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.

COVID-19 の流行は，われわれの生活に影響を与えた．2019 年末から始まった我が国におけるパンデミックで失った社会生活，経済活動における影響には計り知れないものがある．本稿では，COVID-19 における新興感染症としてのこれまでの共通認識できる基礎的・臨床的な知見と本学板橋病院における COVID-19 への対応について概説する．

心停止蘇生後患者の中でも，目撃の無いものについて，その予後を規定する要因について行われた先行研究は極めて少ない．そこで，目撃の無い心停止蘇生後患者の予後を規定する要因について調査した．2015 年 1 月～2019 年 5 月に入院した病院外心停止蘇生後患者のうち目撃例のない症例の生命学的・神経学的予後を規定する予測要因について，後ろ向きに調査した．解析対象例は 857 例であった．解析の結果，目撃の無い院外心停止蘇生後患者の生命学的・神経学的予後を良好にする予測因子として，年齢が若いこと，搬送中の心拍再開があること，発見者による胸骨圧迫が行われていること，初期波形ショックの適応があることであった．以上の結果を考慮し，救命率向上のための方策を検討すべきと考える．

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.

（症例）57 歳，女性．（現症）約 1 週間前より左乳房腫瘤を認めていた．乳腺超音波検査では左乳房 CE 領域に約 2 cm 大の可動性不良な腫瘤を認めた．針生検施行し，腺筋上皮腫の術前診断で腫瘤摘出術施行．しかし，再発し，再度腫瘤摘出術施行．病理組織学検査では，悪性腺筋上皮腫となり，乳癌に準じて乳房切除及びセンチネルリンパ節生検術施行した．（考察）術前検査で悪性腺筋上皮腫を診断することは困難である．再発することがあるので，慎重な診断と過大侵襲にならないように治療することが必要と思われた．