43 results on '"Pacella, G."'
Search Results
2. Prenatal diagnosis of isolated butterfly vertebra
- Author
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Youssef, A., Zagonari, S., Salsi, G., Saleem, S. N., Krsmanovic, J., Pacella, G., Ghi, T., Rizzo, N., and Pilu, G.
- Published
- 2014
- Full Text
- View/download PDF
3. Erice 2018 Charter on the role of the National Health Service in the prevention of doping
- Author
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Romano Spica, V., Di Rosa, E., Savino, G., Pasquarella, C., Liguori, G., Fallace, P., Tripi, F., Fara, G. M., Giammanco, G., Abbafati, E., Alonzo, E., Agostini, D., Aini, M. A., Ajese, P., Amore, G., Antonuccio, G., Assisi, E., Attisani, G., Belfiore, P., Belotti, D., Bernieri, F., Bernini, D., Bolognini, I., Bono, R., Brandimarte, M. A., Buzancic, S., Cala, P., Cagnin, R., Capua, G., Caruso, L., Cattaruzza, M. S., Cella, P., Ciotti, L., Cipolla, A. M., Colucci, M. E., Coppola, L., Covacci, V., Creola, G., Culcasi, S., D'Alterio, A., De Santi, M., Di Benedetto, F., Di Onofrio, V., Donati, A., Dozzini, G., Esposito, R., Fabbro, A., Falcone, M., Fara, T., Fardella, M., Favuzzi, N., Fioretti, E., Frangella, C., Galle, F., Ghizzoni, D., Giampietro, M., Giorgino, A., Grillone, L., Gradilone, A., Greco, S., Grosso, G., Guberti, E., Guida, F., La Carruba, R., La Sala, L., Cadua, E., Landi, A., Lemma, P., Leonardi, F., Lusi, A., Manfredi Selvaggi, T. M., Mandina, G., Marini, S., Mazzeo, F., Menegon, T., Mete, R., Milicia, M. G., Morgado, M., Morgantini, F., Napoli, M., Nucera, S., Occhipinti, V., Orsini, M., Pacella, G., Pacifici, R., Palmi, I., Pandolfi, R., Parisi, A., Parodi, G., Parodi, S., Pasquarella, M. L., Persi, Y., Petrai, G., Petrella, E., Pinelli, M., Pompei, D., Pompili, M., Postiglione, N., Ripani, M., Romano, F., Rondinelli, L., Ricchiuti, R., Ruggeri, J., Santini, A., Scatigna, M., Scuderi, M., Signorelli, C., Sticchi, C., Tamarri, F., Tancredi, S., Tumbarello, A., Ursino, S., Valeriani, F., Vino, F., Zanetti, C., Zotta, I., Zucca, E., Calimeri, S., Privitera, G., Fabiani, L., D'Aloisio, F., Baccari, G., Leoni, E., Tafuri, S., Brandi, G., Gervasi, G., Dell'Eva, A., La Torre, A., Romano Spica, V., Di Rosa, E., Savino, G., Pasquarella, C., Liguori, G., Fallace, P., Tripi, F., Fara, G. M., Giammanco, G., Abbafati, E., Alonzo, E., Agostini, D., Aini, M. A., Ajese, P., Amore, G., Antonuccio, G., Assisi, E., Attisani, G., Belfiore, P., Belotti, D., Bernieri, F., Bernini, D., Bolognini, I., Bono, R., Brandimarte, M. A., Buzancic, S., Calà, P., Cagnin, R., Capua, G., Caruso, L., Cattaruzza, M. S., Cella, P., Ciotti, L., Cipolla, A. M., Colucci, M. E., Coppola, L., Covacci, V., Creola, G., Culcasi, S., D'Alterio, A., De Santi, M., Di Benedetto, F., Di Onofrio, V., Donati, A., Dozzini, G., Esposito, R., Fabbro, A., Falcone, M., Fara, T., Fardella, M., Favuzzi, N., Fioretti, E., Frangella, C., Gallè, F., Ghizzoni, D., Giampietro, M., Giorgino, A., Grillone, L., Gradilone, A., Greco, S., Grosso, G., Guberti, E., Guida, F., La Carruba, R., La Sala, L., Cadua, E., Landi, A., Lemma, P., Leonardi, F., Lusi, A., Manfredi Selvaggi, T. M., Mandina, G., Marini, S., Mazzeo, F., Menegon, T., Mete, R., Milicia, M. G., Morgado, M., Morgantini, F., Napoli, M., Nucera, S., Occhipinti, V., Orsini, M., Pacella, G., Pacifici, R., Palmi, I., Pandolfi, R., Parisi, A., Parodi, G., Parodi, S., Pasquarella, M. L., Persi, Y., Petrai, G., Petrella, E., Pinelli, M., Pompei, D., Pompili, M., Postiglione, N., Ripani, M., Romano, F., Rondinelli, L., Ricchiuti, R., Ruggeri, J., Santini, A., Scatigna, M., Scuderi, M., Signorelli, C., Sticchi, C., Tamarri, F., Tancredi, S., Tumbarello, A., Ursino, S., Valeriani, F., Vino, F., Zanetti, C., Zotta, I., Zucca, E., Calimeri, S., Privitera, G., Fabiani, L., D'Aloisio, F., Baccari, G., Leoni, E., Tafuri, S., Brandi, G., Gervasi, G., Dell'Eva, A., and La Torre, A.
- Subjects
Doping in Sports ,Health Promotion ,Humans ,Italy ,State Medicine ,Public Health ,Department of Prevention ,Doping ,Physical Activity ,Sport ,Doping, Health Promotion, Physical Activity, Sport, Department of Prevention - Abstract
The Erice 2018 Charter was unanimously approved at the conclusion of the 53rd Residential Course of the International School of Epidemiology and Preventive Medicine “Adapted Physical Activity in Sport, Wellness and Fitness; the role of the Departments of Prevention and of the National Health Service in doping prevention and health promotion”, held on 15-19 May 2018 in Erice, Italy, at the “Ettore Majorana” Foundation and Centre for Scientific Culture, and promoted by the Study Group on “Movement Sciences for Health” of the Italian Society of Hygiene, Preventive Medicine and Public Health. The event was part of a larger project supported by the Ministry of Health aimed at preventing doping in the general population involved in sport and physical activities. After an intense discussion the participants focused on ten statements involving the following critical issues: responsibility, priority, message, alphabetization, networks and alliances, school promoting health, player and opportunities, competences, know-how, programming and acting. These statements provide hints to approach doping within a public health frame and summarize the role of the Departments of Prevention and NHS in promoting and coordinating preventive actions with other institutions and stakeholders. Doping represents a complex phenomenon related to cultural, social, economic and legal issues. In addition to regulatory or repressive actions, education to health and legality is proposed as the fundamental strategy to contrast doping by promoting healthy lifestyles, based on scientific knowledge and respect for legality.
- Published
- 2019
4. Il lavoro dei rider: una prospettiva psicologica
- Author
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Cori, E, Neri, M, Maggi, B, Vecchio, L, Pacella, G, Orciani, BM, Salento, A, Barbini, FM, Zamarian, M, Masino, G, Cori, E, Neri, M, Maggi, B, Vecchio, L, Pacella, G, Orciani, BM, Salento, A, Barbini, FM, Zamarian, M, and Masino, G
- Published
- 2021
5. Fundal pressure in second stage of labor (Kristeller maneuver) is associated with increased risk of levator ani muscle avulsion
- Author
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Youssef, A., primary, Salsi, G., additional, Cataneo, I., additional, Pacella, G., additional, Azzarone, C., additional, Paganotto, M. C., additional, Krsmanovic, J., additional, Montaguti, E., additional, Cariello, L., additional, Bellussi, F., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2018
- Full Text
- View/download PDF
6. Is curved three-dimensional ultrasound reconstruction needed to assess the warped pelvic floor plane?
- Author
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Youssef, A., primary, Cavalera, M., additional, Pacella, G., additional, Salsi, G., additional, Morganelli, G., additional, Montaguti, E., additional, Cataneo, I., additional, Pilu, G., additional, and Rizzo, N., additional
- Published
- 2017
- Full Text
- View/download PDF
7. OP04.02: Is a curved 3D ultrasound reconstruction needed to assess the “warped” pelvic floor plane?
- Author
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Youssef, A., primary, Salsi, G., additional, Pacella, G., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2016
- Full Text
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8. OC04.01: Does fundal pressure in the second stage (Kristeller manoeuvre) increase the risk of pelvic floor damage? A prospective case–control study
- Author
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Youssef, A., primary, Salsi, G., additional, Paganotto, M., additional, Bellussi, F., additional, Cataneo, I., additional, Pacella, G., additional, Azzarone, C., additional, Morganelli, G., additional, Krsmanovic, J., additional, Cariello, L., additional, Montaguti, E., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2016
- Full Text
- View/download PDF
9. Fundal pressure in second stage of labor (Kristeller maneuver) is associated with increased risk of levator ani muscle avulsion.
- Author
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Youssef, A., Salsi, G., Cataneo, I., Pacella, G., Azzarone, C., Paganotto, M. C., Krsmanovic, J., Montaguti, E., Cariello, L., Bellussi, F., Rizzo, N., and Pilu, G.
- Subjects
ANUS ,DELIVERY (Obstetrics) ,LABOR (Obstetrics) ,LABOR complications (Obstetrics) ,LONGITUDINAL method ,EVALUATION of medical care ,MUSCLES ,PELVIC floor ,PREGNANCY ,PRESSURE ,CASE-control method ,WOUNDS & injuries - Abstract
Objective: To investigate the association between application of fundal pressure during the second stage of labor (Kristeller maneuver) and the risk of levator ani muscle (LAM) injury.Methods: This was a prospective case-control study of women recruited immediately after their first vaginal delivery in our university hospital between March 2014 and September 2016. Women who underwent the Kristeller maneuver were recruited as cases. For each case, a control (no Kristeller) was recruited matched for body mass index, use of epidural analgesia, duration of second stage of labor and birth weight. All women were invited to undergo four-dimensional (4D) transperineal ultrasound (TPU) 3-6 months postpartum. The main outcome measure was the presence of LAM avulsion on 4D-TPU. TPU results were compared between cases and controls. Multivariate logistic regression analysis was performed to identify independent risk factors for LAM avulsion.Results: During the study period, 134 women in the Kristeller maneuver group and 128 women in the control group underwent TPU assessment. Women who underwent the Kristeller maneuver had a higher prevalence of LAM avulsion than did controls (38/134 (28.4%) vs 18/128 (14.1%); P = 0.005). In addition, women in the Kristeller-maneuver group had a larger hiatal area on maximum Valsalva maneuver and a greater increase in hiatal area from rest to maximum Valsalva. On multivariate logistic regression analysis, use of the Kristeller maneuver was the only independent factor associated with LAM avulsion (odds ratio, 2.5 (95% CI, 1.29-4.51)).Conclusion: The Kristeller maneuver is associated with an increased risk of LAM avulsion when applied in women during their first vaginal delivery. This should be taken into account when deciding to use fundal pressure to accelerate the second stage of labor and when counseling women following childbirth. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
10. EP01.13: A comparison between two 3D ultrasound contrast-enhancing techniques for subpubic arch angle measurement
- Author
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Youssef, A., primary, Bellussi, F., additional, Ghi, T., additional, Pacella, G., additional, Azzarone, C., additional, Salsi, G., additional, Montaguti, E., additional, Morganelli, G., additional, Krsmanovic, J., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2015
- Full Text
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11. EP01.12: A narrow subpubic arch angle is associated with a higher risk of persistent posterior occiput position
- Author
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Youssef, A., primary, Rizzo, G., additional, Martelli, F., additional, Krsmanovic, J., additional, Pacella, G., additional, Aiello, E., additional, Arduini, D., additional, Pilu, G., additional, Rizzo, N., additional, Frusca, T., additional, and Ghi, T., additional
- Published
- 2015
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- View/download PDF
12. P04.08: A comparison between two 3D ultrasound contrast-enhancing techniques for pelvic floor assessment
- Author
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Youssef, A., primary, Krsmanovic, J., additional, Salsi, G., additional, Pacella, G., additional, Azzarone, C., additional, Bellussi, F., additional, Montaguti, E., additional, Pilu, G., additional, and Rizzo, N., additional
- Published
- 2015
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- View/download PDF
13. P04.06: The effect of fundal pressure (Kristeller manoeuvre) on pelvic floor in primiparous women
- Author
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Youssef, A., primary, Pacella, G., additional, Salsi, G., additional, Krsmanovic, J., additional, Montaguti, E., additional, Morganelli, G., additional, Azzarone, C., additional, Paganotto, M., additional, Cataneo, I., additional, Cariello, L., additional, Pilu, G., additional, and Rizzo, N., additional
- Published
- 2015
- Full Text
- View/download PDF
14. OP20.06: Fetal smallness-for-gestational age is associated to reduced short-term variability following administration of betamethasone for fetal lung maturity
- Author
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Ghi, T., primary, Bellussi, F., additional, Mastellari, E., additional, Pacella, G., additional, Youssef, A., additional, Pilu, G., additional, Frusca, T., additional, and Rizzo, N., additional
- Published
- 2015
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15. OP27.02: Prenatal diagnosis of mature teratoma in an undescended testicle: two‐, three‐dimensional ultrasound and Doppler features
- Author
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Youssef, A., primary, Curti, A., additional, Bellussi, F., additional, Adel, N., additional, Pacella, G., additional, Morganelli, G., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2014
- Full Text
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16. P17.10: The subpubic angle measured by a novel three-dimensional ultrasound technique in nulliparous and parous women: a pilot study
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Gabrielli, S., primary, Youssef, A., additional, Martelli, F., additional, Pacella, G., additional, Pilu, G., additional, Rizzo, N., additional, and Ghi, T., additional
- Published
- 2014
- Full Text
- View/download PDF
17. OP03.10: Prenatal diagnosis vs 1st trimester screening of Trisomy 21 among pregnant women aged 35 or more
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Ghi, T., primary, Arcangeli, T., additional, Ravennati, F., additional, Salsi, G., additional, Montaguti, E., additional, Pacella, G., additional, Maroni, E., additional, Pittalis, M., additional, Pompilii, E., additional, Bellussi, F., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2014
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18. P01.08: Risk factors associated to fetal loss after chorionic villus sampling
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Ghi, T., primary, Bellussi, F., additional, Piastra, A., additional, Pini, R., additional, Contro, E., additional, Cariello, L., additional, Pacella, G., additional, Montaguti, E., additional, Salsi, G., additional, Di Giovanni, M., additional, Cataneo, I., additional, Gabrielli, S., additional, Rizzo, N., additional, and Pilu, G., additional
- Published
- 2014
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- View/download PDF
19. P13.15: Maternal diastolic function during twin pregnancies
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Youssef, A., primary, Degli Esposti, D., additional, Montaguti, E., additional, Rosticci, M., additional, Pacella, G., additional, Piastra, A., additional, Pilu, G., additional, Borghi, C., additional, Rizzo, N., additional, and Ghi, T., additional
- Published
- 2013
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20. Osservazioni di piccoli pianeti.
- Author
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Gennaro, A. and Pacella, G. B.
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- 1929
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21. Dos casos de Estrongilosis Renal en el perro
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Pacella, G. and Esquivel, R.
- Subjects
Estrongiloidiasis ,Enfermedades Renales ,Perros - Abstract
Fil: Pacella, G. Instituto Bacteriológico. Departamento Nacional de Higiene; Argentina
- Published
- 1922
22. Correzione dell'Orbita del pianetino 940 [1920 HT]
- Author
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Pacella, G. B., primary
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- 1929
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23. SURGICAL TREATMENT OF SPONTANEOUS EXTRAPLEURAL HAEMORRHAGE AND PULMONARY HERNIA: A CASE REPORT.
- Author
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ARDO, N. P., LOIZZI, D., PACELLA, G., CIALDELLA, F., and SOLLITTO, F.
- Published
- 2014
24. Il lavoro dei rider: una prospettiva psicologica
- Author
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Vecchio, L, Cori, E, Neri, M, Maggi, B, Vecchio, L, Pacella, G, Orciani, BM, Salento, A, Barbini, FM, Zamarian, M, and Masino, G
- Subjects
Gig economy, rider, lavoro atipico, digitalizzazione ,M-PSI/06 - PSICOLOGIA DEL LAVORO E DELLE ORGANIZZAZIONI - Published
- 2021
25. Fundal pressure in second stage of labor (Kristeller maneuver) is associated with increased risk of levator ani muscle avulsion
- Author
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Federica Bellussi, Nicola Rizzo, L. Cariello, Ginevra Salsi, J. Krsmanovic, G. Pacella, Gianluigi Pilu, Aly Youssef, Elisa Montaguti, C. Azzarone, M. Paganotto, I. Cataneo, Youssef, A., Salsi, G., Cataneo, I., Pacella, G., Azzarone, C., Paganotto, M.C., Krsmanovic, J., Montaguti, E., Cariello, L., Bellussi, F., Rizzo, N., and Pilu, G.
- Subjects
Radiology, Nuclear Medicine and Imaging ,medicine.medical_treatment ,Anal Canal ,Avulsion ,0302 clinical medicine ,Risk Factors ,Pregnancy ,pelvic floor ,Valsalva maneuver ,Medicine ,Childbirth ,030212 general & internal medicine ,Prospective Studies ,Obstetric Labor Complication ,030219 obstetrics & reproductive medicine ,Pelvic floor ,Radiological and Ultrasound Technology ,Obstetrics ,Vaginal delivery ,4D transperineal ultrasound ,Pregnancy Outcome ,Obstetrics and Gynecology ,General Medicine ,Pelvic Floor Disorder ,medicine.anatomical_structure ,Italy ,Female ,Case-Control Studie ,Human ,Adult ,medicine.medical_specialty ,Birth weight ,fundal pressure ,Kristeller maneuver ,Pelvic Floor Disorders ,03 medical and health sciences ,Labor Stage, Second ,Pressure ,Humans ,business.industry ,Risk Factor ,Odds ratio ,Delivery, Obstetric ,Obstetric Labor Complications ,Prospective Studie ,Reproductive Medicine ,Case-Control Studies ,levator ani muscle ,business ,Body mass index - Abstract
Objective: To investigate the association between application of fundal pressure during the second stage of labor (Kristeller maneuver) and the risk of levator ani muscle (LAM) injury. Methods: This was a prospective case–control study of women recruited immediately after their first vaginal delivery in our university hospital between March 2014 and September 2016. Women who underwent the Kristeller maneuver were recruited as cases. For each case, a control (no Kristeller) was recruited matched for body mass index, use of epidural analgesia, duration of second stage of labor and birth weight. All women were invited to undergo four-dimensional (4D) transperineal ultrasound (TPU) 3–6 months postpartum. The main outcome measure was the presence of LAM avulsion on 4D-TPU. TPU results were compared between cases and controls. Multivariate logistic regression analysis was performed to identify independent risk factors for LAM avulsion. Results: During the study period, 134 women in the Kristeller maneuver group and 128 women in the control group underwent TPU assessment. Women who underwent the Kristeller maneuver had a higher prevalence of LAM avulsion than did controls (38/134 (28.4%) vs 18/128 (14.1%); P = 0.005). In addition, women in the Kristeller-maneuver group had a larger hiatal area on maximum Valsalva maneuver and a greater increase in hiatal area from rest to maximum Valsalva. On multivariate logistic regression analysis, use of the Kristeller maneuver was the only independent factor associated with LAM avulsion (odds ratio, 2.5 (95% CI, 1.29–4.51)). Conclusion: The Kristeller maneuver is associated with an increased risk of LAM avulsion when applied in women during their first vaginal delivery. This should be taken into account when deciding to use fundal pressure to accelerate the second stage of labor and when counseling women following childbirth. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
- Published
- 2019
26. A simplified theoretical model for the evaluation of structural behaviour of masonry spandrels
- Author
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Bruno Calderoni, Gaetana Pacella, Pietro Lenza, Emilia Angela Cordasco, Calderoni, Bruno, Cordasco, Emilia Angela, Lenza, Pietro, and Pacella, G.
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Engineering ,Cracking ,Mechanics of Materials ,business.industry ,Mechanical Engineering ,Numerical analysis ,General Materials Science ,Structural engineering ,Masonry ,business - Abstract
In this paper, a simplified theoretical model (named 'the arched strut'), useful for the evaluation of the structural behaviour of masonry spandrels subjected to shear, is proposed. It has been defined on the basis of the results of both numerical and experimental analyses performed on reduced scale specimens. The numerical analysis has been carried out in order to obtain confirmation of the collapse mechanisms observed during the experiments and information which cannot be directly obtained from testing and is difficult to obtain theoretically too, such as the extension of the effective area at the edges of the panel and the value of the horizontal component of the force acting in the strut. By means of the proposed model, theoretical expressions corresponding to the different observed failure mechanisms (toe-crushing and tension cracking) have been formulated. Finally, both experimental and theoretical findings have been compared with the Italian code requirements.
- Published
- 2011
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27. Exploring the Efficacy of Combining Radiofrequency Thermal Ablation or Microwave Ablation with Vertebroplasty for Pain Control and Disease Management in Metastatic Bone Disease-A Systematic Review.
- Author
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Faiella E, Vaccarino F, Pacella G, Santucci D, Vergantino E, Bruno A, Ragone R, Zobel BB, and Grasso RF
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- Humans, Bone Neoplasms complications, Bone Neoplasms secondary, Bone Neoplasms therapy, Combined Modality Therapy, Spinal Neoplasms secondary, Spinal Neoplasms complications, Spinal Neoplasms surgery, Microwaves therapeutic use, Pain Management methods, Radiofrequency Ablation methods, Vertebroplasty methods
- Abstract
Background: Interventional radiology techniques have become pivotal in recent years in managing metastatic bone disease, which frequently results in skeletal complications such as fractures and severe pain. Thermoablative methods like radiofrequency ablation (RFA) and microwave ablation (MWA), when combined with vertebroplasty (VP), are proving increasingly beneficial for these patients., Methods: The search was independently conducted by two radiologists on MEDLINE databases, using specified strings up to April 2024. Methodological quality was assessed using PRISMA guidelines. Studies meeting inclusion criteria investigated thermoablation techniques (RFA and/or MWA) combined with VP, focusing on pain management and disease control outcomes in adults., Results: Among 147 results, 42 articles met the criteria, with varied prospective and retrospective designs and sample sizes averaging 49 patients, predominantly involving RFA (30 studies), MWA (11 studies), and one comparative study. Our review highlights significant pain reduction, effective local tumor control, and favorable safety of combined RFA or MWA with VP, supporting its potential in managing vertebral pathologies and warranting further clinical integration., Conclusions: The combined treatment of RFA/MWA with VP demonstrates significant pain reduction and local tumor control, with a rapid onset of analgesic effect. These findings support its crucial role in clinical practice for managing vertebral metastases.
- Published
- 2024
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28. Augmented Reality Navigation System (SIRIO) for Neuroprotection in Vertebral Tumoral Ablation.
- Author
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Faiella E, Casati R, Pileri M, Pacella G, Altomare C, Vergantino E, Bruno A, Beomonte Zobel B, and Grasso RF
- Subjects
- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Spinal Neoplasms surgery, Adult, Neuroprotection, Ablation Techniques methods, Treatment Outcome, Augmented Reality
- Abstract
(1) This study evaluates the impact of the CT-guided SIRIO augmented reality navigation system on the procedural efficacy and clinical outcomes of neuroprotection in vertebral thermal ablation (RTA) for primary and metastatic bone tumors. (2) Methods: A retrospective non-randomized analysis of 28 vertebral RTA procedures was conducted, comparing 12 SIRIO-assisted and 16 non-SIRIO-assisted procedures. The primary outcomes included dose-length product (DLP) and epidural dissection time. The secondary outcomes included technical success, complication rates, and pain scores at procedural time (VAS Time 0) and three months post-procedure (VAS Time 1). The statistical analyses included t-tests, Mann-Whitney U tests, and multiple regression. (3) Results: SIRIO-assisted procedures significantly reduced DLP (307.42 mGycm vs. 460.31 mGycm, p = 2.23 × 10
-8 ) and procedural epidural dissection time (13.48 min vs. 32.26 min, p = 2.61 × 10-12 ) compared to non-SIRIO-assisted procedures. Multiple regression confirmed these reductions were significant (DLP: β = -162.38, p < 0.001; time: β = -18.25, p < 0.001). Pain scores (VAS Time 1) did not differ significantly between groups, and tumor type did not significantly influence outcomes. (4) Conclusions: The SIRIO system enhances neuroprotection efficacy and safety, reducing radiation dose and procedural time during spine tumoral ablation while maintaining consistent pain management outcomes.- Published
- 2024
- Full Text
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29. The Rendezvous Technique: A Minimally Invasive Non-Surgical Approach for the Management of Iatrogenic Ureteral Injuries.
- Author
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Faiella E, Pacella G, Vergantino E, Santucci D, De Cicco Nardone C, Terranova C, Plotti F, Angioli R, Beomonte Zobel B, and Grasso RF
- Abstract
Background/Objectives : The aim of our study is to evaluate the feasibility and efficacy of the rendezvous technique for the treatment of iatrogenic ureteral injuries. Methods : From 2014 to 2019, 29 patients treated with the rendezvous technique for mono- or bilateral iatrogenic ureteral injuries were enrolled in this retrospective study. All the leaks were previously assessed by CT-urography and antegrade pyelography. Ureteral continuity was restored by performing the rendezvous technique, combining antegrade trans-nephrostomic access and a retrograde trans-cystostomic approach. A double J stent was antegradely inserted, and a nephrostomy tube was kept in place at the end of the procedure. A post-procedure CT-urography and a 30-day nephrostogram follow-up were performed. In the absence of a contrast leak, the nephrostomy tube was removed. Patient follow-up was set with CT-urography at 3, 6, and 12 months and stent substitution every 4 months. The CT-urography was performed to confirm the restored integrity of the ureter before stent removal. Results : The rendezvous technique was successful in all cases with the resolution of the ureteral leak. No major complications were observed. In all the patients, the nephrostomy tube was removed after 30 days. After performing CT-urography, the stent was removed permanently after 12 months. Only three cases showed local post-treatment stenosis treated with surgical ureteral reimplantation. Conclusions : The rendezvous technique is a safe and effective minimally invasive procedure that can be used to restore the continuity of the ureter, avoiding open surgery and providing valuable support for the management of complications after gynecological surgery.
- Published
- 2024
- Full Text
- View/download PDF
30. Future Perspectives on Radiomics in Acute Liver Injury and Liver Trauma.
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Brunese MC, Avella P, Cappuccio M, Spiezia S, Pacella G, Bianco P, Greco S, Ricciardelli L, Lucarelli NM, Caiazzo C, and Vallone G
- Abstract
Background : Acute liver injury occurs most frequently due to trauma, but it can also occur because of sepsis or drug-induced injury. This review aims to analyze artificial intelligence (AI)'s ability to detect and quantify liver injured areas in adults and pediatric patients. Methods : A literature analysis was performed on the PubMed Dataset. We selected original articles published from 2018 to 2023 and cohorts with ≥10 adults or pediatric patients. Results : Six studies counting 564 patients were collected, including 170 (30%) children and 394 adults. Four (66%) articles reported AI application after liver trauma, one (17%) after sepsis, and one (17%) due to chemotherapy. In five (83%) studies, Computed Tomography was performed, while in one (17%), FAST-UltraSound was performed. The studies reported a high diagnostic performance; in particular, three studies reported a specificity rate > 80%. Conclusions : Radiomics models seem reliable and applicable to clinical practice in patients affected by acute liver injury. Further studies are required to achieve larger validation cohorts.
- Published
- 2024
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31. Pancreatic Ductal Adenocarcinoma: Update of CT-Based Radiomics Applications in the Pre-Surgical Prediction of the Risk of Post-Operative Fistula, Resectability Status and Prognosis.
- Author
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Pacella G, Brunese MC, D'Imperio E, Rotondo M, Scacchi A, Carbone M, and Guerra G
- Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths worldwide. Surgical resection is the main driver to improving survival in resectable tumors, while neoadjuvant treatment based on chemotherapy (and radiotherapy) is the best option-treatment for a non-primally resectable disease. CT-based imaging has a central role in detecting, staging, and managing PDAC. As several authors have proposed radiomics for risk stratification in patients undergoing surgery for PADC, in this narrative review, we have explored the actual fields of interest of radiomics tools in PDAC built on pre-surgical imaging and clinical variables, to obtain more objective and reliable predictors., Methods: The PubMed database was searched for papers published in the English language no earlier than January 2018., Results: We found 301 studies, and 11 satisfied our research criteria. Of those included, four were on resectability status prediction, three on preoperative pancreatic fistula (POPF) prediction, and four on survival prediction. Most of the studies were retrospective., Conclusions: It is possible to conclude that many performing models have been developed to get predictive information in pre-surgical evaluation. However, all the studies were retrospective, lacking further external validation in prospective and multicentric cohorts. Furthermore, the radiomics models and the expression of results should be standardized and automatized to be applicable in clinical practice.
- Published
- 2023
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32. Mettl3-catalyzed m 6 A regulates histone modifier and modification expression in self-renewing somatic tissue.
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Maldonado López AM, Ko EK, Huang S, Pacella G, Kuprasertkul N, D'souza CA, Reyes Hueros RA, Shen H, Stoute J, Elashal H, Sinkfield M, Anderson A, Prouty S, Li HB, Seykora JT, Liu KF, and Capell BC
- Subjects
- Animals, Mice, Adenosine, Cell Adhesion, RNA, Messenger, Catalysis, Histones, Methyltransferases genetics
- Abstract
N6 -methyladenosine (m
6 A) is the most abundant modification on messenger RNAs (mRNAs) and is catalyzed by methyltransferase-like protein 3 (Mettl3). To understand the role of m6 A in a self-renewing somatic tissue, we deleted Mettl3 in epidermal progenitors in vivo. Mice lacking Mettl3 demonstrate marked features of dysfunctional development and self-renewal, including a loss of hair follicle morphogenesis and impaired cell adhesion and polarity associated with oral ulcerations. We show that Mettl3 promotes the m6 A-mediated degradation of mRNAs encoding critical histone modifying enzymes. Depletion of Mettl3 results in the loss of m6 A on these mRNAs and increases their expression and associated modifications, resulting in widespread gene expression abnormalities that mirror the gross phenotypic abnormalities. Collectively, these results have identified an additional layer of gene regulation within epithelial tissues, revealing an essential role for m6 A in the regulation of chromatin modifiers, and underscoring a critical role for Mettl3-catalyzed m6 A in proper epithelial development and self-renewal.- Published
- 2023
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33. Synthetic molecular motor activates drug delivery from polymersomes.
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Guinart A, Korpidou M, Doellerer D, Pacella G, Stuart MCA, Dinu IA, Portale G, Palivan C, and Feringa BL
- Subjects
- Fluorescent Dyes, Cell Line, Hydrophobic and Hydrophilic Interactions, Drug Carriers chemistry, Polymers chemistry, Drug Delivery Systems
- Abstract
The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS- b -PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.
- Published
- 2023
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34. Imaging of Ganglioneuroma: A Literature Review and a Rare Case of Cystic Presentation in an Adolescent Girl.
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Pacella G, Brunese MC, Donnarumma F, Barrassi M, Bellifemine F, Sciaudone G, Vallone G, Guerra G, and Sallustio G
- Abstract
Retroperitoneal ganglioneuroma is a rare neuroectodermal tumor with a benign nature. We performed a literature review among 338 studies. We included 9 studies, whose patients underwent CT and/or MRI to characterize a retroperitoneal mass, which was confirmed to be a ganglioneuroma by histologic exam. The most common features of ganglioneuroma are considered to be a solid nature, oval/lobulated shape, and regular margins. The ganglioneuroma shows a progressive late enhancement on CT. On MRI it appears as a hypointense mass in T1W images and with a heterogeneous high-intensity in T2W. The MRI-"whorled sign" is described in the reviewed studies in about 80% of patients. The MRI characterization of a primitive retroperitoneal cystic mass should not exclude a cystic evolution from solid masses, and in the case of paravertebral location, the differential diagnosis algorithm should include the hypothesis of ganglioneuroma. In our case, the MRI features could have oriented towards a neurogenic nature, however, the predominantly cystic-fluid aspect and the considerable longitudinal non-invasive extension between retroperitoneal structures, misled us to a lymphatic malformation. In the literature, it is reported that the cystic presentation can be due to a degeneration of a well-known solid form while maintaining a benign character: the distinguishing malignity character is the revelation of immature cells on histological examination.
- Published
- 2023
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35. Microwave ablation using two simultaneous antennas for the treatment of liver malignant lesions: a 3 year single-Centre experience.
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Andresciani F, Pacella G, Vertulli D, Altomare C, Bitonti MT, Bruno A, Cea L, Faiella E, Beomonte Zobel B, and Grasso RF
- Subjects
- Animals, Microwaves therapeutic use, Retrospective Studies, Treatment Outcome, Carcinoma, Hepatocellular pathology, Liver Neoplasms diagnostic imaging, Liver Neoplasms surgery, Liver Neoplasms pathology, Catheter Ablation methods
- Abstract
Background: sequential or simultaneous applications of multiple antennas have been proposed to create larger ablation zone; however, there is a lack of data in patients affected by liver tumors, with potentially different results from animal liver models. The purpose of this study was to evaluate efficacy and safety of liver percutaneous microwave ablation using simultaneous activation of two antennas to treat lesions bigger than 2,5 cm; particularly the focus was assessing whether the ratio of ablation zone volume in millimeters to applied energy in kilojoules [R(AZ:E)] differs between hepatocellular carcinoma in a cirrhotic liver and liver metastasis and if it is correlated to complications incidence or recurrence of disease., Methods: Fifty-five liver microwave ablation performed with two simultaneous antennas from March 2017 to June 2021 were retrospectively reviewed; 9 procedures were excluded due to the association with Chemoembolization. Size, shape, volume of lesions and ablation zones were recorded. Technical success was defined as complete devascularization of the treated area at the post-procedural CT. R(AZ:E) was determined dividing the ablation zone volume in mm3 by the amount of energy in kilojoules applied in each procedure and complications were reported., Results: Technical success was achieved in all the procedures. Mean R(AZ:E) was 0,75 ± 0,58. T-student test for patients with HCC and patients with metastasis about R(AZ:E) was significant ( p = 0.03). The incidence of bilomas was lower for HCC ( p = 0.022). One-month follow-up showed Complete Response (CR) in 44/46 (95,6%) patients; Three-six months follow-up demonstrated: CR in 43/46 (93.5%) cases and 12 months follow-up highlighted CR in 40/45 (88,9%) cases., Conclusions: These results provide preliminary evidence of efficacy and safety of simultaneous liver MWA using two antennas, highlighting the importance of procedural indications.
- Published
- 2023
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36. CT, MR, and CEUS imaging features of recurrent GIST of the pre-sacral space: A case report.
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Andresciani F, Vertulli D, Pacella G, Altomare C, Bernetti C, Bitonti MT, Buoso A, Ferrari U, Zobel BB, and Grasso RF
- Abstract
We present the case of a 50-year-old woman affected by a rectal gastrointestinal stromal tumor (GIST), with a recurrence in pre-sacral and pre-coccygeal space after surgery and Imatinib therapy. GISTs are the most common mesenchymal tumors of the gastrointestinal tract and rectal GISTs are rare (only 2% of cases); magnetic resonance and computed tomography are the main imaging techniques for diagnosis and follow-up, while ultrasound and contrast-enhanced ultrasound may be useful to perform a percutaneous biopsy, as in the case presented: the imaging features of the lesion in all these imaging methods are displayed., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)
- Published
- 2022
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37. Analysis of Risk Factors of Soft Tissue Bleeding in COVID-19 Patients: A Point of View After Two Years of Pandemic.
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Faiella E, Castiello G, Santucci D, Pacella G, Bernetti C, Muley Villamu M, Antonelli Incalzi R, Beomonte Zobel B, Quattrocchi CC, and Grasso RF
- Abstract
Background: The aim of the study was to analyze the relationship between patient characteristics, including anagraphic and laboratoristic data and amount of adipose tissue measured in computed tomography (CT) scans in coronavirus disease 2019 (COVID-19) patients, and incidence of soft tissue bleeding requiring medical and/or interventional radiology management., Methods: A total of 132 patients hospitalized for COVID-19 pathology from October 2020 to May 2021 were included in the study and divided into two groups: a bleeding group of 70 cases with soft tissue bleeding occurring during hospitalization, and a control group of 62 hospitalized COVID-19 patients without bleeding events. In the bleeding group, two subgroups were considered: an embolization group including soft tissue bleeding cases requiring interventional radiology with transarterial embolization (TAE) (16/70; 22.9%) and a non-embolization group, clinically managed without TAE (54/70; 77.1%). Demographics and clinical data, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area measured on CT images and VAT/SAT ratio were compared between bleeding and control groups and between embolization and non-embolization subgroups., Results: Bleeding and control groups did not significantly differ for sex distribution, COVID-19, platelet (PLT) count, international normalized ratio (INR), SAT area, VAT area, and VAT/SAT ratio. Embolization and non-embolization groups did not significantly differ for age, COVID-19, PLT count, INR, SAT area, and VAT/SAT ratio. Bleeding group had lower body mass index (BMI) than control group as well as embolization group compared to non-embolization group. A statistically significant difference was observed between embolization and non-embolization groups for VAT area, with smaller values in embolization group (mean difference: 64.2 cm
2 , 95% confidence interval: 8.3 - 120.1; P < 0.05)., Conclusion: Soft tissue bleeding in COVID-19 is more frequent and severe in patients with low amount of VAT, demonstrating that fat mass may have a containing function on bleeding, limiting its progression in surrounding structures. There are some other factors that influence the risk of bleeding, such as age, thromboprophylaxis therapy and BMI., Competing Interests: All authors declare that they have no conflict of interest., (Copyright 2022, Faiella et al.)- Published
- 2022
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38. Augmented reality 3D navigation system for percutaneous CT-guided pulmonary ground-glass opacity biopsies: a comparison with the standard CT-guided technique.
- Author
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Faiella E, Messina L, Castiello G, Bernetti C, Pacella G, Altomare C, Andresciani F, Sarli M, Longo F, Crucitti P, Beomonte Zobel B, and Grasso RF
- Abstract
Background: Augmented reality navigation system for percutaneous computed tomography (CT)-guided pulmonary biopsies has recently been introduced. There are no studies in literature about its use for ground glass lesions biopsies. The aim of this study is to evaluate the effectiveness of an augmented reality infrared navigation system performance on CT-guided percutaneous lung ground glass opacity (GGO) biopsy compared to a standard CT-guided technique., Methods: A total of 80 patients with lung GGO who underwent to a percutaneous CT-guided lung biopsy with an augmented reality infrared navigation system were retrospectively enrolled in the study. Comparison was performed with a group of 80 patients who underwent to lung biopsy with the standard CT-guided technique. Evaluation of maximum lesion diameter (MLD), distance between lesion and pleural surface (DPS), distance travelled by the needle (DTP), procedural time, validity of histological sample, procedural complications and the radiation dose to the patient's chest were recorded for each patient of both groups. In addition, each group was divided into two subgroups based on lesion size, according to a cut-off of 1.5 cm (<1.5 cm; ≥1.5 cm)., Results: Augmented reality navigation system showed a significant reduction in procedural time, radiation dose administrated to patients and complications rate compared to a standard CT-guided technique. Technical success was achieved in the 100% of cases in both groups, but the diagnostical success was higher in the group where patients underwent to lung biopsies with the use of navigation system. We also found that using an augmented reality navigation system increases the diagnostical success rate for lesion <1.5 cm. MLD, DPS and DTP did not differ significantly between the two groups of patients., Conclusions: The use of an augmented reality navigation system for percutaneous CT-guided pulmonary GGO biopsies has demonstrated a lower incidence of post-procedural complications, a significantly reduction of the radiation dose administered to patients and a higher diagnostical success rate., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1285/coif). PC serves as an unpaid editorial board member of Journal of Thoracic Disease from November 2016 to October 2022. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)
- Published
- 2022
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39. Different Treatments of Symptomatic Angiomyolipomas of the Kidney: Two Case Reports.
- Author
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Pacella G, Faiella E, Altomare C, Andresciani F, Castiello G, Bernetti C, Sarli M, Zobel BB, and Grasso RF
- Abstract
Development of more sensitive imaging techniques has caused an increase in the number of diagnosed small renal tumors. Approximately 2-3% of these lesions are proved to be angiomyolipomas (AML), a rare benign tumor of the kidney sometimes causing pain and hematuria. The most required approach is observation, but in the case of recurrent symptoms or larger tumors, which may cause bleeding, a more active treatment is required. We present two cases of symptomatic AML tumors of different sizes in the kidney: one treated with transarterial embolization (TAE), and the other with percutaneous cryoablation (CRA). The lesions were diagnosed on the basis of contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI). Both treatments proved to be effective and safe for treating renal AMLs. A follow-up carried out, based on contrast-enhanced CT scan, confirmed complete treatment of AML and decreased lesion size. There are myriad minimally invasive approaches for the treatment of renal AMLs, and the preservation of renal function remains a priority. The most popular treatment option is the selective renal artery embolization. Owing to its limited invasiveness, CRA could be an attractive option for the preventive treatment of AML., Competing Interests: This study was not supported by any funding. The authors declare that no conflict of interest exists., (Copyright: Pacella G, et al.)
- Published
- 2021
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40. Lung Thermal Ablation: Comparison between an Augmented Reality Computed Tomography (CT) 3D Navigation System (SIRIO) and Standard CT-Guided Technique.
- Author
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Grasso RF, Andresciani F, Altomare C, Pacella G, Castiello G, Carassiti M, Quattrocchi CC, Faiella E, and Beomonte Zobel B
- Abstract
(1) Background: The aim of this retrospective study is to assess safety and efficacy of lung radiofrequency (RFA) and microwave ablation (MWA) using an augmented reality computed tomography (CT) navigation system (SIRIO) and to compare it with the standard CT-guided technique. (2) Methods: Lung RFA and MWA were performed with an augmented reality CT 3D navigation system (SIRIO) in 52 patients. A comparison was then performed with a group of 49 patients undergoing the standard CT-guided technique. All the procedures were divided into four groups based on the lesion diameter (>2 cm or ≤2 cm), and procedural time, the number of CT scans, radiation dose administered, and complications rate were evaluated. Technical success was defined as the presence of a "ground glass" area completely covering the target lesion at the immediate post-procedural CT. (3) Results: Full technical success was achieved in all treated malignant lesions for all the considered groups. SIRIO-guided lung thermo-ablations (LTA) displayed a significant decrease in the number of CT scans, procedure time, and patients' radiation exposure ( p < 0.001). This also resulted in a dosage reduction in hypnotics and opioids administrated for sedation during LTA. No significant differences were observed between the SIRIO and non-SIRIO group in terms of complications incidence. (4) Conclusions: SIRIO is an efficient tool to perform CT-guided LTA, displaying a significant reduction ( p < 0.001) in the number of required CT scans, procedure time, and patients' radiation exposure.
- Published
- 2021
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41. Impact of an Augmented Reality Navigation System (SIRIO) on Bone Percutaneous Procedures: A Comparative Analysis with Standard CT-Guided Technique.
- Author
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Faiella E, Castiello G, Bernetti C, Pacella G, Altomare C, Andresciani F, Beomonte Zobel B, and Grasso RF
- Subjects
- Carbidopa, Drug Combinations, Humans, Image-Guided Biopsy, Levodopa analogs & derivatives, Retrospective Studies, Tomography, X-Ray Computed, Augmented Reality
- Abstract
(1) Background: The purpose of this study is to evaluate the impact of an augmented reality navigation system (SIRIO) for percutaneous biopsies and ablative treatments on bone lesions, compared to a standard CT-guided technique. (2) Methods: Bioptic and ablative procedures on bone lesions were retrospectively analyzed. All procedures were divided into SIRIO and Non-SIRIO groups and in <2 cm and >2 cm groups. Number of CT-scans, procedural time and patient's radiation dose were reported for each group. Diagnostic accuracy was obtained for bioptic procedures. (3) Results: One-hundred-ninety-three procedures were evaluated: 142 biopsies and 51 ablations. Seventy-four biopsy procedures were performed using SIRIO and 68 under standard CT-guidance; 27 ablative procedures were performed using SIRIO and 24 under standard CT-guidance. A statistically significant reduction in the number of CT-scans, procedural time and radiation dose was observed for percutaneous procedures performed using SIRIO, in both <2 cm and >2 cm groups. The greatest difference in all variables examined was found for procedures performed on lesions <2 cm. Higher diagnostic accuracy was found for all SIRIO-assisted biopsies. No major or minor complications occurred in any procedures. (4) Conclusions: The use of SIRIO significantly reduces the number of CT-scans, procedural time and patient's radiation dose in CT-guided percutaneous bone procedures, particularly for lesions <2 cm. An improvement in diagnostic accuracy was also achieved in SIRIO-assisted biopsies.
- Published
- 2021
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42. Combined trans-arterial embolisation and microwave ablation for the treatment of large unresectable hepatic metastases (>3 cm in maximal diameter).
- Author
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Faiella E, Santucci D, Bernetti C, Schena E, Pacella G, Zobel BB, and Grasso RF
- Subjects
- Humans, Microwaves therapeutic use, Neoplasm Recurrence, Local, Treatment Outcome, Catheter Ablation, Embolization, Therapeutic, Liver Neoplasms surgery, Radiofrequency Ablation
- Abstract
Purpose: To assess the safety and efficacy of a two-step single-session procedure, combining transarterial embolization (TAE) and percutaneous microwave ablation (MWA), in the treatment of > 3 cm unresectable liver metastases. We also compared the final volume obtained by the two techniques (V
E-T ) and the expected ablation volume of the stand-alone MWA (VT )., Methods: From January 2015 to December 2017, 22 consecutive patients, with a total of 24 unresectable hepatic metastases >3 cm in diameter underwent a two-step single-session combined treatment of TAE and MWA. Follow-up computed tomography scans were performed at 1-, 3-, 6-, 12, and 24 months post-procedure. VE-T as final ablation volume induced by the combined treatment (TAE-MWA), VN as initial nodule volume, VT as expected ablation volume of MWA treatment alone were evaluated and compared., Results: Tumor dimensions ranged from 32 to 73 mm. Technical success was achieved in all treated tumors with no local tumor recurrence. Final ablation volumes ranged from 50 to 450 cm3 and the short-axis diameter of the ablation zone ranged from 12 to 48 mm. The mean ΔV increment in the final ablation volume with respect to the stand-alone MWA was 196% (ranging from 25 cm3 - 210 cm3 ) ( p < 0.05). The VE-T mean was four times the VN mean, while the VT mean was about twice the VN mean. No recurrence and only one case of post-embolization bleeding were observed., Conclusions: This study demonstrated the safety and efficacy of a combined two-step single-session TAE-MWA treatment of unresectable hepatic metastases > 3 cm in diameter.- Published
- 2020
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43. LSD1 Inhibition Promotes Epithelial Differentiation through Derepression of Fate-Determining Transcription Factors.
- Author
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Egolf S, Aubert Y, Doepner M, Anderson A, Maldonado-Lopez A, Pacella G, Lee J, Ko EK, Zou J, Lan Y, Simpson CL, Ridky T, and Capell BC
- Subjects
- 3T3 Cells, Adult, Animals, Binding Sites, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Epidermis metabolism, Epithelial Cells metabolism, Gene Expression Regulation, Genome, Human, Histone Demethylases metabolism, Histones metabolism, Humans, Lysine metabolism, Methylation, Mice, Protein Binding, Snail Family Transcription Factors metabolism, Transcription, Genetic, Cell Differentiation genetics, Cell Lineage genetics, Epithelial Cells cytology, Histone Demethylases antagonists & inhibitors, Transcription Factors metabolism
- Abstract
Self-renewing somatic tissues depend upon the proper balance of chromatin-modifying enzymes to coordinate progenitor cell maintenance and differentiation, disruption of which can promote carcinogenesis. As a result, drugs targeting the epigenome hold significant therapeutic potential. The histone demethylase, LSD1 (KDM1A), is overexpressed in numerous cancers, including epithelial cancers; however, its role in the skin is virtually unknown. Here we show that LSD1 directly represses master epithelial transcription factors that promote differentiation. LSD1 inhibitors block both LSD1 binding to chromatin and its catalytic activity, driving significant increases in H3K4 methylation and gene transcription of these fate-determining transcription factors. This leads to both premature epidermal differentiation and the repression of squamous cell carcinoma. Together these data highlight both LSD1's role in maintaining the epidermal progenitor state and the potential of LSD1 inhibitors for the treatment of keratinocyte cancers, which collectively outnumber all other cancers combined., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
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