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Pietra D.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo
Leukemia | Year: 2015

A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation of CALR, the calreticulin gene. A 52-bp deletion (type 1) and a 5-bp insertion (type 2 mutation) are the most frequent variants. These indels might differentially impair the calcium binding activity of mutant calreticulin. We studied the relationship between mutation subtype and biological/clinical features of the disease. Thirty-two different types of CALR variants were identified in 311 patients. Based on their predicted effect on calreticulin C-terminal, mutations were classified as: (i) type 1-like (65%); (ii) type 2-like (32%); and (iii) other types (3%). Corresponding CALR mutants had significantly different estimated isoelectric points. Patients with type 1 mutation, but not those with type 2, showed abnormal cytosolic calcium signals in cultured megakaryocytes. Type 1-like mutations were mainly associated with a myelofibrosis phenotype and a significantly higher risk of myelofibrotic transformation in essential thrombocythemia. Type 2-like CALR mutations were preferentially associated with an essential thrombocythemia phenotype, low risk of thrombosis despite very-high platelet counts and indolent clinical course. Thus, mutation subtype contributes to determining clinical phenotype and outcomes in CALR-mutant myeloproliferative neoplasms. CALR variants that markedly impair the calcium binding activity of mutant calreticulin are mainly associated with a myelofibrosis phenotype.Leukemia advance online publication, 17 November 2015; doi:10.1038/leu.2015.277. © 2015 Macmillan Publishers Limited

Revello M.G.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo | Lazzarotto T.,University of Bologna | Guerra B.,University of Bologna | Spinillo A.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo | And 13 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P = 0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. Copyright © 2014 Massachusetts Medical Society.

Cucchi A.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo | Quaglini S.,University of Pavia | Rovereto B.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo
Journal of Urology | Year: 2010

Purpose: We assessed bladder voiding function in patients with idiopathic detrusor underactivity with and without detrusor overactivity for a different evolution in time. Materials and Methods: We retrospectively analyzed clinical and urodynamic findings in 36 consecutive middle-aged men with idiopathic detrusor underactivity who were referred during 1989 to 2003 for voiding and storage lower urinary tract symptoms. After initial testing at time 1 urodynamics were repeated due to worse lower urinary tract symptoms severity at a median of 45 months (time 2). A total of 17 patients with voiding urgency showed urodynamic detrusor overactivity at times 1 and 2 (group 1) and 19 with no urgency (group 2) never had detrusor overactivity. As controls (group 3) we used 30 age matched, urodynamically normal men. Nonparametric statistics were used for data analysis. Results: Compared with controls at time 1 groups 1 and 2 had lower bladder emptying efficiency and bladder contractility (contraction strength, velocity and energy reserve) with relatively higher contraction velocity and energy reserve in group 1 than in group 2. Compared with time 1 at time 2 the 2 detrusor underactivity groups showed an increased International Prostate Symptom Score (more increased in group 1), and decreased bladder contractility and emptying efficiency (less decreased in group 1). Conclusions: A likely explanation for our findings is that by causing relatively more rapid (less slow) detrusor contractions detrusor overactivity partly decreased the time needed and, thus, the total energy expended by underactive bladders for mounting micturition contractions. This compensatory efficiency would account for the relatively better evolution of bladder voiding function with time. © 2010 American Urological Association.

Filocamo G.,Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini | Davi S.,Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini | Pistorio A.,Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini | Bertamino M.,Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini | And 10 more authors.
Journal of Rheumatology | Year: 2010

Objective. To evaluate the measurement properties of 21-numbered circle visual analog scales (VAS) and traditional 10-cm horizontal line VAS for physician and parent subjective ratings in children with juvenile idiopathic arthritis (JIA). Methods. We studied 2 patient samples in whom physician global rating of overall disease activity, parent global rating of the child's overall well-being, and parent rating of intensity of child's pain were performed using traditional 10-cm horizontal line VAS (n = 397) or 21-numbered circle VAS (n = 471). The measurement performances of the 2 VAS formats were examined by assessing construct validity, score distribution, responsiveness to change over time, and minimal clinically important difference (MCID). Results. Most Spearman correlations with other JIA outcome measures yielded by 21-numbered circle VAS were greater than those obtained with 10-cm horizontal line VAS, revealing that the circle VAS format has better construct validity. Ceiling effects (i.e., score = 0) for physician and parent global ratings were 43.7% and 32.9%, respectively, on 21-numbered circle VAS, and 31.6% and 35.3%, respectively, on 10-cm horizontal line VAS. Responsiveness of 21-numbered circle VAS was good (standardized response mean > 0.8) or moderate (standardized response mean > 0.6) among patients classified as improved or worsened, respectively, by the physician or the parent. Overall, MCID values for 21-numbered circle VAS tended to be greater for worsening than for improvement. Conclusion. The 21-numbered circle VAS are a suitable alternative to the 10-cm horizontal line VAS and may facilitate incorporation of physician and parent subjective ratings in standard clinical practice. The Journal of Rheumatology Copyright © 2010. All rights reserved.

Cattaneo C.,Spedali Civili | Antoniazzi F.,Spedali Civili | Caira M.,University Cattolica ore | Castagnola C.,Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo | And 4 more authors.
International Journal of Infectious Diseases | Year: 2013

Objectives: To describe the clinical characteristics and prognostic factors of hematological patients affected by Nocardia spp infections. Methods: We retrospectively evaluated all the cases diagnosed in four Italian institutions. Results: Between 2002 and 2012, 10 cases of nocardiosis were recorded. The median age of the patients was 66 years (range 24-85 years). The underlying hematological disease was a lymphoproliferative disorder in all but two patients. Eight patients (80%) showed active underlying hematological disease, relapsed or refractory in five (50%); one patient had a history of previous allogeneic bone marrow transplantation. Eight patients (80%) were on steroid therapy; lymphopenia was present in 8/10 (80%) patients. All patients showed lung involvement. Six patients were affected by disseminated nocardiosis. Three patients (30%) were nocardemic and three (30%) showed central nervous system involvement. Skin, lymph nodes, and bone were involved in one patient each. The median overall survival was 65 days. Older age, a longer period between hematological diagnosis and Nocardia spp infection, and relapsed/refractory hematological disease were associated with a worse prognosis. Conclusions: Although rare, nocardiosis should be considered in the differential diagnosis of pulmonary and central nervous system lesions among hematological patients. Lymphoproliferative disorders, prolonged steroid treatment, lymphopenia, and active hematological disease are the conditions that are worth considering as predisposing factors for the development of this disease. © 2013 International Society for Infectious Diseases.

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