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1. Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology

Author

Roberto Miraglia, Matteo Garcovich, Giulia Tosetti, Nicola Caporaso, Agostino Colli, Antonio Rampoldi, Ioannis Petridis, Stella De Nicola, Angelo Andriulli, Marcello Dallio, Giovanni Perricone, G. Gobbo, Filomena Morisco, Antonio Gasbarrini, Pietro Pozzoni, Giuseppe Malizia, Angelo Vanzulli, Gennaro D'Amico, Gianluca Svegliati Baroni, Angelo Luca, Francesco Salerno, Mario D'Amico, Manuela Merli, Luca S. Belli, Vincenzo La Mura, Luchino Chessa, A. Iacobellis, Giuseppe Tarantino, Marco Solcia, Cristiano Sgrazzutti, Lorenzo Ridola, Luigi Maruzzelli, Alessandro Federico, Aldo Airoldi, Luigi Addario, Riccardo Volpes, Massimo Primignani, D'Amico, G., Maruzzelli, L., Airoldi, A., Petridis, I., Tosetti, G., Rampoldi, A., D'Amico, M., Miraglia, R., De Nicola, S., La Mura, V., Solcia, M., Volpes, R., Perricone, G., Sgrazzutti, C., Vanzulli, A., Primignani, M., Luca, A., Malizia, G., Federico, A., Dallio, M., Andriulli, A., Iacobellis, A., Addario, L., Garcovich, M., Gasbarrini, A., Chessa, L., Salerno, F., Gobbo, G., Merli, M., Ridola, L., Baroni, G. S., Tarantino, G., Caporaso, N., Morisco, F., Pozzoni, P., Colli, A., Belli, L. S., D'Amico, Gennaro, Maruzzelli, Luigi, Airoldi, Aldo, Petridis, Ioanni, Tosetti, Giulia, Rampoldi, Antonio, D'Amico, Mario, Miraglia, Roberto, De Nicola, Stella, La Mura, Vincenzo, Solcia, Marco, Volpes, Riccardo, Perricone, Giovanni, Sgrazzutti, Cristiano, Vanzulli, Angelo, Primignani, Massimo, D'Angelo, Luca, Malizia, Giuseppe, Federico, Alessandro, Dallio, Marcello, Andriulli, Angelo, Iacobellis, Angelo, Addario, Luigi, Garcovich, Matteo, Gasbarrini, Antonio, Chessa, Luchino, Salerno, Francesco, Gobbo, Giulia, Merli, Manuela, Ridola, Lorenzo, Baroni, Gianluca Svegliati, Tarantino, Giuseppe, Caporaso, Nicola, Morisco, Filomena, Pozzoni, Pietro, Colli, Agostino, Belli, Luca Saverio, D'Amico, G, Maruzzelli, L, Airoldi, A, Petridis, I, Tosetti, G, Rampoldi, A, D'Amico, M, Miraglia, R, De Nicola, S, La Mura, V, Solcia, M, Volpes, R, Perricone, G, Sgrazzutti, C, Vanzulli, A, Primignani, M, Luca, A, Malizia, G, Federico, A, Dallio, M, Andriulli, A, Iacobellis, A, Addario, L, Garcovich, M, Gasbarrini, A, Chessa, L, Salerno, F, Gobbo, G, Merli, M, Ridola, L, Baroni, G, Tarantino, G, Caporaso, N, Morisco, F, Pozzoni, P, Colli, A, and Belli, L

Subjects
Adult, medicine.medical_specialty, Cirrhosis, Time Factors, medicine.medical_treatment, Validation Studies as Topic, Models, Biological, Severity of Illness Index, Cohort Studies, End Stage Liver Disease, Liver disease, Model for End-Stage Liver Disease, clinical prediction rule, Internal medicine, Post-hoc analysis, Medicine, Humans, Mortality, Aged, Hepatology, business.industry, cirrhosis, Middle Aged, medicine.disease, Prognosis, MELD, body regions, Italy, Cohort, Etiology, TIPS, Steatohepatitis, business, Transjugular intrahepatic portosystemic shunt, cirrhosi, Follow-Up Studies
Abstract

Background & Aims Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. Methods In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. Results In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. Conclusions In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. Lay summary While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.

Published
2021

2. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

3. False-positive results of SARS-CoV-2 IgM/IgG antibody tests in sera stored before the 2020 pandemic in Italy

Author

Giuseppe Corritore, Nicola Andriulli, Anna Latiano, R. Fontana, Giuseppe Miscio, Grazia Anna Niro, Domenica Gioffreda, Fabrizio Bossa, Orazio Palmieri, Giuseppe Biscaglia, Francesca Tavano, Tiziana Latiano, Massimo Carella, Annamaria Gentile, Anna Panza, Lazzaro Di Mauro, and Maria Guerra

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Adolescent, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Enzyme-Linked Immunosorbent Assay, Antibodies, Viral, Article, Immunoglobulin G, Virus, COVID-19 Serological Testing, lcsh:Infectious and parasitic diseases, Serology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Humans, Medicine, False Positive Reactions, lcsh:RC109-216, 030212 general & internal medicine, Pandemics, Aged, Retrospective Studies, Aged, 80 and over, biology, SARS-CoV-2, Serological tests, business.industry, COVID-19, Outbreak, General Medicine, Middle Aged, Virology, Infectious Diseases, Immunoglobulin M, Italy, biology.protein, Female, Antibody, IgM/IgG antibodies, business
Abstract

Objectives: Aside from the outbreak of the coronavirus disease 2019 (COVID-19), serological tests are not well known for their diagnostic value. We assessed the performance of serological tests using stored sera from patients with a variety of pathologic conditions, collected before the 2020 pandemic in Italy. Methods: Rapid lateral flow tests and Enzyme-Linked Immunosorbent Assays (ELISA) that detect Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were carried out using 1150 stored human serum samples that had been collected in 2018 and 2019. The tests were also run using samples from 15 control patients who had positive or negative oral swab test results, as assessed using real-time reverse transcription-polymerase chain reaction (rRT-PCR). The urea dissociation test was employed to rule out false-positive reactivity in the two antibody detection methods. Results: The lateral flow tests revealed 21 positive samples from the stored sera: 12 for IgM, four for IgG, and five for IgM/IgG. Among the nine rRT-PCR- positive controls, six individuals presented IgG and three IgM/IgG positivity. Using the urea (6 mol/L) dissociation test, two of the twelve stored samples that had shown IgM positivity were confirmed to be positive. The ELISA test detected four IgM-positive and three IgG-positive specimens. After treatment with 4 mol/L urea, the IgM-positive samples became negative, whereas the IgG positivity persisted. All of the rRT-PCR-positive controls were found to retain IgM or IgG positivity following the urea treatment. Conclusions: Our findings highlight the limited utility of serological testing for the SARS-CoV-2 virus based on the results of specimens collected before the outbreak of the infection.

Published
2021

4. Accuracy and inter-observer agreement of the nice and kudo classifications of superficial colonic lesions: a comparative study

Author

Francesco Perri, Sonia Carparelli, Antonella Marra, Alfredo Di Leo, Massimiliano Copetti, Rossella Cubisino, Francesco Cocomazzi, Fabrizio Bossa, M. Gentile, Paola Parente, Angelo Andriulli, Mariano Piazzolla, Antonio Massimo Ippolito, Paolo Graziano, Antonio Merla, Rosa Paolillo, and Alessia Mileti

Subjects
medicine.medical_specialty, business.industry, Inter observer agreement, Gastroenterology, Magnification, Nice, Diagnostic accuracy, Gold standard (test), 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, 030211 gastroenterology & hepatology, Radiology, Differential diagnosis, business, computer, health care economics and organizations, computer.programming_language
Abstract

For superficial colonic lesions, the NICE and Kudo classifications are used in the in vivo prediction of histology and as guide to therapy. The NICE system derives information from unmagnified NBI endoscopic images. The Kudo one necessitates a magnification, but, as this tool is not commonly available, it is applied also to characterize unmagnified pictures to compare their diagnostic performances. We conducted a prospective comparison of the NICE versus the Kudo classification for the differential diagnosis of colonic polyps taking histology as the gold standard. The inter-observer agreement for both classifications among 11 colonoscopists was also evaluated. Short unmagnified NBI videoclips of 64 colonic polyps were sent twice to the participants. In the first round, they classified the lesions according to the NICE classification; 4 months later, the same videos were assessed with the Kudo system. The diagnosis provided by the participants was grouped in non-neoplastic, non-invasive neoplasia, invasive neoplasia. Overall, the diagnostic accuracy was 82% (95%CI: 79–85) with the NICE system and 81% (95%CI: 78–84) with the Kudo one (ρ = 0.78). The accuracy of the NICE classification for non-neoplastic lesions was greater compared with the Kudo’s (ρ = 0.03). Sensitivity sub-analyses revealed a higher ability of the NICE in distinguishing between neoplastic vs. non-neoplastic lesions (ρ = 0.01). The overall inter-rater agreement did not differ when the classifications were compared. The NICE and the Kudo classifications might be considered comparable. Our data could allow the use of the NBI Kudo classification even in those centers where magnification is not available.

Published
2021

5. Interobserver agreement of the Paris and simplified classifications of superficial colonic lesions: a Western study

Author

Massimiliano Copetti, Angelo Andriulli, Rossella Cubisino, Sonia Carparelli, Fabrizio Bossa, Arcangela Patrizia Giuliani, Fulvia Terracciano, Francesco Perri, Andrea Fontana, Antonio Massimo Ippolito, Mariano Piazzolla, Antonella Marra, M. Gentile, Alfredo Di Leo, Francesco Cocomazzi, Antonio Merla, Rosa Paolillo, and Alessia Mileti

Subjects
Original article, business.industry, Concordance, Medicine, lcsh:Diseases of the digestive system. Gastroenterology, Pharmacology (medical), lcsh:RC799-869, business, Nuclear medicine, Sensitivity analyses
Abstract

Background and study aims The Paris classification of superficial colonic lesions has been widely adopted, but a simplified description that subgroups the shape into pedunculated, sessile/flat and depressed lesions has been proposed recently. The aim of this study was to evaluate the accuracy and inter-rater agreement among 13 Western endoscopists for the two classification systems. Methods Seventy video clips of superficial colonic lesions were classified according to the two classifications, and their size estimated. The interobserver agreement for each classification was assessed using both Cohen k and AC1 statistics. Accuracy was taken as the concordance between the standard morphology definition and that made by participants. Sensitivity analyses investigated agreement between trainees (T) and staff members (SM), simple or mixed lesions, distinct lesion phenotypes, and for laterally spreading tumors (LSTs). Results Overall, the interobserver agreement for the Paris classification was substantial (κ = 0.61; AC1 = 0.66), with 79.3 % accuracy. Between SM and T, the values were superimposable. For size estimation, the agreement was 0.48 by the κ-value, and 0.50 by AC1. For single or mixed lesions, κ-values were 0.60 and 0.43, respectively; corresponding AC1 values were 0.68 and 0.57. Evaluating the several different polyp subtypes separately, agreement differed significantly when analyzed by the k-statistics (0.08–0.12) or the AC1 statistics (0.59–0.71). Analyses of LSTs provided a κ-value of 0.50 and an AC1 score of 0.62, with 77.6 % accuracy. The simplified classification outperformed the Paris classification: κ = 0.68, AC1 = 0.82, accuracy = 91.6 %. Conclusions Agreement is often measured with Cohen’s κ, but we documented higher levels of agreement when analyzed with the AC1 statistic. The level of agreement was substantial for the Paris classification, and almost perfect for the simplified system.

Published
2021

6. Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis

Author

A. Amoruso, Nicola Caporaso, Grazia Anna Niro, N. Andriulli, Michele Pier Luca Guarino, Monica Greco, M. Librandi, Antonio Massimo Ippolito, Maria Rosa Valvano, Filomena Morisco, Angelo Andriulli, A. Iacobellis, Guarino, Maria, Morisco, Filomena, Valvano, M. R, Ippolito, A. M, Librandi, M, Andriulli, N, Greco, M, Amoruso, A, Iacobellis, A, Niro, G, Caporaso, Nicola, and Andriulli, A.

Subjects
Liver Cirrhosis, Ledipasvir, Simeprevir, medicine.medical_specialty, Cirrhosis, Daclatasvir, Sofosbuvir, Hepatitis C virus, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Humans, Protease Inhibitors, Pharmacology (medical), Hepatology, business.industry, Ribavirin, Gastroenterology, medicine.disease, Hepatitis C, Surgery, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Interferons, business, medicine.drug
Abstract

SummaryBackground It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. Aim To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. Methods A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. Results Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6–82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8–80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4–89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4–89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. Conclusion The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

Published
2017

7. Safety and efficacy of switching from infliximab biosimilar CT-P13 to infliximab biosimilar SB2 in patients with inflammatory bowel disease

Author

Fabrizio Bossa, Giuseppe Biscaglia, R. Lovero, Mariabeatrice Principi, Rosa Federica La Fortezza, M. Nardella, Giuseppe Losurdo, Giuseppina Martino, Fulvia Terracciano, Alfredo Di Leo, and Angelo Andriulli

Subjects
Male, medicine.medical_specialty, Inflammatory bowel disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, Internal medicine, medicine, Humans, Adverse effect, Biosimilar Pharmaceuticals, Retrospective Studies, Univariate analysis, Hepatology, biology, business.industry, C-reactive protein, Antibodies, Monoclonal, Odds ratio, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Infliximab, Confidence interval, Treatment Outcome, 030220 oncology & carcinogenesis, biology.protein, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Introduction For patients with inflammatory bowel diseases, switching from infliximab originator to biosimilars is effective and safe. Few data on single switch have been published, and data on multiple switches of different infliximab are unavailable. Methods A retrospective analysis of patients who switched from CT-P13 to SB2, and of those with multiple switches among different infliximab compounds was conducted. Clinical activity, C reactive protein (CRP), adverse events (AE) and loss of response (LOR) were recorded. Results Thirty-six patients (26 males, 14 Crohn's disease and 22 ulcerative colitis) were enrolled and followed up for >6 months. All patients switched from CT-P13 to SB2; 12 of them (33.3%) had already switched from reference Infliximab to CT-P13, and for the remaining patients CT-P13 was the first infliximab. The clinical remission rate six months before and three months after SB2-switch was the same (58.3%) and the rate of mild activity varied from 27.8 to 33.3% (P = 0.68); the percentage of patients with normal CRP values passed from 94.4 to 91.7% (P = 1). Two patients (5.5%) had AE and 11 (30.5%) a LOR. At univariate analysis, patients with a single switch had a non-significant risk of LOR during SB2 [odds ratio (OR) = 7.86; 95% confidence interval (CI) 0.87-71, P = 0.06]. SB2-LOR was associated with previous AE under CT-P13 (OR = 9.1, 95% CI 0.82-100, P = 0.07). None of such factors was significant at multivariate analysis. Conclusion Switching from CT-P13 to SB2 seems to be safe and effective either in patients with a single than in those with multiple switches.

Published
2020

8. A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies

Author

Juha Taavela, Jorma Isola, Claudia Covelli, Angelo Andriulli, Carmela Lamacchia, Alina Popp, Paola Parente, Paolo Graziano, Markku Mäki, Tampere University, Clinical Medicine, Department of Paediatrics, and BioMediTech

Subjects
Pathology, medicine.medical_specialty, Formalin fixed paraffin embedded, Physiology, Lymphocyte, Histopathology, chemical and pharmacologic phenomena, 3121 Internal medicine, digestive system, 03 medical and health sciences, 0302 clinical medicine, Transplant surgery, medicine, Celiac disease, Diagnostics, Inflammation, T lymphocyte marker, business.industry, fungi, Gastroenterology, Disease classification, hemic and immune systems, Small bowel, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Original Article, 030211 gastroenterology & hepatology, business, tissues, Autoimmune
Abstract

Background: The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal inflammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by flow cytometry or frozen section immunohistochemistry (IHC), is a specific marker for CD. Aim: To establish a new IHC assay for γδ-IELs applicable to formalin-fixed paraffin-embedded (FFPE) duodenal biopsies. Methods: We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis. Results: Compared to those in non-celiac controls (n = 51), γδ-IEL density was significantly increased in newly diagnosed celiac disease patients (n = 22, p < 0.0001). In ROC-curve analysis, the cutoff of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specificity 95%). γδ-IEL density in CD patients on a gluten-free diet (n = 53) were also higher than in controls (p < 0.0001), but lower than those in newly diagnosed CD (p < 0.0001). The diagnostic value of γδ-IELs outperformed that of CD3 + IELs in both patient groups. γδ-IELs were better than CD3 + IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n = 12). Conclusions: Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specificity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease. publishedVersion

Published
2020

9. The 'Hub and Spoke' model has no effect on mortality in acute upper gastrointestinal bleeding: A prospective multicenter cohort study

Author

Cristina Bucci, L. Amitrano, C. Londoni, A. Chirico, O. Triossi, A. Zambelli, F. Bazzoli, B. Germanà, F. Cipolletta, Marco Soncini, S. Mangiafico, F. Parente, E Di-Giulio, A. Andriulli, G. D'Amico, G. Baldassarre, Riccardo Marmo, A. Repici, A. Paterlini, G. Imperiali, Angelo Zullo, V Annese, F. De Nigris, R. Bennato, S. Metrangolo, L. Orsini, S. Bargiggia, I Sorrentino, M. Manno, Maria Elena Riccioni, C. Tomba, A. Nucci, A. Bizzotto, FR De-Filippo, A. Merighi, Guido Costamagna, R de-Franchis, C. Marmo, A. Anderloni, L.G. Cavallaro, P Esposito, A. Russo, R. Pumpo, D. Conte, M.A. Bianco, F Buffoli, L. Cipolletta, R. Conigliaro, P Di-Giorgio, A Filippino, G. Bresci, F Covello, P. Borgheresi, L.M. Montalbano, R.M. Zagari, E. Buscarini, Annalisa Tortora, D. Spotti, L. Ferraris, R. Lamanda, M. Franceschi, G Castrignanò, G. Spinzi, A. Lauri, S. Segato, R Grassia, V. Boarino, P. Cesaro, C De-Fanis, R. Meroni, G. Napolitano, L. Furio, AG Bonanomi, M De-Matthaeis, M. Parravicini, A Dell‘Era, L. Purita, Marmo R., Soncini M., Bucci C., Zullo A., Amitrano L., Anderloni A., Andriulli A., Annese V., Baldassarre G., Bargiggia S., Bazzoli F., Bennato R., Bianco M.A., Bizzotto A., Boarino V., Bonanomi A.G., Borgheresi P., Bresci G., Buffoli F., Buscarini E., Castrignano G., Cavallaro L.G., Cesaro P., Chirico A., Cipolletta F., Cipolletta L., Conigliaro R., Conte D., Costamagna G., Covello F., D'Amico G., De-Fanis C., De-Filippo F.R., de-Franchis R., Dell'Era A., De Nigris F., De-Matthaeis M., Di-Giorgio P., Di-Giulio E., Esposito P., Ferraris L., Filippino A., Franceschi M., Furio L., Germana' B., Grassia R., Imperiali G., Lamanda R., Lauri A., Londoni C., Mangiafico S., Manno M., Marmo C., Merighi A., Meroni R., Metrangolo S., Montalbano L.M., Napolitano G., Nucci A., Orsini L., Parente F., Parravicini M., Paterlini A., Pumpo R., Purita L., Repici A., Riccioni M.E., Russo A., Segato S., Sorrentino I., Spinzi G., Spotti D., Tortora A., Tomba C., Triossi O., Zagari R.M., and Zambelli A.

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, Multivariate analysis, Organizational model, Improved survival, Comorbidity, 03 medical and health sciences, Organizational setting, 0302 clinical medicine, Health care, Spoke-hub distribution paradigm, Medicine, Humans, Hub and spoke network, Mortality, Aged, Hepatology, business.industry, Delivery of Health Care, Integrated, Gastroenterology, Acute upper gastrointestinal bleeding, Length of Stay, Middle Aged, medicine.disease, Italy, 030220 oncology & carcinogenesis, Case-Control Studies, Emergency medicine, 030211 gastroenterology & hepatology, business, Gastrointestinal Hemorrhage, Acute gastrointestinal bleeding, Cohort study
Abstract

Background: the lack of standardized pathways for patients with gastrointestinal bleeding may have led to differences in their management and inequity to medical care access. The "Hub & Spoke" model was adopted to fill this gap in many disciplines, but, to our knowledge, no data exist on its efficacy on mortality in GI bleeding. We aimed to evaluate if the "Hub & Spoke" organizational model has an impact on mortality risk from UGIB. Methods: from January 2014 to December 2015, 3324 consecutive patients admitted for UGIB in 50 Italian hospitals were enrolled (1977 patients in hospitals within the "Hub & Spoke" network for digestive hemorrhagic emergency and 1347 in hospitals outside the "Hub & Spoke" network). Clinical, endoscopic and organizational data were recorded. Results: we observed no differences in mortality between patients admitted to hospitals included or not included in the "Hub & Spoke" network (5.2% vs 6.1%, p = 0.3). On multivariate analysis, admission in gastroenterology wards (OR 0.61, p = 0.001) or an academic hospital (OR 0.65, p < 0.056) were independent protective factors while being in "Hub & Spoke" organization system did not affect mortality (OR 1.09, p = 0.57). Conclusion: the "Hub & Spoke" model per sé does not impact on mortality while being treated in academic hospital or gastroenterology wards improved survival.

Published
2021

10. Microbiome Analysis of Mucosal Ileoanal Pouch in Ulcerative Colitis Patients Revealed Impairment of the Pouches Immunometabolites

Author

Angelo Andriulli, Fabrizio Bossa, Giuseppe Corritore, Francesco Perri, R. Fontana, Anna Latiano, Orazio Palmieri, Maria Guerra, Giuseppe Biscaglia, Tiziana Latiano, Tommaso Mazza, Stefano Castellana, Giuseppina Martino, and Anna Panza

Subjects
Adult, Male, medicine.medical_specialty, QH301-705.5, Entropy, IBD, Faecalibacterium prausnitzii, Colonic Pouches, Gut flora, Gastroenterology, Article, UC, Internal medicine, RNA, Ribosomal, 16S, medicine, Ulcerative Colitis, Humans, Microbiome, Biology (General), Intestinal Mucosa, Phylogeny, pouch, Principal Component Analysis, biology, business.industry, IPAA, Microbiota, General Medicine, Pouchitis, Biodiversity, Middle Aged, biology.organism_classification, medicine.disease, Ulcerative colitis, ulcerative colitis (UC), Metabolome, Colitis, Ulcerative, Female, Roseburia, Pouch, business, Dysbiosis, pouchitis
Abstract

The pathogenesis of ulcerative colitis (UC) is unknown, although genetic loci and altered gut microbiota have been implicated. Up to a third of patients with moderate to severe UC require proctocolectomy with ileal pouch ano-anastomosis (IPAA). We aimed to explore the mucosal microbiota of UC patients who underwent IPAA. Methods: For microbiome analysis, mucosal specimens were collected from 34 IPAA individuals. Endoscopic and histological examinations of IPAA were normal in 21 cases, while pouchitis was in 13 patients. 19 specimens from the healthy control (10 from colonic and 9 from ileum) were also analyzed. Data were analyzed using an ensemble of software packages: QIIME2, coda-lasso, clr-lasso, PICRUSt2, and ALDEx2. Results: IPAA specimens had significantly lower bacterial diversity as compared to normal. The microbial composition of the normal pouch was also decreased also when compared to pouchitis. Faecalibacterium prausnitzii, Gemmiger formicilis, Blautia obeum, Ruminococcus torques, Dorea formicigenerans, and an unknown species from Roseburia were the most uncommon in pouch/pouchitis, while an unknown species from Enterobacteriaceae was over-represented. Propionibacterium acnes and Enterobacteriaceae were the species most abundant in the pouchitis and in the normal pouch, respectively. Predicted metabolic pathways among the IPAA bacterial communities revealed an important role of immunometabolites such as SCFA, butyrate, and amino acids. Conclusions: Our findings showed specific bacterial signature hallmarks of dysbiosis and could represent bacterial biomarkers in IPAA patients useful to develop novel treatments in the future by modulating the gut microbiota through the administration of probiotic immunometabolites-producing bacterial strains and the addition of specific prebiotics and the faecal microbiota transplantation.

Published
2021

11. Circulating levels of cytokines, chemokines and growth factors in patients with achalasia

Author

Anna Panza, Orazio Palmieri, Anna Latiano, Massimiliano Copetti, Antonio Merla, Angelo Andriulli, Annamaria Gentile, Andrea Fontana, Giuseppe Biscaglia, and Antonello Cuttitta

Subjects
Chemokine, medicine.medical_treatment, Achalasia, chemokines, Inflammation, General Biochemistry, Genetics and Molecular Biology, Pathogenesis, otorhinolaryngologic diseases, medicine, General Pharmacology, Toxicology and Pharmaceutics, biology, business.industry, General Neuroscience, Monocyte, Growth factor, growth factor, Articles, General Medicine, medicine.disease, Molecular medicine, cytokines, achalasia, medicine.anatomical_structure, Cytokine, inflammation, Immunology, biology.protein, medicine.symptom, business
Abstract

Idiopathic achalasia is a disease that is characterized by the absence of peristalsis and incomplete relaxation of the lower esophageal sphincter, which is accompanied by dysphagia, regurgitation, chest pain and weight loss. The role of inflammatory infiltrates in the pathogenesis of achalasia remains controversial, although the infiltrating cell profile in the tissue has been previously characterized histologically and immunohistochemically. The present study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with achalasia and the clinical disease characteristics. The cytokine, chemokine and growth factor serum profiles of 68 patients with achalasia and 39 healthy individuals were explored using the 27-Bio-Plex Pro Human Cytokine assay. Reductions in the levels of inflammatory mediators IL-1β, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 (MIP-1)α and MIP-1β, regulated upon activation normal T cell expressed and presumably secreted, TNF-α and VEGF were detected in the serum samples of patients with achalasia compared with those in the control group (P0.05). These results suggest that achalasia is a disease that has a local but not a systemic inflammatory pattern. Further studies are required to improve the current understanding of the mechanism underlying this disease.

Published
2021

12. Genome-wide association study identifies an early onset pancreatic cancer risk locus

Author

Verena Katzke, Jakob R. Izbicki, Francesca Tavano, Rita T. Lawlor, Thilo Hackert, Raffaella Alessia Zuppardo, Giulia Martina Cavestro, Federico Canzian, Frederike Dijk, Martin Oliverius, George Theodoropoulos, Pavel Soucek, Manuel Gentiluomo, Rudolf Kaaks, Erika Darvasi, Yogesh K. Vashist, Bill Greenhalf, Juozas Kupcinskas, Maurizio Lucchesi, Borislav Rusev, Andrea Szentesi, Gabriele Capurso, Ewa Małecka-Panas, Lucia Moletta, Beatrice Mohelnikova-Duchonova, Franco Bambi, Ugo Boggi, Alba Ballerini, Krzysztof Jamroziak, Ben Schöttker, Simona Bursi, Raffaele Pezzilli, Gyula Farkas, Dania Bozzato, Áron Vincze, Stefano Landi, Anna Caterina Milanetto, Péter Hegyi, Michael F. Nentwich, Laura Ginocchi, Pavel Vodicka, Stefania Moz, Ludmila Vodickova, Hermann Brenner, Olivier R. Busch, Viktor Hlavac, Audrius Ivanauskas, John P. Neoptolemos, Domenica Gioffreda, Ofure Obazee, Livia Archibugi, Nathalia A. Giese, Giuseppe Vanella, Xin Gao, Renata Talar-Wojnarowska, Angelo Andriulli, Oliver Strobel, Daniele Campa, Maria Gazouli, Pathology, CCA - Cancer biology and immunology, Surgery, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, AGEM - Re-generation and cancer of the digestive system, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Campa, D., Gentiluomo, M., Obazee, O., Ballerini, A., Vodickova, L., Hegyi, P., Soucek, P., Brenner, H., Milanetto, A. C., Landi, S., Gao, X., Bozzato, D., Capurso, G., Tavano, F., Vashist, Y., Hackert, T., Bambi, F., Bursi, S., Oliverius, M., Gioffreda, D., Schottker, B., Ivanauskas, A., Mohelnikova-Duchonova, B., Darvasi, E., Pezzilli, R., Malecka-Panas, E., Strobel, O., Gazouli, M., Katzke, V., Szentesi, A., Cavestro, G. M., Farkas, G., Izbicki, J. R., Moz, S., Archibugi, L., Hlavac, V., Vincze, A., Talar-Wojnarowska, R., Rusev, B., Kupcinskas, J., Greenhalf, B., Dijk, F., Giese, N., Boggi, U., Andriulli, A., Busch, O. R., Vanella, G., Vodicka, P., Nentwich, M., Lawlor, R. T., Theodoropoulos, G. E., Jamroziak, K., Zuppardo, R. A., Moletta, L., Ginocchi, L., Kaaks, R., Neoptolemos, J. P., Lucchesi, M., and Canzian, F.

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Pancreatic disease, pancreatic cancer, early onset, Single-nucleotide polymorphism, Genome-wide association study, very early onset pancreatic cancer, Polymorphism, Single Nucleotide, 03 medical and health sciences, single nucleotide polymorphisms, 0302 clinical medicine, Risk Factors, Pancreatic cancer, Internal medicine, Genetic predisposition, Medicine, Humans, Genetic Predisposition to Disease, Genetic variability, Pancreas, Genetic association, genome-wide association study, business.industry, Middle Aged, medicine.disease, Pancreatic Neoplasms, 030220 oncology & carcinogenesis, Case-Control Studies, Female, Age of onset, business, Carcinoma, Pancreatic Ductal
Abstract

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1x10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset≤50, and 4142 controls from the PANDoRA consortium while in the in silico data we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15x10-4 ). In conclusion we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature. This article is protected by copyright. All rights reserved.

Published
2020

13. Germline Alterations in Patients With IBD-associated Colorectal Cancer

Author

Anna Panza, Tommaso Mazza, R. Fontana, M. Nardella, Stefano Castellana, Fabrizio Bossa, Annamaria Gentile, Orazio Palmieri, Tiziana Latiano, Angelo Andriulli, Giuseppina Martino, Francesco Perri, Giuseppe Corritore, Anna Latiano, and Giuseppe Biscaglia

Subjects
Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Gastroenterology, Cancer, MLH1, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Germ Cells, Crohn Disease, Dysplasia, MSH2, CDKN2A, MUTYH, Risk Factors, Internal medicine, medicine, Immunology and Allergy, Humans, Colitis, Ulcerative, business, Colorectal Neoplasms, CHEK2
Abstract

Background Patients with inflammatory bowel diseases (IBD), both ulcerative colitis (UC) and Crohn’s disease (CD), are at risk of developing a colorectal cancer (CRC). No information is available on the contribution of patients’ genetic background to CRC occurrence. This study investigates germline alterations in patients with IBD-associated CRC. Methods We profiled a panel of 39 genes potentially involved in cancer predisposition and searched for germline variants in IBD patients with CRC or high-grade dysplasia. Results After clinical exclusion of genetic cancer syndromes, 25 IBD patients (4 CD and 21 UC) with CRC or high-grade dysplasia were studied. After excluding variants with low likelihood of pathogenicity (classes 1 or 2 according the International Agency for Research on Cancer [IARC]), the panel identified pathogenic variants, likely pathogenic, or variants with unknown significance in 18 patients (72%). Six patients (24%) carried pathogenic or likely variants (IARC class 5 or 4). Of the identified variants, 4 encompassed the APC region, 3 the MLH1 gene, and the remaining ones the MSH2, MSH3, monoallelic MUTYH, EPCAM, BRCA1, CHEK2, POLD1, POLE, CDKN2A, and PDGFRA genes. Four patients carried at least 2 variants in different genes. Duration of IBD was significantly shorter in carriers of 4 or 5 IARC variants (7 years; range 0–21; P = .002) and in those with variants with unknown significance (12 years; range 0–22; P = .005) compared with patients without or with only benign variations (23.5 years; range 15–34). Conclusions In silico analysis and sequence-based testing of germline DNA from IBD patients with CRC or high-grade dysplasia detected 24% of variants positioned in pathogenic classes. In patients with type 3, 4, and 5 variants, the onset of high-grade dysplasia or CRC was significantly earlier than in patients with benign or unidentified variants. The screening for these genes could identify IBD patients requiring a more intensive endoscopic surveillance for earlier detection of dysplastic changes.

Published
2021

14. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

Author

Verena Katzke, Rita T. Lawlor, Ugo Boggi, Paola Fogar, Livia Archibugi, George Theodoropoulos, Beatrice Mohelnikova-Duchonova, C. E. Radu, Giulia Martina Cavestro, Christos Dervenis, Francesca Federici, Federico Canzian, Jakob R. Izbicki, Claudio Pasquali, Aldo Scarpa, Valerio Pazienza, Péter Hegyi, Renata Talar-Wojnarowska, Frank Bergmann, Thomas Pausch, Stefano Landi, Maurizio Cantore, Stig E. Bojesen, Theron Johnson, Oliver Strobel, Ewa Małecka-Panas, Thilo Hackert, Angelo Andriulli, Audrius Ivanauskas, Benny V. Jensen, J. Kaiser, Daniele Campa, Andrea Mambrini, Orazio Palmieri, Gabriele Capurso, Ludmila Vodickova, Maria Gazouli, Evaristo Maiello, Roberto Salvia, Elżbieta Iskierka-Jażdżewska, Christine Tjaden, Rudolph Kaaks, M. Di Leo, Anna Caterina Milanetto, Pavel Soucek, Daniela Basso, Julia S. Johansen, H Brenner, Raffaele Pezzilli, Katarina Cuk, Ofure Obazee, Cosimo Sperti, Pavel Vodicka, Juozas Kupcinskas, Kai Uwe Saum, Yogesh K. Vashist, G. Delle Fave, Andrea Szentesi, Cristian Gheorghe, Radmila Lemstrová, and Inna Chen

Subjects
Oncology, Cancer Research, Mutation, medicine.medical_specialty, Pancreatic disease, business.industry, Disease, Odds ratio, medicine.disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, medicine, Family history, business, Risk assessment, CHEK2
Abstract

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

Published
2019

15. Childhood emotional abuse and neglect in obese patients with and without binge eating disorder: Personality and psychopathology correlates in adulthood

Author

Secondo Fassino, Angela Valentina Spalatro, Federico Amianto, Miriam Rainis, Luca Lavagnino, Carla Andriulli, and Giovanni Abbate-Daga

Subjects
Adult, Male, Child abuse, 050103 clinical psychology, media_common.quotation_subject, Adulthood personality and psychopathology, Neglect, 03 medical and health sciences, Emotional abuse, 0302 clinical medicine, Binge eating disorder, Binge-eating disorder, Surveys and Questionnaires, medicine, Humans, Personality, 0501 psychology and cognitive sciences, Child Abuse, Obesity, Child, Psychological abuse, Childhood traumatic questionnaire, Emotional neglect, Binge-Eating Disorder, Female, Middle Aged, Physical Abuse, Psychopathology, Biological Psychiatry, media_common, business.industry, 05 social sciences, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Physical abuse, Sexual abuse, business, Clinical psychology
Abstract

The link between childhood traumatic experiences such as sexual and physical abuse and EDs in adulthood has been widely demonstrated. To date, however, little research focused on the association between emotional abuse and neglect in childhood and Binge Eating Disorder (BED) and obesity in adulthood. We enrolled 127 patients [84 with BED and 43 obese] and 45 healthy controls (HCs). All participants were administered the same battery of psychometric tests. Between-group differences were explored and the relationship between emotional abuse and neglect in childhood and personality and psychopathology in adulthood was tested. Obese patients showed higher scores in emotional abuse and neglect and sexual abuse when compared to HCs. Within obese participants, those with BED reported higher emotional abuse and emotional neglect than obese without BED and HCs; the BED group differed in physical and sexual abuse from obese participants. The association between traumatic experiences in childhood and obesity in adulthood has been confirmed independently of the type of trauma. Therapists should take into account the traumatic etiology of BED, in particular psychological abuse, even in those patients who do not recall physical or sexual abuses. Specific techniques to approach traumatic experiences could be applied to BED or non-BED patients.

Published
2018

16. Accuracy and Inter-Observer Agreement of the Nice and the Kudo Classifications of Superficial Colonic Lesions: A Comparative Study

Author

Fabrizio Bossa, Massimiliano Copetti, Mariano Piazzolla, Francesco Cocomazzi, Rossella Cubisino, Sonia Carparelli, Francesco Perri, Antonella Marra, Angelo Andriulli, Rosa Paolillo, M. Gentile, Alessia Mileti, A. Di Leo, Antonio Merla, Antonio Massimo Ippolito, Paola Parente, and Paolo Graziano

Subjects
Inter observer agreement, business.industry, Nice, Nuclear medicine, business, computer, computer.programming_language, Mathematics
Published
2021

17. Anesthesia for Laser Lead Extraction

Author

Alexander Kahan and John Andriulli

Subjects
business.industry, Anesthesia, Superior vena cava injury, Risk stratification, Medicine, Anesthetic management, business, Lead extraction, Temporary Pacemaker
Abstract

Modern management of cardiovascular disease includes an increasing number of pacemakers, implantable cardioverter defibrillators (AICD), and cardiac implantable electronic devices (CIED) inserted annually. Over time, many of these leads become defective, fractured, or infected. Accordingly, the incidence of laser-lead extraction (LLE) has dramatically increased. This chapter focuses on the indications for LLE, preoperative evaluation and risk stratification, the steps for LLE, and the anesthetic management for LLE.

Published
2021

18. Identification of recessively inherited genetic variants for pancreatic cancer risk

Author

Pavel Soucek, Viktor Hlavac, Markus K. Diener, Daniela Basso, Beatrice Mohelnikova-Duchonova, Balázs Németh, Herman Brenner, Roberto Salvia, Vytautas Kiudelis, Konstantinos Papiris, Domenica Gioffreda, Manuel Gentiluomo, Raffaele Pezzilli, János Novák, Oliver Strobel, Martin Oliverius, Martin Lovecek, John P. Neoptolemos, Paolo Giorgio Arcidiacono, Maria Chiara Petrone, Rita T. Lawlor, Ugo Boggi, Ye Lu, Federico Canzian, Yogesh K. Vashist, Livia Archibugi, Stefano Landi, Krzysztof Jamroziak, Cosimo Sperti, Faik G. Uzunoglu, Pavel Vodicka, Stefania Moz, Andrea Mambrini, Andrea Szentesi, Dezso Kelemen, Maurizio Lucchesi, Péter Hegyi, Gabriele Capurso, Giulia Martina Cavestro, Zdenek Kala, Renata Talar-Wojnarowska, Roger Chammas, Hanneke W. M. van Laarhoven, Luca Morelli, George Theodoropoulos, Mateus Nóbrega Aoki, Daniele Campa, Giuseppe Vanella, Thilo Hackert, Angelo Andriulli, Anna Caterina Milanetto, Sabrina Gloria Giulia Testoni, Xin Gao, Ewa Małecka-Panas, Laura Ginocchi, Marta Puzzono, Angelica Macauda, Olivier R. Busch, Ondrej Strouhal, Audrius Ivanauskas, Bas Bueno-de-Mesquita, Jakob R. Izbicki, William Greenhalf, Silvia Carrara, Francesca Tavano, Feng Guo, Maria Gazouli, Stefano Ermini, and Juozas Kupcinskas

Subjects
Genetics, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Pancreatic cancer, Gastroenterology, Genetic variants, medicine, Identification (biology), medicine.disease, business
Published
2021

19. Impact of the COVID-19 outbreak and the serum prevalence of SARS-CoV-2 antibodies in patients with inflammatory bowel disease treated with biologic drugs

Author

Anna Latiano, M.R. D'Altilia, Giuseppe Corritore, Fabrizio Bossa, A. Marseglia, Sonia Carparelli, Francesca Tavano, Giuseppina Martino, Fulvia Terracciano, Anna Panza, Angelo Andriulli, M. Nardella, Maria Pastore, Francesco Perri, Orazio Palmieri, Michele Sacco, Maria Guerra, and Tiziana Latiano

Subjects
Male, Antibodies, Viral, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, Seroepidemiologic Studies, skin and connective tissue diseases, Child, Aged, 80 and over, Alimentary Tract, Gastroenterology, Antibodies, Monoclonal, Middle Aged, Ulcerative colitis, Thalidomide, Hospitalization, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Ustekinumab, Immunosuppressive Agents, medicine.drug, Biologic therapy, Adult, medicine.medical_specialty, Adolescent, IBD, Enzyme-Linked Immunosorbent Assay, Antibodies, Monoclonal, Humanized, Vedolizumab, COVID-19 Serological Testing, 03 medical and health sciences, Young Adult, Gastrointestinal Agents, Internal medicine, medicine, Adalimumab, Humans, Risk factor, Aged, Biological Products, Hepatology, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Inflammatory Bowel Diseases, Infliximab, Golimumab, Colitis, Ulcerative, business
Abstract

Background Patients receiving biologic therapies are at risk for viral infections. This study investigated the impact of the SARS-CoV-2 infection and the serum prevalence of SARS-CoV-2 antibodies in patients with inflammatory bowel disease (IBD) treated with biologic drugs. Methods Information on demography, co-morbidities, clinical data regarding IBD, symptoms suggestive of the SARS-CoV-2 infection, close contacts with SARS-CoV-2 positive patients, hospitalization, and therapies administered for COVID-19 was collected for all patients who were being treated with biologic drugs. All patients underwent SARS-CoV-2 antibody testing. Results Two hundred and fifty-nine patients (27 children) with a mean age of 42.2 ± 16.7 years (range 9 - 88) and a mean duration of disease of 13.4 ± 10 years (range 0.2 – 49) were enrolled. One hundred four patients (40.2%) had ulcerative colitis, and 155 (59.8%) had Crohn's disease. About the therapy: 62 patients were receiving infliximab, 89 adalimumab, 20 golimumab, 57 vedolizumab, 27 ustekinumab, 1 thalidomide, and 3 an experimental compound. The mean Charlson Comorbidity Index was 2. Thirty-two patients (12.3%) reported respiratory symptoms, and 2 of them were hospitalized (0.77%). Two patients resulted positive for IgG against SARS-CoV-2 (0.77%). Conclusions In patients with IBD, treatment with biologic drug does not represent a risk factor for the SARS-CoV-2 infection.

Published
2020

20. Forecasting Hepatitis C liver disease burden on real-life data. Does the hidden iceberg matter to reach the elimination goals?

Author

Kondili, La, Robbins, S, Blach, S, Gamkrelidze, I, Zignego, Al, Brunetto, Mr, Raimondo, G, Taliani, G, Iannone, A, Russo, Fp, Santantonio, Ta, Zuin, M, Chessa, L, Blanc, P, Puoti, M, Vinci, M, Erne, Em, Strazzabosco, M, Massari, M, Lampertico, P, Rumi, Mg, Federico, A, Orlandini, A, Ciancio, A, Borgia, G, Andreone, P, Caporaso, N, Persico, M, Ieluzzi, D, Madonia, S, Gori, A, Gasbarrini, A, Coppola, C, Brancaccio, G, Andriulli, A, Quaranta, Mg, Montilla, S, Razavi, H, Melazzini, M, Vella, S, Craxì, A, PITER Collaborating, Group., Kondili LA, Robbins S, Blach S, Gamkrelidze I, Zignego AL, Brunetto MR, Raimondo G, Taliani G, Iannone A, Russo FP, Santantonio TA, Zuin M, Chessa L, Blanc P, Puoti M, Vinci M, Erne EM, Strazzabosco M, Massari M, Lampertico P, Rumi MG, Federico A, Orlandini A, Ciancio A, Borgia G, Andreone P, Caporaso N, Persico M, Ieluzzi D, Madonia S, Gori A, Gasbarrini A, Coppola C, Brancaccio G, Andriulli A, Quaranta MG, Montilla S, Razavi H, Melazzini M, Vella S, Craxì Antonio, Kondili, Loreta A., Robbins, Sarah, Blach, Sarah, Gamkrelidze, Ivane, Zignego, Anna L., Brunetto, Maurizia R., Raimondo, Giovanni, Taliani, Gloria, Iannone, Andrea, Russo, Francesco P., Santantonio, Teresa A., Zuin, Massimo, Chessa, Luchino, Blanc, Pierluigi, Puoti, Massimo, Vinci, Maria, Erne, Elke M., Strazzabosco, Mario, Massari, Marco, Lampertico, Pietro, Rumi, Maria G., Federico, Alessandro, Orlandini, Alessandra, Ciancio, Alessia, Borgia, Guglielmo, Andreone, Pietro, Caporaso, Nicola, Persico, Marcello, Ieluzzi, Donatella, Madonia, Salvatore, Gori, Andrea, Gasbarrini, Antonio, Coppola, Carmine, Brancaccio, Giuseppina, Andriulli, Angelo, Quaranta, Maria G., Montilla, Simona, Razavi, Homie, Melazzini, Mario, Vella, Stefano, Craxì, Antonio, Kondili, L. A., Robbins, S., Blach, S., Gamkrelidze, I., Zignego, A. L., Brunetto, M. R., Raimondo, G., Taliani, G., Iannone, A., Russo, F. P., Santantonio, T. A., Zuin, M., Chessa, L., Blanc, P., Puoti, M., Vinci, M., Erne, E. M., Strazzabosco, M., Massari, M., Lampertico, P., Rumi, M. G., Federico, A., Orlandini, A., Ciancio, A., Borgia, G., Andreone, P., Caporaso, N., Persico, M., Ieluzzi, D., Madonia, S., Gori, A., Gasbarrini, A., Coppola, C., Brancaccio, G., Andriulli, A., Quaranta, M. G., Montilla, S., Razavi, H., Melazzini, M., Vella, S., Craxi, A., Kondili, L, Robbins, S, Blach, S, Gamkrelidze, I, Zignego, A, Brunetto, M, Raimondo, G, Taliani, G, Iannone, A, Russo, F, Santantonio, T, Zuin, M, Chessa, L, Blanc, P, Puoti, M, Vinci, M, Erne, E, Strazzabosco, M, Massari, M, Lampertico, P, Rumi, M, Federico, A, Orlandini, A, Ciancio, A, Borgia, G, Andreone, P, Caporaso, N, Persico, M, Ieluzzi, D, Madonia, S, Gori, A, Gasbarrini, A, Coppola, C, Brancaccio, G, Andriulli, A, Quaranta, M, Montilla, S, Razavi, H, Melazzini, M, Vella, S, and Craxi, A

Subjects
HCV, WHO, chronic infection, linkage to care, Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, Sustained Virologic Response, Viral Hepatitis, Settore MED/12 - GASTROENTEROLOGIA, World Health Organization, Antiviral Agents, NO, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Pharmacotherapy, Cost of Illness, Cause of Death, Health care, medicine, Humans, 030212 general & internal medicine, Viremia, chronic infection, HCV, linkage to care, WHO, Disease Eradication, Mortality, Intensive care medicine, Cause of death, Hepatology, business.industry, Public health, Carcinoma, Liver Neoplasms, Hepatocellular, Hepatitis C, medicine.disease, Markov Chains, Italy, 030211 gastroenterology & hepatology, business, Viral hepatitis
Abstract

Background & Aims Advances in direct‐acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked‐to‐care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030. Methods Using a modelling approach grounded in Italian real‐life data of diagnosed and treated patients, different linkage‐to‐care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals. Results Under the 40% linked‐to‐care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948‐1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0‐F3 cases. Under the 60% linked‐to‐care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958‐1978 birth cohorts could capture 55% of F0‐F3 individuals. Under the 80% linked‐to‐care scenario, screening limited in 1968‐1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals. Conclusion In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required.

Published
2018

21. A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study

Author

Michele Barone, Antonio Massimo Ippolito, Angelo Andriulli, Ruggiero Francavilla, Francesco Pesce, Paolo Tundo, Antonio Patrizio Termite, Nicola Napoli, Pietro Gatti, Gianfranco Lauletta, Michele Milella, Endrit Shahini, A. Smedile, Vincenzo Messina, Filomena Morisco, Fabio Conti, Giuseppina Brancaccio, A. Di Leo, Teresa Santantonio, C. Masetti, Andrea Iannone, Barone, M., Iannone, A., Shahini, E., Ippolito, A. M., Brancaccio, G., Morisco, F., Milella, M., Messina, V., Smedile, A., Conti, F., Gatti, P., Santantonio, T., Tundo, Antonio, Lauletta, G., Napoli, N., Masetti, C., Termite, A. P., Francavilla, R., Di Leo, A., Pesce, F., Andriulli, A., Barone, M, Iannone, A, Shahini, E, Ippolito, A M, Brancaccio, G, Morisco, F, Milella, M, Messina, V, Smedile, A, Conti, F, Gatti, P, Santantonio, T, Tundo, P, Lauletta, G, Napoli, N, Masetti, C, Termite, A P, Francavilla, R, Di Leo, A, Pesce, F, and Andriulli, A

Subjects
Liver Cirrhosis, Male, Cirrhosis, Sofosbuvir, Sustained Virologic Response, Gastroenterology, Benzimidazole, chemistry.chemical_compound, 0302 clinical medicine, Ascites, antiviral therapy, Clinical endpoint, Prospective Studies, Chronic, Prospective cohort study, Hepatitis C, Middle Aged, Infectious Diseases, Treatment Outcome, 030220 oncology & carcinogenesis, Combination, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.symptom, medicine.drug, Human, Ledipasvir, medicine.medical_specialty, Genotype, Infectious Disease, Antiviral Agents, 03 medical and health sciences, direct-acting antivirals, hepatitis C, liver cirrhosis, Aged, Benzimidazoles, Fluorenes, Hepatitis C, Chronic, Humans, Ribavirin, Drug Therapy, Internal medicine, Virology, medicine, Antiviral Agent, direct-acting antiviral, Hepatology, business.industry, liver cirrhosi, medicine.disease, Surgery, Fluorene, Prospective Studie, chemistry, business
Abstract

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (p=0.002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (p=0.002), prevalence of Child-Pugh class A (p=0.002), lower MELD scores (p=0.001) and smaller number of non-responders (p=0.04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analysis (p=0.007 and p=0.008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients. This article is protected by copyright. All rights reserved.

Published
2018

22. Platelet count does not predict bleeding in cirrhotic patients: Results from the PRO-LIVER Study

Author

Basili, S. a, Raparelli, V. b., Napoleone, L. b., Talerico, G. a., Corazza, G. R. c., Perticone, F. d., Sacerdoti, D. e., Andriulli, A. f., Licata, A. g., Pietrangelo, A., Picardi, A. i., Raimondo, G. j., Violi, F., Palasciano, G., D’Alitto, F., Palmieri, V. O., Santovito, D., Michele, Di, Croce, D., Brocco, G., Fasolato, S., Cecchetto, S., Bombonato, L., Bertoni, G., Restuccia, M., Andreozzi, T., Liguori, P., Caroleo, M. L., Perticone, B., Staltari, M., Manfredini, O., Giorgi, De, Averna, A., Giammanco, M., Granito, A., Pettinari, A., Marinelli, I., Bolondi, S., Falsetti, L., Salvi, L., Durante-Mangoni, A., Cesaro, E., Farinaro, F., Ragone, V., Morana, E., Ippolito, I., Iacobellis, A., Niro, A., Merla, G., Maimone, A., Cacciola, S., Varvara, I., Drenaggi, D., Staffolani, D., Vespasiani-Gentilucci, S., Galati, U., Gallo, G., Davì, P., Schiavone, G., Santilli, C., Tana, F., Soresi, C., Bianchi, Giovanni, Carderi, B., Pinto, I., Tuttolomondo, A., Ferrari, A., Gresele, G., Fierro, P., Morelli, T., Laffi, O., Romanelli, G., Arena, R. G., Stasi, U., Gasbarrini, A., Garcovich, M., Zocco, M. A., Riccardi, L., Ainora, M. E., Capeci, W., Martino, Giuseppe, Nobili, P., Cavallo, L., Frugiuele, M., Greco, P., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Cesare, Di, Masala, V., Delitala, M., Invernizzi, G., Vincenzo, P., Minno, Di, Tufano, G., Purrello, A., Privitera, F., Forgione, G., Curigliano, A., Senzolo, V., Rodríguez-Castro, M., Giannelli, K. I., Serra, G., Neri, C., Pignataro, S., Rizzetto, P., Debernardi, M., Svegliati, V. W., Bergamaschi, B. G., Masotti, G., Costanzo, M., Antonio, F., Angelico, F., Del, Ben, Polimeni, M., Proietti, L., Cangemi, M., Romiti, R., Toriello, G. F., Sperduti, F., Santangelo, N., Visioli, G., Todisco, G., Vestri, Anna, Farcomeni, R., Corrao, A., Gobbi, S., Corradini, E., Costantino, G., Tripepi, G., Angelico, M., Bolondi, L., D’Amico, G., Franchis, De, Gatta, R., Tassone, A., Anzaldi, E. J., Barone, M., Bazzini, M., Bianchi, C., Boari, P. I., Bracco, B., Buonauro, C., Buttà, A., Buzzetti, E., Calabria, S., Caradio, F., Carleo, P., Carrabba, Maria, Castorani, D., Cecchetto, L., Cicco, L., Cimini, S., Colombo, C., B. M., Vuono, De, Denegri, S., Del, Corso, Giosia, Di, Donnarumma, P., Giorgini, E., Grassi, P., Grembiale, D., Hijazi, A., Iamele, D., Lorusso, L., Marchese, G., Marra, Alberto, Masala, M., Miceli, M., Montebianco, G., Murgia, A. L., Naccarato, G., Padula, P., Pattoneri, D., Perego, P., Pesce, F., Petramala, P., Piano, L., Pinto, S., Pinna, D., Pignataro, M., Pretti, F. S., Pucci, V., Salinaro, G., Salzano, F., Santarossa, A., Scarpini, C., Scicali, F., Sirico, R., Suppressa, D., Talia, P., Torres, M., Traversa, D., Vazzana, M., Vecchio, Claudia, Vettore, R., Vitale, E., Basili, S., Raparelli, V., Napoleone, L., Talerico, G., Corazza, G.R., Perticone, F., Sacerdoti, D., Andriulli, A., Licata, A., Pietrangelo, A., Picardi, A., Raimondo, G., Violi, F., Palasciano, Giuseppe, D’Alitto, Felicia, Palmieri, Vincenzo Ostilio, Santovito, Daniela, Di Michele, Dario, Croce, Giuseppe, Brocco, Silvia, Fasolato, Silvano, Cecchetto, Lara, Bombonato, Giancarlo, Bertoni, Michele, Restuccia, Tea, Andreozzi, Paola, Liguori, Maria Livia, Caroleo, Benedetto, Perticone, Maria, Staltari, Orietta, Manfredini, Roberto, De Giorgi, Alfredo, Averna, Maurizio, Giammanco, Antonina, Granito, Alessandro, Pettinari, Irene, Marinelli, Sara, Bolondi, Luigi, Falsetti, Lorenzo, Salvi, Aldo, Durante-Mangoni, Emanuele, Cesaro, Flavio, Farinaro, Vincenza, Ragone, Enrico, Morana, Ignazio, Ippolito, Antonio, Iacobellis, Angelo, Niro, Grazia, Merla, Antonio, Maimone, Sergio, Cacciola, Irene, Varvara, Doriana, Drenaggi, Davide, Staffolani, Silvia, Vespasiani-Gentilucci, Umberto, Galati, Giovanni, Gallo, Paolo, Davì, Giovanni, Schiavone, Cosima, Santilli, Francesca, Tana, Claudio, Soresi, Maurizio, Bianchi Giovanni, Battista, Carderi, Isabella, Pinto, Antonio, Tuttolomondo, Antonino, Ferrari, Giovanni, Gresele, Paolo, Fierro, Tiziana, Morelli, Olivia, Laffi, Giacomo, Romanelli, Roberto Giulio, Arena, Umberto, Stasi, Cristina, Gasbarrini, Antonio, Garcovich, Matteo, Zocco, Maria Assunta, Riccardi, Laura, Ainora, Maria Elena, Capeci, William, Martino Giuseppe, Pio, Nobili, Lorenzo, Cavallo, Maurizio, Frugiuele, Pierluigi, Greco, Antonio, Ventura, Paolo, Cuoghi, Chiara, Marcacci, Matteo, Serviddio, Gaetano, Vendemiale, Gianluigi, Villani, Rosanna, Gargano, Ruggiero, Vidili, Gianpaolo, Di Cesare, Valentina, Masala, Maristella, Delitala, Giuseppe, Invernizzi, Pietro, Vincenzo, Ronca, Di Minno, Giovanni, Tufano, Antonella, Purrello, Francesco, Privitera, Graziella, Forgione, Alessandra, Curigliano, Valentina, Senzolo, Marco, Rodríguez-Castro, Kryssia Isabel, Giannelli, Gianluigi, Serra, Carla, Neri, Sergio, Pignataro, Pietro, Rizzetto, Mario, Debernardi, Venon Wilma, Svegliati, Baroni Gianluca, Bergamaschi, Gaetano, Masotti, Michela, Costanzo, Filippo, Antonio, Figliomeni, Angelico, Francesco, Del Ben, Maria, Polimeni, Licia, Proietti, Marco, Cangemi, Roberto, Romiti Giulio, Francesco, Toriello, Filippo, Sperduti, Nicolò, Santangelo, Giuseppe, Visioli, Giacomo, Todisco, Tommaso, Vestri Anna, Rita, Farcomeni, Alessio, Corrao, Salvatore, Gobbi, Paolo, Corradini, Elena, Costantino, Giorgio, Tripepi, Giovanni, Angelico, Mario, D’Amico, Gennaro, De Franchis, Roberto, Gatta, Angelo, Tassone, Eliezer Joseph, Anzaldi, Massimiliano, Barone, Milena, Bazzini, Cristina, Bianchi, Paola Ilaria, Boari, Benedetta, Bracco, Christian, Buonauro, Agostino, Buttà, Carmelo, Buzzetti, Elena, Calabria, Stefano, Caradio, Federica, Carleo, Pietro, Carrabba Maria, Domenica, Castorani, Luigi, Cicco, Sebastiano, Cimini, Claudia, Colombo, Barbara Maria, De Vuono, Stefano, Denegri, Andrea, Del Corso, Lisette, Di Giosia, Paolo, Donnarumma, Emilia, Giorgini, Paolo, Grassi, Davide, Grembiale, Alessandro, Hijazi, Daniel, Iamele, Luigi, Lorusso, Giusi, Marchese, Alessandra, Marra Alberto, Maria, Miceli, Giuseppe, Montebianco, Abenavoli Ludovico, Murgia, Giuseppe, Naccarato, Paola, Padula, Donatella, Pattoneri, Paolo, Perego, Francesca, Pesce, Paola, Petramala, Luigi, Piano, Salvatore, Pinto, Daniela, Pinna, Miriam, Pignataro, Francesca Serena, Pretti, Vincenzo, Pucci, Giacomo, Salinaro, Francesco, Salzano, Andrea, Santarossa, Claudia, Scarpini, Francesca, Scicali, Roberto, Sirico, Domenico, Suppressa, Patrizia, Talia, Michela, Torres, Daniele, Traversa, Matteo, Vazzana, Natale, Vecchio Claudia, Rita, Vettore, Elia, Vitale, Francesco, Basili, S, Raparelli, V, Napoleone, L, Talerico, G, Corazza, G, Perticone, F, Sacerdoti, D, Andriulli, A, Licata, A, Pietrangelo, A, Picardi, A, Raimondo, G, Violi, F, Palasciano, G, D'Alitto, F, Palmieri, V, Santovito, D, Di Michele, D, Croce, G, Brocco, S, Fasolato, S, Cecchetto, L, Bombonato, G, Bertoni, M, Restuccia, T, Andreozzi, P, Liguori, M, Caroleo, B, Perticone, M, Staltari, O, Manfredini, R, De Giorgi, A, Averna, M, Giammanco, A, Granito, A, Pettinari, I, Marinelli, S, Bolondi, L, Falsetti, L, Salvi, A, Durante-Mangoni, E, Cesaro, F, Farinaro, V, Ragone, E, Morana, I, Ippolito, A, Iacobellis, A, Niro, G, Merla, A, Maimone, S, Cacciola, I, Varvara, D, Drenaggi, D, Staffolani, S, Vespasiani-Gentilucci, U, Galati, G, Gallo, P, Davi, G, Schiavone, C, Santilli, F, Tana, C, Soresi, M, Bianchi Giovanni, B, Carderi, I, Pinto, A, Tuttolomondo, A, Ferrari, G, Gresele, P, Fierro, T, Morelli, O, Laffi, G, Romanelli, R, Arena, U, Stasi, C, Gasbarrini, A, Garcovich, M, Zocco, M, Riccardi, L, Ainora, M, Capeci, W, Martino Giuseppe, P, Nobili, L, Cavallo, M, Frugiuele, P, Greco, A, Ventura, P, Cuoghi, C, Marcacci, M, Serviddio, G, Vendemiale, G, Villani, R, Gargano, R, Vidili, G, Di Cesare, V, Masala, M, Delitala, G, Invernizzi, P, Vincenzo, R, Di Minno, G, Tufano, A, Purrello, F, Privitera, G, Forgione, A, Curigliano, V, Senzolo, M, Rodriguez-Castro, K, Giannelli, G, Serra, C, Neri, S, Pignataro, P, Rizzetto, M, Debernardi, V, Svegliati, B, Bergamaschi, G, Masotti, M, Costanzo, F, Antonio, F, Angelico, F, Del Ben, M, Polimeni, L, Proietti, M, Cangemi, R, Romiti, G, Toriello, F, Sperduti, N, Santangelo, G, Visioli, G, Todisco, T, Vestri Anna, R, Farcomeni, A, Corrao, S, Gobbi, P, Corradini, E, Costantino, G, Tripepi, G, Angelico, M, D'Amico, G, De Franchis, R, Gatta, A, Tassone, E, Anzaldi, M, Barone, M, Bazzini, C, Bianchi, P, Boari, B, Bracco, C, Buonauro, A, Butta, C, Buzzetti, E, Calabria, S, Caradio, F, Carleo, P, Carrabba Maria, D, Castorani, L, Cicco, S, Cimini, C, Colombo, B, De Vuono, S, Denegri, A, Del Corso, L, Di Giosia, P, Donnarumma, E, Giorgini, P, Grassi, D, Grembiale, A, Hijazi, D, Iamele, L, Lorusso, G, Marchese, A, Marra, A, Miceli, G, Montebianco, A, Murgia, G, Naccarato, P, Padula, D, Pattoneri, P, Perego, F, Pesce, P, Petramala, L, Piano, S, Pinto, D, Pinna, M, Pignataro, F, Pretti, V, Pucci, G, Salinaro, F, Salzano, A, Santarossa, C, Scarpini, F, Scicali, R, Sirico, D, Suppressa, P, Talia, M, Torres, D, Traversa, M, Vazzana, N, Vecchio Claudia, R, Vettore, E, Vitale, F, S Basili, V Raparelli, L Napoleone, G Talerico, G Corazza, F Perticone, D Sacerdoti, A Andriulli, A Licata, A Pietrangelo, A Picardi, G Raimondo, F Violi, MD on behalf of PRO-LIVER Collaborator, Palasciano Giuseppe, D’Alitto Felicia, Palmieri Vincenzo Ostilio, Santovito Daniela, Di Michele Dario, Croce Giuseppe, Brocco Silvia, Fasolato Silvano, Cecchetto Lara, Bombonato Giancarlo, Bertoni Michele, Restuccia Tea, Andreozzi Paola, Liguori Maria Livia, Caroleo Benedetto, Perticone Maria, Staltari Orietta, Manfredini Roberto, De Giorgi Alfredo, Averna Maurizio, Giammanco Antonina, Granito Alessandro, Pettinari Irene, Marinelli Sara, Bolondi Luigi, Falsetti Lorenzo, Salvi Aldo, Durante-Mangoni Emanuele, Cesaro Flavio, Farinaro Vincenza, Ragone Enrico, Morana Ignazio, Ippolito Antonio, Iacobellis Angelo, Niro Grazia, Merla Antonio, Maimone Sergio, Cacciola Irene, Varvara Doriana, Drenaggi Davide, Staffolani Silvia, Vespasiani-Gentilucci Umberto, Galati Giovanni, Gallo Paolo, Davi Giovanni, Schiavone Cosima, Santilli Francesca, Tana Claudio, Soresi Maurizio, Bianchi Giovanni Battista, Carderi Isabella, Pinto Antonio, Tuttolomondo Antonino, Ferrari Giovanni, Gresele Paolo, Fierro Tiziana, Morelli Olivia, Laffi Giacomo, Romanelli Roberto Giulio, Arena Umberto, Stasi Cristina, Gasbarrini Antonio, Garcovich Matteo, Zocco Maria Assunta, Riccardi Laura, Ainora Maria Elena, Capeci William, Martino Giuseppe Pio, Nobili Lorenzo, Cavallo Maurizio, Frugiuele Pierluigi, Greco Antonio, Ventura Paolo, Cuoghi Chiara, Marcacci Matteo, Serviddio Gaetano, Vendemiale Gianluigi, Villani Rosanna, Gargano Ruggiero, Vidili Gianpaolo, Di Cesare Valentina, Masala Maristella, Delitala Giuseppe, Invernizzi Pietro, Vincenzo Ronca, Di Minno Giovanni, Tufano Antonella, Purrello Francesco, Privitera Graziella, Forgione Alessandra, Curigliano Valentina, Senzolo Marco, Rodríguez-Castro Kryssia Isabel, Giannelli Gianluigi, Serra Carla, Neri Sergio, Pignataro Pietro, Rizzetto Mario, Debernardi Venon Wilma, Svegliati Baroni Gianluca, Bergamaschi Gaetano, Masotti Michela, Costanzo Filippo, Antonio Figliomeni, Angelico Francesco, Del Ben Maria, Polimeni Licia, Proietti Marco, Cangemi Roberto, Romiti Giulio Francesco, Toriello Filippo, Sperduti Nicolò, Santangelo Giuseppe, Visioli Giacomo, Todisco Tommaso, Vestri Anna Rita, Farcomeni Alessio, Corrao Salvatore, Gobbi Paolo, Corradini Elena, Costantino Giorgio, Tripepi Giovanni, Angelico Mario, D’Amico Gennaro, de Franchis Roberto, Gatta Angelo, Tassone Eliezer Joseph, Anzaldi Massimiliano, Barone Milena, Bazzini Cristina, Bianchi Paola Ilaria, Boari Benedetta, Bracco Christian, Buonauro Agostino, Buttà Carmelo, Buzzetti Elena, Calabria Stefano, Caradio Federica, Carleo Pietro, Carrabba Maria Domenica, Castorani Luigi, Cicco Sebastiano, Cimini Claudia, Colombo Barbara Maria, De Vuono Stefano, Denegri Andrea, Del Corso Lisette, Di Giosia Paolo, Donnarumma Emilia, Giorgini Paolo, Grassi Davide, Grembiale Alessandro, Hijazi Daniel, Iamele Luigi, Lorusso Giusi, Marchese Alessandra, Marra Alberto Maria, Miceli Giuseppe, Montebianco Abenavoli Ludovico, Murgia Giuseppe, Naccarato Paola, Padula Donatella, Pattoneri Paolo, Perego Francesca, Pesce Paola, Petramala Luigi, Piano Salvatore, Pinto Daniela, Pinna Miriam, Pignataro Francesca Serena, Pretti Vincenzo, Pucci Giacomo, Salinaro Francesco, Salzano Andrea, Santarossa Claudia, Scarpini Francesca, Scicali Roberto, Sirico Domenico, Suppressa Patrizia, Talia Michela, Torres Daniele, Traversa Matteo, Vazzana Natale, Vecchio Claudia Rita, Vettore Elia, Vitale Francesco, Corazza, G. R., Guidacci, Raimondo, Palasciano, G., D'Alitto, F., Palmieri, V. O., Santovito, D., Di Michele, D., Croce, G., Brocco, S., Fasolato, S., Cecchetto, L., Bombonato, G., Bertoni, M., Restuccia, T., Andreozzi, P., Liguori, M. L., Caroleo, B., Perticone, M., Staltari, O., Manfredini, R., De Giorgi, A., Averna, M., Giammanco, A., Granito, A., Pettinari, I., Marinelli, S., Bolondi, L., Falsetti, L., Salvi, A., Durante-Mangoni, E., Cesaro, F., Farinaro, V., Ragone, E., Morana, I., Ippolito, A., Iacobellis, A., Niro, G., Merla, A., Maimone, S., Cacciola, I., Varvara, D., Drenaggi, D., Staffolani, S., Vespasiani-Gentilucci, U., Galati, G., Gallo, P., Davi, G., Schiavone, C., Santilli, F., Tana, C., Soresi, M., Bianchi Giovanni, B., Carderi, I., Pinto, A., Tuttolomondo, A., Ferrari, G., Gresele, P., Fierro, T., Morelli, O., Laffi, G., Romanelli, R. G., Arena, U., Stasi, C., Gasbarrini, A., Garcovich, M., Zocco, M. A., Riccardi, L., Ainora, M. E., Capeci, W., Martino Giuseppe, P., Nobili, L., Cavallo, M., Frugiuele, P., Greco, A., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Di Cesare, V., Masala, M., Delitala, G., Invernizzi, P., Vincenzo, R., Di Minno, G., Tufano, A., Purrello, F., Privitera, G., Forgione, A., Curigliano, V., Senzolo, M., Rodriguez-Castro, K. I., Giannelli, G., Serra, C., Neri, S., Pignataro, P., Rizzetto, M., Debernardi, V. W., Svegliati, B. G., Bergamaschi, G., Masotti, M., Costanzo, F., Antonio, F., Angelico, F., Del Ben, M., Polimeni, L., Proietti, M., Cangemi, R., Romiti, G. F., Toriello, F., Sperduti, N., Santangelo, G., Visioli, G., Todisco, T., Vestri Anna, R., Farcomeni, A., Corrao, S., Gobbi, P., Corradini, E., Costantino, G., Tripepi, G., Angelico, M., D'Amico, G., De Franchis, R., Gatta, A., Tassone, E. J., Anzaldi, M., Barone, M., Bazzini, C., Bianchi, P. I., Boari, B., Bracco, C., Buonauro, A., Butta, C., Buzzetti, E., Calabria, S., Caradio, F., Carleo, P., Carrabba Maria, D., Castorani, L., Cicco, S., Cimini, C., Colombo, B. M., De Vuono, S., Denegri, A., Del Corso, L., Di Giosia, P., Donnarumma, E., Giorgini, P., Grassi, D., Grembiale, A., Hijazi, D., Iamele, L., Lorusso, G., Marchese, A., Marra, A. M., Miceli, G., Montebianco, A. L., Murgia, G., Naccarato, P., Padula, D., Pattoneri, P., Perego, F., Pesce, P., Petramala, L., Piano, S., Pinto, D., Pinna, M., Pignataro, F. S., Pretti, V., Pucci, G., Salinaro, F., Salzano, A., Santarossa, C., Scarpini, F., Scicali, R., Sirico, D., Suppressa, P., Talia, M., Torres, D., Traversa, M., Vazzana, N., Vecchio Claudia, R., Vettore, E., and Vitale, F.

Subjects
Liver Cirrhosis, Male, Settore MED/09 - Medicina Interna, 030204 cardiovascular system & hematology, Gastroenterology, Severity of Illness Index, cjirrhosis, ACTIVATION, 0302 clinical medicine, Risk Factors, Medicine, Platelet, Prospective Studies, Prospective cohort study, RISK, Aged, 80 and over, medicine.diagnostic_test, PRO-LIVER, Platelet, cirrhosis, gastrointestinal bleeding, ASSOCIATION, Middle Aged, Prognosis, Italy, 030211 gastroenterology & hepatology, Female, Gastrointestinal Hemorrhage, Human, Adult, Platelets, medicine.medical_specialty, Prognosi, Liver Cirrhosi, MEDLINE, COAGULATION, gastrointestinal bleeding, Socio-culturale, Hemorrhage, Hepatology, Follow-Up Studie, 03 medical and health sciences, Text mining, Internal medicine, Severity of illness, ENDOTOXEMIA, Pro-Liver Study, Humans, HEMOSTASIS, International Normalized Ratio, Aged, Proportional Hazards Models, Prothrombin time, Cirrhosi, Platelet Count, Bleeding, Liver Cirrhosis, business.industry, Proportional hazards model, Platelet Count, Risk Factor, cirrhosis, bleeding, Thrombocytopenia, Prospective Studie, THROMBOSIS, Platelets, cjirrhosis, bleeding, PRO-LIVER, Proportional Hazards Model, Prothrombin Time, business, DECOMPENSATED CIRRHOSIS, Follow-Up Studies
Abstract

OBJECTIVES: Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. METHODS: We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years. RESULTS: A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child–Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800–1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50×103/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11–3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16–3.62; P=0.013) independently predicted overall bleeding events. CONCLUSIONS: Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

Published
2018

26. Nullspaces of MFIE and Calderon preconditioned EFIE operators applied to toroidal surfaces

Author

Cools, Kristof, Andriulli, Francesco P., Olyslager, Femke, and Michielssen, Eric

Subjects
Integral equations -- Usage, Electromagnetic fields -- Properties, Mobile communication systems -- Research, Wireless communication systems -- Research, Numerical analysis -- Methods, Wireless technology, Business, Computers, Electronics, Electronics and electrical industries
Published
2009

28. Time domain Calderon identities and their application to the integral equation analysis of scattering by PEC objects Part II: stability

Author

Andriulli, Francesco R., Cools, Kristof, Olyslager, Femke, and Michielssen, Eric

Subjects
Integral equations -- Usage, Electric fields -- Properties, Stability -- Evaluation, Electric conductors -- Properties, Electromagnetic waves -- Scattering, Electromagnetic waves -- Methods, Business, Computers, Electronics, Electronics and electrical industries
Published
2009

29. Analysis and regularization of the TD-EFIE low-frequency breakdown

Author

Andriulli, Francesco P., Bagci, Hakan, Vipiana, Francesca, Vecchi, Giuseppe, and Michielssen, Eric

Subjects
Integral equations -- Usage, Wave frequency -- Evaluation, Electric fields -- Evaluation, Business, Computers, Electronics, Electronics and electrical industries
Abstract

Low-frequency breakdown phenomenon plaguing marching-on-in-time solutions of time domain electric field integral equations is analyzed and cured. A theoretical analysis of the breakdown identifies deficiencies in the treatments proposed to date. A scheme for eliminating low frequency breakdown phenomena that leverages hierarchical regularization is presented. It applies to arbitrary meshes and gives rise to linear systems that are better conditioned than those obtained with standard loop-star/tree bases. The scheme's analytical properties and numerical results demonstrate its efficacy in accelerating the iterative solution of the time domain electric field integral equations. Index Terms--Electric field integral equation (EFIE), hierarchical methods, integral equations, marching on in time (MOT), numerical methods, preconditioning, time domain (TD).

Published
2009

30. Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis

Author

Antonino Carlo Privitera, Antonio Rispo, C. Ferracane, Maria Cappello, Raffaele Melina, Francesco William Guglielmi, Angelo Andriulli, Rocco Spagnuolo, Fabrizio Bossa, Giuseppe Costantino, M. Mendolaro, Mariabeatrice Principi, Agnese Miranda, Pietro Paese, Alessandro Azzarone, Ladislava Sebkova, Silvia Mazzuoli, Olga Maria Nardone, R. Clemente, Antonio Tursi, Marco Romano, M. Patturelli, A. Lauria, Endrit Shahini, C. Ricciardelli, Caterina Sgarro, L. Fanigliulo, Laurino Grossi, Gabriele Riegler, Walter Fries, Giuseppe Pranzo, Nello Buccianti, Gaetano Inserra, Giuseppe Biscaglia, Maria Rosa Valvano, Bossa, F, Biscaglia, G, Valvano, Mr, Costantino, G, Lauria, A, Clemente, R, Ferracane, C, Shahini, E, Mendolaro, M, Grossi, L, Mazzuoli, S, Rispo, A, Pranzo, G, Sebkova, L, Tursi, A, Miranda, A, Patturelli, M, Spagnuolo, R, Ricciardelli, C, Sgarro, C, Paese, P, Inserra, G, Azzarone, A, Nardone, O, Fries, W, Buccianti, N, Privitera, Ac, Principi, Mb, Cappello, M, Guglielmi, Fw, Romano, M, Riegler, G, Fanigliulo, L, Melina, R, and Andriulli, A.

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Physiology, Biologics, Inflammatory bowel disease, Golimumab, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Autoinjector, Internal medicine, Medicine, Humans, Adverse effect, Dose-Response Relationship, Drug, business.industry, Gastroenterology, Anti-TNF-alpha, Ulcerative colitis, Antibodies, Monoclonal, Hepatology, Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Colitis, Ulcerative, Female, Calprotectin, business, medicine.drug
Abstract

Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p

Published
2019

31. A multiplicative Calderon preconditioner for the electric field integral equation

Author

Andriulli, Francesco P., Cools, Kristof, Bagci, Hakan, Olyslager, Femke, Buffa, Annalisa, Christiansen, Snorre, and Michielssen, Eric

Subjects
Electric fields -- Properties, Integral equations -- Evaluation, Numerical analysis -- Methods, Wave propagation -- Methods, Business, Computers, Electronics, Electronics and electrical industries
Abstract

In this paper, a new technique for preconditioning electric field integral equations (EFIEs) by leveraging Calderon identities is presented. In contrast to all previous Calderon preconditioners, the proposed preconditioner is purely multiplicative in nature, applicable to open and closed structures, straightforward to implement, and easily interfaced with existing method of moments (MoM) code. Numerical results demonstrate that the MoM EFIE system obtained using the proposed preconditioning converges rapidly, independently of the discretization density. Index Terms--Electric field integral equation (EFIE), integral equations, numerical methods, preconditioning.

Published
2008

32. Hierarchical bases for nonhierarchic 3-D triangular meshes

Author

Andriulli, Francesco P., Vipiana, Francesca, and Vecchi, Giuseppe

Subjects
Antennas (Electronics) -- Design and construction, Finite element method -- Usage, Wavelet transforms -- Evaluation, Integral equations -- Evaluation, Business, Computers, Electronics, Electronics and electrical industries
Abstract

We describe a novel basis of hierarchical, multiscale functions that are linear combinations of standard Rao-Wilton-Glisson (RWG) functions. When the basis is used for discretizing the electric field integral equation (EFIE) for PEC objects it gives rise to a linear system immune from low-frequency breakdown, and well conditioned for dense meshes. The proposed scheme can be applied to any mesh with triangular facets, and therefore it can be used as if it were an algebraic preconditioner. The properties of the new system are confirmed by numerical results that show fast convergence rates of iterative solvers, significantly better than those for the loop-tree basis. As a byproduct of the basis generation, a generalization of the RWG functions to nonsimplex cells is introduced. Index Terms--Antennas, hierarchical bases, method of moments (MoM), multiscale, multiresolution (MR) techniques, wavelets.

Published
2008

33. Early-Onset Diabetes as Risk Factor for Pancreatic Cancer: miRNA Expression Profiling in Plasma Uncovers a Role for miR-20b-5p, miR-29a, and miR-18a-5p in Diabetes of Recent Diagnosis

Author

Andrea Fontana, Angelo Andriulli, Massimo Carella, Francesca Tavano, Domenica Gioffreda, Tommaso Biagini, Tommaso Mazza, and Orazio Palumbo

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, endocrine system diseases, pancreatic cancer, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, diagnostic performance, Mirna expression, Internal medicine, Diabetes mellitus, Pancreatic cancer, microRNA, medicine, Digital polymerase chain reaction, neoplasms, Early onset, Original Research, High prevalence, business.industry, Healthy subjects, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, digestive system diseases, expression profile, 030104 developmental biology, 030220 oncology & carcinogenesis, circulating microRNA, early diabetes, business
Abstract

The high prevalence of early-diabetes in patients with pancreatic cancer (PanC) implies that its recognition could help identify people at high risk of developing PanC. Candidate microRNAs (miRNAs) associated with recent diabetes were screened from our previous miRNA expression profiling on 10 pools of plasma from PanC patients and non-PanC controls, both including also subjects with early- and late-diabetes. The droplet digital PCR (ddPCR) was used to re-test candidate miRNAs in a new independent cohort of 69 subjects (40 PanC, 29 non-PanC) with early- (17 PanC, 13 non-PanC) or late-diabetes (23 PanC, 16 non-PanC), and in 100 non-diabetic healthy subjects (HS). miRNA levels were evaluated for differences between subjects enrolled into the study and for their diagnostic performance, also compared to the CA 19-9 determinations. MiR-20b-5p, miR-29a, and miR-18a-5p were selected from the previous miRNA expression profiling. The ddPCR confirmed the increase of miR-20b-5p and miR-29a levels in PanC with early- compared to those with late-diabetes. Conversely, miR-20b-5p, miR-29a, and miR-18a-5p were over-expressed in both PanC and non-PanC with recent diabetes compared to HS, and each miRNA achieved a similar diagnostic performance in distinguishing either PanC or non-PanC with early-diabetes from HS (miR-20b-5p: AUC = 0.877 vs. AUC = 0.873; miR-29a: AUC = 0.838 vs. AUC = 0.810; miR-18a-5p: AUC = 0.824 vs. AUC = 0.875). Despite miR-20b-5p and miR-29a expressions were also higher both in PanC and non-PanC with late-diabetes with respect to HS, the diagnostic accuracy in PanC with late-diabetes vs. HS reached by each miRNA (miR-20b-5p: AUC = 0.760; miR-29a: AUC = 0.630) was lower than the ones achieved in PanC with early-diabetes vs. HS. Furthermore, miR-20b-5p achieved a higher diagnostic accuracy to discriminate non-PanC with early-diabetes from HS (AUC = 0.868; SP = 81%; PPV = 32.1%) compared to the CA 19-9 (AUC = 0.700; SP = 40.0%; PPV = 15.5%), and the joint (miR-20b-5p and CA 19-9) discrimination ability was higher than the one achieved by the CA 19-9 tested alone (AUC = 0.900, p = 0.003). Our data highlighted the association between miR-18a-5p and early-diabetes, and suggested for miR-20b-5p and miR-29 a role in identifying early diabetes in PanC, albeit not as an early manifestation of cancer. MiR-20b-5p as more informative marker than CA 19-9 in distinguishing non-PanC with recent diabetes from HS was also uncovered.

Published
2020

34. Real-world experience with implantable loop recorder monitoring to detect subclinical atrial fibrillation in patients with cryptogenic stroke: The value of p wave dispersion in predicting arrhythmia occurrence

Author

Bhavika Kakadia, Ryna Then, Joshua Weinstock, Jared A. Collins, Rady Ho, Andrea M. Russo, Ephrem Teklemariam, Krystal Hunter, Matthew Ortman, Daniel Marks, and John Andriulli

Subjects
medicine.medical_specialty, Premature atrial contraction, Population, Diastole, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Atrial Fibrillation, Implantable loop recorder, medicine, Humans, 030212 general & internal medicine, education, Stroke, Subclinical infection, Ischemic Stroke, Retrospective Studies, education.field_of_study, business.industry, Atrial fibrillation, medicine.disease, Cardiology, Etiology, Electrocardiography, Ambulatory, Cardiology and Cardiovascular Medicine, business
Abstract

We hypothesized patients implanted with ILRs for cryptogenic stroke in "real life" clinical practice will show an AF detection rate comparable to prior clinical studies, and that clinical or imaging features may help to identify those at higher risk of AF detection.A retrospective chart review was conducted of all patients who presented with cryptogenic stroke and received an ILR at an academic medical center from 2015 to 2017 with an active inpatient stroke service. The electronic health record and remote monitoring were used to identify occurrence of AF.A total of 178 patients who received ILRs for cryptogenic stroke were included. Overall, after a thorough evaluation for other etiologies of stroke, 35 (19.6%) were found to have AF detected. Mean follow-up was 365 days with a median time to detection of 131 days. Advanced age (p = 0.001), diastolic dysfunction on echo (p = 0.03), as well as ECG findings of premature atrial contractions (PACs) and p wave dispersion (PWD) 40 ms were found to be predictive of AF detection (p = 0.04, p 0.001, respectively). On multiple regression analysis, the only independent predictor of AF detection was PWD 40 ms.After a thorough evaluation to exclude other etiologies for stroke, approximately 20% of patients of our cryptogenic stroke population were found to have AF with ILR surveillance. Advanced age, diastolic dysfunction, as well as ECG findings of PACs and increased PWD may help to predict those at higher risk of AF detection, while PWD was the only independent predictor. This has important clinical implications, as better prediction of AF may help identify those at highest risk and might subsequently aid in guiding therapy.

Published
2020

35. Transabdominal ultrasound-guided pancreatic biopsy: a neglected but safe, effective and inexpensive procedure that needs to be re-juvinalized

Author

Angelo Andriulli, Fabrizio Bossa, Antonella Marra, Fulvia Terracciano, Paola Parente, Krizia Sitajolo, Maria Rosa Valvano, Annabianca Amoruso, Paolo Graziano, and Antonio Massimo Ippolito

Subjects
medicine.medical_specialty, Abdominal pain, Multivariate analysis, 03 medical and health sciences, 0302 clinical medicine, Bloating, Biopsy, Internal Medicine, medicine, Pancreatic mass, Humans, Radiology, Nuclear Medicine and imaging, Sampling (medicine), Endoscopic Ultrasound-Guided Fine Needle Aspiration, Pancreas, Original Paper, medicine.diagnostic_test, business.industry, Ultrasound, General Medicine, medicine.disease, Needles, 030220 oncology & carcinogenesis, Sonographer, 030211 gastroenterology & hepatology, Radiology, medicine.symptom, business
Abstract

BACKGROUND: For solid pancreatic masses, ultrasound endoscopic fine-needle biopsy is suggested as the front-line investigation for tissue achievement, notwithstanding the optimal performance of transabdominal ultrasound (TUS)-guided biopsy. PURPOSE: To reassess the efficacy and effectiveness of TUS-guided sampling and to determine the factors predictive of accurate histology. METHODS: In total, 142 patients with an indication for a TUS-guided biopsy of a pancreatic mass were analyzed. A single pass of an 18-gauge Biomol needle was carried out by the Menghini technique. The accuracy, sensitivity, and specificity of the procedure in terms of correctly diagnosing an inflammatory or neoplastic lesion were determined. The patients’ characteristics, the size and location of the mass, and the sonographers’ experience in performing TUS were recorded. RESULTS: The sampling was unsuccessful in 24 cases, owing to the deep localization of lesions (57%), bloating (33%), or low patient compliance (10%). The accuracy, sensitivity, and specificity of the 118 successful biopsies were 81%, 79%, and 100%, respectively. A biopsy core was obtained in 90 of the 118 patients (76%) in whom the procedure was attempted. In the multivariate analysis, lesion size (≤ 20 mm vs. > 20 mm) (OR = 5.3 [1.7–17.0]) and operator experience (OR = 4.4 [1.6–12.1]) predicted the acquisition of adequate samples. With an expert sonographer, the accuracy, sensitivity, and specificity were 87%, 85%, and 100%, respectively. Two adverse events were registered: mild abdominal pain and a hypotensive crisis. CONCLUSIONS: The present investigation highlights the optimal performance of a TUS-guided biopsy of a pancreatic mass. Because of its simplicity and safety, the procedure needs to be included among the recommended investigative options

Published
2020

36. Distinguishing features between patients with acute diverticulitis and diverticular bleeding: Results from the REMAD registry

Author

Sergio Segato, Mario Grassini, A. Maurano, Matteo Bosani, Antonio Colecchia, Martina Cargiolli, Giovanni Barbara, Antonio Maria Morselli Labate, Ennio Guido, Cesare Cremon, Giuseppe Biscaglia, Marilia Carabotti, Donato Iuliano, E. Galliani, Davide Festi, Bruno Annibale, Biagio Mauro, Alida Andrealli, S. Bargiggia, Carola Severi, R. Reati, Maria Antonia Bianco, Matteo Neri, Santino Marchi, Rosario Cuomo, Francesca Falangone, Agostino Di Ciaula, Franco Iafrate, Simona Bartolozzi, Paolo Andreozzi, Bastianello Germanà, Alessandro Moscatelli, Marco Pennazio, Andrea Laghi, Marco Astegiano, Riccardo Nascimbeni, S. Peralta, Maria Erminia Bottiglieri, Paolo Usai, Piero Portincasa, Carolina Ciacci, Paola Iovino, Pietro Occhipinti, Vincenzo Savarino, Fabio Pace, Alessandro Redaelli, Giovanni Latella, Franco Radaelli, V. Festa, Mirko Di Ruscio, Giuseppe Scaccianoce, Marco Rossi, Marco Dinelli, Francesco Bachetti, Valentina Valle, Angelo Andriulli, M. Parravicini, Marina De Matthaeis, Raffale Salerno, Clara Virgilio, Elisa Marabotto, Sandro Ardizzone, Gian Andrea Binda, Alessandra Dell'Era, Giampiero Manes, Gabrio Bassotti, Carabotti M., Morselli Labate A.M., Cremon C., Cuomo R., Pace F., Andreozzi P., Falangone F., Barbara G., and Annibale B.

Subjects
Adult, Male, medicine.medical_specialty, Diverticular complications, digestive system, Pathogenesis, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, In patient, Prospective Studies, Registries, Family history, Life Style, Diverticulitis, Aged, Aged, 80 and over, Diverticular Diseases, Hepatology, Acute diverticulitis, business.industry, digestive, oral, and skin physiology, Gastroenterology, Middle Aged, medicine.disease, Diverticular diseases, digestive system diseases, surgical procedures, operative, Logistic Models, Italy, 030220 oncology & carcinogenesis, Diverticular complication, Diverticular disease, 030211 gastroenterology & hepatology, Observational study, Female, business, Cohort study
Abstract

Background Pathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications. Aims to assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding. Methods Data were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding. Results Age was significantly lower (OR 0.48, 95% CI: 0.34–0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11–2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60–27.0) and diverticulitis (OR 4.23, 95% CI: 1.11–16.1). Conclusion This ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.

Published
2020

37. Endoscopic stenting for colorectal cancer obstruction as a bridge-to-surgery strategy

Author

Giuseppe Losurdo, R. Lovero, Rosa Federica La Fortezza, M. Gentile, Angelo Andriulli, Fulvio Spirito, and Alfredo Di Leo

Subjects
Laparoscopic surgery, medicine.medical_specialty, Univariate analysis, Colorectal cancer, business.industry, medicine.medical_treatment, Clinical Biochemistry, Cancer, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Biochemistry, Surgery, Stoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Endoscopic stenting, 030212 general & internal medicine, Stage (cooking), business, Adverse effect
Abstract

Background Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self-expanding metal stents (SEMS) have been increasingly used as a bridge-to-surgery (BTS) strategy. Materials and methods In an 8-year period, consecutive patients with acute left-sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease-free survival (DFS) of the two therapeutic options. Results Forty-five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil-lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43-0.98, P = .04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P = .33) and DFS (36 in SEMS; 35 in ES, P = .35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4-16.6, P = .04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08-50, P = .04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16-0.92, P = .03). At multivariate analysis, no feature retained an independent predictive power. Conclusion SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients.

Published
2020

38. Clinical Significance of Circulating miR-1273g-3p and miR-122-5p in Pancreatic Cancer

Author

Massimo Carella, Francesca Tavano, Angelo Andriulli, Evaristo Maiello, Orazio Palumbo, Andrea Fontana, Tommaso Mazza, Domenica Gioffreda, Tommaso Biagini, and Francesca Bazzocchi

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Cancer Research, pancreatic cancer, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, diagnostic performance, Internal medicine, Pancreatic cancer, microRNA, MiR-122, Medicine, Digital polymerase chain reaction, Clinical significance, Original Research, business.industry, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, expression profile, Circulating MicroRNA, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, circulating microRNA, prognosis, business, Pancreas
Abstract

The burden of pancreatic cancer (PanC) requires innovation in the current diagnostic approach. This study aimed to uncover new circulating microRNAs (miRNAs) that would distinguish patients with PanC from healthy subjects (HS) compared with the cancer antigen 19-9 (CA 19-9), and predict patients' clinical phenotypes and outcomes. MiRNA expression profiles in plasma were investigated by using a two-stage process. In a discovery phase, miRNAs levels were analyzed using the GeneChip™ miRNA 4.0 Affymetrix assay in 10 pools of plasma samples from PanC patients and HS; in a validation phase, significantly altered miRNAs were re-tested in independent cohorts of cancer patients and controls by droplet digital PCR (ddPCR). The diagnostic performance of the resulting miRNAs was compared to CA 19-9 determinations, and the associations of miRNAs plasma levels with patients' clinical phenotypes and outcomes were also taken into account. Bioinformatics selection of miRNAs differentially expressed in plasma uncovered miR-18a-5p, miR-122-5p, miR-1273g-3p, and miR-6126 as candidate oncogenic miRNAs in PanC. The ddPCR technology confirmed the significant over-expression of miR-122-5p, miR-1273g-3p, and miR-6126 in PanC compared to HS, in line with the trend of the CA 19-9 levels. Plasma levels of miR-1273g-3p, in combination with CA 19-9, showed higher power in distinguishing PanC patients from HS compared to the CA 19-9 tested alone, with a gain in both sensitivity and negative predictive value indicating a low false-negative rate (SE = 90.2% and NPV = 92.3% vs. SE = 82.1% and NPV = 87.9%). None of the oncogenic miRNAs were able to distinguish between a neoplastic and a proliferative/inflammatory disease of the pancreas, and were not able to stratify subjects according to the clinical risk for the disease. The only valuable association in PanC patients was found between miR-1273g-3p and tumor stage, and increased miR-122-5p levels emerged as independent negative prognostic factor for PanC patients (HR = 1.58, 95% CI = 1.03–2.43, p = 0.037). Our data highlighted a role for circulating miR-1273g-3p and miR-122-5p as new diagnostic and prognostic biomarkers for PanC.

Published
2020
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39. Associations between pancreatic expression quantitative trait loci (eQTLs) and pancreatic ductal adenocarcinoma risk

Author

Paolo Giorgio Arcidiacono, Herman Brenner, Oliver Strobel, Beatrice Mohelnikova-Duchonova, Martin Lovecek, Angelica Macauda, Laura Pistoni, Krzysztof Jamroziak, Luca Pollina, Milena Di Leo, Maria Gazouli, Giulia Martina Cavestro, Emanuele Federico Kauffmann, George Theodoropoulos, Giuseppe Vanella, Jakob R. Izbicki, Edita Kreivėnaitė, Gabriele Capurso, Martin Oliverius, Viktor Hlavac, Domenica Gioffreda, Maria Chiara Petrone, Angelo Andriulli, Livia Archibugi, Raffaele Pezzilli, Ludmila Vodickova, Sabrina Gloria Giulia Testoni, Cosimo Sperti, Audrius Ivanauskas, Michael F. Nentwich, Pavel Vodicka, Daniela Basso, Renata Talar-Wojnarowska, Daniele Campa, Giulia Peduzzi, Thilo Hackert, John P. Neoptolemos, Dania Bozzato, Andrea Szentesi, Péter Hegyi, Federico Canzian, Manuel Gentiluomo, Giuseppe Malleo, Erika Darvasi, Juozas Kupcinskas, Ye Lu, Anna Caterina Milanetto, Pavel Soucek, László Gajdán, Cristian Gheorghe, Luca Morelli, Francesca Tavano, Stefano Landi, Raffaella Alessia Zuppardo, Rita T. Lawlor, and Yogesh K. Vashist

Subjects
Pancreatic ductal adenocarcinoma, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Expression quantitative trait loci, Gastroenterology, Cancer research, Medicine, business
Published
2020

40. A Surrogate Model Based on Artificial Neural Network for RF Radiation Modelling with High-Dimensional Data

Author

Joe Wiart, Xi Cheng, Christian Person, Clement Henry, Francesco P. Andriulli, Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire Traitement et Communication de l'Information (LTCI), Institut Mines-Télécom [Paris] (IMT)-Télécom Paris, Department of Electronics and Telecommunications [Torino] (DET), Politecnico di Torino = Polytechnic of Turin (Polito), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), Institut Polytechnique de Paris (IP Paris), Département Communications & Electronique (COMELEC), Télécom ParisTech, Radio-Fréquences Microondes et Ondes Millimétriques (RFM2), and Institut Mines-Télécom [Paris] (IMT)-Télécom Paris-Institut Mines-Télécom [Paris] (IMT)-Télécom Paris

Subjects
Clustering high-dimensional data, Data Analysis, Computer science, Artificial neural networks, Specific absorption rate, Uncertainty quantification, uncertainty quantification, Health, Toxicology and Mutagenesis, lcsh:Medicine, 02 engineering and technology, Electroencephalography, Article, Surrogate model, 0202 electrical engineering, electronic engineering, information engineering, medicine, Artificial neural network architecture, Humans, Electrodes, [STAT.AP]Statistics [stat]/Applications [stat.AP], medicine.diagnostic_test, Artificial neural network, business.industry, lcsh:R, Rf radiation, Public Health, Environmental and Occupational Health, Uncertainty, Brain, 020206 networking & telecommunications, Pattern recognition, [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, specific absorption rate, 020201 artificial intelligence & image processing, Artificial intelligence, Neural Networks, Computer, business, artificial neural networks
Abstract

This paper focuses on quantifying the uncertainty in the specific absorption rate valuesof the brain induced by the uncertain positions of the electroencephalography electrodes placed onthe patient&rsquo, s scalp. To avoid running a large number of simulations, an artificial neural networkarchitecture for uncertainty quantification involving high-dimensional data is proposed in this paper.The proposed method is demonstrated to be an attractive alternative to conventional uncertaintyquantification methods because of its considerable advantage in the computational expense andspeed.

Published
2020

41. Polymorphic variants within non-coding RNA and risk of pancreatic ductal adenocarcinoma

Author

Raffaella Alessia Zuppardo, Maria Gazouli, Thilo Hackert, Claudio Pasquali, Yogesh K. Vashist, Ye Lu, John P. Neoptolemos, Luca Morelli, Audrius Ivanauskas, Edita Kreivenaite, Sabrina Gloria Giulia Testoni, Cristian Gheorghe, Ewa Małecka-Panas, Francesca Tavano, Andrea Szentesi, Paolo Giorgio Arcidiacono, Martin Oliverius, Klara Cervena, Maria Chiara Petrone, Erika Darvasi, Péter Hegyi, Stefania Moz, Juozas Kupcinskas, Daniele Campa, George Theodoropoulos, Stefano Landi, Cosimo Sperti, Federico Canzian, Matteo Giaccherini, Gabriele Capurso, Raffaele Pezzilli, Beatrice Mohelnikova-Duchonova, Chiara Corradi, Claudio Luchini, Null Archibugi ., Michael F. Nentwich, Pavel Vodicka, Giuseppe Vanella, Domenica Gioffreda, Niccolò Napoli, Viktor Hlavac, Giulia Martina Cavestro, G. Di Franco, Anna Caterina Milanetto, Pavel Soucek, László Gajdán, Silvia Carrara, H Brenner, Manuel Gentiluomo, Krzysztof Jamroziak, Rita T. Lawlor, Angelo Andriulli, Jakob R. Izbicki, and Oliver Strobel

Subjects
Pancreatic ductal adenocarcinoma, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Gastroenterology, Cancer research, Medicine, business, Non-coding RNA
Published
2020

42. A marching-on-in-time hierarchical scheme for the solution of the time domain electric field integral equation

Author

Andriulli, Francesco P., Bagci, Hakan, Vipiana, Francesca, Vecchi, Giuseppe, and Michielssen, Eric

Subjects
Electric fields -- Properties, Integral equations -- Properties, Time-domain analysis -- Usage, Wavelet transforms -- Properties, Business, Computers, Electronics, Electronics and electrical industries
Abstract

A spatially hierarchical current expansion is used to construct a marching-on-in-time based time domain electric field integral equation solver. The formulation gives rise to well-conditioned linear systems and is immune to time domain low-frequency breakdown phenomena. Numerical results that demonstrate the effectiveness of the proposed hierarchical approach in comparison with existing technologies are presented. Index Terms--Electric field integral equation (EFIE), multiresolution techniques, time domain analysis, wavelets.

Published
2007

43. A regularized combined field integral equation for scattering from 2-D perfect electrically conducting objects

Author

Andriulli, Francesco P. and Michielssen, Eric

Subjects
Antennas (Electronics) -- Design and construction, Electric fields -- Properties, Electromagnetic waves -- Scattering, Electromagnetic waves -- Evaluation, Business, Computers, Electronics, Electronics and electrical industries
Abstract

A novel regularized combined field integral equation pertinent to the analysis of scattering from 2-D perfect electrically conducting objects is presented. The equation is immune from illconditioning due to dense spatial discretizations and appears free from internal resonances. The regularization is achieved via analytical inversion of the hypersingular part of the combined field integral equation, without negative repercussions on computational complexity. Numerical results are presented that show the effectiveness of the proposed formulation. Index Terms--Combined field integral equation (CFIE), electric field integral equation (EFIE), electromagnetic scattering.

Published
2007

44. Gender Differences in Presentation, Treatment, and In-Hospital Outcome of Patients Admitted With Heart Failure Complicated by Atrial Fibrillation (from the Get With the Guidelines—Heart Failure [GWTG-HF] Registry)

Author

Mitra Daneshvar, Nayan Desai, Eben Eno, Matthew Ortman, John Andriulli, Krystal Hunter, and Andrea M. Russo

Subjects
Male, medicine.medical_specialty, Patient characteristics, 030204 cardiovascular system & hematology, Logistic regression, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Internal medicine, Atrial Fibrillation, medicine, Humans, Hospital Mortality, Registries, 030212 general & internal medicine, Aged, Demography, Heart Failure, New Jersey, business.industry, Atrial fibrillation, University hospital, medicine.disease, Treatment Outcome, Hospital outcomes, Heart failure, Concomitant, Cardiology, Female, Guideline Adherence, Presentation (obstetrics), Cardiology and Cardiovascular Medicine, business
Abstract

Almost 25% of patients with heart failure (HF) have coexisting atrial fibrillation (AF), the latter of which may increase morbidity and mortality. Despite the high prevalence of HF with concomitant AF, this subgroup of patients remains understudied. This study examines gender differences in presentation, treatment and in-hospital outcome of patients with HF and AF. The Get With the Guidelines-Heart Failure (GWTG-HF) database enrolled 6,496 patients with HF who presented to Cooper University Hospital from 2005 to 2012. Twenty-four percent (1,561 patients) had concomitant AF. Pearson chi-square tests and the Student T-tests were used to compare patient characteristics by gender. Multivariate logistic regression was used to predict in-hospital mortality. Six hundred sixty-nine (42.8%) patients with HF and AF were women. Women were older (p 0.001), had a higher ejection fraction (p 0.001), had systolic hypertension (p 0.001), and were more likely to have health insurance (p 0.001). Despite a higher CHADS2 score in women (p = 0.007), there was no gender difference in percent of anticoagulation medications prescribed before admission. Women were less likely to present with dizziness, lightheadedness, or syncope, and were more likely to be compliant with medications and diet recommendations before admission. Despite differences in presentation, co-morbidities, and therapy, in-hospital mortality was similar between men and women. Decreased appetite or early satiety predicted in-hospital mortality in women, whereas age, chest pain on admission, and decreased appetite or early satiety predicted in-hospital mortality in men. In conclusion, women presenting with HF complicated by AF clinically differ from men, but despite these differences, both groups shared similar symptom presentation and in-hospital mortality rates.

Published
2018

45. A New Spotlight for Biomedical Electromagnetics! [Editor’s Comments]

Author

Francesco P. Andriulli

Subjects
First contact, Engineering, Electromagnetics, business.industry, Engineering ethics, Electrical and Electronic Engineering, Condensed Matter Physics, business, Column (database), Field (computer science)
Abstract

Biomedical applications of electromagnetics is a fundamental field of interest for the antennas and propagation (AP) community, which is why we have decided to debut a new column called “Bioelectromagnetics,” starting with this issue of IEEE Antennas and Propagation Magazine . I am very grateful to Prof. Asimina Kiourti from the ElectroScience Laboratory of The Ohio State University for agreeing to be the column’s founding editor. The column will focus on biomedical applications of electromagnetics, propagation, and antennas. All of the contributions should be written in the magazine’s style, addressing readers in our entire AP community. If the article’s content and style would make it appropriate for one of our technical publications, including IEEE Journal of Electromagnetics, RF and Microwaves in Medicine and Biology , it is probably not suitable for the magazine. Instead, the contributions should be written to be understandable by a large technical audience so that even those AP members with research interests outside bioelectromagnetism could understand and be cross fertilized by the column’s content. Review articles from recognized experts in their respective fields will be equally welcome. All prospective authors should first contact the column editor or editor-in-chief before preparing their manuscripts to check the compatibility of their perspective contribution with the column’s scope. We await your contributions!

Published
2021

46. Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Author

Domenica Gioffreda, Yasuhiro Shimizu, Serena Stigliano, Hidemi Ito, Kay-Tee Khaw, Carlo Lombardo, Martin Oliverius, Ioannis Papaconstantinou, Irena Valantiene, Pavel Soucek, Claudio Pasquali, Kazuo Hara, Verena Katzke, Federico Canzian, Hendrik Strothmann, Andrea Mambrini, Paola Fogar, Gabriele Capurso, Raffaele Pezzilli, Katarina Cuk, Anna Latiano, Olivier R. Busch, Chiara Valsuani, Katja Butterbach, Oliver Strobel, Jakob R. Izbicki, Pavel Vodicka, Thilo Hackert, William Greenhalf, Cosimo Sperti, Anna Katharina König, Angelo Andriulli, Francesca Tavano, Petra H.M. Peeters, Renata Talar-Wojnarowska, Willem Niesen, Giulia Martina Cavestro, Keitaro Matsuo, Beatrice Mohelnikova-Duchonova, Frederike Dijk, Yogesh K. Vashist, Stefano Landi, Maurizio Cantore, Hermann Brenner, Roberto Valente, Daniele Campa, Manuela Pastore, H. Bas Bueno-de-Mesquita, Carlo Federico Zambon, Roberto Salvia, Milena Di Leo, Maria Gazouli, Theron Johnson, Ewa Małecka-Panas, Timothy J. Key, Peter Macinga, Rudolf Kaaks, and Juozas Kupcinskas

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pancreatic disease, endocrine system diseases, business.industry, Case-control study, Context (language use), medicine.disease, Bioinformatics, digestive system diseases, Minor allele frequency, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, medicine, Genetic predisposition, Pancreatitis, chronic, Risk factor, business
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Published
2017

47. Optimal a priori clipping estimation for wavelet-based method of moments matrices

Author

Andriulli, Francesco P., Vecchi, Giuseppe, Vipiana, Francesca, Pirinoli, Paola, and Tabacco, Anita

Subjects
Matrices -- Evaluation, Methods engineering -- Evaluation, Wavelet transforms -- Evaluation, Business, Computers, Electronics, Electronics and electrical industries
Abstract

Wavelet bases are mainly used in the methods of moments (MoM) to render the system matrix sparse; clipping entries below a given threshold is an essential operation to obtain the desired sparse matrix. In this paper, we present a novel a priori way to estimate the clipping threshold that can be used if one wants an error on the solution below a desired accuracy. The procedure has a very low computational complexity, typically of (MoM). Index Terms--Integral equations, methods of moments (MoM), wavelets.

Published
2005

48. Inverted colonic diverticulum (ICD): report of two cases and literature review of a not that unusual endoscopic challenge

Author

Sonia Carparelli, Arcangela Patrizia Giuliani, Paola Parente, Francesco Perri, Giuseppe Biscaglia, Angelo Andriulli, Rossella Cubisino, Fabrizio Bossa, Francesco Cocomazzi, and M. Gentile

Subjects
medicine.medical_specialty, medicine.medical_treatment, Perforation (oil well), Colonoscopy, Diverticulum, Colon, Lesion, 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Biopsy, medicine, Humans, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Endoscopy, medicine.disease, digestive system diseases, Polypectomy, Dysplasia, 030220 oncology & carcinogenesis, Diverticular disease, 030211 gastroenterology & hepatology, Radiology, medicine.symptom, business
Abstract

Inverted colonic diverticulum (ICD) is a rare intraluminal lesion occurring in about 0.7-1.7% of people, often endoscopically indistinguishable from polyps. Some unspecific endoscopic features may assist to distinguish polypoid ICD from true polyps. This differentiation bears relevance for the therapeutic approach, as colonic polyps require snare polypectomy, a practice which may be associated with colonic perforation in case of true ICD. The endoscopist, therefore, should be aware of the likelihood of detecting these lesions during colonoscopy. A close inspection and a gentle probing could assist in a correct diagnosis and avoid risky procedures such as biopsy or polypectomy. Rarely, a neoplasm arising over an ICD and its treatment has been described. We reported two cases, one of which with dysplasia, and their treatment, and reviewed all the ICD endoscopic cases so far reported in the literature, remarking the possibility of finding pedunculated ICDs or neoplasm arising over an ICD.

Published
2021

50. OC.10.1 THE USE OF PRE-ENDOSCOPIC INTRAVENOUS PROTON PUMP INHIBITORS (PPIS) HAD NO IMPACT ON CLINICAL OUTCOMES IN ACUTE UPPER GASTROINTESTINAL BLEEDING: A PROSPECTIVE MULTICENTER ITALIAN COHORT STUDY

Author

A. Andriulli, R. Pumpo, G. Spinzi, L. Amitrano, G. Baldassarre, Marco Soncini, Riccardo Marmo, M. De Matthaeis, C. Londoni, L. Furio, L. Ferraris, S. Metrangolo, A. Balzano, L.G. Cavallaro, G. D'Amico, A. Lauri, E. Buscarini, V. Boarino, A. Merighi, B. Germanà, D. Spotti, P. Di Giorgio, L. Orsini, G. Imperiali, R. Lamanda, F. De Nigris, Alessandra Dell'Era, S. Bargiggia, D. Conte, F. Cipolletta, A. Nucci, P. Cesaro, A. Bizzotto, F.R. De Filippo, A. Anderloni, Maria Elena Riccioni, C. Marmo, A. Repici, A. Paterlini, A. Chirico, G. Napolitano, S. Mangiafico, C. De Fanis, O. Triossi, G. Rotondano, Annalisa Tortora, Guido Costamagna, F. Esposito, P. Borgheresi, L.M. Montalbano, E. Di Giulio, M. Franceschi, Cristina Bucci, R. Bennato, M. Manno, L. Purita, L. Cipolletta, R. Conigliaro, R.M. Zagari, R. De Franchis, A. Zambelli, F. Bazzoli, A. Russo, M.A. Bianco, G. Bresci, M. Parravicini, F. Parente, and S. Segato

Subjects
medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Gastroenterology, Medicine, Acute upper gastrointestinal bleeding, business, Cohort study
Published
2020

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