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1. Clinical presentation and prognosis of COVID-19 in older adults with hypothyroidism: data from the GeroCovid observational study

Author

Bagala, V, Sala, A, Trevisan, C, Okoye, C, Incalzi, R, Monzani, F, Volpato, S, Antognoli, R, Antonietti, M, Bandini, G, Bellelli, G, Benvenuti, E, Bergamin, M, Bertolotti, M, Biagini, C, Bianchetti, A, Bianchi, A, Bianchi, M, Bignamini, S, Blandini, D, Boffelli, S, Bugada, M, Calsolaro, V, Calvani, D, Carpagnano, E, Carrieri, B, Castaldo, V, Cavarape, A, Cazzulani, I, Celesti, C, Ceolin, C, Ceresini, M, Cherubini, A, Chizzoli, A, Ciarrocchi, E, Cicciomessere, P, Coin, A, Corsi, A, Custodero, C, D'Agostino, F, D'Errico, M, De Iorio, A, De Marchi, A, Desideri, G, Di Matteo, E, Espinosa, E, Esposito, L, Fazio, C, Filippini, C, Fiore, L, Fontana, C, Forte, L, Montorzi, R, Fumagalli, C, Fumagalli, S, Gareri, P, Giordano, A, Giuliani, E, Greco, A, Herbst, A, Ielo, G, La Marca, A, Porta, U, Lazzari, I, Lelli, D, Longobucco, Y, Lucchini, F, Lucente, D, Maestri, L, Maggio, M, Mainqua, P, Marengoni, A, Martin, B, Massa, V, Mazza, L, Mazzoccoli, C, Mossello, E, Morellini, F, Mussi, C, Orio, G, Paglia, A, Pelagalli, G, Pelizzoni, L, Picci, A, Ranhoff, A, Remelli, F, Resta, O, Riccardi, A, Rinaldi, D, Rozzini, R, Sabba, C, Sacco, L, Santoliquido, M, Savino, M, Scarso, F, Sergi, G, Serviddio, G, Sidoli, C, Solfrizzi, V, Soli, B, Tafaro, L, Tedde, A, Testa, G, Tinti, M, Tonarelli, F, Tonon, E, Vitali, A, Zoccarato, F, Zotti, S, Bagala V., Sala A., Trevisan C., Okoye C., Incalzi R. A., Monzani F., Volpato S., Antognoli R., Antonietti M. P., Bandini G., Bellelli G., Benvenuti E., Bergamin M., Bertolotti M., Biagini C. A., Bianchetti A., Bianchi A., Bianchi M., Bignamini S., Blandini D., Boffelli S., Bugada M., Calsolaro V., Calvani D., Carpagnano E., Carrieri B., Castaldo V., Cavarape A., Cazzulani I., Celesti C., Ceolin C., Ceresini M. G., Cherubini A., Chizzoli A., Ciarrocchi E., Cicciomessere P., Coin A., Corsi A., Custodero C., D'Agostino F., D'Errico M. M., De Iorio A., De Marchi A., Desideri G., Di Matteo E., Espinosa E., Esposito L., Fazio C., Filippini C., Fiore L., Fontana C., Forte L., Montorzi R. F., Fumagalli C., Fumagalli S., Gareri P., Giordano A., Giuliani E., Greco A., Herbst A., Ielo G., La Marca A., Porta U., Lazzari I., Lelli D., Longobucco Y., Lucchini F., Lucente D., Maestri L., Maggio M., Mainqua P., Marengoni A., Martin B., Massa V., Mazza L., Mazzoccoli C., Mossello E., Morellini F., Mussi C., Orio G., Paglia A., Pelagalli G., Pelizzoni L., Picci A., Ranhoff A. H., Remelli F., Resta O., Riccardi A., Rinaldi D., Rozzini R., Sabba C., Sacco L., Santoliquido M., Savino M., Scarso F., Sergi G., Serviddio G., Sidoli C., Solfrizzi V., Soli B., Tafaro L., Tedde A., Testa G. D., Tinti M. G., Tonarelli F., Tonon E., Vitali A., Zoccarato F., Zotti S., Bagala, V, Sala, A, Trevisan, C, Okoye, C, Incalzi, R, Monzani, F, Volpato, S, Antognoli, R, Antonietti, M, Bandini, G, Bellelli, G, Benvenuti, E, Bergamin, M, Bertolotti, M, Biagini, C, Bianchetti, A, Bianchi, A, Bianchi, M, Bignamini, S, Blandini, D, Boffelli, S, Bugada, M, Calsolaro, V, Calvani, D, Carpagnano, E, Carrieri, B, Castaldo, V, Cavarape, A, Cazzulani, I, Celesti, C, Ceolin, C, Ceresini, M, Cherubini, A, Chizzoli, A, Ciarrocchi, E, Cicciomessere, P, Coin, A, Corsi, A, Custodero, C, D'Agostino, F, D'Errico, M, De Iorio, A, De Marchi, A, Desideri, G, Di Matteo, E, Espinosa, E, Esposito, L, Fazio, C, Filippini, C, Fiore, L, Fontana, C, Forte, L, Montorzi, R, Fumagalli, C, Fumagalli, S, Gareri, P, Giordano, A, Giuliani, E, Greco, A, Herbst, A, Ielo, G, La Marca, A, Porta, U, Lazzari, I, Lelli, D, Longobucco, Y, Lucchini, F, Lucente, D, Maestri, L, Maggio, M, Mainqua, P, Marengoni, A, Martin, B, Massa, V, Mazza, L, Mazzoccoli, C, Mossello, E, Morellini, F, Mussi, C, Orio, G, Paglia, A, Pelagalli, G, Pelizzoni, L, Picci, A, Ranhoff, A, Remelli, F, Resta, O, Riccardi, A, Rinaldi, D, Rozzini, R, Sabba, C, Sacco, L, Santoliquido, M, Savino, M, Scarso, F, Sergi, G, Serviddio, G, Sidoli, C, Solfrizzi, V, Soli, B, Tafaro, L, Tedde, A, Testa, G, Tinti, M, Tonarelli, F, Tonon, E, Vitali, A, Zoccarato, F, Zotti, S, Bagala V., Sala A., Trevisan C., Okoye C., Incalzi R. A., Monzani F., Volpato S., Antognoli R., Antonietti M. P., Bandini G., Bellelli G., Benvenuti E., Bergamin M., Bertolotti M., Biagini C. A., Bianchetti A., Bianchi A., Bianchi M., Bignamini S., Blandini D., Boffelli S., Bugada M., Calsolaro V., Calvani D., Carpagnano E., Carrieri B., Castaldo V., Cavarape A., Cazzulani I., Celesti C., Ceolin C., Ceresini M. G., Cherubini A., Chizzoli A., Ciarrocchi E., Cicciomessere P., Coin A., Corsi A., Custodero C., D'Agostino F., D'Errico M. M., De Iorio A., De Marchi A., Desideri G., Di Matteo E., Espinosa E., Esposito L., Fazio C., Filippini C., Fiore L., Fontana C., Forte L., Montorzi R. F., Fumagalli C., Fumagalli S., Gareri P., Giordano A., Giuliani E., Greco A., Herbst A., Ielo G., La Marca A., Porta U., Lazzari I., Lelli D., Longobucco Y., Lucchini F., Lucente D., Maestri L., Maggio M., Mainqua P., Marengoni A., Martin B., Massa V., Mazza L., Mazzoccoli C., Mossello E., Morellini F., Mussi C., Orio G., Paglia A., Pelagalli G., Pelizzoni L., Picci A., Ranhoff A. H., Remelli F., Resta O., Riccardi A., Rinaldi D., Rozzini R., Sabba C., Sacco L., Santoliquido M., Savino M., Scarso F., Sergi G., Serviddio G., Sidoli C., Solfrizzi V., Soli B., Tafaro L., Tedde A., Testa G. D., Tinti M. G., Tonarelli F., Tonon E., Vitali A., Zoccarato F., and Zotti S.

Abstract

Background: The prevalence of hypothyroidism among older patients hospitalized for COVID-19 and its association with mortality is unclear. This study aims to investigate the prevalence of hypothyroidism in older COVID-19 inpatients and verify if this comorbidity is associated with a specific pattern of onset symptoms and a worse prognosis. Methods: COVID-19 inpatients aged ≥ 60 years, participating in the GeroCovid acute wards cohort, were included. The history of hypothyroidism was derived from medical records and the use of thyroid hormones. Sociodemographic data, comorbidities, symptoms/signs at the disease onset and inflammatory markers at ward admission were compared between people with vs without history of hypothyroidism. The association between hypothyroidism and in-hospital mortality was tested through Cox regression. Results: Of the 1245 patients included, 8.5% had a history of hypothyroidism. These patients were more likely to present arterial hypertension and obesity compared with those without an history of hypothyroidism. Concerning COVID-19 clinical presentation, patients with hypothyroidism had less frequently low oxygen saturation and anorexia but reported muscle pain and loss of smell more commonly than those without hypothyroidism. Among the inflammatory markers, patients with hypothyroidism had higher lymphocytes values. At Cox regression, hypothyroidism was associated with reduced in-hospital mortality only in the univariable model (HR = 0.66, 95% CI 0.45–0.96, p = 0.03); conversely, no significant result were observed after adjusting for potential confounders (HR = 0.69, 95% CI 0.47–1.03, p = 0.07). Conclusions: Hypothyroidism does not seem to substantially influence the prognosis of COVID-19 in older people, although it may be associated with peculiar clinical and biochemical features at the disease onset.

Published
2023

2. Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study

Author

Coin, A, Noale, M, Gareri, P, Trevisan, C, Bellio, A, Fini, F, Abbatecola, A, Del Signore, S, Malara, A, Mossello, E, Fumagalli, S, Volpato, S, Monzani, F, Bellelli, G, Zia, G, Incalzi, R, Andrieri, D, Antognoli, R, Antonietti, M, Bagalà, V, Bandini, G, Bazzano, S, Bellotti, F, Benvenuti, E, Bergamin, M, Bertolotti, M, Biagini, C, Bianchetti, A, Bianchi, A, Bianchi, M, Bianchi, P, Biasin, F, Bignamini, S, Blandini, D, Boffelli, S, Bontempi, C, Bordignon, A, Bracchitta, L, Bugada, M, Cafariello, C, Caleri, V, Calsolaro, V, Calvani, D, Campagna, F, Capasso, A, Capurso, S, Carino, S, Carpagnano, E, Carrieri, B, Castaldo, V, Castelli, M, Castellino, M, Cavarape, A, Cazzulani, I, Celesti, C, Ceolin, C, Ceresini, M, Ceretti, A, Cherubini, A, Chizzoli, A, Ciarrocchi, E, Cicciomessere, P, Colombo, M, Corsi, A, Crispino, A, Cucunato, R, Custodero, C, D’Agostino, F, D’Errico, M, D’Amico, F, De Iorio, A, De Marchi, A, Dell’Armi, A, Delmonte, M, Desideri, G, Devita, M, Di Matteo, E, Espinosa, E, Esposito, L, Fazio, C, Ferro, C, Filippini, C, Fiore, L, Fiorillo, S, Fontana, C, Forte, L, Montorzi, R, Fumagalli, C, Gasbarri, P, Giordano, A, Giuliani, E, Granata, R, Coin A., Noale M., Gareri P., Trevisan C., Bellio A., Fini F., Abbatecola A. M., Del Signore S., Malara A., Mossello E., Fumagalli S., Volpato S., Monzani F., Bellelli G., Zia G., Incalzi R. A., Andrieri D., Antognoli R., Antonietti M. P., Bagalà V., Bandini G., Bazzano S., Bellotti F., Benvenuti E., Bergamin M., Bertolotti M., Biagini C. A., Bianchetti A., Bianchi A., Bianchi M., Bianchi P., Biasin F., Bignamini S., Blandini D., Boffelli S., Bontempi C., Bordignon A., Bracchitta L. M., Bugada M., Cafariello C., Caleri V., Calsolaro V., Calvani D., Campagna F. A., Capasso A., Capurso S., Carino S., Carpagnano E., Carrieri B., Castaldo V., Castelli M., Castellino M., Cavarape A., Cazzulani I., Celesti C., Ceolin C., Ceresini M. G., Ceretti A., Cherubini A., Chizzoli A., Ciarrocchi E., Cicciomessere P., Colombo M., Corsi A., Crispino A., Cucunato R., Custodero C., D’Agostino F., D’Errico M. M., D’Amico F., De Iorio A., De Marchi A., Dell’Armi A., Delmonte M., Desideri G., Devita M., Di Matteo E., Espinosa E., Esposito L., Fazio C., Ferro C., Filippini C., Fiore L., Fiorillo S., Fontana C., Forte L., Montorzi R. F., Fumagalli C., Gasbarri P. P., Giordano A., Giuliani E., Granata R., Coin, A, Noale, M, Gareri, P, Trevisan, C, Bellio, A, Fini, F, Abbatecola, A, Del Signore, S, Malara, A, Mossello, E, Fumagalli, S, Volpato, S, Monzani, F, Bellelli, G, Zia, G, Incalzi, R, Andrieri, D, Antognoli, R, Antonietti, M, Bagalà, V, Bandini, G, Bazzano, S, Bellotti, F, Benvenuti, E, Bergamin, M, Bertolotti, M, Biagini, C, Bianchetti, A, Bianchi, A, Bianchi, M, Bianchi, P, Biasin, F, Bignamini, S, Blandini, D, Boffelli, S, Bontempi, C, Bordignon, A, Bracchitta, L, Bugada, M, Cafariello, C, Caleri, V, Calsolaro, V, Calvani, D, Campagna, F, Capasso, A, Capurso, S, Carino, S, Carpagnano, E, Carrieri, B, Castaldo, V, Castelli, M, Castellino, M, Cavarape, A, Cazzulani, I, Celesti, C, Ceolin, C, Ceresini, M, Ceretti, A, Cherubini, A, Chizzoli, A, Ciarrocchi, E, Cicciomessere, P, Colombo, M, Corsi, A, Crispino, A, Cucunato, R, Custodero, C, D’Agostino, F, D’Errico, M, D’Amico, F, De Iorio, A, De Marchi, A, Dell’Armi, A, Delmonte, M, Desideri, G, Devita, M, Di Matteo, E, Espinosa, E, Esposito, L, Fazio, C, Ferro, C, Filippini, C, Fiore, L, Fiorillo, S, Fontana, C, Forte, L, Montorzi, R, Fumagalli, C, Gasbarri, P, Giordano, A, Giuliani, E, Granata, R, Coin A., Noale M., Gareri P., Trevisan C., Bellio A., Fini F., Abbatecola A. M., Del Signore S., Malara A., Mossello E., Fumagalli S., Volpato S., Monzani F., Bellelli G., Zia G., Incalzi R. A., Andrieri D., Antognoli R., Antonietti M. P., Bagalà V., Bandini G., Bazzano S., Bellotti F., Benvenuti E., Bergamin M., Bertolotti M., Biagini C. A., Bianchetti A., Bianchi A., Bianchi M., Bianchi P., Biasin F., Bignamini S., Blandini D., Boffelli S., Bontempi C., Bordignon A., Bracchitta L. M., Bugada M., Cafariello C., Caleri V., Calsolaro V., Calvani D., Campagna F. A., Capasso A., Capurso S., Carino S., Carpagnano E., Carrieri B., Castaldo V., Castelli M., Castellino M., Cavarape A., Cazzulani I., Celesti C., Ceolin C., Ceresini M. G., Ceretti A., Cherubini A., Chizzoli A., Ciarrocchi E., Cicciomessere P., Colombo M., Corsi A., Crispino A., Cucunato R., Custodero C., D’Agostino F., D’Errico M. M., D’Amico F., De Iorio A., De Marchi A., Dell’Armi A., Delmonte M., Desideri G., Devita M., Di Matteo E., Espinosa E., Esposito L., Fazio C., Ferro C., Filippini C., Fiore L., Fiorillo S., Fontana C., Forte L., Montorzi R. F., Fumagalli C., Gasbarri P. P., Giordano A., Giuliani E., and Granata R.

Abstract

Background and objectives: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. Methods: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. Results: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. Discussion: The use of trazodo

Published
2023

3. Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study

Author

Coin A., Noale M., Gareri P., Trevisan C., Bellio A., Fini F., Abbatecola A. M., Del Signore S., Malara A., Mossello E., Fumagalli S., Volpato S., Monzani F., Bellelli G., Zia G., Incalzi R. A., Andrieri D., Antognoli R., Antonietti M. P., Bagalà V., Bandini G., Bazzano S., Bellotti F., Benvenuti E., Bergamin M., Bertolotti M., Biagini C. A., Bianchetti A., Bianchi A., Bianchi M., Bianchi P., Biasin F., Bignamini S., Blandini D., Boffelli S., Bontempi C., Bordignon A., Bracchitta L. M., Bugada M., Cafariello C., Caleri V., Calsolaro V., Calvani D., Campagna F. A., Capasso A., Capurso S., Carino S., Carpagnano E., Carrieri B., Castaldo V., Castelli M., Castellino M., Cavarape A., Cazzulani I., Celesti C., Ceolin C., Ceresini M. G., Ceretti A., Cherubini A., Chizzoli A., Ciarrocchi E., Cicciomessere P., Colombo M., Corsi A., Crispino A., Cucunato R., Custodero C., D’Agostino F., D’Errico M. M., D’Amico F., De Iorio A., De Marchi A., Dell’Armi A., Delmonte M., Desideri G., Devita M., Di Matteo E., Espinosa E., Esposito L., Fazio C., Ferro C., Filippini C., Fiore L., Fiorillo S., Fontana C., Forte L., Montorzi R. F., Fumagalli C., Gasbarri P. P., Giordano A., Giuliani E., Granata R., Coin, A, Noale, M, Gareri, P, Trevisan, C, Bellio, A, Fini, F, Abbatecola, A, Del Signore, S, Malara, A, Mossello, E, Fumagalli, S, Volpato, S, Monzani, F, Bellelli, G, Zia, G, Incalzi, R, Andrieri, D, Antognoli, R, Antonietti, M, Bagalà, V, Bandini, G, Bazzano, S, Bellotti, F, Benvenuti, E, Bergamin, M, Bertolotti, M, Biagini, C, Bianchetti, A, Bianchi, A, Bianchi, M, Bianchi, P, Biasin, F, Bignamini, S, Blandini, D, Boffelli, S, Bontempi, C, Bordignon, A, Bracchitta, L, Bugada, M, Cafariello, C, Caleri, V, Calsolaro, V, Calvani, D, Campagna, F, Capasso, A, Capurso, S, Carino, S, Carpagnano, E, Carrieri, B, Castaldo, V, Castelli, M, Castellino, M, Cavarape, A, Cazzulani, I, Celesti, C, Ceolin, C, Ceresini, M, Ceretti, A, Cherubini, A, Chizzoli, A, Ciarrocchi, E, Cicciomessere, P, Colombo, M, Corsi, A, Crispino, A, Cucunato, R, Custodero, C, D’Agostino, F, D’Errico, M, D’Amico, F, De Iorio, A, De Marchi, A, Dell’Armi, A, Delmonte, M, Desideri, G, Devita, M, Di Matteo, E, Espinosa, E, Esposito, L, Fazio, C, Ferro, C, Filippini, C, Fiore, L, Fiorillo, S, Fontana, C, Forte, L, Montorzi, R, Fumagalli, C, Gasbarri, P, Giordano, A, Giuliani, E, and Granata, R

Subjects
BPSD, Profile, Clinical characteristic, Depression, Trazodone, Dementia
Abstract

Background and objectives: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. Methods: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. Results: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. Discussion: The use of trazodone was highly prevalent in functionally dependent and comorbid older adults admitted to LTCF or living at home. Clinical conditions associated with its prescription included depression as well as BPSD.

Published
2023

4. How microclimate mitigation affects building thermal-energy performance in residential zero energy Italian settlements

Author

Pisello, A. L., Castaldo, V. L., Fabiani, C., Piselli, C., Cotana, F., and Matthaios Santamouris

Subjects
H2020 ZERO-PLUS project, Microclimate mitigation, Microclimate simulation, Building simulation, Green infrastructures, Cool materials, urban heat island, 15. Life on land, 7. Clean energy, 12. Responsible consumption, 13. Climate action, 11. Sustainability, net zero energy settlement, microclimate, energy efficiency
Abstract

A key research effort has been dedicated toward zero energy buildings in the last decades. Recent interest is currently switching its focus from single‐building scale to the inter‐building scale, by enlarging the thermal‐energy balance up to the settlement level, with the purpose to optimize the whole district energy efficiency and its environmental sustainability. This scale enlargement up to the district size leads to further optimization opportunities that must be considered when performing building thermal‐energy dynamic simulation. In this view, building within net Zero‐Energy Settlements (nZES) can improve their performance thanks to outdoor microclimate improvement techniques, which could be able to mitigate both winter thermal losses and summer overheating risk. In this work, microclimate modeling and building dynamic simulation tools are integrated to assess the impact of varying microclimate conditions on the building energy performance at settlement level. The case study is represented by a residential district in Italy. In particular, microclimate simulations are carried out to predict the mitigation potential of specific strategies applied at settlement scale, i.e. cool materials, greenery, and their combination. Therefore, starting from the results of the microclimate optimization, new microclimate boundary conditions are generated to be used within the dynamic simulation environment. The final aim is to quantify the impact of such optimized microclimate boundary conditions on the buildings energy performance. Results from the microclimate simulations, supported by the European funded Horizon 2020 project ZERO‐PLUS, highlighted how microclimate can play a key role in affecting outdoor thermal comfort conditions. Moreover, the dynamic simulations carried out by using the results from the microclimate optimization as input weather files always show a decrease on the final energy needs of the building in the nZES. The highest and non‐negligible reduction is reached in the final cooling need of the optimized scenario, coupling both cool and green optimization strategies, i.e. about 12% of the initial value.

Published
2018
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9. High Resolution Scanning Ion Microscopy

Author

Castaldo, V. and Kruit, P.

Abstract

The structure of the thesis is the following. The first chapter is an introduction to scanning microscopy, where the path that led to the Focused Ion Beam (FIB) is described and the main differences between electrons and ion beams are highlighted. Chapter 2 is what is normally referred to (which I do not really like) as ‘the theory chapter’. The theory of ion/matter interaction is presented in the first part of the chapter. The treatment is the standard one that can be found in the literature, but of course mine is the choice of the topics and the way in which they are presented. The second part of the chapter is a short introduction toMonte Carlo codes, and in particular to the two pieces of software that I have used for my basic simulations, SRIM/TRIM from J. Ziegler, and IONiSE from D. Joy. The third chapter is almost entirely made up of an article published in Microscopy & Microanalysis in 2011, on the subject of ion-induced Secondary Electron Emission; the paper is introduced by two small sections, the first being an introduction to ion beam imaging, the second presenting a standard theory of noise in scanning microscopy. Chapter 4 introduces the main topic of this thesis work, the one that is more dear to me: resolution in scanning ion microscopy. The chapter is a hybrid, for the theory of resolution that is presented is quite standard, but interlaced with a lot of rethinking and personal points of view, and finally adapted to the specific field of scanning ion microscopy. Chapters 5 and 6 are the first two articles published during my PhD, in Journal of Vacuum Science & Technology B. They both tackle the problem of resolution evaluation in scanning ion microscopy, the first for the Ga-FIB, the second for the He-FIB. The two papers have been published in 2008 and 2009, respectively, a time when the uniformity of the formalism was not yet mature, reason for which symbolic inconsistencies can be found in relation to the rest of the thesis, and to the list of symbols in appendix B. Choice was made to leave the papers in their published version, but this should not represent a problem, because each quantity is clearly defined. The last journal paper published within my project makes chapter 7. The scope of the paper is broad, for it proposes a method to simulate ion imaging that does not employ any Monte Carlo calculation. It can be regarded as a kind of summary of all the studies performed in the course of the project, and is followed by an appendix that explains the details of the noise analysis whose results are presented in the article. Conclusions and recommendations find their place in chapter 8. With referiment to the original main motivation, i.e. exploring the possibility of achieving atomic resolution with a Scanning IonMicroscope, it is shown that this is not possible, at least in the general case, because the sputtering of the sample limits the ultimate obtainable resolution to the nanometer range, even using very light ions. Also, it is pointed out that, in imaging systems causing strong sample modification, the concept of resolution itself can not be thought of as static; it must be regarded as dynamic instead. On the subject of Ion-Induced Secondary Electron Emission, a procedure to obtain curves of Secondary Electron yield versus incident angle of the beam is presented; the behaviour of those curves contributes to explain the much sharper contrast achievable with a He-FIB, as opposite to the more traditional Ga-FIB. Finally, it is shown that simulation of ion imaging based on the ‘yield vs. incidence angle’ curves is feasible, overcoming the computational problems that affect any Monte Carlo based approach.

Published
2011

13. Angular Dependence of the Ion-Induced Secondary Electron Emission for He+ and Ga+ Beams

Author

Castaldo, V. (author), Withagen, J. (author), Hagen, C. (author), Kruit, P. (author), Van Veldhoven, E. (author), Castaldo, V. (author), Withagen, J. (author), Hagen, C. (author), Kruit, P. (author), and Van Veldhoven, E. (author)

Abstract

In recent years, novel ion sources have been designed and developed that have enabled focused ion beam machines to go beyond their use as nano-fabrication tools. Secondary electrons are usually taken to form images, for their yield is high and strongly dependent on the surface characteristics, in terms of chemical composition and topography. In particular, the secondary electron yield varies characteristically with the angle formed by the beam and the direction normal to the sample surface in the point of impact. Knowledge of this dependence, for different ion/atom pairs, is thus the first step toward a complete understanding of the contrast mechanism in scanning ion microscopy. In this article, experimentally obtained ion-induced secondary electron yields as a function of the incidence angle of the beam on flat surfaces of Al and Cr are reported, for usual conditions in Ga+ and He+ microscopes. The curves have been compared with models and simulations, showing a good agreement for most of the angle range; deviations from the expected behavior are addressed and explanations are suggested. It appears that the maximum value of the ion-induced secondary electron yield is very similar in all the studied cases; the yield range, however, is consistently larger for helium than for gallium, which partially explains the enhanced topographical contrast of helium microscopes over the gallium focused ion beams., IST/Imaging Science and Technology, Applied Sciences

Published
2011
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14. High Resolution Scanning Ion Microscopy

Author

Castaldo, V. (author) and Castaldo, V. (author)

Abstract

The structure of the thesis is the following. The first chapter is an introduction to scanning microscopy, where the path that led to the Focused Ion Beam (FIB) is described and the main differences between electrons and ion beams are highlighted. Chapter 2 is what is normally referred to (which I do not really like) as ‘the theory chapter’. The theory of ion/matter interaction is presented in the first part of the chapter. The treatment is the standard one that can be found in the literature, but of course mine is the choice of the topics and the way in which they are presented. The second part of the chapter is a short introduction toMonte Carlo codes, and in particular to the two pieces of software that I have used for my basic simulations, SRIM/TRIM from J. Ziegler, and IONiSE from D. Joy. The third chapter is almost entirely made up of an article published in Microscopy & Microanalysis in 2011, on the subject of ion-induced Secondary Electron Emission; the paper is introduced by two small sections, the first being an introduction to ion beam imaging, the second presenting a standard theory of noise in scanning microscopy. Chapter 4 introduces the main topic of this thesis work, the one that is more dear to me: resolution in scanning ion microscopy. The chapter is a hybrid, for the theory of resolution that is presented is quite standard, but interlaced with a lot of rethinking and personal points of view, and finally adapted to the specific field of scanning ion microscopy. Chapters 5 and 6 are the first two articles published during my PhD, in Journal of Vacuum Science & Technology B. They both tackle the problem of resolution evaluation in scanning ion microscopy, the first for the Ga-FIB, the second for the He-FIB. The two papers have been published in 2008 and 2009, respectively, a time when the uniformity of the formalism was not yet mature, reason for which symbolic inconsistencies can be found in relation to the rest of the thesis, and to the list of sym, IST/Imaging Science and Technology, Applied Sciences

Published
2011

15. On the influence of the sputtering in determining the resolution of a scanning ion microscope

Author

Castaldo, V. (author), Hagen, C.W. (author), Kruit, P. (author), Van Veldhoven, E. (author), Maas, D. (author), Castaldo, V. (author), Hagen, C.W. (author), Kruit, P. (author), Van Veldhoven, E. (author), and Maas, D. (author)

Abstract

The determination of the quality of an imaging system is not an easy task for, in general, at least three parameters, strictly interdependent, concur in defining it: resolution, contrast, and signal-to-noise ratio. The definition of resolution itself in scanning microscopy is elusive and the case of scanning ion microscopy is complicated by the damage of the sample under the ion beam, which, especially for small features, can be the limiting factor. This is indeed the case for most focused ion beam systems, which exploit beams of Ga+. The only way to overcome this limit is to exploit sources of low mass ions, such as H+ and He+. In this article the authors analyze the way the sputtering may affect the resolution, defined as smallest detectable feature in an image, of a scanning ion microscope, for heavy and light ions, in the case of spherical features. It appears that the fundamental limit to the resolution in scanning microscopy is not given by the spot size, but by the dynamics of the interaction of the beam with the sample and the consequent modification of the sample’s geometry, even for beams of light ions. For example, in the case of Sn nanospheres under a He+ beam, the authors found a minimum theoretical detectable particle size limit of ? 1?nm and an experimental limit of ? 5?nm., IST/Imaging Science and Technology, Applied Sciences

Published
2009

16. Sputtering limits versus signal-to-noise limits in the observation of Sn balls in a Ga+ microscope

Author

Castaldo, V. (author), Hagen, C.W. (author), Rieger, B. (author), Kruit, P. (author), Castaldo, V. (author), Hagen, C.W. (author), Rieger, B. (author), and Kruit, P. (author)

Abstract

In principle, a scanning ion microscope can produce smaller probe sizes than a scanning electron microscope because the diffraction contribution is smaller. However, the imaging resolution is often severely limited by the sputtering damage. In this article, an experimental procedure to establish the limit of a focused ion beam system for imaging purposes is proposed. The procedure is based on the observation of the change in geometry (i.e., shrinking) of the features in a Sn-ball sample imaged with a Ga+ beam. Plots of the balls’ diameter versus the irradiation time give a straightforward visual evaluation of the time allowed for the observation of a single feature before the removal of material due to the ion bombardment becomes unacceptable. For each particle, the curve, together with the error band connected with the imaging process, gives the values of uncertainty/resolution due to the two competing processes, collecting of information (for example, from secondary electrons) and damaging of the target. A plot of the uncertainty that is derived from these two processes for different sampling times allows the determination of the limiting factor of the imaging mode in use, and, ultimately, the highest possible resolution obtainable with a given machine for the observation of a certain sample. Together with simulations and theoretical studies, the described procedure will be able to confirm the effectiveness of the new ion sources that are currently being developed., IST/Imaging Science and Technology, Applied Sciences

Published
2008

27. Sputtering limits versus signal-to-noise limits in the observation of Sn balls in a Ga+ microscope.

Author

Castaldo, V., Hagen, C. W., Rieger, B., and Kruit, P.

Subjects
FIELD ion microscopes, SCANNING electron microscopes, ION bombardment, ELECTRONS, IRRADIATION
Abstract

In principle, a scanning ion microscope can produce smaller probe sizes than a scanning electron microscope because the diffraction contribution is smaller. However, the imaging resolution is often severely limited by the sputtering damage. In this article, an experimental procedure to establish the limit of a focused ion beam system for imaging purposes is proposed. The procedure is based on the observation of the change in geometry (i.e., shrinking) of the features in a Sn-ball sample imaged with a Ga+ beam. Plots of the balls’ diameter versus the irradiation time give a straightforward visual evaluation of the time allowed for the observation of a single feature before the removal of material due to the ion bombardment becomes unacceptable. For each particle, the curve, together with the error band connected with the imaging process, gives the values of uncertainty/resolution due to the two competing processes, collecting of information (for example, from secondary electrons) and damaging of the target. A plot of the uncertainty that is derived from these two processes for different sampling times allows the determination of the limiting factor of the imaging mode in use, and, ultimately, the highest possible resolution obtainable with a given machine for the observation of a certain sample. Together with simulations and theoretical studies, the described procedure will be able to confirm the effectiveness of the new ion sources that are currently being developed. [ABSTRACT FROM AUTHOR]

Published
2008
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32. Basophils infiltrate human gastric mucosa at sites of Helicobacter pylori infection, and exhibit chemotaxis in response to H. pylori-derived peptide Hp(2-20)

Author

Gianni Marone, Amato de Paulis, Monica Curto, Vincenza Castaldo, Paola Ceppa, Andrew F. Walls, Angelica Petraroli, Roberto Fiocca, Isabella Fiorentino, Nella Prevete, DE PAULIS, Amato, Prevete, Nella, Fiorentino, I., Walls, A. F., Curto, M., Petraroli, A., Castaldo, V., Ceppa, P., Fiocca, R., Marone, Gianni, Fiorentino, I, Walls, Af, Curto, M, Petraroli, A, Castaldo, V, Ceppa, P, Fiocca, R, and Marone, G.

Subjects
Biopsy, Immunology, chemical and pharmacologic phenomena, Basophil, Humans, Basophils, Gastric mucosa, Helicobacter pylori, Chemotaxis, Allergic inflammation, Helicobacter Infections, Bacterial Proteins, medicine, Immunology and Allergy, Helicobacter, RNA, Messenger, Receptor, biology, hemic and immune systems, biology.organism_classification, Receptors, Formyl Peptide, Peptide Fragments, Chemotaxis, Leukocyte, medicine.anatomical_structure, Gastric Mucosa, Case-Control Studies, Gastritis, medicine.symptom
Abstract

Basophils, which are normally confined to the circulation, can migrate to sites of allergic inflammation. Using the specific mAb, BB1, we detected basophil infiltration of the gastric mucosa of Helicobacter pylori-infected patients affected by moderate and severe gastritis. Basophils were not found in H. pylori-free individuals or in subjects with mild gastritis. The H. pylori-derived peptide, Hp(2–20), was a potent basophil chemoattractant in vitro, whereas the control peptide, Hp1, was ineffective. Basophils from peripheral blood of healthy volunteers expressed mRNA for the formyl peptide receptors, N-formyl-peptide receptor (FPR), FPR-like (FPRL)1, and FPRL2. Preincubation of basophils with FMLP or Hp(2–20) caused complete desensitization to a subsequent challenge with homologous stimulus. Incubation of basophils with a low concentration of FMLP, which binds with high affinity to FPR, but not to FPRL1 or FPRL2, did not affect the chemotactic response to Hp(2–20). In contrast, a high concentration of FMLP, which binds to FPRL1 and FPRL2, reduced the chemotactic response to Hp(2–20). The FPR antagonist, cyclosporin H, prevented chemotaxis induced by FMLP, but not by Hp(2–20). Hp(2–20) could be responsible, at least in part, for basophil infiltration of the gastric mucosa of H. pylori-infected patients presumably through the interaction with FPRL1 and FPRL2.

Published
2004

33. A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes

Author

F. De Berardinis, Fortunato Lombardo, G. Zanette, R. Cardani, Ivana Rabbone, C. Zecchino, Barbara Predieri, C. Arnaldi, Barbara Piccini, B. Felappi, Riccardo Bonfanti, D. Lo Presti, B. Mainetti, G. Ignaccolo, F. Stamati, Roberto Franceschi, G. Ponzi, M. S. Coccioli, F. Citriniti, C. Ripoli, F. Chiarelli, Valeria Calcaterra, M. Trada, Giovanni Federico, A. Sabbion, D. Cirillo, Enza Mozzillo, C. Salvo, Francesco Prisco, G. Piredda, Alessandro Salvatoni, Maurizio Delvecchio, R. A. Taccardi, Valentino Cherubini, Gianluca Tornese, G. Morganti, Giulio Maltoni, Nicola Minuto, Giovanni Chiari, S. Zonca, M. Bensa, Franco Meschi, V. De Donno, Martina Biagioni, Silvia Savastio, L. Guerraggio, A. Gualtieri, T. Suprani, A. Franzese, M. G. Berioli, D. Iafusco, Francesco Cadario, Andrea Scaramuzza, A. Favia, Luciano Beccaria, Gian Vincenzo Zuccotti, Sonia Toni, Riccardo Schiaffini, F. Cerutti, N. Lazzaro, Lorenzo Iughetti, B. Pasquino, Francesco Fontana, P. Banin, G. Cardinale, A. Marsciani, Anna Paola Frongia, S. Lucchesi, E. Schieven, R. Lera, R. De Marco, F. Cardella, F. Gallo, Vittoria Cauvin, P. Sogno Valin, E. Prandi, L. Tomaselli, Vanna Graziani, M Bruzzese, Lorenzo Lenzi, F. Mammì, Giuseppe d'Annunzio, Ippolita Patrizia Patera, Stefano Zucchini, C. Maffeis, A. Bobbio, A. Gaiero, V. Castaldo, Alfonso Galderisi, Stefano Tumini, P Buono, C. Monciotti, Elvira Piccinno, D. Pardi, Marco Cappa, Renata Lorini, Marco Marigliano, Zucchini, Stefano, Scaramuzza, Andrea E, Bonfanti, Riccardo, Buono, Pietro, Cardella, Francesca, Cauvin, Vittoria, Cherubini, Valentino, Chiari, Giovanni, D'Annunzio, Giuseppe, Frongia, Anna Paola, Iafusco, Dario, Maltoni, Giulio, Patera, Ippolita Patrizia, Toni, Sonia, Tumini, Stefano, Tornese, Gianluca, Rabbone, Ivana, Lera, R., Bobbio, A., Gualtieri, A., Piccinno, E., Zecchino, C., Pasquino, B., Felappi, B., Prandi, E., Gallo, F., Morganti, G., Ripoli, C., Cardinale, G., Ponzi, G., Castaldo, V., Stamati, F., Lo Presti, D., Tomaselli, L., Citriniti, F., Suprani, T., Bensa, M., Graziani, V., De Berardinis, F., Chiarelli, F., De Marco, R., Lazzaro, N., De Donno, V., Banin, P., Piccini, B., Lenzi, L., Mainetti, B., Coccioli, M. S., Minuto, N., Lorini, R., Trada, M., Sogno Valin, P., Beccaria, L., Lucchesi, S., Bruzzese, M., Mammì, F., Cirillo, D., Pardi, D., Taccardi, R. A., Lombardo, F., Zuccotti, G. V., Meschi, F., Iughetti, L., Predieri, B., Franzese, A., Mozzillo, Enza., Prisco, F., Cadario, F., Savastio, S., Piredda, G., Monciotti, C., Galderisi, A., Salvo, C., Calcaterra, V., Berioli, M. G., Federico, G., Favia, A., Zanette, G., Marsciani, A., Schiaffini, R., Cappa, M., Delvecchio, M., Gaiero, A., Ignaccolo, G., Cerutti, F., Fontana, F., Guerraggio, L., Zonca, S., Franceschi, R., Tornese, G., Biagioni, M., Salvatoni, A., Cardani, R., Marigliano, M., Sabbion, A., Maffeis, C., Schieven, E., Arnaldi, C., Zucchini, S., Scaramuzza, A. E., Bonfanti, R., Buono, P., Cardella, F., Cauvin, V., Cherubini, V., Chiari, G., D'Annunzio, G., Frongia, A. P., Iafusco, D., Maltoni, G., Patera, I. P., Toni, S., Tumini, S., Rabbone, I., Mammi, F., Mozzillo, E., and Prisco, Francesco

Subjects
0301 basic medicine, Male, Pediatrics, Endocrinology, Diabetes and Metabolism, Endocrinology, endocrine system diseases, type 1 diabetes, Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1, Diabetic Ketoacidosis, Female, Health Care Surveys, Humans, Infant, Infant, Newborn, Insulin, Italy, Rehydration Solutions, Retrospective Studies, Treatment Outcome, lcsh:Diseases of the endocrine glands. Clinical endocrinology, ketoacidosis, Retrospective Studie, Medicine, Diabetology, Diabetes and Metabolism, Newly diagnosed diabetes, Research Article, Type 1, Human, medicine.medical_specialty, Article Subject, Referral, Diabetic ketoacidosis, Diabetic Ketoacidosi, 03 medical and health sciences, children, Retrospective survey, Diabetes mellitus, Diabetes Mellitus, Preschool, Type 1 diabetes, lcsh:RC648-665, business.industry, Rehydration Solution, nutritional and metabolic diseases, Retrospective cohort study, Newborn, medicine.disease, 030104 developmental biology, Health Care Survey, business
Abstract

We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0–18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records(n=2453)of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n=1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05–0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers.

Published
2016

35. Survival after Locoregional Treatments for Hepatocellular Carcinoma: A Cohort Study in Real-World Patients

Author

Paolo Chiodini, Francesco Perrone, Mario Fusco, Nicola Lama, Vincenzo Castaldo, F. Calise, Massimo Di Maio, Ilario de Sio, Graziano Olivieri, Ciro Gallo, Bruno Daniele, Giovanni Battista Gaeta, Giovanni G. Di Costanzo, Guido Piai, Giuseppe Signoriello, Simona Signoriello, Giampiero Marone, Mario Visconti, Rosario Lanzetta, Annalisa Annunziata, Signoriello, Simona, Annunziata, A, Lama, N, Signoriello, Giuseppe, Chiodini, Paolo, De Sio, I, Daniele, B, Di Costanzo, Gg, Calise, F, Olivieri, G, Castaldo, V, Lanzetta, R, Piai, G, Marone, G, Visconti, M, Fusco, M, Di Maio, M, Perrone, F, Gallo, Ciro, and Gaeta, Giovanni Battista

Subjects
Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Article Subject, Radiofrequency ablation, medicine.medical_treatment, lcsh:Medicine, Kaplan-Meier Estimate, lcsh:Technology, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, law.invention, Randomized controlled trial, law, Internal medicine, Medicine, Humans, lcsh:Science, General Environmental Science, Aged, Proportional Hazards Models, Retrospective Studies, Chemotherapy, lcsh:T, business.industry, Proportional hazards model, lcsh:R, Liver Neoplasms, technology, industry, and agriculture, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Surgery, surgical procedures, operative, Treatment Outcome, Hepatocellular carcinoma, lcsh:Q, Female, Percutaneous ethanol injection, business, Cohort study, Research Article
Abstract

Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79–1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64–1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66–1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment.

Published
2012

36. L’influenza sull’ordinamento italiano del diritto penale europeo delle organizzazioni criminali

Author

CAVALIERE, ANTONIO, S. MIR PUIG – M. CORCOY BIDASOLO – V. GÒMEZ MARTÌN, Cavaliere, Antonio, AA.VV., and A. CASTALDO, V. DE FRANCESCO, M. DEL TUFO, S. MANACORDA, L. MONACO

Subjects
Convenzione europea dei diritti dell'Uomo, criminalità organizzata, Costituzione e diritto penale, diritto penale dell'Unione europea, terrorismo
Abstract

Il lavoro tratta, in una prima parte, dell'influenza della CEDU e della giurisprudenza della Corte europea dei diritti dell'Uomo sul diritto penale italiano in materia di criminalità organizzata. Nella seconda parte, viene analizzata la normativa dell'Unione europea in materia di criminalità organizzata e terrorismo. Conclusivamente, vengono delineati i profili critici del rapporto tra principi fondamentali, di rango costituzionale, del diritto penale ed armonizzazione europea, segnalando carenze nella griglia di principi penalistici dei trattati europei e della stessa CEDU e, conseguentemente, il rischio di una produzione normativa secondaria dell'Unione non rispettosa di garanzie quali l'offensività, la determinatezza e la funzione rieducativa della pena.

Published
2012

37. Upregulated expression of miR-4443 and miR-4488 in drug resistant melanomas promotes migratory and invasive phenotypes through downregulation of intermediate filament nestin.

Author

Castaldo V, Minopoli M, Di Modugno F, Sacconi A, Liguoro D, Frigerio R, Ortolano A, Di Martile M, Gesualdi L, Madonna G, Capone M, Cirombella R, Catizone A, Del Bufalo D, Vecchione A, Carriero MV, Ascierto PA, Mancini R, Fattore L, and Ciliberto G

Subjects
Humans, Cell Line, Tumor, Cell Movement, Cell Proliferation, Down-Regulation, Gene Expression Regulation, Neoplastic, Intermediate Filaments metabolism, Intermediate Filaments pathology, Nestin genetics, Nestin metabolism, Phenotype, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, MicroRNAs metabolism
Abstract

Background: BRAF-mutant melanoma patients benefit from the combinatorial treatments with BRAF and MEK inhibitors. However, acquired drug resistance strongly limits the efficacy of these targeted therapies in time. Recently, many findings have underscored the involvement of microRNAs as main drivers of drug resistance. In this context, we previously identified a subset of oncomiRs strongly up-regulated in drug-resistant melanomas. In this work, we shed light on the molecular role of two as yet poorly characterized oncomiRs, miR-4443 and miR-4488., Methods: Invasion and migration have been determined by wound healing, transwell migration/invasion assays and Real Time Cell Analysis (RTCA) technology. miR-4488 and miR-4443 have been measured by qRT-PCR. Nestin levels have been tested by western blot, confocal immunofluorescence, immunohistochemical and flow cytometry analyses., Results: We demonstrate that the two oncomiRs are responsible for the enhanced migratory and invasive phenotypes, that are a hallmark of drug resistant melanoma cells. Moreover, miR-4443 and miR-4488 promote an aberrant cytoskeletal reorganization witnessed by the increased number of stress fibers and cellular protrusions-like cancer cell invadopodia. Mechanistically, we identified the intermediate filament nestin as a molecular target of both oncomiRs. Finally, we have shown that nestin levels are able to predict response to treatments in melanoma patients., Conclusions: Altogether these findings have profound translational implications in the attempt i) to develop miRNA-targeting therapies to mitigate the metastatic phenotypes of BRAF-mutant melanomas and ii) to identify novel biomarkers able to guide clinical decisions., (© 2023. The Author(s).)

Published
2023
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38. Dalbavancin in catheter-related bloodstream infections: a pilot study.

Author

Venturini S, Reffo I, Avolio M, Basaglia G, Del Fabro G, Callegari A, Grembiale A, Garlatti E, Castaldo V, Tonizzo M, Balbi M, Cevolani M, Basso B, Pellis T, and Crapis M

Abstract

Background: Catheter-related bloodstream infections (CRBSI) represent a frequent complication of vascular catheterization, with high morbidity, mortality, and associated costs. Most infections are caused by Gram-positive bacteria; thus dalbavancin, a new long-acting lipoglicopeptide, may have a role in early patient discharge strategies optimizing treatment and reducing overall costs., Methods: In this small pilot feasibility study, we assessed the efficacy and safety of a "single step" treatment strategy combining dalbavancin administration (1500 mg IV single dose), catheter removal, and early discharge in adult patients admitted to medical wards in a three-year period., Results: We enrolled sixteen patients with confirmed Gram-positive CRBSI, with a mean age of 68 years and relevant comorbidities (median Charlson Comorbidity index=7). The most frequent causative agents were staphylococci, with 25% of methicillin-resistant strains, and the majority of infected devices were short term central venous catheter (CVC) and peripherally inserted central catheter (PICC). Ten out of sixteen patients had been treated empirically before dalbavancin administration. The mean time from dalbavancin administration to discharge was 2 days; none of the patients had adverse drug-related reactions; at 30- and 90-day follow-up, no patients have been readmitted to the hospital due to bacteraemia recurrence., Conclusions: Our results indicate that single-dose dalbavancin is highly effective, well-tolerated, and cost-saving for Gram-positive CRBSI., Competing Interests: Competing interests No conflict of interest must be declared for any of the authors.

Published
2023
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39. Oncosuppressive miRNAs loaded in lipid nanoparticles potentiate targeted therapies in BRAF-mutant melanoma by inhibiting core escape pathways of resistance.

Author

Fattore L, Cafaro G, Di Martile M, Campani V, Sacconi A, Liguoro D, Marra E, Bruschini S, Stoppoloni D, Cirombella R, De Nicola F, Pallocca M, Ruggiero CF, Castaldo V, Catizone A, Del Bufalo D, Viglietto G, Vecchione A, Blandino G, Aurisicchio L, Fanciulli M, Ascierto PA, De Rosa G, Mancini R, and Ciliberto G

Subjects
Humans, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, Protein Kinase Inhibitors pharmacology, Drug Resistance, Neoplasm genetics, Neoplasm Recurrence, Local drug therapy, Cell Line, Tumor, MicroRNAs genetics, MicroRNAs metabolism, Melanoma drug therapy, Melanoma genetics
Abstract

BRAF-mutated melanoma relapsing after targeted therapies is an aggressive disease with unmet clinical need. Hence the need to identify novel combination therapies able to overcome drug resistance. miRNAs have emerged as orchestrators of non-genetic mechanisms adopted by melanoma cells to challenge therapies. In this context we previously identified a subset of oncosuppressor miRNAs downregulated in drug-resistant melanomas. Here we demonstrate that lipid nanoparticles co-encapsulating two of them, miR-199-5p and miR-204-5p, inhibit tumor growth both in vitro and in vivo in combination with target therapy and block the development of drug resistance. Mechanistically they act by directly reducing melanoma cell growth and also indirectly by hampering the recruitment and reprogramming of pro-tumoral macrophages. Molecularly, we demonstrate that the effects on macrophages are mediated by the dysregulation of a newly identified miR-204-5p-miR-199b-5p/CCL5 axis. Finally, we unveiled that M2 macrophages programs are molecular signatures of resistance and predict response to therapy in patients. Overall, these findings have strong translational implications to propose new combination therapies making use of RNA therapeutics for metastatic melanoma patients., (© 2022. The Author(s).)

Published
2023
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40. Doege-Potter Syndrome; A Case of Solitary Fibrous Pleura Tumor Associated with Severe Hypoglycemia: A Case Report in Internal Medicine.

Author

Castaldo V, Domenici D, Biscosi MV, Ubiali P, Miranda C, Zanette G, Mazzon C, and Tonizzo M

Subjects
Male, Humans, Middle Aged, Pleura pathology, Syndrome, Solitary Fibrous Tumor, Pleural diagnosis, Solitary Fibrous Tumor, Pleural diagnostic imaging, Hypoglycemia diagnosis, Hypoglycemia etiology
Abstract

Background: Doege-Potter syndrome is a rare paraneoplastic entity that is often diagnosed incidentally during the work-up of hypoglycemia of unclear etiology. It is characterized by a non-islet cell tumor hypoglycemia mostly associated with solitary fibrous tumors. These uncommon tumors have been reported in <5% of solitary fibrous tumors. Although not unique in its kind, this case is extremely important as this syndrome often conceals unrecognized tumors that can be surgically resolved., Case Presentation: We present the case of a 59-year-old non-diabetic man with a 2-month history of severe and recurrent fasting hypoglycaemia presenting with severe dyspnea and sweating. Further workup revealed low insulin, C-peptide, and IGF-1 levels and a large right in-trathoracic solitary fibrous tumor. Unfortunately, bioassays for IGF-2 were unavailable at our hos-pital. Nevertheless, as hypoglycemia completely resolved after resection of the mass, Doege-Potter syndrome was highly suspected., Conclusion: Doege-Potter syndrome is a complication of rare tumors. If hy-poglycemia is unexplained, this syndrome should always be suspected, and the presence of un-known masses should be investigated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2023
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41. Identification of a miRNA-based non-invasive predictive biomarker of response to target therapy in BRAF-mutant melanoma.

Author

Ruggiero CF, Fattore L, Terrenato I, Sperati F, Salvati V, Madonna G, Capone M, Valenti F, Di Martino S, Mandoj C, Liguoro D, Castaldo V, Cafaro G, Simeone E, Vanella V, Russillo M, Conti L, Cuda G, Giannarelli D, Ascierto PA, Mancini R, and Ciliberto G

Subjects
Humans, Biomarkers, Tumor genetics, Proto-Oncogene Proteins B-raf genetics, Circulating MicroRNA genetics, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, MicroRNAs genetics, Skin Neoplasms drug therapy, Skin Neoplasms genetics, Skin Neoplasms pathology
Abstract

Rationale: Metastatic melanoma is the most aggressive and dangerous form of skin cancer. The introduction of immunotherapy with Immune checkpoint Inhibitors (ICI) and of targeted therapy with BRAF and MEK inhibitors for BRAF mutated melanoma, has greatly improved the clinical outcome of these patients. Nevertheless, response to therapy remains highly variable and the development of drug resistance continues to be a daunting challenge. Within this context there is a need to develop diagnostic tools capable of predicting response or resistance to therapy in order to select the best therapeutic approach. Over the years, accumulating evidence brought to light the role of microRNAs (miRNAs) as disease biomarkers. Methods: In particular, the detection of miRNAs in whole blood or specific blood components such as serum or plasma, allows these molecules to be good candidates for diagnosis, prognosis and for monitoring response to anticancer therapy. In this paper, we evaluated circulating basal levels of 6 previously identified miRNAs in serum samples of 70 BRAF-mutant melanoma patients before starting targeted therapy. Results: Results show that the circulating levels of the oncosuppressor miR-579-3p and of the oncomiR miR-4488 are able to predict progression free survival (PFS) but not overall survival (OS). Most importantly, we observed that the best predictor of disease outcome is represented by the ratio of circulating miR-4488 vs. miR-579-3p (miRatio). Finally, the combination of the Lactate dehydrogenase (LDH) blood levels with the two circulating miRNAs alone or together did not produce any improvement in predicting PFS indicating that miR-579-3p and miR-4488 are independent predictors of PFS as compared to LDH. Conclusions: All together these data underscored the relevance of circulating miRNAs as suitable tools to predict therapy response in melanoma and maybe further developed as companion diagnostics in the clinic., Competing Interests: Competing Interests: All the authors declare no conflict of interest with the exception of P.A.A. Paolo A. Ascierto has/had a consultant/advisory role for Bristol MyersSquibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, Replimmune. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. Travel support by Pfizer. The funders of this study had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© The author(s).)

Published
2022
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42. The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma.

Author

Fattore L, Ruggiero CF, Liguoro D, Castaldo V, Catizone A, Ciliberto G, and Mancini R

Abstract

Metastatic melanoma is the deadliest form of skin cancer whose incidence has been rising dramatically over the last few decades. Nowadays, the most successful approach in treating advanced melanoma is immunotherapy which encompasses the use of immune checkpoint blockers able to unleash the immune system's activity against tumor cells. Immunotherapy has dramatically changed clinical practice by contributing to increasing long term overall survival. Despite these striking therapeutic effects, the clinical benefits are strongly mitigated by innate or acquired resistance. In this context, it is of utmost importance to develop methods capable of predicting patient response to immunotherapy. To this purpose, one major step forward may be provided by measuring non-invasive biomarkers in human fluids, namely Liquid Biopsies (LBs). Several LB approaches have been developed over the last few years thanks to technological breakthroughs that have allowed to evaluate circulating components also when they are present in low abundance. The elements of this so-called "circulome" mostly encompass: tumor DNA, tumor and immune cells, soluble factors and non-coding RNAs. Here, we review the current knowledge of these molecules as predictors of response to immunotherapy in metastatic melanoma and predict that LB will soon enter into routine practice in order to guide clinical decisions for cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fattore, Ruggiero, Liguoro, Castaldo, Catizone, Ciliberto and Mancini.)

Published
2021
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43. Monomorphic Epitheliotropic Intestinal T Cell Lymphoma of the Appendix: a Case Report and Review of Literature.

Author

Soardo G, Castaldo V, Donnini D, Uzzau A, Pizzolitto S, and Sechi LA

Subjects
Aged, Appendiceal Neoplasms complications, Appendiceal Neoplasms surgery, Enteropathy-Associated T-Cell Lymphoma complications, Enteropathy-Associated T-Cell Lymphoma surgery, Humans, Male, Prognosis, Skin Neoplasms complications, Skin Neoplasms surgery, Appendiceal Neoplasms pathology, Enteropathy-Associated T-Cell Lymphoma pathology, Skin Neoplasms pathology
Published
2020
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44. Survival after locoregional treatments for hepatocellular carcinoma: a cohort study in real-world patients.

Author

Signoriello S, Annunziata A, Lama N, Signoriello G, Chiodini P, De Sio I, Daniele B, Di Costanzo GG, Calise F, Olivieri G, Castaldo V, Lanzetta R, Piai G, Marone G, Visconti M, Fusco M, Di Maio M, Perrone F, Gallo C, and Gaeta GB

Subjects
Aged, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular therapy, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms surgery, Liver Neoplasms therapy, Male, Middle Aged, Proportional Hazards Models, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular mortality, Liver Neoplasms mortality
Abstract

Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79-1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64-1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66-1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment.

Published
2012
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45. Angular dependence of the ion-induced secondary electron emission for He+ and Ga+ beams.

Author

Castaldo V, Withagen J, Hagen C, Kruit P, and van Veldhoven E

Abstract

In recent years, novel ion sources have been designed and developed that have enabled focused ion beam machines to go beyond their use as nano-fabrication tools. Secondary electrons are usually taken to form images, for their yield is high and strongly dependent on the surface characteristics, in terms of chemical composition and topography. In particular, the secondary electron yield varies characteristically with the angle formed by the beam and the direction normal to the sample surface in the point of impact. Knowledge of this dependence, for different ion/atom pairs, is thus the first step toward a complete understanding of the contrast mechanism in scanning ion microscopy. In this article, experimentally obtained ion-induced secondary electron yields as a function of the incidence angle of the beam on flat surfaces of Al and Cr are reported, for usual conditions in Ga+ and He+ microscopes. The curves have been compared with models and simulations, showing a good agreement for most of the angle range; deviations from the expected behavior are addressed and explanations are suggested. It appears that the maximum value of the ion-induced secondary electron yield is very similar in all the studied cases; the yield range, however, is consistently larger for helium than for gallium, which partially explains the enhanced topographical contrast of helium microscopes over the gallium focused ion beams.

Published
2011
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46. Treatment of advanced non-small-cell lung cancer in the elderly.

Author

Gridelli C, Maione P, Rossi A, Ferrara ML, Castaldo V, Palazzolo G, and Mazzeo N

Subjects
Age Factors, Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Bevacizumab, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung epidemiology, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung radiotherapy, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Cisplatin administration & dosage, Cisplatin adverse effects, Clinical Trials as Topic, Comorbidity, Contraindications, ErbB Receptors antagonists & inhibitors, Erlotinib Hydrochloride, Gefitinib, Humans, Lung Neoplasms complications, Lung Neoplasms epidemiology, Lung Neoplasms pathology, Lung Neoplasms radiotherapy, Quinazolines administration & dosage, Quinazolines adverse effects, Radiation-Sensitizing Agents, Vascular Endothelial Growth Factor A immunology, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
Abstract

Lung cancer in the older individual is an increasingly common problem faced by the oncologist. Elderly patients have more co-morbidities and tend to tolerate toxic medical treatments more poorly than their younger counterparts. Thus, clinical data obtained in a younger population cannot be automatically extrapolated to the great majority of non-selected elderly patients with non-small-cell lung cancer (NSCLC). The bulk of prospective clinical data regarding chemotherapy and molecularly targeted therapy for elderly NSCLC patients comes from studies in advanced disease. In elderly advanced NSCLC patients single-agent chemotherapy with third-generation agents (vinorelbine, gemcitabine, taxanes) is to be considered as the standard treatment for unselected patients, based on several phase II and III trials specifically designed for this special population. Retrospective analyses found no differences in survival between elderly and younger patients treated with cisplatin-based chemotherapy, with a small but significant increase in toxicity in the elderly. Cisplatin-based chemotherapy with cisplatin at attenuated doses has demonstrated to be an active and feasible option in phase II trials and deserves prospective phase III comparison against monochemotherapy. Among targeted therapies, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib are the most promising agents and have relevant phase II prospective data showing activity and good tolerability as first-line treatment in this population. Concerning the anti-vascular endothelial growth factor monoclonal antibody bevacizumab, particular care must be taken for elderly patients because of a possible higher incidence of cardiovascular co-morbidities. However its role in this population remains controversial and specific prospective studies are warranted to clarify this topic. Further specifically designed phase III randomized trials are needed to optimize medical treatment of NSCLC in elderly patients.

Published
2009
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47. Vaccines for the treatment of non-small cell lung cancer: a renewed anticancer strategy.

Author

Gridelli C, Rossi A, Maione P, Ferrara ML, Castaldo V, and Sacco PC

Subjects
Antigens, Neoplasm therapeutic use, Cancer Vaccines immunology, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung mortality, Clinical Trials, Phase III as Topic, Combined Modality Therapy, Humans, Lung Neoplasms immunology, Lung Neoplasms mortality, Neoplasm Invasiveness, Survival Analysis, Treatment Outcome, Antigens, Neoplasm immunology, Cancer Vaccines therapeutic use, Carcinoma, Non-Small-Cell Lung therapy, Immunotherapy, Active, Lung Neoplasms therapy
Abstract

Carcinoma of the lung is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) constituting about 85% of all new diagnoses. Standard approaches for each NSCLC stage have reached a plateau in effectiveness. A variety of novel approaches are now being investigated to improve the outcome of this disease. Despite decades of research, no specific active cancer vaccine has, to date, been approved for NSCLC therapy; nevertheless, vaccine therapy has recently re-emerged as a potential therapeutic approach. In particular, several new paradigms have stemmed from recent clinical findings both in the use of combination therapy approaches with more sophisticated specific vaccines and in clinical trial design and endpoint analyses. Several vaccine therapies have been investigated in NSCLC, including in the early and advanced disease stages. The best results appear to be in the adjuvant settings and in locally advanced NSCLC. In fact, in these two settings, phase III randomized trials are ongoing evaluating the melanoma-associated antigen A3 vaccine and the liposomal BLP25 vaccine. This paper reviews the main clinical trials involving several different cancer vaccines employed in the treatment of early and advanced stage NSCLC, focusing on those in advanced stages of development.

Published
2009
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48. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer.

Author

Schettino C, Bareschino MA, Rossi A, Maione P, Castaldo V, Mazzeo N, Sacco PC, Ferrara ML, Palazzolo G, Ciardiello F, and Gridelli C

Abstract

Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection - in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease.

Published
2009
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49. Vascular disrupting agents: a novel mechanism of action in the battle against non-small cell lung cancer.

Author

Gridelli C, Rossi A, Maione P, Rossi E, Castaldo V, Sacco PC, and Colantuoni G

Subjects
Animals, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung blood supply, Clinical Trials as Topic, Diketopiperazines, Humans, Imidazoles pharmacology, Imidazoles therapeutic use, Lung Neoplasms blood supply, Piperazines pharmacology, Piperazines therapeutic use, Stilbenes pharmacology, Stilbenes therapeutic use, Sulfonamides pharmacology, Sulfonamides therapeutic use, Xanthones pharmacology, Xanthones therapeutic use, Antineoplastic Agents pharmacology, Carcinoma, Non-Small-Cell Lung drug therapy, Endothelial Cells drug effects, Lung Neoplasms drug therapy, Pericytes drug effects
Abstract

Targeting vasculature, essential in oxygen and nutrient supply, represents a new frontier in the treatment of cancer. Apart from angiogenesis inhibitors that compromise the formation of new blood vessels, a second class of vascular disrupting agents (VDAs) targets endothelial cells and pericytes of the already established tumor vasculature, resulting in tumor ischemia and necrosis. VDAs have been divided into two types: ligand-directed VDAs and small molecules. Ligand-directed VDAs consist of targeting and effector moieties that are linked together. Their clinical efficacy appears limited because of cost and a lack of specificity and toxicity. Small molecules include two classes: the synthetic flavonoids, which work through induction of local cytokine production, and the tubulin-binding agents. The aim of this review is to discuss the hypothesized molecular mechanisms of action of VDAs and their early preclinical and clinical results, emphasizing ASA404, combretastatin A-4 disodium phosphate, ABT-751, and NPI-2358, reported in the treatment of non-small cell lung cancer, which is the leading cause of cancer death worldwide, and also to discuss future developments in this cancer population.

Published
2009
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50. Melnick-Needles syndrome and GH-deficiency: a possible new association feature.

Author

Femiano P, Castaldo V, Iossa C, and Pascarella F

Subjects
Adult, Child, Chromosomes, Human, X genetics, Female, Genotype, Humans, Phenotype, Growth Hormone deficiency, Osteochondrodysplasias genetics, Osteochondrodysplasias metabolism
Abstract

We report a rare genetic disorder, the Melnick-Needles syndrome (MNS) in 3 members of the same family, the mother and 2 daughters. This syndrome is a rare X-linked genetic disorder characterized by abnormal bone development, showing a particular facial appearance; moreover, these patients may also have a relatively small chest cavity with irregular ribbon-like ribs, a short clavicle and narrow shoulders. Stature is mildly reduced. The 3 members of this family shared the same common clinical and radiographic features designating MNS. The mother and the younger daughter were of short stature, while the other daughter was of normal stature within her parental target height. The evaluation of the GH/IGF-I axis evidenced a GH deficiency in 1 out of 3 members of the family, specifically in the younger daughter. The auxological evaluation also showed her stature was nearly below a 3 standard deviation score. This case report describes for the first time a family affected by MNS, in which one of the members shows a truly severe idiopathic, isolated GH deficiency, the likely cause of the severe short stature.

Published
2005

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