In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.

the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.

ObjectiveTo assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).MethodsWe measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients’ follow-up was maintained for 2 years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.ResultsSerum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7 ng/mL (sensitivity 46%, specificity 84%).ConclusionsIn patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.

Mutations in genes coding for subunits of the neuronal nicotinic acetylcholine receptor (nAChR) have been involved in familial sleep-related hypermotor epilepsy (also named autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE). Most of these mutations reside in CHRNA4 and CHRNB2 genes, coding for the α4 and β2 nAChR subunits, respectively. Two mutations with contrasting functional effects were also identified in the CHRNA2 gene coding for the α2 subunit. Here, we report the third mutation in the CHRNA2 , found in a patient showing ADNFLE. The patient was examined by scalp EEG, contrast-enhanced brain magnetic resonance imaging (MRI), and nocturnal video-polysomnographic recording. All exons and the exon-intron boundaries of CHRNA2 , CHRNA4 , CHRNB2 , CRH , KCNT1 were amplified and Sanger sequenced. In the proband, we found a c.754T>C (p.Tyr252His) missense mutation located in the N-terminal ligand-binding domain and inherited from the mother. Functional studies were performed by transient co-expression of α2 and α2 Tyr 252 His , with either β2 or β4, in human embryonic kidney (HEK293) cells. Equimolar amounts of subunits expression were obtained by using F2A-based multi-cistronic constructs encoding for the genes relative to the nAChR subunits of interest and for the enhanced green fluorescent protein. The mutation reduced the maximal currents by approximately 80% in response to saturating concentrations of nicotine in homo- and heterozygous form, in both the α2β4 and α2β2 nAChR subtypes. The effect was accompanied by a strong right-shift of the concentration-response to nicotine. Similar effects were observed using ACh. Negligible effects were produced by α2 Tyr252His on the current reversal potential. Moreover, binding of (±)-[ 3 H]Epibatidine revealed an approximately 10-fold decrease of both K d and B max (bound ligand in saturating conditions), in cells expressing α2 Tyr252His . The reduced B max and whole-cell currents were not caused by a decrease in mutant receptor expression, as minor effects were produced by α2 Tyr252His on the level of transcripts and the membrane expression of α2β4 nAChR. Overall, these results suggest that α2 Tyr252His strongly reduced the number of channels bound to the agonist, without significantly altering the overall channel expression. We conclude that mutations in CHRNA2 are more commonly linked to ADNFLE than previously thought, and may cause a loss-of-function phenotype.

Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na+-gated K+ channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns α4 and β2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant α2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of α2-containing (α2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have different effects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.

There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.

INTRODUZIONEL'artrite reumatoide (AR) è una delle più severe malattie croniche, con sintomatologia dolorosa, che comporta una progressiva perdita della mobilità e la diminuzione della qualità della vita a causa della progressiva distruzione delle strutture articolari [1]. L'esordio avviene tra i 25/50 anni, ma non sono rari i casi di artrite reumatoide infantile [2]. È una malattia invalidante che colpisce l'organismo nel suo insieme; le articolazioni colpite più frequentemente sono mani, ginocchia, anche e piedi, la cui struttura, nei casi più gravi viene alterata causando deformità [3]. La prevalenza dell'AR in Italia è stimata pari allo 0,5%, circa 300.000 persone, in prevalenza donne [2]. A causa dei gravi effetti invalidanti presenta costi elevati per il sistema sanitario nazionale e per la società anche quando è trattata con le migliori terapie tradizionali [4]. Nel lavoro di Leardini [5] sul costo sociale dell'artrite reumatoide in Italia, si è stimato un costo diretto annuo che varia tra 1.643 euro e 5.697 euro per persona, a seconda delle 4 classi di gravità della malattia, e dei costi indiretti annui (le perdite di produzione sul sistema economico) che variano da 2.705 euro a 17.249 euro secondo la gravità della malattia.Il trattamento con farmaci antinfiammatori (FANS e corticosteroidi) e con i cosiddetti DMARD, Disease Modifying Antirheumatic Drugs (ad esempio methotrexate), purtroppo cura solo i sintomi, ma non il progredire della malattia e nemmeno i danni irreversibili alla capacità motoria, che rendono impossibili le normali attività quotidiane [6]. Studi anglosassoni indicano che a 10 anni dalla diagnosi il 44% dei pazienti risulta inabile al lavoro e dopo ABSTRACTRheumatoid arthritis is one of the most severe chronic pathologies, affecting the whole organism, with invalidating outcomes that affect the quality of life of the patients. Its prevalence is estimated to be about 0,5% in Italy, with elevated costs for the national health system (NHS) and the society, in spite of the best treatment with traditional therapies that include anti-inflammatory and disease modifying antirheumatic drugs (DMARDs). The introduction of new drugs with biological activity, mainly acting through an antagonism of tumor necrosis factor (anti-TNF), is a great advance in the management of the disease, as their use has been shown to be effective in slowing the progression of the joint damage, and sometimes in reversing it,.The present article present a cost-minimization study conducted by comparing the two anti-TNFs available in Italy, etanercept and infliximab, assuming equal efficacy and approached from the perspectives of the Italian NHS and society. Only differential costs were considered, i.e. drug acquisition, drug administration and patient monitoring costs, and the analysis comprised two treatment years, in order two account for the cost differences between the first treatment year and the following. The analysis showed that infliximab represents the more convenient alternative from both the NHS and the societ...