Publications

The long-term safety of drug-eluting stent (DES) implantation in the treatment of unprotected left main coronary artery (LMCA) stenosis is still a matter of debate. Some concerns have been recently raised regarding the risk of late and very late stent thrombosis (ST). Methods: All consecutive patients (pts) who had sirolimus (SES, Cypher, Cordis, Johnson and Johnson Company, Warren, NJ) or paclitaxel-eluting stent (PES, Taxus, Boston Scientific, Natick, MA) electively implanted in de novo lesions on LMCA between March 2002 and June 2006 were included in this multicentre registry. Stent thromboses were defined according to Academic Research Consortium (ARC) definitions. Results Five-hundred and thirty-four consecutive patients were analyzed: 357 patients were treated with SES, 168 with PES and 9 with both of them. One-hundred and thirty-eight (25.8%) patients were diabetics, 171 (32.0%) unstable angina, mean age 62.4 ± 11.4 years, EF 54.1 ± 11.2 %. Distal location occurred in 417 (78.0%) of the patients. Fifty-seven (10.6%) patients had a peri-procedural myocardial infarction (defined as CK-MB elevation ≥3 ULN). At 1044 ± 361 day clinical follow-up, 32 (5.9%) patients died: 23 (4.3%) were adjudicated as cardiac according to ARC definition. One patient had an acute ST (with cardiogenic shock treated with CABG), 1 a sub-acute ST (occlusion of circumflex artery treated with PCI) and 1 a late definite ST (in the left anterior descending artery with MI at 3 months while on antiplatelet therapy). None of the patients had a very late definite ST. In the Table are reported probable and possibile ST. Conclusions Treatment of LMCA stenosis with DES appears safe at long-term clinical follow-up with a 0.6% incidence of definite and probable ST at a median follow-up of almost 3 years. Table.

No abstract is provided for this article.

Aims We sought to evaluate the value of GRACE risk score in stratifying acute coronary syndrome patients undergoing percutaneous coronary intervention in the Global Leaders study. Methods Global Leaders study was a prospective, multi-center, open-label, all-comers, randomized controlled trial comparing ticagrelor monotherapy after 1 month of dual antiplatelet therapy (DAPT) as experimental therapy with aspirin monotherapy after 12 months of conventional DAPT (reference therapy) in patients who received PCI with biolimus-A9 eluting stent. We assessed the predictive value of GRACE risk score in ACS patients undergoing PCI in the present analysis. Patients were stratified according to GRACE risk score into low (1–108), moderate (109–140), High (141–372) risk group. Clinical outcomes at 2 years after PCI were assessed and compared among risk groups. Interaction between GRACE risk score and antiplatelet regimen were analyzed by the interaction term in Cox model. Results GRACE risk score was calculated from 8 clinical parameters at presentation. Among ACS patients, 1664 patients were categorized in low risk group, 2903 patients were in moderate risk group, and 2028 patients were in high risk group. The rate of all-cause mortality, any stroke, patient-oriented composite endpoint (POCE) were highest in the high-risk group at 2 years (All-cause mortality; low risk 1.4%, moderate risk 2.5%, high risk 6.1%, log rank test p value <0.0001, any stroke; low risk 0.7%, moderate risk 1.0%, high risk 2.0%, log rank test p value 0.001, POCE; low risk 12.4%, moderate risk 11.9%, high risk 16.61%, log rank test p value <0.0001). The rate of myocardial infarction, all revascularization and definite or probable stent thrombosis were not different among three groups. There was no interaction between GRACE risk score and treatment regimen on clinical outcomes at 2 years. Conclusion GRACE risk score is valuable in identifying ACS patients with highest risk of all-cause mortality, any stroke and POCE at 2 years after PCI. In ACS, ticagrelor monotherapy did not improve the outcomes at 2 years in the three strata of the GRACE risk score.

No abstract is provided for this article.

The effect of intradermal injection of leukotriene B4 alone and in combination with prostaglandin D2 and E2 and the effect of inhaled leukotriene B4 in combination with prostaglandin D2 were studied in six non-asthmatic men. The intradermal injection of leukotriene B4 (1 microgram) alone caused no immediate or late response in five of the six subjects but greatly potentiated the flare response to intradermal prostaglandin D2 (0.5 microgram) and E2 (0.5 microgram) in all subjects. In contrast, inhaled prostaglandin D2 (6 micrograms) alone and in combination with inhaled leukotriene B4 (12 micrograms) caused no change in the response to inhaled histamine, measured 30 minutes and three and six hours after the inhalation. These findings provide no support for the suggestion that leukotriene B4 has an important role in causing bronchial hyperresponsiveness. The possibility that higher doses of inhaled leukotriene B4 may alter bronchial responsiveness cannot, however, be ruled out.

The aim of this study is to demonstrate the non-inferiority of the BiOSS LIM C sirolimus-eluting cobalt-chromium bifurcation dedicated stent against the XIENCE stent regarding the patient-oriented composite endpoint (POCE) at 12 months among patients with left main coronary artery disease (LMCA).The POLBOS LM study is a single-arm, prospective, multicentre study enrolling 260 patients (SYNTAX score ≤32) with a pre-specified performance goal based on the results of the EXCEL trial with contemporary percutaneous coronary intervention (PCI) for LMCA disease. Patient enrolment will comply with objective inclusion criteria of diameter stenosis ≥50% in the LMCA based on off-line quantitative coronary angiography (QCA) analysed by an independent core laboratory using dedicated bifurcation QCA software. The BiOSS LIM C is used for the treatment of LMCA disease with the same specific technical classification as for the BiOSS LIM (modified MADS classification) and the stent implantation is optimised by using pre-specified intravascular ultrasound criteria. The primary endpoint is POCE (a composite of all-cause death, stroke, any myocardial infarction, and any revascularisation) at 12 months.The POLBOS LM study will indicate the efficacy of the BiOSS LIM C stent with contemporary PCI for distal left main bifurcation lesions in comparison with the XIENCE stent from the recent EXCEL trial, as a performance index.

No abstract is provided for this article.

Parental smoking is known to worsen asthma symptoms in children and to make them refractory to asthma treatment, but the molecular mechanism is unclear. Oxidative stress from tobacco smoke has been reported to impair histone deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and, thus, to reduce corticosteroid sensitivity. The aim of this study was to investigate passive smoking-dependent molecular abnormalities in alveolar macrophages (AMs) by comparing passive smoke-exposed children and non-passive smoke-exposed children with uncontrolled severe asthma.BAL fluid (BALF) was obtained from 19 children with uncontrolled severe asthma (10 non-passive smoking-exposed subjects and nine passive smoking-exposed subjects), and HDAC2 expression/activity, Akt/HDAC2 phosphorylation levels, and corticosteroid responsiveness in AMs were evaluated.Parental smoking reduced HDAC2 protein expression by 54% and activity by 47%, with concomitant enhancement of phosphorylation of Akt1 and HDAC2. In addition, phosphorylation levels of Akt1 correlated positively with HDAC2 phosphorylation levels and negatively with HDAC2 activity. Furthermore, passive smoke exposure reduced the inhibitory effects of dexamethasone on tumor necrosis factor-α-induced CXCL8 release in AMs. There were relatively higher neutrophil counts and CXCL8 concentrations in BALF and lower Asthma Control Test scores compared with non-passive smoke-exposed children with uncontrolled severe asthma.Passive smoking impairs HDAC2 function via PI3K signaling activation, which could contribute to corticosteroid-insensitive inflammation in children with severe asthma. This novel mechanism will be a treatment target in children with severe asthma and stresses the need for a smoke-free environment for asthmatic children.