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1. Achieving Effective Process Safety Through Incident Investigation

Author: Sara Perelli, Gianluca Zanon, and Leonardo M. Carluccio
Subjects: Chemical engineering, TP155-156, Computer engineering. Computer hardware, TK7885-7895
Abstract: A robust Process Safety system is crucial in reducing the risk of a catastrophic event to tolerable levels. Among the twenty PSM elements identified by CCPS, Incident Investigation provides an opportunity for organizations to learn valuable lessons from minor incidents that then help prevent major disasters. Choosing the right methodology for Incident Investigation facilitates the process and must be tailored to the purpose and available resources in order to be effective. Care should be exercised, however, when searching for the relationship between minor incidents and full-blown catastrophes, in order to fully exploit the potential of Incident Investigations and use their results as drivers for Process Safety risk reduction. While most organizations have Incident Investigation processes in place, statistical evidence shows that the lessons learned during investigations seldom take root, resulting in repeated accidents. This is most likely caused by the lack of implementation of the changes (or root actions) required. A particularly important role in incident investigation is played by near-misses, as they represent valuable sources of information and provide helpful opportunities for learning. A near-miss is much less grievous than a full-blown disaster: evidence is usually easier to find; people are more willing to be frank; and greater frequency means learning can happen more often and more consistently. This article discusses how thorough investigations and appropriate follow-up combined with increased attention on near-miss events can translate into safer operations and fewer tragedies.
Published: 2023
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2. Hazardous Area Classification Due to Combustible Dust Atmospheres and Layers: Avoiding Common Mistakes

Author: Sara Perelli and Leonardo M. Carluccio
Subjects: Chemical engineering, TP155-156, Computer engineering. Computer hardware, TK7885-7895
Abstract: In areas and workplaces where combustible dusts are produced, handled or stored, Hazardous Area Classification is required to assess the likelihood of formation of a dust explosive atmosphere. The resulting dust zoning is of paramount importance in deciding the type and protection modes of electrical and non-electrical apparatuses to install in those areas. Dust zoning is a widespread and well-known technique, covered by dedicated technical Standards such as IEC 60079-10-2 and NFPA 499. As such, it also represents the first step for a dust explosion risk assessment, therefore its quality and completeness are of the utmost importance in order to achieve a high-value, robust explosion risk management. The behavior of fires and explosions from dust clouds or layers is strictly dependent on the chemical-physical characteristics of the dust: the first section of this paper shall analyze those characteristics, and how their variations affect the classification of areas. After this overview, the paper shall illustrate the most common misconceptions and mistakes that can be encountered in Hazardous Area Classifications and provide insights and suggestions on how to avoid them.
Published: 2023
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3. Quantitative Risk Assessment: Best Practices and Limitations

Author: Mauro Gotti and Leonardo M. Carluccio
Subjects: Chemical engineering, TP155-156, Computer engineering. Computer hardware, TK7885-7895
Abstract: Over the past decades, safety has been permeating process industry with the aim to ensure the protection of people involved in process plants and to prevent catastrophic events and industrial accidents that could be dangerous for the environment and the entire society. Nowadays, process industry requires specific and validated hazard assessment methods to understand the risks to which people are exposed. As a matter of fact, industrial accidents involving either installations or transportation of chemical compounds occur with relative high frequency and lead to many major accidents. QRA analysis (QRA is an acronym for Quantitative Risk Assessment) is a formal and systematic risk analysis approach for quantifying the risks associated with the operation of an engineering process. It can be used for the calculation of the economic and environmental impact that an industry could face after an incidental scenario has occurred, but its focus is on the loss of life; however, many pitfalls are hidden in this analysis, and we need to be aware of them and to avoid them. The paper aims to show the so-called “Seven Deadly Sins” and the “Five Commandments” of QRA, highlighting through real cases and examples from more than thirty years long experience how small mistakes in the input data can generate enormous mistakes. It will also show the golden rules to ensure that a QRA will give as an output useful and meaningful results.
Published: 2023
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4. Ventricular tachycardia site of origin prediction by a QRS axis-based algorithm confirmed by heterogenous tissue channel localization obtained from artificial-intelligence-powered CMR analysis

Author: L Mazzocchetti, M Parollo, S Sbragi, V Barletta, L Segreti, A Di Cori, R De Lucia, G Grifoni, E Soldati, S Viani, G Branchitta, M Carluccio, A Canu, L Paperini, and G Zucchelli
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Funding Acknowledgements Type of funding sources: None. Introduction A previously validated algorithm allows to accurately identify ventricular tachycardia (VT) exit site in a 17-segments American Heart Association left ventricle model in patients with structural heart disease (SHD). ADAS3D is a novel artificial-intelligence cardiac magnetic resonance (CMR) post-processing software which enables heterogeneous tissue channel (HTC) identification. Purpose The aim of this study is to compare inferred VT exit site between QRS-axis based model and HTC identification from CMR post-processing. Methods All subjects allocated to a CMR-guided or aided approach from a multicenter randomized clinical trial were analyzed. Patients with available 12-lead ECG of clinical VT obtained before ablation were analyzed in terms of concordance between VT site of origin inferred from a QRS-axis and location of HTCs in a 17-segments model. Results 10 out of 15 patients had 12-lead ECG of clinical VT (80% male, 60% with ischemic cardiomyopathy, mean age 63,5±16,95 years, mean tachycardia cycle length 373,7±99,55 ms). 7 out of 10 patients (70,00%) had at least one HTC located at VT exit site as predicted by a QRS axis-based algorithm. In all remaining cases (3 out of 10) HTC location was found in a segment adjacent to ECG-derived exit site. All patients underwent CMR-guided or CMR-aided VT ablation with acute clinical success (noninducibility of the clinical VT). Conclusion VT site of origin prediction via a QRS axis-based algorithm allows for reasonable prediction of HTC presence at inferred site of origin. Larger studies are needed in order to confirm such findings and their potential clinical implications.
Published: 2023
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5. C8 INSTITUTIONAL VALIDATION OF THE JOINT ANMCO AND AIOM TUSCANY CLINICAL CARDIO–ONCOLOGY PATHWAY FOR THE CARDIOLOGY MANAGEMENT OF CANCER OUTPATIENTS

Author: M Canale, A Camerini, I Bisceglia, F Orso, L Misuraca, M Carluccio, E Talini, C Sorini Dini, G Magnaghi, G Grippo, F Simonetti, D Amoroso, G Allegrini, C Bengala, and G Casolo
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Background Given the relevance and the growing complexity of the management of cardio–oncology (CO) outpatients, a common care pathway has been recently proposed by ANMCO and AIOM Tuscany. Materials and methods: The proposal: 1) defined 3 categories of patients to be entered into the pathway (A: known cardiac disease needing active oncology treatment; B: undergoing cancer treatments with potential cardiac toxicity; C: experiencing cardiac toxicity and/or worsening of cardiovascular risk profile); 2) proposed two standard request forms for oncology (ONCO) and hematology (HEM); 3) set the minimum requirements for a cardio–oncology path; 4) indicated follow–up strategies during and after oncological treatments. Given the short observation interval we focused on points 1 and 2. Medical records of all cancer patients for whom a CO examination was required were analized to check if proposed forms have been used and if cases fulfilled into appropriate categories. Observation period was retrospectively set to 1 year starting from October 2022. Minimum appropriateness threshold for each process index was set to 80%. Results A total of 480 requests for a CO visit were retrospectively identified, 322 out of 480 (67%) from medical oncology and 158 out of 480 (33%) from hematology units. Appropriate request form was used in 95% of cases (456 out of 480) with no difference between ONCO and HEM units. All patients but 20 (460 out of 480, 95.8%) fulfilled (at least) one of the 3 pre–defined categories with no difference between ONCO and HEM units. Categories distribution was: A group 25%, B group 60%, and C group 15%. Patients from medical oncology were more likely to belong to A and B groups while cases from hematology to B and C groups. Conclusions Our data indicate that minimum thresholds were met for both index 1 and 2 (with values that are approaching to 100%) so supporting the use of the proposed clinical CO pathway.
Published: 2023
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6. P255 A GOOD PERSPECTIVE NEEDS TWO POINT OF VIEW: TRANSVENOUS CRT–D LEAD EXTRACTION COMPLICATED BY INTRAOSSEUS COURSE OF THE CORONARY SINUS LEAD

Author: S Sbragi, M Parollo, L Segreti, A Del Corso, M Carluccio, A Di Cori, V Barletta, L Mazzocchetti, L Paperini, R De Lucia, S Viani, A Canu, G Grifoni, T Cellamaro, G Branchitta, E Soldati, and G Zucchelli
Subjects: Cardiology and Cardiovascular Medicine
Abstract: A 66 year old woman with dilated cardiomyopathy, carrier of CRT–D device in secondary prevention since 2013 and a mitralic mechanical prosthesis, suffered of CIED infection, confirmed by PET imaging exam. She was scheduled in our Hospital Unit for transvenous lead extraction. The procedure was performed by the subclavian approach, and the transvenous lead extraction was staged using mechanical telescopic sheats. After the extraction of the atrial and ventricular leads, the advance of the sheats was hampered by tenacious adherences along the site of vascular subclavian access of the coronary sinus lead. Firstly the portion of the lead running inside the coronary sinus was retracted with a pigtail by femoral vein approach. The inability to pass over the tenacious adherences at the point of the subclavian vein access were overcome expanding the surgical field with the help of the Vascular Surgeon, finding out that the adherence was determined by the presence of an osteophyte embracing the lead to the clavicle. The osteophyte was then surgically removed and the lead was finally extracted by jugular vein access. In this case the CIED leads were implanted using a intrathoracic subclavian venous access, where the vein lies behind the medial region of the clavicle. This approach could rarely lead to a periosteal penetration during needle advance that can generate osteophytes between the lead and the bone. In those circumstances the transvenous lead extraction could become extremely complicated, whatever technique is used.
Published: 2023
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7. ELECTRa Registry Outcome Score (EROS): validation in a single center population

Author: L Segreti, F Fiorentini, M Giannotti Santoro, V Barletta, G Zucchelli, A Di Cori, R De Lucia, A Canu, S Viani, L Paperini, T Cellamaro, E Soldati, M Carluccio, G Branchitta, and MG Bongiorni
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Funding Acknowledgements Type of funding sources: None. Introduction The ELECTRa Registry Outcome Score (EROS) was developed to identify patients at increased transvenous lead extraction (TLE) risk Purpose Aim of the study is to explore the efficiency of EROS for stratifying patients undergoing TLE. Methods We performed a retrospective analysis of 1293 patients who underwent to TLE in our center. We performed extraction procedures with manual traction or mechanical dilatation. We calculated EROS, and we divided patients into 3 groups depending on the EROS class. For this purpose, we made statistical analysis and comparison between EROS 1+2 vs. EROS 3 groups. We used an X2 for among-group comparisons or Fisher’s exact test if the expected cell count was less than five. Results Our analysis included 1293 patients. EROS-1 counted 726 patients (56,1%), EROS-2 367 (28,4%) patients and EROS-3 200 (15,5%) patients. There was no statistical difference in peri-procedural death between EROS-1+2 and EROS-3 (0.18% vs 1.50%, p=0.134). Major complications (0.82% vs. 3.00%, p=0.014), minor complications (3.11% vs. 6.50%, p=0.019) and use of internal jugular approach (6.13% vs. 14.50%, p Conclusion EROS effectively separates patients at higher risk of complications. Use of internal jugular approach was significantly higher in EROS 3 patients.
Published: 2022
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8. Left atrial thrombus and smoke resolution in patients with atrial fibrillation or flutter under chronic oral anticoagulation

Author: A Di Cori, V Barletta, L Meola, M Carluccio, G Branchitta, T Cellamaro, M Parollo, L Mazzocchetti, F Gentile, L Segreti, S Viani, R De Lucia, E Soldati, G Zucchelli, and MG Bongiorni
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Funding Acknowledgements Type of funding sources: None. Introduction Data on left atrial/left atrial appendage (LA/LAA) thrombus resolution after non–vitamin K antagonist (VKA) oral anticoagulant treatment (OAT) are scarce. Purpose The aim of this study was to explore retrospectively the resolution of LA/LAA spontaneous echo-contrast or thrombus in patients with nonvalvular atrial fibrillation (AF) or atrial flutter (AFL) after OAT in a real-world single center practice. Methods A single center retrospective analysis of patients with AF/AFL who underwent a transesophageal echocardiography (TEE) for an electrical cardioversion and/or atrial fibrillation ablation was performed. Patients showing LA/LAA echo-contrast or thrombus and with at least one TEE follow up to detect the resolution of LA/LAA echo-contrast/thrombus were included and analyzed. Results Among 277 TEE performed, 73 cases (26%) of LA/LAA echo-contrast or thrombus were detected in our hospital. Among them, a total of 53 patients showed LAA/LA echo-contrast (19%) and 20 (7%) patients showed a thrombus. Patients with echo-contrast or thrombus were usually male (78% vs 72%, p=0.05) with more comorbidities, as hypertension (90% vs 72%, p=0.03) and congestive heart failure (36% vs 17%, p=0.007) and with an overall higher CHA2DS2-Vasc score (3.5±1.5 vs 3±1, p=0.0001). All they were under chronic anticoagulation with a VKA (65%) or with a NOAC (35%), without differences between groups. (p=NS). At the TTE/TEE analysis, they showed a comparable ejection fraction (55±11 vs 55±22%, p=NS), a trend for an increased LA dilatation (27±8 vs 26±6 cm2, p=0.07) and a low LAA peak velocity (94% vs 19%, p=0.0001). The Echo-contrast Group maintained the same OAT strategy in 49 patients (93%), switching from VKA to NOAC in 3 cases (6%) and from NOAC to NOAC in 1 (1%). The Thrombus Group kept the same OAT strategy with a NOAC in 6 cases (30%) and changed the strategy in 14 patients (70%). Particularly, they titrated NOAC dose in 1 (5%) and the VKA dose in 4 (20%), switched from NOAC to VKA in 5 (25%), from VKA to NOAC in 3(15%) and from NOAC to NOAC in 1 (5%). Smoke resolution was observed in LA/LAA smoke group in 1/10 cases (10%) after a median time of 52 days (20-135) and LA/LAA thrombus resolution 8/15 (53%) after a median time of 45 days (25-180). Patients with the thrombus resolution had a lower CHA2DS2-Vasc score (3.5±2 vs 4±1, p=0.05), and showed a trend for a more frequent use of a NOAC (37.5 vs 28%, p=0.07) and a longer overall anticoagulation time (7.5 vs 4 months, p=0.08). At one-year follow-up, 1 ischemic stroke (1.9%) and 2 deaths (3.8%) were observed only in the Echo-contrast group. Conclusion(s) In OAT patients with an LA/LAA thrombus changing the OAT strategy is associated with thrombus resolution in more than 50% of cases, after an appropriate anticoagulation period and in lower CHAD2S2Vasc patients. Chronic OAT strategy confirmation, also with NOAC, is rarely effective, also in case of echo-contrast resolution.
Published: 2022
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9. Real-time local impedance monitoring to assess tissue lesion during pulmonary vein isolation: a new tool for AF ablation

Author: M Carluccio, R De Lucia, Luca Paperini, M G Bongiorni, A Di Cori, Valentina Barletta, Luca Segreti, Ezio Soldati, Stefano Viani, M Parollo, Giulio Zucchelli, G Branchitta, M Giannotti Santoro, F Tarasco, and T Cellamaro
Subjects: medicine.medical_specialty, medicine.diagnostic_test, Radiofrequency ablation, business.industry, medicine.medical_treatment, Atrial fibrillation, Cardiac Ablation, medicine.disease, Ablation, law.invention, Pulmonary vein, Lesion, law, medicine, Fluoroscopy, Radiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Atrial tachycardia
Abstract: Background Contact force catheter ablation is the gold standard for treatment of atrial fibrillation (AF). Local tissue impedance (LI) evaluation has been recently studied to evaluate lesion formation during radiofrequency ablation. Purpose Aim of the study was to assess the outcomes of an irrigated catether with LI alghorithm compared to contact force (CF)-sensing catheters in the treatment of symptomatic AF. Methods A prospective, single-center, nonrandomized study was conducted, to compare outcomes between CF-AF ablation (Group 1) and LI-AF ablation (Group 2). For Group 1 ablation was performed using the Carto 3© System with the SmartTouch SF catheter and, as ablation target, an ablation index value of 500 anterior and 400 posterior. For Group 2, ablation was performed using the Rhythmia™ System with novel ablation catheter with a dedicated algorithm (DirectSense) used to measure LI at the distal electrode of this catheter. An absolute impedance drop greater than 20Ω was used at each targeted. According to the Close Protocol, ablation included a point by point pulmonary vein isolation (PVI) with an Inter-lesion space ≤5 mm in both Groups. Procedural endpoint was PVI, with confirmed bidirectional block. Results A total of 116 patients were enrolled, 59 patients in Group 1 (CF) and 57 in Group 2 (LI), 65 (63%) with a paroxismal AF and 36 (37%) with a persistent AF. Baseline patients features were not different between groups (P=ns). LI-Group showed a comparable procedural time (180±89 vs 180±56, P=0.59) but with a longer fluoroscopy time (20±12 vs 13±9 min, P=0.002). Wide antral isolation was more often observed in CF-Group (95% vs 80%, P=0.022), while LI-Group 2 required frequently additional right or left carina ablation (28% vs 14%, P=0.013). The mean LI was 106±14Ω prior to ablation and 92.5±11Ω after ablation (mean LI drop of 13.5±8Ω) during a median RF time of 26 [19–34] sec for each ablation spot. No steam pops or complications during the procedures were reported. The acute procedural success was 100%, with all PVs successfully isolated in all study patients. Regarding safety, only minor vascular complications were observed (5%), without differences between groups (p=0.97). During follow up, 9-month freedom from atrial fibrillation/atrial flutter/atrial tachycardia recurrence was 86% in Group 1 and 75% in Group 2 (P=0.2). Conclusions An LI-guided PV ablation strategy seems to be safe and effective, with acute and mid-term outcomes comparable to the current contact force strategy. LI monitoring could be a promising complementary parameter to evaluate not only wall contact but also lesion formation during power delivery. Procedural Outcomes Funding Acknowledgement Type of funding source: None
Published: 2020
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10. Leptin and exercise: an update

Author: M. Carluccio, A. Kaltsatou, E. Scoditti, M. Massaro, A. Cicchella, Cicchella A., Carluccio M., Scoditti E., Kaltsatou A., and Massaro M.
Subjects: Leptin, Starvation, medicine.medical_specialty, business.industry, digestive, oral, and skin physiology, General Medicine, Endocrinology, Internal medicine, medicine, Disease, medicine.symptom, business, Exercise, hormones, hormone substitutes, and hormone antagonists
Abstract: Leptin is a multifunctional hormone (adipocytokine) involves in several biological processes. From brain metabolism, to signalling, in sexual development, inflammation, fat metabolism, as an ergogenic aid for sport and in the regulation of food intake and body weight. however, recent studies investigated some new aspects of leptin, elucidating the genetics mechanisms of production, relationships with starvation and environmental variables, and even some methodological issues in leptin measurement. Some interesting new studies deals with aerospace medicine, investigating effect of space flights on leptin. Relationships with rare disease such as HIV and with psychiatric disorders are also among the recent development of leptin studies. physical activity remain the most important factor associate with leptin metabolism, and recent studies shows how the leptin levels are influenced by exercise in extreme sport, such ultramarathon. Relationships between leptin levels and amount of exercise is well known, but still exist some controversial point about what is the shape of the relationships (if linear or polynomial) between leptin and moderate and heavy exercise. it is emerging the need for multifactorial studies which take into account phenotype, environmental variables, nutritional status, as well as cultural aspects influencing nutrition, and controlled timing in leptin measurements.
Published: 2020
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11. P1358Atrial electromechanical interval in patients with arrhythmias: is everyone the same?

Author: M G Bongiorni, A Canu, G Branchitta, M Giannotti Santoro, C Ridolfi, Giulio Zucchelli, V Della Tommasina, M Carluccio, M Parollo, and Valentina Barletta
Subjects: medicine.medical_specialty, business.industry, Physiology (medical), Internal medicine, Cardiology, Medicine, Interval (graph theory), In patient, Cardiology and Cardiovascular Medicine, business
Abstract: Background Atrial electromechanical delay, assessed calculating the PA-TDI interval using tissue Doppler imaging, is a known and promising determinant for atrial fibrillation recurrence prediction after pulmonary vein isolation and electrical cardioversion. Purpose To determine the relationship between atrial electromechanical delay and the presence of atrial fibrillation. Methods We prospectively enrolled patients presenting at our Unit in sinus rhythm scheduled for an arrhythmogenic substrate ablation (atrial fibrillation -AF-, supraventricular tachycardia -SVT- and premature ventricular contractions -PVC-). Demographic and echocardiographic characteristics were evaluated upon admission. Atrial electromechanical delay was inferred via the PA-TDI interval, obtained by calculating the time difference between the P wave onset and the A" wave peak on TDI recordings. Results From October 2018 to August 2019, 200 patients (60% male, mean age 58,21 ± 14,26, mean BSA 1,9 ± 0,21 m2, mean BMI 26,42 ± 6,28 kg/m2, mean EF 60,91% ± 5,43%) were admitted to our unit to undergo AF (group 1: n = 145; 72,50%), SVT or PVC ablation (group 2: n = 55; 27,5%). Compared with the control group (group 2), patients admitted for AF ablation had a larger LA size (group 1 vs group 2: mean LA area 23,21 ± 5,07 vs 16,87 ± 4,01 cm2, p < 0,001; mean indexed LA volume 46,71 ± 20,41 ml vs 32,04 ± 14,7 ml, p Conclusion The PA-TDI interval is a non-invasive and easily achievable echocardiographic parameter, which is demonstrated to be prolonged in patients with a history of AF in contrast with patients with other arrhythmias, as expression of atrial conduction heterogeneity. Abstract Figure. PA-TDI measurement
Published: 2020
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12. Does the purinergic system affect extracellular matrix functions in the central nervous system?

Author: M, Zuccarini, M, Carluccio, S, Ziberi, P, Giuliani, S, Buccella, C, Conti, R, Ciccarelli, and P, Di Iorio
Subjects: Central Nervous System, Receptors, Purinergic, Brain, Humans, Extracellular Matrix
Abstract: Exracellular matrix (ECM) consists of a plethora of proteins and polysaccharides, which aggregate into an organized network connected to the surface of the producing cells. It is structurally and functionally present in all components of tissues and organs and represents the substrate on which cells adhere, migrate, proliferate and differentiate, influencing their survival, shape and function. In response to acute (trauma) or chronic (degenerative) insults, brain ECM modifies its composition and function, actively contributing to "scar forming" gliosis or tissue degeneration/remodelling. Moreover, morphological changes in dendritic spines associated with extracellular matrix remodeling play key roles in rewiring synaptic circuitry pertinent to memory formation. In the present report, we collected the main acquisitions on the functional interplay between ECM alterations and the adenine-/guaninebased purine system with particular regard on how purine compounds and their respective receptors may affect and be affected by changes of the cerebral ECM.
Published: 2018

13. P2932Safety and efficacy of the subcutaneous implantable defibrillator after trans-venous ICD explant: experience in a high volume centre for treatment of CIED complications

Author: Diana Andreini, A Di Cori, M G Bongiorni, R De Lucia, Ezio Soldati, Luca Segreti, Luca Paperini, Stefano Viani, Giulio Zucchelli, T Cellamaro, Valentina Barletta, M Carluccio, and G Branchitta
Subjects: medicine.medical_specialty, business.industry, Medicine, Implantable defibrillator, Cardiology and Cardiovascular Medicine, business, Volume (compression), Surgery, Explant culture
Published: 2018
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14. 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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15. Saturday, 17 July 2010

Author: I. Dimova, R. Hlushchuk, A. Makanya, V. Djonov, M. Theurl, W. Schgoer, K. Albrecht, A. Beer, J. R. Patsch, P. Schratzberger, S. Mahata, R. Kirchmair, M. Didie, P. Christalla, T. Rau, T. Eschenhagen, U. Schumacher, Q. Lin, M. Zenke, W. Zimmmermann, M. Hoch, P. Fischer, B. Stapel, E. Missol-Kolka, S. Erschow, M. Scherr, H. Drexler, D. Hilfiker-Kleiner, I. Diebold, A. Petry, P. Kennel, T. Djordjevic, J. Hess, A. Goerlach, J. Castellano, R. Aledo, J. Sendra, P. Costales, L. Badimon, V. Llorente-Cortes, E. Dworatzek, S. Mahmoodzadeh, V. Regitz-Zagrosek, A. Posa, C. Varga, A. Berko, M. Veszelka, P. Szablics, B. Vari, I. Pavo, F. Laszlo, M. Brandenburger, J. Wenzel, R. Bogdan, D. Richardt, M. Reppel, J. Hescheler, H. Terlau, A. Dendorfer, J. Heijman, Y. Rudy, R. Westra, P. Volders, R. Rasmusson, V. Bondarenko, M. D. Ertas Gokhan, M. D. Ural Ertan, P. H. D. Karaoz Erdal, P. H. D. Aksoy Ayca, M. D. Kilic Teoman, M. D. Kozdag Guliz, M. D. Vural Ahmet, M. D. Ural Dilek, C. Poulet, T. Christ, E. Wettwer, U. Ravens, C. Van Der Pouw Kraan, S. Schirmer, J. Fledderus, P. Moerland, T. Leyen, J. Piek, N. Van Royen, A. Horrevoets, F. Fleissner, V. Jazbutyte, J. Fiedler, P. Galuppo, M. Mayr, G. Ertl, J. Bauersachs, T. Thum, S. Protze, A. Bussek, F. Li, R. Hoo, K. Lam, A. Xu, P. Subramanian, E. Karshovska, R. Megens, S. Akhtar, K. Heyll, Y. Jansen, C. Weber, A. Schober, M. Zafeiriou, C. Noack, A. Renger, R. Dietz, L. Zelarayan, M. Bergmann, I. Meln, A. Malashicheva, S. Anisimov, N. Kalinina, V. Sysoeva, A. Zaritskey, A. Barbuti, A. Scavone, N. Mazzocchi, A. Crespi, D. Capilupo, D. Difrancesco, L. Qian, W. Shim, Y. Gu, S. Mohammed, P. Wong, M. Zafiriou, H. Schaeffer, P. Kovacs, J. Simon, A. Varro, P. Athias, J. Wolf, O. Bouchot, D. Vandroux, A. Mathe, A. De Carvalho, G. Laurent, P. Rainer, M. Huber, F. Edelmann, T. Stojakovic, A. Trantina-Yates, M. Trauner, B. Pieske, D. Von Lewinski, A. De Jong, A. Maass, S. Oberdorf-Maass, I. Van Gelder, Y. Lin, J. Li, F. Wang, Y. He, X. 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Hurle, J. Nistal, V. Vera, P. Karuppasamy, S. Chaubey, T. Dew, R. Sherwood, J. Desai, L. John, M. Marber, G. Kunst, E. Cipolletta, A. Attanasio, C. Del Giudice, P. Campiglia, M. Illario, A. Berezin, E. Koretskaya, E. Bishop, I. Fearon, J. Heger, B. Warga, Y. Abdallah, B. Meyering, K. Schlueter, H. Piper, G. Euler, A. Lavorgna, S. Cecchetti, T. Rio, G. Coluzzi, C. Carrozza, E. Conti, F. Andreotti, A. Glavatskiy, O. Uz, E. Kardesoglu, O. Yiginer, S. Bas, O. Ipcioglu, N. Ozmen, M. Aparci, B. Cingozbay, F. Ivanes, M. Hillaert, S. Susen, F. Mouquet, P. Doevendans, B. Jude, G. Montalescot, E. Van Belle, C. Castellani, A. Angelini, O. De Boer, C. Van Der Loos, G. Gerosa, A. Van Der Wal, I. Dumitriu, P. Baruah, J. Kaski, O. Maytham, J. D Smith, M. Rose, A. Cappelletti, A. Pessina, M. Mazzavillani, G. Calori, A. Margonato, S. Cassese, C. D'anna, A. Leo, A. Silenzi, M. Baca', L. Biasucci, D. Baller, U. Gleichmann, J. Holzinger, T. Bitter, D. Horstkotte, A. Antonopoulos, A. Miliou, C. Triantafyllou, W. Masson, D. Siniawski, P. Sorroche, L. Casanas, W. Scordo, J. Krauss, A. Cagide, T. Huang, A. Wiedon, S. Lee, K. Walker, K. O'dea, P. Perez Berbel, V. Arrarte Esteban, M. Garcia Valentin, M. Sola Villalpando, C. Lopez Vaquero, L. Caballero, M. Quintanilla Tello, F. Sogorb Garri, G. Duerr, N. Elhafi, T. Bostani, L. Swieny, E. Kolobara, A. Welz, W. Roell, O. Dewald, N. Kaludercic, E. Takimoto, T. Nagayama, K. Chen, J. Shih, D. Kass, F. Di Lisa, N. Paolocci, L. Vinet, M. Pezet, F. Briec, M. Previlon, P. Rouet-Benzineb, A. Hivonnait, F. Charpentier, J. Mercadier, M. Cobo, M. Llano, C. Montalvo, V. Exposito, L. Meems, B. Westenbrink, L. Biesmans, V. Bito, R. Driessen, C. Huysmans, I. Mourouzis, C. Pantos, G. Galanopoulos, M. Gavra, P. Perimenis, D. Spanou, D. Cokkinos, T. Panasenko, S. Partsch, C. Harjung, A. Bogdanova, D. Mihov, P. Mocharla, S. Yakushev, J. Vogel, M. Gassmann, R. Tavakoli, D. Johansen, E. Sanden, C. Xi, R. Sundset, K. Ytrehus, M. Bliksoen, A. Rutkovskiy, L. Mariero, I. Vaage, K. Stenslokken, O. Pisarenko, V. Shulzhenko, I. Studneva, L. Serebryakova, O. Tskitishvili, Y. Pelogeykina, A. Timoshin, A. Vanin, L. Ziberna, M. Lunder, G. Drevensek, S. Passamonti, L. Gorza, B. Ravara, C. Scapin, M. Vitadello, F. Zigrino, J. Gwathmey, F. Del Monte, G. Vilahur, O. Juan-Babot, B. Onate, L. Casani, S. Lemoine, G. Calmettes, B. Jaspard-Vinassa, C. Duplaa, T. Couffinhal, P. Diolez, P. Dos Santos, A. Fusco, D. Sorriento, P. Cervero, A. Feliciello, E. Barnucz, K. Kozichova, M. Hlavackova, J. Neckar, F. Kolar, O. Novakova, F. Novak, C. Barsanti, N. Abraham, D. Muntean, S. Mirica, O. Duicu, A. Raducan, M. Hancu, O. Fira-Mladinescu, V. Ordodi, J. Voelkl, B. Haubner, G. Neely, C. Moriell, S. Seidl, O. Pachinger, J. Penninger, and B. Metzler
Subjects: Physiology, Physiology (medical), Cardiology and Cardiovascular Medicine
Published: 2010
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16. Is CRT Useful in Patients with Atrial Fibrillation?

Author: M. Carluccio, l. Paperini, and E. Pardini
Subjects: Cardiovascular event, education.field_of_study, medicine.medical_specialty, business.industry, medicine.medical_treatment, Population, Atrial fibrillation, medicine.disease, Ablation, Internal medicine, Heart failure, cardiovascular system, Cardiology, Medicine, Sinus rhythm, In patient, cardiovascular diseases, business, education, Left Ventricular Failure
Abstract: It may be said that CRT has a role in improving functional capacity over conventional right ventricular pacing in patients with left ventricular failure who require permanent ventricular stimulation and/or in those with an indication for AV nodal ablation. As for the great majority of patients with advanced heart failure and AF without conventional indications for permanent cardiac pacing — a wide and progressively expanding population in the “border zone” of current indications for CRT — no definite data are available. Some promising results from ablated patients show a favourable trend in major cardiac event reduction after CRT. More controlled clinical data are required to achieve definite conclusions about the indications for CRT in heart failure patients with AF.
Published: 2006
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17. [Stress imaging in coronary artery disease: state of the art]

Author: U, Baldini, C, Venturini, A, Genovesi-Ebert, M T, Savoia, M, Raugi, M, Pauletti, M, Carluccio, A, Digiorgio, G, Gasperetti, and M, Galli
Subjects: Tomography, Emission-Computed, Single-Photon, Electrocardiography, Thallium Radioisotopes, Dobutamine, Research, Exercise Test, Humans, Coronary Disease, Prognosis, Echocardiography, Stress, Tomography, Emission-Computed
Abstract: To date, several diagnostic tools allow an accurate non-invasive evaluation of coronary artery disease; this is due to the great progress in echocardiographic and nuclear imaging techniques in the last 10 years. The large availability of different stress imaging techniques allows to choose the most appropriate technique for each patient according to the clinical characteristics. This paper presents the state of the art of echocardiographic and nuclear stress imaging for the diagnosis of coronary artery disease and for the prognostic stratification of infarcted patients. Advantages and limits of the different techniques are described rather than putting in competition echo and nuclear cardiology as has often been done in the past. Cardiologists should select among the various techniques on the basis of clinical characteristics of single patients, center's experience and an objective evaluation of economical aspects.
Published: 2004

18. [Membrane platelet receptors and cardiovascular risk: from structure to potential clinical implications]

Author: M, Carluccio, N, Vesentini, and R, De Caterina
Subjects: Arteriosclerosis, Risk Factors, von Willebrand Factor, Humans, Thrombosis, Platelet Membrane Glycoproteins
Abstract: Platelets exhibit membrane receptor proteins the structure of which has adapted, in the course of evolution, to halt hemorrhage. These receptors are also implicated in thrombosis, and their structural variability is likely able to account for part of the variability in intraindividual susceptibility to thrombotic events. This review offers a summary of current knowledge on the molecular structure and function of platelet membrane receptors, here studied also in relation to the variability of platelet function in the general population, with the aim of discussing possible implications for the atherothrombotic risk.
Published: 2001

19. Aspects of gene polymorphisms in cardiovascular disease: the renin-angiotensin system

Author: M, Carluccio, M, Soccio, and R, De Caterina
Subjects: Renin-Angiotensin System, Polymorphism, Genetic, Cardiovascular Diseases, Animals, Humans, Genetic Predisposition to Disease
Abstract: The renin-angiotensin system (RAS) plays a central role in cardiovascular homeostasis. Angiotensin is the key peptide of the RAS, and exerts its influence on the heart and blood vessels both through its haemodynamic effects (via its influence on after-load and pre-load and determining coronary vasoconstriction) and through its direct cellular effects (via its actions on cell proliferation). Numerous studies in the past 10 years have demonstrated that the pharmacological inhibition of angiotensin converting enzyme (ACE), one of the two critical enzymes of the RAS, improves the outcome in patients with several cardiovascular disorders (hypertension, heart failure, ischaemic heart disease). These studies suggest a role of the RAS as a major determinant of cardiovascular risk. Recent data suggest that genetics may in turn contribute to modulating the effects of angiotensin on coronary vascular biology and ischaemia. This paper reviews the physiologic characteristics of the RAS and recent research developments related to angiotensin cell biology and pathobiology in heart disease. In particular, this review will cover the genetic aspects of RAS and their implications in cardiovascular disease.
Published: 2001

20. [The genetic component of coronary risk. II]

Author: M, Carluccio, D, Vanuzzo, L, Pilotto, P, Fioretti, F, Quadrifoglio, S, Diviacco, M, Mariani, and R, De Caterina
Subjects: Blood Platelets, Polymorphism, Genetic, Genotype, Models, Genetic, Research, Coronary Disease, Thrombosis, Blood Coagulation Factors, Renin-Angiotensin System, Plasminogen Activators, Cardiovascular Diseases, Risk Factors, Case-Control Studies, Mutation, Animals, Humans, Prospective Studies, Blood Coagulation, Homocysteine, Alleles, Retrospective Studies
Published: 1999

21. A reconsideration of cf. Psilophyton princeps (Croft & Lang, 1942), a zosterophyll widespread in the Lower Old Red Sandstone of South Wales

Author: Leeds M. Carluccio, Paul Kenrick, and Dianne Edwards
Subjects: Paleontology, Permineralization, Psilophyton, biology, Paleozoic, Genus, Sporangium, Tracheid, Xylem, Plant Science, biology.organism_classification, Ecology, Evolution, Behavior and Systematics, Devonian
Abstract: EE WARDS, D., KENRICK, P. & CARLUCCIO, L. M., 1988. A reconsideration of cf. P lophyton princeps (Croft & Lang, 1942), a zosterophyll widespread in the Lower Old Rt 1 Sandstone of South Wales. The Lower Devonian plant from Llanover Quarry, Gwent, cal ed cf. Psilophyton princeps, is shown to be a zosterophyll and placed in a new genus. It comprises an ere t planar pseudomonopodial and isotomously branching system of spiny axes with subaxillary pre ections (axillary tubercles) with circinate tips, sometimes replaced by a downwardly directed, spiring, branching axis. Its xylem, strap-shaped in cross-section and exarch, is composed of directly and ndirectly connected annular thickenings. An extended distal fertile zone consists of axes with spot ingia in two opposite or sub-opposite rows. Each sporangium comprises two equal valves, ellip'ical to reniform in face view, and is held upright on a short curved stalk. Dehiscence is around the convex margin which is bordered by a narrow strip of thickening. The Welsh plants are comp ired with other zosterophylls and appear closest to Sawdonia ornata except that they possess sub-axillay branches and lack the characteristic dark-tipped spines. Detailed analysis of coalified mater: and the distribution and fabric of pyrite in permineralizations shows that the original structure of the tracheids was similar to that in Gosslingia and most other zosterophylls, and that the taphonomic processes, with lignified walls preserved as coalified layers and softer tissues replaced by pyrite, were also broadly the same. Permineralizations in pyrite and limonite allow an evaluation of the effects of oxidation of pyrite on original cell structure.
Published: 1989
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22. ARCHAEOPTERIS MACILENTA, ANATOMY AND MORPHOLOGY OF ITS FROND

Author: Leeds M. Carluccio, Harlan P. Banks, and Francis M. Hueber
Subjects: Frond, Sporangium, fungi, Morphology (biology), Plant Science, Anatomy, Biology, Arborescent, biology.organism_classification, Archaeopteris macilenta, Genus, Archaeopteris, Progymnosperm, Botany, Genetics, Ecology, Evolution, Behavior and Systematics
Abstract: from which leaf traces arise in a spiral sequence. The anatomy of the "rachis" and of the "'pinnae" is shown to be similar to that of the stem, Callixylon, which bore these "fronds." Branching, epidermal pattern and stomates are described for the spirally arranged leaves (fertile pinnules). Attachment and dehiscence of sporangia as well as their stomates are reported. Archaeopteris is retained in the Class Progymnospermopsida which includes plants with gymnospermous anatomy and pteridophytic reproduction. It is suggested that Actinopodium, Svalbardia and Siderella are related closely to Archaeopteris and that this group of genera shows evolutionary stages in webbing of leaves and planation of branch systems. The opportunities for ontogenetic studies of the arborescent genus Archaeopteris are pointed out.
Published: 1966
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23. Off-label combination of leadless pacemakers and subcutaneous defibrillators in bilateral venous occlusion: a new reimplantation strategy after lead extraction

Author: M G Bongiorni, Stefano Viani, Luca Segreti, Luca Paperini, Ezio Soldati, M Parollo, R De Lucia, A Di Cori, G Branchitta, Valentina Barletta, M Giannotti Santoro, M Carluccio, Silvio Tolve, T Cellamaro, and Giulio Zucchelli
Subjects: Secondary prevention, medicine.medical_specialty, Venous occlusion, business.industry, medicine.disease, Device implant, law.invention, Surgery, law, Primary prevention, medicine, Artificial cardiac pacemaker, Cardiology and Cardiovascular Medicine, business, Atrioventricular block, Surgical Replantation, Lead extraction
Abstract: Background Subcutaneous implantable cardioverter-defibrillator (S-ICD) and leadless pacemakers (LPM) provide an alternative to transvenous implantable devices. Sometimes, after transvenous (TV) lead extraction, patients show a bilateral venous occlusion, resulting not eligible for TV reimplantation. Purpose This analysis was designed to provide preliminary data on feasibility and short-term outcome of an hybrid combination (Hyb) of s-ICD plus LPM after TV-ICD explantation, in patients without anatomical transvenous reimplantation options. Methods Among 2684 consecutive extracted patients, 31 (1.1%) were reimplanted with a LPM, 66 (2.4%) with a s-ICD and 6 (0.2%) patients with an Hyb combination. Hyb strategy was considered in patients with a pacing plus defibrillating indication, and an anatomical barrier, as bilateral superior venous occlusion or massive bilateral skin erosion. Results Hyb patients were old (72±10 years), with a prevalent ischemic disease (4/6) and a reduced ejection fraction (43±16%). Extraction indication was infection in 4 and severe venous occlusion in 2, and included 2 single chamber, 2 dual chamber and 2 biventricular ICD. After extraction, reimplantation timing was 7±6 days, LPM was implanted before and sICD the day after. LPM reimplantation indication was sinus node dysfunction in 2 and AV block in 4. Implantation duration was 68±23 and fluoroscopy time 9.4±2.3 min. ICD reimplantation indication was primary prevention in 4 and secondary prevention in 2. Implantation duration was 118±10 min. No complications were observed. At 1 year, no complications were observed, including device related cross-talks. Conclusions The Hyb strategy is a potential option after TV-ICD explantation in pacemaker dependent patients, when transvenous implantation is not available. Extraction and Reimplantation Session Funding Acknowledgement Type of funding source: None

24. L’analisi della performance e la valutazione degli asset manager

Author: CUCURACHI, Paolo Antonio, Emanuele M. Carluccio, and Cucurachi, Paolo Antonio
Published: 1999

25. Pulmonary embolism: incidence and outcomes in a twelve-year historical series, in Tuscany - Italy (2010-2021).

Author: Cerini G, Lunetta C, Szasz C, Misuraca L, Gemmi F, Carluccio M, Lorini C, Bonaccorsi G, and Forni S
Abstract: Background: Pulmonary embolism poses a global health concern. Administrative databases serve as valuable sources for broad epidemiological studies on the prevalence and incidence of major diagnoses or diseases. The primary scope is to provide up-to-date insights into Pulmonary Embolism incidence trends, examining shifts in management and outcomes., Design: This retrospective observational study examines a 12-year dataset from hospitals in the Tuscany Region, covering the first two years of the Covid-19 pandemic., Methods: Administrative data from residents aged 18 and older discharged from hospital between 2010 and 2021 were used for the analysis., Results: Hospitalized pulmonary embolism incidence slightly declined from 2010 to 2019 (64.7 to 60.9 x 100,000; p=0.152). Males under 75 showed a higher incidence rate, while females had higher incidence rates in older age groups. In-hospital and 30-day mortality decreased from 2010 to 2019 (p=0.001 and 0.020 respectively). In 2020, 30-day mortality increased (12.4% vs 10.1%, p=0.029), while in-hospital mortality remained stable. One-year mortality was stable from 2010-2019 but increased in 2020 (32.6% vs 29.4%, p=0.037). Considering the multivariable model, one-year mortality is significantly associated with sex, age, and comorbidities., Conclusions: Our study shows that Pulmonary Embolism persists as a relevant burden in Tuscany region, but with improvements in management over the past decade and a decisive change in pharmacological treatment. Gender-related differences emerge, highlighting the need for a gender-specific healthcare approach.
Published: 2024
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26. Retraction Note: Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells.

Author: Zuccarini M, Giuliani P, Buccella S, Di Liberto V, Mudò G, Belluardo N, Carluccio M, Rossini M, Condorelli DF, Rathbone MP, Caciagli F, Ciccarelli R, and Di Iorio P
Published: 2023
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27. [Arrhythmias in adult congenital heart disease at the emergency department: ANMCO Tuscany clinical pathway].

Author: Favilli S, Assanta N, Carluccio M, Ricciardi G, Segreti L, Canale ML, Grippo G, Selvaggia Magnaghi GC, Misuraca L, Orso F, Sorini Dini C, Talini E, Mirizzi G, Spaziani G, Garibaldi S, Viacava C, Porcedda G, and Casolo G
Subjects: Adult, Humans, Critical Pathways, Arrhythmias, Cardiac therapy, Arrhythmias, Cardiac complications, Emergency Service, Hospital, Heart Defects, Congenital complications, Heart Defects, Congenital epidemiology, Cardiac Surgical Procedures adverse effects
Abstract: Arrhythmias are a common complication in the adult population with congenital heart disease (ACHD). Arrhythmias often lead to hemodynamic instability and, on the other hand, may be a marker of hemodynamic impairment in ACHD patients, both in natural history and after cardiac surgery. Treatment requires knowledge of basic anatomy and any previous cardiac surgery; the availability of patient's health records, if possible, is therefore crucial for therapeutic choices. In the emergency setting, the first target is represented by the patient's hemodynamic stabilization; mainly in moderate or high complexity ACHD, the connection with the referral center is recommended, to which patients should be entrusted for follow-up. A regional epidemiological observatory, aiming to assess the number, type and outcomes of emergency admissions of ACHD patients could be a useful tool for analyzing the effectiveness of the collaboration network between the different structures involved and for implementing organizational pathways.
Published: 2023
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28. [Pulmonary hypertension clinical pathway: ANMCO Tuscany Board model].

Author: Spaziani G, Monti S, Misuraca L, Airò E, Traini AM, Bauleo C, Canale ML, Carluccio M, Grippo G, Selvaggia Magnaghi GC, Orso F, Sorini Dini C, Talini E, Poddighe R, Picchi A, Limbruno U, Favilli S, and Casolo G
Subjects: Humans, Critical Pathways, Cardiac Catheterization, Echocardiography, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary etiology, Hypertension, Pulmonary therapy, Heart Diseases
Abstract: Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure >20 mmHg at rest during right heart catheterization. PH prevalence is about 1% of the global population. The PH clinical classification includes five groups: pulmonary arterial hypertension, PH associated with left heart disease, PH associated with lung disease, PH associated with pulmonary artery obstructions, PH with unclear and/or multifactorial mechanisms. In case of clinical suspicion, echocardiography is the first-line tool to start the diagnostic process. Right heart catheterization is the gold standard for diagnosis of PH, requires great experience and should be performed in expert centers. The classification of the PH patient in a specific subgroup requires multidisciplinary clinical and instrumental skills that only a reference center can provide. This document proposes a clinical pathway for the management of PH patients in the Tuscany region in order to standardize access to specialized care.
Published: 2023
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29. Left atrial thrombus and smoke resolution in patients with atrial fibrillation under chronic oral anticoagulation.

Author: Di Cori A, Barletta V, Meola L, Parollo M, Mazzocchetti L, Carluccio M, Branchitta G, Cellamaro T, Gentile F, Segreti L, Viani S, De Lucia R, Soldati E, Zucchelli G, and Bongiorni MG
Subjects: Anticoagulants, Echocardiography, Transesophageal, Humans, Retrospective Studies, Smoke, Atrial Appendage diagnostic imaging, Atrial Fibrillation complications, Atrial Fibrillation diagnostic imaging, Atrial Fibrillation drug therapy, Heart Diseases, Thrombosis complications, Thrombosis diagnostic imaging, Thrombosis prevention & control
Abstract: Background: The study aimed to explore the resolution of left atrial and left atrial appendage (LAA) spontaneous echo-contrast or thrombus in patients with nonvalvular atrial fibrillation/flutter (AF/AFL) under chronic oral anticoagulation (OAC)., Methods: A single-center retrospective analysis of patients who underwent a transesophageal echocardiography (TOE) for an electrical cardioversion was conducted., Results: Among 277 TOE performed, 73 cases (26%) of LAA echo-contrast or thrombus were detected, 53 patients with LAA/LA echo-contrast (19%) and 20 (7%) with a thrombus. All patients were under chronic anticoagulation with a VKA (65%) or with a NOAC (35%). The Echo-contrast Group maintained the same OAC strategy in 49 patients (93%). The Thrombus Group kept the same OAC strategy with a NOAC in 6 cases (30%) and changed the strategy in 14 patients (70%), titrating NOAC dose in 1 (5%) and the VKA dose in 4 (20%) and switching from NOAC to VKA in 5 (25%), from VKA to NOAC in 3 (15%), and from NOAC to NOAC in 1 (5%). Smoke resolution was observed in 4/40 cases (10%) of the smoke group and thrombus resolution in 8/15 (53%) of the thrombus group. Patients with thrombus resolution had a lower CHA2DS2-Vasc score (3.5 ± 2 vs 4 ± 1, p = 0.05), were more often under NOAC (37.5 vs 28%, p = 0.07), and had a longer anticoagulation time (7.5 vs 4 months, p = 0.08)., Conclusion (s): Changing OAC strategy is associated with thrombus resolution in more than 50% of chronically anticoagulated patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2022
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30. [A clinical cardio-oncology pathway for the cardiology management of cancer outpatients: a joint proposal by ANMCO and AIOM Tuscany].

Author: Canale ML, Camerini A, Orso F, Misuraca L, Carluccio M, Talini E, Sorini Dini C, Grippo G, Simonetti F, Amoroso D, Allegrini G, Bengala C, and Casolo G
Subjects: Critical Pathways, Humans, Medical Oncology, Outpatients, Cardiology, Neoplasms therapy
Abstract: Cardio-oncology is now part of the standard clinical approach for patients with cancer and cannot be overlooked anymore. While its scientific background is solid and its clinical relevance is well known, its application in daily practice varies greatly among hospitals. To provide the best cardio-oncology care to cancer patients and to make cardio-oncology's clinical use uniform, we developed a shared multidisciplinary proposal for a dedicated clinical pathway. Our proposition presents the minimum requirements needed to which this path caters for, identifies patient categories to be entered into the path, highlights the role of a specific inter-hospital clinical and imaging network and indicates follow-up strategies during and after oncological treatments. The proposed pathway is based on some key elements and is easily adaptable to different hospitals with minimal changes.
Published: 2022
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31. Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A 1 Receptor Ligands.

Author: Zuccarini M, Lambertucci C, Carluccio M, Giuliani P, Ronci M, Spinaci A, Volpini R, Ciccarelli R, and Di Iorio P
Subjects: Adenosine A1 Receptor Agonists pharmacology, Adult, Apoptosis drug effects, Biomarkers metabolism, Cell Proliferation drug effects, Female, Humans, Ligands, Mesenchymal Stem Cells cytology, Necrosis, Phosphatidylinositol 3-Kinase metabolism, Phosphorylation drug effects, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects, Adipogenesis drug effects, Body Weight, Mesenchymal Stem Cells pathology, Obesity pathology, Receptor, Adenosine A1 metabolism, Subcutaneous Fat pathology
Abstract: Adenosine A 1 receptor (A 1 R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A 1 R agonists induce harmful side-effects, while partial agonists show a better pharmacological profile, we investigated the influence of two derivatives of the full A 1 R agonist 2-chloro- N 6 -cyclopentyladenosine (CCPA), C1 and C2 behaving as A 1 R partial agonists in animal models, on the adipogenic differentiation of stromal/stem cells (ASCs) from human subcutaneous adipose tissue, which mainly contribute to increase fat mass in obesity. The ASCs from normal-weight subjects showed increased proliferation and A 1 R expression but reduced adipogenic differentiation compared to obese individual-derived ASCs. Cell exposure to CCPA, C1, C2 or DPCPX, an A 1 R antagonist, did not affect ASC proliferation, while mainly C2 and DPCPX significantly decreased adipogenic differentiation of both ASC types, reducing the activity of glycerol-3-phosphate dehydrogenase and the expression of PPARγ and FABP-4, all adipogenic markers, and phosphorylation of Akt in the phosphatidylinositol-3-kinase pathway, which plays a key-role in adipogenesis. While requiring confirmation in in vivo models, our results suggest that A 1 R partial agonists or antagonists, by limiting ASC differentiation into adipocytes and, thereby, fat mass expansion, could favor development/worsening of metabolic syndrome in obese subjects without a dietary control.
Published: 2021
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32. Role of Purinome, A Complex Signaling System, In Glioblastoma Aggressiveness.

Author: Giuliani P, Carluccio M, and Ciccarelli R
Abstract: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Published: 2021
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33. Proteomic Characterization of Two Extracellular Vesicle Subtypes Isolated from Human Glioblastoma Stem Cell Secretome by Sequential Centrifugal Ultrafiltration.

Author: Di Giuseppe F, Carluccio M, Zuccarini M, Giuliani P, Ricci-Vitiani L, Pallini R, De Sanctis P, Di Pietro R, Ciccarelli R, and Angelucci S
Abstract: Extracellular vesicles (EVs) released from tumor cells are actively investigated, since molecules therein contained and likely transferred to neighboring cells, supplying them with oncogenic information/functions, may represent cancer biomarkers and/or druggable targets. Here, we characterized by a proteomic point of view two EV subtypes isolated by sequential centrifugal ultrafiltration technique from culture medium of glioblastoma (GBM)-derived stem-like cells (GSCs) obtained from surgical specimens of human GBM, the most aggressive and lethal primary brain tumor. Electron microscopy and western blot analysis distinguished them into microvesicles (MVs) and exosomes (Exos). Two-dimensional electrophoresis followed by MALDI TOF analysis allowed us to identify, besides a common pool, sets of proteins specific for each EV subtypes with peculiar differences in their molecular/biological functions. Such a diversity was confirmed by identification of some top proteins selected in MVs and Exos. They were mainly chaperone or metabolic enzymes in MVs, whereas, in Exos, molecules are involved in cell-matrix adhesion, cell migration/aggressiveness, and chemotherapy resistance. These proteins, identified by EVs from primary GSCs and not GBM cell lines, could be regarded as new possible prognostic markers/druggable targets of the human tumor, although data need to be confirmed in EVs isolated from a greater GSC number.
Published: 2021
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34. Adult mesenchymal stem cells: is there a role for purine receptors in their osteogenic differentiation?

Author: Carluccio M, Ziberi S, Zuccarini M, Giuliani P, Caciagli F, Di Iorio P, and Ciccarelli R
Subjects: Adult, Animals, Humans, Mesenchymal Stem Cells cytology, Osteoblasts cytology, Mesenchymal Stem Cells metabolism, Osteoblasts metabolism, Osteogenesis physiology, Receptors, Purinergic metabolism
Abstract: The role played by mesenchymal stem cells (MSCs) in contributing to adult tissue homeostasis and damage repair thanks to their differentiation capabilities has raised a great interest, mainly in bone regenerative medicine. The growth/function of these undifferentiated cells of mesodermal origin, located in specialized structures (niches) of differentiated organs is influenced by substances present in this microenvironment. Among them, ancestral and ubiquitous molecules such as adenine-based purines, i.e., ATP and adenosine, may be included. Notably, extracellular purine concentrations greatly increase during tissue injury; thus, MSCs are exposed to effects mediated by these agents interacting with their own receptors when they act/migrate in vivo or are transplanted into a damaged tissue. Here, we reported that ATP modulates MSC osteogenic differentiation via different P2Y and P2X receptors, but data are often inconclusive/contradictory so that the ATP receptor importance for MSC physiology/differentiation into osteoblasts is yet undetermined. An exception is represented by P2X7 receptors, whose expression was shown at various differentiation stages of bone cells resulting essential for differentiation/survival of both osteoclasts and osteoblasts. As well, adenosine, usually derived from extracellular ATP metabolism, can promote osteogenesis, likely via A2B receptors, even though findings from human MSCs should be implemented and confirmed in preclinical models. Therefore, although many data have revealed possible effects caused by extracellular purines in bone healing/remodeling, further studies, hopefully performed in in vivo models, are necessary to identify defined roles for these compounds in favoring/increasing the pro-osteogenic properties of MSCs and thereby their usefulness in bone regenerative medicine.
Published: 2020
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35. Upregulation of Epithelial-To-Mesenchymal Transition Markers and P2X7 Receptors Is Associated to Increased Invasiveness Caused by P2X7 Receptor Stimulation in Human Glioblastoma Stem Cells.

Author: Ziberi S, Zuccarini M, Carluccio M, Giuliani P, Ricci-Vitiani L, Pallini R, Caciagli F, Di Iorio P, and Ciccarelli R
Subjects: Biomarkers, Cell Line, Tumor, Cell Movement, Cell Survival genetics, Glioblastoma pathology, Humans, Neoplasm Invasiveness, Neoplastic Stem Cells pathology, Phosphorylation, Signal Transduction, Transforming Growth Factor beta1 metabolism, Tumor Microenvironment, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Glioblastoma metabolism, Neoplastic Stem Cells metabolism, Receptors, Purinergic P2X7 genetics, Receptors, Purinergic P2X7 metabolism
Abstract: Glioblastoma (GBM) stem cells (GSCs), which contribute to GBM unfavorable prognosis, show high expression levels of ATP/P2X7 receptors (P2X7R). Here, we reported that cells exposure to 2'(3')- O -(4-benzoylbenzoyl)-ATP (BzATP), a P2X7R agonist, up-regulated the expression of markers associated to epithelial-to-mesenchymal transition (EMT), a process likely contributing to GSC malignancy, and increased GSC migration/invasiveness like the known EMT inducer, Transforming Growth Factor β1 (TGFβ1). These effects were coupled to phosphorylation of SMAD2, a downstream effector in the TGFβ pathway, suggesting its involvement in P2X7R-mediated activity in GSCs. All BzATP effects, including a decrease in the caspase 3/7 activity in GSC medium, were mostly counteracted by the P2X7R antagonist A438079. Finally, BzATP increased the subunit expression of two main human P2X7R splice variants, the full-length P2X7A and the truncated P2X7B, lacking the carboxylic tail, which have different functional properties depending on their arrangement. Since up-regulation of A/B subunits might favor their assembly into a heterotrimeric P2X7R with great sensitivity towards agonists and cell energy support, this is in line with increased EMT markers expression, cell migration/invasion and GSC survival observed following P2X7R stimulation. As in GBM microenvironment extracellular ATP levels may activate P2X7R, our data suggest a P2X7R role in GBM recurrence/invasiveness.
Published: 2019
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36. Involvement of P2X7 Receptors in the Osteogenic Differentiation of Mesenchymal Stromal/Stem Cells Derived from Human Subcutaneous Adipose Tissue.

Author: Carluccio M, Zuccarini M, Ziberi S, Giuliani P, Morabito C, Mariggiò MA, Lonardo MT, Adinolfi E, Orioli E, Di Iorio P, Caciagli F, and Ciccarelli R
Subjects: Adenosine Triphosphate analogs & derivatives, Adenosine Triphosphate pharmacology, Humans, Mesenchymal Stem Cells cytology, Subcutaneous Fat cytology, Cell Differentiation, Mesenchymal Stem Cells metabolism, Osteogenesis, Receptors, Purinergic P2X7 metabolism, Subcutaneous Fat metabolism
Abstract: The ionotropic P2X7 receptor (P2X7R) is involved in bone homeostasis but its role in osteogenesis is controversial. Thus, we investigated the expression of P2X7R and the effects exerted by its modulation in mesenchymal stromal cells from human subcutaneous adipose tissue (S-ASCs), which have potential therapeutic application in bone regenerative medicine. We found that undifferentiated S-ASCs expressed P2X7R and its functional splice variants P2X7AR and P2X7BR. Cell stimulation by P2X7R agonist BzATP (100 μM) neither modified proliferation nor caused membrane pore opening while increasing intracellular Ca 2+ levels and migration. The P2X7R antagonist A438079 reversed these effects. However, 25-100 μM BzATP, administered to S-ASCs undergoing osteogenic differentiation, dose-dependently decreased extracellular matrix mineralization and expression of osteogenic transcription factors Runx2, alkaline phosphatase and osteopontin. These effects were not coupled to cell proliferation reduction or to cell death increase, but were associated to decrease in P2X7AR and P2X7BR expression. In contrast, expression of P2X7R, especially P2X7BR isoform, significantly increased during the osteogenic process. Noteworthy, the antagonist A438079, administered alone, at first restrained cell differentiation, enhancing it later. Accordingly, A438079 reversed BzATP effects only in the second phase of S-ASCs osteogenic differentiation. Apyrase, a diphosphohydrolase converting ATP/ADP into AMP, showed a similar behavior. Altogether, findings related to A438079 or apyrase effects suggest an earlier and prevailing pro-osteogenic activity by endogenous ATP and a later one by adenosine derived from endogenous ATP metabolism. Conversely, P2X7R pharmacological stimulation by BzATP, mimicking the effects of high ATP levels occurring during tissue injuries, depressed receptor expression/activity impairing MSC osteogenic differentiation.
Published: 2019
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37. Does the purinergic system affect extracellular matrix functions in the central nervous system?

Author: Zuccarini M, Carluccio M, Ziberi S, Giuliani P, Buccella S, Conti C, Ciccarelli R, and Di Iorio P
Subjects: Humans, Brain physiology, Central Nervous System physiology, Extracellular Matrix physiology, Receptors, Purinergic physiology
Abstract: Exracellular matrix (ECM) consists of a plethora of proteins and polysaccharides, which aggregate into an organized network connected to the surface of the producing cells. It is structurally and functionally present in all components of tissues and organs and represents the substrate on which cells adhere, migrate, proliferate and differentiate, influencing their survival, shape and function. In response to acute (trauma) or chronic (degenerative) insults, brain ECM modifies its composition and function, actively contributing to "scar forming" gliosis or tissue degeneration/remodelling. Moreover, morphological changes in dendritic spines associated with extracellular matrix remodeling play key roles in rewiring synaptic circuitry pertinent to memory formation. In the present report, we collected the main acquisitions on the functional interplay between ECM alterations and the adenine-/guaninebased purine system with particular regard on how purine compounds and their respective receptors may affect and be affected by changes of the cerebral ECM.
Published: 2018

38. Uncovering the Signaling Pathway behind Extracellular Guanine-Induced Activation of NO System: New Perspectives in Memory-Related Disorders.

Author: Zuccarini M, Giuliani P, Frinchi M, Mudò G, Serio RM, Belluardo N, Buccella S, Carluccio M, Condorelli DF, Caciagli F, Ciccarelli R, and Di Iorio P
Abstract: Mounting evidence suggests that the guanine-based purines stand out as key player in cell metabolism and in several models of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. Guanosine (GUO) and guanine (GUA) are extracellular signaling molecules derived from the breakdown of the correspondent nucleotide, GTP, and their intracellular and extracellular levels are regulated by the fine-tuned activity of two major enzymes, purine nucleoside phosphorylase (PNP) and guanine deaminase (GDA). Noteworthy, GUO and GUA, seem to play opposite roles in the modulation of cognitive functions, such as learning and memory. Indeed GUO, despite exerting neuroprotective, anti-apoptotic and neurotrophic effects, causes a decay of cognitive activities, whereas GUA administration in rats results in working memory improvement (prevented by L-NAME pre-treatment). This study was designed to investigate, in a model of SH-SY5Y neuroblastoma cell line, the signal transduction pathway activated by extracellular GUA. Altogether, our results showed that: (i) in addition to an enhanced phosphorylation of ASK1, p38 and JNK, likely linked to a non-massive and transient ROS production, the PKB/NO/sGC/cGMP/PKG/ERK cascade seems to be the main signaling pathway elicited by extracellular GUA; (ii) the activation of this pathway occurs in a pertussis-toxin sensitive manner, thus suggesting the involvement of a putative G protein coupled receptor; (iii) the GUA-induced NO production, strongly reduced by cell pre-treatment with L-NAME, is negatively modulated by the EPAC-cAMP-CaMKII pathway, which causes the over-expression of GDA that, in turn, reduces the levels of GUA. These molecular mechanisms activated by GUA may be useful to support our previous observation showing that GUA improves learning and memory functions through the stimulation of NO signaling pathway, and underscore the therapeutic potential of oral administration of guanine for treating memory-related disorders.
Published: 2018
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39. The Role of Wnt Signal in Glioblastoma Development and Progression: A Possible New Pharmacological Target for the Therapy of This Tumor.

Author: Zuccarini M, Giuliani P, Ziberi S, Carluccio M, Iorio PD, Caciagli F, and Ciccarelli R
Abstract: Wnt is a complex signaling pathway involved in the regulation of crucial biological functions such as development, proliferation, differentiation and migration of cells, mainly stem cells, which are virtually present in all embryonic and adult tissues. Conversely, dysregulation of Wnt signal is implicated in development/progression/invasiveness of different kinds of tumors, wherein a certain number of multipotent cells, namely "cancer stem cells", are characterized by high self-renewal and aggressiveness. Hence, the pharmacological modulation of Wnt pathway could be of particular interest, especially in tumors for which the current standard therapy results to be unsuccessful. This might be the case of glioblastoma multiforme (GBM), one of the most lethal, aggressive and recurrent brain cancers, probably due to the presence of highly malignant GBM stem cells (GSCs) as well as to a dysregulation of Wnt system. By examining the most recent literature, here we point out several factors in the Wnt pathway that are altered in human GBM and derived GSCs, as well as new molecular strategies or experimental drugs able to modulate/inhibit aberrant Wnt signal. Altogether, these aspects serve to emphasize the existence of alternative pharmacological targets that may be useful to develop novel therapies for GBM., Competing Interests: The authors declare no conflict of interest.
Published: 2018
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40. A New Investigational Perspective for Purines Against Glioblastoma Invasiveness.

Author: Giuliani P, Zuccarini M, Carluccio M, Ziberi S, Di Iorio P, Caciagli F, and Ciccarelli R
Subjects: Antineoplastic Agents therapeutic use, Brain Neoplasms pathology, Cell Movement drug effects, Clinical Trials as Topic, Epithelial-Mesenchymal Transition drug effects, Glioblastoma pathology, Humans, Molecular Targeted Therapy methods, Neoplasm Invasiveness prevention & control, Purinergic Antagonists therapeutic use, Purines pharmacology, Receptors, Purinergic metabolism, Signal Transduction drug effects, Treatment Outcome, Antineoplastic Agents pharmacology, Brain Neoplasms drug therapy, Glioblastoma drug therapy, Purinergic Antagonists pharmacology, Purines therapeutic use
Abstract: Background: Glioblastoma Multiforme (GBM) is the most common and lethal brain malignancy. Recent evidence suggests that the presence of stem-like cells (GSCs) inside the tumor with high self-renewal, resistance to chemotherapy and invasiveness/migration potential is associated with poor GBM prognosis. GSC aggressiveness seems to be linked to an important process involved in tumorigenesis and cancer metastasis called Epithelial-to-Mesenchymal Transition (EMT), which is responsible for several biochemical changes and the acquisition of a more mesenchymal phenotype by GSCs, that enhance their migration, invasiveness and resistance to apoptosis., Objective: Since previous reports demonstrated that purines, interacting with their own receptors, exerted anti-tumor effects in GBM and derived cells, we tried to investigate the ability of these compounds to reduce tumor cell migration/invasion acting on EMT-associated genes/activators and/or signal pathways., Methods: Search in the literature of relevant articles related to the objective., Results: Papers examining the activity of purines on EMT signaling pathways/markers in GSCs are still few whereas literature is more abundant as for other kinds of tumors., Conclusion: Considering the significance of EMT in GBM aggressiveness and the promising involvement of purines in this process, we think that further research in this regard may open the way towards a new therapeutic approach for the control of GBM invasiveness/recurrence., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
Published: 2018
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41. Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells.

Author: Zuccarini M, Giuliani P, Buccella S, Di Liberto V, Mudò G, Belluardo N, Carluccio M, Rossini M, Condorelli DF, Rathbone MP, Caciagli F, Ciccarelli R, and Di Iorio P
Subjects: Animals, Dogs, Fibrosis metabolism, Madin Darby Canine Kidney Cells, Transforming Growth Factor beta1 metabolism, Epithelial-Mesenchymal Transition physiology, Receptors, Purinergic P1 metabolism, Receptors, Purinergic P2 metabolism
Abstract: Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-β1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-β1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents.
Published: 2017
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42. [The EARLY ACS study].

Author: Galli M, Carluccio M, and Campo G
Subjects: Acute Coronary Syndrome mortality, Acute Coronary Syndrome physiopathology, Acute Coronary Syndrome therapy, Angioplasty, Balloon, Coronary, Confidence Intervals, Double-Blind Method, Electrocardiography, Eptifibatide, Humans, Italy, Myocardial Infarction mortality, Myocardial Infarction physiopathology, Myocardial Infarction therapy, Odds Ratio, Randomized Controlled Trials as Topic, Research Design, Survival Analysis, Time Factors, Acute Coronary Syndrome drug therapy, Myocardial Infarction drug therapy, Peptides therapeutic use, Platelet Aggregation Inhibitors therapeutic use
Published: 2010

43. [Coronary angiography in stable angina: friends and foes].

Author: Galli M, Ebert AG, and Carluccio M
Subjects: Humans, Patient Selection, Angina Pectoris diagnostic imaging, Coronary Angiography statistics & numerical data
Abstract: Preventive intervention presupposes a threat that can be averted at an acceptable cost; in patients with stable coronary artery disease, the threat of subsequent myocardial infarction and death is generally low, and proper management can usually control symptoms and improve prognosis substantially. In general, patients who have indications for coronary angiography are also potential candidates for revascularization. The relation of typical angina to prognosis is mediated by its relation to the extent of coronary disease; since the risk of coronary occlusion is not proportional to stenosis severity, it is not surprising that treating one or more stable tight lesions does not reduce the rates of subsequent major cardiac events. Clinical evaluation, ventricular function, response to stress testing, and the extent of coronary artery disease are the key pieces of information to stratify patient risk. In subjects without a markedly positive stress test, the ischemic burden is helpful in decision-making with respect to selecting initial therapy, and contributes to risk assessment. An initial invasive strategy without prior functional testing is rarely indicated, and may only be considered for patients with severe valve disease, serious arrhythmias or when therapy has failed to control symptoms satisfactorily, with a view to revascularization. In the absence of uncontrolled symptoms, patients are potentially eligible for coronary angiography if noninvasive tests reveal a substantial area of myocardium at risk. Coronary angiography should also be undertaken in patients with moderate to severe ischemia who do not have a significant reduction of the ischemic burden with therapy, given their worse prognosis. Because the treatment of asymptomatic patients cannot improve their symptoms, recommendations for coronary angiography in this subset are weaker and limited to risk stratification in subjects with high-risk criteria. Invasive procedures require a high likelihood of success and acceptable risk of morbidity and mortality and patients should be fully informed of the risks of the therapeutic modality individually. Regardless of the treatment modality used (early invasive vs selectively invasive), noninvasive imaging of the ischemic burden may assist in both decision-making for initial therapy and determining therapeutic efficacy related to long-term outcome.
Published: 2008

44. The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk. Two case-control studies and a meta-analysis.

Author: Di Castelnuovo A, Soccio M, Iacoviello L, Evangelista V, Consoli A, Vanuzzo D, Diviacco S, Carluccio M, Rignanese L, and De Caterina R
Subjects: Aged, Asian People genetics, Cardiovascular Diseases enzymology, Cardiovascular Diseases ethnology, Case-Control Studies, Coronary Artery Disease enzymology, Coronary Artery Disease ethnology, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Italy, Male, Middle Aged, NADPH Oxidases metabolism, Odds Ratio, Reactive Oxygen Species metabolism, Risk Assessment, Risk Factors, White People genetics, Cardiovascular Diseases genetics, Coronary Artery Disease genetics, NADPH Oxidases genetics, Polymorphism, Genetic
Abstract: NAD(P)H oxidase is a prominent source of reactive oxygen species in the vasculature. Vascular NAD(P)H oxidase is comprised of several subunits, one of which, p22phox, is encoded by a gene exhibiting several allelic variants. Here the C(242)T nucleotide transition has been found to alter superoxide anion production and associated with an altered risk of coronary artery disease (CAD). We assessed the role of this variant in two case-control studies, and performed a meta-analysis of previously reported investigations relating it to vascular risk. Population I was comprised of 492 subjects with type 2 diabetes, with or without macrovascular disease, matched for age, sex, and duration of diabetes. Population II was comprised of 158 subjects with or without either CAD or cerebro-vascular disease, and matched for age, sex, smoking status, weight category and the presence of hypertension, dyslipidemia, and diabetes. Our findings were meta-analyzed together with additional studies retrieved from the literature. The C(242)T polymorphism distribution did not differ between cases and controls in populations I and II both at univariate and multivariate analyses, and this was confirmed in a meta-analysis with 11 previously published populations. The meta-analysis, however, suggested a protective role of the T allele on CAD as an end point in Asian populations. In conclusion, these data suggest a significant heterogeneity for a modulating role of the T allele in the C(242)T polymorphism of p22-phox for the occurrence of CAD across ethnicities, with the absence of a significant effect in Caucasians.
Published: 2008
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45. Homocysteine induces VCAM-1 gene expression through NF-kappaB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants.

Author: Carluccio MA, Ancora MA, Massaro M, Carluccio M, Scoditti E, Distante A, Storelli C, and De Caterina R
Subjects: Antioxidants therapeutic use, Cell Adhesion drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Endothelial Cells enzymology, Endothelial Cells metabolism, Flavonoids therapeutic use, Homocysteine pharmacology, Humans, Hyperhomocysteinemia enzymology, Hyperhomocysteinemia metabolism, Hyperhomocysteinemia prevention & control, I-kappa B Proteins metabolism, Monocytes drug effects, Monocytes metabolism, Mutation, Phenols therapeutic use, Phenylethyl Alcohol analogs & derivatives, Phenylethyl Alcohol pharmacology, Phosphorylation, Polyphenols, Promoter Regions, Genetic drug effects, Proteasome Endopeptidase Complex metabolism, Protein Transport, RNA, Messenger metabolism, Reactive Oxygen Species metabolism, Resveratrol, Stilbenes pharmacology, Transcription, Genetic drug effects, Transfection, Tumor Necrosis Factor-alpha metabolism, Up-Regulation, Vascular Cell Adhesion Molecule-1 genetics, Antioxidants pharmacology, Diet, Mediterranean, Endothelial Cells drug effects, Flavonoids pharmacology, Homocysteine metabolism, NADPH Oxidases metabolism, Phenols pharmacology, Transcription Factor RelA metabolism, Vascular Cell Adhesion Molecule-1 metabolism
Abstract: Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-kappaB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-kappaB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 micromol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-kappaB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-kappaB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IkappaB-alpha and IkappaB-beta by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47(phox) subunit. NF-kappaB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60% at 10(-6) mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-kappaB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage.
Published: 2007
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46. Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects.

Author: Vanuzzo D, Pilotto L, Lombardi R, Lazzerini G, Carluccio M, Diviacco S, Quadrifoglio F, Danek G, Gregori D, Fioretti P, Cattaneo M, and De Caterina R
Subjects: Adult, C-Reactive Protein metabolism, Case-Control Studies, Coronary Artery Disease etiology, Coronary Thrombosis etiology, Female, Humans, Intracranial Arteriosclerosis etiology, Intracranial Thrombosis etiology, Male, Middle Aged, Prospective Studies, Risk Factors, Stroke blood, Stroke etiology, Coronary Artery Disease blood, Coronary Thrombosis blood, Homocysteine metabolism, Intracranial Arteriosclerosis blood, Intracranial Thrombosis blood, Vitamin B 6 metabolism
Abstract: Aims: The contribution of homocysteine and group B vitamins in determining cardiovascular risk is debated. We assessed the predictive value of total homocysteine (tHcy), vitamin B12, folate, and vitamin B6 on the long-term occurrence of coronary and cerebral atherothrombotic events in a nested case-control study., Methods and Results: Within a cohort of 1021 healthy subjects (490 men and 531 women) recruited in 1987, 66 first-ever coronary and 43 first-ever cerebrovascular events were recorded at a 12-year follow-up (cases, n=109). A total of 109 control subjects (remaining free from events) were matched with cases according to age, sex, smoking, hypertension, dyslipidaemia, and body mass index. Serum samples obtained in 1987 at baseline were used to measure tHcy, folate, and vitamins B12 and B6, as well as C-reactive protein plasma concentrations. We found a significant graded association between tHcy levels and the risk of coronary and cerebrovascular events [odds ratio (OR) for uppermost vs. lowermost quartile=1.34, 95% CI 1.01-1.76)]. Folate and vitamin B12 did not significantly differ between cases and controls, but were negatively (P<0.01) correlated with tHcy. Vitamin B6 did not correlate with tHcy levels, but differed significantly between cases and controls: for subjects in the uppermost quartile vs. the lowermost quartile of vitamin B6, OR=0.69 (95% CI 0.49-0.98). For subjects in the lowermost quartile of vitamin B6 and the uppermost quartile of tHcy, OR=17.50 (95% CI 1.97, 155.59). Cases and controls were not different as to C-reactive protein., Conclusion: tHcy and plasma vitamin B6 are long-term independent risk factors for coronary and cerebrovascular events.
Published: 2007
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47. [Sudden cardiac death: prevention when is right! From evidence-based medicine to family-based medicine].

Author: Paperini L, Genovesi A, and Carluccio M
Subjects: Angiotensin-Converting Enzyme Inhibitors therapeutic use, Antihypertensive Agents therapeutic use, Carbazoles therapeutic use, Carvedilol, Europe, Family Practice, Humans, Propanolamines therapeutic use, Randomized Controlled Trials as Topic, Risk Factors, Stroke Volume, United States, Vasodilator Agents therapeutic use, Ventricular Dysfunction, Left drug therapy, Death, Sudden, Cardiac prevention & control, Defibrillators, Implantable statistics & numerical data, Evidence-Based Medicine
Published: 2006

48. Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants.

Author: Soccio M, Toniato E, Evangelista V, Carluccio M, and De Caterina R
Subjects: Coronary Artery Disease genetics, Endothelium, Vascular metabolism, Gene Frequency, Humans, Membrane Transport Proteins genetics, Membrane Transport Proteins metabolism, Mutation genetics, NADPH Oxidases genetics, Phosphoproteins genetics, Phosphoproteins metabolism, Polymorphism, Genetic, Reactive Oxygen Species metabolism, Risk Factors, Coronary Artery Disease etiology, NADPH Oxidases metabolism, Oxidative Stress physiology
Abstract: Several risk factors for coronary artery disease (CAD) induce atherosclerosis through endothelial activation and dysfunction, and ample evidence now suggests that the balance between production and removal of reactive oxygen species (ROS) - a condition termed oxidative stress - is implicated in such processes. A main source of ROS in vascular cells is the reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase system. This is a membrane-associated enzyme, composed of five subunits, catalyzing the one-electron reduction of oxygen, using NADH or NADPH as the electron donor. One of the system subunits, termed p22-phox, has a polymorphic site on exon 4, associated with variable enzyme activity. This polymorphism is generated by a point mutation (C(242)T) producing a substitution of histidine with tyrosine at position 72, which affects one of the heme binding sites essential for the NAD(P)H enzyme activity. The consequent decrease of superoxide production thus characterizes a phenotype candidate for conferring to the carrier a reduced susceptibility to CAD. At present, however, the body of evidence from current literature is not yet sufficient to confirm or exclude the hypothesis that the C(242)T polymorphism protects from CAD. The functional effects of this polymorphism and the potential and its pathophysiological consequences also need further investigation.
Published: 2005
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49. Heart involvement in T cell lymphoma through hypereosinophilic syndrome: a common complication of a rare condition.

Author: Genovesi-Ebert A, Lombardi M, Capochiani E, Simi U, Savoia MT, Baldini U, Digiorgio A, Carluccio M, Di Santo D, and Galli M
Subjects: Adult, Contrast Media, Electrocardiography, Endomyocardial Fibrosis etiology, Gadolinium DTPA, Humans, Magnetic Resonance Imaging, Cine, Male, Endomyocardial Fibrosis diagnosis, Hypereosinophilic Syndrome complications, Lymphoma, T-Cell diagnosis
Abstract: This case describes a 42-year-old male affected by hypereosinophilic syndrome associated with angioimmunoblastic lymphoma. Heart involvement was suspected at ECG mimicking left ventricular hypertrophy. MRI clarified the extensive endomyocardial fibrosis, confirming the role of this technique in in-vivo tissue characterization. Finally, the study investigates the association of T cell lymphoma, hypereosinophilic syndrome, and Loeffler endomyocardial disease.
Published: 2005
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50. [Stress imaging in coronary artery disease: state of the art].

Author: Baldini U, Venturini C, Genovesi-Ebert A, Savoia MT, Raugi M, Pauletti M, Carluccio M, Digiorgio A, Gasperetti G, and Galli M
Subjects: Coronary Disease economics, Dobutamine, Electrocardiography, Exercise Test, Humans, Prognosis, Research, Thallium Radioisotopes, Coronary Disease diagnostic imaging, Echocardiography, Stress economics, Tomography, Emission-Computed methods, Tomography, Emission-Computed, Single-Photon methods
Abstract: To date, several diagnostic tools allow an accurate non-invasive evaluation of coronary artery disease; this is due to the great progress in echocardiographic and nuclear imaging techniques in the last 10 years. The large availability of different stress imaging techniques allows to choose the most appropriate technique for each patient according to the clinical characteristics. This paper presents the state of the art of echocardiographic and nuclear stress imaging for the diagnosis of coronary artery disease and for the prognostic stratification of infarcted patients. Advantages and limits of the different techniques are described rather than putting in competition echo and nuclear cardiology as has often been done in the past. Cardiologists should select among the various techniques on the basis of clinical characteristics of single patients, center's experience and an objective evaluation of economical aspects.
Published: 2004

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