Congenital metabolic diseases are inherited disorders caused by a lack of a single specific enzymatic activity.Left untreated, patients suffer multiple sequelae, including intellectual disability and eventual death. Althoughthe prevalence of individual diseases is low, the overall prevalence is increasing as newborn screening systemsimprove. Several therapeutic approaches, including diet therapy, oral medication, and enzyme replacement therapy, have been developed. Recently, a novel enzyme replacement therapy for phenylketonuria, pegvaliase, wasapproved.Considering curative therapy, several of these diseases have shown great benefits from liver transplantation.However, this approach is limited by the morbidity associated with this invasive procedure and a shortage ofdonor organs. One possible solution is regenerative therapy using hepatocytes generated from stem cells. We focuson one of the placental stem cell types, human amniotic epithelial cells (hAECs), to treat patients with congenitalmetabolic diseases. Our strategy to obtain therapeutic cells derived from the term placenta is innovative in severalrespects. First, the placenta is commonly discarded as medical waste and is readily available without additional invasive procedures. Second, a sufficient number of hAECs can be obtained from one human placenta. Third, it hasbeen shown that hAECs express stem cell markers and can differentiate into cells of all three germ layers. Fourth,hAECs do not form tumors when transplanted into immunocompromised mice. A preclinical study was conductedto demonstrate the therapeutic efficacy of hAECs for the treatment of congenital metabolic diseases using a rodentmodel of maple syrup urine disease. These studies demonstrated that liver-targeted hAEC transplantation ameliorated the disease phenotype and rescued lethal model mice.Based on this evidence, we are working on hAEC research for clinical application. Analyzing the signalingpathways involved in maintaining the pluripotency of cells and gene expression at the single-cell transcriptionallevel will help us achieve effective cell therapies. In addition, we have started manufacturing hAEC products on atrial basis to establish a clinical protocol for cell transplantation therapy using hAECs.

Since the discovery of insulin more than 100 years ago, the treatment of type 1 diabetes has evolved, especiallyin recent years, with remarkable advances in drugs and medical devices. Continuous glucose monitoring (CGM)is now widely used worldwide for glycemic control of diabetes mellitus, and the concept of time in range was proposed as the new glycemic control metric using CGM beyond A1c. This metric indicates the percentage of time inthe target glycemic range (70–180 mg/dl) at CGM, with a TIR of at least 70%, which corresponds to an HbA1c ofless than 7.0%. Sensor-augmented insulin pumps with automatic regulation of basal insulin are now available inJapan as insulin therapy devices. This system has been shown to safely improve glycemic control in pediatric type1 diabetes patients. Nasal glucagon is approved for the treatment of severe hypoglycemia in patients with diabetesin Japan. The launch of nasal glucagon has made it possible to administer glucagon easily and quickly to childrenwith severe hypoglycemia. We expect that advances in the treatment and management of pediatric type 1 diabeteswill contribute to improving the quality of life of children with type 1 diabetes.

The spread of COVID-19 has had an impact on our lives. Since late 2019, we have experienced the greatestimplications inflicted by the pandemic in our lifestyle and economic activities. I overview both basic and clinicalacknowledgments that can be shared as an emerging infectious disease and our correspondences on how to addressCOVID-19 in Nihon University Itabashi Hospital.

Very few previous studies have been conducted on the prognostic factors among postcardiac arrest patientswho were not witnessed. Therefore, we investigated the factors governing the prognosis of postcardiac arrestresuscitation patients without witnesses: we retrospectively investigated the predictive factors governing the vitaland neurological prognosis of out-of-hospital postcardiac arrest resuscitation patients admitted between January2015 and May 2019 who had no witnesses. A total of 857 cases were analyzed. It was found that the predictors ofgood vital and neurological prognosis in postresuscitation patients with unwitnessed out-of-hospital cardiac arrestwere young age, return of spontaneous circulation during transport, bystander cardiopulmonary resuscitation, andshockable initial rhythm. Considering these results, we believe these measures should be considered to improvethe life-saving rate.

Background: Intra-Aortic Balloon Pump (IABP) has the potential to recover cardiogenic shock, blood flow to thecoronary arteries, or both; but bleeding events negatively affect the cardioprotective effects of IABP. Nonetheless,the real-world data in Japan regarding bleeding events after IABP implantation in patients with acute myocardialinfarction (AMI) remains insufficient.Methods: We investigated the incidence of major bleeding events in 249 AMI patients who underwent percutaneous coronary intervention (PCI) and IABP, with and without cardiogenic shock. In 97 (39%) patients, IABP wasused for cardiogenic shock, while 152 (61%) patients had IABP for other indications.Results: Patients with cardiogenic shock were significantly older and had a lower body weight, higher NT-proBNP and lactate levels, lower left ventricle ejection fraction (LVEF), and higher CREDO-Kyoto bleeding and PRECISE-DAPT scores than those without. During the follow-up period, 26 (10%) patients experienced a majorbleeding event, and 19 (8%) had major adverse cardiac events (MACE), but there were no significant differencesin those rates between those with and without cardiogenic shock. After multivariate analysis, anemia remained associated with a major bleeding event (adjusted odds ratio 2.40, 95% confidence interval 1.01–5.73, p = 0.047).Conclusions: Despite the low risk in patients who did not have cardiogenic shock, major bleeding events andMACE rates were similar to that of those with cardiogenic shock. Anemia was independently associated withmajor bleeding events in AMI patients who had IABP. The use of IABP should be carefully decided in AMI patients, especially in patients with noncardiogenic shock or anemia.

Objective: To assess the lipid-controlling effect of elobixibat (EB), a bile acid transporter inhibitor, in patientswith cardiovascular diseases.Methods: Over the last 3 years, 45 patients have been prescribed EB for constipation as a substitute for magnesium oxide in the outpatient clinic. The average age of the patients was 77.5 ± 9.7 years, ranging from 55 to 93years old. Seventeen patients were female. All patients were being treated with statins for dyslipidemia. We compared the low-density (LDL) and high-density (HDL) lipoprotein cholesterol levels and mean carotid intimamedia thickness (IMT) during magnesium oxide use and 2 years after the prescription change to EB.Results: The LDL level was significantly decreased after 2 years of EB use (82.7 ± 20.2 mg/L, P < 0.0001) compared with treatment with magnesium oxide (96.82 ± 19.4 mg/L). However, the HDL levels were comparable.Therefore, the LDL/HDL ratio was significantly decreased after 2 years of EB use (1.61 ± 0.62, P < 0.0001); theLDL/HDL ratio during magnesium oxide use was 1.83 ± 0.65. The mean IMT was 1.246 ± 0.344 mm and 1.188 ±0.293 mm during magnesium oxide use and at 2 years after EB use, respectively. However, the difference was notstatistically significant (P = 0.0689). There were no cardiovascular events during the study.Conclusion: EB had an additional effect of controlling lipid profiles and might prove beneficial in patients withatherosclerotic cardiovascular diseases.

(Case) 57 years old, female. (present case) A left breast mass had been observed approximately one week before. Breast ultrasonography showed a poorly mobile mass of approximately 2 cm in size in the CE region of theleft breast. A needle biopsy was performed, and the mass was removed for adenomyoepithelioma. However, themass recurred and was removed again. Histopathological examination revealed malignant adenomyoepithelioma,and mastectomy and sentinel node biopsy were performed as for breast cancer.(Discussion) It is difficult to diagnose malignant adenomyoepithelioma by preoperative examination. Since thedisease can recur, careful diagnosis and treatment to avoid overinvasiveness are necessary.