Toxic environment and obesity pandemia: Is there a relationship?

Data about the natural evolution of subclinical hypothyroidism (SH) in pediatric age are very scanty. Moreover all the available reports in both aged and young patients were based on unselected study populations including also patients with either thyroid disorders or other pathological causes that are well known to be able to affect SH development and evolution. Aim of the study by Wasniewska et al was to prospectively evaluate for the first time the natural course of SH in children and adolescents with no underlying diseases and no risk factors that might interfere with the progression of SH. On the basis of the 2-year follow-up results, the Authors concluded that: a) the natural course of TSH values in a pediatric population with idiopathic SH is characterized by a progressive decrease over time; b) the majority of patients (88%) normalized or maintained unchanged their TSH; and c) TSH changes were not associated with changes of either FT4 values or clinical status or auxological parameters. Study design of this study is very accurate and the results are robust, thus supporting the Authors' conclusions.     

Signs and symptoms in chronic heart failure: relevance of clinical trial results to point of care-data from Val-HeFT

BACKGROUND: Clinical trials emphasize mortality and morbidity endpoints. AIMS: To bring relevance of trial results to point of care by examining the prognostic and therapeutic value of individual signs and symptoms (S&S). METHODS: We analysed data from 5010 patients with stable chronic heart failure and left ventricular dysfunction who were participants in the Val-HeFT study. Individual S&S were stratified by severity. Treatment differences between valsartan and placebo were analysed by S&S strata at baseline and endpoint by logistical regression, and an overall S&S score by ANCOVA. Hazard ratios of S&S strata were calculated for mortality and heart failure hospitalisation. Prognostic contributions of S&S to other variables were determined by multivariate analysis. RESULTS: At endpoint, there were significantly fewer valsartan and more placebo patients with severe symptoms. Over time, improvement in the S&S overall score was significantly more favourable for valsartan than placebo. S&S strata were significantly predictive of risk for hospitalisation and death. S&S were each independent and incremental predictors of mortality compared to other variables. Symptom strata separated out moderately symptomatic patients with a mortality rate which was intermediate between that for NYHA Class II and III. CONCLUSION: Risk stratification of individual S&S defined prognosis, identified patients with an intermediate mortality between Class II and III, and treatment benefits of valsartan over placebo.     

Incremental prognostic value of changes in B-type natriuretic peptide in heart failure

Purpose

B-type natriuretic peptide is one of the most sensitive and specific biohumoral markers of heart failure. We hypothesized that B-type natriuretic peptide changes during treatment of heart failure may provide independent information on disease progression and outcome in patients enrolled in the Val-HeFT trial.

Methods

Patients were divided into four groups according to concentrations of B-type natriuretic peptide at baseline versus 4 months (n = 3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL): low→low (stable below median, 44%-46%), high→high (stable above median, 32%-37%), high→low (above to below median, 12%-14%), and low→high (below to above median, 6%-9%). Cox multivariate regression analysis was used to assess the risk of death and morbidity, with adjustment for baseline B-type natriuretic peptide concentrations.

Results

Patients who improved their B-type natriuretic peptide at 4 months (high→low) had a similar risk for mortality (hazard ratio = 1.191, 95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low→low patients. Conversely, patients who worsened in their B-type natriuretic peptide (low→high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P <.0001) higher than patients in the low→low group, and indistinguishable from the high→high group. Worsening of B-type natriuretic peptide (low→high) was associated with 0.03 cm/m² increase in left ventricular end-diastolic diameter, whereas it decreased by 0.10 cm/m² in high→low and low→low groups (P <.001).

Conclusions

Changes in B-type natriuretic peptide over time with respect to a threshold value of 97 pg/mL convey an independent and additional prognostic value compared with a single determination of B-type natriuretic peptide in a large population of patients with chronic symptomatic heart failure and might be helpful in the management of these patients.     

Characterization and expression of different pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide receptors in rat ovarian follicles

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide transiently expressed in preovulatory follicles. PACAP acts by interacting with three types of PACAP receptors. PACAP type I receptor (PAC(1)-R), which binds specifically to both PACAPs and vasoactive intestinal polypeptide (VIP), although with lower affinity, and two VIP receptors, VPAC(1)-R and VPAC(2)-R, which bind to PACAP and VIP with equal affinity. In the present study, we showed the expression of all three receptors in whole ovaries obtained from juvenile and gonadotropin-treated immature rats. A more detailed analysis on cells from preovulatory follicles showed that PAC(1)-R and VPAC(2)-R were expressed in granulosa cells, whereas only VIP receptors were expressed in theca/interstitial (TI) cells and fully grown oocytes presented only PAC(1)-R. The distribution of the VIP receptors was confirmed by immunofluorescence. HCG treatment induced stimulation of PAC(1)-R in granulosa cells and VPAC(2)-R in TI cells. The presence of functional PACAP/VIP receptors was also supported by metabolic studies. We further evaluated the presence of PACAP and VIP receptors by testing the effect of these peptides on apoptosis in granulosa cells cultured, isolated or in whole follicles. Treatment of follicles with PACAP and VIP dose-dependently inhibited apoptosis, while only PACAP significantly inhibited isolated granulosa cells. These results demonstrate a different expression of PACAP/VIP receptors in the various follicle compartments and suggest a possible role for PACAP and VIP on granulosa and TI cells, both during follicle development and ovulation.     

Update on antimicrobial susceptibility and genotype of Neisseria gonorrhoeae isolated in Italy

Antimicrobial susceptibilities and genotypes of Neisseria gonorrhoeae collected in 2006-2010 from 6 medical centers located in Italy were compared with those from a previous survey conducted in 2003-2005. Resistance to ciprofloxacin increased from 34.2% to 62% whereas penicillin resistance declined from 25.5% to 14%. Important change in antimicrobial resistance rates and a high genetic variability among N. gonorrhoeae from Italy were observed.     

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial

Abstract. Latini R, Masson S, Pirelli S, Barlera S, Pulitano G, Carbonieri E, Gulizia M, Vago T, Favero C, Zdunek D, Struck J, Staszewsky L, Maggioni AP, Franzosi MG, Disertori M on the behalf of the GISSI‐AF Investigators (Istituto di Ricerche Farmacologiche “Mario Negri”, Milan; Istituti Ospitalieri, Cremona; POL Madonna della Consolazione, Reggio Calabria; Ospedale Nuovo Girolimo Fracastoro, San Bonifacio; Ospedale Garibaldi‐Nesima, Catania; Ospedale Luigi Sacco, Milan, Italy; Roche Diagnostics, Rotkreuz, Switzerland; B.R.A.H.M.S. AG, Henningsdorf, Germany; ANMCO Research Center, Florence; and Ospedale Santa Chiara, Trento, Italy). Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI‐Atrial Fibrillation Trial. J Intern Med 2011; 269 : 160–171. Objective. We evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). Background. Predicting long‐term maintenance of sinus rhythm in patients with AF is difficult. Methods. Plasma concentrations of three specific cardiac markers [high‐sensitivity troponin T (hsTnT), N‐terminal probrain natriuretic peptide (NT‐proBNP) and mid‐regional proatrial natriuretic peptide (MR‐proANP)] and three stable fragments of vasoactive peptides [mid‐regional proadrenomedullin (MR‐proADM), copeptin (CT‐proAVP) and CT‐proendothelin‐1 (CT‐proET‐1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI‐AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. Results. Mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04–1.28], P = 0.007), MR‐proANP (1.15 [1.01–1.30], P = 0.04), NT‐proBNP (1.24 [1.11–1.39], P = 0.0001) and CT‐proET‐1 (1.16 [1.01–1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR‐proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98–2.37], P = 0.06). Conclusion. Circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.