Impact of serum haemoglobin-to-creatinine ratio after transcatheter aortic valve implantation.

OBJECTIVE: The association between a combined anaemia and renal failure index and 1-year prognosis of patients undergoing transcatheter aortic valve implantation (TAVI) is unexplored. We aimed to investigate a simple risk score in patients undergoing TAVI. METHODS: A total of 469 consecutive patients undergoing TAVI between 2015 and 2021 were enrolled. After excluding patients undergoing dialysis, the remaining 458 patients were classified according to three tertiles of the serum haemoglobin-to-creatinine (Hgb/Cr) ratio 1 day before TAVI. The primary clinical outcome measure was all-cause mortality and heart failure hospitalisation 1 year after TAVI. RESULTS: In the first, second and third tertiles, the 1-year cumulative incidence of all-cause mortality was 16.9% versus 7.2% versus 2.0%, respectively (p<0.01), and that of heart failure hospitalisation was 10.7% versus 3.4% versus 0.7%, respectively (p<0.01). The indexes of the area under the curve of the Hgb/Cr ratio for all-cause mortality and heart failure hospitalisation 1 year after TAVI were both 0.73. Cut-off values were 10.1 for all-cause mortality 1 year after TAVI (OR, 4.78; 95% CI 2.43 to 9.74; p<0.01) and 10.4 for heart failure hospitalisation 1 year after TAVI (OR, 5.3; 95% CI 2.21 to 14.1; p<0.01). In the multivariate analysis, the Hgb/Cr ratio was an independent predictor of all-cause mortality and heart failure hospitalisation 1 year after TAVI. CONCLUSIONS: Hgb/Cr ratio calculation 1 day before TAVI may help predict midterm all-cause mortality and heart failure hospitalisation in patients with severe aortic valve stenosis undergoing TAVI. TRIAL REGISTRATION NUMBER: 4143 (The Institutional Review Board of Kurashiki Central Hospital).

COVID-19 fulminant myocarditis recovered with veno-arterial extracorporeal membrane oxygenation and Impella CP.

A 38-year-old man without a history of coronavirus disease 2019 (COVID-19) vaccination presented with dyspnea and fever. Polymerase chain reaction nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 was positive. Electrocardiogram showed diffuse ST-segment elevation, and chest radiography showed mild pulmonary congestion. The left ventricular (LV) function was markedly impaired. Vital signs were unstable, and serum lactate level was elevated. The patient was diagnosed with cardiogenic shock due to COVID-19 fulminant myocarditis and received veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella CP (Abiomed, Inc., Danvers, MA, USA). Remdesivir and intravenous immunoglobulin were also administered. Corticosteroids were not administered because of the absence of pneumonia. On admission, endomyocardial biopsy showed a small direct inflammatory infiltrate of the myocardium. During mechanical support, the cardiac function improved, the patient was weaned off VA-ECMO on day 6, and Impella CP on day 7. Cardiac magnetic resonance imaging implied recent myocardial damage. The patient was discharged on day 30, and the LV function fully recovered. Since the treatment and prognosis of COVID-19 fulminant myocarditis remain unclear, we report the course of COVID-19 fulminant myocarditis with favorable outcomes. Mechanical circulatory support might be an important factor in determining the prognosis of COVID-19 fulminant myocarditis. Learning objective: Coronavirus disease 2019 fulminant myocarditis sometimes requires mechanical circulatory support. The prognosis and treatment have not yet been adequately established. The prognosis is favorable if adequate hemodynamic support is provided.

Trends in prognosis after hospitalization for acute heart failure in Kurashiki Central hospital 2015-2018: single-center prospective study.

Recently, we have been working on enhancing the effectiveness of treatment for acute heart failure (HF) through team-based care. This study was designed to assess the benefits of this initiative by quantifying the prognostic impact on HF patients receiving treatment at our hospital. We identified 1977 consecutive HF patients (mean age 78.3 ± 11.9 years) being discharged from our hospital between February 2015 and December 2018, divided them by admission year, and tracked changes over time, with 2015 as a reference. The postdischarge clinical outcome measures were defined as a composite of all-cause death or rehospitalization for HF, all-cause death, and rehospitalization for HF. The risk of a composite of all-cause death or rehospitalization for HF was lower in 2017 (adjusted hazard ratio, 0.72; 95% confidence interval: 0.57 to 0.91; p = 0.005) and 2018 (adjusted hazard ratio, 0.78; 95% confidence interval: 0.61 to 0.99; p = 0.045) than in 2015, and that of all-cause death was lower in 2017 (adjusted hazard ratio, 0.72; 95% confidence interval: 0.53 to 0.98; p = 0.04) and 2018 (adjusted hazard ratio, 0.60; 95% confidence interval: 0.43 to 0.85; p = 0.004) than in 2015, but that of rehospitalization for HF was not significantly different through the study period. The mortality rate decreased at the end of the study period, but the rate of rehospitalization for HF did not. The benefits of team-based care were difficult to evaluate by quantification.

Overview of the Premarketing and Postmarketing Requirements for Drugs Granted Japanese Conditional Marketing Approval.

For drugs that are intended to fill unmet medical needs, such as the treatment of rare diseases or a subtype of cancer, it can take a long time to conduct confirmatory clinical trials due to limited patient availability. Delayed access to these drugs increases the risk of mortality of patients with these diseases. To address this issue, the Ministry of Health, Labour, and Welfare of Japan has decided to implement the Conditional Early Approval System with issuing the Ministry Notification in 2017. Drugs eligible for conditional early approval are those that are indicated for the treatment of a serious disease, have proven safety and efficacy, and cannot be examined easily by confirmatory clinical trials. When the benefit of immediate availability outweighs the risk of having less comprehensive data with which to confirm the clinical benefit of a product in the premarketing phase, products can be approved under the Conditional Early Approval System, accompanied by postmarketing regulatory requirements to manage postmarketing risks and, if needed, conduct postmarketing confirmatory clinical studies. Overview of the pre-approval and post-approval regulatory considerations will promote to more efficiently develop pharmaceutical products that fill unmet medical needs, leading to the prompt delivery of safe and effective drugs to patients who often have few therapeutic options available. As of March 2020, four drugs had been approved under the Conditional Early Approval System. In this review, we describe the premarketing and postmarketing requirements of these drugs and discuss the regulatory landscape around the Conditional Early Approval System.

The Roadmap to Approval under Japan's Two-Track Regulatory System: Comparing Six Regenerative Medical Products.

The Japanese conditional and time-limited (CTL) approval framework, a tiered system for regenerative medical products, was initiated in 2014. Here, we compare the dossiers of six regenerative medical products with either direct full approval or CTL approval, and we discuss the regulatory considerations for obtaining approval under the CTL approval framework.

The Clinical Innovation Network: a policy for promoting development of drugs and medical devices in Japan.

The continuous increase in the costs of developing new drugs and medical devices drives increases in medical expenses. Seventy to ninety percent of these costs are associated with clinical trials. Therefore, the development of cost-effective methods to perform clinical trials remains a challenge. One approach is to use patient registries, collections of data related to patients with a specific diagnosis, condition, or procedure. Patient registries are used in Denmark, Sweden, and the USA for the enrollment of patients into clinical trials, and to evaluate endpoints. In Japan, a national project for registry-oriented clinical research, termed the 'Clinical Innovation Network' (CIN), was initiated in 2016. Here, we provide an overview of the CIN and discuss its impact on drug and device development in Japan.

Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes.

BACKGROUND: Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity. METHODS: BVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated. RESULTS: We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus. CONCLUSIONS: BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright © 2016 John Wiley & Sons, Ltd.