Neglected features of lifestyle: Their relevance in non-alcoholic fatty liver disease.

AIM: To investigated in non-alcoholic-fatty-liver-disease (NAFLD), with ultrasound (US)-detected fatty liver, and in a group of non-alcoholic and otherwise healthy subjects, relationship of neglected features of lifestyle with NAFLD and obesity. METHODS: Five hundred and thirty-two NAFLD and 667 non-NAFLD healthy subjects, age 21-60 years were studied. Severity of liver steatosis was assessed by US bright liver score. The adherence to mediterranean diet score (AMDS) was assessed on the basis of a 1-wk recall computerized questionnaire which included a detailed physical activity reports (Baecke questionnaire). The western dietary profile score, as a simplified paradigm of unhealthy diet, a questionnaire quantifying sun exposure score and a sleep habits questionnaires provided a further comprehensive lifestyle assessment. RESULTS: Body mass index (BMI), insulin resistance (HOMA), and triglycerides, poorer adherence to a mediterranean diet profile, sedentary habits, minor sun exposure and use of "western diet" foods are greater in NAFLD. Multiple linear regression analysis, weighted by years of age, displays BMI, HOMA and AMDS as the most powerful independent predictors of fatty liver severity; however, also the physical activity score, the western diet habit and the sun exposure score are acting inside the model with significant independent effects. CONCLUSION: Articulated clinical intervention, according to our results, are justified in NAFLD and can be pursued addressing by focused intervention nutritional profile, physical exercise mainly in open-air subsets for enhancing sun exposure and healthier sleep duration and rhythm.

Echocardiography and NAFLD (non-alcoholic fatty liver disease).

UNLABELLED: Non-alcoholic-fatty-liver-disease (NAFLD) is associated with atherosclerosis, increased cardiovascular risks and mortality. We investigated if, independently of insulin resistance, diet, physical activity and obesity, fatty liver involvement has any relationship with echocardiographic measurements in NAFLD. PATIENTS AND METHODS: 660 NAFLD and 791 non-NAFLD subjects, referred to the same out-patients medical unit for lifestyle-nutritional prescription, were studied. Congestive heart failure, myocardial infarction, malignancies, diabetes mellitus, extreme obesity, underweight-bad-nourished subjects and renal insufficiency were exclusion criteria. Liver steatosis was assessed by Ultrasound-Bright-Liver-Score (BLS), left ventricular ejection fraction (LVEF), trans-mitral E/A doppler ratio (diastolic relaxation) and left ventricular myocardial mass (LVMM/m(2)) by echocardiography. Doppler Renal artery Resistive Index (RRI), insulin resistance (HOMA) and lifestyle profile were also included in the clinical assessment. RESULTS: LVMM/m(2) is significantly greater in NAFLD, 101.62±34.48 vs. 88.22±25.61, p<0.0001 both in men and in women. Ejection fraction is slightly smaller only in men with NAFLD; no significant difference was observed for the E/A ratio. BMI (30.42±5.49 vs. 24.87±3.81; p<0.0001) and HOMA (2.90±1.70 vs. 1.85±1.25; p: 0.0001) were significantly greater in NAFLD patients. By Multiple-Linear-Regression, NAFLD and unhealthy dietary profile are associated also in lean non-diabetic subjects with lower systolic function, independently of BMI, dietary profile, physical activity, RRI and insulin resistance. CONCLUSION: NAFLD may be a meaningful early clue suggestive of diminishing heart function, with similar determining factors. NAFLD is amenable to management and improvement by lifestyle change counseling, addressing a dual target: reducing fatty liver, which is easily monitored by ultrasound, and, independently, maintaining a normal heart function.

Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion.

BACKGROUND & AIMS: Fatty liver is associated with alcohol habits and/or overweight/obesity. We challenged several lifestyle features associated with fatty liver and, particularly, with non-alcoholic fatty liver disease (NAFLD). Among them, sleep shortage as a result of nightlife habits and a preference for plus-size fashion were assessed. The latter consists of fashionable plus-sized clothing for actual individuals' size and reflects a frequent attitude of some social or age groups, conceivably indicating more global and widespread trend and behaviour. METHODS: We studied a group of 708 non-diabetic youngsters, 458 women and 250 men, 21.72 ± 3.71 years old (range 15-35 years), referred for minor digestive ailments for clinical assessment, ultrasound detection of fatty liver and nutritional counselling. Details of personal history regarding lifestyle, food intake frequency and alcohol intake, dietary and physical exercise profile, sleep duration and clothing preferences were recorded. RESULTS: The prevalence of NAFLD in this cohort of youngsters is 67/708 (9.4%). Even if it is quantitatively very low in both groups, the average alcohol intake, always below 20 g/day, is greater in NAFLD subjects (5.83 ± 4.32 g) vs. subjects with normal liver (2.02 ± 3.20 g). The number of meals/day and adherence to a Mediterranean diet profile are smaller in NAFLD subjects. By multiple regression, BMI, sedentary life, plus-sized clothing for their actual size, sleep shortage and lower frequency of daily food intake are associated with the presence of NAFLD. CONCLUSIONS: Onset and continuation of fatty liver disease, beyond food and exercise quantity and quality, with their effects on obesity, may also be associated with other aspects of lifestyle.

Liver and spleen transient elastography and Acoustic Radiation Force Impulse Measurements. Performance and comparison of measurements in the same area concurrently assessed for liver fibrosis by biopsy.

PURPOSE: The estimation of the degree of liver fibrosis is important for prognosis, surveillance, and treatment of chronic liver disease. Although liver biopsy is the gold standard for diagnosis, it is subject to sampling error, while ultrasound-based techniques, such as Acoustic Radiation Force Impulse (ARFI) and transient elastography, have gained popularity. However, no previous comparative study has performed these ultrasound techniques at the time of biopsy. The aim of this study was to compare the reliability of these techniques to define the severity of liver fibrosis in viral hepatitis patients. PATIENTS AND METHODS: We compared liver transient elastography and Acoustic Radiation Force Impulse measurements, performed along the intended biopsy track, with liver biopsy results in 46 viral hepatitis patients, all measured on the same morning. Fibrosis was measured by histology using the Ishak fibrosis staging. RESULTS: The relative sensitivity and specificity of different incremental cut-off values for both techniques, and the predictive ability of pairwise comparison of the 3 tests (including APRI) and of their combined use with more severe grades of histology-measured liver fibrosis, show that the single variable with greatest sensitivity and specificity is TE with a cut-off of >10.0. CONCLUSION: Transient elastography has a better performance than ARFI, which has a lower sensitivity, in the diagnosis of severe stages of fibrosis. Also ARFI of the spleen is correlated with Ishak fibrosis staging, and could be a possible additional tool for the diagnosis of liver fibrosis.

Lung transthoracic ultrasound elastography imaging and guided biopsies of subpleural cancer: a preliminary report.

BACKGROUND: Despite the usefulness of elastography in assessing the stiffness/elasticity of tissues, and its proven diagnostic accuracy in thyroid, breast, and prostate cancers, among others, it is not yet applied in transthoracic ultrasound (TUS) scans to investigate lung nodules. PURPOSE: To investigate the potential clinical utility of TUS elastography in diagnosing lung cancer proven by fine-needle aspiration biopsy (FNAB). MATERIAL AND METHODS: TUS elastography was performed in 95 consecutive patients (71 men, 24 women; age, 62.84 ± 7.37 years) with lesions suspected of involving the chest wall or the pleura detected on chest X-ray or computed tomography (CT). Patients with pleural effusions were not enrolled, but were further evaluated by pleural fluid cytology. Patients were excluded from the study if a diagnosis had already been made based on sputum cytology and/or bronchoscopic histology (making TUS biopsy unnecessary) or if their lung lesions could not be visualized under standard US. Under FNAB, 34 consolidations were ascribed to pneumonia and 65 to cancer. Under TUS, tissue stiffness, detected using a convex multifrequency 2-8-mHz probe and a MyLab™Twice - ElaXto, was scored from 1 (greatest elasticity) to 5 (no elasticity). Subpleural solid masses (2-5 cm) were initially detected by TUS and subsequently assessed by FNAB. RESULTS: Histological diagnoses were: small cell lung cancer (4/61), adenocarcinoma (29/61), squamous cell carcinoma (SCC) (12/61), large cell lung carcinoma (12/61), and lymphomas (4/61). Patients' age and mass sizes (3.06 ± 0.88 cm) were not significantly associated with any histological type. A significant lower elasticity of SCC (4.67 ± 0.492) was observed versus other types of lung cancer (P < 0.005), and versus pneumonia (2.35 ± 0.48). CONCLUSION: Since only squamous cell lung carcinoma displays the feature of significantly reduced elasticity, and since no clear-cut diagnostic key is yet available, the clinical usefulness of TUS elastography is currently limited with a view to characterizing tumors. Nevertheless, it does enable good non-invasive imaging of lung nodules, providing information on their stiffness, and can improve the accuracy and yield of FNAB.

Dipyridamole decreases inflammatory metalloproteinase-9 expression and release by human monocytes.

Matrix metalloproteinase (MMP)-9 plays an important role in stroke by accelerating matrix degradation, disrupting the blood-brain barrier and increasing infarct size. Dipyridamole is an antiplatelet agent with recognised benefits in ischaemic stroke prevention. In addition to its antiplatelet properties, recent studies have reported that dipyridamole also features anti-inflammatory and anti-oxidant properties. We therefore investigated whether dipyridamole can ameliorate the proinflammatory profile of human monocytes, a source of MMP-9 in stroke, in terms of regulation of MMP-9 activity and expression, and explored underlying mechanisms. Human peripheral blood mononuclear cells (PBMC) and U937 cells were treated with increasing concentrations of dipyridamole (up to 10 µg/ml) for 60 minutes before stimulation with tumour necrosis factor (TNF)-α or phorbol myristate acetate (PMA). Exposure of PBMC and U937 to dipyridamole reduced TNF-α- and PMA-induced MMP-9 activity and protein release as well as MMP-9 mRNA, without significantly affecting the release of TIMP-1. This inhibitory effect was independent of dipyridamole-induced cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) increase. Correspondingly, dipyridamole also significantly inhibited TNF-α-induced nuclear factor (NF)-κB activation and nuclear translocation of the p65 NF-κB subunit through a mechanism involving the inhibition of IkBα degradation and p38 MAPK activation. In conclusion, dipyridamole, at therapeutically achievable concentrations, reduces the expression and release of MMP-9 through a mechanism involving p38 MAPK and NF-κB inhibition. These results indicate that dipyridamole exerts anti-inflammatory properties in human monocytes that may favourably contribute to its actions in the secondary prevention of stroke, independent of its antiplatelet properties.

Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer.

Diets with high content of antioxidant polyphenols are associated with low prevalence of cardiovascular diseases and cancer. Inflammatory angiogenesis is a key pathogenic process both in cancer and atherosclerosis, and is tightly regulated by the proinflammatory enzyme cyclooxygenase (COX)-2 and the matrix degrading enzymes matrix metalloproteinases (MMPs). We studied the effects of antioxidant polyphenols from virgin olive oil (oleuropein and hydroxytyrosol) and red wine (resveratrol and quercetin) on endothelial cell angiogenic response in vitro, and explored underlying mechanisms. Cultured endothelial cells were pre-incubated with 0.1-50 µmol/L polyphenols before stimulation with phorbol myristate acetate (PMA). All tested polyphenols reduced endothelial cell tube formation on matrigel and migration in wound healing assays. The reduced angiogenesis was associated with the inhibition of PMA-induced COX-2 protein expression and prostanoid production, as well as MMP-9 protein release and gelatinolytic activity. These effects were accompanied by a significant reduction in the stimulated intracellular reactive oxygen species levels and in the activation of the redox-sensitive transcription factor nuclear factor (NF)-κB. Our findings reveal that olive oil and red wine polyphenols reduce inflammatory angiogenesis in cultured endothelial cells, through MMP-9 and COX-2 inhibition, supporting a potential protective role for dietary polyphenols in atherosclerotic vascular disease and cancer.

Obesity-independent association of human adenovirus Ad37 seropositivity with nonalcoholic fatty liver disease.

OBJECTIVE: Adenoviruses Ad36 and Ad37 increase adiposity in animals and are associated with obesity in humans; effects on the liver have been reported. The association of Adenovirus Ad36 seropositivity (Ad36+) with obesity but not with the severity of nonalcoholic fatty liver disease (NAFLD) has been previously shown. We investigate whether nondiabetic Ad37+ patients show a different prevalence of NAFLD and ultrasound Bright Liver score. PATIENTS: A total of 268 adult nondiabetic patients (146 men, 122 women) were included after lifestyle counseling including a personalized Mediterranean diet, increase in physical activity, and smoking withdrawal. After an Ad37+/Ad36+ assay, overweight obesity, insulin resistance, C-reactive protein, and bright liver prevalence and severity were compared according to Ad37+. RESULTS: Sixty-five of 268 patients were Ad37+ and 82/268 patients were both Ad37 seronegative (Ad37-) and Ad36-. The prevalence of obesity, defined as body mass index≥30, was not significantly different in Ad37+ (11/65; 16.9%) vs. Ad37- (15/82; 18.2%) patients; Bright Liver was present in 22/65 (33.8%) Ad37+ patients vs. 13/82 (15.8%) Ad37- patients (P<0.019). By odds ratio (OR), a consistent risk for NAFLD was associated with Ad37+, greater insulin resistance, and C-reactive protein. By a predictive multiple linear regression model, 40.0% of variance toward NAFLD and 50.4% toward the severity of Bright Liver score was explained significantly and independently by Ad37+ and by body mass index. CONCLUSIONS: Ad37+ status in nondiabetic patients on an appropriate diet is significantly associated with NAFLD; because fatty liver improves even without weight loss by a "healthy" diet, and not only by lower food caloric intake, Ad37+ may be an adjunctive hallmark of an unfavorable clinical-metabolic profile, if not a causative factor of NAFLD.

Renal resistive index and parathyroid hormone relationship with renal function in nondiabetic patients.

INTRODUCTION: The renal resistive index (RRI) reflects intrarenal vascular resistance and stiffness, which are associated with chronic kidney disease. The links connecting renal function, intrarenal arterial resistance, and parathyroid hormone (PTH) with hypertension and metabolic factors remain elusive. The aim of this study is to investigate the possible relationship of RRI with glomerular filtration rate, PTH, hypertension, obesity (body mass index and waist-to-hip ratio), bioelectrical impedance analysis in body composition assessment, serum lipids, and insulin resistance assessed by homoeostasis model insulin resistance index. PATIENTS AND METHODS: This study was carried out on 387 (246 women, 141 men) nondiabetic patients, between >25 and <75 years, referred to an Internal Medicine Clinic and Day Hospital for essential hypertension, overweightness-obesity, and/or dyslipidemia. Lower salt/lower calorie Mediterranean diet, physical activity increase, smoking withdrawal, and lifestyle counseling, provided by a health psychologist support, were prescribed. RESULTS: Higher hypertension risk, present in 42.5% of the overall group of eligible patients (164/387), is associated with high PTH and high RRI, along with greater renal insufficiency, insulin resistance, and obesity. There is a straight linear relationship of RRI to PTH (0.202; p=0.009) in arterial hypertension, which is not observed in normal blood pressure patients. By gender-adjusted multiple linear regression analysis, it was found that fat mass, waist-to-hip ratio, and PTH account significantly for 62.3% of the variance to RRI in hypertensive patients. CONCLUSION: Increased arterial stiffness and intrarenal arterial resistance are associated with higher PTH in arterial hypertension; obesity (defined by greater fat mass and waist-to-hip ratio) and PTH are the independent conditions that account significantly for higher RRI.

Adenovirus-36 seropositivity enhances effects of nutritional intervention on obesity, bright liver, and insulin resistance.

BACKGROUND: Obesity and liver steatosis are both currently attributed to inappropriate lifestyle and nutrition. Higher prevalence of human adenovirus Ad36 seropositivity (Ad36+) is reported only in obesity. AIMS: To investigate whether a lifestyle-nutritional intervention achieves different outcomes in NAFLD patients, i.e., if is blunted or enhanced according to Ad36 seropositivity status. METHODS: One-year nutritional intervention was planned and accomplished for 62 non-alcoholic fatty liver disease overweight-obese patients, studied by liver ultrasound, evaluating Bright Liver Score (BLS), by Homeostatic Model assessment of Insulin Resistance (HOMA), by body composition and Ad36+ assay. Lower salt/lower calories Mediterranean diet, physical activity increase, smoking withdrawal and lifestyle counseling, provided by a health psychologist, were given. RESULTS: Ad36 seropositive patients have baseline greater BMI with the same level of BLS. Different prevalence of post-interventional response, significantly greater among Ad36+ patients, is observed: greater decrease of obesity, assessed by BMI, greater reduction of insulin resistance, assessed by HOMA and higher prevalence of bright liver disappearance. A BMI-adjusted multiple linear regression model explains significantly 23.8% (p < 0.04) of the variance; significant predictive variables are Ad36 seropositivity (p < 0.012) and fat mass loss (p < 0.011) accounting for the variance of the occurrence of bright liver disappearance. CONCLUSIONS: Ad36 previous infection is significantly associated with enhanced weight loss, bright liver disappearance, and recovery of insulin sensitivity through the chosen tailored nutritional interventional treatment. Nonetheless, Ad36 seronegative NAFLD patients' fatty liver pattern improves, at a lower extent, also without significant weight loss: an effect of dietary changes profile, Mediterranean diet, not only of lowered food caloric intake, is conceivably operating.

Renal function and severity of bright liver. Relationship with insulin resistance, intrarenal resistive index, and glomerular filtration rate.

AIMS: Relationships of renal function and liver disease are described in acute and chronic liver failure. The aim of the study is to investigate which relationship, if any, is present between severity of non-alcoholic fatty liver disease (NAFLD), assessed by bright liver score (BLS) versus mild-moderate renal insufficiency assessed by glomerular filtration rate (GFR) and by ultrasound intra-renal arterial resistive index (RRI). Moreover, which difference, if any, can be found in NAFLD patients with normal versus increased transaminases. PATIENTS: The study enrolled 323 NAFLD and 176 non-NAFLD consecutive patients, comparable for age, gender distribution, GFR, and RRI referred to a university clinical day hospital after an ultrasound diagnosis of bright liver, for clinical-nutritional counselling. Personalized computerized mediterranean diet, physical activity increase, and smoking withdrawal integrated counselling were provided. RESULTS: In NAFLD patients, homoeostasis model (HOMA) has a significant correlation with BLS. According to the severity of BLS, grade II-III versus grade I patients have significantly higher values of HOMA, body mass index (BMI), triglycerides, and longitudinal right liver length. By odds ratio, more severe BLS, increased HOMA, and transaminases are associated with lower GFR. Increased transaminases are associated with higher grades of BLS, HOMA, and BMI. By multiple linear regression waist-to-hip ratio, RRI, and BLS, as significant independent factors (p < 0.0001), explain significantly variance to GFR. This is not observed in normal control group, in which only RRI is a factor explaining GFR. CONCLUSION: Greater RRI, abdominal obesity, and greater BLS account for a lower GFR in NAFLD patients suggesting the hypothesis that inter-related factors can be operating early in the natural history of obesity-related kidney and liver disease.

Coffee, nutritional status, and renal artery resistive index.

BACKGROUND: The relationship between nutrition and atherosclerosis is known, even dissociated from protein malnutrition. Cardiovascular impact of several nutrients is known; among them the action of coffee is still debated and cardiovascular effect of caffeine has been investigated without definite results. OBJECTIVE: The aim of this study is to investigate whether coffee habits, and/or quantity of coffee consumption, have any relationship with renal resistive index (RRI), a hallmark of arterial stiffness (AS). The relationship of AS with nutritional status assessed by body composition and serum albumin, insulin resistance (assessed by HOMA), and renal function assessed by glomerular filtration rate (GFR) is concurrently investigated. METHODS: This study was done with 221 consecutive patients, without diabetes, cancer, liver, renal, and heart disease, referred for clinical noninvasive assessment and nutritional counseling: 124 essential hypertensive and 97 nonhypertensive patients were eligible. Personalized Mediterranean diet, physical activity increase, and smoking withdrawal counseling were provided. RESULTS: By multiple linear regression, fat-free mass (FFM), HOMA (positive relationship), and number of cups of coffee/day (negative relationship) account for 17.2% of the variance to RRI. By odds ratios lower risk to increased RRI is associated with higher serum albumin, higher hemoglobin, and FFM; greater risk is associated with hypertension, insulin resistance (HOMA ≥ 3.0), and renal insufficiency (GFR ≤ 90); coffee, assessed by number of cups/day, reduces risk. CONCLUSION: Coffee use is inversely associated with RRI. Habitual coffee users have risk protection to higher RRI; lower serum albumin, insulin resistance, and renal insufficiency are associated with greater RRI.

Lifestyle interventions, insulin resistance, and renal artery stiffness in essential hypertension.

The study investigates lifestyle and effective anti-hypertensive intervention in overweight-obese patients can influence insulin-resistance (HOMA-IR) and US Renal-Resistive-Index (RRI). After a 1-year interventional program (including a personalized Mediterranean diet, physical activity increase, smoking withdrawal counseling), 156 Essential Hypertension (EH) patients still have abnormal HOMA-IR, significantly higher in comparison to 159 control group patients. Body mass index (BMI) and cholesterol-high-density-lipoprotein improvement are the best predictors of a HOMA-IR decrease; RRI improves in EH according to lifestyle interventions, but no predictor to RRI is identified. Persistence of IR can be tentatively assumed as a steady sign, persistent also after extended lifestyle intervention in EH, further warranting more intensive dietary interventions.

Minimally invasive radiofrequency ablation of lone atrial fibrillation by monolateral right minithoracotomy: operative and early follow-up results.

BACKGROUND: Although an increasing number of symptomatic patients with atrial fibrillation (AF) are being treated with percutaneous radiofrequency ablation, the actual long-term success rate of this procedure remains uncertain. The increasing availability of minimally invasive techniques has made surgery progressively more appealing, especially because of its superior capacity to create transmural lesions. METHODS: In a group of 46 patients with paroxysmal or persistent "lone" AF, who were refractory to medical treatment or had arrhythmia recurrences after a transcatheter procedure, we performed epicardial radiofrequency ablation by a minimally invasive, monolateral thoracoscopic approach. Mean operative time was 85 +/- 35 minutes, and intensive care unit and hospital stays were, respectively, 18.7 +/- 5.1 hours and 4.1 +/- 1.4 days. There were no deaths and only 1 serious complication due to severe bleeding requiring conversion to median sternotomy. RESULTS: At the 6-month follow-up (Holter monitoring), 40 patients (87%) were in stable sinus rhythm. Of the 6 recurrences that we observed, 5 occurred in patients with persistent AF and 1 in a patient with paroxysmal AF (p < 0.01). CONCLUSIONS: Minimally invasive monolateral thoracoscopic radiofrequency ablation is safe and apparently effective. If these findings are confirmed on larger populations followed for longer periods, this procedure may become a viable proposal for treating refractory lone AF.

Elective coronary stent patients: preinterventional functional status and clinical-instrumental assessment.

The functional status of ischemic heart disease (IHD) is currently assessed using the Seattle Angina Questionnaire (SAQ), a tool for monitoring and predicting the patient's prognosis. Illness perceptions (IP) are associated with IHD behavioral risk factors. The aim of the study was to find whether different IP, as evaluated by the IP Questionnaire (IPQr), can predict any of the features of the SAQ, i.e., to determine whether the SAQ is influenced and/or biased by illness perceptions. Moreover, whether New York Heart Association class and Ejection Fraction (EF%) are predictors of IHD severity measured as need of subsequent stenting procedures was also assessed. Eighty IHD patients eligible for percutaneous coronary intervention (PCI) and drug-eluting stent implant were asked to complete the IPQr and the SAQ. Laboratory analyses, echocardiography, and coronary diagnostic and interventional procedures were performed concurrently. Physical limitations of the SAQ are predicted by IPQr emotional representation. Ischemic heart disease functional status is regulated by illness perceptions and beliefs. Thus, some of the inferences drawn from the SAQ regarding IHD prognosis and even interventional indications may be biased and compromise the prognostic reliability of the SAQ information on physical function. This can also have consequences for therapeutic indications.