KEIO JOURNAL OF MEDICINE最新文献

In 2016, the Rome criteria were updated as Rome IV, and only minor changes were introduced for functional dyspepsia (FD). The major symptoms of FD now include not only postprandial fullness, but also epigastric pain and burning, and early satiation at above the "bothersome" level. Investigations into the effect of meal ingestion on symptom generation have indicated that not only postprandial fullness and early satiety but also epigastric pain and burning sensation and nausea (not vomiting) may increase after meals. Helicobacter pylori infection is considered to be the cause of dyspepsia if successful eradication leads to sustained resolution of symptoms for more than 6 months, and such a condition has been termed H. pylori-associated dyspepsia. Prompt esophagogastroduodenoscopy and H. pylori "test and treat" may be beneficial, especially in regions with a high prevalence of gastric cancer, such as east Asia. In terms of treatment, acotiamide, tandospirone, and rikkunshito are newly listed in Rome IV as treatment options for FD. Clinical studies in the field of FD should be strictly based on the Rome IV criteria until the next Rome V is published in 2026.

Proton pump inhibitors (PPIs) are widely used medicines worldwide. However, a rare etiology of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) related to PPI was recently reported. Therefore, the putative role of PPIs in SIADH cannot be underestimated. A 78-year-old Japanese woman was admitted to our hospital for treatment of left Bell's palsy. On admission, the patient was oriented with normal laboratory data, including a serum Na level of 135 mEq/L. Oral glucocorticoids and a proton pump inhibitor were initiated in combination with oral valaciclovir. Six days later, the patient's consciousness became impaired. Laboratory data showed a serum Na level of 103 mEq/L, a urine Na level of 64.8 mEq/L, a urine K level of 43.6 mEq/L, and a urine osmolality of 450 mOsm/kg H₂O. The patient met the criteria for SIADH. The initial treatment included water restriction and 3% hypertonic saline administration. The cessation of PPI significantly improved the urine diluting capacity and concomitantly increased serum Na, which indicated that the use of PPI had been responsible for the etiology of SIADH. The present case illustrates that physicians need to be aware of the uncommon adverse effects of PPI, such as SIADH.

As the Director General of Keio University Hospital, I hereby document the recent outbreak of health care-associated novel coronavirus (SARS-CoV-2) COVID-19 infections at our hospital in the spring of 2020.

Hypertrophic cardiomyopathy (HCM) is an intractable disease that causes heart failure mainly due to unexplained severe cardiac hypertrophy and diastolic dysfunction. HCM, which occurs in 0.2% of the general population, is the most common cause of sudden cardiac death in young people. HCM has been studied extensively using molecular genetic approaches. Genes encoding cardiac β-myosin heavy chain, cardiac myosin-binding protein C, and troponin complex, which were originally identified as causative genes, were subsequently reported to be frequently implicated in HCM. Indeed, HCM has been considered a disease of sarcomere gene mutations. However, fewer than half of patients with HCM have mutations in sarcomere genes. The others have been documented to have mutations in cardiac proteins in various other locations, including the Z disc, sarcoplasmic reticulum, plasma membrane, nucleus, and mitochondria. Next-generation sequencing makes it possible to detect mutations at high throughput, and it has become increasingly common to identify multiple cardiomyopathy-causing gene mutations in a single HCM patient. Elucidating how mutations in different genes contribute to the disease pathophysiology will be a challenge. In studies using animal models, sarcomere mutations generally tend to increase myocardial Ca²⁺ sensitivity, and some mutations increase the activity of myosin ATPase. Clinical trials of drugs to treat HCM are ongoing, and further new therapies based on pathophysiological analyses of the causative genes are eagerly anticipated.

Imidazole antifungal compounds exert their antipathogenic effects through inhibition of sterol biosynthesis. These drugs have also recently been identified as candidate anticancer agents for several solid tumors including glioblastoma. However, their effects on glioma-initiating cells (GICs), i.e., glioma cells with stemlike properties that are able to initiate tumors, remain unclear. Consequently, we examined the effects of the optically active imidazole compound luliconazole on mouse GICs and GIC-based tumors. Luliconazole impaired in a concentration-dependent manner the growth of spheres formed by GICs in vitro. In contrast to the inhibitory effects of ionizing radiation and temozolomide on sphere growth, that of luliconazole was attenuated by the addition of exogenous cholesterol. Exposure to luliconazole of brain slices derived from mice with orthotopic GIC implants for 4 days in culture resulted in a marked increase in the number of tumor cells positive for cleaved caspase-3, but without a similar effect on normal cells. Furthermore, in brain slices, luliconazole inhibited the expansion of GIC-based tumors and the parenchymal infiltration of tumor cells. Our findings therefore indicate that luliconazole effectively targets GICs, thereby providing further support for the antitumorigenic effects of imidazole antifungal compounds.

Early detection of cancer is crucial for its ultimate control and the prevention of malignant progression. In Japan, a nationwide project was conducted between 2014 and 2019 to develop novel cancer detection tools using serum microRNAs (miRNAs). Using the National Cancer Center Biobank, we collected more than 10,000 serum samples from patients with malignant diseases, including rare cancers such as ovarian cancer, gliomas, and sarcomas. Subsequently, comprehensive miRNA microarray analyses were performed for all samples. This serum miRNA database provides insights regarding miRNA biomarker candidates for each cancer type. Here, we summarize the major achievements of this national project. Notably, although circulating miRNAs packaged in extracellular vesicles are thought to be a cell-to-cell communication tool, the functional characteristics of the miRNAs listed in the project are still unknown. We hope that our findings will help elucidate the biological functions of circulating miRNAs.

The importance of aerobic fitness in rowing has been widely studied, and it is accepted that aerobic fitness is a key factor in rowing performance. In contrast, the impact of rowing efficacy, especially rowing form, on rowing performance has not yet been fully elucidated. The present study aimed to investigate this subject via the analysis of hip kinematics and the association of this variable with 2000 m ergometer rowing test performance. Eleven adult male rowers underwent a 2000 m rowing test on an ergometer and the exhaled gas was analyzed. The hip joint angle, the pelvic rotation, and the knee joint angle were measured at the catch position throughout the test. Peak VO₂ was strongly associated with the time taken to complete the test (ρ=-0.96, P<0.01), thereby confirming the importance of aerobic capacity in rowing performance. The variance of the hip joint angle of each rower was associated with peak VO₂, lean mass, and test time (ρ=-0.72, -0.84, and 0.66, respectively, all P<0.05). Greater knee flexion was accompanied by larger posterior rotation of the pelvis (ρ=0.74, P<0.05), and was negatively associated with hip flexion (ρ=-0.76, P<0.05). Although we cannot confirm whether the consistency of the hip joint angle actually leads to better rowing performance, our results suggest that there are associations between the consistency of the hip joint angle, aerobic capacity, lean mass, and the time taken to complete the 2000 m ergometer rowing test.

Cardiovascular disease is the leading cause of death worldwide. Cardiomyocytes have limited regenerative capacity; consequently, regenerative therapies are in high demand. There are currently several potential strategies for heart regeneration, with one approach involving in situ generation of new cardiomyocytes from endogenous cell sources. Direct cardiac reprogramming has emerged as a novel therapeutic approach to regenerating the damaged heart by directly converting endogenous cardiac fibroblasts into cardiomyocyte-like cells. Following our first report of direct cardiac reprogramming, significant advances have elucidated the molecular mechanisms associated with cardiac reprogramming. These advances have also improved cardiac-reprogramming efficiency by enabling direct in vivo cardiac reprogramming. Moreover, progress has been made in cardiac reprogramming of human fibroblasts. Although basic research has supported substantial progress in this field, numerous challenges remain in terms of clinical application. Here, we review the current state of cardiac reprogramming as a new technology for understanding and treating cardiovascular diseases.