunity for corrective action. However, the concepts of clinical significance and opportunity are difficult to define in automated systems, and effectiveness of alerting algorithms is difficult to measure. This paper describes recent efforts on the Simon project to capture information from ICU care providers about patient state and therapy in response to alerts, in order to assess the value of event definitions and progressively refine alerting algorithms. Event definitions for intracranial pressure and cerebral perfusion pressure were studied by implementing a reliable system to automatically deliver alerts to clinical users' alphanumeric pagers, and to capture associated documentation about patient state and therapy when the alerts occurred. During a 6-month test period in the trauma ICU at Vanderbilt University Medical Center, 530 alerts were detected in 2280 hours of data spanning 14 patients. Clinical users electronically documented 81% of these alerts as they occurred. Retrospectively classifying documentation based on therapeutic actions taken, or reasons why actions were not taken, provided useful information about ways to potentially improve event definitions and enhance system utility. [ABSTRACT FROM AUTHOR]

A novel thermoacidophilic archeaon, strain J1 T (=DSM 112778 T ,=JCM 34702 T ), was isolated from a hot pool in a volcanic area of Java, Indonesia. Cells of the strain were irregular, motile cocci of 1.0-1.2 µm diameter. Aerobic, organoheterotrophic growth with casamino acids was observed at an optimum temperature of 70 °C in a range of 55-78 °C and at an optimum pH of 3 in a range of 1.5 to 5. Various organic compounds were utilized, including a greater variety of sugars than has been reported for growth of other species of the genus. Chemolithoautotrophic growth was observed with reduced sulphur compounds, including mineral sulphides. Ferric iron was reduced during anaerobic growth with elemental sulphur. Cellular lipids were calditoglycerocaldarchaeol and caldarchaeol with some derivates. The organism contained the respiratory quinone caldariellaquinone. On the basis of phylogenetic and chemotaxonomic comparison with its closest relatives, it was concluded that strain J1 T represents a novel species, for which the name Metallosphaera javensis is proposed. Low DNA-DNA relatedness values (16S rRNA gene <98.4%, average nucleotide identity (ANI) <80.1%) distinguished J1 T from other species of the genus Metallosphaera and the DNA G+C content of 47.3% is the highest among the known species of the genus.

Ferrous iron- and sulfur-oxidizing Acidihalobacter species and similar so far unclassified bacteria have been isolated from the islands of Vulcano (Italy) and Milos (Greece), specifically from where seawater was acidified at sulfide-rich geothermal sites. Acidithiobacillus species which tolerated concentrations of chloride that inhibit most Acidithiobacillus spp. were also isolated from sites on both islands: these were At. thiooxidans strains and an unclassified species, Acidithiobacillus sp. strain V1. The potential of salt-tolerant acidophiles for industrial application in promoting copper extraction from mineral sulfides where chloride is naturally present at concentrations which would inhibit most acidophiles, or where seawater rather than fresh water is available, appears to be limited by the sensitivity of ferrous-iron oxidizing Acidihalobacter spp. to copper. However, tolerance of copper and chloride shown by At. thiooxidans strain A7 suggests it could oxidize sulfur and benefit acid leaching if ferric iron or copper was provided as the primary oxidant of sulfide ores.

Strain MG, isolated from an acidic pond sediment on the island of Milos (Greece), is proposed as a novel species of ferrous iron- and sulfur-oxidizing Acidithiobacillus. Currently, four of the eight validated species of this genus oxidize ferrous iron, and strain MG shares many key characteristics with these four, including the capacities for catalyzing the oxidative dissolution of pyrite and for anaerobic growth via ferric iron respiration. Strain MG also grows aerobically on hydrogen and anaerobically on hydrogen coupled to ferric iron reduction. While the 16S rRNA genes of the iron-oxidizing Acidi-thiobacillus species (and strain MG) are located in a distinct phylogenetic clade and are closely related (98-99% 16S rRNA gene identity), genomic relatedness indexes (ANI/dDDH) revealed strong genomic divergence between strain MG and all sequenced type strains of the taxon, and placed MG as the first cultured representative of an ancestral phylotype of iron oxidizing acidithiobacilli. Strain MG is proposed as a novel species, Acidithiobacillus ferrianus sp. nov. The type strain is MG T (= DSM 107098 T  = JCM 33084 T ). Similar strains have been found as isolates or indicated by cloned 16S rRNA genes from several mineral sulfide mine sites.

The mineral sulfide-oxidising Acidithiobacillus ferrooxidans has been extensively studied over many years but some fundamental aspects of its metabolism remain uncertain, particularly with regard to its anaerobic oxidation of sulfur. This label-free, liquid chromatography-electron spray ionisation-mass spectrometry-based proteomic analysis estimated relative protein abundance during aerobic and anaerobic growth of At. ferrooxidans. One of its two bc1 complexes, that encoded by the petII operon, was strongly implicated in anaerobic ferric iron-coupled sulfur oxidation, probably in conjunction with two cytochromes. These two cytochromes are homologs of the Cyc2 and Cyc1 proteins that are involved in ferrous iron oxidation. The previously undetected cytochromes apparently associated with anaerobic growth in At. ferrooxidans appear to be absent in many other ferrous iron-oxidising acidophiles that can also reduce ferric iron, which suggests a diversity in the ferric-iron-coupled sulfur oxidation pathways. For aerobic growth of At. ferrooxidans, this analysis was consistent with the generally accepted mechanism for its oxidation of ferrous iron. Unexpectedly, proteins encoded by the petI operon were not abundant and generally not detected in the proteomic analyses of cells grown aerobically on sulfur, although there was some expression of genes of the petI and petII operons in these cells.

Analysis of phylogenomic metrics of a recently released draft genome sequence of the halotolerant, acidophile 'Thiobacillus prosperus' DSM 5130 indicates that it is not a member of the genus Thiobacillus within the class Betaproteobacteria as originally proposed. Based on data from 16S rRNA gene phylogeny, and analyses of multiprotein phylogeny and average nucleotide identity (ANI), we show that it belongs to a new genus within the family Ectothiorhodospiraceae, for which we propose the name Acidihalobacter gen. nov. In accordance, it is proposed that 'Thiobacillus prosperus' DSM 5130 be named Acidihalobacter prosperus gen. nov., sp. nov. DSM 5130T ( = JCM 30709T) and that it becomes the type strain of the type species of this genus.

Purpose: Changes in insulin resistance (IR) cause stress-induced hyperglycemia after trauma, but the numerous factors involved in IR have not been delineated clearly. We hypothesized that a statistical model could help determine the relative contribution of different clinical co-variates to IR in critically injured patients., Patients and Methods: We retrospectively studied 726 critically injured patients managed with a computer-assisted glycemic protocol at an academic level I trauma center (639 ventilated controls without pneumonia (VWP) and 87 patients with ventilator-associated pneumonia (VAP). Linear regression using age, gender, body mass index (BMI), diabetes mellitus, pneumonia, and glycemic provision was used to estimate M, a marker of IR that incorporates both the serum blood glucose concentration (BG) and insulin dose., Results: Increasing M (p<0.001) was associated with age (1.62%; 95% confidence interval [CI] 1.27%-1.97% per decade), male gender (9.78%; 95% CI 8.28%-12.6%), BMI (4.32% [95% CI 4.02%-4.62%] per 5 points), diabetes mellitus (21.2%; 95% CI 19.2%-23.2%), pneumonia (10.9%; 95% CI 9.31%-12.6%), and glycemic provision (27.3% [95% CI 6.6%-28.1%] per 100 g of glucose). Total parenteral nutrition was associated with a decrease in M of 10.3%; 95% CI 8.52%-12.1%; p<0.001., Conclusions: Clinical factors can be used to construct a model of IR. Prospective validation might enable early detection and treatment of infection or other conditions associated with increased IR.

Background: Ventilator-associated pneumonia (VAP) remains a common complication in critically ill surgical patients, and its diagnosis remains problematic. Exhaled breath contains aerosolized droplets that reflect the lung microbiota. We hypothesized that exhaled breath condensate fluid (EBCF) in hygroscopic condenser humidifier/heat and moisture exchanger (HCH/HME) filters would contain bacterial DNA that qualitatively and quantitatively correlate with pathogens isolated from quantitative BAL samples obtained for clinical suspicion of pneumonia., Methods: Forty-eight adult patients who were mechanically ventilated and undergoing quantitative BAL (n = 51) for suspected pneumonia in the surgical ICU were enrolled. Per protocol, patients fulfilling VAP clinical criteria undergo quantitative BAL bacterial culture. Immediately prior to BAL, time-matched HCH/HME filters were collected for study of EBCF by real-time polymerase chain reaction. Additionally, convenience samples of serially collected filters in patients with BAL-diagnosed VAP were analyzed., Results: Forty-nine of 51 time-matched EBCF/BAL fluid samples were fully concordant (concordance > 95% by κ statistic) relative to identified pathogens and strongly correlated with clinical cultures. Regression analysis of quantitative bacterial DNA in paired samples revealed a statistically significant positive correlation (r = 0.85). In a convenience sample, qualitative and quantitative polymerase chain reaction analysis of serial HCH/HME samples for bacterial DNA demonstrated an increase in load that preceded the suspicion of pneumonia., Conclusions: Bacterial DNA within EBCF demonstrates a high correlation with BAL fluid and clinical cultures. Bacterial DNA within EBCF increases prior to the suspicion of pneumonia. Further study of this novel approach may allow development of a noninvasive tool for the early diagnosis of VAP.

Background: Hemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients., Methods: We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann–Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support., Results: Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02–1.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22–1.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model., Conclusion: In critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.

Background: Hyperglycemia caused by stress-induced insulin resistance is associated with both infection and mortality in critically injured patients. The onset of infection may increase stress-induced insulin resistance, leading to hyperglycemia. Hyperglycemia has been shown to precede the diagnosis of ventilator-associated pneumonia (VAP) in critically injured adults and has been suggested to have potential diagnostic importance. However, glycemic control (GC) protocols in critically ill patients limit the development of hyperglycemia despite increasing insulin resistance. Our computer-assisted GC protocol achieves excellent GC, limiting infection-related hyperglycemia while capturing prospectively all glucose values, insulin infusion rates, and the multiplier (M) used to calculate the insulin rate. We hypothesized that surrogate measures of insulin resistance, the insulin infusion rate and multiplier M, would increase prior to the clinical suspicion of VAP, even in euglycemic critically injured patients., Methods: All critically injured patients (2,656) on the computerized glycemic control protocol were included in the analysis and categorized by those developing VAP and those without pneumonia on days 3-10 of their intensive care unit (ICU) stay. Median blood glucose concentration (BG), insulin infusion rate (IDR), and multiplier (M) [Insulin Drip Rate=M*(BG-60)] were determined for VAP patients (n=329) and non-infected ventilated (NIV) patients (n=2,327) on each day of mechanical ventilation. The day of VAP diagnosis according to U.S. Centers for Disease Control and Prevention (CDC) criteria was defined as day zero and VAP patients matched with NIV patients according to ventilator day from -10 to +10. Comparisons were conducted using the Mann-Whitney U test., Results: Baseline characteristics between VAP and NIV groups did not differ. Measures of insulin resistance increased from the time of injury in both groups. Patients with VAP had significantly greater change in both measures of insulin resistance, IDR and M, in the 48 hours preceding the diagnosis of VAP. These changes occurred despite the fact that the computer-assisted GC protocol achieved lower glucose values in VAP patients for the majority of study days., Conclusions: Measures of insulin resistance increase in the two days prior to the clinical suspicion of VAP for critically injured patients on the GC protocol. These changes occur despite the protocol maintaining euglycemia. This data suggests that markers of insulin resistance may provide clinically useful information in the early diagnosis of VAP.

Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes.

Aims: To develop a method to detect bacteria from environmental samples that are able to metabolize lignin., Methods and Results: A previously developed UV-vis assay method for lignin degradation activity has been developed for use as a spray assay on agar plates. Nine mesophilic strains were isolated using this method from woodland soil incubated in enrichment cultures containing wheat straw lignocellulose: four Microbacterium isolates, two Micrococcus isolates, Rhodococcus erythropolis (all Actinobacteria) and two Ochrobactrum isolates (Alphaproteobacteria). Three thermotolerant isolates were isolated from the same screening method applied at 45°C to samples of composted wheat straw from solid-state fermentation: Thermobifida fusca and two isolates related to uncharacterized species of Rhizobiales and Sphingobacterium (Bacteroidetes), the latter strain showing tenfold higher lignin degradation activity than other isolates. The isolated strains were able to depolymerize samples of size-fractionated high molecular weight and low molecular weight Kraft lignin, and produced low molecular weight metabolites oxalic acid and protocatechuic acid from incubations containing wheat straw lignocellulose., Conclusions: A new method for the isolation of bacteria able to metabolize lignin has been developed, which has been used to identify 12 bacterial isolates from environmental sources. The majority of isolates cluster into the Actinobacteria and the Alphaproteobacteria., Significance and Impact of the Study: Lignin-degrading bacterial strains could be used to convert lignin-containing feedstocks into renewable chemicals and to identify new bacterial lignin-degrading enzymes., (© 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.)

Ventilator associated pneumonia is a common and costly complication in critically ill and injured surgical patients. The diagnosis of pneumonia remains problematic and non-specific. Using clinical criteria, a diagnosis of pneumonia is typically not made until an infection is well established. Semi-quantitative cultures of endotracheal aspirate and broncho-alveolar lavage are employed to improve the accuracy of diagnosis but are invasive and require time for culture results to become available. We report data that show that an inexpensive, rapid and non-invasive alternative may exist. In particular we show that: 1). Bio-aerosols evolved in the breath of ventilated patients and captured in the hygroscopic condenser humidifier filter of the ventilator circuit contain pathogenic micro-organisms. 2). The number (CFU/ml) and identity (Genus, species) of the pathogens in the aerosol samples can rapidly and inexpensively be determined by PCR. 3). Data from a convenience sample of filters correlate with clinical findings from standard microbiological methods such as broncho-alveolar lavage. The evaluation of the bacterial load evolved in exhaled breath by PCR is amenable to repeated sampling. Since increasing bacterial burden is believed to correlate with the establishment of infection, the use of quantitative PCR may provide a method to rapidly, inexpensively, and effectively detect and diagnose the early onset of pneumonia and identify pathogens involved.

Background: Intensive insulin therapy lowers blood glucose and improves outcomes but increases the risk of hypoglycemia. Typically, insulin protocols require a dextrose solution to prevent hypoglycemia. The authors hypothesized that the provision of balanced nutrition (enteral nutrition [EN] or parenteral nutrition [PN]) would be more protective against hypoglycemia (≤50 mg/dL) than carbohydrate alone., Methods: A retrospective analysis was performed of patients treated with intensive insulin therapy and surviving ≥24 hours. The computer-based insulin protocol requires infusion of D10W at 30 mL/h if EN or PN is not provided. Nutrition provision was assessed in 2-hour increments, comparing periods of blood glucose control with and without balanced nutrition. The risk of hypoglycemia for each blood glucose measurement was estimated by multivariable regression., Results: In total, 66,592 glucose measurements were collected on 1392 patients. Hypoglycemic events occurred in 5.8/1000 glucose tests after 2 hours without balanced nutrition compared to 2.2/1000 tests when balanced nutrition was given in the preceding 2 hours. In multivariable regression models, balanced nutrition was the strongest protective factor against hypoglycemia. Patients who did not receive balanced nutrition in the preceding 2 hours had a 3 times increase in the odds of a hypoglycemic event at their next glucose check (odds ratio = 3.6, P < .001). Providing carbohydrate alone was not protective., Conclusions: Balanced nutrition is associated with reduced risk of hypoglycemia. These results suggest that balanced nutrition should be given when insulin therapy is initiated. Future studies should evaluate the efficacy of EN vs PN in preventing hypoglycemia.

Purpose: The purpose of this study is to determine if temperature extremes are associated with reduced heart rate variability (HRV) and "cardiac uncoupling.", Materials and Methods: This was a retrospective, observational cohort study performed on 278 trauma intensive care unit admissions that had continuous HR, cardiac index (CI), and core temperature data from "thermodilution" Swan-Ganz catheter. Dense (captured second-by-second) physiologic data were divided into 5-minute intervals (N = 136 133; 11 344 hours of data). Mean CI, mean temperature, and integer HR SD were computed for each interval. Critically low HRV was defined as HR SD from 0.3 to 0.6 beats per minute. Temperature extremes were defined as less than 36°C or greater than 39°C., Results: Low HRV and CI vary with temperature. Temperature extremes are associated with increased risk for critically low HRV (odds ratio, >1.8). Cardiac index increases with temperature until hyperthermia (>40°C). At temperature extremes, changes in CI were not explained solely by changes in HR., Conclusions: The conclusions of this study are (1) temperature extremes are associated with low HRV, potentially reflecting cardiac autonomic dysfunction; (2) CI increases with temperature; and (3) HRV provides additional physiologic information unobtainable via current invasive cardiac monitoring and current vital signs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Control of hyperglycemia improves outcomes, but increases the risk of hypoglycemia. Recent evidence suggests that blood glucose variability (BGV) is more closely associated with mortality than either isolated or mean BG. We hypothesized that differences in BGV over time are associated with hypoglycemia and can be utilized to estimate risk of hypoglycemia (<50 mg/dL)., Materials and Methods: Patients treated with intravenous insulin in the Surgical Intensive Care Unit of a tertiary care center formed the retrospective cohort. Exclusion criteria included death within 24 h of admission. We describe BGV in patients over time and its temporal relationship to hypoglycemic events. The risk of hypoglycemia for each BG measurement was estimated in a multivariable regression model. Predictors were measures of BGV, infusions of dextrose and vasopressors, patient demographics, illness severity, and BG measurements., Results: A total of 66,592 BG measurements were collected on 1392 patients. Hypoglycemia occurred in 154 patients (11.1%). Patient BGV fluctuated over time, and increased in the 24 h preceding a hypoglycemic event. In crude and adjusted analyses, higher BGV was positively associated with a hypoglycemia (OR 1.41, P < 0.001). Previous hypoglycemic events and time since previous BG measurement were also positively associated with hypoglycemic events. Severity of illness, vasopressor use, and diabetes were not independently associated with hypoglycemia., Conclusions: BGV increases in the 24 h preceding hypoglycemia, and patients are at increased risk during periods of elevated BG variability. Prospective measurement of variability may identify periods of increased risk for hypoglycemia, and provide an opportunity to mitigate this risk., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: During the initial development of an Emergency General Surgery (EGS) service, severity of illness (SOI) can be expected to be high and should decrease as the service matures. We hypothesize that a matured regional EGS service would show decreasing mortality and length of stay (LOS) over time., Methods: We performed a retrospective study of a prospectively collected EGS registry data from 2004 to 2009. Patients were included if they had been discharged from the EGS service and were stratified by year of discharge. Systemic inflammatory response syndrome, sepsis, shock, peritonitis, perforation, and acute renal failure were used as markers of SOI. Patients were defined as high acuity if they had one or more of these SOI markers. Differences in mortality, LOS, intensive care unit admissions, SOI, charges, and distance were compared across and between years using nonparametric statistical tests (Fisher's exact, Wilcoxon rank-sum, and Kruskal-Wallis tests)., Results: A total of 3,439 patients met study criteria. The mean age was 47 years ± 17.5 years. The majority of the patients were female (1,813, 47.3%). The overall LOS was 6.4 days ± 9.4 days (median, 4 days). In all, 2,331 (67.8%) of the patients underwent operation. Over the course of the study period, the SOI indicators stabilized at between 13% and 17% of the patient population with at least one indicator. During that time period, mortality steadily decreased from 4.9% to 1.3% (p < 0.5)., Conclusion: Despite consistently high SOI, a dedicated and matured EGS service demonstrated a decrease in mortality and LOS.

Background: We have previously demonstrated that elevated serum estradiol (E(2)) at intensive care unit (ICU) admission is associated with death in the critically ill, regardless of sex. However, little is known about how changes in initial E(2) during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E(2) during the course of critical illness are more strongly associated with mortality than a single E(2) level at admission., Study Design: A prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for ≥48 hours with admission and subsequent E(2) levels was studied. Demographics, illness severity, and E(2) levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E(2) were examined by both analysis of variance and logistic regression., Results: Overall mortality was 14.1% [95% confidence interval (CI) 12.3% to 16%]. Both admission and subsequent E(2) levels were independently associated with mortality [admission E(2) odds ratio 1.1 (CI 1.0 to 1.2); repeat estradiol odds ratio 1.3 (CI 1.2 to1.4)], with subsequent values being stronger. Changes in E(2) were independently associated with mortality [odds ratio 1.1 (CI 1.0 to 1.16)] and improved regression model performance. The regression model produced an area under the receiver operating characteristic curve of 0.80 (CI 0.77 to 0.83)., Conclusions: Although high admission levels of E(2) are associated with mortality, changes from baseline E(2) in critically ill or injured adults are independently associated with mortality. Future studies of E(2) dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Within the traumatic brain injury population, outcomes are affected by hypoxic events in the early injury period. Previous work shows a high prevalence of cognitive deficits in patients with multiple injuries who do not have intracranial hemorrhage identified on admission head computed tomography scan. We hypothesize that intensive care unit (ICU) delirium and long-term cognitive impairment (LTCI) are more likely in patients who have a hypoxic event within the first 48 hours of ICU admission., Methods: A total of 173 patients with multiple injuries (Injury Severity Score [ISS] >15) who presented to a Level I trauma center from July 2006 to July 2007 were enrolled in a study on long-term cognitive deficit. Ninety-seven patients required ICU management and all had continuous oxygen saturation data collected. The Confusion Assessment Method for the ICU was collected twice a day on all patients in ICU. Of the total enrolled population, 108 (62%) were evaluated 12 months after discharge by neuropsychological tests. Cognitive impairment was defined as having 2 neuropsychological test scores, 1.5 standard deviations below the mean or 1 neuropsychological test score, and 2 standard deviations below the mean. Demographic data, ISS, initial 24-hour blood requirements, presence of hypoxia (SpO(2) <90% and <85%) or hypotension (systolic blood pressure <90 mm Hg), emergency department (ED) pulse, Glasgow Coma Scale score, ventilator and ICU days were recorded. Significant univariate identification of clinical variables was used for multivariate analysis., Results: Fifty-five of 97 ICU patients (57%) were Confusion Assessment Method-ICU positive for delirium and 59 of 108 (55%) demonstrated cognitive impairment at 12-month follow-up. There was no significant association between hypoxia and ICU delirium (74.5% vs. 74%; p = 0.9) or LTCI (89% vs. 83%; p = 0.5). Ventilator days (8.7 ± 8.9 vs. 2.9 ± 4.6; p < 0.0001), ED pulse (109 ± 28.5 vs. 94 ± 22.8; p = 0.01), and blood transfusions (10 U ± 10.8 U vs. 5 U ± 5.3 U; p = 0.015) were significant independent predictors of delirium. Ventilator days (odds ratio, 1.16; 95% confidence interval, 1.05-1.29; p = 0.004) and ED pulse (odds ratio, 1.02; 95% confidence interval, 1.00-1.04; p = 0.03) remained significant predictors of ICU delirium after adjusting for ISS, hypoxic state, blood transfusions, and ED blood pressure. Among ED Glasgow Coma Scale score (10.5 ± 5.1 vs. 11.4 ±5.5; p = 0.7), ISS (33.3 ± 10.1 vs. 32.2 ± 9.0; p = 0.5), ventilator days (6.5 ± 7.5 vs. 6.2 ± 8.8; p = 0.4), blood transfusions (8.1 ± 6.8 vs. 9.4 ± 8.1; p = 0.4), and delirium (62% vs. 62.5%; p = 0.9), there were no significant univariate associations with LTCI., Conclusions: Hypoxic events in the ICU do not have a direct correlation with ICU delirium or LTCI in the patients with multiple injuries without evidence of intracranial hemorrhage.

Background: Primary colonic anastomosis in trauma patients has been demonstrated to be safe. However, few studies have investigated this in the setting of damage control laparotomy. We hypothesized that colonic anastomosis for trauma patients requiring an open abdomen (OA) would have a higher anastomotic leak (AL) rate when compared with patients having an immediate abdominal closure following trauma laparotomy., Methods: We performed a cohort comparison study of all trauma patients who underwent colectomy, between the years 2004 and 2009. Exclusion criteria were mortality within 24 hours of admission or colectomy for indications unrelated to injury. Data collected included age, gender, injury severity score, mechanism, length of stay, and mortality. Multivariable logistic regression was performed to assess the relationship of OA to our primary outcome measure, AL., Results: Totally, 174 patients met study criteria. Fecal diversion was performed in 58 patients, and colonic anastomosis was performed in the remaining 116 patients. Patients with OA had a clinically significant increase in AL rate compared with immediate abdominal closure (6% vs. 27%, p=0.002). Logistic regression demonstrated that OA was independently associated with AL, with OA patients having more than a sixfold increase in odds of AL compared with those who were closed (odds ratio=6.37, p=0.002, area under the receiver operator curve=0.72). Transfusion requirement and left-sided anastomosis were risk factors for leak., Conclusions: Patients with a colonic anastomosis and an OA have an unacceptably high leak rate compared with those who undergo reconstruction with immediate closure. Given the significant risk of AL, colonic anastomosis should not be routinely performed in patients with OA., (Copyright © 2011 by Lippincott Williams & Wilkins)

Some novel actinobacteria from geothermal environments were shown to grow autotrophically with sulfur as an energy source. These bacteria have not been formally named and are referred to here as "Acidithiomicrobium" species, as the first of the acidophilic actinobacteria observed to grow on sulfur. They are related to Acidimicrobium ferrooxidans with which they share a capacity for ferrous iron oxidation. Ribulose bisphosphate carboxylase/oxygenase (RuBisCO) is active in CO(2) fixation by Acidimicrobium ferrooxidans, which appears to have acquired its RuBisCO-encoding genes from the proteobacterium Acidithiobacillus ferrooxidans or its ancestor. This lateral transfer of RuBisCO genes between a proteobacterium and an actinobacterium would add to those noted previously among proteobacteria, between proteobacteria and cyanobacteria and between proteobacteria and plastids. "Acidithiomicrobium" has RuBisCO-encoding genes which are most closely related to those of Acidimicrobium ferrooxidans and Acidithiobacillus ferrooxidans, and has additional RuBisCO genes of a different lineage. 16S rRNA gene sequences from "Acidithiomicrobium" species dominated clone banks of the genes extracted from mixed cultures of moderate thermophiles growing on copper sulfide and polymetallic sulfide ores in ore leaching columns.

Background: Acute care surgery programs have demonstrated that trauma patient outcomes have not changed with the addition of emergency general surgery (EGS) responsibilities. EGS patient outcomes and the mentoring of fellows on EGS service have not been previously studied. We hypothesize that EGS patient outcomes would not differ by provider on a service driven by evidence-based medicine (EBM) protocols., Patients and Methods: Retrospective study of prospectively collected EGS repository. academic level I trauma center, and regional EGS referral center from 2003 to 2007. There were 14 faculty and seven fellows during the study period. EGS coverage is a full week, with weeknight coverage by the in-house trauma/EGS faculty. Fellows are mentored by designated faculty while on service, who discuss patients, assist in the OR, or assume care if necessary. Data collected included age, gender, LOS, ICU LOS, ventilator days, disposition (home/rehab), and infectious complications(IC) (VAP, BSI, UTI, SSI). Primary outcome was mortality., Results: 1769 patients met study criteria. The mean age was 47.1 (+/-18), 47% were males. The average ICU LOS was 2.9 d (+/-7.9), ventilator d 2.6 (+/-7.6); 82.1% were discharged home and 13.7% were referred to rehab. There was no statistical difference in mortality, LOS, ICU LOS, disposition, ventilator d, and IC between faculty and fellow providers., Conclusions: An EGS service with EBM protocols assures consistency in patient outcomes independent of provider level: faculty or fellows. Our model for mentoring fellows did not decrease EGS patient outcomes., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Reduced heart rate (HR) complexity (e.g., a lack of randomness or unpatterned variability) is an established predictor of trauma patient mortality. However, this finding has not been validated across the diverse spectrum of traumatic injury, and underlying mechanisms of this relationship are poorly understood., Materials and Methods: Two thousand one hundred seventy-eight trauma patients were admitted directly to the intensive care unit (ICU), and had sufficient (>6h) continuous integer heart rate data within the first d. Patients were stratified by location of isolated severe injury (head, torso, both, or neither), primary mechanism (blunt or penetrating), and probability of survival, an accepted scoring system based on age, admission vital signs, and injury type and severity. HR multiscale entropy (MSE) was calculated (sum of scales, Costa's algorithm, physionet.org, m=2, r=0.15) to estimate complexity. Univariate analysis was performed by comparing MSE between survivors and nonsurvivors in each subgroup. Multivariate analysis incorporated logistic regression to characterize the relationship between MSE and risk of death, controlling for probability of survival. The MSE odds ratios (OR) and area under the receiver operator curve (AUC) were calculated., Results: Reduced MSE was significantly associated with increasing mortality, and was independent of probability of survival in all multivariate analyses (OR 0.87-0.94). This range of odds ratios implies that a patient with an MSE of 15 has roughly a 2- to 6-fold increase in odds of death versus a patient with an MSE of 25. The relationship between MSE and death was moderately stronger in patients with isolated severe head injury versus torso injury, and significantly stronger in patients with penetrating versus blunt mechanism of injury. MSE measured early in the hospital stay remained a robust predictor of mortality in all subgroups, even stratified by narrow ranges of probability of survival., Conclusions: Early reduction of heart rate complexity is an important risk factor across diverse injury etiology. This suggests common underlying physiologic mechanisms linking the loss of biologic complexity to death.

Objective: Personalized medicine merges genetics, physiology, and patient outcome. Loss of physiologic complexity (heart rate [HR] variability) is a bedside biomarker for autonomic nervous system (ANS) dysfunction. We hypothesized that variability in ANS receptor proteins (genetics) and loss of complexity (physiology) are independently associated with mortality in critical illness., Summary Background Data: Decreased HR complexity has been associated with increased mortality and morbidity in trauma and other critically ill populations. Genetic variations in alpha-1A and beta-2 adrenergic receptors (ADRA1A, ADRB2) have been associated with changes in smooth muscle tone in various tissues, and implicated in bronchial hyper-responsiveness, metabolic syndrome, and other disorders., Methods: A cohort of 644 trauma intensive care unit (ICU) admissions had complexity data and genetic samples. Two ANS receptor polymorphisms (rs1048101, Alpha ADRA1A and rs1042714, Beta ADRB2) were genotyped. Physiologic complexity at various points in the ICU stay was measured using previously-studied integer HR multiscale entropy (MSE) over 6-hour intervals (~21,600 HR data points/interval/patient). Logistic regression assessed the concurrent relationship of genotypes, complexity, and probability of survival, an acuity score incorporating age, injury mechanism/severity, and admission vitals, to risk of death., Results: Of total, 96 patients (15%) died. Nonsurvivors had lower complexity at early, middle, and late portions of ICU stay (median MSE at least 25% less in nonsurvivors, P < 0.001) and lower incidence of the GG ADRB2 genotype (7.5% vs. 18.3%, P < 0.001). In multivariable logistic regression, the GG ADRB2 genotype carried ~3-fold decrease in mortality odds (odd ratio [OR] = 0.33, P = 0.01), independent of significant effects in HR MSE (OR = 0.93, P < 0.001), and probability of survival (OR = 0.22, P < 0.001)., Conclusions: This first study to simultaneously examine ANS genetics, the biomarker complexity, and mortality concludes: (1) ANS genetics and physiologic complexity are independently related to mortality; (2) Genetics and complexity add information over traditional acuity scoring (probability of survival); and (3) Simultaneous assessment of ANS physiology and genetics may yield novel research, diagnostic, and therapeutic opportunities in critical illness.

Background: The hyperglycemic state following trauma and surgery is related partially to insulin resistance (IR). The objective is to determine if critically ill surgical patients vary in their extent of IR and is IR associated with mortality., Methods: Prospective observational study in trauma and surgical intensive care units. There were 925 ventilated, critically ill surgical patients who were placed on an automated euglycemia protocol. A mathematic multiplier (M) employed by the protocol was used as a measure of IR. Outcome, phenotypic, laboratory, and treatment variables were analyzed., Results: 54,141 entries for glucose (mg/dl) and M were analyzed. Median glucose was 118mg/dL, with 45% of values between 80-110mg/dL, 81% between 80-150 mg/dL, and 0.2% less than 40 mg/ dL. M varied by 42 fold over the entire population, and by an average of 11-fold among individual patients. The median blood glucose was not different between groups (118 mg/dl for survivors and 118 mg/dl for non-survivors, P = 0.36). The median insulin dose and M were significantly higher in non-survivors (4.1 U/hr versus 3.4 U/hr, P = 0.005; 0.061 versus 0.058, P = 0.02)., Conclusions: There was a large amount of variation in insulin resistance, as measured by an adapting multiplier, both across the population and within patients. In the setting of tight glucose control measures of glucose control (median blood glucose and percent in range) do not differentiate between patients who lived and died while measures of insulin resistance (median insulin dose and multiplier) do, suggesting that the insulin resistance is a better predictor of outcome.

Background: We have previously demonstrated an unappreciated link between the autonomic nervous system and mortality, heart rate variability, and physiologic complexity., Study Design: Genetic variation in adrenergic receptors or key enzymes in catecholamine degradation could be associated with, and potentially explain, autonomic nervous system dysfunction and its impact on mortality after severe trauma. Three genetic polymorphisms critical to the adrenergic pathway were evaluated: beta-2 adrenergic receptor (ADBR2: Q27E), alpha-1a adrenergic receptor (ADRA1A:R347C), and catechol-O-methyl transferase (COMT: V158M). The study population consisted of 1,095 trauma admissions between April 2005 and April 2007. These patients all had genotyping performed using mass spectrometric analysis (Sequenom, Inc). The genetic data were linked with detailed demographic and clinical data. Trauma Related Injury Severity Score (TRISS) probability of survival was used as a composite measure of injury severity, admission physiology, and demographic factors in the multivariate logistic regression analyses of mortality outcomes data., Results: The overall mortality rate for the study population was 14.2% (155 of 1,095). Univariate comparisons of genotypes with mortality revealed a significant association with the ADBR2 polymorphism: CC=15.9%, GC=14.8% and GG=7.6%, p=0.02. The apparently protective ADBR2 GG genotype was seen in 15.5% (170 of 1,095) of the study population. In multivariate analysis, which included adjustment for TRISS, the ADBR2 GG genotype was associated with reduced mortality (odds ratio 0.36, p=0.002)., Conclusions: Genetic variation in the beta-2 adrenergic receptor (ADBR2:Q27E) associated with bronchial constriction appears protective (odds ratio 0.36), perhaps by making the receptor resistant to downregulation. These genetic data support the emerging understanding of critical role of the autonomic nervous system in the response to injury.

The halotolerant acidophile 'Thiobacillus prosperus' was shown to require chloride for growth. With ferrous iron as substrate, growth occurred at a rate similar to that of the well-studied acidophile Acidithiobacillus ferrooxidans. Previously, the salt (NaCl) requirement of 'T. prosperus' was not clear and its growth on ferrous iron was described as poor. A subtractive hybridization of cDNAs from ferrous-iron-grown and sulfur-grown 'T. prosperus' strain V6 led to identification of a cluster of genes similar to the rus operon reported to encode ferrous iron oxidation in A. ferrooxidans. However, the 'T. prosperus' gene cluster did not contain a homologue of cyc1, which is thought to encode a key cytochrome c in the pathway of electron transport from ferrous iron in A. ferrooxidans. Rusticyanin, another key protein in ferrous iron oxidation by A. ferrooxidans, was present in 'T. prosperus' at similar concentrations in cells grown on either ferrous iron or sulfur.

Background: A noninvasive tool reflecting intracranial hypertension (ICH) should prompt early invasive monitoring and reduce secondary injury after traumatic brain injury. We hypothesized that integer heart rate variability (HRV) may be associated with rises in intracranial pressure (ICP); changes in HRV may precede changes in ICP; and both increases in ICP and cardiac uncoupling (low HRV) predict mortality., Methods: Of 14,330 consecutive trauma admissions, 291 of these patients had an injury requiring intracranial monitoring. Of these patients 145 had simultaneous HRV and ICP monitoring with a Camino monitor. ICP and heart rate (HR) data were matched and divided into 5-minute intervals (N = 117,956, representing 24.4 million HR and ICP data points). In each interval, the median ICP, and SD of HR (HRSD5) were calculated. Cardiac uncoupling was defined as an interval with HRSD5 between 0.3 bpm and 0.6 bpm. Cardiac uncoupling was compared between ICP categories using the Wilcoxon Rank-Sum test, and logistic regression was used to assess the continuous relationship between ICP and risk of uncoupling., Results: Cardiac uncoupling increases as ICP increases (p < 0.001). Uncoupling nearly doubles when comparing acceptable ICP (<20 mm Hg, 11% uncoupled) to ICH (31-50 mm Hg, 18% uncoupled), with uncoupling = 13% in the intermediate group (ICP 21-30 mm Hg). This trend continues at the level of malignant ICH (>50 mm Hg, 22% uncoupled)., Conclusion: Cardiac uncoupling increases as ICP increases. Both cardiac uncoupling and ICH predict mortality. Cardiac uncoupling may precede ICH but is not yet an indication for invasive monitoring.

Purpose: We have shown previously that reduced integer heart rate variability (HRVi) predicts death in trauma patients. We hypothesized that heart rate multiscale entropy (MSE), a potential measurement of physiologic complexity, would predict death more robustly than HRVi., Materials and Methods: Two hundred eighty-five patients had heart rate data meeting completeness and density criteria (>12 hours, >/=0.4 Hz) available in the first 24 hours after admission. Missing data points were interpolated, and a publicly available algorithm (MSE of Costa et al; Phys Rev E Stat Nonlin Soft Matter Phys. 2005;71[2 Pt 1]) was applied (www.physionet.org, m = 2, r = 0.15). Integer heart rate variability was computed using methods described previously (percentage of 5-minute intervals having heart rate SD between 0.3 and 0.6). Sample entropy was compared between survivors and nonsurvivors at each scale factor using Wilcoxon rank sum test. Logistic regression was used to assess risk of death based on HRVi, MSE, and/or covariates (age, sex, injury severity)., Results: Decreased HRVi and MSE each predicted hospital mortality (median day of death, 3; mean, 7.1). Multiscale entropy-based risk stratification (area under the receiver operating characteristic curve [AUC] = 0.76, scale 15) was superior to HRVi (AUC = 0.70), but this difference in AUC was not statistically significant. Multiscale entropy stratified patients by mortality at every scale factor (P < .001)., Conclusions: Multiscale entropy and HRVi measured within the first 24 hours each identify trauma patients at increased risk of subsequent hospital death.

Complexity is a measure of variation and randomness potentially indicating improvement or deterioration in critically ill patients. Previously, we have shown integer heart rate (HR) multiscale entropy (MSE), an indicator of complexity, predicts death based on long duration (12 h) and dense (>or=0.4 Hz) windows of HR data. However, such restrictions reduce the use of MSE in the clinical setting. We hypothesized MSE predicts death using HR data of shorter duration and lower density. During the initial 24 h of intensive care unit stay, 3,154 patients had at least 3 h of continuous integer HR sampled. The first continuous window of 3, 6, 9, and 12 h was selected for each patient regardless of density, and an open-source MSE algorithm was applied (M. Costa, www.physionet.org; m = 2; r = 0.15). Risk of death based on MSE, alone and with covariates (age, sex, injury severity score), was assessed using randomly selected logistic regression in half of the cases. Area under the receiver operator curve (AUC) was computed in the other half in subgroups having various durations and densities of HR data. At days 2.3 (median) and 4.9 (mean), 441 patients (14%) died. Multiscale entropy stratified patients by mortality and was an independent predictor of death using 3 h or more of data. Multiscale entropy alone (AUC = 0.66 - 0.71) predicted death comparably to covariates alone (AUC = 0.72). We conclude: (1) Heart rate MSE within hours of admission predicts death occurring days later. (2) Multiscale entropy is robust to variation in bedside data duration and density occurring in a working intensive care unit. (3) Complexity may be a new clinical biomarker of outcome.

Objective: To determine whether specific genetic variations in the mtDNA that impact energy production and free-radical generation are potential new risk factors for in-hospital mortality after severe trauma., Summary Background Data: Each of the 3 mitochondrial DNA polymorphisms selected for this study (at positions 4216, 10398, 4917) alter the amino acid sequence of different key subunits of Complex I in the electron transport chain. They have been previously implicated in phenotypes involving tissues with high-energy demand, such as the brain and retina., Methods: Seven hundred forty-five consecutive patients admitted to the trauma intensive care unit at Vanderbilt University Medical Center between April 11, 2005, and February 27, 2006, were potentially eligible for this study. Under an Institutional Review Board-approved protocol (which excluded patients <18 years of age and prisoners), 666 patients had DNA extracted from a blood sample. Detailed demographic and clinical covariates were also obtained (including age, gender, ethnicity, lactate measurements, and injury severity score). A flurogenic 5' nuclease allelic discrimination Taqman assay and the ABI 7900HT Sequence Detection System (v2.1) was used to genotype the T4216C, A10398G, and A4917G polymorphisms. The primary outcome was in-hospital mortality., Results: Multivariate logistic regression analysis revealed that the 4216T allele was a significant independent predictor of in-hospital mortality (OR = 2.63, 95% CI 1.14-6.07, P = 0.02) after adjustment for age, gender, injury severity score, highest lactate level, mechanism of injury, and the 10398 polymorphism., Conclusions: Variation in the mtDNA, specifically the 4216T allele, appears to increase the risk of in-hospital mortality after severe injury.

A novel species of Acidimicrobium appeared to be the predominant ferrous iron oxidizer in a mixed culture that effected the continuous, efficient extraction of nickel from a mineral concentrate at 49 degrees C, but it was not isolated in pure culture. It outcompeted Acidimicrobium ferrooxidans, which was expected to have a major role in iron oxidation in reactors gassed with air, and was outnumbered at 49 degrees C only by the sulfur-oxidizing Acidithiobacillus caldus. Sulfobacillus species were expected to compete with Acidimicrobium species when culture aeration was enriched with carbon dioxide, but they were a minor component of the populations with and without this enrichment. Sulfobacillus thermosulfidooxidans replaced the Acidimicrobium species and Acidithiobacillus caldus when the temperature was increased to 55 degrees C.

The Calvin-Benson-Bassham (CBB) cycle has been extensively studied in proteobacteria, cyanobacteria, algae and plants, but hardly at all in Gram-positive bacteria. Some characteristics of ribulose bisphosphate carboxylase/oxygenase (RuBisCO) and a cluster of potential CBB cycle genes in a Gram-positive bacterium are described in this study with two species of Sulfobacillus (Gram-positive, facultatively autotrophic, mineral sulfide-oxidizing acidophiles). In contrast to the Gram-negative, iron-oxidizing acidophile Acidithiobacillus ferrooxidans, Sulfobacillus thermosulfidooxidans grew poorly autotrophically unless the CO(2) concentration was enhanced over that in air. However, the RuBisCO of each organism showed similar affinities for CO(2) and for ribulose 1,5-bisphosphate, and similar apparent derepression of activity under CO(2) limitation. The red-type, form I RuBisCO of Sulfobacillus acidophilus was confirmed as closely related to that of the anoxygenic phototroph Oscillochloris trichoides. Eight genes potentially involved in the CBB cycle in S. acidophilus were clustered in the order cbbA, cbbP, cbbE, cbbL, cbbS, cbbX, cbbG and cbbT.

Background: Reduction in integer heart rate variability (HRVi), one potential measurement of complex biologic systems, is common in ICU patients and is strongly associated with hospital mortality. Adrenal insufficiency (AI) and reduced HRVi are associated with autonomic dysfunction. Failure of the autonomic nervous system can be associated with loss of biologic complexity. We hypothesize decreased HRVi is associated with AI, and HRVi improves after treatment of AI, suggesting "recomplexification" (resumption of normal stress response to injury)., Study Design: Of 4,116 trauma ICU admissions from December 2000 to November 2005, 1,871 patients had sufficient physiologic, laboratory, pharmacy, and demographic data for analysis. Seventy-five patients failing cosyntropin-stimulation testing were defined as AI; the remaining 1,796 were defined as no AI. HRVi was calculated as integer heart rate standard deviation over 5-minute intervals. HRVi 10th, 50th (median), and 90th percentiles were calculated over the 72 hours pre-, or poststeroid, or both administration (AI). HRVi percentiles in non-AI patients were evaluated at the same interval and compared with AI using Wilcoxon's rank-sum test. In patients with AI, daily HRVi was computed 3 days before and after steroid administration, and compared between survivors and nonsurvivors., Results: There were 2.9 million heart-rate intervals measured. HRVi stratified patients with AI (cosyntropin failure), and without AI. HRVi was similar in AI survivors and nonsurvivors before steroid treatment, but differed after treatment. HRVi increased substantially in survivors after steroid administration, yet did not change in nonsurvivors. HRVi does not increase in patients who are unresponsive to steroids and die., Conclusions: Reduced heart-rate variability, a potential measurement of complex biologic systems, is associated with cosyntropin-confirmed AI; improved in patients responding to steroid therapy; and is a noninvasive, real-time biomarker suggesting AI.

Genes of Sulfolobus metallicus that appeared to be upregulated in relation to growth on either ferrous iron or sulfur were identified using subtractive hybridization of cDNAs. The genes upregulated during growth on ferrous iron were found in a cluster, and most were predicted to encode membrane proteins. Quantitative reverse transcription-PCR of cDNA showed upregulation of most of these genes during growth on ferrous iron and pyrite compared to results during growth on sulfur. The highest expression levels observed included those for genes encoding proteins with similarities to cytochrome c oxidase subunits and a CbsA-like cytochrome. The genes identified here that may be involved in oxidation of ferrous iron by S. metallicus are termed fox genes. Of three available genomes of Sulfolobus species (S. tokodaii, S. acidocaldarius, and S. solfataricus), only that of S. tokodaii has a cluster of highly similar open reading frames, and only S. tokodaii of these three species was also able to oxidize ferrous iron. A gene encoding sulfur oxygenase-reductase was identified as the source of the dominant transcript in sulfur-grown cells of S. metallicus, with the predicted protein showing high identities to the previously described examples from S. tokodaii and species of Acidianus.

Background: Measurements of a patient's physiologic reserve (age, injury severity, admission lactic acidosis, transfusion requirements, and coagulopathy) reflect robustness of response to surgical insult. We have previously shown that cardiac uncoupling (reduced heart rate variability, HRV) in the first 24 hours after injury correlates with mortality and autonomic nervous system failure. We hypothesized: Deteriorating physiologic reserve correlates with reduced HRV and cardiac uncoupling., Methods: There were 1,425 trauma ICU patients that satisfied the inclusion criteria. Differences in mortality across categorical measurements of the domains of physiologic reserve were assessed using the chi test. The relationship of cardiac uncoupling and physiologic reserve was examined using multivariate logistic regression models for various levels of cardiac uncoupling (>0 through 28% reduced HRV in the first 24 hours)., Results: Of these, 797 (55.9%) patients exhibited cardiac uncoupling. Deteriorating measures of physiologic reserve reflected increased risk of death. Measures of acidosis (admission lactate, time to lactate normalization, and lactate deterioration over the first 24 hours), coagulopathy, age, and injury severity contributed significantly to the risk of cardiac uncoupling (area under receiver operator curve, ROC=0.73). The association between deteriorating reserve and cardiac uncoupling increases with the threshold for uncoupling (ROC=0.78)., Conclusions: Reduced heart rate variability is a new biomarker reflecting the loss of command and control of the heart (cardiac uncoupling). Risk of cardiac uncoupling increases significantly as a patient's physiologic reserve deteriorates and physiologic exhaustion approaches. Cardiac uncoupling provides a noninvasive, overall measure of a patient's clinical trajectory over the first 24 hours of ICU stay.

Objective: We have previously shown that cardiac uncoupling (reduced heart rate variability) in the first 24 hours of trauma ICU stay is a robust predictor of mortality. We hypothesize that cardiac uncoupling over the entire ICU stay independently predicts mortality, reveals patterns of injury, and heralds complications., Methods: A total of 2088 trauma ICU patients satisfied the inclusion criteria for this study. Cardiac uncoupling by outcome was compared using the Wilcoxon rank sum test. Risk of death from cardiac uncoupling and covariates (age, ISS, AIS Head Score, total transfusion requirements) was assessed using multivariate logistic regression models at each ICU day. Univariate logistic regression was used to assess risk of death from uncoupling irrespective of covariates at each ICU day., Results: A total of 1325 (63.5%) patients displayed some degree of uncoupling over their ICU stay. The difference in uncoupling between survivors and nonsurvivors is both dramatic and consistent across the entire ICU stay, indicating that the presence of uncoupling is unrelated to the cause of death. However, the magnitude of uncoupling varies by day when data is stratified by cause of death., Conclusions: Cardiac uncoupling: 1) is an independent predictor of death throughout the ICU stay, 2) has a predictive window of 2 to 4 days, and 3) appears to increase in response to inflammation, infection, and multiple organ failure.

Background: Resuscitation regimens based on stroke work index (SWI) and ventricular-arterial coupling (VAC) are controversial. The Signal Interpretation and Monitoring (SIMON) system continuously collects and stores physiologic intensive care unit (ICU) bedside data at 3- to 5-second intervals. The purpose of this study was to demonstrate the capabilities of a completely automated data management system by further evaluating SWI-based resuscitation., Methods: This study was a retrospective review of all severely injured patients requiring a pulmonary artery catheter (PAC) for acute postinjury resuscitation. Patients with a severe head injury were excluded. Hemodynamic (HD) data (21 million datapoints) were densely acquired and archived by SIMON. Mean values of HD variables were compared between survivors and nonsurvivors. Receiver operator characteristic (ROC) curves were constructed for HD variables. Threshold values which maximized sensitivity and specificity were determined., Results: Eighty-eight patients over a 19-month time period met criteria and were included in the analysis. SWI was significantly greater in survivors versus nonsurvivors (4421 +/- 1278 versus 3163 +/- 1066 mm Hg . mL/m, p = 0.0008). VAC was quantified by the ratio (RATIO) of afterload (Ea) to contractility (Ees). RATIO (Ea/Ees) in survivors was significantly better than in nonsurvivors (1.9 +/- 1.1 vs. 2.9 +/- 1.0, p = 0.002). ROC curves identified threshold values of 3250 mm Hg x mL/m for SWI and 2.1 for RATIO (AUC = 0.78 and 0.82, respectively)., Conclusion: Previous work demonstrating the use of SWI and VAC as resuscitation guidelines was supported through the use of a powerful ICU data management system (SIMON). The emergence of these "new vital signs" may change the way injured patients are evaluated and resuscitated in the ICU.

Background: Our previous work demonstrated dense physiological data capture in the intensive care unit (ICU), defined a new vital sign Cardiac Volatility Related Dysfunction (CVRD) reflecting reduced heart rate variability, and demonstrated CVRD predicts death during the hospital stay adjusting for age and injury severity score (ISS). We hypothesized a more precise definition of variability in integer heart rate improves predictive power earlier in ICU stay, without adjusting for covariates., Methods: Approximately 120 million integer heart rate (HR) data points were prospectively collected and archived from 1316 trauma ICU patients, linked to outcome data, and de-identified. HR standard deviation was computed in each 5-min interval (HR(SD5)). HR(SD5) logistic regression identified ranges predictive of death. The study group was randomly divided. Integer heart rate variability (% time HR(SD5) in predictive distribution ranges) models were developed on the first set (N = 658) at 1, 2, 4, 6, 8, 12, and 24 h after ICU admission, and validated on the second set (N = 658)., Results: HR(SD5) is bimodal, predicts death at low (0.1-0.9 bpm) and survival at high (1.8-2.6 bpm) ranges. HRV predicts death as early as 12 h (ROC = 0.67). HRV in a moving 1-h window is a simple graphic display technique., Conclusions: Dense physiological data capture allows calculation of HRV, which: 1) Independently predicts hospital death in trauma patients at 12 h; 2) Shows early differences by mortality in groups of patients when viewed in a moving window; and 3) May have implications for military and civilian triage.

Background: SIMON (Signal Interpretation and Monitoring) monitors and archives continuous physiologic data in the ICU (HR, BP, CPP, ICP, CI, EDVI, SVO2, SPO2, SVRI, PAP, and CVP). We hypothesized: heart rate (HR) volatility predicts outcome better than measures of central tendency (mean and median)., Methods: More than 600 million physiologic data points were archived from 923 patients over 2 years in a level one trauma center. Data were collected every 1 to 4 seconds, stored in a MS-SQL 7.0 relational database, linked to TRACS, and de-identified. Age, gender, race, Injury Severity Score (ISS), and HR statistics were analyzed with respect to outcome (death and ventilator days) using logistic and Poisson regression., Results: We analyzed 85 million HR data points, which represent more than 71,000 hours of continuous data capture. Mean HR varied by age, gender and ISS, but did not correlate with death or ventilator days. Measures of volatility (SD, % HR >120) correlated with death and prolonged ventilation., Conclusions: 1) Volatility predicts death better than measures of central tendency. 2) Volatility is a new vital sign that we will apply to other physiologic parameters, and that can only be fully explored using techniques of dense data capture like SIMON. 3) Densely sampled aggregated physiologic data may identify sub-groups of patients requiring new treatment strategies.