Publications by authors named "Giuseppe Barbaro"

95 Publications

Blood SIRT1 Shows a Coherent Association with Leptin and Adiponectin in Relation to the Degree and Distribution of Adiposity: A Study in Obesity, Normal Weight and Anorexia Nervosa.

Nutrients 2020 Nov 14;12(11). Epub 2020 Nov 14.

Department of Experimental Medicine, Section of Medical Physiopathology, Food Science and Endocrinology, "Sapienza" University of Rome, Rome, Italy.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups ( < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R was recorded for EFT (R = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.
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http://dx.doi.org/10.3390/nu12113506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696683PMC
November 2020

Epicardial adipose tissue feeding and overfeeding the heart.

Nutrition 2019 03 24;59:1-6. Epub 2018 Jul 24.

Department of Experimental Medicine, Section of Medical Pathophysiology, University of Rome Sapienza, Rome, Italy.

Epicardial adipose tissue is a particular visceral fat depot with unique anatomic, biomolecular, and genetic features. Epicardial fat displays both physiological and pathological properties. Epicardial fat expresses genes and secretes cytokines actively involved in the thermogenesis and regulation of lipid and glucose metabolism of the adjacent myocardium. A disequilibrium between epicardial fat feeding and overfeeding the myocardium with free fatty acids leads to intramyocardial fat infiltration causing organ damage and clinical consequences. The upregulation of epicardial fat proinflammatory and lipogenic genes contributes to the fat build up in the proximal coronary arteries. Epicardial fat is a measurable and modifiable risk factor that can serve as a novel and additional tool for cardiovascular risk stratification. Pharmacologically targeting epicardial fat with drugs such as glucagon peptide-like 1 analogs or sodium glucose transport 2 inhibitors reduces the epicardial fat burden and induces beneficial cardiometabolic effects. Assessment and manipulation of epicardial fat transcriptome might open new avenues in the prevention of cardiometabolic diseases.
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http://dx.doi.org/10.1016/j.nut.2018.07.002DOI Listing
March 2019

Inverse Association of Circulating SIRT1 and Adiposity: A Study on Underweight, Normal Weight, and Obese Patients.

Front Endocrinol (Lausanne) 2018 7;9:449. Epub 2018 Aug 7.

Section of Medical Physiopathology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation. To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals. 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured. SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = -0.026 ± 0.011, = 0.025, and β = -0.516 ± 0.083, < 0.001, respectively). Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here.
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http://dx.doi.org/10.3389/fendo.2018.00449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090043PMC
August 2018

Targeting the organ-specific adiposity.

Eat Weight Disord 2019 02 14;24(1):1-2. Epub 2018 Aug 14.

Department of Experimental Medicine, Section of Medical Pathophysiology, University of Rome Sapienza, Rome, Italy.

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http://dx.doi.org/10.1007/s40519-018-0554-6DOI Listing
February 2019

Cardiovascular disease burden among human immunodeficiency virus-infected individuals.

Int J Cardiol 2018 Aug;265:195-203

Interventional Cardiology Division, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Milan, Italy. Electronic address:

Human Immunodeficiency Virus (HIV) infection affects 36.7 million people worldwide, it accounted for 1.1 million deaths in 2015. The advent of combined antiretroviral therapy (cART) has been associated with a decrease in HIV-related morbidity and mortality. However, there are increasing concerns about long-lasting effects of chronic inflammation and immune activation, leading to premature aging and HIV-related mortality. Cardiovascular diseases, especially coronary artery disease, are among the leading causes of death in HIV-infected patients, accounting for up to 15% of total deaths in high income countries. Furthermore, as cART availability expands to low-income countries, the burden of cardiovascular related mortality is likely to rise. Hence, over the next decade HIV-associated cardiovascular disease burden is expected to increase globally. In this review, we summarize our understanding of the pathogenesis and risk factors associated with HIV infection and cardiovascular disease, in particular coronary artery disease.
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http://dx.doi.org/10.1016/j.ijcard.2018.03.137DOI Listing
August 2018

Epicardial adipose tissue and signs of metabolic syndrome in children.

Eat Weight Disord 2016 Jun 22;21(2):269-76. Epub 2015 Sep 22.

Centre for Paediatric Dietetics and Nutrition, Department of Paediatrics and Paediatric Neuropsychiatry, Rome "Sapienza" University, Viale Regina Elena 324, Rome, Italy.

Purpose: The aim of this study was to investigate the possible correlation between epicardial adipose tissue (EAT) thickness and predictive parameters for metabolic syndrome (MS) in overweight/obese prepubertal children.

Methods: 73 prepubertal children, average age of 8.22 years, with no endocrine or syndromic causes of obesity or under drug therapy for chronic disease were enrolled. Weight, height, body circumferences and skinfolds' thickness were measured. BMI, BMI z score (z-BMI) and waist-to-height ratio (WtHR) were calculated. Standard MS-related laboratory parameters were assessed. Finally, all children underwent echocardiographic measurement of EAT.

Results: A positive correlation between EAT and z-BMI was found only among overweight/obese children (r = 0.43, p = 0.001). In particular, data showed that 89 % of our sample had a waist (W) >90th percentile. Statistical differences in diastolic blood pressure (DBP; p < 0.01) and EAT (p = 0.02) were observed on comparing W <90th percentile vs W >90th percentile patients. Besides, in patients with W >90th percentile and family history of risk factors for MS, the value of EAT correlated positively with z-BMI, W, WtHR, triglycerides (Tg), insulin and homeostatic model assessment of insulin resistance and negatively with HDL.

Conclusions: The EAT and the markers of MS probably share the same pathogenetic factors. Further studies might elucidate whether EAT deserves to be included among the diagnostic factors of MS.
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http://dx.doi.org/10.1007/s40519-015-0221-0DOI Listing
June 2016

Severe growth hormone deficiency and empty sella in obesity: a cross-sectional study.

Endocrine 2015 Jun 23;49(2):503-11. Epub 2015 Jan 23.

Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, University of Rome "La Sapienza", Policlinico Umberto I, 00161, Rome, Italy.

Obesity is associated with blunted growth hormone (GH) secretion. In some individuals, hypothalamic-pituitary (HP) structural lesions may contribute to GH deficiency (GHD). We explored pituitary morphology in obese patients with suspected GHD and its association with cardiovascular risk factors, body composition, and cardiac morphology. One hundred and eighty-four adults obese patients with symptoms and signs of GHD (147 females and 37 males; mean age 46.31 ± 12.11 years), out of 906 consecutive white obese outpatients, were evaluated. The main measures were anthropometric data, blood pressure, lipid profile, glycemic parameters, pituitary hormones, and insulin-like growth factor-1 values, echocardiography, magnetic resonance imaging (MRI) of the HP region, body composition, and growth hormone-releasing hormone plus arginine test. Seventy patients had GHD (GH peak values <4.2 μg/mL). GHD patients showed significantly higher body mass index and fat mass, lower lumbar bone mineral density, increased left ventricular mass index, and epicardial fat thickness. The MRI of the HP region showed empty sella (ES) in 69 and normal pituitary in one of the 70 GHD patients; the 114 patients with normal GH response had ES (n = 62, 54 %), normal pituitary (n = 37, 32 %), microadenomas (n = 10, 8 %), and other pituitary abnormalities (n = 5, 4 %). ES was a significant independent predictor of GH secretory capacity as determined by multiple regression analysis. The close relationship between ES and GH secretory capacity points out to the possibility of the organic nature of GHD in a portion of obese individuals and opens a new scenario with regard to the potential of GH treatment on metabolic consequences of obesity.
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http://dx.doi.org/10.1007/s12020-015-0530-0DOI Listing
June 2015

Epicardial fat thickness and nonalcoholic fatty liver disease in obese subjects.

Obesity (Silver Spring) 2014 Feb 17;22(2):332-6. Epub 2013 Oct 17.

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

Objective: Ectopic fat accumulation within the heart and the liver are linked to an increased cardiovascular risk. Ultrasound-measured cardiac and liver steatosis are easily accessible markers of intra-organ ectopic fat accumulation. The hypothesis that echocardiographic epicardial fat thickness is independently associated with nonalcoholic fatty liver disease (NAFLD) in obese subjects is tested.

Design And Methods: Sixty-two obese (BMI > 30 kg m⁻²) subjects with ultrasonographic evidence of NAFLD and 62 control obese subjects without history or signs of NAFLD underwent echocardiographic epicardial fat thickness measurement.

Results: Epicardial fat thickness was significantly higher (P < 0.01) in obese subjects with NAFLD when compared to those without NAFLD. Epicardial fat thickness was significantly higher (9.7 ± 0.2 vs. 8 ± 0.7 mm, P < 0.01) in subjects with severe (ultrasound score 3) than those with moderate (score 2) liver steatosis. Among waist circumference and BMI, epicardial fat thickness resulted in the best independent correlate of liver steatosis (R²  = 0.77, P < 0.001).

Conclusions: Our study suggests that epicardial fat is a good predictor of liver steatosis in obese subjects. Echocardiographic epicardial fat predicts ultrasound-measured fatty liver better than BMI or waist circumferences does. Patients with severe fatty liver infiltration presented with the highest amount of cardiac fat accumulation.
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http://dx.doi.org/10.1002/oby.20624DOI Listing
February 2014

Epicardial fat thickness and left ventricular mass in subjects with adrenal incidentaloma.

Endocrine 2013 Oct 21;44(2):532-6. Epub 2013 Feb 21.

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, 1400 NW 10th Ave., Dominion Tower Suite 805-807, Miami, FL, 33136, USA,

Emerging evidences indicate that patients diagnosed with adrenal incidentaloma may present with cardiovascular complications. Epicardial fat is known to play a role in left ventricle (LV) changes. Whether epicardial fat can be associated with LV mass (LVM) in patients with incidentaloma is unknown. We test the hypothesis that echocardiographic epicardial fat thickness is independently related to LVM in a well-studied group of subjects with adrenal incidentaloma. 46 consecutive patients (age 59 ± 9 years) with imaging diagnosis of adrenal incidentaloma and 30 healthy controls underwent echocardiogram for epicardial fat thickness and LVM measurement. Non-functional incidentaloma was confirmed in 40 subjects, whereas 6 patients were actually diagnosed with mild Cushing's syndrome. Epicardial fat thickness was significantly higher in patients with incidentaloma and mild Cushing's syndrome when compared to controls, (p < 0.01 for both). LVM(h2.7) was higher in subjects with adrenal incidentaloma than in controls and higher in subjects with mild Cushing's syndrome than in those with adrenal incidentaloma (p < 0.05 and p < 0.01). Multiple regression analysis showed that epicardial fat thickness was the best correlate (R (2) = 0.36, β 2.8, p < 0.01) of LVM in overall study patients. We showed for the first time that (1) epicardial fat thickness and LVM are higher in subjects with adrenal incidentaloma and (2) epicardial fat thickness independently correlates with LVM. Echocardiographic epicardial fat may serve as non-invasive marker of visceral fat and earlier cardiac abnormalities in patients with adrenal incidentaloma.
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http://dx.doi.org/10.1007/s12020-013-9902-5DOI Listing
October 2013

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BMC Gastroenterol 2012 Nov 16;12:162. Epub 2012 Nov 16.

Liver Unit Azienda Ospedaliera San Camillo Forlanini, Circonvallazione Gianicolense, 87 00149, Rome, Italy.

Background: The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.

Methods: For 48 weeks, 388 "naïve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).

Results: The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.

Conclusion: Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.

Trial Registration: ClinicalTrials.gov Identifier: NCT01342003.
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http://dx.doi.org/10.1186/1471-230X-12-162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526494PMC
November 2012

Relationships between body fat distribution, epicardial fat and obstructive sleep apnea in obese patients with and without metabolic syndrome.

PLoS One 2012 8;7(10):e47059. Epub 2012 Oct 8.

Department of Experimental Medicine, Section of Medical Physiopathology, Endocrinology and Food Science, University of Rome "Sapienza", Italy.

Background: Obstructive sleep apnea (OSA) and metabolic syndrome, both closely related to obesity, often coexist in affected individuals; however, body mass index is not an accurate indicator of body fat and thus is not a good predictor of OSA and other comorbidities. The aim of this study was to investigate whether the occurrence of OSA could be associated with an altered body fat distribution and a more evident cardio metabolic risk independently from obesity and metabolic syndrome.

Methods And Results: 171 consecutive patients (58 men and 113 women) were included in the study and underwent overnight polysomnography. Anthropometric data, blood pressure, lipid profile, glycaemic parameters were recorded. Body composition by DXA, two-dimensional echocardiography and carotid intima/media thickness measurement were performed. 67 patients (39.2%) had no OSA and 104 (60.8%) had OSA. The percentage of patients with metabolic syndrome was significantly higher among OSA patients (65.4%) that were older, heavier and showed a bigger and fatter heart compared to the control group. Upper body fat deposition index , the ratio between upper body fat (head, arms and trunk fat in kilograms) and lower body fat (legs fat in kilograms), was significantly increased in the OSA patients and significantly related to epicardial fat thickness. In patients with metabolic syndrome, multivariate regression analyses showed that upper body fat deposition index and epicardial fat showed the best association with OSA.

Conclusion: The occurrence of OSA in obese people is more closely related to cardiac adiposity and to abnormal fat distribution rather than to the absolute amount of adipose tissue. In patients with metabolic syndrome the severity of OSA is associated with increase in left ventricular mass and carotid intima/media thickness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047059PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466221PMC
May 2013

Association of epicardial fat thickness with the severity of obstructive sleep apnea in obese patients.

Int J Cardiol 2013 Sep 20;167(5):2244-9. Epub 2012 Jun 20.

Department of Experimental Medicine, Section of Medical Physiopathology and Endocrinology, Sapienza University of Rome, Rome, Italy.

Background: The correlation between obesity and severity of obstructive sleep apnea (OSA) is controversial. Although fat excess is a predisposing factor for the development of OSA, it has not been determined whether fat distribution rather than obesity per se is associated with OSA severity. Epicardial fat thickness (EFT) is an independent index of visceral adiposity and cardiometabolic risk. We investigated the relation between fat distribution and cardiometabolic risk factors, including EFT and common carotid intima-media thickness (cIMT), with the severity of OSA in obese patients.

Methods: One hundred and fifteen obese patients (56 males, 59 females) with polysomnographic evidence of OSA (≥ 5 apnea/hypopnea events per hour) of various degrees, without significant differences in grade of obesity as defined by body mass index (BMI), were evaluated. The following parameters were measured: BMI, body composition by dual energy X-ray absorptiometry, EFT, right ventricular end-diastolic diameter (RVEDD) and cIMT by ultrasound, and parameters of metabolic syndrome (waist circumference, arterial blood pressure, fasting glucose, HDL-cholesterol and triglycerides).

Results: EFT, RVEDD, cIMT and trunk/leg fat mass ratio showed a positive correlation with OSA severity in univariate analysis (r=0.536, p<0.001; r=0.480, p<0.001; r=0.345, p<0.001; r=0.330, p<0.001, respectively). However, multiple linear regression analysis showed that EFT was the most significant independent correlate of the severity of OSA (R(2)=0.376, p=0.022).

Conclusions: The present study suggests that, in obese patients, EFT may be included among the clinical parameters associating with OSA severity. The association of EFT with OSA, both cardiovascular risk factors, is independent of obesity as defined by classical measures.
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http://dx.doi.org/10.1016/j.ijcard.2012.06.011DOI Listing
September 2013

Human immunodeficiency virus-associated malignancies: a therapeutic update.

Curr HIV Res 2012 Mar;10(2):123-32

Department of Infectious Diseases, Unit of Infectious and Tropical Diseases, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Implementation of highly active antiretroviral therapy (HAART) has deeply changed the landscape of HIV-associated malignancies. Some AIDS-defining tumors, namely Primitive Lymphoma of Central Nervous System, have drastically declined, whereas a steady increase has been observed for non-AIDS-defining tumors, maybe due to longer survival of HIV-infected people. Easier immune restoration, subsequent to availability of a number of drugs targeting HIV at different points, has decreased opportunistic infections which hampered treatment of HIV-associated cancers. As a matter of fact these patients have been assimilated more and more with their negative counterpart, undergoing the same aggressive approach. Consistently, procedures that have been so far precluded to HIV+ subjects, such as transplant of hemopoietic stem cells, either autologous or allogenic, and liver transplant are expected to be performed more and more extensively in this population. Which also would mean a full removal of the stigma which has weighed on it. Hence, it is true-like that malignancies and related problems may in the next future make up a main concern for the HIV specialist. Old and new challenges might be the drug-drug interaction of antiretrovirals or biotherapy-related infections or the debated question of an earlier HAART implementation in the course of HIV disease, with CD4+ cells > 500/μl. In fact, if assimilation of HIV patients with cancer and the general population is a remarkable achieved goal, uniqueness of HIV infection in terms of immune status still makes HIV-associated cancer a unique chapter in the setting of Oncology.
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http://dx.doi.org/10.2174/157016212799937227DOI Listing
March 2012

Human immunodeficiency virus & cardiovascular risk.

Indian J Med Res 2011 Dec;134(6):898-903

Department of Medical Pathophysiology, University La Sapienza, Rome, Italy.

Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines.
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http://dx.doi.org/10.4103/0971-5916.92634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284097PMC
December 2011

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma.

World J Hepatol 2011 Nov;3(11):278-84

Adriano M Pellicelli, Cecilia D'Ambrosio, Roberto Villani, Arnaldo Andreoli, Liver Unit, Azienda Ospedaliera San Camillo Forlanini, Circonvallazione Gianicolense 87, 00149 Rome, Italy.

Aim: To evaluate if indolent B cell-non Hodgkin's lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.

Methods: A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared.

Results: Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%).

Conclusion: HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.
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http://dx.doi.org/10.4254/wjh.v3.i11.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225032PMC
November 2011

Gender differences in the clinical presentation of heart disease.

Curr Pharm Des 2011 ;17(11):1056-8

Brompton Hospital, Imerial College of Science & Technology, London, UK.

The clinical presentation of heart disease is different between men and women and this distinction is pivotal for a correct diagnosis and an adequate treatment. However, the definition of symptoms classically associated with heart disease is mainly based on the characteristics of those reported in men. Chest pain or chest discomfort in women are therefore often regarded as "atypical" and these symptoms tend to be misdiagnosed and under-treated. Further, women are less likely to receive appropriate invasive and non invasive investigations. They are less likely to refer for medical help and tend to present late in the process of the cardiovascular disease, with delays in the start of effective treatment. Therefore, a gender-specific assessment of cardiovascular risk is strongly advised for patients presenting with symptoms suggestive of heart disease.
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http://dx.doi.org/10.2174/138161211795656927DOI Listing
August 2011

Heart and HAART: Two sides of the coin for HIV-associated cardiology issues.

Authors:
Giuseppe Barbaro

World J Cardiol 2010 Mar;2(3):53-7

Giuseppe Barbaro, Cardiology Unit, Department of Medical Pathophysiology, Policlinico Umberto I°, University "La Sapienza", 00174 Rome, Italy.

The introduction of highly active antiretroviral therapy (HAART) has generated a contrast in the cardiac manifestations of acquired immunodeficiency syndrome. In developed countries, we have observed an approximately 30% reduction in the prevalence of human immunodeficiency virus (HIV)-associated cardiomyopathy, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availablity of HAART is limited and the pathogenic impact of nutritional factors is significant, we have observed an approximately 32% increase in the prevalence of HIV-associated cardiomyopathy and a related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, have been shown to cause, in a high proportion of HIV-infected patients, an iatrogenic metabolic syndrome (HIV-lipodystrophy syndrome) that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis, even in young HIV-infected people. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving, HAART regimens, particularly for those with known underlying cardiovascular risk factors. A close collaboration between cardiologists and infectious disease specialists is needed for decisions regarding the use of antiretrovirals, for a careful stratification of cardiovascular risk factors, and for cardiovascular monitoring of HIV-infected patients receiving HAART, according the most recent clinical guidelines.
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http://dx.doi.org/10.4330/wjc.v2.i3.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999028PMC
March 2010

Patent foramen ovale and thromboembolic complications.

Curr Pharm Des 2010 ;16(31):3497-502

Cardiology Unit, Department of Medical Pathophysiology, University La Sapienza, Rome, Italy.

The foramen ovale, an atrial septal defect which is essential in the fetal circulation, remains patent through adulthood in approximately 25% of the general population and so it represents the most common persistent abnormality of fetal origin. Patent foramen ovale (PFO) allows interatrial right-to-left blood shunting during those periods of the cardiac cycle in which the right atrial pressure exceeds the left one. An increasing number of pathological manifestations of PFO has been recently identified; among these, paradoxical systemic embolism, refractory hypoxemia in patients with right ventricular myocardium infarction or severe pulmonary disease, orthostatic oxygen desaturation in the rare platypnea-orthodeoxia syndrome, neurological decompression illness in divers, high altitude pilots and astronauts, and finally, migraine headache with aura. Nowadays many techniques allow to detect a PFO. In this study we investigated each of them, assessing their potential diagnostic role even in comparison with the main features of the other methods.
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http://dx.doi.org/10.2174/138161210793563310DOI Listing
April 2011

Protrhombotic effects of contraceptives.

Curr Pharm Des 2010 ;16(31):3490-6

Cardiology Unit, Department of Medical Pathophysiology, University La Sapienza, Rome, Italy.

The use of oral contraceptives first became widespread some 40 years ago, and reports of an excess risk of cardiovascular disease among women who used these agents soon followed. Few drugs have been the object of such intensive epidemiological research, the outcome of which has provided clinicians with detailed information about risks not only of specific thrombotic diseases but also important non-contraceptive benefits from the pill. Recently, oral contraceptives have been classified by some according to "generation" (first, second, third, and most recently, fourth generation): first-generation formulations containing lynestrenol or norethindrone, second-generation formulations containing levonorgestrel, third-generation formulations containing desogestrel or gestodene, and oral contraceptives containing an estrogen and other progestagens (cyproterone or norgestimate) or a progestagen alone. The results of several study was that the use of the older high-dose oral contraceptives increased the risk of cardiovascular disease by modifying the Low-density lipoprotein and High-Density lipoprotein cholesterol level, increasing triglyceride serum level, reducing glucose tolerance, raising blood pressure, and promoting clotting mechanisms. In this review we investigate the mechanism of the oral contraceptives and performed a risk assessment of every generation.
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http://dx.doi.org/10.2174/138161210793563374DOI Listing
April 2011

Diagnosis and prognosis of fetal cardiomyopathies: a review.

Curr Pharm Des 2010 ;16(26):2929-34

Division of Cardiology, Casa del Sole Hospital, Palermo.

Cardiomyopathies (CM) are a very rare disease in fetuses with a very poor outcome. Only isolated case reports and small case series were reported. According with published studies we will describe the fetal CM starting from their echocardiographic presentation: dilated cardiomyopathy (DCM) with dilatation of either or both ventricles and impaired ventricular function, and hypertrophic cardiomyopathy (HCM) with different degree of disproportionate hypertrophy of the myocardial walls. The term of the "noncompaction" of the left ventricular myocardium, is used in cases with DCM with evidence of numerous prominent trabeculations with deep myocardial recesses. In series of neonates and infant the CM occur in about 2-7%, but probably during the fetal life the prevalence is higher: 6% - 11%. The high intrauterine loss, occurring in one third of affected fetuses, likely accounts for these differences. Fetal echocardiography, B and M-mode, is the main diagnostic tool and it is useful for the therapeutic orientation and to determine the neonatal outcome. A haemodynamic evaluation can be performed by Doppler mode. Systolic and diastolic fetal cardiac function have become part of the routine evaluation of the fetal heart. Cardiomyopathies can be isolated or associated with other cardiac and non cardiac malformations. All the studies confirm a great variability of DCM in the fetal age as for the anatomical and functional forms, etiology and hemodynamic impact with different final outcome. Genetic, metabolic, infective, and cardiac diseases may present with DCM. Ventricular dysfunction may be progressive in utero and after birth, but possibility of improvement or even normalization of the left ventricular dysfunction is known in all forms of DCM, "idiopathic", post infective or in noncompaction of left ventricle. The outcome is worse in presence of fetal hydrops, significant atrioventricular valve regurgitation, for the earlier age at presentation and when diastolic dysfunction is associated with systolic dysfunction. Etiologically primary fetal HCM is a heterogeneous condition that can be the result of intrinsic fetal pathology as well as of extrinsic factors. It can be concentric or asymmetric. Prognosis of infants with HCM associated with maternal diabetes is good while a bad prognosis has been reported in fetuses without diabetic mother. HCM may be evolutive, mainly after birth; otherwise there are also cases that improve or regress completely. Unfortunately, a poor outcome is observed in most, particularly in DCM, with only a few therapeutic options available. Detailed evaluation of fetal and maternal condition provide prognostic information for prenatal counselling and may lead to improved outcome of at least some affected pregnancies.
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http://dx.doi.org/10.2174/138161210793176428DOI Listing
August 2011

Plasma cytokines and portopulmonary hypertension in patients with cirrhosis waiting for orthotopic liver transplantation.

Angiology 2010 Nov 24;61(8):802-6. Epub 2010 May 24.

Liver Unit, Azienda Ospedaliera San Camillo, Forlanini, Rome, Italy.

Portopulmonary hypertension (PPHTN) is a rare complication in patients with portal hypertension. A role of endothelin 1 (ET-1) and other cytokines was demonstrated in primary pulmonary hypertension but not in PPHTN. We evaluated the possible role of ET-1, interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α) in the pathogenesis of PPHTN. Plasmatic concentrations of ET-1, IL-6, IL-1β, and TNF-α were measured in patients with pulmonary systolic arterial pressure (PAPs) >30 mm Hg and in patients with cirrhosis. In all, Six out of 11 patients with PAPs >30 mm Hg had PPHTN on right heart catheterization. The remaining 10 patients had an hyperdynamic circulation (HC). In PPHTN patients, ET-1 and IL-6 were significantly higher compared with HC and patients with cirrhosis. Endothelin 1 and IL-6 could be implicated in the pathogenesis of PPHTN. On the basis of these results, ET-1 receptor antagonists or anti-IL-6 could have a rationale in the treatment of PPHTN.
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http://dx.doi.org/10.1177/0003319710369101DOI Listing
November 2010

Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial.

BMC Gastroenterol 2010 Feb 19;10:21. Epub 2010 Feb 19.

Liver Unit San Camillo Forlanini Hospital, Rome, Italy.

Background: In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment.

Methods: Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment.

Results: At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse.

Conclusion: In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR.

Trial Registration: Trial number ISRCTN29259563.
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http://dx.doi.org/10.1186/1471-230X-10-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837223PMC
February 2010

Tako-tsubo cardiomyopathy and microcirculation.

J Clin Monit Comput 2010 Apr 8;24(2):101-5. Epub 2010 Jan 8.

Department of Cardiology, University of Palermo, Palermo, Italy.

Background: Takotsubo cardiomyopathy was described for the first time in Japan in the 1990s. It is very similar to the ischemic cardiopathy both for clinical and instrumental characteristics. His peculiarity is an alteration of the ventricular contraction mechanism with hypo-akinesis of the apex and lateral segments of the left ventricle, associated with hyper-kinesis of the heart base which is responsible for the typical echocardiographic aspect of a cruet during the systole. However, the etiology of this cardiomyopathy is still unknown despite the fact that numerous hypothesis have been made. A single study of 16 patients proved multivasal damage by a BLASH SCORE analysis of the coronary radiography. In our study, performed on 24 patients, we intended to assess the actual implication of the microcirculation by analyzing the TIMI frame count (TFC), so as reporting correlations between alterations of each single artery and its respective myocardial area.

Methods And Results: Six Cardiology Centres performed an International multi-centre collection of a consecutive series of 24 patients, of which 20 were women and four men. The average age was 67.4 years. All patients admitted to one of the Cardiology divisions were previously listed for symptoms and signs of Takotsubo cardiomyopathy. An electrocardiographic (ECG), echocardio-gram and a hemodynamic study were carried out on each patient. The patients were evaluated with a follow up lasting 7 weeks. On the coronary radiography film, the microcirculation was examined by an analysis of the TFC according to the Gibson technique. The value obtained was considered pathological if it was >30 frames. The evaluation of the microcirculation by the TFC analysis showed that in 23 of the 24 patients there was a pathological slow down of the flow in the coronary micro- circulation. By analysing the number of involved vessels it was noted that nine patients had a slowdown of the general flow in all three vessels, six patients in only two vessels and the remaining nine in one vessel. In particular: in 14 patients there was an abnormal TFC in left anterior descending coronary artery (LAD), 16 in the right coronary artery (RCA) and 18 in the left circumflex coronary artery (LCX), while in one patient the picture quality in the acute phase did not allow an evaluation of the score in the RCA and in another patient in the LDA. None of the explored vessels that was responsible for the disorder of the microcirculation showed any stenosis.

Conclusion: From the data evaluated by us, microcirculatory dysfunction seems to be present very often during acute phases of Takotsubo illness, but it is not the only determining factor of the illness.
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http://dx.doi.org/10.1007/s10877-009-9217-5DOI Listing
April 2010

Cardiovascular complications in the acquired immunodeficiency syndrome.

Rev Assoc Med Bras (1992) 2009 Sep-Oct;55(5):621-30

Departamento de Fisiopatologia Médica, Policlínica Umberto Primo, Universidade La Sapienza, Roma, Itália.

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease, with increased survival rates. However, the introduction of HAART has generated a contrast in the cardiac manifestations of AIDS. In developed countries, we observed an approximate 30% reduction in the prevalence of HIV-associated cardiomyopathy, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited and the pathogenic impact of nutritional factors is significant, we observed an increase of approximately 32% in the prevalence of HIV-associated cardiomyopathy and a related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, have been shown to cause, in a high proportion of HIV-infected patients, a iatrogenic metabolic syndrome (HIV-lipodystrophy syndrome).This is associated with an increased risk of atherosclerosis-related cardiovascular events even in young HIV-infected people. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce cardiovascular risk in HIV-infected patients receiving HAART.
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http://dx.doi.org/10.1590/s0104-42302009000500031DOI Listing
September 2010

New options in the treatment of lipid disorders in HIV-infected patients.

Open AIDS J 2009 Jul 16;3:31-7. Epub 2009 Jul 16.

Federal University of São Paulo, R Loefgren, 1588, Zip Code 04040 002, São Paulo, Brazil.

Since the introduction of HAART, there was a remarkably change in the natural history of HIV disease, leading to a notable extension of life expectancy, although prolonged metabolic imbalances could significantly act on the longterm prognosis and outcome of HIV-infected persons, and there is an increasing concern about the cardiovascular risk in this population. Current recommendations suggest that HIV-infected perons undergo evaluation and treatment on the basis of the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines for dyslipidemia, with particular attention to potential drug interactions with antiretroviral agents and maintenance of virologic control of HIV infection. While a hypolipidemic diet and physical activity may certainly improve dyslipidemia, pharmacological treatment becomes indispensable when serum lipid are excessively high for a long time or the patient has a high cardiovascular risk, since the suspension or change of an effective antiretroviral therapy is not recommended. Moreover, the choice of a hypolipidemic drug is often a reason of concern, since expected drug-drug interactions (especially with antiretroviral agents), toxicity, intolerance, effects on concurrent HIV-related disease and decrease patient adherence to multiple pharmacological regimens must be carefully evaluated. Often the lipid goals of patients in this group are not achieved by the therapy recommended in the current lipid guidelines and in this article we describe other possibilities to treat lipid disorders in HIV-infected persons, like rosuvastatin, ezetimibe and fish oil.
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http://dx.doi.org/10.2174/1874613600903010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714525PMC
July 2009

Ongoing change in the treatment of HIV-associated malignancies in the HAART era.

Expert Rev Clin Pharmacol 2009 May;2(3):283-93

Department of Infectious and Tropical Diseases Foundation IRCCS San Matteo, University of Pavia, Pizzale Golgi 2, 27100 Pavia, Italy.

Implementation of highly active antiretroviral therapy (HAART) has changed the epidemiology, clinical outcome and therapeutic approach of HIV-associated malignancies. Whereas Kaposi sarcoma and primary CNS non-Hodgkin lymphoma have decreased dramatically, systemic non-Hodgkin lymphoma incidence seems unchanged, perhaps increasing as with other tumor incidence. Owing to HAART-induced immune function preservation, response rates to chemotherapy and survival times in patients with HIV-associated malignancies have neared those observed in their HIV-negative counterparts. Hence, intensive regimens have been more and more extensively used with promising results. This may also apply to other therapeutic options, such as biotherapy, and procedures, such as stem cell rescue following high-dose chemotherapy or heterologous stem cell transplant, which have so far been precluded to HIV-infected subjects as a matter of fact. A trend toward a full assimilation of HIV-infected people with cancer and the general population with the same pathology is ongoing.
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http://dx.doi.org/10.1586/ecp.09.1DOI Listing
May 2009

Metabolic syndrome associated with HIV and highly active antiretroviral therapy.

Curr Diab Rep 2009 Feb;9(1):37-42

Cardiology Unit, Department of Medical Pathophysiology, University La Sapienza, Viale Anicio Gallo 63, 00174 Rome, Italy.

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease with increased survival rates. However, some HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients metabolic (dyslipidemia, insulin resistance) and somatic (lipodystrophy/lipoatrophy) changes that are associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). The pathogenesis of HAART-associated metabolic syndrome and of its atherogenic profile is complex, and several factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, activation of proinflammatory cytokines, and mitochondrial dysfunction. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients facing long-term HAART.
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http://dx.doi.org/10.1007/s11892-009-0008-7DOI Listing
February 2009

Takotsubo cardiomyopathy: a new form of acute, reversible heart failure.

Circulation 2008 Dec;118(25):2754-62

Division of Cardiology, Department of Internal Medicine, St Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki City, Kanagawa Prefecture, 216-8511, Japan.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.108.767012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893309PMC
December 2008
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