Publications by authors named "Andrea Berni"

60 Publications

SERUM SODIUM ALTERATIONS IN SARS CoV2 (COVID19) INFECTION: IMPACT ON PATIENT OUTCOME.

Eur J Endocrinol 2021 May 1. Epub 2021 May 1.

A Peri, Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, 50139, Italy.

Objective: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients Design and Methods. In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital) data from 380 patients were analyzed.

Results: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7 fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.7% increased risk of death.

Conclusions: These results suggest that serum sodium at admission may be considered an early prognostic marker of disease severity in hospitalized COVID-19 patients.
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http://dx.doi.org/10.1530/EJE-20-1447DOI Listing
May 2021

Use of the FebriDx point-of-care test for the exclusion of SARS-CoV-2 diagnosis in a population with acute respiratory infection during the second (COVID-19) wave in Italy.

Int J Infect Dis 2021 Apr 23. Epub 2021 Apr 23.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy. Electronic address:

Objective: Evaluate the real-world accuracy of Myxovirus resistance protein A (MxA) detected by the rapid, point-of-care FebriDx test during the second-wave pandemic in Italy in patients with acute respiratory infection (ARI) and a clinical suspicion of COVID-19.

Design And Methods: Prospective, observational, diagnostic accuracy study whereby hospitalized patients with ARI were consecutively enrolled in a single tertiary care center in Italy from August 1, 2020 to January 31, 2021.

Results: COVID-19 was diagnosed in 136/200 (68.0%) patients and Non-COVID-19 was diagnosed in64/200 (32.0%) patients. COVID-19 patients were younger and had a lower Charlson comorbidity index compared to non-COVID-19 patients (p < 0.001). Concordance between FebriDx, MxA and rt-PCR for SARS-CoV-2 (gold standard) was good (k 0.93, 95%CI 0.87-0.99). Overall sensitivity and specificity were 97.8% [95%CI 93.7-99.5] and 95.3% [95%CI 86.9%-99.0%], respectively. FebriDx demonstrated a negative predictive value of 95.3% (95%CI 86.9-99.0) for an observed disease prevalence of 68%.

Conclusions: FebriDx MxA showed high diagnostic accuracy to identify COVID-19 and could be considered as a real-time triage tool to streamline the management of suspected COVID-19 patients. FebriDx also detected bacterial etiology in non-COVID-19 patients suggesting good performance to distinguish bacterial from viral respiratory infection.
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http://dx.doi.org/10.1016/j.ijid.2021.04.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064815PMC
April 2021

Interplay between COVID-19, pollution, and weather features on changes in the incidence of acute coronary syndromes in early 2020.

Int J Cardiol 2021 04 30;329:251-259. Epub 2020 Dec 30.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Mediterranea Cardiocentro, Napoli, Italy. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area.

Methods And Results: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI cases. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all p<0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death (p<0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature (p<0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data (p<0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both p<0.001).

Conclusions: Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant epidemiologic and pathophysiologic mechanisms. In particular, recent changes in STEMI may depend on COVID-19 scare, leading to excess all-cause mortality, or effective reduced incidence, whereas reductions in NSTEMI may also be due to beneficial reductions in NO2 emissions in the lockdown phase.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833791PMC
April 2021

Impact of temporary traffic bans on the risk of acute coronary syndromes in a large metropolitan area.

Panminerva Med 2020 Dec 6;62(4):252-259. Epub 2020 Oct 6.

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy -

Background: Strong epidemiologic evidence has highlighted the role of pollution, on top of adverse climate features, as a novel cardiovascular risk factor. However, mechanistic proof that reducing pollution may be beneficial to prevent atherothrombotic events is limited. We aimed at appraising the impact of temporary traffic bans in a large metropolitan area on the risk of acute coronary syndromes.

Methods: Aggregate and anonymized data from 15 tertiary cardiac care centers were obtained detailing precoronavirus disease 2019 (COVID-19) daily cases of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including those treated with percutaneous coronary intervention (PCI). Data on pollutants and climate were sought for the same days. Mixed level regression was used to compare the week before vs after the traffic ban (Fortnight analysis), the 3 days before vs. after (Weekly analysis) and the Sunday before vs. after (Sunday analysis).

Results: A total of 8 days of temporary traffic bans were included, occurring between 2017 and 2020, totaling 802 STEMI and 1196 NSTEMI in the Fortnight analysis, 382 STEMI and 585 in the Weekly analysis, and 148 STEMI and 210 NSTEMI in the Sunday analysis.Fortnight and Sunday analyses did not disclose a significant impact of traffic ban on STEMI or NSTEMI (all P>0.05). Conversely, Weekly analysis showed non-significant changes for STEMI, but a significant decrease in daily NSTEMI when comparing the 3 days before the traffic ban with the ban day (P=0.043), as well as the 3 days before vs. the 3 days after the ban (P=0.025). No statistically significant effect of traffic ban was found at Fortnight, Weekly or Sunday analyses for daily mean concentrations of benzene, carbon monoxide, nitric oxide, nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM) <2.5 µm or PM <10 µm (all P>0.05). However, minimum daily concentrations showed a significant reduction of ozone during the ban in comparison to the week preceding it (P=0.034), nitric oxide during the ban in comparison to the 3 days preceding it (P=0.046), and an increase in benzene during the ban in comparison to the Sunday before (P=0.039).

Conclusions: Temporary traffic ban may favorably reduce coronary atherothrombotic events, and in particular NSTEMI, even if not globally and immediately impacting on environmental pollution. Further controlled studies are required to confirm and expand this hypothesis-generating results.
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http://dx.doi.org/10.23736/S0031-0808.20.04161-0DOI Listing
December 2020

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Leukemia 2021 04 19;35(4):1121-1133. Epub 2020 Aug 19.

Center Research Innovation of Myeloproliferative Neoplasms (CRIMM), SOD Hematology, University of Florence and AOU Careggi, Florence, Italy.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.
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http://dx.doi.org/10.1038/s41375-020-01018-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437386PMC
April 2021

The HScore for secondary hemophagocytic lymphohistiocytosis, calculated without a marrow biopsy, is consistently low in patients with COVID-19.

Int J Lab Hematol 2020 12 10;42(6):e270-e273. Epub 2020 Aug 10.

Department of Experimental and Clinical Medicine, CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1111/ijlh.13310DOI Listing
December 2020

Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study.

J Allergy Clin Immunol Pract 2020 Sep 19;8(8):2575-2581.e2. Epub 2020 Jun 19.

Immunoallergology Unit, Careggi University Hospital, Florence, Italy. Electronic address:

Background: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms.

Objective: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19.

Methods: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used.

Results: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO/FiO (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up.

Conclusions: Combining IL-6, CRP, and SaO/FiO in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.
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http://dx.doi.org/10.1016/j.jaip.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303032PMC
September 2020

Are disease-related pulmonary perfusion abnormalities detectable in COVID-19 patients? Suspicious findings in a lung perfusion SPECT performed for ruling out classical pulmonary embolism.

Eur J Nucl Med Mol Imaging 2020 Aug 26;47(9):2211-2213. Epub 2020 May 26.

Internal Medicine 3, Department of Experimental and Clinical Medicine, University of Florence, Careggi University Hospital, Florence, Italy.

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http://dx.doi.org/10.1007/s00259-020-04868-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248457PMC
August 2020

Functional Role of Natriuretic Peptides in Risk Assessment and Prognosis of Patients with Mitral Regurgitation.

J Clin Med 2020 May 5;9(5). Epub 2020 May 5.

Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy.

The management of mitral valve regurgitation (MR), a common valve disease, represents a challenge in clinical practice, since the indication for either surgical or percutaneous valve replacement or repair are guided by symptoms and by echocardiographic parameters which are not always feasible. In this complex scenario, the use of natriuretic peptide (NP) levels would serve as an additive diagnostic and prognostic tool. These biomarkers contribute to monitoring the progression of the valve disease, even before the development of hemodynamic consequences in a preclinical stage of myocardial damage. They may contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations, thus requiring surgical management rather than a conservative approach. This article provides a comprehensive overview of the available evidence on the role of NPs in the management, risk evaluation, and prognostic assessment of patients with MR both before and after surgical or percutaneous valve repair. Despite largely positive evidence, a series of controversial findings exist on this relevant topic. Recent clinical trials failed to assess the role of NPs following the interventional procedure. Future larger studies are required to enable the introduction of NP levels into the guidelines for the management of MR.
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http://dx.doi.org/10.3390/jcm9051348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290430PMC
May 2020

Unexpected Clues From Positron Emission Tomography in a Case of Fever of Unknown Origin.

J Clin Rheumatol 2020 Feb 4. Epub 2020 Feb 4.

Internal Medicine Unit 3, Careggi University Hospital, Firenze, Italy.

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http://dx.doi.org/10.1097/RHU.0000000000001377DOI Listing
February 2020

[Position paper of the Italian Society of Interventional Cardiology (SICI-GISE): Management of patent foramen ovale in patients with cerebral or systemic thromboembolism - 2020].

G Ital Cardiol (Rome) 2020 04;21(4 Suppl 2):50S-59S

U.O.C. Emodinamica, P.O. San Filippo Neri, ASL Roma 1, Roma.

Patent foramen ovale (PFO) is implicated in the pathogenesis of different clinical syndromes in which it plays variable roles. In 2017 and 2018, four randomized clinical trials were published, allowing for the clarification of certain issues pertaining to cryptogenic stroke. Recently, eight European scientific societies collaborated to the writing of an interdisciplinary international position paper on PFO and cryptogenic stroke, based upon best available evidence, with the aim of defining the principles needed to guide decision making. Nonetheless, a tailored approach is not suitably addressed by standard position documents, considering that decisions about optimal management of PFO patients with left circulation thromboembolism are often challenging, mostly due to comorbidities and complex clinical scenarios.A panel of Italian cardiology experts gathered under the auspices of the Italian Society of Interventional Cardiology (SICI-GISE) for comprehensive discussion and consensus development, with the aim of providing practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of PFO in patients with cerebral or systemic thromboembolism. In this position paper, various clinical scenarios in patients with and without high-risk PFO features are presented and discussed, including PFO patients with associated conditions (e.g. hypercoagulable states, deep vein thrombosis/pulmonary embolism, short runs of atrial fibrillation), and special subsets (e.g. patients with risk factors for atrial fibrillation, patients aged ≥65 years, patients who refused percutaneous PFO closure), with the Panel's recommendations being provided for each scenario.
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http://dx.doi.org/10.1714/3336.33075DOI Listing
April 2020

Long-Term Follow-Up of Transcatheter Aortic Valve Implantation With Portico Versus Evolut Devices.

Am J Cardiol 2020 04 30;125(8):1209-1215. Epub 2020 Jan 30.

Unità Operativa di Interventistica Cardiovascolare, Pineta Grande Hospital, Castel Volturno, Italy.

New-generation devices such as Evolut and Portico have provided favorable results in patients who underwent transcatheter aortic valve implantation (TAVI) for aortic stenosis, but their comparative effectiveness remains debated, despite its relevance when envisioning TAVI in low-risk patients. We evaluated the safety and efficacy of 2 leading TAVI devices (Evolut and Portico) used by the same team of experienced TAVI operators, focusing on long-term outcomes, including major adverse events (i.e., the composite of death, stroke, myocardial infarction, major vascular complication, or major bleeding). Unadjusted and propensity score-adjusted analyses were carried out. A total of 233 patients were included, 119 (51.1%) receiving Evolut and 114 (49%) Portico. Baseline and procedural data showed significant between-device differences, including functional class, surgical risk, chronic obstructive pulmonary disease, renal function, transesophageal guidance, device size, postdilation, and procedural time (all p <0.05). Yet, acute and in-hospital outcomes were not significantly different (all p >0.05). Follow-up status was ascertained in 228 (98%) patients after 15.0 ± 7.6 months. Unadjusted analysis showed similar rates of major adverse events, as well as the individual risk of death, stroke, myocardial infarction, major vascular complication, major bleeding, and pacemaker implantation (all p >0.05). Even at propensity score-adjusted analysis outcomes were not significantly different with Evolut and Portico (all p >0.05). In conclusion, Evolut and Portico devices yield similarly favorable results at long-term follow-up when used by experienced TAVI operators.
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http://dx.doi.org/10.1016/j.amjcard.2020.01.018DOI Listing
April 2020

Cryptic severe malaria in a Moroccan man living in Tuscany, Italy, August 2018.

Euro Surveill 2018 10;23(41)

Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy.

In August 2018 a Moroccan man living in Tuscany developed malaria. The patient declared having not recently visited any endemic country, leading to diagnostic delay and severe malaria. As susceptibility to of Anopheles species in Tuscany is very low, and other risk factors for acquiring malaria could not be completely excluded, the case remains cryptic, similar to other malaria cases previously reported in African individuals living in Apulia in 2017.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.41.1800527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194912PMC
October 2018

[Updated SICI-GISE position paper on institutional and operator requirements for transcatheter aortic valve implantation].

G Ital Cardiol (Rome) 2018 Sep;19(9):519-529

Azienda Socio Sanitaria Territoriale, Monza (MB).

Transcatheter aortic valve implantation (TAVI) has revolutionized the management of patients with symptomatic severe aortic stenosis and has become the standard of care for inoperable patients and the preferred therapy for those at increased surgical risk with peculiar clinical and anatomic features. Technology advances, growing experience and accumulating data prompted the update of the 2011 Italian Society of Interventional Cardiology (SICI-GISE) position paper on institutional and operator requirements to perform TAVI. The main objective of this document is to provide a guidance to assess the potential of institutions and operators to initiate and maintain an efficient TAVI program.
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http://dx.doi.org/10.1714/2951.29672DOI Listing
September 2018

Meta-Analysis of Head-to-Head Comparison of Intracoronary Versus Intravenous Adenosine for the Assessment of Fractional Flow Reserve.

Am J Cardiol 2017 Aug 30;120(4):563-568. Epub 2017 May 30.

Emergency Department, Sandro Pertini Hospital, Azienda Sanitaria Locale Roma 2, Rome, Italy.

Intravenous (IV) infusion of adenosine represents the gold standard for measuring fractional flow reserve (FFR). However, IV adenosine is more expensive and time-consuming compared with intracoronary (IC) boluses of adenosine. We conducted a meta-analysis of studies comparing IC with IV adenosine for FFR assessment in the same coronary lesions. We searched for studies comparing IC with IV adenosine and reporting absolute FFR values or rate of abnormal FFR for both routes. Prespecified subgroup analysis was performed to appraise studies using low-dose (<100 μg) or high-dose IC adenosine (≥100 μg). We retrieved 11 studies amounting to 587 patients and 621 lesions. Six studies evaluated low-dose IC boluses (15 to 80 μg) and 5 studies high-dose boluses (120 to 600 μg). Absolute FFR values were slightly, yet significantly lower with IV adenosine compared with IC adenosine (mean difference 0.02, 95% confidence interval [CI] 0.00 to 0.03, p = 0.02). This difference, however, did not translate into a significant difference in the rate of abnormal FFR between IC and IV adenosine (hazard ratio 0.93, 95% CI 0.76 to 1.13, p = 0.57); moreover, no statistically significant difference was observed between low-dose and high-dose IC adenosine subgroups. Adverse events were less frequent with IC adenosine compared with IV adenosine (risk ratio 0.17, 95% CI 0.07 to 0.43, p <0.001). In conclusion, IC administration of adenosine, although inducing a slightly lower amount of hyperemia compared with IV infusion of adenosine, yields a similar diagnostic accuracy in identifying hemodynamically significant coronary stenosis and is better tolerated by the patients.
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http://dx.doi.org/10.1016/j.amjcard.2017.05.024DOI Listing
August 2017

Tortuosity, Recurrent Segments, and Bridging of the Epicardial Coronary Arteries in Patients With the Takotsubo Syndrome.

Am J Cardiol 2017 Jan 8;119(2):243-248. Epub 2016 Oct 8.

Cardiology Department, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. Electronic address:

Myocardial bridging (MB) and a long recurrent wraparound left anterior descending artery (wrap-LAD) are coronary anatomic variants that have been recently suggested to be associated with takotsubo syndrome (TS). Until now, coronary artery tortuosity (CAT) has never been investigated in this setting. Our study sought to evaluate the prevalence of the aforementioned anatomic variants in a large population with TS. In this retrospective angiographic study, 109 patients with TS were compared with 109 age- and gender-matched subjects without coronary artery disease, valve heart disease, or cardiomyopathy. CAT was identified by ≥3 consecutive curvatures ≥90° (criteria 1) or by ≥2 consecutive curvatures ≥180° (criteria 2). Wrap-LAD was defined if any part of the vessel outreached the apex of the left ventricle and MB as the presence of a milking effect or a step-up and step-down phenomenon. An anatomic variant was found in 79 patients with TS (72%) and in 48 controls (44%) (p <0.001). CAT in at least 1 vessel (criteria 1: 49% vs 20%, p <0.001; criteria 2: 38% vs 13%, p <0.001), ≥2 vessels (criteria 2: 14% vs 3%, p = 0.005), and wrap-LAD (41% vs 27%, p = 0.02) were significantly more frequent in patients with TS than in controls. The prevalence of MB (9% vs 5%, p = 0.18) did not differ between groups. In conclusion, CAT and wrap-LAD have higher prevalence in patients with TS than in matched controls. These findings could support the hypothesis that anatomic variants might act as potential pathogenic substrates in TS.
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http://dx.doi.org/10.1016/j.amjcard.2016.09.055DOI Listing
January 2017

Comparison Between Radial Approach and Femoral Approach With Vascular Closure Devices on the Occurrence of Access-Site Complications and Periprocedural Bleeding After Percutaneous Coronary Procedures: A Systematic Review and Meta-Analysis.

J Invasive Cardiol 2016 Dec 15;28(12):473-479. Epub 2016 Sep 15.

Interventional Cardiology Unit and Emergency Department, Sandro Pertini Hospital, Via dei Monti Tiburtini 385, 00157, Rome, Italy.

Objectives: Periprocedural bleedings, often related to vascular access site, represent an important drawback of percutaneous coronary procedures and are associated with worse outcomes. Radial access (RA) and, potentially, femoral access (FA) with vascular closure device (VCD) are useful strategies in order to mitigate periprocedural bleedings; nevertheless, their relative efficacy is largely undetermined. We aimed to perform a systematic review and meta-analysis of available studies comparing the efficacy of RA and FA with hemostasis by VCD (FA + VCD) on the reduction of access-site complications and/or periprocedural bleedings.

Methods: Published studies reporting outcomes on access-site complications and periprocedural bleedings were included in the analysis. Data were extracted by two independent reviewers; odds ratio (OR) and 95% confidence interval (CI) were calculated by random-effects model and were used as summary statistics.

Results: We included in the analysis 13 studies, of which 5 were randomized. Access-site complications were reported by 11 studies, amounting to 157,031 patients (77,713 in the RA group and 79,318 in the FA + VCD group), whereas periprocedural bleedings were reported by 12 studies, amounting to 600,196 patients (137,277 in the RA group and 462,919 in the FA + VCD group). RA was associated with a significant reduction in access-site complications (OR, 0.25; 95% CI ,0.21-0.31; P<.001) and periprocedural bleedings (OR, 0.40; 95% CI, 0.34-0.48; P<.001) as compared with FA + VCD; the results were consistent among randomized and observational studies.

Conclusions: This meta-analysis shows that RA is superior to FA + VCD in the reduction of access-site complications and periprocedural bleedings.
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December 2016

Outcomes of early invasive treatment strategy in elderly patients with non-ST elevation acute coronary syndromes.

J Cardiovasc Med (Hagerstown) 2016 Oct;17(10):736-43

aDivision of Cardiology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Ospedale Sant'AndreabDepartment of Epidemiology, Lazio Regional Health Service, RomecIRCCS Neuromed, Pozzilli (IS), Italy.

Background: As benefits of revascularization in non-ST elevation acute coronary syndromes (NSTEACSs) in the elderly are still unproven, we sought to assess the association between invasive or conservative management of NSTEACS and short-, mid- and long-term mortality or composite outcome of all-cause mortality and myocardial infarction in a cohort of consecutive elderly patients.

Methods And Results: Consecutive NSTEACS patients older than 75 years discharged between 2006 and 2010 from a single intensive cardiac care unit, and managed with invasive or conservative strategy according to available guidelines were retrospectively surveyed. By multivariate regression and sensitivity analysis, crude and adjusted mortality and composite outcome were estimated at prespecified time points of short-term (in-hospital or 30 days mortality), mid-term (T1: 31 days to 6 months), and long-term (T2: 31 days to 12 months). A total of 453 patients (median age 80 years, 47% men) were evaluated; 301 (66.5%) underwent invasive treatment. Invasive was associated with significantly lower risk of short- [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.12-0.67, P = 0.004], mid- (OR 0.33, 95% CI 0.16-0.67, P = 0.003) and long-term mortality (OR 0.34, 95% CI 0.20-0.58, P < .0001). Invasive strategy was also associated with nonsignificant lower short- (OR 0.55, 95% CI 0.28-1.07, P = 0.077), and highly significant lower mid- (OR 0.52, 95% CI 0.34-0.81, P = 0.003) and long-term adjusted cumulative composite outcome rate (OR 0.68, 95% CI 0.46-0.98, P = 0.004).

Conclusion: In NSTEACS elderly patients, invasive strategy is independently associated with lower short-, mid- and long-term mortality and composite outcome.
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http://dx.doi.org/10.2459/JCM.0000000000000364DOI Listing
October 2016

Long term follow-up of "full metal jacket" of de novo coronary lesions with new generation Zotarolimus-eluting stents.

Int J Cardiol 2016 Oct 5;221:1008-12. Epub 2016 Jul 5.

Unità Operativa Complessa di Cardiologia, Ospedale Valduce, Como, Italy.

Background: Diffuse coronary artery disease treatment still remains a challenge for interventional cardiologists and cardiac surgeons. There are few data on full metal jacket (FMJ) stenting, especially with new-generation drug-eluting stents. We aimed to assess the efficacy and safety of FMJ with new-generation Zotarolimus-eluting stents (n-ZES).

Methods And Results: All patients who underwent FMJ with n-ZES (≥60mm stent length) in eleven Italian interventional centers participating in the Clinical Service® project were included in this analysis. The project population consisted of 120 patients and 122 lesions. Mean age was 67±10years and 95 (79.2%) patients were male. A chronic total occlusion was present in 34 lesions (27.9%). The number of stents implanted per lesion was 2.9±0.8, and the diameter of the stents was 3.0±0.5mm. Predilation and post-dilatation were performed in 107 (87.7%) and 92 (75.4%) patients, respectively. At 41±21month follow-up there were 2 patients with subacute definite stent thrombosis, 6 patients (5.0%) had cardiac death and 5 patients (4.2%) had non-fatal myocardial infarction. Seven patients (5.8%) underwent clinically-driven target lesion revascularization. Fourteen patients (11.7%) had at least one major adverse cardiac event.

Conclusion: The treatment of diffuse coronary artery disease with FMJ stenting with n-ZES appears to be effective and safe. Late and very-late ST does not seem to be an issue and the rate of restenosis and of major cardiac adverse events after more than 3-year follow-up is rather low.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.050DOI Listing
October 2016

The micronucleus assay in mammalian cells in vitro to assess health benefits of various phytochemicals.

Mutat Res Genet Toxicol Environ Mutagen 2015 Nov 30;793:79-85. Epub 2015 Jun 30.

Department of Ecological and Biological Sciences, University of Tuscia, Via San Camillo de Lellis snc, 01100 Viterbo, Italy.

We evaluated the protective effects of Gentiana lutea extracts (GLEx) and 6-Gingerol (6-G) on clastogenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 7,12-dimethylbenz(α) anthracene (DMBA) in vitro on HepG2 cells using the frequencies of induced micronuclei (MN) as the end point. Pre-, post- and simultaneous treatments with GLEx or 6-G and the carcinogens were carried out. Both GLEx post- and simultaneous treatments reduced the frequencies of MN induced by MNNG and DMBA. Probably this effect is due to an increase of cytostasis and a physico-chemical interaction between GLEx and DMBA under simultaneous treatment. Pre- and simultaneous treatments with 6-G significantly reduced the yield of MNNG-induced micronuclei without affecting % of cytostasis. Simultaneous treatment with 6-G plus DMBA resulted in reduction in the frequency of MN and an increase in cytotoxicity compared to sample treated alone with DMBA, whereas a post-treatment, caused a significant decrease in the yield of MN compared with DMBA alone without any cytotoxic effect. These results are compared with our earlier data obtained in the same system with other phytochemicals. It is concluded that for a critical evaluation of the protective effects of phytochemicals, both the influence on the induced MN and induced cytostasis have to be considered.
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http://dx.doi.org/10.1016/j.mrgentox.2015.06.016DOI Listing
November 2015

Blood Pressure Levels at the Time of Percutaneous Coronary Revascularization and Risk of Coronary In-Stent Restenosis.

Am J Hypertens 2016 Apr 13;29(4):509-18. Epub 2015 Aug 13.

Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy; IRCCS Neuromed, Pozzilli (IS), Italy;

Background: High blood pressure (BP) levels expose patients treated with percutaneous coronary interventions (PCI) to very high risk of 10-year cardiovascular morbidity and mortality.

Objective: To investigate the role of BP levels at the time of PCI on the risk of in-stent restenosis (ISR).

Methods: We retrospectively included 796 patients previously treated with PCI, who underwent repeated angiography for recurrent angina or reversible myocardial ischemia. Patients were stratified into either case (n = 354) and control (n = 442) groups in the presence or absence of ISR (defined as in-stent diameter stenosis ≥50%). BP levels were measured at the time of first and second procedures. Normal BP levels were defined for <140/90 mm Hg.

Results: Patients with normal BP showed significantly higher ISR-free survival (Log-rank: 5.937; P = 0.015). Both systolic (HR (95% CI): 0.731 (0.590-0.906)) and systolic/diastolic BP (HR (95% CI): 0.757 (0.611-0.939)) were significantly and independently associated with lower risk of ISR at Cox-regression analysis, adjusted for potential confounding factors, including stent type and concomitant medications. Patients with ISR showed lower rates of normal systolic/diastolic BP values (166 (47%) vs. 254 (57%); P = 0.003) compared to controls. They also received higher stent number (1.40±0.74 vs. 1.24±0.51; P < 0.001) with higher stent length (24.3±15.6 vs. 21.7±13.9 mm; P = 0.012), and lower rate of drug-eluting stents (DESs) (210 (48%) vs. 139 (40%); P = 0.025) compared to controls.

Conclusions: Normal BP at the time of PCI is associated with nearly 24% risk reduction of ISR as evaluated in a new angiography in patients with coronary artery disease.
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http://dx.doi.org/10.1093/ajh/hpv131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886488PMC
April 2016

Impaired Femoral Vascular Compliance and Endothelial Dysfunction in 30 Healthy Male Soccer Players: Competitive Sports and Local Detrimental Effects.

Sports Health 2015 Jul;7(4):335-40

Department of Experimental and Clinical Medicine, University of Florence, Italy.

Background: Despite beneficial effects of physical activity on cardiovascular risk, discordant data on elite athletes (high atherosclerotic damage in activity comprising strenuous exertion) and retired sportsmen are reported in the literature.

Hypothesis: We hypothesize that long-lasting daily physical activity could affect the morphology and function of the carotid and femoral vessel walls differently, as assessed in elite male athletes aged 20 to 30 years compared with age- and sex-matched healthy controls.

Study Design: Retrospective case-control study.

Level Of Evidence: Level 3.

Methods: Sixty male subjects (30 athletes and 30 controls) underwent medical examination for ankle brachial index, augmentation index (AIX) and AIX corrected for heart rate (AIXr), peripheral arterial tonometry (PAT), and intima media thickness and pulse wave velocity assay at common carotid (carotid-intima media thickness [c-IMT], carotid-pulse wave velocity [c-PWv]) and femoral arteries (femoral-intima media thickness [f-IMT], femoral-pulse wave velocity [f-PWv]) assessed by ultrasonography using Doppler ultrasound.

Results: Athletes showed a significantly lower heart rate (HR) at rest and a better lipid profile than controls. In athletes, c-PWv (5.87 ± 0.80 vs 6.62 ± 1.02 m/s, P = 0.001) and f-PWv (8.96 ± 1.29 vs 7.89 ± 1.39, P = 0.002) were, respectively, significantly lower and higher than values found in controls; accordingly, carotid AIX (4.03 ± 6.21 vs 7.81 ± 5.21, P = 0.003) and femoral AIX (8.56 ± 10.21 vs 6.09 ± 7.95, P = 0.042) were lower and higher than control values, even after correction for heart rate (P = 0.03). On the other hand, IMT values were significantly higher in controls than in athletes (c-IMT, P < 0.0001; f-IMT, P < 0.0001). A positive significant correlation between HR and c-IMT and f-IMT (r = 0.527, P < 0.001 and r = 0.539, P < 0.0001, respectively) and between HR and c-PWv (r = 0.410, P = 0.01) was found when controls and athletes were considered as a whole group. Soccer players showed lower PAT values in comparison with controls (P = 0.002).

Conclusion: Elite sports positively affect c-IMT, f-IMT, and carotid PWv and AIX but not femoral PWv, AIX, AIXr, or PAT.

Clinical Relevance: Physical activity affects vascular beds in elite athletes differentially, depending on the rate of superior or inferior limb involvement in different sports. In soccer players, physical activity has a protective effect on carotid and femoral vessel walls but worsens femoral arterial and endothelial function. These findings highlight how different results can be shown on carotid and femoral districts, when these vascular districts are differently stressed during sport activity.
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http://dx.doi.org/10.1177/1941738115577931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481678PMC
July 2015

Transfemoral approach with systematic use of FemoSeal™ closure device compared to transradial approach in primary angioplasty.

Catheter Cardiovasc Interv 2016 Apr 23;87(5):849-54. Epub 2015 Jun 23.

Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Rome, and IRCCS Neuromed, Pozzilli (IS), Italy.

Objectives: To compare the incidence of major adverse cardiac and cerebrovascular events (MACCE) and thrombolysis in myocardial infarction (TIMI) bleedings in primary percutaneous coronary intervention (pPCI) performed through transradial approach (TRA) or transfemoral approach (TFA) with systematic closure by FemoSeal™.

Background: Although the risk of bleeding can be reduced using vascular closure devices (VCD), there are few data comparing TRA and TFA with VCD, particularly in the setting of pPCI.

Methods: we included in this retrospective registry 777 patients who underwent pPCI at two centers from years 2010 to 2013. Exclusion criteria were implantation of intra-aortic balloon pump and achievement of femoral hemostasis by other means than FemoSeal™. We performed propensity-score matching and multivariate analysis to adjust for clinical and procedural confounders.

Results: We enrolled 511 patients in TRA group and 266 in TFA group. Both in the general population and in the propensity-matched population, the incidence of MACCE was comparable in TRA vs. TFA patients (3.5 vs. 3.4% and 4.4 vs. 2.6%, respectively; P = ns). On the contrary, we observed a higher incidence of TIMI bleedings in TFA vs. TRA patients (5.6 vs. 2.2% in the general population and 6.6 vs. 1.3% in the propensity-matched population; P < 0.05); this difference was mainly driven by TIMI major bleedings. TFA was an independent predictor of bleeding at multivariate analysis.

Conclusions: In pPCI the rate of TIMI major bleedings was higher in TFA with closure by FemoSeal™ as compared to TRA, whereas the rates of minor bleedings and of MACCE were similar.
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http://dx.doi.org/10.1002/ccd.26076DOI Listing
April 2016

Role of chromatin structure modulation by the histone deacetylase inhibitor trichostatin A on the radio-sensitivity of ataxia telangiectasia.

Mutat Res 2015 Jul 20;777:52-9. Epub 2015 Apr 20.

Department of Ecological and Biological Sciences (DEB), University of Tuscia, Via San Camillo de Lellis snc, 01100 Viterbo, Italy.

At present, a lot is known about biochemical aspects of double strand breaks (DBS) repair but how chromatin structure affects this process and the sensitivity of DNA to DSB induction is still an unresolved question. Ataxia telangiectasia (A-T) patients are characterised by very high sensitivity to DSB-inducing agents such as ionising radiation. This radiosensitivity is revealed with an enhancement of chromosomal instability as a consequence of defective DNA repair for a small fraction of breaks located in the heterochromatin, where they are less accessible. Besides, recently it has been reported that Ataxia Telangiectasia Mutated (ATM) mediated signalling modifies chromatin structure. In order to study the impact of chromatin compaction on the chromosomal instability of A-T cells, the response to trichostatin-A, an histone deacetylase inhibitor, in normal and A-T lymphoblastoid cell lines was investigated testing its effect on chromosomal aberrations, cell cycle progression, DNA damage and repair after exposure to X-rays. The results suggest that the response to both trichostatin-A pre- and continuous treatments is independent of the presence of either functional or mutated ATM protein, as the reduction of chromosomal damage was found also in the wild-type cell line. The presence of trichostatin-A before exposure to X-rays could give rise to prompt DNA repair functioning on chromatin structure already in an open conformation. Differently, trichostatin-A post-treatment causing hyperacetylation of histone tails and reducing the heterochromatic DNA content might diminish the requirement for ATM and favour DSBs repair reducing chromosomal damage only in A-T cells. This fact could suggest that trichostatin-A post-treatment is favouring the slow component of DSB repair pathway, the one impaired in absence of a functionally ATM protein. Data obtained suggest a fundamental role of chromatin compaction on chromosomal instability in A-T cells.
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http://dx.doi.org/10.1016/j.mrfmmm.2015.04.009DOI Listing
July 2015

Comparison of risk of acute kidney injury after primary percutaneous coronary interventions with the transradial approach versus the transfemoral approach (from the PRIPITENA urban registry).

Am J Cardiol 2014 Sep 1;114(6):820-5. Epub 2014 Jul 1.

Interventional Cardiology, Sant'Andrea Hospital, University La Sapienza, Roma, Italy.

The risk of acute kidney injury (AKI) is a major issue after percutaneous coronary interventions (PCIs), especially in the setting of ST-elevation myocardial infarction. Preliminary data from large retrospective registries seem to show a reduction of AKI when a transradial (TR) approach for PCI is adopted. Little is known about the relation between vascular access and AKI after emergent PCI. We here report the results of the Primary PCI from Tevere to Navigli (PRIPITENA), a retrospective database of primary PCI performed at high-volume centers in the urban areas of Rome and Milan. Primary end point of this study was the occurrence of AKI in the TR and transfemoral (TF) access site groups. Secondary end points were major adverse cardiovascular events, stent thrombosis, and Thrombolysis in Myocardial Infarction major and minor bleedings. The database included 1,330 patients, 836 treated with a TR and 494 with a TF approach. After a propensity-matched analysis performed to exclude possible confounders, we identified 450 matched patients (225 TR and 225 TF). The incidence of AKI in the 2 matched groups was lower in patients treated with TR primary PCI (8.4% vs 16.9%, p = 0.007). Major adverse cardiovascular events and stent thrombosis were not different among study groups, whereas major bleedings were more often seen in the TF group. At multivariate analysis, femoral access was an independent predictor of AKI (odds ratio 1.654, 95% confidence interval 1.084 to 2.524, p = 0.042). In conclusion, in this database of primary PCI, the risk of AKI was lower with a TR approach, and the TF approach was an independent predictor for the occurrence of this complication.
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http://dx.doi.org/10.1016/j.amjcard.2014.06.010DOI Listing
September 2014

Chagas disease as a cause of heart failure and ventricular arrhythmias in patients long removed from endemic areas: an emerging problem in Europe.

J Cardiovasc Med (Hagerstown) 2015 Dec;16(12):817-23

aReferral Center for Myocardial Diseases, Internal Medicine and Infectious Disease Unit, Careggi University Hospital, Florence bDipartimento di Medicina Sperimentale e Clinica, Sezione Medicina Critica e Medicine Specialistiche, Clinica Malattie Infettive, Università degli Studi di Firenze, Firenze cInternal and Emergency Medicine Unit, Careggi Uninersity Hospital, Florence dMedicina Interna all'Orientamento all'alta complessità aziendale 2, Università degli Studi di Firenze, Firenze, Italia eDepartment of Medicine, Imperial College, Hammersmith Campus, London, UK.

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi. In endemic areas (South and Central America), Chagas disease represents a relevant public health issue, and is the most frequent cause of cardiomyopathy. In nonendemic areas, such as Europe, Chagas disease represents an emerging problem following the establishment of sizeable communities from Brazil and Bolivia. Chagas cardiomyopathy represents the most frequent and serious complication of chronic Chagas disease, affecting about 20-30% of patients, potentially leading to heart failure, arrhythmias, thromboembolism, stroke and sudden death. Because late complications of Chagas disease may develop several years or even decades after the acute infection, it may be extremely challenging to reach the correct diagnosis in patients long removed from the countries of origin. We report two examples of Chagas cardiomyopathy in South American women permanently residing in Italy for more than 20 years, presenting with cardiac manifestations ranging from left ventricular dysfunction and heart failure to isolated ventricular arrhythmias. The present review emphasizes that Chagas disease should be considered as a potential diagnosis in patients from endemic areas presenting with 'idiopathic' cardiac manifestations, even when long removed from their country of origin, with potential implications for treatment and control of Chagas disease transmission.
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http://dx.doi.org/10.2459/JCM.0000000000000045DOI Listing
December 2015

Framing comorbidities and co-occurrences in a migraine with aura patient: author's reply.

Intern Emerg Med 2014 Aug 7;9(5):605-6. Epub 2014 Jun 7.

Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, AOU Careggi, Florence, Italy.

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http://dx.doi.org/10.1007/s11739-014-1088-1DOI Listing
August 2014

A challenging multifactorial migraine with aura.

Intern Emerg Med 2014 Mar 14;9(2):201-5. Epub 2014 Jan 14.

Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni, 85-50134, Florence, Italy.

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http://dx.doi.org/10.1007/s11739-013-1038-3DOI Listing
March 2014

Evaluation of the effects of ellagic acid (EA) on 7,12-dimethylbenz(α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo.

Toxicol Lett 2014 Jan 1;224(2):240-5. Epub 2013 Nov 1.

Department of Ecological and Biological Sciences, Università degli Studi della Tuscia, Largo dell'Università, snc, I-01100 Viterbo, Italy.

We evaluated the protective effects of EA, a promising dietary constituent against degenerative diseases, on the clastogenic action of the model carcinogen DMBA in vitro on human hepatoma cells (HepG2) and in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with EA and the carcinogen were carried out in vitro. Simultaneous treatment with EA caused a statistically significant increase of DMBA induced MN, suggesting a direct interaction between the two agents. No significant reduction in DMBA induced MN was found by pre- or post treatment with EA. Similar effects were observed in the toxicity assay. In in vivo experiments, EA pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by DMBA. A good correlation was found between in vitro and in vivo experiments. Our results did not reveal any clear indication on the efficacy of EA on the induction of micronuclei by DMBA. EA by itself did not show any harmful effects.
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http://dx.doi.org/10.1016/j.toxlet.2013.10.012DOI Listing
January 2014

Effect of blueberries (BB) on micronuclei induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 7,12-dimethylbenz(a)anthracene (DMBA) in mammalian cells, assessed in in vitro and in vivo assays.

Mutat Res 2013 Dec 20;758(1-2):6-11. Epub 2013 Sep 20.

Department of Ecological and Biological Sciences, Università degli Studi della Tuscia, Largo dell'Università, snc, I-01100 Viterbo, Italy.

The protective effect of blueberry (BB) on the clastogenic effects of MNNG and DMBA was evaluated with the induced micronucleus (MN) frequency as a biomarker, both in vitro and in vivo. Human hepatoma HepG2 cells, which contain most of the metabolic activating enzymes was used for the in vitro test. MN frequencies were determined in binucleated cells generated by blocking cytokinesis by use of cytochalasin-B. The MN frequency in vivo was determined in polychromatic erythrocytes (PCEs) from the bone marrow of treated mice. BB by itself was not toxic both in vivo and in vitro. There was no evidence of a potential physico-chemical interaction between BB and the test carcinogens in vitro. Pre-treatment with BB reduced the MN frequency induced by MNNG. But, simultaneous treatment and post-treatment with BB did not affect the frequency of MNNG-induced MN. BB did not affect the frequency of DMBA-induced MN in vitro under any test condition. Under in vivo conditions, BB reduced the frequencies of MNNG- and DMBA-induced MN in PCEs, but in the case of the protective effect of BB against DMBA a dramatic reduction in the percentage of PCEs was observed, suggesting increased cytotoxicity.
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http://dx.doi.org/10.1016/j.mrgentox.2013.07.012DOI Listing
December 2013