Hemodynamics with mechanical circulatory support devices using a cardiogenic shock model.

Mechanical circulatory support (MCS) devices, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, have been widely used for patients with cardiogenic shock (CS). However, hemodynamics with each device and combination therapy is not thoroughly understood. We aimed to elucidate the hemodynamics with MCS using a pulsatile flow model.

A tissue-silicone integrated simulator for right ventricular pulsatile circulation with severe functional tricuspid regurgitation.

There is a great demand for development of a functional tricuspid regurgitation (FTR) model for accelerating development and preclinical study of tricuspid interventional repair devices. This study aimed to develop a severe FTR model by creating a tissue-silicone integrated right ventricular pulsatile circulatory simulator. The simulator incorporates the porcine tricuspid annulus, valve leaflets, chordae tendineae, papillary muscles, and right ventricular wall as one continuous piece of tissue, thereby preserving essential anatomical relationships of the tricuspid valve (TV) complex.

Difference in tissue temperature change between two cryoballoons.

Background: Cryoballoon ablation, especially Arctic Front Advance Pro (AFA-Pro) (Medtronic, Minneapolis, Minnesota, USA), has been widely recognised as a standard approach to atrial fibrillation (AF). Recently, Boston Scientific has released a novel cryoballoon system (POLARx). Despite comparable acute clinical outcomes of these two cryoballoons, the recent study reported a higher complication rate, especially for phrenic nerve palsy, with POLARx.

Repairable ex vivo model of functional and degenerative mitral regurgitation.

Objectives: Transcatheter mitral valve repair is an emerging alternative to the surgical repair. This technology requires preclinical studies to assess efficacy in mitigating mitral regurgitation (MR). However, ex vivo MR models are not established.

Importance of optimal rewiring guided by 3-dimensional optical frequency domain imaging during double-kissing culotte stenting demonstrated through a novel bench model.

The usefulness of optical frequency domain imaging (OFDI) guidance on two-stenting at left main bifurcation has not been evaluated. Here, we used a novel bench model to investigate whether pre-defined optimal rewiring with OFDI-guidance decreases acute incomplete stent apposition (ISA) at the left main bifurcation segment. A novel bench simulation system was developed to simulate the foreshortening and overlapping of daughter vessels as well as left main bifurcation motion under fluoroscopy.

Biaxial tensile testing system for measuring mechanical properties of both sides of biological tissues.

The aortic wall exhibits a unique elastic behavior, periodically expanding in aortic diameter by approximately 10% during heartbeats. This elastic behavior of the aortic wall relies on the distinct yet interacting mechanical properties of its three layers: intima, media, and adventitia. Aortic aneurysms develop as a result of multifactorial remodeling influenced by mechanical vulnerability of the aortic wall.

Performance evaluation methods for improvements at post-market of artificial intelligence/machine learning-based computer-aided detection/diagnosis/triage in the United States.

Computer-aided detection (CADe), computer-aided diagnosis (CADx), and computer-aided simple triage (CAST), which incorporate artificial intelligence (AI) and machine learning (ML), are continually undergoing post-market improvement. Therefore, understanding the evaluation and approval process of improved products is important. This study intended to conduct a comprehensive survey of AI/ML-based CAD products approved by the U.

Estimation Failure Risk by 0.5-mm Differences in Autologous Hamstring Graft Diameter in Anterior Cruciate Ligament Reconstruction: A Meta-analysis.

Background: Because grafts are made in 0.5-mm increments clinically for anterior cruciate ligament (ACL) reconstruction, it is important to clarify how the failure rate decreases as the diameter increases. Moreover, it is important to know whether even a slight increase in the graft diameter decreases the risk of failure.

Nephroprotective Effects of Dapagliflozin in Patients with Type 2 Diabetes.

Objective This study analyzed changes in the estimated glomerular filtration rate calculated using cystatin C (eGFRcys) and sodium excretion in the urine after administering dapagliflozin as an add-on therapy to conventional treatment for diabetes. Methods This was a single-center, single-group, prospective interventional study. Dapagliflozin was administered to improve the plasma glucose control in 30 subjects with type 2 diabetes mellitus (age 53±8 years old; 66.

Comparison of hemodynamics and root configurations between remodeling and reimplantation methods for valve-sparing aortic root replacement: a pulsatile flow study.

Purpose: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator.

Methods: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18).

Analysis of Off-target Effects and Risk Assessment Leading from Preclinical to Clinical Trials of Gene-edited Therapeutic Products.

Objective: Concerns about off-target effects (OTEs) of genomic DNA cleavages by gene-editing enzymes have been raised, especially for OTEs that go undetected due to technical limitations. Since no explicit guidelines have been in place for risk assessment of OTEs, the regulatory authorities' concept of an acceptable evaluation scheme for OTEs in the investigational drug application (IND) has not been clear. Here, we clarify the regulatory expectations by examining reports on OTE evaluations of leading gene-editing products that have achieved IND clearance.

The actual status of drug prices and adjustment factors for drug price calculation: an analysis of ultra-orphan drug development in Japan.

Background: Extremely high prices facilitate drug development for ultra-rare diseases (ultra-orphan drugs). However, various problems arise in terms of healthcare financing and fairness, and the status of ultra-orphan drug pricing remains ambiguous. In this study, we investigated ultra-orphan drug prices in Japan relative to that of other drugs.

Systematic analysis of the test design and performance of AI/ML-based medical devices approved for triage/detection/diagnosis in the USA and Japan.

The development of computer-aided detection (CAD) using artificial intelligence (AI) and machine learning (ML) is rapidly evolving. Submission of AI/ML-based CAD devices for regulatory approval requires information about clinical trial design and performance criteria, but the requirements vary between countries. This study compares the requirements for AI/ML-based CAD devices approved by the US Food and Drug Administration (FDA) and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.

Comprehensive Analysis of Clinical Studies and Regulations of Therapeutic Applications in the United States and Japan.

Background: Digital therapeutics (DTx), the provision of treatment through mobile devices such as smartphones, have attracted great interest as a new medical modality. However, the number of authorized therapeutic applications in the US and Japan is low. Understanding the obstacles in obtaining regulatory authorizations will be the key in promoting timely development of therapeutic applications.

Gap distribution mapping to visualize regions associated with type 1 endoleak in a fenestrated thoracic stent graft.

Objectives: Our goal was to analyse the relationships between aortic surface irregularity and a type 1 endoleak (T1EL) after a thoracic endovascular repair using the Najuta fenestrated stent graft.

Methods: The patients who were treated using the Najuta stent graft for an intact aortic arch aneurysm at the Saitama Cardiovascular and Respiratory Center between June 2013 and June 2017 were analysed retrospectively. The primary end point was the occurrence of a T1EL.

Time-series biological responses toward decellularized bovine tendon graft and autograft for 52 consecutive weeks after rat anterior cruciate ligament reconstruction.

There is an essential demand for developing biocompatible grafts for knee anterior cruciate ligament reconstruction (ACLR). This study investigated cell infiltration into decellularized bovine tendon xenografts using a rat knee ACLR model. Twelve-week-old Sprague-Dawley rats were used.

Biodesign program introduction in Japan: promotion of entrepreneurship and viewpoints of education on medical technology innovation.

The Stanford Biodesign program was first introduced in Japan in 2015 at three national universities to develop medical technology innovation and its talent. This study aimed to (1) show the outcomes of leadership talent development, (2) indicate the educational results of the program, and (3) objectively analyze the ways in which the program executed in Japan, effectively promoted entrepreneurship orientation and the origination of new businesses. The latter is especially relevant as Japan has low entrepreneurial awareness and new business entry rates compared to the United States and Europe.

Latest outcomes of transcatheter left atrial appendage closure devices and direct oral anticoagulant therapy in patients with atrial fibrillation over the past 5 years: a systematic review and meta-analysis.

Left atrial appendage closure (LAAC) are emerging treatment for patients with atrial fibrillation (AF). However, data on the safety, efficacy, and medications for LAAC devices in patients with AF are lacking. We aimed to investigate the incidence of all-cause mortality, stroke, and major bleeding in AF patients with LAAC devices and DOACs.

Characteristics of anatomical difficulty for cryoballoon ablation: insights from CT.

Background: The limited availability of balloon sizes for cryoballoon leads to anatomical limitations for pulmonary vein (PV) isolation. We conducted a comprehensive systematic analysis on procedural success rate, atrial fibrillation (AF) recurrence rate and complications of cryoballoon ablation in association with the anatomy of the left atrium and PV based on preprocedural CT to gain insights into proper treatments of patients with AF using cryoballoon.

Method: A systematic search of literature databases, including PubMed, Web of Science and Cochrane Library, from the inception of each database through February 2021 was conducted.

Effectiveness of drug postmarketing all-case surveillance as a safety measure in Japan.

Introduction: The drug pharmacovigilance system in Japan is similar to those in the European Union (EU) and the United States. As a unique Japanese pharmacovigilance program, postmarketing all-case surveillance (PMACS) is required. PMACS plays a key role for postmarketing activities, but there are challenges that place much burden on PMACS conduct.

Comprehensive Risk Analysis of the Wingspan Stent in Relation to Target Vessels.

Objective: To facilitate understanding for the safe use of the Wingspan stent, a comprehensive literature analysis was conducted, and incidence rates of 30-day stroke or death before and after the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial were compared. We also investigated the associations between 30-day stroke or death rate and four lesion vessels, the internal carotid artery (ICA), middle cerebral artery (MCA), basilar artery (BA), and vertebral artery (VA).

Methods: We searched MEDLINE, Embase, Web of Science, and Cochrane Library databases.

Toward Global Harmonization of Training and Certification of Specialists in Laboratory Animal Veterinary Medicine.

Laboratory animal medicine (LAM) is a corner stone of animal-based research and has been a veterinary specialty for over 60 y. Today 5 Colleges of LAM (American, European, Japanese, Korean, and Indian) that certify specialists (Diplomates) in LAM are members of the International Association of Colleges of LAM (IACLAM). Goals of IACLAM are to support the development of new Colleges of LAM, to harmonize expectations for the knowledge and skills of newly certified LAM Diplomate, and to harmonize the standards (best practices) for training and examination of candidates among the member Colleges.

New Visualization Models of Designation Pathway and Group Categorization of Device-Drug and Device-Biologic Combination Products Classification in the United States: Analysis of FDA Capsular Decisions.

Objective: The developer and sponsor of new combination products in US needs to forecast which classification and designation to the regulatory scheme of drug, biological product, or device would be required for the new products by the Food and Drug Administration (FDA). To improve the predictability and acceptability of the designation of new combination products for innovators, developers, and sponsors, and to encourage the development and early access of new combination products, we proposed new visualization models of the designation pathway and group categorization.

Method: We searched the website of the FDA on 15 November, 2020 to identify the regulatory scheme of the FDA's 129 capsular decision cases of device-drug and device-biologics combination products and other publicly available cases the FDA designated to the drug/biologic or device regulatory scheme.