Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the FINEARTS-HF Trial.

Background: The effects of treatments for heart failure (HF) may vary among patients according to left ventricular ejection fraction (LVEF). In FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), the nonsteroidal mineralocorticoid receptor antagonist finerenone reduced the risk of cardiovascular death and total worsening HF events in patients with HF with mildly reduced or preserved ejection fraction. We examined the effect of finerenone according to LVEF in FINEARTS-HF.

Use of Poly(vinyl alcohol) in Spray-Dried Dispersions: Enhancing Solubility and Stability of Proteolysis Targeting Chimeras.

PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol).

Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

Background: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown.

Methods: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement.

Bone and Skin/Subcutaneous Tissue Concentrations of Cefiderocol During Treatment of Extensively Drug-Resistant Pseudomonas aeruginosa.

Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol.

Functional connectivity MRI provides an imaging correlate for chimeric antigen receptor T-cell-associated neurotoxicity.

Background: Treatment of hematological malignancies with chimeric antigen receptor modified T cells (CART) is highly efficient, but often limited by an immune effector cell-associated neurotoxicity syndrome (ICANS). As conventional MRI is often unremarkable during ICANS, we aimed to examine whether resting-state functional MRI (rsfMRI) is suitable to depict and quantify brain network alterations underlying ICANS in the individual patient.

Methods: The dysconnectivity index (DCI) based on rsfMRI was longitudinally assessed in systemic lymphoma patients and 1 melanoma patient during ICANS and before or after clinical resolution of ICANS.

Self-reported Cardiovascular Disease in Career Firefighters With and Without World Trade Center Exposure.

To assess the effect of World Trade Center (WTC) exposure on cardiovascular disease (CVD) in career firefighters. Methods: Firefighters from four US cities completed health questionnaires that provide information about demographics, CVD diagnoses, and CVD risk factors. Firefighters were also compared with respondents of the 2019 National Health Interview Survey.

A Feature-Specific Local Cooling System to Control Tensile Strength and Dimensional Accuracy in Fused Filament Fabrication.

There is in-depth understanding of the effects and interactions of various process parameters on the mechanical properties and dimensional accuracy of parts produced through fused filament fabrication (FFF). Surprisingly, local cooling in FFF has been largely overlooked and is only rudimentarily implemented. It is, however, a decisive element of the thermal conditions governing the FFF process and of particular importance when processing high-temperature polymers such as polyether ether ketone (PEEK).

Endoluminal Biopsy for Molecular Profiling of Human Brain Vascular Malformations.

Background And Objectives: Ras-mitogen-activated protein kinase (MAPK) signaling abnormalities occur in most brain arteriovenous malformations (bAVMs). No means exist to molecularly profile bAVMs without open surgery, limiting precision medicine approaches to treatment. Here, we report use of endoluminal biopsy of the vessel lumen of bAVMs to characterize gene expression and blood flow-mediated transcriptional changes in living patients.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

Background: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI).

Purpose: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms.

Data Sources: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020.

Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

Background: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

Methods: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

Results: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants).

Digital endpoints for self-administered home-based functional assessment in pediatric Friedreich's ataxia.

Background: Friedreich's ataxia is an inherited, progressive, neurodegenerative disease that typically begins in childhood. Disease severity is commonly assessed with rating scales, such as the modified Friedreich's Ataxia Rating Scale, which are usually administered in the clinic by a neurology specialist.

Objective: This study evaluated the utility of home-based, self-administered digital endpoints in children with Friedreich's ataxia and unaffected controls and their relationship to standard clinical rating scales.

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care : A Randomized, Controlled, Multicenter Trial.

Background: Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort.

Objective: To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care.

Design: Randomized, controlled, parallel-group trial.

Strong and sustainable primary healthcare is associated with a lower risk of hospitalization in high risk patients.

In 2004, Germany introduced a program based on voluntary contracting to strengthen the role of general practice care in the healthcare system. Key components include structured management of chronic diseases, coordinated access to secondary care, data-driven quality improvement, computerized clinical decision-support, and capitation-based reimbursement. Our aim was to determine the long-term effects of this program on the risk of hospitalization of specific categories of high-risk patients.

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention.

Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.

Interrater Reliability in the Measurement of Flow Characteristics on Color-Coded Quantitative DSA of Brain AVMs.

Background And Purpose: Hemodynamic features of brain AVMs may portend increased hemorrhage risk. Previous studies have suggested that MTT is shorter in ruptured AVMs as assessed on quantitative color-coded parametric DSA. This study assesses the interrater reliability of MTT measurements obtained using quantitative color-coded DSA.

Results of the Austrian National Lung Cancer Audit.

Objectives: The Austrian Lung Cancer Audit (ALCA) is a pilot study to evaluate clinical and organizational factors related to lung cancer care across Austria.

Materials And Methods: The ALCA is a prospective, observational, noninterventional cohort study conducted in 17 departments in Austria between September 2013 and March 2015. Participating departments were selected based on an annual case load of >50 patients with lung cancer.

Improved glycaemic variability and basal insulin dose reduction during a running competition in recreationally active adults with type 1 diabetes-A single-centre, prospective, controlled observational study.

Introduction: To investigate the glycaemic response, macronutrient intake and insulin management in people with type 1 diabetes (T1D) compared to healthy individuals around a running competition.

Material And Methods: This was a single-centre, prospective, controlled observational study performed in individuals with T1D and healthy people. 24 people (12 T1D) were included in this study (age: T1D 41±12 vs.

Intensified ambulatory cardiology care: effects on mortality and hospitalisation-a comparative observational study.

Since 2010, an intensified ambulatory cardiology care programme has been implemented in southern Germany. To improve patient management, the structure of cardiac disease management was improved, guideline-recommended care was supported, new ambulatory medical services and a morbidity-adapted reimbursement system were set up. Our aim was to determine the effects of this programme on the mortality and hospitalisation of enrolled patients with cardiac disorders.

A Novel Next-Generation Sequencing and Analysis Platform to Assess the Identity of Recombinant Adeno-Associated Viral Preparations from Viral DNA Extracts.

Recombinant adeno-associated virus (rAAV) vectors are increasingly popular gene delivery tools in biological systems. They are safe and lead to high-level, long-term transgene expression. rAAV are available in multiple serotypes, natural or engineered, which enable targeting to a wide array of tissues and cell types.

Brain Damage With Heart Failure: Cardiac Biomarker Alterations and Gray Matter Decline.

Rationale: Heart failure (HF) following heart damage leads to a decreased blood flow due to a reduced pump efficiency of the heart muscle. A consequence can be insufficient oxygen supply to the organism including the brain. While HF clearly shows neurological symptoms, such as fatigue, nausea, and dizziness, the implications for brain structure are not well understood.

Data Descriptor: Daily observations of stable isotope ratios of rainfall in the tropics.

We present precipitation isotope data (δH and δO values) from 19 stations across the tropics collected from 2012 to 2017 under the Coordinated Research Project F31004 sponsored by the International Atomic Energy Agency. Rainfall samples were collected daily and analysed for stable isotopic ratios of oxygen and hydrogen by participating laboratories following a common analytical framework. We also calculated daily mean stratiform rainfall area fractions around each station over an area of 5° x 5° longitude/latitude based on TRMM/GPM satellite data.