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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Elkoumy, Ahmed, et al.
(författare)
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ACURATE neo2 Transcatheter aortic valve implantation without balloon aortic valvuloplasty : direct ACURATE neo2
- 2024
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Ingår i: International Journal of Cardiology. - 0167-5273 .- 1874-1754. ; 400
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Tidskriftsartikel (refereegranskat)abstract
- Background: ACURATE neo2 (Neo2) implantation is performed after systematic Balloon Aortic Valvuloplasty (BAV) in most patients. No reports exist about the feasibility and safety of direct Neo2 transcatheter aortic valve implantation (TAVI) in comparison to the standard practice. Aim: We aimed to identify the patients' baseline anatomical characteristics, procedural, and early post-procedural outcomes in patients treated using Neo2 with and without BAV. Methodology: This is a retrospective multicentre analysis of 499 patients with severe aortic stenosis who underwent TAVI using Neo2. The comparison was done according to the performance or omission of BAV. Echocardiography and computed tomography were analysed by an independent Core Lab. Propensity score matching (PSM) was performed based on the annular diameter and AV calcium volume, which identified 84 matched pairs. Results: Among the cohort included, 391 (78%) patients received BAV (BAV-yes) and 108 (22%) were not attempted (BAV-no or Direct TAVI). Patients in BAV-no cohort had smaller annular diameter (22.6 vs 23.4 mm; p < 0.001) and lower calcium volume (163 vs 581 mm3; p < 0.001) compared to BAV-yes cohort. In the matched cohort, VARC-3 device technical success was similar (95%) and all other outcome measures were statistically comparable between cohorts. Conclusion: Direct TAVI using ACURATEneo2 without pre-TAVI balloon aortic valvuloplasty in patients with mild or less valve calcifications might be feasible and associated with comparable early outcomes compared to patients with similar anatomical features undergoing systematic balloon valvuloplasty.
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| 4. |
- Elkoumy, Ahmed, et al.
(författare)
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Core Lab Adjudication of the ACURATE neo2 Hemodynamic Performance Using Computed-Tomography-Corrected Left Ventricular Outflow Tract Area
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:20, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Hemodynamic assessment of prosthetic heart valves using conventional 2D transthoracic Echocardiography-Doppler (2D-TTE) has limitations. Of those, left ventricular outflow tract (LVOT) area measurement is one of the major limitations of the continuity equation, which assumes a circular LVOT. (2) Methods: This study comprised 258 patients with severe aortic stenosis (AS), who were treated with the ACURATE neo2. The LVOT area and its dependent Doppler-derived parameters, including effective orifice area (EOA) and stroke volume (SV), in addition to their indexed values, were calculated from post-TAVI 2D-TTE. In addition, the 3D-LVOT area from pre-procedural MDCT scans was obtained and used to calculate corrected Doppler-derived parameters. The incidence rates of prosthesis patient mismatch (PPM) were compared between the 2D-TTE and MDCT-based methods (3) Results: The main results show that the 2D-TTE measured LVOT is significantly smaller than 3D-MDCT (350.4 ± 62.04 mm2 vs. 405.22 ± 81.32 mm2) (95% Credible interval (CrI) of differences: −55.15, −36.09), which resulted in smaller EOA (2.25 ± 0.59 vs. 2.58 ± 0.63 cm2) (Beta = −0.642 (95%CrI of differences: −0.85, −0.43), and lower SV (73.88 ± 21.41 vs. 84.47 ± 22.66 mL), (Beta = −7.29 (95% CrI: −14.45, −0.14)), respectively. PPM incidence appears more frequent with 2D-TTE- than 3D-MDCT-corrected measurements (based on the EOAi) 8.52% vs. 2.32%, respectively. In addition, significant differences regarding the EOA among the three valve sizes (S, M and L) were seen only with the MDCT, but not on 2D-TTE. (4) Conclusions: The corrected continuity equation by combining the 3D-LVOT area from MDCT with the TTE Doppler parameters might provide a more accurate assessment of hemodynamic parameters and PPM diagnosis in patients treated with TAVI. The ACURATE neo2 THV has a large EOA and low incidence of PPM using the 3D-corrected LVOT area than on 2D-TTE. These findings need further confirmation on long-term follow-up and in other studies.
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| 5. |
- Kim, Won Keun, et al.
(författare)
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Outcomes and performance of the ACURATE neo2 transcatheter heart valve in clinical practice : one-yearresults of the ACURATE neo2 PMCF Study
- 2024
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Ingår i: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - 1969-6213. ; 20:1, s. 85-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transcatheter aortic valve implantation is an effective treatment for patients with aortic stenosis; however, complications related to paravalvular leakage (PVL) persist, including increased risk of mortality, cardiovascular mortality, and rehospitalisation. AIMS: We sought to evaluate the clinical outcomes and valve performance at 1 year in patients with severe aortic stenosis treated with the ACURATE neo2 valve in a post-market clinical setting. METHODS: Valve Academic Research Consortium-2 safety events were assessed up to 1 year. Independent core laboratories evaluated echocardiographic measures of valve performance and hypoattenuated leaflet thickening (HALT; as measured by four-dimensional computed tomography). RESULTS: The study enrolled 250 patients (64% female; mean age: 81 years; baseline Society of Thoracic Surgeons risk score: 2.9±2.0%); 246 patients were implanted with ACURATE neo2. All-cause mortality was 0.8% at 30 days and 5.1% at 1 year. The 1-year rates for stroke and disabling stroke were 3.0% and 1.3%, respectively. Overall, HALT of >50% leaflet involvement of at least one leaflet was present in 9% of patients at 30 days and in 12% of patients at 1 year. No association was observed between the presence of HALT and 1-year clinical or haemodynamic outcomes. Early haemodynamic improvements were maintained up to 1 year (mean aortic valve gradient: 47.6±14.5 mmHg at baseline, 7.6±3.2 mmHg at 1 year; mean aortic valve area: 0.7±0.2 cm2 at baseline, 1.7±0.4 cm2 at 1 year). At 1 year, 99% of patients had mild or no/trace PVL (<1% had moderate PVL; no patient had severe PVL). CONCLUSIONS: The study outcomes confirm favourable performance and safety up to 1 year in patients treated with ACURATE neo2 in routine clinical practice. (ClinicalTrials.gov: NCT04655248).
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| 6. |
- Rück, Andreas, et al.
(författare)
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The Early neo2 Registry : Transcatheter Aortic Valve Implantation With ACURATE neo2 in a European Population
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ACURATE neo2 is a transcatheter aortic valve implantation system consisting of a self-expanding bioprosthetic valve with supra-annular leaflet position and featuring innovations to facilitate placement accuracy and reduce paravalvular regurgitation. METHODS AND RESULTS: The goal of the Early neo2 (Early neo2 Registry of the ACURATE neo2 TAVI Prosthesis) was to gather real-life data on safety and efficacy in a European transcatheter aortic valve implantation population treated with ACURATE neo2. Data were collected from 554 consecutive patients treated with ACURATE neo2 at 12 European sites (mean age, 82 years; 66% women; mean European System for Cardiac Operative Risk Evaluation II, 4.5%±3.8%) between September 2020 and March 2021. The composite primary end point was the occurrence of any of the following: postoperative (in-hospital) paravalvular regurgitation grade ≥2, in-hospital acute kidney injury stage 3, postoperative pacemaker implantation, 30-day death, and 30-day stroke. The primary end point occurred in 12.6% of patients. The 30-day rates for all-cause death and all stroke were 1.3% and 2.7%, respectively, and 1.5% of patients exhibited stage 3 acute kidney injury. A total of 34 patients (6.2%) received a postoperative permanent pacemaker. Per core laboratory–adjudicated echocardiographic analysis, mean postoperative aortic valve gradient was 7.6±3.3 mm Hg, and 2.8% of patients exhibited paravalvular regurgitation grade ≥2. CONCLUSIONS: In this report of postmarket use of the ACURATE neo2 valve in a real-world transcatheter aortic valve implantation population, patients exhibited favorable postoperative hemodynamics and clinical outcomes and a low rate of postoperative pacemaker implantation.
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