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Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain.

IMPORTANCE: The Global Registry of Acute Coronary Events (GRACE) risk score, a guideline-recommended risk stratification tool for patients presenting with acute coronary syndromes (ACS), does not consider the extent of myocardial injury. OBJECTIVE: To assess the incremental predictive value of a modified GRACE score incorporating high-sensitivity cardiac troponin (hs-cTn) T at presentation, a surrogate of the extent of myocardial injury. DESIGN, SETTING, AND PARTICIPANTS: This retrospectively designed longitudinal cohort study examined 3 independent cohorts of 9803 patients with ACS enrolled from September 2009 to December 2017; 2 ACS derivation cohorts (Heidelberg ACS cohort and Newcastle STEMI cohort) and an ACS validation cohort (SPUM-ACS study). The Heidelberg ACS cohort included 2535 and the SPUM-ACS study 4288 consecutive patients presenting with a working diagnosis of ACS. The Newcastle STEMI cohort included 2980 consecutive patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Data were analyzed from March to June 2023. EXPOSURES: In-hospital, 30-day, and 1-year mortality risk estimates derived from an updated risk score that incorporates continuous hs-cTn T at presentation (modified GRACE). MAIN OUTCOMES AND MEASURES: The predictive value of continuous hs-cTn T and modified GRACE risk score compared with the original GRACE risk score. Study end points were all-cause mortality during hospitalization and at 30 days and 1 year after the index event. RESULTS: Of 9450 included patients, 7313 (77.4%) were male, and the mean (SD) age at presentation was 64.2 (12.6) years. Using continuous rather than binary hs-cTn T conferred improved discrimination and reclassification compared with the original GRACE score (in-hospital mortality: area under the receiver operating characteristic curve [AUC], 0.835 vs 0.741; continuous net reclassification improvement [NRI], 0.208; 30-day mortality: AUC, 0.828 vs 0.740; NRI, 0.312; 1-year mortality: AUC, 0.785 vs 0.778; NRI, 0.078) in the derivation cohort. These findings were confirmed in the validation cohort. In the pooled population of 9450 patients, modified GRACE risk score showed superior performance compared with the original GRACE risk score in terms of reclassification and discrimination for in-hospital mortality end point (AUC, 0.878 vs 0.780; NRI, 0.097), 30-day mortality end point (AUC, 0.858 vs 0.771; NRI, 0.08), and 1-year mortality end point (AUC, 0.813 vs 0.797; NRI, 0.056). CONCLUSIONS AND RELEVANCE: In this study, using continuous rather than binary hs-cTn T at presentation, a proxy of the extent of myocardial injury, in the GRACE risk score improved the mortality risk prediction in patients with ACS.

Graphical Abstract

Graphical Abstract

The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics.

Left atrium (LA) plays a key role in the overall cardiac performance. However, it remains unclear how LA adapts, in terms of function and volumes, to left ventricular dysfunction in the acute and post-acute phases of myocardial infarction. LA volumes and function were evaluated in patients in the acute phase of ST-segment elevation myocardial infarction (acute-STEMI group) and in the post-acute phase after STEMI (post-acute STEMI group). Ten age and sex-matched healthy controls served as control group. In all subjects LA was assessed by a compressed-sensing cine pulse sequence and by a 3D non-model-based reconstruction. LV infarct size and microvascular obstruction were determined on late-gadolinium-enhancement data and LV myocardial oedema and myocardial haemorrhage were measured on T2-mapping data. Indexed LA maximum and minimum volumes did not differ between the acute (n = 50) and post-acute (n = 47) STEMI groups. LA active emptying fraction (LAAEF) was higher in the acute-STEMI as compared with the post-acute STEMI groups (0.63 ± 0.23 vs 0.37 ± 0.24, p < 0.0001). Conversely, LA passive emptying fraction (LAPEF) was lower in the acute-STEMI compared with post-acute-STEMI (0.34 ± 0.15 vs 0.65 ± 0.15, p < 0.0001) patients. In the acute-STEMI group, LAAEFwas positively and LAPEFnegatively correlated with LV myocardial tissue damage (r = 0.523 p = 0.0001; r = − 0.451 p = 0.0013). Negative and positive correlations were also found between LAAEFand LAPEFand time after STEMI (r = − 0.559 p = 0.0013 and r = 0.589 p = 0.0006, respectively). LA increases its active contractile function in the acute phase of STEMI to support LV filling. The extent (but not the type) of LV damage determines LA adaptions which normalizes over time.

While the treatment of locally advanced lower and middle rectal cancer with total mesorectal excision (TME) after neoadjuvant therapy is now well defined, the treatment of locally advanced upper rectal cancer (LAURC) remains controversial. Although most teams and academic societies recommend upfront surgery (US) with partial mesorectal excision (PME), as this appears to be sufficient for these tumors, the literature remains conflicting regarding the additional use of neoadjuvant therapy and TME. Current recommendations for the treatment of LAURC do not reflect actual clinical practice. Notably, there is a paucity of published data specific to the treatment of LAURC since most of the data are from sub-analyses of different cohorts. Another important point responsible for the inconsistent data situation is the fact that the current definition of upper rectal cancer is based on anatomical criteria that are difficult to reproduce and therefore also differ between international professional societies.

Aim: Cystatin C, neutrophil gelatinase-associated lipocalin and galectin-3 have emerged as biomarker candidates to predict cardiovascular outcomes and mortality in the general population as well as in patients with coronary artery or renal disease. However, their predictive role and clinical utility in patients with acute coronary syndromes alone or in combination beyond currently used risk scores remains to be determined.Methods and results: Cystatin C, neutrophil gelatinase-associated lipocalin, and galectin-3 were measured in plasmas of 1832 patients at the time of presentation with acute coronary syndromes requiring percutaneous coronary intervention or coronary artery bypass grafting. The primary outcomes were major adverse cardiac and cerebrovascular events (defined as the composite of all-cause mortality, cerebrovascular events, any repeat revascularization or myocardial infarction) and all-cause mortality after 1 year and occurred in 192 (10.5%) and 78 (4.3%) of patients, respectively. All three biomarkers were increased in those with major adverse cardiac and cerebrovascular events compared with those without (p<0.001). However, only galectin-3 (all-cause mortality: hazard ratio=1.027 (95% confidence interval (1.011–1.043); p=0.001), major adverse cardiac and cerebrovascular events: hazard ratio=1.025 (95% confidence interval (1.012–1.037); p<0.001)) but not cystatin C nor neutrophil gelatinase-associated lipocalin emerged as independent predictors of both major adverse cardiac and cerebrovascular events and death. The risks were particularly high in the highest quartile of galectin-3. The integration of galectin-3 into the global registry of acute coronary events (GRACE) score improved the prediction of major adverse cardiac and cerebrovascular events and all-cause mortality significantly. The areas under the receiver operator characteristics curves increased from 0.6701 to 0.6932 for major adverse cardiac and cerebrovascular events (p=0.0474) and from 0.804 to 0.8199 for all-cause mortality (p=0.0197). Finally, we applied net reclassification improvement index using different cut-offs for major adverse cardiac and cerebrovascular events which showed negative results (for the cut-offs of 5% and 15%, net reclassification improvement index 0.028, p=0.586, for the cut-offs of 10% and 20%, net reclassification improvement index 0.072, p=0.1132 and for the cut-offs of 10% and 30% the net reclassification improvement index is 0.0843, p=0.077).Conclusion: In acute coronary syndromes patients, galectin-3 has moderate prognostic accuracy, provides statistically significant incremental value in some, but not all models, and that the magnitude of any improvement would seem of questionable clinical value.

15 à 20 % des patients ne sont pas éligibles à une approche trans-fémorale classique dans le cadre d’un remplacement valvulaire aortique percutané.

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes.Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria.Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

The transcaval (TCv) vascular approach is increasingly used in transcatheter aortic valve replacement (TAVR) in patients unsuitable for the gold-standard transfemoral approach. We aimed to evaluate the efficacy, safety, and clinical outcomes associated with TCv-TAVR.

Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.

To describe temporal trends in adoption and performance of transcatheter aortic valve implantation (TAVI) in Switzerland over a period of 5 years.

Recent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y12 receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to assess the influence of intravenous fentanyl compared with morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI.

A 64-year-old man presented with severe myocarditis 6 weeks after an initial almost asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection. He was found to have a persistent positive swab. Mechanisms explaining myocardial injury in patients with COVID-19 remains unclear, but this case suggests that severe acute myocarditis can develop in the late phase of COVID-19 infection, even after a symptom-free interval.

Drug-eluting stents combining an ultrathin cobalt-chromium stent platform with a biodegradable polymer eluting sirolimus have been shown to be non-inferior or superior to thin-strut, durable-polymer, everolimus-eluting stents in terms of 1 year safety and efficacy outcomes.

The circadian variation of platelet aggregation is well demonstrated. However, whether this has an impact on antiplatelet inhibition therapy is poorly documented. We aimed to observe whether ticagrelor-induced platelet inhibition follows a circadian rhythm.

Commercial off-the-shelf (COTS) Field-Programmable Gate Arrays (FPGAs) are becoming increasingly powerful. In addition to their huge hardware resources, they are also integrated into complete systems on chips (SOCs), e.g., in the latest Xilinx Zynq or Altera Stratix platforms. However, cooperation between FPGAs and their surroundings, and the flexibility of hardware task management could still be improved. For instance, mechanisms have yet to be automated to allow multi-user approaches. A reconfigurable resource can be shared between applications or users only if it has a context-switch ability allowing applications to be paused and resumed in response to system demands. Here, we present a high-level synthesis (HLS) design flow producing a context-switch-capable circuit. The design flow manipulates the intermediate representation of an HLS tool to build the context extraction mechanism and to optimize performance for the circuit produced. The method is based on efficient checkpoint selection and insertion of a powerful scan-chain into the initial circuit. This scan-chain can extract flip-flops or memory content. Experiments with the system produced show that it has a low hardware overhead for many benchmark applications, and that the hardware added has a negligible impact on application performance. Comparisons with current standard methods highlight the efficiency of our contributions.

Aims: The present study aimed to document a local pattern of care in consecutive patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) in a tertiary centre in Switzerland.Methods: A retrospective study was conducted at the University Hospital of Lausanne, Switzerland. A total of 389 consecutive patients undergoing primary percutaneous coronary intervention for STEMI between 2009 and 2010 were studied. The audit focused on 14 items derived from the American College of Cardiology/American Heart Association 2008 quality performance measures position paper on STEMI management. These indicators all corresponded to a class 1 recommendation at the time of the study period.Results: All patients received aspirin and anticoagulation within 24 hours after admission. Only 31.3% of patients received beta-blocking agents within 24 hours of admission. Left ventricular function was evaluated in 89.2% of cases and referral for cardiac rehabilitation was achieved in 78.5% of eligible patients. Patients subsequently transferred to another facility for further inpatient care had significantly less evaluation of left ventricular function (82.0% vs. 97.5%, P<0.0001). Global adherence to all performance measures was significantly higher among younger patients (45.9% vs. 31.4%, P<0.0075).Conclusions: The present study, which provides a snapshot on quality performance between 2009 and 2010 in a referral centre for primary percutaneous coronary intervention, demonstrates a suboptimal application of the global guidelines on STEMI management. This observation is mainly driven by a low prescription of beta-blocking agents, a class IA indication at that time. This observation should be put in perspective to current practice.

Supplemental Digital Content is available in the text.

The nonlinear optical mechanisms and the optical limiting behavior of porphyrin functionalized detonation nanodiamonds are investigated and compared to the conventional detonation nanodiamonds (DNDs). The optical limiting behavior is characterized by means of nonlinear transmittance, Z-scan, and scattered intensity measurements when submitted to a nanosecond pulsed Nd:YAG laser operating at the second harmonic wavelength. We found that the largest nonlinear attenuation was observed on the 4,4^′,4^′′,4^′′′–(porphyrin–5, 10, 15, 20–tetrayl) tetrakis benzoic acid (PCOOH) suspension. Using Z-scan experiments, it is shown that nonlinear refraction predominates in the unfunctionalized DND suspension, while nonlinear absorption is the most relevant mechanism in the porphyrin functionalized DNDs. Furthermore, a stronger backscattered intensity signal is highlighted for the unfunctionalized DNDs through nonlinear scattering measurements.

Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent.

No-reflow phenomenon is a consequence of percutaneous coronary intervention (PCI) which arises most of the time in the setting of myocardial infarction, but can be also the consequence of PCI in stable angina patients (rotatablator ablation technique or angioplasty in saphenous vein grafts). In this review, we summarize two ways of treating the noreflow according to the current literature. First through the pharmacological approach where several compounds have been assessed like adenosine, nitruprusside, verapamil, nicorandil, dipyridamole, epinephrine or cyclosporine. Second through the mechanical approach where few strategies have been examined like intra-aortic ballon pumping or postconditioning. Finally, we provide an algorithm for treating a no-reflow even though no studies showed a beneficial effect in terms of clinical endpoints.

The optical limiting behavior of silver nanoparticles with different sizes and shapes is investigated and compared to the optical limiting performance of conventional carbon black suspension (CBS). The optical limiting behavior is characterized by means of nonlinear transmittance and scattered intensity measurements when submitted to nanosecond pulsed Nd:YAG lasers operating at the fundamental or the second harmonic wavelength. We found that the optical limiting effect is strongly particle size dependent and the best performance is achieved with the smaller particles. Moreover, it is shown that the surface plasmon resonance is not the main effect responsible for the nonlinear processes. A theoretical model based on the computation of the Mie scattering functions is exposed, and it is shown that the experimental results can be well explained from the calculations.

To quantify the changes in arterial dimensions after the acute changes in pressure associated with percutaneous coronary intervention (PCI).

Although most antidepressants suppress serotonin (5-HT) and/or noradrenaline reuptake, blockade of 5-HT(2C) receptors and α(2)-adrenoceptors likewise enhances monoaminergic transmission. These sites are targeted by the urea derivative N- [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-1,2-dihydro-3-H-benzo[e]indole-3-carboxamide (S32212). S32212 was devoid of affinity for monoamine reuptake sites, yet displayed pronounced affinity (pK(i), 8.2) for constitutively active human 5-HT(2CINI) (h5-HT(2CINI)) receptors, behaving as an inverse agonist in reducing basal Gα(q) activation, [(3)H]inositol-phosphate production, and the spontaneous association of h5-HT(2CINI)-Renilla luciferase receptors with β-arrestin2-yellow fluorescent protein. Furthermore, upon 18-h pretreatment, S32212 enhanced the plasma membrane expression of h5-HT(2CINI) receptors as visualized by confocal microscopy and quantified by enzyme-linked immunosorbent assay. Its actions were prevented by the neutral antagonist 6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl]indoline-1-carboxamide (SB242,084), which also impeded the induction by long-term exposure to S32212 of otherwise absent Ca(2+) mobilization in mouse cortical neurones. In vivo, S32212 blunted the inhibitory influence of the 5-HT(2C) agonist 2-(3-chlorobenzyloxy)-6-(1-piperazinyl)pyrazine (CP809,101) on ventrotegmental dopaminergic neurones. S32212 also blocked 5-HT-induced Gα(q) and phospholipase C activation at the h5-HT(2A) and, less potently, h5-HT(2B) receptors and suppressed the discriminative stimulus properties of the 5-HT(2A) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane in rats. S32212 manifested marked affinity for human α(2A)- (pK(i) 7.2), α(2B)- (pK(i) 8.2), and α(2C)- (pK(i) 7.4) adrenoceptors, at which it abolished noradrenaline-induced recruitment of Gα(i3), Gα(o), adenylyl cyclase, and extracellular-regulated kinase1/2. Moreover, S32212 dose-dependently abolished the discriminative stimulus effects of the α(2)-adrenoceptor agonist (S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4,2'-(1',2',3',4'-tetrahydronaphthalene)] (S18616). Finally, S32212 displayed negligible affinity for α(1A)-adrenoceptors, histamine H(1) receptors, and muscarinic M(1) receptors. In conclusion, S32212 behaves as an inverse agonist at h5-HT(2C) receptors and as an antagonist at human α(2)-adrenoceptors (and h5-HT(2A) receptors). Its promising profile in preclinical models potentially relevant to the treatment of depression is described in J Pharmacol Exp Ther 340:765-780, 2012.

Thermites prepared from nanoparticles are currently the subject of growing interest due to their increased performances compared to classical micrometer‐sized thermites. Here, we studied the combustion behavior of energetic composite composed of Al and chromium (III) oxide (Cr2O3) as function of the oxide particle size. Homogeneous composites were prepared by mixing Al nanoparticles (Φ≈50 nm) with Cr2O3micro‐ and nanoparticles (Φ≈20 nm), respectively, in hexane solution. The dried Cr2O3/Al composite powders were ignited by using a CO2laser beam. The use of nanosized Cr2O3particles incontestably improves the energetic performances of the Al/Cr2O3thermite since the ignition delay time was shortened by a factor 3.5 (16±2 vs 54±4 ms) and the combustion rate (340±10 mm s−1) was significantly accelerated in contrast to those reported until now. Interestingly, the sensitivity to friction of the Al‐based thermites formulated from Cr2O3is two orders of magnitude lower than the thermite prepared from other metal oxide nanoparticles (MnO2, WO3). Finally, our study shows that the decrease of Cr2O3particle size has an interesting and beneficial effect on the energetic properties of Cr2O3/Al thermites and appears as an alternative to tune the properties of these energetic materials.

In previous studies on the effect of renal stenting on arterial hypertension, patients were selected mainly on the basis of angiographic parameters of the renal artery stenosis. The aim of the present study was to evaluate whether translesional pressure gradients could identify the patients with renal artery stenosis who might benefit from stenting.

Nanothermites are versatile pyrotechnic systems composed of a metal oxide and a reducing metal powder, such as aluminum. The high mechanical sensitivity of some of these mixtures (e.g., MnO2/Al) makes their handling hazardous. Enclosing the metal oxide inside carbon nanofibersthus separating oxidizer and reducing agentis a new way to lower the sensitivity of nanothermites. In this study, we filled herringbone carbon nanofibers (CNF) with manganese oxide MnOx(x≈ 1.9) by a two-step opening/filling treatment using nitric acid and molten manganese nitrate, followed by a heat treatment; the resulting nanocomposite is used to prepare a MnOx@CNF/Al nanothermite. A dramatic decrease in the friction sensitivity (threshold >360 N) as compared to a MnO2/Al nanothermite (threshold <5 N) is found. The electrostatic discharge sensitivity was also strongly decreased (from 1.0 to 5300 mJ). The combustion was studied by time-resolved cinematography. Analysis of the combustion residues indicates that metallic Mn was formed along with less oxygenated manganese oxides and aluminum carbide. This study shows a new route for the design of safer pyrotechnic systems.

The optical limiting behavior of multiwalled carbon nanotube (MWCNT) powder in chloroform solution under CO_2 infrared laser irradiations is reported for, to our knowledge, the first time. Here we demonstrate the pure thermal origin of the optical limiting effect in the 160 ns time scale studied. The Z-scan technique appears to be an excellent tool for xperimental evaluation of the nonlinear refractive index. An experimental model for the optical limiting behavior of MWCNT suspensions in chloroform is presented. The occurrence of a laser-induced thermal lens through the absorption of energy by the MWCNTs and subsequent heat transfer to the solvent, followed by solvent vapur bubble growth, is the main factor governing the observed drop in transmittance. Pump-probe experiments have been performed to obtain some quantitative estimation of both the rise and decay times of the thermal lensing phenomenon. It was found that the early probe signal decay, τ_1=149 ns, was of the same order of magnitude as the rise time of the thermal lens, τ_r=121 ns. When the nonlinear scattering was considered, a total decay time of τ=1.8 μs was obtained. A recovery time for the thermal lens of several tens of milliseconds has been experimentally determined, which is in good accordance with the theoretical value.

Supplemental Digital Content is available in the text.

New polysubstituted tetrahydronaphthalene derivatives were prepared as thromboxane receptor (TP-receptor) antagonists. Within this series of compounds S 18886has been identified as an orally active, highly potent antagonist with a very long duration of action in different species.

Supplemental Digital Content is available in the text.

In an era where transcatheter aortic valve implantation (TAVI) indications and utilization are expanding beyond high-risk patients, paravalvular leak remains the intervention’s Achilles heel. Effective reduction of paravalvular leak is important in order to ensure an optimal clinical outcome. We present here the first case report in which percutaneous valvular closure using Amplatzer plugs followed by a TAV-in-TAV intervention during the same procedure managed to resolve a severe paravalvular leak with haemodynamic instability, after TAVI for a bicuspid aortic stenosis.