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38 results on '"Mariani, P. R."'

1. Allele-specific loss and transcription of the miR-15a/16-1 cluster in chronic lymphocytic leukemia

Author

Veronese, A, Pepe, F, Chiacchia, J, Pagotto, S, Lanuti, P, Veschi, S, Di Marco, M, D'Argenio, A, Innocenti, I, Vannata, B, Autore, F, Marchisio, M, Wernicke, D, Verginelli, F, Leone, G, Rassenti, LZ, Kipps, TJ, Mariani-Costantini, R, Laurenti, L, Croce, CM, and Visone, R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Rare Diseases, Lymphoma, Hematology, Genetics, Cancer, Alleles, Base Sequence, Biomarkers, Tumor, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA, DNA Copy Number Variations, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, MicroRNAs, Molecular Sequence Data, Polymorphism, Single Nucleotide, Real-Time Polymerase Chain Reaction, Transcription, Genetic, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Abstract

Deregulation of the miR-15a/16-1 cluster has a key role in the pathogenesis of chronic lymphocytic leukemia (CLL), a clinically heterogeneous disease with indolent and aggressive forms. The miR-15a/16-1 locus is located at 13q14, the most frequently deleted region in CLL. Starting from functional investigations of a rare SNP upstream the miR cluster, we identified a novel allele-specific mechanism that exploits a cryptic activator region to recruit the RNA polymerase III for miR-15a/16-1 transcription. This regulation of the miR-15a/16- locus is independent of the DLEU2 host gene, which is often transcribed monoallellically by RPII. We found that normally one allele of miR-15a/16-1 is transcribed by RNAPII, the other one by RNAPIII. In our subset of CLL patients harboring 13q14 deletions, exclusive RNA polymerase III (RPIII)-driven transcription of the miR-15a/16-1 was the consequence of loss of the RPII-regulated allele and correlated with high expression of the poor prognostic marker ZAP70 (P=0.019). Thus, our findings point to a novel biological process, characterized by double allele-specific transcriptional regulation of the miR-15a/16-1 locus by alternative mechanisms. Differential usage of these mechanisms may distinguish at onset aggressive from indolent forms of CLL. This provides a basis for the clinical heterogeneity of the CLL patients carrying 13q14 deletions.

Published
2015

7. Precipitating factors and decision-making processes of short-term worsening heart failure despite 'optimal' treatment (from the IN-CHF Registry)

Author

Opasich, C., Rapezzi, C., Lucci, D., Gorini, M., Pozzar, F., Zanelli, E., Tavazzi, L., Mezzani, Maggioni A. P. AND THE IN CHF Investigators: A., Bielli, M., Milanese, U., Ugliengo, G., Pozzi, R., Rabajoli, F., Bosimini, E., Valsecchi, M. G., Dadda, F., Faggiano, P., Castiglioni, G., Gibelli, G., Turelli, A. L., Belluschi, R., Bianchi, C., Emanuelli, C., Gramenzi, S., Foti, G., Agnelli, D., Volterrani, M., Moroni, E., Gara, E., Turiel, A., Recalcati, F., Valenti, D., Rusconi, F., Palvarini, M., Giusti, A., Inserra, C., Nassiacos, D., Meloni, S., Nicoli, T., Bandini, P., Moizi, M., Pedretti, R., Paolucci, M., Amati, L., Ravetta, M., Morandi, F., Provasoli, S., Planca, E., Quorso, P., Ferro, A., Pedrolli, C., Riggi, L., Tarantini, L., Candelpergher, G., Berton, G., Stefanini, M. G., Cacciavillani, L., Boffa, G. M., Mario, L., Renosto, G., Stritoni, P., Perini, G., Bonadiman, C., Varotto, L., Penzo, M., Giuliano, G., Marini, R., Barducci), E., Humar, F., Albanese, M. C., Fresco, C., Camerini, A., Griffo, R., Derchi, G., Vengo, P., Fazzini, L., Pizzorno, L., Bertoli, D., Morgagni, G., Bruno, G., Iori, E., Melandri, F., Cionini, F., Reggianini, L., Passerini, F., Del Corso, P., Rusconi, L., Marzaloni, M., Mezzetti, M., Gambarati, G. P., Mariani, P. R., Volterrani, C., Venturi, F., Zambaldi, G., Geri Brandinelli, A., Taddei, T., Dalle Luche, A., Arcuri, G., Giannini, R., Gasperini, U., Alunni, G., Bosi, E., Cocchieri, M., Severini, D., Maragoni, G., C. Ferroni, G. Saccomanno, Pasetti, L., Budini, A., Manfrin, M., Coderoni, B., Mori, A., Midi, P., D. Del Sindaco, F. Leggio, Terranova, A., Pulignano, G., Cacciatore, G., Menichelli, M., Ansalone, G., Magris, B., Scaffidi, G., Valtorta, C., Salustri, A., Amaddeo, F., Barbato, G., Aspromonte, N., Renzi, M., Mantini, L., Frattaroli, C., Mariani, A., Di Marco, G., Levantesi, G., Colonna, N., Montano, A., Di Maggio, O., Toscano, G., Capuano, V., Scherillo, M., Sensale, P., Rullo, V., Maurea, N., Miceli, D., Somelli, A., Napolitano, F., Provvisiero, P., Di Muro, M. R., Bottiglieri, P., Rufolo, F., Ciriello, N., Angelini, E., Andriulo, C., De Santis, F., Cocco, F., Zecca, A., Pennetta, A., Mariello, F., Magliari, F., De Giorgi, A., Santoro, V., Pede, S., Renna, A., De Donno, O., De Lorenzi, E., Polimeni, G., Russo, V. A., Mangia, R., Cariello, F. P., Affinita, M., Perticone, F., Cloro, C., Misuraca, G., Caporale, R., Chiappetta, P., Tripodi, E., Tassone, F., Salituri, S., Errigo, C., Meringolo, G., Donnangelo, L., Canonico, G., Coco, R., Franco, M., Coglitore, A., Donato, A., Di Tano, G., Cento, D., DE GREGORIO, Cesare, Mongiovì, M., Schillaci, A. M., Mirto, U., Clemenza, F., Ingrillì, F., Aloisi, B., Porcu, M., Pili, G., and Piras, S.

Subjects
Male, medicine.medical_specialty, Heart disease, Decision Making, Risk Factors, Internal medicine, Heart rate, Humans, Medicine, Decompensation, Prospective Studies, Registries, Practice Patterns, Physicians', Intensive care medicine, Prospective cohort study, Aged, Heart Failure, business.industry, Atrial fibrillation, Middle Aged, Prognosis, medicine.disease, Blood pressure, Heart failure, Multivariate Analysis, Emergency medicine, Ambulatory, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

This study sought to prospectively assess which factors were related to short-term worsening heart failure (HF) leading to or not to hospital admission, in long-term outpatients followed by cardiologists. The subsequent decision-making process was also analyzed. The study population consisted of 2,701 outpatients enrolled in the registry of the Italian Network on Congestive Heart Failure (IN-CHF) and followed by 133 cardiology centers (19% of all existing Italian cardiology centers). Clinical and follow-up data were collected by local trained clinicians; 215 patients (8%) had short-term decompensation (on average 2 months after the index outpatient visit). Multivariate analysis showed that previous hospitalization, long duration of symptoms, ischemic etiology, atrial fibrillation, higher functional class (New York Heart Association classification III to IV), higher heart rate, and low systolic blood pressure were independently associated with HF destabilization. Poor compliance (21%) and infection (12%) were the most frequent precipitating factors, but a precipitating factor was not identified in 40% of the patients. Poor compliance was more common in women, but no other clinical characteristics emerged as being related with a specific precipitating factor. Fifty-seven percent of the patients with a short-term recurrence of worsening HF required hospital admission; infusion treatment with inotropes and/or vasodilators was necessary in 19% of them. Long-term therapy was changed in 48% of the patients. Thus, in ambulatory HF patients, short-term worsening HF can be predicted according to the clinical characteristics on an outpatient basis. Nearly 1/3 of precipitating factors can be prevented. Patient education and avoidance of inappropriate treatment may reduce the number of relapses.

Published
2001
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10. Use of digitalis in the treatment of heart failure: data from the Italian Network on Congestive Heart Failure (IN-CHF)

Author

Camerini, A, Griffo, R, Aspromonte, N, Ingrilli', F, Lucci, D, Naccarella, F, Maggioni, Ap, IN-CHF INVESTIGATORS- Piemonte Borgomanero (M. Zanetta, A. M. Paino), Casale Monferrato (M. Ivaldi, A. Giusti), Uslenghi, Cuneo (E., Milanese, U., Deorsola), A., Greco Lucchina, Orbassano (P., Pozzi, R., Rabajoli), F., Veruno (P. Giannuzzi, E. Bosimini), Valle d’Aosta Aosta (M. De Marchi, G. Begliuomini), Richichi, Lombardia Belgioioso (I., Ferrari, A., Barzizza), F., Bergamo Riabilitazione Cardiologica (A. Gavazzi, F. Dadda), Bergamo U. O. Cardiologia Cardiovascolare (A. Gavazzi, A. Fontana), Brescia (C. Rusconi, P. Faggiano), Cogo, Cassano D’Adda (R., Castiglioni, G., Gibelli), G., Chiari (F. Bortolini, A. L. Turelli), Como (G. Ferrari, R. Jemoli), Pirelli, Cremona (S., Bianchi, C., Emanuelli), C., De Martini), Desio (M., Erba (G. Maggi, D. Agnelli), Ferrara), Esine (E., Rovelli, Garbagnate Milanese (G., Lureti, G., Cazzani), E., Giordano, Gussago (A., Zanelli, E., Domenighini), D., Legnano (S. De Servi, C. Castelli), Mariano Comense (G. Bellati, E. Moroni), Milano Fondazione Don Carlo Gnocchi IRCCS (M. Ferratini, E. Gara), Malliani, Milano Sacco (A., Muzzupappa, S., Turiel, M., Guzzetti, S., Cappiello), E., Milano Niguarda (S. Klugmann, F. Recalcati), Milano Pio Albergo Trivulzio (S. Corallo, D. Valenti), Cobelli), Montescano (F., Monza (A. Grieco, A. Vincenzi), Schweiger, Passirana-Rho (C., Rusconi, F., Palvarini), M., Ferrari, Pavia IIAARR S. Margherita (E., Carbone), M., Tavazzi, Pavia IRCCS Policlinico San Matteo (L., Campana, C., Serio), A., Croce, Saronno (A., Nassiacos, D., Meloni), S., Seriate (P. Giani, T. Nicoli), Sondalo (G. Occhi, P. Bandini), Sondrio (S. Giustiniani, M. Moizi), Tradate Fondazione S. Maugeri (R. Pedretti, M. Paolucci), Onofri, Tradate Ospedale di Circolo Galmarini (M., Amati, L., Ravetta), M., Venco, Varese Medicina Interna Azienda Ospedaliera e Universitaria (A., Bertolini, A., Saggiorato), P., Salerno Uriarte, Varese U. O. Cardiologia Azienda Ospedaliera e Universitaria (J., Morandi, F., Provasoli), S., Vizzolo Predabissi (M. Lombardo, P. Quorso), P. A. Trento Rovereto Cardiologia Ospedale Civile (G. Vergara, A. Ferro), Rovereto Medicina Ospedale Civile (M. Mattarei, C. Pedrolli), Catania, Veneto Belluno (G., Tarantini, L., Russo), P., Castelfranco Veneto (L. Celegon, G. Candelpergher), Conegliano Veneto (P. Delise, C. Marcon), Guarnerio, Feltre (M., De Cian, F., Agnoli), A., Montebelluna (G. Neri, M. G. Stefanini), Iliceto, Padova (S., Boffa, G. M., Tiso), E., Pieve di Cadore (J. Dalle Mule, A. Stefania), San Bonifacio (R. Rossi, E. Carbonieri), Treviso (P. Stritoni, G. Renosto), Fontanelli, Vicenza (A., Ottani, F., Varotto), L., Perini), Villafranca (G., Friuli Venezia Giulia Gorizia (D. Igidbashian, G. Giuliano), Monfalcone (T. Morgera, E. Barducci), San Vito al Tagliamento (M. Carone, G. Pascottini), Fioretti, Udine A. O. S. Maria della Misericordia (P., Albanese, M. C., Fresco), C., Udine Casa di Cura Città di Udine (P. Venturini, F. Picco), Liguria Arenzano (R. Griffo, A. Camerini), Chierchia, Genova Ospedali Civili (S., Mazzantini, S., Torre), F., Spirito, Genova Ospedali Galliera (P., Derchi, G., Delfino), L., Genova-Sestri Ponente (S. Domenicucci, L. Pizzorno), Località S. Caterina-Sarzana (G. Filorizzo, D. Bertoli), Rapallo (G. Gigli, S. Orlandi), Gentile), Sestri Levante (A., Emilia Romagna Bentivoglio (G. Di Pasquale, R. Vandelli), Bologna Cardiologia Tiarini-Corticella (F. Naccarella, M. Gatti), Forlì (F. Rusticali, G. Morgagni), Modena Medicina d’Urgenza Ospedale Civile S. Agostino (S. Zucchelli, M. Pradelli), Modena U. O. Cardiologia Ospedale Civile S. Agostino (G. R. Zennaro, G. Alfano), Modena, Modena Ospedale Policlinico (M. G., Reggianini, L., Coppi), F., Parma (D. Ardissino, W. Serra), Piacenza (A. Capucci, F. Passerini), Riccione (L. Rusconi, P. Del Corso), Piovaccari, Rimini (G., Bologna, F., Caccamo), L., Gambarati), Scandiano (G., Bernardi, Toscana Castelnuovo Garfagnana (D., Mariani, P. R., Volterrani), C., Cosmi), Cortona (F., Empoli (V. Mazzoni, F. Venturi), Firenze Divisione di Cardiologia A. O. Careggi (D. Antoniucci, G. Moschi), Zuppiroli, Firenze U. O. Cardiologia 3 A. O. Careggi (A., Pieri, F., Beligni), C., Firenze U. O. Cardiologia 2 A. O. Careggi (M. Ciaccheri, G. Castelli), Santoro, Firenze Nuovo Ospedale San Giovanni di Dio (G. M., Minneci, C., Sulla), A., Firenze P. O. di Camerata (F. Marchi, G. Zambaldi), Fucecchio (A. Zipoli, A. Geri Brandinelli), Grosseto (S. Severi, G. Miracapillo), Pesola, Lido di Camaiore (A., Comella, A., Magnacca), M., Lucca (E. Nannini, A. Boni), Mantini, Montevarchi (G., Bongini, M., Palmerini), L., Vergoni, Pescia (W., Italiani, G., Di Marco), S., Pisa A. O. Pisana (M. De Tommasi, A. M. Paci), Pontedera (G. Tartarini, B. Reisenhofer), Umbria Città di Castello (M. Cocchieri, D. Severini), Foligno (L. Meniconi, U. Gasperini), Ambrosio, Perugia (G., Alunni, G., Murrone), A., Spoleto (G. Maragoni, G. Bardelli), Mocchegiani, Marche Ancona Centro Cardiologia Ambulatoriale G. M. Lancisi (R., Pasetti, L., Budini), A., Ancona Divisione di Cardiologia G. M. Lancisi (G. Perna, D. Gabrielli), Russo, Ancona Geriatrico Sestilli-INRCA IRCCS (P., Testarmata, P., Antonicelli), R., Camerino (R. Amici, B. Coderoni), Lazio Albano Laziale (G. Ruggeri, P. Midi), Frascati (G. Giorgi, F. Comito), Frosinone (G. Faticanti, F. Qualandri), Grottaferrata (D. Galileo Faroni, C. Romaniello), Roma INRCA (F. Leggio, D. del Sindaco), Majid Tamiz, Roma C. Forlanini (A., Avallone, A., Suglia), F., Roma Cristo Re (V. Baldo, E. Baldo), Roma I U. O. Cardiologia San Camillo (E. Giovannini, G. Pulignano), Roma II Divisione di Cardiologia con UTIC San Camillo (S. F. Vajola, E. Picchio), Tanzi, Roma Serv. Centr. Cardiologia-PS Cardiologico San Camillo (P., Pozzar, F., Terranova), A., Santini, Roma San Filippo Neri (M., Ansalone, G., Magris), B., Boccanelli, Roma San Giovanni (A., Cacciatore, G., Bottero), G., Palamara, Roma Sandro Pertini (A., Valtorta, C., Salustri), A., Roma S. Andrea (M. Volpe, L. De Biase), Gaspardone, Roma S. Eugenio (A., Amaddeo, F., Barbato), G., Ceci, Roma Santo Spirito (V., Aspromonte, N., Chiera), A., Scabbia, Viterbo (E. V., Pontillo, D., Castellani), R., Abruzzo Popoli (C. Frattaroli, A. Mariani), De Simone, Vasto (G., Levantesi, G., Di Marco), G., Molise Larino Medicina Generale-U. O. Geriatria (F. Porfilio, A. Pasquale Potena), Staniscia, Termoli (D., Colonna, N., Montano), A., Mininni, Campania Napoli Divisione di Cardiologia A. O. V. Monaldi (N., Miceli, D., Scherillo), M., Napoli I Divisione Med-Centro Diagnosi e Cura SCC A. O. V. Monaldi (P. Sensale, O. Maiolica), Napoli Medicina Incurabili (M. Visconti, A. Costa), Napoli Cardiologia San Gennaro (P. Capogrosso, A. Somelli), Vergara, Nola U. O. Cardiologia e UTIC P. O. Maria della Pietà (G., Napolitano, F., Provvisiero), P., Oliveto Citra (G. D’Angelo, P. Bottiglieri), Puglia Bari (G. Antonelli, N. Ciriello), Ignone, Brindisi (G., Angelini, E., Andriulo), C., Casarano (G. Pettinati, F. De Santis), Francavilla Fontana (V. Cito, F. Cocco), Galatina (F. Daniele, A. Zecca), Gallipoli (F. Cavalieri, C. Picani), Lecce Vito Fazzi (F. Magliari, A. De Giorgi), Santoro), Mesagne (V., San Pietro Vernotico (S. Pede, A. Renna), Scorrano (E. De Lorenzi, O. De Donno), Baldi, Taranto S. S. Annunziata (N., Polimeni, G., Russo), V. A., Tricase (A. Galati, R. Mangia), Basilicata Policoro (B. D’Alessandro, L. Truncellito), Calabria Belvedere Marittimo (F. P. Cariello, F. Rosselli), Catanzaro U. O. Cardiologia Policlinico (G. Borrello, M. Affinita), Catanzaro U. O. Malattie Cardiovascolari Policlinico (F. Perticone, C. Cloro), Sollazzo, Cetraro (G., Matta, M., Lopresti), Venneri, Cosenza Cardiologia Annunziata (N., Misuraca, G., Caporale), R., Cosenza Medicina Annunziata (A. Noto, P. Chiappetta), Tassone), Reggio Calabria E. Morelli (F., Salituri), Rossano (S., Iannopollo, Siderno (M., Errigo, C., Marando), G., Trebisacce (L. Donnangelo, G. Meringolo), Canonico), Sicilia Avola (G., Carini, Catania Cannizzaro (V., Coco, R., Franco), M., Catania Cardiochirurgia Ferrarotto (M. Abbate, G. Leonardi), Messina Papardo (R. Grassi, G. Di Tano), Consolo), Messina Piemonte (G., Coglitore, Messina (S., Cento, D., De Gregorio), C., Palermo Casa del Sole Lanza di Trabia (V. Sperandeo, M. Mongiovì), Palermo Buccheri La Ferla FBF (A. Castello, A. M. Schillaci), Palermo Civico e Benfratelli (E. D’Antonio, U. Mirto), Di Pasquale), Palermo G. F. Ingrassia (P., Palermo V. Cervello (A. Canonico, M. Floresta), Battaglia, Palermo P. O. Villa Sofia (A., Ingrillì, F., Cirrincione), V., Piazza Armerina M. Chiello (B. Aloisi, A. Cavallaro), Braschi, Trapani (G. B., Ledda, G., Rizzo), C., Sanna, Sardegna Cagliari San Michele Brotzu (A., Porcu, M., Salis), S., Lai, Cagliari SS. Trinità (C., Pili, G., Piras), S., Iglesias (E. Spiga, G. Pes), Nuoro (G. Mureddu, I. Maoddi), and Sassari SS. Annunziata (P. Terrosu, F. Uras).

Subjects
Adult, Heart Failure, Male, Dose-Response Relationship, Drug, Digitalis Glycosides, Middle Aged, Prognosis, Risk Assessment, Severity of Illness Index, Survival Analysis, Drug Administration Schedule, Drug Utilization, Treatment Outcome, Italy, Atrial Fibrillation, Heart Function Tests, Multivariate Analysis, Ambulatory Care, Confidence Intervals, Odds Ratio, Humans, Female, Registries, Aged, Retrospective Studies
Abstract

Since the large multicenter DIG trial has shown no effects of digitalis on the all-cause mortality of patients with chronic heart failure (HF), the broad prescription of this drug in patients with HF appears to be at the very least, questionable. The aims of this study were: to analyze prescription patterns of digitalis, from 1995 to 2000, in a large group of outpatients with HF; to analyze the independent predictors of digitalis prescription and to evaluate the impact of the results of the DIG trial on the prescription rate of this drug.From 1995 to 2000, 11 070 HF outpatients (mean age 64 +/- 12 years, ejection fraction 35 +/- 12%) were enrolled in a large Italian database.Out of 11 070 patients, 7198 (65%) were treated with digitalis. At multivariate analysis, the following variables were independently associated with digitalis prescription; atrial fibrillation (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.9-3.8), ejection fraction30% (OR 1.7, 95% CI 1.5-1.9), NYHA class III-IV vs II-III (OR 1.3, 95% CI 1.2-1.5), admission for HF during the previous year (OR 1.4, 95% CI 1.2-1.5). After the publication of the DIG trial, there was a significant reduction in the rate of digitalis prescription: the percentage of patients taking digitalis fell from 68% in 1996-1997 to 61% in 1998-1999 (p0.001).Over 60% of Italian outpatients with HF were treated with digitalis; as expected, patients with a low ejection fraction, atrial fibrillation and in a more advanced stage of HF are more likely to receive this drug. Finally, after the publication of the DIG trial, the rate of digitalis prescription significantly decreased.

Published
2004

11. Immunotoxicity and Sensitizing Capacity of Metal Compounds Depend on Speciation

Author

Di Gioacchino, M., Verna, N., Di Giampaolo, L., Di Claudio, F., Turi, M.C., Perrone, A., Petrarca, C., Mariani-Costantini, R., Sabbioni, E., and Boscolo, P.

Abstract

Immunotoxicity of metal compounds is an issue of great importance due to the recent industrial application of metals with unknown toxicity on the immune system and the discovery of metal intermediary compounds not sufficiently studied yet. In this report we show results of our study on the immunotoxicity of the following metals: the Platinum group elements (Platinum, Palladium, Rhodium), Titanium and Arsenic. We applied functional and non functional assays and investigated both innate and adaptive immune systems, in particular, cell proliferation, cytokine production by PBMCs and O-2production by neutrophils. We obtained the following results: only some Ti compounds (Titanocene, Ti ascorbate and Ti oxalate) show immunotoxicity. Trivalent As compounds (Sodium arsenite and tetraphenyl arsonium chloride) are more immunotoxic than the other investigated As compounds. Genotoxicity of Pt group compounds is in the following order: Pt < Rh < Pd. Immunotoxicity of Pt group compounds is in the following order: Pd < Pt < Rh. Lymphocytes and macrophages show a different reaction of neutrophils to metal toxicity. We can conclude that these studies show that metal immunotoxicity depends on speciation. In general speciation provides additional and often essential information in evaluating metal toxicity. However, there are many difficulties in applying speciation in investigating toxico-kinetic aspects to many metals, mainly due to the lack of information about the existence and significance of species and to the lack of analytical methods for measuring species in biological samples.

Published
2007
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12. Gastric adenomas: relationship between clinicopathological findings, Helicobacter pyloriinfection, APC mutations and COX-2 expression

Author

Rocco, A., Caruso, R., Toracchio, S., Rigoli, L., Verginelli, F., Catalano, T., Neri, M., Curia, M.C., Ottini, L., Agnese, V., Bazan, V., Russo, A., Pantuso, G., Colucci, G., Mariani-Costantini, R., and Nardone, G.

Abstract

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pyloriinfection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pyloriinfection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269–1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES1. Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development.

Published
2006
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13. Patterns of K-rasmutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin

Author

Bishehsari, F., Mahdavinia, M., Malekzadeh, R., Verginelli, F., Catalano, T., Sotoudeh, M., Bazan, V., Agnese, V., Esposito, D.L., De Lellis, L., Semeraro, D., Colucci, G., Hormazdi, M., Rakhshani, N., Cama, A., Piantelli, M., Iacobelli, S., Russo, A., and Mariani-Costantini, R.

Abstract

K-rasmutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different.

Published
2006
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14. NK‐active cytokines IL‐2, IL‐12, and IL‐15 selectively modulate specific protein kinase C (PKC) isoforms in primary human NK cells

Author

Vitale, Marco, Bassini, Alessandra, Secchiero, Paola, Mirandola, Prisco, Ponti, Cristina, Zamai, Loris, Mariani, Adriana R., Falconi, Mirella, and Azzali, Giacomo

Abstract

Natural killer (NK) cell function is largely modulated by growth factors and cytokines. In particular, interleukin (IL)‐2, IL‐12, and IL‐15 have major effects on the proliferative and cytotoxic activities of NK cells against tumor and virus‐infected cells. It is thought that the members of the protein kinase C (PKC) family of serine/threonine kinases play an important role in mediating the pleiotropic effects of cytokines on their target cells. We have investigated the downstream effects generated in purified human NK cells by IL‐2, IL‐12, and IL‐15 on PKCα and PKCϵ—a canonical and a novel isoform of PKC, respectively. By means of Western blotting, PKC activity assays, and immunofluorescence performed on highly purified preparations of primary human NK cells, we demonstrate that: 1) the three cytokines have similar effects on PKCα and PKCϵ activities; 2) whereas PKCϵ activity is induced by cytokine stimulation, PKCα activity is inhibited; and 3) both the induction of PKCϵ and the inhibition of PKCα functional activity are relatively early events in NK cells, while longer cytokine stimulations do not generate significant variations in enzyme activity, suggesting that the activation of both the canonical and novel isoforms of PKC are events required in the early phases of cytokine‐induced NK cell stimulation. Anat Rec 266:87–92, 2002. © 2002 Wiley‐Liss, Inc.

Published
2002
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15. Apoptotic pathways depend on the target enzymatic activity and not on the triggering agent

Author

Luchetti, F., Mariani, A. R., Columbaro, M., di Baldassarre, A., Cinti, C., and Falcieri, E.

Abstract

Molt‐4 human leukemia cells were triggered to apoptosis by various agents with different mechanisms of action. Staurosporine, a protein kinase C (PKC) inhibitor; camptothecin, a topoisomerase I blocking drug; and tiazo‐furin, an inhibitor of inosine 5′‐phosphate dehydrogenase (IMPDH), were used. Ultrastructural analysis showed morphologic changes characteristic of apoptosis that were very similar for all three agents. Nevertheless, DNA oligonucleosomic fragmentation was not detectable by agarose gel electrophoresis. However, a genomic DNA cleavage appeared after pulse‐field gel electrophoresis (PFGE) in cells treated with these agents for 24 h. Furthermore, in situ nick translation (NT) showed a finely spotted nuclear labelling in staurosporine‐treated cells and a compact fluorescence after camptothecin incubation. In tiazofurin‐treated cells an intermediate pattern was found. Therefore, apoptotic agents with different mechanisms of action induced the formation of large genomic DNA fragments and very similar ultrastructural changes. Therefore, both phenomena and the closely related apoptosis progression depend on target cell machinery and not on the triggering agent.

Published
1999
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16. In situ detection of c-myc mRNA in adenocarcinomas, adenomas, and mucosa of human colon.

Author

Mariani-Costantini, R, Theillet, C, Hutzell, P, Merlo, G, Schlom, J, and Callahan, R

Abstract

We used a sensitive RNA:RNA in situ hybridization technique to study steady-state levels of c-myc proto-oncogene mRNA in primary human colon adenocarcinomas, villous adenomas, and normal mucosa samples. Frozen tissue sections, fixed in 4% buffered paraformaldehyde, were hybridized to 35S-labeled anti-sense transcripts of a c-myc clone and processed for autoradiography. The specificity of the hybridization was controlled by using 35S-labeled plasmid transcripts as a negative control, while RNA preservation in the tissue sample was assessed by using 35S-labeled anti-sense transcripts of a murine 28S rRNA clone. c-myc RNA was detectable in all the carcinomas (eight) and villous adenomas (four), but steady-state levels varied from high to low in different tumors with similar histology. Low levels of c-myc RNA were detected in epithelial stem cells of some of the normal mucosa samples (five). No genetic alterations of the c-myc locus were found by Southern analysis of DNAs extracted from the carcinomas.

Published
1989
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18. Selective Hypermethylation of Transcribed Nucleosomal DNA by Sodium Butyrate

Author

Boffa, Lidia C., Mariani, Maria R., and Parker, M.Iqbal

Abstract

Previous studies have shown that treatment of cultured fibroblasts with millimolar concentrations of sodium butyrate results in increased methylation of cytosine residues in DNA. In this study, active nucleosomes were fractionated from the inactive ones by organomercurial agarose column chromatography. DNA in each fraction was hydrolyzed to its constituent bases and subjected to HPLC analysis in order to determine the 5-methylcytosine content. In control cells, the active nucleosomal DNA was hypomethylated (0.97 ± 0.27% 5-methylcytosine) when compared with the inactive DNA fraction (1.61 ± 0.15%). This result was not unexpected since DNA hypermethylation is generally associated with gene inactivation. Treatment of cells with sodium butyrate, however, resulted in increased methylation of the active nucleosomal DNA such that it was comparable to that of the inactive fraction of control cells (1.73 ± 0.02% 5-methylcytosine). A much smaller increase in 5-methylcytosine content was detected in the inactive DNA fraction of sodium butyrate-treated cells (from 1.61 to 1.89%). Removal of the sodium butyrate followed by a chase in butyrate-free medium for up to 120 h failed to reverse the butyrate-induced hypermethylation. Reversal was achieved only after continuous culture in butyrate-free medium for 10 days.

Published
1994
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19. Kinetics of in vitro natural killer activity against K562 cells as detected by flow cytometry

Author

Zamai, Loris, Mariani, Adriana R., Zauli, Giorgio, Rodella, Luigi, Rezzani, Rita, and Manzoli, Francesco A.

Abstract

Natural killer (NK) cells bind to K562 tumor target cells in vitro and kill them. The binding and cytotoxic activities of NK cells are tightly related to each other: degranulation of the cytotoxic effector is the basis for target cell damage and a consequence of effector-target recognition and binding. However, the two phases of NK activity, binding and killing, have always been measured separately by various methodologies and under different experimental conditions, because of the lack of a comprehensive methodology able to measure both of them at one time. Here we describe the simultaneous measurement of the binding and killing activities against K562 of resting and cytokine (IL-2 or IL-12)–stimulated NK cells by flow cytometry. NK, K562 and conjugates can be identified and measured by flow cytometry on the basis of NK mAb staining and target cells autofluorescence (Binding Plot). Within each population of the binding plot, killed targets can be identified and measured by their scatter characteristics (Cytotoxicity Plot). We show that i) the conjugate formation is enhanced in cytokine-stimulated cells, even at relatively short co-incubation times; ii) the conjugate release is also accelerated by cytokines; iii) the conjugate release is always quicker than the induction of the morphological changes in the target cell that generate its modified scattering properties. Cytometry 32:280–285, 1998. © 1998 Wiley-Liss, Inc.

Published
1998
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20. Apoptosis induced by NK cells is modulated by the NK-active cytokines IL-2 and IL-12.

Author

Rodella, L, Rezzani, R, Zauli, G, Mariani, A R, Rizzoli, R, and Vitale, M

Abstract

NK cells kill sensitive targets via exocytosis of cytoplasmic granules containing membrane damaging perforins and DNA damaging granzymes. Therefore, the target cell can either die by necrosis or by apoptosis. A third, non-secretory, mechanism of killing mediated by Fas-FasL interaction can be used by activated NK cells to kill Fas+ targets. Here, we have studied the modulation exerted by two NK active cytokines, IL-2 and IL-12, on the apoptosis-inducing activity of NK cells in NK-sensitive Fas- K562 and NK-insensitive Fas+ Raji cells. Our results show that apoptosis is preferentially induced at low target:effector ratios. Resting NK cells virtually do not induce apoptosis in target cells while IL-2 stimulation endows NK cells with the capacity of inducing apoptosis and IL-12 further enhances this effect against both targets. Finally, we demonstrate that cytokine-stimulated NK cells use both granzyme and Fas-FasL pathways of apoptosis induction.

Published
1998
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21. Age-dependent decreases of NK cell phosphoinositide turnover during spontaneous but not Fc-mediated cytolytic activity.

Author

Mariani, E, Mariani, A R, Meneghetti, A, Tarozzi, A, Cocco, L, and Facchini, A

Abstract

The progressive increase in the number of peripheral NK cells found in the elderly does not correlate with a corresponding increase in lytic activity. On the contrary, a decreased function of circulating NK cells purified from old subjects was observed on a per cell basis. Most of the studies on NK cells have focused on late events such as lytic activity. In view of this, little is currently known about the modification of the early signalling pathways of NK cells in elderly people. This study investigated whether the modification of NK lytic activity could be related to differences in the metabolic pattern of activation of these cells in the elderly. NK cells were negatively purified by immunomagnetic depletion from the peripheral blood of selected old and young healthy subjects. Hydrolysis of inositol phospholipids was measured following incubation with K562 target cells and/or CD16 mAb for different times. Our data show that there is a pronounced age-related decrease in the ability to generate total inositol monophosphates and, particularly, inositol trisphosphates by NK cells following K562 stimulation (spontaneous cytolytic activity) together with an attenuated and delayed hydrolysis of phosphatidylinositol bisphosphate, while phosphoinositide turnover is preserved following Fc triggering (antibody-dependent cell-mediated cytotoxicity). These results confirm that, also in old subjects, different biochemical pathways of activation are involved in NK cells when target or antibody-mediated triggering occurs and may aid the development of experimental and therapeutic strategies to counteract declines in cell mediated immune functions associated to advancing age.

Published
1998
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22. Ancestry of a human endogenous retrovirus family

Author

Mariani-Costantini, R, Horn, T M, and Callahan, R

Abstract

The human endogenous retrovirus type II (HERVII) family of HERV genomes has been found by Southern blot analysis to be characteristic of humans, apes, and Old World monkeys. New World monkeys and prosimians lack HERVII proviral genomes. Cellular DNAs of humans, common chimpanzees, gorillas, and orangutans, but not lesser ape lar gibbons, appear to contain the HERVII-related HLM-2 proviral genome integrated at the same site (HLM-2 maps to human chromosome 1). This suggests that the ancestral HERVII retrovirus(es) entered the genomes of Old World anthropoids by infection after the divergence of New World monkeys (platyrrhines) but before the evolutionary radiation of large hominoids.

Published
1989
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23. Analysis of adenomatous polyposis coli gene in thyroid tumours

Author

Colletta, G, Sciacchitano, S, Palmirotta, R, Ranieri, A, Zanella, E, Cama, A, Mariani Costantini, R, Battista, P, and Pontecorvi, A

Abstract

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma.

Published
1994
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24. Origin and Gender Determination of Dried Blood on a Statue of the Virgin Mary

Author

Palmirotta, R, Verginelli, F, Cama, A, Mariani-Costantini, R, Frati, L, and Battista, P

Abstract

In Italy, blood exudation from objects of worship recurs frequently in ancient chronicles and literature, in popular beliefs, and even in modern mass-media reports. This phenomenon, that was associated with epochal or catastrophic events, has roots that reach classical antiquity. In the last few years, several events connected with the detection of bloody “tears” on statues of the Virgin Mary required forensic medicine investigations. In the present report we describe genetic investigations conducted on dried blood of unknown derivation found on a statuette representing the Virgin Mary. To test the human or animal origin of the blood, we amplified Alu-specific sequences from DNAs obtained from the unknown sample and from humans, large apes, various Old and New World monkeys, a prosimian, mouse, common domestic artiodactyls and chicken. This investigation restricted the range of possible origin of the statue blood to humans, apes and Old World monkeys. To test the male or female origin of the blood, we used a multiplex nested polymerase chain reaction method, that allows the simultaneous amplification of the X-specific locus DXZ4 and of the Y-specific locus SRY. Considering the unlikelihood of an origin from simian Old World primates, the exclusive amplification of the X-specific product from the unknown sample and from human female blood controls, compared to the amplification of distinct X- and Y-specific bands from human male blood controls, strongly supports a human female origin of the statue blood.

Published
1998
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35. Prognostic Impact of Diabetes and Prediabetes on Survival Outcomes in Patients With Chronic Heart Failure: A Post-Hoc Analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial

Author

Marco Dauriz, Giovanni Targher, Pier Luigi Temporelli, Donata Lucci, Lucio Gonzini, Gian Luigi Nicolosi, Roberto Marchioli, Gianni Tognoni, Roberto Latini, Franco Cosmi, Luigi Tavazzi, Aldo Pietro Maggioni, Simona Barlera, Maria Grazia Franzosi, Aldo P. Maggioni, Maurizio Porcu, Salim Yusuf, Fulvio Camerini, Jay N. Cohn, Adriano Decarli, Bertram Pitt, Peter Sleight, Philip A. Poole‐Wilson, Enrico Geraci, Marino Scherillo, Gianna Fabbri, Barbara Bartolomei, Daniele Bertoli, Franco Cobelli, Claudio Fresco, Antonietta Ledda, Giacomo Levantesi, Cristina Opasich, Franco Rusconi, Gianfranco Sinagra, Fabio Turazza, Alberto Volpi, Martina Ceseri, Gianluca Alongi, Antonio Atzori, Filippo Bambi, Desiree Bastarolo, Francesca Bianchini, Iacopo Cangioli, Vittoriana Canu, Concetta Caporusso, Gabriele Cenni, Laura Cintelli, Michele Cocchio, Alessia Confente, Eva Fenicia, Giorgio Friso, Marco Gianfriddo, Gianluca Grilli, Beatrice Lazzaro, Giuseppe Lonardo, Alessia Luise, Rachele Nota, Mariaelena Orlando, Rosaria Petrolo, Chiara Pierattini, Valeria Pierota, Alessandro Provenzani, Velia Quartuccio, Anna Ragno, Chiara Serio, Alvise Spolaor, Arianna Tafi, Elisa Tellaroli, Stefano Ghio, Elisa Ghizzardi, Serge Masson, Lella Crociati, Maria Teresa La Rovere, Ugo Corrà, Andrea Finzi, Marco Gorini, Valentina Milani, Giampietro Orsini, Elisa Bianchini, Silvia Cabiddu, Ilaria Cangioli, Laura Cipressa, Maria Lucia Cipressa, Giuseppina Di Bitetto, Barbara Ferri, Luisa Galbiati, Andrea Lorimer, Carla Pera, Paola Priami, Antonella Vasamì, T. Moccetti, M.G. Rossi, E. Pasotti, F. Vaghi, P. Roncarolo, M.T. Zunino, F. Matta, E. Actis Perinetto, F. Gaita, G. Azzaro, M. Zanetta, A.M. Paino, U. Parravicini, D. Vegis, R. Conte, P. Ferraro, A. De Bernardi, S. Morelloni, M. Fagnani, P. Greco Lucchina, L. Montagna, E. Bellone, D. Sappè, F. Ferraro, M. Delucchi, S.G. Reynaud, M. Dore, A. La Brocca, N. Massobrio, L. Bo, R. Trinchero, M. Imazio, G. Brocchi, A. Nejrotti, L. Rissone, S. Gabasio, C. Zocchi, S. Randazzo, A. Crenna, P. Giannuzzi, E. Bonanomi, A. Mezzani, M. De Marchi, G. Begliuomini, C.A. Gianonatti, A. Gavazzi, A. Grosu, L. Dei Cas, S. Nodari, P. Garyfallidis, A. Bertoletti, C. Bonifazi, S. Arisi, F. Mascaro, M. Fraccarollo, S. Dell'Orto, M. Sfolcini, F. Bortolini, D. Raccagni, A. Turelli, M. Santarone, E. Miglierina, L. Sormani, R. Jemoli, F. Tettamanti, S. Pirelli, C. Bianchi, S. Verde, M. Mariani, V. Ziacchi, A. Ferrazza, A. Russo, M. Bortolotti, G.F. Pasini, A. Volpi, K.N. Jones, D. Cuzzucrea, G. Gullace, C. Carbone, A. Granata, S. De Servi, G. Del Rosso, C. Inserra, E. Renaldini, C. Zappa, M. Moretti, R. Zanini, M. Ferrari, E. Moroni, A. Cei, C. Lissi, E. Dovico, C. Fiorentini, P. Palermo, B. Brusoni, M. Negrini, J. Heyman, G.B. Danzi, A. Finzi, M. Frigerio, F. Turazza, L. Beretta, A. Sachero, F. Casazza, L. Squadroni, F. Lombardi, L. Marano, A. Margonato, G. Fragasso, O.C. Febo, E. Aiolfi, F. Olmetti, A. Grieco, V. Antonazzo, G. Specchia, A. Mortara, F. Robustelli, M.G. Songini, C. Schweiger, A. Frisinghelli, M. Palvarini, C. Campana, L. Scelsi, N. Ajmone Marsan, F. Cobelli, A. Gualco, C. Opasich, S. De Feo, R. Mazzucco, M.A. Iannone, T. Diaco, D. Zaniboni, G. Milanesi, D. Nassiacos, S. Meloni, P. Giani, T. Nicoli, C. Malinverni, A. Gusmini, L. Pozzoni, G. Bisiani, P. Margaroli, A. Schizzarotto, A. Daverio, G. Occhi, N. Partesana, P. Bandini, M.G. Rosella, S. Giustiniani, G. Cucchi, R. Pedretti, R. Raimondo, R. Vaninetti, A. Fedele, I. Ghezzi, E. Rezzonico, J.A. Salerno Uriarte, F. Morandi, F. Salvucci, C. Valenti, G. Graziano, M. Romanò, C. Cimminiello, I. Mangone, M. Lombardo, P. Quorso, G. Marinoni, M. Breghi, M. Erckert, A. Dienstl, G. Mirante Marini, C. Stefenelli, G. Cioffi, E. Buczkowska, A. Bonanome, F. Bazzanini, L. Parissenti, C. Serafini, G. Catania, L. Tarantini, G. Rigatelli, S. Boni, A. Pasini, E. Masini, A.A. Zampiero, M. Zanchetta, L. Franceschetto, P. Delise, C. Marcon, A. Sacchetta, L. Borgese, L. Artusi, P. Casolino, F. Corbara, A. Banzato, M. Barbiero, M.P. Aldegheri, R. Bazzucco, G. Crivellenti, A. Raviele, C. Zanella, P. Pascotto, P. Sarto, S. Milan, E. Barbieri, P. Girardi, W. Dalla Villa, J. Dalle Mule, M.L. Di Sipio, R. Cazzin, D. Milan, P. Zonzin, M. Carraro, R. Rossi, E. Carbonieri, I. Rossi, P. Stritoni, P. Meneghetti, G. Risica, P.L. Tenderini, C. Vassanelli, L. Zanolla, G. Perini, G. Brighetti, R. Chiozza, G. Giuliano, R. Gortan, R. Cesanelli, G.L. Nicolosi, R. Piazza, L. Mos, O. Vriz, D. Pavan, G. Pascottini, E. Alberti, M. Werren, L. Solinas, G. Sinagra, F. Longaro, P. Fioretti, M.C. Albanese, D. Miani, R. Gianrossi, A. Pende, P. Rubartelli, O. Magaia, S. Domenicucci, D. Caruso, A.S. Faraguti, L. Magliani, F. Miccoli, G. Guglielmino, D. Bertoli, A. Cantarelli, S. Orlandi, A. Vallebona, A. Pozzati, G. Brega, L.G. Pancaldi, R. Vandelli, S. Urbinati, M.G. Poci, M. Zoli, G.M. Costa, U. Guiducci, G. Zobbi, F. Tartagni, A. Tisselli, A. Gentili, P. Pieri, E. Cagnetta, S. Bendinelli, A. Barbieri, R. Conti, R. Ferrari, F. Merlini, A. Fucili, P. Moruzzi, E. Buia, M. Galvani, D. Ferrini, G. Baggioni, P. Yiannacopulu, G. Canè, A. Bonfiglioli, R. Zandomeneghi, L. Brugioni, A. Giannini, R. Di Ruvo, M. Giuliani, L. Rusconi, P. Del Corso, G. Piovaccari, F. Bologna, P. Venturi, F. Melandri, E. Bagni, L. Bolognese, R. Perticucci, A. Zuppiroli, M. Nannini, N. Consoli, P. Petrone, C. Pipitò, L. Colombi, D. Bernardi, P.R. Mariani, R. Testa, F. Mazzinghi, F. Cosmi, D. Cosmi, A. Zipoli, A. Cecchi, G. Castelli, M. Ciaccheri, F. Mori, F. Pieri, P. Valoti, D. Chiarantini, G.M. Santoro, C. Minneci, F. Marchi, M. Milli, G. Zambaldi, A.A. Brandinelli Geri, M. Cipriani, M. Alessandri, S. Severi, S. Stefanelli, A. Comella, R. Poddighe, A. Digiorgio, M. Carluccio, S. Berti, A. Rizza, V. Bonatti, V. Molendi, A. Brancato, N. D'Aprile, G. Giappichini, S. Del Vecchio, G. Mantini, F. De Tommasi, G. Meucci, M. Cordoni, S. Bechi, L. Barsotti, P. Baldini, M. Romei, G. Scopelliti, G. Lauri, F. Pestelli, F. Furiozzi, M. Cocchieri, D. Severini, F. Patriarchi, P. Chiocchi, M. Buccolieri, S. Martinelli, A. Wee, F. Angelici, M. Bernardinangeli, G. Proietti, B. Biscottini, R. Panciarola, L. Marinacci, G.P. Perna, D. Gabrielli, A. Moraca, L. Moretti, L. Partemi, G. Gregori, R. Amici, G. Patteri, P. Capone, E. Savini, G.L. Morgagni, L. Paccaloni, F. Pezzuoli, S. Carincola, S. Papi, S. De Crescentini, P. Gerardi, P. Midi, E. Gallenzi, G. Pajes, C. Mancone, V. Di Spirito, M. Di Gennaro, S. Calcagno, S. Toscano, S. Antonicoli, F. Carta, G. Giorgi, F. Comito, E. Daniele, O. Ciarla, P.G. Gelfo, A. Acquaviva, D. Testa, G. Testa, F.A. Pagliaro, F. Russo, F. Vetta, I. Marchese, G. Di Sciascio, A. D'Ambrosio, F. Leggio, D. Del Sindaco, A. Lacchè, A. Avallone, M.P. Risa, P. Azzolini, E. Baldo, E. Giovannini, G. Pulignano, C. Tondo, E. Picchio, E. ani, P. Tanzi, F. Pozzar, F. Farnetti, M. Azzarito, M. Santini, A. Varveri, G. Ferraiuolo, C. Valtorta, A. Gaspardone, G. Barbato, V. Ceci, N. Aspromonte, F. Bellocci, C. Colizzi, F. Fedele, F.I. Perez, A. Galati, A. Rossetti, A. Mainella, D. etta, C. Matteucci, G. Busi, A. De Angelis, G. Farina, A. Granatelli, F. Leone, F. Frasca, R. Di Giovambattista, G. Castellani, G. Massaro, G. Mastrogiuseppe, A. Vacri, F. De Sanctis, M. Cioli, S. Di Luzio, C. Napoletano, L.L. Piccioni, G. De Simone, A. Ottaviano, V. Mazza, C. Spedaliere, D. Staniscia, E. Calgione, G. De Marco, T. Chiacchio, T. Di Napoli, S. Romanzi, G. Salvatore, P. Golino, A. Palermo, F. Mascia, A. Vetrano, A. Vinciguerra, L. Caliendo, R. Longobardi, G. De Caro, R. Di Nola, F. Piemonte, D. Prinzi, P. De Rosa, V. De Rosa, F. Riello, V. Capuano, G. Vecchio, M. Landi, S. Amato, M. Garofalo, M. D'Avino, P. Sensale, O. Maiolica, R. Santoro, P. Caso, D. Miceli, N. Maurea, U. Bianchi, C. Crispo, M. Chiariello, P. Perrone Filardi, L. Russo, N. Capuano, G. Ungaro, G. Vergara, F. Scafuro, G. D'Angelo, C. Campaniello, P. Bottiglieri, A. Volpe, R. Battista, L. De Risi, G. Cardillo, G. Sibilio, A.P. Marino, F. Silvestri, P. Predotti, A. Iervoglini, C. De Matteis, P. Sarnicola, M.M. Matarazzo, S. Baldi, V. Iuliano, C. Astarita, P. Cuccaro, A. Liguori, G. Liguori, G. Gregorio, L. Petraglia, G. Antonelli, G. Amodio, I. De Luca, D. Traversa, G. Franchini, M.L. Lenti, D. Cavallari, C. D'Agostino, G. Scalera, C.M. Altamura, M. Russo, A.R. Mascolo, G. Pettinati, S.A. Ciricugno, D. Scrutinio, A. Passantino, D. Mastrangelo, A. Di Masi, R. De Carne, M. Cannone, F. Dibiase, M. Pensato, F. Loliva, F. Trapani, I. Panettieri, L. Leone, M. Di Biase, M. Carrone, V. Gallone, F. Cocco, M. Costantini, C. Tritto, F. Cavalieri, L. Stella, F. Magliari, M. Callerame, A. De Giorgi, L. Pellegrino, M. Correra, V. Portulano, G.L. Nisi, G. Grassi, E. Cristallo, D. De Laura, C. Salerno, R. Fanelli, M. Villella, S. Pede, A. Renna, E. De Lorenzi, L. Urso, V. Lenti, A. Peluso, N. Baldi, G. Polimeni, P. Palma, R. Lauletta, E. Tagliamonte, T. Cirillo, B. Silvestri, G. Centonze, B. D'Alessandro, L. Truncellito, D. Mecca, M.A. Petruzzi, R.O.M. Coviello, A. Lopizzo, M. telli, S. Barbuzzi, S. Gubelli, G. Germinario, N. Cosentino, A. Mingrone, R. Vico, G. Borrello, M.L. Mazza, R. Cimino, D. Galasso, F. Cassadonte, U. Talarico, F. Perticone, S. Cassano, F. Catapano, S. Calemme, E. Feraco, C. Cloro, G. Misuraca, R. Caporale, L. Vigna, V. Spagnuolo, F. De Rosa, G. Spadafora, G. Zampaglione, R. Russo, F.A. Schipani, A.F. Ferragina, D. Stranieri, G. Musca, C. Carpino, P. Bencardino, F. Raimondo, D. Musacchio, G. Pulitanò, A. Ruggeri, A. Provenzano, S. Salituri, M. Musolino, S. Calandruccio, A. Marrari, E. Tripodi, R. Scali, L. Anastasio, A. Arone, P. Aragona, L. Donnangelo, M.G.A. Comito, F. Bilotta, I. Vaccaro, R. Rametta, V. Ventura, A. Bonvegna, A. Alì, C. Cinnirella, M. Raineri, F. Pompeo, N. Cascio Ingurgio, V. Carini, R. Coco, G. Giunta, G. Leonardi, V. Randazzo, V. Di Blasi, C. Tamburino, G. Russo, S. Mangiameli, R. Cardillo, D. Castelli, V. Inserra, A. Arena, M.M. Gulizia, S. Raciti, G. Rapisarda, R. Romano, P. Prestifilippo, G.B. Braschi, G. Ledda, R. Terrazzino, M. De Caro, G. Scilabra, B. agnino, R. Grassi, G. Di Tano, G.F. Scimone, L. Vasquez, C. Coppolino, A. Casale, M. Castelli, G. D'Urso, E. D'Antonio, L. Lo Presti, E. Badalamenti, P. Conti, N. Sanfilippo, V. Cirrincione, M.T. Cinà, G. Cusimano, A. Taormina, P. Giuliano, A. Bajardi, V. Mandalà, A. Canonico, G. Geraci, F.P. Sabella, F. Enia, A.M. Floresta, I. Lo Cascio, D. Gumina, A. Cavallaro, G. Piccione, R. Ferrante, M. Blandino, M.S. Iudicello, E. Mossuti, G. Romano, L. Lombardo, P. Monastra, D. Di Vincenzo, M. Porcu, P. Orrù, F. Muscas, G. Giardina, M. Corda, G. Locci, A. Podda, M. Ledda, P. Siddi, C. Lai, G. Pili, G. Mercuro, G. Mureddu, A. Ganau, G. Meloni, G. Poddighe, G. Sanna, Dauriz, Marco, Targher, Giovanni, Temporelli, Pier Luigi, Lucci, Donata, Gonzini, Lucio, Nicolosi, Gian Luigi, Marchioli, Roberto, Tognoni, Gianni, Latini, Roberto, Cosmi, Franco, Tavazzi, Luigi, Maggioni, Aldo Pietro, on behalf of the GISSI-HF, Investigator, Margonato, Alberto, Moccetti, T., Rossi, M. G., Pasotti, E., Vaghi, F., Roncarolo, P., Zunino, M. T., Matta, F., Actis Perinetto, E., Gaita, F., Azzaro, G., Zanetta, M., Paino, A. M., Parravicini, U., Vegis, D., Conte, R., Ferraro, P., De Bernardi, A., Morelloni, S., Fagnani, M., Greco Lucchina, P., Montagna, L., Bellone, E., Sappè, D., Ferraro, F., Delucchi, M., Reynaud, S. G., Dore, M., La Brocca, A., Massobrio, N., Bo, L., Trinchero, R., Imazio, M., Brocchi, G., Nejrotti, A., Rissone, L., Gabasio, S., Zocchi, C., Randazzo, S., Crenna, A., Giannuzzi, P., Bonanomi, E., Mezzani, A., De Marchi, M., Begliuomini, G., Gianonatti, C. A., Gavazzi, A., Grosu, A., Dei Cas, L., Nodari, S., Garyfallidis, P., Bertoletti, A., Bonifazi, C., Arisi, S., Mascaro, F., Fraccarollo, M., Dell'Orto, S., Sfolcini, M., Bortolini, F., Raccagni, D., Turelli, A., Santarone, M., Miglierina, E., Sormani, L., Jemoli, R., Tettamanti, F., Pirelli, S., Bianchi, C., Verde, S., Mariani, M., Ziacchi, V., Ferrazza, A., Russo, A., Bortolotti, M., Pasini, G. F., Volpi, A., Jones, K. N., Cuzzucrea, D., Gullace, G., Carbone, C., Granata, A., De Servi, S., Del Rosso, G., Inserra, C., Renaldini, E., Zappa, C., Moretti, M., Zanini, R., Ferrari, M., Moroni, E., Cei, A., Lissi, C., Dovico, E., Fiorentini, C., Palermo, P., Brusoni, B., Negrini, M., Heyman, J., Danzi, G. B., Finzi, A., Frigerio, M., Turazza, F., Beretta, L., Sachero, A., Casazza, F., Squadroni, L., Lombardi, F., Marano, L., Margonato, A., Fragasso, G., Febo, O. C., Aiolfi, E., Olmetti, F., Grieco, A., Antonazzo, V., Specchia, G., Mortara, A., Robustelli, F., Songini, M. G., Schweiger, C., Frisinghelli, A., Palvarini, M., Campana, C., Scelsi, L., Ajmone Marsan, N., Cobelli, F., Gualco, A., Opasich, C., De Feo, S., Mazzucco, R., Iannone, M. A., Diaco, T., Zaniboni, D., Milanesi, G., Nassiacos, D., Meloni, S., Giani, P., Nicoli, T., Malinverni, C., Gusmini, A., Pozzoni, L., Bisiani, G., Margaroli, P., Schizzarotto, A., Daverio, A., Occhi, G., Partesana, N., Bandini, P., Rosella, M. G., Giustiniani, S., Cucchi, G., Pedretti, R., Raimondo, R., Vaninetti, R., Fedele, A., Ghezzi, I., Rezzonico, E., Salerno Uriarte, J. A., Morandi, F., Salvucci, F., Valenti, C., Graziano, G., Romanò, M., Cimminiello, C., Mangone, I., Lombardo, M., Quorso, P., Marinoni, G., Breghi, M., Erckert, M., Dienstl, A., Mirante Marini, G., Stefenelli, C., Cioffi, G., Buczkowska, E., Bonanome, A., Bazzanini, F., Parissenti, L., Serafini, C., Catania, G., Tarantini, L., Rigatelli, G., Boni, S., Pasini, A., Masini, E., Zampiero, A. A., Zanchetta, M., Franceschetto, L., Delise, P., Marcon, C., Sacchetta, A., Borgese, L., Artusi, L., Casolino, P., Corbara, F., Banzato, A., Barbiero, M., Aldegheri, M. P., Bazzucco, R., Crivellenti, G., Raviele, A., Zanella, C., Pascotto, P., Sarto, P., Milan, S., Barbieri, E., Girardi, P., Dalla Villa, W., Dalle Mule, J., Di Sipio, M. L., Cazzin, R., Milan, D., Zonzin, P., Carraro, M., Rossi, R., Carbonieri, E., Rossi, I., Stritoni, P., Meneghetti, P., Risica, G., Tenderini, P. L., Vassanelli, C., Zanolla, L., Perini, G., Brighetti, G., Chiozza, R., Giuliano, G., Baldin, M. G., Gortan, R., Cesanelli, R., Nicolosi, G. L., Piazza, R., Mos, L., Vriz, O., Pavan, D., Pascottini, G., Alberti, E., Werren, M., Solinas, L., Sinagra, G., Longaro, F., Fioretti, P., Albanese, M. C., Miani, D., Gianrossi, R., Pende, A., Rubartelli, P., Magaia, O., Domenicucci, S., Caruso, D., Faraguti, A. S., Magliani, L., Miccoli, F., Guglielmino, G., Bertoli, D., Cantarelli, A., Orlandi, S., Vallebona, A., Pozzati, A., Brega, G., Pancaldi, L. G., Vandelli, R., Urbinati, S., Poci, M. G., Zoli, M., Costa, G. M., Guiducci, U., Zobbi, G., Tartagni, F., Tisselli, A., Gentili, A., Pieri, P., Cagnetta, E., Bendinelli, S., Barbieri, A., Conti, R., Ferrari, R., Merlini, F., Fucili, A., Moruzzi, P., Buia, E., Galvani, M., Ferrini, D., Baggioni, G., Yiannacopulu, P., Canè, G., Bonfiglioli, A., Zandomeneghi, R., Brugioni, L., Giannini, A., Di Ruvo, R., Giuliani, M., Rusconi, L., Del Corso, P., Piovaccari, G., Bologna, F., Venturi, P., Melandri, F., Bagni, E., Bolognese, L., Perticucci, R., Zuppiroli, A., Nannini, M., Consoli, N., Petrone, P., Pipitò, C., Colombi, L., Bernardi, D., Mariani, P. R., Testa, R., Mazzinghi, F., Cosmi, F., Cosmi, D., Zipoli, A., Cecchi, A., Castelli, G., Ciaccheri, M., Mori, F., Pieri, F., Valoti, P., Chiarantini, D., Santoro, G. M., Minneci, C., Marchi, F., Milli, M., Zambaldi, G., Brandinelli Geri, A. A., Cipriani, M., Alessandri, M., Severi, S., Stefanelli, S., Comella, A., Poddighe, R., Digiorgio, A., Carluccio, M., Berti, S., Rizza, A., Bonatti, V., Molendi, V., Brancato, A., D'Aprile, N., Giappichini, G., Del Vecchio, S., Mantini, G., De Tommasi, F., Meucci, G., Cordoni, M., Bechi, S., Barsotti, L., Baldini, P., Romei, M., Scopelliti, G., Lauri, G., Pestelli, F., Furiozzi, F., Cocchieri, M., Severini, D., Patriarchi, F., Chiocchi, P., Buccolieri, M., Martinelli, S., Wee, A., Angelici, F., Bernardinangeli, M., Proietti, G., Biscottini, B., Panciarola, R., Marinacci, L., Perna, G. P., Gabrielli, D., Moraca, A., Moretti, L., Partemi, L., Gregori, G., Amici, R., Patteri, G., Capone, P., Savini, E., Morgagni, G. L., Paccaloni, L., Pezzuoli, F., Carincola, S., Papi, S., De Crescentini, S., Gerardi, P., Midi, P., Gallenzi, E., Pajes, G., Mancone, C., Di Spirito, V., Di Gennaro, M., Calcagno, S., Toscano, S., Antonicoli, S., Carta, F., Giorgi, G., Comito, F., Daniele, E., Ciarla, O., Gelfo, P. G., Acquaviva, A., Testa, D., Testa, G., Pagliaro, F. A., Russo, F., Vetta, F., Marchese, I., Di Sciascio, G., D'Ambrosio, A., Leggio, F., Del Sindaco, D., Lacchè, A., Avallone, A., Risa, M. P., Azzolini, P., Baldo, E., Giovannini, E., Pulignano, G., Tondo, C., Picchio, E., Biffani, E., Tanzi, P., Pozzar, F., Farnetti, F., Azzarito, M., Santini, M., Varveri, A., Ferraiuolo, G., Valtorta, C., Gaspardone, A., Barbato, G., Ceci, V., Aspromonte, N., Bellocci, F., Colizzi, C., Fedele, F., Perez, F. I., Galati, A., Rossetti, A., Mainella, A., Ciuffetta, D., Matteucci, C., Busi, G., De Angelis, A., Farina, G., Granatelli, A., Leone, F., Frasca, F., Di Giovambattista, R., Castellani, G., Massaro, G., Mastrogiuseppe, G., Vacri, A., De Sanctis, F., Cioli, M., Di Luzio, S., Napoletano, C., Piccioni, L. L., De Simone, G., Ottaviano, A., Mazza, V., Spedaliere, C., Staniscia, D., Calgione, E., De Marco, G., Chiacchio, T., Di Napoli, T., Romanzi, S., Salvatore, G., Golino, P., Palermo, A., Mascia, F., Vetrano, A., Vinciguerra, A., Caliendo, L., Longobardi, R., De Caro, G., Di Nola, R., Piemonte, F., Prinzi, D., De Rosa, P., De Rosa, V., Riello, F., Capuano, V., Vecchio, G., Landi, M., Amato, S., Garofalo, M., D'Avino, M., Sensale, P., Maiolica, O., Santoro, R., Caso, P., Miceli, D., Maurea, N., Bianchi, U., Crispo, C., Chiariello, M., Perrone Filardi, P., Russo, L., Capuano, N., Ungaro, G., Vergara, G., Scafuro, F., D'Angelo, G., Campaniello, C., Bottiglieri, P., Volpe, A., Battista, R., De Risi, L., Cardillo, G., Sibilio, G., Marino, A. P., Silvestri, F., Predotti, P., Iervoglini, A., De Matteis, C., Sarnicola, P., Matarazzo, M. M., Baldi, S., Iuliano, V., Astarita, C., Cuccaro, P., Liguori, A., Liguori, G., Gregorio, G., Petraglia, L., Antonelli, G., Amodio, G., De Luca, I., Traversa, D., Franchini, G., Lenti, M. L., Cavallari, D., D'Agostino, C., Scalera, G., Altamura, C. M., Russo, M., Mascolo, A. R., Pettinati, G., Ciricugno, S. A., Scrutinio, D., Passantino, A., Mastrangelo, D., Di Masi, A., De Carne, R., Cannone, M., Dibiase, F., Pensato, M., Loliva, F., Trapani, F., Panettieri, I., Leone, L., Di Biase, M., Carrone, M., Gallone, V., Cocco, F., Costantini, M., Tritto, C., Cavalieri, F., Stella, L., Magliari, F., Callerame, M., De Giorgi, A., Pellegrino, L., Correra, M., Portulano, V., Nisi, G. L., Grassi, G., Cristallo, E., De Laura, D., Salerno, C., Fanelli, R., Villella, M., Pede, S., Renna, A., De Lorenzi, E., Urso, L., Lenti, V., Peluso, A., Baldi, N., Polimeni, G., Palma, P., Lauletta, R., Tagliamonte, E., Cirillo, T., Silvestri, B., Centonze, G., D'Alessandro, B., Truncellito, L., Mecca, D., Petruzzi, M. A., Coviello, R. O. M., Lopizzo, A., Chiaffitelli, M., Barbuzzi, S., Gubelli, S., Germinario, G., Cosentino, N., Mingrone, A., Vico, R., Borrello, G., Mazza, M. L., Cimino, R., Galasso, D., Cassadonte, F., Talarico, U., Perticone, F., Cassano, S., Catapano, F., Calemme, S., Feraco, E., Cloro, C., Misuraca, G., Caporale, R., Vigna, L., Spagnuolo, V., De Rosa, F., Spadafora, G., Zampaglione, G., Russo, R., Schipani, F. A., Ferragina, A. F., Stranieri, D., Musca, G., Carpino, C., Bencardino, P., Raimondo, F., Musacchio, D., Pulitanò, G., Ruggeri, A., Provenzano, A., Salituri, S., Musolino, M., Calandruccio, S., Marrari, A., Tripodi, E., Scali, R., Anastasio, L., Arone, A., Aragona, P., Donnangelo, L., Comito, M. G. A., Bilotta, F., Vaccaro, I., Rametta, R., Ventura, V., Bonvegna, A., Alì, A., Cinnirella, C., Raineri, M., Pompeo, F., Cascio Ingurgio, N., Carini, V., Coco, R., Giunta, G., Leonardi, G., Randazzo, V., Di Blasi, V., Tamburino, C., Russo, G., Mangiameli, S., Cardillo, R., Castelli, D., Inserra, V., Arena, A., Gulizia, M. M., Raciti, S., Rapisarda, G., Romano, R., Prestifilippo, P., Braschi, G. B., Ledda, G., Terrazzino, R., De Caro, M., Scilabra, G., Graffagnino, B., Grassi, R., Di Tano, G., Scimone, G. F., Vasquez, L., Coppolino, C., Casale, A., Castelli, M., D'Urso, G., D'Antonio, E., Lo Presti, L., Badalamenti, E., Conti, P., Sanfilippo, N., Cirrincione, V., Cinà, M. T., Cusimano, G., Taormina, A., Giuliano, P., Bajardi, A., Mandalà, V., Canonico, A., Geraci, G., Sabella, F. P., Enia, F., Floresta, A. M., Lo Cascio, I., Gumina, D., Cavallaro, A., Piccione, G., Ferrante, R., Blandino, M., Iudicello, M. S., Mossuti, E., Romano, G., Lombardo, L., Monastra, P., Di Vincenzo, D., Porcu, M., Orrù, P., Muscas, F., Giardina, G., Corda, M., Locci, G., Podda, A., Ledda, M., Siddi, P., Lai, C., Pili, G., Mercuro, G., Mureddu, G., Ganau, A., Meloni, G., Poddighe, G., Sanna, G., Barlera, Simona, Franzosi, Maria Grazia, Porcu, Maurizio, Yusuf, Salim, Camerini, Fulvio, Cohn, Jay N., Decarli, Adriano, Pitt, Bertram, Sleight, Peter, Poole-Wilson, Philip A., Geraci, Enrico, Scherillo, Marino, Fabbri, Gianna, Bartolomei, Barbara, Bertoli, Daniele, Cobelli, Franco, Fresco, Claudio, Ledda, Antonietta, Levantesi, Giacomo, Opasich, Cristina, Rusconi, Franco, Sinagra, Gianfranco, Turazza, Fabio, Volpi, Alberto, Ceseri, Martina, Alongi, Gianluca, Atzori, Antonio, Bambi, Filippo, Bastarolo, Desiree, Bianchini, Francesca, Cangioli, Iacopo, Canu, Vittoriana, Caporusso, Concetta, Cenni, Gabriele, Cintelli, Laura, Cocchio, Michele, Confente, Alessia, Fenicia, Eva, Friso, Giorgio, Gianfriddo, Marco, Grilli, Gianluca, Lazzaro, Beatrice, Lonardo, Giuseppe, Luise, Alessia, Nota, Rachele, Orlando, Mariaelena, Petrolo, Rosaria, Pierattini, Chiara, Pierota, Valeria, Provenzani, Alessandro, Quartuccio, Velia, Ragno, Anna, Serio, Chiara, Spolaor, Alvise, Tafi, Arianna, Tellaroli, Elisa, Ghio, Stefano, Ghizzardi, Elisa, Masson, Serge, Crociati, Lella, La Rovere, Maria Teresa, Corrà, Ugo, Di Giulio, Paola, Finzi, Andrea, Gorini, Marco, Milani, Valentina, Orsini, Giampietro, Bianchini, Elisa, Cabiddu, Silvia, Cangioli, Ilaria, Cipressa, Laura, Cipressa, Maria Lucia, Di Bitetto, Giuseppina, Ferri, Barbara, Galbiati, Luisa, Lorimer, Andrea, Pera, Carla, Priami, Paola, and Vasamì, Antonella

Subjects
Blood Glucose, Male, Glycated Hemoglobin A, heart failure, Kaplan-Meier Estimate, prediabetes, 030204 cardiovascular system & hematology, time factors, Settore MED/11, cause of death, 0302 clinical medicine, Glycemic control, prediabetic state, Cause of Death, italy, middle aged, Prevalence, 80 and over, double-blind method, blood glucose, risk factors, 030212 general & internal medicine, Prediabetes, Rosuvastatin Calcium, humans, rosuvastatin calcium, Cause of death, Original Research, Metabolic Syndrome, Aged, 80 and over, adult, Chronic heart failure, Diabetes mellitus, Heart failure, Mortality, Cardiology and Cardiovascular Medicine, Hazard ratio, chronic heart failure, diabetes mellitus, glycemic control, mortality, Treatment Outcome, Adolescent, Biomarkers, Chronic Disease, Diabetes Mellitus, Fatty Acids, Omega-3, Double-Blind Method, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hospitalization, Heart Failure, Italy, Prediabetic State, Risk Assessment, Proportional Hazards Models, Risk Factors, Time Factors, risk assessment, Middle Aged, kaplan-meier estimate, aged, female, Prediabete, young adult, Female, omega-3, Human, hospitalization, Adult, medicine.medical_specialty, Diabetes mellitu, proportional hazards models, Time Factor, hydroxymethylglutaryl-coa reductase inhibitors, prevalence, fatty acids, 03 medical and health sciences, Young Adult, male, Internal medicine, Post-hoc analysis, glycated hemoglobin a, medicine, Intensive care medicine, Aged, Glycated Hemoglobin, Proportional hazards model, business.industry, Risk Factor, biomarkers, Biomarker, medicine.disease, Clinical trial, adolescent, Proportional Hazards Model, treatment outcome, aged, 80 and over, chronic disease, fatty acids, omega-3, cardiology and cardiovascular medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitor, business
Abstract

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Published
2017
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36. Vasodilator stress echocardiography for risk stratification of medically stabilized unstable angina.

Author

Gigli G, Cortigiani L, Vallebona A, Orlandi S, Mariani PR, and Volterrani C

Subjects
Aged, Angina, Unstable diagnosis, Angina, Unstable mortality, Atropine, Dipyridamole, Electrocardiography, Female, Humans, Male, Prognosis, Prospective Studies, Risk Assessment, Survival Rate, Angina, Unstable diagnostic imaging, Echocardiography, Stress, Vasodilator Agents
Abstract

Aims: The aims of this study were to assess the safety, feasibility and prognostic value of dipyridamole-atropine stress echo in patients with medically stabilized unstable angina., Methods: The initial population consisted of 173 patients consecutively admitted at two different Coronary Care Units with class IIIB unstable angina. Of these, 56 were excluded: five had poor acoustic window, 24 did not stabilize with medical therapy and underwent urgent coronary angiography, 26 evolved in non-Q wave myocardial infarction and one patient died. The remaining 117 patients underwent dipyridamole-atropine stress echo after 48 h without symptoms or electrocardiographic evidence of myocardial ischaemia., Results: No complications or side effects occurred. An ischaemic response was found in 61 patients. During follow-up (10+/-9 months), three cardiac deaths, eight infarctions, 13 unstable anginas, and seven late (>3 months from stress testing) revascularizations occurred. There were 22 events (36%) in patients with, and nine events (16%) in patients without, inducible ischaemia (P=0.01). At Cox analysis peak-stress wall-motion score index (HR=5.5; 95% CI, 1.9 to 15.5; P=0.0015), and admission ST-segment depression (HR=4.2; 95% CI, 1.7 to 10.7; P=0.0022) were independent predictors of spontaneous events (cardiac death, infarction, unstable angina). The 12-month event-free survival was 69% for ischaemic and 83% for non-ischaemic group (P=0.03). In considering major events as end-points (spontaneous events, and late revascularization), again multivariate prognostic indicators were peak-stress wall-motion score index (HR=14.2; 95% CI, 2.6 to 76.6; P=0.0021), and admission ST-segment depression (HR=3.1; 95% CI, 1.4 to 6.9; P=0.0055). The 12-month event-free survival rate was 58% for ischaemic and 81% for non-ischaemic group (P=0.002). With an interactive stepwise procedure, stress echo findings were found to provide incremental prognostic contribution to that of clinical data alone., Conclusions: With proper selection of patients, dipyridamole-atropine stress echo is extremely safe and feasible in patients with medically stabilized unstable angina, and can be useful in identification of subjects at risk for future cardiac events., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Published
2002
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37. The stress echo prognostic gender gap.

Author

Cortigiani L, Gigli G, Vallebona A, Mariani PR, Bigi R, and Desideri A

Subjects
Age Factors, Aged, Cardiotonic Agents pharmacology, Coronary Angiography, Dipyridamole pharmacology, Dobutamine pharmacology, Endpoint Determination, Exercise Test, Female, Follow-Up Studies, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Myocardial Ischemia chemically induced, Myocardial Ischemia diagnosis, Myocardial Ischemia mortality, Predictive Value of Tests, Prognosis, Risk Factors, Sex Factors, Survival Analysis, Treatment Outcome, Vasodilator Agents pharmacology, Echocardiography, Stress, Sex
Abstract

Aims: To investigate whether myocardial ischaemia elicitable during pharmacological stress echocardiography portends different prognosis in men and women., Methods and Results: The study group was made by 1733 patients (941 men, 792 women) who underwent dipyridamole (n=1008) or dobutamine (n=725) stress echo for evaluation of known or suspected coronary artery disease. An ischaemic response was found in 460 patients (308 men, 152 women). Considering the whole ischaemic population, women were older (P<0.0001) and more likely to have hypertension (P=0.02) and hypercholesterolaemia (P=0.04) than men. No difference in age and risk factors was evidenced between the two sexes in the subset of 203 patients with ischaemia and suspected coronary artery disease. During follow-up (25 +/- 24 months for the ischaemic and 37 +/- 25 months for the non-ischaemic sample), there were 113 cardiac events (45 deaths and 68 infarctions) and 232 revascularizations. Revascularization rate in ischaemic population was similar in both sexes (P=0.36). Multivariate predictors of cardiac events in the whole ischaemic group were resting WMSI (HR=2.7, 95% CI 1.3--3.3;P=0.0050), female gender (HR=2.2, 95% CI 1.2--3.7;P=0.0062), age > or = l65 years (HR=1.9, 95% CI=1.0--3.6;P=0.0427), and Delta WMSI (HR=2.1, 95% CI=1.0--3.7;P=0.0447). Female gender (HR=2.7, 95% CI 1.1--6.3;P=0.0233) was the only independent prognostic predictor in patients with ischaemia and suspected coronary artery disease. Five-year infarction-free survival was 82% in men and 71% in women in the whole ischaemic population (P=0.0041) as well as in the ischaemic group with suspected coronary artery disease (CAD) (P=0.0175). In the non-ischaemic sample resting WMSI (HR=4.8), history of myocardial infarction (HR=2.5), and hypercholesterolaemia (HR=1.8) were independent predictors of outcome at multivariate analysis, whilst the gender had no prognostic importance., Conclusions: Our results show that female gender is an independent predictor of cardiac events in patients with myocardial ischaemia induced by pharmacological stress echocardiography.

Published
2001
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38. [Variation in the evoked ventricular potentials after the implantation of an endocardiac catheter; the correlation with stimulation thresholds].

Author

Azzarelli A, Paolini E, Masini M, Lazzari M, Mariani PR, Cortigiani L, Nannini E, and Bernardi D

Subjects
Aged, Atrial Fibrillation physiopathology, Electrocardiography statistics & numerical data, Evoked Potentials physiology, Female, Heart Ventricles physiopathology, Humans, Male, Patient Selection, Sensory Thresholds physiology, Time Factors, Heart physiopathology, Pacemaker, Artificial statistics & numerical data
Abstract

Background: The drop in T wave amplitude of the ventricular pace-evoked response (VER) is a well-recognized and reliable mean of detecting localized conditions of myocardial hypoxia. In patients who undergo pacemaker implantation, the post-implant change at the electrode-tissue interface consists of an early inflammatory reaction. The aim of this study was to establish whether the extent of the inflammatory reaction following an endocardial lead can be assessed by the changes in the T wave amplitude of VER., Methods: Modifications in VER amplitude and the correlation between these changes and pacing threshold time-course were evaluated in 30 patients receiving an endocardial catheter. Telemetered endocardial recordings of T wave amplitude and pacing thresholds were measured at the time of implant and after 1, 2, 3, 7, 14 and 30 days., Results: A biphasic time-course was observed for T wave, characterized by reduction in amplitude of 48% (p < 0.005) from baseline at day 3 and subsequent increment up to 84% (p = ns) of the baseline value at day 30. By using a linear regression analysis, a significant correlation between T wave changes and increment in pacing threshold was found (r = 0.81; p < 0.002). A higher pacing threshold increment was observed in patients having a decrease in VER amplitude > or = 1 mV at 3rd in comparison with patients with a decrease in VER amplitude < 1 mV (1.1 +/- 0.4 vs 0.2 +/- 0.2 V; p < 0.001)., Conclusions: VER recordings during the first days after endocardial lead implantation may be a valuable means of assessing the extent of the inflammatory reaction developing at the electrode-tissue interface. This method may be useful for early identification of patients at risk of increases in pacing threshold and for evaluation of the biocompatibility of different leads.

Published
1999

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