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Imazio M.,Maria Vittoria Hospital | Brucato A.,Ospedali Riuniti | Maestroni S.,Ospedali Riuniti | Cumetti D.,Ospedali Riuniti | And 3 more authors.
Circulation | Year: 2011

Background-: Constrictive pericarditis (CP) is considered a rare, dreaded possible complication of acute pericarditis. Nevertheless, there is a lack of prospective studies that have evaluated the specific risk according to different etiologies. The aim of this study is to evaluate the risk of CP after acute pericarditis in a prospective cohort study with long-term follow-up. Methods and Results-: From January 2000 to December 2008, 500 consecutive cases with a first episode of acute pericarditis (age, 51±16 years; 270 men) were prospectively studied to evaluate the evolution toward CP. Etiologies were viral/idiopathic in 416 cases (83.2%), connective tissue disease/pericardial injury syndromes in 36 cases (7.2%), neoplastic pericarditis in 25 cases (5.0%), tuberculosis in 20 cases (4.0%), and purulent in 3 cases (0.6%). During a median follow-up of 72 months (range, 24 to 120 months), CP developed in 9 of 500 patients (1.8%): 2 of 416 patients with idiopathic/viral pericarditis (0.48%) versus 7 of 84 patients with a nonviral/nonidiopathic etiology (8.3%). The incidence rate of CP was 0.76 cases per 1000 person-years for idiopathic/viral pericarditis, 4.40 cases per 1000 person-years for connective tissue disease/pericardial injury syndrome, 6.33 cases per 1000 person-years for neoplastic pericarditis, 31.65 cases for 1000 person-years for tuberculous pericarditis, and 52.74 cases per 1000 person-years for purulent pericarditis. Conclusions-: CP is a relatively rare complication of viral or idiopathic acute pericarditis (<0.5%) but, in contrast, is relatively frequent for specific etiologies, especially bacterial. © 2011 American Heart Association. All rights reserved.

Cerutti M.,French National Center for Scientific Research | Golay J.,Ospedali Riuniti
mAbs | Year: 2012

Monoclonal antibodies are used with great success in many different therapeutic domains. In order to satisfy the growing demand and to lower the production cost of these molecules, many alternative systems have been explored. Among them, the baculovirus/insect cells system is a good candidate. This system is very safe, given that the baculoviruses have a highly restricted host range and they are not pathogenic to vertebrates or plants. But the major asset is the speed with which it is possible to obtain very stable recombinant viruses capable of producing fully active proteins whose glycosylation pattern can be modulated to make it similar to the human one. These features could ultimately make the difference by enabling the production of antibodies with very low costs. However, efforts are still needed, in particular to increase production rates and thus make this system commercially viable for the production of these therapeutic agents. © 2012 Landes Bioscience.

Falanga A.,Ospedali Riuniti | Russo L.,Ospedali Riuniti
Hamostaseologie | Year: 2012

Cancer is associated with a fourfold increased risk of venous thromboembolism (VTE). The risk of VTE varies according to the type of malignancy (i. e. pancreatic cancer, brain cancer, lymphoma) and its disease stage and individual factors (i. e. sex, race, age, previous VTE history, immobilization, obesity). Preventing cancer-associated VTE is important because it represents a significant cause of morbidity and mortality. In order to identify cancer patient at particularly high risk, who need thromboprophylaxis, risk prediction models have become available and are under validation. These models include clinical risk factors, but also begin to incorporate biological markers. The major American and European scientific societies have issued their recommendations to guide the management of VTE in patients with cancer. In this review the principal aspects of epidemiology, risk factors and outcome of cancer-associated VTE are summarized. © Schattauer 2012.

Imazio M.,Maria Vittoria Hospital | Brucato A.,Ospedali Riuniti | Maestroni S.,Ospedali Riuniti | Cumetti D.,Ospedali Riuniti | And 3 more authors.
Circulation | Year: 2011

Background-The role of inflammatory markers is not well defined for either diagnosis or treatment of pericarditis. The aim of this study is to prospectively evaluate the frequency of high-sensitivity C-reactive protein (hs-CRP) elevation in patients with acute pericarditis, its time course of normalization, and the possible importance for diagnosis, therapy, and prognosis. Methods and Results-Two hundred consecutive patients with viral or idiopathic acute pericarditis (mean age, 53±15.5 years; 103 men) were studied from August 2005 to August 2007 in 2 Italian referral centers. Hs-CRP was determined at presentation and then every week until normalization. Hs-CRP elevation was recorded in 156 of 200 cases (78%) at presentation. Recognized causes of a negative hs-CRP at presentation were early assessment in 15 of 44 cases (34%) and previous anti-inflammatory therapies in 22 of 44 cases (50%). Hs-CRP normalization was achieved with the following time course: 120 of 200 (60%) at week 1, 170 of 200 (85%) at week 2, 190 of 200 (95%) at week 3, and all cases (100%) at week 4. In multivariable analysis, incomplete response to empirical anti-inflammatory therapy at week 1 (hazard ratio, 2.98; 95% confidence interval, 1.80 to 4.94; P<0.001), corticosteroid therapy (hazard ratio, 2.80; 95% confidence interval, 1.59 to 4.95; P<0.001), and the presence of elevated hs-CRP at week 1 (hazard ratio, 2.36; 95% confidence interval, 1.32 to 4.21; P=0.004) were independent risk factors for recurrence. Conclusions-Hs-CRP is elevated at the initial presentation in 3 of 4 cases of acute pericarditis, identifies patients at higher risk of recurrence, and could be used to monitor disease activity and select appropriate therapy length. © 2011 American Heart Association. All rights reserved.

Galli M.,Ospedali Riuniti
Hamostaseologie | Year: 2011

The antiphospholipid syndrome (APS) is defined by the association of arterial and/or venous thrombosis and/or pregnancy complications with the presence of at least one among the main antiphospholipid antibodies (aPL) (i. e., Lupus anticoagulants, LA, IgG and/or IgM anticardiolipin antibodies, aCL, IgG and/or IgM antiβ2-glycoprotein I antibodies, aβ2-GPI). Several clinical studies have consistently reported that LA is a stronger risk factor for both arterial and venous thrombosis compared to aCL and aβ2-GPI. In particular, LA activity dependent on the first domain of β2-GPI and triple aPL positivity are associated with the risk of thrombosis and obstetrical complications. Asymptomatic aPL-positive subjects do not require primary thromboprophylaxis. Venous thromboembolism is the most common initial clinical manifestation of APS. To prevent its recurrence indefinite anticoagulation is recommended. Long duration treatment with warfarin or aspirin is used after a first cerebral arterial thrombosis. Low molecular weight heparin (LMWH) with or without aspirin is recommended to reduce the rate of obstetrical complications of APS pregnant women. © Schattauer 2011.

Falanga A.,Ospedali Riuniti | Marchetti M.,Ospedali Riuniti | Vignoli A.,Ospedali Riuniti
Journal of Thrombosis and Haemostasis | Year: 2013

Malignancy affects the hemostatic system and the hemostatic system affects malignancy. In cancer patients there are a number of coagulation abnormalities which provide the background for an increased tendency of these patients to both thrombosis and hemorrhage. The causes of this coagulation impairment rely on general risk factors which are common to other categories of patients, and other factors which are specific to cancer, such as tumor type and disease stage. In addition, data from basic research indicate that the hemostatic components and the cancer biology are interconnected in multiple ways. Notably, while cancer cells are able to activate the coagulation system, the hemostatic factors play a role in tumor progression. This opens the way to the development of bifunctional therapeutic approaches that are both capable of attacking the malignant process and resolving the coagulation impairment. On the other hand, the management of thrombosis and hemorrhages in cancer patients can be different. To approach these problems, some guidelines have been released by prominent international scientific societies. Also actively investigated is the issue of identifying new biomarkers to classify the subjects at a higher risk, thus improving the prevention of thrombohemorrhagic events in these patients. Finally, novel prophylactic and therapeutic approaches are currently under development. This review provides an overview of the hemostatic complications in cancer, together with new insights into the interaction between hemostasis and cancer biology. We also review the assessment of the risk of thrombohemorrhagic events in cancer patients, and the prophylaxis and treatment of such manifestations. © 2012 International Society on Thrombosis and Haemostasis.

Galli M.,Ospedali Riuniti
Seminars in Thrombosis and Hemostasis | Year: 2012

The antiphospholipid syndrome (APS) is defined by the association of arterial and/or venous thrombosis and/or pregnancy complications with the presence of at least one of the main laboratory-detected antiphospholipid antibodies (aPL) (i.e., lupus anticoagulants [LA], IgG and/or IgM anticardiolipin antibodies [aCL], and IgG and/or IgM anti-glycoprotein I antibodies [aPI]). During the last decade efforts have been made to improve the harmonization and reproducibility of laboratory detection of aPL and guidelines have been published. The prognostic significance of aPL is being clarified through the fine elucidation of their antigenic targets and pathogenic mechanisms. Several clinical studies have consistently reported that LA is a stronger risk factor for both arterial and venous thrombosis compared with aCL and aPI. In particular, LA activity dependent on the first domain of glycoprotein I and triple aPL positivity are prognosticators of the thrombotic and obstetric risks. Hopefully, this increasing knowledge will help improve diagnostic and treatment strategies for APS. Copyright © 2012 by Thieme Medical Publishers, Inc.

Rambaldi A.,Ospedali Riuniti
International Journal of Hematology | Year: 2010

Myelofibrosis shows a progressive clinical course and usually a poor, lethal prognosis. Allogeneic transplantation is an effective, potentially curable treatment approach although only a minority of patients may currently benefit from it. New effective treatment strategies are becoming available for this disease, including not only JAK2 inhibitors, but also other innovative drugs, targeting more general oncogenic mechanisms and the epigenetic control of cell proliferation and differentiation. © 2010 The Japanese Society of Hematology.

Finazzi G.,Ospedali Riuniti
Current Hematologic Malignancy Reports | Year: 2011

Special issues in myeloproliferative neoplasms (MPN) comprise clinical conditions with high relevance for the duration and quality of the patient's life, but with limited evidence to support sound diagnostic and therapeutic recommendations and a low probability of being solved by the current standard of clinical research. These issues include MPN in pregnancy and in children, abdominal vein thrombosis, bleeding complications, surgery, pruritus, and leukemic transformation. Practical suggestions to guide clinical decisions in these settings remain largely empirical, but recently developed guidelines based on experts' consensus may help to tackle these problems. This article reviews the state of the art regarding these issues, with special emphasis on experts' consensus recommendations. © 2010 Springer Science+Business Media, LLC.

Brunelli A.,Ospedali Riuniti
Seminars in Thoracic and Cardiovascular Surgery | Year: 2010

Risk assessment for pulmonary resection must include a preliminary cardiac evaluation. Patients deemed at prohibitive cardiac risk should be evaluated and treated as per American Heart Association/American Society of Cardiology guidelines. Those with low cardiac risk or with optimized treatment can proceed with pulmonary assessment. A systematic measurement of lung carbon monoxide diffusing capacity is recommended. In addition, predicted postoperative forced expiratory volume in 1 second should not be used alone for patient selection because it is not an accurate predictor of complications, particularly in patients with chronic obstructive pulmonary disease. The use of exercise testing should be emphasized. Low-technology tests, such as stair climbing, can be used whenever a formal cardiopulmonary exercise test is not readily available. However, in case of suboptimal performance (ie, <22 m in the stair-climbing test) patients should be referred to cardiopulmonary exercise testing with measurement of Vo2max for a better definition of their aerobic reserve. A Vo2max less than 10 mL/kg/min (or <35% of predicted) indicates a high risk for major lung resection. © 2010 Elsevier Inc.

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