Fabrizio Pasanisi

Could inflammatory markers help diagnose nonalcoholic steatohepatitis

Background Nonalcoholic fatty liver disease describes a set of conditions that range from fatty liver to nonalcoholic steatohepatitis (NASH), and is considered the hepatic manifestation of metabolic syndrome. Obesity and insulin resistance are strongly associated with systemic markers of inflammation. Objective Focusing on this aspect, we have attempted to find a noninvasive method that could likely assess the presence of NASH and help to decide the liver biopsy performance. Methods Using histology as a gold standard to diagnose nonalcoholic fatty liver disease, we consecutively studied 43 patients with NASH and 40 with fatty liver, comparing their data with those of 48 healthy control participants. The outcomes evaluated were ultrasonographic spleen longitudinal diameter coupled with the splenic artery resistive index, serum IL-6 and vascular endothelial growth factor concentrations. Results The NASH group had higher spleen longitudinal diameter values (P=0.0001) as well as significantly higher IL-6 and vascular endothelial growth factor concentrations than the other groups (P=0.0001). The optimal cut-off value for spleen longitudinal diameter that best discriminated NASH from fatty liver patients was 116 mm (specificity 95% and sensitivity 88%); the sensitivity and specificity of this parameter was better than both IL-6 and vascular endothelial growth factor in the same setting (area under the receiver operating characteristic curve 0.920 vs. 0.817 and 0.678). Splenic artery resistive index was similar between patients with NASH and those with fatty liver, but differed when compared with controls, P=0.0001. Conclusions IL-6 was highly specific in confirming the absence of NASH at normal values. In our series, normal values of spleen longitudinal diameter and IL-6 were strongly associated with fatty liver.

Link of nonhemodynamic factors to hemodynamic determinants of left ventricular hypertrophy.

Despite current evidence suggesting that hemodynamic load is the fundamental stimulus to begin the sequence of biological events leading to the development of left ventricular hypertrophy, genotype, gender, body size, and less easily recognizable environmental factors may contribute to generate the cascade of molecular changes that eventually yield the increase in protein synthesis needed to increase left ventricular mass. However, even nonhemodynamic factors such as gender and body size eventually regulate the growth of left ventricular mass by at least in part influencing loading conditions. Consideration of measurable factors, such as gender, body size, and hemodynamic load, allows evaluation of individual echocardiographic left ventricular mass as the deviation from the level that would be required to face a gender-specific hemodynamic load at a given body size. Values of left ventricular mass that are inappropriately high for individual gender, body size, and hemodynamic load are associated with a high cardiovascular risk phenotype, even independent of the presence of arterial hypertension. Thus, the condition of inappropriately high left ventricular mass may be recognized as a more advanced stage of pathological structural changes initially induced by overload, going beyond the compensatory needs. The biological process that yields inappropriate left ventricular mass is probably linked to the protracted activity over time of biological mediators of left ventricular hypertrophy, such as proto-oncogenes and other growth factors, neurohormones, and cytokines, inducing structural modifications that initially compensate imposed overload but eventually change the structure of myocardial tissue and the composition of motor units.

Left ventricular mass reduction during salt depletion in arterial hypertension.

Long-term therapy with antihypertensive agents that reduce sympathetic nervous system activity has been demonstrated by echocardiographic measurements to reverse left ventricular hypertrophy. This investigation evaluated the effects of salt depletion obtained by both chlorthalidone (25 mg/day) and severe restriction of salt intake (about 1016 mg Na+/day) on left ventricular mass (LVM) in as short a time as 12 weeks. Before the study, the patients had been off medication and on a balanced diet without salt restriction for at least 2 weeks; they were then randomly allocated to either the diuretic or low-salt regimen for 6 weeks and finally to alternative treatment according to a crossover model. Blood pressure, body weight, myocardial mass, and noninvasive measurements of left ventricular function (LVF) were determined at baseline and at the end of both periods of treatment. Results were evaluated by two-way analysis of variance in randomized blocks. Systolic and diastolic blood pressure and LVM were significantly and similarly reduced by diuretic therapy or salt restriction. A significant correlation was demonstrated between noninvasive measurements of LVM, expressed as cross-sectional area, and systolic blood pressure. No impairment of LVF could be detected over the treatment period.

Nutritional screening and early treatment of malnutrition in cancer patients

BackgroundMalnutrition is a frequent complication in patients with cancer and can negatively affect the outcome of treatments. On the other hand, side effects of anticancer therapies can also lead to inadequate nutrient intake and subsequent malnutrition. The nutritional screening aims to identify patients at risk of malnutrition for prompt treatment and/or careful follow-up.Methods and resultsThis manuscript highlights the need of an interdisciplinary approach (oncologist, nutritionist, dietitian, psychologist, etc.) to empower patients who are experiencing loss of physiological and biological function, fatigue, malnutrition, psychological distress, etc., as a result of cancer disease or its treatment, and maintain an acceptable quality of life.ConclusionsIt is necessary to make all healthcare professionals aware of the opportunity to identify cancer patients at risk of malnutrition early in order to plan the best possible intervention and follow-up during cancer treatment and progression.

Non-Alcoholic Fatty Liver Disease in Young Adult Severely Obese Non-Diabetic Patients in South Italy

Background/Aims: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II–III obesity in a metropolitan area of South Italy. Methods: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18–50 years (mean 31.9 ± 8.8), body mass index (BMI) ≧30 (mean 47.5 ± 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0–39.9, and (2) BMI≧40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. Results: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesi ty, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotrasferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI≧40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (γGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and γGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. Conclusion: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.

Butyrylcholinesterase as a prognostic marker: a review of the literature

BackgroundButyrylcholinesterase (BChE) is an α-glycoprotein synthesized in the liver. Its serum level decreases in many clinical conditions such as acute and chronic liver damage, inflammation, injury and infections, and malnutrition.Methods and resultsThis review collects the main evidence on the emerging role of butyrylcholinesterase as a prognostic marker of liver and nonliver diseases as well as a marker of protein-energy malnutrition and obesity. In fact, serum concentrations and BChE activity seem to accurately reflect the availability of amino acidic substrates and/or derangement in protein synthesis due to hepatocellular damage. In cancer, with or without liver impairment, serum BChE levels serve as an accurate functional and prognostic indicator, useful for monitoring clinical and therapeutic interventions according to patients’ prognosis. In the absence of inflammation, BChE could also serve as an index of the effectiveness of nutritional support.ConclusionsSerum BChE assessment should be included in routine clinical diagnostic procedures to evaluate patient clinical conditions, in particular in cases of inflammation and/or protein-energy malnutrition.

Fasting Respiratory Quotient as a Predictor of Long-Term Weight Changes in Non-Obese Women

Background/Aims: The identification of metabolic and environmental predictors of excess body fat is still far from being achieved. The aim of this study was to evaluate whether respiratory quotient in non-obese women is a predictor of body weight changes after a 6-year follow-up period. Methods: Forty-three non-obese healthy women participated in the study. Their baseline general characteristics were: age 40.5 ± 12.8 years; height 159 ± 7 cm; weight 61.8 ± 10.1 kg, and body mass index (BMI) 24.4 ± 3.8 kg/m². At baseline basal metabolic rate and respiratory quotient were determined by indirect calorimetry, while weight and BMI were recorded at the first observation and after the 3- and 6-year follow-ups. Results: At the first observation basal metabolic rate was 5,360 ± 713 kJ/day and respiratory quotient 0.850 ± 0.052. After 6 years, with weight changes equal to 1.4 ± 4.5 kg, baseline respiratory quotient was a significant predictor (p < 0.05) of changes in body weight or BMI together with baseline BMI. Conclusions: This follow-up study confirms that a high respiratory quotient (measured on free diet) predisposes to weight gain, especially in women with the highest baseline respiratory quotient (above the 90th percentile of the distribution for this variable).

Appropriate or inappropriate left ventricular mass in the presence or absence of prognostically adverse left ventricular hypertrophy.

Objectives To evaluate whether assessment of appropriateness of left ventricular mass (LVM) adds to the traditional definition of left ventricular hypertrophy (LVH). Design Cross-sectional, relational. Methods Echocardiographic LVH and appropriateness of LVM were studied in 562 subjects (231 normotensive controls, aged 35 ± 11 years, 142 women; 331 hypertensive patients, aged 47 ± 11 years, 135 women) classified on the basis of either the presence or the absence of both LVH (LVM index ⩾ 51 g/m2.7) and inappropriate LVM (LVM > 128% of the value predicted by an equation including age, sex and stroke work). Results Body mass index was comparable in hypertensive patients and controls. Hypertensive patients without LVH but with inappropriate LVM (n = 21) had higher relative wall thickness and total peripheral resistance than all other groups, whereas cardiac output was lower (all P < 0.001). Midwall mechanics was normal with appropriate LVM, independently of presence of LVH, whereas it was depressed in inappropriate LVM, either with or without LVH (both P < 0.0001). There was no substantial difference in ejection fraction among controls and hypertensive groups. Stress-corrected midwall shortening was more closely related to deviation of LVM from the value appropriate for stroke work, body size and gender (r =− 0.56, P < 0.0001) than to LVM index (r =− 0.26). Conclusions Inappropriate LVM is associated with concentric geometry, high peripheral resistance and depressed wall mechanics. The deviation of LVM from the value appropriate for stroke work, body size and sex correlates with measures of myocardial function better than LVM.

High Leptin/Adiponectin Ratio and Serum Triglycerides Are Associated With an "At-Risk" Phenotype in young Severely Obese Patients

“At‐risk” severely obese subjects are characterized by insulin resistance, and higher visceral fat and plasma lipid levels compared with metabolically healthy obese (MHO) subjects, although both groups have a high BMI and fat mass. The aim of this study was to measure several serum adipokines and gastrointestinal hormones in a young severely obese population from Southern Italy to identify biochemical markers of the “at‐risk” insulin‐resistant obese profile. We studied 160 unrelated white young adults (mean age = 25.2 years, mean BMI = 44.9 kg/m2, 65% women) affected by obesity for at least 5 years. Serum concentrations of glucagon, ghrelin, gastric inhibitory peptide, glucagon like peptide‐1, interleukin‐6, tumor necrosis factor α, leptin, adiponectin, adipsin, and visfatin were measured. The leptin/adiponectin (L/A) ratio and fatty liver index (FLI) were calculated. We found a prevalence of 21.3% of MHO patients in our young severely obese patients. At univariate analysis, the “at‐risk” group had higher mean levels of BMI (P < 0.0001), leptin (P = 0.039, men) and the L/A ratio (P = 0.003), and lower mean levels of visfatin (P = 0.026) than the MHO group. The L/A ratio, serum triglycerides, and male sex were significantly associated with “at‐risk” obesity and accounted for 19.5% of insulin resistance at multivariate analysis. In conclusion, we demonstrate that a high serum L/A ratio and high levels of serum triglycerides may be markers of “at‐risk” obesity, independent of waist circumference (WC) and BMI, in young severely obese population.

Predictors of survival in terminal-cancer patients with irreversible bowel obstruction receiving home parenteral nutrition

Clinical, anthropometric, hematologic, and biochemical variables, evaluated immediately before starting nutritional treatment, were related to survival in 76 terminal-cancer patients with irreversible bowel obstruction receiving home parenteral nutrition. At baseline, abnormally low values were observed in the following percentages of patients: 40.8% for body mass index, 59.2% for serum albumin, 84.2% for hemoglobin, 48.7% for lymphocyte count, and 60% for serum cholesterol. Survival on home parenteral nutrition ranged between 6 and 301 d, with a median of 74 d. Hemoglobin, serum albumin and serum cholesterol were lower in patients with a survival of less than 3 mo. With regard to Karnofsky performance status, median survival times were 63 d for a score below or equal to 50 and 128 d for a score between 60 and 70. Albumin and a Karnofsky score above 50 (but not age, weight, body mass index, lymphocyte count, or cholesterol) emerged (with a positive sign) as predictors of survival. In conclusion, terminal-cancer patients with irreversible bowel obstruction are often malnourished, showing a high prevalence of anemia and hypoalbuminemia. Survival differs widely and can be predicted only to a limited extent from initial values of serum albumin and Karnofsky performance status.