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1. Stereotactic Radiotherapy after Incomplete Transarterial (Chemo-) Embolization (TAE\TACE) versus Exclusive TAE or TACE for Treatment of Inoperable HCC: A Phase III Trial (NCT02323360)

Author

Tiziana Comito, Mauro Loi, Ciro Franzese, Elena Clerici, Davide Franceschini, Marco Badalamenti, Maria Ausilia Teriaca, Lorenza Rimassa, Vittorio Pedicini, Dario Poretti, Luigi Alessandro Solbiati, Guido Torzilli, Roberto Ceriani, Ana Lleo, Alessio Aghemo, Armando Santoro, and Marta Scorsetti

Subjects
ablative therapy, liver neoplasms, clinical trial, radiotherapy, local treatment, TACE, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.

Published
2022
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2. Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life

Author

Nicola Pugliese, Davide Polverini, Ivan Arcari, Stella De Nicola, Francesca Colapietro, Chiara Masetti, Monica Ormas, Roberto Ceriani, Ana Lleo, and Alessio Aghemo

Subjects
HCV, antiviral therapy, elderly, drug–drug interactions, special populations, Medicine
Abstract

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Published
2023
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3. Machine learning using the extreme gradient boosting (XGBoost) algorithm predicts 5-day delta of SOFA score at ICU admission in COVID-19 patients

Author

Jonathan Montomoli, Luca Romeo, Sara Moccia, Michele Bernardini, Lucia Migliorelli, Daniele Berardini, Abele Donati, Andrea Carsetti, Maria Grazia Bocci, Pedro David Wendel Garcia, Thierry Fumeaux, Philippe Guerci, Reto Andreas Schüpbach, Can Ince, Emanuele Frontoni, Matthias Peter Hilty, Mario Alfaro-Farias, MD, Gerardo Vizmanos-Lamotte, MD, PhD, Thomas Tschoellitsch, MD, Jens Meier, MD, Hernán Aguirre-Bermeo, MD, PhD, Janina Apolo, BSc, Alberto Martínez, MD, Geoffrey Jurkolow, MD, Gauthier Delahaye, MD, Emmanuel Novy, MD, Marie-Reine Losser, MD, PhD, Tobias Wengenmayer, MD, Jonathan Rilinger, MD, Dawid L. Staudacher, MD, Sascha David, MD, Tobias Welte, MD, Klaus Stahl, MD, “Agios Pavlos”, Theodoros Aslanidis, MD, PhD, Anita Korsos, MD, Barna Babik, MD, PhD, Reza Nikandish, MD, Emanuele Rezoagli, MD, PhD, Matteo Giacomini, MD, Alice Nova, MD, Alberto Fogagnolo, MD, Savino Spadaro, MD, PhD, Roberto Ceriani, MD, Martina Murrone, MD, Maddalena A. Wu, MD, Chiara Cogliati, MD, Riccardo Colombo, MD, Emanuele Catena, MD, Fabrizio Turrini, MD, MSc, Maria Sole Simonini, MD, Silvia Fabbri, MD, Antonella Potalivo, MD, Francesca Facondini, MD, Gianfilippo Gangitano, MD, Tiziana Perin, MD, Maria Grazia Bocci, MD, Massimo Antonelli, MD, Diederik Gommers, MD, PhD, Raquel Rodríguez-García, MD, Jorge Gámez-Zapata, MD, Xiana Taboada-Fraga, MD, Pedro Castro, MD, Adrian Tellez, MD, Arantxa Lander-Azcona, MD, Jesús Escós-Orta, MD, Maria C. Martín-Delgado, MD, Angela Algaba-Calderon, MD, Diego Franch-Llasat, MD, Ferran Roche-Campo, MD, PhD, Herminia Lozano-Gómez, MD, Begoña Zalba-Etayo, MD, PhD, Marc P. Michot, MD, Alexander Klarer, Rolf Ensner, MD, Peter Schott, MD, Severin Urech, MD, Nuria Zellweger, Lukas Merki, MD, Adriana Lambert, MD, Marcus Laube, MD, Marie M. Jeitziner, RN, PhD, Beatrice Jenni-Moser, RN, MSc, Jan Wiegand, MD, Bernd Yuen, MD, Barbara Lienhardt-Nobbe, Andrea Westphalen, MD, Petra Salomon, MD, Iris Drvaric, MD, Frank Hillgaertner, MD, Marianne Sieber, Alexander Dullenkopf, MD, Lina Petersen, MD, Ivan Chau, MD, Hatem Ksouri, MD, PhD, Govind Oliver Sridharan, MD, Sara Cereghetti, MD, Filippo Boroli, MD, Jerome Pugin, MD, PhD, Serge Grazioli, MD, Peter C. Rimensberger, MD, Christian Bürkle, MD, Julien Marrel, MD, Mirko Brenni, MD, Isabelle Fleisch, MD, Jerome Lavanchy, MD, Marie-Helene Perez, MD, Anne-Sylvie Ramelet, MD, Anja Baltussen Weber, MD, Peter Gerecke, MD, Andreas Christ, MD, Samuele Ceruti, MD, Andrea Glotta, MD, Katharina Marquardt, MD, Karim Shaikh, MD, Tobias Hübner, MD, Thomas Neff, MD, Hermann Redecker, MD, Mallory Moret-Bochatay, MD, FriederikeMeyer zu Bentrup, MD, MBA, Michael Studhalter, MD, Michael Stephan, MD, Jan Brem, MD, Nadine Gehring, MD, Daniela Selz, MD, Didier Naon, MD, Gian-Reto Kleger, MD, Urs Pietsch, MD, Miodrag Filipovic, MD, Anette Ristic, MD, Michael Sepulcri, MD, Antje Heise, MD, Marilene Franchitti Laurent, MD, Jean-Christophe Laurent, MD, Pedro D. Wendel Garcia, MSc, Reto Schuepbach, MD, Dorothea Heuberger, PhD, Philipp Bühler, MD, Silvio Brugger, MD, PhD, Patricia Fodor, MD, Pascal Locher, MD, Giovanni Camen, MD, Tomislav Gaspert, MD, Marija Jovic, MD, Christoph Haberthuer, MD, Roger F. Lussman, MD, and Elif Colak, MD

Subjects
Machine learning, Extreme gradient boosting (XGBoost), COVID-19, Multiple organ failure, Clinical decision support system (CDSS), Organ dysfunction score, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86 vs. 0.69, P

Published
2021
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4. Survival analysis of 230 patients with unresectable hepatocellular carcinoma treated with bland transarterial embolization.

Author

Ezio Lanza, Riccardo Muglia, Isabella Bolengo, Dario Poretti, Felice D'Antuono, Roberto Ceriani, Guido Torzilli, and Vittorio Pedicini

Subjects
Medicine, Science
Abstract

Locoregional therapies for hepatocellular carcinoma (HCC) include endovascular treatments such as chemoembolization (TACE) and bland embolization (TAE). TACE is the most adopted technique, despite a lack of definitive evidence of superiority over TAE, which is less costly and better tolerated due to the absence of chemotherapy. However, few studies have reported data on TAE monotherapy for unresectable HCC. We report our results in a cohort of 230 patients with unresectable HCC treated with TAE (TAE with 40-100micron microparticles, TAE with microparticles plus n-butyl-2-cyanoacrylate, TAE with Lipiodol) over the course of seven years. Thirty-seven patients (14%) were down-staged during observation and also received a percutaneous ablation. We observed 1-, 2-, 3-, 4- and 5-year rates of 84,8%, 58,7%, 38,3%, 28,3%, and 18,7%. Patients who also received percutaneous treatment performed best. Our results broaden the body of evidence for the use of TAE in advanced HCC.

Published
2020
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5. Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

Author

Ezio Lanza, Chiara Masetti, Gaia Messana, Riccardo Muglia, Nicola Pugliese, Roberto Ceriani, Ana Lleo de Nalda, Lorenza Rimassa, Guido Torzilli, Dario Poretti, Felice D'Antuono, Letterio Salvatore Politi, Vittorio Pedicini, Alessio Aghemo, and Humanitas HCC Multidisciplinary Group

Subjects
Medicine, Science
Abstract

Sarcopenia has been associated with lower overall survival in patients with cirrhosis and hepatocellular carcinoma (HCC) undergoing surgical resection, TACE, TARE, or transplantation. This monocentric study evaluated the prognostic significance of sarcopenia in patients affected by HCC who received bland transarterial embolization (TAE) therapy, by analyzing its impact on survival and treatment-related complications. All consecutive patients who underwent the 1st TAE between March 1st 2011 and July 1st 2019 in our Institution were retrospectively studied. To evaluate sarcopenia, the skeletal muscle index (SMI) was calculated by normalizing the cross-sectional muscle area at the level of L3 on an abdominal CT scan prior to embolization (cm2) by patient height (m2). SMI cut-off values for sarcopenia were considered ≤ 39 cm2/m2 for women and ≤55 cm2/m2 for men. Data about age, gender, body mass index (BMI), underlying liver disease, liver function, MELD score, Child-Pugh score, multifocal disease, performance status, previous interventions, length of stay (LOS), complications after the procedure, readmission rate within 30 days, survival time from TAE and total number and type of TAE received following the first procedure were collected. From 2011 to 2019, 142 consecutive patients underwent 305 TAEs. Observation time ranged from 1.4 to 100.5 months (median 20.1 SD = 22). Sarcopenia at baseline was present in 121 (85%) patients. Overall 87 (61.2%) patients died during follow-up with survival rates at 1-, 2-, 3-, 4-, and 5-year of 71%, 41%, 22%, 16% and 11% respectively. After multivariate analysis sarcopenia (HR = 2.22, p = 0.046), previous ablation/resection (HR = 0.51, p = 0.005) and multifocal disease (HR = 1.84, p = 0.02) were associated with reduced survival. Sarcopenia did not influence the safety of TAE in terms of LOS (2 days vs 1.5 days, p = 0.2), early complications rate (8% vs 5%, p = 0.5) and readmission rate within 30 days (7% vs 5%, p = 0.74). Sarcopenia, estimated by the L3SMI method, is an emerging prognostic factor in patients with HCC undergoing bland TAE therapy as it is associated with increased mortality, without impairing the safety of the locoregional treatment. Measures to ameliorate the SMI, such as nutritional support and physical exercise, should be evaluated in clinical trials for HCC patients receiving liver embolization to determine their impact on overall survival.

Published
2020
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6. Correction: Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

Author

Ezio Lanza, Chiara Masetti, Gaia Messana, Riccardo Muglia, Nicola Pugliese, Roberto Ceriani, Ana Lleo de Nalda, Lorenza Rimassa, Guido Torzilli, Dario Poretti, Felice D'Antuono, Letterio Salvatore Politi, Vittorio Pedicini, Alessio Aghemo, and Humanitas HCC Multidisciplinary Group

Subjects
Medicine, Science
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0232371.].

Published
2020
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7. Acute Kidney Injury in Diabetic Patients With Acute Myocardial Infarction: Role of Acute and Chronic Glycemia

Author

Giancarlo Marenzi, Nicola Cosentino, Valentina Milazzo, Monica De Metrio, Mara Rubino, Jeness Campodonico, Marco Moltrasio, Ivana Marana, Marco Grazi, Gianfranco Lauri, Alice Bonomi, Simone Barbieri, Emilio Assanelli, Alessia Dalla Cia, Roberto Manfrini, Roberto Ceriani, and Antonio Bartorelli

Subjects
acute hyperglycemia, acute kidney injury, acute myocardial infarction, diabetes mellitus, glycosylated hemoglobin, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundIn acute myocardial infarction, acute hyperglycemia is a predictor of acute kidney injury (AKI), particularly in patients without diabetes mellitus. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission. We investigated whether, in diabetic patients with acute myocardial infarction, the combined evaluation of acute and chronic glycemic levels may have better prognostic value for AKI than admission glycemia. Methods and ResultsAt admission, we prospectively measured glycemia and estimated average chronic glucose levels (mg/dL) using glycosylated hemoglobin (HbA1c), according to the following formula: 28.7×HbA1c (%)−46.7. We evaluated the association with AKI of the acute/chronic glycemic ratio and of the difference between acute and chronic glycemia (ΔA−C). We enrolled 474 diabetic patients with acute myocardial infarction. Of them, 77 (16%) experienced AKI. The incidence of AKI increased in parallel with the acute/chronic glycemic ratio (12%, 14%, 22%; P=0.02 for trend) and ΔA−C (13%, 13%, 23%; P=0.01) but not with admission glycemic tertiles (P=0.22). At receiver operating characteristic analysis, the acute/chronic glycemic ratio (area under the curve: 0.62 [95% confidence interval, 0.55–0.69]; P=0.001) and ΔA−C (area under the curve: 0.62 [95% confidence interval, 0.54–0.69]; P=0.002) accurately predicted AKI, without difference in the area under the curve between them (P=0.53). At reclassification analysis, the addition of the acute/chronic glycemic ratio and ΔA−C to acute glycemia allowed proper AKI risk prediction in 16% of patients. ConclusionsIn diabetic patients with acute myocardial infarction, AKI is better predicted by the combined evaluation of acute and chronic glycemic values than by assessment of admission glycemia alone.

Published
2018
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8. Scientific education and European citizenship. Suggestions and results from the European project SEDEC

Author

Roberto Ceriani

Subjects
Democracy and science communication, Public engagement with science and technology, Social participation to science and technology, Perceptions of science and technology, Public communication of and discourses on science and technology, Policy-making, communication and governance of science, Communication. Mass media, P87-96, Science (General), Q1-390
Abstract

Two concepts seemingly distant from each other, scientific education and European citizenship, have been the basis for "SEDEC - Science Education for the Development of European Citizenship", a European project funded by the European Commission in the framework of the Socrates/Comenius programme, aiming at producing training material addressed to European teachers. Started in autumn 2005, the project will end in 2008 with an in-service training course for European teachers and educators.

Published
2007

9. Machine learning using the Extreme Gradient Boosting (XGBoost) algorithm predicts 5-day delta of SOFA score at ICU admission in COVID-19 patients

Author

Marie M. Jeitziner, Iris Drvaric, Jan Wiegand, Abele Donati, Janina Apolo, Emanuele Rezoagli, Jesús Escós-Orta, Herminia Lozano-Gómez, Mirko Brenni, Giovanni Camen, Frank Hillgaertner, Sara Moccia, Antje Heise, Alexander Dullenkopf, Michael Stephan, Can Ince, Marcus Laube, Julien Marrel, Michele Bernardini, Barbara Lienhardt-Nobbe, Hernán Aguirre-Bermeo, Alberto Fogagnolo, Dorothea M. Heuberger, Severin Urech, Reto A. Schuepbach, Andrea Glotta, Samuele Ceruti, Isabelle Fleisch, Marc P. Michot, Alice Nova, Matthias P. Hilty, Tomislav Gaspert, Gianfilippo Gangitano, Savino Spadaro, Ivan Chau, Daniele Berardini, Tiziana Perin, Andrea Westphalen, Marie-Reine Losser, Hatem Ksouri, Marie-Hélène Perez, Theodoros Aslanidis, Christoph Haberthuer, Gerardo Vizmanos-Lamotte, Jorge Gámez-Zapata, Filippo Boroli, Adriana Lambert, Serge Grazioli, Petra Salomon, Christian Bürkle, Didier Naon, Philipp Bühler, Dawid L. Staudacher, Miodrag Filipovic, Hermann Redecker, Mario Alfaro-Farias, Massimo Antonelli, Rolf Ensner, Jerome Lavanchy, Lukas Merki, Roberto Ceriani, Anette Ristic, Chiara Cogliati, Reto Andreas Schüpbach, Daniela Selz, Begoña Zalba-Etayo, Anne-Sylvie Ramelet, Thierry Fumeaux, Andrea Carsetti, Peter Gerecke, Riccardo Colombo, Marilene Franchitti Laurent, Fabrizio Turrini, Tobias Wengenmayer, Tobias Welte, Philippe Guerci, Antonella Potalivo, Lucia Migliorelli, Barna Babik, Reza Nikandish, Pedro D. Wendel Garcia, Alberto Martínez, Maria Sole Simonini, Diederik Gommers, Xiana Taboada-Fraga, Jerome Pugin, Peter C. Rimensberger, Angela Algaba-Calderon, FriederikeMeyer zu Bentrup, Agios Pavlos, Thomas Tschoellitsch, Marianne Sieber, Karim Shaikh, Nuria Zellweger, Silvio Brugger, Geoffrey Jurkolow, Anja Baltussen Weber, Maria C. Martín-Delgado, Anita Korsós, Gian-Reto Kleger, Alexander Klarer, Emmanuel Novy, Diego Franch-Llasat, Adrian Tellez, Peter Schott, Jonathan Rilinger, Andreas Christ, Bernd Yuen, Jean-Christophe Laurent, Nadine Gehring, Pedro Castro, Sascha David, Francesca Facondini, Arantxa Lander-Azcona, Maria Grazia Bocci, Maddalena Alessandra Wu, Mallory Moret-Bochatay, Sara Cereghetti, Urs Pietsch, Martina Murrone, Gauthier Delahaye, Luca Romeo, Pascal Locher, Pedro David Wendel Garcia, Michael Sepulcri, Marija Jovic, Katharina Marquardt, Emanuele Frontoni, Patricia Fodor, Emanuele Catena, Tobias Hübner, Thomas Neff, Roger F. Lussman, Matteo Giacomini, Govind Oliver Sridharan, Beatrice Jenni-Moser, Jan Brem, Michael Studhalter, Elif Colak, Raquel Rodríguez-García, Silvia Fabbri, Jens Meier, Lina Petersen, Jonathan Montomoli, Ferran Roche-Campo, Klaus Stahl, Montomoli, J, Romeo, L, Moccia, S, Bernardini, M, Migliorelli, L, Berardini, D, Donati, A, Carsetti, A, Bocci, M, Wendel Garcia, P, Fumeaux, T, Guerci, P, Schupbach, R, Ince, C, Frontoni, E, Hilty, M, Alfaro-Farias, M, Vizmanos-Lamotte, G, Tschoellitsch, T, Meier, J, Aguirre-Bermeo, H, Apolo, J, Martinez, A, Jurkolow, G, Delahaye, G, Novy, E, Losser, M, Wengenmayer, T, Rilinger, J, Staudacher, D, David, S, Welte, T, Stahl, K, Pavlos, A, Aslanidis, T, Korsos, A, Babik, B, Nikandish, R, Rezoagli, E, Giacomini, M, Nova, A, Fogagnolo, A, Spadaro, S, Ceriani, R, Murrone, M, Wu, M, Cogliati, C, Colombo, R, Catena, E, Turrini, F, Simonini, M, Fabbri, S, Potalivo, A, Facondini, F, Gangitano, G, Perin, T, Grazia Bocci, M, Antonelli, M, Gommers, D, Rodriguez-Garcia, R, Gamez-Zapata, J, Taboada-Fraga, X, Castro, P, Tellez, A, Lander-Azcona, A, Escos-Orta, J, Martin-Delgado, M, Algaba-Calderon, A, Franch-Llasat, D, Roche-Campo, F, Lozano-Gomez, H, Zalba-Etayo, B, Michot, M, Klarer, A, Ensner, R, Schott, P, Urech, S, Zellweger, N, Merki, L, Lambert, A, Laube, M, Jeitziner, M, Jenni-Moser, B, Wiegand, J, Yuen, B, Lienhardt-Nobbe, B, Westphalen, A, Salomon, P, Drvaric, I, Hillgaertner, F, Sieber, M, Dullenkopf, A, Petersen, L, Chau, I, Ksouri, H, Sridharan, G, Cereghetti, S, Boroli, F, Pugin, J, Grazioli, S, Rimensberger, P, Burkle, C, Marrel, J, Brenni, M, Fleisch, I, Lavanchy, J, Perez, M, Ramelet, A, Weber, A, Gerecke, P, Christ, A, Ceruti, S, Glotta, A, Marquardt, K, Shaikh, K, Hubner, T, Neff, T, Redecker, H, Moret-Bochatay, M, Bentrup, F, Studhalter, M, Stephan, M, Brem, J, Gehring, N, Selz, D, Naon, D, Kleger, G, Pietsch, U, Filipovic, M, Ristic, A, Sepulcri, M, Heise, A, Franchitti Laurent, M, Laurent, J, Schuepbach, R, Heuberger, D, Buhler, P, Brugger, S, Fodor, P, Locher, P, Camen, G, Gaspert, T, Jovic, M, Haberthuer, C, Lussman, R, Colak, E, Biomedical Engineering and Physics, ACS - Microcirculation, Translational Physiology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, AII - Infectious diseases, and University of Zurich

Subjects
610 Medicine & health, Organ dysfunction score, Machine learning, computer.software_genre, Logistic regression, Clinical decision support system, law.invention, law, Medicine, Clinical decision support system (CDSS), Receiver operating characteristic, RC86-88.9, business.industry, Clinical decision support systems, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Extreme Gradient Boosting (XGBoost), Intensive care unit, Multiple organ failure, Cohort, Population study, SOFA score, Original Article, Artificial intelligence, 10023 Institute of Intensive Care Medicine, business, Algorithm, computer, Predictive modelling
Abstract

Background : Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods : We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results : The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model {0.86 vs. 0.69, P

Published
2021

10. Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: Initial report of the international RISC-19-ICU prospective observational cohort

Author

Pedro David Wendel Garcia, Thierry Fumeaux, Philippe Guerci, Dorothea Monika Heuberger, Jonathan Montomoli, Ferran Roche-Campo, Reto Andreas Schuepbach, Matthias Peter Hilty, Mario Alfaro Farias, Antoni Margarit, Gerardo Vizmanos-Lamotte, Thomas Tschoellitsch, Jens Meier, Francesco S. Cardona, Josef Skola, Lenka Horakova, Hernan Aguirre-Bermeo, Janina Apolo, Emmanuel Novy, Marie-Reine Losser, Geoffrey Jurkolow, Gauthier Delahaye, Sascha David, Tobias Welte, Tobias Wengenmayer, Dawid L. Staudacher, Theodoros Aslanidis, Barna Babik, Anita Korsos, Janos Gal, Hermann Csaba, Abele Donati, Andrea Carsetti, Fabrizio Turrini, Maria Sole Simonini, Roberto Ceriani, Martina Murrone, Emanuele Rezoagli, Giovanni Vitale, Alberto Fogagnolo, Savino Spadaro, Maddalena Alessandra Wu, Chiara Cogliati, Riccardo Colombo, Emanuele Catena, Francesca Facondini, Antonella Potalivo, Gianfilippo Gangitano, Tiziana Perin, Maria Grazia Bocci, Massimo Antonelli, Diederik Gommers, Can Ince, Eric Mayor-Vázquez, Maria Cruz, Martin Delgado, Raquel Rodriguez Garcia, Jorge Gamez Zapata, Begoña Zalba-Etayo, Herminia Lozano-Gomez, Pedro Castro, Adrian Tellez, Adriana Jacas, Guido Muñoz, Rut Andrea, Jose Ortiz, Eduard Quintana, Irene Rovira, Enric Reverter, Javier Fernandez, Miquel Ferrer, Joan R. Badia, Arantxa Lander Azcona, Jesus Escos Orta, Philipp Bühler, Silvio Brugger, Daniel Hofmaenner, Simone Unseld, Frank Ruschitzka, Mallory Moret-Bochatay, Bernd Yuen, Thomas Hillermann, Hatem Ksouri, Govind Oliver Sridharan, Anette Ristic, Michael Sepulcri, Miodrag Filipovic, Urs Pietsch, Petra Salomon, Iris Drvaric, Peter Schott, Severin Urech, Adriana Lambert, Lukas Merki, Marcus Laube, Frank Hillgaertner, Marianne Sieber, Alexander Dullenkopf, Lina Petersen, Serge Grazioli, Peter C. Rimensberger, Isabelle Fleisch, Jerome Lavanchy, Katharina Marquardt, Karim Shaikh, Hermann Redecker, Michael Stephan, Jan Brem, Bjarte Rogdo, Andre Birkenmaier, Friederike Meyer zu Bentrup, Patricia Fodor, Pascal Locher, Giovanni Camen, Martin Siegemund, Nuria Zellweger, Marie-Madlen Jeitziner, Beatrice Jenni-Moser, Christian Bürkle, Gian-Reto Kleger, Marilene Franchitti Laurent, Jean-Christophe Laurent, Tomislav Gaspert, Marija Jovic, Michael Studhalter, Christoph Haberthuer, Roger F. Lussman, Daniela Selz, Didier Naon, Romano Mauri, Samuele Ceruti, Julien Marrel, Mirko Brenni, Rolf Ensner, Nadine Gehring, Antje Heise, Tobias Huebner, Thomas A. Neff, Sara Cereghetti, Filippo Boroli, Jerome Pugin, Nandor Marczin, Joyce Wong, University of Zurich, Wendel Garcia, Pedro David, RISC-19 ICU investigators, Graduate School, Translational Physiology, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Intensive Care, Grazioli, Serge, and Rimensberger, Peter

Subjects
medicine.medical_specialty, ARDS, medicine.medical_treatment, 610 Medicine & health, Disease, 2700 General Medicine, 01 natural sciences, Article, NO, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Medicine, 030212 general & internal medicine, 0101 mathematics, Disease burden, Mechanical ventilation, lcsh:R5-920, Public health, ddc:618, Acute respiratory distress syndrome, Pandemic, business.industry, Incidence (epidemiology), 010102 general mathematics, COVID-19, General Medicine, medicine.disease, Intensive care unit, Coronavirus, Cohort, Absolute neutrophil count, 10209 Clinic for Cardiology, 10023 Institute of Intensive Care Medicine, lcsh:Medicine (General), business
Abstract

Background Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p

Published
2020
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11. High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study

Author

Jeness Campodonico, Alice Bonomi, Monica De Metrio, Daniela Riggio, Maria Luisa Biondi, Nicola Cosentino, Mara Rubino, Claudia Lucci, Marco Moltrasio, Stefano Genovese, Fabrizio Veglia, Valentina Milazzo, Giancarlo Marenzi, Katia Celentano, Roberto Ceriani, and Antonio L. Bartorelli

Subjects
medicine.medical_specialty, acute myocardial infarction, 030204 cardiovascular system & hematology, urologic and male genital diseases, Article, Pathogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, in-hospital prognosis, Internal medicine, Clinical endpoint, medicine, 030212 general & internal medicine, Myocardial infarction, Creatinine, biology, business.industry, urogenital system, Incidence (epidemiology), Cardiogenic shock, C-reactive protein, Acute kidney injury, General Medicine, medicine.disease, female genital diseases and pregnancy complications, chemistry, acute kidney injury, Cardiology, biology.protein, high-sensitivity C-reactive protein, business
Abstract

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L, p &lt, 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend &lt, 0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23, 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p &lt, 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome.

Published
2019
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12. Breast Cancer Immunodiagnosis and Immunotherapy

Author

Roberto Ceriani and Roberto Ceriani

Subjects
Breast--Cancer--Immunodiagnosis--Congresses, Breast--Cancer--Immunotherapy--Congresses, Monoclonal antibodies--Diagnostic use--Congres, Monoclonal antibodies--Therapeutic use--Congre, Antibodies, Monoclonal--diagnostic use--congre, Breast Neoplasms--diagnosis--congresses, Breast Neoplasms--therapy--congresses, Immunologic Tests--congresses, Immunotherapy--congresses
Abstract

The convening of the 3rd International Workshop on Monoclonal Antibodies and Breast Cancer had the character of a self-search exercise. After almost a decade of research in the basic and applied aspects of the use of serological means to diagnose and possibly treat breast cancer several milestones have been reached. Among them a clear understanding of immunopathological use and limitations of monoclonal antibodies against breast epithelium, the complete development and clinical use of immunoassays for circulating breast epithelial antigens, the striking advances in the diagnostic use of monoclonal antibodies to estrogen and progesterone receptor proteins and the first communications on proposed immunotherapeutic use of different conjugates of anti-breast antibodies. New areas of investigation have developed in our field, some which are reaching a full blossom while others are still facing obstacles and at times a re-definition of their goals and objectives. These meetings have acted in a way as a clearing house and have permitted their attendees to derive predictions that have helped shape future research and fine-tune objectives. But above all, the re-evaluation of past research at these Workshops and the renewed excitement brought to them by new information has helped generate a momentum and enthusiasm that assures for the future large scientific gains.

Published
2013

14. Sustained response to combination therapy in patients with chronic hepatitis C who failed to respond to interferon

Author

Lorenzo Morini, Gemino Fiorelli, Roberto Ceriani, Mauro Borzio, A. Chiesa, Savino Bruno, Silvia Fargion, Andrea Crosignani, Annarosa Orlandi, A. Maraschi, Mauro Podda, Franco Bissoli, Anna Ludovica Fracanzani, and Pier Maria Battezzati

Subjects
Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Combination therapy, Genotype, Anemia, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Gastroenterology, Antiviral Agents, chemistry.chemical_compound, Liver disease, Internal medicine, Drug Resistance, Viral, Ribavirin, Mucositis, Medicine, Humans, Adverse effect, Aged, Hepatology, business.industry, Interferon-alpha, Odds ratio, Hepatitis C, Chronic, Middle Aged, medicine.disease, chemistry, Immunology, Drug Therapy, Combination, Female, business
Abstract

Background/Aims : The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size. Methods : One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000–1200 mg/day for 48 weeks (Group A, n =74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000–1200 mg/day for 44 weeks (Group B, n =45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response. Results : Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged ≤40 years (36% vs. 13%; P =0.006) and in those with non-1 genotype (44% vs. 14%; P =0.002). Among genotype 1 patients, the younger ones showed higher response rates (32% vs. 7%; P =0.005). Compared with patients harboring non-1 genotypes, the odds ratio of being a non-responder was 1.68 (confidence interval (CI): 0.53–5.37; P =0.381) in younger genotype 1 patients and 9.53 (CI: 2.84–32; P Conclusions : Chronic hepatitis C patients who are non-responders to interferon monotherapy and infected by non-1 genotypes should undergo re-treatment with combination therapy. Treatment should be extended to younger genotype 1 patients who are more susceptible to liver disease worsening because of longer life expectancy and have a higher probability of being long lasting responders than their older counterparts.

Published
2003

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