Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.

PURPOSE: The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. PATIENTS AND METHODS: Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. RESULTS: The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. CONCLUSION: The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.     

Synthesis and Antimuscarinic Activity of Derivatives of 2-Substituted-1,3-Dioxolanes

Geometric cis, trans isomers, derivatives of 2-substituted-1,3-dioxanes were designed and studied as antimuscarinic agents. The synthesized compounds were evaluated as perchlorides and methiodides by functional tests with rabbit vas deferens (putative M₁), guinea-pig heart (M₂) and guinea-pig ileum (M₃). The effect of the replacement of a trimethylammonium group with a dimethysulfonium in the two rings was also evaluated. Pharmacological results indicate that the 1,3-dioxane nucleus shows the highest stereoselective values on the studied receptors.     

Densiron 68 heavy silicone oil in the management of inferior retinal detachment recurrence: analysis on functional and anatomical outcomes and complications

AIM: To assess the efficacy and safety of a heavy silicone oil (Densiron 68) in the management of inferior retinal detachment recurrence. METHODS: A retrospective non-comparative consecutive case series study. Forty-nine cases of complex inferior retinal detachment were treated using Densiron 68 heavy silicone oil (HSO) as the endotamponade. Our main purpose was anatomic reattachment following Densiron 68 removal. Functional outcomes, rate of recurrences, the presence of inflammatory complications and intraocular pressure alterations were evaluated. RESULTS: Forty-nine patients affected by complex retinal re-detachment were recruited. The mean follow-up was 7.6 (±1.5) mo. The mean best corrected visual acuity after Densiron 68 removal was 0.95 logMAR, standard error (SE: 0.068). Retinal reattachment was 61.2% after first surgery and 81.6% after second surgery. Nineteen cases (38.8%) had recurrences when intraocular heavy silicon oil was in situ, 26.3% (5 cases) of which involved the inferior retina. CONCLUSION: Densiron 68 ef?ciently fills the inferior retinal periphery and might lower the risk of inferior proliferative vitreoretinopathy development, in particular after a standard silicon oil tamponade that reduces the proliferative process in the upper quadrants of the retina.     

Reassessing the two-year rodent carcinogenicity bioassay: A review of the applicability to human risk and current perspectives

The 2-year rodent carcinogenicity test has been the regulatory standard for the prediction of human outcomes for exposure to industrial and agro-chemicals, food additives, pharmaceuticals and environmental pollutants for over 50 years. The extensive experience and data accumulated over that time has spurred a vigorous debate and assessment, particularly over the last 10 years, of the usefulness of this test in terms of cost and time for the information obtained. With renewed interest in the United States and globally, plus new regulations in the European Union, to reduce, refine and replace sentinel animals, this review offers the recommendation that reliance on information obtained from detailed shorter-term, 6 months rodent studies, combined with genotoxicity and chemical mode of action can realize effective prediction of human carcinogenicity instead of the classical two year rodent bioassay. The aim of carcinogenicity studies should not be on the length of time, and by obligation, number of animals expended but on the combined systemic pathophysiologic influence of a suspected chemical in determining disease. This perspective is in coordination with progressive regulatory standards and goals globally to utilize effectively resources of animal usage, time and cost for the goal of human disease predictability.     

Usefulness of Left Ventricular Vortex Flow Analysis for Predicting Clinical Outcomes in Patients with Chronic Heart Failure: A Quantitative Vorticity Imaging Study Using Contrast Echocardiography

The goal of the study described here was to evaluate whether left ventricular vortex flow parameters, as assessed by contrast echocardiography, enhance prediction of major adverse cardiac events (MACE) in patients with chronic heart failure and systolic dysfunction. A total of 75 patients with contrast echocardiography and systolic dysfunction (ejection fraction ≤45%) were prospectively enrolled and underwent vortex flow analysis with particle image velocimetry using contrast echocardiography. Vortex flow parameters, including kinetic energy fluctuation (KEF), were evaluated. Patients were followed up for a primary endpoint of MACE that comprised hospital admission for cardiovascular causes and cardiac deaths. Across a median 277-d follow-up, 29 patients (38.7%) experienced MACE. Among these, the incidence of diabetes and the E/e' ratio were significantly higher in patients with MACE than in those without, whereas the hemoglobin level and ejection fraction were significantly lower. KEF was significantly lower in patients with MACE. In the multivariate analysis, higher KEF was associated with a lower risk of MACE (hazard ratio?=?0.18, 95% confidence interval: 0.04–0.97, p?=?0.046). The addition of KEF to a model with conventional parameters (e.g., age, diabetes, ejection fraction and the E/e' ratio) significantly improved the model's discrimination. Elevations in the quantitative left ventricular vortex flow parameter, KEF, as determined by contrast echocardiography, are associated with a lower risk of MACE and improved functional status among patients with chronic heart failure.