Sirtuins Link Inflammation and Metabolism.

Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1-7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to "defend and mend" against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to "defend" against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to "mend," leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis.

Surgical intensive care unit mobility is increased after institution of a computerized mobility order set and intensive care unit mobility protocol: a prospective cohort analysis.

In some populations, intensive care unit (ICU) mobility has been shown to be safe and beneficial. We gathered data on 50 nonintubated surgical patients in a 10-bed surgical ICU (SICU) who met physiologic inclusion criteria beginning in May 2008 (A group). In January 2009, we began mandatory entry of computerized mobility orders as part of a standardized ICU order set. We also created a mobility protocol for nurses in this ICU. We then collected data on 50 patients in this postintervention cohort (B group). Both groups had similar baseline characteristics. A group patients had some form of mobility orders entered in 29 patients (58%) versus 47 patients (82%) in the B group, P < 0.05. In the A group, 11 patients (22%) were mobilized; in the B group, 40 patients (80%) were mobilized, P < 0.05. In our SICU patient population, mandatory entry of computerized mobility orders as part of a standard SICU order set and establishment of an ICU mobility nursing protocol was associated with an increase in number of mobility orders entered as well as an increase in SICU patient activity. Further studies should focus on measurement of the effect of mobility interventions on patient outcomes.

National nosocomial infection surveillance system: from benchmark to bedside in trauma patients.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in the injured patient. Identification of those with VAP is important both in immediate clinical decision making as well as for the epidemiologic evaluation of the disease and benchmarking of rates across institutions with variable practice patterns. Despite this, controversy exists over the optimal method of VAP diagnosis. Many centers currently use invasive culture methods such as bronchoalveolar lavage (BAL) for diagnosis. Another diagnostic method, and the most common epidemiologic tool used to track VAP, is the definition employed by the National Nosocomial Infections Surveillance (NNIS) system. This relies on a combination of clinical and culture data. Our goal was to evaluate the accuracy of the NNIS definition as compared with BAL diagnosis in trauma patients. METHODS: Records of all ventilated patients admitted to the trauma intensive care unit at a Level I center who were evaluated for the presence of pneumonia over a 2.5-year period were reviewed. VAP diagnosis was established if > or =10 cfu/mL were cultured on BAL. VAP rates and time of onset were compared with the hospital infection control database, which defines VAP by NNIS criteria. Assuming BAL to be correct, sensitivity, specificity, and positive and negative predictive values were calculated for NNIS VAP. RESULTS: From September 1, 2001, through December 31, 2003, 292 patients underwent BAL for suspected pneumonia. The pneumonia rate in this group was 34 per 1,000 ventilator days. The NNIS definition showed excellent overall agreement, with a rate of 36 per 1,000 ventilator days. The use of the NNIS definition for bedside decision making, however, is less accurate. Sensitivity and positive predictive value were reasonably good (84% and 83%, respectively), whereas specificity and negative predictive value suffer (69% and 69%, respectively). Most importantly, the use of NNIS would have led to no treatment in 16% of patients diagnosed with VAP by BAL. CONCLUSIONS: Compared with strict bacteriologic criteria for VAP, the NNIS definition has good overall agreement and seems to have utility as an epidemiologic benchmarking tool in trauma patients. However, the NNIS definition has less utility as a bedside decision-making tool in this population, leading to under-treatment in a significant number of patients.

Are plain radiographs of the spine necessary during evaluation after blunt trauma? Accuracy of screening torso computed tomography in thoracic/lumbar spine fracture diagnosis.

BACKGROUND: Fracture of the thoracolumbar (TL) spine is reported in 8 to 15% of victims of blunt trauma. Current screening of these patients is done with conventional radiography. This may require repeated sets of films and take hours to days. It is imperative that these patients get timely, accurate evaluation to allow for treatment planning and early mobilization; alternatives to plain films would aid in this. The objective of this study is to determine whether the data obtained from admission chest/abdomen/pelvis (CAP) computed tomography (CT) scans after blunt trauma has utility in thoracolumbar spine evaluation. METHODS: The records of all patients admitted to a Level I trauma center over a 2-month period who underwent CAP CT were reviewed for the presence of TL spine fracture, time to completion of plain film evaluation, and clinical course. Admission CT scans were reviewed by an attending radiologist who was blinded to any previously diagnosed spine fractures. The two tests were compared for diagnostic accuracy and their discriminatory ability was compared using receiver operating characteristic (ROC) curves. Significance was defined as p < 0.05. RESULTS: In all, 103 patients were admitted from January 1, 2003 to February 28, 2003 and underwent CAP CT scan as part of their initial trauma evaluation. Of these, 26 (25%) had thoracolumbar fractures. Seven (27%) thoracolumbar fractures were not seen on plain radiographs taken during the trauma evaluation. Average time until plain film completion in this group was 8 hours (range, 44 minutes to 38 hours). All 26 (100%) patients with fractures, however, were diagnosed on CT scan performed shortly after admission. Of the remaining 77 patients, two (2.6%) were falsely read as positive for fracture on CT. Sensitivity and specificity of CT scan for thoracolumbar fracture were excellent at 100% and 97%, respectively, with a negative predictive value of 100%. Plain radiographs were 73% sensitive, 100% specific, and had a negative predictive value of 92%. Area under the ROC curve for CT was 0.98, but for plain film was 0.86 (p < 0.02). CONCLUSION: Admission CAP CT obtained as part of the routine trauma evaluation in these high-risk patients is more sensitive than plain radiographs for evaluation of the TL spine after blunt trauma. In addition, CAP CT can be performed faster. Omission of plain radiographs will expedite accurate evaluation allowing earlier treatment and mobilization.

Thoracotomy for blunt trauma: traditional indications may not apply.

The indications for performing as urgent thoractomy after trauma are based on the criteria used for penetrating injuries. However, few data are available on the use of these indications for patients with blunt injuries. In a retrospective study (June 1996 to July 2001), we compared the indications of urgent thoracotomy after blunt injury and penetrating injury in patients who underwent thoracotomy within 24 hours of hospital admission at our institution. Patients with blunt aortic injuries or emergency department thoracotomies were excluded from evaluation. Fifty-nine patients were identified (37 penetrating injuries, 22 blunt injuries). Blunt trauma victims had a higher mortality rate than penetrating trauma victims (73% vs. 22%). Chest tube output was the indication for nontherapuetic thoracotomy in 5 patients with blunt injuries whereas this occurred in only 1 penetrating injury victim (P = 0.04). All 5 blunt injury patients underwent a prior procedure and were coagulopathic when thoracotomy was performed. In conclusion, thoracotomy following blunt trauma is associated with a high rate of mortality. The rate of nontherapeutic exploration is increased when chest tube output is the indication for thoracotomy after blunt trauma. Since the majority of such patients have multicavitary injuries that require prior operation and are commonly coagulopathic, caution should be exercised when deciding whether to proceed with thoracotomy based solely on chest tube output.