Paola Anna Erba

2015 ESC Guidelines for the management of infective endocarditis

3D : three-dimensional AIDS : acquired immune deficiency syndrome b.i.d. : bis in die (twice daily) BCNIE : blood culture-negative infective endocarditis CDRIE : cardiac device-related infective endocarditis CHD : congenital heart disease CIED : cardiac implantable electronic device

Expression of the oncofetal ED-B containing fibronectin isoform in hematologic tumors enables ED-B targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients

Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with (131)I-labeled L19 small immunoprotein ((131)I-L19SIP). In 2 relapsed Hodgkin lymphoma patients(131)I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.

Added Value of 99mTc-HMPAO–Labeled Leukocyte SPECT/CT in the Characterization and Management of Patients with Infectious Endocarditis

The clinical performance of the Duke Endocarditis Service criteria to establish the diagnosis of infectious endocarditis (IE) can be improved through functional imaging procedures such as radiolabeled leukocytes (99mTc-hexamethylpropyleneamine oxime [HMPAO]–labeled white blood cells [WBC]). Methods: We assessed the value of 99mTc-HMPAO-WBC scintigraphy including SPECT/CT acquisitions in a series of 131 consecutive patients with suspected IE. Patients with permanent cardiac devices were excluded. 99mTc-HMPAO-WBC scintigraphy results were correlated with transthoracic or transesophageal echocardiography, blood cultures, and the Duke criteria. Results: Scintigraphy was true-positive in 46 of 51 and false-negative in 5 of 51 cases (90% sensitivity, 94% negative predictive value, and 100% specificity and positive predictive value). No false-positive results were found, even in patients with early IE evaluated within the first 2 mo from the surgical procedure. In 24 of 51 patients with IE, we also found extracardiac uptake, indicating septic embolism in 21 of 24. Despite the fact that septic embolism was found in 11 of 18 cases of Duke-definite IE, most of the added value from the 99mTc-HMPAO-WBC scan for decision making was seen in patients in whom the Duke criteria yielded possible IE. The scan was particularly valuable in patients with negative or difficult-to-interpret echocardiographic findings because it correctly classified 11 of 88 of these patients as having IE. Furthermore, 3 patients were falsely positive at echocardiography but correctly negative at 99mTc-HMPAO-WBC scintigraphy: these patients had marantic vegetations. Conclusion: Our results demonstrate the ability of 99mTc-HMPAO-WBC scintigraphy to reduce the rate of misdiagnosed cases of IE when combined with standard diagnostic tests in several situations: when clinical suspicion is high but echocardiographic findings are inconclusive; when there is a need for differential diagnosis between septic and sterile vegetations detected at echocardiography; when echocardiographic, laboratory, and clinical data are contradictory; and when valve involvement (especially of a prosthetic valve) needs to be excluded during febrile episodes, sepsis, or postsurgical infections.

Nuclear medicine imaging of bone infections.

The inflammation and infection of bone include a wide range of processes that can result in a reduction of function or in the complete inability of patients. Apart from the inflammation, infection is sustained by pyogenic microorganisms and results mostly in massive destruction of bones and joints. The treatment of osteomyelitis requires long and expensive medical therapies and, sometimes, surgical resection for debridement of necrotic bone or to consolidate or substitute the compromised bones and joints. Radiographs and bone cultures are the mainstays for the diagnosis but often are useless in the diagnosis of activity or relapse of infection in the lengthy management of these patients. Imaging with radiopharmaceuticals, computed tomography and magnetic resonance are also used to study secondary and chronic infections and their diffusion to soft or deep tissues. The diagnosis is quite easy in acute osteomyelitis of long bones when the structure of bone is still intact. But most cases of osteomyelitis are subacute or chronic at the onset or become chronic during their evolution because of the frequent resistance to antibiotics. In chronic osteomyelitis the structure of bones is altered by fractures, surgical interventions and as a result of bone reabsorption produced by the infection. Metallic implants and prostheses produce artefacts both in computed tomography and magnetic resonance images, and radionuclide studies should be essential in these cases. Vertebral osteomyelitis is a specific entity that can be correctly diagnosed by computed tomography or magnetic resonance imaging at the onset of symptoms but only with radionuclide imaging is it possible to assess the activity of the disease after surgical stabilization or medical therapy. The lack of comparative studies showing the accuracy of each radiopharmaceutical for the study of bone infection does not allow the best nuclear medicine techniques to be chosen in an evidence-based manner. To this end we performed a meta-analysis of peer reviewed articles published between 1984 and 2004 describing the use of nuclear medicine imaging for the study of the most frequent causes of bone infections, including prosthetic joint, peripheric post-traumatic bone infections, vertebral and sternal infections. Guidelines for the choice of the optimal radiopharmaceuticals to be used in each clinical condition and for different aims is provided.

Linee guida ESC 2015 per il trattamento dell'endocardite infettiva: Task Force per il Trattamento dell'Endocardite Infettiva della Società Europea di Cardiologia (ESC): Con il patrocinio dell'Associazione Europea di Chirurgia Cardiotoracica (EACTS) e dell'Associazione Europea di Medicina Nucleare (EANM)

Authors/Task Force Members: Gilbert Habib* (Chairperson) (France), Patrizio Lancellotti* (co-Chairperson) (Belgium), Manuel J. Antunes (Portugal), Maria Grazia Bongiorni (Italy), Jean-Paul Casalta (France), Francesco Del Zotti (Italy), Raluca Dulgheru (Belgium), Gebrine El Khoury (Belgium), Paola Anna Erba (Italy), Bernard Iung (France), Jose M. Miro (Spain), Barbara J. Mulder (The Netherlands), Edyta Plonska-Gosciniak (Poland), Susanna Price (UK), Jolien Roos-Hesselink (The Netherlands), Ulrika Snygg-Martin (Sweden), Franck Thuny (France), Pilar Tornos Mas (Spain), Isidre Vilacosta (Spain), and Jose Luis Zamorano (Spain)Autori/Membri della Task Force Gilbert Habib (Chairperson) (Francia), Patrizio Lancellotti (co-Chairperson) (Belgio), Manuel J. Antunes (Portogallo), Maria Grazia Bongiorni (Italia), Jean-Paul Casalta (Francia), Francesco Del Zotti (Italia), Raluca Dulgheru (Belgio), Gebrine El Khoury (Belgio), Paola Anna Erbaa (Italia), Bernard Iung (Francia), Jose M. Mirob (Spagna), Barbara J. Mulder (Olanda), Edyta Plonska-Gosciniak (Polonia), Susanna Price (UK), Jolien Roos-Hesselink (Olanda), Ulrika Snygg-Martin (Svezia), Franck Thuny (Francia), Pilar Tornos Mas (Spagna), Isidre Vilacosta (Spagna), Jose Luis Zamorano (Spagna)

Nanoparticles in Cancer

Nano-engineered particles have been developed to reach specific molecular targets on diseased cells and have been used in various experimental and clinical conditions. The medical application involves diagnostic and therapeutic applications and a large deal of this research concerns malignant disease. Various approaches have been tried to effectively reach the cancer cell and PEGylated liposomes have demonstrated targeting and controlled release of antineoplastic drugs. For cancer diagnostics nanoparticles have been engineered to optimize magnetic resonance imaging, ultrasound imaging and nuclear medicine imaging. Radiolabeled nanoparticles can also be used for therapeutic purposes when tagged with appropriate radionuclides. This article aims to provide an overview how nanomedicine is presently influencing drug design and, more specifically, the development of radiopharmaceuticals for cancer management.

FDG-PET in Cardiac Infections

Cardiac infections include a group of conditions involving the heart muscle, the pericardium, or the endocardial surface of the heart. Infections can extend to prosthetic material or the leads in case of the implantation of devices. Despite their relative low incidence, these conditions that are associated with high morbidity and mortality involve a relevant burden of diagnostic workup. Early diagnosis is crucial for adequate management of patient, as early treatment improves the prognosis; unfortunately, the clinical manifestations are often nonspecific. Accurate and timely diagnosis typically requires the correlation of imaging findings with laboratory data. (18)F-FDG-PET is a well-established imaging modality for the diagnosis and management of malignancies, and evidence is also increasing regarding its value for assessing infectious and inflammatory diseases. This article summarizes published evidence on the usefulness of (18)F-FDG-PET for the diagnosis of cardiac infections, mainly focused on endocarditis and cardiovascular device infections. Nevertheless, the diagnostic potential of (18)F-FDG-PET in patients with pericarditis and myocarditis is also briefly reviewed, considering the most likely future advances and new perspectives that the use of PET/magnetic resonance would open in the diagnosis of such conditions.

Radioimmunotherapy with Radretumab in Patients with Relapsed Hematologic Malignancies

We present here a systematic analysis of lymphoma and MM patients recruited into 2 clinical trials or treated with radretumab according to compassionate use, describing the biodistribution, dosimetry, safety, and clinical activity of radretumab. Methods: Uptake in lymphoma lesions, safety, and clinical activity of radretumab radioimmunotherapy (R-RIT) were evaluated in 18 relapsed lymphoma or multiple myeloma patients. Results: In 14 of 18 patients, selective tumor uptake was found; 11 of 15 lymphoma patients, including 9 of 11 with Hodgkin lymphoma (HL), were eligible for R-RIT (a priori criteria–based target-to-bone marrow ratio > 10:1 for EudraCT no. 2005-000545 or > 4:1 for EudraCT no. 2007-007241-12 at dosimetric imaging). Two HL and 1 diffuse large B cell lymphoma patient achieved complete response; 1 HL patient had partial response. Both multiple myeloma patients receiving R-RIT experienced stabilization of disease. Therefore, the overall objective response rate was 40%. Uncomplicated grade 3–4 thrombocytopenia or leukocytopenia was observed in 5 R-RIT patients, lasting 4–129 d. Conclusion: R-RIT showed a favorable benefit and risk profile in advanced relapsed lymphoma patients and induced complete response in 2 heavily pretreated, relapsed HL patients and in 1 diffuse large B cell lymphoma patient. These results warrant further exploration of R-RIT in larger phase II clinical trials.

Distribution of exogenous [125I]-3-iodothyronamine in mouse in vivo: relationship with trace amine-associated receptors

3-Iodothyronamine (T1AM) is a novel chemical messenger, structurally related to thyroid hormone, able to interact with G protein-coupled receptors known as trace amine-associated receptors (TAARs). Little is known about the physiological role of T1AM. In this prospective, we synthesized [125I]-T1AM and explored its distribution in mouse after injecting in the tail vein at a physiological concentration (0.3 nM). The expression of the nine TAAR subtypes was evaluated by quantitative real-time PCR. [125I]-T1AM was taken up by each organ. A significant increase in tissue vs blood concentration occurred in gallbladder, stomach, intestine, liver, and kidney. Tissue radioactivity decreased exponentially over time, consistent with biliary and urinary excretion, and after 24 h, 75% of the residual radioactivity was detected in liver, muscle, and adipose tissue. TAARs were expressed only at trace amounts in most of the tissues, the exceptions being TAAR1 in stomach and testis and TAAR8 in intestine, spleen, and testis. Thus, while T1AM has a systemic distribution, TAARs are only expressed in certain tissues suggesting that other high-affinity molecular targets besides TAARs exist.

Scintigraphic imaging of vertebral osteomyelitis with 111in-biotin.

Study Design. Early diagnosis of vertebral infection (hematogenous or postsurgical) is necessary to choose a correct therapy and to minimize dramatic complications. All patients suspected to have vertebral infection underwent radiologic imaging and 111In-Biotin scintigraphy. Objective. Biotin is a growth factor used by many bacteria. The aim of our study is to use 111In-Biotin to diagnose vertebral infections. Summary of Background Data. Magnetic resonance imaging, even if endowed with fairly good sensitivity and specificity, shows some limitations in the study of the onset of pathology and in postsurgical conditions. Conventional scintigraphic imaging, like bone scintigraphy with 99mTc-MDP, 67Ga-citrate scintigraphy, or Positron Emission Tomography with [18F]FDG, are limited by relatively low specificity; the use of Streptavidin/111In-Biotin scintigraphy, based on aspecific uptake of tracer in the site of infection, shows good results in term of sensibility and specificity but the use of heterologous protein might engender immunogenic reactions. Methods. All patients (pts) (n = 110) of the study underwent 111In-biotin scintigraphy 2 hours after intravenous injection of the tracer, 71 pts were suspected to have hematogenous vertebral infection (Group I) and 39 pts were suspected to have postsurgical infection (Group II). The reference for final diagnosis was either bacterial cultures, histopathologic analysis, and/or clinical/imaging follow-up for at least 1 year. Results. 111In-biotin scintigraphy showed a sensitivity of 84% and specificity of 98% in Group I and a sensitivity of 100% and specificity of 84% in Group II. Conclusion. Our results showed that 111In-Biotin scintigraphy possess high diagnostic accuracy. This technique is easy to perform and requires short imaging time-point after intravenous tracer injection. Moreover if 111In-Biotin uptake is due only to high proliferation rate of bacteria presents in site of infection, it will be further investigated to discriminate definitely bacterial from sterile inflammation.