KEIO JOURNAL OF MEDICINE最新文献

Heart failure is a life-threatening disease prevalent worldwide. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages represent a critical issue. Cardiac regenerative therapy is beneficial, but it is currently unsuitable as a substitute for cardiac transplantation. Human induced pluripotent stem cells (hiPSCs) are excellent sources for the generation of terminally differentiated cells. The preparation of a large number of pure cardiomyocytes (CMs) is the major premise for translational studies. To control the quality of the generated CMs, an efficient differentiation method, purification strategy, and mass-scale culture must be developed. Metabolic purification and large-scale culture systems have been established, and pure hiPSC-derived CMs of clinical grade are now available for translational research. The most critical challenge in cell therapy is the engraftment of transplanted cells. To overcome the low engraftment ratio of single CMs, aggregations of CMs are developed as cardiac spheroids. A cardiac transplantation device with domed tips and lateral holes has been developed for the transplantation of cardiac spheroids. Large animal models are necessary as the next step in the process toward clinical application. The transplant device has successfully been used to inject cardiac spheroids uniformly into myocardial layers in swine, and this approach is progressing toward clinical use. Remaining issues include immunological rejection and arrhythmia, which will require further investigation to establish safe and effective transplantation. This review summarizes the present status and future challenges of cardiac regenerative therapies.

Uterus transplantation (UTx) has seen increasing global adoption as an alternative for women with uterine factor infertility to achieve pregnancy. However, several medical, ethical, and social issues need to be addressed before UTx can be applied clinically. Since 2009, Japan has amassed a large database of basic research on UTx in non-human primates, but clinical application has not been realized because of conservative attitudes and prudent concerns. Nonetheless, UTx may be viable in Japan after comprehensive resolution of the concerns associated with this medical technology.

Pulmonary hypertension (PH) is a progressive disease characterized by increased pulmonary vascular resistance that leads to right ventricular (RV) failure, a condition that determines its prognosis. This review focuses on the clinical value of the evaluation of RV function in PH. First, the pathophysiology of PH, including hemodynamics, RV function, and their interaction (known as ventriculoarterial coupling), are summarized. Next, non-invasive imaging modalities and the parameters of RV function, mainly assessed by echocardiography, are reviewed. Finally, the clinical impacts of RV function in PH are described. This review will compare the techniques that yield comprehensive information on RV function and their roles in the assessment of PH.

SARS-CoV-2 whole-genome sequencing of samples from COVID-19 patients is useful for informing infection control. Datasets of these genomes assembled from multiple hospitals can give critical clues to regional or national trends in infection. Herein, we report a lineage summary based on data collected from hospitals located in the Tokyo metropolitan area. We performed SARS-CoV-2 whole-genome sequencing of specimens from 198 patients with COVID-19 at 13 collaborating hospitals located in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions were performed to differentiate and classify the viral lineages. More than 90% of the identified strains belonged to Clade 20B, which has been prevalent in European countries since March 2020. Only two lineages (B.1.1.284 and B.1.1.214) were found to be predominant in Japan. However, one sample from a COVID-19 patient admitted to a hospital in the Kanto region in November 2020 belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in the western United States since November 2020. The patient had no history of overseas travel or any known contact with anyone who had travelled abroad. Consequently, the Clade 20C strain belonging to the B.1.346 lineage appeared likely to have been imported from the western United States to Japan across the strict quarantine barrier. B.1.1.284 and B.1.1.214 lineages were found to be predominant in the Kanto region, but a single case of the B.1.346 lineage of clade 20C, probably imported from the western United States, was also identified. These results illustrate that a decentralized network of hospitals offers significant advantages as a highly responsive system for monitoring regional molecular epidemiologic trends.

In late March 2020, we faced a nosocomial outbreak of novel coronavirus disease 2019 (COVID-19) at Keio University Hospital, Tokyo, Japan. Presently, COVID-19 is an unprecedented worldwide biohazard, and a nosocomial outbreak can occur in any hospital at any time. Therefore, we reviewed the literature regarding hospital preparedness, the initial management of COVID-19, and the surveillance of healthcare workers (HCWs) to find information that would be generally useful for physicians when confronted with COVID-19. In terms of hospital preparedness, each hospital should develop an incident management system and establish a designated multidisciplinary medical team. To initiate case management, COVID-19 should be suspected based on patient symptoms and/or high-risk history and then should be confirmed by viral testing, such as reverse transcription polymerase chain reaction (RT-PCR) analysis. Although some patients will become critically ill, the guidelines for respiratory failure and septic shock for non-COVID-19 cases can be followed for supportive treatment. Antiviral medications should be carefully selected because the available information is confused by the large volume of preprint literature and unreliable data. HCWs who have come into contact with patients with COVID-19 can generate new in-hospital clusters of COVID-19 cases. Quarantine following contact tracking with risk stratification is effective in preventing transmission, and the essentials of medical surveillance include monitoring different types of symptoms, delegation of supervision, and continuation of surveillance regardless of the RT-PCR results. Preparation for COVID-19 is recommended before the first COVID-19 case is encountered.