Predictive value of Cardiac Magnetic Resonance: new and old parameters in the natural history of repaired Tetralogy of Fallot.

BACKGROUND: Patients with repaired Tetralogy of Fallot (rTOF) often develop pulmonary regurgitation (PR) and right ventricle (RV) dysfunction, experiencing increased mortality and morbidity rates in adulthood. Pulmonary valve replacement (PVR) timing to address PR is controversial. Cardiac Magnetic Resonance (CMR) is the gold standard for morpho-functional evaluation of complex cardiopathies. This study aims to identify CMR parameters predictive of adverse outcomes to help defining the best therapeutic management of rTOF patients. METHODS: 130 rTOF patients who underwent CMR (2006-2019) were enrolled in this retrospective single-center study. CMR, clinical, ECG and exercise data were analyzed. Univariate and multivariate analyses identified clinical and CMR parameters predictive of adverse outcomes both individually (e.g., death, arrhythmias, heart failure (HF), pharmacological therapy, QRS ≥ 160ms) and as composite outcome. RESULTS: Univariate analysis confirmed RV volumes and RV ejection fraction corrected for PR as adverse outcome predictors and identified interesting correlations: pulmonary artery bifurcation geometry and abnormal interventricular septum (IVS) motion with arrhythmias (p < .001; p = .037), HF (p = .049; p = .005), composite outcome (p = .039; p = .009); right atrium (RA) dimensions with the composite outcome and the outcomes individually (p < .001). The best predictive models by multivariate analysis included sex (male), RV and RA dilation for QRS ≥ 160ms, time form repair to CMR, age at TOF repair and IVS fibrosis for pharmacological therapy. CONCLUSIONS: Besides RV volumes, new adverse prognostic factors could guide rTOF therapeutic management: pulmonary arteries morphology, abnormal IVS motion, RV dysfunction, RA dilation. Perspective multicentric evaluation is needed to specify their effective role.

Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking.

Background: Electrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease. Aim and Methods: To perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation. Results: The study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9 mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p < 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p < 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%). Conclusions: ECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined.

Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone.

OBJECTIVE: We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC-MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping. METHODS: Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (17OHP) ≥ 2.00 ng/mL underwent CYP21A2 gene analysis and 1-24ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC-MS/MS. RESULTS: Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2 mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline 17OHP and testosterone, and after ACTH stimulation, higher 17OHP (17OHP60) and lower cortisol, whereas LC-MS/MS revealed higher 17OHP (17OHPLC-MS/MS), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of 17OHPLC-MS/MS ≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated 17OHP ≥ 6.77 ng/mL and cortisol ≤ 240 ng/mL by immunoassay, showed 100% specificity. CONCLUSIONS: LC-MS/MS measurement of basal follicular 21-deoxycortisol, 17OHP and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test.

Novel Way to Search for Light Dark Matter in Lepton Beam-Dump Experiments.

A novel mechanism to produce and detect light dark matter in experiments making use of GeV electrons (and positrons) impinging on a thick target (beam dump) is proposed. The positron-rich environment produced by the electromagnetic shower allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}→γ+A^{'}) and resonant (e^{+}+e^{-}→A^{'}) annihilation on atomic electrons. The latter mechanism, for some selected kinematics, results in a larger sensitivity with respect to limits derived by the commonly used A^{'}-strahlung. This idea, applied to beam-dump experiments and active beam-dump experiments, pushes down the current limits by an order of magnitude.

Testing the efficacy and efficiency of a single "universal warming protocol" for vitrified human embryos: prospective randomized controlled trial and retrospective longitudinal cohort study.

PURPOSE: To study the efficacy and efficiency of a "universal warming protocol" for vitrified human embryos, based on subsequent steps with 1 and 0.5 M concentration of extracellular cryoprotectant (ECCP). METHOD: Two studies on patients undergoing fertility treatments via ICSI: a prospective randomized controlled trial (RCT) and a retrospective cohort study (CS). SETTING: Private assisted reproductive (AR) center. RCT: duration 01/03/2017-01/10/2017; 315 embryos at blastocyst stage obtained from 169 patients. Each patient's embryos were first randomized for vitrification with two different kits: Vitrification Kit (Kitazato, Japan) and Sage Vitrification Kit (Origio, Denmark). The embryos were randomly warmed with either Kitazato (K) or Sage (S) warming kits, specifically: group A (KK), group B (KS), group C (SK), and group D (SS). PRIMARY OUTCOME MEASURE: survival rate (number of embryos surviving per number of embryos warmed). Secondary: implantation rate (number of embryos implanted per number of embryos transferred). CS: duration 01/01/2013-31/12/2015 embryos from patients' own oocytes; 10/04/2015-31/07/2017 embryos from donors' oocytes. A total of 1055 embryos vitrified at cleavage stage obtained from 631 warming cycles: 847 of these obtained from patients' own oocytes, 208 egg-donation-derived embryos. Each patient's embryos were vitrified and warmed in various combinations of three different vitrification/warming kits: Kitazato (K), Sage (S), or made in-house in our laboratory (H). Vitrification/warming kits from different manufacturers are routinely used in our AR center, and the warming procedures are randomly performed with any available kit on a "first-in-first-out" basis, irrespective of the kit used for vitrification. Group names: KK, KS, SK, SS, SH, HK, HS, HH (embryos from patients' own oocytes); eKK, eKS, eSK, eSS (egg-donation-derived embryos). RESULTS: Cryo-survival rates were comparable in all study groups. RCT. Group A 99.0% (96/97), group B 98.8% (83/84), group C 98.4% (61/62), and group D 98.6% (71/72). CS. Embryos from patients' own oocytes: KK 96.4% (54/56), KS 100.0% (13/13), SK 98.8% (80/81), SS 97.2% (174/179), SH 97.6% (40/41), HK 95.2% (20/21), HS 99.5% (187/188), and HH 97.4% (261/268). Egg-donation-derived embryos: eKK 100.0% (91/91), eKS 98.4% (60/61), eSK 100.0% (26/26), and eSS 96.7 (29/30). Implantation was generally comparable in all study groups-exceptions were in CS: KS vs. SK (P = 0.049), SS (P = 0.012), HS (P = 0.010), HH (P = 0.025); and SH vs. SS (P = 0.042), HS (P = 0.035). CONCLUSION: Worldwide, millions of embryos have been cryopreserved using different vitrification kits; these studies establish that it is possible to combine different kits for vitrification and warming using a universal warming protocol. This can optimize costs, simplify lab routines, and favor embryo exchange between IVF centers. RCT REGISTRATION NUMBER: ISRCTN12342851.

Observational prospective study comparing mucoactive and antibiotic treament in the management of acute cough from upper respiratory tract infections.

AIM: Since the efficacy of antibiotics in the management of cough from upper respiratory tract infections (URTI) is unclear, we conducted an observational study to evaluate the efficacy of antibiotic compared to symptomatic treatment in adults with productive cough from URTI in a real life setting. METHODS: One-hundred and 50 subjects presenting to five general practice ambulatories with productive cough due to URTI were included in the study. According to the physician judgment, patients were treated with either oral antibiotics (group A, 50 patients), a mucoactive syrup (sobrerol: group S, 50 patients) as symptomatic treatment, or both sobrerol and oral antibiotics (group SA, 50 patients). Cough severity was assessed daily with a diary, by means of a validated verbal category-descriptive (VCD) Scale. RESULTS: In every treatment group cough severity decreased over time (P<0.001); however, during the first week of treatment patients in groups S and SA experienced significantly lower VCD score values in comparison to Group A (P=0.045 and P=0.010, respectively). On the other hand, the VCD score was never significantly different between the two groups that received symptomatic treatment at any of the 4 weeks of the study, suggesting that the effect observed was due to the action of the mucoactive syrup. CONCLUSION: Our data confirm the lack of efficacy of antibiotics in the management of productive cough in URTI and suggest that symptomatic treatment should be preferred to antibiotics in acute cough from URTI.

Relationships between mild hyperuricaemia and aortic stiffness in untreated hypertensive patients.

BACKGROUND AND AIMS: Clinical studies exploring the relationship between serum uric acid (SUA) and arterial stiffness yielded conflicting results. Only in a few of these studies, arterial distensibility was examined by measuring aortic pulse wave velocity (PWV), which is considered the gold standard for evaluating arterial stiffness. In none of the previous investigations was the influence of SUA on aortic distensibility assessed, taking into account the effect of albuminuria. The purpose of our study was to comprehensively analyse the relationships between SUA and aortic PWV in a group of essential hypertensive patients. METHODS AND RESULTS: We enrolled 222 untreated and uncomplicated hypertensive subjects (mean age: 44 ± 10 years; 60% males), without gout. In all patients, SUA and urinary albumin excretion rate (AER) were determined. Moreover, carotid-femoral (c-f) PWV was measured. C-f PWV was significantly higher in hypertensive patients belonging to the uppermost tertile of SUA distribution, compared to subjects of the lowest tertiles (10.9 ± 2.2 vs. 10 ± 1.8 vs. 9.9 ± 1.7 m s(-1); p = 0.001). In univariate analysis, SUA correlated with c-f PWV (r = 0.24; p < 0.001). This association disappeared when AER was added in a multiple regression model, including SUA, age, mean arterial pressure, gender, metabolic syndrome components and glomerular filtration rate. CONCLUSION: The results of our study showed that, in essential hypertensive subjects, there is a positive relationship between mild hyperuricaemia and aortic stiffness. This association weakened after adjustment for covariates and lost statistical significance after further correction for albuminuria.

Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men.

BACKGROUND AND AIM: Experimentally uric acid may induce cardiomyocyte growth and interstitial fibrosis of the heart. However, clinical studies exploring the relationship between serum uric acid (SUA) and left ventricular (LV) mass yielded conflicting results. The aim of our study was to evaluate the relationships between SUA and LV mass in a large group of Caucasian essential hypertensive subjects. METHODS AND RESULTS: We enrolled 534 hypertensive patients free of cardiovascular complications and without severe renal insufficiency. In all subjects routine blood chemistry, including SUA determination, echocardiographic examination and 24 h ambulatory blood pressure (BP) monitoring were obtained. In the overall population we observed no significant correlation of SUA with LV mass indexed for height(2.7) (LVMH(2.7)) (r = 0.074). When the same relationship was analysed separately in men and women, we found a statistically significant correlation in female gender (r = 0.27; p < 0.001), but not in males (r = -0.042; p = NS). When we grouped the study population in sex-specific tertiles of SUA, an increase in LVMH(2.7) was observed in the highest tertiles in women (44.5 ± 15.6 vs 47.5 ± 16 vs 55.9 ± 22.2 g/m(2.7); p < 0.001), but not in men. The association between SUA and LVMH(2.7) in women lost statistical significance in multiple regression analyses, after adjustment for age, 24 h systolic BP, body mass index, serum creatinine and other potential confounders. CONCLUSIONS: Our findings do not support an independent association between SUA and LV mass in Caucasian men and women with arterial hypertension.

SU-E-T-279: A Novel Electron-Beam Combined with Magnetic Field Application for Radiotherapy.

PURPOSE: The new beam and delivery system consists of an electron accelerator and a system of magnets (one or more). Introducing a transverse magnetic field in and near the tumor, causes the electrons to spiral in this region, thereby producing an effective peak in the depth dose distribution, within the tumor volume. Although the basic idea is not new, we suggest here for the first time, a viable as well as a workable, magnetic field configuration, which in addition to focusing the beam does not interfere with its propagation to the target. METHODS: The electron accelerator: can be a linear accelerator or any other type electron accelerator, capable of producing different electron energies for different depths and dose absorption accumulation. The Field size can be as small as a pencil beam and as big as any of the other standard field sizes that are used in radiotherapy. The scatter filter can be used or removed. The dose rate accumulation can be as higher as possible.The magnets are able to produce magnetic fields. The order, direction, width, place, shape and number of the magnetic fields define the shape and the Percentage Depth Dose (PDD) curve of the electron beam. Prototypes were successfully tested by means of computer simulation, using:COMSOL-Multiphsics for magnetic fields calculations. FLUKA package, for electron beam MC simulation. RESULTS: Our results suggest that by using an electron beam at different energies, combined with magnetic fields, we could modify the delivered dose. This is caused by manipulating the electron motion via the Lorentz force. The applied magnetic field, will focus the electron beam at a given depth and deposit the energy in a given volume and depth, where otherwise the electron energy will have spread deeper. The direction and magnitude of the magnetic fields will prevent the scattering of the electron beam and its absorption in remote volumes. In practice, we get a pseudo Bragg peak depth dose distribution, applying a relatively low cost system. The therapeutic efficiency induced by the system is of similar efficiency as the ion beam therapy techniques. CONCLUSIONS: Our novel concept demonstrates treatment that is almost similar to proton therapy and in some parameters even better performance.Unlike the current high-energy electron therapy, our system's beam deposit almost all of its energy on its target, with a low amount of radiation deposited in tissues from the surface of the skin to the front of tumor, and almost no "exit dose" beyond the tumor. This property will enables to hit tumors with higher, potentially more effective radiation doses, while being considerably less expensive.

Young woman with branchio-oto-renal syndrome and a novel mutation in the EYA-1 gene.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease clinically characterized by the coexistence of some or all of the following major disorders: deafness, cervical branchial fistulae, preauricular pits, and renal abnormalities. Most families with BOR syndrome have mutations on the EYA-1 gene on chromosome 8q. We present the case of a 23-year-old Italian woman without a familial history of BOR syndrome. The patient, who had hearing loss and a history of surgeries for correction of bilateral cervical branchial fistulae and bilateral preauricular pits, presented with renal impairment, hypertension and overt proteinuria. DNA sequencing showed a novel heterozygous mutation 1420-1421delCC in exon 14 of EYA-1 gene.

Impact of type 2 diabetes on left ventricular geometry and diastolic function in hypertensive patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and diastolic dysfunction are very common in patients with chronic kidney disease (CKD). Aim of this study was to evaluate the impact of type 2 diabetes on LV geometry and diastolic function in hypertensive patients with CKD. We enrolled 288 Caucasian subjects with hypertension and CKD; of them, 112 had diabetes. Patients with cardiovascular (CV) diseases, glomerular filtration rate (GFR) >60 ml min(-1) per 1.73 m(2), dialysis treatment and other major non-CV diseases were excluded. All patients underwent routine biochemical analyses and echocardiographic examination with tissue Doppler imaging (TDI). Patients with diabetes had significantly higher LV wall thicknesses (P=0.0001), relative wall thickness (RWT) (P=0.0001) and left atrium volume index (P=0.03), when compared with patients without diabetes. Further, diabetic patients had very high prevalence of concentric LVH. Em, evaluated by TDI, was significantly lower in patients with diabetes (P=0.005). However, the difference lost statistical significance after correction by analysis of covariance for RWT. Multiple stepwise linear regression analysis showed that the variables independently associated with Em were: age (ß 0.364; P=0.0001), GFR (beta 0.101; P=0.019), and the presence of diabetes (ß 0.166; P=0.002). Our study showed that in hypertensive patients with CKD the presence of diabetes is associated with increased LV-wall thicknesses and concentric geometry; further, diabetes together with renal function (GFR) is associated with worse diastolic function, independently of potential confounders, such as age, gender, body mass index and blood pressure.

Clinical correlates of renal dysfunction in hypertensive patients without cardiovascular complications: the REDHY study.

Our study was aimed to assess the clinical correlates of different degrees of renal dysfunction in a wide group of non-diabetic hypertensive patients, free from cardiovascular (CV) complications and known renal diseases, participating to the REDHY (REnal Dysfunction in HYpertension) study. A total of 1856 hypertensive subjects (mean age: 47+/-14 years), attending our hypertension centre, were evaluated. The glomerular filtration rate (GFR) was estimated by the simplified Modification of Diet in Renal Disease Study prediction equation. A 24-h urine sample was collected to determine albumin excretion rate (AER). Albuminuria was defined as an AER greater than 20 microg min(-1). We used the classification proposed by the US National Kidney Foundation's guidelines for chronic kidney disease (CKD) to define the stages of renal function impairment. In multiple logistic regression analysis, the probability of having stage 1 and stage 2 CKD was significantly higher in subjects with greater values of systolic blood pressure (SBP) and with larger waist circumference. SBP was also positively related to stage 3 CKD. Stage 3 and stages 4-5 CKD were inversely associated with waist circumference and directly associated with serum uric acid. Age was inversely related to stage 1 CKD and directly related to stage 3 CKD. The factors associated with milder forms of kidney dysfunction are, in part, different from those associated with more advanced stages of renal function impairment.

Relationships between metabolic syndrome and left ventricular mass in hypertensive patients: does sex matter?

Several studies documented an association between metabolic syndrome (MetS) and left ventricular (LV) hypertrophy. However, only in a few of these studies the impact of MetS on left ventricular mass (LVM) was separately analysed by gender, with conflicting results. The aim of our study was to verify, in a wide sample of essential hypertensive patients, the influence of gender, if any, on the relationship between MetS and LVM. We enrolled 475 non-diabetic subjects (mean age: 46 +/- 11 years), with mild-to-moderate essential hypertension, of whom 40% had MetS, defined on the basis of Adult Treatment Panel III (ATPIII) criteria. All the patients underwent a 24-h ambulatory blood pressure monitoring and an echocardiogram. LVM indexed for height (2.7) (LVMH (2.7)) was significantly (P < 0.001) higher in women with MetS (n=83) than in those without it (n=97; 54+/-17 vs 42+/-11 g m(-2.7)). An equally significant difference in LVMH (2.7) was documented also in male gender between the two groups with (n=105) and without MetS (n=190; 51+/-14 vs 43+/-11 g m(-2.7); P < 0.001). The relationship between MetS and LVMH (2.7) remained statistically significant (P < 0.001) in both sexes, in multiple regression analyses, even after adjustment for potential confounding factors. Our results seem to suggest that the relationship between MetS and LVM is not significantly affected by gender, being LVM increased in both hypertensive women and men with MetS.

Metabolic syndrome in subjects with white-coat hypertension: impact on left ventricular structure and function.

Some reports have suggested that white-coat hypertension (WCH) is associated with some features of the metabolic syndrome (MetS). These metabolic disturbances, instead of WCH per se, may potentially explain the greater extent of end-organ damage sometimes observed in WCH subjects (WCHs) when compared to normotensive individuals (NTs). The aim of the present cross-sectional study was to compare left ventricular (LV) structure and function in three groups of subjects: WCHs with MetS, WCHs without MetS and NTs. A total of 145 WCHs, 35% of whom had MetS, were enrolled. As controls, 35 NTs were also studied. In all subjects, routine blood chemistry, echocardiographic examination and 24-h ambulatory blood pressure monitoring were performed. When compared with WCHs without MetS, those with MetS showed higher LV mass indexed by height elevated by a power of 2.7 (LVMH(2.7)) (49.6+/-14.8 vs 38.9+/-9.8 g/m(2.7); P<0.0001). The same parameter was greater in WCHs without MetS than in NTs (32+/-8 g/m(2.7); P=0.004). Moreover, the E-wave deceleration time was longer in WCHs with MetS than in those without it (236.2+/-66.4 vs 200.5+/-30.8 ms; P<0.0001). The relationship of MetS with LVMH(2.7) was confirmed in multivariate regression models. Our results seem to suggest that MetS may have a deleterious influence on LV structure and function in WCH. However, WCH, being associated with an increased LV mass, also in subjects without MetS, may not be considered as an innocuous phenomenon.

Association between biomarkers of inflammation and left ventricular hypertrophy in moderate chronic kidney disease.

AIMS: Left ventricular hypertrophy (LVH) is a predictor for cardiovascular mortality, and it is considered to be a surrogate marker of preclinical cardiovascular disease. This study aimed at evaluating whether fetuin-A plasma levels are decreased in patients with moderate chronic kidney disease (CKD) and their linkage to plasma concentrations of hs-C-reactive protein (CRP), cardiotrophyn-1 (CT-1), tumor necrosis factor-ac (TNF-alpha), propeptide of collagen Type I (PIP) and to LVH. MATERIAL AND METHODS: We enrolled 64 moderate CKD and 55 essential hypertensives (EH) with normal renal function as controls. All the patients underwent an echocardiographic examination; plasma samples were obtained to measure routine clinical parameters and the molecules listed above (measured by ELISA). RESULTS: Among CKD there were 30/64 patients with LVH, and in EH group 14/55 subjects had LVH. Fetuin A was reduced in CKD when compared with EH (p < 0.0001). The comparison between CKD having LVH with those without LVH showed significant differences in plasma levels of fetuin-A (p < 0.002), TNF-alpha (p < 0.01) and hs-CRP (p < 0.001), CT-1 and PIP (p < 0.002). CKD with LVH had lower values of fetuin-A (p < 0.001), and higher values of hs-CRP (p < 0.001) TNF-alpha (p < 0.001), CT-1 (p < 0.001) and PIP (p < 0.001) than EH with LVH. The multivariate analysis of correlation demonstrated that in CKD patients hs-CRP (beta 0.42, p < 0.00006), and systolic blood pressure (beta 0.29, p < 0.02) were independent predictors of LV mass index. The relationship between LV mass index and fetuin-A did not reach statistical significance. CONCLUSIONS: For the first time in moderate CKD patients, we demonstrate that fetuin-A is decreased and relates to LVH depending on C-reactive protein.

Microalbuminuria and early endothelial activation in essential hypertension.

We hypothesized that in essential hypertensive patients (EHs), plasma levels of pro-atherogenic adhesion molecules would be increased and related with urine albumin excretion (UAE). Thus, this study was aimed at evaluating biochemical markers of endothelial activation and their relationship with UAE in a group of patients with uncomplicated EH. In basal condition soluble forms of adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, as well as 24-h UAE were assayed. One hundred patients with essential hypertension and no diabetes or ultrasonographic evidence of atherosclerosis were included in the study. Seventy normotensive healthy subjects served as controls. EHs were first studied overall, than were divided into two subgroups: those with UAE > or =20 mcg/min MAUs and those with UAE <20 mcg/min (non-MAUs). ICAM-1 (P<0.001) and VCAM-1 (P<0.0001) plasma concentrations were higher in EHs than in controls. Microalbuminuric EHs had greater levels of adhesion molecules than non-MAUs (ICAM-1 P=0.04; VCAM-1 P=0.02, respectively). In EHs UAE was correlated with ICAM-1 (r=0.29, P=0.003), and VCAM-1 (r=0.30, P=0.002). These associations were confirmed in multiple regression models (P=0.02 for both ICAM-1 and VCAM-1) including, along with adhesion molecules, age, body mass index and blood pressures. Our findings show that in essential hypertension there is a very early activation of endothelial adhesion molecules favouring atherosclerosis.

Reduction of Pb and Zn bioavailable forms in metal polluted soils due to paper mill sludge addition. Effects on Pb and Zn transferability to barley.

In the last few years solidification/stabilisation of acidic soils polluted by heavy metals with low-cost sorbents has been investigated. Paper mill sludges are produced in large amounts and their disposal is a serious environmental problem. The possibility was therefore studied of using paper mill sludge as a stabilizer to reduce the bioavailable metal forms in polluted soils and thus the transferability of metals to plants (barley). We first investigated the sorbing properties of paper mill sludge for Zn(II) and Pb(II) and then their fractionation both in a polluted soil and in the same soil amended with paper mill sludge in order to check the decrease in mobile forms. Finally in both soils we tested the uptake of two metals by common barley in order to assess the performance of soil remediation from an ecological point of view. The addition of paper mill sludge to a soil contaminated by lead and zinc induces a decrease in the mobile forms of both metals, probably due to the presence in sludge of organic matter and kaolinite, which are able to bind the metals very strongly. The decrease in the mobile forms, which are the most readily available for uptake by plants, corresponds to a decrease in plant uptake.

Metabolic syndrome in subjects with essential hypertension: relationships with subclinical cardiovascular and renal damage.

It has long been recognized that arterial hypertension is often a part of a larger constellation of anthropometric and metabolic abnormalities that includes abdominal (or visceral) obesity, a characteristic dyslipidemia (low high-density lipoprotein cholesterol and high triglycerides), glucose intolerance, insulin-resistance and hyperuricemia. These traits occur simultaneously to a greater degree than would be expected by chance alone, supporting the existence of a discrete disorder that, over the years, has been defined by a variety of terms, including plurimetabolic syndrome, the deadly quartet, dysmetabolic syndrome, insulin resistance syndrome, cardiometabolic syndrome and more recently metabolic syndrome (MS). In last years some scientific organizations proposed working definitions for MS. Among these definitions, the one suggested by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII) is the simplest and the most commonly applied. The MS is extremely common worldwide. This high prevalence is of considerable concern because accumulating evidences suggest that the MS, even without type 2 diabetes, carries an increased risk for cardiovascular and renal events. Recently it has been demonstrated that the adverse prognostic impact of MS may also be extended to hypertensive patients. Some recent studies reported an increased prevalence of left ventricular hypertrophy, diastolic dysfunction, early carotid atherosclerosis, impaired aortic distensibility, hypertensive retinopathy and microalbuminuria in hypertensive patients with MS when compared to those without it. The increased occurrence of these early signs of subclinical target organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular and renal outcomes, may partially explain the association of the MS with a higher cardiovascular and renal risk.

Colon and gastric metastases from a primary signet-ring cell carcinoma of the urinary bladder.

Signet-ring cell carcinoma is a relatively rare neoplasm that rarely occurs in the urinary bladder. We report a case of a 60-year-old man who presented with gross haematuria. Cystoscopy revealed a white sessile tumour of the anterior bladder wall. The histological diagnosis showed a primary signet-ring cell carcinoma of the bladder (T3bN0M0). Eighteen months after radical cystectomy, the patient developed colon and stomach metastases. This case represents the first description of a primary signet-ring cell carcinoma of the urinary bladder with gastrointestinal metastases.