Prehospital ticagrelor in ST-segment elevation myocardial infarction

Background:The direct-acting platelet P2Y receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. Methods: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. Results: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition use

Iliofemoral Tortuosity Increases the Risk of Access-Site-Related Complications After Aortic Valve Implantation and Plug-Based Access-Site Closure

Background: Access-site-related complications are often related to high-risk anatomy and technical pitfalls and impair the outcomes of transfemoral aortic valve implantations (TAVIs). Calcification and tortuosity are widely recognized risk factors, and their impact on procedural planning is left to the implanting experts' discretion. To facilitate decision-making, we introduced a quantitative measure for iliofemoral tortuosity and assessed its predictive value for access-site-related vascular and bleeding complications. Methods: We performed a single-centre prospective cohort study of consecutive, percutaneous transfemoral TAVI performed between April 2019 and March 2020. Medical history and all-cause mortality were extracted from the electronic patient files. Arterial anatomy and calcifications were evaluated using 3mensio Structural Heart software. The primary outcome was access-site-related vascular or bleeding complications. Results: In this elderly, intermediate-risk population, we registered the primary outcome in 43 patients (39%), and major access-site complications in 10 patients (9.2%). Complete hemostasis was achieved in 77 patients (70.6%), by the application of the MANTA plug alone. In the group with access-site-related adverse events, compared with the group without, the tortuosity index was higher median (26% interquartile range [IQR 18%-33%] vs median 19% [IQR 13%-29%], respectively; P = 0.012), as was maximal angulation median (50° [IQR 40°-59°] vs median 43° [IQR 36°-51°], respectively; P = 0.026) were higher. Both variables had a significant effect on our primary outcome, with odds ratios (OR) of 3.1 (tortuosity, P = 0.005) and 2.6 (angulation, P = 0.020). The degree of angulation was a predictor of major complications too (odds ratio 7 [1.4-34.8]; P = 0.017). Conclusions: Steeper angles and greater arterial elongation increase the risk of vascular and bleeding complications after femoral TAVI with the utilization of a plug-based closure device

Iliofemoral Tortuosity Increases the Risk of Access-Site-Related Complications After Aortic Valve Implantation and Plug-Based Access-Site Closure

BACKGROUND: Access-site-related complications are often related to high-risk anatomy and technical pitfalls and impair the outcomes of transfemoral aortic valve implantations (TAVIs). Calcification and tortuosity are widely recognized risk factors, and their impact on procedural planning is left to the implanting experts’ discretion. To facilitate decision-making, we introduced a quantitative measure for iliofemoral tortuosity and assessed its predictive value for access-site-related vascular and bleeding complications. METHODS: We performed a single-centre prospective cohort study of consecutive, percutaneous transfemoral TAVI performed between April 2019 and March 2020. Medical history and all-cause mortality were extracted from the electronic patient files. Arterial anatomy and calcifications were evaluated using 3mensio Structural Heart software. The primary outcome was access-site-related vascular or bleeding complications. RESULTS: In this elderly, intermediate-risk population, we registered the primary outcome in 43 patients (39%), and major access-site complications in 10 patients (9.2%). Complete hemostasis was achieved in 77 patients (70.6%), by the application of the MANTA plug alone. In the group with access-site-related adverse events, compared with the group without, the tortuosity index was higher median (26% interquartile range [IQR 18%-33%] vs median 19% [IQR 13%-29%], respectively; P = 0.012), as was maximal angulation median (50° [IQR 40°-59°] vs median 43° [IQR 36°-51°], respectively; P = 0.026) were higher. Both variables had a significant effect on our primary outcome, with odds ratios (OR) of 3.1 (tortuosity, P = 0.005) and 2.6 (angulation, P = 0.020). The degree of angulation was a predictor of major complications too (odds ratio 7 [1.4-34.8]; P = 0.017). CONCLUSIONS: Steeper angles and greater arterial elongation increase the risk of vascular and bleeding complications after femoral TAVI with the utilization of a plug-based closure device

Natural and Synthetic Sortase A Substrates Are Processed by Staphylococcus aureus via Different Pathways

Endogenous Staphylococcus aureus sortase A (SrtA) covalently incorporates cell wall anchored proteins equipped with a SrtA recognition motif (LPXTG) via a lipid II-dependent pathway into the staphylococcal peptidoglycan layer. Previously, we found that the endogenous S. aureus SrtA is able to recognize and process a variety of exogenously added synthetic SrtA substrates, including K(FITC)LPMTG-amide and K(FITC)-K-vancomycin-LPMTG-amide. These synthetic substrates are covalently incorporated into the bacterial peptidoglycan (PG) of S. aureus with varying efficiencies. In this study, we examined if native and synthetic substrates are processed by SrtA via the same pathway. Therefore, the effect of the lipid II inhibiting antibiotic bacitracin on the incorporation of native and synthetic SrtA substrates was assessed. Treatment of S. aureus with bacitracin resulted in a decreased incorporation of protein A in the bacterial cell wall, whereas incorporation of exogenous synthetic substrates was increased. These results suggest that natural and exogenous synthetic substrates are processed by S. aureus via different pathways

Natural and Synthetic Sortase A Substrates Are Processed by Staphylococcus aureus via Different Pathways

Endogenous Staphylococcus aureus sortase A (SrtA) covalently incorporates cell wall anchored proteins equipped with a SrtA recognition motif (LPXTG) via a lipid II-dependent pathway into the staphylococcal peptidoglycan layer. Previously, we found that the endogenous S. aureus SrtA is able to recognize and process a variety of exogenously added synthetic SrtA substrates, including K(FITC)LPMTG-amide and K(FITC)-K-vancomycin-LPMTG-amide. These synthetic substrates are covalently incorporated into the bacterial peptidoglycan (PG) of S. aureus with varying efficiencies. In this study, we examined if native and synthetic substrates are processed by SrtA via the same pathway. Therefore, the effect of the lipid II inhibiting antibiotic bacitracin on the incorporation of native and synthetic SrtA substrates was assessed. Treatment of S. aureus with bacitracin resulted in a decreased incorporation of protein A in the bacterial cell wall, whereas incorporation of exogenous synthetic substrates was increased. These results suggest that natural and exogenous synthetic substrates are processed by S. aureus via different pathways

Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization.

A number of cationic antimicrobial peptides, among which are histatin 5 and the derived peptides dhvar4 and dhvar5, enter their target cells and interact with internal organelles. There still are questions about the mechanisms by which antimicrobial peptides translocate across the membrane. We used a liposome model to study membrane binding, translocation and membrane-perturbing capacities of histatin 5, dhvar4 and dhvar5. Despite the differences in amphipathic characters of these peptides, they bound equally well to liposomes, whereas their membrane activities differed remarkably: dhvar4 translocated at the fastest rate, followed by dhvar5, whereas the histatin 5 translocation rate was much lower. The same pattern was seen for the extent of calcein release: highest with dhvar4, less with dhvar5 and almost none with histatin 5. The translocation and disruptive actions of dhvar5 did not seem to be coupled, because translocation occurred on a much longer timescale than calcein release, which ended within a few minutes. We conclude that peptide translocation can occur through peptide-phospholipid interactions, and that this is a possible mechanism by which antimicrobial peptides enter cells. However, the translocation rate was much lower in this model membrane system than that seen in yeast cells. Thus it is likely that, at least for some peptides, additional features promoting the translocation across biological membranes are involved as well