Search

OBJECTIVE: The effect of baseline differences between men and women on early outcomes after percutaneous coronary intervention (PCI). DESIGN, SETTING, PARTICIPANTS: This is an observational study of all participants in the GenesisCare Cardiovascular Outcomes Registry, undergoing PCI. The registry holds data for both emergency and elective procedures. Data was collected on 10,989 consecutive patients from 12 Australian Private Hospitals, including baseline demographics, co-morbidities, risk factors, PCI procedures, and lesion characteristics. MAIN OUTCOME MEASURES: Outcome was measured for complications (in-hospital death, peri-procedural myocardial infarctions, and bleeding events), at discharge and at 30-days for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiac events (MACE), and unplanned readmissions. RESULTS: Women represented 23% of the study population, were significantly older, with a higher rate of hypertension and hyperlipidaemia. Heart failure was more common in women and was associated with a significantly higher average ejection fraction than in men. Women had a lower rate of pre-existing coronary artery disease (CAD), had less complex CAD, and needed fewer stents. Periprocedural complications were similar, but major bleeding was more common in women. The 30-day outcome was similar between men and women for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiovascular events (MACE), and unplanned readmissions. CONCLUSIONS: Although significant differences were observed between women and men in both clinical presentation and complexity of disease, the 30-day outcome was similar for death and MACE. Women had a higher rate of major bleeding events, and lower adherence to statins and dual antiplatelet therapy (DAPT).

Contains fulltext : 284814.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Fibroblast Growth Factor 12 (FGF12) may represent an important modulator of neuronal network activity and has been associated with developmental and epileptic encephalopathy (DEE). We sought to identify the underlying pathomechanism of FGF12-related disorders. METHODS: Patients with pathogenic variants in FGF12 were identified through published case reports, GeneMatcher and whole exome sequencing of own case collections. The functional consequences of two missense and two copy number variants (CNVs) were studied by co-expression of wildtype and mutant FGF12 in neuronal-like cells (ND7/23) with the sodium channels Na(V)1.2 or Na(V)1.6, including their beta-1 and beta-2 sodium channel subunits (SCN1B and SCN2B). RESULTS: Four variants in FGF12 were identified for functional analysis: one novel FGF12 variant in a patient with autism spectrum disorder and three variants from previously published patients affected by DEE. We demonstrate the differential regulating effects of wildtype and mutant FGF12 on Na(V)1.2 and Na(V)1.6 channels. Here, FGF12 variants lead to a complex kinetic influence on Na(V)1.2 and Na(V)1.6, including loss- as well as gain-of function changes in fast and slow inactivation. INTERPRETATION: We could demonstrate the detailed regulating effect of FGF12 on Na(V)1.2 and Na(V)1.6 and confirmed the complex effect of FGF12 on neuronal network activity. Our findings expand the phenotypic spectrum related to FGF12 variants and elucidate the underlying pathomechanism. Specific variants in FGF12-associated disorders may be amenable to precision treatment with sodium channel blockers. FUNDING: DFG, BMBF, Hartwell Foundation, National Institute for Neurological Disorders and Stroke, IDDRC, ENGIN, NIH, ITMAT, ILAE, RES and GRIN.

Background and aim: poor quality of life (QoL) has been identified as an independent risk factor for mortality and major cardiac events (MACE) in patients with cardiovascular disease (CVD). The aim of this study was to assess health-related quality of life (HRQoL) at baseline and its association with outcome in patients with coronary artery disease presenting for percutaneous coronary intervention (PCI). The outcome was measured by mortality and MACE at 1-year, and whether there was any difference for sex and different age groups. Methods and results: all patients prospectively enrolled into the GenesisCare Outcome Registry (GCOR) over a 11-year period were included in the study. The EQ-5D-5L and VAS patient survey were used for assessment of baseline HRQoL. Of the 15,198 patients, only 6591 (43.4%) completed the self-assessment. Women had significantly more impairment of all five dimensions of the EQ-5D-5L survey, and their self-reported QoL was significantly lower than men (68.3 in women vs. 71.9 in men, p < 0.001). Poor QoL was strongly associated with increased mortality (HR 2.85; 95% CI 1.76 to 4.62, p < 0.001) and MACE (HR 1.40; 95% CI 1.10 to 1.79, p = 0.01). A similar trend was noted for women and men, but did not reach significance in women due to the smaller number of female patients. Conclusion: poor HRQoL is associated with subsequent mortality and MACE in patients undergoing PCI. By not assessing quality of life as a standard of care, an opportunity is lost to identify high-risk patients who may benefit from targeted interventions to improve health outcomes.

Introduction: Several large registries have evaluated outcomes after percutaneous coronary intervention (PCI) in the USA, however there are no contemporary data regarding long-term outcomes after PCI, particularly comparing new generation drug-eluting stents (DES) with other stents in Australia. Additionally, approval of new-generation drug-eluting stents (DES) is almost exclusively based on non-inferiority trials comparing outcomes with early generation DES, and there are limited data comparing safety and efficacy outcomes of new-generation DES with bare metal stents (BMS). This study reports in-hospital and long-term outcomes after PCI with the Xience DES from a large national registry, the GenesisCare Outcomes Registry (GCOR). Methods: The first 1500 patients consecutively enrolled from January 2015 to January 2019 and treated exclusively with either Xience DES or BMS and eligible for 1-year follow-up were included. Baseline patient and procedural data, major adverse cardiovascular events (MACE) in-hospital, at 30 days and 1-year, and medications were reported and analysed with respect to Xience DES (n = 1000) or BMS (n = 500) use. Results: In this cohort the mean age was 68.4 ± 10.7 years, 76.9% were male, 24.6% had diabetes mellitus and 45.9% presented with acute coronary syndromes. Of the overall cohort of 4765 patients from this period including all DES types, and patients who received multiple DES or a combination of DES and BMS, DES were exclusively used in 3621 (76.0%) patients, and BMS were exclusively used in 596 (12.5%). In comparison to international cohorts, adverse clinical event rates were low at 30 days in terms of mortality (0.20%), target lesion revascularisation (TLR, 0.27%) and MACE (0.47%), and at 12 months for mortality (1.26%) TLR (1.16%) and MACE (1.78%). Conclusions: Clinical practice and long-term outcomes of PCI with the Xience DES in Australia are consistent with international series. Recent trends indicate DES use has increased in para

Background and aim: Unplanned cardiac readmissions in patients with percutaneous intervention (PCI) is very common and is seen as a quality indicator of in-hospital care. Most studies have reported on the 30-day cardiac readmission rates, with very limited information being available on 1-year readmission rates and their association with mortality. The aim of this study was to investigate the impact of biological sex at 1-year post-PCI on unplanned cardiac readmissions. Methods and results: Patients enrolled into the GenesisCare Cardiovascular Outcomes Registry (GCOR-PCI) from December 2008 to December 2020 were included in the study. A total of 13,996 patients completed 12 months of follow-up and were assessed for unplanned cardiac readmissions. All patients with unplanned cardiac readmissions in the first year of post-PCI were followed in year 2 (post-PCI) for survival status. The rate of unplanned cardiac readmissions was 10.1%. Women had a 29% higher risk of unplanned cardiac readmission (HR 1.29, 95% CI 1.11 to 1.48; p = 0.001), and female sex was identified as an independent predictor of unplanned cardiac readmissions. Any unplanned cardiac readmission in the first year was associated with a 2.5-fold higher risk of mortality (HR 2.50, 95% CI 1.67 to 3.75; p < 0.001), which was similar for men and women. Conclusion: Unplanned cardiac readmissions in the first year post-PCI was strongly associated with increased all-cause mortality. Whilst the incidence of all-cause mortality was similar between women and men, a higher incidence of unplanned cardiac readmissions was observed for women, suggesting distinct predictors of unplanned cardiac readmissions exist between women and men.

The knowledge of complexation reactions of early actinides with nitrogen donor ligands serves not only as fundamental research in this underrepresented field of chemistry but also contributes to a deeper understanding of their reactivity and coordination chemistry. In contrast to the lanthanides, with the dominating oxidation state of + III, actinides, especially the early actinides up to Plutonium, can exist in a variety of different oxidation states ranging from +II to +VI. The coordination chemistry of tri- and tetravalent actinides with selective soft nitrogen donor ligands is of special interest, with a potential use as extraction and/or decontamination agents. In order to understand the bonding trends and electronic structure, the nitrogen donor ligand 2,6-bis(1-(4-bromo-2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)pyridine, a BPTP-type ligand, was used as the compound of choice in this contribution. BPTP-type ligands are based on the commonly known BTP-ligand, a tridentate chelating ligand which was designed for the purpose of separating lanthanides from actinides.[1] The BPTP ligand was synthesized by a copper mediated click reaction of 2,6-diethynylpyridine with the corresponding azide. Within this ongoing study, we focus on the synthesis and characterization of tetravalent actinides, which are readily available for all of the early actinides from Thorium up to Plutonium. The obtained U(IV) complex was characterized by single crystal X-ray diffraction (SC-XRD). Further characterization of the novel coordination complex using NMR, IR, and EPR, as well as an expansion to the transuranic elements will complete this study.

Understanding the subtle differences between lanthanide and actinide complexation chemistry with different ligand systems is an ongoing field of resarch. Soft donor ligands, especially ligands containing nitrogen, have shown to be promising for the investigation of the small differences in bonding behavior of actinides compared to lanthanides particularly with regards to the covalent contribution within the bond. BTP type ligands have been used as an extacting ligand for the separation of lanthanides from actinides.1 Therefore, new soft nitrogen donor ligands based on the BTP type ligand (2,6-Bis(1,2,4-Triazin-3-yl)Pyridine) or Schiff base lig-ands have been synthesized to explore the fundamental chemistry of the early 5f-elements. In order to investigate the coordination environment, ligand selectivity, bonding trends and electronic properties a series of actinide complexes ranging from thorium to plutonium has been characterized in solid state as well as in solution. In the present study the synthesis of the new soft donor ligand L1 was carried out via a copper mediated click reaction of the corresponding alkyne and azide. The bipyridine based ligand L2 was obtainend in a three step synthesis starting from bipyridine via the corresponding N-oxide and cyanide to give the tetrazine. Both ligands L1 and L2 were succesfully applied in the complexation reaction with trivalent lanthanides e.g. Er and Sm. In this contribution the investigation of the coordination chemistry of these soft N-donor ligands is exended to the early actinides in their tri- and tetravalent oxidation state. First experimental results show the formation of a 3:1 complex in the case of trivalent Er. In contrast, the same ligand system L1 forms a 2:1 complex with U(IV) including methanolato and iodo ligands for charge compensation. Further results including first structural characterization as well as results from quantum chemical calculations to elucidate the binding situation, will be presented in

Understanding the subtle differences between lanthanide and actinide complexation chemistry with different ligand systems is an ongoing field of resarch. Soft donor ligands, especially ligands containing nitrogen, have shown to be promising for the investigation of the small differences in bonding behavior of actinides compared to lanthanides particularly with regards to the covalent contribution within the bond. BTP type ligands have been used as an extacting ligand for the separation of lanthanides from actinides.1 Therefore, new soft nitrogen donor ligands based on the BTP type ligand (2,6-Bis(1,2,4-Triazin-3-yl)Pyridine) or Schiff base lig-ands have been synthesized to explore the fundamental chemistry of the early 5f-elements. In order to investigate the coordination environment, ligand selectivity, bonding trends and electronic properties a series of actinide complexes ranging from thorium to plutonium has been characterized in solid state as well as in solution. In the present study the synthesis of the new soft donor ligand L1 was carried out via a copper mediated click reaction of the corresponding alkyne and azide. The bipyridine based ligand L2 was obtainend in a three step synthesis starting from bipyridine via the corresponding N-oxide and cyanide to give the tetrazine. Both ligands L1 and L2 were succesfully applied in the complexation reaction with trivalent lanthanides e.g. Er and Sm. In this contribution the investigation of the coordination chemistry of these soft N-donor ligands is exended to the early actinides in their tri- and tetravalent oxidation state. First experimental results show the formation of a 3:1 complex in the case of trivalent Er. In contrast, the same ligand system L1 forms a 2:1 complex with U(IV) including methanolato and iodo ligands for charge compensation. Further results including first structural characterization as well as results from quantum chemical calculations to elucidate the binding situation, will be presented in

The knowledge of complexation reactions of early actinides with nitrogen donor ligands serves not only as fundamental research in this underrepresented field of chemistry but also contributes to a deeper understanding of their reactivity and coordination chemistry. In contrast to the lanthanides, with the dominating oxidation state of + III, actinides, especially the early actinides up to Plutonium, can exist in a variety of different oxidation states ranging from +II to +VI. The coordination chemistry of tri- and tetravalent actinides with selective soft nitrogen donor ligands is of special interest, with a potential use as extraction and/or decontamination agents. In order to understand the bonding trends and electronic structure, the nitrogen donor ligand 2,6-bis(1-(4-bromo-2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)pyridine, a BPTP-type ligand, was used as the compound of choice in this contribution. BPTP-type ligands are based on the commonly known BTP-ligand, a tridentate chelating ligand which was designed for the purpose of separating lanthanides from actinides.[1] The BPTP ligand was synthesized by a copper mediated click reaction of 2,6-diethynylpyridine with the corresponding azide. Within this ongoing study, we focus on the synthesis and characterization of tetravalent actinides, which are readily available for all of the early actinides from Thorium up to Plutonium. The obtained U(IV) complex was characterized by single crystal X-ray diffraction (SC-XRD). Further characterization of the novel coordination complex using NMR, IR, and EPR, as well as an expansion to the transuranic elements will complete this study.