Clinical epidemiology in Italian Registry of Infective Endocarditis (RIEI): Focus on age, intravascular devices and enterococci.

INTRODUCTION: The epidemiology of infective endocarditis (IE) is changing due to a number of factors, including aging and health related comorbidities and medical procedures. The aim of this study is to describe the main clinical, epidemiologic and etiologic changes of IE from a large database in Italy. METHODS: We prospectively collected episodes of IE in 17 Italian centers from July 2007 to December 2010. RESULTS: We enrolled 677 patients with definite IE, of which 24% health-care associated. Patients were male (73%) with a median age of 62 years (IQR: 49-74) and 61% had several comorbidities. One hundred and twenty-eight (19%) patients had prosthetic left side IE, 391 (58%) native left side IE, 94 (14%) device-related IE and 54 (8%) right side IE. A predisposing cardiopathy was present in 50%, while odontoiatric and non odontoiatric procedures were reported in 5% and 21% of patients respectively. Symptoms were usually atypical and precocious. The prevalent etiology was represented by Staphylococcus aureus (27%) followed by coagulase-negative staphylococci (CNS, 21%), Streptococcus viridans (15%) and enterococci (14%). CNS and enterococci were relatively more frequent in patients with intravascular devices and prosthesis and S. viridans in left native valve. Diagnosis was made by transthoracic and transesophageal echocardiography in 62% and 94% of cases, respectively. The in-hospital mortality was 14% and 1-year mortality was 21%. CONCLUSION: The epidemiology is changing in Italy, where IE more often affects older patients with comorbidities and intravascular devices, with an acute onset and including a high frequency of enterococci. There were few preceding odontoiatric procedures.

The diagnostic utility of transthoracic echocardiography for the diagnosis of infective endocarditis in the real world of the Italian Registry on Infective Endocarditis.

BACKGROUND: The choice of the imaging modality (transthoracic [TTE] vs. transesophageal echocardiography [TEE]) for the diagnosis of infective endocarditis (IE) depends on different variables. Aim of the present study is to provide updated data on the diagnostic sensitivity and the clinical usefulness of TTE vs. TEE from the Italian Registry on IE (RIEI). METHODS: The RIEI has enrolled consecutive cases of IE in every participating centre, evaluating diagnostic and therapeutic data from a real world practice perspective. RESULTS: From July 2007 to October 2010, 658 consecutive cases with definite IE according to Duke criteria have been enrolled in the RIEI (483 males). The following diagnostic echocardiographic exams were performed: 616 TTE (94%) and 476 TEE (72%). A positive TTE was recorded in 399 cases (65%), an uncertain TTE in 108 cases (17%), and a negative TTE in 109 cases (18%). For TEE, a positive study was reported in 451 cases (95%), uncertain in 13 cases (2.7%), and negative in 12 cases (2.5%) (P < 0.001). This difference is not evident in patients with tricuspid valve IE or i.v. drug addiction, and in Streptococcus bovis or Streptococcus viridans IE. TTE was significantly more performed before the admission and earlier than TEE during admission (P = 0.000). TTE was mainly responsible for the initial diagnosis in 59%. TEE contributed to changing the therapeutic approach in 42%. CONCLUSIONS: In the real world, TTE is performed earlier and more commonly, and it is the major echocardiographic tool for the initial diagnosis. TEE confirms its superior diagnostic sensitivity in most cases, although it is relatively underused.

Structural and functional properties of proteasomes purified from the human kidney.

BACKGROUND: Proteasomes are 'proteolytic machineries' implicated in many cellular functions, including protein turnover, inflammatory response and immunosurveillance. They exist in various forms sharing the same catalytic core - the 20S proteasome. This core consists of 28 subunits codified by 14 different genes, 3 of which - beta 1, beta 2 and beta 5 - are catalytically active and show peptidyl-glutamyl peptide hydrolyzing (PGPH), trypsin-like and chymo-trypsin-like activities, respectively. Under IFN- delta and TNF- alfa stimuli, the 3 active constitutive subunits are replaced by the corresponding ones - i.e., LMP2, MECL-1, LMP7 - known as inducible subunits, thus resulting in the constitution of the 'immunoproteasome' that is specifically implicated in MHC class I-presented peptide generation. This process is enhanced when the proteasome is associated with the polymeric protein 11S regulator/PA28 made up of 4 alfa and 3 beta subunits. METHODS: The 20S proteasome was purified from post mortem specimens of human kidney cortex by chromatographic and ultracentrifugation techniques. It was then characterized on the basis of (i) multicatalytic activity evaluated using specific fluorogenic peptides, (ii) electrophoretic mobility on non-denaturating polyacrylamide gels followed by in-gel visualization by fluorogenic peptide overlaying and Coomassie blue staining and (iii) subunit composition as ascertained by SDS-PAGE and 2-dimensional electrophoresis followed by silver staining or Western immunoblotting using specific antibodies against the proteasome subunits. The 20S proteasome was also studied for its association with the 11S regulator by Western immunoblotting using an antibody to the regulator alfa subuniT. RESULTS: T he purified proteasome was shown to have PGPH, trypsin-like and chymotrypsin-like activities. Furthermore, it incorporated the inducible subunits and was associated with the 11S regulator. CONCLUSIONS: The features we observed make renal cells susceptible to an over-expression of inflammatory response to immunological challenges.

Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis.

BACKGROUND: Type II mixed cryoglobulinaemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, and sustained by proliferation of oligoclonal cells. Systemic B-cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (Rituximab). Similar effects could be expected in type II MC. METHODS: Six patients, mean age 64.2 years (range: 37-76 years), with HCV infection genotype 2a2c (three cases) or 1b (three cases) and symptomatic type-II MC with systemic manifestations, including renal involvement (five cases) and bone marrow clonal restriction (three cases), were considered eligible for Rituximab therapy. Rituximab was administered intravenously at a dose of 375 mg/m(2) on days 1, 8, 15 and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms and laboratory parameters for < or = 18 months. RESULTS: Levels of proteinuria, erythrocyte sedimentation rate and cryocrit significantly decreased at 2, 6 and 12 months. Rheumatoid factor and IgM significantly decreased at 6 months whereas C4 values significantly increased at 2 and 6 months. HCV viral load and immunoglobulin G remained stable. Bone marrow abnormalities were found to reverse to normal in all three positive cases. Constitutional symptoms (skin ulcers, purpura, arthralgia, weakness, paraesthesia and fever) disappeared or improved. No acute or delayed side effects were observed. CONCLUSIONS: Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC glomerulonephritis and signs of systemic vasculitis.

Exhaled nitric oxide during exercise and dobutamine stress echocardiography in patients with mitral stenosis.

BACKGROUND: Pulmonary hypertension (PH) is an important limiting factor of exercise tolerance in patients with mitral stenosis (MS). We wished to investigate the relationship between respiratory nitric oxide (NO), a potent vasodilator, and exercise tolerance in patients with moderate MS. In the same patients, we wondered whether acute change in pulmonary hemodynamics could affect respiratory NO. METHODS: Ten patients with moderate MS (valve area 1.4+/-0.2 cm(2)) were studied at rest, during incremental cycle ergometry exercise, and during dobutamine stress echocardiography (DSE). The concentration of NO in exhaled air (FE(NO)) and NO output (V'(NO)) were measured at baseline, at the end of exercise, and at the end of DSE. Eight healthy subjects served as normal controls for NO output during exercise. RESULTS: During exercise, FE(NO) decreased both in patients and in controls, while V'(NO) increased in both. At the end of exercise, both VO(2) max and V'(NO) were significantly higher in controls than in patients. The increase in V'(NO) during exercise was significantly correlated with VO(2) max, both in patients and in controls. During DSE, cardiac output (CO), pulmonary artery pressure (PAP), and mitral valve gradient increased. No changes in mean FE(NO), V'(NO), or ventilation were observed during DSE. There was a significant inverse correlation between FE(NO) and mitral valve gradient at the end of DSE. CONCLUSIONS: In patients with moderate MS, exercise performance is correlated with respiratory NO output. In the same patients, during DSE, the increase in CO, which is not accompanied by an increase in ventilation, is not associated with an increase in respiratory V'(NO).