Persistent systemic inflammatory response syndrome is predictive of nosocomial infection in trauma

BACKGROUND: Admission systemic inflammatory response syndrome (SIRS) score has been previously reported to be an accurate predictor of infection and outcome in trauma. However, these data were limited to only one SIRS score at admission. A prior study in surgical intensive care unit (ICU) patients reported that the SIRS score on ICU day 2 declined after completion of resuscitation, and was a more accurate predictor of outcome. Our objective in this follow-up study was to prospectively evaluate the utility of daily SIRS scores in prediction of nosocomial infection and outcome in high-risk trauma patients. METHODS: Prospective data were collected on 702 consecutive trauma patients admitted over a 12-month period to the ICU. SIRS scores were calculated daily. Centers for Disease Control and Prevention guidelines were used for the diagnosis of infection. Multivariate linear regression was used for statistical analysis. RESULTS: Five hundred seventy-three (82%) patients sustained blunt injuries and 129 (18%) sustained penetrating injuries. The mean age was 43 +/- 21 years, with an overall mortality of 11.4%. Two hundred ninety (41.3%) of the study patients acquired a nosocomial infection (respiratory site most common), with an associated mortality rate of 12.4%. SIRS (defined as SIRS score >/= 2) on hospital days 3 through 7 was a significant predictor of nosocomial infection and hospital length of stay. Persistent SIRS to hospital day 7 was associated with a significant risk for increased mortality (relative risk, 4.7; 95% confidence interval, 1.41-12.87; p = 0.047). CONCLUSION: Persistent SIRS is predictive of nosocomial infection in trauma. Daily monitoring of SIRS scores is easily accomplished and should be considered in all high-risk trauma patients. Persistent SIRS in trauma should initiate early diagnostic interventions for determination of source of infection, and consideration of early empiric antimicrobial therapy.     

All patients with truncal gunshot wounds deserve trauma team activation

BACKGROUND: Traditional criteria for trauma team activation (TTA) include hypotension, tachycardia, tachypnea, and unresponsiveness. In a recent revision of the Resources for Optimal Care of the Trauma Patient, gunshot wound to the trunk (GSWT) was recommended as an independent criterion for major resuscitation and TTA. To validate this suggestion, we reviewed records of patients with GSWT to see if patients not meeting standard TTA criteria had serious injuries that would benefit from TTA. METHODS: This study was a retrospective trauma registry study at a large Level I trauma center. Records of all patients over an 8.5-year period with GSW to chest, back, or abdomen/pelvis were included in the study. Patients who died in hospital, required ICU admission within 24 hours, had non-orthopedic operation within 24 hours, or had ISS > 15 were considered severely injured, and were assumed to benefit from TTA. RESULTS: Between January 1993 and June 2000, 4,198 patients were admitted with GSWT, 94% of whom met traditional TTA criteria. Sixty-one percent of patients meeting traditional TTA criteria had severe injury, compared with 45.7% for those without TTA criteria. Of the 234 patients who did not meet traditional TTA criteria, 9.4% required early ICU admission, 29.5% required non-orthopedic operation within 24 hours, and 1.3% died. CONCLUSION: Patients with GSWT often require high-level care, even when physiologic TTA criteria are absent on admission. Gunshot wound to the trunk should be an independent criterion for TTA.     

Low-dose ethanol alters the cardiovascular,metabolic, and respiratory compensation for severe blood loss

BACKGROUND: Compensation for hemorrhage and shock requires coordination of responses and sufficient physiologic reserve capacity of the cardiovascular, respiratory, renal, and neuroendocrine systems. Intake of ethanol (EtOH) is known to degrade physiologic response to stress. The purpose of this study was to investigate how acute EtOH exposure changes responses to severe blood loss, shock, and resuscitation. METHODS: Conscious male Duncan Hartley guinea pigs were given an intraperitoneal injection of either EtOH (1 g/kg) or an equal volume of water 30 minutes before controlled hemorrhage (60% blood volume), resuscitated after 30 minutes of hypovolemia with a lactated Ringer's solution volume equal to that of the shed blood volume, and observed for 24 hours. Hemodynamic (heart rate, arterial blood pressure), clinical laboratory (arterial blood gases, glucose, lactate, hematocrit), and metabolic gas exchange (oxygen consumption, carbon dioxide production) indicators of shock were monitored. RESULTS: Of the animals that survived 24 hours, changes in arterial pH and lactate were significantly greater in the experiment group than in the control group. Mortality at 24 hours was 77% in the experiment group (EtOH-treated) and 42% (p = 0.39) in the control group (water-treated). CONCLUSION: Acute EtOH exposure, with blood EtOH concentration similar to legal intoxication levels, limits physiologic reserve during hemorrhagic shock and resuscitation. In survivors of shock and resuscitation, compensation is compromised and physiologic reserve is adversely affected by acute EtOH intake.     

Aldosterone-secreting adrenocortical carcinomas are associated with unique operative risks and outcomes

BACKGROUND: Adrenocortical carcinoma (ACC) that produces aldosterone is an extremely rare, uncharacterized endocrine malignancy. Our aim was to characterize this neoplasm in terms of its clinical behavior and patient outcomes. METHODS: A retrospective review was made of all patients who had operative management of aldosterone-secreting ACC from 1957 to 2000 at the Mayo Clinic. Comparisons were made to patients with non-aldosterone-secreting ACC treated during the same period. RESULTS: Of 141 patients with ACC, we identified 15 patients with aldosterone-secreting ACC. Isolated aldosterone hypersecretion was present in 10 patients, and mixed hormonal secretion was detected in 5. Mean tumor size and weight were 10.8 cm and 453 g, respectively. Surgical management included curative resection in 10 patients (67%). Perioperative mortality was 20%. Disease recurred in 7 patients (70%) with a median interval of 17 months. Five-year survival was 52%. Patients with aldosterone-secreting ACC had an increased risk of perioperative mortality (20% vs 5%), yet they had an overall survival of 63 months compared to 19 months for patients with non-aldosterone-secreting ACC. CONCLUSIONS: Aldosterone hypersecretion occurs in 11% of all ACCs and is associated with unique operative risk and outcome. Although patients harboring aldosterone-secreting ACC appear to have an increased risk of perioperative death, survivors may have an improved overall survival rate compared with patients with non-aldosterone-secreting ACC.     

Prevention of bronchiolitis obliterans in rat lung allografts by type V collagen-induced oral tolerance

BACKGROUND: We have reported that feeding type V collagen (col(V)) to lung allograft recipients induces immune tolerance that prevents acute lung allograft rejection. Repeated acute rejection is a risk factor for or associated with chronic rejection, known as bronchiolitis obliterans (BO), the leading cause of death in lung allograft recipients. The current study examines if col(V)-induced oral tolerance prevents BO. METHODS: WKY rats (RT1l) were fed either col(V) or diluent before orthotopic transplantation of F344 (RT1lvl) lung allografts. No rats received any immunosuppression. At 10 weeks posttransplantation the time to onset of BO, delayed type hypersensitivity (DTH) responses to donor antigens, and col(V) were examined. In addition, proliferative responses of recipient T lymphocytes to donor antigens, and ability of recipient antigen presenting cells to present alloantigens in lung allografts were evaluated. RESULTS: The data show that recipient rats have sustained DTH responses to donor antigens and col(V). T lymphocytes from col(V)-fed lung allograft recipients were unable to proliferate in response to donor antigens, but feeding col(V) had no effect on the presentation of donor alloantigens by recipient antigen presenting cells. All diluent fed rats developed BO, but only mild acute rejection (grade 2) was present in all rats fed col(V). Transforming growth factor (TGF)-beta production was up-regulated systemically in col(V)-fed, but not diluent fed, lung allograft recipients, and neutralizing TGF-beta [corrected] recovered the DTH response to donor antigens in col(V)-fed rats. CONCLUSIONS: Collectively these data show that col(V)-induces oral tolerance that prevents BO, and that tolerance may be mediated by systemic production of TGF-beta [corrected].     

How correctly does an intramedullary rod represent the longitudinal tibial axes?

In a robot-assisted procedure for preparing the tibia in total knee arthroplasty, developed in the authors' laboratory, an intramedullary rod is used to register the tibia. In 18 formalin-fixed tibias, the difference in orientation was calculated between the intramedullary rod and several longitudinal tibial axes used in clinical practice. This was done using roentgenstereophotogrammetric analysis. Three tibial axes and two insertion techniques were considered. In three-dimensional space, small differences between the axes are observed. The results showed a high standard deviation, indicating the importance of anatomic differences. In the frontal plane, the difference in orientation between rod and tibial axes never exceeded +/- 2 degrees. In the sagittal plane, the observed differences were larger. Significant differences between the considered axes appeared. The results of the two insertion techniques were not significantly different. Because an intramedullary rod frequently is used for alignment of the tibia in conventional surgery, these results also are valuable for conventional surgery. In the current study, the accuracy of the intramedullary alignment is examined, without influences of the sawing procedure. Moreover, the study is not limited to the frontal plane; the total accuracy in three-dimensional space, and the accuracy in the frontal and the sagittal planes were studied.     

A tailored therapy for the metabolic syndrome: the dual peroxisome proliferator-activated receptor-alpha/gamma agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models

A novel nonthiazolidinedione dual peroxisome proliferator- activated receptor (PPAR)-alpha/gamma agonist, LY465608, was designed to address the major metabolic disturbances of type 2 diabetes. LY465608 altered PPAR-responsive genes in liver and fat of db/db mice and dose-dependently lowered plasma glucose in hyperglycemic male Zucker diabetic fatty (ZDF) rats, with an ED(50) for glucose normalization of 3.8 mg small middle dot kg(-1) small middle dot day(-1). Metabolic improvements were associated with enhanced insulin sensitivity, as demonstrated in female obese Zucker (fa/fa) rats using both oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. Further characterization of LY465608 revealed metabolic changes distinct from a selective PPAR-gamma agonist, which were presumably due to the concomitant PPAR-alpha agonism, lower respiratory quotient, and less fat accumulation, despite a similar impact on glycemia in male ZDF rats. In addition to these alterations in diabetic and insulin-resistant animals, LY465608 dose-dependently elevated HDL cholesterol and lowered plasma triglycerides in human apolipoprotein A-I transgenic mice, demonstrating that this compound significantly improves primary cardiovascular risk factors. Overall, these studies demonstrate that LY465608 beneficially impacts multiple facets of type 2 diabetes and associated cardiovascular risk, including those facets involved in the development of micro- and macrovascular complications, which are the major sources for morbidity and mortality in these patients.