Characterization and Management of Stable Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background/Objectives: To date, data regarding the characteristics and management of obstructive, stable coronary artery disease (CAD) encountered in patients undergoing transcatheter aortic valve implantation (TAVI) are sparse. The aim of the study was to analyze granular details, treatment, and outcomes of patients undergoing TAVI with obstructive, stable CAD from real-world practice. Methods: REVASC-TAVI (Management of myocardial REVASCularization in patients undergoing Transcatheter Aortic Valve Implantation with coronary artery disease) is an investigator-initiated, multicenter registry, which collected data from patients undergoing TAVI with obstructive stable CAD found during the pre-TAVI work-up. Results: A total of 2025 patients from 30 centers worldwide with complete follow-up were included in the registry. Most patients had single-vessel CAD (56.1%). An involvement of proximal coronary tracts was detected in 62.5% of cases, with 12.0% of patients having CAD in left main (LM). Most patients received percutaneous coronary intervention (PCI) (n = 1617, 79.9%), especially those with proximal CAD (90.4%). At 2 years, the rates of all-cause death [Kaplan-Meier (KM) estimates 20.1% vs. 18.8%, plog-rank = 0.86] and of the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure (KM estimates 29.7% vs. 27.5%, plog-rank = 0.82) did not differ between patients undergoing PCI and those who were not. Conclusions: Patients undergoing TAVI with obstructive CAD more commonly had a single-vessel disease and an involvement of proximal coronary tracts. They were commonly treated with PCI, with similar outcomes compared to those treated conservatively.

Clinical impact of complex percutaneous coronary intervention in the pre-TAVR workup.

INTRODUCTION AND OBJECTIVES: In patients undergoing percutaneous coronary intervention (PCI) in the workup pre-transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup. METHODS: This was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated. RESULTS: A total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiac death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.31; 95%CI, 1.01-1.71; P=.042). CONCLUSIONS: In TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population.

Partial replacement of mineral fertilisers with animal manures in an apple orchard: Effects on GHG emission.

Partial replacement of mineral fertilisers (MF) with animal manures is a good alternative to reduce MF use and increase both nutrient cycling in agriculture and soil organic matter. However, the adoption of this practice must not lead to increased environmental impacts. In this two-year study conducted in an apple orchard, MF were partially replaced with various animal manures, including cattle slurry (CS), acidified cattle slurry (ACS), solid cattle manure (CsM), or poultry manure (PM), and their impacts on greenhouse gas emission (GHG: CO2, N2O and CH4) were examined. A control (CTRL) receiving only MF served as the baseline, representing the conventional scenario in orchard fertilisation. Overall, replacing MF with manures increased GHG emissions, with the magnitude of the impacts depending on the specific characteristics of the manures and the amount of nutrients and organic matter applied. Comparing to the CTRL, application of ACS and CS led to higher CH4 and N2O emissions, while PM application increased both N2O and CO2 emissions. In contrast, replacement with PM and CsM decreased CH4 emissions. Nevertheless, results varied between the two years, influenced by several factors, including soil conditions. While acidification showed potential to mitigate CH4 emissions, it also led to increased N2O emissions compared to CS, particularly in 2022, suggesting the need for further investigation to avoid emission trade-offs. Replacement with CS (20.49 t CO2-eq ha-1) and CsM (20.30 t CO2-eq ha-1) showed comparable global warming potential (GWP) to the conventional scenario (CTRL, 19.49 t CO2-eq ha-1), highlighting their potential as viable MF substitutes.

Interlayer engineering of Fe3GeTe2: From 3D superlattice to 2D monolayer.

The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.

Comparative analysis of different risk prediction tools after mitral Transcatheter edge-to-edge repair.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) has become an established treatment for primary and secondary mitral regurgitation (PMR and SMR). The objective of this study was to compare the accuracy of different risk scores for predicting 1-year mortality and the composite endpoint of 1-year mortality and/or heart failure (HF) hospitalization after TEER. METHODS: We analyzed data from 206 patients treated for MR at a tertiary European center between 2011 and 2023 and compared the accuracy of different mitral and surgical risk scores: EuroSCORE II, GRASP, MITRALITY, MitraScore, TAPSE/PASP-MitraScore, and STS for predicting 1-year mortality and the composite of 1-year mortality and/or HF hospitalization in PMR and SMR. A subanalysis of SMR-only patients with the addition of COAPT Risk Score and baseline N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) list was also performed. RESULTS: MITRALITY had the best discriminative ability for 1-year mortality and the composite endpoint of 1-year mortality and/or HF hospitalization, with an area under the curve (AUC) of 0.74 and 0.74, respectively, in a composed group of PMR and SMR. In a SMR-only population, MITRALITY also presented the best AUC for 1-year mortality and the composite endpoint of 1-year mortality and/or HF hospitalization, with values of 0.72 and 0.72, respectively. CONCLUSION: MITRALITY was the best mitral TEER risk model for both 1-year mortality and the composite endpoint of 1-year mortality and/or HF hospitalization in a population of PMR and SMR patients, as well as in SMR patients only. Surgical risk scores, MitraScore, TAPSE/PASP-MitraScore and NT-proBNP alone showed poor predictive values.

End-of-life experiences in the dying process: scoping and mixed-methods systematic review.

OBJECTIVES: To identify the current state of understanding about end-of-life experiences (ELEs) and examine evidence concerning prevalence, the impact on the process of dying and the perceptions/explanations of patients, relatives and healthcare professionals (HCPs) with regard to ELEs. METHODS: Scoping review and mixed-methods systematic review (ScR and MMSR). Nine academic databases were searched for a screening of the available scientific literature (ScR). Articles reporting qualitative, quantitative or mixed-methods studies were selected (MMSR), the quality of which was assessed using the Joanna Briggs Institute (JBI) standardised critical appraisal tools. The quantitative data were synthesised in narrative form while a meta-aggregation approach was adopted for the qualitative results. RESULTS: The ScR identified 115 reports, with 70.4% published after 2010, 55.6% from the USA and the most common terminology for ELE was deathbed visions (29%). The MMSR included 36 papers, describing 35 studies in various settings. The combination of quantitative and qualitative evidence indicated a greater prevalence of ELEs in samples of patients and HCPs compared with relatives. The most common ELEs were visions and dreams of the presence of deceased relatives/friends with references to making ready for a journey. The impact of ELEs was mainly positive, and there was a tendency to interpret them as spiritual experiences inherent to the process of dying. CONCLUSIONS: ELEs are often reported by patients, relatives and HCPs and have a significant, generally positive impact on the process of dying. Guidelines for the furtherance of studies and clinical applications are discussed.

Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

Myocardial Injury After Transcatheter Mitral Valve Replacement Versus Surgical Reoperation.

This study aimed to evaluate the incidence and clinical implications of myocardial injury, as determined by cardiac biomarker increase, in patients who underwent mitral bioprosthesis dysfunction treatment with transcatheter mitral valve replacement (TMVR) versus surgical mitral valve replacement reoperation (SMVR-REDO). Between 2014 and 2023, 310 patients with mitral bioprosthesis failure were included (90 and 220 patients for TMVR and SMVR-REDO, respectively). Multivariable analysis and propensity score matching were performed to adjust for the intergroup differences in baseline characteristics. Creatinine kinase-MB (CK-MB) and cardiac troponin I (cTn) were collected at baseline and 6 to 12, 24, 48, and 72 hours after intervention. The cardiac biomarkers values were evaluated in relation to their reference values. The outcomes were determined according to the Mitral Valve Academic Research Consortium criteria. CK-MB and cTn increased above the reference level in almost all patients after SMVR-REDO and TMVR (100% vs 94%, respectively), with the peak occurring within 6 to 12 hours. SMVR-REDO was associated with a two- to threefold higher increase in cardiac biomarkers. After 30 days, the mortality rates were 13.3% in the TMVR and 16.8% in the SMVR-REDO groups. At a median follow-up of 19 months, the mortality rates were 21.1% in the TMVR and 17.7% in the SMVR-REDO groups. Left ventricular ejection fraction, estimated glomerular filtration rate, CK-MB, and cTn were predictors of mortality. In conclusion, some degree of myocardial injury occurred systematically after the treatment of mitral bioprosthetic degeneration, especially after SMVR, and higher CK-MB and cTn levels were associated with increased cumulative late mortality, regardless of the approach.

Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure. / Estratégias Percutâneas em Doenças Estruturais: Foco em Insuficiência Cardíaca Crônica.

BACKGROUND: Central Illustration : Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure Transcatheter devices for monitoring and treating advanced chronic heart failure patients. PA: pulmonary artery; LA: left atrium; AFR: atrial flow regulator; TASS: Transcatheter Atrial Shunt System; VNS: vagus nerve stimulation; BAT: baroreceptor activation therapy; RDN: renal sympathetic denervation; F: approval by the American regulatory agency (FDA); E: approval by the European regulatory agency (CE Mark). BACKGROUND: Innovations in devices during the last decade contributed to enhanced diagnosis and treatment of patients with cardiac insufficiency. These tools progressively adapted to minimally invasive strategies with rapid, widespread use. The present article focuses on actual and future directions of device-related diagnosis and treatment of chronic heart failure.

Resource utilization and costs related to the management of obstructive hypertrophic cardiomyopathy under the Brazilian supplementary healthcare system´s perspective: results from a modified Delphi panel / Utilização de recursos e custos relacionados ao manejo da cardiomiopatia hipertrófica obstrutiva sob a perspectiva do sistema de saúde suplementar brasileiro: resultados de um painel Delphi modificado

Objective: To generate data on the costs associated with the diagnosis and treatment of obstructive ypertrophic cardiomyopathy (HCM) from the perspective of the private health system in Brazil. Methods: A modified Delphi panel including seven different specialists (three clinical cardiologists with experience in obstructive HCM, two hemodynamicists with experience in septal ablation and two cardiac surgeons with expertise in myectomy), from two Brazilian states (São Paulo and Pernambuco), was conducted between August and November 2022. Two rounds of questions about the use of healthcare resources according to the functional class (NYHA I-IV) and a panel in a virtual platform were conducted to obtain the final consensus. Micro-costing defined costs and unit values were determined based on official price lists. Results: The total diagnosis cost per patient was estimated at BRL 11,486.81. The obstructive HCM management costs analysis showed average annual costs per patient of BRL 17,026.74, BRL 19,401.46, BRL 73,310.07, and BRL 94,885.75 for the functional classes NYHA I, NYHA II, NYHA III, and NYHA IV, respectively. The average costs per patient related to procedures in a year were BRL 12,698.53, BRL 13,462.30, BRL 58,841.67, and BRL 75,595.90 for the functional classes NYHA I, II, III, and IV, respectively. Conclusions: The annual costs of HCM management increased according to the functional class, highlighting the need for safe and effective strategies to improve patient's NYHA functional class while promoting a decrease in the need for invasive therapies.

Objetivo: Gerar dados acerca dos custos associados ao diagnóstico e tratamento da cardiomiopatia hipertrófica (CMH) obstrutiva, sob a perspectiva do sistema de saúde privado no Brasil. Métodos: Um painel Delphi modificado incluindo sete especialistas (três cardiologistas clínicos com experiência em CMH obstrutiva, dois hemodinamicistas com experiência em ablação de septo e dois cirurgiões cardíacos com experiência em miectomia) de dois estados brasileiros (São Paulo e Pernambuco) foi conduzido entre agosto e novembro de 2022. Foram realizadas duas rodadas de perguntas acerca da utilização de recursos de acordo com a classe funcional (NYHA I-IV) e uma reunião virtual para obtenção do consenso final. Os custos foram definidos por meio de microcusteio, e os valores unitários foram definidos com base em listas de preço oficiais. Resultados: O custo total do diagnóstico por paciente foi estimado em R$ 11.486,81. A análise de custos de manejo da CMH obstrutiva mostrou custos médios anuais por paciente de R$ 17.026,74, R$ 19.401,46, R$ 73.310,07 e R$ 94.885,75 para as classes funcionais NYHA I, NYHA II, NYHA III e NYHA IV, respectivamente. Os custos médios por paciente relacionados a procedimentos em um ano foram de R$ 12.698,53, R$ 13.462,30, R$ 58.841,67 e R$ 75.595,90 para as classes NYHA I, II, III e IV, respectivamente. Conclusões: Os custos anuais com o manejo da CMH aumentam de acordo com a classe funcional, destacando a necessidade de estratégias seguras e eficazes capazes de melhorar a classe funcional NYHA do paciente, ao mesmo tempo que promove diminuição da necessidade de terapias invasivas.

Impact of periprocedural myocardial injury after transcatheter aortic valve implantation on long-term mortality: a meta-analysis of Kaplan-Meier derived individual patient data.

Background: Periprocedural myocardial injury (PPMI) frequently occurs after transcatheter aortic valve implantation (TAVI), although its impact on long-term mortality is uncertain. Methods: We performed a pooled analysis of Kaplan-Meier-derived individual patient data to compare survival in patients with and without PPMI after TAVI. Flexible parametric models with B-splines and landmark analyses were used to determine PPMI prognostic value. Subgroup analyses for VARC-2, troponin, and creatine kinase-MB (CK-MB)-defined PPMI were also performed. Results: Eighteen observational studies comprising 10,094 subjects were included. PPMI was associated with lower overall survival (OS) after two years (HR = 1.46, 95% CI 1.30-1.65, p < 0.01). This was also observed when restricting the analysis to overall VARC-2-defined PPMI (HR = 1.23, 95% CI 1.07-1.40, p < 0.01). For VARC-2 PPMI criteria and VARC-2 troponin-only, higher mortality was restricted to the first 2 months after TAVI (HR = 1.64, 95% CI 1.31-2.07, p < 0.01; and HR = 1.32, 95% CI 1.05-1.67, p = 0.02, respectively), while for VARC-2 defined CK-MB-only the increase in mortality was confined to the first 30 days (HR = 7.44, 95% CI 4.76-11.66, p < 0.01). Conclusion: PPMI following TAVI was associated with lower overall survival compared with patients without PPMI. PPMI prognostic impact is restricted to the initial months after the procedure. The analyses were consistent for VARC-2 criteria and for both biomarkers, yet CK-MB was a stronger prognostic marker of mortality than troponin.

Clinical and Hemodynamic Outcomes of Balloon-Expandable Mitral Valve-in-Valve Positioning and Asymmetric Deployment: The VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) is associated with suboptimal hemodynamics and rare left ventricular outflow tract (LVOT) obstruction. OBJECTIVES: This study aimed to determine whether device position and asymmetry are associated with these outcomes. METHODS: Patients undergoing SAPIEN 3 (Edwards Lifesciences) mitral ViV included in the VIVID (Valve-in-Valve International Data) Registry were studied. Clinical endpoints are reported according to Mitral Valve Academic Research Consortium definitions. Residual mitral valve stenosis was defined as mean gradient ≥5 mm Hg. Depth of implantation (percentage of transcatheter heart valve [THV] atrial to the bioprosthesis ring) and asymmetry (ratio of 2 measures of THV height) were evaluated. RESULTS: A total of 222 patients meeting the criteria for optimal core lab evaluation were studied (age 74 ± 11.6 years; 61.9% female; STS score = 8.3 ± 7.1). Mean asymmetry was 6.2% ± 4.4%. Mean depth of implantation was 19.0% ± 10.3% atrial. Residual stenosis was common (50%; mean gradient 5.0 ± 2.6 mm Hg). LVOT obstruction occurred in 7 cases (3.2%). Implantation depth was not a predictor of residual stenosis (OR: 1.19 [95% CI: 0.92-1.55]; P = 0.184), but more atrial implantation was protective against LVOT obstruction (0.7% vs 7.1%; P = 0.009; per 10% atrial, OR: 0.48 [95% CI: 0.24-0.98]; P = 0.044). Asymmetry was found to be an independent predictor of residual stenosis (per 10% increase, OR: 2.30 [95% CI: 1.10-4.82]; P = 0.027). CONCLUSIONS: Valve stenosis is common after mitral ViV. Asymmetry was associated with residual stenosis. Depth of implantation on its own was not associated with residual stenosis but was associated with LVOT obstruction. Technical considerations to reduce postdeployment THV asymmetry should be considered.

Advanced Manufacturing, Formulation and Microencapsulation of Therapeutic Phages.

Manufacturing and formulation of stable, high purity, and high dose bacteriophage drug products (DPs) suitable for clinical usage would benefit from improved process monitoring and control of critical process parameters that affect product quality attributes. Chemistry, Manufacturing, and Controls (CMC) for both upstream (USP) and downstream processes (DSP) need mapping of critical process parameters (CPP) and linking these to critical quality attributes (CQA) to ensure quality and consistency of phage drug substance (DS) and DPs development. Single-use technologies are increasingly becoming the go-to manufacturing option with benefits both for phage bioprocess development at the engineering run research stage and for final manufacture of the phage DS. Future phage DPs under clinical development will benefit from implementation of process analytical technologies (PAT) for better process monitoring and control. These are increasingly being used to improve process robustness (to reduce batch-to-batch variability) and productivity (yielding high phage titers). Precise delivery of stable phage DPs that are suitably formulated as liquids, gels, solid-oral dosage forms, and so forth, could significantly enhance efficacy of phage therapy outcomes. Pre-clinical development of phage DPs must include at an early stage of development, considerations for their formulation including their characterization of physiochemical properties (size, charge, etc.), buffer pH and osmolality, compatibility with regulatory approved excipients, storage stability (packaging, temperature, humidity, etc.), ease of application, patient compliance, ease of manufacturability using scalable manufacturing unit operations, cost, and regulatory requirements.

An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value.

INTRODUCTION: Bipolar disorder (BD) is a complex psychiatric disease characterized by alternating mood episodes. As for any other psychiatric illness, currently there is no biochemical test that is able to support diagnosis or therapeutic decisions for BD. In this context, the discovery and validation of biomarkers are interesting strategies that can be achieved through proteomics and metabolomics. AREAS COVERED: In this descriptive review, a literature search including original articles and systematic reviews published in the last decade was performed with the objective to discuss the results of BD proteomic and metabolomic profiling analyses and indicate proteins and metabolites (or metabolic pathways) with potential clinical value. EXPERT OPINION: A large number of proteins and metabolites have been reported as potential BD biomarkers; however, most studies do not reach biomarker validation stages. An effort from the scientific community should be directed toward the validation of biomarkers and the development of simplified bioanalytical techniques or protocols to determine them in biological samples, in order to translate proteomic and metabolomic findings into clinical routine assays.

Genome characterization of the novel lytic phage vB_AbaAut_ChT04 and the antimicrobial activity of its lysin peptide against Acinetobacter baumannii isolates from different time periods.

Acinetobacter baumannii is an important opportunistic pathogen, usually associated with immunocompromised individuals with a prolonged period of stay in a hospital. Currently, the incidence of multi-drug resistant A. baumannii (MDR-AB) and extensively drug-resistant A. baumannii (XDR-AB) is increasing rapidly in Thailand, mirroring the trend worldwide. Novel therapeutic approaches for the treatment of A. baumannii infection using bacteriophages are being evaluated, and the use of phage-derived peptides is being tested as alternative approach to fighting infection. In this study, we isolated and determined the biological features of a lytic A. baumannii phage called vB_AbaAut_ChT04 (vChT04). The vChT04 phage was classified as a member of the family Autographiviridae of the class Caudoviricetes. It showed a short latent period (10 min) and a large burst size (280 PFU cell-1), and it was able to infect 52 out of 150 clinical MDR-AB strains tested (34.67%). Most of the phage-sensitive strains were A. baumannii strains that had been isolated during the same year that the phage was isolated. The phage showed activity across a broad pH (pH 5.0-8.0) and temperature (4-37°C) range. Whole-genome analysis revealed that the vChT04 genome comprises 41,158 bp with a 39.3% GC content and contains 48 open reading frames (ORFs), 28 of which were assigned putative functions based on homology to previously identified phage genes. Comparative genomic analysis demonstrated that vChT04 had the highest similarity to phage vB_AbaP_WU2001, which was isolated in the southern part of Thailand. An endolysin gene found in the vChT04 genome was used to synthesize an antimicrobial peptide (designated as PLysChT04) and its antimicrobial activity was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The MIC and MBC values of peptide PLysChT04 against MDR-AB and XDR-AB were 312.5-625 µg/mL, and it was able to inhibit both phage-susceptible and phage-resistant isolates collected over different time periods. PLysChT04 showed good efficacy in killing drug-resistant A. baumannii and other bacterial strains, and it is a promising candidate for development as an alternative therapeutic agent targeting A. baumannii infections.

Late Bleeding Events in Patients Undergoing Percutaneous Coronary Intervention in the Workup Pre-TAVR.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the work-up pre-transcatheter aortic valve replacement (TAVR), the incidence and clinical impact of late bleeding events (LBEs) remain largely unknown. OBJECTIVES: This study sought to determine the incidence, clinical characteristics, associated factors, and outcomes of LBEs in patients undergoing PCI in the work-up pre-TAVR. METHODS: This was a multicenter study including 1,457 consecutive patients (mean age 81 ± 7 years; 41.5% women) who underwent TAVR and survived beyond 30 days. LBEs (>30 days post-TAVR) were defined according to the Valve Academic Research Consortium-2 criteria. RESULTS: LBEs occurred in 116 (7.9%) patients after a median follow-up of 23 (IQR: 12-40) months. Late bleeding was minor, major, and life-threatening or disabling in 21 (18.1%), 63 (54.3%), and 32 (27.6%) patients, respectively. Periprocedural (<30 days post-TAVR) major bleeding and the combination of antiplatelet and anticoagulation therapy at discharge were independent factors associated with LBEs (P ≤ 0.02 for all). LBEs conveyed an increased mortality risk at 4-year follow-up compared with no bleeding (43.9% vs 36.0; P = 0.034). Also, LBE was identified as an independent predictor of all-cause mortality after TAVR (HR: 1.39; 95% CI: 1.05-1.83; P = 0.020). CONCLUSIONS: In TAVR candidates with concomitant significant coronary artery disease requiring percutaneous treatment, LBEs after TAVR were frequent and associated with increased mortality. Combining antiplatelet and anticoagulation regimens and the occurrence of periprocedural bleeding determined an increased risk of LBEs. Preventive strategies should be pursued for preventing late bleeding after TAVR, and further studies are needed to provide more solid evidence on the most safe and effective antithrombotic regimen post-TAVR in this challenging group of patients.

Angiotensin Receptor-Neprilysin Inhibitor Effects on Atherosclerotic Cardiovascular Disease Events: A Meta-Analysis of Randomized Controlled Trials.

Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with heart failure (HF). However, its association with improved atherosclerotic cardiovascular disease (ASCVD) events remains unclear. We performed a meta-analysis to evaluate the association of ARNI with ASCVD events in patients with HF. We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for studies comparing ARNIs with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in terms of myocardial infarction, stroke, angina pectoris, peripheral artery disease, and the composite end point in patients with HF. A total of 8 randomized controlled trials were included, with 17,541 patients assigned to either the ARNI (8,764 patients) or ACEi/ARB (8,777 patients) groups. The incidence of composite end point (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.93 to 1.13, p = 0.63), myocardial infarction (RR 1.02, 95% CI 0.81 to 1.30, p = 0.85), angina pectoris (RR 0.96, 95% CI 0.80 to 1.17, p = 0.70), and stroke (RR 0.99, 95% CI 0.85 to 1.16, p = 0.93) were not statistically different between the ARNI and ACEi/ARB groups. However, ARNI was associated with a higher incidence of peripheral artery disease (RR 1.63, 95% CI 1.05 to 2.52, p = 0.03). In conclusion, this meta-analysis found no association between ARNI therapy and improved ASCVD events in patients with HF.

Selective Electron-Phonon Coupling in Dimerized 1T-TaS2 Revealed by Resonance Raman Spectroscopy.

The layered transition-metal dichalcogenide material 1T-TaS2 possesses successive phase transitions upon cooling, resulting in strong electron-electron correlation effects and the formation of charge density waves (CDWs). Recently, a dimerized double-layer stacking configuration was shown to form a Peierls-like instability in the electronic structure. To date, no direct evidence for this double-layer stacking configuration using optical techniques has been reported, in particular through Raman spectroscopy. Here, we employ a multiple excitation and polarized Raman spectroscopy to resolve the behavior of phonons and electron-phonon interactions in the commensurate CDW lattice phase of dimerized 1T-TaS2. We observe a distinct behavior from what is predicted for a single layer and probe a richer number of phonon modes that are compatible with the formation of double-layer units (layer dimerization). The multiple-excitation results show a selective coupling of each Raman-active phonon with specific electronic transitions hidden in the optical spectra of 1T-TaS2, suggesting that selectivity in the electron-phonon coupling must also play a role in the CDW order of 1T-TaS2.

Comparison of different percutaneous revascularisation timing strategies in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown. AIMS: We sought to compare different PCI timing strategies in TAVI patients. METHODS: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method. RESULTS: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days. CONCLUSIONS: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.