JMA Journal

Research and Development Strategy for Future Embryonic Stem Cell-Based Therapy in Japan

2020-09-23T08:30:01+09:00

Herewith, we review an updated progress of regenerative medical products using human embryonic stem cells (ESCs) in Japan. Two groups from Kyoto University and the National Center for Child Health and Development (NCCHD) established a novel derivation/cultivation system of ESCs for potential application in translational and clinical research. At the first stage of ESC derivation, murine feeder cells have been used in line with Japanese guidelines on public health associated with the implementation of the xenograft. To avoid exposure of ESCs to animal products in culture media, a xeno-free cultivating system has been established. Twelve ESCs (KhES-1, KhES-2, KhES-3, KhES-4, KhES-5, SEES-1, SEES-2, SEES-3, SEES-4, SEES-5, SEES-6, and SEES-7) are now available under a clinically relevant platform for industrially and clinically applicable regenerative medical products. NCCHD submitted an investigative new drug application to the Pharmaceuticals and Medical Devices Agency (PMDA) for using ESC-based products in patients with hyperammonemia due to genetic defects on March 2018 under the Pharmaceutical Affairs Law (now revised to the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act). Currently, up to ten ESC-based products are being prepared for intractable and rare disorders in Japan.

Time Trends of the Outcomes and Treatment Options for Disseminated Intravascular Coagulation: A Nationwide Observational Study in Japan

2020-09-23T08:30:01+09:00

Existing evidence on the mortality time trends of patients with disseminated intravascular coagulation (DIC) is limited, and whether the mortality trend or quality of care of DIC patients has improved remains unknown. This study aimed to investigate the temporal trend in mortality, patient outcomes, and treatment preferences of several anticoagulants in Japan.　 This retrospective observational study used the Japanese Diagnosis Procedure Combination inpatient database, which contains data from more than 1200 acute-care hospitals in Japan. We identified all adult patients that were diagnosed with DIC from July 2010 to March 2018 and sorted them into one of five predefined underlying conditions: sepsis, solid cancer, leukemia, trauma, or obstetric. The data collected as general outcomes were the 28-day mortality and major bleeding events. We also evaluated anticoagulant use for DIC treatment.　 A total of 325,327 DIC patients were included in this study. Regarding the baseline characteristics, an increase in median age, worsened comorbid conditions, and higher illness severity were observed over time. The underlying conditions for DIC were largely unchanged. Over the study period, the 28-day mortality for overall DIC patients decreased from 41.8% (95% CI 41.2%-42.3%) to 36.1% (95% CI 35.6%-36.6%), which is a 14% decrease over the 8-year period (　 < 0.001). The downward trend in mortality was more evident in patients with sepsis and leukemia (15% and 14% decreases, respectively), whereas no clinically meaningful change in mortality occurred in trauma and obstetrics patients. Over time, major bleeding events modestly increased, and the length of hospital stay decreased. The temporal trend in the treatment preferences of anticoagulants for DIC patients clearly changed over time.　 The overall 28-day mortality for DIC patients clearly decreased from 2010 to 2017. The downward trend in mortality might have resulted from the advances made in the fundamental treatment of underlying diseases and from the changes in anti-DIC strategies.

Underlying Disorders, Clinical Phenotypes, and Treatment Diversity among Patients with Disseminated Intravascular Coagulation

2020-09-23T08:30:01+09:00

Clinical guidelines state that disseminated intravascular coagulation (DIC) treatment should be based on three clinical phenotypes: the marked bleeding type (e.g. leukemia, trauma, obstetric diseases, or aortic diseases); organ failure type (sepsis or pancreatitis); and asymptomatic type of DIC (solid cancer). However, among the various underlying disorders of DIC, the clinical presentations of bleeding or organ failure have not to date been well documented. The present study aimed to evaluate whether underlying disorders of DIC would affect clinical outcome including death, organ failure, and bleeding.　 Using the Japanese Diagnosis Procedure Combination inpatient database, we identified all adult patients diagnosed with DIC during hospitalization from July 1, 2010, to March 31, 2018. We collected data on patient characteristics and underlying disorders of DIC including sepsis, solid cancer, leukemia, trauma, obstetric diseases, aortic diseases, pancreatitis, and miscellaneous diseases. We counted major bleeding events and calculated an organ failure score for patients during hospitalization.　 We identified 337,132 patients with DIC. The major disorders underlying DIC were sepsis (42%) and solid cancer (31%). The average organ failure scores of patients with aortic diseases, sepsis, and trauma were 2.8, 2.2, and 2.2, respectively. The percentages with major bleeding events among patients with aortic diseases, trauma, obstetric diseases, and solid cancer were 24%, 15%, 10%, and 10%, respectively.　 This study suggests that the clinical presentations of bleeding and organ failure are not associated with the three existing clinical phenotypes of DIC or with the underlying disorders of DIC. Therefore, clinical presentation alone may not be sufficient for identifying the clinical phenotypes of DIC. Further research is necessary to develop new strategies for identifying the phenotypes of DIC and improving treatment strategies for individual patients.