Application of anti-Xa assay in monitoring unfractionated heparin therapy in contemporary antithrombotic management.

INTRODUCTION: Unfractionated heparin remains the most widely used agent in the prevention and acute treatment of thrombosis. Pharmacological complexities of this intriguing agent mandate frequent monitoring of its anticoagulant properties to maintain safe and effective hematological outcomes. Although activated partial thromboplastin time has been the standard test to monitor unfractionated heparin therapy for many decades, the anti-Xa assay has emerged as a substitute or adjunct in many institutions. AREAS COVERED: This brief report outlines the key features of anti-Xa assay in monitoring unfractionated heparin in acute management of thrombosis in various contemporary settings, with emphasis on evidence for clinical outcomes. PubMed.gov database was utilized to obtain the pertinent literature. EXPERT OPINION: The anti-Xa activity is primarily a reflection of UFH concentration and does not account for other hematological variables frequently present in contemporary anticoagulation management. The advantage of the anti-Xa assay in monitoring UFH therapy is predicated upon its limitations to account for global physiological hemostasis. There are significant disease and drug interactions that may potentially result in false in-vitro analysis of anti-Xa activity. Routine application of the anti-Xa assay is not evidence-based at this time.

A Technique of Awake Bronchoscopic Endotracheal Intubation for Respiratory Failure in Patients With Right Heart Failure and Pulmonary Hypertension.

OBJECTIVE: Patients with pulmonary hypertension and right heart failure have a high risk of clinical deterioration and death during or soon after endotracheal intubation. The effects of sedation, hypoxia, hypoventilation, and changes in intrathoracic pressure can lead to severe hemodynamic instability. In search for safer approach to endotracheal intubation in this cohort of patients, we evaluate the safety and feasibility of an alternative intubation technique. DATA SOURCES: Retrospective data analysis. STUDY SELECTION: Two medical ICUs in large university hospitals in the United States. DATA EXTRACTION: We report a case series of nine nonconsecutive patients with compromised right heart function, pulmonary hypertension, and severe acute hypoxemic respiratory failure who underwent endotracheal intubation with a novel technique combining awake bronchoscopic intubation supported with nasally delivered noninvasive positive pressure ventilation or high-flow nasal cannula. DATA SYNTHESIS: All patients were intubated in the first attempt without major complications and eight patients (88%) were alive 24 hours after intubation. Systemic hypotension was the most frequent complication following the procedure. CONCLUSIONS: Awake bronchoscopic intubation supported with a noninvasive positive pressure delivery systems may be feasible alternative to standard direct laryngoscopy approach. Further studies are needed to better assess its safety and applicability.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

RATIONALE: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes. OBJECTIVES: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. METHODS: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. MEASUREMENTS AND MAIN RESULTS: The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. CONCLUSIONS: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.

Cocaine-induced vasoconstriction in the human coronary microcirculation: new evidence from myocardial contrast echocardiography.

BACKGROUND: Cocaine is a major cause of acute coronary syndrome, especially in young adults; however, the mechanistic underpinning of cocaine-induced acute coronary syndrome remains limited. Previous studies in animals and in patients undergoing cardiac catheterization suggest that cocaine constricts coronary microvessels, yet direct evidence is lacking. METHODS AND RESULTS: We used myocardial contrast echocardiography to test the hypothesis that cocaine causes vasoconstriction in the human coronary microcirculation. Measurements were performed at baseline and after a low, nonintoxicating dose of intranasal cocaine (2 mg/kg) in 10 healthy cocaine-naïve young men (median age, 32 years). Postdestruction time-intensity myocardial contrast echocardiography kinetic data were fit to the equation y=A(1-e(-ßt)) to quantify functional capillary blood volume (A), microvascular flow velocity (ß), and myocardial perfusion (A×ß). Heart rate, mean arterial pressure, and left ventricular work (2-dimensional echocardiography) were measured before and 45 minutes after cocaine. Cocaine increased mean arterial pressure (by 14±2 mm Hg [mean±SE]), heart rate (by 8±3 bpm), and left ventricular work (by 50±18 mm Hg·mL(-1)·bpm(-1)). Despite the increases in these determinants of myocardial oxygen demand, myocardial perfusion decreased by 30% (103.7±9.8 to 75.9±10.8 arbitrary units [AU]/s; P<0.01) mainly as a result of decreased capillary blood volume (133.9±5.1 to 111.7±7.7 AU; P<0.05) with no significant change in microvascular flow velocity (0.8±0.1 to 0.7±0.1 AU). CONCLUSIONS: In healthy cocaine-naïve young adults, a low-dose cocaine challenge evokes a sizeable decrease in myocardial perfusion. Moreover, the predominant effect is to decrease myocardial capillary blood volume rather than microvascular flow velocity, suggesting a specific action of cocaine to constrict terminal feed arteries.

Is cardiovascular disease in women inevitable?: preparing for menopause and beyond.

Cardiovascular disease (CVD) is the leading cause of death for American women. Women share many of the same risk factors (RFs) for CVD as men, and in both, women and men, these RFs are associated with age. Additionally, the prevalence of multiple RFs increases with age. Though menopause has been thought to increase CVD risk in women, the association between menopause and age obfuscates a causal relationship. While men's CVD mortality has decreased since the 1980s, women's CVD mortality has climbed until 2000. This has resulted in a sex-related CVD mortality gap, with women having higher mortality than men since 1984. Contributing to this female-majority CVD mortality gap is a lack of awareness of CVD risk among women and their physicians. Awareness campaigns, such as the Heart Truth and the Red Dress symbol, appear to have improved recognition of CVD risk in women. Further, female-specific guidelines have been developed to prevent and reduce CVD in women. Though the current understanding of the role of menopause in CVD is controversial, studies suggest that menopause does not exacerbate CVD independent of aging, and hormone replacement therapy is not effective for secondary prevention of CVD.

Secondary lymphedema in the mouse tail: Lymphatic hyperplasia, VEGF-C upregulation, and the protective role of MMP-9.

Disturbances in the microcirculation can lead to secondary lymphedema, a common pathological condition that, despite its frequency, still lacks a cure. Lymphedema is clinically well described, but while the genetic underpinnings that cause lymphatic malformations and primary lymphedema are being discovered, the pathophysiology and pathobiology of secondary lymphedema remain poorly understood, partly due to the lack of well-described experimental models. Here, we provide a detailed characterization of secondary lymphedema in the mouse tail and correlate the evolution of tissue swelling to changes in tissue architecture, infiltration of immune cells, deposition of lipids, and proliferation and morphology of the lymphatic vessels. We show that sustained swelling leads to lymphatic hyperplasia and upregulation of vascular endothelial growth factor (VEGF)-C, which may exacerbate the edema because the hyperplastic vessels are poorly functional. The onset of lymphatic hyperplasia occurred prior to the onset of lipid accumulation and peak VEGF-C expression. Langerhans dendritic cells were seen in the dermis migrating from the epidermis to the lymphatic capillaries in edematous tissue. Furthermore, these results were consistent between two different normal mouse strains, but swelling was significantly greater in a matrix metalloproteinase (MMP)-9 null strain. Thus, by characterizing this highly reproducible model of secondary lymphedema, we conclude that VEGF-C upregulation and lymphatic hyperplasia resulting from dermal lymphatic ligation and lymphedema leads to decreased drainage function and that MMP-9 may be important in counteracting tissue swelling.