Finding the partner: FRET and beyond.

Given the importance of aberrant protein-protein interactions (PPIs) in disease, the recent drug discovery focuses on targeting the altered PPIs to treat the disease. In this context, identifying the atypical PPIs underlying the disease is critical for the development of diagnostics and therapeutics. Various biochemical, biophysical, and genetic methods have been reported to study PPIs. Here, we are giving a short account of those techniques with more emphasis on Forster resonance energy transfer (FRET), which can be used to monitor macromolecular interactions in live cells. Besides the basics of FRET, we explain the modifications of its application, like Single molecule FRET (smFRET), Fluorescence Lifetime Imaging Microscopy- FRET (FLIM-FRET), and photoswitching FRET. While smFRET is extensively used for evaluating the biology of nucleic acids and also to develop diagnostics, FLIM-FRET is widely exploited to study the PPIs underlying neurological disorders and cancer. Photoswitching FRET is a relatively newer technique and it has tremendous potential to unravel the significance of different PPIs. Besides these modifications, there are several advancements in the field by introducing new fluorophores. Identification of lanthanide chelates, quantum dots, and other nanoparticle fluorophores has revolutionized the applications of FRET in diagnostics and basic biology. Yet, these methods can be employed to study the interactions of only two molecules. Since the majority of the PPIs are multimeric complexes, we still need to improve our technologies to study these interactions in live cells in real-time.

Layer-over-Layer Electrostatic Self-Assembly of Bioresourced Compounds in Thermoreversible Polylactide Gels as an Effective Approach to Enhance the Flame Retardancy of Aerogels.

Polylactide is a high potential polymer that can satisfy the growing demand for sustainable and lightweight materials in construction, packaging, and structural applications. However, their high flammability poses a serious concern. Herein, with the aid of solvent exchange and noncovalent interactions, poly(l-lactide) (PLLA) thermoreversible gel was modified with sodium alginate (SA), chitosan (CS), and phytic acid (PA) via a layer-over-layer approach. Freeze-drying of the modified hydrogel furnished a highly flame retardant aerogel with shape stability and no shrinkage. The modified PLLA aerogel (PLLA@SA@CS@PA) exhibited self-extinguishment of flame, the highest limiting oxygen index of any porous polylactide (∼32%), and a tremendous reduction in flammability parameters such as the heat release rate, heat release capacity, total heat release, etc. A comprehensive mechanism of flame retardancy was proposed. This work provides a sustainable strategy for the flame retardant modification of semicrystalline polymer-based aerogels and is expected to expand their practical applications in various industrial sectors.

Two-Year Clinical Outcomes of Staged Transcatheter Mitral Edge-to-Edge Repair After Transcatheter Aortic Valve Replacement.

Residual significant mitral regurgitation (MR) can increase the risk of adverse events after transcatheter aortic valve replacement (TAVR). The clinical benefits of staged transcatheter edge-to-edge repair (TEER) after TAVR remain underexplored. This study aimed to investigate the clinical outcomes of staged TEER for residual significant MR after TAVR. This observational study included 314 consecutive patients with chronic residual grade 3+ or 4+ MR at the 30-day follow-up after TAVR, with 104 patients (33.1%) treated with staged TEER (TEER group) and 210 (66.9%) with medical therapy alone. The primary composite outcomes were all-cause mortality and heart failure hospitalization at 2 years. Additional analysis, including changes in MR grade and the New York Association functional classification, and subgroup outcome comparisons based on MR etiology were also conducted. In our study, the rate of primary composite outcome was lower in the TEER group than in the medical therapy alone group (33.7% vs 48.1%, p = 0.015). Significant improvement in MR grade and New York Association class was observed in the TEER group after 2 years. The subgroup analysis demonstrated that in patients with degenerative MR, a lower incidence of composite outcome and heart failure hospitalization was observed in the TEER group (hazard ratio 0.35, 95% confidence interval 0.23 to 0.53, p <0.001). In conclusion, staged TEER after TAVR was associated with reduced MR and improved clinical outcomes. The clinical significance of MR after TAVR should be carefully evaluated, and TEER should be considered for patients with significant residual MR, particularly, those with degenerative MR.

A comprehensive study on engineering and sustainability characteristics with emphasizing on 3R's approach in building construction.

The study assesses the mechanical efficiency, long-lasting characteristics, microstructure, and sustainability of sustainable concrete (SC) samples through several optimization methods, emphasizing the significance of the 3Rs (recycle, reuse, reduce) approach in the construction sector. The study uses advanced techniques like the Taguchi method, grey relational analysis (GRA), analysis of variance (ANOVA), and signal-noise ratio (SNR) to optimize parameters affecting the performance of SC. In this study, the properties of SC are assessed by considering various parameters. These parameters include the use of 10 %, 20 %, and 30 % of ground granulated blast furnace slag (GGBFS) as a replacement for fly ash (FA). Additionally, six different binder contents ranging from 300 kg/m3 to 600 kg/m3 are examined. The study also investigates three different molarities of sodium hydroxide (NaOH) (8 M, 12 M, and 16 M), three different ratios of alkaline activators (AA) (1.5, 2.0, and 2.5), three different AA to-binder ratios (0.30, 0.35, and 0.40), and curing temperature (CT) of 30 °C, 60 °C, and 90 °C. The study includes fresh properties such as fresh density (FD) and slump, mechanical properties such as tensile strength (TS), flexural strength (FS), modulus of elasticity (MOE), and compressive strength (CS), and durability studies such as dry density (DD), impact strength, water absorption (WA), and sorptivity. The blended proportions were obtained using the Taguchi method. The study shows that GGBFS accelerates geopolymerization in FA-based concrete, reducing setting time and early-age CS. FA is crucial for setting time, workability, and CS enhancement. GGBFS increases the densities of fresh and hardened concrete, with a highly correlated increase, allowing accurate hardened density prediction with a coefficient of 0.9057. The CS of the cube SC surpassed 40 MPa, irrespective of variables such as the AA ratio, CT, and NaOH molarity. The trail mix with a binder concentration of 600 kg/m3, 30 % GGBFS content, 12 M NaOH molarity, 1.5 AA ratio, 0.35 AA to binder ratio, and 90 °C CT exhibited the greatest strength. Mixtures containing 10 % GGBFS can attain a CS above 30 MPa after 28 days, making them suitable for structural purposes. The T18 mix exhibited a compact Calcium (alumino) silicate hydrate (C-A-S-H) and N-A-S-H gel, whereas the T3 mix displayed a varied and permeable structure. The study used GRA, ANOVA, and SNR methods to analyze properties varying by six variables, finding GGBFS content as the most influencing parameter. The study found that the SC had a lower sustainability score than the OPC mix, but had better energy efficiency.

Incidence, Predictors, and Outcomes of Paravalvular Regurgitation After TAVR in Sievers Type 1 Bicuspid Aortic Valves.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR). OBJECTIVES: The aim of this study was to identify the incidence, predictors, and clinical outcomes of PVR after TAVR in Sievers type 1 BAV stenosis. METHODS: Consecutive patients with Sievers type 1 BAV stenosis undergoing TAVR with current-generation transcatheter heart valves (THVs) in 24 international centers were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAEs), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up. RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%)-mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were a larger virtual raphe ring perimeter (adjusted OR: 1.07; 95% CI: 1.02-1.13), severe annular or left ventricular outflow tract calcification (adjusted OR: 5.21; 95% CI: 1.45-18.77), a self-expanding valve (adjusted OR: 9.01; 95% CI: 2.09-38.86), and intentional supra-annular THV positioning (adjusted OR: 3.31; 95% CI: 1.04-10.54). At a median follow-up of 1.3 years (Q1-Q3: 0.5-2.4 years), moderate or severe PVR was associated with an increased risk of MAEs (adjusted HR: 2.52; 95% CI: 1.24-5.09). CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAEs during follow-up.

Fracture Strength of Tooth Roots Following Canal Preparation by Three Rotary File Systems: An In Vitro Study.

BACKGROUND: Since the beginning of modern endodontics, there have been many concepts, strategies, and techniques for root canal preparation. A mind-boggling variety of files have developed for negotiating and shaping them throughout the years. Today's most secure, most effective, and simplest file system combines the most reliable design elements of the past with the latest technological advances to create the most effective file system. So, the need for the study is to evaluate the fracture strength of tooth roots following canal preparation by three rotary file systems: ProTaper Universal file system (Dentsply, USA), ProTaper Next file system (Dentsply Sirona USA), and Neolix A1 nickel-titanium (NiTi) file system (Orikam Healthcare India Pvt Ltd., New Delhi, India). METHOD: Ninety human mandibular molars were selected for the study. Inclusion criteria include human mandibular first and second molars and teeth removed for routine clinical reasons, and intact apices were selected, excluding cases with root surface caries, root surface fissures, teeth with immature root apex, mesial canal fusion, extremely short roots, thin roots, or curved roots. All teeth were preserved in a solution of 10% neutral buffered formalin for two weeks and then transferred to distilled water for examination. The teeth were randomly divided into three groups. Access cavities were created, and working lengths were determined. Groups 1, 2, and 3 underwent shaping using ProTaper Universal, ProTaper Next, and Neolix A1 (NiTi) file systems, respectively, following guidelines. Canals were irrigated with sodium hypochlorite and ethylenediaminetetraacetic acid (EDTA) and were obturated up to the mid-root region with AH Plus sealer. To facilitate fracture testing, obturation was performed to distribute the load from the spreader to the canal wall. The EndoSequence and Quick-Fill obturation system were utilized to fill the apical half of the canal with gutta-percha material. After obturation, the distal root of each tooth was cut, while the mesial root was securely positioned in a putty material. A universal testing machine was employed for the fracture tests, operating at a cross-head speed of 1 mm/min. The machine was equipped with a D11 hand spreader tip, which was inserted into the root canal to make contact with the gutta-percha. Gradual force was applied to the root canal until a fracture occurred, at which point the force application was stopped. The amount of force required to cause the fracture was measured in newtons. Data were collected and recorded using IBM SPSS Statistics for Windows, Version 17.0 (Released 2008; IBM Corp., Armonk, New York, United States) and then transferred to Microsoft Excel for analysis. Descriptive statistics, mean, and standard deviation were used for continuous data. The fracture resistance of dental roots treated with three types of files was compared using a one-way ANOVA. Graphs were generated using Excel and Word. A significance level of p<0.01 was chosen. RESULT: ANOVA indicated significant differences in mean fracture resistance: Neolix A1 (NiTi) (95.3 N) > NEXT (91.0 N) > universal (86.6 N), with a p-value of 0.004 (<0.001), confirming statistical significance. CONCLUSION: The study concludes that the canal instrumented with Neolix A1 (NiTi) exhibits higher fracture resistance after canal instrumentation compared to ProTaper Next and ProTaper Universal.

One- versus three-month dual antiplatelet therapy in high bleeding risk patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: A short dual antiplatelet therapy (DAPT) duration has been proposed for patients at high bleeding risk (HBR) undergoing drug-eluting coronary stent (DES) implantation. Whether this strategy is safe and effective after a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains uncertain. AIMS: We aimed to compare the impact of 1-month versus 3-month DAPT on clinical outcomes after DES implantation among HBR patients with or without NSTE-ACS. METHODS: This is a prespecified analysis from the XIENCE Short DAPT programme involving three prospective, international, single-arm studies evaluating the safety and efficacy of 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT among HBR patients after implantation of a cobalt-chromium everolimus-eluting stent. Ischaemic and bleeding outcomes associated with 1- versus 3-month DAPT were assessed according to clinical presentation using propensity score stratification. RESULTS: Of 3,364 HBR patients (1,392 on 1-month DAPT and 1,972 on 3-month DAPT), 1,164 (34.6%) underwent DES implantation for NSTE-ACS. At 12 months, the risk of the primary endpoint of death or myocardial infarction was similar between 1- and 3-month DAPT in patients with (hazard ratio [HR] 1.09, 95% confidence interval [CI]: 0.71-1.65) and without NSTE-ACS (HR 0.88, 95% CI: 0.63-1.23; p-interaction=0.34). The key secondary endpoint of Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding was consistently reduced in both NSTE-ACS (HR 0.57, 95% CI: 0.37-0.88) and stable patients (HR 0.84, 95% CI: 0.61-1.15; p-interaction=0.15) with 1-month DAPT. CONCLUSIONS: Among HBR patients undergoing implantation of an everolimus-eluting stent, 1-month, compared to 3-month DAPT, was associated with similar ischaemic risk and reduced bleeding at 1 year, irrespective of clinical presentation.

Immersive virtual reality-based learning as a supplement for biomedical engineering labs: challenges faced and lessons learned.

Introduction: Immersive virtual reality (VR) based laboratory demonstrations have been gaining traction in STEM education as they can provide virtual hands-on experience. VR can also facilitate experiential and visual learning and enhanced retention. However, several optimizations of the implementation, in-depth analyses of advantages and trade-offs of the technology, and assessment of receptivity of modern techniques in STEM education are required to ensure better utilization of VR-based labs. Methods: In this study, we developed VR-based demonstrations for a biomolecular engineering laboratory and assessed their effectiveness using surveys containing free responses and 5-point Likert scale-based questions. Insta360 Pro2 camera and Meta Quest 2 headsets were used in combination with an in-person lab. A cohort of 53 students watched the experimental demonstration on VR headsets in the lab after a brief lab overview in person and then performed the experiments in the lab. Results: Only 28.29% of students reported experiencing some form of discomfort after using the advanced VR equipment as opposed to 63.63% of students from the previous cohort. About 40% of the students reported that VR eliminated or reduced auditory and visual distractions from the environment, the length of the videos was appropriate, and they received enough information to understand the tasks. Discussion: The traditional lab method was found to be more suitable for explaining background information and lab concepts while the VR was found to be suitable for demonstrating lab procedures and tasks. Analyzing open-ended questions revealed several factors and recommendations to overcome the potential challenges and pitfalls of integrating VR with traditional modes of learning. This study provides key insights to help optimize the implementation of immersive VR to effectively supplement in-person learning experiences.

TAVR-in-TAVR with a balloon-expandable valve for paravalvular leak.

Introduction: Paravalvular leak (PVL) is a severe complication of transcatheter aortic valve replacement (TAVR) that can lead to poor outcomes. TAVR-in-TAVR is a promising treatment for PVL; however, reports on its safety or efficacy are limited. In this study, we aimed to investigate the clinical outcomes of TAVR-in-TAVR using balloon-expandable prostheses for PVLs after TAVR. Methods: We retrospectively analyzed data from patients who underwent TAVR-in-TAVR using balloon-expandable Sapien prostheses for PVL after an initial TAVR at our institution. The procedural success, in-hospital complications, all-cause mortality, and echocardiographic data for up to 2 years post-surgery were evaluated. Results: In total, 31 patients with a mean age of 81.1 ± 7.9 years and mean Society of Thoracic Surgeons score of 8.8 ± 5.4% were identified. The procedural success rate of TAVR-in-TAVR was 96.8% (30/31). No in-hospital deaths, cardiac tamponade, or conversion to sternotomy occurred. Re-intervention was performed in only one patient (3.2%) during hospitalization. The all-cause mortality rates at 30 days and 2 years were 0% and 16.1%, respectively. A significant reduction in the PVL rate was observed at 30 days compared with that at baseline (p < 0.01). Discussion: Our findings suggest that TAVR-in-TAVR using balloon-expandable prostheses is safe and effective for PVL after TAVR with low complication rates and acceptable long-term outcomes. Further studies with larger sample sizes are needed to confirm our findings.

Comparative Evaluation of Debris Expulsion Beyond Apex During Re-root Canal Treatment by Utilizing Two Re-treatment Rotary Files and Two Reciprocating Files: An In-Vitro Study.

AIM: This study aimed to assess and compare debris quality expelled beyond the apex during re-treatment using two reciprocating and two re-treatment rotary files. MATERIALS AND METHODS: A total of 80 healthy human mandibular premolars excised for orthodontic therapy were selected. Distilled water was used to sterilize the teeth before they were preserved. The canals were widened and coronal access was created so that the F2 ProTaper universal system could be used. For the obturation, we utilized gutta-percha cones and AH plus sealant. All samples were cone-beam computed tomography (CBCT) recorded. Teeth were separated into four groups (n=20); Group 1: ProTaper re-treatment, Group 2: Mtwo re-treatment, Group 3: WaveOne gold, and Group 4: Reciproc. The re-instrumented process included collecting the extruded debris in Eppendorf tubes and then drying it off by evaporating the distilled water. The weight of the tube with debris was subtracted from the weight of the tube without debris to get the dry debris weight. Post-retreatment CBCT was recorded for all samples. Mean apical debris extrusion values were obtained, after which necessary statistical analysis was obtained using SPSS Statistics, version 21 (IBM Corp., Armonk, NY) to obtain the results. A one-way analysis of variance (ANOVA) and the student t-test were utilized for statistical analysis to compare the different experimental groups. Post-hoc Bonferroni tests were used to compare several groups. RESULT: No statistical difference (p>0.05) was identified in the filler material that was left over across all groups. The reciprocating files discharged more material compared with re-treatment file systems. CONCLUSION: The Reciproc files expelled more waste than WaveOne gold, ProTaper re-treatment, and Mtwo re-treatment file systems. Reciprocating file systems showed better cleaning efficiency compared to the re-treatment file systems.

Prognostic Value of Left Ventricular Global Longitudinal Strain in Transcatheter Edge-to-Edge Repair for Chronic Primary Mitral Regurgitation.

AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-center, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9-(-16)%, -15.9-(-12)%, > -12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability - all along the first year after intervention. Subjects with worse (i.e., less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9 vs 6.3%, Log-Rank p = 0.005, HR 1.75, 95% CI 1.08-4.74, p = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1 vs 11.5%, Log-Rank p = 0.037, HR 1.68, 95% CI 1.02-5.46, p = 0.047). No association was demonstrated with other endpoints. Upon exploratory analysis, 1-month postprocedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value - but not the presence/extent of deterioration - conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favorable postprocedural course, presumably reflecting a higher-risk patient profile.

The challenges and prospects of smooth muscle tissue engineering.

Many vascular disorders arise as a result of dysfunctional smooth muscle cells. Tissue engineering strategies have evolved as key approaches to generate functional vascular smooth muscle cells for use in cell-based precision and personalized regenerative medicine approaches. This article highlights some of the challenges that exist in the field and presents some of the prospects for translating research advancements into therapeutic modalities. The article emphasizes the need for better developing synergetic intracellular and extracellular cues in the processes to generate functional vascular smooth muscle cells from different stem cell sources for use in tissue engineering strategies.

This paper explores the potential of engineering smooth muscle tissues to treat vascular diseases, focusing on challenges like sourcing the right cells and creating supportive environments for cell growth. It highlights advances in materials that mimic the body's conditions and the use of 3D fabrication methods for creating complex structures. Additionally, it discusses the significance of mitochondrial function in blood vessel muscle cells. The research emphasizes interdisciplinary efforts and personalized treatments as key to developing effective therapies. The goal is to engineer lab-grown tissues that can repair or replace damaged blood vessels, offering hope for addressing major health challenges associated with vascular diseases.

Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study.

BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.

Real-World Outcomes for the Fifth-Generation Balloon Expandable Transcatheter Heart Valve in the United States.

BACKGROUND: The fifth-generation SAPIEN 3 Ultra Resilia valve (S3UR) incorporates several design changes as compared with its predecessors, the SAPIEN 3 (S3) and SAPIEN 3 Ultra (S3U) valves, including bovine leaflets treated with a novel process intended to reduce structural valve deterioration via calcification, as well as a taller external skirt on the 29-mm valve size to reduce paravalvular leak (PVL). The clinical performance of S3UR compared with S3 and S3U in a large patient population has not been previously reported. OBJECTIVES: The aim of this study was to compare S3UR to S3/S3U for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR). METHODS: Patients enrolled in the STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between January 1, 2021, and June 30, 2023, who underwent TAVR with S3UR or S3U/S3 valve platforms were propensity-matched and evaluated for procedural, in-hospital, and 30-day clinical and echocardiographic outcomes. RESULTS: 10,314 S3UR patients were propensity matched with 10,314 patients among 150,539 S3U/S3 patients. At 30 days, there were no statistically significant differences in death, stroke, or bleeding, but a numerically higher hospital readmission rate in the S3UR cohort (8.5% vs 7.7%; P = 0.04). At discharge, S3UR patients exhibited significantly lower mean gradients (9.2 ± 4.6 mm Hg vs 12.0 ± 5.7 mm Hg; P < 0.0001) and larger aortic valve area (2.1 ± 0.7 cm2 vs 1.9 ± 0.6 cm2; P < 0.0001) than patients treated with S3/S3U. The 29-mm valve size exhibited significant reduction in mild PVL (5.3% vs 9.4%; P < 0.0001). CONCLUSIONS: S3UR TAVR is associated with lower mean gradients and lower rates of PVL than earlier generations of balloon expandable transcatheter heart valve platforms.

Mitral Transcatheter Edge-to-Edge Repair in Nonagenarians.

BACKGROUND: There are scarce data regarding mitral transcatheter edge-to-edge repair (TEER) in individuals aged 90 years and above. We aimed to evaluate patient characteristics, procedural aspects, and outcomes in this rapidly growing group. METHODS: We retrospectively studied a single-centre database of 967 isolated, first-time interventions, 103 (10.7%) of which were performed in nonagenarians. Outcomes included all-cause mortality, heart failure (HF) hospitalizations, and the persistence of significant mitral regurgitation (MR) or New York Heart Association functional class III/IV during the first postprocedural year. Analyses were repeated on a 204-patient, propensity score-matched subcohort, controlling for MitraScore elements, sex, race, MR etiology, functional status, atrial fibrillation/flutter, and procedural urgency. RESULTS: Compared with subjects below 90 years of age, nonagenarians were more likely to be white women of higher socioeconomic status; had a higher interventional risk, driven mainly by age and chronic kidney disease; presented more often with primary MR (71.8 vs 39.1%, P < 0.001); and exhibited less advanced biochemical/echocardiographic indices of cardiac remodelling. Further, their procedures were more commonly nonurgent and used fewer devices. A similarly high (> 97%) technical success rate was achieved in the 2 study groups. Likewise, no intergroup differences were observed in the rates or cumulative incidences of any of the explored endpoints, and neither of the outcomes' risks was associated with age 90 and above. Comparable outcomes were also noted in the propensity score-matched subgroups. CONCLUSIONS: In our experience, mitral TEER was equally feasible, safe, and efficacious in patients below and above 90 years of age.

A New Intervention for Implementation of Pharmacogenetics in Psychiatry: A Description of the PSY-PGx Clinical Study.

(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. (2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants escitalopram and sertraline or antipsychotics risperidone and aripiprazole according to the latest state-of-the-art international dosing recommendations for CYP2C19 and CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. (3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.

1- Versus 3-Month DAPT in Older Patients at a High Bleeding Risk Undergoing PCI: Insights from the XIENCE Short DAPT Global Program.

This analysis aimed to evaluate the effect of 1- versus 3-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in older patients. Data from 3 prospective, single-arm studies (XIENCE Short DAPT Program), including patients with high bleeding risk successfully treated with an everolimus-eluting stent (XIENCE, Abbott) were analyzed. DAPT was discontinued at 1 or at 3 months in patients free from ischemic events and adherent to DAPT. Patients were stratified according to age (≥75 and <75 years). The primary end point was all-cause death or myocardial infarction (MI). The key secondary end point was Bleeding Academic Research Consortium type 2 to 5 bleeding. The outcomes were assessed from 1 to 12 months after index PCI. Of 3,364 patients, 2,241 (66.6%) were aged ≥75 years. The risk of death or MI was similar with 1- versus 3-month DAPT in patients aged ≥75 (8.5% vs 8.0%, adjusted hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69 to 1.30) and <75 years (6.9% vs 7.8%, adjusted HR 0.97, 95% CI 0.60 to 1.57, interaction p = 0.478). Bleeding Academic Research Consortium type 2 to 5 bleeding was consistently lower with 1- than with 3-month DAPT in patients aged ≥75 years (7.2% vs 9.4%, adjusted HR 0.66, 95% CI 0.48 to 0.91) and <75 years (9.7% vs 11.9%, adjusted HR 0.86, 95% CI 0.57 to 1.29, interaction p = 0.737). In conclusion, in patients at high bleeding risk who underwent PCI, patients older and younger than 75 years derived a consistent benefit from 1- compared with 3-month DAPT in terms of bleeding reduction, with no increase in all-cause death or MI at 1 year.

Implications of Mitral Annular Calcification on Outcomes Following Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Limited data exist regarding the impact of mitral annular calcification (MAC) on outcomes of transcatheter edge-to-edge repair for mitral regurgitation (MR). METHODS: We retrospectively analyzed 968 individuals (median age, 79 [interquartile range, 70-86] years; 60.0% males; 51.8% with functional MR) who underwent an isolated, first-time intervention. Stratified by MAC extent per baseline transthoracic echocardiogram, the cohort was assessed for residual MR, functional status, all-cause mortality, heart failure hospitalizations, and mitral reinterventions post-procedure. RESULTS: Patients with above-mild MAC (n=101; 10.4%) were older and more likely to be female, exhibited a greater burden of comorbidities, and presented more often with severe, primary MR. Procedural aspects and technical success rate were unaffected by MAC magnitude, as was the significant improvement from baseline in MR severity and functional status along the first postprocedural year. However, the persistence of above-moderate MR or functional classes III and IV at 1 year and the cumulative incidence of reinterventions at 2 years were overall more pronounced within the above-mild MAC group (significant MR or functional impairment, 44.7% versus 29.9%, P=0.060; reinterventions, 11.9% versus 6.2%, P=0.033; log-rank P=0.035). No link was demonstrated between MAC degree and the cumulative incidence or risk of mortality and mortality or heart failure hospitalizations. Differences in outcomes frequencies were mostly confined to the primary MR subgroup, in which patients with above-mild MAC also experienced earlier, more frequent 2-year heart failure hospitalizations (20.8% versus 9.6%; P=0.016; log-rank P=0.020). CONCLUSIONS: Mitral transcatheter edge-to-edge repair in patients with and without above-mild MAC is equally feasible and safe; however, its postprocedural course is less favorable among those with primary MR.

A quad DC source switched three-phase multilevel DC-link inverter topology.

The concept of an isolated DC source cascaded multilevel inverter finds good solutions for generating quality output voltage for low-medium power applications. It shapes the output voltage from three levels into a number of steps closer to a sinusoidal shape using small DC sources or batteries. Several advantages have been sighted like lower voltage stress and bearing noise, and lesser THD. However, a common issue in the MLIs is the total components required which increase with the rise in voltage levels. This paper proposes a three-phase MLI design having several isolated quad voltage source modules including an H-Bridge inverter. The design suggested claims reduced switching components for current conduction paths showing improved output quality. The operational features of the suggested MLI have been analyzed using Matlab/Simulink software, furthermore, an experimental module is constructed for demonstrating the effectiveness of the simulated results.