Clinical Pharmacokinetics and Pharmacodynamics of CSL112.

Cardiovascular diseases are the leading cause of death worldwide. Although there have been substantial advances over the last decades, recurrent adverse cardiovascular events after myocardial infarction are still frequent, particularly during the first year of the index event. For decades, high-density lipoprotein (HDL) has been among the therapeutic targets for long-term prevention after an ischemic event.

Effects of ultrasound with an automatic vessel detection system using artificial intelligence on the selection of puncture points among ultrasound beginner clinical nurses.

Background: Ultrasound guidance increases the success rate of peripheral intravenous catheter placement. However, the longer time required to obtain ultrasound-guided access poses difficulties for ultrasound beginners. Notably, interpretation of ultrasonographic images is considered as one of the main reasons of difficulty in using ultrasound for catheter placement.

Factor XI Inhibitors in Early Clinical Trials: A Meta-analysis.

Background:  Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes.

Methods:  We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy.

Results:  Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included.

Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Studies.

Background: Hypertension imposes substantial health and economic burden worldwide. Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, causing cardiovascular events at higher risk compared with essential hypertension. However, the germline genetic contribution to the susceptibility of PA has not been well elucidated.

P2Y Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions.

Background: It remains unclear whether P2Y inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI).

Objectives: We sought to assess the effects of P2Y inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity.

Methods: We pooled patient-level data from randomized controlled trials comparing P2Y inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization.

A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy.

Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan.

Non-Invasive Imaging Biomarkers to Predict the Hepatopulmonary Shunt Fraction Before Transarterial Radioembolization in Patients with Hepatocellular Carcinoma.

Purpose: To identify disease-specific profiles comprising patient characteristics and imaging biomarkers on contrast-enhanced (CE)-computed tomography (CT) that enable the non-invasive prediction of the hepatopulmonary shunt fraction (HPSF) in patients with hepatocellular carcinoma (HCC) before resin-based transarterial radioembolization (TARE).

Patients And Methods: This institutional review board-approved (EA2/071/19) retrospective study included 56 patients with HCC recommended for TARE. All patients received tri-phasic CE-CT within 6 weeks prior to an angiographic TARE evaluation study using technetium-99m macroaggregated albumin.

Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy.

Background: Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse.

Objectives: This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins.

CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany.

Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product.

Sex-related differences in left ventricular assist device utilization and outcomes: results from the PCHF-VAD registry.

Aims: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort.

Methods And Results: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients.

Clinical outcomes of the ACURATE neo2 transcatheter heart valve: a prospective, multicenter, observational, post-market surveillance study.

Background: The next-generation ACURATE neo2 transcatheter aortic valve was designed for simplified implantation and to mitigate the risk of paravalvular leak (PVL) compared to the earlier device.

Aims: To collect clinical outcomes and device performance data, including echocardiography and 4-dimensional computed tomography (4D-CT) data, with the ACURATE neo2 transcatheter heart valve in patients with severe aortic stenosis (AS).

Methods: ACURATE neo2 PMCF is a single-arm, multicentre study of patients with severe AS treated in routine clinical practice.

Inflammatory bowel disease-specific findings are common morphological changes in the ileal pouch with ulcerative colitis.

Why inflammation is common in ileal pouches with ulcerative colitis (UC) is unclear. We therefore clarified the morphological changes in pouches and afferent limbs (AL) of patients with UC and explored the relationship between these findings. We evaluated the morphological findings (histological and endoscopic inflammation as the Pouchitis Disease Activity Index [PDAI] histology subscore [hPDAI] and endoscopy subscore [ePDAI], inflammatory bowel disease [IBD]-specific findings using the IBD score [S], colonic metaplasia using the colonic metaplasia score [CMS], and goblet cell [GC] ratio) in the pouch and AL of patients with UC.

Antigen stabilizing hydrogels based on cyclodextrins and polyethylene glycol act as type-2 adjuvants with suppressed local irritation.

Recent viral pandemics have increased global demand for vaccines. However, the supply of effective and safe vaccine not only to developed countries but also developing countries with inadequate storage equipment is still challenging due to the lack of robust systems which improve the efficacy and the stability of vaccines with few side effects. In our previous study, polypseudorotaxane (PPRX) hydrogels based on cyclodextrin (CyD) and polyethylene glycol (PEG) significantly improved the stability of antibody preparations and showed no serious adverse effects after subcutaneous injection, suggesting the possibility as safe vaccine formulations to stabilize an antigen protein.

Relationships between neighborhood disadvantage and cardiovascular findings at autopsy in subjects with sudden death.

Background: Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland.

Not to Rush-Laboratory Parameters and Procedural Complications in Patients Undergoing Left Atrial Appendage Closure.

Background: As a preventive procedure, minimizing periprocedural risk is crucially important during left atrial appendage closure (LAAC). Methods: We included consecutive patients receiving LAAC at nine centres and assessed the relationship between baseline characteristics and the acute procedural outcome. Major procedural complications were defined as all complications requiring immediate invasive intervention or causing irreversible damage.

Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1.

The monarchE Cohort 1 patient population was enrolled based on high-risk clinicopathological features that can easily be identified as part of routine clinical breast cancer evaluation. Efficacy data from Cohort 1 demonstrate substantial evidence of benefit for adjuvant abemaciclib+ET in patients with HR+, HER2- early breast cancer at high risk of recurrence (ClinicalTrials.gov: NCT03155997 [monarchE]).

Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study.

Background And Aims: Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy.

Development and validation of a scoring system for predicting clinical coronary artery perforation during percutaneous coronary intervention of chronic total occlusions: the PROGRESS-CTO perforation score.

Background: Coronary artery perforation is a feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and often leads to serious adverse clinical events.

Aims: We sought to develop a risk score to predict clinical coronary artery perforation in patients undergoing CTO PCI.

Methods: We analysed clinical and angiographic parameters from 9,618 CTO PCIs in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO).