Bone mineral density, osteoporosis, and fractures among people with eating disorders: a systematic review and meta-analysis.

OBJECTIVE: To provide meta-analytical evidence of bone mineral density (BMD), fractures, and osteoporosis rates in eating disorders (ED) vs. healthy controls (HCs). METHOD: Three independent authors searched major electronic databases from inception till August 2015 for cross-sectional studies reporting BMD in people with ED (anorexia nervosa, (AN); bulimia nervosa, (BN); eating disorders not otherwise specified, (EDNOS)) vs. HCs. Standardized mean differences (SMDs) ±95% and confidence intervals (CIs) were calculated for BMD, and odds ratios (ORs) for osteopenia, osteoporosis, and fractures. RESULTS: Overall, 57 studies were eligible, including 21 607 participants (ED = 6485, HCs = 15 122). Compared to HC, AN subjects had significantly lower BMD values at lumbar spine (SMD = -1.51, 95% CI = -1.75, -1.27, studies = 42), total hip (SMD = -1.56, 95%CI = -1.84, -1.28, studies = 23), intertrochanteric region (SMD = -1.80, 95%CI = -2.46, -1.14, studies = 7), trochanteric region (SMD = -1.05, 95%CI = -1.44, -0.66, studies = 7), and femoral neck (SMD = -0.98, 95%CI = -1.12, -0.77, studies = 20). Reduced BMD was moderated by ED illness duration and amenorrhea (P < 0.05). AN was associated with an increased likelihood of osteoporosis (OR = 12.59, 95%CI = 3.30-47.9, P < 0.001, studies = 4) and fractures (OR = 1.84, 95% CI = 1.17-2.89, I(2) = 56, studies = 6). No difference in BMD was found between BN and EDNOS vs. HC. CONCLUSION: People with AN have reduced BMD, increased odds of osteoporosis and risk of fractures. Proactive monitoring and interventions are required to ameliorate bone loss in AN.

Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study.

Previous clinical studies have shown that oral administration of sugar cane policosanol (SCP) reduces plasma total cholesterol and low-density lipoprotein cholesterol levels. A double blind, randomized, placebo controlled trial was performed in hypercholesterolaemic, diet-resistant patients. Seventy patients meeting the selection criteria were enrolled. Each subject was treated with policosanol 10 mg/d in addition to a dietetic regimen for 8 weeks. At the start and at the end of the study body weight, body mass index (BMI), total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides (TG) plasma levels were measured. Thirty-three subjects in the policosanol and Thirty-one subjects in the control group completed the study. During the study body mass index, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides plasma levels did not change significantly within and between groups. In conclusion, sugar cane policosanol at a dose of 10mg/d showed no lipid lowering effects in subjects with primitive, diet-resistant hypercholesterolaemia.

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Comparison of sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. A randomized, single-blind clinical trial.

Sublingual captopril (25 mg) was compared with sublingual nifedipine (10 mg) to determine their effectiveness and safety in the treatment of hypertensive emergencies. In nine of 10 patients who received sublingual captopril, mean (+/- SD) systolic blood pressure and diastolic blood pressure dropped from 245 +/- 39 to 190 +/- 25 mm Hg (P less than .0025) and from 144 +/- 8 to 115 +/- 8 mm Hg (P less than .001) at 50 minutes, respectively. The hypotensive effect of the drug was maintained for a mean of 4 hours. In six of nine responders to sublingual captopril, blood pressure-lowering effect was associated with a clear improvement of end-organ failure within 60 minutes. There were no side effects, including a dangerous fall in blood pressure or reflex tachycardia. Sublingual nifedipine lowered diastolic blood pressure and systolic blood pressure in eight of 10 patients. The hypotensive effect of nifedipine was more rapid than that of captopril (10 vs 20 minutes for diastolic blood pressure and 20 vs 30 minutes for systolic blood pressure, respectively), but no difference was observed in the time or in the magnitude of peak hypotensive effect between the two treatments, nor was a difference observed in the duration of hypotensive effect. In six of eight responders to nifedipine therapy, a clear improvement of symptoms and signs of end-organ failure was observed within 60 minutes. In three patients, minor side effects were observed. We conclude that sublingual captopril effectively and safely lowers arterial blood pressure in patients with hypertensive emergencies.

Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis.

BACKGROUND: Several studies carried out in a limited number of patients demonstrated a wide range of overestimation of glomerular filtration rate (GFR) by serum creatinine level and creatinine clearance (Ccr) in liver disease. METHODS: We simultaneously evaluated Ccr, inulin clearance, and predicted GFR calculated from serum creatinine level in 56 cirrhotic patients. Inulin clearance was considered the gold standard for GFR evaluation. RESULTS: The sensitivity of serum creatinine level, predicted GFR, and Ccr in detecting renal failure was 18.5%, 51%, and 74%, respectively. On the basis of inulin clearance, patients were divided into two groups: those with normal GFR (mean, 106 +/- 34 mL/min per 1.73 m2) (group 1, 29 patients) and those with reduced GFR (mean, 56 +/- 19 mL/min per 1.73 m2) (group 2, 27 patients). Predicted GFR and Ccr were accurate markers of GFR in group 1 patients, while both overestimated GFR by about 50% in group 2 patients. An increased tubular secretion of creatinine accounted for the disparity between Ccr and inulin clearance in these patients. CONCLUSIONS: Our results indicate that renal failure is greatly underestimated on the basis of serum creatinine level and Ccr in cirrhotic patients. Clinical implications of this observation include excessive dosage of potentially nephrotoxic drugs and failure to recognize renal impairment induced by such medical treatments as diuretic therapy or paracentesis.

Effects of iloprost, a prostacyclin analog derivative, on renal plasma flow, renal function, and renin-aldosterone system in humans.

The effects of iloprost, a stable analog derivative of prostacyclin, on heart rate, blood pressure, renal plasma flow (RPF), glomerular filtration rate, filtration fraction, urine flow, fractional excretion of sodium (FENa), proximal fractional sodium reabsorption (PFRNa), fractional sodium resorption at the ascending limb of Henle's loop (HFRNa), plasma renin activity (PRA), and plasma aldosterone concentration (PA) were evaluated in patients with peripheral vascular disease and normal renal function. In 10 patients the drug was administered intravenously for 6 hours daily for 6 days at a rate of 1 ng/kg/min. In 7 patients iloprost was also administered at a dose of 2 ng/kg/min for the same time. There was no significant change in heart rate and blood pressure at both iloprost doses. At the dose of 1 ng/kg/min the drug had no effect on renal hemodynamics and function, PRA, and PA. At the dose of 2 ng/kg/min iloprost significantly increased RPF (p less than 0.025) and FENa (p less than 0.025) and significantly decreased HFRNa (p less than 0.025) without affecting glomerular filtration rate, filtration fraction, urine flow, PFRNa, PRA, and PA. No correlation was found between the increase in RPF and FENa (r = 0.01). We conclude that at a dose of 2 ng/kg/min, but not 1 ng/kg/min, iloprost has a natriuretic effect secondary to inhibition of sodium reabsorption at the ascending limb of the Henle's loop and not related to the renal hemodynamic effect.

Malnutrition in alcoholic and virus-related cirrhosis.

The study aimed to define the prevalence, characteristics, and clinical importance of nutritional disorders in patients with liver cirrhosis. Nutritional status was evaluated in 120 hospitalized patients--77 with alcoholic and 43 with virus-related cirrhosis--by anthropometric, visceral, and immunologic measurements. Energy malnutrition, defined as triceps skinfold thickness (TSF) and/or midarm muscle circumference (MAMC) below the 5th percentile of standard values, was found in 34% of the study population. Patients below the 5th percentile for MAMC and/or TSF showed significantly lower survival rates at e, 6, 12, and 24 mo compared with patients above the 5th percentile. Protein malnutrition (low albumin, transthyretin, transferrin, and retinol-binding-protein concentrations) and immunoincompetence (abnormal response to skin tests) were much more frequent (81% and 59%) than energy malnutrition (34%). Serum proteins correlated with the degree of liver function impairment, but not with immunologic tests. The prevalence, characteristics, and severity of protein-energy malnutrition were comparable in alcoholic and viral cirrhosis. Malnutrition was correlated with the clinical severity of the liver disease. The study shows that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appear to be related to the degree of liver injury rather than to its etiology. Compared with other methods, which have important limitations in liver disease, anthropometry is currently the most reliable method for nutritional assessment in clinical practice and may be valuable for predicting survival in cirrhotic patients.

Concomitant release of renin, angiotensin I, and angiotensin II during superfusion of human juxtaglomerular cell tumor.

Increasing evidence indicates that angiotensin II can be formed by juxtaglomerular cells (JGC) and cosecreted with renin. We investigated the existence of this local renin-angiotensin system in a human JGC tumor, using an in vitro superfusion. The JGC tumor was found concomitantly to release renin and angiotensin I and II. Sequential addition of atrial natriuretic peptide, dopamine, and a somatostatin analog in the superfusion did not affect renin or angiotensin I and II release. The data provide evidence that the human JGC tumor in vitro generates angiotensin II, and supports its possible role as a local in vivo regulator of kidney function.

Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders.

BACKGROUND AND AIMS: Though low levels of insulin-like growth factor-1 (IGF-1) have been repeatedly reported in patients with eating disorders, the nutritional significance of IGF-1 has not been evaluated. The study aimed to assess the utility of IGF-1 for screening malnutrition and for monitoring nutrition intervention in patients with eating disorders. METHODS: IGF-1 and nutritional status were evaluated in 82 patients, 59 with anorexia nervosa (AN), and 23 with bulimia nervosa (BN). Nutritional assessment included the evaluation of body mass index (BMI), body fat (FAT) and muscle mass (MM), assessed by skinfold anthropometry, serum albumin, transthyretin and retinol-binding protein, energy and protein intake. IGF-1 and nutritional parameters were reevaluated in the early phase of refeeding (2-4 weeks) in 20 AN patients who entered a refeeding program. RESULTS: Mean IGF-1 z-score was -1.74+/-0.74 in AN, and -0.74+/-0.91 in BN. Serum proteins were reduced in only a minority of patients. IGF-1 correlated with BMI (r=0.64), FAT (r=0.57), MAMC (mid-arm muscle circumference) (r=0.58) and MM (r=0.66) (P<0.001), while it did not correlate with serum proteins. In the early phase of nutritional repletion serum proteins and anthropometric parameters did not vary significantly, while a prompt and marked increase (73.9%) of IGF-1 was observed. CONCLUSIONS: IGF-1 represents a biochemical marker of malnutrition and a sensitive index of nutritional repletion in patients with eating disorders.

Optimizing the time-frame for the definition of bleeding-related death after acute variceal bleeding in cirrhosis.

OBJECTIVE: To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. DESIGN: Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. SETTING: Eight medical departments in seven hospitals in north-eastern Italy. METHODS: Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. RESULTS: Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. CONCLUSION: Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.

Vegetarian diets in hepatic encephalopathy: facts or fantasies?

Diet treatment characterized by a reduction in or a selection of food proteins is currently suggested in hepatic encephalopathy. This article is a review of the present knowledge about the characteristics and the rationale of vegetarian diets in cirrhotic patients with overt or latent encephalopathy. In addition, evidence relating diet and encephalopathy and the nutritional features and needs of cirrhotic patients is reported. Finally, the rationale of a diet based on vegetable and milk-derived proteins that may overcome the limits and the possible adverse effects of a strict vegetarian diet is presented.

Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis.

Most of the traditional parameters for nutrition assessment have important limitations in patients with chronic liver disease. Insulin-like growth factor 1 (IGF-1) has been found to be regulated by nutrition and proposed as a nutritional marker. Its nutritional significance in patients with liver cirrhosis, however, has not been investigated. Serum IGF-1 as well as traditional anthropometric, visceral, and immunologic parameters were evaluated in 64 hospitalized cirrhotics, followed up clinically for 2 y. IGF-1Z-score averaged -2.16 +/- 1.08 and inversely correlated with Child-Pugh score (P < 0.01), the most reliable composite score reflecting the severity of liver disease. IGF-1Z-score was not different in patients with or without signs of energy malnutrition, as defined by values of midarm muscle circumference (MAMC) and/or triceps skinfold (TSF) < 5th percentile. Moreover, IGF-1Z-score did not correlate with MAMC or TSF. Despite its correlation with all visceral proteins, the reduction of IGF-1 was much greater and more frequent than that of visceral proteins. Patients with IGF-1Z-score < median values (-2.5) showed lower long-term survival rates compared with patients with IGF-1Z-score > -2.5 (P < 0.01). These data indicate that serum IGF-1 is not related to energy malnutrition in cirrhotic patients, while it appears to be a good predictor of survival and an early marker of liver dysfunction. Multiple factors, most of which are related to the severity of the liver disease, may contribute to the reduction of IGF-1. This multifactorial pathogenesis probably accounts for its prognostic significance.

Nutrition and survival in patients with liver cirrhosis.

Although the effect of malnutrition on survival has been demonstrated by a number of studies, it is not clear whether malnutrition represents an independent risk factor in patients with liver disease. We studied 212 hospitalized patients with liver cirrhosis who were followed clinically for 2 y or until death. Body fat and muscle mass were evaluated by triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC), respectively. Multivariate analysis according to Cox's model assessed the predictive power of nutritional parameters on survival. Thirty-four percent of patients had severe malnutrition as determined by MAMC and/or TSF below the 5th percentile and 20% had moderate malnutrition (MAMC and/or TSF < 10th percentile). Twenty-six percent of patients were overnourished (MAMC and/or TSF > 75th percentile). Severely and moderately malnourished patients had lower survival rates than normal and overnourished patients. When analyzed with Cox's regression analysis, severe depletion of muscle mass and body fat were found to be independent predictors of survival. The inclusion of MAMC and TSF in the Child-Pugh score, the prognostic score used most with liver disease, improved its prognostic accuracy. The prognostic power of MAMC was higher than that of TSF. These data demonstrate that malnutrition is an independent predictor of survival in patients with liver cirrhosis. The inclusion of anthropometric measures in the assessment of these patients might provide better prognostic information.

Distal renal tubular acidosis in hepatic cirrhosis: clinical and pathogenetic study.

The mechanism of the renal tubular acidosis (RTA) occurring in patients with hepatic cirrhosis remains uncertain although it has been suggested that renal and intrarenal hemodynamic alterations could play a role in its pathogenesis. To verify this hypothesis, renal acidification was studied with an intravenous acid load of arginine hydrochloride in 51 patients with cirrhosis due to various causes. In 22 patients renal and intrarenal blood flow was also measured using the 133-Xe washout technique. RTA was found in 17 of 51 patients (33%) with the greatest incidence in alcoholic cirrhosis. The tubular defect did not appear related either to the degree of liver functional impairment or to the renal and intrarenal hemodynamic alterations.

[Liver metabolism of indocyanine green and aminopyrine in liver cirrhosis: relations with functioning liver cell mass]. / Il metabolismo epatico del verde indocianina e dell'aminopirina nella cirrosi epatica: rapporti con la massa epatica funzionante.

Hepatic clearance of indocyanine green, a drug with a high hepatic extraction rate, and breath tests with aminopyrine, a drug with a low hepatic extraction ratio, were calculated in 26 patients with liver cirrhosis. In addition galactose elimination capacity was calculated as an index of functional liver cell mass. All these parameters resulted significantly correlated with each other. These results confirm the view that during liver cirrhosis, metabolism of drugs with high and low hepatic extraction rates can be described according to the intact hepatocyte theory.

[Acid-base metabolism in patients with hepatic cirrhosis treated with portacaval anastomosis at various intervals after the operation]. / Il ricambio acido-base nell'epatocirrotico sottoposto ad anastomosi porto-cava a diversa distanza dall'intervento.

In a series of 68 cirrhotics subjected to portacaval anastomosis for digestive haemorrhage, alterations in the acid base balance, 3, 6, 12, 24 and 48 weeks after anastomosis, were examined. Following operation, an increase in the incidence of the usual acid base disturbances of liver cirrhosis is observed. Respiratory alkalosis increases with no direct relationship to teh postoperative increase in ammoniemia, the main stimulating agent of the resporatory centres. This is probably because the active fraction on the nerve cells is the non-ionized one only, freely diffusible through the haematoencephalic barrier, the plasma concentration of which is a function of blood pH. Postoperative metabolic alkalosis is secondary to the potassium and chloride depletion consequent on operative trauma, on the malnutrition syndrome and, in the case of potassium, on secondary hyperaldosteronism which, unlike what is observed in the other groups of cirrhotics, is uncorrected by anastomosis. After the shunt, metabolic acidosis may be the expression of an increase in lactates and pyruvates following on further liver function deterioration, and of a functional renal insufficiency which anastomosis makes more manifest.

[Nutritional therapy in chronic hepatopathy]. / La terapia nutrizionale nelle epatopatie croniche.

Severe protein-energy malnutrition, a common complication in patients with advanced liver disease, negatively influences clinical evolution and survival, while appropriate nutritional intervention has been found to improve liver function and prognosis. Although the importance of nutritional factors has been greatly emphasized in the last decade, nutritional therapy remains a controversial issue in clinical hepatology. Because a considerable heterogeneity exists among patients regarding both nutritional needs and the pathophysiology of malnutrition, adequate assessment of nutritional status is mandatory to identify the type and the degree of malnutrition for the individualization of therapy. In this paper we first summarize the pathophysiology of malnutrition and the principles for the assessment of nutritional status in patients with chronic liver disease. We then offer rational, cost-conscious recommendations for therapy, with special emphasis on the role of nutritional support in the prevention and treatment of several complications.

[Zinc deficiency in liver cirrhosis: a curiosity or a problem?]. / La carenza di zinco nella cirrosi epatica: curiosità o problema?

This article reviews the literature on the role of zinc in liver cirrhosis and dietary zinc supplementation for cirrhotic patients with hepatic encephalopathy. Zinc is a trace metal found in many proteins and enzymes having catalytical, cocatalytical and structural functions. Zinc deficiency has been demonstrated in cirrhotic patients, and dietary supplementation of this metal could benefit the urea cycle, glucose and protein metabolism, and central nervous system neurotransmission in these subjects. After some brief considerations on normal zinc metabolism, the role zinc plays in the central nervous system, and its conduct in patients with hepatic encephalopathy, possible links between zinc deficiency and the pathophysiology of central nervous system dysfunction in cirrhotic patients are discussed. The article concludes with a critical review of favorable and unfavorable evidence for zinc supplementation in patients with hepatic encephalopathy.

Tryptophan levels, excessive exercise, and nutritional status in anorexia nervosa.

OBJECTIVE: It has been hypothesized that reduced dietary availability of tryptophan may be the cause of impaired serotonin activity in underweight anorexics. The study reported here evaluated the relationship between tryptophan availability in the blood and nutritional status in anorexia nervosa. METHODS: The total amount of tryptophan and the ratio between tryptophan and other large neutral amino acids (TRP/LNAA) were assessed in a sample of 16 starving anorexic patients. Body weight and composition and energy intake were evaluated in all patients. All subjects also completed self-reported questionnaires such as the Hopkins Symptom Checklist and Eating Disorders Inventory (EDI). RESULTS: The TRP/LNAA ratio seems to be higher in patients with a more severe catabolic status. It is, in fact, significantly inversely correlated with body mass index, body fat, muscle mass, daily energy intake, and daily tryptophan intake. The TRP/LNAA ratio also correlates with growth hormone and the EDI drive for thinness. Patients who exercise excessively had significantly higher TRP/LNAA ratios. CONCLUSIONS: In starving anorexic patients, the TRP/LNAA ratio does not seem to be determined by the content of tryptophan in the diet, but it correlates with measures of catabolism. The relationship of the TRP/LNAA ratio to excessive exercise and starvation indicates the importance of further investigations exploring the role of tryptophan availability in maintaining anorexia nervosa.