Claimed effects, outcome variables and methods of measurement for health claims proposed under regulation (EC) 1924/2006 and related to cognitive function in adults.

Some food/food components have been the object of request of authorization to the use of health claims related to cognitive function in adults and compliant with the Regulation (EC) 1924/2006. Most of the requests have received a negative opinion by the European Food Safety Authority (EFSA) also because of the choice of not appropriate outcome variables (OVs) and methods of measurement (MMs) selected in the trials used to substantiate the claim. This manuscript referes to the collection, collation and critical analysis of OVs and MMs related to cognitive function in adults. OVs and MMs were collected from the EFSA Guidance document and the applications for authorization of health claims pursuant to the Articles 13(5). The critical analysis of OVs and MMs, performed by a literature review, was aimed at defining their appropriateness in the context of a specific claimed effect. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims related to cognitive functioning. The information provided in this document may serve to EFSA for updating the guidance on the scientific requirements for health claims related to cognitive functions, but also for a better design of randomized controlled trials aimed at substantiating such health claims.

Claimed effects, outcome variables and methods of measurement for health claims proposed under European Community Regulation 1924/2006 in the framework of protection against oxidative damage and cardiovascular health.

BACKGROUND AND AIMS: The high number of negative opinions from the European Food Safety Authority (EFSA) to the requests for authorization of health claims is largely due to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed to collect, collate and critically analyse the information in relation to claimed effects, OVs and MMs, in the context of protection against oxidative damage and cardiovascular health compliant with Regulation 1924/2006. METHODS AND RESULTS: Claimed effects, OVs and the related MMs were collected from EFSA Guidance documents and applications for authorization of health claims under Articles 13.5 and 14. The OVs and their MMs were evaluated only if the claimed effect was sufficiently defined and was considered beneficial by EFSA. The collection, collation and critical analysis of the relevant scientific literature consisted in the definition of the keywords, the PubMed search strategies and the creation of databases of references. The critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context of the specific claimed effects. CONCLUSIONS: The information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims, as well as to the stakeholders for the proper design of human intervention studies aimed to substantiate such health claims.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Nutritional status, metabolic state and nutrient intake in children with bronchiolitis.

Nutrition has a coadjuvant role in the management of children with acute diseases. We aimed to examine nutritional status, macronutrient requirements and actual macronutrient delivery in bronchiolitis. The nutritional status was classified according to WHO criteria and resting energy expenditure (MREE) was measured using an indirect calorimeter. Bland-Altman analysis was used to examine the agreement between MREE and estimated energy expenditure (EEE) with standard equations. Based on the ratio MREE/EEE in relation to Schofield equation on admission, we defined the subjects' metabolic status. A total of 35 patients were enrolled and 46% were malnourished on admission, and 25.8% were hypermetabolic, 37.1% hypometabolic and 37.1% normometabolic. We performed a 24-h recall in 10 children and 80% were overfed (AEI: MREE >120%). Mean bias (limits of agreement) with MREE was 8.9 (-73.9 to 91.8%) for Schofield; 61.0 (-41 to 163%) for Harris-Benedict; and 9.9 (-74.4 to 94.2%) for FAO-WHO equation. Metabolism of infants with bronchiolitis is not accurately estimated by equations.

Predictors of blood pressure at 7-13 years: The "new millennium baby" study.

BACKGROUND AND AIMS: The purpose of this study is to evaluate the association between blood pressure (BP) at 7-13 years of age and body mass index (BMI), early feeding, lifestyle indicators, and parental characteristics. METHODS AND RESULTS: Retrospective plus cross-sectional cohort study was started in 1294 children born in 2000-2004, right from their birth in primary care settings. Early feeding was estimated by measuring breast-feeding (BF) duration, complementary feeding (CF) introduction time, and lifestyle indicators such as daily screen time and weekly extracurricular sports activity time. Parental education, smoking, and obesity-related diseases were also considered. Multivariable linear regression and mediation analysis were used. CF introduction at 5-6 months of age was a negative predictor of systolic and diastolic BP (mean systolic BP-standard deviation score (SDS) -0.38 [95% CI: -0.47, -0.29] (p < 0.001); mean diastolic BP-SDS -0.32 [95% CI: -0.40, -0.24]) (p < 0.001); BMI was a positive predictor of systolic and diastolic BP (p < 0.001); and parental hypertension was a positive predictor of diastolic BP (p < 0.05). Predictors of mean BMI-SDS at 7-13 years of age were birth weight, screen time, and parental obesity and smoking (p < 0.001). BF had no effect on BP or BMI. Mediation analysis showed virtually no indication of the effect of CF on BP mediated by BMI. CONCLUSIONS: CF introduction between 5 and 6 months of age could be associated with low BP at 7-13 years. The effect of CF on BP seems to be independent of BMI. Low screen time is associated with low BMI. CF time may play a role in the occurrence of surrogates of noncommunicable disorders in future.

Does segmental body composition differ in women with Prader-Willi syndrome compared to women with essential obesity?

BACKGROUND: Subjects with Prader-Willi syndrome (PWS) have a higher fat mass and a lower fat-free mass compared to subjects with essential obesity. However, few data are presently available on the segmental body composition (BC) of PWS subjects. AIM: To evaluate whether women with PWS and women with essential obesity, matched for age and percent body fat, differ in segmental fat distribution and surrogate markers of cardiometabolic disease (CMD). SUBJECTS AND METHODS: 35 women with PWS and 50 women with essential obesity were matched for age and percent body fat using coarsened exact matching. BC was measured by dual-energy X-ray absorptiometry. Oral glucose tolerance testing and measurements of cholesterol, triglycerides, C-reactive protein, and blood pressure were performed. Comparisons between PWS and obese women were performed using generalized linear models. RESULTS: Trunk fat was lower in PWS than in obese women on both absolute [-7.3 (95% confidence interval -9.4 to -5.2) kg] and relative [-4.1 (-6.9 to -1.4)% of body fat] grounds. PWS and obese women had similar surrogate markers of CMD, with the exception of HDL-cholesterol, which was higher in PWS women. CONCLUSION: Trunk fat is lower in obese women with PWS than in those with essential obesity. Surrogate markers of CMD are, however, mostly similar in the two groups.

Early retesting by GHRH + arginine test shows normal GH response in most children with idiopathic GH deficiency.

PURPOSE: Most children with idiopathic isolated GH deficiency (IGHD) normalize GH response to stimulation tests when retested at the completion of growth. The objective of this study was to test the effectiveness of early retesting in challenging the diagnosis of idiopathic IGHD and critically review the diagnostic workup leading to this diagnosis in children with short stature. METHODS: We cross-sectionally retested 38 children with idiopathic IGHD and still on GH treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH responses to two stimulation tests and normal brain imaging or minor/nonspecific findings at magnetic resonance. The GH response normalization at retesting was considered as the main outcome measure. Clinical features of children who were falsely classified as idiopathic IGHD based on first GH testing were retrospectively analyzed. RESULTS: GH secretion was normal in 36/38 children (95%). Two children showed slightly reduced peak GH responses and normal IGF-I levels. Fourteen children underwent GH retesting before puberty, 24 children during puberty. CONCLUSION: The diagnostic process should be improved to minimize the rate of false positive at GH testing and, in case of unsatisfactory response to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged with early retesting.

Waist circumference-to-height ratio predicts adiposity better than body mass index in children and adolescents.

OBJECTIVE: Body mass index (BMI) is the surrogate measure of adiposity most commonly employed in children and adults. Waist circumference (WC) and the waist circumference-to-height ratio (WCHt) have been proposed as markers of adiposity-related morbidity in children. However, no study to date has compared WCHt, WC, BMI and skinfolds thickness for their ability to detect body adiposity. AIM: To compare WCHt, WC, BMI and skinfolds for their accuracy in predicting percent body fat (PBF), percent trunk fat (PTF) and fat mass index (FMI) in a large sample of children and adolescents. DESIGN, SETTING AND PARTICIPANTS: We studied 2339 children and adolescents aged 8-18 years from the US National Health and Nutrition Examination Survey 2003/2004. Body fat was measured using dual-energy X-ray absorptiometry. Multivariable regression splines were used to model the association between PBF, PTF, FMI and the predictors of interest. RESULTS: WCHt alone explained 64% of PBF variance as compared with 31% for WC, 32% for BMI and 72% for the sum of triceps and subscapular skinfolds (SF2) (P<0.001 for all). When age and gender were added to the predictors, the explained variance increased to 80% for the WCHt model, 72% for the WC model, 68% for the BMI model and 84% for the SF2 model. There was no practical advantage to add the ethnic group as further predictor. Similar relationships were observed with PTF and FMI. CONCLUSIONS: WCHt is better than WC and BMI at predicting adiposity in children and adolescents. It can be a useful surrogate of body adiposity when skinfold measurements are not available.

Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children. We tested whether dietary supplementation with docosahexaenoic acid (DHA) can decrease liver fat content in children with NAFLD. METHODS AND RESULTS: We performed a randomized controlled trial of DHA supplementation (250 mg/day and 500 mg/day) vs. placebo in 60 children with NAFLD (20 children per group). The main outcome was the change in liver fat as detected by ultrasonography after 6, 12, 18 and 24 months of treatment. Secondary outcomes were changes in triglycerides, alanine transaminase (ALT), body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA). The odds of more severe versus less severe liver steatosis decreased to the same degree at 6 months in children treated with DHA 250 mg/day and DHA 500 mg/day vs. placebo and persisted virtually unmodified for 24 months (OR ≤ 0.02, p ≤ 0.05 for all time points). Triglycerides were lower in the DHA groups than in the placebo group at any time point and ALT was lower in these groups from month 12 onwards. HOMA was lower in the DHA 250 mg group vs. placebo at months 6 and 12. CONCLUSION: DHA supplementation improves liver steatosis in children with NAFLD. Doses of 250 mg/day and 500 mg/day of DHA appear to be equally effective in reducing liver fat content.

Changes of body mass index in celiac children on a gluten-free diet.

BACKGROUND AND AIM: Studies of adults and children with celiac disease (CD) performed mostly in tertiary care centers have reported an increased risk of overweight during gluten-free diet (GFD). We measured body mass index (BMI) of CD children followed by family pediatricians in order to estimate prevalence of underweight and overweight at diagnosis and to describe BMI changes during GFD. METHODS AND RESULTS: We compared 150 CD children (age range 2-16 yrs) under GFD from a median (IQR) time of 4.4 (4.2) years with 288 healthy children matched for gender and age. We also evaluated retrospectively BMI changes between CD diagnosis and the current evaluation. The median (IQR) BMI of CD patients was significantly lower than that of controls [-0.38 (1.46) vs. 0.09 (1.18) SDS, p < 0.0001, Italian reference data]. Using the International Obesity Task Force classifications, CD children were less frequently overweight or obese (12% vs. 23.3%, p = 0.014) and more frequently underweight (16% vs. 4.5%, p < 0.001) than controls. During GFD, there was a marked decrease of number of underweight subjects (13 vs. 27) and a minimal increase of number of overweight subjects (9 vs. 6) (p < 0.001). CONCLUSIONS: The frequency of overweight and obesity at diagnosis of CD and during GFD in children followed by family pediatricians is substantially lower than that reported in tertiary care centers. On the other hand, the high frequency of underweight at diagnosis confirms the need of careful personalized nutritional management.

Metabolic syndrome in adult patients with Prader-Willi syndrome.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most common genetic cause of obesity, is characterized by elevated morbility and mortality in all ages. In this context, non-obese PWS children showed low frequency of metabolic syndrome (MetS), while a comparable prevalence was observed in obese PWS and obese controls. Aim of this study was to estimate the occurrence of MetS and its components in a large group of PWS adults, according to obesity status. METHODS AND RESULTS: A cross-sectional study was performed in 108 PWS aged 18.0-43.2 years (87 obese and 21 non-obese) and in 85 controls with nonsyndromic obesity matched for age, gender, and BMI with obese PWS. Non-obese PWS showed lower waist circumference, insulin, HOMA-index, triglycerides, diastolic blood pressure, and higher HDL-C than both obese PWS and obese controls (p < 0.017). Obese PWS showed higher glucose and systolic blood pressure than both non-obese PWS and obese controls (p < 0.017). MetS was found in 1/21 (4.8%) non-obese PWS, 36/87 (41.4%) obese PWS and 39/85 (45.9%) obese controls. Non-obese PWS showed lower frequency for each MetS component as compared with obese PWS and obese controls. PWS patients with deletion of the chromosome 15q11-13 showed a lower risk for low HDL-C (p < 0.01) and a trend towards a lower MetS risk (p < 0.06) compared to subjects without deletion. CONCLUSION: Our findings suggest the main role that obesity status plays on the individual metabolic risk clustering in PWS adults. Early identification of MetS could be helpful to improve morbidity and prevent mortality in such patients.

Effect of intrauterine growth retardation on liver and long-term metabolic risk.

Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction.

Relationship between fatty liver and glucose metabolism: a cross-sectional study in 571 obese children.

BACKGROUND AND AIMS: Early onset type 2 diabetes mellitus (T2DM) is associated with obesity, insulin resistance and impaired beta-cell function. Non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for T2DM. We investigated the relationship between NAFLD and glucose metabolism in a large sample of obese children. METHODS AND RESULTS: A total of 571 obese children (57% males and 43% females) aged 8-18 years were consecutively studied at a tertiary care centre specialised in paediatric obesity. Liver ultrasonography was used to diagnose NAFLD after exclusion of hepatitis B and C and alcohol consumption. Oral-glucose tolerance testing (OGTT) was performed; insulin sensitivity was evaluated by using the insulin sensitivity index (ISI) and beta-cell function by using the ratio between the incremental areas under the curve (AUC) of insulin and glucose (incAUCins/incAUCglu). A total of 41% of the obese children had NAFLD. Impaired glucose tolerance or T2DM was present in 25% of the children with NAFLD versus 8% of those without it (p<0.001). Children with NAFLD had higher body mass index (BMI), fasting glucose, 120-min OGTT glucose, incAUCins/incAUCglu and lower ISI as compared with children without NAFLD (p≤0.002). At bootstrapped multivariable median regression analysis controlling for gender, age, pubertal status and BMI, NAFLD was an independent predictor of 120-min OGTT glucose and ISI, but not of incAUCins/incAUCglu. Similar findings were obtained using continuous liver steatosis as the predictor, instead of dichotomous NAFLD. CONCLUSION: NAFLD was present in 41% of our obese children and was associated with higher insulin resistance, but not with impaired beta-cell function.

Impact of percent body fat on oral glucose tolerance testing: a cross-sectional study in 1512 obese children.

BACKGROUND: Although an association between insulin resistance (IR) and body adiposity has been reported in obese children, this relationship has not been studied as thoroughly as in adults. AIM: We evaluated the association between oral glucose tolerance testing (OGTT) and percent body fat (PBF) in a sample of 1512 obese children followed at a Pediatric Obesity Clinic. SUBJECTS AND METHODS: Six hundred and twenty-eight male and 884 female obese children aged 6 to 18 yr were consecutively enrolled into the study. OGTT was performed with administration of 1.75 g of glucose per kg of body weight (up to 75 g). PBF was estimated through bioelectrical impedance analysis (BIA) using a population- specific formula recently published by our group. Multivariable median regression was used to evaluate the association between 4 outcomes [glucose area under the curve (AUC), insulin AUC, insulin sensitivity index (ISI), and insulinogenic index (IGI)] and gender, age or pubertal status and PBF. RESULTS: Median PBF was 52% (range 26 to 70%). After correction for age and gender, a 10% increase of PBF was associated with a decrease of -0.50 [95% confidence interval (CI): -0.65 to -0.35] units of ISI and an increase of 0.15 units of IGI (95%CI 0.07 to 0.24). CONCLUSIONS: In obese children, PBF is inversely associated with IR and directly associated to ß-cell response as detected by OGTT.

ASH and NASH.

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) have a similar pathogenesis and histopathology but a different etiology and epidemiology. NASH and ASH are advanced stages of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). NAFLD is characterized by excessive fat accumulation in the liver (steatosis), without any other evident causes of chronic liver diseases (viral, autoimmune, genetic, etc.), and with an alcohol consumption ≤20-30 g/day. On the contrary, AFLD is defined as the presence of steatosis and alcohol consumption >20-30 g/day. The most common phenotypic manifestations of primary NAFLD/NASH are overweight/obesity, visceral adiposity, type 2 diabetes, hypertriglyceridemia and hypertension. The prevalence of NAFLD in the general population in Western countries is estimated to be 25-30%. The prevalence and incidence of NASH and ASH are not known because of the impossibility of performing liver biopsy in the general population. Up to 90% of alcoholics have fatty liver, and 5-15% of these subjects will develop cirrhosis over 20 years. The risk of cirrhosis increases to 30-40% in those who continue to drink alcohol. About 10-35% of alcoholics exhibit changes on liver biopsy consistent with alcoholic hepatitis. Natural histories of NASH and ASH are not completely defined, even if patients with NASH have a reduced life expectancy due to liver-related death and cardiovascular diseases. The best treatment of AFLD/ASH is to stop drinking, and the most effective first-line therapeutic option for NAFLD/NASH is non-pharmacologic lifestyle interventions through a multidisciplinary approach including weight loss, dietary changes, physical exercise, and cognitive-behavior therapy.

Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status. METHODS AND RESULTS: A cross-sectional study was performed in 109 PWS children aged 2-18 years (50 obese and 59 non-obese) and in 96 simple obese controls matched for age, gender, and also for BMI with obese PWS. Obesity was defined when SDS-BMI was >2. Non-obese PWS showed significantly lower frequency of hypertension (12%) than obese PWS (32%) and obese controls (35%)(p=0.003). The same was observed for low HDL-cholesterol (3% vs 18% and 24%, p=0.001) and high triglycerides (7% vs 23% and 16%, p=0.026). Frequency of altered glucose metabolism was not different among groups (2% vs 10% and 5%), but type 2 diabetes (four cases) was present only in obese PWS. Non-obese PWS showed lower insulin and HOMA-index respect to obese PWS and obese controls (p ≤ 0.017). Overall MS frequency in PWS was 7.3%. None of the non-obese PWS showed MS compared with 16% of obese PWS and controls (p<0.001). When obesity was excluded from the analysis, a significantly lower frequency for clustering of ≥ 2 factors was still found in non-obese PWS (p=0.035). CONCLUSION: Non-obese PWS showed low frequency of MS and its components, while that observed in obese PWS was very close to those of obese controls, suggesting the crucial role of obesity status. Prevention of obesity onset remains the most important goal of PWS treatment. Early identification of MS could be helpful to improve morbidity and mortality in such patients.

Three-dimensional CAD/CAM reconstruction of the iliac bone following DCIA composite flap harvest.

This article reports a new technique to restore iliac bone integrity with a customized titanium device designed by CAD/CAM, in patients undergoing deep circumflex iliac artery (DCIA) composite flap harvest. Eight consecutive patients who underwent the repair of major head and neck defects with DCIA flaps were enrolled retrospectively. Computed tomography scans of the pelvis were obtained preoperatively. Starting from DICOM data, each personalized device was designed using modelling software and was finally made by additive manufacturing using a laser sintering machine. After surgery, the patients were followed up at 3-month intervals to evaluate the incidence of complications and the long-term outcome at the donor site. A subcutaneous seroma developed in one patient and an inguinal skin burn occurred in another. At a median follow-up of 12 months, the patients did not report pain, or any gait or sensory disturbance at the donor site. There was no occurrence of bulging, herniation, or instability or inflammation near the device for the entire follow-up duration. All patients were satisfied with the aesthetic result. In conclusion, reconstruction of the iliac bone with a customized device is safe and well tolerated. We recommend use of this device in patients deemed at high risk of herniation. Further studies are needed to confirm the stability of the device in the long term.

HCV, HBV and alcohol - the Dionysos study.

Population-based studies on the natural history of chronic viral liver disease that consider co-morbidity factors, such as alcohol or metabolic diseases, are lacking. We report here the contribution of ethanol intake and non-organ-specific autoantibodies (NOSA) to the course of chronic viral disease in the Dionysos cohort. As reported elsewhere, the Dionysos study was performed in two towns of Northern Italy, started in 1992 with 10 years of follow-up in 2002, and allowed us to quantify the burden of chronic liver disease in Northern Italy. We followed 139 subjects with chronic hepatitis C virus (HCV) infection and 61 with chronic hepatitis B virus (HBV) infection for a median (IQR) time of 8.4 (1.0) and 8.3 (0.9) years, respectively. The incidence and remission rates of steatosis were 9.0 and 29.7 per 1,000 person-years in the HCV cohort and 4.0 and 30.4 per 1,000 person-years in the HBV cohort. Progression to cirrhosis and hepatocarcinoma was more common in the HCV than in the HBV cohort. In the HCV cohort, ethanol intake was an independent predictor of liver cirrhosis and of death rate in both cohorts. We found no association between baseline NOSA and 8.4-year mortality. We conclude that morbidity and mortality rate of HBV and HCV infection in the general population is lower than that reported in secondary care populations, blood donors, or clinical series, and that ethanol intake >30 g/day is the most important and evitable risk factor for cirrhosis and death in patients with chronic HCV or HBV infection.

Massive hemobilia and papillomatosis of the gallbladder in metachromatic leukodystrophy: a life-threatening condition.

Polyposis of the gallbladder is rare during childhood. This condition can be associated with three other conditions: metachromatic leukodystrophy, Peutz-Jeghers' syndrome, and pancreaticobiliary maljunction. We report the case of a child with hemobilia in metachromatic leukodystrophy, which rendered cholecystectomy necessary. Macroscopically, the gallbladder measured 4.6 cm in length and showed an opaque serous surface and focal brown petechiae. Moreover, a yellow polypoid lesion of 2 cm in diameter and a diffuse thickening of the fundus wall were observed. Many reports describe the importance of the association of gallbladder papillomatosis with metachromatic leukodystrophy, but only three cases presented with massive intestinal bleeding, such as our young patient had. It is thus imperative that this life-threatening condition should be well known.

Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis.

OBJECTIVE: Waist circumference is widely accepted as a risk factor for cardiovascular disease and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is a feature of the metabolic syndrome. A contribution of metabolic syndrome, and especially of waist circumference, to liver fibrosis in children with NAFLD is strongly suspected. DESIGN: Cross-sectional study. SETTING: Department of Hepatogastroenterology and Nutrition, Paediatric Hospital "Bambino Gesù", Rome, Italy. PATIENTS: 197 consecutive Caucasian children with NAFLD (136 males and 61 females) aged 3-19 years. MAIN OUTCOME MEASURES: Multivariable logistic regression models were used to examine the contribution of gender, age, body mass index (BMI) and metabolic syndrome components (waist circumference, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure and glucose) to the odds of liver fibrosis as detected by liver biopsy. RESULTS: 92% of the children had BMI > or = 85(th) percentile and 84% had a waist > or = 90(th) percentile for gender and age. Ten per cent of the children had metabolic syndrome and 67% had liver fibrosis, mostly of low degree. At multivariable analysis, waist was the only metabolic syndrome component to be associated with liver fibrosis. This was seen both when the components of the metabolic syndrome were coded as dichotomous (odds ratio (OR) = 2.40; 95% confidence interval (CI), 1.04 to 5.54) and continuous (OR = 2.07; 95% CI, 1.43 to 2.98 for a 5 cm increase). In the latter case, age was also associated with the outcome (OR = 0.70; 95% CI, 0.55 to 0.89 for a 1 year increase). CONCLUSIONS: Abdominal rather than generalised obesity contributes to liver fibrosis in children with NAFLD. Waist is also the only component of the metabolic syndrome to be associated with fibrosis in these children. Therefore, the presence of abdominal obesity is an additional criterion for the selection of children and adolescents who should undergo extensive investigation, including liver biopsy.