Impact of high-dose antioxidants on outcomes in acutely injured patients

BACKGROUND: The profound oxidative stress that occurs following injury results in significant depletion of many endogenous antioxidants (vitamin C, E, selenium). Increasing evidence suggests antioxidant supplementation reduces infectious complications and organ dysfunction following injury and hemorrhagic shock. The purpose of this study was to evaluate the impact of high-dose antioxidant administration on the mortality rate of acutely injured patients. METHODS: In October 2005, we implemented a 7-day high-dose antioxidant protocol for acutely injured patients admitted to our trauma center. A retrospective cohort study, evaluating all patients admitted to the trauma service between October 2005 and September 2006 following protocol implementation (AO+), was performed. The comparison cohort (AO-) was made up of those patients admitted in the year prior to protocol implementation. RESULTS: A total of 4,294 patients met criteria (AO+, N = 2,272; AO-, N = 2022). Hospital (4 vs 3 days, P < .001) and ICU (3 vs 2 days, P = .001) median length of stays were significantly shorter in the AO+ group. Mortality was significantly lower in the AO+ group (6.1% vs 8.5%, P = .001), translating into a 28% relative risk reduction for mortality in patients exposed to high-dose antioxidants. After adjusting for age, gender, and probability of survival, AO exposure was associated with even lower mortality (OR 0.32, 95% CI 0.22-0.46). Patients with an expected survival <50% benefited most (OR 0.24, 95% CI 0.15-0.37). CONCLUSIONS: A high-dose antioxidant protocol resulted in a 28% relative risk reduction in mortality and a significant reduction in both hospital and ICU length of stay. This protocol represents an inexpensive intervention to reduce mortality/morbidity in the trauma patient.     

Transesophageal Echocardiographic Correlates of Clinical Risk of Thromboembolism in Nonvalvular Atrial Fibrillation

Objectives. This study explored the mechanisms linking clinical and precordial echocardiographic predictors to thromboembolism in atrial fibrillation (AF) by assessing transesophageal echocardiographic (TEE) correlations.

Background. Clinical predictors of thromboembolism in patients with nonvalvular AF have been identified, but their mechanistic links remain unclear. TEE provides imaging of the left atrium, its appendage and the proximal thoracic aorta, potentially clarifying stroke mechanisms in patients with AF.

Methods. Cross-sectional analysis of TEE features correlated with low, moderate and high thromboembolic risk during aspirin therapy among 786 participants undergoing TEE on entry into the Stroke Prevention in Atrial Fibrillation III trial.

Results. TEE features independently associated with increased thromboembolic risk were appendage thrombi (relative risk [RR] 2.5, p = 0.04), dense spontaneous echo contrast (RR 3.7, p < 0.001), left atrial appendage peak flow velocities ≤20 cm/s (RR 1.7, p = 0.008) and complex aortic plaque (RR 2.1, p < 0.001). Patients with AF with a history of hypertension (conferring moderate risk) more frequently had atrial appendage thrombi (RR 2.6, p < 0.001) and reduced flow velocity (RR 1.8, p = 0.003) than low risk patients. Among low risk patients, those with intermittent AF had similar TEE features to those with constant AF.

Conclusions. TEE findings indicative of atrial stasis or thrombosis and of aortic atheroma were independently associated with high thromboembolic risk in patients with AF. The increased stroke risk associated with a history of hypertension in AF appears to be mediated primarily through left atrial stasis and thrombi. The presence of complex aortic plaque distinguished patients with AF at high risk from those at moderate risk of thromboembolism.     

Characterization of a Rab11-like GTPase,EhRab11, of Entamoeba histolytica

The Entamoeba histolytica Rab11 family of small molecular weight GTPases consists of three members, EhRab11, EhRab11B, and EhRab11C. The functions of these Rabs in Entamoeba have not been determined. Therefore, as an approach to elucidate the role of the Rab11 family of GTPases in Entamoeba, immunofluorescence microscopy was undertaken to define the subcellular localization of one member of this family, EhRab11. Under conditions of growth, EhRab11 displayed a punctate pattern in the cytoplasm of trophozoites. EhRab11 did not colocalize with markers for the Golgi apparatus, endoplasmic reticulum, pinosomes, phagosomes, or compartments formed by receptor-mediated endocytosis, suggesting that this Rab may not play a role in vesicle trafficking between these organelles. Under conditions of iron and serum starvation, EhRab11 was translocated to the periphery of the cell. The altered cellular localization was accompanied by multinucleation of the cells as well as the acquisition of detergent resistance by the cells, features that are characteristic of Entamoeba cysts. The translocation of EhRab11 to the periphery of the cell during iron and serum starvation was specific as the subcellular localizations of two other Rab GTPases, EhRab7 and EhRabA, were not altered under the same conditions. In addition, the formation of multinucleated cells by inhibition of cytokinesis was not sufficient to induce the translocation of EhRab11 to the cell periphery. Taken together, the data suggest that iron and serum starvation may induce encystation in E. histolytica and that EhRab11 may play a role in this process. Moreover, these studies are the first to describe a putative role for a Rab GTPase in encystation in Entamoeba sp.     

Prognostic value of the Ortho Vitros cardiac troponin I assay in patients with symptoms of myocardial ischemia. Risk stratification using European Society of Cardiology/American College of Cardiology recommended cutoff values

We evaluated the risk assessment value of a commercial cardiac troponin (cTn; Ortho Vitros ECi, Ortho-Clinical Diagnostics, Raritan, NJ) I assay in patients with symptoms of myocardial ischemia suggestive of acute coronary syndrome and compared findings with those for a commercial cTnT assay in the same population. The cTn levels were measured by both assays in plasma samples from 273 patients during 24 hours after admission. Baseline and maximum concentrations were used for risk stratification; cutoffs were the 99th percentile and 10% coefficient of variation. End points were all-cause death and cardiac events within 60 days. Relative risks (RRs) were estimated using Cox proportional hazards regression models and Kaplan-Meier curves. RRs of cardiac events and death were significantly higher with increased baseline and maximum concentrations using either cTnI cutoff. The respective mortality rates for baseline cTnI of more than 0.08 microgram/L vs 0.08 microgram/L or less were 17.4% vs 2.9% (P = .001); cardiac event rates were 11.5% vs 3.6% (P = .03). Exclusion of patients with ST-segment elevation had no significant effect on rates for either assay. Mortality was higher in the intermediate (0.09-0.2 microgram/L) than in the low (< or = 0.08 microgram/L) group for cTnI, with directionally similar results for cTnT. Our findings validate the Ortho cTnI assay as a risk stratification biomarker in patients with symptoms of myocardial ischemia.     

Localization of Phosphatidylinositol 4,5-Bisphosphate to Lipid Rafts and Uroids in the Human Protozoan Parasite Entamoeba histolytica

Entamoeba histolytica is an intestinal protozoan parasite and is the causative agent of amoebiasis. During invasive infection, highly motile amoebae destroy the colonic epithelium, enter the blood circulation, and disseminate to other organs such as liver, causing liver abscess. Motility is a key factor in E. histolytica pathogenesis, and this process relies on a dynamic actomyosin cytoskeleton. In other systems, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] is known to regulate a wide variety of cellular functions, including signal transduction, actin remodeling, and cell motility. Little is known about the role of PI(4,5)P₂ in E. histolytica pathogenicity. In this study, we demonstrate that PI(4,5)P₂ is localized to cholesterol-rich microdomains, lipid rafts, and the actin-rich fractions of the E. histolytica membrane. Microscopy revealed that the trailing edge of polarized trophozoites, uroids, are highly enriched in lipid rafts and their constituent lipid, PI(4,5)P₂. Polarization and enrichment of uroids and rafts with PI(4,5)P₂ were enhanced upon treatment of E. histolytica cells with cholesterol. Exposure to cholesterol also increased intracellular calcium, which is a downstream effector of PI(4,5)P₂, with a concomitant increase in motility. Together, our data suggest that in E. histolytica, PI(4,5)P₂ may signal from lipid rafts and cholesterol may play a role in triggering PI(4,5)P₂-mediated signaling to enhance the motility of this pathogen.     

Thyroid follicular carcinoma presenting as skull and dural metastasis mimicking a meningioma: a case report

Follicular thyroid cancer rarely manifests itself as a distant metastatic lesion. We report a case of a 61-year-old woman presented with a solid mass located in the left temporo-occipital region. The 3D computed tomography showed a large solid mass with high vascularity, skull erosion and supra-infratentorial epidural mass effect. After magnetic resonance imaging (MRI) a suspect diagnosis of meningioma was made. The patient underwent surgery where a soft mass with transverse sinus invasion was encountered, the tumor was successfully resected employing microsurgical techniques. Histological examination revealed a thyroid follicular neoplasm with positive staining for follicular carcinoma in immunohistochemical analysis. Postoperatively levels of thyroid hormones were normal. Treatment was planned for the thyroid gland, but the patient did not consent. The present case emphasizes that although they are uncommon, dural metastasis can be mistaken for meningiomas. The definitive diagnosis of a meningioma should be established only after the histopathological analysis. Thyroid follicular carcinoma should be included in the differential diagnosis in cases of extrinsic tumoral lesions.     

Contradicting fears, California's nurse-to-patient mandate did not reduce the skill level of the nursing workforce in hospitals

When California passed a law in 1999 establishing minimum nurse-to-patient staffing ratios for hospitals, it was feared that hospitals might respond by disproportionately hiring lower-skill licensed vocational nurses. This article examines nurse staffing ratios for California hospitals for the period 1997-2008. It compares staffing levels to those in similar hospitals in the United States. We found that California's mandate did not reduce the nurse workforce skill level as feared. Instead, California hospitals on average followed the trend of hospitals nationally by increasing their nursing skill mix, and they primarily used more highly skilled registered nurses to meet the staffing mandate. In addition, we found that the staffing mandate resulted in roughly an additional half-hour of nursing per adjusted patient day beyond what would have been expected in the absence of the policy. Policy makers in other states can look to California's experience when considering similar approaches to improving patient care.