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2. A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data

Author

Alessandro Vinceti, Raffaele M. Iannuzzi, Isabella Boyle, Lucia Trastulla, Catarina D. Campbell, Francisca Vazquez, Joshua M. Dempster, and Francesco Iorio

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to generate similar gene-independent responses to CRISPR-Cas9 targeting (proximity bias), possibly due to Cas9-induced whole chromosome-arm truncations or other genomic structural features and different chromatin accessibility levels. Results We benchmarked eight computational methods, rigorously evaluating their ability to reduce both CN and proximity bias in the two largest publicly available cell-line-based CRISPR-Cas9 screens to date. We also evaluated the capability of each method to preserve data quality and heterogeneity by assessing the extent to which the processed data allows accurate detection of true positive essential genes, established oncogenetic addictions, and known/novel biomarkers of cancer dependency. Our analysis sheds light on the ability of each method to correct biases under different scenarios. AC-Chronos outperforms other methods in correcting both CN and proximity biases when jointly processing multiple screens of models with available CN information, whereas CRISPRcleanR is the top performing method for individual screens or when CN information is not available. In addition, Chronos and AC-Chronos yield a final dataset better able to recapitulate known sets of essential and non-essential genes. Conclusions Overall, our investigation provides guidance for the selection of the most appropriate bias-correction method, based on its strengths, weaknesses and experimental settings.

Published
2024
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11. Average absorbed breast dose (2ABD): an easy radiation dose index for digital breast tomosynthesis

Author

Antonio C. Traino, Patrizio Barca, Rocco Lamastra, Raffaele M. Tucciariello, Chiara Sottocornola, Carolina Marini, Giacomo Aringhieri, Davide Caramella, and Maria E. Fantacci

Subjects
Digital breast tomosynthesis, Mammography, Phantoms (imaging), X-rays, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Abstract Background To propose a practical and simple method to individually evaluate the average absorbed dose for digital breast tomosynthesis. Methods The method is based on the estimate of incident air kerma (k a,i ) on the breast surface. An analytical model was developed to calculate the k a,i from the tube voltage, tube load, breast thickness, x-ray tube yield, and anode-filter combination. A homogeneous phantom was employed to simulate the breast in experimental measurements and to assess the dose-depth relationship. The k a,i values were employed to calculate the “average absorbed breast dose” (2ABD) index. Four mammographic units were used to develop and test our method under many conditions close to clinical settings. The average glandular dose (AGD) calculated following the method described by Dance et al., and the 2ABD computed through our method (i.e., from the exposure parameters) were compared in a number of conditions. Results A good agreement was obtained between the k a,i computed through our model and that measured under different clinical conditions: discrepancies < 6% were found in all conditions. 2ABD matches with a good accuracy the AGD for a 100% glandular-breast: the minimum, maximum, and mean differences were < 0.1%, 7%, and 2.4%, respectively; the discrepancies increase with decreasing breast glandularity. Conclusions The proposed model, based on only few exposure parameters, represents a simple way to individually calculate an index, 2ABD, which can be interpreted as the average absorbed dose in a homogeneous phantom, approximating a 100% glandular breast. The method could be easily implemented in any mammographic device performing DBT.

Published
2020
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12. Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Author

Di Lisa, F, Krasniqi, E, Pizzuti, L, Barba, M, Cannita, K, De Giorgi, U, Borella, F, Foglietta, J, Cariello, A, Ferro, A, Picardo, E, Mitidieri, M, Sini, V, Stani, S, Tonini, G, Santini, D, La Verde, N, Gambaro, A, Grassadonia, A, Tinari, N, Garrone, O, Sarobba, G, Livi, L, Meattini, I, D'Auria, G, Vergati, M, Gamucci, T, Pistelli, M, Berardi, R, Risi, E, Giotta, F, Lorusso, V, Rinaldi, L, Artale, S, Cazzaniga, M, Zustovich, F, Cappuzzo, F, Landi, L, Torrisi, R, Scagnoli, S, Botticelli, A, Michelotti, A, Fratini, B, Saltarelli, R, Paris, I, Muratore, M, Cassano, A, Gianni, L, Gaspari, V, Veltri, E, Zoratto, F, Fiorio, E, Fabbri, M, Mazzotta, M, Ruggeri, E, Pedersini, R, Valerio, M, Filomeno, L, Minelli, M, Scavina, P, Raffaele, M, Astone, A, De Vita, R, Pozzi, M, Riccardi, F, Greco, F, Moscetti, L, Giordano, M, Maugeri-Sacca, M, Zennaro, A, Botti, C, Pelle, F, Cappelli, S, Cavicchi, F, Vizza, E, Sanguineti, G, Tomao, F, Cortesi, E, Marchetti, P, Tomao, S, Speranza, I, Sperduti, I, Ciliberto, G, Vici, P, Di Lisa F. S., Krasniqi E., Pizzuti L., Barba M., Cannita K., De Giorgi U., Borella F., Foglietta J., Cariello A., Ferro A., Picardo E., Mitidieri M., Sini V., Stani S., Tonini G., Santini D., La Verde N., Gambaro A. R., Grassadonia A., Tinari N., Garrone O., Sarobba G., Livi L., Meattini I., D'Auria G., Vergati M., Gamucci T., Pistelli M., Berardi R., Risi E., Giotta F., Lorusso V., Rinaldi L., Artale S., Cazzaniga M. E., Zustovich F., Cappuzzo F., Landi L., Torrisi R., Scagnoli S., Botticelli A., Michelotti A., Fratini B., Saltarelli R., Paris I., Muratore M., Cassano A., Gianni L., Gaspari V., Veltri E. M., Zoratto F., Fiorio E., Fabbri M. A., Mazzotta M., Ruggeri E. M., Pedersini R., Valerio M. R., Filomeno L., Minelli M., Scavina P., Raffaele M., Astone A., De Vita R., Pozzi M., Riccardi F., Greco F., Moscetti L., Giordano M., Maugeri-Sacca M., Zennaro A., Botti C., Pelle F., Cappelli S., Cavicchi F., Vizza E., Sanguineti G., Tomao F., Cortesi E., Marchetti P., Tomao S., Speranza I., Sperduti I., Ciliberto G., Vici P., Di Lisa, F, Krasniqi, E, Pizzuti, L, Barba, M, Cannita, K, De Giorgi, U, Borella, F, Foglietta, J, Cariello, A, Ferro, A, Picardo, E, Mitidieri, M, Sini, V, Stani, S, Tonini, G, Santini, D, La Verde, N, Gambaro, A, Grassadonia, A, Tinari, N, Garrone, O, Sarobba, G, Livi, L, Meattini, I, D'Auria, G, Vergati, M, Gamucci, T, Pistelli, M, Berardi, R, Risi, E, Giotta, F, Lorusso, V, Rinaldi, L, Artale, S, Cazzaniga, M, Zustovich, F, Cappuzzo, F, Landi, L, Torrisi, R, Scagnoli, S, Botticelli, A, Michelotti, A, Fratini, B, Saltarelli, R, Paris, I, Muratore, M, Cassano, A, Gianni, L, Gaspari, V, Veltri, E, Zoratto, F, Fiorio, E, Fabbri, M, Mazzotta, M, Ruggeri, E, Pedersini, R, Valerio, M, Filomeno, L, Minelli, M, Scavina, P, Raffaele, M, Astone, A, De Vita, R, Pozzi, M, Riccardi, F, Greco, F, Moscetti, L, Giordano, M, Maugeri-Sacca, M, Zennaro, A, Botti, C, Pelle, F, Cappelli, S, Cavicchi, F, Vizza, E, Sanguineti, G, Tomao, F, Cortesi, E, Marchetti, P, Tomao, S, Speranza, I, Sperduti, I, Ciliberto, G, Vici, P, Di Lisa F. S., Krasniqi E., Pizzuti L., Barba M., Cannita K., De Giorgi U., Borella F., Foglietta J., Cariello A., Ferro A., Picardo E., Mitidieri M., Sini V., Stani S., Tonini G., Santini D., La Verde N., Gambaro A. R., Grassadonia A., Tinari N., Garrone O., Sarobba G., Livi L., Meattini I., D'Auria G., Vergati M., Gamucci T., Pistelli M., Berardi R., Risi E., Giotta F., Lorusso V., Rinaldi L., Artale S., Cazzaniga M. E., Zustovich F., Cappuzzo F., Landi L., Torrisi R., Scagnoli S., Botticelli A., Michelotti A., Fratini B., Saltarelli R., Paris I., Muratore M., Cassano A., Gianni L., Gaspari V., Veltri E. M., Zoratto F., Fiorio E., Fabbri M. A., Mazzotta M., Ruggeri E. M., Pedersini R., Valerio M. R., Filomeno L., Minelli M., Scavina P., Raffaele M., Astone A., De Vita R., Pozzi M., Riccardi F., Greco F., Moscetti L., Giordano M., Maugeri-Sacca M., Zennaro A., Botti C., Pelle F., Cappelli S., Cavicchi F., Vizza E., Sanguineti G., Tomao F., Cortesi E., Marchetti P., Tomao S., Speranza I., Sperduti I., Ciliberto G., and Vici P.

Abstract

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning ef

Published
2023

13. Average Absorbed Breast Dose (2ABD) to Mean Glandular Dose (MGD) Conversion Function for Digital Breast Tomosynthesis: A New Approach

Author

‪Raffaele M Tucciariello, Rocco Lamastra, Patrizio Barca, Marine Evelina Fantacci, and Antonio C Traino

Subjects
Digital breast tomosybthesis, Breast dosimetry, Absorbed breast dose, Mean glandular dose, Average glandular dose, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: In this work a new method for the Mean Glandular Dose evaluation in digital breast tomosynthesis (DBT) is presented. Methods: Starting from the experimental-based dosimetric index, 2ABD, which represents the average absorbed breast dose, the mean glandular dose MGD2ABD was calculated using a conversion function of glandularity f(G), obtained through the use of Monte Carlo simulations. Results: f(G) was computed for a 4.5 cm thick breast: from its value MGD2ABD for different compressed breast thicknesses and glandularities was obtained. The comparison between MGD2ABD estimates and the dosimetric index provided in the current dosimetry protocols, following the Dance's approach, MGDDance, showed a good agreement (

Published
2021
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16. Detection of cell-free histones in the cerebrospinal fluid of pediatric central nervous system malignancies by imaging flow cytometry

Author

Buzova, D, Frohlich, J, Zapletalova, D, Raffaele, M, Lo Re, O, Tsoneva, DK, Sterba, J, Cerveny, J, Vinciguerra, M, Buzova, D, Frohlich, J, Zapletalova, D, Raffaele, M, Lo Re, O, Tsoneva, DK, Sterba, J, Cerveny, J, and Vinciguerra, M

Abstract

Introduction: Pediatric brain tumours (PBT) are one of the most common malignancies during childhood, with variable severity according to the location and histological type. Certain types of gliomas, such a glioblastoma and diffuse intrinsic pontine glioma (DIPG), have a much higher mortality than ependymoma and medulloblastoma. Early detection of PBT is essential for diagnosis and therapeutic interventions. Liquid biopsies have been demonstrated using cerebrospinal fluid (CSF), mostly restricted to cell free DNA, which display limitations of quantity and integrity. In this pilot study, we sought to demonstrate the detectability and robustness of cell free histones in the CSF.Methods: We collected CSF samples from a pilot cohort of 8 children with brain tumours including DIPG, medulloblastoma, glioblastoma, ependymoma and others. As controls, we collected CSF samples from nine children with unrelated blood malignancies and without brain tumours. We applied a multichannel flow imaging approach on ImageStream(X) to image indiviual histone or histone complexes on different channels.Results: Single histones (H2A, macroH2A1.1, macroH2A1.2 H2B, H3, H4 and histone H3 bearing the H3K27M mutation), and histone complexes are specifically detectable in the CSF of PBT patients. H2A and its variants macroH2A1.1/macroH2A1/2 displayed the strongest signal and abundance, together with disease associated H3K27M. In contrast, mostly H4 is detectable in the CSF of pediatric patients with blood malignancies.Discussion: In conclusion, free histones and histone complexes are detectable with a strong signal in the CSF of children affected by brain tumours, using ImageStream(X) technology and may provide additive diagnostic and predictive information.

Published
2023

19. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author

Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Enia G., Giussani G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., Lattanzi S., La N. A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F. G. S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., Bravar G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Enia G., Giussani G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., Lattanzi S., La N. A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F. G. S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., and Bravar G.

Abstract

Objective: The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods: This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results: Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of

Published
2021

20. Average Absorbed Breast Dose (2ABD) to Mean Glandular Dose (MGD) Conversion Function for Digital Breast Tomosynthesis: A New Approach

Author

Marine Evelina Fantacci, Raffaele M. Tucciariello, Antonio C. Traino, Patrizio Barca, and Rocco Lamastra

Subjects
Materials science, business.industry, Monte Carlo method, Breast dosimetry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Conversion function, General Medicine, Digital Breast Tomosynthesis, Average glandular dose, Absorbed breast dose, Dose assessment, Dosimetry, Digital breast tomosybthesis, Mean glandular dose, Nuclear medicine, business, RC254-282
Abstract

Background: In this work a new method for the Mean Glandular Dose evaluation in digital breast tomosynthesis (DBT) is presented. Methods: Starting from the experimental-based dosimetric index, 2ABD, which represents the average absorbed breast dose, the mean glandular dose MGD2ABD was calculated using a conversion function of glandularity f(G), obtained through the use of Monte Carlo simulations.Results: f(G) was computed for a 4.5 cm thick breast: from its value MGD2ABD for different compressed breast thicknesses and glandularities was obtained. The comparison between MGD2ABD estimates and the dosimetric index provided in the current dosimetry protocols, following the Dance's approach, MGDDance, showed a good agreement (

Published
2021
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21. Profiling of cell-free DNA methylation and histone signatures in pediatric NAFLD: A pilot study

Author

Buzova, D, Braghini, MR, Bianco, SD, Lo Re, O, Raffaele, M, Frohlich, J, Kisheva, A, Crudele, A, Mosca, A, Sartorelli, MR, Balsano, C, Cerveny, J, Mazza, T, Alisi, A, and Vinciguerra, M

Subjects
Histones, Adolescent, Non-alcoholic Fatty Liver Disease, Humans, Membrane Proteins, Pilot Projects, Lipase, DNA Methylation, Child, Cell-Free Nucleic Acids
Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and adolescents, increasing the risk of its progression toward nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. There is an urgent need for noninvasive early diagnostic and prognostic tools such as epigenetic marks (epimarks), which would replace liver biopsy in the future. We used plasma samples from 67 children with biopsy-proven NAFLD, and as controls we used samples from 20 children negative for steatosis by ultrasound. All patients were genotyped for patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O-acyltransferase domain containing 7 (MBOAT7), and klotho-β (KLB) gene variants, and data on anthropometric and biochemical parameters were collected. Furthermore, plasma cell-free DNA (cfDNA) methylation was quantified using a commercially available kit, and ImageStream(X) was used for the detection of free circulating histone complexes and variants. We found a significant enrichment of the levels of histone macroH2A1.2 in the plasma of children with NAFLD compared to controls, and a strong correlation between cfDNA methylation levels and NASH. Receiver operating characteristic curve analysis demonstrated that combination of cfDNA methylation, PNPLA3 rs738409 variant, coupled with either high-density lipoprotein cholesterol or alanine aminotransferase levels can strongly predict the progression of pediatric NAFLD to NASH with area under the curve >0.87. Conclusion: Our pilot study combined epimarks and genetic and metabolic markers for a robust risk assessment of NAFLD development and progression in children, offering a promising noninvasive tool for the consistent diagnosis and prognosis of pediatric NAFLD. Further studies are necessary to identify their pathogenic origin and function.

Published
2022

22. The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study

Author

Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Giussani G., Enia G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., La Neve A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F., Galletta S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., Bravar G., Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Giussani G., Enia G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., La Neve A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F., Galletta S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., and Bravar G.

Abstract

Purpose: The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods: In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results: Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion: Patients and physicians' priorities in the mana

Published
2020

24. Navigating Human Immunodeficiency Virus Screening Recommendations for People on Pre-Exposure Prophylaxis and the Need to Update Testing Algorithms

Author

Meyerowitz, Eric A, primary, Bernardo, Raffaele M, additional, Collins-Ogle, Michelle D, additional, Czeresnia, Jonathan M, additional, Matos, Cariane M, additional, Mullis, Caroline, additional, Root, Heather B, additional, Torres-Isasiga, Julián A, additional, Tsai, Helen, additional, and Zingman, Barry S, additional

Published
2022
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25. Navigating Human Immunodeficiency Virus Screening Recommendations for People on Pre-Exposure Prophylaxis and the Need to Update Testing Algorithms

Author

Eric A Meyerowitz, Raffaele M Bernardo, Michelle D Collins-Ogle, Jonathan M Czeresnia, Cariane M Matos, Caroline Mullis, Heather B Root, Julián A Torres-Isasiga, Helen Tsai, and Barry S Zingman

Subjects
Infectious Diseases, Oncology, virus diseases
Abstract

Incident HIV infections occurring in people on PrEP may have delayed seroconversion. New CDC guidelines recommend the addition of HIV-1 viral load for screening for all on PrEP. We believe antigen/antibody screening should continue for tenofovir-based PrEP at this time.

Published
2022

27. A 35-Year-Old Man With An Itch

Author

Raffaele M Bernardo and Eric A. Meyerowitz

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, Infectious Diseases, business.industry, Pruritus, Medicine, Humans, business, Dermatology
Published
2021

32. Eribulin Mesylate as Third or Subsequent Line Chemotherapy for Elderly Patients with Locally Recurrent or Metastatic Breast Cancer: A Multicentric Observational Study of GIOGer (Italian Group of Geriatric Oncology)-ERIBE

Author

Leo, S, Arnoldi, E, Repetto, L, Coccorullo, Z, Cinieri, S, Fedele, P, Cazzaniga, M, Lorusso, V, Latorre, A, Campanella, G, Ciccarese, M, Accettura, C, Pisconti, S, Rinaldi, A, Brunetti, C, Raffaele, M, Coltelli, L, Spazzapan, S, Fratino, L, Petrucelli, L, Biganzoli, L, Leo S., Arnoldi E., Repetto L., Coccorullo Z., Cinieri S., Fedele P., Cazzaniga M., Lorusso V., Latorre A., Campanella G., Ciccarese M., Accettura C., Pisconti S., Rinaldi A., Brunetti C., Raffaele M., Coltelli L., Spazzapan S., Fratino L., Petrucelli L., Biganzoli L., Leo, S, Arnoldi, E, Repetto, L, Coccorullo, Z, Cinieri, S, Fedele, P, Cazzaniga, M, Lorusso, V, Latorre, A, Campanella, G, Ciccarese, M, Accettura, C, Pisconti, S, Rinaldi, A, Brunetti, C, Raffaele, M, Coltelli, L, Spazzapan, S, Fratino, L, Petrucelli, L, Biganzoli, L, Leo S., Arnoldi E., Repetto L., Coccorullo Z., Cinieri S., Fedele P., Cazzaniga M., Lorusso V., Latorre A., Campanella G., Ciccarese M., Accettura C., Pisconti S., Rinaldi A., Brunetti C., Raffaele M., Coltelli L., Spazzapan S., Fratino L., Petrucelli L., and Biganzoli L.

Abstract

Background: Metastatic breast cancer (MBC) is highly prevalent in middle-aged or elderly patients. Eribulin is a nontaxane microtubule inhibitor, approved for the treatment of pretreated MBC. This multicentric study (sponsored by GIOGer, Italian Group for Geriatric Oncology) was designed to assess the efficacy and tolerability of eribulin, according to parameters usually used in geriatric oncology. Subjects, Materials, and Methods: An observational study was conducted on 50 consecutive elderly patients with MBC. The primary endpoint was to evaluate the change in items score of comprehensive geriatric assessment (CGA) and health-related quality of life (HRQL). Italian versions of the CGA and HRQL questionnaires were administered at baseline, before the third and fifth cycles, and then every three cycles until treatment discontinuation. Secondary endpoints were efficacy and safety. Results: Overall, both EQ-5D scores and EQ-5D-3 L visual analogic scale did not significantly change from baseline; the percentage of subjects without problems doing usual activities tended to decrease during treatment (p for linear trend.018), and the percentage of patients with minor problems performing usual activities tended to increase (p for linear trend.012). Among CGA items, Instrumental Activities of Daily Living tended to decrease during treatment and Geriatric Depression Scale tended to increase. After 12 months follow-up, 24 patients (out of 47) showed clinical benefits; median progression-free survival was 4.49 months (2.10–10.33) and median OS was 7.31 months (3.70–14.03). The treatment was associated with mild toxicity. Conclusion: Eribulin treatment preserved quality of life and geriatric parameters included in the CGA, except for instrumental functioning and geriatric depression, in elderly patients with MBC. Implications for Practice: A collaboration between oncologist and geriatric specialists is essential in the management of patients with metastatic breast cancer, who a

Published
2019

34. Comprehensive assessment of image quality in synthetic and digital mammography: a quantitative comparison

Author

Raffaele M. Tucciariello, A. C. Traino, Maria Evelina Fantacci, Giacomo Aringhieri, Rocco Lamastra, and Patrizio Barca

Subjects
Digital mammography, Image quality, Computer science, Biomedical Engineering, Biophysics, Contrast Media, General Physics and Astronomy, Signal-To-Noise Ratio, Contrast-detail analysis, Digital breast tomosynthesis, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Optical transfer function, Humans, Radiology, Nuclear Medicine and imaging, Image resolution, Synthetic mammography, Phantoms, Imaging, business.industry, C-view™, Pattern recognition, Digital Breast Tomosynthesis, Radiographic Image Enhancement, 030220 oncology & carcinogenesis, Absorbed dose, Female, Noise (video), Artificial intelligence, business, Algorithms, Mammography
Abstract

Recent advances in digital breast tomosynthesis (DBT) technology were focused on the reconstruction of 2D "Synthesized Mammograms" (SMs) from DBT dataset. The introduction of SMs could avoid an additional digital mammography (DM) which is often required in complement to DBT examinations. Therefore, breast absorbed dose and compression time can be significantly reduced in DBT+SM procedures with respect to DBT+DM modality. However, to date, a limited number of studies have objectively characterised the image quality of SMs with respect to DM images. Therefore, the aim of this phantom study was to comprehensively compare SMs and DM images in terms of several image quality parameters. A Selenia Dimensions system (Hologic, Bedford, Mass, USA) was employed in this work. Five different phantoms were adopted to study noise, contrast and spatial resolution properties of the images. Specifically, noise power spectrum (NPS), maps of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), modulation transfer function (MTF) and contrast-detail (CD) thresholds were evaluated both for SM and DM modalities. SMs were characterised by different texture, noise and SNR spatial distribution properties with respect to DM images. Additionally, while in some conditions SM provides higher CNR than DM, lower overall performances in terms spatial resolution and CD curves were found in comparison to DM images. Therefore, given the great benefits of SMs in terms of dose and compression time saving, further clinical investigations on SMs image quality properties could be of practical interest to integrate our findings.

Published
2019
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35. Safety profile of enhanced thromboprophylaxis strategies for critically ill COVID-19 patients during the first wave of the pandemic: observational report from 28 European intensive care units

Author

Lavinio, A., Ercole, A., Battaglini, D., Magnoni, S., Badenes, R., Taccone, F. S., Helbok, R., Thomas, W., Pelosi, P., Robba, C., Innerhofer, N., Miori, S., Librizzi, A., Bertuetti, R., Faria, N. F., Peluso, L., Montrucchio, G., Sales, G., Brazzi, L., Alampi, D., Manca, M. B., Sepe, L., Natalini, G., Bellino, A., Bocci, M. G., Mattana, C., Corradi, F., Forfori, F., Cundari, F., Bonvecchio, E., Busani, Z., Bianchin, A., Federico, C., Santoro, A., Bilotta, F., Rajani, G., Lopez, B. M., Aspide, R., Raffaele, M., Cabrini, L., Motta, A., Frattini, L., Godon, A., Bouzat, P., Grappa, E., Bonvecchio, A., Fries, D., Hernandez, C. P., Thome, C., Klein, S., Joannidis, M., Ball, L., Patroniti, N., Brunetti, I., Bassetti, M., Giacobbe, D. R., Vena, A., Valbusa, A., Porto, I., Bona, R. D., Badenes, Rafael [0000-0001-7017-0150], and Apollo - University of Cambridge Repository

Subjects
Male, Soins intensifs réanimation, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 01 natural sciences, Anticoagulation, COVID-19, Heparin, Intensive care medicine, Prophylaxis, Thrombosis, Adult, Aged, Aged, 80 and over, Anticoagulants, Critical Care, Critical Illness, Europe, Female, Humans, Intensive Care Units, Middle Aged, Treatment Outcome, Venous Thromboembolism, Pandemics, law.invention, 010104 statistics & probability, 0302 clinical medicine, law, 80 and over, Medical emergencies. Critical care. Intensive care. First aid, Intensive care unit, Pulmonary embolism, Cohort, Median body, medicine.medical_specialty, 03 medical and health sciences, Intensive care, medicine, 0101 mathematics, business.industry, RC86-88.9, Research, medicine.disease, COVID-19 Drug Treatment, Clinical trial, Emergency medicine, Observational study, business
Abstract

INTRODUCTION: Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. METHODS: Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. RESULTS: A total of 852 (79% male, age 66 [37-85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1-30.7) Kg/m2 and 13 (7-22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18-1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI - 0.591 to - 0.964; p = 0.64]). CONCLUSIONS: In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

37. Implant of Self-Expandable Artificial Anal Sphincter in Patients With Fecal Incontinence Improves External Anal Sphincter Contractility

Author

Litta, Francesco M. D. 1, Marra, Angelo A. M. D. 1, Ortega Torrecilla, Nuria M. D. 2, Orefice, Raffaele M. D. 1, Parello, Angelo M. D. 1, De Simone, Veronica M. D. 1, Campennì, Paola M. D. 1, Goglia, Marta, and Ratto Carlo M. D. 1, 3

Subjects
Artificial anal sphincter , Contractility , Fecal incontinence , SphinKeeper, Fecal incontinence, SphinKeeper, Contractility, Artificial anal sphincter
Published
2021

38. Voxelized breast phantoms for dosimetry in mammography

Author

Rocco Lamastra, Alessandra Retico, A. C. Traino, Antonio Sarno, Paolo Russo, Giovanni Mettivier, Maria Evelina Fantacci, Raffaele M. Tucciariello, D. Del Sarto, Patrizio Barca, Fantacci, M., Traino, A., Sarno, A., Russo, P., Retico, A., Mettivier, G., Lamastra, R., Sarto, D., Barca, P., and Tucciariello, R.

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Digital Mammography, GEANT4, Heterogeneous Breast Phantoms, Monte Carlo Simulations, Voxelized Phantoms, X-Ray Breast Dosimetry, medicine, Dosimetry, Mammography, Monte Carlo Simulations, Digital Mammography, X-Ray Breast Dosimetry, Voxelized Phantoms, Heterogeneous Breast Phantoms, GEANT4, Medical physics, business
Abstract

X-ray breast imaging techniques are an essential part of breast cancer screening programs and their improvements lead to gain in performance and accuracy. Radiation dose estimate and control play an important role in digital mammography and digital breast tomosynthesis investigations, since the risk of radioinduced cancer to the gland must be contained and dose delivered to the gland must be declared in the medical report. The actual dosimetric protocols suggest the assessment of radiation dose by means of Monte Carlo calculation on digital breast phantoms, providing the assumption of the homogeneous mixture of glandular and adipose tissues within the breast organ, leading to a drastic approximation. In line with the trend of other research groups, with the aim of improving the Monte Carlo model, in the current work a new heterogeneous digital breast model is proposed, involving a voxelized approach and disengaging from the concept of homogeneous phantom. The proposed model is based on new findings in the literature and after a validation process, the model is adopted to evaluate mean glandular dose discrepancies with the traditional model which is adopted in clinic for decades.

Published
2021

39. Technical evaluation of image quality in synthetic mammograms obtained from 15° and 40° digital breast tomosynthesis in a commercial system: a quantitative comparison

Author

Davide Caramella, Carolina Marini, Maria Evelina Fantacci, Raffaele M. Tucciariello, Giacomo Aringhieri, Patrizio Barca, Antonio C. Traino, and Rocco Lamastra

Subjects
Synthetic mammogram, Digital mammography, S-view, Computer science, Image quality, media_common.quotation_subject, Biomedical Engineering, Biophysics, Signal-To-Noise Ratio, Imaging phantom, Digital breast tomosynthesis, Wide angle DBT, Optical transfer function, medicine, Mammography, Contrast (vision), Humans, Radiology, Nuclear Medicine and imaging, Instrumentation, Image resolution, Early Detection of Cancer, media_common, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Phantoms, Imaging, Calcinosis, Pattern recognition, Artificial intelligence, Noise (video), business, Biotechnology
Abstract

Digital breast tomosynthesis (DBT) has recently gained interest both for breast cancer screening and diagnosis. Its employment has increased also in conjunction with digital mammography (DM), to improve cancer detection and reduce false positive recall rate. Synthetic mammograms (SMs) reconstructed from DBT data have been introduced to replace DM in the DBT + DM approach, for preserving the benefits of the dual-acquisition modality whilst reducing radiation dose and compression time. Therefore, different DBT models have been commercialized and the effective potential of each system has been investigated. In particular, wide-angle DBT was shown to provide better depth resolution than narrow-angle DBT, while narrow-angle DBT allows better identification of microcalcifications compared to wide-angle DBT. Given the increasing employment of SMs as supplement to DBT, a comparison of image quality between SMs obtained in narrow-angle and wide-angle DBT is of practical interest. Therefore, the aim of this phantom study was to evaluate and compare the image quality of SMs reconstructed from 15° (SM15) and 40° (SM40) DBT in a commercial system. Spatial resolution, noise and contrast properties were evaluated through the modulation transfer function (MTF), noise power spectrum, maps of signal-to-noise ratio (SNR), image contrast, contrast-to-noise ratio (CNR) and contrast-detail (CD) thresholds. SM40 expressed higher MTF than SM15, but also lower SNR and CNR levels. SM15 and SM40 were characterized by slight different texture, and a different behavior in terms of contrast was found. SM15 provided better CD performances than SM40. These results suggest that the employment of wide/narrow-angle DBT + SM images should be optimized based on the specific image task.

Published
2020

40. Advanced Monte Carlo application for in-silico clinical trials in x-ray breast imaging

Author

Gianfranco Paternò, Giovanni Mettivier, F. di Franco, M. E. Fantacci, Kristina Bliznakova, P. Cardarelli, Angelo Taibi, Antonio Sarno, A. H. Hernandez, John M. Boone, Raffaele M. Tucciariello, Paolo Russo, Van Ongeval, Chantal, Sarno, A., Mettivier, G., Di Franco, F., Paterno, G., Taibi, A., Cardarelli, P., Tucciariello, R. M., Fantacci, M. E., Bliznakova, K., Hernandez, A. H., Boone, J. M., and Russo, P.

Subjects
Virtual clinical trials, DBT, BCT, mammography, x-ray breast imaging, Monte Carlo, patient-like phantoms, medicine.medical_specialty, x-ray breast imaging, Digital mammography, medicine.diagnostic_test, Breast imaging, business.industry, In silico clinical trials, mammography, Patient-like phantom, Virtual clinical trial, Socio-culturale, DBT, Imaging phantom, BCT, Spectral imaging, Uncompressed video, Software, medicine, Mammography, Medical physics, Virtual clinical trials, business, Monte Carlo, patient-like phantoms
Abstract

In silico reproductions of clinical exams represent an alternative strategy in the research and development of medical devices, which permit to avoid issues and costs related to clinical trials on patient population. In this work, we present a platform for virtual clinical trials in 2D and 3D x-ray breast imaging. The platform, developed by the medical physics team at University of Naples, Italy, permits to simulate digital mammography (DM), digital breast tomosynthesis (DBT) and CT dedicated to the breast (BCT) examinations. It relies on Monte Carlo simulations based on Geant4 toolkit and adopts digital models of patients derived from high-resolution 3D clinical breast images acquired at UC Davis, USA. Uncompressed digital breast models for BCT exam simulations were produced by means of a tissue classification algorithm; the compressed digital breast models for simulating DM and DBT are derived by the uncompressed ones via a simulated tissue compression. For a selected exam, specifications and digital patient, the platform computes breast image projections and glandular dose maps within the organ. Energy integrating a well as photon counting and spectral imaging detection scheme have been simulated. The current version of the software uses the Geant4 standard physics list Option4 and simulates and tracks

Published
2020

42. 3D Printing Materials for Physical Breast Phantoms: Monte Carlo Assessment and Experimental Validation

Author

Rocco Lamastra, Davide Caramella, Alessandra Retico, Maria Evelina Fantacci, Raffaele M. Tucciariello, Patrizio Barca, and A. C. Traino

Subjects
XR-QA2, Computer science, business.industry, 3D-printing Materials, Monte Carlo method, Radiochromic Films, 3D printing, Experimental validation, Breast Phantoms, Digital Mammography, Monte Carlo Simulations, Dosimetry, GEANT4, RADIOMA, business, Simulation
Published
2020
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43. Average absorbed breast dose (2ABD): an easy radiation dose index for digital breast tomosynthesis

Author

Davide Caramella, Giacomo Aringhieri, Carolina Marini, A. C. Traino, Raffaele M. Tucciariello, Rocco Lamastra, Maria Evelina Fantacci, Chiara Sottocornola, and Patrizio Barca

Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine, lcsh:R895-920, Breast Neoplasms, Radiation Dosage, Imaging phantom, Digital breast tomosynthesis, Kerma, X-rays, medicine, Humans, Mammography, Radiology, Nuclear Medicine and imaging, Breast, Mathematics, medicine.diagnostic_test, Phantoms, Imaging, business.industry, Radiation dose, Ultrasound, Digital Breast Tomosynthesis, Homogeneous, Absorbed dose, Female, Original Article, Phantoms (imaging), business, Nuclear medicine
Abstract

Background To propose a practical and simple method to individually evaluate the average absorbed dose for digital breast tomosynthesis. Methods The method is based on the estimate of incident air kerma (k a,i ) on the breast surface. An analytical model was developed to calculate the k a,i from the tube voltage, tube load, breast thickness, x-ray tube yield, and anode-filter combination. A homogeneous phantom was employed to simulate the breast in experimental measurements and to assess the dose-depth relationship. The k a,i values were employed to calculate the “average absorbed breast dose” (2ABD) index. Four mammographic units were used to develop and test our method under many conditions close to clinical settings. The average glandular dose (AGD) calculated following the method described by Dance et al., and the 2ABD computed through our method (i.e., from the exposure parameters) were compared in a number of conditions. Results A good agreement was obtained between the k a,i computed through our model and that measured under different clinical conditions: discrepancies < 6% were found in all conditions. 2ABD matches with a good accuracy the AGD for a 100% glandular-breast: the minimum, maximum, and mean differences were < 0.1%, 7%, and 2.4%, respectively; the discrepancies increase with decreasing breast glandularity. Conclusions The proposed model, based on only few exposure parameters, represents a simple way to individually calculate an index, 2ABD, which can be interpreted as the average absorbed dose in a homogeneous phantom, approximating a 100% glandular breast. The method could be easily implemented in any mammographic device performing DBT.

Published
2020

44. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author

Enia, G., Giussani, G., Bianchi, E., Mecarelli, O., Beghi, E., Pulitano, P., Cagnetti, C., Baldinelli, S., Lattanzi, S., La Neve, A., Tappata, M., Francavilla, T., De Maria, G., Sofia, V., Giuliano, L., Mainieri, G., Fatuzzo, D., Belcastro, V., Elia, M., D'Orsi, G., Lalla, A., Salmaggi, A., Brigo, F., Magaudda, A., Pisani, F., Galletta, S., Pisani, L. R., Raffaele, M., Cosenza, D., Villani, F. S., Quintas, R. M. M., Cervellione, R., Borroni, S., Meletti, S., Ferrarese, C., Barbella, G., Di Francesco, J., Bogliun, G., Beretta, S., Galimberti, C. A., Cantisani, T. A., Cecconi, M., Celani, M. G., Papetti, R., Giorgi, F. S., Aguglia, U., Gasparini, S., Ferlazzo, E., Manganotti, P., Crichiutti, G., Bravar, G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, and Bravar, G

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Concordance, Need, Disease, Epilepsy, Needs, Patients, Physicians, Priorities, Newly diagnosed epilepsy, Young Adult, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Seizures, Anticonvulsant, medicine, Humans, 030212 general & internal medicine, Young adult, Aged, Aged, 80 and over, Patient, Prioritie, business.industry, Middle Aged, Caregiver, medicine.disease, Seizure, Clinical Practice, Caregivers, Italy, Neurology, Physician, Recurrent seizures, Family medicine, Population study, Anticonvulsants, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract

Objective The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients. Significance Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.

Published
2021
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46. Advanced Monte Carlo application for in-silico clinical trials in x-ray breast imaging

Author

Sarno, Antonio, primary, Mettivier, Giovanni, additional, di Franco, Francesca, additional, Paternò, Gianfranco, additional, Taibi, Angelo, additional, Cardarelli, Paolo, additional, Tucciariello, Raffaele M., additional, Fantacci, Evelina, additional, Bliznakova, Kristina, additional, Hernandez, Andrew H., additional, Boone, John M., additional, and Russo, Paolo, additional

Published
2020
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49. Monte Carlo evaluation of glandular dose in cone-beam X-ray computed tomography dedicated to the breast: Homogeneous and heterogeneous breast models

Author

Francesca Di Lillo, John M. Boone, Kristina Bliznakova, Raffaele M. Tucciariello, Ioannis Sechopoulos, Antonio Sarno, Giovanni Mettivier, Paolo Russo, Sarno, Antonio, Mettivier, Giovanni, Tucciariello, Raffaele M., Bliznakova, Kristina, Boone, John M., Sechopoulos, Ioanni, Di Lillo, Francesca, and Russo, Paolo

Subjects
Materials science, Patient specific digital breast phantom, Biophysics, General Physics and Astronomy, Patient specific digital breast phantoms, Radiation Dosage, DgNCT, 030218 nuclear medicine & medical imaging, Physics and Astronomy (all), 03 medical and health sciences, Kerma, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, X ray computed, Breast CT, Radiology, Nuclear Medicine and imaging, Monte carlo evaluation, Breast, business.industry, Phantoms, Imaging, General Medicine, Patient specific, Cone-Beam Computed Tomography, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Biophysic, Homogeneous, 030220 oncology & carcinogenesis, Tomography, Mean glandular dose, Nuclear medicine, business, Half-value layer, Monte Carlo Method, Beam (structure)
Abstract

Purpose: In cone-beam computed tomography dedicated to the breast (BCT), the mean glandular dose (MGD) is the dose metric of reference, evaluated from the measured air kerma by means of normalized glandular dose coefficients (DgNCT). This work aimed at computing, for a simple breast model, a set of DgNCT values for monoenergetic and polyenergetic X-ray beams, and at validating the results vs. those for patient specific digital phantoms from BCT scans. Methods: We developed a Monte Carlo code for calculation of monoenergetic DgNCT coefficients (energy range 4.25–82.25 keV). The pendant breast was modelled as a cylinder of a homogeneous mixture of adipose and glandular tissue with glandular fractions by mass of 0.1%, 14.3%, 25%, 50% or 100%, enveloped by a 1.45 mmthick skin layer. The breast diameter ranged between 8 cm and 18 cm. Then, polyenergetic DgNCT coefficients were analytically derived for 49-kVp W-anode spectra (half value layer 1.25–1.50mm Al), as in a commercial BCT scanner. We compared the homogeneous models to 20 digital phantoms produced from classified 3D breast images. Results: Polyenergetic DgNCT resulted 13% lower than most recent published data. The comparison vs. patient specific breast phantoms showed that the homogeneous cylindrical model leads to a DgNCT percentage difference between −15% and +27%, with an average overestimation of 8%. Conclusions: A dataset of monoenergetic and polyenergetic DgNCT coefficients for BCT was provided. Patient specific breast models showed a different volume distribution of glandular dose and determined a DgNCT 8% lower, on average, than homogeneous breast model.

Published
2018

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