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1. Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19

Author

de Marzo, V., Di Biagio, A., della Bona, R., Vena, A., Arboscello, E., Emirjona, H., Mora, S., Giacomini, M., da Rin, G., Pelosi, P., Bassetti, M., Ameri, P., Porto, I., Alessandrini, A., Camera, M., Delfino, E., de Maria, A., Dentone, C., Dodi, F., Ferrazin, A., Mazzarello, G., Mikulska, M., Nicolini, L., Toscanini, F., Giacobbe, D. R., Taramasso, L., Balletto, E., Portunato, F., Schenone, E., Rosseti, N., Baldi, F., Berruti, M., Briano, F., Dettori, S., Labate, L., Magnasco, L., Mirabella, M., Pincino, R., Russo, C., Sarteschi, G., Sepulcri, C., Tutino, S., Pontremoli, R., Beccati, V., Casciaro, S., Casu, M., Gavaudan, F., Ghinatti, M., Gualco, E., Leoncini, G., Pitto, P., Salam, K., Gratarola, A., Bixio, M., Amelia, A., Balestra, A., Ballarino, P., Bardi, N., Boccafogli, R., Caserza, F., Calzolari, E., Castelli, M., Cenni, E., Cortese, P., Cuttone, G., Feltrin, S., Giovinazzo, S., Giuntini, P., Nat-Ale, L., Orsi, D., Pastorino, M., Perazzo, T., Pescetelli, F., Schenone, F., Serra, M. G., Sottano, M., Brunetti, I., Loconte, M., Ball, L., Battaglini, D., Robba, C., Patroniti, N., Tallone, R., Amelotti, M., Majabo, M. J., Merlini, M., Perazzo, F., Ahamd, N., Barbera, P., Bovio, M., Cam-Podonico, P., Collida, A., Cutuli, O., Lomeo, A. -N., Fezza, F., Gentilucci, N., Hussein, N., Malvezzi, E., Mas-Sobrio, L., Motta, G., Pastorino, L., Pol-Licardo, N., Sartini, S., Vacca, P., Virga, V., Bezante, G. P., la Malfa, G., Valbusa, A., V. G., Ad, Bari-Sione, E., Bellotti, M., Teresita, A., Blanco, A., Grosso, M., Piroddi, M. G., Mosca-Telli, P., Caiti, M., Magnani, O., Sukkar, S., Cogorno, L., Gradaschi, R., Guiddo, E., Martino, E., Pisciotta, L., Cavagliere, B., Cristina, R., Francesca, F., Garibotto, G., Esposito, P., Passalacqua, G., Bagnasco, D., Braido, F., Riccio, A., Tagliabue, E., Gustavino, C., Ferraiolo, A., Giuffrida, S., Rosso, N., Morando, A., Papalia, R., Passerini, D., Tiberio, G., Orengo, G., Battaglini, A., Ruffoni, S., and Caglieris, S.

Subjects
Reseach Article
Abstract

BACKGROUND Increases in cardiac troponin (cTn) in coronavirus disease 2019 (COVID-19) have been associated with worse prognosis. Nonetheless, data about the significance of cTn in elderly subjects with COVID-19 are lacking. METHODS From a registry of consecutive patients with COVID-19 admitted to a hub hospital in Italy from 25/02/2020 to 03/07/2020, we selected those ≥ 60 year-old and with cTnI measured within three days from the molecular diagnosis of SARS-CoV-2 infection. When available, a second cTnI value within 48 h was also extracted. The relationship between increased cTnI and all-cause in-hospital mortality was evaluated by a Cox regression model and restricted cubic spline functions with three knots. RESULTS Of 343 included patients (median age: 75.0 (68.0−83.0) years, 34.7% men), 88 (25.7%) had cTnI above the upper-reference limit (0.046 µg/L). Patients with increased cTnI had more comorbidities, greater impaired respiratory exchange and higher inflammatory markers on admission than those with normal cTnI. Furthermore, they died more (73.9%vs. 37.3%, P < 0.001) over 15 (6−25) days of hospitalization. The association of elevated cTnI with mortality was confirmed by the adjusted Cox regression model (HR = 1.61, 95%CI: 1.06−2.52, P = 0.039) and was linear until 0.3 µg/L, with a subsequent plateau. Of 191 (55.7%) patients with a second cTnI measurement, 49 (25.7%) had an increasing trend, which was not associated with mortality (univariate HR = 1.39, 95%CI: 0.87−2.22, P = 0.265). CONCLUSIONS In elderly COVID-19 patients, an initial increase in cTn is common and predicts a higher risk of death. Serial cTn testing may not confer additional prognostic information.

Published
2021

2. Extensive activation, tissue trafficking, turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity

Author

Bozzano, F., Dentone, C., Perrone, C., Di Biagio, A., Fenoglio, D., Parodi, A., Mikulska, M., Bruzzone, B., Giacobbe, D. R., Vena, A., Taramasso, L., Nicolini, L., Patroniti, N., Pelosi, P., Gratarola, A., de Palma, R., Filaci, G., Bassetti, M., de Maria, A., Alessandrini, A., Camera, M., Delfino, E., Dodi, F., Ferrazin, A., Mazzarello, G., Toscanini, F., Balletto, E., Portunato, F., Schenone, E., Rosseti, N., Baldi, F., Berruti, M., Briano, F., Dettori, S., Labate, L., Magnasco, L., Mirabella, M., Pincino, R., Russo, C., Sarteschi, G., Sepulcri, C., Tutino, S., Pontremoli, R., Beccati, V., Casciaro, S., Casu, M., Gavaudan, F., Ghinatti, M., Gualco, E., Leoncini, G., Pitto, P., Salam, K., Bixio, M., Amelia, A., Balestra, A., Ballarino, P., Bardi, N., Boccafogli, R., Caserza, F., Calzolari, E., Castelli, M., Cenni, E., Cortese, P., Cuttone, G., Feltrin, S., Giovinazzo, S., Giuntini, P., Natale, L., Orsi, D., Pastorino, M., Perazzo, T., Pescetelli, F., Schenone, F., Serra, M. G., Sottano, M., Brunetti, I., Robba, C., Ball, L., Loconte, M., Battaglini, D., de Rito, M. R., Cerana, M., Fasce, R., Insorsi, A., Molin, A., Tallone, R., Amelotti, M., Majabo, M. J., Merlini, M., Perazzo, F., Ahamd, N., Barbera, P., Bovio, M., Cam-Podonico, P., Collida, A., Cutuli, O., Lomeo, A., Fezza, F., Genti-Lucci, N., Hussein, N., Malvezzi, E., Massobrio, L., Motta, G., Pastorino, L., Pollicardo, N., Sartini, S., Virga, P. V. V., Porto, I., Bezante, G. P., Bona, R. D., Malfa, G. L., Valbusa, A., V. G., Ad, Barisione, E., Bellotti, M., Teresita, A., Blanco, A., Grosso, M., Piroddi, M. G., Moscatelli, P., Caiti, M., Magnani, O., Sukkar, S., Cogorno, L., Gradaschi, R., Guiddo, E., Martino, E., Pisciotta, L., Cavagliere, B., Cristina, R., Francesca, F., Garibotto, G., Esposito, P., Passalacqua, G., Bagnasco, D., Braido, F., Riccio, A., Tagliabue, E., Gustavino, C., Ferraiolo, A., Giuffrida, S., Rosso, N., Morando, A., Papalia, R., Passerini, D., Tiberio, G., Orengo, G., Battaglini, A., Ruffoni, S., and Caglieris, S.

Subjects
RNA viruses, Male, Viral Diseases, Coronaviruses, medicine.medical_treatment, Cytotoxicity, Cell, NK cells, Aged, Aged, 80 and over, COVID-19, Cohort Studies, Female, Flow Cytometry, Humans, Interferon-gamma, Italy, Killer Cells, Natural, Lymphocyte Activation, Middle Aged, Severity of Illness Index, Toxicology, 0302 clinical medicine, Medical Conditions, Spectrum Analysis Techniques, Cellular types, 80 and over, Killer Cells, Lymphocytes, Biology (General), Receptor, Immune Response, Pathology and laboratory medicine, 0303 health sciences, medicine.diagnostic_test, Immune cells, hemic and immune systems, Medical microbiology, Cytokine, medicine.anatomical_structure, Infectious Diseases, Spectrophotometry, Viruses, Natural, White blood cells, Cytophotometry, medicine.symptom, SARS CoV 2, Pathogens, Research Article, Cell biology, Blood cells, SARS coronavirus, Precursor Cells, QH301-705.5, Immunology, Inflammation, chemical and pharmacologic phenomena, Biology, Research and Analysis Methods, Microbiology, Flow cytometry, 03 medical and health sciences, Immune system, Signs and Symptoms, Virology, Genetics, medicine, Molecular Biology, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, Organisms, Viral pathogens, Covid 19, RC581-607, NKG2D, Microbial pathogens, Perforin, Animal cells, biology.protein, Parasitology, Clinical Medicine, Immunologic diseases. Allergy, 030215 immunology
Abstract

The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5–20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19. Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and “memory” KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells. Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches., Author summary This is a detailed study of activating and inhibitory receptors in NK cells of COVID-19 patients when first admitted to the hospital for respiratory insufficiency. NK cells are known to be the first line of defense against invading viruses, and regulate downstream B and T cell responses, including antibody production. We observed intense NK cell activation with decreased functional activity, as well as intense circulation of putative tissue resident CD69+CD103+CXCR6+ NK cells, with a related surge in inflammatory CD34+ precursors from the bone marrow. The findings suggest that there is unprecedented trafficking of NK cells from peripheral tissues, their increased death with recruitment of emergency precursors from the bone marrow, and a relationship with the subsequent course of the disease of the patients. This in turn suggests possible areas of treatment and prevention.

Published
2021

3. The SWALIS 2020 new model to prioritize access to urgent, elective and backlog waiting lists. facing the challenge in the COVID era

Author

Di Domenico, S., primary, Santori, G., additional, Mascherini, M., additional, Papadia, F., additional, Orengo, G., additional, Gratarola, A., additional, Martigli, S.P., additional, Iakubovska, M., additional, Torretta, A., additional, Cafiero, F., additional, de Cian, F., additional, and Valente, R., additional

Published
2021
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5. A 10-17 DOF Sensory Gloves with Harvesting Capability for Smart Healthcare.

Author

Stornelli, V., Leoni, A., Ferri, G., Errico, V., Pallotti, A., Orengo, G., and Saggio, G.

Subjects
ARTIFICIAL hands, RADIO relay systems, GLOVES, ENERGY harvesting, RADIO frequency, POWER electronics, FINGERS
Abstract

We present a 10-17 Degrees of Freedom (DoF) sensory gloves for Smart Healthcare implementing an energy harvesting architecture, aimed at enhancing the battery lasting when powering the electronics of the two different types of gloves, used to sense fingers movements. In particular, we realized a comparison in terms of measurement repeatability and reliability, as well as power consumption and battery lasting, between two sensory gloves implemented by means of different technologies. The first is a 3D printed glove with 10 DoF, featuring low-cost, loweffort fabrication and low-power consumption. The second is a classical Lycra® glove with 14 DoF suitable for a more detailed assessment of the hand postures, featuring a relatively higher cost and power consumption. An electronic circuitry was designed to gather and elaborate data from both types of sensory gloves, equipped with flex sensors, differing for number of inputs only. Both gloves allow the control of hand virtual limbs or mechanical arts in surgical, military, space and civil applications. The proposed gloves were already individually evaluated in terms of repeatability, reproducibility and reliability, but in this work their performances are compared also in terms of power consumption, because a particular effort was devoted in this case to increase battery lasting for both systems, developing an Energy Harvesting (EH) system with the electronics relaying on Radio Frequency, Piezoelectric and Thermoelectric harvesters, and applying it to the gloves for the first time. The harvesting part was built and tested as a prototype discrete element board, that is interfaced with an external microcontroller and a radiofrequency transmitter board. Measurement results demonstrated a meaningful improvement in battery operation time up to 25%, considering different operating scenarios, for both glove systems, which exhibited not very different power consumption and therefore battery duration, in spite of different DoF measuring capabilities. [ABSTRACT FROM AUTHOR]

Published
2019
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8. Advanced Neural Network Techniques for GaN-HEMT Dynamic Behavior Characterization

Author

Orengo, G., Colantonio, P., Giannini, F., Pirola, Marco, Camarchia, Vittorio, DONATI GUERRIERI, Simona, and Ghione, Giovanni

Subjects
GaN-HEMT, Artificial neural network, Computer science, Electronic engineering, Neural Network, High-electron-mobility transistor, Thermal model, Settore ING-INF/01 - Elettronica, Power (physics), Characterization (materials science)
Abstract

This paper presents a new approach to build RF dynamic behavioral models, based on time-delay neural networks (TDNNs), suitable for FET devices, and capable to identify the working class and to characterize both short- and long-term device memory, through a time-domain training procedure, for a wide range of input power levels. The presented model has been effectively applied to GaN-based devices, working in class A, AB and B

Published
2006

9. RF Dynamic Behavioral Model Suitable for GaN-HEMT Devices

Author

Stegmayer, G, Pirola, M, Camarchia, V, Teppati, V, Orengo, G, Colantonio, P, and Serino, A

Subjects
Engineering, Artificial neural network, business.industry, Wide-bandgap semiconductor, Electrical engineering, Electronic engineering, High-electron-mobility transistor, business, Settore ING-INF/01 - Elettronica, Behavioral modeling, Power (physics)
Abstract

This paper presents a new RF dynamic behavioral model based on a neural network (NN) approach suitable for FET devices in a wide range of working classes, and capable to identify the device response, through the training procedure, for a wide range of input power levels. The presented model has been effectively applied to GaN-based devices at 1 GHz, working in class A and B.

Published
2006

12. Distortion Characterization and Neural Network Modeling for Microwave Devices

Author

Giannini, F, Colantonio, P, Orengo, G, and Serino, A

Subjects
ING-INF/01 Elettronica, Settore ING-INF/01 - Elettronica
Abstract

A new method for characterization of HEMT distortion parameters, which extracts the coefficents of Taylor series expansion of Ids(Vgs,Vds), including all crossterms, from low-frequency harmonic measurements, has been developed. The extracted parameters will be used either in a Volterra series model around a fixed bias point for third order characterization of small-signal Ids nonlinearity, and in a large-signal model of Ids characteristic, where its partial derivatives have been locally characterized up to the third order in the whole bias region, using a novel neural network representation. The two models have been verified by harmonic measurements on a AMS HEMT at 5 GHz.

Published
2004
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14. Neural-Based Nonlinear Device Models for Intermodulation Analysis

Author

Giannini, F., Colantonio, P., Leuzzi, G., Orengo, G., and Serino, A.

Subjects
ING-INF/01 Elettronica, Settore ING-INF/01 - Elettronica
Abstract

A new procedure to learn a nonlinear model together with its derivative parameters using a composite neural network is presented.So far neural networks have never been used to extract large-signal device model accounting for distortion parameters.Applying this method to FET devices leads to nonlinear models for current- voltage functions which allow improved prediction of weak and mildly device nonlinearities in the whole bias region. The resulting models have demonstrated to be suitable for both small-signal and large-signal analyses,including intermodulation distortion prediction.

Published
2003
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15. Fast Tuning Electronically Switched 16 x 1 Channel Receiver For Packet-Switched WDM Systems

Author

Manfrin, S.K., De Dominicis, M., Orengo, G., Giannini, F., and Romero, M.A.

Subjects
Computer Science::Hardware Architecture, ING-INF/01 Elettronica, Physics::Optics, Computer Science::Information Theory
Abstract

This paper revisits an optical receiver topology, for a wavelength division multiplexing (WDM) optical network at 2.5 Gbps bit rate, based on non-tunable wavelength demultiplexing and electronic switching.We demonstrate novel, monolithically integrated, four-channel optical receiver module composed of MESFET transimpedance amplifiers and switches that can be independently switched “on” or “off” electronically by a digital signal. The selector chips have also been reconfigured as a 16 channel selector array. Frequency and noise performance as well as switching speed and crosstalk between neighboring channels have been investigated.

Published
2002

16. High tuning speed optical receiver front-end for packet-switched WDM Networks

Author

Manfrin, S.K., Orengo, G., Giannini, F., and Romero, M. A.

Subjects
ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, ING-INF/01 Elettronica, Data_CODINGANDINFORMATIONTHEORY
Abstract

In this work two distinct optical receiver conjurations are investigated for use in the downstream direction of ATM PON networks based on wavelength division multiplexing (WDM). The goal is to overcome the slow tuning speed of optical filters, achieving channel selection in the nanosecond time frame and allowing the implementation of an efficient ATM/WDM protocol.

Published
2001

17. Artificial neural network approach for MMIC passive and active device characterization

Author

Giannini, F., Leuzzi, G., Orengo, G., and Albertini, M.

Subjects
ING-INF/01 Elettronica
Abstract

Artificial neural networks (ANNs)are presented for the fast and accurate modeling of passive and active devices in MMICs.ANNs trained with S-parameter over a wide range of frequencies were used for rectangular spiral inductor modeling and HEMT device small-signal models.After training and testing the ANN S-parameter model can be implemented as a two-port network into commercial circuit simulators.This enable the ANN model to be used in the design,analysis,and optimization of microwave circuits.A combination of ANN models trained with S-parameter and dc drain current measurements was implemented into an HP microwave circuit simulator to provide a small- signal bias-dependent active model.The proposed technique is capable of providing easy,fast and accurate simulation models for MMIC components where models based on equivalent circuit parameters (ECPs)do not exist or are not accurate over the desired region of operation.

Published
2000

18. Impact of influenza during the post-pandemic season: epidemiological picture from syndromic and virological surveillance

Author

De Florentiis, D, Parodi, V, Orsi, Giovanni Battista, Rossi, Flora, Altomonte, F, Canepa, P, Ceravolo, A, Valle, L, Zancolli, M, Piccotti, E, Renna, S, Macrina, G, Martini, M, Durando, Paolo, Padrone, D, Moscatelli, P, Orengo, G, Icardi, Giancarlo, Ansaldi, Filippo, De Florentiis, D, Parodi, V, Orsi, Giovanni Battista, Rossi, Flora, Altomonte, F, Canepa, P, Ceravolo, A, Valle, L, Zancolli, M, Piccotti, E, Renna, S, Macrina, G, Martini, M, Durando, Paolo, Padrone, D, Moscatelli, P, Orengo, G, Icardi, Giancarlo, and Ansaldi, Filippo

Abstract

Introduction. Following the observation that 1 or 2 pandemic peak due to the circulation of AH1N1v had occurred in most countries and in most World Health Organization (WHO) Regions, WHO declared on August 10th, 2010 that the world was moving into the post-pandemic period, whose surveillance presents considerable interest both from epidemiological and clinical point of view. We described the epidemiological picture emerged from syndromic and virological surveillance during the post-pandemic season in Liguria, Italy. Materials and methods. An Emergency Department Syndrome surveillance system, based on data collected at ?San Martino? and IRCCS ?G. Gaslini? Liguria Regional Reference University Hospitals for adults and children is active since July 2007. Monitored syndromes include ?Influenza-Like Illness? (ILI) and ?Low Respiratory Tract Infections? (LRTI). The Ligurian Regional Reference laboratory for Influenza virological surveillance and diagnosis offers rapid detection of influenza viruses by real-time and block RT-PCR, viral culture and genetic characterization by entire sequence analysis of haemagglutinin- and neuraminidase-coding regions in accordance with the international standards established by the global laboratory network. Results and discussion. The integration of syndromic surveillance system and laboratory surveillance for rapid detection and characterization of the disease responsible agent represented a specific and sensitive tool for influenza surveillance. The post-pandemic season was characterized by early onset and by the heaviest impacts for ILI and LRTI among the recent epidemic seasons. In contrast to the picture observed during the pandemic season, the 2010/11 winter was characterized by the intensive circulation of pandemic AH1N1v coupled with sustained activity due to influenza B and Respiratory Syncytial Virus (RSV). Antigenic and molecular characterization of influenza strains confirmed the good matching between circulating and 2010/11 v

Published
2011

19. Hospital-acquired infections and leading pathogens detected in a regional university adult acute-care hospital in Genoa, Liguria, Italy: results from a prevalence study

Author

Durando, Paolo, Bassetti, M, Orengo, G, Crimi, P, Battistini, A, Tiberio, G, Bellina, D, Talamini, A, Dodi, F, Ansaldi, Filippo, Alicino, C, Iudici, R, Sticchi, Laura, De Florentiis, D, Viscoli, C, Icardi G; Prevalence Study Working Group of the San Martino University Hospital of, Genoa, Durando, Paolo, Bassetti, M, Orengo, G, Crimi, P, Battistini, A, Tiberio, G, Bellina, D, Talamini, A, Dodi, F, Ansaldi, Filippo, Alicino, C, Iudici, R, Sticchi, Laura, De Florentiis, D, Viscoli, C, and Icardi G; Prevalence Study Working Group of the San Martino University Hospital of, Genoa

Abstract

Background. A prevalence study aimed to update the epide- miological scenario of Hospital-Acquired Infections (HAI) was performed at the San Martino University Hospital of Genoa, the Regional Reference Adult-care Center in Liguria, Italy, with more than 1300 beds. Materials and methods. The investigation was performed in all the wards, except the Psychiatric Units, between 19th March and 6th April, 2007, using a one-day monitoring system for each ward. International standardized criteria and definitions for the surveillance of HAI were used for the collection of data, which were recorded in specific software for subsequent consolidation, analysis and quality control. Results. The hospital infection control staff actively monitored 912 inpatients: a total of 84 HAI among 72 patients were diag- nosed, with an overall prevalence of infections and affected cases of 9.2% (95% CI: 7.3-11.1) and 7.9% (95% CI: 6.1-9.7), respectively. Urinary Tract Infections (UTI) (30.9%), Respira- tory Tract Infections (RTI) (28.6%) and Blood Stream Infections (BSI) (21.4%) were found to be the most frequent infections. As expected, both specific prevalence and localization of HAI var- ied considerably between wards, with the highest values recorded in Intensive Care Units (ICU) and in Functional Rehabilitation wards. RTI (26.3%) and BSI (13.2%) were found primarily rep- resented in ICU, while the highest values of UTI (13.3%) were registered in Functional Rehabilitation Units. Enterococcus spp. (16.8%), Candida spp. (14%), Pseudomonas spp. (12.2), Staphylococcus aureus (10.7%), Escherichia coli (10.3%) and Coagulase-negative staphylococci (CNS) (9.3%) were the most frequent pathogens isolated. The overall rate of administration of antibiotics was 55.3% and penicillin (26.7%), cephalosporins (22.8%) and fluoroquinolones (17.9%) were found to be the leading antibacterial administered. Conclusion. Results of the present study have been, and are currently, used for orientating surveillance an

Published
2010

20. Epidemiological and molecular approaches for management of a measles outbreak in Liguria, Italy

Author

Orsi, Giovanni Battista, Alicino, C, Patria, AG, Parodi, V, Carloni, R, Turello, V, Comaschi, M, Moscatelli, P, Orengo, G, Martini, M, De Florentiis, D, Orsi, Giovanni Battista, Alicino, C, Patria, AG, Parodi, V, Carloni, R, Turello, V, Comaschi, M, Moscatelli, P, Orengo, G, Martini, M, and De Florentiis, D

Abstract

Since March 2010 a measles outbreak has been occurred in Genoa, Liguria, an administrative Region in Northern Italy. Epi- demiological and molecular data on the outbreak, obtained from the passive mandatory notification system, the laboratory surveillance and an innovative syndrome surveillance system, were investigated. Overall 39 cases were reported in the urban area. Information about demography, vaccination status, hospitalization and geographic distribution of measles cases are available. 19 cases (48.7%) were laboratory-confirmed and were characterized by sequence analysis: 18 strains belonged to genotype D8, so identifying a new measles variant within the Liguria population. Adopted control measures seem to have limited viral circulation. The outbreak allowed to test the efficacy of the 3 surveillance systems active in Liguria, highlighting their advantages and some important limitations. More efforts are needed to collect and integrate any epidemiological and virological available data in order to better describe the local measles transmission dynamics.

Published
2010

21. An 8-channels GaAs IC front-end discriminator for RPC particle detectors

Author

Cardarelli, R., Ciorciolini, S., Chiostri, V., and Orengo, G.

Subjects
ING-INF/01 Elettronica
Abstract

A front-end discriminator for application in readout electronics of gas chamber particle detectors, composed of a high-gain pulse amplifier integrated with a threshold comparator and an ECL logic buffer, has been designed. An 8-channels full custom chip has been fabricated in GaAs IC technology. The chip turns out very stable, featuring high voltage gain (>1000), gain-bandwidth product (1011) and sensitivity (~50uV), fast rise time (1.5ns), and only 25mW per channel of power consumption, while providing the ECL dynamic to the output pulses.

Published
1998

22. Multichannels GaAs MMIC front-ends for GAS chamber particle detectors

Author

Orengo, G., Cardarelli, R., Chiostri, V., and Johansen, E.

Subjects
Computer Science::Hardware Architecture, Physics::Instrumentation and Detectors, Hardware_INTEGRATEDCIRCUITS, ING-INF/01 Elettronica
Abstract

A front-end circuit composed of a high gain pulse amplifier cascaded by a threshold comparator has been designed for application in readout electronics of particle detectors. A prototype realized with a 8CH full custom chip in GaAs technology by GIGA foundry for application in gas chamber particle detector (RPC) is described. The chip exhibits a 0.2 mV minimum threshold, 150 MHz bandwidth and 50 mW per channel of power consumption.

Published
1997

23. A GaAs Equalizer-amplifier for 1 Gbit/s data transmission on coaxial cable up to 200 meters

Author

Orengo, G., Giannini, F., Limiti, E., and Cardarelli, R.

Subjects
ING-INF/01 Elettronica
Abstract

A simple amplitude equalization technique has been applied to coaxial cables to allow binary data transmission up to 1 Gbit/s in a domestic or office environment, where data link lenght is less than 200 m., and cable installation appears economically advantageous as compared to fiber optic. A new monolithic integrated equalizer-amplifier has been designed to fit to different cable types and lenghts by mean of a voltage-controlled equalization.

Published
1997

24. GaAs pixel detectors with integrated electronics: experimental basis and feasibility study

Author

Bertuccio, G., Canali, C., Cetronio, A., De Geronimo, G., Giannini, F., Graffitti, R., Lanzieri, C., Longoni, A., Nava, F., Orengo, G., Padovini, G., and Peroni, M.

Subjects
Condensed Matter::Materials Science, Condensed Matter::Other, ING-INF/01 Elettronica, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect
Abstract

This work aims to study the feasibility of the integration, on the same chip, of GaAs pixel detectors and front-end electronics employing GaAs MESFETs or HEMTs. Interest of a full GaAs integrated systems are in X and y-ray spectroscopy and imaging for scientific, industrial and medical applications. The current status and recent experimental results regarding radiation detectors on semi-insulating GaAs are presented. Measurements of the relevant parameters of GaAs FETs suitable for the stringent requirements of a spectroscopy-graded front-end amplifier are analysed. Some still open problems regarding the detector-electronics integration are highlighted.

Published
1997
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25. Time-domain neural network characterization for dynamic behavioral models of power amplifiers

Author

Orengo, G., Colantonio, P., Serino, A., Giannini, F., Ghione, G., Orengo, G., Colantonio, P., Serino, A., Giannini, F., and Ghione, G.

Abstract

This paper presents a black-box model that can be applied to characterize the nonlinear dynamic behavior of power amplifiers. We show that time-delay feed-forward Neural Networks can be used to make a large-signal input-output time-domain characterization, and to provide an analytical form to predict the amplifier response to multitone excitations. Furthermore, a new technique to immediately extract Volterra series models from the Neural Network parameters has been described. An experiment based on a power amplifier, characterized with a two-tone power swept stimulus to extract the behavioral model, validated with spectra measurements, is demonstrated.

Published
2005

26. Distortion Characterization and Neural Network Modeling for Microwave Devices

Author

Giannini, F., Colantonio, P., Orengo, G., Serino, A., Giannini, F., Colantonio, P., Orengo, G., and Serino, A.

Abstract

A new method for characterization of HEMT distortion parameters, which extracts the coefficents of Taylor series expansion of Ids(Vgs,Vds), including all crossterms, from low-frequency harmonic measurements, has been developed. The extracted parameters will be used either in a Volterra series model around a fixed bias point for third order characterization of small-signal Ids nonlinearity, and in a large-signal model of Ids characteristic, where its partial derivatives have been locally characterized up to the third order in the whole bias region, using a novel neural network representation. The two models have been verified by harmonic measurements on a AMS HEMT at 5 GHz.

Published
2004

28. Multiproject array of GaAs MMIC front-end amplifiers for detection in accelerator physics

Author

Giannini, F., Orengo, G., Paoluzi, G., and Magrini, P.F.

Subjects
Physics::Instrumentation and Detectors, ING-INF/01 Elettronica
Abstract

The present paper describes an array of GaAs monolithic front-end amplifiers, to be used in a large number of applications in present and future high-energy physics experimental apparatus. A transimpedance amplifier of 66 dBohm gain for optical data transmission between 0.3 and 1.2 Gbit/s have been realized. Two types of front-end voltage amplifiers for amplification of gas detector discharge pulses are presented too. Fast rise times (less than 200 ps) with 30 dB voltage gain, to amplify the weak charge pulses from gas detectors, have been reached.

Published
1994
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29. A High Gain-Bandwidth Product Distributed Transimpedance Amplifier IC for High-Speed Optical Transmission Using Low-Cost GaAs Technology.

Author

Giannini, F., Limiti, E., Orengo, G., Serino, A., De Dominicis, M., Giannini, F., Limiti, E., Orengo, G., Serino, A., and De Dominicis, M.

Abstract

This paper reports a distributed baseband transimpedance amplifier for optical links up to 10 Gb/s. The amplifier operates as a baseband amplifier with a transimpedance gain of 48 dB Ω and a DC-to-9 GHz bandwidth. Some innovative design techniques to improve gain-bandwidth performance at low and high frequency with an available low-cost GaAs MESFET technology have been developed.

Published
2002

30. Neural-Based Large-Signal Device Models Learning First-Order Derivative Parameters for Intermodulation Distortion Prediction

Author

Giannini, F., Leuzzi, G., Orengo, G., Colantonio, P., Giannini, F., Leuzzi, G., Orengo, G., and Colantonio, P.

Abstract

A detailed procedure to learn a nonlinear model together with its first-order derivative data is presented. Two correlated multilayer perceptron (MLP) neural networks providing the model and its first-order derivatives, respectively, are trained simultaneously. Applying this method to FET devices leads to nonlinear models for current and charge fitting derivative parameters. The training data is the bias-dependent equivalent circuit parameters extracted from S-parameter measurements. The resulting models are suitable for both small-signal and large-signal analyses, in particular for intermodulation distortion prediction. Examples for power amplifier simulations of power transfer, efficiency and intermodulation distortion performances are presented.

Published
2002

31. MMIC Bandwidth-gain control optical preamplifier

Author

Giannini, F., Paoloni, C., Orengo, G., Giannini, F., Paoloni, C., and Orengo, G.

Abstract

A GaAs monolithic bandwidth-gain control transimpedance amplifier for optical communication links adaptable to different Gigabit transmission rate is presented. A gain dynamic of 22 dB is obtained in .6-2.8 GHz range with a control voltage range of .5v. The circuital topology, the theoretical and experimental results are also presented. The complete study has been carried under the frame of the ESPRIT Project 5018 COSMIC.

Published
1993

32. An advanced GaAs monolithic transimpedance amplifier for high-speed optical communication systems

Author

GIANNINI, F, PAOLONI, C, ORENGO, G, GIANNINI, F, PAOLONI, C, and ORENGO, G

Abstract

An advanced design procedure for MMIC GaAs direct-coupled transimpedance amplifier for gigabit/second-rate optical communication systems is presented. A transimpedance gain of 67 dBOMEGA up to 2.5 GHz has been demonstrated. A complete set of simulated and measured results are presented to confirm the effectiveness of the design approach. The design and the realization have been performed within the framework of ESPRIT Project No. 5018 COSMIC.

Published
1993

33. Comparison between three GaAs monolithic transimpedance amplifiers for optical communication systems

Author

Casao, J. A., Dorta, P., Caceres, J. L., Salazar-Palma, M., Perez, J., Orengo, G., Paoloni, C., Giannini, F., Casao, J. A., Dorta, P., Caceres, J. L., Salazar-Palma, M., Perez, J., Orengo, G., Paoloni, C., and Giannini, F.

Abstract

Three different GaAs Monolithic Transimpedance Amplifier topologies for low noise and high speed optical communication systems are compared. The first one consists of a simple cascode stage enhanced in terms of bandwidth and noise. The second one is also based in a cascode stage followed by a differential amplifier in order to increase the transimpedance gain-bandwidth product. The third one was designed with that same scope in one hand and in the other to obtain a very low power consumption; it consists of a three stage inverter amplifier with reactive feedback loop. Measurements show that excellent results have been obtained for the first topology; for the second one a remarkable improvement of the bandwidth has been obtained; finally, for the third one, high gain and extremely low power consumption have been obtained. In all cases the equivalent noise current is low enough to achieve a sensitivity of the receiver between -28 and -33 dBm.

Published
1992

34. Wide band high-gain optical preamplifier

Author

Selvarajan, A, Sonde, BS, Shenai, K, Tripathi, VK, GIANNINI, F, PAOLONI, C, ORENGO, G, Selvarajan, A, Sonde, BS, Shenai, K, Tripathi, VK, GIANNINI, F, PAOLONI, C, and ORENGO, G

Published
1992

35. Time-domain Neural Network characterization for dynamic behavioral models of power amplifiers

Author

Orengo, G., Colantonio, P., Serino, A., Giannini, F., Giovanni Ghione, Pirola, M., and Stegmayer, G.

Subjects
Multitone excitations, Mathematical models, Electric excitation, Neural networks, Signal theory, Spectrum analysis, Time domain analysis, Amplifier response, Neural Network characterization, Nonlinear dynamic behavior, Power amplifiers, power amplifier, Neural Network, Settore ING-INF/01 - Elettronica, ING-INF/01 Elettronica
Abstract

This paper presents a black-box model that can be applied to characterize the nonlinear dynamic behavior of power amplifiers. We show that time-delay feed-forward Neural Networks can be used to make a large-signal input-output time-domain characterization, and to provide an analytical form to predict the amplifier response to multitone excitations. Furthermore, a new technique to immediately extract Volterra series models from the Neural Network parameters has been described. An experiment based on a power amplifier, characterized with a two-tone power swept stimulus to extract the behavioral model, validated with spectra measurements, is demonstrated.

36. Monitoring emergency and urgent surgery: an improvement in a Healthcare Management Unit at a third-level hospital in Italy.

Author

Inglese L, Barberis I, Korshunova M, Amato R, Zangrillo F, Arata L, Tisa V, Papalia R, Santo M, Tiberio G, Morando A, and Orengo G

Subjects
Humans, Italy, Surgical Procedures, Operative, Emergencies, Emergency Service, Hospital
Abstract

Introduction: At San Martino IRCCS Hospital in Genoa, Italy, emergency and urgent surgery is classified according to the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) classification, whereby cases are divided into two categories and colour-coded accordingly: - EMERGENCY - (Colour-code: RED) "Surgery to be performed within minutes"; - URGENCY - (colour-code: YELLOW) "Surgery to be performed within hours". In this context, it is essential that the emergency surgical team gets clear and complete information from the proposing surgeon, in order to complete the surgical list., Methods: Between 14 th April 2023 and 23 th July 2023, a new method of requesting urgent and emergency surgery by filling out an online form was tested., Results: A total of 406 online requests were made, resulting in 367 E/U surgeries. The greatest number of emergency operations concerned thoracic-abdominal surgery (45%), followed by urology (19%). The requests analysed classified 18% of cases as red and 71% as yellow. The remaining 11% contained compilation errors. Moreover, 11% of the interventions were not performed within the time limits defined according to the severity code., Conclusions: By means of this new tool, San Martino IRCCS Hospital's Healthcare Management Unit can monitor requests for surgery in real time, thereby achieving greater efficiency and implementing corrective measures in the use of Operating Room resources., Competing Interests: None declared., (©2024 Pacini Editore SRL, Pisa, Italy.)

Published
2024
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37. Ventilator-associated pneumonia in neurocritically ill patients: insights from the ENIO international prospective observational study.

Author

Battaglini D, Parodi L, Cinotti R, Asehnoune K, Taccone FS, Orengo G, Zona G, Uccelli A, Ferro G, Robba M, Pelosi P, and Robba C

Subjects
Humans, Male, Female, Respiration, Artificial adverse effects, Prospective Studies, Ventilators, Mechanical adverse effects, Pneumonia, Ventilator-Associated diagnosis, Pneumonia, Ventilator-Associated epidemiology, Hypothermia complications, Bronchitis
Abstract

Background: Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality., Methods: Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included., Results: Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43-1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01-3.23, p < 0.001)., Conclusions: VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS., (© 2023. The Author(s).)

Published
2023
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38. Resveratrol and resveratrol-hydroxypropyl-β-cyclodextrin complex recovered the changes of creatine kinase and Na+, K+-ATPase activities found in the spleen from streptozotocin-induced diabetic rats.

Author

Kolling J, Kolling J, Franceschi ID, Nishihira VSK, Baldissera MD, Pinto CG, Mezzomo NJ, Carmo GMD, Feksa LR, Fernandes LS, Orengo G, Vaucher RA, Giongo JL, Wyse ATS, Wannmacher CMD, and Rech VC

Subjects
Animals, Antioxidants metabolism, Blood Glucose analysis, Body Weight, Creatine Kinase metabolism, Diabetes Mellitus, Experimental chemically induced, Energy Metabolism drug effects, Hyperglycemia metabolism, Male, Organ Size, Rats, Rats, Wistar, Streptozocin, 2-Hydroxypropyl-beta-cyclodextrin pharmacology, Antioxidants pharmacology, Diabetes Mellitus, Experimental metabolism, Resveratrol pharmacology, Sodium-Potassium-Exchanging ATPase metabolism, Spleen metabolism
Abstract

Type 1 diabetes (T1D) is the result of the selective destruction of the pancreatic β-cells by T cells of the immune system. Although spleen is a secondary lymphoid organ, it is also involved in the T1D pathogenesis. However, the alterations in a variety of cellular processes of this disease need to be further understood. We aimed to analyze the benefits of resveratrol, and its complexed form on diabetic complications in the spleen of rats. To this end, we investigated important enzymes of phosphoryl transfer network, and Na+, K+-ATPase activity. Wistar rats were divided into non-diabetic groups: Control, Ethanol, Resveratrol, Hydroxypropyl-β-cyclodextrin, Resveratrol-hydroxypropyl-β-cyclodextrin, and diabetic groups with the same treatments. Diabetes was induced by a single dose of 60 mg/kg of streptozocin intraperitoneally, and treatments by intragastric gavage once daily for 60 days. Hyperglycemia reduced creatine kinase activity, which was reversed by the administration of resveratrol. Na+, K+-ATPase activity was greatly affected, but it was reversed by resveratrol and resveratrol-hydroxypropyl-β-cyclodextrin. This suggest an energetic imbalance in the spleen of diabetic rats, and in case this also occurs in the diabetic patients, it is possible that resveratrol supplementation could be beneficial to the better functioning of the spleen in diabetic patients.

Published
2019
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39. Latent tuberculosis infection among a large cohort of medical students at a teaching hospital in Italy.

Author

Durando P, Alicino C, Orsi A, Barberis I, Paganino C, Dini G, Mazzarello G, Del Bono V, Viscoli C, Copello F, Sossai D, Orengo G, Sticchi L, Ansaldi F, and Icardi G

Subjects
Adolescent, Adult, Female, Hospitals, Teaching, Humans, Italy, Latent Tuberculosis pathology, Male, Mycobacterium tuberculosis isolation & purification, Mycobacterium tuberculosis pathogenicity, Surveys and Questionnaires, Latent Tuberculosis diagnosis, Latent Tuberculosis epidemiology, Students, Medical, Tuberculin Test
Abstract

The surveillance of latent tuberculosis infection (LTBI) in both healthcare workers and healthcare students is considered fundamental for tuberculosis (TB) prevention. The aim of the present study was to estimate LTBI prevalence and evaluate potential risk-factors associated with this condition in a large cohort of medical students in Italy. In a cross-sectional study, performed between March and December 2012, 1511 eligible subjects attending the Medical School of the University of Genoa, trained at the IRCCS San Martino-IST Teaching Hospital of Genoa, were actively called to undergo the tuberculin skin test (TST). All the TST positive cases were confirmed with an interferon-gamma release assay (IGRA). A standardized questionnaire was collected for multivariate risk analysis. A total of 1302 (86.2%) students underwent TST testing and completed the questionnaire. Eleven subjects (0.8%) resulted TST positive and LTBI diagnosis was confirmed in 2 (0.1%) cases. Professional exposure to active TB patients (OR 21.7, 95% CI 2.9-160.2; P value 0.003) and previous BCG immunization (OR 28.3, 95% CI 3.0-265.1; P value 0.003) are independently associated with TST positivity. Despite the low prevalence of LTBI among Italian medical students, an occupational risk of TB infection still exists in countries with low circulation of Mycobacterium tuberculosis.

Published
2015
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40. Identification of a New Delhi metallo-β-lactamase-4 (NDM-4)-producing Escherichia coli in Italy.

Author

Coppo E, Del Bono V, Ventura F, Camera M, Orengo G, Viscoli C, and Marchese A

Subjects
Aged, DNA, Bacterial genetics, Electrophoresis, Gel, Pulsed-Field, Escherichia coli classification, Escherichia coli drug effects, Genotype, Humans, Imipenem pharmacology, Italy, Male, Middle Aged, Multilocus Sequence Typing, beta-Lactamases pharmacology, Bacterial Proteins metabolism, Drug Resistance, Multiple, Bacterial, Escherichia coli enzymology, Escherichia coli isolation & purification, Escherichia coli Infections microbiology, beta-Lactamases metabolism
Abstract

Background: During June-July 2012, six imipenem-resistant Escherichia coli isolates were isolated from two patients hospitalized in a ward of one large tertiary-care hospital in Genoa, Italy. Genetic features associated with blaNDM-4 gene were investigated., Results: The isolates exhibited the same PFGE profile and a multidrug-resistant (MDR) phenotype to aminoglycosides, fluoroquinolones, and β-lactams. The strains produced the NDM-4 carbapenemase and the blaNDM-4 gene was part of the variable region of a class 1 integron. MLST analysis revealed that all isolates belonged to sequence type 405 (ST405)., Conclusions: This is the first report on the emergence of an MDR strain of E.coli producing the NDM-4 MBL in Italy.

Published
2014
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41. An economic evaluation of an abdominal aortic aneurysm screening program in Italy.

Author

Giardina S, Pane B, Spinella G, Cafueri G, Corbo M, Brasseur P, Orengo G, and Palombo D

Subjects
Aged, Aortic Aneurysm, Abdominal surgery, Cost-Benefit Analysis, Health Status, Humans, Italy, Male, Markov Chains, Models, Economic, Predictive Value of Tests, Prognosis, Program Evaluation, Quality-Adjusted Life Years, Time Factors, Ultrasonography, Vascular Surgical Procedures economics, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Abdominal economics, Health Care Costs, Mass Screening economics, National Health Programs economics
Abstract

Objectives: Abdominal aortic aneurysm (AAA) is defined as a localized dilatation of an aortic vessel. Though predominantly asymptomatic, it is a chronic degenerative condition associated with life-threatening risk of rupture. The early diagnosis of AAA, ie, before it ruptures, is therefore important; a simple, effective diagnostic method is ultrasound examination. To assess the benefit of screening in Italy, we developed a cost-effective Markov model comparing screening vs nonscreening scenarios., Methods: A 13-health-states Markov model was developed to compare two cohorts of 65- to 75-year-old men: the first group undergoing screening for AAA by means of ultrasound (US), the second following the current practice of incidental detection. The following health states were distinguished: no AAA, unknown small AAA (3-3.9 cm), followed-up small AAA (1 year), unknown medium-sized AAA (4-4.9 cm), followed-up medium-sized AAA (6 months), unknown large AAA (>5 cm), elective repair, emergency repair, postelective-repair AAA, postemergency-repair AAA, rejected large AAA, and death. Transitions between health states were simulated by using 6-month cycles. Transition probabilities were derived from a literature review of relevant randomized controlled trial and from a screening program that is currently ongoing at San Martino Hospital in Genoa, Italy. The Italian National Health Service (NHS) perspective was adopted and incremental cost per life-year saved was calculated with a lifetime horizon; costs and health benefits were discounted at an annual rate of 3% from year 2 onward. Uncertainty surrounding the model inputs was tested by means of univariate, multivariate, and probabilistic sensitivity analyses., Results: Considering an attendance rate of 62%, the individual cost per invited subject was €60 (US $83.2); 0.011 additional quality adjusted life years (QALY) were gained per patient in the screened cohort, corresponding to an incremental cost-effectiveness ratio (ICER) of €5673/QALY (US $7870/QALY). The results were sensitive to some parameter variations but consistent with the base case scenario. They suggest that on the basis of a willingness-to-pay threshold of €50,000/QALY, screening for AAA is cost-effective, with a probability approaching 100%., Conclusions: As in economic evaluations developed in other countries, such as the UK, Canada, and The Netherlands, setting up a screening program for AAA can be considered cost-effective from the Italian NHS perspective., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Published
2011
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42. Potentiation of topoisomerase I and II inhibitors cell killing by tumor necrosis factor: relationship to DNA strand breakage formation.

Author

Orengo G, Noviello E, Cimoli G, Pagnan G, Parodi S, Venturini M, Conte P, Schenone F, Conzi G, and Russo P

Subjects
Camptothecin pharmacology, Cell Death drug effects, Cisplatin pharmacology, Drug Synergism, Epirubicin pharmacology, Etoposide pharmacology, Female, Humans, Mitomycin pharmacology, Ovarian Neoplasms drug therapy, Ovarian Neoplasms enzymology, Recombinant Proteins pharmacology, Tumor Cells, Cultured, DNA Damage physiology, DNA, Neoplasm drug effects, Topoisomerase I Inhibitors, Topoisomerase II Inhibitors, Tumor Necrosis Factor-alpha pharmacology
Abstract

Recombinant human tumor necrosis factor (rHuTNF) synergistically potentiates the cytotoxicity of the topoisomerase I inhibitor camptothecin, and the topoisomerase II inhibitors epidoxorubicin, etoposide, mitoxantrone, ellipticine, actinomycin D and 4'-(9-acridinylamino)methanesulfon-m-anisidide on A2780 human ovarian cancer cell line. Similar synergy was not observed with a combination of rHuTNF and cis-platinum or mitomycin C. When A2780 cells were incubated with rHuTNF simultaneously with camptothecin or mitoxantrone or VP16, increased numbers of DNA single-strand breaks were produced. rHuTNF alone did not induce DNA strand breakage. These data provide evidence that the enhancing effect of rHuTNF is closely related to the DNA damage mediated by topoisomerase-targeted drugs. These observations may have relevance for ovarian cancer treatment.

Published
1992
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