Pulsed Field Ablation as First-Line Therapy for Atrial Fibrillation: A Substudy of the EU-PORIA Registry.

Background: Recent studies have demonstrated the benefit of early ablation in preventing the progression of atrial fibrillation (AF). Clinical practice has reflected this shift in AF management and no longer requires patients to fail antiarrhythmic drugs (AADs) before receiving ablation. However, there is limited evidence on outcomes with pulsed field ablation (PFA) as a first-line therapy.

Left Atrial Appendage Closure after Ablation for Atrial Fibrillation.

Background: Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking.

Methods: We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated score (≥2 in men and ≥3 in women) on the CHADS-VASc scale (range, 0 to 9, with higher scores indicating a greater risk of stroke) and who underwent catheter ablation.

Microaxial Flow Pump Use and Renal Outcomes in Infarct-Related Cardiogenic Shock: A Secondary Analysis of the DanGer Shock Trial.

Background: In DanGer Shock (the Danish-German Cardiogenic Shock trial), use of a microaxial flow pump (mAFP) in patients with ST-segment-elevation myocardial infarction-related cardiogenic shock led to lower all-cause mortality but higher rates of renal replacement therapy (RRT). In this prespecified analysis, rates and predictors of acute kidney injury (AKI) and RRT were assessed.

Methods: In this international, randomized, open-label, multicenter trial, 355 adult patients with ST-segment-elevation myocardial infarction-related cardiogenic shock were randomized to mAFP (n=179) or standard care alone (n=176).

Toward a CRISPR-based mouse model of -deficient clear cell kidney cancer: Initial experience and lessons learned.

CRISPR is revolutionizing the ability to do somatic gene editing in mice for the purpose of creating new cancer models. Inactivation of the tumor suppressor gene is the signature initiating event in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). Such tumors are usually driven by the excessive HIF2 activity that arises when the gene product, pVHL, is defective.

Relevance of age and hypertension for blood pressure targets in comatose survivors of cardiac arrest: a BOX-trial sub-study.

Aims: To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension.

Methods And Results: A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg.

Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.

Background: Alterations in the buffering of intracellular Ca, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca buffering profile in persAF remains obscure. Therefore, we aimed to investigate the intracellular buffering of Ca and its potential arrhythmogenic role in persAF.

The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study, JAXA CFE study, SpaceX Inspiration4 crew, Axiom and Polaris.

Impact of Blood Pressure Targets in Patients With Heart Failure Undergoing Postresuscitation Care: A Subgroup Analysis From a Randomized Controlled Trial.

Background: To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure.

Methods: The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy.

Optimizing human performance in extreme environments through precision medicine: From spaceflight to high-performance operations on Earth.

Humans operating in extreme environments often conduct their operations at the edges of the limits of human performance. Sometimes, they are required to push these limits to previously unattained levels. As a result, their margins for error in execution are much smaller than that found in the general public.

Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi-ascending dose study with a bioequivalence arm in healthy volunteers.

PF614, a trypsin-activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two-part design including a multi-ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses.

RGS4 Actions in Mouse Prefrontal Cortex Modulate Behavioral and Transcriptomic Responses to Chronic Stress and Ketamine.

The signal transduction protein, regulator of G protein signaling 4 (RGS4), plays a prominent role in physiologic and pharmacological responses by controlling multiple intracellular pathways. Our earlier work identified the dynamic but distinct roles of RGS4 in the efficacy of monoamine-targeting versus fast-acting antidepressants. Using a modified chronic variable stress (CVS) paradigm in mice, we demonstrate that stress-induced behavioral abnormalities are associated with the downregulation of RGS4 in the medial prefrontal cortex (mPFC).

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy.

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

Aims: Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter.

Methods And Results: All-comer AF patients from seven high-volume centres were consecutively enrolled.

ADMANI: Annotated Digital Mammograms and Associated Non-Image Datasets.

Mammography, Screening, Convolutional Neural Network (CNN) Published under a CC BY 4.0 license. See also the commentary by Cadrin-Chênevert in this issue.

Molecular Magnetic Resonance Imaging of Aneurysmal Inflammation Using a Redox Active Iron Complex.

Objectives: Inflammation plays a key role in driving brain aneurysmal instability and rupture, but clinical tools to noninvasively differentiate between inflamed and stable aneurysms are lacking. We hypothesize that imaging oxidative changes in the aneurysmal microenvironment driven by myeloid inflammatory cells may represent a noninvasive biomarker to evaluate rupture risk. In this study, we performed initial evaluation of the oxidatively activated probe Fe-PyC3A as a tool for magnetic resonance imaging (MRI) of inflammation in a rabbit model of saccular aneurysm.