Successful pulmonary administration of activated recombinant factor VII in diffuse alveolar hemorrhage

INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a serious pulmonary complication seen in patients with autoimmune disorders and patients treated with chemotherapy or after hematopoietic stem cell transplantation. The clinical management of DAH is complex and the condition has a high mortality rate. Tissue factor is expressed in the lung alveoli during inflammation and therefore pulmonary administration of human recombinant activated factor VIIa (rFVIIa) could be a rational treatment option. METHODS: Six patients with acute, bronchoscopically confirmed DAH from a single intensive care unit university hospital center were included in the study of acute DAH in critically ill patients. The patients were treated with intrapulmonary administration of 50 μg/kg rFVIIa in 50 ml of sodium chloride by bronchoalveolar lavage (BAL) with 25 ml in each of the main bronchi, which was repeated after 24 hours in case of treatment failure. RESULTS: An excellent response, defined as complete and sustained hemostasis after a single dose of rFVIIa, was seen in three patients. A good response, meaning that sustained hemostasis was achieved by a repeated rFVIIa administration, was seen in the remaining three patients. In one of these patients, the BAL treatment was repeated twice; in another patient, the second dose of rFVIIa was administered by nebulizer after extubation after the initial BAL. The hemostatic effect was statistically significant (p = 0.031). The oxygenation capacity, as reflected by the PaO(2)/FiO(2 )(arterial oxygen pressure/inspiratory fractional oxygen content) ratio, increased significantly (p = 0.024) in all six patients following the local rFVIIa therapy. CONCLUSION: Symptomatic therapy of DAH after intrapulmonary administration of one or more doses of rFVIIa was found to have a good to excellent hemostatic effect in six consecutive patients with DAH. The intrapulmonary administration of rFVIIa seemed to have a high benefit-to-risk ratio. Larger series should confirm the safety of this approach

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| < 0.8) in the transverse momentum range 1 < pt < 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes