Age-adjusted and Expanded Lactate Thresholds as Predictors of All-Cause Mortality in the Emergency Department.

INTRODUCTION: While numerous studies have found emergency department (ED) lactate levels to be associated with increased in-hospital mortality, little information is available on the role age plays in this association. This study investigates whether age is a necessary variable to consider when using lactate levels as a marker of prognosis and a guide for management decisions in the ED. METHODS: This was a retrospective cohort study in an urban, tertiary-care teaching hospital. A total of 13,506 lactate levels were obtained over a 4.5-year period. All adult patients who had a lactate level obtained by the treating provider in the ED were screened for inclusion. The main outcome measure was in-hospital mortality using age-adjusted cohorts and expanded lactate thresholds with secondary outcomes comparing mortality based on the primary clinical impression. RESULTS: Of the 8796 patients in this analysis, there were 474 (5.4%) deaths. Mortality rates increased with both increasing lactate levels and increasing age. For all ages, mortality rates increased from 2.8% in the less than 2.0 millimoles per liter (mmol/L) lactate level, to 5.6% in the 2.0-2.9 mmol/L lactate level, to 8.0% in the 3.0-3.9 mmol/L lactate level, to 13.9% in the 4.0-4.9 mmol/L lactate level, to 13.7% in the 5.0-5.9 mmol/L lactate level, and to 39.1% in the 6.0 mmol/L or greater lactate level (p <0.0001). Survivors, regardless of age, had a mean lactate level <2.0 whereas non-survivors had mean lactate levels of 6.5, 4.5, and 3.7 mmol/L for age cohorts 18-39, 40-64, and ≥ 65 years, respectively. CONCLUSION: Our findings suggest that although lactate levels can be used as a prognostic tool to risk stratify ED patients, the traditional lactate level thresholds may need to be adjusted to account for varying risk based on age and clinical impressions.

Oxidative stress and antioxidant treatment in patients with peripheral artery disease.

Peripheral artery disease is an atherosclerotic disease of arterial vessels that mostly affects arteries of lower extremities. Effort induced cycles of ischemia and reperfusion lead to increased reactive oxygen species production by mitochondria. Therefore, the pathophysiology of peripheral artery disease is a consequence of metabolic myopathy, and oxidative stress is the putative major operating mechanism behind the structural and metabolic changes that occur in muscle. In this review, we discuss the evidence for oxidative damage in peripheral artery disease and discuss management strategies related to antioxidant supplementation. We also highlight the major pathways governing oxidative stress in the disease and discuss their implications in disease progression. Potential therapeutic targets and diagnostic methods related to these mechanisms are explored, with an emphasis on the Nrf2 pathway.

Preoperative optimization of the vascular surgery patient.

It is well known that patients who suffer from peripheral (noncardiac) vascular disease often have coexisting atherosclerotic diseases of the heart. This may leave the patients susceptible to major adverse cardiac events, including death, myocardial infarction, unstable angina, and pulmonary edema, during the perioperative time period, in addition to the many other complications they may sustain as they undergo vascular surgery procedures, regardless of whether the procedure is performed as an open or endovascular modality. As these patients are at particularly high risk, up to 16% in published studies, for postoperative cardiac complications, many proposals and algorithms for perioperative optimization have been suggested and studied in the literature. Moreover, in patients with recent coronary stents, the risk of non-cardiac surgery on adverse cardiac events is incremental in the first 6 months following stent implantation. Just as postoperative management of patients is vital to the outcome of a patient, preoperative assessment and optimization may reduce, and possibly completely alleviate, the risks of major postoperative complications, as well as assist in the decision-making process regarding the appropriate surgical and anesthetic management. This review article addresses several tools and therapies that treating physicians may employ to medically optimize a patient before they undergo noncardiac vascular surgery.

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae.

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.

The genome sequence of the rice blast fungus Magnaporthe grisea.

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.

The genome sequence of the filamentous fungus Neurospora crassa.

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.