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1. Subclinical Target Organ Damage in a Sample of Children with Autosomal Dominant Polycystic Kidney Disease: A Pilot Study

Author

Simone Romano, Denise Marcon, Lorella Branz, Angela Tagetti, Giada Monamì, Alice Giontella, Francesca Malesani, Luca Pecoraro, Pietro Minuz, Milena Brugnara, and Cristiano Fava

Subjects
ADPKD, hypertension, vascular damages, cardiac remodeling, cardiac hypertrophy, Medicine (General), R5-920
Abstract

Background and Objectives: Hypertension and vascular damage can begin in adolescents affected by Autosomal Dominant Polycystic Kidney Disease (ADPKD). This study aimed to evaluate markers of vascular damage and left ventricular geometry in a sample of children with ADPKD. Materials and Methods: Several vascular measurements were obtained: ambulatory blood pressure monitoring (ABPM), carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), pulse wave velocity (PWV), and echocardiographic measurements (relative wall thickness (RWT) and left ventricular mass index (LVMI)). Results: Eleven ADPKD children were recruited (four females and seven males, mean age 9.5 ± 3.2 years). Four children were hypertensive at the ABPM, five were normotensive, and for two ABPM was not available. RWT was tendentially high (mean 0.47 ± 0.39). Eight patients had concentric cardiac remodeling, while one patient had cardiac hypertrophy. cIMT was above the 95° percentile for sex and height in 80% of the children (0.5 ± 0.005 mm). The average PWV and cDC were between the normal range (5.5 ± 4.6 m/s and 89.6 ± 16.1 × 10−3/KPa, respectively). We observed a positive correlation between the PWV and RWT (r = 0.616; p = 0.044) and a negative correlation between cDC and RWT (r = −0.770; p = 0.015). Cardiovascular damages (cIMT > 95° percentile) were found in normotensive patients. Conclusions: Increased RWT and high cIMT, indicating subclinical organ damage, are already present in ADPKD children. RWT was significantly correlated to that of cDC and PWV, implying that vascular stiffening is associated with cardiac remodeling. None of the children had an alteration in renal function. Subclinical cardiovascular damage preceded the decline in glomerular filtration rate.

Published
2023
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2. Platelets in Non-alcoholic Fatty Liver Disease

Author

Andrea Dalbeni, Marco Castelli, Mirko Zoncapè, Pietro Minuz, and David Sacerdoti

Subjects
non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, inflammation, fibrosis, platelets, Kupffer cells, Therapeutics. Pharmacology, RM1-950
Abstract

Non alcoholic steatohepatitis (NASH) is the inflammatory reaction of the liver to excessive accumulation of lipids in the hepatocytes. NASH can progress to cirrhosis and hepatocellular carcinoma (HCC). Fatty liver is the hepatic manifestation of metabolic syndrome. A subclinical inflammatory state is present in patients with metabolic alterations like insulin resistance, type-2 diabetes, obesity, hyperlipidemia, and hypertension. Platelets participate in immune cells recruitment and cytokines-induced liver damage. It is hypothesized that lipid toxicity cause accumulation of platelets in the liver, platelet adhesion and activation, which primes the immunoinflammatory reaction and activation of stellate cells. Recent data suggest that antiplatelet drugs may interrupt this cascade and prevent/improve NASH. They may also improve some metabolic alterations. The pathophysiology of inflammatory liver disease and the implication of platelets are discussed in details.

Published
2022
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3. Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension

Author

Guido Iaccarino, Guido Grassi, Claudio Borghi, Stefano Carugo, Francesco Fallo, Claudio Ferri, Cristina Giannattasio, Davide Grassi, Claudio Letizia, Costantino Mancusi, Pietro Minuz, Stefano Perlini, Giacomo Pucci, Damiano Rizzoni, Massimo Salvetti, Riccardo Sarzani, Leonardo Sechi, Franco Veglio, Massimo Volpe, Maria Lorenza Muiesan, and on Behalf of the SARS-RAS Investigators

Subjects
Medicine, Science
Published
2022

4. Interference of C6O4 on platelet aggregation pathways: Cues on the new-generation of perfluoro-alkyl substance

Author

Pietro Minuz, Luca De Toni, Stefano Dall'Acqua, Andrea Di Nisio, Iva Sabovic, Marco Castelli, Alessandra Meneguzzi, and Carlo Foresta

Subjects
Cardiovascular risk, Platelets micro-particles, Flow cytometry, Toxicokinetics, Acetylsalicylic acid, Environmental sciences, GE1-350
Abstract

Background: Health concerns associated with the exposure to legacy perfluoro-alkyl substances (PFAS) led to the development of new-generation PFAS, such as C6O4. Here we investigated the possible effects of C6O4 on the platelet’s activation profile, by incubating human platelets from healthy donors with C6O4 at different concentrations and evaluating the effects on activation, production and phenotype of platelets micro-particles (MPV) and aggregation under-flow. Based on the eventual platelet pro-aggregation profile detected, the preventive effect of acetylsalicylic acid (ASA) was also explored. Methods: Adhesion-induced platelet aggregation of platelet rich plasma (PRP) under flow was evaluated on collagen-coated microchip at a shear stress of 10 Dyne. The turbidimetric method was used to investigate platelet aggregation. Finally, the in vitro generation of pro-coagulant MPV in PRP was evaluated by flow cytometry, as characterized by CD41 and annexin V positive events, under resting conditions and after stimulation with agonists at low shear stress. Results: The generation of platelet aggregates under flow was significantly increased by the pretreatment of PRP with 100–200 ng/mL C6O4, compared to both the control condition and the experiment performed in presence of ASA. Arachidonic acid (AA), ADP and collagen induced an higher maximal aggregation, at turbidimetric evaluation, when PRP was pretreated with 100–500 ng/mL C6O4. In addition, PRP stimulated with AA also showed a steeper slope of the aggregation curve. The aggregation induced by the tested agonists was almost abolished by ASA. Finally, pretreatment with C6O4 increased the number of MPV in resting conditions and in presence of ADP and TRAP. ASA tended to reduce MPV generation. Conclusions: Exposure to C6O4 associates with an increased platelet response to agonists, translating into a possible increased risk of cardiovascular events. Pending a further clarification on the toxicokinetics of this compound, our results claim the possible prophylactic use of ASA.

Published
2021
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5. Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence

Author

Alessandra Meneguzzi, Cristiano Fava, Marco Castelli, and Pietro Minuz

Subjects
perfluoroalkyl substances, cardiovascular disease, obesity, diabetes mellitus, arterial hypertension, platelets, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Polyfluoro- and perfluoro–alkyl substances (PFAS) are organic chemicals extensively used worldwide for industry and consumer products. Due to their chemical stability, PFAS represent a major cause of environmental pollution. PFAS accumulate in animal and human blood and tissues exerting their toxicity. We performed a review of the epidemiological studies exploring the relationship between exposure to PFAS and thromboembolic cardiovascular disease. An increase in cardiovascular disease or death related to PFAS exposure has been reported from cross-sectional and longitudinal observational studies with evidence concerning the relation with early vascular lesions and atherosclerosis. Several studies indicate an alteration in lipid and glucose metabolism disorders and increased blood pressure as a possible link with cardiovascular thromboembolic events. We also examined the recent evidence indicating that legacy and new PFAS can be incorporated in platelet cell membranes giving a solid rationale to the observed increase risk of cardiovascular events in the populations exposed to PFAS by directly promoting thrombus formation. Exposure to PFAS has been related to altered plasma membrane fluidity and associated with altered calcium signal and increased platelet response to agonists, both in vitro and ex vivo in subjects exposed to PFAS. All the functional responses are increased in platelets by incorporation of PFAS: adhesion, aggregation, microvesicles release and experimental thrombus formation. These findings offer mechanistic support the hypothesis that platelet-centred mechanisms may be implicated in the increase in cardiovascular events observed in populations chronically exposed to PFAS.

Published
2021
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6. Causal Effect of Adiposity Measures on Blood Pressure Traits in 2 Urban Swedish Cohorts: A Mendelian Randomization Study

Author

Alice Giontella, Luca A. Lotta, John D. Overton, Aris Baras, Pietro Minuz, Olle Melander, Dipender Gill, and Cristiano Fava

Subjects
adiposity, blood pressure, genetics, Mendelian randomization, polymorphisms, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. Methods and Results In this study, we used 4 different genetic risk scores (GRS; GRS‐BMI565, GRS‐WHR324, GRS‐VAT208, GRS‐BF81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist‐to‐hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban‐based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive 795Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist‐to‐hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow‐up in the Malmö Preventive Project. Conclusions We support a causal link between genetically mediated adiposity, especially waist‐to‐hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk.

Published
2021
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7. Unusual presentation of primary aldosteronism with advanced target organ damage: A case report

Author

Cristiano Fava, MD, PhD, Filippo Cattazzo, MD, Riccardo Bernasconi, MD, Simone Romano, MD, and Pietro Minuz, MD

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Patients with primary aldosteronism have greater cardiovascular morbidity and mortality than patients with primary hypertension and a comparable cardiovascular risk profile. Herein we present the case of a patient who developed multiple end-organ damage due to unrecognized and uncontrolled hypertension caused by an aldosterone-producing adrenal adenoma. Clinical and radiological evaluation revealed hypertensive encephalopathy, cardiomyopathy, retinopathy and nephropathy which required hemodialysis. Blood pressure control before surgery was difficult due to renal impairment that precluded the administration of anti-aldosterone drugs. Primary aldosteronism was cured by laparoscopic adrenalectomy and all antihypertensive drugs were suspended.A remarkable aspect of this case is the discordant results at screening test for primary aldosteronism: even though aldosterone-to-renin ratio is the most reliable method to identify possible cases of primary aldosteronism it can be misleading especially in case of multiple comorbidities and concomitant antihypertensive treatment. Furthermore, anti-aldosterone drugs are worrisome to use when renal damage is advanced but can be reconsidered when hemodialysis begins. Keywords: Primary aldosteronism, Hypertension, Advanced target organ damage, End stage renal disease, Case report

Published
2019
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8. Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report

Author

Angela Tagetti, Denise Marcon, Paolo Moghetti, Giovanna Spiazzi, Cristiano Fava, and Pietro Minuz

Subjects
Addison disease, pregnancy, therapy, twins, Medicine, Medicine (General), R5-920
Abstract

Key Clinical Message Addison Disease is an uncommon, life‐threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.

Published
2021
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9. Correction: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

Author

Guido Iaccarino, Guido Grassi, Claudio Borghi, Stefano Carugo, Francesco Fallo, Claudio Ferri, Cristina Giannattasio, Davide Grassi, Claudio Letizia, Costantino Mancusi, Pietro Minuz, Stefano Perlini, Giacomo Pucci, Damiano Rizzoni, Massimo Salvetti, Riccardo Sarzani, Leonardo Sechi, Franco Veglio, Massimo Volpe, Maria Lorenza Muiesan, and SARS-RAS Investigators

Subjects
Medicine, Science
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0237297.].

Published
2021
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10. The role of sacubitril/valsartan in the treatment of chronic heart failure with reduced ejection fraction in hypertensive patients with comorbidities: From clinical trials to real-world settings

Author

Alberto Mazza, Danyelle M. Townsend, Gioia Torin, Laura Schiavon, Alessandro Camerotto, Gianluca Rigatelli, Stefano Cuppini, Pietro Minuz, and Domenico Rubello

Subjects
Ejection fraction, Chronic heart failure, Hypertension, Internal medicine, Mortality, Sacubitril/valsartan, Therapeutics. Pharmacology, RM1-950
Abstract

Background: Sacubitril/valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs), has been shown to reduce cardiovascular mortality and morbidity compared to enalapril in outpatient subjects with chronic heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, there is little real-world evidence about the efficacy of ARNIs in elderly hypertensive patients with HFrEF and comorbidities. Methods: In this prospective open-label study, 108 subjects, 54 of them (mean age 78.6 ± 8.2 years, 75.0 % male), with HFrEF (29.8 ± 4.3 %) and New York Heart Association (NYHA) class II-III symptoms were assigned to receive ARNIs twice daily, according to the recommended dosage of 24/26, 49/51, 97/103 mg. Patients were gender- and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated hemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months. During the follow-up, the clinical outcomes, including mortality and re-hospitalization for HF, were collected. Results: NYHA class significantly improved in the ARNI arm compared to the control (24.9 vs. 6.4 %, shifting from class III to II, and 55.4 vs. 25.2 %, from class II to I, p

Published
2020
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11. The 2020 Italian Society of Arterial Hypertension (SIIA) practical guidelines for the management of primary aldosteronism

Author

Gian Paolo Rossi, Valeria Bisogni, Alessandra Violet Bacca, Anna Belfiore, Maurizio Cesari, Antonio Concistrè, Rita Del Pinto, Bruno Fabris, Francesco Fallo, Cristiano Fava, Claudio Ferri, Gilberta Giacchetti, Guido Grassi, Claudio Letizia, Mauro Maccario, Francesca Mallamaci, Giuseppe Maiolino, Dario Manfellotto, Pietro Minuz, Silvia Monticone, Alberto Morganti, Maria Lorenza Muiesan, Paolo Mulatero, Aurelio Negro, Gianfranco Parati, Martino F. Pengo, Luigi Petramala, Francesca Pizzolo, Damiano Rizzoni, Giacomo Rossitto, Franco Veglio, and Teresa Maria Seccia

Subjects
Primary aldosteronism, Hypertension, Guidelines, Diagnosis, Treatment, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background and aim: Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism. Methods: To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered. Results: Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review. Conclusions: After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.

Published
2020
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12. Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

Author

Guido Iaccarino, Guido Grassi, Claudio Borghi, Stefano Carugo, Francesco Fallo, Claudio Ferri, Cristina Giannattasio, Davide Grassi, Claudio Letizia, Costantino Mancusi, Pietro Minuz, Stefano Perlini, Giacomo Pucci, Damiano Rizzoni, Massimo Salvetti, Riccardo Sarzani, Leonardo Sechi, Franco Veglio, Massimo Volpe, Maria Lorenza Muiesan, and SARS-RAS Investigators

Subjects
Medicine, Science
Abstract

BackgroundThe global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.Methods and findingsWe designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 pConclusionsOur study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders.Trial registrationClinicaltrials.gov: NCT04331574.

Published
2020
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13. Lycopene inhibits endothelial cells migration induced by vascular endothelial growth factor A increasing nitric oxide bioavailability

Author

Davide Treggiari, Andrea Dalbeni, Alessandra Meneguzzi, Pietro Delva, Cristiano Fava, Barbara Molesini, Tiziana Pandolfini, and Pietro Minuz

Subjects
Lycopene, Nitric oxide, Endothelial cell migration, VEGF pathway, Nutrition. Foods and food supply, TX341-641
Abstract

Lycopene is a carotenoid found in tomatoes previously shown bioactive in endothelial cells. We studied in vitro cell migration, key step in angiogenesis using the scratch wound healing assay to test the effects of lycopene (2 µmol/L) on Human Umbilical Vein Endothelial Cells. To explore the cellular mechanism, we measured nitric oxide (NO) release and protein kinase B (Akt) phosphorylation. Lycopene inhibited cell migration induced by vascular endothelial growth factor-A (VEGFA) and reduced Akt phosphorylation. NO generation in endothelial cells, assessed by using difluorofluorescein diacetate, was increased by lycopene alone or in combination with VEGFA and blunted by NO synthase inhibition. Increased nitrite-nitrate concentration in culture medium indicates effects of lycopene on NO bioavailability, potentially implicated in the reduction in VEGFA-induced cell migration, as observed with a NO-donor. In conclusion, lycopene inhibits endothelial cells migration modulating VEGFA signalling system. Increased NO generation partly explains lycopene bioactivity.

Published
2018
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14. Calcium, Its Regulatory Hormones, and Their Causal Role on Blood Pressure: A Two-Sample Mendelian Randomization Study

Author

Alice Giontella, Luca A Lotta, Aris Baras, Pietro Minuz, Dipender Gill, Olle Melander, and Cristiano Fava

Subjects
calcium homeostasis, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, Blood Pressure, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Biochemistry, Calcium, Dietary, Endocrinology, Parathyroid Hormone, Mendelian randomization, Humans, Calcium, Vitamin D, Genome-Wide Association Study
Abstract

Context Vitamin D (Vit-D), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium itself or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear. Objective To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study. Methods From 4 large genome-wide association studies (GWAS) we obtained independent (r2 < 0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs), PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with systolic BP (SBP) and diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer study (n = 29 298). Causality was evaluated by the inverse variance weighted method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses. Results Genetically predicted serum calcium level was found to be associated with DBP (IVW: beta = 0.10, SE = 0.04, P = 0.007) and SBP (IVW: beta = 0.07, SE = 0.04, P = 0.04). Genetically predicted Vit-D and PTH showed no association with the traits, while FGF23 was inversely associated with SBP (IVW: beta = −0.11, SE = 0.04, P = 0.01), although this association lost statistical significance in sensitivity analysis. Conclusion Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormone levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies.

Published
2022

15. Platelet-Derived Extracellular Vesicles as Target of Antiplatelet Agents. What Is the Evidence?

Author

Francesco Taus, Alessandra Meneguzzi, Marco Castelli, and Pietro Minuz

Subjects
platelets, microvesicles, aspirin, thromboxane, P2Y12 inhibitors, atherothrombosis, Therapeutics. Pharmacology, RM1-950
Abstract

Platelet-derived large extracellular vesicles (often referred to as microparticles in the field of cardiovascular disease) have been identified as effector in the atherothrombotic process, therefore representing a target of pharmacological intervention of potential interest. Despite that, limited evidence is so far available concerning the effects of antiplatelet agents on the release of platelet-derived extracellular vesicles. In the present narrative review, the mechanisms leading to vesiculation in platelets and the pathophysiological processes implicated will be discussed. This will be followed by a summary of the present evidence concerning the effects of antiplatelet agents under experimental conditions and in clinical settings.

Published
2019
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16. P169 RELATIONSHIP BETWEEN COMMON CAROTID DISTENSIBILITY/AORTIC STIFFNESS AND LEFT VENTRICULAR MORPHOLOGY AND FUNCTION IN RHEUMATOLOGIC PATIENTS

Author

Michele Bevilacqua, Andrea Dalbeni, Angela Tagetti, Luca Gomarasca, Giovanni Orsolini, Andrea Giollo, Maurizio Rossini, Ombretta Viapiana, Giovanni Cioffi, Pietro Minuz, and Cristiano Fava

Subjects
Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Introduction: Arterial stiffness is known to be associated with atherosclerosis, cardiac remodelling and cardiovascular diseases. In recent studies, common carotid artery rigidity was seen to better predict cardiac morphology and function if compared to aortic parameters. The aim of the study was to determine the relation between carotid/aortic stiffness indices and the main echocardiographic measures in patients with rheumatological disease. Methods: 208 participants were evaluated (57,4 ± 11,4 yr; males = 36,1%); 65,9% were previously diagnosed with rheumatoid arthritis, 20,2% with psoriatic arthritis and 13,9% with ankylosing spondylitis. In each subjects medical history, use of drugs and glico-metabolic status was assessed. Echocardiography, blood pressure (BP) measurement and carotid ultrasonography were performed. Carotid Distensibility (CD) and Aortic Stiffness (AoS) were measured as indices of arterial stiffness. Results: Mean Left Ventricular Mass indexed by body surface area (LVM/BSA) and Relative Wall Thickness (RWT) were 98,8 ± 20,7 g/m2 and 0,46 ± 0,06, respectively. In multiple regression analysis, DC was correlated with age (β = 0,325, p < 0,0001) and mean BP (β = 0,502, p < 0,0001) while AoS was not associated with any anthropometric, anamnestic and vascular parameters. DC has been seen to inversely correlate with LVM/BSA (r = −0,20, p = 0,005), Intraventricular Septum and Posterior Wall Thickenss; a direct correlation between AoS and left E/e’ (a diastolic function indicator) has emerged (r = 0,191, p = 0,007). Conclusion: Results are consistent with a possible predictive role of DC assessment in left cardiac hypertrophy and remodelling and a direct link between AoS and left ventricular diastolic function.

Published
2018
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17. Global Longitudinal Strain to Predict Respiratory Failure and Death in Patients Admitted for COVID-19–Related Disease

Author

Michele Bevilacqua, Paolo De Togni, Filippo Cattazzo, Davide Dell'Atti, Andrea Dalbeni, Fulvia Mazzaferri, Evelina Tacconelli, Afshin Farzaneh-Far, Cristiano Fava, Pietro Minuz, and Simone Romano

Subjects
Aged, 80 and over, Male, Respiratory Distress Syndrome, SEPSIS, MORTALITY, COVID-19, ASSOCIATION, Middle Aged, Respiration, Artificial, Article, Hospitalization, Survival Rate, Ventricular Dysfunction, Left, LONG-AXIS FUNCTION, ECHOCARDIOGRAPHY, ASSOCIATION, MORTALITY, SEPSIS, LONG-AXIS FUNCTION, Italy, Echocardiography, Predictive Value of Tests, Humans, Female, Prospective Studies, Cardiology and Cardiovascular Medicine, Aged
Abstract

Evidence of the involvement of the cardiovascular system in patients with COVID-19 is increasing. The evaluation of the subclinical cardiac involvement is crucial for risk stratification at admission, and left ventricular global longitudinal strain (LVGLS) may be useful for this purpose. A total of 87 consecutive patients admitted to the COVID Center were enrolled from December 2020 to April 2021. A complete echocardiography examination was performed within 72 hours from admission. The main outcome was the need for mechanical ventilation by way of orotracheal intubation (OTI) and mortality, and the secondary outcome was the worsening of the respiratory function during hospitalization, interpreted as a decrease of the ratio between the partial pressure of oxygen and the fraction of inspired oxygen (P/F)

Published
2022

18. Tumor-Educated Platelet Extracellular Vesicles: Proteomic Profiling and Crosstalk with Colorectal Cancer Cells

Author

Annalisa Contursi, Rosa Fullone, Paulina Szklanna-Koszalinska, Simone Marcone, Paola Lanuti, Francesco Taus, Alessandra Meneguzzi, Giulia Turri, Melania Dovizio, Annalisa Bruno, Corrado Pedrazzani, Stefania Tacconelli, Marco Marchisio, Patrizia Ballerini, Pietro Minuz, Patricia Maguire, and Paola Patrignani

Subjects
epithelial-mesenchymal transition, cyclooxygenase-2, thromboxane A2, platelet-derived extracellular vesicles, colorectal cancer, Cancer Research, Oncology, Epithelial-mesenchymal transition
Abstract

Background: Platelet–cancer cell interactions modulate tumor metastasis and thrombosis in cancer. Platelet-derived extracellular vesicles (EVs) can contribute to these outcomes. Methods: We characterized the medium-sized EVs (mEVs) released by thrombin-stimulated platelets of colorectal cancer (CRC) patients and healthy subjects (HS) on the capacity to induce epithelial-mesenchymal transition (EMT)-related genes and cyclooxygenase (COX)-2(PTGS2), and thromboxane (TX)B2 production in cocultures with four colorectal cancer cell lines. Platelet-derived mEVs were assessed for their size distribution and proteomics signature. Results: The mEV population released from thrombin-activated platelets of CRC patients had a different size distribution vs. HS. Platelet-derived mEVs from CRC patients, but not from HS, upregulated EMT marker genes, such as TWIST1 and VIM, and downregulated CDH1. PTGS2 was also upregulated. In cocultures of platelet-derived mEVs with cancer cells, TXB2 generation was enhanced. The proteomics profile of mEVs released from activated platelets of CRC patients revealed that 119 proteins were downregulated and 89 upregulated vs. HS. Conclusions: We show that mEVs released from thrombin-activated platelets of CRC patients have distinct features (size distribution and proteomics cargo) vs. HS and promote prometastatic and prothrombotic phenotypes in cancer cells. The analysis of platelet-derived mEVs from CRC patients could provide valuable information for developing an appropriate treatment plan.

Published
2023
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19. Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients

Author

Sebastiano, Cicco, D'Abbondanza, Marco, Proietti, Marco, Vincenzo, Zaccone, Chiara, Pes, Federica, Caradio, Mattioli, Massimo, Salvatore, Piano, Alberto Maria Marra, Alessandro, Nobili, Pier Mannuccio Mannucci, Antonello, Pietrangelo, Giorgio, Sesti, Elena, Buzzetti, Andrea, Salzano, Antonio, Cimellaro, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Alessio, Novella, Gabriella, Miglio, Alessia Antonella Galbussera, Ilaria, Ardoino, Prisco, Domenico, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Pirro, Matteo, Lupattelli, Graziana, Bianconi, Vanessa, Alcidi, Riccardo, Giotta, Alessia, Massimo, R Mannarino, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Federica, Cavallaro, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Serafini, Giovanni, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta, Mancarella, Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Conti, Federica, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra, Cambiè, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico, Cattaneo, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D'Ardes, Lucia, Esposito, Simona, Sestili, Ermanno, Angelucci, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giovanni, Imbimbo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto, Zucchelli, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Mazzola, Paolo, Piazzoli, Andrea, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta, Cosi, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Ilenia, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca, Loparco, Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore, D'Aniano, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice, Cinque, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Erica, Pagliaro, Eleonora, Semproni, Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian, Folli, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca, Liberale, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia, Cesaroni, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Francesca, Rotunno, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Francesco, Dentali, Bertolotti, Marco, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Pellegrini, Elisa, Laura, Orlandi, Giulia, Dondi, Lucia, Carulli, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco, Filice, Elvira, Clausi, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Ilaria, Benzoni, Andrea, Salvi, Leonardi, Roberto, Giampaolo, Damiani, Gianluca, Moroncini, William, Capeci, Giuseppe Pio Martino, Biondi, Lorenzo, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto, Romiti, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Samuele, Pignataro, Francesca, Mete, Miriam, Gino, Guido, Moreo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla, Scarsi, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca, Losa, Montalto, GIUSEPPE ALBERT, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Sarah, Morellini, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Tarquini, Roberto, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Volpi, Riccardo, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Franco Laghi Pasini, Pier Leopoldo Capecchi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Vittorio, Durante, Daniela, Tirotta, Giovanna, Eusebi, Cattaneo, Marco Natale, Amoruso, MARIA VALENTINA, Paola, Fracasso, Cristina, Fasolino, Moreno, Tresoldi, Enrica, Bozzolo, Sarah, Damanti, Massimo, Porta, Giuseppe, Armentaro, Maria Immacolata Arnone, Milena, Barone, Lorenzo, Bertolino, Sara, Bianco, Nicolò, Binello, Simona, Brancati, Agostino, Buonauro, William, Cordeddu, Curcio, Rosa, Andrea, Dalbeni, Salvatore, D'Agnano, Damiano, D'Ardes, Martina De Feo, Emilia, Donnarumma, Marco, Fei, Carmine Gabriele Gambino, Paolo, Giorgini, Lombardi, Rosa, Giuseppe, Miceli, Paola, Naccarato, Silvia, Noviello, Gaia, Olivieri, Roberta, Parente, Francesca Serena Pignataro, Sonia, Poma, Enrica, Porceddu, Pucci, Giacomo, Marco, Ricchio, Anna, Sabena, Marco, Salice, Claudia, Santarossa, Ambra, Savona, Caterina, Savrié, Roberto, Scicali, Mario, Stabile, Giovanni, Talerico, Michela, Talia, Eliezer Joseph Tassone, Thomas, Teatini, Elisabetta, Tombolini, Matteo, Traversa, Elia, Vettore, Alessandro, Vignal, Luca, Vilardi, Rosanna, Villani, Francesco, Vitale, Cicco, Sebastiano, D Abbondanza, Marco, Proietti, Marco, Zaccone, Vincenzo, Pes, Chiara, Caradio, Federica, Mattioli, Massimo, Piano, Salvatore, Marra, Alberto Maria, Nobili, Alessandro, Mannucci, Pier Mannuccio, Pietrangelo, Antonello, Sesti, Giorgio, Buzzetti, Elena, Salzano, Andrea, Cimellaro, Antonio, Antonio Cimellaro, Salvatore, Corrao, Mario, Barbagallo, Anna, Licata, Giuseppe, Montalto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, and Cimellaro, Antonio - Giovani Internisti Società Italiana di Medicina Interna (GIS-SIMI) and of the REPOSI Investigators

Subjects
cardiovascular events, older patient, hypertension, antihypertensive drugs, older patients, survival, Clinical Biochemistry, antihypertensive drug, General Medicine, Biochemistry, cardiovascular event
Abstract

Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

Published
2023

20. Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Author

Crisafulli, Ernesto, Sartori, Giulia, Vianello, Alice, Busti, Fabiana, Nobili, Alessandro, Mannucci, Pier Mannuccio, Girelli, Domenico Investigators—Domenico Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene Mattioli (Azienda Ospedaliero Universitaria Careggi Firenze, SOD Medicina Interna Interdisciplinare), Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massi- miliano Chiuch (Azienda Sanitaria Universitaria Integrata di Trieste, Clinica Medica Generale, e Terapia Medica), Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi (Azienda Ospedaliera della Pro- vincia di Lecco, Ospedale di Merate, Lecco, Medicina, Interna), Matteo, Pirro, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Alessia, Giotta, Mannarino (Azienda Ospedaliera Santa Maria della Misericordia, Massimo R., Perugia, Medicina, Interna, Angiologia Malattie da Arteriosclerosi), Domenico, Girelli, Fabiana, Busti, Giacomo Marchi (Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Medicina Generale e Malattie Aterotrombotiche, e Degenerative), Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica Cacioppo (Azienda Ospedaliera Universitaria Policlinico Giaccone Policlinico di Palermo, Palermo, Unità Operativa di Geriatria, e Lun- godegenza), Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Civico, Federica Cavallaro (A. R. N. A. S., Cristina, Di, Benfratelli, Palermo, UOC Medicina Interna ad Indirizzo Geriatrico- Riabilitativo), Marco, Zoli, Maria Laura Mata- cena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Orsola-Malpighi, Angelo Simili (Azienda Ospe- daliera Universitaria Policlinico S., Bologna, Unità Operativa di Medicina Interna Zoli), Maria Domenica Cappellini, Gio- vanna Fabio, Margherita Migone De Amicis, Giacomo De Luca, Nata- lia Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta Mancarella (Fon- dazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Unità Operativa Medicina Interna IA), Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Federica, Conti, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Paola Nicolini (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Geriatria), Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra Cambiè (IRCCS Policlinico San Matteo di Pavia, Pavia, Clinica Medica, I, Reparto, 11), Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico Cattaneo (IRCCS Azienda Ospedaliera Universitaria San Martino-IST di Genova, Gen-, Ova, Clinica di Medicina Interna 2), Luigi, Anastasio, Lucia, Sofia, Maria Carbone (Ospedale Civile Jazzolino di Vibo Valentia, Vibo Val- entia, Medicina, Generale), Francesco, Cipollone, Maria Teresa Guag- nano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D’Ardes, Lucia, Esposito, Simona, Sestili, Annunziata, Ermanno Angelucci (Ospedale Clinicizzato SS., Chieti, Clinica, Medica), Gerardo, Mancuso, Daniela, Calipari, Mosè Bartone (Ospedale Giovanni Paolo II Lamezia Terme, Catanzaro, Unità Operativa Complessa Medicina Interna), Giuseppe, Delitala, Maria, Berria, Alessandro Delitala (Azienda ospedaliera- universitaria di Sassari, Maurizio, Muscaritoli, Ales- sio Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Gio- vanni Imbimbo (Policlinico Umberto, I, Sapienza Università di Roma, Medicina Interna, e Nutrizione Clinica Policlinico Umberto I), Giuseppe, Zuccalà, Gemelli, Gabriella D’Aurizio (Policlinico Universitario A., Roma, Roma, Unità Operativa Complessa Medicina d'Urgenza, e Pronto Soccorso)Giuseppe Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto Zucchelli (Unità Operativa Complessa di Medicina I, a indirizzo geriatrico, Spedali, Civili, Montichiari, Brescia), Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara Dell’Unto (Università Campus Bio- Medico, Roma, Medicina Clinica-Epatolo- gia), Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Paolo, Mazzola, Andrea, Piazzoli, Gerardo, Maurizio Corsi (Università degli studi di Milano-Bicocca Ospedale S., Monza, Unità Operativa di Geri- atria), Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica Giofrè (Università degli Studi Magna Grecia, Policlinico Mater Domini, Cat-, Anzaro, Unità Operativa Complessa di Medicina Interna), Maria Grazia Serra, Maria Antonietta Bleve (Azienda Ospedaliera, Lecce, Unità Operativa Complessa Medicina), Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani (ASST FatebenefratelliSacco, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta Cosi (Azienda Ospe- daliera Università di Padova, Padova, Clinica Medica I), Roberto Man- fredini, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giulia Marta Viglione, Caterina Savriè (Azienda OspedalieraUniversitaria Sant'Anna, Ferrara, Unità Operativa Clinica Medica), Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo (Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Napoli, VI Divisione di Medicina Interna, e Malattie Nutrizionali dell'Invecchiamento), Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, 13 Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Orsola-Malpighi, Ilenia Pareo (Azienda Ospedaliera Universitaria Poli- clinico S., Unità Operativa di Medicina Interna Borghi), Carlo, Sabbà, Francesco Saverio Vella, Patrizia Sup- pressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Ema- nuele Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca Loparco (Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Frugoni), Medicina Interna Universitaria C., Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore D’Aniano (Azienda Sanitaria Ospedaliera Santa Croce, e Carle di Cuneo, Cuneo, Ademe, Medicina Interna), S. C., Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice Cinque (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOC Medicina Generale ad Indirizzo Metabolico), Flora, Peyvandi, Raffaella, Rossio, Colombo, Giulia, Pasquale, Agosti, Erica, Pagliaro, Eleonora Semproni (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna, 2, Emato- logia non tumorale, e Coagulopatie), Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian Folli (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna Alta Intensità di Cure), Francesco, Salerno, Giada Pallini (IRCCS Policlinico San Donato, e Università di Milano, San Donato Milanese, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca Liberale (IRCCS Ospedale Policlinico San Martino, e Università di Genova, Genova, Clinica Medica, 1, Medicina Interna, e Specialità Mediche), Nicola Lucio Liberato, Tiziana Tognin (ASST di Pavia, UOSD Medicina Interna, Ospedale di Casorate Primo, Pavia), Francesco, Purrello, Antonino Di Pino, Salvatore Piro (Ospedale Garibaldi Nesima, Catania, Giorgia, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano Buf- felli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia Cesaroni (Ospedale Poliambulanza, Brescia, Medicina Interna, e Geriatria), Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura Sanino (Dipartimento di Scienze Mediche, Università di Torino, Città della Scienza, e della Salute, Torino, Medicina Interna, 2 Unità Indirizzo d'Urgenza), Franc- esco Violi, Ludovica Perri (Policlinico Umberto, I, Prima Clinica Medica), Guasti, Luigina, Rotunno, Francesca, Castiglioni, Luana, Maresca, ANDREA MARIA, Squizzato, Alessandro, Campiotti, Leonardo, Ales- sandra Grossi, Diprizio, ROBERTO DAVIDE, Francesco Dentali (Università degli Studi dell'Insubria, Ospedale di Circolo, e Fondazione Macchi, Varese, Elena, Medicina, e Geriatria), Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Elisa, Pellegrini, Laura, Orlandi, Giulia, Dondi, Lucia Carulli (Università di Modena, e Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Unità Operativa di Geriatria), Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco Filice, Elvira Clausi (Università Geriatriche), Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vec- chio, Ilaria Benzoni (Dipartimento di Scienze Mediche, e Chirurgiche, Unità Operativa di Medicina Interna, Orsola-Malpighi, Università degli Studi di Bologna/ Azienda Ospedaliero- Universitaria S., Bologna), Andrea, Salvi, Roberto, Leonardi, Giampaolo Damiani (Spedali Civili di Brescia, Medicina Generale), U. O. 3a., Gianluca, Moroncini, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto Romiti (Clinica Medica, Azienda Ospedaliera Universitaria- Ospedali Riuniti di Ancona), Riccardo, Ghio, Anna Dal Col (Azienda Ospedaliera Università San Martino, Medicina, III), Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo Labbadia (Poli- clinico Umberto, I, SMSC03Medicina Interna F, e Malattie Meta- boliche dell'osso), Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita (Policlinico Campus Biomedico Roma, Medicina, Clinica), Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Emanuele, Samuele Pignataro (Azienda Ospedaliera Universitaria Poli- clinico – V., Catania, Dipartimento di Medicina), Francesca, Mete, Miriam Gino (Ospedale degli Infermi di Rivoli, Medicina Interna)Guido Moreo, Gloria Pina (Clinica San Carlo Casa di Cura Polispecialistica, Paderno, Dugnano, Unità Operativa di Medicina Generale Emilio Bernardelli), Alberto Balle- strero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla Scarsi (Clinica Di Medicina Interna ad Indirizzo Oncologico, Azienda Ospedaliera Università San Martino di Genova), Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella Gruden (Medicina Interna III, Giovanni Battista Molinette, Ospedale S., Torino), Franco, Berti, Giuseppe, Famularo, Patrizia Tarsitani (Azienda Ospedaliera San Camillo Forlanini, Medicina Interna II), Roberto, Castello, Michela Pasino (Ospedale Civile Maggiore Borgo Trento, Medicina Generale, e Sezione di Decisione Cli- nica), Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta Mor- ganti, Andrea, Artoni, Margherita Grossi (Azienda Ospedaliero Uni- versitaria di Parma, Clinica Geriatrica), U. O. C., Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca Losa (Policlinico Universitario Duilio Casula, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Allergologia ed Immunologia Clinica), Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Angelo Rizzo (Azienda Ospe- daliera Universitaria Policlinico Paolo Giaccone, UOC di Medicina Interna), Francesco, Corica, Giorgio, Basile, Antonino Cata- lano, Federica, Bellone, Martino, Concetto Principato (Azienda Ospedaliera Universitaria Policlinico G., Messina, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella Caruso (Azienda Ospedaliera per l'Emergenza Cannizzaro, Clinica Medica Università di Catania), Patrizia, Mecocci, Carmelinda, Ruggiero, della Misericordia, Virginia Boccardi (Università degli Studi di Perugia-Azienda Ospedaliera S. M., Struttura Complessa di Geriatria), Tiziana, Meschi, Andrea, Ticinesi, Antonio Nouvenne (Azienda Ospedaliera Universitaria di Parma, Medicina Interna e Lungodegenza Critica), U. O., Pietro, Minuz, Luigi, Fondrieschi, Giandomen- ico Nigro Imperiale, Sarah Morellini (Azienda Ospedaliera Universi- taria Verona, Policlinico GB Rossi, Medicina Generale per lo Studio ed il Trattamento dell’Ipertensione Arteriosa), Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia Bellan (Azienda Ospedaliera Universitaria Maggiore della Carità, Medicina Interna 1), Roberto, Quadri, Erica, Larovere, Marco Novelli (Ospedale di Ciriè, Asl, To4, Emilio, Simeone, Rosa, Scurti, Fabio Tolloso (Ospedale Spirito Santo di Pescara, Geriatria), Roberto Tar- quini, Alice, Valoriani, Silvia, Dolenti, Giulia Vannini (Ospedale San Giuseppe, Empoli, USL Toscana Centro, Firenze, Medicina Interna I), Riccardo, Volpi, Pietro, Bocchi, Alessandro Vignali (Azienda Ospe- daliera Universitaria di Parma, Clinica, e Terapia Medica), Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia Aiello (Divisione di Medicina Interna, Multimedica, Ircss, Milano), Antonino Di Pino (Ospedale GaribaldiNesima, – Catania, Medicina Interna), U. O. C., Teresa, Salvatore, Lucio, Monaco, Vanvitelli, Carmen Ricozzi (Policlinico Università della Campania L., UOC Medicina Interna), Alberto, Pilotto, Ilaria, Indiano, Federica Gandolfo (Ente Ospe- daliero Ospedali Galliera Genova, SC Geriatria Dipartimento Cure Geriatriche, Ortogeriatria, e Riabilitazione)Franco Laghi Pasini, Pier Leopoldo Capecchi (Azienda Ospedaliera Universitaria Senese, Siena, Unità Operativa Complessa Medicina 2), Ranuccio, Nuti, Roberto Val- enti, Martina, Ruvio, Silvia, Cappelli, Alberto Palazzuoli (Azienda Ospedaliera Università Senese, Mauro Ber- nardi, Silvia Li Bassi, Luca, Santi, Giacomo Zaccherini (Azienda Ospe- daliera Policlinico Sant’Orsola-Malpighi, Semeiotica Medica Bernardi), Vittorio, Durante, Daniela, Tirotta, Giovanna Eusebi (Ospedale di Cattolica, Rimini, Marco, Cattaneo, Maria Valentina Amoruso, Paola, Fracasso, Cristina Fasolino (Azienda ospedaliera San Paolo, Moreno, Tresoldi, Enrica 13 Internal and Emergency Medicine Internal and Emergency Medicine Bozzolo, Sarah Damanti (IRCCS Ospedale San Raffaele, – Milano, Medicina Generale, e delle Cure Avanzate), Massimo, Porta, Miriam Gino (AOU Città della Salute e della Scienza di Torino, – Torino, and Medicina Interna, 1U).

Subjects
Hospital cure, Chronic obstructive pulmonary disease, Heart failure, Mortality, Multimorbidity, Prognosis
Published
2023

21. Calcium-Dependent Src Phosphorylation and Reactive Oxygen Species Generation Are Implicated in the Activation of Human Platelet Induced by Thromboxane A2 Analogs

Author

Pietro Minuz, Alessandra Meneguzzi, Laura Fumagalli, Maurizio Degan, Stefano Calabria, Roberta Ferraro, Marco Ricci, Dino Veneri, and Giorgio Berton

Subjects
thromboxane A2, platelets, tyrosine kinase, calcium, NADPH oxidase, Therapeutics. Pharmacology, RM1-950
Abstract

The thromboxane (TX) A2 elicits TP-dependent different platelet responses. Low amounts activate Src kinases and the Rho–Rho kinase pathway independently of integrin αIIbβ3 and ADP secretion and synergize with epinephrine to induce aggregation. Aim of the present study was to investigate the role Src kinases and the interplay with calcium signals in reactive oxygen species (ROS) generation in the activatory pathways engaged by TXA2 in human platelets. All the experiments were performed in vitro or ex vivo. Washed platelets were stimulated with 50–1000 nM U46619 and/or 10 μM epinephrine in the presence of acetylsalicylic acid and the ADP scavenger apyrase. The effects of the ROS scavenger EUK-134, NADPH oxidase (NOX) inhibitor apocynin, Src kinase inhibitor PP2 and calcium chelator BAPTA were tested. Intracellular calcium and ROS generation were measured. Platelet rich plasma from patients treated with dasatinib was used to confirm the data obtained in vitro. We observed that 50 nM U46619 plus epinephrine increase intracellular calcium similarly to 1000 nM U46619. ROS generation was blunted by the NOX inhibitor apocynin. BAPTA inhibited ROS generation in resting and activated platelets. Phosphorylation of Src and MLC proteins were not significantly affected by antioxidants agents. BAPTA and antioxidants reduced P-Selectin expression, activation of integrin αIIbβ3and platelet aggregation. TXA2-induced increase in intracellular calcium is required for Src phosphorylation and ROS generation. NADPH oxidase is the source of ROS in TX stimulated platelets. The proposed model helps explain why an incomplete inhibition of TP receptor results in residual platelet activation, and define new targets for antiplatelet treatment.

Published
2018
Full Text
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22. P154 VASCULAR STRUCTURE AND FUNCTION IN RELATION TO WEIGHT EXCESS AND BLOOD PRESSURE IN A SAMPLE OF OBESE CHILDREN

Author

Sara Bonafini, Angela Tagetti, Francesco Dalle Vedove, Sara Raimondi, Alice Giontella, Paolo Cavarzere, Rossella Gaudino, Pietro Minuz, Claudio Maffeis, Franco Antoniazzi, and Cristiano Fava

Subjects
Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective: To investigate the influence of weight excess and blood pressure (BP) on vascular structure and function in a sample of obese children. Methods: We measured office and ambulatory BP (ABPM), carotid intima-media thickness (cIMT), endothelial function by the Flow Mediated Dilation (FMD) technique, carotid distensibility (cDC) (ultrasonograph: LogiQ P5 Pro; software: Multimedia Video Engine II, DSP Lab, Pisa CNR, Italy) (1) and stiffness index (SI) by photopletismography (Pulce Trace PT1000, MicroMedical Ltd, UK) (2) in overweight and obese children (BMI > 90th percentile for sex and age). Results: Seventy children with weight excess were enrolled (age 11.5±2.4 years; female n: 30). cDC showed inverse correlation with BMI and waist circumference (rSpearman = −0.403 and rs = −0.346, respectively), 24h-SBP (rs = −0.449) and nighttime-SBP (rs = −0.490). SI inversely correlated with BMI (rs = −0.359) and waist/height ratio (rs = −0.303). When comparing normotensive and hypertensive children, as defined on the basis of the ABPM, no significant differences in vascular tests were found, although cDC tended to be lower in hypertensive. In normotensive subjects (n: 53) cIMT directly correlated with nighttime-SBP and DBP. Most of the correlations remained significant after adjustment for age, sex, BMI and BP. Conclusions: These data suggest that arterial elasticity is negatively affected by weight excess and 24h-BP levels even in childhood. In the normotensive subgroup it is detectable an effect of BP also on arterial structure.

Published
2017
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23. Long-Term Patient-Centred Follow-up in a Prospective Cohort of Patients with COVID-19

Author

Enrico Polati, Elisa Razzaboni, Amina Zaffagnini, Fulvia Mazzaferri, Ilaria Dalla Vecchia, Pietro Minuz, Anna Erbogasto, Domenico Girelli, Michele Milella, Nina Auerbach, Claudio Micheletto, Maria Mongardi, Oliviero Olivieri, Federico Ivaldi, Sara Mehrabi, Massimo Mirandola, Evelina Tacconelli, and Elda Righi

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Barthel index, 030106 microbiology, Disease, COVID-19, Long-term follow-up, Saint George Respiratory Questionnaire, Symptoms persistence, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Prospective cohort study, Original Research, business.industry, Cancer, medicine.disease, Icu admission, Infectious Diseases, business, Patient centred, Clinical progression
Abstract

Introduction To better define COVID-19 long-term impact we prospectively analysed patient-centred outcomes, including general health and symptom duration. Methods Barthel index (BI), St. George’s Respiratory Questionnaire adapted to patients with COVID-19 (aSGRQ) and WHO Clinical Progression Scale (CPS) were measured at enrolment and at 6 weeks from the onset of symptoms. Persistence of most frequently reported symptoms was assessed at 6 weeks and, among symptomatic patients, at 12 weeks from the onset of symptoms. Predictors of impaired general health over time were identified using an ordinal multilevel multivariate model. Results A total of 448 patients (55% men, median age 56 years) were enrolled. WHO-CPS showed mild, moderate and severe disease in 48%, 42% and 10% of patients at admission and mild disease in all patients at follow-up, respectively. BI and aSGRQ were normal in 96% and 93% patients before COVID-19 but only in 47% and 16% at COVID-19 diagnosis and in 87% and 65% at 6-week follow-up. Male gender was identified by all three assessments as a predictor of impaired general health (BI, OR 2.14, p

Published
2021

24. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author

Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, Gaudenzi, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Giulia, Dondi, Elisa, Pellegrini, Lucia, Carulli, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Armando, Gabrielli, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Samuele, Pignataro, Alfio, Gennaro, Julien, Blanco, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesca, Gasparini, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Stefano Del Giacco, Davide, Firinu, Francesca, Losa, Giovanni, Paoletti, Giulia, Costanzo, Giuseppe, Montalto, Anna, Licata, Valentina, Malerba, Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F

Subjects
Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

Published
2021

25. How to 'SAVE' antibiotics: effectiveness and sustainability of a new model of antibiotic stewardship intervention in the internal medicine area

Author

Elena Carrara, Marcella Sibani, Lorenzo Barbato, Fulvia Mazzaferri, Nicola Duccio Salerno, Michela Conti, Anna Maria Azzini, Andrea Dalbeni, Luca Pellizzari, Giorgia Fontana, Vincenzo Di Francesco, Luisa Bissoli, Letizia Del Monte, Mauro Zamboni, Oliviero Olivieri, Pietro Minuz, Laura Maccacaro, Giovanna Ghirlanda, and Evelina Tacconelli

Subjects
Microbiology (medical), Antibiotic stewardship, Infectious Diseases, Pharmacology (medical), General Medicine, Antimicrobial resistance, Behavior change intervention, Quality improvement
Abstract

Antibiotic stewardship (AS) is a cornerstone of the fight against antimicrobial resistance; however, evidence on the best practice to improve antibiotic prescription in various hospital settings is still scarce. This study aimed to measure the efficacy of a non-restrictive AS intervention in the internal medicine area of a tertiary-care hospital across a 3-year period.The intervention comprised a 3-month 'intensive phase' based on education and guidelines provision, followed by 9 months of audits and feedback activities. The primary outcome was the overall antibiotic consumption measured as days of therapy (DOTs) and defined daily doses (DDDs). Secondary outcomes were carbapenem and fluoroquinolone consumption, all-cause in-hospital mortality, length of stay, incidence of Clostridioides difficile and carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSIs). All outcomes were measured in the intervention wards comparing the pre-phase with the post-phase using an interrupted time-series model.A total of 145 337 patient days (PDs) and 14 159 admissions were included in the analysis. The intervention was associated with reduced DOTs*1000PDs (-162.2/P = 0.005) and DDDs*1000PDs (-183.6/P ≤ 0.001). A sustained decrease in ward-related antibiotic consumption was also detected during the post-intervention phase and in the carbapenem/fluoroquinolone classes. The intervention was associated with an immediate reduction in length of stay (-1.72 days/P0.001) and all-cause mortality (-3.71 deaths*100 admissions/P = 0.002), with a decreasing trend over time. Rates of Clostridioides difficile infections and CRE-BSIs were not significantly impacted by the intervention.The AS intervention was effective and safe in decreasing antibiotic consumption and length of stay in the internal medicine area. Enabling prescribers to judicious use of antimicrobials through active participation in AS initiatives is key to reach sustained results over time.

Published
2022

26. May Measurement Month 2019: an analysis of blood pressure screening results from Italy

Author

Massimo Volpe, Stefano Carugo, Riccardo Sarzani, Martino F. Pengo, Andrea Faini, Camilla Torlasco, Paolo Mulatero, Claudio Borghi, Guido Grassi, Neil R Poulter, Gianfranco Parati, Claudio Ferri, Massimo Salvetti, Xin Xia, Maria Lorenza Muiesan, Giacomo Pucci, Pietro Minuz, Thomas Beaney, Giuseppe Mulè, Leonardo Sechi, Torlasco, Camilla, Faini, Andrea, Pengo, Martino F, Borghi, Claudio, Grassi, Guido, Ferri, Claudio, Muiesan, Maria Lorenza, Salvetti, Massimo, Minuz, Pietro, Mulatero, Paolo, Pucci, Giacomo, Volpe, Massimo, Carugo, Stefano, Sarzani, Riccardo, Mule', Giuseppe, Beaney, Thoma, Poulter, Neil R, Xia, Xin, Parati, Gianfranco, Camilla Torlasco, Andrea Faini, Martino F Pengo, Claudio Borghi, Guido Grassi, Claudio Ferri, Maria Lorenza Muiesan, Massimo Salvetti, Leonardo Sechi, Pietro Minuz, Paolo Mulatero, Giacomo Pucci, Massimo Volpe, Stefano Carugo, Riccardo Sarzani, Giuseppe Mulè, Thomas Beaney, Neil R Poulter, Xin Xia 14 , Gianfranco Parati, Torlasco, C, Faini, A, Pengo, M, Borghi, C, Grassi, G, Ferri, C, Muiesan, M, Salvetti, M, Sechi, L, Minuz, P, Mulatero, P, Pucci, G, Volpe, M, Carugo, S, Sarzani, R, Mule, G, Beaney, T, Poulter, N, Xia, X, and Parati, G

Subjects
Mean arterial pressure, 030204 cardiovascular system & hematology, 03 medical and health sciences, Health personnel, 0302 clinical medicine, Health campaign, Diabetes mellitus, Control, Medicine, Blood pressure, Control, Screening, Treatment, AcademicSubjects/MED00200, 030212 general & internal medicine, Myocardial infarction, Risk factor, Treatment, 1102 Cardiorespiratory Medicine and Haematology, Settore MED/14 - Nefrologia, business.industry, Articles, medicine.disease, Settore MED/11 - Malattie Dell'Apparato Cardiovascolare, Blood pressure, Cardiovascular System & Hematology, Hypertension, Screening, Cardiology and Cardiovascular Medicine, business, Body mass index, Demography
Abstract

Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively >10 000 and >5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. BP measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. Screening was conducted in multiple sites by health personnel. Among the 10 182 people screened (females: 52.3%, mean age 58 ± 16years) mean BP was 127/78 mmHg, and 3171 (31.1%) participants had arterial hypertension, of whom 62.1% were aware of being hypertensive. Diabetes, body mass index >25 kg/m2 were associated with higher BP and previous myocardial infarction with lower BP. For the third consecutive year we collected a nation-wide snapshot of BP control in a large sample of individuals. The high participation, with some yearly fluctuations likely due to the limitations of the sampling technique, confirms the power of this kind of health campaign in reaching a significant number of people to raise awareness on health topics.

Published
2021

27. World Hypertension Day 2021 in Italy: Results of a Nationwide Survey

Author

Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, Ferri, C, Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, Claudio Ferri, Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, Ferri, C, Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, and Claudio Ferri

Abstract

Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in the previous month/week) was administered. Due to the ongoing SARS-CoV-2 pandemic, BP was measured with standard procedures in a subset of participants (24.4%). Results: A total of 1354 participants (mean age 56.3 ± 15.3 years; 57.3% women; mean BP: 131.2 ± 17.5/81.6 ± 10.5 mmHg; 42.3% self-declared hypertensive; 41.4% on antihypertensive medications) were enrolled; 73.6% declared being aware of their BP status. Among treated individuals with measured BP, 26.9% showed BP levels within the predefined therapeutic goals. Interestingly, BP status awareness rates were the highest among individuals with uncontrolled hypertension (85.1%) and the lowest among those with normal measured BP (54.4%). Conclusions: This survey provides an updated insight into hypertension awareness and control in a setting of daily clinical practice, emphasizing the centricity of patients in the therapeutic alliance for a successful reduction of cardiovascular risk.

Published
2022

28. Antiplatelet Agents Inhibit The Generation Of Platelet-Derived Microparticles

Author

Alice Giacomazzi, Maurizio Degan, Stefano Calabria, Alessandra Meneguzzi, and Pietro Minuz

Subjects
Apyrase, Collagen, microparticles, platelets, Thromboxane, acetylsalicylic acid, Therapeutics. Pharmacology, RM1-950
Abstract

Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMP shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid, U46619, collagen type-I (10 and 1.5 µg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 µmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide. PMPs were detected by flow-cytometry using CD61 and annexin-V as fluorescent markers. Platelet agonists induced annexin V-positive PMP shedding. The strongest response was to high concentration collagen. ADP-triggered PMP shedding was dose-independent. ASA reduced PMPs induced by arachidonic acid- (645, 347-2946 vs 3061, 446-4901 PMPs/µL; median ad range, n=9, P

Published
2016
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29. Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low‐moderate liver fibrosis

Author

Angela Donato, Donatella Ieluzzi, Andrea Dalbeni, Veronica Paon, Gioia Torin, Simone Romano, Filippo Cattazzo, A. Mantovani, Marco Benati, Flavio Ribichini, Pietro Minuz, Anna Piccoli, Franco Capra, Davide Roccarina, Cinzia Monaco, Martina Montagnana, Michele Bevilacqua, Egidio Imbalzano, Laura Iogna Prat, Cristiano Fava, and Angela Tagetti

Subjects
Liver Cirrhosis, Male, Cardiac function curve, medicine.medical_specialty, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Antiviral Agents, Inferior vena cava, Virus, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, Virology, Internal medicine, medicine, echocardiography, Humans, 030212 general & internal medicine, Hepatology, business.industry, Incidence (epidemiology), DAAs, Hepatitis C, Hepatitis C, Chronic, medicine.disease, Infectious Diseases, medicine.anatomical_structure, medicine.vein, Ventricle, HCV, Cardiology, 030211 gastroenterology & hepatology, business
Abstract

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

Published
2020

30. Traditional cardiovascular risk factors and residual disease activity are associated with atherosclerosis progression in rheumatoid arthritis patients

Author

Alessandro Giollo, Filippo Cattazzo, Giovanni Orsolini, Pietro Minuz, Ombretta Viapiana, Michele Bevilacqua, Andrea Dalbeni, Maurizio Rossini, Giovanni Cioffi, Federica Ognibeni, Angela Tagetti, and Cristiano Fava

Subjects
Male, Longitudinal study, medicine.medical_specialty, Mean arterial pressure, Physiology, Disease, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Residual disease activity, Internal Medicine, medicine, Humans, Subclinical atherosclerosis, Longitudinal Studies, Prospective Studies, 030212 general & internal medicine, Rheumatoid arthritis, Traditional cardiovascular risk factors, Aged, Subclinical infection, business.industry, Incidence (epidemiology), Ultrasound, Middle Aged, Atherosclerosis, medicine.disease, Heart Disease Risk Factors, Disease Progression, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Patients with rheumatoid arthritis (RA) have an increased incidence of cardiovascular events. Ultrasound examination of the carotid arteries can show the presence of plaques and detect the atherosclerotic subclinical process through the evaluation of intima-media thickness (cIMT) and carotid segmental distensibility (cCD). The aim of the present study was to identify which factors could independently influence the evolution of atherosclerosis (plaques, cIMT, and cCD) after 1 year of follow-up in a sample of patients with RA. A total of 137 patients with RA without previous cardiovascular (CV) events were enrolled at baseline, and 105 (M/F: 21/84, age 59.34 ± 11.65 years) were reassessed after one year using ultrasound of carotid arteries to detect atheromatous plaques and to measure cIMT and cCD. After one year, all the indices of subclinical atherosclerosis worsened with respect to baseline (Δ-cIMT = 0.030 ± 0.10 mm, p = 0.005; Δ-cCD = -1.64 ± 4.83, 10-3/KPa, p = 0.005; Δ-plaques = 8.6%, p = 0.035). Traditional CV risk factors (age, mean arterial pressure, and diabetes) and corticosteroid therapy were independently associated with the worsening of subclinical atherosclerosis. Interestingly, when considering RA patients divided according to the degree of disease activity score 28 with C-reactive protein (DAS28 [CRP] ≥2.6), the worsening of subclinical atherosclerosis indices was detectable exclusively in the group of patients with active disease. Our longitudinal study supports the hypothesis of a key role of both traditional CV risk factors and the inflammatory activity of arthritic disease in the progression of subclinical atherosclerosis in RA patients. In addition, corticosteroids might have a deleterious effect.

Published
2020

31. Pregnancy-Related Complications in Patients With Fibromuscular Dysplasia: A Report From the European/International Fibromuscular Dysplasia Registry

Author

Pappaccogli, M, Prejbisz, A, Ciurică, S, Bruno, Rm, Aniszczuk-Hybiak, A, Bracalente, I, De Backer, T, Debiève, F, Delmotte, P, Di Monaco, S, Jarraya, F, Gordin, D, Kosiński, P, Kroon, Aa, Maas, Ahem, Marcon, D, Minuz, P, Montagud-Marrahi, E, Pasquet, A, Poch, E, Rabbia, F, Stergiou, Gs, Tikkanen, I, Toubiana, L, Vinck, W, Warchoł-Celińska, E, Van der Niepen, P, de Leeuw, P, Januszewicz, A, Persu, A, European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI) and the Working Group 'Hypertension and the Kidney' of the ESH: Alexandre Persu, Marco, Pappaccogli, Christophe, Beauloye, Patrick, Chenu, Jean-Philippe, Lengelé, Frank, Hammer, Pierre, Goffette, Parla, Astarci, André, Peeters, Robert, Verhelst, Miikka, Vikkula, Patricia Van der Niepen, Frank Van Tussenbroek, Tine De Backer, Sofie, Gevaert, Philippe, Delmotte, Wouter, Vinck, Daniel, T Gordin, Ilkka, Tikkanen, Maarit, Venermo, George, S Stergiou, Rosa Maria Bruno, Stefano, Taddei, Caterina, Romanini, Ilaria, Petrucci, Franco, Rabbia, Silvia Di Monaco, Pietro, Minuz, Mansueto, Giancarlo, DE MARCHI, Sergio, Denise, Marcon, Bram, Kroon, Peter de Leeuw, Andrzej, Januszewicz, Ewa, Warchol-Celinska, Aleksander, Prejbisz, Adam, Witkowski, Helena, Witowicz, Anna, Aniszczuk-Hybiak, Krzysztof, Pieluszczak, Magdalena, Januszewicz, Piotr, Dobrowolski, Esteban, Poch, Enrique, Montagud-Marrahi, Alicia, Molina, Elena, Guillen, Marta, Burrel, Hanen, Chaker, Faiçal, Jarraya, Anita, Mäkelä, Katarzyna, Józwik-Plebanek, Elżbieta, Florczak, Jacek, Kądziela, Clinical sciences, Clinical Pharmacology and Clinical Pharmacy, Nephrology, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), and RS: Carim - V02 Hypertension and target organ damage

Subjects
Gestational hypertension, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], fibromuscular dysplasia, Comorbidity, Fibromuscular dysplasia, 030204 cardiovascular system & hematology, Aneurysm rupture, pregnancy-induced, Renal Artery, 0302 clinical medicine, Registries, CARDIOLOGY, OUTCOMES, 030219 obstetrics & reproductive medicine, Obstetrics, WOMEN, Middle Aged, EUROPEAN-SOCIETY, follow-up studies, 3. Good health, PREVALENCE, hypertension, pregnancy-induced, preeclampsia, pregnancy, Lower prevalence, cardiovascular system, Premature Birth, Female, Adult, medicine.medical_specialty, hypertension, Revascularization, DIAGNOSIS, CLASSIFICATION, Preeclampsia, Young Adult, 03 medical and health sciences, ANEURYSM, Internal Medicine, medicine, CORONARY-ARTERY DISSECTION, MANAGEMENT, Humans, In patient, cardiovascular diseases, Pregnancy, business.industry, medicine.disease, Pregnancy Complications, RISK-FACTORS, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract

Current literature suggests a higher risk of pregnancy-related complications in patients with renal fibromuscular dysplasia (FMD). The aim of our study was to assess the nature and prevalence of pregnancy-related complications in patients subsequently diagnosed with FMD. A call for participation was sent to centers contributing to the European/International FMD Registry. Patients with at least 1 pregnancy were included. Data on pregnancy were collected through medical files and FMD characteristics through the European/International FMD Registry. Data from 534 pregnancies were obtained in 237 patients. Despite the fact that, in 96% of cases, FMD was not diagnosed before pregnancy, 40% of women (n=93) experienced pregnancy-related complications, mostly gestational hypertension (25%) and preterm birth (20%), while preeclampsia was reported in only 7.5%. Only 1 patient experienced arterial dissection and another patient an aneurysm rupture. When compared with patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 versus 51 years old; P P =0.003) but underwent more often renal revascularization (63% versus 40%, P

Published
2020

32. Pre- and in-hospital anticoagulation therapy in coronavirus disease 2019 patients: a propensity-matched analysis of in-hospital outcomes

Author

Ilaria Battistoni, Matteo Francioni, Nuccia Morici, Andrea Rubboli, Gian Marco Podda, Andrea Pappalardo, Mohamed E.A. Abdelrahim, Marwa O. Elgendy, Sara O. Elgendy, Ahmed M. Khalaf, Ahmed Abdel M. Hamied, Héctor Hernández Garcés, Omar E.S. Abdelhamid, Karim A.M. Tawfik, Anna Zeduri, Gabriele Bassi, Giulia Pongetti, Luca Angelini, Stefano Giovinazzo, Pablo Martinez Garcia, Francesco Saverio Serino, Giorgio Emanuele Polistina, Giuseppe Fiorentino, Giovanni Barbati, Anna Toniolo, Azzurra Fabbrizioli, Alberto Belenguer-Muncharaz, Italo Porto, Sibel Ocak, Pietro Minuz, Francisco Bernal, Irina Hermosilla, and Josip A. Borovac

Subjects
chronic anticoagulant therapy, coronavirus disease 2019, COVID-19, heparin, hospital outcomes, low molecular weight heparin (LMWH), SARS-COV-2, coronavirus 2, bleeding, death, propensity score matching, PMS, analysis, SARS- coronavirus 2, SARS-CoV-2, Anticoagulants, General Medicine, heparin, Acute Kidney Injury, Hospitals, Cohort Studies, hospital outcomes, COVID-19 Testing, Risk Factors, Low Molecular Weight Heparin, Humans, Hospital Mortality, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract

AIMS: To estimate if chronic anticoagulant (CAC) treatment is associated with morbidity and mortality outcomes of patients hospitalized for SARS-CoV-2 infection. METHODS: In this European multicentric cohort study, we included 1186 patients of whom 144 were on CAC (12.1%) with positive coronavirus disease 2019 testing between 1 February and 30 July 2020. The average treatment effect (ATE) analysis with a propensity score-matching (PSM) algorithm was used to estimate the impact of CAC on the primary outcomes defined as in-hospital death, major and minor bleeding events, cardiovascular complications (CCI), and acute kidney injury (AKI). We also investigated if different dosages of in-hospital heparin were associated with in-hospital survival. RESULTS: In unadjusted populations, primary outcomes were significantly higher among CAC patients compared with non-CAC patients: all-cause death (35% vs. 18% P < 0.001), major and minor bleeding (14% vs. 8% P = 0.026; 25% vs. 17% P = 0.014), CCI (27% vs. 14% P < 0.001), and AKI (42% vs. 19% P < 0.001). In ATE analysis with PSM, there was no significant association between CAC and primary outcomes except for an increased incidence of AKI (ATE +10.2%, 95% confidence interval 0.3-20.1%, P = 0.044). Conversely, in-hospital heparin, regardless of dose, was associated with a significantly higher survival compared with no anticoagulation. CONCLUSIONS: The use of CAC was not associated with the primary outcomes except for the increase in AKI. However, in the adjusted survival analysis, any dose of in-hospital anticoagulation was associated with significantly higher survival compared with no anticoagulation.

Published
2022

33. Impact of Diabetes Mellitus and Its Comorbidities on Elderly Patients Hospitalized in Internal Medicine Wards: Data from the RePoSi Registry

Author

Christiano, Argano, Giuseppe, Natoli, Salvatore, Mularo, Alessandro, Nobili, Marika Lo Monaco, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Argano C., Natoli G., Mularo S., Nobili A., Lo Monaco M., Mannucci P.M., Perticone F., Pietrangelo A., and Corrao S.

Subjects
Leadership and Management, 1-year mortality, cancer, comorbidities, diabetes, heart rate, in-hospital mortality, male sex, Heart rate, Socio-culturale, Health Informatics, comorbidities, Article, Comorbidities, Health Information Management, diabetes, heart rate, cancer, male sex, in-hospital mortality, 1-year mortality, Cancer, Diabetes, In-hospital mortality, Male sex, LS4_4, Health Policy, Medicine, 1-year mortality, Cancer, Comorbidities, Diabetes, Heart rate, In-hospital mortality, Male
Abstract

Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes.

Published
2022

34. The Caliber of Segmental and Subsegmental Vessels in COVID-19 Pneumonia Is Enlarged: A Distinctive Feature in Comparison with Other Forms of Inflammatory and Thromboembolic Diseases

Author

Maria-Chiara Ambrosetti, Giulia Battocchio, Stefania Montemezzi, Filippo Cattazzo, Tissjana Bejko, Evelina Tacconelli, Pietro Minuz, Ernesto Crisafulli, Cristiano Fava, and Giancarlo Mansueto

Subjects
CT scan, COVID-19 virus disease, SARS-CoV, pulmonary vessel dilatation, Medicine (miscellaneous)
Abstract

Background: The purpose of this study was to compare COVID-19 patients’ vessel caliber with that of normal lungs and lungs affected by other inflammatory and thromboembolic processes. Methods: between March and April 2020, 42 patients affected by COVID-19 pneumonia (COV-P) underwent CT scans of the lungs at Verona University Hospital for clinical indications. The lung images of four different groups of patients were compared (normal lung (NL), distal thromboembolism (DTE), and bacterial and fungal pneumonia (Bact-P, Fung-P)) by a radiologist with four years of experience. Results: The COV-P patients’ segmental and subsegmental vessels, evaluated as the ratio with the corresponding bronchial branch (V/B ratio), were larger, with respect to the NL the DTE groups, in the apparently healthy parenchyma, a result confirmed in the zones of opacification with respect to the Bact-P and Fung-P groups. Conclusions: This was the first study to show, by comparative analysis, that COVID-19 patients’ segmental and subsegmental vessel calibers are significantly enlarged. This is a distinctive feature of COVID-19 pneumonia, suggesting its distinct pathophysiology as compared to other inflammatory and thromboembolic diseases and alerting radiologists to consider it when evaluating the CT scans of suspected patients.

Published
2022

35. Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults

Author

Alessio, Novella, Chiara, Elli, Mauro, Tettamanti, Alessandro, Nobili, Aladar, Ianes, Pier Mannuccio Mannucci, Luca, Pasina, Carlotta, Franchi, Gualberto, Gussoni, Stefano, Bonassi, Antonella, Valerio, Federica, Mammarella, Codjo Djignefa Djade, Raffaella, Rossio, Barbara, Ferrari, Daniela, Mari, Marco, Ferretti, Francesco, Salerno, Alessio, Conca, Antonino, Tuttolomondo, Anna, Cirrincione, Antonio, Pinto, Antonio, Cherubini, Giuseppina, Dell’Aquila, Roberto, Bernabei, Graziano, Onder, Michele, Ciaburri, Dario, Manfellotto, Irene, Caridi, Enzo, Lancia, Alessandra, Forgione, Concetta, Donato, Serra Maria Grazia, Luigi, Lusiani, Bullo, Cristina, Brocco, Stefano, Pedretti, Giovanni, Pattacini, Corrado, Francesco, Violi, Ludovica, Perri, Luigi Di Cioccio, Carlo Di Meo, Laura, Minchella, Moira, Ceci, Alberto, Ferrari, Salvatore, Foderaro, Antonio, Brucato, Anna, Valenti, Silvia, Ghidoni, Renzo, Rozzini, Lina, Falanga, Alessandra, Marengoni, Simona, Ghibelli, Chiara, Mussi, Maria Alice Ferri, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Antonietta Bleve, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, and Federica, Gandolfo.

Subjects
Aging, Comorbidity indices, Health (social science), Socio-culturale, Multimorbidity, Comorbidity, Chronic disease, Hospitalization, Italy, Older adults, Chronic disease, Comorbidity indices, Excessive polypharmacy, Mortality, Multimorbidity, Older adults, Excessive polypharmacy, Polypharmacy, Humans, LS4_4, Geriatrics and Gerontology, Mortality, Gerontology, Aged
Abstract

Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available.This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy.Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE).Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings.On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

Published
2022

36. World Hypertension Day 2021 in Italy: Results of a Nationwide Survey

Author

Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, Claudio Ferri, Del Pinto, Rita, Grassi, Guido, Muiesan, Maria Lorenza, Borghi, Claudio, Carugo, Stefano, Cicero, Arrigo F G, Di Meo, Luciano, Iaccarino, Guido, Minuz, Pietro, Mulatero, Paolo, Mule', Giuseppe, Parati, Gianfranco, Pucci, Giacomo, Salvetti, Massimo, Sarzani, Riccardo, Savoia, Carmine, Sechi, Leonardo, Tocci, Giuliano, Volpe, Massimo, Vulpis, Vito, Ferri, Claudio, Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, and Ferri, C

Subjects
Adult, Male, Settore MED/14 - Nefrologia, awareness, blood pressure, hypertension, survey, Settore MED/09 - Medicina Interna, SARS-CoV-2, Awarene, COVID-19, Middle Aged, Awareness, Cross-Sectional Studies, Risk Factors, Surveys and Questionnaires, Awareness, Blood pressure, Hypertension, Survey, Hypertension, Internal Medicine, Blood pressure, Humans, Female, Survey, Aged, Antihypertensive Agents, Cardiology and Cardiovascular Medicine
Abstract

Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥18years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in the previous month/week) was administered. Due to the ongoing SARS-CoV-2 pandemic, BP was measured with standard procedures in a subset of participants (24.4%). Results: A total of 1354 participants (mean age 56.3±15.3years; 57.3% women; mean BP: 131.2±17.5/81.6±10.5mmHg; 42.3% self-declared hypertensive; 41.4% on antihypertensive medications) were enrolled; 73.6% declared being aware of their BP status. Among treated individuals with measured BP, 26.9% showed BP levels within the predefined therapeutic goals. Interestingly, BP status awareness rates were the highest among individuals with uncontrolled hypertension (85.1%) and the lowest among those with normal measured BP (54.4%). Conclusions: This survey provides an updated insight into hypertension awareness and control in a setting of daily clinical practice, emphasizing the centricity of patients in the therapeutic alliance for a successful reduction of cardiovascular risk.

Published
2022

37. Association of thyroid function with blood pressure and cardiovascular disease: a mendelian randomization

Author

Alice Giontella, Luca A. Lotta, John D. Overton, Aris Baras, on behalf of Regeneron Genetics Center, Andrea Sartorio, Pietro Minuz, Dipender Gill, Olle Melander, and Cristiano Fava

Subjects
RISK, HYPERTHYROIDISM, endocrine system, Science & Technology, hypertension, endocrine system diseases, Medicine (miscellaneous), Article, thyroid, cardiovascular diseases, genetics, polymorphisms, Mendelian randomization, Health Care Sciences & Services, Medicine, General & Internal, HORMONE, General & Internal Medicine, ATRIAL-FIBRILLATION, Medicine, Life Sciences & Biomedicine
Abstract

Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper- or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), hyper- and hypothyroidism, and anti-thyroid peroxidase antibodies (TPOAb), from genome-wide association studies (GWAS), were selected as MR instrumental variables. SNPs–outcome (BP, CVD) associations were evaluated in a large-scale cohort, the Malmö Diet and Cancer Study (n = 29,298). Causal estimates were computed by inverse-variance weighted (IVW), weighted median, and MR-Egger approaches. Genetically increased levels of TSH were associated with decreased systolic BP and with a lower risk of atrial fibrillation. Hyperthyroidism and TPOAb were associated with a lower risk of atrial fibrillation. Our data support a causal association between genetically decreased levels of TSH and both atrial fibrillation and systolic BP. The lack of significance after Bonferroni correction and the sensitivity analyses suggesting pleiotropy, should prompt us to be cautious in their interpretation. Nevertheless, these findings offer mechanistic insight into the etiology of CVD. Further work into the genes involved in thyroid functions and their relation to cardiovascular outcomes may highlight pathways for targeted intervention.

Published
2021

39. Kidney Disease Management in the Hospital Setting: A Focus on Inappropriate Drug Prescriptions in Older Patients

Author

Vincenzo, Arcoraci, Maria Antonietta Barbieri, Michelangelo, Rottura, Alessandro, Nobili, Giuseppe, Natoli, Christiano, Argano, Giovanni, Squadrito, Francesco, Squadrito, Salvatore, Corrao, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Massimo, Raspanti, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Matteo, Cesari, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Simona, Leoni, Alessandra Danuta Di Mauro, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Luigi, Anastasio, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giuseppe, Zuccalà, Gabriella, D’Aurizio, Giuseppe, Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Benedetta, Boari, DE GIORGI, Alfredo, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Luigi, Fenoglio, Andrea, Falcetta, Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Francesco, Salerno, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Francesco, Violi, Ludovica, Perri, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Carlo, Vigorito, Antonio, Cittadini, Guido, Moreo, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Leonardo, Sechi, Cristiana, Catena, Gianluca, Colussi, Alessandro, Cavarape, Andea Da Porto, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Silvia, Ghidoni, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo., Arcoraci V., Barbieri M.A., Rottura M., Nobili A., Natoli G., Argano C., Squadrito G., Squadrito F., and Corrao S.

Subjects
medicine.medical_specialty, appropriateness of prescription, prescribing patterns, Renal function, Context (language use), RM1-950, Logistic regression, NO, chemistry.chemical_compound, older patient, Internal medicine, hospital setting, medicine, Pharmacology (medical), LS4_4, Medical prescription, prescribing pattern, appropriateness of prescriptions, chronic kidney disease, hospital setting, older patients, prescribing patterns, real-world data, Original Research, Pharmacology, Creatinine, real-world data, business.industry, Retrospective cohort study, medicine.disease, older patients, appropriateness of prescriptions, chronic kidney disease, chemistry, Observational study, Therapeutics. Pharmacology, business, Kidney disease
Abstract

Aging with multimorbidity and polytherapy are the most significant factors that could led to inappropriate prescribing of contraindicated medications in patients with chronic kidney disease (CKD). The aim of this study was to evaluate the prescriptions of contraindicated drugs in older adults in CKD and to identify their associated factors in a hospital context. An observational retrospective study was carried out considering all patients ≥65 years with at least one serum creatinine value recorded into the REPOSI register into 2010–2016 period. The estimated glomerular filtration rate (eGFR) was applied to identify CKD. A descriptive analysis was performed to compare demographic and clinical characteristics; logistic regression models were used to estimate factors of inappropriate and percentage changes of drug use during hospitalization. A total of 4,713 hospitalized patients were recorded, of which 49.8% had an eGFR 2; the 21.9% were in treatment with at least one inappropriate drug at the time of hospital admission with a decrease of 3.0% at discharge (p = 0.010). The probability of using at least one contraindicated drug was significantly higher in patients treated with more several drugs (OR 1.21, 95% CI 1.16–1.25, p p < 0.001; G5: 19.38, 11.51–32.64, p < 0.001). Low-dose acetylsalicylic acid was the contraindicated drug mainly used at the time of admission, reducing 1.2% at discharge. An overall increase in therapeutic appropriateness in hospitalized older patients with CKD was observed, despite a small percentage of therapeutic inappropriateness at discharge that underlines the need for a closer collaboration with the pharmacologist to improve the drug management.

Published
2021

40. Renin-Angiotensin System Inhibition in Cardiovascular Patients at the Time of COVID19: Much Ado for Nothing? A Statement of Activity from the Directors of the Board and the Scientific Directors of the Italian Society of Hypertension

Author

Arrigo F G Cicero, Carmine Savoia, Maria Lorenza Muiesan, Pietro Minuz, Guido Grassi, Claudio Borghi, Giacomo Pucci, Massimo Salvetti, Paolo Mulatero, Giuseppe Mulè, Claudio Ferri, Guido Iaccarino, Massimo Volpe, Leonardo Sechi, Iaccarino, Guido, Borghi, Claudio, Cicero, Arrigo F G, Ferri, Claudio, Minuz, Pietro, Muiesan, Maria Lorenza, Mulatero, Paolo, Mulè, Giuseppe, Pucci, Giacomo, Salvetti, Massimo, Savoia, Carmine, Sechi, Leonardo Alberto, Volpe, Massimo, Grassi, Guido, Iaccarino, G, Borghi, C, Cicero, A, Ferri, C, Minuz, P, Muiesan, M, Mulatero, P, Mulè, G, Pucci, G, Salvetti, M, Savoia, C, Sechi, L, Volpe, M, Grassi, G, Iaccarino, G., Borghi, C., Cicero, A. F. G., Ferri, C., Minuz, P., Muiesan, M. L., Mulatero, P., Mule, G., Pucci, G., Salvetti, M., Savoia, C., Sechi, L. A., Volpe, M., Grassi, G., and Guido Iaccarino , Claudio Borghi , Arrigo F G Cicero , Claudio Ferri , Pietro Minuz , Maria Lorenza Muiesan , Paolo Mulatero , Giuseppe Mulè , Giacomo Pucci , Massimo Salvetti , Carmine Savoia , Leonardo Alberto Sechi , Massimo Volpe , Guido Grassi

Subjects
0301 basic medicine, Angiotensin-Converting Enzyme Inhibitors, Disease, outcomes, cardiovascular diseases, COVID-19, hypertension, infection, Betacoronavirus, Cardiovascular Diseases, Humans, Hypertension, Italy, SARS-CoV-2, Angiotensin Receptor Antagonists, Antihypertensive Agents, Coronavirus Infections, Pandemics, Pneumonia, Viral, Renin-Angiotensin System, 0302 clinical medicine, cardiovascular disease, Viral, biology, Angiotensin Receptor Antagonist, Antihypertensive Agent, outcome, Angiotensin Receptor Blockers, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 03 medical and health sciences, Pharmacotherapy, Renin–angiotensin system, Internal Medicine, medicine, Intensive care medicine, Betacoronaviru, Pandemic, Coronavirus Infection, business.industry, Outbreak, Angiotensin-Converting Enzyme Inhibitor, Angiotensin-converting enzyme, Pneumonia, 030104 developmental biology, biology.protein, betacoronavirus, humans, angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, antihypertensive agents, coronavirus infections, pandemics, pneumonia, viral, renin-angiotensin system, business, 030217 neurology & neurosurgery
Abstract

Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms areactually occurring in the present COVID-19 outbreak. Here we present the reasoned statement of the Italian Society of Hypertension to maintain ongoing antihypertensive treatments. Furthermore, the Italian Society of Hypertension presents its own initiative to investigate the issue using an online questionnaire to collect relevant data in human disease.

Published
2020

41. Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence

Author

Cristiano Fava, Marco Castelli, Alessandra Meneguzzi, and Pietro Minuz

Subjects
Blood Platelets, arterial hypertension, obesity, Endocrinology, Diabetes and Metabolism, Physiology, Environmental pollution, Review, Disease, 010501 environmental sciences, 01 natural sciences, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, cardiovascular disease, Glucose Metabolism Disorder, Diabetes mellitus, medicine, Humans, Platelet, 030212 general & internal medicine, perfluoroalkyl substances, thrombosis, 0105 earth and related environmental sciences, Fluorocarbons, business.industry, RC648-665, medicine.disease, Microvesicles, Cardiovascular Diseases, diabetes mellitus, platelets, Toxicity, Environmental Pollutants, Metabolic syndrome, business
Abstract

Polyfluoro- and perfluoro–alkyl substances (PFAS) are organic chemicals extensively used worldwide for industry and consumer products. Due to their chemical stability, PFAS represent a major cause of environmental pollution. PFAS accumulate in animal and human blood and tissues exerting their toxicity. We performed a review of the epidemiological studies exploring the relationship between exposure to PFAS and thromboembolic cardiovascular disease. An increase in cardiovascular disease or death related to PFAS exposure has been reported from cross-sectional and longitudinal observational studies with evidence concerning the relation with early vascular lesions and atherosclerosis. Several studies indicate an alteration in lipid and glucose metabolism disorders and increased blood pressure as a possible link with cardiovascular thromboembolic events. We also examined the recent evidence indicating that legacy and new PFAS can be incorporated in platelet cell membranes giving a solid rationale to the observed increase risk of cardiovascular events in the populations exposed to PFAS by directly promoting thrombus formation. Exposure to PFAS has been related to altered plasma membrane fluidity and associated with altered calcium signal and increased platelet response to agonists, both in vitro and ex vivo in subjects exposed to PFAS. All the functional responses are increased in platelets by incorporation of PFAS: adhesion, aggregation, microvesicles release and experimental thrombus formation. These findings offer mechanistic support the hypothesis that platelet-centred mechanisms may be implicated in the increase in cardiovascular events observed in populations chronically exposed to PFAS.

Published
2021

42. Opportunistic Screening for Atrial Fibrillation in the Pharmacies: A Population-Based Cross-Sectional Study

Author

Marco Bacchini, Cristiano Fava, Samuele Bonometti, Federico Realdon, Pietro Minuz, Francesco Del Zotti, and Alessandro Lechi

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Cross-sectional study, Population, Blood Pressure, Atrial fibrillation, Blood pressure, Opportunistic screening, Pharmacy, Risk factor, Aged, Aged, 80 and over, Atrial Fibrillation, Blood Pressure Determination, Cross-Sectional Studies, Electrocardiography, Equipment Design, Feasibility Studies, Female, Humans, Italy, Mass Screening, Middle Aged, Predictive Value of Tests, Prognosis, Community Pharmacy Services, Heart Rate, Disease, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, 80 and over, Internal Medicine, medicine, education, Stroke, education.field_of_study, business.industry, medicine.disease, 030104 developmental biology, Heart failure, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Opportunistic screening of atrial fibrillation is a valuable approach to the identification of subjects with unknown or non-symptomatic atrial fibrillation (AF) with the potential of reducing the burden of ischemic stroke in the population. To evaluate the feasibility of a large-scale screening for atrial fibrillation using a blood pressure monitor (MicrolifeAFIB) endowed with a validated algorithm able to detect AF calculating the irregularity of interval times between heartbeats. In this cross-sectional study conducted in 74 pharmacies in Verona participated 3071 people aged 50 years or more. In 6 months, information about drugs, previous diagnoses of cardiovascular diseases, anthropometric and demographic data was recorded, together with the measurement of blood pressure and cardiac rhythm by using the MicrolifeAFIB device. Pharmacists also collected anthropometric and demographic data of the participants, along with information concerning their personal history of cardiovascular disease and the use of antihypertensive and antithrombotic agents. All those who were positive at the screening for atrial fibrillation were referred to their family doctor. The screening revealed 98 subjects (3.2%) positive for AF; 44 of these reported a previous diagnosis of AF and were treated with anticoagulants (77%) or with antiplatelet agents (7%). By logistic regression analysis, age, male sex and heart failure were independently associated with positivity for AF. Association between positive test and previous stroke/TIA was found in the 54 subjects without a previous diagnosis of AF (9% had a previous stroke/TIA). Opportunistic screening for atrial fibrillation in the pharmacies is feasible and allows to identify a number of subjects with silent, non-previously diagnosed AF, therefore is potentially useful in large-scale projects aimed at the prevention of cardiovascular morbidity and mortality.

Published
2019

43. Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

Author

Rajagopal Krishnamoorthy, Yusuke Nakamura, Alice Giontella, Elisa Danese, Munir Pirmohamed, Hoi Y. Tong, Angela Tagetti, Marie-Anne Loriot, Pietro Minuz, Anke H. Maitland-van der Zee, Sheng-Lan Tan, Jim K Burmester, Richard B. Kim, Jamila Alessandra Perini, Ming Ta Michael Lee, Nita A. Limdi, Min Huang, Mohamed H. Shahin, Guilherme Suarez-Kurtz, Vanessa Roldán, Carlos Isaza, Hersh Sagreiya, Hye Sun Gwak, Vijay Kumar Kutala, Han-Jing Cen, Russ B. Altman, Antonio J. Carcas, Kunihiko Itoh, Vaiva Lesauskaite, Richard L. Berg, Cristina Mazzaccara, Kyung Eun Lee, Mariana R. Botton, Jieying Eunice Zhang, Anthonius de Boer, Yumao Zhang, Inna Y. Gong, Marianne K. Kringen, Paola Borgiani, Taimour Y. Langaee, Monica Taljaard, Vacis Tatarunas, Panos Deloukas, Chrisly Dillon, Alberto M. Borobia, Michael D. Caldwell, Katarzyna Drozda, Larisa H. Cavallari, Julie A. Johnson, Stephane Bourgeois, Lucia Sacchetti, Saurabh Singh Rathore, Stuart A. Scott, Martina Montagnana, Li-Zi Zhao, Charles A. Rivers, Mahmut Ozer, Taisei Mushiroda, Cristina Lucía Dávila-Fajardo, Andras Paldi, Marisa Cañadas-Garre, Rocío González-Conejero, Talitha I. Verhoef, Sherief Khalifa, Ivet Suriapranata, Carlo Federico Zambon, Balraj Mittal, Sara Raimondi, Ece Genc, Virginie Siguret, Andrea H. Ramirez, Cinzia Ciccacci, Keita Hirai, Enrique Jiménez-Varo, Hong-Hao Zhou, Anil Pathare, Steven A. Lubitz, Josh C. Denny, Aditi Shendre, Leonardo Beltrán, Kari Bente Foss Haug, Cristiano Fava, Vittorio Pengo, Department of Biochemistry, Università degli Studi di Pavia = University of Pavia (UNIPV), Department of Morphological and Biomedical Sciences, Università degli studi di Verona = University of Verona (UNIVR), Laboratoire de Mécanique et d'Acoustique [Marseille] (LMA ), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Queen Mary University of London (QMUL), Merck and Co., Merck & Co. Inc, Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d’Hématologie Biologique [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paediatric Pulmonology, Pulmonology, APH - Personalized Medicine, Danese, Elisa, Raimondi, Sara, Montagnana, Martina, Tagetti, Angela, Langaee, Taimour, Borgiani, Paola, Ciccacci, Cinzia, Carcas, Antonio J, Borobia, Alberto M, Tong, Hoi Y, Dávila-Fajardo, Cristina, Rodrigues Botton, Mariana, Bourgeois, Stephane, Deloukas, Pano, Caldwell, Michael D, Burmester, Jim K, Berg, Richard L, Cavallari, Larisa H, Drozda, Katarzyna, Huang, Min, Zhao, Li-Zi, Cen, Han-Jing, Gonzalez-Conejero, Rocio, Roldan, Vanessa, Nakamura, Yusuke, Mushiroda, Taisei, Gong, Inna Y, Kim, Richard B, Hirai, Keita, Itoh, Kunihiko, Isaza, Carlo, Beltrán, Leonardo, Jiménez-Varo, Enrique, Cañadas-Garre, Marisa, Giontella, Alice, Kringen, Marianne K, Haug, Kari Bente Fo, Gwak, Hye Sun, Lee, Kyung Eun, Minuz, Pietro, Lee, Ming Ta Michael, Lubitz, Steven A, Scott, Stuart, Mazzaccara, Cristina, Sacchetti, Lucia, Genç, Ece, Özer, Mahmut, Pathare, Anil, Krishnamoorthy, Rajagopal, Paldi, Andra, Siguret, Virginie, Loriot, Marie-Anne, Kutala, Vijay Kumar, Suarez-Kurtz, Guilherme, Perini, Jamila, Denny, Josh C, Ramirez, Andrea H, Mittal, Balraj, Rathore, Saurabh Singh, Sagreiya, Hersh, Altman, Ru, Shahin, Mohamed Hossam A, Khalifa, Sherief I, Limdi, Nita A, Rivers, Charle, Shendre, Aditi, Dillon, Chrisly, Suriapranata, Ivet M, Zhou, Hong-Hao, Tan, Sheng-Lan, Tatarunas, Vaci, Lesauskaite, Vaiva, Zhang, Yumao, Maitland-van der Zee, Anke H, Verhoef, Talitha I, de Boer, Anthoniu, Taljaard, Monica, Zambon, Carlo Federico, Pengo, Vittorio, Zhang, Jieying Eunice, Pirmohamed, Munir, Johnson, Julie A, and Fava, Cristiano

Subjects
CYP2C9, CYP4F2, VKORC1, coumarin drugs, meta-analysis, pharmacogenetics, predictive models, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030226 pharmacology & pharmacy, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Coumarins, Internal medicine, Vitamin K Epoxide Reductases, Taverne, medicine, Humans, Pharmacology (medical), heterocyclic compounds, Dosing, Cytochrome P450 Family 4, Aged, Cytochrome P-450 CYP2C9, Pharmacology, Aged, 80 and over, Acenocoumarol, Dose-Response Relationship, Drug, business.industry, Middle Aged, Confidence interval, Settore MED/03 - Genetica Medica, 030220 oncology & carcinogenesis, Meta-analysis, Female, business, Pharmacogenetics, medicine.drug
Abstract

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at individual patients' level to capture the possible effect of ethnicity, gene-gene interaction or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived. This article is protected by copyright. All rights reserved.

Published
2019

44. A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm

Author

Therese Ohlsson, Cristiano Fava, Olle Melander, Sara Bonafini, Gunnar Engström, Angela Tagetti, Pietro Minuz, Gustav Smith, and Peter Almgren

Subjects
Male, medicine.medical_specialty, Time Factors, Blood Pressure, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Risk Assessment, genetic risk score, Thoracic aortic aneurysm, 03 medical and health sciences, Aortic aneurysm, 0302 clinical medicine, Aneurysm, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, thoracic aneurism, Genetic Predisposition to Disease, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, genetic risk score, atherosclerosis, thoracic aneurism, Aged, Sweden, Aortic dissection, Aortic Aneurysm, Thoracic, Proportional hazards model, business.industry, Gene Expression Profiling, Incidence, fungi, Hazard ratio, Middle Aged, medicine.disease, Phenotype, Blood pressure, Hypertension, Cardiology, Female, atherosclerosis, Transcriptome, business
Abstract

A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdominal (AAA) aortic aneurysm. More than 25,000 people from the Swedish Malmo Diet and Cancer Study had information on at least 24 SNPs and were followed up for a median ≥ 18 years. The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS. In Cox regression models, adjusted for traditional cardiovascular risk factors including hypertension, we found significant associations of the BP-GRS, prospectively, with incident TAA (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.081-2.475 comparing the third vs. the first tertile; p = 0.020) but not with either AAA or aortic dissection. Calibration, discrimination and reclassification analyses show modest improvement in prediction using the BP-GRS in addition to the model which used only traditional risk factors. A GRS for hypertension associates with TAA suggesting a link between genetic determinants of BP and aortic disease. The effect size is small but the addition of more SNPs to the GRS might improve its discriminatory capability.

Published
2019

46. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

Author

Patrizia Noris, Nicole Schlegel, Catherine Klersy, Paula G. Heller, Elisa Civaschi, Nuria Pujol-Moix, Fabrizio Fabris, Remi Favier, Paolo Gresele, Véronique Latger-Cannard, Adam Cuker, Paquita Nurden, Andreas Greinacher, Marco Cattaneo, Erica De Candia, Alessandro Pecci, Marie-Françoise Hurtaud-Roux, Ana C. Glembotsky, Eduardo Muñiz-Diaz, Maria Luigia Randi, Nathalie Trillot, Loredana Bury, Thomas Lecompte, Caterina Marconi, Anna Savoia, Carlo L. Balduini, Sophie Bayart, Anne Bauters, Schéhérazade Benabdallah-Guedira, Françoise Boehlen, Jeanne-Yvonne Borg, Roberta Bottega, James Bussel, Daniela De Rocco, Emmanuel de Maistre, Michela Faleschini, Emanuela Falcinelli, Silvia Ferrari, Alina Ferster, Tiziana Fierro, Dominique Fleury, Pierre Fontana, Chloé James, Francois Lanza, Véronique Le Cam Duchez, Giuseppe Loffredo, Pamela Magini, Dominique Martin-Coignard, Fanny Menard, Sandra Mercier, Annamaria Mezzasoma, Pietro Minuz, Ilaria Nichele, Lucia D. Notarangelo, Tommaso Pippucci, Gian Marco Podda, Catherine Pouymayou, Agnes Rigouzzo, Bruno Royer, Pierre Sie, Virginie Siguret, Catherine Trichet, Alessandra Tucci, Béatrice Saposnik, and Dino Veneri

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 109/L.

Published
2014
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47. Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report

Author

Denise Marcon, Pietro Minuz, Giovanna Spiazzi, Angela Tagetti, Paolo Moghetti, and Cristiano Fava

Subjects
medicine.medical_specialty, Medicine (General), Case Report, Case Reports, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, R5-920, Medicine, Twin Pregnancy, Pregnancy, therapy, business.industry, Obstetrics, Addison Disease, Addison disease, General Medicine, twins, medicine.disease, First trimester, 030220 oncology & carcinogenesis, pregnancy, business, Hormone
Abstract

Key Clinical Message Addison Disease is an uncommon, life‐threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced., Addison Disease is an uncommon, life‐threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.

Published
2021

48. Expression and functional characterization of the large-conductance calcium and voltage-activated potassium channel K

Author

Alessandra, Balduini, Cristiano, Fava, Christian A, Di Buduo, Vittorio, Abbonante, Alessandra, Meneguzzi, Paolo M, Soprano, Francesco, Taus, Marco, Castelli, Alice, Giontella, Melania, Dovizio, Stefania, Tacconelli, Paola, Patrignani, and Pietro, Minuz

Subjects
Blood Platelets, Potassium Channels, Humans, Benzimidazoles, Calcium, Megakaryocytes
Abstract

Ion channels are transmembrane proteins that play important roles in cell function regulation modulating ionic cell permeability. In megakaryocytes and platelets, regulated ion flows have been demonstrated to modulate platelet production and function. However, a relatively limited characterization of ion channel expression and function is available in the human megakaryocyte-platelet lineage.We analyzed the expression and function of the large-conductance calcium and voltage-activated potassium channel KTo investigate the functionality of KIn megakaryocytes, KThe present study reveals new mechanisms in platelet formation and activation, suggesting that targeting K

Published
2021

49. Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over PrasugreL: a MUlticenter Randomized Open-label Trial in PatientS with ST-elevation Myocardial InFarction Referred for PrimAry PercutaneouS InTERvention (FABOLUS FASTER) Trial: Design and Rationale : The FABOLUS FASTER Trial

Author

Marisa Avvedimento, Plinio Cirillo, Stephan Windecker, Dik Heg, Lukas Hunziker, Giuseppe Gargiulo, Michael Nagler, Michael Billinger, Raffaele Piccolo, Andreas Wahl, Matteo Tebaldi, Gianluca Campo, Pietro Minuz, Giovanni Esposito, Felice Gragnano, Marco Valgimigli, Negar Manavifar, University of Zurich, Gargiulo, Giuseppe, Esposito, Giovanni, Cirillo, Plinio, Nagler, Michael, Minuz, Pietro, Campo, Gianluca, Gragnano, Felice, Manavifar, Negar, Piccolo, Raffaele, Avvedimento, Marisa, Tebaldi, Matteo, Wahl, Andrea, Hunziker, Luka, Billinger, Michael, Heg, Dik, Windecker, Stephan, and Valgimigli, Marco

Subjects
Male, 0301 basic medicine, Prasugrel, medicine.medical_treatment, Pharmaceutical Science, 030204 cardiovascular system & hematology, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Platelet aggregation, Prospective Studies, Infusions, Intravenous, 610 Medicine & health, Genetics (clinical), Primary PCI, Cangrelor, Tirofiban, Middle Aged, Injections, Intravenous, Cardiology, Cangrelor, Platelet aggregation, Prasugrel, Primary PCI, Tirofiban, Adenosine Monophosphate, Molecular Medicine, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug, medicine.medical_specialty, 11171 Cardiocentro Ticino, NO, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, Genetics, medicine, Humans, cardiovascular diseases, Aged, Dose-Response Relationship, Drug, business.industry, Percutaneous coronary intervention, Adenosine Monophosphate, Clinical trial, 030104 developmental biology, chemistry, Conventional PCI, Purinergic P2Y Receptor Antagonists, ST Elevation Myocardial Infarction, business, Prasugrel Hydrochloride, Platelet Aggregation Inhibitors, Follow-Up Studies
Abstract

Antithrombotic therapy is a critical component of the management of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Rapid and profound inhibition of platelet reactivity has been shown to mitigate the ischemic risks and improve myocardial salvage. High residual platelet reactivity (HRPR) has been reported up to 4 or 6 h after loading dose of prasugrel or ticagrelor; therefore, multiple alternative strategies, including crushed or chewed oral tables or intravenous agents, have been investigated to provide a more rapid and sustained inhibition of platelet function and bridge the initial treatment gap. The FABOLUS FASTER is the first investigator-initiated, multicentre, open-label, prospective, randomized study to directly compare the pharmacodynamics effects of cangrelor, tirofiban, chewed or integer prasugrel. This study will add new insights in the management of antiplatelet therapy in patients with STEMI undergoing primary PCI and might be hypothesis-generating for future clinical trials in this field. The trial is registered on clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24.

Published
2021

50. Thrombin Generation in Patients with Coronavirus Disease 2019

Author

Barbara Lavorgna, Marco Benati, Cristiano Fava, Simone De Nitto, Pietro Minuz, Giuseppe Lippi, Gian Luca Salvagno, and Matteo Gelati

Subjects
Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Thrombomodulin, Thrombin generation, Coronavirus Disease 2019, Medicine, Humans, Thrombin Generation, Coronavirus Disease 2019, COVID-19, In patient, Aged, Inpatients, business.industry, SARS-CoV-2, Fibrinolysis, Thrombin, Hematology, Middle Aged, Virology, Thrombin Generation, Case-Control Studies, Female, Blood Coagulation Tests, Cardiology and Cardiovascular Medicine, business
Published
2021

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