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1. Pain assessment in animal models: do we need further studies?

Author

Gigliuto C, De Gregori M, Malafoglia V, Raffaeli W, Compagnone C, Visai L, Petrini P, Avanzini MA, Muscoli C, Viganò J, Calabrese F, Dominioni T, Allegri M, and Cobianchi L

Subjects
Medicine (General), R5-920
Abstract

Carmelo Gigliuto,1 Manuela De Gregori,2 Valentina Malafoglia,3 William Raffaeli,3 Christian Compagnone,4 Livia Visai,5,6 Paola Petrini,7 Maria Antonietta Avanzini,9 Carolina Muscoli,8 Jacopo Viganò,11 Francesco Calabrese,11 Tommaso Dominioni,11 Massimo Allegri,2,10 Lorenzo Cobianchi111Anaesthesia and Intensive Care, University of Pavia, Pavia, 2Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 3ISAL Foundation, Institute for Research on Pain, Torre Pedrera, Rimini, 4Department of Anaesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 5Department of Molecular Medicine, Center for Tissue Engineering (CIT), INSTM UdR of Pavia, University of Pavia, Pavia, 6Department of Occupational Medicine, Ergonomy and Disability, Laboratory of Nanotechnology, Salvatore Maugeri Foundation, IRCCS, Veruno, 7Dipartimento di Chimica, Materiali e Ingegneria Chimica 'G Natta' and Unità di Ricerca Consorzio INSTM, Politecnico di Milano, Milan, 8Department of Health Science, University Magna Grecia of Catanzaro and Centro del Farmaco, IRCCS San Raffaele Pisana, Roma, 9Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico "San Matteo", Pavia, 10Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, 11University of Pavia, Department of Surgical, Clinical, Paediatric and Diagnostic Science, General Surgery 1, IRCCS Fondazione Policlinico San Matteo, Pavia, ItalyAbstract: In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals.Keywords: pain assessment, experimental model, translational research

Published
2014

3. Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe

Author

Hofman, P., Calabrese, F., Kern, I., Adam, J., Alarcão, A., Alborelli, I., Anton, N.T., Arndt, A., Avdalyan, A., Barberis, M., Bégueret, H., Bisig, B., Blons, H., Boström, P., Brcic, L., Bubanovic, G., Buisson, A., Caliò, A., Cannone, M., Carvalho, L., Caumont, C., Cayre, A., Chalabreysse, L., Chenard, M.P., Conde, E., Copin, M.C., Côté, J.F., D’Haene, N., Dai, H.Y., de Leval, L., Delongova, P., Denčić-Fekete, M., Fabre, A., Ferenc, F., Forest, F., de Fraipont, F., Garcia-Martos, M., Gauchotte, G., Geraghty, R., Guerin, E., Guerrero, D., Hernandez, S., Hurník, P., Jean-Jacques, B., Kashofer, K., Kazdal, D., Lantuejoul, S., Leonce, C., Lupo, A., Malapelle, U., Matej, R., Merlin, J.L., Mertz, K.D., Morel, A., Mutka, A., Normanno, N., Ovidiu, P., Panizo, A., Papotti, M.G., Parobkova, E., Pasello, G., Pauwels, P., Pelosi, G., Penault-Llorca, F., Picot, T., Piton, N., Pittaro, A., Planchard, G., Poté, N., Radonic, T., Rapa, I., Rappa, A., Roma, C., Rot, M., Sabourin, J.C., Salmon, I., Prince, S. Savic, Scarpa, A., Schuuring, E., Serre, I., Siozopoulou, V., Sizaret, D., Smojver-Ježek, S., Solassol, J., Steinestel, K., Stojšić, J., Syrykh, C., Timofeev, S., Troncone, G., Uguen, A., Valmary-Degano, S., Vigier, A., Volante, M., Wahl, S.G.F., Stenzinger, A., and Ilié, M.

Published
2023
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5. Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

Author

Hofman, P., Ilié, M., Chamorey, E., Brest, P., Schiappa, R., Nakache, V., Antoine, M., Barberis, M., Begueret, H., Bibeau, F., Bonnetaud, C., Boström, P., Brousset, P., Bubendorf, L., Carvalho, L., Cathomas, G., Cazes, A., Chalabreysse, L., Chenard, M.-P., Copin, M.-C., Côté, J.-F., Damotte, D., de Leval, L., Delongova, P., Thomas de Montpreville, V., de Muret, A., Dema, A., Dietmaier, W., Evert, M., Fabre, A., Forest, F., Foulet, A., Garcia, S., Garcia-Martos, M., Gibault, L., Gorkiewicz, G., Jonigk, D., Gosney, J., Hofman, A., Kern, I., Kerr, K., Kossai, M., Kriegsmann, M., Lassalle, S., Long-Mira, E., Lupo, A., Mamilos, A., Matěj, R., Meilleroux, J., Ortiz-Villalón, C., Panico, L., Panizo, A., Papotti, M., Pauwels, P., Pelosi, G., Penault-Llorca, F., Pop, O., Poté, N., Cajal, S.R.Y., Sabourin, J.-C., Salmon, I., Sajin, M., Savic-Prince, S., Schildhaus, H.-U., Schirmacher, P., Serre, I., Shaw, E., Sizaret, D., Stenzinger, A., Stojsic, J., Thunnissen, E., Timens, W., Troncone, G., Werlein, C., Wolff, H., Berthet, J.-P., Benzaquen, J., Marquette, C.-H., Hofman, V., and Calabrese, F.

Published
2021
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7. A two-step methodology for product platform design and assessment in high-variety manufacturing

Author

Bortolini M., Calabrese F., Galizia F. G., Regattieri A., Bortolini M., Calabrese F., Galizia F.G., and Regattieri A.

Subjects
Operations and logistic, Product platform, Industrial plant, Control and Systems Engineering, Mechanical Engineering, Delayed product differentiation, Variety, Make to stock, Industrial and Manufacturing Engineering, Software, Make to order, Computer Science Applications
Abstract

The delayed product differentiation (DPD) recently rose as a hybrid production strategy able to overcome the main limits of make to stock (MTS) and make to order (MTO), guaranteeing the management of high variety and keeping low storage cost and quick response time by using the so-called product platforms. These platforms are a set of sub-systems forming a common structure from which a set of derivative variants can be efficiently produced. Platforms are manufactured and stocked following an MTS strategy. Then, they are customized into different variants, following an MTO strategy. Current literature proposes methods for platform design mainly using optimization techniques, which usually have a high computational complexity for efficiently managing real-size industrial instances in the modern mass customization era. Hence, efficient algorithms need to be developed to manage the product platforms design for such instances. To fill this gap, this paper proposes a two-step methodology for product platforms design and assessment in high-variety manufacturing. The design step involves the use of a novel modified algorithm for solving the longest common subsequence (LCS) problem and of the k-medoids clustering for the identification of the platform structure and the assignment of the variants to the platforms. The platforms are then assessed against a set of industrial and market metrics, i.e. the MTS cost, the variety, the customer responsiveness, and the variants production cost. The evaluation of the platform set against such a combined set of drivers enhancing both company and market perspectives is missing in the literature. A real case study dealing with the manufacturing of a family of valves exemplifies the efficiency of the methodology in supporting companies in managing high-variety to best balance the proposed metrics.

Published
2023

8. Urban Gravity: a Model for Intercity Telecommunication Flows

Author

Krings, G., Calabrese, F., Ratti, C., and Blondel, V. D.

Subjects
Physics - Physics and Society
Abstract

We analyze the anonymous communication patterns of 2.5 million customers of a Belgian mobile phone operator. Grouping customers by billing address, we build a social network of cities, that consists of communications between 571 cities in Belgium. We show that inter-city communication intensity is characterized by a gravity model: the communication intensity between two cities is proportional to the product of their sizes divided by the square of their distance.

Published
2009
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9. PL03.07 Invasion or No Invasion, That’s the Question. A Large Reproducibility Study in Pulmonary Adenocarcinoma, Supporting a Modified Classification

Author

Thunnissen, E., primary, Blaauwgeers, H., additional, Filipello, F., additional, Lissenberg-Witte, B., additional, Minami, Y., additional, Noguchi, M., additional, Le Quense, J., additional, Papotti, M.G., additional, Flieder, D., additional, Pelosi, G., additional, Sansano, I., additional, Berezowska, S., additional, Ryška, A., additional, Brcic, L., additional, Motoi, N., additional, Nakatani, Y., additional, Kuempers, C., additional, Hofman, P., additional, Hofman, V., additional, Grotnes Dale, V., additional, Rossi, G., additional, Ambrosi, F., additional, Matsubara, D., additional, Ishikawa, Y., additional, Weynand, B., additional, Calabrese, F., additional, Pezzuto, F., additional, Kern, I., additional, Nicholson, S., additional, Mutka, A.-L., additional, Dacic, S., additional, Beasley, M.B., additional, Arrigoni, G., additional, Timens, W., additional, Ooft, M., additional, Brinkhuis, M., additional, Bulkmans, N., additional, Britstra, R., additional, Vreuls, W., additional, Jones, K., additional, von der Thüsen, J., additional, Hager, H., additional, Perner, S., additional, Moore, D., additional, Leonte, D.G., additional, Al-Janabi, S., additional, Schønau, A., additional, Stenzinger, A., additional, and Kazdal, D., additional

Published
2023
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10. P1.23-06 Liquid Biopsy Predicts Differential Benefit from First Line Pembrolizumab in Advanced Non-small Cell Lung Cancer

Author

Bonanno, L., primary, Zulato, E., additional, Del Bianco, P., additional, Boscolo Bragadin, A., additional, Attili, I., additional, Pavan, A., additional, Nardo, G., additional, Dal Maso, A., additional, Frega, S., additional, Ferro, A., additional, Pasello, G., additional, Fassan, M., additional, Calabrese, F., additional, Guarneri, V., additional, and Indraccolo, S., additional

Published
2023
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11. P2.20-01 A Precision Medicine Approach by Performing Comprehensive Cancer Genome Profiling of Thymomas and Recurrent Thymomas

Author

Lococo, F., primary, Evangelista, J., additional, De Paolis, E., additional, Chiappetta, M., additional, Dell'Amore, A., additional, Comacchio, G.M., additional, Perrucci, A., additional, Nero, C., additional, Scambia, G., additional, Giacò, L., additional, Pezzuto, F., additional, Calabrese, F., additional, Minucci, A., additional, Bria, E., additional, Rea, F., additional, and Margaritora, S., additional

Published
2023
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13. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Author

Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri C., De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Lazzaroni M. G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri C., De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Lazzaroni M. G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., and Matucci-Cerinic M.

Abstract

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Published
2022

14. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author

De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Dall'Ara F., Lazzaroni M. G., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Risa A. M., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., Ferri C., De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Dall'Ara F., Lazzaroni M. G., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Risa A. M., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., and Ferri C.

Abstract

OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Published
2022

15. Gut microbiota composition is altered in a preclinical model of type 1 diabetes mellitus: Influence on gut steroids, permeability, and cognitive abilities

Author

Diviccaro, S, Falvo, E, Piazza, R, Cioffi, L, Herian, M, Brivio, P, Calabrese, F, Giatti, S, Caruso, D, Melcangi, R, Diviccaro, Silvia, Falvo, Eva, Piazza, Rocco, Cioffi, Lucia, Herian, Monika, Brivio, Paola, Calabrese, Francesca, Giatti, Silvia, Caruso, Donatella, Melcangi, Roberto Cosimo, Diviccaro, S, Falvo, E, Piazza, R, Cioffi, L, Herian, M, Brivio, P, Calabrese, F, Giatti, S, Caruso, D, Melcangi, R, Diviccaro, Silvia, Falvo, Eva, Piazza, Rocco, Cioffi, Lucia, Herian, Monika, Brivio, Paola, Calabrese, Francesca, Giatti, Silvia, Caruso, Donatella, and Melcangi, Roberto Cosimo

Abstract

Sex steroid hormones are not only synthesized from the gonads but also by other tissues, such as the brain (i.e., neurosteroids) and colon (i.e., gut steroids). Gut microbiota can be shaped from sex steroid hormones synthesized from the gonads and locally interacts with gut steroids as in turn modulates neurosteroids. Type 1 diabetes mellitus (T1DM) is characterized by dysbiosis and also by diabetic encephalopathy. However, the interactions of players of gut-brain axis, such as gut steroids, gut permeability markers and microbiota, have been poorly explored in this pathology and, particularly in females. On this basis, we have explored, in streptozotocin (STZ)induced adult female rats, whether one month of T1DM may alter (I) gut microbiome composition and diversity by 16S next-generation sequencing, (II) gut steroid levels by liquid chromatography-tandem mass spectrometry, (III) gut permeability markers by gene expression analysis, (IV) cognitive behavior by the novel object recognition (NOR) test and whether correlations among these aspects may occur. Results obtained reveal that T1DM alters gut beta-, but not alpha-diversity. The pathology is also associated with a decrease and an increase in colonic pregnenolone and allopregnanolone levels, respectively. Additionally, diabetes alters gut permeability and worsens cognitive behavior. Finally, we reported a significant correlation of pregnenolone with Blautia, claudin-1 and the NOR index and of allopregnanolone with Parasutterella, Gammaproteobacteria and claudin-1. Altogether, these results suggest new putative roles of these two gut steroids related to cognitive deficit and dysbiosis in T1DM female experimental model.

Published
2023

17. EP07.01-004 Long Survivor Epithelioid Pleural Mesotheliomas Are Characterized by Tertiary Lymphoid Structures: An Update to the MATCH Study

Author

Grosso, F., primary, Mannarino, L., additional, Paracchini, L., additional, Pezzuto, F., additional, Moracci, L., additional, Olteanu, G.-E., additional, Delfanti, S., additional, Callari, M., additional, Penpa, S., additional, Maconi, A., additional, De Simone, I., additional, Bosetti, C., additional, Allavena, P., additional, Marchini, S., additional, Calabrese, F., additional, and D'Incalci, M., additional

Published
2022
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18. Crescere con la matematica: officine esperienziali di matematica per la formazione degli insegnanti della scuola dell'infanzia e primaria. Guida didattica per docenti e formatori

Author

Lizasoain Iriso, M. I, Magrone, P, Millan Gasca, A, Arlotti, F, Scaramuzzo, G, Subania, F., Celi, V, Regoliosi, L., Calabrese, F., Mazzitelli, A., Migliucci, M. C., Neri Macchiaverna, F., Spagnoletti Zeuli, E., García Catalán, O. R., Abaurrea Larrayoz, J., Cogolludo, J. I., Gil Clemente, E., Agudo Carnicer, A., Gil Clemente, A. C., Marcuello Servós, C., Paricio Abadías, R., Lizasoain Iriso, M. I, Magrone, P, Millan Gasca, A, Arlotti, F, Scaramuzzo, G, Subania, F., Celi, V, Regoliosi, L., Calabrese, F., Mazzitelli, A., Migliucci, M. C., Neri Macchiaverna, F., Spagnoletti Zeuli, E., García Catalán, O. R., Abaurrea Larrayoz, J., Cogolludo, J. I., Gil Clemente, E., Agudo Carnicer, A., Gil Clemente, A. C., Marcuello Servós, C., and Paricio Abadías, R.

Subjects
Educazione matematica universitaria, educazione matematica pre-servizio degli insegnanti primari, officine matematiche sperienziali, educazione dei bambini con disabilità intellettiva
Abstract

Il progetto Erasmus+ ANFoMAM, "Imparare dai bambini per formare insegnanti nell'area della matematica" è nato da un incontro tra un gruppo di insegnanti responsabili delle materie matematiche nei corsi di laurea in Formazione Primaria in diverse università in Francia, Italia e Spagna. L'incontro è avvenuto all'interno del Simposio dal titolo "Oltre l'alfabetizzazione numerica" che si è svolto presso il 5° Congresso Internazionale di Scienze dell'Educazione e dello Sviluppo (Santander, maggio 2017), in cui sono state condivise diverse esperienze che si stavano realizzando nelle istituzioni di formazione iniziale e continua degli insegnanti di istruzione elementare. Ciò che è stato osservato in questi paesi è che, in generale, i partecipanti ai corsi di laurea in formazione primaria avevano avuto un cattivo rapporto con la matematica durante i loro anni di studio, spesso accompagnato da sentimenti di rifiuto o angoscia, oltre ad aver acquisito una visione della matematica ridotta al calcolo e alle procedure meccaniche. Evitando il falso dibattito tra il concentrarsi sul miglioramento delle competenze matematiche o l'insegnamento delle tecniche didattiche, tutte le iniziative presentate al Congresso di Santander hanno perseguito l'obiettivo comune di fornire agli insegnanti sia una profonda comprensione dei concetti di base della matematica sia le risorse didattiche necessarie per l'insegnamento efficace in classe. I ricercatori hanno convenuto che era l'Università che avrebbe dovuto fornire a questi insegnanti in formazione nuove esperienze con la matematica, in modo che potessero trasmettere ai bambini la fiducia e l'entusiasmo necessari per imparare. La progettazione e la realizzazione di esperienze di questo tipo è l'obiettivo fondamentale del progetto ANFoMAM, che è stato finanziato dal programma Erasmus+ di Partenariati Strategici nel settore dell'istruzione superiore, e al quale hanno partecipato le seguenti istituzioni: Université de Bordeaux (Istituto Superiore Nazionale di Insegnanti e Istruzione dell'Accademia di Bordeaux), in Francia; Università Roma Tre (Dipartimento di Scienze della Formazione), in Italia; Università di Saragozza e Università Pubblica di Navarra, in Spagna; Associazione Sesdown, che si dedica alla ricerca nell'educazione dei bambini con Trisomia 21, sempre in Spagna, e l'Associazione ToKalon, che opera in Italia nell'ambito della formazione continua degli insegnanti in servizio.

Published
2022

19. Growing with mathematics: experiential math workshops for education of pre-school and primary school teachers a teaching guide for professional development and instruction of future teachers

Author

Lizasoain Iriso, M. I, Magrone, P, Millan Gasca, A, Arlotti, F, Scaramuzzo, G, Subania, F., Celi, V, Regoliosi, L., Calabrese, F., Mazzitelli, A., Migliucci, M. C., Neri Macchiaverna, F., Spagnoletti Zeuli, E., García Catalán, O. R., Abaurrea Larrayoz, J., Cogolludo, J. I., Gil Clemente, E., Agudo Carnicer, A., Gil Clemente, A. C., Marcuello Servós, C., Paricio Abadías, R, Lizasoain Iriso, M. I, Magrone, P, Millan Gasca, A, Arlotti, F, Scaramuzzo, G, Subania, F., Celi, V, Regoliosi, L., Calabrese, F., Mazzitelli, A., Migliucci, M. C., Neri Macchiaverna, F., Spagnoletti Zeuli, E., García Catalán, O. R., Abaurrea Larrayoz, J., Cogolludo, J. I., Gil Clemente, E., Agudo Carnicer, A., Gil Clemente, A. C., Marcuello Servós, C., and Paricio Abadías, R

Abstract

The Erasmus+ ANFoMAM project, "Learning from children to train teachers in the area of mathematics" was born from a meeting between a group of teachers responsible for mathematics subjects in Primary Education degree courses in different universities in France, Italy and Spain. The meeting took place within the Symposium entitled "Beyond numerical literacy" which took place at the 5th International Congress of Education and Development Sciences (Santander, May 2017), in which different experiences that were taking place in initial and continuing education institutions for elementary education teachers were shared. What was observed in these countries is that, in general, participants in primary education degree courses had a poor relationship with mathematics during their student years, often accompanied by feelings of rejection or distress, as well as having acquired a view of mathematics reduced to calculation and mechanical procedures. All the initiatives presented at the Santander Congress pursued the common goal of providing teachers with both a deep understanding of the basic concepts of mathematics and the educational resources necessary for effective teaching in the classroom. The researchers agreed that it was the university that should provide these trainee teachers with new experiences with mathematics, so that they could give children the confidence and enthusiasm to learn. The design and implementation of experiences of this type is the fundamental objective of the ANFoMAM project, which was funded by the Erasmus+ program of Strategic Partnerships in the Higher Education Sector, and in which the following institutions participated: Université de Bordeaux (Institute National Superior of Teachers and Education of the Academy of Bordeaux), in France; Roma Tre University (Department of Education), in Italy; University of Zaragoza and Public University of Navarra, in Spain; Sesdown Association, which is dedicated to research in the education of children with Trisomy 21, also in Spain, and the ToKalon Association, which operates in Italy in the field of continuous training of in-service teachers. This innovative didactic material is a didactic guide for teacher mathematical training, made up of 6 mathematical workshops: 1. Understanding of arithmetic algorithms. 2. Resolution of arithmetic problems. 3. Relationship between arithmetic and geometry. 4. Mental calculation and use of the calculator. 5. History of mathematics and its teaching. 6. Geometry.

Published
2022

20. Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison

Author

Famularo, S, Donadon, M, Cipriani, F, Bernasconi, D, Labarba, G, Dominioni, T, Iaria, M, Molfino, S, Conci, S, Ferrari, C, Garatti, M, Delvecchio, A, Troci, A, Patauner, S, Frassani, S, Cosimelli, M, Zanus, G, Giuliante, F, Jovine, E, Valsecchi, M, Grazi, G, Antonucci, A, Frena, A, Crespi, M, Memeo, R, Zimmitti, G, Griseri, G, Ruzzenente, A, Baiocchi, G, Dallavalle, R, Maestri, M, Ercolani, G, Aldrighetti, L, Torzilli, G, Romano, F, Ciulli, C, Giani, A, Carissimi, F, Costa, G, Ratti, F, Cucchetti, A, Calabrese, F, Cremaschi, E, Lazzari, G, Franceschi, A, Sega, V, Conticchio, M, Pennacchi, L, Ciola, M, Sciannamea, I, De Peppo, V, Famularo S., Donadon M., Cipriani F., Bernasconi D. P., LaBarba G., Dominioni T., Iaria M., Molfino S., Conci S., Ferrari C., Garatti M., Delvecchio A., Troci A., Patauner S., Frassani S., Cosimelli M., Zanus G., Giuliante F., Jovine E., Valsecchi M. G., Grazi G., Antonucci A., Frena A., Crespi M., Memeo R., Zimmitti G., Griseri G., Ruzzenente A., Baiocchi G., DallaValle R., Maestri M., Ercolani G., Aldrighetti L., Torzilli G., Romano F., Ciulli C., Giani A., Carissimi F., Costa G., Ratti F., Cucchetti A., Calabrese F., Cremaschi E., Lazzari G., Franceschi A., Sega V., Conticchio M., Pennacchi L., Ciola M., Sciannamea I., De Peppo V., Famularo, S, Donadon, M, Cipriani, F, Bernasconi, D, Labarba, G, Dominioni, T, Iaria, M, Molfino, S, Conci, S, Ferrari, C, Garatti, M, Delvecchio, A, Troci, A, Patauner, S, Frassani, S, Cosimelli, M, Zanus, G, Giuliante, F, Jovine, E, Valsecchi, M, Grazi, G, Antonucci, A, Frena, A, Crespi, M, Memeo, R, Zimmitti, G, Griseri, G, Ruzzenente, A, Baiocchi, G, Dallavalle, R, Maestri, M, Ercolani, G, Aldrighetti, L, Torzilli, G, Romano, F, Ciulli, C, Giani, A, Carissimi, F, Costa, G, Ratti, F, Cucchetti, A, Calabrese, F, Cremaschi, E, Lazzari, G, Franceschi, A, Sega, V, Conticchio, M, Pennacchi, L, Ciola, M, Sciannamea, I, De Peppo, V, Famularo S., Donadon M., Cipriani F., Bernasconi D. P., LaBarba G., Dominioni T., Iaria M., Molfino S., Conci S., Ferrari C., Garatti M., Delvecchio A., Troci A., Patauner S., Frassani S., Cosimelli M., Zanus G., Giuliante F., Jovine E., Valsecchi M. G., Grazi G., Antonucci A., Frena A., Crespi M., Memeo R., Zimmitti G., Griseri G., Ruzzenente A., Baiocchi G., DallaValle R., Maestri M., Ercolani G., Aldrighetti L., Torzilli G., Romano F., Ciulli C., Giani A., Carissimi F., Costa G., Ratti F., Cucchetti A., Calabrese F., Cremaschi E., Lazzari G., Franceschi A., Sega V., Conticchio M., Pennacchi L., Ciola M., Sciannamea I., and De Peppo V.

Abstract

Background: Management of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC. Methods: This is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups. Results: 1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14–2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22–2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54–0.69; p<0.001). Conclusion: Curative approaches may guarantee long-term survival in case of recurrence.

Published
2021

21. The Impact of Postoperative Ascites on Survival After Surgery for Hepatocellular Carcinoma: a National Study

Author

Famularo, S, Donadon, M, Cipriani, F, Ardito, F, Iaria, M, Carissimi, F, Perri, P, Dominioni, T, Zanello, M, Conci, S, Molfino, S, D'Acapito, F, Germani, P, Ferrari, C, Patauner, S, Pinotti, E, Sciannamea, I, Garatti, M, Lodo, E, Troci, A, Delvecchio, A, Floridi, A, Bernasconi, D, Fumagalli, L, Chiarelli, M, Memeo, R, Crespi, M, Zanus, G, Zimmitti, G, Antonucci, A, Zago, M, Frena, A, Griseri, G, Tarchi, P, Ercolani, G, Baiocchi, G, Ruzzenente, A, Jovine, E, Maestri, M, Grazi, G, Valle, R, Giuliante, F, Aldrighetti, L, Romano, F, Torzilli, G, Costa, G, Ciulli, C, Giani, A, Ratti, F, Bellobono, M, Cremaschi, E, Valsecchi, M, De Peppo, V, Calabrese, F, Desario, G, Lazzari, G, Cucchetti, A, Cosola, D, Percivale, A, Ciola, M, Montuori, M, Frassani, S, Manzoni, A, Salvador, L, Pennacchi, L, Corleone, P, Conticchio, M, Famularo S., Donadon M., Cipriani F., Ardito F., Iaria M., Carissimi F., Perri P., Dominioni T., Zanello M., Conci S., Molfino S., D'Acapito F., Germani P., Ferrari C., Patauner S., Pinotti E., Sciannamea I., Garatti M., Lodo E., Troci A., Delvecchio A., Floridi A., Bernasconi D. P., Fumagalli L., Chiarelli M., Memeo R., Crespi M., Zanus G., Zimmitti G., Antonucci A., Zago M., Frena A., Griseri G., Tarchi P., Ercolani G., Baiocchi G. L., Ruzzenente A., Jovine E., Maestri M., Grazi G. L., Valle R. D., Giuliante F., Aldrighetti L., Romano F., Torzilli G., Costa G., Ciulli C., Giani A., Ratti F., Bellobono M., Cremaschi E., Valsecchi M. G., De Peppo V., Calabrese F., DeSario G., Lazzari G., Cucchetti A., Cosola D., Percivale A., Ciola M., Montuori M., Frassani S., Manzoni A., Salvador L., Pennacchi L., Corleone P., Conticchio M., Famularo, S, Donadon, M, Cipriani, F, Ardito, F, Iaria, M, Carissimi, F, Perri, P, Dominioni, T, Zanello, M, Conci, S, Molfino, S, D'Acapito, F, Germani, P, Ferrari, C, Patauner, S, Pinotti, E, Sciannamea, I, Garatti, M, Lodo, E, Troci, A, Delvecchio, A, Floridi, A, Bernasconi, D, Fumagalli, L, Chiarelli, M, Memeo, R, Crespi, M, Zanus, G, Zimmitti, G, Antonucci, A, Zago, M, Frena, A, Griseri, G, Tarchi, P, Ercolani, G, Baiocchi, G, Ruzzenente, A, Jovine, E, Maestri, M, Grazi, G, Valle, R, Giuliante, F, Aldrighetti, L, Romano, F, Torzilli, G, Costa, G, Ciulli, C, Giani, A, Ratti, F, Bellobono, M, Cremaschi, E, Valsecchi, M, De Peppo, V, Calabrese, F, Desario, G, Lazzari, G, Cucchetti, A, Cosola, D, Percivale, A, Ciola, M, Montuori, M, Frassani, S, Manzoni, A, Salvador, L, Pennacchi, L, Corleone, P, Conticchio, M, Famularo S., Donadon M., Cipriani F., Ardito F., Iaria M., Carissimi F., Perri P., Dominioni T., Zanello M., Conci S., Molfino S., D'Acapito F., Germani P., Ferrari C., Patauner S., Pinotti E., Sciannamea I., Garatti M., Lodo E., Troci A., Delvecchio A., Floridi A., Bernasconi D. P., Fumagalli L., Chiarelli M., Memeo R., Crespi M., Zanus G., Zimmitti G., Antonucci A., Zago M., Frena A., Griseri G., Tarchi P., Ercolani G., Baiocchi G. L., Ruzzenente A., Jovine E., Maestri M., Grazi G. L., Valle R. D., Giuliante F., Aldrighetti L., Romano F., Torzilli G., Costa G., Ciulli C., Giani A., Ratti F., Bellobono M., Cremaschi E., Valsecchi M. G., De Peppo V., Calabrese F., DeSario G., Lazzari G., Cucchetti A., Cosola D., Percivale A., Ciola M., Montuori M., Frassani S., Manzoni A., Salvador L., Pennacchi L., Corleone P., and Conticchio M.

Abstract

Background: Postoperative ascites (POA) is the most common complication after liver surgery for hepatocarcinoma (HCC), but its impact on survival is not reported. The aim of the study is to investigate its impact on overall survival (OS) and disease-free survival (DFS), and secondarily to identify the factors that may predict the occurrence. Method: Data were collected from 23 centers participating in the Italian Surgical HCC Register (HE.RC.O.LE.S. Group) between 2008 and 2018. POA was defined as ≥500 ml of ascites in the drainage after surgery. Survival analysis was conducted by the Kaplan Meier method. Risk adjustment analysis was conducted by Cox regression to investigate the risk factors for mortality and recurrence. Results: Among 2144 patients resected for HCC, 1871(88.5%) patients did not experience POA while 243(11.5%) had the complication. Median OS for NO-POA group was not reached, while it was 50 months (95%CI = 41–71) for those with POA (p < 0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352–2.129, p < 0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921–1.822, p < 0.001) and bilobar disease (OR = 1.940, 95%CI = 0.921–1.822, p: 0.004) were predictors of POA, while laparoscopic surgery was protective (OR = 0.445, 95%CI = 0.295–0.668, p < 0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p < 0.001). Conclusion: The occurrence of POA after surgery for HCC strongly increases the risk of long-term mortality and its occurrence is relatively frequent. More efforts in surgical planning should be made to limit its occurrence.

Published
2021

22. The Impact of Postoperative Ascites on Survival After Surgery for Hepatocellular Carcinoma: a National Study

Author

Famularo, S., Donadon, M., Cipriani, F., Ardito, F., Iaria, M., Carissimi, F., Perri, P., Dominioni, T., Zanello, M., Conci, S., Molfino, S., D'Acapito, F., Germani, P., Ferrari, C., Patauner, S., Pinotti, E., Sciannamea, I., Garatti, M., Lodo, E., Troci, A., Delvecchio, A., Floridi, A., Bernasconi, D. P., Fumagalli, L., Chiarelli, M., Memeo, R., Crespi, M., Zanus, G., Zimmitti, G., Antonucci, A., Zago, M., Frena, A., Griseri, G., Tarchi, P., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, M., Grazi, G. L., Valle, R. D., Giuliante, F., Aldrighetti, L., Romano, F., Torzilli, G., Costa, G., Ciulli, C., Giani, A., Ratti, F., Bellobono, M., Cremaschi, E., Valsecchi, M. G., De Peppo, V., Calabrese, F., Desario, G., Lazzari, G., Cucchetti, A., Cosola, D., Percivale, A., Ciola, M., Montuori, M., Frassani, S., Manzoni, A., Salvador, L., Pennacchi, L., Corleone, P., Conticchio, M., Famularo, S., Donadon, M., Cipriani, F., Ardito, F., Iaria, M., Carissimi, F., Perri, P., Dominioni, T., Zanello, M., Conci, S., Molfino, S., D'Acapito, F., Germani, P., Ferrari, C., Patauner, S., Pinotti, E., Sciannamea, I., Garatti, M., Lodo, E., Troci, A., Delvecchio, A., Floridi, A., Bernasconi, D. P., Fumagalli, L., Chiarelli, M., Memeo, R., Crespi, M., Zanus, G., Zimmitti, G., Antonucci, A., Zago, M., Frena, A., Griseri, G., Tarchi, P., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, M., Grazi, G. L., Valle, R. D., Giuliante, F., Aldrighetti, L., Romano, F., Torzilli, G., Costa, G., Ciulli, C., Giani, A., Ratti, F., Bellobono, M., Cremaschi, E., Valsecchi, M. G., De Peppo, V., Calabrese, F., Desario, G., Lazzari, G., Cucchetti, A., Cosola, D., Percivale, A., Ciola, M., Montuori, M., Frassani, S., Manzoni, A., Salvador, L., Pennacchi, L., Corleone, P., Conticchio, M., Famularo S., Donadon M., Cipriani F., Ardito F., Iaria M., Carissimi F., Perri P., Dominioni T., Zanello M., Conci S., Molfino S., D'Acapito F., Germani P., Ferrari C., Patauner S., Pinotti E., Sciannamea I., Garatti M., Lodo E., Troci A., Delvecchio A., Floridi A., Bernasconi D.P., Fumagalli L., Chiarelli M., Memeo R., Crespi M., Zanus G., Zimmitti G., Antonucci A., Zago M., Frena A., Griseri G., Tarchi P., Ercolani G., Baiocchi G.L., Ruzzenente A., Jovine E., Maestri M., Grazi G.L., Valle R.D., Giuliante F., Aldrighetti L., Romano F., Torzilli G., Costa G., Ciulli C., Giani A., Ratti F., Bellobono M., Cremaschi E., Valsecchi M.G., De Peppo V., Calabrese F., DeSario G., Lazzari G., Cucchetti A., Cosola D., Percivale A., Ciola M., Montuori M., Frassani S., Manzoni A., Salvador L., Pennacchi L., Corleone P., Conticchio M., Famularo, S, Donadon, M, Cipriani, F, Ardito, F, Iaria, M, Carissimi, F, Perri, P, Dominioni, T, Zanello, M, Conci, S, Molfino, S, D'Acapito, F, Germani, P, Ferrari, C, Patauner, S, Pinotti, E, Sciannamea, I, Garatti, M, Lodo, E, Troci, A, Delvecchio, A, Floridi, A, Bernasconi, D, Fumagalli, L, Chiarelli, M, Memeo, R, Crespi, M, Zanus, G, Zimmitti, G, Antonucci, A, Zago, M, Frena, A, Griseri, G, Tarchi, P, Ercolani, G, Baiocchi, G, Ruzzenente, A, Jovine, E, Maestri, M, Grazi, G, Valle, R, Giuliante, F, Aldrighetti, L, Romano, F, Torzilli, G, Costa, G, Ciulli, C, Giani, A, Ratti, F, Bellobono, M, Cremaschi, E, Valsecchi, M, De Peppo, V, Calabrese, F, Desario, G, Lazzari, G, Cucchetti, A, Cosola, D, Percivale, A, Ciola, M, Montuori, M, Frassani, S, Manzoni, A, Salvador, L, Pennacchi, L, Corleone, P, and Conticchio, M

Subjects
Laparoscopic surgery, medicine.medical_specialty, endocrine system, Carcinoma, Hepatocellular, Disease-free survival, Hepatocellular carcinoma, medicine.medical_treatment, Settore MED/18 - CHIRURGIA GENERALE, 030230 surgery, NO, Liver surgery, Overall survival, Postoperative ascites, Postoperative complications, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Ascites, Risk of mortality, Medicine, Hepatectomy, Humans, Survival analysis, LS7_4, Retrospective Studies, business.industry, Proportional hazards model, Carcinoma, Liver Neoplasms, Gastroenterology, Hepatocellular, medicine.disease, Surgery, Postoperative complication, Postoperative ascite, Neoplasm Recurrence, Local, 030220 oncology & carcinogenesis, Ascite, medicine.symptom, Neoplasm Recurrence, Local, business, Complication, Varices, Human
Abstract

Background: Postoperative ascites (POA) is the most common complication after liver surgery for hepatocarcinoma (HCC), but its impact on survival is not reported. The aim of the study is to investigate its impact on overall survival (OS) and disease-free survival (DFS), and secondarily to identify the factors that may predict the occurrence. Method: Data were collected from 23 centers participating in the Italian Surgical HCC Register (HE.RC.O.LE.S. Group) between 2008 and 2018. POA was defined as ≥500 ml of ascites in the drainage after surgery. Survival analysis was conducted by the Kaplan Meier method. Risk adjustment analysis was conducted by Cox regression to investigate the risk factors for mortality and recurrence. Results: Among 2144 patients resected for HCC, 1871(88.5%) patients did not experience POA while 243(11.5%) had the complication. Median OS for NO-POA group was not reached, while it was 50 months (95%CI = 41–71) for those with POA (p < 0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352–2.129, p < 0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921–1.822, p < 0.001) and bilobar disease (OR = 1.940, 95%CI = 0.921–1.822, p: 0.004) were predictors of POA, while laparoscopic surgery was protective (OR = 0.445, 95%CI = 0.295–0.668, p < 0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p < 0.001). Conclusion: The occurrence of POA after surgery for HCC strongly increases the risk of long-term mortality and its occurrence is relatively frequent. More efforts in surgical planning should be made to limit its occurrence.

Published
2021

23. Hepatocellular carcinoma surgical and oncological trends in a national multicentric population: the HERCOLES experience

Author

Famularo, S, Donadon, M, Cipriani, F, Ardito, F, Carissimi, F, Perri, P, Iaria, M, Dominioni, T, Zanello, M, Conci, S, Molfino, S, Labarba, G, Ferrari, C, Germani, P, Patauner, S, Pinotti, E, Lodo, E, Garatti, M, Sciannamea, I, Troci, A, Conticchio, M, Floridi, A, Chiarelli, M, Fumagalli, L, Memeo, R, Crespi, M, Antonucci, A, Zimmitti, G, Zanus, G, Zago, M, Frena, A, Tarchi, P, Griseri, G, Ercolani, G, Baiocchi, G, Ruzzenente, A, Jovine, E, Maestri, M, Dallavalle, R, Grazi, G, Giuliante, F, Aldrighetti, L, Torzilli, G, Romano, F, Bernasconi, D, Ciulli, C, Giani, A, Costa, G, Ratti, F, Bellobono, M, Calabrese, F, Cremaschi, E, De Peppo, V, Cucchetti, A, Lazzari, G, Percivale, A, Ciola, M, Sega, V, Frassani, S, Del Vecchio, A, Pennacchi, L, Corleone, P, Cosola, D, Salvador, L, Montuori, M, Famularo S., Donadon M., Cipriani F., Ardito F., Carissimi F., Perri P., Iaria M., Dominioni T., Zanello M., Conci S., Molfino S., LaBarba G., Ferrari C., Germani P., Patauner S., Pinotti E., Lodo E., Garatti M., Sciannamea I., Troci A., Conticchio M., Floridi A., Chiarelli M., Fumagalli L., Memeo R., Crespi M., Antonucci A., Zimmitti G., Zanus G., Zago M., Frena A., Tarchi P., Griseri G., Ercolani G., Baiocchi G. L., Ruzzenente A., Jovine E., Maestri M., DallaValle R., Grazi G. L., Giuliante F., Aldrighetti L., Torzilli G., Romano F., Bernasconi D. P., Ciulli C., Giani A., Costa G., Ratti F., Bellobono M., Calabrese F., Cremaschi E., De Peppo V., Cucchetti A., Lazzari G., Percivale A., Ciola M., Sega V., Frassani S., Del Vecchio A., Pennacchi L., Corleone P., Cosola D., Salvador L., Montuori M., Famularo, S, Donadon, M, Cipriani, F, Ardito, F, Carissimi, F, Perri, P, Iaria, M, Dominioni, T, Zanello, M, Conci, S, Molfino, S, Labarba, G, Ferrari, C, Germani, P, Patauner, S, Pinotti, E, Lodo, E, Garatti, M, Sciannamea, I, Troci, A, Conticchio, M, Floridi, A, Chiarelli, M, Fumagalli, L, Memeo, R, Crespi, M, Antonucci, A, Zimmitti, G, Zanus, G, Zago, M, Frena, A, Tarchi, P, Griseri, G, Ercolani, G, Baiocchi, G, Ruzzenente, A, Jovine, E, Maestri, M, Dallavalle, R, Grazi, G, Giuliante, F, Aldrighetti, L, Torzilli, G, Romano, F, Bernasconi, D, Ciulli, C, Giani, A, Costa, G, Ratti, F, Bellobono, M, Calabrese, F, Cremaschi, E, De Peppo, V, Cucchetti, A, Lazzari, G, Percivale, A, Ciola, M, Sega, V, Frassani, S, Del Vecchio, A, Pennacchi, L, Corleone, P, Cosola, D, Salvador, L, Montuori, M, Famularo S., Donadon M., Cipriani F., Ardito F., Carissimi F., Perri P., Iaria M., Dominioni T., Zanello M., Conci S., Molfino S., LaBarba G., Ferrari C., Germani P., Patauner S., Pinotti E., Lodo E., Garatti M., Sciannamea I., Troci A., Conticchio M., Floridi A., Chiarelli M., Fumagalli L., Memeo R., Crespi M., Antonucci A., Zimmitti G., Zanus G., Zago M., Frena A., Tarchi P., Griseri G., Ercolani G., Baiocchi G. L., Ruzzenente A., Jovine E., Maestri M., DallaValle R., Grazi G. L., Giuliante F., Aldrighetti L., Torzilli G., Romano F., Bernasconi D. P., Ciulli C., Giani A., Costa G., Ratti F., Bellobono M., Calabrese F., Cremaschi E., De Peppo V., Cucchetti A., Lazzari G., Percivale A., Ciola M., Sega V., Frassani S., Del Vecchio A., Pennacchi L., Corleone P., Cosola D., Salvador L., and Montuori M.

Abstract

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63–75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5 years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

Published
2020

24. Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of scleroderma spectrum

Author

Ferri, C, Giuggioli, D, Guiducci, S, Lumetti, F, Bajocchi, G, Magnani, L, Codullo, V, Ariani, A, Girelli, F, Riccieri, V, Pellegrino, G, Bosello, S, Foti, R, Visalli, E, Amato, G, Benenati, A, Cuomo, G, Iannone, F, Cacciapaglia, F, De Angelis, R, Ingegnoli, F, Talotta, R, Campochiaro, C, Dagna, L, De Luca, G, Bellando-Randone, S, Spinella, A, Murdaca, G, Romeo, N, De Santis, M, Generali, E, Barsotti, S, Della Rossa, A, Cavazzana, I, Dall'Ara, F, Lazzaroni, M, Cozzi, F, Doria, A, Pigatto, E, Zanatta, E, Ciano, G, Beretta, L, Abignano, G, D'Angelo, S, Mennillo, G, Bagnato, G, Calabrese, F, Caminiti, M, Pagano Mariano, G, Battaglia, E, Lubrano, E, Zanframundo, G, Iuliano, A, Furini, F, Zanetti, A, Carrara, G, Rumi, F, Scirè, C, Matucci-Cerinic, M, Ferri C, Giuggioli D, Guiducci S, Lumetti F, Bajocchi G, Magnani L, Codullo V, Ariani A, Girelli F, Riccieri V, Pellegrino G, Bosello S, Foti R, Visalli E, Amato G, Benenati A, Cuomo G, Iannone F, Cacciapaglia F, De Angelis R, Ingegnoli F, Talotta R, Campochiaro C, Dagna L, De Luca G, Bellando-Randone S, Spinella A, Murdaca G, Romeo N, De Santis M, Generali E, Barsotti S, Della Rossa A, Cavazzana I, Dall'Ara F, Lazzaroni MG, Cozzi F, Doria A, Pigatto E, Zanatta E, Ciano G, Beretta L, Abignano G, D'Angelo S, Mennillo G, Bagnato G, Calabrese F, Caminiti M, Pagano Mariano G, Battaglia E, Lubrano E, Zanframundo G, Iuliano A, Furini F, Zanetti A, Carrara G, Rumi F, Scirè CA, Matucci-Cerinic M, Ferri, C, Giuggioli, D, Guiducci, S, Lumetti, F, Bajocchi, G, Magnani, L, Codullo, V, Ariani, A, Girelli, F, Riccieri, V, Pellegrino, G, Bosello, S, Foti, R, Visalli, E, Amato, G, Benenati, A, Cuomo, G, Iannone, F, Cacciapaglia, F, De Angelis, R, Ingegnoli, F, Talotta, R, Campochiaro, C, Dagna, L, De Luca, G, Bellando-Randone, S, Spinella, A, Murdaca, G, Romeo, N, De Santis, M, Generali, E, Barsotti, S, Della Rossa, A, Cavazzana, I, Dall'Ara, F, Lazzaroni, M, Cozzi, F, Doria, A, Pigatto, E, Zanatta, E, Ciano, G, Beretta, L, Abignano, G, D'Angelo, S, Mennillo, G, Bagnato, G, Calabrese, F, Caminiti, M, Pagano Mariano, G, Battaglia, E, Lubrano, E, Zanframundo, G, Iuliano, A, Furini, F, Zanetti, A, Carrara, G, Rumi, F, Scirè, C, Matucci-Cerinic, M, Ferri C, Giuggioli D, Guiducci S, Lumetti F, Bajocchi G, Magnani L, Codullo V, Ariani A, Girelli F, Riccieri V, Pellegrino G, Bosello S, Foti R, Visalli E, Amato G, Benenati A, Cuomo G, Iannone F, Cacciapaglia F, De Angelis R, Ingegnoli F, Talotta R, Campochiaro C, Dagna L, De Luca G, Bellando-Randone S, Spinella A, Murdaca G, Romeo N, De Santis M, Generali E, Barsotti S, Della Rossa A, Cavazzana I, Dall'Ara F, Lazzaroni MG, Cozzi F, Doria A, Pigatto E, Zanatta E, Ciano G, Beretta L, Abignano G, D'Angelo S, Mennillo G, Bagnato G, Calabrese F, Caminiti M, Pagano Mariano G, Battaglia E, Lubrano E, Zanframundo G, Iuliano A, Furini F, Zanetti A, Carrara G, Rumi F, Scirè CA, and Matucci-Cerinic M

Abstract

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

Published
2020

25. Performance of comprehensive complication index and clavien‐dindo complication scoring system in liver surgery for hepatocellular carcinoma

Author

Giani, A, Cipriani, F, Famularo, S, Donadon, M, Bernasconi, D, Ardito, F, Fazio, F, Nicolini, D, Perri, P, Giuffrida, M, Pontarolo, N, Zanello, M, Lai, Q, Conci, S, Molfino, S, Germani, P, Pinotti, E, Romano, M, La Barba, G, Ferrari, C, Patauner, S, Manzoni, A, Sciannamea, I, Fumagalli, L, Troci, A, Ferraro, V, Floridi, A, Memeo, R, Crespi, M, Chiarelli, M, Antonucci, A, Zimmitti, G, Frena, A, Percivale, A, Ercolani, G, Zanus, G, Zago, M, Tarchi, P, Baiocchi, G, Ruzzenente, A, Rossi, M, Jovine, E, Maestri, M, Valle, R, Grazi, G, Vivarelli, M, Ferrero, A, Giuliante, F, Torzilli, G, Aldrighetti, L, Gianotti, L, Romano, F, Ciulli, C, Braga, M, Ratti, F, Costa, G, Razionale, F, Russolillo, N, Marinelli, L, De Peppo, V, Cremaschi, E, Calabrese, F, Laureiro, Z, Lazzari, G, Cosola, D, Montuori, M, Salvador, L, Cucchetti, A, Franceschi, A, Ciola, M, Sega, V, Calcagno, P, Pennacchi, L, Tedeschi, M, Giani A., Cipriani F., Famularo S., Donadon M., Bernasconi D. P., Ardito F., Fazio F., Nicolini D., Perri P., Giuffrida M., Pontarolo N., Zanello M., Lai Q., Conci S., Molfino S., Germani P., Pinotti E., Romano M., La Barba G., Ferrari C., Patauner S., Manzoni A., Sciannamea I., Fumagalli L., Troci A., Ferraro V., Floridi A., Memeo R., Crespi M., Chiarelli M., Antonucci A., Zimmitti G., Frena A., Percivale A., Ercolani G., Zanus G., Zago M., Tarchi P., Baiocchi G. L., Ruzzenente A., Rossi M., Jovine E., Maestri M., Valle R. D., Grazi G. L., Vivarelli M., Ferrero A., Giuliante F., Torzilli G., Aldrighetti L., Gianotti L., Romano F., Ciulli C., Braga M., Ratti F., Costa G., Razionale F., Russolillo N., Marinelli L., De Peppo V., Cremaschi E., Calabrese F., Laureiro Z. L., Lazzari G., Cosola D., Montuori M., Salvador L., Cucchetti A., Franceschi A., Ciola M., Sega V., Calcagno P., Pennacchi L., Tedeschi M., Giani, A, Cipriani, F, Famularo, S, Donadon, M, Bernasconi, D, Ardito, F, Fazio, F, Nicolini, D, Perri, P, Giuffrida, M, Pontarolo, N, Zanello, M, Lai, Q, Conci, S, Molfino, S, Germani, P, Pinotti, E, Romano, M, La Barba, G, Ferrari, C, Patauner, S, Manzoni, A, Sciannamea, I, Fumagalli, L, Troci, A, Ferraro, V, Floridi, A, Memeo, R, Crespi, M, Chiarelli, M, Antonucci, A, Zimmitti, G, Frena, A, Percivale, A, Ercolani, G, Zanus, G, Zago, M, Tarchi, P, Baiocchi, G, Ruzzenente, A, Rossi, M, Jovine, E, Maestri, M, Valle, R, Grazi, G, Vivarelli, M, Ferrero, A, Giuliante, F, Torzilli, G, Aldrighetti, L, Gianotti, L, Romano, F, Ciulli, C, Braga, M, Ratti, F, Costa, G, Razionale, F, Russolillo, N, Marinelli, L, De Peppo, V, Cremaschi, E, Calabrese, F, Laureiro, Z, Lazzari, G, Cosola, D, Montuori, M, Salvador, L, Cucchetti, A, Franceschi, A, Ciola, M, Sega, V, Calcagno, P, Pennacchi, L, Tedeschi, M, Giani A., Cipriani F., Famularo S., Donadon M., Bernasconi D. P., Ardito F., Fazio F., Nicolini D., Perri P., Giuffrida M., Pontarolo N., Zanello M., Lai Q., Conci S., Molfino S., Germani P., Pinotti E., Romano M., La Barba G., Ferrari C., Patauner S., Manzoni A., Sciannamea I., Fumagalli L., Troci A., Ferraro V., Floridi A., Memeo R., Crespi M., Chiarelli M., Antonucci A., Zimmitti G., Frena A., Percivale A., Ercolani G., Zanus G., Zago M., Tarchi P., Baiocchi G. L., Ruzzenente A., Rossi M., Jovine E., Maestri M., Valle R. D., Grazi G. L., Vivarelli M., Ferrero A., Giuliante F., Torzilli G., Aldrighetti L., Gianotti L., Romano F., Ciulli C., Braga M., Ratti F., Costa G., Razionale F., Russolillo N., Marinelli L., De Peppo V., Cremaschi E., Calabrese F., Laureiro Z. L., Lazzari G., Cosola D., Montuori M., Salvador L., Cucchetti A., Franceschi A., Ciola M., Sega V., Calcagno P., Pennacchi L., and Tedeschi M.

Abstract

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien‐Dindo complication (CDC) scale to predict excessive length of hospital stay (e‐LOS) in patients undergoing liver resection for hepatocellular carcinoma. Methods: Patients were identified from an Italian multi‐institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e‐LOS were fitted to compare predictive performance. E‐LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication. Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201; 7.438) for CCI and 5.507 (4.152; 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896; 4.115) for CCI and 2.439 (1.666; 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set. Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.

Published
2020

26. Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review

Author

Vinelli V., Biscotti P., Martini D., Del Bo' C., Marino M., Merono T., Nikoloudaki O., Calabrese F. M., Turroni S., Taverniti V., Caballero A. U., Andres-Lacueva C., Porrini M., Gobbetti M., De Angelis M., Brigidi P., Pinart M., Nimptsch K., Guglielmetti S., Riso P., Vinelli V., Biscotti P., Martini D., Del Bo' C., Marino M., Merono T., Nikoloudaki O., Calabrese F.M., Turroni S., Taverniti V., Caballero A.U., Andres-Lacueva C., Porrini M., Gobbetti M., De Angelis M., Brigidi P., Pinart M., Nimptsch K., Guglielmetti S., and Riso P.

Subjects
Adult, Dietary Fiber, Prebiotics, human gut microbiota, intervention studie, Microbiota, prebiotic, short chain fatty acid, Humans, Fatty Acids, Volatile, Human, Gastrointestinal Microbiome
Abstract

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are needed to better elucidate the relationship between DFs and gut microbiota in terms of SCFA production and impact on health-related markers.

Published
2022

27. Peripheral serotonin deficiency affects anxiety-like behavior and the molecular response to an acute challenge in rats

Author

Sbrini, G., Hanswijk, S.I., Brivio, P., Middelman, A., Bader, M., Fumagalli, F., Alenina, N., Homberg, J.R., and Calabrese, F.

Subjects
Cardiovascular and Metabolic Diseases
Abstract

Serotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1 have been related to stress sensitivity and an increased susceptibility for psychiatric pathologies. On these bases, we took advantage of newly generated TPH1(-/-)rats, and we evaluated the impact of the lack of peripheral serotonin on the behavior and expression of brain plasticity-related genes under basal conditions and in response to stress. At a behavioral level, TPH1(-/-) rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of (Bdnf) and the immediate early gene (Arc) and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1(-/-) rats in comparison to TPH1 animals(+/+). Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations.

Published
2022

28. Repeated testing modulates chronic unpredictable mild stress effects in male rats

Author

Bosch, K., Sbrini, G., Burattini, I., Nieuwenhuis, D., Calabrese, F., Schubert, D., Henckens, M.J.A.G., Homberg, J.R., Bosch, K., Sbrini, G., Burattini, I., Nieuwenhuis, D., Calabrese, F., Schubert, D., Henckens, M.J.A.G., and Homberg, J.R.

Abstract

Contains fulltext : 251390.pdf (Publisher’s version ) (Open Access), Depression is a highly prevalent, debilitating mental disorder. Chronic unpredictable mild stress (CUMS) is the most widely applied model to study this affliction in rodents. While studies incorporating CUMS prior to an intervention often require long-lasting stress effects that persist after exposure is ceased, the longevity of these effects is rarely studied. Additionally, it is unclear whether behavioural assessments can be performed before and after interventions without repeated testing effects. In rats, we investigated CUMS effects on components of depressive-like behaviour both acutely after stress cessation and after a recovery period, as well as effects of repeated testing. We observed acute disruptions of the circadian locomotor rhythm and a reduced sucrose preference immediately after CUMS exposure. While circadian locomotor rhythm effects persisted up until four weeks after stress cessation, independently of repeated testing, sucrose preference effects did not. Interestingly, CUMS animals tested once after a recovery period of four weeks showed reduced anxiety-like behaviour in the open field and elevated plus maze compared to their control group and repeatedly-tested CUMS animals. These findings suggest that distinct CUMS-induced components of depressive-like behaviour are affected differentially by recovery time and repeated testing; these aspects should be considered carefully in future study designs.

Published
2022

29. Tryptophan Hydroxylase 2 Knockout Male Rats Exhibit a Strengthened Oxytocin System, Are Aggressive, and Are Less Anxious

Author

Meng, X, Grandjean, J., Sbrini, G., Schipper, P., Hofwijks, N., Stoop, J., Calabrese, F., Homberg, J.R., Meng, X, Grandjean, J., Sbrini, G., Schipper, P., Hofwijks, N., Stoop, J., Calabrese, F., and Homberg, J.R.

Abstract

Item does not contain fulltext, The central serotoninergic system is critical for stress responsivity and social behavior, and its dysregulations have been centrally implicated in virtually all neuropsychiatric disorders. Genetic serotonin depletion animal models could provide a tool to elucidate the causes and mechanisms of diseases and to develop new treatment approaches. Previously, mice lacking tryptophan hydroxylase 2 (Tph2) have been developed, showing altered behaviors and neurotransmission. However, the effect of congenital serotonin deficiency on emotional and social behavior in rats is still largely unknown, as are the underlying mechanisms. In this study, we used a Tph2 knockout (Tph2(-/-)) male rat model to study how the lack of serotonin in the rat brain affects anxiety-like and social behaviors. Since oxytocin is centrally implicated in these behaviors, we furthermore explored whether the effects of Tph2 knockout on behavior would relate to changes in the oxytocin system. We show that Tph2(-/-) rats display reduced anxiety-like behavior and a high level of aggression in social interactions. In addition, oxytocin receptor expression was increased in the infralimbic and prelimbic cortices, paraventricular nucleus, dorsal raphe nucleus, and some subregions of the hippocampus, which was paralleled by increased levels of oxytocin in the medial frontal cortex and paraventricular nucleus but not the dorsal raphe nucleus, central amygdala, and hippocampus. In conclusion, our study demonstrated reduced anxiety but exaggerated aggression in Tph2(-/-) male rats and reveals for the first time a potential involvement of altered oxytocin system function. Meanwhile, the research of oxytocin could be distinguished in almost any psychiatric disorder including anxiety and mental disorders. This research potentially proposes a new target for the treatment of such disorders, from a genetic serotonin deficiency aspect.

Published
2022

30. Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review

Author

Vinelli, V, Biscotti, P, Martini, D, Del Bo', C, Marino, M, Meroño, T, Nikoloudaki, O, Calabrese, F, Turroni, S, Taverniti, V, Caballero, A, Andrés-Lacueva, C, Porrini, M, Gobbetti, M, De Angelis, M, Brigidi, P, Pinart, M, Nimptsch, K, Guglielmetti, S, Riso, P, Calabrese, FM, Caballero, AU, Vinelli, V, Biscotti, P, Martini, D, Del Bo', C, Marino, M, Meroño, T, Nikoloudaki, O, Calabrese, F, Turroni, S, Taverniti, V, Caballero, A, Andrés-Lacueva, C, Porrini, M, Gobbetti, M, De Angelis, M, Brigidi, P, Pinart, M, Nimptsch, K, Guglielmetti, S, Riso, P, Calabrese, FM, and Caballero, AU

Abstract

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are

Published
2022

31. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author

de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., Bosello S. (ORCID:0000-0002-4837-447X), Sebastiani G. D., de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., Bosello S. (ORCID:0000-0002-4837-447X), and Sebastiani G. D.

Abstract

Objective. There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. Methods. A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. Results. The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Conclusion. Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Published
2022

32. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Author

Ferri, C., De Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Lazzaroni, M. G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Bosello S. (ORCID:0000-0002-4837-447X), Sebastiani G. D., Ferri, C., De Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Lazzaroni, M. G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Bosello S. (ORCID:0000-0002-4837-447X), and Sebastiani G. D.

Abstract

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Published
2022

36. 119P Evolution of the management of stage III non-small cell lung cancer (NSCLC): A single-center real-world scenario over 10 years

Author

Ferro, A., primary, Sepulcri, M., additional, Schiavon, M., additional, Scagliori, E., additional, Gennaro, G., additional, Costa, M., additional, Bonanno, L., additional, Frega, S., additional, Dal Maso, A., additional, Calabrese, F., additional, Rea, F., additional, Caumo, F., additional, Guarneri, V., additional, and Pasello, G., additional

Published
2022
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41. Hepatocellular carcinoma surgical and oncological trends in a national multicentric population: the HERCOLES experience

Author

Famularo, S., Donadon, M., Cipriani, Fabrizio, Ardito, Francesco, Carissimi, F., Perri, Pierluigi, Iaria, M., Dominioni, T., Zanello, M., Conci, S., Molfino, S., Labarba, G., Ferrari, C., Germani, P., Patauner, S., Pinotti, E., Lodo, E., Garatti, M., Sciannamea, I., Troci, A., Conticchio, M., Floridi, A., Chiarelli, M., Fumagalli, L., Memeo, R., Crespi, M., Antonucci, Anna Maria, Zimmitti, Giuseppe, Zanus, G., Zago, M., Frena, A., Tarchi, P., Griseri, G., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, Marta, Dallavalle, R., Grazi, G. L., Giuliante, Felice, Aldrighetti, L., Torzilli, Guido, Romano, Federica, Bernasconi, D. P., Ciulli, C., Giani, A., Costa, G., Ratti, F., Bellobono, M., Calabrese, F., Cremaschi, E., De Peppo, V., Cucchetti, A., Lazzari, Giovanni, Percivale, A., Ciola, M., Sega, V., Frassani, S., Del Vecchio, Arianna, Pennacchi, L., Corleone, P., Cosola, D., Salvador, L., Montuori, M., Famularo, Simone, Donadon, Matteo, Cipriani, Federica, Ardito, Francesco, Carissimi, Francesca, Perri, Pasquale, Iaria, Maurizio, Dominioni, Tommaso, Zanello, Matteo, Conci, Simone, Molfino, Sarah, LaBarba, Giuliano, Ferrari, Cecilia, Germani, Paola, Patauner, Stefan, Pinotti, Enrico, Lodo, Enrico, Garatti, Marco, Sciannamea, Ivano, Troci, Albert, Conticchio, Maria, Floridi, Antonio, Chiarelli, Marco, Fumagalli, Luca, Memeo, Riccardo, Crespi, Michele, Antonucci, Adelmo, Zimmitti, Giuseppe, Zanus, Giacomo, Zago, Mauro, Frena, Antonio, Tarchi, Paola, Griseri, Guido, Ercolani, Giorgio, Baiocchi, Gian Luca, Ruzzenente, Andrea, Jovine, Elio, Maestri, Marcello, DallaValle, Raffaele, Grazi, Gian Luca, Giuliante, Felice, Aldrighetti, Luca, Torzilli, Guido, Romano, Fabrizio, Famularo, S., Donadon, M., Cipriani, F., Ardito, F., Carissimi, F., Perri, P., Iaria, M., Dominioni, T., Zanello, M., Conci, S., Molfino, S., Labarba, G., Ferrari, C., Germani, P., Patauner, S., Pinotti, E., Lodo, E., Garatti, M., Sciannamea, I., Troci, A., Conticchio, M., Floridi, A., Chiarelli, M., Fumagalli, L., Memeo, R., Crespi, M., Antonucci, A., Zimmitti, G., Zanus, G., Zago, M., Frena, A., Tarchi, P., Griseri, G., Ercolani, G., Baiocchi, G. L., Ruzzenente, A., Jovine, E., Maestri, M., Dallavalle, R., Grazi, G. L., Giuliante, F., Aldrighetti, L., Torzilli, G., Romano, F., Bernasconi, D. P., Ciulli, C., Giani, A., Costa, G., Ratti, F., Bellobono, M., Calabrese, F., Cremaschi, E., De Peppo, V., Cucchetti, A., Lazzari, G., Percivale, A., Ciola, M., Sega, V., Frassani, S., Del Vecchio, A., Pennacchi, L., Corleone, P., Cosola, D., Salvador, L., and Montuori, M.

Subjects
Male, Cirrhosis, Outcome Assessment, Hepatocellular carcinoma, Settore MED/18 - CHIRURGIA GENERALE, Datasets as Topic, HERCOLES, Hepatocarcinoma recurrence, Liver surgery, Redo surgery, Outcome Assessment, Health Care, Ascites, Registries, Laparoscopy, education.field_of_study, medicine.diagnostic_test, Liver Neoplasms, Middle Aged, Italy, Local, Radiological weapon, Female, medicine.symptom, Reoperation, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, NO, Internal medicine, medicine, Hepatectomy, Humans, education, LS7_4, Aged, business.industry, Carcinoma, Hepatocellular, Perioperative, Hepatology, medicine.disease, Surgery, Health Care, Neoplasm Recurrence, Neoplasm Recurrence, Local, business
Abstract

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63-75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power. Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63–75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

Published
2020

42. MA07.01 Dynamic Liquid Biopsy During Immunotherapy Anticipates Hyperprogression And Early Death in Advanced Non-Small Cell Lung Cancer

Author

Bonanno, L., primary, Zulato, E., additional, Del Bianco, P., additional, Nardo, G., additional, Attili, I., additional, Pavan, A., additional, Bragadin, A. Boscolo, additional, Marra, L., additional, Calabrese, F., additional, Fassan, M., additional, Pasello, G., additional, Guarneri, V., additional, Conte, P., additional, and Indraccolo, S., additional

Published
2021
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43. 1811P Molecular characterization of epidermal growth factor receptor-mutated (EGFR-m) non-small cell lung cancer (NSCLC) undergoing histological transformation

Author

Bonanno, L., primary, Reale, M.L., additional, Ferro, A., additional, Righi, L., additional, Indraccolo, S., additional, Listì, A., additional, Zulato, E., additional, Nardo, G., additional, Bennati, C., additional, Rossi, G., additional, Verderame, F., additional, Guddo, F., additional, Pasello, G., additional, Bironzo, P., additional, Calabrese, F., additional, Guarneri, V., additional, Conte, P., additional, and Novello, S., additional

Published
2021
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45. Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification

Author

Urso, L., Silic-Benussi, M., Boscolo, A., Lorenzi, M., Bonanno, L., Lunardi, F., Guarneri, V., Calabrese, F., Rea, F., Conte, P., and Pasello, G.

Subjects
Inflammation, Mesothelioma, TGF-β, Adult, Aged, 80 and over, Immunosuppression Therapy, Pleural Neoplasms, Mesothelioma, Malignant, Kaplan-Meier Estimate, Middle Aged, Prognosis, Monocytes, Treatment Outcome, IL-10, Biomarkers, Tumor, Cytokines, Humans, Aged
Abstract

No data on circulating biomarkers for the prognostic stratification of Malignant Pleural Mesothelioma (MPM) patients are available. We prospectively explored the prognostic role of circulating monocyte and cytokine levels and their dynamic change during chemotherapy.MPM patients receiving a first line treatment based on a platinum compound plus pemetrexed were eligible. Blood samples were collected at the baseline and at the end of induction chemotherapy. CCL-2, IL-10 and TGF-β levels in plasma were quantified by Enzyme-Linked Immunosorbent Assay (ELISA); white blood cells, monocytes and platelets were evaluated by blood count test.Thirty-one patients were included in the study. Median overall survival (OS) was 12.13 months versus 9.6 months in patients with lower and higher monocytes count, respectively (p value = 0.02). We further stratified patients according to a combined score based on the association of IL-10, TGF-β levels and monocytes count. High combined score was associated with shorter OS and PFS in univariate and multivariate analysis. Chemotherapy induced an increase in monocytes, IL-10, but not TGF-β levels.The prognostic value of circulating levels of multiple immunosuppressive cytokines and inflammatory cells should be confirmed in a wider validation set of MPM patients.

Published
2021

46. Mountain pygmies of western New Guinea: a morphological and molecular approach

Author

Tommaseo-Ponzetta, M., Mona, S., Calabrese, F., Konrad, G., Vacca, E., and Attimonelli, M.

Subjects
Morphology -- Research, Molecular biology -- Research, Pygmies -- Natural history, Biological sciences
Abstract

The presence of 'pygmy' or pygmoid groups among New Guinea populations has been the object of scientific interest since the end of the nineteenth century. Morphological and molecular data are used here to study western New Guinea population variability, focusing in particular on two pygmoid groups living in the eastern fringe highlands of Papua: the Una and the Ketengban. Various kinds of anthropometric data are examined, as well as height, weight, and body mass index, to carry out comparisons with nearby ethnic groups living in the highland and lowland regions. The Ketengban data were also compared with other data recorded 20 years before. The results of previous research on the sequencing of the mitochondrial DNA hypervariable segment 1 region and nuclear DNA nonrecombining Y-chromosome polymorphisms are presented. Both morphological and molecular studies involve adult subjects of both genders, representative of the same ethnic groups and/ or geographic regions. The pygmoid groups turn out to be significantly different from all other study groups, due to their small size, as confirmed by analysis of variance, although significant height and weight increments are observed with respect to those previously recorded. However, putative neutral genetic variation estimated from mitochondrial DNA and Y-chromosome markers support a recent shared common history between these pygmoid populations and the other central Papua groups (except for the Dani-Lani). These findings suggest that the short-stature phenotype is an independent secondary adaptation, possibly driven by an iodine-deficient environment, which leaves the potential for further investigations. KEY WORDS: NEW GUINEA, PYGMIES, MORPHOLOGY, MTDNA, HYPERVARIABLE SEGMENT 1, NONRECOMBINING Y CHROMOSOME., New Guinea (NG), together with Australia, was an early point of arrival of the first modern human expansion out of Africa, at least 50--K) kya (Groube et al. 1986; Summerhayes [...]

Published
2013

48. Real-world data on treatment outcomes in EGFR-mutant non-small-cell lung cancer patients receiving osimertinib in second or further lines

Author

Dal Maso, A, Lorenzi, M, Ferro, A, Pilotto, S, Cecere, F, Follador, A, Polo, V, Del Conte, A, Sartori, G, Giavarra, M, Scattolin, D, Indraccolo, S, Frega, S, De Maglio, G, Menis, J, Bonanno, L, Calabrese, F, Guarneri, V, Conte, P, and Pasello, G

Subjects
non-small-cell lung cancer, T790M mutation, acquired resistance, EGFR T790M mutation, epidermal growth factor receptor, tyrosine kinase inhibitors
Published
2021

49. 51P Liver kinase B1 (LKB1) and phosphorylated AMP kinase (AMPK) expression in small cell lung cancer (SCLC): Association with prognosis and tumour immune microenvironment (TIME) features

Author

Bonanno, L., primary, Dal Maso, A., additional, Pavan, A., additional, Zulato, E., additional, Esposito, G., additional, Fassan, M., additional, Nardo, G., additional, Pasello, G., additional, Guarneri, V., additional, Calabrese, F., additional, Rea, F., additional, Indraccolo, S., additional, and Conte, P.F., additional

Published
2021
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50. Combined Immunoscore for Prognostic Stratification of Early Stage Non-Small-Cell Lung Cancer

Author

Boscolo, A., Fortarezza, F., Lunardi, F., Comacchio, G., Urso, L., Frega, S., Menis, J., Bonanno, L., Guarneri, V., Rea, F., Conte, P., Calabrese, F., and Pasello, G.

Subjects
PD-L1, Cancer Research, Oncology, NSCLC, early stage, immune microenvironment, prognosis, Original Research
Abstract

Background To date, no combined immunoscore has been evaluated for prognostic stratification of early stage non-small-cell lung cancer (NSCLC). The main goal of this study was to investigate the prognostic impact of programmed death ligand 1 (PD-L1) expression and different immune cell components (CD4+, CD8+ T-lymphocytes, and CD68+ macrophages) in early stage NSCLC patients, distinguishing peritumoral (PT) and intratumoral (IT) localizations. The secondary aim was to identify a combined immunoscore to optimize the prognostic stratification of NSCLC patients. Methods This retrospective study included surgical specimens from consecutive chemo-naive stage II–III radically resected NSCLC patients. Immunohistochemistry was carried out to evaluate PD-L1 expression and to quantify IT and PT CD4+, CD8+ T-lymphocytes, and CD68+ macrophages. The impact of a single marker and of a combination of multiple markers on overall survival (OS) was investigated. Results Seventy-nine patients were included in the study. PD-L1 expression was associated with worse prognosis (3 years OS: 58% in high- compared with 67% in low-expressing tumors), even though without statistical significance. When integrating PT CD8+, CD4+, and CD68 into a combined PT immunoscore, a significant prognostic stratification of patients was obtained and confirmed at multivariate analysis (3 years OS: 86% in patients with low PT immunoscore vs. 59% in patients with high PT immunoscore, p = 0.018). The integration of derived neutrophil/lymphocyte ratio (dNLR) with combined PT immunoscore improved prognostic stratification, with longer OS in patients with low PT immunoscore and low dNLR (p = 0.002). Conclusion The combined PT immunoscore (CD8+, CD4+, and CD68) integrated with dNLR may be a promising marker for the development of an integrated Tumor, Node, Metastasis (TNM) immunoscore.

Published
2020
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