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3. OP0073 UNRAVELING PATHOPHYSIOLOGY AND HEMATOPOIESIS OF VEXAS SYNDROME BY MULTI-OMICS ANALYSIS AND TARGETED GENE EDITING

Author

Campochiaro, C., primary, Molteni, R., additional, Pacini, G., additional, Fiumara, M., additional, Tomelleri, A., additional, Diral, E., additional, Stefanoni, D., additional, Varesi, A., additional, Weber, A., additional, Alfieri, R., additional, Albano, L., additional, Panigada, M., additional, Cantoni, E., additional, Canarutto, D., additional, Bassoricci, L., additional, Quaranta, P., additional, ’alessandro, A. D, additional, Matucci-Cerinic, M., additional, DI Micco, R., additional, Aiuti, A., additional, Ciceri, F., additional, Merelli, I., additional, Dagna, L., additional, Scala, S., additional, Cenci, S., additional, Naldini, L., additional, Ferrari, S., additional, and Cavalli, G., additional

Published
2024
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5. White Blood Cells in Patients Treated with Programmed Cell Death-1 Inhibitors for Non-small Cell Lung Cancer

Author

Sibille, A., Henket, M., Corhay, J. L., Alfieri, R., Louis, R., and Duysinx, B.

Subjects
Biochemistry, Medical research, Medicine, Experimental, Blood cell count, Lung cancer, Small cell -- Care and treatment -- Prognosis, Lung cancer, Non-small cell -- Prognosis -- Care and treatment, Apoptosis, Health
Abstract

Purpose To investigate whether eosinophils and other white blood cell subtypes could be used as response and prognostic markers to anti-Programmed cell Death-1 or anti-PD-Ligand-1 treatments in non-small cell lung cancer patients. Methods We retrospectively analyzed data from the NSCLC patients consecutively treated at our hospital with a PD-1/PD-L1 inhibitor in monotherapy for advanced disease. A total of 191 patients were evaluated at three time-points to investigate any relation between tumor response and WBC counts. Results Baseline WBC and subtypes did not differ according to the type of response seen under treatment. A higher relative eosinophil count (REC) correlated with more objective responses (p = 0.019 at t1 and p = 0.014 at t2; OR for progression = 0.54 and 0.53, respectively) independently of the smoking status, PD-L1 status, and immune-related toxicity (IRT). Higher REC was also associated with a longer duration of treatment (p = 0.0096). Baseline absolute neutrophil count was prognostic (p = 0.049). At t1 relative lymphocytes, absolute and relative neutrophils, and neutrophil-to-lymphocyte ratio were prognostic (p = 0.044, p = 0.014, p = 0.0033, and p = 0.029, respectively). Conclusion Our results show that in NSCLC patients anti-PD-1/PD-L1 therapy induces an early increase only in blood eosinophils, more prominent in responding patients and independent of the smoking status, PD-L1 status, and IRT. Eosinophils are also associated with a longer duration of treatment. Furthermore, our data support a prognostic role of neutrophils, lymphocytes, and their ratio for NSCLC patients with advanced disease treated with PD(L)-1 blockade., Author(s): A. Sibille [sup.1], M. Henket [sup.2], J. L. Corhay [sup.1], R. Alfieri [sup.3], R. Louis [sup.1], B. Duysinx [sup.1] Author Affiliations: (1) grid.411374.4, 0000 0000 8607 6858, Department of [...]

Published
2021
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6. PD-L1 overexpression induces STAT signaling and promotes the secretion of pro-angiogenic cytokines in non-small cell lung cancer (NSCLC)

Author

Cavazzoni, A., primary, Digiacomo, G., additional, Volta, F., additional, Alfieri, R., additional, Giovannetti, E., additional, Gnetti, L., additional, Bellini, L., additional, Galetti, M., additional, Fumarola, C., additional, Xu, G., additional, Bonelli, M., additional, La Monica, S., additional, Verzè, M., additional, Leonetti, A., additional, Eltayeb, K., additional, D'Agnelli, S., additional, Moron Dalla Tor, L., additional, Minari, R., additional, Petronini, P.G., additional, and Tiseo, M., additional

Published
2023
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7. Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies

Author

Leonetti, A., primary, Verzè, M., additional, Minari, R., additional, Perrone, F., additional, Gnetti, L., additional, Bordi, P., additional, Pluchino, M., additional, Nizzoli, R., additional, Azzoni, C., additional, Bottarelli, L., additional, Lagrasta, C. A. M., additional, Mazzaschi, G., additional, Buti, S., additional, Gasparro, D., additional, Cosenza, A., additional, Ferri, L., additional, Majori, M., additional, De Filippo, M., additional, Ampollini, L., additional, La Monica, S., additional, Alfieri, R., additional, Silini, E. M., additional, and Tiseo, M., additional

Published
2023
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8. Managing Dynamic User Communities in a Grid of Autonomous Resources

Author

Alfieri, R., Cecchini, R., Ciaschini, V., dell'Agnello, L., Gianoli, A., Spataro, F., Bonnassieux, F., Broadfoot, P., Lowe, G., Cornwall, L., Jensen, J., Kelsey, D., Frohner, A., Groep, D. L., de Cerff, W. Som, Steenbakkers, M., Venekamp, G., Kouril, D., McNab, A., Mulmo, O., Silander, M., Hahkala, J., and Lhorentey, K.

Subjects
Computer Science - Distributed, Parallel, and Cluster Computing, C.2.4, D.4.6
Abstract

One of the fundamental concepts in Grid computing is the creation of Virtual Organizations (VO's): a set of resource consumers and providers that join forces to solve a common problem. Typical examples of Virtual Organizations include collaborations formed around the Large Hadron Collider (LHC) experiments. To date, Grid computing has been applied on a relatively small scale, linking dozens of users to a dozen resources, and management of these VO's was a largely manual operation. With the advance of large collaboration, linking more than 10000 users with a 1000 sites in 150 counties, a comprehensive, automated management system is required. It should be simple enough not to deter users, while at the same time ensuring local site autonomy. The VO Management Service (VOMS), developed by the EU DataGrid and DataTAG projects[1, 2], is a secured system for managing authorization for users and resources in virtual organizations. It extends the existing Grid Security Infrastructure[3] architecture with embedded VO affiliation assertions that can be independently verified by all VO members and resource providers. Within the EU DataGrid project, Grid services for job submission, file- and database access are being equipped with fine- grained authorization systems that take VO membership into account. These also give resource owners the ability to ensure site security and enforce local access policies. This paper will describe the EU DataGrid security architecture, the VO membership service and the local site enforcement mechanisms Local Centre Authorization Service (LCAS), Local Credential Mapping Service(LCMAPS) and the Java Trust and Authorization Manager., Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 7 pages, LaTeX, 5 eps figures. PSN TUBT005

Published
2003

9. Understanding stochastic perturbation theory: toy models and statistical analysis

Author

Alfieri, R., Di Renzo, F., Onofri, E., and Scorzato, L.

Subjects
High Energy Physics - Lattice
Abstract

The numerical stochastic perturbation method based on Parisi-Wu quantisation is applied to a suite of simple models to test its validity at high orders. Large deviations from normal distribution for the basic estimators are systematically found in all cases (``Pepe effect''). As a consequence one should be very careful in estimating statistical errors. We present some results obtained on Weingarten's ``pathological'' model where reliable results can be obtained by an application of the bootstrap method. We also present some evidence that in the far less trivial application to Lattice Gauge Theory a similar problem should not arise at moderately high loops (up to O(\alpha^{10}))., Comment: 16 pages, LaTeX, 11 eps figure

Published
2000
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16. Current practice on the use of prophylactic drain after gastrectomy in Italy: the Abdominal Drain in Gastrectomy (ADiGe) survey

Author

Mengardo, V, Weindelmayer, J, Veltri, A, Giacopuzzi, S, Torroni, L, de Manzoni, G, Agresta, F, Alfieri, R, Alfieri, S, Antonacci, N, Baiocchi, G, Bencini, L, Bencivenga, M, Benedetti, M, Berselli, M, Biondi, A, Capolupo, G, Carboni, F, Casadei, R, Casella, F, Catarci, M, Cerri, P, Chiari, D, Cocozza, E, Colombo, G, Cozzaglio, L, Dalmonte, G, Degiuli, M, De Luca, M, De Luca, R, De Manzini, N, De Pasqual, C, De Pascale, S, De Ruvo, N, Di Cosmo, M, Di Leo, A, Di Paola, M, Elio, A, Ferrara, F, Ferrari, G, Fiscon, V, Fumagalli, U, Garulli, G, Gennai, A, Gentile, I, Germani, P, Gualtierotti, M, Guerini, F, Gurrado, A, Inama, M, La Torre, F, Laterza, E, Losurdo, P, Macri, A, Marano, A, Marano, L, Marchesi, F, Marino, F, Massani, M, Menghi, R, Milone, M, Molfino, S, Montuori, M, Moretto, G, Morgagni, P, Morpurgo, E, Abdallah, M, Nespoli, L, Olmi, S, Palaia, R, Pallabazer, G, Parise, P, Pasculli, A, Pericoli Ridolfini, M, Pesce, A, Pinotti, E, Pisano, M, Poiasina, E, Postiglione, V, Rausei, S, Rella, A, Rosa, F, Rosati, R, Rossi, G, Rossit, L, Rovatti, M, Ruspi, L, Sacco, L, Saladino, E, Sansonetti, A, Sartori, A, Scaglione, D, Scaringi, S, Schoenthaler, C, Sena, G, Simone, M, Solaini, L, Strignano, P, Tartaglia, N, Testa, S, Testini, M, Tiberio, G, Treppiedi, E, Vagliasindi, A, Valmasoni, M, Vigano, J, Zanchettin, G, Zanoni, A, Zardini, C, Zerbinati, A, Mengardo V., Weindelmayer J., Veltri A., Giacopuzzi S., Torroni L., de Manzoni G., Agresta F., Alfieri R., Alfieri S., Antonacci N., Baiocchi G. L., Bencini L., Bencivenga M., Benedetti M., Berselli M., Biondi A., Capolupo G. T., Carboni F., Casadei R., Casella F., Catarci M., Cerri P., Chiari D., Cocozza E., Colombo G., Cozzaglio L., Dalmonte G., Degiuli M., De Luca M., De Luca R., De Manzini N., De Pasqual C. A., De Pascale S., De Ruvo N., Di Cosmo M., Di Leo A., Di Paola M., Elio A., Ferrara F., Ferrari G., Fiscon V., Fumagalli U., Garulli G., Gennai A., Gentile I., Germani P., Gualtierotti M., Guerini F., Gurrado A., Inama M., La Torre F., Laterza E., Losurdo P., Macri A., Marano A., Marano L., Marchesi F., Marino F., Massani M., Menghi R., Milone M., Molfino S., Montuori M., Moretto G., Morgagni P., Morpurgo E., Abdallah M., Nespoli L., Olmi S., Palaia R., Pallabazer G., Parise P., Pasculli A., Pericoli Ridolfini M., Pesce A., Pinotti E., Pisano M., Poiasina E., Postiglione V., Rausei S., Rella A., Rosa F., Rosati R., Rossi G., Rossit L., Rovatti M., Ruspi L., Sacco L., Saladino E., Sansonetti A., Sartori A., Scaglione D., Scaringi S., Schoenthaler C., Sena G., Simone M., Solaini L., Strignano P., Tartaglia N., Testa S., Testini M., Tiberio G. A. M., Treppiedi E., Vagliasindi A., Valmasoni M., Vigano J., Zanchettin G., Zanoni A., Zardini C., Zerbinati A., Mengardo, V, Weindelmayer, J, Veltri, A, Giacopuzzi, S, Torroni, L, de Manzoni, G, Agresta, F, Alfieri, R, Alfieri, S, Antonacci, N, Baiocchi, G, Bencini, L, Bencivenga, M, Benedetti, M, Berselli, M, Biondi, A, Capolupo, G, Carboni, F, Casadei, R, Casella, F, Catarci, M, Cerri, P, Chiari, D, Cocozza, E, Colombo, G, Cozzaglio, L, Dalmonte, G, Degiuli, M, De Luca, M, De Luca, R, De Manzini, N, De Pasqual, C, De Pascale, S, De Ruvo, N, Di Cosmo, M, Di Leo, A, Di Paola, M, Elio, A, Ferrara, F, Ferrari, G, Fiscon, V, Fumagalli, U, Garulli, G, Gennai, A, Gentile, I, Germani, P, Gualtierotti, M, Guerini, F, Gurrado, A, Inama, M, La Torre, F, Laterza, E, Losurdo, P, Macri, A, Marano, A, Marano, L, Marchesi, F, Marino, F, Massani, M, Menghi, R, Milone, M, Molfino, S, Montuori, M, Moretto, G, Morgagni, P, Morpurgo, E, Abdallah, M, Nespoli, L, Olmi, S, Palaia, R, Pallabazer, G, Parise, P, Pasculli, A, Pericoli Ridolfini, M, Pesce, A, Pinotti, E, Pisano, M, Poiasina, E, Postiglione, V, Rausei, S, Rella, A, Rosa, F, Rosati, R, Rossi, G, Rossit, L, Rovatti, M, Ruspi, L, Sacco, L, Saladino, E, Sansonetti, A, Sartori, A, Scaglione, D, Scaringi, S, Schoenthaler, C, Sena, G, Simone, M, Solaini, L, Strignano, P, Tartaglia, N, Testa, S, Testini, M, Tiberio, G, Treppiedi, E, Vagliasindi, A, Valmasoni, M, Vigano, J, Zanchettin, G, Zanoni, A, Zardini, C, Zerbinati, A, Mengardo V., Weindelmayer J., Veltri A., Giacopuzzi S., Torroni L., de Manzoni G., Agresta F., Alfieri R., Alfieri S., Antonacci N., Baiocchi G. L., Bencini L., Bencivenga M., Benedetti M., Berselli M., Biondi A., Capolupo G. T., Carboni F., Casadei R., Casella F., Catarci M., Cerri P., Chiari D., Cocozza E., Colombo G., Cozzaglio L., Dalmonte G., Degiuli M., De Luca M., De Luca R., De Manzini N., De Pasqual C. A., De Pascale S., De Ruvo N., Di Cosmo M., Di Leo A., Di Paola M., Elio A., Ferrara F., Ferrari G., Fiscon V., Fumagalli U., Garulli G., Gennai A., Gentile I., Germani P., Gualtierotti M., Guerini F., Gurrado A., Inama M., La Torre F., Laterza E., Losurdo P., Macri A., Marano A., Marano L., Marchesi F., Marino F., Massani M., Menghi R., Milone M., Molfino S., Montuori M., Moretto G., Morgagni P., Morpurgo E., Abdallah M., Nespoli L., Olmi S., Palaia R., Pallabazer G., Parise P., Pasculli A., Pericoli Ridolfini M., Pesce A., Pinotti E., Pisano M., Poiasina E., Postiglione V., Rausei S., Rella A., Rosa F., Rosati R., Rossi G., Rossit L., Rovatti M., Ruspi L., Sacco L., Saladino E., Sansonetti A., Sartori A., Scaglione D., Scaringi S., Schoenthaler C., Sena G., Simone M., Solaini L., Strignano P., Tartaglia N., Testa S., Testini M., Tiberio G. A. M., Treppiedi E., Vagliasindi A., Valmasoni M., Vigano J., Zanchettin G., Zanoni A., Zardini C., and Zerbinati A.

Abstract

Evidence against the use of prophylactic drain after gastrectomy are increasing and ERAS guidelines suggest the benefit of drain avoidance. Nevertheless, it is unclear whether this practice is still widespread. We conducted a survey among Italian surgeons through the Italian Gastric Cancer Research Group and the Polispecialistic Society of Young Surgeons, aiming to understand the current use of prophylactic drain. A 28-item questionnaire-based survey was developed to analyze the current practice and the individual opinion about the use of prophylactic drain after gastrectomy. Groups based on age, experience and unit volume were separately analyzed. Response of 104 surgeons from 73 surgical units were collected. A standardized ERAS protocol for gastrectomy was applied by 42% of the respondents. Most of the surgeons, regardless of age, experience, or unit volume, declared to routinely place one or more drain after gastrectomy. Only 2 (1.9%) and 7 surgeons (6.7%) belonging to high volume units, do not routinely place drains after total and subtotal gastrectomy, respectively. More than 60% of the participants remove the drain on postoperative day 4–6 after performing an assessment of the anastomosis integrity. Interestingly, less than half of the surgeons believe that drain is the main tool for leak management, and this percentage further drops among younger surgeons. On the other hand, drain’s role seems to be more defined for duodenal stump leak treatment, with almost 50% of the surgeons recognizing its importance. Routine use of prophylactic drain after gastrectomy is still a widespread practice even if younger surgeons are more persuaded that it could not be advantageous.

Published
2022

17. Considering weights in real social networks: A review

Author

Bellingeri, M., primary, Bevacqua, D., additional, Sartori, F., additional, Turchetto, M., additional, Scotognella, F., additional, Alfieri, R., additional, Nguyen, N. K. K., additional, Le, T. T., additional, Nguyen, Q., additional, and Cassi, D., additional

Published
2023
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18. VOMS, an Authorization System for Virtual Organizations

Author

Alfieri, R., Cecchini, R., Ciaschini, V., dell’Agnello, L., Frohner, Á., Gianoli, A., Lõrentey, K., Spataro, F., Goos, Gerhard, editor, Hartmanis, Juris, editor, van Leeuwen, Jan, editor, Fernández Rivera, Francisco, editor, Bubak, Marian, editor, Gómez Tato, Andrés, editor, and Doallo, Ramón, editor

Published
2004
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19. Anastomotic leak following oesophagectomy: research priorities from an international Delphi consensus study

Author

Kamarajah, Sivesh K, Mohamed, Imran, Nepogodiev, Dmitri, Evans, Richard PT, Hodson, James, Griffiths, Ewen A, Singh, Pritam, Committee, Steering, Alderson, Derek, Bundred, James, Evans, Richard, Gossage, James, Jefferies, Benjamin, Mckay, Siobhan, Siaw-Acheampong, Kobby, van Hillegersberg, Richard, Vohra, Ravinder, Wanigsooriya, Kasun, Whitehouse, Tony, Bekele, A, Achiam, Mp, Ahmed, H, Ainsworth, A, Akhtar, K, Akkapulu, N, Al-Khyatt, W, Alasmar, M, Alemu, Bn, Alfieri, R, Alkhaffaf, B, Alvarez, Ls, Amahu, V, Andreollo, Na, Arias, F, Ariyarathenam, A, Arndt, A, Athanasiou, A, Azagra, Js, Baban, C, Babor, R, Baili, E, Balla, A, Beenen, E, Bendixen, M, Bennett, J, Bergeat, D, Bernardes, Aj, Bernardi, D, Berrisford, R, Bianchi, A, Bjelovic, M, Blencowe, N, Boddy, A, Bogdan, S, Bolger, J, Bonavina, L, Bouras, G, Bouwense, S, Bowrey, D, Bragg, D, Bright, Tn, Broderick, S, Buduhan, G, Byrne, B, Carey, D, Carroll, P, Carrott, P, Casaca, R, Castro, Rg, Catton, J, Cerdeira, Mp, Chang, Ac, Charalabopoulos, A, Chaudry, A, Choh, C, Ciprian, B, Ciubotaru, C, Coe, P, Colak, E, Colino, Rb, Colucci, N, Costa, Pm, Daniela, K, Das, N, Davies, A, Davies, N, de Manzoni, G, del Val, Id, Dexter, S, Dolan, J, Donlon, N, Donohoe, C, Duffy, J, Dwerryhouse, S, Egberts, Jh, Ekwunife, C, Elhadi, A, Elhadi, M, Elliott, Ja, Elnagar, H, Elnagar, F, Faraj, Ha, Farooq, N, Fearon, N, Fekaj, E, Forshaw, M, Freire, J, Gacevski, G, Gaedcke, J, Giacopuzzi, S, Gijón, Mm, Gisbertz, S, Golcher, H, Gordon, A, Gossage, J, Griffiths, E, Grimminger, P, Guner, A, Gutknecht, S, Harustiak, T, Hedberg, J, Heisterkamp, J, Hii, M, Hindmarsh, A, Holm, J, Hornby, S, Isik, A, Izbicki, J, Jagadesham, V, Jaunoo, S, Johansson, J, Johnson, Ma, Johnston, B, Kapoulas, S, Kauppi, J, Kauppila, Jh, Kechagias, A, Kelly, M, Kelty, C, Kennedy, A, Khan, M, Khattak, S, Kidane, B, Kjaer, Dw, Klarenbeek, B, Korkolis, Dp, Koshy, Rm, Krantz, S, Lagarde, S, Larsen, Mh, Lau, Pc, Leeder, Pc, Leite, Js, Liakakos, T, Madhavan, A, Mahdi, Si, Mahendran, Ha, Mahmoodzadeh, H, Majbar, A, Manatakis, D, Markar, S, Martijnse, I, Matei, B, Matos da Costa, P, Mccormack, K, Mcnally, S, Meriläinen, S, Merrett, N, Migliore, M, Mingol, F, Mitton, D, Mogoanta, Ss, Mönig, Sp, Moorthy, K, Muhinga, M, Mwachiro, M, Naeem, A, Nasir, I, Navidi, M, Negoi, I, Negoiţă, V, Niazi, Sk, Nilsson, M, Pazdro, A, Pera, M, Perez, Cj, Perivoliotis, K, Peters, C, Phillips, Aw, Powell, A, Prove, L, Pucher, Ph, Rahman, S, Räsänen, Jv, Read, M, Reeh, M, Reim, D, Reynolds, J, Robb, Wb, Robertson, K, Rodica, B, Rosero, G, Rosman, C, Saadeh, L, Santos, Eg, Saunders, J, Sayyed, R, Schizas, D, Scurtu, Rr, Sekhniaidze, D, Serralheiro, Pa, Sevinç, B, Sgromo, B, Shakeel, O, Siemsen, M, Skipworth, R, Smith, B, Soares, A, Spillane, J, Steliga, Ma, Sundbom, M, Sydiuk, A, Takahashi, Aml, Talbot, M, Tan, B, Tareen, Ma, Tewari, N, Tez, M, Theodorou, D, Tita, A, Toledo, E, Townend, Pj, Triantafyllou, T, Trugeda, M, Tucker, O, Turner, P, Turrado, V, Underwood, T, Vaccari, S, Valmasoni, M, van Berge Henegouwen, M, van Boxel, G, van den Berg, Jw, van der Sluis, P, van Hillegersberg, R, van Lanschot, Jjb, van Workum, F, Vickers, J, Videira, J, Viswanath, Y, Vohra, R, Voon, K, Wadley, M, Walker, R, Wallner, B, Walsh, Tn, Weindelmayer, J, Welch, N, Wheatley, T, Wijnhoven, B, Wong, Lf, Yanni, F, Yeung, J, Zacharakis, Null, and Moenig, Stefan Paul

Subjects
medicine.medical_specialty, Leak, Biomedical Research, Delphi Technique, Steering committee, medicine.medical_treatment, Delphi method, Anastomotic Leak, 030230 surgery, Esophagectomy, Evidence-Based Medicine, Humans, Surveys and Questionnaires, Research, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, medicine, computer.programming_language, ddc:617, business.industry, General surgery, 030220 oncology & carcinogenesis, Surgery, business, computer, Delphi
Abstract

Background The Oesophago-Gastric Anastomosis Audit (OGAA) is an international collaborative group set up to study anastomotic leak outcomes after oesophagectomy for cancer. This Delphi study aimed to prioritize future research areas of unmet clinical need in RCTs to reduce anastomotic leaks. Methods A modified Delphi process was overseen by the OGAA committee, national leads, and engaged clinicians from high-income countries (HICs) and low/middle-income countries (LMICs). A three-stage iterative process was used to prioritize research topics, including a scoping systematic review (stage 1), and two rounds of anonymous electronic voting (stages 2 and 3) addressing research priority and ability to recruit. Stratified analyses were performed by country income. Results In stage 1, the steering committee proposed research topics across six domains: preoperative optimization, surgical oncology, technical approach, anastomotic technique, enhanced recovery and nutrition, and management of leaks. In stages 2 and stage 3, 192 and 171 respondents respectively participated in online voting. Prioritized research topics include prehabilitation, anastomotic technique, and timing of surgery after neoadjuvant chemo(radio)therapy. Stratified analyses by country income demonstrated no significant differences in research priorities between HICs and LMICs. However, for ability to recruit, there were significant differences between LMICs and HICs for themes related to the technical approach (minimally invasive, width of gastric tube, ischaemic preconditioning) and location of the anastomosis. Conclusion Several areas of research priority are consistent across LMICs and HICs, but discrepancies in ability to recruit by country income will inform future study design.

Published
2020

20. Identifying a core symptom set triggering radiological and endoscopic investigations for suspected recurrent esophago-gastric cancer:a modified Delphi consensus process

Author

Chidambaram, S. (Swathikan), Patel, N. M. (Nikhil M.), Sounderajah, V. (Viknesh), Alfieri, R. (Rita), Bonavina, L. (Luigi), Cheong, E. (Edward), Cockbain, A. (Andy), D’Journo, X. B. (Xavier Benoit), Ferri, L. (Lorenzo), Griffiths, E. A. (Ewen A.), Grimminger, P. (Peter), Gronnier, C. (Caroline), Gutschow, C. (Christian), Hedberg, J. (Jakob), Kauppila, J. H. (Joonas H.), Lagarde, S. (Sjoerd), Low, D. (Donald), Nafteux, P. (Philippe), Nieuwenhuijzen, G. (Grard), Nilsson, M. (Magnus), Rosati, R. (Riccardo), Schroeder, W. (Wolfgang), Smithers, B. M. (B. Mark), van Berge Henegouwen, M. I. (Mark I.), van Hillegesberg, R. (Richard), Watson, D. I. (David I.), Vohra, R. (Ravinder), Maynard, N. (Nick), Markar, S. R. (Sheraz R.), Chidambaram, S. (Swathikan), Patel, N. M. (Nikhil M.), Sounderajah, V. (Viknesh), Alfieri, R. (Rita), Bonavina, L. (Luigi), Cheong, E. (Edward), Cockbain, A. (Andy), D’Journo, X. B. (Xavier Benoit), Ferri, L. (Lorenzo), Griffiths, E. A. (Ewen A.), Grimminger, P. (Peter), Gronnier, C. (Caroline), Gutschow, C. (Christian), Hedberg, J. (Jakob), Kauppila, J. H. (Joonas H.), Lagarde, S. (Sjoerd), Low, D. (Donald), Nafteux, P. (Philippe), Nieuwenhuijzen, G. (Grard), Nilsson, M. (Magnus), Rosati, R. (Riccardo), Schroeder, W. (Wolfgang), Smithers, B. M. (B. Mark), van Berge Henegouwen, M. I. (Mark I.), van Hillegesberg, R. (Richard), Watson, D. I. (David I.), Vohra, R. (Ravinder), Maynard, N. (Nick), and Markar, S. R. (Sheraz R.)

Abstract

Summary Background: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients. Methods: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set. Results: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice. Conclusion: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value.

Published
2022

23. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author

Di Maio, V. C., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M. C., Antonucci, F. P., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L. A., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C. F., Babudieri, S., Mura, M. S., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C. F., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Vecchiet, J., Bruzzone, B., De Maria, A., Di Biagio, A., Marenco, S., Nicolini, L. A., Picciotto, A., Viscoli, C., Casinelli, K., Monache, M. Delle, Lichtner, M., Mastroianni, C., Aghemo, A., Bruno, S., Cerrone, M., Colombo, M., Monforte, A. DʼArminio, Danieli, E., Donato, F., Gubertini, G., Landonio, S., Magni, C. F., Mancon, A., Micheli, V., Monico, S., Niero, F., Puoti, M., Rizzardini, G., Russo, M. L., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Romagnoli, D., Brancaccio, G., Caporaso, N., Gaeta, G. B., Lembo, V., Morisco, F., Calvaruso, V., Craxì, A., Di Marco, V., Mazzola, A., Petta, S., DʼAmico, E., Cacciatore, P., Consorte, A., Palitti, V. Pace, Parruti, G., Pieri, A., Polilli, E., Tontodonati, M., Andreoni, M., Angelico, M., Antenucci, F., Antonucci, F. P., Aragri, M., Armenia, D., Baiocchi, L., Bellocchi, M., Bertoli, A., Biliotti, E., Biolato, M., Carioti, L., Ceccherini-Silberstein, F., Cento, V., Cerasari, G., Cerva, C., Ciotti, M., DʼAmbrosio, C., DʼEttorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Francioso, S., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Gianserra, L., Grieco, A., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Milana, M., Nosotti, L., Palazzo, D., Pasquazzi, C., Pellicelli, A., Perno, C. F., Romano, M., Santopaolo, F., Santoro, M. M., Sarmati, L., Sarrecchia, C., Sforza, D., Siciliano, M., Sorbo, M. C., Spaziante, M., Svicher, V., Taliani, G., Teti, E., Tisone, G., Vespasiani-Gentilucci, U., Vullo, V., Mangia, A., Babudieri, S., Maida, I., Melis, M., Mura, M. S., Falconi, L., Di Giammartino, D., and Tarquini, P.

Published
2016
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26. Patient-reported outcomes after oesophagectomy in the multicentre LASER study

Author

Markar, S R, primary, Sounderajah, V, additional, Johar, A, additional, Zaninotto, G, additional, Castoro, C, additional, Lagergren, P, additional, Elliott, J A, additional, Gisbertz, S S, additional, Mariette, C, additional, Alfieri, R, additional, Huddy, J, additional, Pinto, E, additional, Scarpa, M, additional, Klevebro, F, additional, Sunde, B, additional, Murphy, C F, additional, Greene, C, additional, Ravi, N, additional, Piessen, G, additional, Brenkman, H, additional, Ruurda, J, additional, van Hillegersberg, R, additional, Lagarde, S M, additional, Wijnhoven, B P, additional, Pera, M, additional, Roigg, J, additional, Castro, S, additional, Matthijsen, R, additional, Findlay, J, additional, Antonowicz, S, additional, Maynard, N, additional, McCormack, O, additional, Ariyarathenam, A, additional, Sanders, G, additional, Cheong, E, additional, Jaunoo, S, additional, Allum, W, additional, van Lanschot, J, additional, Nilsson, M, additional, Reynolds, J V, additional, van Berge Henegouwen, M I, additional, and Hanna, G B, additional

Published
2021
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27. Patient-reported outcomes after oesophagectomy in the multicentre LASER study

Author

Markar, S. R., Sounderajah, V., Johar, A., Zaninotto, G., Castoro, C., Lagergren, P., Elliott, J. A., Gisbertz, S. S., Mariette, C., Alfieri, R., Huddy, J., Pinto, E., Scarpa, M., Klevebro, F., Sunde, B., Murphy, C. F., Greene, C., Ravi, N., Piessen, G., Brenkman, H., Ruurda, J., van Hillegersberg, R., Lagarde, S. M., Wijnhoven, B. P., Pera, M., Roigg, J., Castro, S., Matthijsen, R., Findlay, J., Antonowicz, S., Maynard, N., McCormack, O., Ariyarathenam, A., Sanders, G., Cheong, E., Jaunoo, S., Allum, W., van Lanschot, J., Nilsson, M., Reynolds, J. V., van Berge Henegouwen, M. I., Hanna, G. B., Markar, S. R., Sounderajah, V., Johar, A., Zaninotto, G., Castoro, C., Lagergren, P., Elliott, J. A., Gisbertz, S. S., Mariette, C., Alfieri, R., Huddy, J., Pinto, E., Scarpa, M., Klevebro, F., Sunde, B., Murphy, C. F., Greene, C., Ravi, N., Piessen, G., Brenkman, H., Ruurda, J., van Hillegersberg, R., Lagarde, S. M., Wijnhoven, B. P., Pera, M., Roigg, J., Castro, S., Matthijsen, R., Findlay, J., Antonowicz, S., Maynard, N., McCormack, O., Ariyarathenam, A., Sanders, G., Cheong, E., Jaunoo, S., Allum, W., van Lanschot, J., Nilsson, M., Reynolds, J. V., van Berge Henegouwen, M. I., and Hanna, G. B.

Abstract

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.

Published
2021

28. Patient-reported outcomes after oesophagectomy in the multicentre LASER study

Author

MS CGO, Cancer, Markar, S R, Sounderajah, V, Johar, A, Zaninotto, G, Castoro, C, Lagergren, P, Elliott, J A, Gisbertz, S S, Mariette, C, Alfieri, R, Huddy, J, Pinto, E, Scarpa, M, Klevebro, F, Sunde, B, Murphy, C F, Greene, C, Ravi, N, Piessen, G, Brenkman, H, Ruurda, J, van Hillegersberg, R, Lagarde, S M, Wijnhoven, B P, Pera, M, Roigg, J, Castro, S, Matthijsen, R, Findlay, J, Antonowicz, S, Maynard, N, McCormack, O, Ariyarathenam, A, Sanders, G, Cheong, E, Jaunoo, S, Allum, W, van Lanschot, J, Nilsson, M, Reynolds, J V, van Berge Henegouwen, M I, Hanna, G B, MS CGO, Cancer, Markar, S R, Sounderajah, V, Johar, A, Zaninotto, G, Castoro, C, Lagergren, P, Elliott, J A, Gisbertz, S S, Mariette, C, Alfieri, R, Huddy, J, Pinto, E, Scarpa, M, Klevebro, F, Sunde, B, Murphy, C F, Greene, C, Ravi, N, Piessen, G, Brenkman, H, Ruurda, J, van Hillegersberg, R, Lagarde, S M, Wijnhoven, B P, Pera, M, Roigg, J, Castro, S, Matthijsen, R, Findlay, J, Antonowicz, S, Maynard, N, McCormack, O, Ariyarathenam, A, Sanders, G, Cheong, E, Jaunoo, S, Allum, W, van Lanschot, J, Nilsson, M, Reynolds, J V, van Berge Henegouwen, M I, and Hanna, G B

Published
2021

29. Allelic Imbalance Analysis in Liquid Biopsy to Monitor Locally Advanced Esophageal Cancer Patients During Treatment

Author

Boldrin, E., Curtarello, M., Fassan, M., Rugge, M., Realdon, S., Alfieri, R., Amadori, A., and Saggioro, D.

Subjects
allelic imbalance, circulating cell free DNA (cfDNA), esophageal adenocarcinoma (EADC), esophageal cancer, esophageal squamous cell carcinoma (ESCC), liquid biopsy, longitudinal studies, loss of heterozygosis (LOH), Cancer Research, Oncology, Original Research
Abstract

Esophageal cancer (EC) is a highly aggressive tumor, and the current monitoring procedures are partially inadequate to evaluate treatment efficacy. The aim of this study was to investigate whether allelic imbalance analysis in liquid biopsy could be used as an additional tool to monitor tumor burden in EC patients. For this purpose, circulating cell-free DNA (cfDNA) from 52 patients with a locally advanced EC, which underwent neoadjuvant treatment and resection, was analyzed. Data from four representative longitudinally followed patients are also reported. Furthermore, 17 DNAs from formalin-fixed paraffin-embedded (FFPE) tumor samples were analyzed and compared to time-matched cfDNAs. To look for allelic imbalance, which is the main genetic alteration in both EC histotypes, we used a panel of five microsatellites (MSs) and three single-nucleotide polymorphisms (SNPs) near genes described as frequently altered. The Fisher exact and Mann-Whitney U tests were used to analyze categorical and continuous data, respectively. The correlation coefficient between cfDNA and FFPE-DNA was calculated with the Pearson's correlation test. We found that the selected tumor-related alterations are present in cfDNA of both adenocarcinoma (EADC) and squamous cell carcinoma (ESCC) with similar frequencies. The only exception were the MSs, one downstream and one upstream, of SMAD4 of which the loss was only observed in EADC (26 vs. 0%, P = 0.018). More interestingly, longitudinal studies disclosed that in patients with disease progression, tumor-related alterations were present in cfDNA before overt clinical or instrumental signs of relapse. In conclusion, our data indicate that the evaluation of tumor-related gene allelic imbalance in cfDNA might be a useful tool to complement the current monitoring procedures for EC patients and to guide their management.

Published
2020

33. 257 CHEMORADIOTHERAPY FOLLOWED BY ACTIVE SURVEILLANCE VERSUS SURGERY FOR ESOPHAGEAL CANCER: A SYSTEMATIC REVIEW AND INDIVIDUAL PATIENT DATA META-ANALYSIS

Author

Van Der Wilk, B, primary, Eyck, B, additional, Hofstetter, W, additional, Ajani, J, additional, Piessen, G, additional, Castoro, C, additional, Alfieri, R, additional, Kim, J, additional, Kim, S, additional, Furlong, H, additional, Walsh, T, additional, Nieboer, D, additional, Wijnhoven, B, additional, Lagarde, S, additional, and Lanschot, J, additional

Published
2020
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37. The INFN-Grid Testbed

Author

Alfieri, R., Barbera, R., Belluomo, P., Cavalli, A., Cecchini, R., Chierici, A., Ciaschini, V., Dell’Agnello, L., Donno, F., Ferro, E., Forte, A., Gaido, L., Ghiselli, A., Gianoli, A., Italiano, A., Lusso, S., Luvisetto, M., Mastroserio, P., Mazzucato, M., Mura, D., Reale, M., Salconi, L., Sava, G., Serra, M., Spataro, F., Taurino, F., Tortone, G., Vaccarossa, L., Verlato, M., and Vita Finzi, G.

Published
2005
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40. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author

Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, Collaborators (129) Mariani R, HCV Italian Resistance Network Study Group., Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio VC, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, Ms, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, HCV Italian Resistance Network Study Group., Collaborators (129) Mariani R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio, Vc, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, M, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V. C, Bellocchi, M. C, Antonucci, F. P, Nicolini, L. A, Magni, C. F, Mura, M. S, Vespasiani Gentilucci, U, Morisco, Filomena, Perno, C. F, Ceccherini Silberstein, F., Caporaso, Nicola, Di Maio, V., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M., Antonucci, F., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C., Babudieri, S., Mura, M., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Bruzzone, B., De Maria, A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Mancon, A., Monico, S., Niero, F., Puoti, M., Russo, M., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Caporaso, N., Gaeta, G., Lembo, V., Calvaruso, V., Craxã­, A., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pace Palitti, V., Pieri, A., Polilli, E., Antenucci, F., Armenia, D., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Sanctis, A., Furlan, C., Gallo, P., Grieco, A., Grieco, S., Lattanzi, B., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Palazzo, D., Santopaolo, F., Santoro, M., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Teti, E., Mangia, A., Maida, I., Falconi, L., and Di Giammartino, D.

Subjects
0301 basic medicine, ns3, Genotyping Techniques, viruses, Drug Resistance, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, Telaprevir, chemistry.chemical_compound, genotype, genotyping techniques, hepacivirus, hepatitis C, humans, RNA viral, retrospective studies, sequence analysis, DNA, viral nonstructural proteins, drug resistance, viral, mutation, pharmacology, infectious diseases, 0302 clinical medicine, Retrospective Studie, Genotype, Pharmacology (medical), Viral, Hepatitis C, Humans, RNA, Viral, Retrospective Studies, Sequence Analysis, DNA, Drug Resistance, Viral, Mutation, Proteolytic enzymes, virus diseases, Settore MED/07 - Microbiologia e Microbiologia Clinica, hcv-rna levels, Infectious Diseases, HCV-RNA, 030211 gastroenterology & hepatology, Sequence Analysis, medicine.drug, Human, Microbiology (medical), medicine.medical_specialty, Hepatitis C virus, Concordance, Settore MED/12 - GASTROENTEROLOGIA, Pharmacology, Biology, 03 medical and health sciences, Boceprevir, Internal medicine, medicine, hcv, Genotyping, Hepaciviru, Viral Nonstructural Protein, Settore MED/09 - MEDICINA INTERNA, Virology, digestive system diseases, 030104 developmental biology, chemistry, Sequence Analysi, RNA, Genotyping Technique
Abstract

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Published
2016

41. Status of APE projects

Author

Alfieri, R., Di Renzo, R., Onofri, E., Bartoloni, A., Battista, C., Cabibbo, N., Cosimi, M., Lonardo, A., Michelotti, A., Proietti, B., Rapuano, F., Rossetti, D., Sacco, G., Tassa, S., Torelli, M., Vicini, P., Boucaud, Ph., Pène, O., Errico, W., Magazzù, G., Sartori, L., Schifano, F., Tripiccione, R., De Riso, P., Petronzio, R., Destri, C., Frezzotti, R., Marchesini, G., Gensch, U., Jansen, K., Kretzschmann, A., Leich, H., Paschedag, N., Pleiter, D., Schwendicke, U., Simma, H., Sommer, R., Sulanke, K., Wegner, P., Fucci, A., Martin, B., Pech, J., Panizzi, E., and Petricola, A.

Published
2001
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42. DESMOPLAKIN ASSOCIATED NON DILATED LEFT VENTRICULAR CARDIOMYOPATHY TREATED WITH ANAKINRA

Author

Pezzullo, E, Caputo, A, Catapano, D, Alfieri, R, Covino, S, D‘Elia, S, Golino, P, and Loffredo, F

Abstract

A 24 year old female patient experienced,from 2010 to November 2023,12 myocarditis–like episodes, often related to emotional stress, characterized by chest pain,increased markers of myocardial necrosis, normal C–reactive Protein values,normal left ventricular systolic function on echocardiogram.She was admitted to our division for the first time in July 2019 because of recurrent acute myocarditis, extensive non–ischemic fibrosis and myocardial edema on magnetic resonance imaging (MRI) and interstitial edema with monocytic lymphocytic infiltrates (CD3 +>7/mm2) and cardiomyocyte necrosis at endomyocardial biopsy.A genetic test was performed leading to the identification of a novel frameshift mutation in the tail C domain of desmoplakin (DSP) producing a truncated protein.Destabilization of desmosome can be associated,to massive troponin release,innate immune activation resulting in autoantibody formation to intracellular cardiomyocyte protein.Mutations in DSP can link to arrhythmogenic cardiomyopathy,characterized by intermittent myocardial inflammatory episodes that appear clinically similar to myocarditis,leading to left ventricular fibrosis and to high incidence of ventricular arrhythmias.Our patient was initially treated with intravenous high dose corticosteroid therapy with oral tapering at discharge but two relapses(December 2020 and April 2021)occurred at corticosteroid withdrawal.In April 2021 immunosuppressive therapy with azathioprine was initiated in association with colchicine and oral corticosteroids,however after three months a new recurrence occurred.In July 2021 off–label Anakinra 100 mg subcutaneously daily was started.Anakinra is an interleukin (IL)–1 beta recombinant receptor antagonist used to treat idiopathic recurrent pericarditis.A number of studies have stressed the possible role IL–1 in the pathogenesis of myocardial inflammation involving inflammasome activation,cardiomyocytes loss ultimately leading to heart failure and arrhythmias.Anakinra showed a good response and tolerability and allowed corticosteroid withdrawal.The patient did not experience any further recurrence until November 2023.This episode was however characterized by milder and shorter chest pain,lower release of troponin in absence of edema on magnetic resonance imaging and inflammation on cardiac (18)F–fluoro–2–deoxyglucose positron emission tomography suggesting that modulation of cardiac inflammation may be crucial also when associated with pathogenic mutations.

Published
2024
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49. Acute Hepatitis B After the Implementation of Universal Vaccination in Italy: Results From 22 Years of Surveillance (1993-2014)

Author

Tosti, Me, Alfonsi, V, Lacorte, E, Mele, A, Galli, C, Zanetti, Ar, Romanò, L, SEIEVA Collaborating Group including Ferrigno, L, Crateri, S, Iantosca, G, Badoni, G, D'Angelo, F, Sudano, L, Ruffier, M, Fischer, M, Augschiller, M, Gamper, S, Foppa, A, Lechthaler, T, Thaler, J, Steinmair, B, Grandi, C, Carraro, V, Franchini, S, Zotti, C, Lanzafame, P, Malaspina, S, Gallone, A, Castella, A, Valenza, G, Silano, V, Tacca, M, Iodice, S, Marchisio, A, Costantino, A, Giovanetti, F, Susani, F, Tagliacarne, C, Donadini, A, Nespoli, C, Trezzi, L, Gennati, G, Monteverdi, A, Boldori, L, De Grada, P, Gattinoni, A, Brugnoli, R, Belloni, A, Binotto, M, Pinciroli, G, Pesci, L, Senegaglia, P, Crippa, S, Altomonte, G, Lodola, S, Aquino, I, Castelli, N, Zecca, E, Nieri, M, Zecca, F, Pasquale, L, Piedacci, G, Giompapa, E, Zorzut, F, Rocco, G, Brianti, G, Gallo, T, Zuliani, M, Breda, A, Feltrin, O, Russo, F, Zanella, F, Mel, R, Soppelsa, M, Zolin, R, Todescato, A, Bacciolo, N, Rizzato, D, Pupo, A, Nicolardi, L, Flora, M, Boin, F, De Sisti, C, D'Ettore, G, Caracciolo, V, Penon, M, Bellè, M, Cafarra, L, Zivelonghi, G, Soffritti, S, Foroni, M, Finarelli, A, Borrini, B, Gualanduzzi, C, Capra, A, Sacchi, A, Mattei, G, Gardenghi, L, Gianninoni, A, Sancini, R, Dalle Donne, E, Rangoni, R, Cova, M, Bevilacqua, L, Fiumana, E, Bondi, B, Pecci, A, Mela, M, Briata, M, Michele, P, Turello, V, Opisso, A, Zoppi, G, Torracca, P, Ricci, M, Capellini, A, Pecori, L, Mazzotta, F, Balocchini, E, Ghiselli, G, Marchini, P, Di Vito, A, Wanderlingh, W, Raso, E, Mazzoli, F, Berti, C, Galletti, N, Grandi, E, Ferrentino, M, Marinari, M, Lombardi, A, Barbieri, A, Bagnoli, A, Bandini, M, Lezzi, I, Verdelli, F, Beltrano, A, Bindi, R, Sansone, C, Boncompagni, G, Zacchini, F, Baretti, S, Baroncini, O, Staderini, C, Filidei, P, Chiapparini, L, Barghini, F, Cadoni, M, Tagliavento, G, Fiacchini, D, Damiani, N, Pelliccioni, A, Liverani, A, Peccerillo, G, Vaccaro, A, Spadoni, M, Rossini, R, Pasqualini, F, Priori, A, Burattini, N, Cimica, S, Vitale, V, Laici, F, Migliozzi, F, Moretti, G, Ciarrocchi, G, Impullitti, S, Angelini, C, Tosti, A, Giaimo, M, Buscosi, A, Pasquale, A, Ciani, C, Santocchia, F, Proietti, M, Paoloni, Mc, Ercole, A, Russo, P, Cerocchi, C, Grillo, P, Loffredo, M, Labriola, V, Pendenza, A, Nappi, M, Bueti, P, Santucci, L, Mangiagli, F, Varrenti, D, Aquilani, S, Dionette, P, Corpolongo, D, Di Luzio, G, Di Giacomo, M, Graziani, M, Mancini, C, Turchi, C, Granchelli, C, Soldato, G, D'Eugenio, F, Albanesi, I, Ferrara, M, Citarella, A, Fossi, E, Parlato, A, Alfieri, R, Scotto, M, Caiazzo, Al, Chironna, M, Prato, R, Matera, R, Menolascina, S, Colamaria, R, Azzollini, N, Madaro, A, Scalzo, G, Ancona, A, Pedote, P, Moffa, G, Pagano, I, Angelillis, R, Ferraro, M, Aprile, V, Turco, Gl, Minerba, S, Caputi, G, Negrone, F, Maldini, M, Russo, T, Aloia, F, Giuffrida, S, Mangione, R, Consacra, R, Cuccia, M, Rinnone, S, Delogu, F, Fracasso, D, Saba, A, Puggioni, A, Frongia, O, Marras, M, Crasta, M, Mereu, G, Steri, G, and Santus, S

Subjects
Male, HBsAg, Pediatrics, Health Knowledge, Attitudes, Practice, breakthrough infections, HBV, hepatitis B vaccination, surveillance, vaccination failure, Adolescent, Adult, Child, Child, Preschool, Female, Hepatitis B, Hepatitis B virus, Humans, Infant, Infant, Newborn, Italy, Mass Vaccination, Middle Aged, Retrospective Studies, Risk Factors, Treatment Failure, Vaccination, Young Adult, Hepatitis B Vaccines, Microbiology (medical), Infectious Diseases, medicine.disease_cause, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Practice, Health Knowledge, 030211 gastroenterology & hepatology, Viral hepatitis, medicine.medical_specialty, Hepatitis B vaccine, 03 medical and health sciences, Preschool, business.industry, Retrospective cohort study, medicine.disease, Newborn, Immunization, Attitudes, Immunology, business
Abstract

Background Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. Methods We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. Results A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. Conclusions Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection.

Published
2016

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