Pharmacokinetics, Safety, and Tolerability of Single-Dose Dazukibart in Healthy Adults in China and Japan: Results From 2 Randomized, Double-Blind, Phase 1 Studies.

Dazukibart is a humanized monoclonal antibody selectively targeting interferon-β. The pharmacokinetics (PK), safety, tolerability, and immunogenicity of dazukibart were evaluated in 2 double-blind, randomized, placebo-controlled, single-dose, Phase 1 studies in healthy adults in China (Study 1: N = 18; dazukibart 900 mg = 15; placebo = 3) and Japan (Study 2: N = 12; Cohort 1: dazukibart 300 mg = 5, placebo = 1; and Cohort 2: dazukibart 900 mg = 5, placebo = 1). PK parameters were assessed after dosing in Study 1 and Study 2, and no significant differences were observed between PK findings among participants in both studies.

Temporal effects of lascufloxacin on human gut and salivary microbiota: Analysis using next-generation sequencing method.

Introduction: Antimicrobial treatment disrupts human microbiota. The effects of lascufloxacin (LSFX), a new fluoroquinolone, on human microbiota remains unknown. Therefore, in this study, we aimed to evaluate the effects of LSFX administration on the gut and salivary microbiota of healthy participants and those with pneumonia.

Immunogenicity and Safety Following 1 Dose of AS01E-Adjuvanted Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults: A Phase 3 Trial.

Background: The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds.

Methods: This ongoing phase 3 study in ≥60-year-olds evaluates immune persistence until 3 years after RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until 1 year post-dose 1.

Long Term Follow-Up Study of a Randomized, Open-Label, Uncontrolled, Phase I/II Study to Assess the Safety and Immunogenicity of Intramuscular and Intradermal Doses of COVID-19 DNA Vaccine (AG0302-COVID19).

Pharmacological studies have demonstrated antibody production and infection prevention with an intradermal coronavirus disease 2019 (COVID-19) DNA vaccine (AG0302-COVID-19). This clinical trial aimed to investigate the safety and immunogenicity of high doses of AG0302-COVID19 when injected intramuscularly and intradermally. Healthy adults were randomly divided into three intramuscular vaccination groups (2 mg, three times at 2-week intervals; 4 mg, twice at 4-week intervals; and 8 mg, twice at 4-week intervals) and two intradermal groups (1 mg, three times at 2-week intervals or twice at 4-week intervals).

DS-5670a, a novel mRNA-encapsulated lipid nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2: Results from a phase 2 clinical study.

Background: DS-5670a is a vaccine candidate for coronavirus disease 2019 (COVID-19) harnessing a novel modality composed of messenger ribonucleic acid (mRNA) encoding the receptor-binding domain (RBD) from the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encapsulated in lipid nanoparticles. Here, we report the safety, immunogenicity, and pharmacokinetic profile of DS-5670a from a phase 2 clinical trial in healthy adults who were immunologically naïve to SARS-CoV-2.

Methods: The study consisted of an open-label, uncontrolled, dose-escalation part and a double-blind, randomized, uncontrolled, 2-arm, parallel-group part.

Sex Differences in Blood Pressure and Potential Implications for Cardiovascular Risk Management.

Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements.

Twenty-Four-Hour Intraocular Pressure Control with Omidenepag Isopropyl 0.002% in Patients with Glaucoma and Ocular Hypertension.

Purpose: To clarify the intraocular pressure (IOP)-lowering effect of a selective prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI) during a 24-hour period.

Patients And Methods: Subjects aged ≥20 years and with diagnosed, untreated primary open-angle glaucoma or ocular hypertension were enrolled. IOP measurements were performed every 4 hours over a 24-hour period using a Goldmann applanation tonometer (GAT) and Icare PRO tonometer (PRO).

[Danaparoid Sodium Controlled Chronic Disseminated Intravascular Coagulation Associated with Chronic Aortic Dissection and Patent False Lumen for a Long Term:Report of a Case].

The management of chronic disseminated intravascular coagulation( DIC) caused by aortic dissection has not yet been established. We report the successful treatment of a case of aortic dissection with a patent false lumen using danaparoid sodium for acute exacerbation of chronic DIC. 2,000 U danaparoid sodium per day has been stabilizing the coagulative and fibrinolytic parameters and has been relieving bleeding tendencies with no side effects for a long term.

Impending rupture of abdominal aortic aneurysm due to apixaban use.

Direct oral anticoagulants (DOAC) are useful for preventing embolism and venous thrombosis in patients with atrial fibrillation. There are also reports that DOAC can dissolve existing intracardiac thrombus. Here, we report a case in which DOAC lysed a thrombus in an abdominal aortic aneurysm (AAA), resulting in impending rupture of the AAA.

Identifying Isolated Systolic Hypertension From Upper-Arm Cuff Blood Pressure Compared With Invasive Measurements.

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP.

Influence of Age on Upper Arm Cuff Blood Pressure Measurement.

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium.

High central blood pressure is associated with incident cardiovascular events in treated hypertensives: the ABC-J II Study.

It is not established whether central blood pressure (BP) evaluated by a radial pulse wave analysis is useful to predict cardiovascular prognoses. We tested the hypothesis that central BP predicts future cardiovascular events in treated hypertensive subjects. We conducted a multicenter, observational cohort study of 3566 hypertensives being treated with antihypertensive medications at 27 institutions in Japan.

Accuracy of Cuff-Measured Blood Pressure: Systematic Reviews and Meta-Analyses.

Background: Hypertension (HTN) is the single greatest cardiovascular risk factor worldwide. HTN management is usually guided by brachial cuff blood pressure (BP), but questions have been raised regarding accuracy.

Objectives: This comprehensive analysis determined the accuracy of cuff BP and the consequent effect on BP classification compared with intra-arterial BP reference standards.

Comparison of direct effects of clinically available vasodilators; nitroglycerin, nifedipine, cilnidipine and diltiazem, on human skeletonized internal mammary harvested with ultrasonic scalpel.

Direct vasodilator effects of nitroglycerin, nifedipine, cilnidipine and diltiazem on human skeletonized internal mammary artery graft harvested with ultrasonic scalpel were assessed in the presence of 0.1 or 0.2 µM of noradrenaline.

Older age is associated with greater central aortic blood pressure following the exercise stress test in subjects with similar brachial systolic blood pressure.

Brachial systolic pressure (BSP) is often monitored during exercise by the stress test; however, central systolic pressure (CSP) is thought to be a more direct measure of cardiovascular events. Although some studies reported that exercise and aging may play roles in changes of both BSP and CSP, the relationship between BSP and CSP with age following the exercise stress test remains unclear. The aim of this study was to evaluate the effect of age on the relationship between BSP and CSP measured after exercise.

Prognostic significance of dipping in older hypertensive patients.

Background And Aims: Arterial hypertension doubles the risk of coronary heart disease, heart and kidney failure, and peripheral arterial disease. Less variation in diurnal ambulatory blood pressure monitoring (ABPM) patterns may affect mortality outcome. Therefore, as hypertension occurs in over 95% of older subjects, the prognostic value of dipping status in older hypertensive patients will be assessed.

Complete His-ventricular block, atrial flutter and ventricular tachycardia as arrhythmogenic activities in a patient with takotsubo cardiomyopathy.

An association of atrial arrhythmias with takotsubo cardiomyopathy (TTC) has not been described previously. Here we report a 65-year-old male patient with TTC. The sudden appearance of atrioventricular block and subsequent bradycardia are believed to be key contributing factors for the development of TTC.

Local pulse wave velocity directly reflects increased arterial stiffness in a restricted aortic region with progression of atherosclerotic lesions.

We investigated local pulse wave velocity (LPWV) in different aortic segments with respect to the rheological properties of the aorta with age-related progression of atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Normal and KHC rabbits aged 10-12, 22-24 and 34-36 months were anesthetized with pentobarbital sodium (30 mg kg(-1), intravenous). Pulse waves at the ascending aorta were recorded simultaneously with those at the proximal, middle and distal thoracic and abdominal aortas by moving a catheter with three micromanometers (40-mm intervals) at 80-mm intervals from the origin of the descending thoracic aorta.

Correlation between the brachial blood pressure values obtained using the cuff method and the central blood pressure values obtained invasively.

Objective: This study was designed to identify why the central blood pressure (cSBP) values obtained using the catheter method tend to be higher than brachial systolic blood pressure (bSBP) values obtained using the cuff method.

Methods: This study enrolled 20 patients who underwent coronary angiography (CAG) (mean age, 68.9 years; 13 men).

Plaque stabilization by intensive LDL-cholesterol lowering therapy with atorvastatin is delayed in type 2 diabetic patients with coronary artery disease-Serial angioscopic and intravascular ultrasound analysis.

Background: Diabetes mellitus (DM) is a major risk factor for cardiovascular events. The study purpose was to compare DM and non-DM (nDM) patients in terms of statin-induced change of plaque characteristics using intravascular ultrasound (IVUS) and coronary angioscopy.

Methods: Patients with coronary artery disease and hypercholesterolemia who were enrolled to the TWINS were selected and classified into two groups: DM group and nDM group.

Does the augmentation index of pulse waves truly increase with progression of atherosclerosis? An experimental study with hypercholesterolemic rabbits.

Background: Recently, the central augmentation index (AIx) has been reported to show a nonlinear correlation with age. We investigated whether the AIx of the central artery changes with the progression of atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits.

Methods: We simultaneously recorded pressure and flow waves in the ascending aorta in normal and KHC rabbits aged 10-12, 22-24, and 34-36 months, under pentobarbital anesthesia.