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Despite the clinical importance of metastasis to the skeleton, the diagnostic tools for early detection and monitoring of bone metastasis lack sensitivity and specificity. We evaluated a promising new serum biomarker, the soluble form of the Receptor of Advanced Glycosylated End-products (sRAGE). sRAGE is involved in the Wnt-signaling pathway, and has been reported to reduce the risk of cancer. We investigated the diagnostic potential of sRAGE to improve the detection and monitoring of bone metastasis. We measured sRAGE in the serum of control healthy subjects, patients with primary tumors and patients with bone metastasis. sRAGE was also correlated with the Wnt inhibitors DKK-1 and sclerostin, the bone resorption markers MMP-2, MMP-9 and TRAP5, and the metastatic marker survivin. sRAGE was significantly lower in primary tumor and metastatic patients than in healthy subjects. sRAGE also showed a strong negative correlation with DKK-1, sclerostin, MMP-2, MMP-9, TRAP5b and survivin. These results indicated that sRAGE might play a protective role in bone metastasis progression, and it may diagnostic significance for detecting and monitoring osteolytic metastases.

Calcium and phosphate are essential for cell functions, and their serum concentrations result from the balance between intestinal absorption, bony storage, and urinary excretion. Fibroblast growth factor 23 (FGF23), expressed by osteocytes and osteoblasts, acts in the kidney, leading to hypophosphatemia and low 1,25-dihydroxycholecalciferol synthesis, but suppresses parathyroid function. The aim of this study was to explore the effects of a high-energy demanding cycling race on this bone-kidney-parathyroid axis. We studied nine cyclists during the 2011 Giro d'Italia stage race. Pre-analytical and analytical phases followed academic and anti-doping recommendations. Serum parathyroid hormone (PTH), 25(OH)D, total calcium, inorganic phosphorus, and plasma FGF23 were measured on days -1, 12, and 22 and corrected for changes in plasma volume. Dietary calcium and phosphorus, anthropometric parameters (height, weight, and body mass index) and indexes of metabolic effort (net energy expenditure, power output) were recorded. Dietary calcium and phosphorus intakes were kept at the same levels throughout the race. Twenty-five (OH)D, PTH, and calcium concentrations remained stable. FGF23 increased 50% with a positive correlation with the indexes of metabolic effort and, consequently, phosphorous decreased, although only in the first half. The strong metabolic effort acts on the bone-kidney-parathyroid system, and the rise in FGF23 plasma concentration might be aimed at maintaining calcium and phosphorus homeostasis.

BACKGROUND--In some infants with liver disease, 3-oxo-delta 4 bile acids are the major bile acids in urine, a phenomenon attributed to reduced activity of the delta 4-3-oxosteroid 5 beta-reductase required for synthesis of chenodeoxycholic acid and cholic acid. These patients form a heterogeneous group. Many have a known cause of hepatic dysfunction and plasma concentrations of chenodeoxycholic acid and cholic acid that are actually greater than those of the 3-oxo-delta 4 bile acids. It is unlikely that these patients have a primary genetic deficiency of the 5 beta-reductase enzyme. AIMS--To document the bile acid profile, clinical phenotype, and response to treatment of an infant with cholestasis, increased plasma concentrations of 3-oxo-delta 4 bile acids, low plasma concentrations of chenodeoxycholic acid and cholic acid, and no other identifiable cause of liver disease. PATIENTS--This infant was compared with normal infants and infants with cholestasis of known cause. METHODS--Analysis of bile acids by liquid secondary ionisation mass spectrometry and gas chromatography-mass spectrometry. RESULTS--The plasma bile acid profile of the patient was unique. She had chronic cholestatic liver disease associated with malabsorption of vitamins D and E and a normal gamma-glutamyltranspeptidase when the transaminases were increased. The liver disease failed to improve with ursodeoxycholic acid but responded to a combination of chenodeoxycholic acid and cholic acid. CONCLUSION--Treatment of primary 5 beta-reductase deficiency requires the use of bile acids that inhibit cholesterol 7 alpha-hydroxylase.

To evaluate (i) the clinical course and outcome in a cohort of 250 children affected with Kawasaki disease (KD) in northern Italy; (ii) the prevalence of coronary aneurysms and their correlation with treatment; and (iii) the prevalence of incomplete and atypical KD in the series as a whole.The male to female ratio was 1.8 to 1 and the median age at diagnosis 37 months. The majority of cases occurred in children under five years, with the youngest patient aged 51 days. Median duration offever was 8 days; median erythrocyte sedimentation rate (ESR) and C Reactive protein (CRP) values, performed before any treatment, were 77 mm/1st h and 10.4 mg/dl respectively. Median haemoglobin (Hb) levels was 9.2 g/dl and median platelet (PTL) count 408,000/mm3. Out of 250 patients, 209 (83.6%) fulfilled all criteria for the diagnosis of KD whilst 41/250 (16.4%) had an incomplete disease and 11/250 (4.4%) had an atypical onset. Fifty-four children (21.6%) were treated with aspirin alone (50-80 mg/kg/day, during the acute phase), while 196/250 (78.4%) were given aspirin (50-80 mg/kg day, during the acute phase and then 3-5 mg/Kg/day) and high-dose intravenous gammaglobulin (IVIG, 400 mg/Kg/day or 2 g/Kg/day). Coronary artery abnormalities, including aneurysms and dilatation, were reported in 7/54 patients (5 males and 2 females) who had not received IVIG and 53/196 patients (27 males and 26 females) who were treated with the IVIG in addition to aspirin. Other clinical manifestations included abdominal pain/diarrhoea (11), arthritis (10), hydrops of the gallbladder (8), disseminated intravascular coagulation (3), and hemiparesis (1). All patients except one infant are still alive. In most of the patients coronary alterations normalised, while in 20 patients they persisted for more than one year; in 12/20 patients they were permanent.Pediatricians should be aware of the increasing number of children with atypical and incomplete KD, in order to diagnose and treat the disease even in the absence of all typical manifestations and to prevent coronary complications.

Kawasaki disease (KD) is a new, well characterized pediatric syndrome. In this work the last epidemiologic, diagnostic and clinical data are pointed. Especially the heart-disease and its monitoring and therapy are studied. Our casuistry (5 cases in 4 years) is also presented. The international literature and our clinical experience suggest that KD is more spread than we think and therefore in needs to be studied carefully by the pediatricians.

Five children from one to seven years of age with intrahepatic ductular hypoplasia are presented. Clinical and biochemical characteristics of the disease are specifically considered as well as differential diagnosis. In three patients a severe hemolytic anemia, only partially corrected with vitamine E, was present. All subjects received continuous cholestyramine therapy. Variable follow up from nine months to seven years demonstrated persistent intrahepatic cholestasis with hypercholesterolemia in two cases, clinical and biochemical improvement in one case. One child died two years and six months after diagnosis was made an one patient was lost to follow up. The Authors confirm the literature clinic, diagnostic and therapeutic data concerning ductular hypoplasia, while, on the basis of their experience, the prognosis seems poor also in some cases of syndromic ductular hypoplasia.

Fourteen cases of Wilson's disease, 9 of which in pure hepatic form are presented. Earliest clinical sign of liver disease was hepatosplenomegaly with altered indexes of hepatic function. The disease was found in 4 couples of brothers and sisters of families reported. For all cases diagnosis was based on the values of ceruloplasmin, serum copper, basal urine copper and urine copper after D-penicillamine. Furthermore in 8 cases very increased copper concentration in the liver was demonstrated. D-penicillamine therapy produced hepatic improvement in 8 cases, 6 of which affected by only hepatic form and the treatment was fairly tolerated. In 1 case this therapy caused nephrotic syndrome it was replaced with Trien-2HCL. Wilson's disease in its pure hepatic form must be considered in the differential diagnosis of liver diseases in pediatric age, especially when markers of viral hepatitis are absent. The identification of pure hepatic form provides early diagnosis of Wilson's disease, basic requirement for an effective therapy.

Background . Intense training can lead to a pathophysiological change in serum concentration of a variety of biomarkers. Traditional biomarkers of cardiac injury are very useful in monitoring CVD patients, but in healthy subjects or athletes they cannot be informative enough about the cardiovascular risk, because in these cases their serum levels do not increase over the pathological limit. Therefore novel cardiovascular biomarkers are required in order to allow a better monitoring of sport performance, prediction of overtraining and diagnosis of sport-related cardiac injuries. Growth differentiation factor-15 (GDF-15) is emerging as a powerful cardiovascular injury risk indicator. In this study we investigate the effect of intense physical training of on the circulating levels of GDF-15 in rugby professional players. Methods . Serum GDF-15, Erythropoietin, IL-6, the cardiovascular parameter ST-2, NT-proBNP and routine hematological parameters were measured in a group of 30 rugby players before and after a session of intense training. Results . While ST-2, IL-6 and hsCRP displayed no signifi cant changes after intense training, NT-proBNP and GDF-15 showed a signifi cant increase, even without reaching the pathological level. Discussion . The measure of GDF-15 in professional rugby players could be a useful tool to monitoring their cardiovascular status during training and competition session in order to prevent the onset of collateral cardiovascular adverse event due to the intense training and, in the case of cardiac injury, it could possibly allow a very early diagnosis at the beginning of the pathogenic process.