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Viterbo, Italy

Agrati C.,National Institute for Infectious Diseases Lazzaro Spallanzani | Agrati C.,National Institute for Infectious Diseases | Gioia C.,National Institute for Infectious Diseases Lazzaro Spallanzani | Lalle E.,National Institute for Infectious Diseases Lazzaro Spallanzani | And 9 more authors.
Journal of Infectious Diseases

Background. Pandemic A/H1N1v influenza is characterized by a mild clinical course. However, a small subset of patients develops a rapidly progressive course caused by primary viral pneumonia or secondary bacterial infections that, in many cases, lead to death due to respiratory failure. The aim of the present study was to analyze the involvement of the immune response in the clinical presentation of H1N1v influenza. Methods. The differentiation and functional capability of T cells from H1N1v-infected patients presenting with either mild disease ( ) or severe or np22 fatal disease (np6) were compared. Moreover, plasma cytokines and chemokines were quantified Results. T cells from H1N1v-infected patients presenting with a severe clinical course resulted in impaired effector cell differentiation and failed to respond to mitogenic stimulation. T cell anergy was strictly associated with a severe acute phase of infection, but T cells could be restored in patients able to recover. Of interest, massive expression of CD95 marker was found on anergic T cells, suggesting an apoptosis-related mechanism. Finally, lower plasma levels of interferon-α and monocyte chemoattractant protein-1 were found in patients with a worse clinical course of influenza, suggesting impaired production of these cytokines. Conclusions. Our results show a strict association between host immune competence and the severity of the clinical course of H1N1v infection. By monitoring host functional response, patients with an enhanced risk of developing influenza-associated severe complications could be identified in a timely manner. © 2010 by the Infectious Diseases Society of America. Source

Feriozzi S.,Belcolle Hospital | Torras J.,University of Barcelona | Cybulla M.,University Hospital Freiburg | Nicholls K.,Royal Melbourne Hospital | And 2 more authors.
Clinical Journal of the American Society of Nephrology

Background and objectives Fabry disease is a rare X-linked disease with multisystemic manifestations. This study investigated the effectiveness of long-term enzyme replacement therapy with agalsidase alfa in Fabry nephropathy treatment. Design, setting, participants, & measurements In this observational study, data on patients receiving agalsidase alfa (0.2 mg/kg every other week) were extracted from the Fabry Outcome Survey, an international registry of patients with Fabry disease. Serum creatinine and estimated GFR (eGFR) at baseline and after ≥5 years of treatment were assessed; 24-hour urinary protein excretion and BP measurements were also reviewed. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. Patients with an eGFR<30 ml/min per 1.73 m 2 were excluded. Results Renal function was assessed in 208 patients (mean enzyme replacement therapy, 7.4 years; range, 5.0-11.2 years). Mean yearly change in eGFR was 22.2 ml/min per 1.73 m 2 in men and 20.7 ml/min per 1.73 m 2 in women (95% confidence limits, 22.8; 21.7 and 21.4; 0.0, respectively). Patients with 24-hour protein excretion.1 >/24h had poorer renal function at baseline and follow-up compared with patients with protein excretion of 500-1000 mg/24 h or with proteinuria<500 mg/24 h. Renal function was worse in patients with baseline arterial hypertension, and there was a more rapid yearly decline compared with normotensive patients. Conclusions This study suggests that long-term agalsidase alfa therapy is able to stabilize the rate of Fabry nephropathy progression in women and is associated with a mild to moderate decline of renal function in men. © 2012 by the American Society of Nephrology. Source

Mignani R.,Infermi Hospital | Feriozzi S.,Belcolle Hospital | Schaefer R.M.,University of Munster | Breunig F.,University of Wurzburg | And 3 more authors.
Clinical Journal of the American Society of Nephrology

ESRD is a major cause of morbidity and premature mortality in Fabry disease, particularly in classically affected males. The decline of renal function in Fabry nephropathy is adversely affected by male gender, advanced chronic kidney disease (CKD), and severe proteinuria. The diagnosis of Fabry nephropathy may be missed if not specifically addressed in progressive CKD and patients have been first identified in screening programs of dialysis patients. Fabry patients have worse 3-year survival rates on dialysis as compared with nondiabetic controls. The 5-year survival rate of transplanted Fabry patients is also lower than that of controls. However, because Fabry nephropathy does not recur in the allograft and transplanted Fabry patients appear to have better overall outcomes than those maintained on dialysis, kidney transplantation should be recommended as a first choice in renal replacement therapy (RRT) for Fabry disease. Appropriately designed and powered studies are not available to answer the question whether enzyme replacement therapy (ERT) influences outcomes, the course of cardiomyopathy, events, or survival in Fabry patients on RRT. The authors are not aware of compelling indications for ERT in RRT patients because progression of cardiomyopathy was documented during ERT. Whether the excess mortality risk of Fabry patients on RRT can be prevented by ERT is unknown. Despite observational reports of symptomatic improvement, the available evidence supporting ERT for such patients is not compelling enough. To clarify this issue, studies are needed to test the effectiveness of agalsidases in preventing cardiac and cerebrovascular complications in Fabry patients with ESRD. Copyright © 2010 by the American Society of Nephrology. Source

Kurschat C.,University of Cologne | West M.,Dalhousie University | Nicholls K.,Royal Melbourne Hospital | Torras J.,University of Barcelona | And 2 more authors.
Journal of Nephrology

During Fabry disease, progressive glycosphingolipid deposition in the kidney causes gradual deterioration of renal function with proteinuria, uremia and hypertension. This results in end-stage renal disease (ESRD) which is one of the leading causes of morbidity and premature mortality in affected patients. Given the excellent graft and patient survival generally nowadays, kidney transplantation is the first choice to correct renal dysfunction and improve the overall prognosis of patients with renal failure because of Fabry disease. The benefit of enzyme-replacement therapy (ERT) in kidney transplanted Fabry patients has been controversially discussed and long-term trials focusing on the effectiveness of agalsidase in this patient population are needed. © 2012 Società Italiana di Nefrologia. Source

Introduction: Anderson-Fabry disease (AFD) is a hereditary disorder caused by lysosomal enzyme α-galactosidase A deficiency, previously thought to affect adult males only. Recently, it has become clear that women and children are also affected. Clinical data for enzyme replacement therapy (ERT) show that the two available agents, agalsidase α and β, improve or stabilize AFD in men; however, data in women and children are limited. Areas covered: The authors review AFD clinical phenotype and ERT clinical data, and discuss the timing of ERT initiation in women and children. Clinical trials and registry data were found from PubMed literature searches using search terms 'Anderson-Fabry disease' AND 'enzyme replacement therapy' AND 'children/paediatric' OR 'women/female'. Papers were selected manually from the search results. Expert opinion: Doubts remain about the correct time to start treatment in women and children. Early treatment is supported by the observation that ERT effects are reduced in advanced AFD. However, pre-symptomatic ERT does not appear to be advocated, unless, in an individual patient, a marked improvement in QoL would be achieved. Tools to identify those who are likely to progress to overt disease are required. Currently, assessment of disease burden entails accurate and detailed evaluation by AFD-related specialists. © 2013 Informa UK, Ltd. Source

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