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Objectives: The purpose of this analysis was to assess 5-year outcomes of transcatheter aortic valve implantation (TAVI) using the current technology of the self-expanding CoreValve prosthesis (Medtronic Inc., Minneapolis, Minnesota)., Background: There is a paucity of evidence on long-term durability of currently available transcatheter heart valves., Methods: Starting in June 2007, all consecutive patients with severe aortic stenosis undergoing TAVI with the third-generation 18-F CoreValve device in 8 Italian centers were prospectively included in the ClinicalService Project. For the purposes of this study, we included only consecutive patients with 5-year follow-up data available (n = 353) treated from June 2007 to August 2009. All outcomes were reported according to VARC (Valve Academic Research Consortium)-1 criteria., Results: All-cause mortality rates at 1, 2, 3, 4, and 5 years were 21%, 29%, 38%, 48%, and 55.0%, respectively. Cardiovascular mortality rates at 1, 2, 3, 4, and 5 years were 10%, 14%, 19%, 23%, and 28.0%, respectively. The overall neurological event rate at 5 years was 7.5%, of which more than two-thirds occurred early after the procedure. During follow-up, there were 241 rehospitalizations for cardiovascular reasons in 164 (46%) patients. Among all rehospitalizations, acute heart failure was the most frequently reported (42.7%), followed by requirement of permanent pacemaker implantation (17.4%). On echocardiography, mean transaortic gradients decreased from 55.6 ± 16.8 mm Hg (pre-TAVI) to 12.8 ± 10.9 mm Hg (5-year post-TAVI) (p < 0.001). Late prosthesis failure occurred in 5 cases (1.4%); among these, redo TAVI was successfully carried out in 2 patients (0.6%) presenting with symptomatic prosthesis restenosis. The remaining 3 cases of prosthesis failure did not undergo further invasive interventions. Ten patients (2.8%) showed late mild stenosis with a mean transaortic gradient ranging from 20 to 40 mm Hg. No other cases of structural or nonstructural valvular deterioration were observed. Valve thrombosis or late valve embolization were not reported., Conclusions: TAVI with the currently adopted CoreValve generation was associated with sustained clinical outcomes up to 5-year follow-up, with a low rate (1.4%) of significant prosthetic valve degeneration. The procedure appears to be an adequate and lasting resolution of aortic stenosis in selected high-risk patients., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The clinical outcome, response to treatment, and occurrence of acute complications were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and correlated with serological characteristics and severity of anemia at onset. Patients had been followed up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly direct antiglobulin test negative). The latter 2 categories more frequently showed a severe onset (hemoglobin [Hb] levels ≤6 g/dL) along with reticulocytopenia. The majority of warm AIHA patients received first-line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants, and rituximab. The cumulative incidence of relapse was increased in more severe cases (hazard ratio 3.08; 95% confidence interval, 1.44-6.57 for Hb ≤6 g/dL; P < .001). Thrombotic events were associated with Hb levels ≤6 g/dL at onset, intravascular hemolysis, and previous splenectomy. Predictors of a fatal outcome were severe infections, particularly in splenectomized cases, acute renal failure, Evans syndrome, and multitreatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians., (© 2014 by The American Society of Hematology.)

In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is due mainly to deficiency of the complement regulator CD59 on the surface of red blood cells (RBCs). Eculizumab, an antibody that targets complement fraction 5 (C5), has proven highly effective in abolishing complement-mediated intravascular hemolysis in PNH; however, the hematologic benefit varies considerably among patients. In the aim to understand the basis for this variable response, we have investigated by flow cytometry the binding of complement fraction 3 (C3) on RBCs from PNH patients before and during eculizumab treatment. There was no evidence of C3 on RBCs of untreated PNH patients; by contrast, in all patients on eculizumab (n = 41) a substantial fraction of RBCs had C3 bound on their surface, and this was entirely restricted to RBCs with the PNH phenotype (CD59(-)). The proportion of C3(+) RBCs correlated significantly with the reticulocyte count and with the hematologic response to eculizumab. In 3 patients in whom (51)Cr labeling of RBCs was carried out while on eculizumab, we have demonstrated reduced RBC half-life in vivo, with excess (51)Cr uptake in spleen and in liver. Binding of C3 by PNH RBCs may constitute an additional disease mechanism in PNH, strongly enhanced by eculizumab treatment and producing a variable degree of extravascular hemolysis.

Bdelloid rotifers are suitable model systems for space experiments. Due to their developmental pattern they appear adequate to investigate the role of the cytoskeleton during oogenesis and during early developmental stages, and to reflect the effects of disturbances in the spatial arrangement of cytoskeletal components. The effect of weightlessness on the developmental pattern of a bdelloid rotifer will be studied in the International Space Station: in preparation for it we are performing ground-based experiments on the development of rotifer embryos under either increased or decreased gravity. The model studied is Macrotrachela quadricornifera, a species of rotifers belonging to the Bdelloidea class. Samples exposed to gravity disturbance were analyzed for morphology and fitness-related parameters. Rotifers were exposed over several days to altered gravity conditions and the morphology of eggs laid during this period were investigated using a confocal laser microscope. A subset of eggs was allowed to hatch to determine newborn developmental time and age at maturity. High (up to 20 g) gravity was obtained in a slow centrifuge suitable for animal cultivation over several days. To produce low (simulated 0.0001 g) gravity a Random Positioning Machine equipped with a 'rotifer bioreactor' was used. Under all conditions the rotifer retained normal life-history traits, and did not show permanent changes in embryo morphology, regardless to the stresses to which it was exposed. Only some modification of the shape of early embryos, experiencing 20 g, has been noted, but later developmental stages appeared unaffected, and normal juveniles hatched. Whether this result indicates any capacity to repair damage during embryogenesis of these Spiralia experiencing 20 g is an open question. The significance of the result as well as the use of instruments to simulate gravity perturbations are discussed.

In this paper are reported the basal results of a multidisciplinary, multicenter study designed to explore in a population with ischemic disease the relation between hemostatic variables, conventional risk factors and atherothrombotic sequelae. 953 patients less than or equal to 69 yrs with documented coronary, cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months. Examinations included hemostatic and lipid laboratory assays, arterial Doppler examination, cerebral computerized tomography and nuclear magnetic resonance, exercise electrocardiogram and coronary angiography. Fibrinogen (301.4 +/- 71.52 mg/dl) correlated positively with antithrombin III (r = 0.27) and leukocytes (r = 0.25), negatively with HDL-cholesterol (r = 0.18) and tended to increase with smoking. Heavy smokers had higher leukocyte counts than non-smokers (8.0 +/- 2.0 vs. 7.2 +/- 2.1 x 10(3)/microliters), higher triglycerides (1.87 +/- 1.12 vs. 1.53 +/- 1.35 mmol/l) and lower HDL-cholesterol (0.93 +/- 0.27 vs. 1.00 +/- 0.25 mmol/l). FVII correlated positively with triglycerides (r = 0.16) and protein C (r = 0.45). vWF:Ag (145.4 +/- 70.58%) ad FVII:C (139.7 +/- 59.10%) were positively correlated (r = 0.44). FVIII:C correlated positively with fibrinogen (r = 0.21). Myocardial infarction survivors with associated cerebral and peripheral vascular lesions had higher FVIII:C, FVII, fibronogen and vWF:Ag. These findings suggest that hemostatic factors may enhance and/or mediate the effects of conventional risk factors in atherothrombotic ischemic events.