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Aims: To assess the long-term outcomes of patients treated with sirolimus-eluting Stentys stent in a real-life setting., Background: Few data regarding the safety and effectiveness of self-apposing sirolimus-eluting Stentys stent are available., Methods: 278 patients (30% stable coronary artery disease, 70% acute coronary syndromes, and 54% on unprotected left main) treated with sirolimus eluting Stentys stent were retrospectively included in the self-aPposing, bAlloon-delivered, siRolimus-eluting stent for the Treatment of the coronary Artery disease multicenter registry. Major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, target lesion revascularization, stent thrombosis) were the primary end-point, single components of MACE were the secondary ones., Results: After 13 months (interquartile range 5-32), MACE was 14%. Stent thrombosis occurred in 3.9% of the patients (2.5% definite stent thrombosis and 1.4% probable stent thrombosis), 66% of them presenting with ST-segment elevation myocardial infarction (STEMI) at admission. Cardiovascular death, target lesion revascularization and myocardial infarction was 4.7%, 8.3%, and 7.2%, respectively. At multivariate analysis, risk of MACE was increased by diabetes (hazard ratios 4.76; P = 0.002) but was not affected by the indication leading to sirolimus-eluting Stentys stent implantation (marked vessel tapering vs. coronary ecstasies, hazard ratios 0.74, P = 0.71)., Conclusion: Sirolimus-eluting Stentys stent may represent a potential solution for specific coronary anatomies such as bifurcation, ectasic, or tapered vessels. Risk of stent thrombosis appears related to clinical presentation with STEMI and to anatomic features, stressing the importance of the use of intracoronary imaging for self-expandable stents implantation.

Background: Radial artery approach is currently the most common access site for coronary angiography and percutaneous coronary intervention. It rarely results in complications, improves patient comfort, and reduces the duration of hospitalization., Case Presentation: A 91-year-old woman presented to our institution with ST-segment elevation myocardial infarction (STEMI). The right radial access was chosen for the performance of percutaneous coronary intervention. After the introduction of 6 F sheath, there was difficulty in the advancement of 0.035 J wire that was exchanged with a Terumo hydrophilic wire. After the procedure and before sheath removal, radial arteriography was done and revealed perforation. Protamine sulfate was administered and prolonged balloon inflation was attempted but failed to seal the perforation, so a 7-F-long vascular sheath was inserted to internally tamponade the vessel, and the patient was sent to the coronary care unit for monitoring. Over the next 3 days, serial radial angiographies were done revealing the persistence of the perforation, and on the fourth day, angiography revealed multiple thrombi. Thrombus aspiration was done using Pronto V4 extraction catheter (Vascular Solutions, USA) and was followed by the deployment of a covered stent. The stent was dislodged and successfully snared. Finally, the perforation was sealed spontaneously and there were no signs of intra-arterial thrombi., Conclusion: Despite the very low complication rate of radial approach, the interventional cardiologist should be aware of any possible complication, and how to avoid or, eventually, manage it.

Aims: To evaluate the angiographic performance of a novel sirolimus-coated balloon (SCB) in de novo coronary lesions., Methods: Out of an all-comer prospective registry of patients treated with the SCB at our center from April 2016 to September 2017, we selected those treated for a de novo stenosis on a native vessel, with a scheduled angiographic control at at least 4 months after the index procedure. We performed a centralized, blinded core-lab adjudicated quantitative coronary angiography analysis. Primary endpoint was late lumen loss. Secondary endpoints were binary restenosis and target-lesion revascularization., Results: A total of 27 patients with native coronary arteries treated with SCB and with angiographic follow-up entered the study; seven patients were excluded because a stent was implanted at the lesion site during the index procedure. The degree of calcification (assessed with coronary angiography) was high in six patients (30%) and the average lesion length was 20.52 ± 6.88 mm. The reference vessel diameter was 2.32 ± 0.44 mm and the percentage diameter stenosis was 67 ± 12. Procedural success was obtained in all patients. After a median of 6.6 ± 2.5 months, late lumen loss was 0.09 ± 0.34 mm and the percentage diameter stenosis was 31 ± 18. We observed two cases (10%) of binary restenosis which underwent subsequent target-lesion revascularization: in one a drug-eluting stent was implanted, whereas the other patient was treated with paclitaxel-coated balloon. No myocardial infarction or death was observed during follow-up., Conclusion: The use of a novel SCB in native coronary arteries was associated with good angiographic outcome at 6-month follow-up.

The ability to design surfaces with reversible, high-affinity protein binding sites represents a significant step forward in the advancement of analytical methods for diverse biochemical and biomedical applications. Herein, we report a dynamic supramolecular strategy to directly assemble proteins on surfaces based on multivalent host-guest interactions. The host-guest interactions are achieved by one-step nanofabrication of a well-oriented β-cyclodextrin host-derived self-assembled monolayer on gold (β-CD-SAM) that forms specific inclusion complexes with hydrophobic amino acids located on the surface of the protein. Cytochrome c, insulin, α-chymotrypsin, and RNase A are used as model guest proteins. Surface plasmon resonance and static time-of-flight secondary ion mass spectrometry studies demonstrate that all four proteins interact with the β-CD-SAM in a specific manner via the hydrophobic amino acids on the surface of the protein. The β-CD-SAMs bind the proteins with high nanomolar to single-digit micromolar dissociation constants ( K D ). Importantly, while the proteins can be captured with high affinity, their release from the surface can be achieved under very mild conditions. Our results expose the great advantages of using a supramolecular approach for controlling protein immobilization, in which the strategy described herein provides unprecedented opportunities to create advanced bioanalytic and biosensor technologies.

Background: The aim of the Nanoluté registry was to observe the clinical performance of a novel sirolimus coated balloon (SCB) (Concept Medical Research Private Limited, India) for the treatment of coronary de-novo and restenotic lesions., Methods: All patients treated with SCB between July 2012 and September 2015 were enrolled at Indian centres and clinically followed for 1, 3, 6 and 12 months post-procedure. Primary endpoints were procedural success and device-oriented adverse cardiac events (DOCE) at 12 months. DOCE were defined as a composite of cardiac death, target lesion revascularization (TLR) and target vessel-myocardial infarction., Results: A total of 394 SCB were used in 332 patients to treat 356 lesions. In-stent restenosis and small coronary vessel disease occurred in 46% and 43% of the patients respectively. Mean balloon length and diameter (average ± SD) were 21.83 ± 6.70 mm and 2.69 ± 0.45 mm respectively. All patients with 1 year follow-up were included. Overall DOCE rate was 4.2% (n = 14) which included death 0.3% (n = 1), TLR 3.6% (n = 12) and myocardial infarction 0.3% (n = 1)., Conclusion: The Nanoluté prospective registry, is the first clinical evidence of the safety and feasibility of this type of SCB, both in patients with in-stent restenosis or de novo lesions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Kinesins are a family of proteins for anterograde transport of the molecules from the neuronal cell body and their impairment has been widely associated with neurodegeneration of the motor neurons. KIF5A gene causes autosomal dominant spastic paraplegia 10, a neurological disorder characterized by spasticity and weakness of the lower limbs (SPG10). We carried out a screening of KIF5A gene in 50 subjects affected by HSP negative to diagnostic test for SPG4, ATL1 and REEP1. We identified a novel variation p.Ile255Met in a 58-year-old man who developed progressive gait disturbance due to spastic paraparesis complicated by axonal neuropathy.

Background: In the recent years percutaneous treatment of the left main stem (LM) has gained a precise role as a result of consistent scientific evidence vs. coronary artery bypass. A self-apposing stent offers an improved adaptation to the vessel wall, especially in case of tapered vessels; aim of this study was to investigate the role of a novel self-apposing, sirolimus-eluting stent (Stentys, France) for the treatment of LM coronary artery disease., Methods and Results: MATISSE is a retrospective, multicenter registry, which enrolled 151 patients treated with the device at 17 international centers. Primary study endpoint was the occurrence of major adverse cardiovascular events (MACE), a composite endpoint of cardiac death, target lesion revascularization (TLR) and target-vessel myocardial infarction, at 9months clinical follow-up. Secondary endpoints included procedural success, the single determinants of MACE and stent thrombosis. Lesions were located in distal LM bifurcation in 84% of the patients. Procedural success was achieved in 150 patients. The average follow-up length was 348±52days. MACE occurred in 14 (9.3%) patients with 2 (1.3%) cardiac deaths. TLR occurred in 8 patients (5.3%). There were 2 cases of definite stent thrombosis, 1 acute and 1 very late., Conclusions: A self-apposing stent, when used for LM PCI in a real world, high risk population, showed good immediate procedural results with low rates of adverse events at mid-term follow-up., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Drug-coated balloons (DCB) have been developed in recent years to overcome some of the drug-eluting stents limitations. There is an established indication for the use of DCB in the treatment of in-stent restenosis and they are also variably used in various setting, in particular small coronary vessels and bifurcations. Until 2016, all DCBs available in Europe eluted paclitaxel, a highly lipophilic drug with narrow therapeutic window. In April 2016 a new sirolimus-coated balloon (Magic Touch®, Envision Scientific PVT, Bhatpore, India) obtained the CE Mark. This device shares a new-generation delivery system and is able to release in a few seconds an effective dosage of sirolimus.

Background: Patients with small vessel disease (SVD) are at higher risk of adverse events after PCI compared to non-SVD patients. In this subset, the use of bioresorbable vascular scaffolds (BVS) has raised particular concern., Objective: We aimed to compare outcomes of Absorb BVS versus a 2nd-generation metallic everolimus-eluting stents (EES) in the SVD setting, by pooling patients from three large, prospective studies., Methods: Patients with SVD (reference vessel diameter ≤2.75 mm by QCA) and treated with Absorb BVS were identified in the Italian RAI and the MAASSTAD-Absorb registries. EES controls were identified in the COMPARE II Trial. We performed a propensity-score matching using several clinical and angiographic variables. Implantation technique was not object of matching, being device-specific., Results: Out of 4635 enrolled subjects, 1147 belonged to the SVD population. After matching, we obtained 337 pairs of patients. High clinical and angiographic complexity was found in both groups. Predilation and postdilation rates were significantly higher in BVS patients. No differences were found in terms of the device-oriented composite end-point at 1-year (HR = 1.08, 95%CI 0.5-2.3, P = .8) and 2-years (HR = 1.28, 95% CI: 0.68-2.43, P = .5). Notwithstanding, higher incidence of definite/probable stent thrombosis was observed in the BVS group at 1 year (HR 4.7, 95%CI 0.8-31.4, P = .08) and 2-years (HR = 8.34 95%CI 1.1-60.2, P = .04)., Conclusion: In this propensity-matched analysis pooling SVD patients of three large prospective studies, incidence of composite device-related events was comparable between BVS and EES up to 2 years follow-up. However, higher rates of stent thrombosis were found in the BVS group., (© 2018 Wiley Periodicals, Inc.)

Coronary Sinus Reducer (Neovasc, Inc., Richmond B.C., Canada) has shown to be an effective and safe treatment option for the treatment of refractory angina. Until now, a few number of complications related to its implantation have been reported. Coronary sinus perforation is a rare complication, more often related to cardiac surgery procedures. We report the first case of coronary sinus perforation after a sinus Reducer implantation., (© 2018 Wiley Periodicals, Inc.)

Percutaneous treatment of the unprotected left main trunk (ULM), defined as a vessel without patent bypass graft either to the left circumflex (LCX) or left anterior descending (LAD) artery, has gained a precise role thanks to recent scientific evidence. Although new generation drug-eluting stents have already proven to be safer, there is still a consistent risk of restenosis and late adverse events. The optimal management of a ULM restenosis is still debated. Here we aim at presenting a review of the available data in literature and show our choice for treating it., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Drug-coated balloons (DCBs) are a recognized alternative to stents for the treatment of in-stent restenosis (ISR), and there is some initial clinical evidence about their efficacy for the treatment of small coronary vessels. Newer-generation DCBs were developed to overcome the reduced deliverability of the previous generation, also warranting a more effective drug delivery to vessel wall. However, the vast majority of new-generation DCBs still lack of reliability due to paucity of clinical data., Methods: Between 2012 and 2015, all patients treated with Elutax SV DCB (Aachen Resonance, Germany) at nine Italian centers were enrolled in this retrospective registry. Primary outcome was the occurrence of target-lesion revascularization (TLR) at the longest available follow-up. Secondary endpoints were procedural success and occurrence of device-oriented adverse cardiovascular events including cardiac death, target-vessel myocardial infarction, stroke, and TLR. A minimum 6-month clinical follow-up was required., Results: We enrolled 544 consecutive patients treated at 583 sites. Fifty-three per cent of the patients had ISR, and the rest native vessel coronary artery disease. Procedural success occurred in 97.5%. At the longest available clinical follow-up (average 13.3 ± 7.4 months), 5.9% of the patients suffered a TLR and 7.1% a device-oriented adverse cardiovascular event. We did not register cases of target-vessel abrupt occlusion. At multivariate analysis, severe calcification at the lesion site was the first determinant for the occurrence of TLR., Conclusion: This registry on the performance of a new-generation DCB shows an adequate profile of safety and efficacy at mid-term clinical follow-up.

Drug-coated balloons (DCB) are being used for in-stent restenosis treatment and there is some preliminary experience in other coronary settings, including small vessels and side branches. Scoring balloons (SB) are a useful tool for the preparation of fibro-calcific lesions. Because of the controlled micro-dissections that SB induce, it has been hypothesized that they may have a role in helping paclitaxel deliverability inside the vessel wall. The AngioSculpt®X (Spectranetics) is a novel paclitaxel-coated SB with encouraging preliminary data for the treatment of in-stent restenosis. We here describe our first experience treating two de novo coronary lesions with angiographic follow up., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: to understand the role of a transradial (TR) secondary approach during complex percutaneous interventions., Background: The value of the TR route for ancillary vascular approach has not been adequately validated in this setting, and there is scant data on its role in reducing bleeding complications., Methods: In the present study we retrospectively included patients undergoing the following interventions requiring two vascular approaches at nine high-volume centers in Italy: structural cardiac interventions, complex PCI, endovascular aortic repair (EVAR) and complex lower limb angioplasty. We compared procedural outcomes according to the type of ancillary vascular approach selected, namely TR or transfemoral/transbrachial (TF/TB). Primary endpoints of the study were procedural success and in-hospital BARC grade 3-5 bleedings., Results: We included 906 patients, 433 receiving TR and 473 TF/TB ancillary approaches. Baseline characteristics did not differ significantly. Patients underwent the following types of intervention: structural 50%, complex coronary PCI 37%, EVAR 11%, peripheral angioplasty 2%. Procedural success was similar (90% in TR and 92% TF/TB, P = NS). In-hospital BARC 3/5 bleedings were more common in TF/TB group as compared to TR group (19.7% vs. 6.7%,P < 0.001). In TF/TB group we also observed a higher postprocedural hemoglobin drop (1.92 vs 1.13 g/dl, P = 0.008) and longer hospital stay as compared to TR group. Similar results were observed in a propensity score-matched population of 450 patients., Conclusions: In our study TR ancillary approach was associated with a significant reduction in the risk of major bleedings, without jeopardizing the success of complex structural, coronary, and peripheral percutaneous interventions. The value of the transradial route for ancillary vascular approach during percutaneous interventions has not been adequately validated yet. We retrospectively included 906 patients, 433 receiving TR and 473 TF/TB ancillary approach at nine high-volume centers for the following interventions: structural cardiac interventions, complex PCI, EVAR and complex peripheral angioplasty. Procedural success was similar, whereas in-hospital BARC bleedings were more common in the transfemoral/brachial group. Similar results were observed in a propensity score-matched population. In our study TR ancillary approach was associated with a significant reduction in the risk of major bleedings, without jeopardizing the success of complex interventions. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Purposes: Drug-coated balloons (DCB) currently represent an alternative to drug-eluting stents (DES) for the treatment of in-stent restenosis and they are also variably used for small coronary vessel and bifurcation lesion management. All DCB variably elute paclitaxel as an anti-proliferative drug. The first sirolimus coated balloon (SCB) received the CE mark in 2016, but its clinical performance has not been shown yet., Methods and Results: FASICO in an all-comer registry of the first consecutive patients with at least one lesion treated with SCB between March and July 2016 at the first European centre that used this device. All patients were prospectively enrolled in a dedicated database. Primary endpoint was procedural success; co-primary endpoint was the rate of major adverse cardiac events at short-term follow-up. The 32 patients (34 lesions) enrolled had at least 6-month clinical follow up available. Forty-five percent had diabetes and indication to PCI was ISR in 47% of the cases. Lesions were always pre-dilated and device deployment was successful in all the cases. Procedural success was achieved in 100% of patients. We observed 3 cases of TLR at follow-up., Conclusions: SCB shows high immediate technical performance and adequate short-term efficacy and safety. The ongoing EASTBOURNE registry will shed light on mid-and long-term performance of this device in an adequately powered population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bioresorbable vascular scaffolds (BVS) are being increasingly used in complex, real-world lesions. The possibility of strut fractures is a rare entity with the use of drug eluting stents (DES), but has not yet been adequately described for the BVS technology. In this report, we present a case of scaffold fracture of DEsolve BVS (Elixir Medical Corporation, USA) that was diagnosed both angiographically and by optical coherence tomography(OCT). Scaffold fracture with the newer BVS is a new Achilles' heel in the BVS technology. This gap in knowledge about the etiology such as over-expansion and potential predictors of strut fracture need to be deeply investigated before a widespread use of such technologies is adopted. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objectives: The aim of this study is to evaluate the role of drug-coated balloons (DCB) for the management of bioresorbable vascular scaffold (BVS) restenosis., Methods and Results: In a series of 25 BVS restenosis discovered during systematic angiographic follow up of 246 consecutive BVS implantations at our institution, DCB was used as a primary therapeutic tool in 9 patients and 3 different types of DCB were used. Follow-up coronary angiography at 12months after DCB treatment was performed to all the patients. Among the 9 patients treated with DCB, angiographic follow up revealed failure in two patients that experienced type III restenosis (both of them treated with the same type of DCB). Both patients were treated with drug eluting stent implantation., Conclusions: In this case series of consecutive patients with BVS restenosis, the use of certain types of DCB is safe and effective in order to maintain vessel patency at mid-term follow up. Despite the small sample size and the study limitations, DCB can provide therefore an alternative treatment option in this setting, avoiding the implantation of further metallic stents in a patient where a different strategy was initially planned., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: With this prospective study we aim at investigating the long-term outcome of a consecutive cohort of patients successfully treated with bioresorbable scaffold (BVS) implantation., Background: It is not clearly understood if there is a relation between the technique of BVS implantation and the outcome., Methods: Between December 2012 and December 2014, all consecutive patients treated with BVS were included in this registry and received an angiographic follow-up. After a run-in phase, all BVS were implanted using a specific technique consisting of aggressive predilation, correct scaffold sizing, visually determined, and high-pressure post-dilation with a noncompliance balloon. Primary endpoint was late lumen loss (LLL) at 1-year angiographic follow-up and ischemia-driven target-lesion revascularization (ID-TLR) at 2-year clinical follow-up. Secondary endpoints were the occurrence of binary restenosis, major adverse cardiac events (MACE), and every single component of MACE (cardiac death, myocardial infarction, TLR) at 2 years., Results: A total of 144 lesions in 122 patients treated consecutively with BVS, were enrolled. Diabetics were 29.5% and acute coronary syndrome at presentation occurred in 29.5% of patients. At the angiographic follow-up LLL was 0.38 ± 0.9. At 2-year clinical follow-up, ID-TLR occurred in eight patients (5.6%). We observed two cases of scaffold thrombosis (1.38%, one early and one very late). At multivariate statistical analysis, STEMI presentation remained a significant predictor for TLR., Conclusions: In a complex, all-comers real world population, BVS implantation with a specific, and standardized technique showed to be feasible, with acceptable mid-term angiographic and long-term clinical outcome., (© 2017, Wiley Periodicals, Inc.)

Background: Due to the inherent limitations of current generation BVSs, complex coronary artery disease often contains BVS unsuitable segments. Our aim was to assess the feasibility of a hybrid approach using bioresorbable vascular scaffolds (BVSs) and drug-eluting stents (DESs) for the treatment of complex coronary artery lesions not suitable for a scaffolding only approach., Methods: A retrospective multicenter cohort analysis was performed on patients with complex de novo or in-stent restenosis lesions treated with a hybrid BVS (Absorb BVS, Abbott Vascular, Santa Clara, CA) and DES strategy. The primary endpoint was target lesion failure (TLF) defined as a composite of cardiac death, target-vessel myocardial infarction (MI) and target lesion revascularization (TLR)., Results: A total of 98 patients (105 lesions) were treated with the hybrid strategy. Isolated long lesions in which either proximal or distal reference vessel diameters were not suitable for BVS were an indication in 36.2% (n=38) of cases. In contrast, 28% (n=29) of lesions treated with the hybrid strategy were bifurcations in which the side branch was predominantly treated with DES (n=28). DES bailout after BVS implantation was an indication in 21.9% (n=23 lesions). The rates of type B2/C and long lesions (>28mm) were 95.2% and 74.3% respectively. The mean total BVS and DES lengths implanted were 37.5±24.1mm and 25.0±14.7mm respectively. The rate of TLF in the overall cohort of patients (median follow-up 405days [interquartile range 189-658]) was 11.4% at 1-year. This was primarily driven by TLR (9.5%), with rates of cardiac death and target vessel MI of 2.1% and 1.4% respectively. No cases of definite or probable BVS/DES thrombosis occurred., Conclusion: In conclusion, the use of a hybrid BVS/DES strategy was feasible and associated with acceptable outcomes at 1-year, considering the length and complexity of lesions treated. Further, larger studies with longer follow-up are needed to confirm our findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Drug-eluting stents (DES) represent nowadays the gold standard treatment for coronary artery disease. Despite the safety and efficacy, and favorable long-term clinical outcomes of new generation DES, their use is still associated with a not negligible risk of long-term events, related to the presence of a definitive prosthesis in the vessel wall. In addition, DES implantation is not always desirable in particular anatomic settings (small vessels, bifurcations) or in patients with higher bleeding risk. In recent years, drug-coated balloons (DCB) have been developed to overcome some of these limitations, offering a combined mechanical (balloon dilation) and biological therapy (drug-release). In the coronary setting, there is already a clear indication for the treatment of in-stent restenosis, but recent studies showed favorable results also when DCB are used for the treatment of de novo lesions.Regarding peripheral artery disease management, conventional transcatheter therapies with balloon angioplasty, atherectomy and stents are limited by high restenosis rates; in addition, stent implantation in lower limb vessels alter artery wall compliance, increasing stiffness, with a higher risk of restenosis and stent fracture. DCB represent a good alternative and have shown good safety and efficacy also in this setting.

In contrast with conventional single-molecule junctions, in which the current flows parallel to the long axis or plane of a molecule, we investigate the transport properties of M(II)-5,15-diphenylporphyrin (M-DPP) single-molecule junctions (M=Co, Ni, Cu, or Zn divalent metal ions), in which the current flows perpendicular to the plane of the porphyrin. Novel STM-based conductance measurements combined with quantum transport calculations demonstrate that current-perpendicular-to-the-plane (CPP) junctions have three-orders-of-magnitude higher electrical conductances than their current-in-plane (CIP) counterparts, ranging from 2.10 -2 G 0 for Ni-DPP up to 8.10 -2 G 0 for Zn-DPP. The metal ion in the center of the DPP skeletons is strongly coordinated with the nitrogens of the pyridyl coated electrodes, with a binding energy that is sensitive to the choice of metal ion. We find that the binding energies of Zn-DPP and Co-DPP are significantly higher than those of Ni-DPP and Cu-DPP. Therefore when combined with its higher conductance, we identify Zn-DPP as the favoured candidate for high-conductance CPP single-molecule devices.

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

Increasing evidence links dysregulation of NR2B-containing N-methyl-D-aspartate receptor remodelling and trafficking to Alzheimer's disease (AD). This theme offers the possibility that the GRIN2B gene, encoding this selective NR2B subunit, represents a potential molecular modulating factor for this disease. Based on this hypothesis, we carried out a mutation scanning of exons and flanking regions of GRIN2B in a well-characterized cohort of AD patients, recruited from Southern Italy. A "de novo" p.K1293R mutation, affecting a highly conserved residue of the protein in the C-terminal domain, was observed for the first time in a woman with familial AD, as the only genetic alteration of relevance. Moreover, an association study between the other detected sequence variants and AD was performed. In particular, the study was focused on five identified single nucleotide polymorphisms: rs7301328, rs1805482, rs3026160, rs1806191 and rs1806201, highlighting a significant contribution from the GRIN2B rs1806201 T allele towards disease susceptibility [adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI) 1.40-2.63, p < 0.001, after correction for sex, age, and APOE ε4 genotype]. This was confirmed by haplotype analysis that identified a specific haplotype, carrying the rs1806201 T allele (CCCTC), over-represented in patients versus controls (adjusted OR = 6.03; p < 0.0001). Although the pathogenic role of the GRIN2B-K1293R mutation in AD is not clear, our data advocate that genetic variability in the GRIN2B gene, involved in synaptic functioning, might provide valuable insights into disease pathogenesis, continuing to attract significant attention in biomedical research on its genetic and functional role.

Unlabelled: γ-Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid-β (Aβ) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer's disease (FAD). Presenilin enhancer-2 gene (PEN-2) is a necessary component of the γ-Secretase complex. Recently, it has been shown that PEN-2 mutations could be involved in Alzheimer's disease (AD). We performed a mutational screening of all PEN-2 coding and promoter regions in a FAD cohort derived from Southern Italy. Four hundred and fifty-two subjects (FAD: 97;, Controls: 355) were recruited for this study. We identified for the first time in a key region necessary for the promoter activity a novel 3 bp deletion in a subject with early-FAD. Our genetic data demonstrate that the mutant allele may influence the transcriptional activity of the PEN-2 gene. Although the effective role of the PEN-2 promoter deletion in AD is not entirely clear, these findings might lead to more studies on its functional and genetic role., (Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

As with other autoimmune diseases, susceptibility to multiple sclerosis (MS) is believed to result from the complex interaction of a number of genes, each with modest effect. Several genome-wide screens have implicated the nitric oxide synthase 2A gene (NOS2A), which encodes the inducible form of nitric oxide synthase, as being potentially associated with MS. To determine whether genetic variants within this gene may constitute a risk factor for causing MS, we investigated 13 single nucleotide polymorphisms in the NOS2A gene, in a case-control group of 214 Italian patients with MS and 121 controls. All these single nucleotide polymorphisms (SNPs) were analyzed using the SNPlex™ Genotyping System (Applied Biosystems). Data were analyzed using Genemapper 4.0 and Haploview 4.1. No significant association between cases and controls (P>0.05) was observed for the alleles of the SNPs. Defining the haplotype blocks also failed to detect any associated haplotypes. Our results suggest that polymorphic variation within the NOS2A gene does not influence the susceptibility to MS in patients of Italian origin., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an estimated incidence of one in 3,500 births. Clinically, NF1 is characterized by café-au-lait (CAL) spots, neurofibromas, freckling of the axillary or inguinal region, Lisch nodules, optic nerve glioma, and bone dysplasias. NF1 is caused by inactivating mutations of the 17q11.2-located NF1 gene. We present a clinical and molecular study of an Italian family with NF1., Methods: The proband, a 10-year-old boy, showed large CAL spots and freckling on the axillary region and plexiform neurofibromas on the right side only. His father (47 years old) showed, in addition to the similar signs, numerous neurofibromas of various sizes on his thorax, abdomen, back, and shoulder. Two additional family members (a brother and a sister of the proband) presented only small CAL spots. The coding exons of NF1 gene were analyzed for mutations by denaturing high-performance liquid chromatography and sequencing in all family members., Results: The mutational analysis of the NF1 gene revealed a novel frameshift insertion mutation in exon 4c (c.654 ins A) in all affected family members. This novel mutation creates a shift on the reading frame starting at codon 218 and leads to the introduction of a premature stop at codon 227., Conclusions: The segregation of the mutation with the affected phenotype and its absence in the 200 normal chromosomes suggest that it is responsible for the NF1 phenotype.

Pheochromocytoma is a rare tumor that produces a distant effect by secretion of catecholamines. This tumor usually presents with hypertension and palpitations but it may also cause cardiogenic shock because of catecholamine-induced myocardial dysfunction. We describe a rare case of Takotsubo-like cardiomyopathy as first manifestation of pheochromocytoma with an unusual onset characterized by severe hypotension and transient basal left ventricular ballooning ('inverted' Takotsubo-like cardiomyopathy).

The human DRD2 gene is located on chromosome 11q22-q23 and contains one specific functional polymorphism called TaqIA, which characteristically presents two alleles referred to as A1 and A2. Evidence indicates that the A1 allele impacts brain dopaminergic function and may confer an increased risk of developing Parkinson's disease. However, possible morphological changes underlying such genetic variant remain to be clarified. The aim of this study was to provide an in vivo demonstration of changes in brain structures associated with the TaqIA polymorphism of the DRD2 gene. Optimized voxel-based morphometry (VBM) was applied to high-resolution MR brain images of 70 healthy controls divided into two groups according to their DRD2 genotype (A1/A2, n = 15; A2/A2, n = 55). Compared with individuals' homozygous for the A2 allele, the A1 carriers had significantly smaller areas of a specific part of the midbrain, encompassing the substantia nigra bilaterally. Our findings showed an association of the DRD2 TaqIA polymorphism with the changed volumes of a specific subcortical region strongly involved in the dopaminergic system.

This report is part of a 2-year study assessing the functional effect of Brain-Derived Neurotrophic Factor (BDNF) and its Val66Met polymorphism on a selected population of Relapsing-Remitting Multiple Sclerosis (RRMS) patients from Southern Italy. For this purpose, we measured the peripheral BDNF expression in RRMS patients compared to healthy controls. The influence of concomitant IFNbeta therapy was also evaluated. Thirty-six inactive RRMS patients and 37 healthy controls were genotyped for BDNF Val66Met, and total RNA was extracted at time-points 0-24 months. The BDNF level was quantified by ABI Prism 7900 HT Sequence Detection System, and its relative expression was calculated by the comparative method of 2(-DeltaDeltaCt). At baseline and after 24 months, the BDNF levels of RRMS patients resulted significantly higher than controls (p=0.001), independently of the concomitant IFNbeta treatment; no correlations were found with the investigated clinical and MRI features of MS. Otherwise, carriers of the Met-allele showed significantly higher levels of BDNF in RRMS patients than healthy controls (p=0.005). These data was replicated after a 24-month interval. The present study confirms the increased levels of peripheral BDNF levels in RRMS, even during the inactive phase of the disease. Although with caution due to the small sample size, it also underscores the potential role of the Val66Met polymorphism on the peripheral BDNF expression in RRMS. Functional studies are needed to better clarify this issue.

The gene encoding the inducible form of Nitric Oxide Synthase (NOS2A) has been considered with interest in the evaluation of the genetic predisposition to Multiple Sclerosis (MS). The aim of the present study was to address the possible contribution of two microsatellites repeats of the NOS2A promoter region - (CCTTT)(n) and (AAAT)(n) - to MS susceptibility. One hundred and thirteen Italian patients with clinically definite RRMS and 237 age and sex matched healthy controls from Calabria (South Italy) were studied. The distribution analysis of the markers frequencies showed that the (CCTTT)(14) allele was found in 11.5% of the RRMS patients and in 25.3% of the healthy subjects, with a statistically significant difference (chi(2)=8.843, p=0.003). This data seems to confer a significant protection against MS (OR=0.348; 95% CI=0.174-0.693, corrected for age and gender). No association with MS susceptibility was observed for the bi-allelic (AAAT)(n) microsatellite. In conclusion, we found that the NOS2A (CCTTT)(14) allele was detected more frequently in the control group than in the RRMS patients, thus confirming the scientific interest on this marker.

Radiofrequency thermoablation (RFA) in performing parenchymal liver section has been tested. Eleven patients with primary cancer or colorectal cancer metastasis underwent anatomical major liver resection after vascular control. Parenchymal section was performed by knife after coagulative necrosis. No deaths, clinical or technical complications or blood losses occurred. Such technique is feasible and effective.

MAGE is a family of genes specifically associated to human melanoma, but also found in hepatocellular carcinoma (HCC). In this study we evaluated the expression of such genes in 41 HCC patients, their correlation with pathological and clinical aspects of cancer, and the impact on prognosis. MAGE are expressed in most of HCC samples (28/41), no correlation was found with type and stage but they may be used as potential target for IT.

Sixty-nine unselected SLE patients were studied to evaluate the prevalence of avascular osteonecrosis (AVN) and its relationship with steroid therapy and with anticardiolipin antibodies (aCL). All the patients were under treatment with corticosteroids. AVN occurred in seven occurred in seven of the 69 patients (10.14%) and was not related to corticosteroid intake. Seventeen of the 69 patients were also treated with methylprednisolone pulse therapy (MPPT) and cumulated the highest corticosteroid doses but none of them suffered from AVN. Excluding the 17 MPPT-treated SLE patients, corticosteroid intake was significantly higher in the AVN-SLE patients. Abnormal IgG and/or IgM aCL serum levels were found in two of the seven AVN-SLE patients and in 24 of the 62 non-AVN SLE, without a statistically significant difference. None of the seven AVN-SLE patients showed features of antiphospholipid syndrome. We conclude that in SLE patients a continuous high-dose steroid treatment may be considered a risk factor for AVN. On the contrary, MPPT regimen may reduce this risk. Anticardiolipin antibodies might represent an added factor which could play a role in some patients but not in all.