The world is presently undergoing a recovery phase following the unexpected challenges posed by the coronavirus disease 2019 (COVID-19) pandemic. The loss of lives and the economic setbacks experienced by the global population will require considerable time to address. It is clear that future outbreaks, epidemics, or even pandemic caused by unknown bacterial, fungal, or viral pathogens are inevitable. In this context, public health front-liners will be essential in minimizing the impact of such incidents. This mini-review briefly discusses sociocultural issues, diagnostic capacities, surveillance, and screening strategies for potential future viral pandemic - referred to as Pandemic X. Additionally, it addresses treatment responses, vaccine development efforts, scientific advancements, policy considerations, and prospects for science communication related to forthcoming viral pandemics. While this review does not encompass all scientific approaches available on these topics, it aims to serve as a guideline for informing public health sectors about appropriate measures that should be undertaken.

• MeSH
• COVID-19 * epidemiology   prevention & control   diagnosis   MeSH
• Humans MeSH
• Pandemics * prevention & control   MeSH
• SARS-CoV-2 MeSH
• Public Health MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. METHODS: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. RESULTS: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. CONCLUSION: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

• MeSH
• Biomarkers blood   MeSH
• Risk Assessment methods   MeSH
• Bone Density Conservation Agents therapeutic use   MeSH
• Collagen Type I blood   MeSH
• Consensus MeSH
• Humans MeSH
• Osteoporotic Fractures prevention & control   etiology   MeSH
• Osteoporosis * diagnosis   physiopathology   drug therapy   blood   therapy   MeSH
• Peptide Fragments blood   MeSH
• Peptides blood   MeSH
• Procollagen blood   MeSH
• Bone Remodeling * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Consensus Development Conference MeSH
• Review MeSH

The neurotoxicity of phosphorylated tau protein (P-tau) and mitochondrial dysfunction play a significant role in the pathophysiology of Alzheimer's disease (AD). In vitro studies of the effects of P-tau oligomers on mitochondrial bioenergetics and reactive oxygen species production will allow us to evaluate the direct influence of P-tau on mitochondrial function. We measured the in vitro effect of P-tau oligomers on oxygen consumption and hydrogen peroxide production in isolated brain mitochondria. An appropriate combination of specific substrates and inhibitors of the phosphorylation pathway enabled the measurement and functional analysis of the effect of P-tau on mitochondrial respiration in defined coupling control states achieved in complex I-, II-, and I&II-linked electron transfer pathways. At submicromolar P-tau concentrations, we found no significant effect of P-tau on either mitochondrial respiration or hydrogen peroxide production in different respiratory states. The titration of P-tau showed a nonsignificant dose-dependent decrease in hydrogen peroxide production for complex I- and I&II-linked pathways. An insignificant in vitro effect of P-tau oligomers on both mitochondrial respiration and hydrogen peroxide production indicates that P-tau-induced mitochondrial dysfunction in AD is not due to direct effects of P-tau on the efficiency of the electron transport chain and on the production of reactive oxygen species.

• MeSH
• Cell Respiration MeSH
• Phosphorylation MeSH
• Rats MeSH
• Humans MeSH
• Mitochondria * metabolism   MeSH
• Brain metabolism   MeSH
• Hydrogen Peroxide * metabolism   MeSH
• tau Proteins * metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Oxygen Consumption MeSH
• Electron Transport MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

AIMS: Pulsed field ablation (PFA) is a growing ablation modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients. This study assesses the 6-month safety and effectiveness of a novel balloon-in-basket, mapping-integrated PFA system, with a purpose-built form factor for PVI. METHODS AND RESULTS: The VOLT CE Mark Study is a prospective, multi-center, pre-market study. A total of 150 patients with drug-refractory paroxysmal (PAF) or persistent AF (PersAF) were enrolled between 8 November 2023 and 14 March 2024, of which 146 patients (age 64.1 ± 10.0 years, 63.0% male, 70.5% PAF) underwent PVI with the balloon-in-basket PFA catheter and system featuring integrated electroanatomic mapping with contact-sensing. Study endpoints were the rate of primary serious adverse events within 7 days as well as acute procedural effectiveness and 6-month freedom from recurrence. Acute effectiveness was achieved in 99.1% (573/578) of treated PVs (98.6% of patients, 144/146) with 17.6 ± 5.7 PFA applications/patient. Procedure, fluoroscopy, LA dwell, and transpired ablation times were 100.4 ± 33.0, 17.3 ± 12.1, 39.4 ± 20.6, and 31.4 ± 16.8 min, respectively. There were 4 (2.7%; 4/146) primary serious adverse events. The rate of freedom from documented atrial arrhythmias was 88.2% in PAF patients and 76.7% in PersAF patients (freedom from symptomatic recurrence was documented in 90.2% of PAF patients and 74.4% of PersAF patients) through 6-months post-index procedure. CONCLUSION: The VOLT CE Mark Study primary results demonstrate the safety and effectiveness of the novel balloon-in-basket PFA system to perform PVI in PAF and PersAF.

• MeSH
• Time Factors MeSH
• Atrial Fibrillation * surgery   physiopathology   diagnosis   MeSH
• Catheter Ablation * instrumentation   adverse effects   methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Recurrence MeSH
• Aged MeSH
• Pulmonary Veins * surgery   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH

Conduction system pacing (CSP) is being increasingly adopted as a more physiological alternative to right ventricular and biventricular pacing. Since the 2021 European Society of Cardiology pacing guidelines, there has been growing evidence that this therapy is safe and effective. Furthermore, left bundle branch area pacing was not covered in these guidelines due to limited evidence at that time. This Clinical Consensus Statement provides advice on indications for CSP, taking into account the significant evolution in this domain.

• MeSH
• Action Potentials MeSH
• Cardiology * standards   MeSH
• Cardiac Pacing, Artificial * standards   adverse effects   methods   MeSH
• Consensus MeSH
• Humans MeSH
• Heart Conduction System * physiopathology   MeSH
• Societies, Medical MeSH
• Arrhythmias, Cardiac * therapy   physiopathology   diagnosis   MeSH
• Heart Rate MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH

AIMS: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. New treatments are needed to cardiovert recent-onset paroxysmal AF quickly and safely. RESTORE-1 was a multicentre, randomized, double-blind, placebo-controlled trial of a 120 mg orally inhaled solution of flecainide acetate (FlecIH-103) for cardioversion of symptomatic, recent-onset (≤48 h) paroxysmal AF. The study aim was to evaluate the efficacy and safety of FlecIH-103 administered via oral inhalation. METHODS AND RESULTS: Patients experiencing a recent-onset paroxysmal AF episode were randomized to receive a single dose of FlecIH-103 or placebo delivered over two 3.5 min inhalation periods, while patients were monitored using 12-lead electrocardiograms and Holter. The trial was stopped prematurely after treating 55 patients, due to lower-than-expected conversion rates and plasma levels. Mean age was 59.6 years, 31.5% of patients were female, and 59.2% were having their first AF episode. Conversion rate was 30.8% (95% confidence interval: 14.7-43.8) for the active group (n = 39) and 0.0% for the placebo group (n = 12) (P = 0.04). Median time to conversion was 12.8 min (IQR: 17.2). In the active group, the mean flecainide plasma level was 198 ng/mL (SD: 156), which is ∼50% lower than in the previous studies. The most common adverse events (AEs) were dysgeusia, dyspnoea, and cough. All AEs were short-lasting and of mild or moderate intensity. CONCLUSION: Despite early termination of the trial, FlecIH-103 was significantly more effective than placebo in cardioverting AF. Safety data did not show any serious AEs. Further studies of FlecIH-103 are needed to optimize the combination of drug formulation and inhalation delivery platform. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov, unique identifier: NCT05039359.

• MeSH
• Anti-Arrhythmia Agents * administration & dosage   adverse effects   MeSH
• Administration, Inhalation MeSH
• Time Factors MeSH
• Double-Blind Method MeSH
• Electrocardiography, Ambulatory MeSH
• Atrial Fibrillation * drug therapy   diagnosis   physiopathology   MeSH
• Flecainide * administration & dosage   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Early Termination of Clinical Trials MeSH
• Aged MeSH
• Heart Rate * drug effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

OBJECTIVES: In an effort to maintain the technical aspects of traditional prosthetic surgical aortic valve replacement (AVR) while reducing invasiveness and facilitate options for concomitant operations, transaxillary lateral mini-thoracotomy endoscopic robotic-assisted aortic valve replacement (RAVR) has been introduced. The present data highlight the contemporary international collaborative experience. METHODS: All consecutive patients undergoing standardized RAVR across 10 international sites (1/2020-7/2024) were evaluated using a central database with 1 year follow-up. RESULTS: A total of 300 patients were analysed with a median predicted risk of 1.6% with aortic stenosis in 85.7%, nearly half with bicuspid valves. Biological prostheses were implanted in 220 (73.3%) with a median valve size 23 mm, 10% receiving aortic root enlargement, with 17% of all patients undergoing concomitant procedures. Median cross-clamp 120 min with no conversions to sternotomy. Median length of stay was 5 days, 4.3% with prolonged ventilation, 1.7% renal failure, 1.0% stroke and 8.3% required re-thoracotomy for evacuation of haemothorax. There were two 30-day operative mortalities (0.7%). The new permanent pacemaker rate for the full cohort was 2.6%. Of 163 patients with complete 1-year clinical and echocardiographic follow-up, mean aortic valve gradient was 10 mmHg and all but 2 patients (1.2%) had trace to no prosthetic or paravalvular insufficiency. CONCLUSIONS: RAVR is safe and effective, providing the reproducible benefits of surgical AVR while affording a less invasive approach that permits the opportunity for concomitant procedures. For low and intermediate risk patients with aortic valve disease, RAVR is a potential reproducible alternative for patients and heart teams.

• MeSH
• Aortic Valve * surgery   MeSH
• Aortic Valve Stenosis * surgery   MeSH
• Heart Valve Prosthesis Implantation * methods   adverse effects   mortality   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Follow-Up Studies MeSH
• Robotic Surgical Procedures * methods   adverse effects   mortality   statistics & numerical data   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Heart Valve Prosthesis MeSH
• Thoracotomy methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

OBJECTIVES: Long-term evidence about bioprosthetic tricuspid valve replacement is scarce. This study aims to investigate the long-term clinical outcomes of patients who underwent tricuspid valve replacement with bioprostheses. METHODS: This multicentre retrospective study included patients from 10 high-volume centres in 7 different countries, who underwent tricuspid valve replacement with bioprostheses. Echocardiographic and clinical data were reviewed. Long-term outcomes were investigated using Kaplan-Meier estimates, Cox regression, and competing risk analysis. RESULTS: Of 675 patients, isolated tricuspid valve replacement was performed in 358 patients (53%), while 317 (47%) underwent concomitant procedures. Between these 2 groups, patients who underwent combined procedures reported a significantly higher incidence of infection, atrioventricular block, multi-organ failure, longer intensive care unit and hospital stay and higher 30-day mortality over patients who underwent isolated procedure. The overall 30-day mortality occurred in 70 patients (10.4%) [46 (14.6%) combined vs 24 (6.74%) isolated, P = 0.001]. During the follow-up, there was a continuous rate of attrition due to death, with cumulative incidences of death at 5, 10 and 15 years being 27.2%, 46.2% and 60.6%, respectively. In contrast, the risk of reintervention starts to significantly increase after 10 years of follow-up, with cumulative incidences of reintervention being 6.1%, 10.8% and 23.3%, respectively. Freedom from tricuspid valve reintervention, pacemaker implantation, tricuspid valve endocarditis and major thromboembolic events at 15 years were 56.5%, 77.3%, 84.0% and 86.4%, respectively. CONCLUSIONS: Tricuspid valve replacement with bioprostheses is an effective treatment for valvular disease, despite being associated with relatively high early and long-term mortality. However, the risk of structural valve degeneration rises significantly after 10 years.

• MeSH
• Bioprosthesis * adverse effects   MeSH
• Heart Valve Prosthesis Implantation * mortality   adverse effects   methods   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Heart Valve Diseases * surgery   mortality   MeSH
• Postoperative Complications epidemiology   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Heart Valve Prosthesis * adverse effects   MeSH
• Tricuspid Valve * surgery   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering the pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including aetiology-specific aspects and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before the expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.

• MeSH
• Action Potentials MeSH
• Cardiology * standards   MeSH
• Tachycardia, Ventricular * physiopathology   surgery   diagnosis   MeSH
• Consensus MeSH
• Humans MeSH
• Radiosurgery * adverse effects   standards   methods   MeSH
• Risk Factors MeSH
• Patient Selection * MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH