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6. Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Author

Salton, F, Confalonieri, P, Centanni, S, Mondoni, M, Petrosillo, N, Bonfanti, P, Lapadula, G, Lacedonia, D, Voza, A, Carpene, N, Montico, M, Reccardini, N, Meduri, G, Ruaro, B, Confalonieri, M, Citton, G, Bozzi, C, Tavano, S, Pozzan, R, Andrisano, A, Jaber, M, Mari, M, Trotta, L, Mondini, L, Barbieri, M, Ruggero, L, Antonaglia, C, Soave, S, Torregiani, C, Bogatec, T, Baccelli, A, Nalesso, G, Re, B, Pavesi, S, Barbaro, M, Giuliani, A, Ravaglia, C, Poletti, V, Scala, R, Guidelli, L, Golfi, N, Vianello, A, Achille, A, Lucernoni, P, Gaccione, A, Romagnoli, M, Fraccaro, A, Malacchini, N, Malerba, M, Ragnoli, B, Zamparelli, A, Bocchino, M, Blasi, F, Spotti, M, Miele, C, Piedepalumbo, F, Barone, I, Baglioni, S, Dodaj, M, Franco, C, Andrani, F, Mangia, A, Mancini, A, Carrozzi, L, Rafanelli, A, Casto, E, Rogliani, P, Ora, J, Carpagnano, G, Di Lecce, V, Tamburrini, M, Papi, A, Contoli, M, Luzzati, R, Zatta, M, Di Bella, S, Caraffa, E, Francisci, D, Tosti, A, Pallotto, C, De Rosa, F, Pecori, A, Franceschini, M, Carlin, M, Orsini, V, Pollastri, E, Rugova, A, Sabbatini, F, Soria, A, Rossi, M, Santantonio, T, Meli, R, Sauro, S, Fedeli, C, Mangini, E, Biolo, G, Nunnari, A, Pietrangelo, A, Corradini, E, Bocchi, D, Boarini, C, Zucchetto, A, Lanini, S, Salton F., Confalonieri P., Centanni S., Mondoni M., Petrosillo N., Bonfanti P., Lapadula G., Lacedonia D., Voza A., Carpene N., Montico M., Reccardini N., Meduri G. U., Ruaro B., Confalonieri M., Citton G. M., Bozzi C., Tavano S., Pozzan R., Andrisano A. G., Jaber M., Mari M., Trotta L., Mondini L., Barbieri M., Ruggero L., Antonaglia C., Soave S., Torregiani C., Bogatec T., Baccelli A., Nalesso G., Re B., Pavesi S., Barbaro M. P. F., Giuliani A., Ravaglia C., Poletti V., Scala R., Guidelli L., Golfi N., Vianello A., Achille A., Lucernoni P., Gaccione A. T., Romagnoli M., Fraccaro A., Malacchini N., Malerba M., Ragnoli B., Zamparelli A. S., Bocchino M., Blasi F., Spotti M., Miele C., Piedepalumbo F., Barone I., Baglioni S., Dodaj M., Franco C., Andrani F., Mangia A., Mancini A., Carrozzi L., Rafanelli A., Casto E., Rogliani P., Ora J., Carpagnano G. E., Di Lecce V., Tamburrini M., Papi A., Contoli M., Luzzati R., Zatta M., Di Bella S., Caraffa E., Francisci D., Tosti A., Pallotto C., De Rosa F. G., Pecori A., Franceschini M., Carlin M., Orsini V., Pollastri E., Rugova A., Sabbatini F., Soria A., Rossi M., Santantonio T., Meli R., Sauro S., Fedeli C., Mangini E., Biolo G., Nunnari A., Pietrangelo A., Corradini E., Bocchi D., Boarini C., Zucchetto A., Lanini S., Salton, F, Confalonieri, P, Centanni, S, Mondoni, M, Petrosillo, N, Bonfanti, P, Lapadula, G, Lacedonia, D, Voza, A, Carpene, N, Montico, M, Reccardini, N, Meduri, G, Ruaro, B, Confalonieri, M, Citton, G, Bozzi, C, Tavano, S, Pozzan, R, Andrisano, A, Jaber, M, Mari, M, Trotta, L, Mondini, L, Barbieri, M, Ruggero, L, Antonaglia, C, Soave, S, Torregiani, C, Bogatec, T, Baccelli, A, Nalesso, G, Re, B, Pavesi, S, Barbaro, M, Giuliani, A, Ravaglia, C, Poletti, V, Scala, R, Guidelli, L, Golfi, N, Vianello, A, Achille, A, Lucernoni, P, Gaccione, A, Romagnoli, M, Fraccaro, A, Malacchini, N, Malerba, M, Ragnoli, B, Zamparelli, A, Bocchino, M, Blasi, F, Spotti, M, Miele, C, Piedepalumbo, F, Barone, I, Baglioni, S, Dodaj, M, Franco, C, Andrani, F, Mangia, A, Mancini, A, Carrozzi, L, Rafanelli, A, Casto, E, Rogliani, P, Ora, J, Carpagnano, G, Di Lecce, V, Tamburrini, M, Papi, A, Contoli, M, Luzzati, R, Zatta, M, Di Bella, S, Caraffa, E, Francisci, D, Tosti, A, Pallotto, C, De Rosa, F, Pecori, A, Franceschini, M, Carlin, M, Orsini, V, Pollastri, E, Rugova, A, Sabbatini, F, Soria, A, Rossi, M, Santantonio, T, Meli, R, Sauro, S, Fedeli, C, Mangini, E, Biolo, G, Nunnari, A, Pietrangelo, A, Corradini, E, Bocchi, D, Boarini, C, Zucchetto, A, Lanini, S, Salton F., Confalonieri P., Centanni S., Mondoni M., Petrosillo N., Bonfanti P., Lapadula G., Lacedonia D., Voza A., Carpene N., Montico M., Reccardini N., Meduri G. U., Ruaro B., Confalonieri M., Citton G. M., Bozzi C., Tavano S., Pozzan R., Andrisano A. G., Jaber M., Mari M., Trotta L., Mondini L., Barbieri M., Ruggero L., Antonaglia C., Soave S., Torregiani C., Bogatec T., Baccelli A., Nalesso G., Re B., Pavesi S., Barbaro M. P. F., Giuliani A., Ravaglia C., Poletti V., Scala R., Guidelli L., Golfi N., Vianello A., Achille A., Lucernoni P., Gaccione A. T., Romagnoli M., Fraccaro A., Malacchini N., Malerba M., Ragnoli B., Zamparelli A. S., Bocchino M., Blasi F., Spotti M., Miele C., Piedepalumbo F., Barone I., Baglioni S., Dodaj M., Franco C., Andrani F., Mangia A., Mancini A., Carrozzi L., Rafanelli A., Casto E., Rogliani P., Ora J., Carpagnano G. E., Di Lecce V., Tamburrini M., Papi A., Contoli M., Luzzati R., Zatta M., Di Bella S., Caraffa E., Francisci D., Tosti A., Pallotto C., De Rosa F. G., Pecori A., Franceschini M., Carlin M., Orsini V., Pollastri E., Rugova A., Sabbatini F., Soria A., Rossi M., Santantonio T., Meli R., Sauro S., Fedeli C., Mangini E., Biolo G., Nunnari A., Pietrangelo A., Corradini E., Bocchi D., Boarini C., Zucchetto A., and Lanini S.

Abstract

Background Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. Methods We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (PaO2/FIO2) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. Results 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in PaO2/FIO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. Conclusion Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID

Published
2023

9. AM404, an anandamide transport inhibitor, reduces plasma extravasation in a model of neuropathic pain in rat: Role for cannabinoid receptors

Author

La Rana, G, Russo, R, D'Agostino, G, Sasso, O, Raso, G Mattace, Iacono, A, Meli, R, Piomelli, D, and Calignano, A

Subjects
Neurosciences, Chronic Pain, Pain Research, Substance Misuse, Neurodegenerative, Drug Abuse (NIDA only), Peripheral Neuropathy, Analgesics, Analysis of Variance, Animals, Arachidonic Acids, Benzoxazines, Capillary Permeability, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Evans Blue, Hyperalgesia, Male, Morpholines, Motor Activity, Naphthalenes, Pain Measurement, Pain Threshold, Plasma, Rats, Rats, Wistar, Reaction Time, Receptors, Cannabinoid, Sciatica, AM404, WIN 55, 212-2, plasma extravasation, neuropathic pain, mechanical allodynia, thermal hyperalgesia, Pharmacology and Pharmaceutical Sciences, Psychology, Neurology & Neurosurgery
Abstract

Neuropathic pain consequent to peripheral nerve injury has been associated with local inflammation. Following noxious stimulation afferent fibres release substance P (SP) and calcitonin-gene related peptide (CGRP), which are closely related to oedema formation and plasma leakage. The effect of the anandamide transport blocker AM404 has been studied on plasma extravasation after chronic constriction injury (CCI) which consists in a unilateral loose ligation of the rat sciatic nerve (Bennett and Xie, 1988). AM404 (1-3-10 mg kg(-1)) reduced plasma extravasation in the legated paw, measured as mug of Evans Blue per gram of fresh tissue. A strong effect on vascular permeability was also produced by the synthetic cannabinoid agonist WIN 55,212-2 (0.1-0.3-1 mg kg(-1)). Using specific antagonists or enzyme inhibitors, we demonstrate that cannabinoids act at several levels: data on the 3rd day suggest a strong involvement of substance P (SP) and calcitonin gene-related peptide (CGRP) in the control of vascular tone, whereas at the 7th and 14th days the major role seems to be played by prostaglandins (PGs) and nitric oxide (NO). Capsaicin injection in ligated paws of AM404- or WIN 55,212-2-treated rats resulted in an increase of Evans Blue extravasation, suggesting the involvement of the cannabinergic system in the protective effect of C fibres of ligated paws. Taken together, these data demonstrate the efficacy of cannabinoids in controlling pain behaviour through the modulation of several pain mediators and markers of vascular reactivity, such as SP, CGRP, PGs and NO.

Published
2008

12. Modulation of Neuropathic and Inflammatory Pain by the Endocannabinoid Transport Inhibitor AM404 [N-(4-Hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide]

Author

La Rana, G, Russo, R, Campolongo, P, Bortolato, M, Mangieri, RA, Cuomo, V, Iacono, A, Raso, G Mattace, Meli, R, Piomelli, D, and Calignano, A

Subjects
Pain Research, Chronic Pain, Substance Misuse, Drug Abuse (NIDA only), Neurosciences, Cannabinoid Research, Peripheral Neuropathy, Neurodegenerative, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Animals, Arachidonic Acids, Biological Transport, Cannabinoid Receptor Modulators, Disease Models, Animal, Dose-Response Relationship, Drug, Endocannabinoids, Freund's Adjuvant, Furans, Hyperalgesia, Inflammation, Male, Mice, Pain, Pain Measurement, Polyunsaturated Alkamides, Rats, Rats, Wistar, Sciatic Neuropathy, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy
Abstract

The endocannabinoid system may serve important functions in the central and peripheral regulation of pain. In the present study, we investigated the effects of the endocannabinoid transport inhibitor AM404 [N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide] on rodent models of acute and persistent nociception (intraplantar formalin injection in the mouse), neuropathic pain (sciatic nerve ligation in the rat), and inflammatory pain (complete Freund's adjuvant injection in the rat). In the formalin model, administration of AM404 (1-10 mg/kg i.p.) elicited dose-dependent antinociceptive effects, which were prevented by the CB(1) cannabinoid receptor antagonist rimonabant (SR141716A; 1 mg/kg i.p.) but not by the CB2 antagonist SR144528 (1 mg/kg i.p.) or the vanilloid antagonist capsazepine (30 mg/kg i.p.). Comparable effects were observed with UCM707 [N-(3-furylmethyl)-eicosa-5,8,11,14-tetraenamide], another anandamide transport inhibitor. In both the chronic constriction injury and complete Freund's adjuvant model, daily treatment with AM404 (1-10 mg/kg s.c.) for 14 days produced a dose-dependent reduction in nocifensive responses to thermal and mechanical stimuli, which was prevented by a single administration of rimonabant (1 mg/kg i.p.) and was accompanied by decreased expression of cyclooxygenase-2 and inducible nitric-oxide synthase in the sciatic nerve. The results provide new evidence for a role of the endocannabinoid system in pain modulation and point to anandamide transport as a potential target for analgesic drug development.

Published
2006

13. Deep learning applications in structure-based drug discovery

Author

Meli, R, Biggin, P, and Morris, G

Subjects
Computational biology, Computational chemistry, Ensemble learning (Machine learning), QSAR (Biochemistry), Deep learning (Machine learning), Structure-activity relationships (Biochemistry), Pharmaceutical chemistry, Ligand binding (Biochemistry), Supervised learning (Machine learning), Chemistry, Physical and theoretical
Abstract

In recent years, machine learning and deep learning applications have permeated all fields of science thanks to rapid algorithmic advances and computer hardware developments. A very active area of research is the use of deep learning in structure-based drug design, where the goal is to design effective drugs against a pharmacological target of interest. In this work, we explored the use of deep learning in the early stages of drug discovery. In particular, we focussed on structure-based virtual screening, binding affinity prediction, and de novo drug design. First, we enabled docking with flexible residues within Gnina, a state-of-the- art docking software based on convolutional neural networks, and we performed a large-scale cross-docking study of such methodology, outlining its strengths and weaknesses. Second, we extracted the convolutional neural network scoring function from the docking software into a standalone package for fast prototyping. With the new software at hand, we explored different annotations for supervised learning to improve the convolutional neural network scoring function for docking with flexible residues. Third, we developed a novel scoring function for binding affinity prediction based on a successful deep learning architecture used to develop machine learning force fields. Finally, we carefully evaluate a generative model for de novo design for the application in industrial drug discovery pipelines. We outline the weaknesses of the method and the problems with current evaluations of generative models.

Published
2023

14. Oleoylethanolamide mitigates cardiac metabolic alterations secondary to obesity induced by high-fat diet in C57/BL6J mice

Author

Comella, F, primary, Lama, A, additional, Pirozzi, C, additional, Feijoo-Bandin, S, additional, Aragon-Herrera, A, additional, Annunziata, C, additional, Del Piano, F, additional, Morana-Fernandez, S, additional, Anido-Valera, L, additional, Melini, S, additional, Opallo, N, additional, Meli, R, additional, Mattace Raso, G, additional, Gonzalez-Juanatey, J R, additional, and Lago Paz, F, additional

Published
2022
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16. Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Author

Salton F., Confalonieri P., Centanni S., Mondoni M., Petrosillo N., Bonfanti P., Lapadula G., Lacedonia D., Voza A., Carpene N., Montico M., Reccardini N., Meduri G. U., Ruaro B., Confalonieri M., Citton G. M., Bozzi C., Tavano S., Pozzan R., Andrisano A. G., Jaber M., Mari M., Trotta L., Mondini L., Barbieri M., Ruggero L., Antonaglia C., Soave S., Torregiani C., Bogatec T., Baccelli A., Nalesso G., Re B., Pavesi S., Barbaro M. P. F., Giuliani A., Ravaglia C., Poletti V., Scala R., Guidelli L., Golfi N., Vianello A., Achille A., Lucernoni P., Gaccione A. T., Romagnoli M., Fraccaro A., Malacchini N., Malerba M., Ragnoli B., Zamparelli A. S., Bocchino M., Blasi F., Spotti M., Miele C., Piedepalumbo F., Barone I., Baglioni S., Dodaj M., Franco C., Andrani F., Mangia A., Mancini A., Carrozzi L., Rafanelli A., Casto E., Rogliani P., Ora J., Carpagnano G. E., Di Lecce V., Tamburrini M., Papi A., Contoli M., Luzzati R., Zatta M., Di Bella S., Caraffa E., Francisci D., Tosti A., Pallotto C., De Rosa F. G., Pecori A., Franceschini M., Carlin M., Orsini V., Pollastri E., Rugova A., Sabbatini F., Soria A., Rossi M., Santantonio T., Meli R., Sauro S., Fedeli C., Mangini E., Biolo G., Nunnari A., Pietrangelo A., Corradini E., Bocchi D., Boarini C., Zucchetto A., Lanini S., Salton, F, Confalonieri, P, Centanni, S, Mondoni, M, Petrosillo, N, Bonfanti, P, Lapadula, G, Lacedonia, D, Voza, A, Carpene, N, Montico, M, Reccardini, N, Meduri, G, Ruaro, B, Confalonieri, M, Citton, G, Bozzi, C, Tavano, S, Pozzan, R, Andrisano, A, Jaber, M, Mari, M, Trotta, L, Mondini, L, Barbieri, M, Ruggero, L, Antonaglia, C, Soave, S, Torregiani, C, Bogatec, T, Baccelli, A, Nalesso, G, Re, B, Pavesi, S, Barbaro, M, Giuliani, A, Ravaglia, C, Poletti, V, Scala, R, Guidelli, L, Golfi, N, Vianello, A, Achille, A, Lucernoni, P, Gaccione, A, Romagnoli, M, Fraccaro, A, Malacchini, N, Malerba, M, Ragnoli, B, Zamparelli, A, Bocchino, M, Blasi, F, Spotti, M, Miele, C, Piedepalumbo, F, Barone, I, Baglioni, S, Dodaj, M, Franco, C, Andrani, F, Mangia, A, Mancini, A, Carrozzi, L, Rafanelli, A, Casto, E, Rogliani, P, Ora, J, Carpagnano, G, Di Lecce, V, Tamburrini, M, Papi, A, Contoli, M, Luzzati, R, Zatta, M, Di Bella, S, Caraffa, E, Francisci, D, Tosti, A, Pallotto, C, De Rosa, F, Pecori, A, Franceschini, M, Carlin, M, Orsini, V, Pollastri, E, Rugova, A, Sabbatini, F, Soria, A, Rossi, M, Santantonio, T, Meli, R, Sauro, S, Fedeli, C, Mangini, E, Biolo, G, Nunnari, A, Pietrangelo, A, Corradini, E, Bocchi, D, Boarini, C, Zucchetto, A, Lanini, S, Salton, Francesco, Confalonieri, Paola, Centanni, Stefano, Mondoni, Michele, Petrosillo, Nicola, Bonfanti, Paolo, Lapadula, Giuseppe, Lacedonia, Donato, Voza, Antonio, Carpenè, Nicoletta, Montico, Marcella, Reccardini, Nicolò, Meduri, Gianfranco Umberto, Ruaro, Barbara, MEDEAS Collaborative, Group, and Confalonieri, Marco

Subjects
Pulmonary and Respiratory Medicine, glucocorticoids, Settore MED/10 - Malattie dell'Apparato Respiratorio, pneumonia, COVID-19, glucocorticoid, dexamethasone, ARDS, acute respiratory distress syndrome, methylprednisolone
Abstract

BackgroundDysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7–10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking.MethodsWe conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow taperingversusdexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (PaO2/FIO2) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14.Results677 randomised patients were included. Findings are reported as methylprednisolone (n=337)versusdexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%)versus41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14)versus24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%)versus45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%)versus9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11)versus14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not inPaO2/FIO2ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points.ConclusionProlonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Published
2022

17. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Author

Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta M. G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P. L., Margotti M., Ieluzzi D., Brunetto M. R., Barbaro F., Russo F. P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L. A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A. D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E. M., Zignego A. L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T. A., Bruno S. R., Cela E. M., Bassetti M., Mazzarello G., Alessandrini A. I., Biagio A. D., Nicolini L. A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A. L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M. G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M. L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D. C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A. R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E. M., Licata A., Amodeo S., Capitano A. R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P. D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M. D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P. D., Marturano M., Saracco G. M., Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta M. G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P. L., Margotti M., Ieluzzi D., Brunetto M. R., Barbaro F., Russo F. P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L. A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A. D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E. M., Zignego A. L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T. A., Bruno S. R., Cela E. M., Bassetti M., Mazzarello G., Alessandrini A. I., Biagio A. D., Nicolini L. A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A. L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M. G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M. L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D. C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A. R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E. M., Licata A., Amodeo S., Capitano A. R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P. D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M. D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P. D., Marturano M., and Saracco G. M.

Abstract

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

Published
2021

18. High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV-infected patients treated in a real-life setting

Author

Fabbiani, M, Lombardi, A, Colaneri, M, Del Poggio, P, Perini, P, D'Ambrosio, R, Degasperi, E, Dibenedetto, C, Giorgini, A, Pasulo, L, Maggiolo, F, Castelli, F, Brambilla, P, Spinelli, O, Re, T, Lleo, A, Rumi, M, Uberti-Foppa, C, Soria, A, Aghemo, A, Lampertico, P, Baiguera, C, Schiavini, M, Fagiuoli, S, Bruno, R, Borghi, M, Soffredini, R, Perbellini, R, Gori, A, Ferroni, V, Colpani, M, Manini, M, Cologni, G, Lazzaroni, S, Vinci, M, De Nicola, S, Mazzarelli, C, Angelini Zucchetti, T, Picciotto, V, Puoti, M, Rossotti, R, Landonio, S, Magni, C, Rizzardini, G, Colella, E, Columpsi, P, Gambaro, A, Spolti, A, Magnani, C, Vigano, P, Mena, M, Villa, M, Caramma, I, Basilico, C, Capelli, F, Biagiotti, S, Mazzone, A, Saladino, V, Baldacci, M, Gatti, F, Varalli, L, Morini, L, Menzaghi, B, Farinazzo, M, Meli, R, Plaz Torres, M, Fanetti, I, Orellana, D, Zermiani, P, Zuin, M, De Bona, A, D'Arminio Monforte, A, Capretti, A, Taddei, M, Soncini, M, Spinetti, A, Zaltron, S, Pigozzi, M, Rossini, A, Pan, A, Dal Zoppo, S, Zoncada, A, Memoli, M, Salpietro, S, Hamid, H, Messina, E, Colombo, A, Giglio, O, Bonfanti, P, Molteni, C, Terreni, N, Spinzi, G, Conforti, S, Clerici, E, Menozzi, F, Buscarini, E, Centenaro, R, Corbellini, A, Noventa, F, Gritti, S, Giani, P, Fabbiani M., Lombardi A., Colaneri M., Del Poggio P., Perini P., D'Ambrosio R., Degasperi E., Dibenedetto C., Giorgini A., Pasulo L., Maggiolo F., Castelli F., Brambilla P., Spinelli O., Re T., Lleo A., Rumi M., Uberti-Foppa C., Soria A., Aghemo A., Lampertico P., Baiguera C., Schiavini M., Fagiuoli S., Bruno R., Borghi M., Soffredini R., Perbellini R., Gori A., Ferroni V., Colpani M., Manini M., Cologni G., Lazzaroni S., Vinci M., De Nicola S., Mazzarelli C., Angelini Zucchetti T., Picciotto V., Puoti M., Rossotti R., Landonio S., Magni C. F., Rizzardini G., Colella E., Columpsi P., Gambaro A., Spolti A., Magnani C., Vigano P., Mena M., Villa M., Caramma I., Basilico C., Capelli F., Biagiotti S., Mazzone A., Saladino V., Baldacci M. P., Gatti F., Varalli L., Morini L., Menzaghi B., Farinazzo M., Meli R., Plaz Torres M. C., Fanetti I., Orellana D., Zermiani P., Zuin M., De Bona A., D'Arminio Monforte A., Capretti A., Taddei M. T., Soncini M., Spinetti A., Zaltron S., Pigozzi M. G., Rossini A., Pan A., Dal Zoppo S., Zoncada A., Memoli M., Salpietro S., Hamid H., Messina E., Colombo A. E., Giglio O., Bonfanti P., Molteni C., Terreni N., Spinzi G., Conforti S., Clerici E., Menozzi F., Buscarini E., Centenaro R., Corbellini A., Noventa F., Gritti S., Giani P., Fabbiani, M, Lombardi, A, Colaneri, M, Del Poggio, P, Perini, P, D'Ambrosio, R, Degasperi, E, Dibenedetto, C, Giorgini, A, Pasulo, L, Maggiolo, F, Castelli, F, Brambilla, P, Spinelli, O, Re, T, Lleo, A, Rumi, M, Uberti-Foppa, C, Soria, A, Aghemo, A, Lampertico, P, Baiguera, C, Schiavini, M, Fagiuoli, S, Bruno, R, Borghi, M, Soffredini, R, Perbellini, R, Gori, A, Ferroni, V, Colpani, M, Manini, M, Cologni, G, Lazzaroni, S, Vinci, M, De Nicola, S, Mazzarelli, C, Angelini Zucchetti, T, Picciotto, V, Puoti, M, Rossotti, R, Landonio, S, Magni, C, Rizzardini, G, Colella, E, Columpsi, P, Gambaro, A, Spolti, A, Magnani, C, Vigano, P, Mena, M, Villa, M, Caramma, I, Basilico, C, Capelli, F, Biagiotti, S, Mazzone, A, Saladino, V, Baldacci, M, Gatti, F, Varalli, L, Morini, L, Menzaghi, B, Farinazzo, M, Meli, R, Plaz Torres, M, Fanetti, I, Orellana, D, Zermiani, P, Zuin, M, De Bona, A, D'Arminio Monforte, A, Capretti, A, Taddei, M, Soncini, M, Spinetti, A, Zaltron, S, Pigozzi, M, Rossini, A, Pan, A, Dal Zoppo, S, Zoncada, A, Memoli, M, Salpietro, S, Hamid, H, Messina, E, Colombo, A, Giglio, O, Bonfanti, P, Molteni, C, Terreni, N, Spinzi, G, Conforti, S, Clerici, E, Menozzi, F, Buscarini, E, Centenaro, R, Corbellini, A, Noventa, F, Gritti, S, Giani, P, Fabbiani M., Lombardi A., Colaneri M., Del Poggio P., Perini P., D'Ambrosio R., Degasperi E., Dibenedetto C., Giorgini A., Pasulo L., Maggiolo F., Castelli F., Brambilla P., Spinelli O., Re T., Lleo A., Rumi M., Uberti-Foppa C., Soria A., Aghemo A., Lampertico P., Baiguera C., Schiavini M., Fagiuoli S., Bruno R., Borghi M., Soffredini R., Perbellini R., Gori A., Ferroni V., Colpani M., Manini M., Cologni G., Lazzaroni S., Vinci M., De Nicola S., Mazzarelli C., Angelini Zucchetti T., Picciotto V., Puoti M., Rossotti R., Landonio S., Magni C. F., Rizzardini G., Colella E., Columpsi P., Gambaro A., Spolti A., Magnani C., Vigano P., Mena M., Villa M., Caramma I., Basilico C., Capelli F., Biagiotti S., Mazzone A., Saladino V., Baldacci M. P., Gatti F., Varalli L., Morini L., Menzaghi B., Farinazzo M., Meli R., Plaz Torres M. C., Fanetti I., Orellana D., Zermiani P., Zuin M., De Bona A., D'Arminio Monforte A., Capretti A., Taddei M. T., Soncini M., Spinetti A., Zaltron S., Pigozzi M. G., Rossini A., Pan A., Dal Zoppo S., Zoncada A., Memoli M., Salpietro S., Hamid H., Messina E., Colombo A. E., Giglio O., Bonfanti P., Molteni C., Terreni N., Spinzi G., Conforti S., Clerici E., Menozzi F., Buscarini E., Centenaro R., Corbellini A., Noventa F., Gritti S., and Giani P.

Abstract

In routine clinical practice, hepatitis C virus-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5 years, and 53 (14.5%) patients were HIV-co-infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n = 168, 46%) and 3 (n = 59, 16.2%). DAA was discontinued a median of 1 (IQR 1–4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2 weeks before the planned schedule. In patients with F0–F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for <4 weeks: 50% (n = 2/4) vs. 99.1% (n = 109/110) for ≥4 weeks, p = 0.003. In patients with liver cirrhosis, lower rates of SVR12 were observed in patients treated <8 weeks: 83.3% (n = 25/30) vs. 94.6% (n = 209/221) for ≥8 weeks, p = 0.038. Despite premature discontinuation of DAA, high SVR12 rates were observed in a real-life setting for treatment lasting at least 4 weeks in patients with liver fibrosis F0–F3 and 8 weeks in those with liver cirrhosis. On this basis, feasibility of reducing DAA treatment duration should be explored in randomized clinical trials.

Published
2021

20. High rates of sustained virological response despite premature discontinuation of directly acting antivirals in HCV-infected patients treated in a real-life setting

Author

Fabbiani M., Lombardi A., Colaneri M., Del Poggio P., Perini P., D'Ambrosio R., Degasperi E., Dibenedetto C., Giorgini A., Pasulo L., Maggiolo F., Castelli F., Brambilla P., Spinelli O., Re T., Lleo A., Rumi M., Uberti-Foppa C., Soria A., Aghemo A., Lampertico P., Baiguera C., Schiavini M., Fagiuoli S., Bruno R., Borghi M., Soffredini R., Perbellini R., Gori A., Ferroni V., Colpani M., Manini M., Cologni G., Lazzaroni S., Vinci M., De Nicola S., Mazzarelli C., Angelini Zucchetti T., Picciotto V., Puoti M., Rossotti R., Landonio S., Magni C. F., Rizzardini G., Colella E., Columpsi P., Gambaro A., Spolti A., Magnani C., Vigano P., Mena M., Villa M., Caramma I., Basilico C., Capelli F., Biagiotti S., Mazzone A., Saladino V., Baldacci M. P., Gatti F., Varalli L., Morini L., Menzaghi B., Farinazzo M., Meli R., Plaz Torres M. C., Fanetti I., Orellana D., Zermiani P., Zuin M., De Bona A., D'Arminio Monforte A., Capretti A., Taddei M. T., Soncini M., Spinetti A., Zaltron S., Pigozzi M. G., Rossini A., Pan A., Dal Zoppo S., Zoncada A., Memoli M., Salpietro S., Hamid H., Messina E., Colombo A. E., Giglio O., Bonfanti P., Molteni C., Terreni N., Spinzi G., Conforti S., Clerici E., Menozzi F., Buscarini E., Centenaro R., Corbellini A., Noventa F., Gritti S., Giani P., Fabbiani, Massimiliano, Lombardi, Andrea, Colaneri, Marta, Del Poggio, Paolo, Perini, Paolo, D'Ambrosio, Roberta, Degasperi, Elisabetta, Dibenedetto, Clara, Giorgini, Alessia, Pasulo, Luisa, Maggiolo, Franco, Castelli, Francesco, Brambilla, Paola, Spinelli, Ombretta, Tiziana, Re, Lleo, Ana, Rumi, Mariagrazia, Uberti-Foppa, Caterina, Soria, Alessandro, Aghemo, Alessio, Lampertico, Pietro, Baiguera, Chiara, Schiavini, Monica, Fagiuoli, Stefano, Bruno, Raffaele, Fabbiani, M, Lombardi, A, Colaneri, M, Del Poggio, P, Perini, P, D'Ambrosio, R, Degasperi, E, Dibenedetto, C, Giorgini, A, Pasulo, L, Maggiolo, F, Castelli, F, Brambilla, P, Spinelli, O, Re, T, Lleo, A, Rumi, M, Uberti-Foppa, C, Soria, A, Aghemo, A, Lampertico, P, Baiguera, C, Schiavini, M, Fagiuoli, S, Bruno, R, Borghi, M, Soffredini, R, Perbellini, R, Gori, A, Ferroni, V, Colpani, M, Manini, M, Cologni, G, Lazzaroni, S, Vinci, M, De Nicola, S, Mazzarelli, C, Angelini Zucchetti, T, Picciotto, V, Puoti, M, Rossotti, R, Landonio, S, Magni, C, Rizzardini, G, Colella, E, Columpsi, P, Gambaro, A, Spolti, A, Magnani, C, Vigano, P, Mena, M, Villa, M, Caramma, I, Basilico, C, Capelli, F, Biagiotti, S, Mazzone, A, Saladino, V, Baldacci, M, Gatti, F, Varalli, L, Morini, L, Menzaghi, B, Farinazzo, M, Meli, R, Plaz Torres, M, Fanetti, I, Orellana, D, Zermiani, P, Zuin, M, De Bona, A, D'Arminio Monforte, A, Capretti, A, Taddei, M, Soncini, M, Spinetti, A, Zaltron, S, Pigozzi, M, Rossini, A, Pan, A, Dal Zoppo, S, Zoncada, A, Memoli, M, Salpietro, S, Hamid, H, Messina, E, Colombo, A, Giglio, O, Bonfanti, P, Molteni, C, Terreni, N, Spinzi, G, Conforti, S, Clerici, E, Menozzi, F, Buscarini, E, Centenaro, R, Corbellini, A, Noventa, F, Gritti, S, and Giani, P

Subjects
Simeprevir, Male, medicine.medical_specialty, Cirrhosis, SVR, Sofosbuvir, Sustained Virologic Response, liver cirrhosis, antiviral treatment, Hepacivirus, Antiviral Agents, law.invention, Randomized controlled trial, law, Virology, Internal medicine, Medicine, Humans, chronic hepatitis C, Prospective cohort study, DAA, Retrospective Studies, Hepatology, liver cirrhosi, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Discontinuation, Regimen, Infectious Diseases, Treatment Outcome, business, medicine.drug
Abstract

In routine clinical practice, hepatitis C virus-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5years, and 53 (14.5%) patients were HIV-co-infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n=168, 46%) and 3 (n=59, 16.2%). DAA was discontinued a median of 1 (IQR 1–4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2weeks before the planned schedule. In patients with F0–F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for

Published
2021

22. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Author

Quaranta, M. G., Ferrigno, L., Tata, X., D'Angelo, Francesca Bice, Massari, Massimo, Coppola, C., Biliotti, E., Giorgini, A., Laccabue, D., Ciancio, A., Blanc, P. L., Margotti, M., Ieluzzi, D., Brunetto, M. R., Barbaro, Federico, Russo, F. P., Beretta, I., Morsica, G., Verucchi, G., Saracino, A., Galli, M., Kondili, L. A., Mazzaro, C., Bertola, M., Benedetti, A., Schiada, L., Cucco, Marco, Giacometti, A., Brescini, L., Castelletti, S., Fiorentini, A., Angarano, G., Milella, M., Leo, A. D., Rendina, Marco, Salvatore D'ABRAMO, F., Lillo, C., Iannone, A., Piazzolla, M., Badia, L., Piscaglia, F., Benevento, F., Serio, I., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Bruno, Rosa Anna, Mondelli, M., Chessa, L., Loi, M., Torti, Carlo, Costa, C., Mazzitelli, M., Pisani, V., Scaglione, V., Trecarichi, Enrico Maria, Zignego, A. L., Monti, M., Madia, Francesca, Attala, L., Pierotti, P., Salomoni, E., Mariabelli, E., Santantonio, T. A., Bruno, S. R., Cela, E. M., Bassetti, M., Mazzarello, G., Alessandrini, A. I., Biagio, A. D., Nicolini, L. A., Raimondo, G., Filomia, R., Aghemo, A., Meli, R., Lazzarin, A., Salpietro, S., Fracanzani, A. L., Fatta, E., Lombardi, Roberto, Lampertico, P., Borghi, Margherita, D'Ambrosio, Roberto, Degasperi, E., Puoti, M., Baiguera, C., D'Amico, F., Vinci, Maria Rosaria, Rumi, M. G., Zuin, M., Zermiani, P., Andreone, P., Caraceni, P., Guarneri, V., Villa, E., Bernabucci, V., Bristot, Luca, Paradiso, M. L., Migliorino, G., Gambaro, A., Lapadula, G., Spolti, A., Soria, A., Invernizzi, P., Ciaccio, A., Luca, M., Malinverno, F., Ratti, L., Amoruso, D. C., Pisano, Francesco, Scarano, F., Staiano, L., Morisco, F., Cossiga, V., Gentile, I., Buonomo, A. R., Foggia, M., Zappulo, E., Federico, A., Dallio, M., Coppola, N., Sagnelli, C., Martini, Simone, Monari, C., Nardone, G., Sgamato, C., Chemello, L., Cavalletto, L., Sterrantino, D., Zanetto, A., Zanaga, P., Brancaccio, G., Craxi, A., Petta, S., Calvaruso, V., Crapanzano, L., Madonia, S., Cannizzaro, Maria Chiara, Bruno, E. M., Licata, Maria Angela Vittoria Anna Chiara, Amodeo, Silvia, Capitano, A. R., Ferrari, C., Negri, Erica, Orlandini, A., Pesci, M., Gulminetti, R., Pagnucco, L., Parruti, G., Stefano, P. D., Coco, B., Corsini, R., Garlassi, E., Andreoni, M., Teti, E., Cerva, C., Baiocchi, Luca, Grassi, G., Gasbarrini, Antonio, Pompili, Maurizio, Siena, M. D., Taliani, G., Spaziante, M., Persico, M., Masarone, M., Aglitti, A., Calvanese, G., Anselmo, M., Leo, P. D., Marturano, Monia, Saracco, G. M., D'Angelo F., Massari M. (ORCID:0000-0001-7048-6374), Barbaro F., Cucco M., Rendina M., Bruno R., Torti C., Trecarichi E. M., Madia F., Lombardi R., Borghi M., D'ambrosio R., Vinci M., Bristot L., Pisano F., Martini S., Cannizzaro M., Licata A., Amodeo S., Negri E., Baiocchi L., Gasbarrini A. (ORCID:0000-0002-7278-4823), Pompili M. (ORCID:0000-0001-6699-7980), Marturano M., Quaranta, M. G., Ferrigno, L., Tata, X., D'Angelo, Francesca Bice, Massari, Massimo, Coppola, C., Biliotti, E., Giorgini, A., Laccabue, D., Ciancio, A., Blanc, P. L., Margotti, M., Ieluzzi, D., Brunetto, M. R., Barbaro, Federico, Russo, F. P., Beretta, I., Morsica, G., Verucchi, G., Saracino, A., Galli, M., Kondili, L. A., Mazzaro, C., Bertola, M., Benedetti, A., Schiada, L., Cucco, Marco, Giacometti, A., Brescini, L., Castelletti, S., Fiorentini, A., Angarano, G., Milella, M., Leo, A. D., Rendina, Marco, Salvatore D'ABRAMO, F., Lillo, C., Iannone, A., Piazzolla, M., Badia, L., Piscaglia, F., Benevento, F., Serio, I., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Bruno, Rosa Anna, Mondelli, M., Chessa, L., Loi, M., Torti, Carlo, Costa, C., Mazzitelli, M., Pisani, V., Scaglione, V., Trecarichi, Enrico Maria, Zignego, A. L., Monti, M., Madia, Francesca, Attala, L., Pierotti, P., Salomoni, E., Mariabelli, E., Santantonio, T. A., Bruno, S. R., Cela, E. M., Bassetti, M., Mazzarello, G., Alessandrini, A. I., Biagio, A. D., Nicolini, L. A., Raimondo, G., Filomia, R., Aghemo, A., Meli, R., Lazzarin, A., Salpietro, S., Fracanzani, A. L., Fatta, E., Lombardi, Roberto, Lampertico, P., Borghi, Margherita, D'Ambrosio, Roberto, Degasperi, E., Puoti, M., Baiguera, C., D'Amico, F., Vinci, Maria Rosaria, Rumi, M. G., Zuin, M., Zermiani, P., Andreone, P., Caraceni, P., Guarneri, V., Villa, E., Bernabucci, V., Bristot, Luca, Paradiso, M. L., Migliorino, G., Gambaro, A., Lapadula, G., Spolti, A., Soria, A., Invernizzi, P., Ciaccio, A., Luca, M., Malinverno, F., Ratti, L., Amoruso, D. C., Pisano, Francesco, Scarano, F., Staiano, L., Morisco, F., Cossiga, V., Gentile, I., Buonomo, A. R., Foggia, M., Zappulo, E., Federico, A., Dallio, M., Coppola, N., Sagnelli, C., Martini, Simone, Monari, C., Nardone, G., Sgamato, C., Chemello, L., Cavalletto, L., Sterrantino, D., Zanetto, A., Zanaga, P., Brancaccio, G., Craxi, A., Petta, S., Calvaruso, V., Crapanzano, L., Madonia, S., Cannizzaro, Maria Chiara, Bruno, E. M., Licata, Maria Angela Vittoria Anna Chiara, Amodeo, Silvia, Capitano, A. R., Ferrari, C., Negri, Erica, Orlandini, A., Pesci, M., Gulminetti, R., Pagnucco, L., Parruti, G., Stefano, P. D., Coco, B., Corsini, R., Garlassi, E., Andreoni, M., Teti, E., Cerva, C., Baiocchi, Luca, Grassi, G., Gasbarrini, Antonio, Pompili, Maurizio, Siena, M. D., Taliani, G., Spaziante, M., Persico, M., Masarone, M., Aglitti, A., Calvanese, G., Anselmo, M., Leo, P. D., Marturano, Monia, Saracco, G. M., D'Angelo F., Massari M. (ORCID:0000-0001-7048-6374), Barbaro F., Cucco M., Rendina M., Bruno R., Torti C., Trecarichi E. M., Madia F., Lombardi R., Borghi M., D'ambrosio R., Vinci M., Bristot L., Pisano F., Martini S., Cannizzaro M., Licata A., Amodeo S., Negri E., Baiocchi L., Gasbarrini A. (ORCID:0000-0002-7278-4823), Pompili M. (ORCID:0000-0001-6699-7980), and Marturano M.

Abstract

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

Published
2021

25. Preventive effect of human milk against food allergy: new insights into butyrate activities

Author

Canani, Berni R., Aitoro, R., Paparo, L., Amoroso, A., Trinchese, G., Meli, R., Calignano, A., Caro, C., Passariello, A., Montella, M., Messina, F., RITA NOCERINO, Nagler, C., Berni canani R, Aitoro R, Paparo L, Amoroso A, Trinchese G, Meli R, Calignano A, De Caro C, Passariello A, Montella M, Messina F, Nocerino R, Nagler C., Berni canani, R, Aitoro, R, Paparo, L, Amoroso, A, Trinchese, G, Meli, R, Calignano, A, De Caro, C, Passariello, A, Montella, M, Messina, F, Nocerino, R, and Nagler, C

Published
2017

29. Assessing upper limb function in multiple sclerosis using an engineered glove

Author

Carmisciano, L., primary, Signori, A., additional, Pardini, M., additional, Novi, G., additional, Lapucci, C., additional, Nesi, L., additional, Gallo, E., additional, Laroni, A., additional, Cellerino, M., additional, Meli, R., additional, Sbragia, E., additional, Filippi, L., additional, Uccelli, A., additional, Inglese, M., additional, and Sormani, M. P., additional

Published
2020
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41. International guideline for seismic design of low-rise confined masonry buildings in regions of high seismic risk

Author

Brzev, S., Meli, R., Mebarki, Ahmed, Farsi, M.N., Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), CGS, National Center of Applied Research in Earthquake Engineering, National Center of Applied Research in Earthquake Engineering, CTC Chlef + Univ. Chlef, Mebarki, Ahmed, and National Center of Applied Research in Earthquake Engineering = Centre National de Recherche Appliquée en Génie Parasismique (CGS)

Subjects
[SPI.GCIV]Engineering Sciences [physics]/Civil Engineering, [SPI.GCIV] Engineering Sciences [physics]/Civil Engineering, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

42. Seismic Design Guide for Low-Rise Confined Masonry Buildings

Author

Meli, R., Brzev, S., Astroza, M., Boen, T., Crisafulli, F., Dai, J., Farsi, M., Hart, T., Mebarki, Ahmed, Moghadam, A.S., Quinn, D., Tomazevic, M., Yamin, L., Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), EERI - WHE (World Housing Encyclopedia), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), and Mebarki, Ahmed

Subjects
[SPI.GCIV]Engineering Sciences [physics]/Civil Engineering, [SPI.GCIV] Engineering Sciences [physics]/Civil Engineering
Published
2011

43. Breast milk butyrate as protective factor against food allergy

Author

Aitoro, R., primary, Paparo, L., additional, Di Costanzo, M., additional, Nocerino, R., additional, Amoroso, A., additional, Amato, F., additional, Pirozzi, C., additional, Calignano, A., additional, Meli, R., additional, Simeoli, R., additional, Nagler, C., additional, Guandalini, S., additional, and Berni, C., additional

Published
2015
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46. Effect of thalidomide on signal transduction pathways and secondary damage in experimental spinal cord trauma

Author

Genovese, Tiziana, Mazzon, E, Esposito, Emanuela, DI PAOLA, R, Caminiti, R, Meli, R, Bramanti, Placido, Cuzzocrea, Salvatore, and DI PAOLA, Rosanna

Subjects
Male, Pathology, medicine.medical_specialty, medicine.medical_treatment, Nitric Oxide Synthase Type II, Inflammation, Apoptosis, Critical Care and Intensive Care Medicine, Neuroprotection, Mice, chemistry.chemical_compound, Animals, Medicine, Spinal cord injury, Spinal Cord Injuries, Peroxidase, Neutrophil infiltration, biology, Tumor Necrosis Factor-alpha, business.industry, Nitrotyrosine, Laminectomy, medicine.disease, Spinal cord, Thalidomide, Disease Models, Animal, medicine.anatomical_structure, Spinal Cord, chemistry, SCI, Myeloperoxidase, TNF-α, Emergency Medicine, biology.protein, Cytokines, Lipid Peroxidation, medicine.symptom, business, Immunosuppressive Agents, Apoptosis, Neutrophil infiltration, SCI, Thalidomide, TNF-α, Signal Transduction, medicine.drug
Abstract

TNF-alpha seems to play a central role in the inflammatory process of spinal cord injury. We tested the neuroprotective effects of thalidomide, an immunomodulatory agent that inhibits TNF-alpha production, which have not been investigated so far. The aim of our study was to evaluate the therapeutic efficacy of thalidomide in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a 4-level T5 to T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production that is followed by recruitment of other inflammatory cells, production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Thalidomide treatment significantly reduced the degree of: 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) iNOS, nitrotyrosine, lipid peroxidation, and cytokine expression (TNF-alpha and IL-1beta); 4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and Bax and Bcl-2 expression); and 5) nuclear factor-kappaB activation. In a separate set of experiments, we have also clearly demonstrated that thalidomide significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with thalidomide reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Published
2008

48. Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury

Author

Genovese, Tiziana, Esposito, Emanuela, Mazzon, E, Muia, C, DI PAOLA, R, Meli, R, Bramanti, Placido, Cuzzocrea, Salvatore, and DI PAOLA, Rosanna

Subjects
Male, Pathology, medicine.medical_specialty, MAP Kinase Signaling System, Apoptosis, Mice, Inbred Strains, Inflammation, Fas ligand, Proinflammatory cytokine, Mice, chemistry.chemical_compound, medicine, Animals, Enzyme Inhibitors, Protein kinase A, Spinal cord injury, Spinal Cord Injuries, Mitogen-Activated Protein Kinase 1, Pharmacology, Mitogen-Activated Protein Kinase 3, business.industry, Nitrotyrosine, medicine.disease, Spinal cord, medicine.anatomical_structure, Neutrophil Infiltration, Spinal Cord, chemistry, Terminal deoxynucleotidyl transferase, Cytokines, Molecular Medicine, medicine.symptom, business
Abstract

Mitogen-activated protein kinase (MAPK) signaling pathways involve two closely related MAPKs, known as extracellular signal-regulated kinase (ERK)1 and ERK2. The aim of the present study was to evaluate the contribution of MAPK3/MAPK1 in the secondary damage in experimental spinal cord injury (SCI) in mice. To this purpose, we used 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059), which is an inhibitor of MAPK3/MAPK1. Spinal cord trauma was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis. PD98059 treatment (10 mg/kg i.p.) at 1 and 6 h after the SCI significantly reduced 1) the degree of spinal cord inflammation and tissue injury (histological score), 2) neutrophil infiltration (myeloperoxidase activity), 3) nitrotyrosine formation, 4) proinflammatory cytokines expression, 5) nuclear factor-kappaB activation, 6) phospho-ERK1/2 expression, and 6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, Fas ligand, Bax, and Bcl-2 expression). Moreover, PD98059 significantly ameliorated the recovery of limb function (evaluated by motor recovery score) in a dose-dependent manner. Taken together, our results clearly demonstrate that PD98059 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Published
2008

49. PROTECTIVE EFFECT OF HYPERICUM PERFORATUM IN ZYMOSAN-INDUCED MULTIPLE ORGAN DYSFUNCTION SYNDROME: RELATIONSHIP TO ITS INHIBITORY EFFECT ON NITRIC OXIDE PRODUCTION AND ITS PEROXYNITRITE SCAVENGING ACTIVITY

Author

DI PAOLA, R, Mazzon, E, Muia, C, Crisafulli, Concetta, Genovese, Tiziana, DI BELLA, P, Esposito, Emanuela, Menegazzi, M, Meli, R, Suzuki, H, Cuzzocrea, Salvatore, DI PAOLA, Rosanna, R., DI PAOLA, E., Mazzon, C., Muia, C., Crisafulli, T., Genovese, P., DI BELLA, Esposito, Emanuela, M., Menegazzi, Meli, Rosaria, H., Suzuki, and S., Cuzzocrea

Subjects
Male, Cancer Research, antioxidant, Physiology, Neutrophils, Multiple Organ Failure, Clinical Biochemistry, Nitric Oxide Synthase Type II, Pharmacology, Biochemistry, Nitric oxide, chemistry.chemical_compound, Mice, nitric oxide, medicine, Hypericum perforatum, Animals, oxidative stress, Lung, biology, Chemistry, Plant Extracts, Nitrotyrosine, Zymosan, medicine.disease, zymosan induced multiple organ failure, Immunohistochemistry, Nitric oxide synthase, Intestines, Myeloperoxidase, Immunology, biology.protein, Multiple organ dysfunction syndrome, Peroxynitrite, Hypericum
Abstract

Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Since polyphenolic compounds have high antioxidant potential, we have investigated the effects of H. perforatum extract on the development of multiple organ dysfunction syndrome caused by zymosan (500 mg/kg, administered i.p. as a suspension in saline) in mice. Organ failure and systemic inflammation in rats was assessed 18 h after administration of zymosan and/or H. perforatum extract and monitored for 12 days (for loss of body weight and mortality). Treatment of mice with H. perforatum extract (30 mg/kg i.p., 1 and 6h after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan, pulmonary, intestinal and pancreatic injury, and renal dysfunction as well as the increase in myeloperoxidase in the lung and intestine. Immunohistochemical analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly(ADP-ribose) (PAR) revealed positive staining in lung and intestine tissues obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, iNOS, and PAR was markedly reduced in tissue sections obtained from zymosan-treated mice, which received H. perforatum extract. In conclusion, this study provides evidence, for the first time, that H. perforatum extract attenuates the degree of zymosan-induced multiple organ dysfunction syndrome in mice.

Published
2007

50. Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma

Author

Genovese, Tiziana, Mazzon, E, Crisafulli, Concetta, Esposito, Emanuela, DI PAOLA, R, Muia, C, DI BELLA, P, Meli, R, Bramanti, Placido, Cuzzocrea, Salvatore, DI PAOLA, Rosanna, T., Genovese, E., Mazzon, C., Crisafulli, Esposito, Emanuela, R., DI PAOLA, C., Miua, P., DI BELLA, Meli, Rosaria, P., Bramanti, and S., Cuzzocrea

Subjects
Male, Combination therapy, Neutrophils, medicine.medical_treatment, Central nervous system, Interleukin-1beta, Anti-Inflammatory Agents, Nitric Oxide Synthase Type II, Inflammation, Pharmacology, Dexamethasone, Receptors, Tumor Necrosis Factor, Proinflammatory cytokine, Etanercept, Mice, medicine, In Situ Nick-End Labeling, Animals, Spinal cord injury, Spinal Cord Injuries, Peroxidase, bcl-2-Associated X Protein, nitrotyrosine, business.industry, Tumor Necrosis Factor-alpha, General Neuroscience, Laminectomy, Spinal cord, medicine.disease, dexamethasone, etanercept, iNOS, myeloperoxidase activity, nitrotyrosine, spinal cord injury, spinal cord injury, iNOS, Disease Models, Animal, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Immunoglobulin G, Immunology, myeloperoxidase activity, Tyrosine, Drug Therapy, Combination, medicine.symptom, business, medicine.drug
Abstract

The aim of our study was to evaluate the therapeutic efficacy of combination therapy with etanercept and dexamethasone (DEX) in vivo in experimental murine model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5–T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production followed by recruitment of other inflammatory cells, production of inflammation mediators, tissue damage, apoptosis and disease. Treatment of the mice with etanercept (1.25 mg/kg) and DEX (0.025 mg/kg) when administered as a combination therapy but not as a single treatment significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) inducible nitric oxide synthase, nitrotyrosine, and cytokines expression (tumor necrosis factor-α and interleukin-1β), (4) and apoptosis (Terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, Fas-ligand expression and Bax and Bcl-2 expression). In a separate set of experiments we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of spinal cord trauma.

Published
2007

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