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.

Japan, like many other parts of the world, is under threat from newly emerging, potentially fatal diseases. Severe fever with thrombocytopenia syndrome (SFTS), first clinically identified in 2009, is an emerging tick-borne hemorrhagic viral disease, currently limited in distribution to East Asia. Relatively little is known about the disease with an initial Case Fatality Rate ranging from 5% to 40%. It primarily affects the elderly living in rural areas, which is particularly troublesome given Japan's rapidly aging population. Control efforts are severely hampered by lack of specific knowledge of the disease and its means of transmission, coupled with the absence of both a vaccine and an effective treatment regime, although some antiviral drugs and blood transfusions are successful in treating the disease. Despite both the causative virus and vector ticks being commonly found throughout Japan, the disease shows a very specific, limited geographical distribution for as yet unknown reasons.

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious health and economic problems worldwide. One of the worst scenarios is the collapse of the medical care system due to nosocomial infections. SARS-CoV-2 quickly spreads in closed spaces, crowded areas, and close physical distances, which frequently occur in Japanese medical facilities. Although we are making efforts to avoid such situations, healthcare workers always face the risk of developing a SARS-CoV-2 infection in the workplace because of proximity. Thus, we need to battle SARS-CoV-2 using a unique strategy.

We propose a novel strategy to eliminate SARS-CoV-2 infections: measurement of antibodies against SARS-CoV-2 and using the power of "immune survivors." We agree with using standard precautions and early isolation of patients with coronavirus disease 2019 (COVID-19) to block the spread of SARS-CoV-2 infection. However, we face difficulties carrying out these fundamental missions. Now, we focus on "immune survivors." If healthcare workers acquired the neutralizing antibody against SARS-CoV-2, they are considered "immune survivors" with a low risk of reinfection with SARS-CoV-2. These "immune survivors" can contribute to the care of patients with COVID-19 on the front line. Also, these "immune survivors" can function as an envelope by surrounding COVID-19 patients. As a result, "immune survivors" can eliminate the spread of SARS-CoV-2 in medical facilities as well as in society.

We understand that the concept of "immune survivors" needs further discussion. No information is available on how long or the titer of neutralizing antibody required for protection from infection. We have just started to measure antibody levels against SARS-CoV-2 in healthcare workers in our hospital. This project will provide further information in the battle against the SARS-CoV-2 infection. (Clinical trial registration number: UMIN 000039997)

Introduction: To support pregnant women with serious social problems, we retrospectively examined the current status of social problems during pregnancy in Japan.

Methods: We examined the frequency, associated factors, and outcomes of the pregnant women with social problems at our institute for each year from 2016 to 2019.

Results: The frequency of pregnant women with social problems significantly increased year by year (p < 0.01). The breakdown of high-risk factors associated with the social problems has remained almost unchanged; however, the frequency of unmarried pregnant women, unplanned pregnancy, foreigners who cannot speak either Japanese or English, and pregnant women who are somehow anxious significantly increased (p < 0.05).

Conclusions: We will endeavor to solve the various social problems of pregnant women through multidisciplinary collaboration.

Introduction: 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.

Methods: 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.

Results: 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 (P_trend < 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.

Conclusions: 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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Introduction: Pediatric emergency physicians commonly experience cases of infantile trauma as a result of a child falling from the arms or the back of a parent while the parent is operating a bicycle.

Methods: 1. We conducted a retrospective case-series study which included children younger than 1 year who were injured after falling from the arms or the back of the parent while the latter was operating a bicycle.

2. We conducted a dynamics experiment by recreating the circumstances of the accident using dummies representing a 6-month-old infant being carried on the back of the mother. We assessed the score of the Head Injury Criterion (HIC) and the maximum impact load on the head of the dummy infant.

Results: 1. We found eight injured patients, two of whom required intensive care. One of the latter experienced neurological sequelae.

2. The HIC score and the maximum impact load varied from 7.7 to 17.0 and 2.26 to 3.47 times the reference values for 6-month-old infants, respectively.

Conclusions: Our study revealed that a strong impact on an infant's head can result in severe head trauma due to the mechanics of the injury type studied. Preventive strategies for the safe transportation of infants are needed.

Introduction: Opioid analgesics are the mainstay of cancer pain management. The annual opioid consumption globally indicates adequate opioid availability and the quality of palliative care. We investigated the current situation regarding the adequacy of opioid availability in individual prefectures in Japan and explored the determinants of adequacy.

Methods: We analyzed nationwide databases open to public inspection depicting the current Japanese healthcare situation. Opioid consumption for cancer pain was estimated from oxycodone and morphine data in the nationwide database. On the basis of the World Health Organization recommendations, we calculated adequacy based on the annual cancer deaths in each prefecture in 2013 and 2015. We investigated the associations between adequacy and either outpatient medical expenditure for hypertension and diabetes as a proxy of primary care practice or ratios of these risk holders in community. Outpatient medical expenditures for musculoskeletal disorders and neoplasms were also investigated.

Results: The nationwide adequacy of opioid availability was approximately 75%. The largest gaps in adequacy between prefectures were more than 65%. The adequacy correlated with expenditure but not local volumes of hypertension and diabetes in both years. The other two expenditures did not relate to opioid availability.

Conclusions: Although precise data are required, our preliminary findings indicate that primary care practice is the key regulator of adequate opioid availability. Opioid adequacy in Japan is thus delayed in matching the global standard, and gaps in opioid adequacy among prefectures should be bridged rapidly to expand universal access to effective palliative care and cancer pain relief.

Introduction: The STOP-Bang test was used to detect patients at high risk of obstructive sleep apnea (OSA). We evaluated the usefulness of the STOP-Bang test for predicting the severity of OSA in Japanese patients.

Methods: We retrospectively evaluated the patients who performed full polysomnography at the Mihara Medical Association Hospital. We evaluated the correlation between the STOP-Bang score and the apnea hypopnea index (AHI) using Spearman's rank correlation analysis. We then used multivariate analyses to examine the independent risk factor for severe OSA (AHI ≥ 30/hr).

Results: One hundred seven patients were diagnosed as no (n = 5), mild (n = 17), moderate (n = 30), and severe (n = 55) OSA. The median age was 67 years old (range: 35-84), and 73 of the 107 patients were males. The correlation coefficient between the STOP-Bang score and AHI was 0.701 (P < 0.001). A STOP-Bang score ≥ 5 had sensitivity of 80.0% and specificity of 76.9% for detecting severe OSA. A STOP-Bang score ≥ 5 and BMI ≥ 30 kg/m² were the independent risk factor for severe OSA.

Conclusions: The STOP-Bang score correlates with AHI and is useful for predicting OSA severity. Polysomnography should be performed actively for the patients with high STOP-Bang scores.