A Mineral-Doped Micromodel Platform Demonstrates Fungal Bridging of Carbon Hot Spots and Hyphal Transport of Mineral-Derived Nutrients.

Soil fungi facilitate the translocation of inorganic nutrients from soil minerals to other microorganisms and plants. This ability is particularly advantageous in impoverished soils because fungal mycelial networks can bridge otherwise spatially disconnected and inaccessible nutrient hot spots. However, the molecular mechanisms underlying fungal mineral weathering and transport through soil remains poorly understood primarily due to the lack of a platform for spatially resolved analysis of biotic-driven mineral weathering. Here, we addressed this knowledge gap by demonstrating a mineral-doped soil micromodel platform where mineral weathering mechanisms can be studied. We directly visualize acquisition and transport of inorganic nutrients from minerals through fungal hyphae in the micromodel using a multimodal imaging approach. We found that Fusarium sp. strain DS 682, a representative of common saprotrophic soil fungus, exhibited a mechanosensory response (thigmotropism) around obstacles and through pore spaces (~12 µm) in the presence of minerals. The fungus incorporated and translocated potassium (K) from K-rich mineral interfaces, as evidenced by visualization of mineral-derived nutrient transport and unique K chemical moieties following fungus-induced mineral weathering. Specific membrane transport proteins were expressed in the fungus in the presence of minerals, including those involved in oxidative phosphorylation pathways and the transmembrane transport of small-molecular-weight organic acids. This study establishes the significance of a spatial visualization platform for investigating microbial induced mineral weathering at microbially relevant scales. Moreover, we demonstrate the importance of fungal biology and nutrient translocation in maintaining fungal growth under water and carbon limitations in a reduced-complexity soil-like microenvironment. IMPORTANCE Fungal species are foundational members of soil microbiomes, where their contributions in accessing and transporting vital nutrients is key for community resilience. To date, the molecular mechanisms underlying fungal mineral weathering and nutrient translocation in low-nutrient environments remain poorly resolved due to the lack of a platform for spatial analysis of biotic weathering processes. Here, we addressed this knowledge gap by developing a mineral-doped soil micromodel platform. We demonstrate the function of this platform by directly probing fungal growth using spatially resolved optical and chemical imaging methodologies. We found the presence of minerals was required for fungal thigmotropism around obstacles and through soil-like pore spaces, and this was related to fungal transport of potassium (K) and corresponding K speciation from K-rich minerals. These findings provide new evidence and visualization into hyphal transport of mineral-derived nutrients under nutrient and water stresses.

Profiling How the Gut Microbiome Modulates Host Xenobiotic Metabolism in Response to Benzo[a]pyrene and 1-Nitropyrene Exposure.

The gut microbiome is a key contributor to xenobiotic metabolism. Polycyclic aromatic hydrocarbons (PAHs) are an abundant class of environmental contaminants that have varying levels of carcinogenicity depending on their individual structures. Little is known about how the gut microbiome affects the rates of PAH metabolism. This study sought to determine the role that the gut microbiome has in determining the various aspects of metabolism in the liver, before and after exposure to two structurally different PAHs, benzo[a]pyrene and 1-nitropyrene. Following exposures, the metabolic rates of PAH metabolism were measured, and activity-based protein profiling was performed. We observed differences in PAH metabolism rates between germ-free and conventional mice under both unexposed and exposed conditions. Our activity-based protein profiling (ABPP) analysis showed that, under unexposed conditions, there were only minor differences in total P450 activity in germ-free mice relative to conventional mice. However, we observed distinct activity profiles in response to corn oil vehicle and PAH treatment, primarily in the case of 1-NP treatment. This study revealed that the repertoire of active P450s in the liver is impacted by the presence of the gut microbiome, which modifies PAH metabolism in a substrate-specific fashion.

Causes and consequences of variation in heterospecific pollen receipt in Oenothera fruticosa.

PREMISE: Heterospecific pollen transfer, the transfer of pollen between species, is common among co-flowering plants, yet the amount of pollen received is extremely variable among species. Intraspecific variation in heterospecific pollen receipt can be even greater, but we lack an understanding of its causes and fitness consequences in wild populations. METHODS: We examined potential drivers of variation in heterospecific pollen receipt in Oenothera fruticosa. We evaluated the relationship between heterospecific and conspecific pollen receipt and considered how visitation by different pollinator groups, local floral neighborhood composition, and flowering phenology affect the total amount and proportion of heterospecific pollen received. Finally, we tested whether variation in heterospecific pollen receipt translated into lower seed production. RESULTS: Heterospecific pollen was ubiquitous on O. fruticosa stigmas, but the amount received was highly variable and unrelated to conspecific pollen receipt. Heterospecific pollen receipt depended on pollinator type, the proportion of nearby conspecific flowers, and flowering date. Significant interactions revealed that the effects of pollinator type and neighborhood were not independent, further contributing to variation in heterospecific pollen. Naturally occurring levels of heterospecific pollen were sufficient to negatively impact seed set, but large amounts of conspecific pollen counteracted this detrimental effect. CONCLUSIONS: Although selection could act on floral traits that attract quality pollinators and promote synchronous flowering in O. fruticosa, the risk of heterospecific pollen is equally dependent on local floral context. This work highlights how extrinsic and intrinsic factors contribute to intraspecific variation in heterospecific pollen receipt in wild plants, with significant fitness consequences.

Activity-Based Protein Profiling of Chitin Catabolism.

The microbial catabolism of chitin, an abundant and ubiquitous environmental organic polymer, is a fundamental cog in terrestrial and aquatic carbon and nitrogen cycles. Despite the importance of this critical bio-geochemical function, there is a limited understanding of the synergy between the various hydrolytic and accessory enzymes involved in chitin catabolism. To address this deficit, we synthesized activity-based probes (ABPs) designed to target active chitinolytic enzymes by modifying the chitin subunits N-acetyl glucosamine and chitotriose. The ABPs were used to determine the active complement of chitinolytic enzymes produced over time by the soil bacterium Cellvibrio japonicus treated with various C substrates. We demonstrate the utility of these ABPs in determining the synergy between various enzymes involved in chitin catabolism. The strategy can be used to gain molecular-level insights that can be used to better understand microbial roles in soil bio-geochemical cycling in the face of a changing climate.

Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk non-ST-segment elevation acute coronary syndrome.

BACKGROUND: We examined the prevalence of undiagnosed diabetes or prediabetes and associations with ischemic outcomes among non-ST-segment elevation acute coronary syndrome (ACS) patients. METHODS: We categorized 8795 EARLY ACS trial patients into one of the following groups: "known diabetes" (n = 2860 [32.5%]; reported on the case report form), "undiagnosed diabetes" (n = 1069 [12.2%]; no diabetes history and fasting glucose ≥126 mg/dL or hemoglobin A1c ≥6.5%), "prediabetes" (n = 947 [10.8%]; fasting glucose ≥110 to <126 mg/dL, or "normal" (n = 3919 [44.5%]). Adjusted associations of known diabetes, undiagnosed diabetes, and prediabetes (versus normal) with 30-day and 1-year outcomes were determined. RESULTS: Undiagnosed diabetes was associated with greater 30-day death or myocardial infarction (MI) (ORadj 1.28, 95% CI 1.05-1.57), driven primarily by greater 30-day mortality (ORadj 1.65, 95% CI 1.09-2.48). Known diabetic patients had 30-day death or MI outcomes similar to those of normal patients, but 30-day mortality was higher (ORadj 1.40, 95% CI 1.01-1.93). Prediabetic patients had 30-day death or MI outcomes similar to those of normal patients. One-year mortality was greater among known diabetic patients (HRadj 1.38, 95% CI 1.13-1.67) but not among those with undiagnosed diabetes or prediabetes. CONCLUSIONS: Undiagnosed diabetes and prediabetes were common among high-risk non-ST-segment elevation ACS patients. Routine screening for undiagnosed diabetes may be useful since these patients seem to have worse short-term outcomes and deserve consideration of alternative management strategies.

Age, treatment, and outcomes in high-risk non-ST-segment elevation acute coronary syndrome patients: insights from the EARLY ACS trial.

BACKGROUND: Elderly patients with acute coronary syndromes (ACS) are at high risk for death and recurrent thrombotic events. We evaluated the efficacy and safety of intensive treatment with glycoprotein IIb/IIIa inhibitors in an elderly population, and the relationships between age, timing of administration, and clinical outcomes. METHODS: We used data from high-risk non-ST-segment elevation ACS patients randomized to early eptifibatide vs. delayed provisional use at percutaneous coronary intervention. In multivariable models, we included age×treatment interaction terms to assess whether treatment effect varied by age after adjusting for confounders. RESULTS: Of 9406 patients, 13.9% were aged <55 years; 27.6%, 55-64 years; 33.2%, 65-74 years; and 25.3%, ≥ 75 years. For each 10-year age increase, the adjusted odds ratio (OR) (95% confidence interval [CI]) for 96-hour death, myocardial infarction (MI), recurrent ischemia requiring urgent revascularization, or thrombotic bailout was 1.13 (1.04-1.23) and for 30-day death or MI was 1.13 (1.04-1.22). Increasing age was also associated with greater 1-year mortality (adjusted hazard ratio per 10 years: 1.44, 95% CI 1.30-1.60). There was no interaction between age and treatment (p interaction=0.99, 0.54, and 0.87, respectively). Increasing age was associated with more non-coronary artery bypass grafting-related TIMI major bleeding (adjusted OR and 95% CI per 10 years: 1.54 [1.24-1.92]), GUSTO moderate/severe bleeding (1.52 [1.33-1.75]), and transfusion (1.25 [1.07-1.45]). The amount by which TIMI major bleeding was increased with early vs. delayed provisional eptifibatide use was significantly greater with increasing age (p interaction=0.02), but the age×treatment interactions were not significant for GUSTO moderate/severe bleeding or transfusion (p interaction=0.33 and 0.54, respectively). CONCLUSION: Increasing age was associated with greater risk for ischemic events and more bleeding. Despite higher baseline ischemic risk in older patients, there was no preferential benefit of early vs. delayed provisional eptifibatide use for ischemic outcomes as age increased, but the incremental bleeding risk was amplified.

ED to catheterization laboratory: a roundtable integrating trials with practice.

BACKGROUND: Clinical trials are the foundation underlying clinical decision-making. However, stringent inclusion and exclusion criteria may reduce the generalizability of their results, especially for patients seen in the emergency department (ED). Guideline recommendations, based on clinical trials and pertinent registries, apply to broad populations, but not all patients cared for at the bedside fit the predefined categories that make guidelines practical. Furthermore, these documents may not incorporate the latest evidence. As a result, other factors (eg, individual patient characteristics, clinician experience, cost, regulatory labels, expert opinions) often result in clinical decision-making that varies from strict adherence to guideline recommendations. OBJECTIVES: These challenges demonstrate a need to integrate clinical data and guidelines advice with actual ED practice in a manner that will be consistent with decisions made later in the continuum of care. DISCUSSION: In recognition of these issues, a roundtable was convened in New York City on June 5, 2009, to discuss the implications of recent trials involving patients with non-ST-segment elevation acute coronary syndromes. Eight physicians, representing both emergency medicine and cardiology, shared information on advances and clinical trial results in antiplatelet treatment, guidelines, and other developments in patient care. This article is based on transcripts of their presentations and the ensuing discussions that were of particular importance for emergency physicians. CONCLUSIONS: Although guidelines and clinical registries can provide broad direction for practice, there is no substitute for a prospective, multidisciplinary, institution-specific, consistent, evidence-based approach to patient management.

Acute coronary syndromes: from the emergency department to the catheterization laboratory-integrating evidence from recent ACS/NSTEMI trials into clinical practice: an evidence-based review of recent clinical trial results and report on a roundtable discussion.

Over the past 2 years, multiple clinical trials have reported results that will influence the treatment of patients with non-ST-segment elevation acute coronary syndromes (ACS) for many years to come. However, large-scale clinical trials take years to complete, during which time the underlying landscape may shift. Thus, while clinical trials provide baseline information to help physicians make evidence-based decisions regarding patient care, trials must be interpreted in the context of current treatment guidelines and practices. In addition, regulatory and advisory board decisions, case reports, clinician experience, and patient factors have a clear but difficult-to-measure impact on practice patterns. In recognition of the wide range of information affecting physicians' decision-making processes in patients with ACS, a roundtable was convened on June 5, 2009, in New York City to discuss the implications of recent data for clinical practice. Eight clinicians from the disciplines of cardiology and emergency medicine shared information and opinions on recent advances in antiplatelet treatment, clinical trial results, guidelines, and other issues related to patient care. This article is derived from transcripts of their presentations and the surrounding discussions at this meeting, with the intent of reporting both quantitative information on recent advances in the management of ACS and qualitative information and opinions from participants. Each author held primary responsibility for the writing and editing of his or her section, and participated in the editing of the entire manuscript.

Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations.

BACKGROUND: Leber congenital amaurosis (LCA) is the earliest and most severe inherited retinal degeneration. Isolated forms of LCA frequently result from mutation of the CEP290 gene which is expressed in various ciliated tissues. METHODS: Seven LCA patients with CEP290 mutations were investigated to study otorhinolaryngologic phenotype and respiratory cilia. Nasal biopsies and brushing were performed to study cilia ultrastructure using transmission electron microscopy and ciliary beating using high-speed videomicroscopy, respectively. CEP290 expression in normal nasal epithelium was studied using real-time RT-PCR. RESULTS: When electron microscopy was feasible (5/7), high levels of respiratory cilia defects were detected. The main defects concerned dynein arms, central complex and/or peripheral microtubules. All patients had a rarefaction of ciliated cells and a variable proportion of short cilia. Frequent but moderate and heterogeneous clinical and ciliary beating abnormalities were found. CEP290 was highly expressed in the neural retina and nasal epithelial cells compared with other tissues. DISCUSSION: These data provide the first clear demonstration of respiratory cilia ultrastructural defects in LCA patients with CEP290 mutations. The frequency of these findings in LCA patients along with the high expression of CEP290 in nasal epithelium suggest that CEP290 has an important role in the proper development of both the respiratory ciliary structures and the connecting cilia of photoreceptors. The presence of respiratory symptoms in patients could represent additional clinical criteria to direct CEP290 genotyping of patients affected with the genetically heterogeneous cone-rod dystrophy subtype of LCA.

[Clinical inertia in geriatrics]. / Prescription inappropriée chez la personne agée: une forme d'inertie thérapeutique? Généralités et opportunités pour la pharmacie clinique en gériatrie.

Therapeutic inertia is a phenomenon with multiple etiologies, characterized by a "lack of initiation or modification of therapy when appropriate" and mainly affecting common chronic diseases (hypertension, diabetes, dyslipidemia). Caused by various processes including the lack of clinical evidence for the elderly, it can lead, in the elderly fragile by nature, to inappropriate prescribing. In a multidisciplinary approach, integrating the expertise of a pharmacist in the health care team improves the pharmacotherapeutic management of the geriatric patient.

Safety and efficacy of bivalirudin in high-risk patients admitted through the emergency department.

OBJECTIVES: The objective was to assess the safety and efficacy of bivalirudin monotherapy in patients with high-risk acute coronary syndrome (ACS) presenting to the emergency department (ED). METHODS: Data from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial were used to conduct a post hoc subgroup analysis of high-risk ACS patients (cardiac biomarker elevation or ST-segment deviation) who initially presented to the ED. The ACUITY trial randomized patients to receive heparin (unfractionated [UFH] or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Endpoints included composite ischemia, major bleeding (not coronary artery bypass graft (CABG) related), and net clinical outcome (major bleeding plus composite ischemia). RESULTS: Of 13,819 participants in the ACUITY trial, 6,441 presented initially to the ED, met high-risk criteria, and were included in the primary analysis. Bivalirudin alone when compared to heparin plus GPI, after adjusting for covariates, was associated with an improvement in net clinical outcome (12.3% vs. 14.3%, adjusted odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.66 to 0.99), similar composite ischemia (9.3% vs. 9.1%, adjusted OR = 0.98, 95% CI = 0.77 to 1.24), and less major bleeding (4.0% vs. 6.8%, adjusted OR = 0.57, 95% CI = 0.42 to 0.75). Bivalirudin plus GPI when compared to heparin plus GPI had similar net clinical outcome (13.8% vs. 14.3%, adjusted OR = 0.91, 95% CI = 0.75 to 1.11), composite ischemia (8.8% vs. 9.1%, adjusted OR = 0.87, 95% CI = 0.69 to 1.11), and major bleeding (6.8% vs. 6.8%, adjusted OR = 1.01, 95% CI = 0.79 to 1.30). CONCLUSIONS: Bivalirudin monotherapy decreases major bleeding while providing similar protection from ischemic events compared to heparin plus GPI in patients with high-risk ACS admitted through the ED.

Real-time monitoring of cell transplantation in mouse dystrophic muscles by a secreted alkaline phosphatase reporter gene.

Transplantation of muscle precursor cells (MPCs) is a promising approach for the treatment of muscular dystrophies. However, preclinical and clinical results have shown that the technology is not yet efficient enough for most therapeutic applications. Among the problems that remain unsolved are low cellular survival, poor proliferation and lack of migration of the transplanted cells. One major technical hurdle for the optimization of transplantation protocols is how to follow precisely the fate of the cells after transplantation. In this study, we examined the use of a secreted form of the mouse alkaline phosphatase (mSeAP) enzyme as the reporter system transduced into MPCs using a retroviral vector. We show that circulating mSeAP could be detected in the serum of the transplanted mice at different time points after MPC transplantation. We also found that the level of circulating mSeAP is highly correlated with the number of transplanted cells and that mSeAP is an excellent histological marker. Further, studying the levels of circulating mSeAP compared with the number of muscle fibers positive to mSeAP and to dystrophin, enabled detailed analyses of bottleneck steps for successful transplantation. Taken together, our results show that mSeAP is an excellent quantitative 'real-time' reporter gene for cell therapy preclinical studies.

Insurance coverage and care of patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: The impact of insurance coverage on the care of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. OBJECTIVE: To compare NSTE ACS care patterns by insurance type. DESIGN: Comparison of Medicaid patients younger than 65 years of age and Medicare patients 65 years of age or older with patients of similar age who have health maintenance organization (HMO) or private insurance coverage. SETTING: 521 U.S. hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC [American College of Cardiology]/AHA [American Heart Association] Guidelines) quality improvement initiative from January 2001 through March 2005. PATIENTS: 37,345 NSTE ACS patients younger than 65 years of age and 59,550 patients 65 years of age or older. MEASUREMENTS: Guideline-recommended treatments, and in-hospital outcomes. RESULTS: Medicaid was the primary payer for 18.7% (6999 of 37,345) of patients younger than age 65 years, whereas Medicare was the primary payer for 67.5% (40,199 of 59,550) of patients age 65 years or older. Medicaid patients were statistically significantly less likely to receive short-term (less than 24 hours) medications and to undergo invasive cardiac procedures than patients covered by HMO and private insurance. They also had higher mortality rates (2.9% vs. 1.2%; adjusted odds ratio, 1.33; 95% CI, 1.08 to 1.63). Medications and invasive procedures were used to a similar extent in patients with Medicare and HMO or private insurance, and respective mortality rates were not significantly different (6.2% vs. 5.6%; adjusted odds ratio, 1.08; 95% CI, 0.99 to 1.18). LIMITATIONS: Self-pay patients and patients without insurance were not assessed. CONCLUSIONS: NSTE ACS patients with Medicaid (but not Medicare) as the primary payer were less likely to receive evidence-based therapies and had worse outcomes than patients with HMO or private insurance as the primary payer. The causes of these treatment differences and solutions for narrowing the gaps in quality require further investigation.

The impact of emergency department structure and care processes in delivering care for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: We sought to assess the influence of emergency department (ED) structure and care processes on adherence to practice guidelines for the treatment of patients with non-ST-segment elevation acute coronary syndromes. METHODS: We surveyed emergency physicians and nurses from 316 hospitals participating in the CRUSADE Quality Improvement Initiative and used multivariable modeling to correlate ED-specific characteristics with guidelines adherence. RESULTS: Factors that were significantly associated with improved guidelines adherence included collaboration between emergency physicians and hospital administration, northeast region, adequate nursing support, use of locum tenens physicians, an independent ED (not a division of another clinical department), and use of a care algorithm for acute coronary syndromes. CONCLUSIONS: Quality improvement strategies that have the full support of hospital administration, focus on increasing collaboration between emergency physicians and other health care providers, and specified protocol-driven management algorithm may be the most successful methods for improving the care and outcomes of patients with non-ST-segment elevation acute coronary syndromes.

Treatment disparities in the care of patients with and without diabetes presenting with non-ST-segment elevation acute coronary syndromes.

OBJECTIVE: The objective of this study was to characterize treatment patterns among patients with diabetes presenting with non-ST-segment elevation (NSTE) acute coronary syndromes (ACSs). RESEARCH DESIGN AND METHODS: We compared adherence to treatment recommendations from the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for NSTE ACS among 46,410 patients from 413 U.S. hospitals that were included in the Can Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) quality improvement initiative. Patients were stratified as nondiabetic, non-insulin-dependent diabetic (type 2 diabetic), and insulin-treated diabetic. RESULTS: Insulin-treated diabetic patients were less likely than nondiabetic patients to receive aspirin (adjusted odds ratio 0.83 [95% CI 0.74-0.93]), beta-blockers (0.89 [0.83-0.96]), heparin (0.90 [0.83-0.98]), and glycoprotein IIb/IIIa inhibitors (0.86 [0.79-0.93]). Type 2 diabetic patients were treated similarly to nondiabetic patients. After adjustment for differences in clinical characteristics, insulin-treated diabetic patients were significantly less likely than nondiabetic patients to receive cardiac catheterization within 48 h of presentation (0.80 [0.74-0.86]) or percutaneous coronary intervention (0.87 [0.82-0.94]). Compared with nondiabetic patients, insulin-treated diabetic and type 2 diabetic patients were more likely to undergo coronary artery bypass grafting (1.34 [1.21-1.49] and 1.35 [1.26-1.44]). In-hospital mortality rates were higher in insulin-treated diabetic (6.8%) and type 2 diabetic (5.4%) than in nondiabetic (4.4%) patients. CONCLUSIONS: Diabetic patients have a higher risk of mortality than nondiabetic patients, yet physicians adhere to the ACC/AHA NSTE ACS guidelines less often when treating diabetic patients, particularly insulin-treated diabetic patients. Increased use of guideline-recommended therapies and early invasive management strategies in diabetic patients may improve their outcomes.

Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative.

OBJECTIVES: We hypothesized that significant disparities in gender exist in the management of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). BACKGROUND: Gender-related differences in the diagnosis and treatment of ACS have important healthcare implications. No large-scale examination of these disparities has been completed since the publication of the revised American College of Cardiology/American Heart Association guidelines for management of patients with NSTE ACS. METHODS: Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative, we examined differences of gender in treatment and outcomes among patients with NSTE ACS. RESULTS: Women (41% of 35,875 patients) were older (median age 73 vs. 65 years) and more often had diabetes and hypertension. Women were less likely to receive acute heparin, angiotensin-converting enzyme inhibitors, and glycoprotein IIb/IIIa inhibitors and less commonly received aspirin, angiotensin-converting enzyme inhibitors, and statins at discharge. The use of cardiac catheterization and revascularization was higher in men, but among patients with significant coronary disease, percutaneous revascularization was performed in a similar proportion of women and men. Women were at higher risk for unadjusted in-hospital death (5.6% vs. 4.3%), reinfarction (4.0% vs. 3.5%), heart failure (12.1% vs. 8.8%), stroke (1.1% vs. 0.8%), and red blood cell transfusion (17.2% vs. 13.2%), but after adjustment, only transfusion was higher in women. CONCLUSIONS: Despite presenting with higher risk characteristics and having higher in-hospital risk, women with NSTE ACS are treated less aggressively than men.

Update on acute coronary syndromes and implications for therapy.

Our understanding of the pathophysiology of acute coronary syndromes (ACS), including acute ST elevation myocardial infarction, unstable angina and non-ST-segment elevation (NSTE) myocardial infarction, has evolved considerably over the years, with atherothrombosis playing a pivotal role. This review will discuss the recent advances/recommendations for drug therapy based on this enhanced understanding of the pathophysiology of thrombosis. More recently developed agents, such as low-molecular-weight heparins (LMWHs), glycoprotein (GP) IIb-IIIa inhibitors, direct thrombin inhibitors, Factor Xa inhibitors and thienopyridines, offer several potential advantages, either as an alternative to unfractionated heparin (i.e., LMWHs) or as an add-on therapy to aspirin and unfractionated heparin (or LMWHs; e.g., GP IIb-IIIa inhibitors, thienopyridines). The purpose of this review is to describe recent studies with novel antithrombotic agents (e.g., LMWHs, thienopyridines, GP IIb-IIIa inhibitors, bivalirudin) in patients with NSTE ACS, as well as to highlight recommendations for management of patients with NSTE ACS in the recently updated American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including the appropriate use of antithrombotic therapies.

Bench to bedside: pathophysiology of acute coronary syndromes and implications for therapy.

Our understanding of the pathophysiology of unstable angina (UA) and non-ST-segment elevation (NSTE) myocardial infarction (MI) [commonly referred to as NSTE acute coronary syndrome(s) (ACS)] has evolved considerably over the years, with atherothrombosis playing a pivotal role. This review discusses the molecular interactions in coronary thrombosis that may serve as therapeutic targets for more effective management of these syndromes. The purposes of this review are: 1) to discuss current understanding of the pathophysiology of NSTE ACS; 2) to describe recent studies with novel antithrombotic agents [e.g., low-molecular-weight heparin, thienopyridines, glycoprotein (GP) IIb-IIIa inhibitors] in patients with NSTE ACS; and 3) to highlight recommendations for management of patients with NSTE ACS in the recently updated American College of Cardiology (ACC)/ American Heart Association (AHA) guidelines, including the appropriate use of antithrombotic therapies.