Background: As the number of non-native patients in Japan is increasing, emergency departments must provide proper care for international patients. However, no research has been conducted to determine the demographics of international patients that visit Japanese hospitals or the requirements to accept them. We aimed to organize the existing research and its patterns for foreign patients in Japan's emergency departments and to identify the areas that require further research.

Methods: Systematic review of research articles indexed in MEDLINE and Ichushi-web (Japanese medical literature) was conducted. The search strategy was based on a previous study in Japanese, and the search was limited to manuscripts published from 2015.

Results: Nine publications that reported on the demographic characteristics of foreign patients who visited the emergency department were among the study's 13 references. Injury diagnoses and the Asian population were both common. Dealing with overseas patients can be challenging due to linguistic barriers, cultural differences, and payment issues. However, studies describing the spoken language and the type of healthcare insurance used were lacking. Furthermore, neither the definition of "foreign patients" nor the distinction between short-term visitors and long-term residents were made in the majority of the research.

Conclusions: The demographic characteristics of patients differed depending on the location and facility, despite the fact that several characteristics of foreign patients in emergency departments appeared to be generalizable. The COVID-19 pandemic may modify the demographic characteristics of immigrants; thus, more research from a broad range of locations and medical facilities is still necessary.

Gene regulation by microRNAs (miRNAs) plays important roles in development, physiology, and disease. miRNAs are an abundant class of noncoding RNAs that are generated through multistep biosynthetic pathways and typically repress gene expression through target destabilization and translational inhibition. Complex interactions between miRNAs and target mRNAs are associated with characteristic molecular mechanisms, including miRNA cotargeting, target-directed miRNA degradation, and crosstalk with various RNA-binding proteins. Consistent with the broad influence on cellular function, miRNA deregulation is commonly observed in various diseases, particularly cancer, with both tumor-suppressive and oncogenic roles. Mutations in the miRNA biosynthetic pathway and several miRNA genes have been linked to diverse types of cancer and a subset of genetic diseases, respectively. Additionally, super-enhancers play important roles in the regulation of cell type-specific and disease-associated miRNAs. This review summarizes the molecular features of miRNA biogenesis and target regulation along with the roles of miRNAs in disease biology, with recent examples expanding the pathophysiological roles of miRNAs.

It is estimated that approximately 280 million people worldwide suffer from depression. Depression is a common disease to us all, and the socioeconomic loss caused by depression is very large. However, there is currently a problem that many depressed patients do not respond to existing antidepressants, including selective serotonin reuptake inhibitors (SSRIs). Therefore, novel and effective therapeutic agents are highly desirable. It has been reported that exercise has preventive effects on depression (antidepressant effects) and that serotonin, whose release increases in the brain with exercise, is involved in exercise-induced antidepressant effects. We focused on the action of serotonin and investigated its role in the antidepressant effect of exercise using gene knockout mice, and then, we found that serotonin type 3 (5-HT3) receptors play an essential role in the antidepressant effect of exercise. We then further investigated the antidepressant effects mediated by 5-HT3 receptors. Our detailed analyses revealed that neurons expressing 5-HT3 receptors are abundant in the subgranular zone of the hippocampal dentate gyrus and produce insulin-like growth factor-1 (IGF-1). In addition, we newly found that the stimulation of 5-HT3 receptors by agonists promotes IGF-1 release in the hippocampus and increases hippocampal neurogenesis via the IGF-1 signaling pathway, resulting in antidepressant effects. Furthermore, we further showed that a 5-HT3 receptor agonist increases hippocampal neurogenesis and exhibits antidepressant effects in mice with depressive-like behavior. A comparison with the effects of existing antidepressant SSRIs revealed that the 5-HT3 receptor-mediated antidepressant action is a new therapeutic mechanism that differs from existing drugs. Our findings suggest a novel 5-HT3 receptor-IGF-1 mechanism, which could lead to the development of new antidepressant drugs for depression based on the molecular mechanism of exercise-induced antidepressant effects and could bring significant benefits to many depressed patients who do not respond to existing drugs such as SSRIs.

The phenomenon of hematocephalus is still not fully understood. Intraventricular hemorrhage volume and intracranial pressure play a substantial role in the outcome and survival of the patients. The intraventricular hemorrhage resulting in an increased intracranial pressure is known by the term "hematocephalus." The mortality rate ranges from 60% to 91% when hemorrhage affects all four ventricles. Even for partial hematocephalus, the mortality rate has been reported to be 32% to 44%. Therefore, the main objective in managing hematocephalus is to remove intraventricular blood efficiently and quickly because doing so will reduce ventricular dilatation and will rebalance cerebrospinal fluid circulation. However, the current standard management, which is inserting a ventricular drain immediately after an intraventricular hemorrhage, appeared to be of little value as the catheters are invariably clogged with blood clots. Long-term outcomes from the external ventricular drainage insertion plus subsequent intraventricular fibrinolytic therapy have been encouraging, but it also carries a substantial risk of new intracranial bleeding. The neuroendoscopic approach was created to aid in the treatment of hematocephalus and to enable the hematoma to be reduced or removed quickly without invasive surgery or the administration of fibrinolytic medications, preventing the intraventricular inflammatory reactions that result from hematoma degradation products. A controlled trial is necessary to ascertain whether this procedure enhances patient outcomes when compared to ventricular draining with or without thrombolysis.

Introduction: Torrential rains occurred in Okayama in western Japan in July 2018, forcing local residents to evacuate. Few studies have reported early-phase disease and injury trends among patients following torrential rains. Thus, in this study, we assessed the illness and injury trends among patients who visited temporary medical facilities located in the areas affected by the 2018 torrential rains; these facilities opened 10 d after the disaster.

Methods: We evaluated the trends among patients who visited a medical clinic located in the area in western Japan affected by heavy rains in 2018. We reviewed medical charts related to 1,301 outpatient visits and conducted descriptive analyses.

Results: More than half of the patients were over 60 years old. The patients experienced mild injuries (7.9% of total visits) as well as common diseases such as hypertensive diseases (30%), diabetes mellitus (7.8%), acute upper respiratory infections (5.4%), skin diseases (5.4%), and eye diseases (4.8%). Hypertensive diseases were the main cause of a visit in any week. Eye problems were the second-highest reason for a visit in the first week, but there was a relative decrease from the first to the third week. Additionally, the proportion of injuries and skin diseases increased from the first to the second week, from 7.9% to 11.1% for injuries, and from 3.9% to 6.7% for skin diseases.

Conclusions: The types of diseases changed on a weekly basis. Older adults needed medical support for longer than other age groups. Prior preparedness such as earlier deployment of such temporary clinics can help mitigate the damage to the victims.

Introduction: Regulated medical waste (RMW) management, particularly, improper discharges of RMW from small-scale medical institutions (less than 20 sickbeds), has drawn attentions. This study investigated improper discharges of RMW containers from small clinics to analyze improper discharge mechanisms.

Methods: Inspectional survey categorized improper discharges into improper sealing, container deformation, overweight, container contamination, container damaging, etc. The inspection surveys were performed from April 2018 to March 2019. In total, 2364 containers were inspected, which was equivalent to 64317 Litters in container volume and around 13.19 Mg in weight.

Results: About 38% of RMW containers were categorized to improper discharges. They consist mainly of improper sealing (67.0%), container deformation (24.6%), and overweight (6.31%). It was hypothesized that frequent RMW discharges allow short interval of container discharge, which prevents clinic staff from human errors due to forgetting and might reduce improper discharges. However, the inspection results rejected this hypothesis. The survey proposes that improper discharges were likely not sporadic events, which possibly occurred in any clinics, but repeated events in certain clinics. It was also hypothesized that saving discharge cost likely induced overpacking of RMW to containers, particularly larger volume containers, and caused improper sealing, container deformation, and eventually overweight. The inspection results and statistical analyses validated this hypothesis. This study also validated one more hypothesis that large compressive force required for complete sealing might cause improper sealing. The measurement results rejected it. However, they also suggest that gender and age of clinic staff might be partially associated with improper sealing.

Conclusions: Improper discharges of RMW containers seem to be non-random events. Specific clinics likely repeat improper discharges using larger volume containers. It is proposed that decreasing discharge cost induces overpacking of RMW to containers, and causes subsequent problems like container deformation.

Introduction: The evaluation of hospital performance often receives great attention. Hospitals refer to patient ratings to undertake quality-improvement activities. However, little is known about the factors that contribute the most to these patient ratings. This study aimed to investigate the association of relevant factors, such as doctors' and nurses' performance, with patients' ratings of hospitals, using the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS^®) questionnaire.

Methods: A cross-sectional study was conducted among patients who were hospitalized in Japan, from January 2020 to September 2021. Patients' hospital rating scale scores between 0 and 10 were collected and dichotomized. A score of 8 or higher was defined as a high rating. A multivariate logistic regression analysis was conducted to investigate the association between patients' ratings of the hospital and other items in the HCAHPS^® questionnaire.

Results: The frequency of patients' high and poor hospital ratings were 207 (69%) and 93 (31%), respectively, of 300 respondents. A significant association was observed for the patient's age (adjusted odds ratio (AOR): 1.02; 95% confidence interval (CI): 1.00-1.04), doctor's communication (AOR: 10.47; 95% CI: 3.17-34.58), and discharge planning (AOR: 3.53; 95% CI: 1.96-6.36) with a positive patient rating of the hospital.

Conclusions: An emphasis on doctor communication and discharge planning is essential in improving patients' ratings of hospitals. Further research is needed to determine the factors that contribute the most to patients' ratings of hospitals.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) for asymptomatic common bile duct stones (CBDS) has been associated with an increased risk of post-ERCP pancreatitis (PEP). Patients with asymptomatic CBDS at the time of ERCP include those with incidentally discovered CBDS (group A) and previously symptomatic patients with CBDS who became asymptomatic after conservative treatment for symptomatic CBDS, including obstructive jaundice or acute cholangitis (group B). In this study, we aimed to examine PEP risk in group B by comparing PEP risks between groups A, B, and currently symptomatic patients (group C).

Methods: In this multicenter retrospective study, we examined 77 patients in group A, 41 patients in group B, and 1225 patients in group C who had native papillae. PEP incidence rates between asymptomatic patients at the time of ERCP (groups A and B) and symptomatic patients (group C) were compared using one-to-one propensity score matching. Bonferroni's correction analysis was also performed to compare PEP incidence rates among the three groups.

Results: As per our findings, PEP incidence rate in propensity score-matched groups A and B was significantly higher than that of propensity score-matched group C (13.2% [15/114] versus 4.4% [5/114], respectively, P = 0.033). In groups A and B, PEP incidence rates were 11.7% (9/77) and 14.6% (6/41), respectively. PEP risk in group B was similar to that in group A (P = 1.0). PEP incidence in group B was significantly higher than PEP incidence in group C (14.6% (6/41)) vs. 2.9% (35/1225)) (P = 0.005)).

Conclusions: ERCP for previously symptomatic patients with CBDS who became asymptomatic after conservative treatment for symptomatic CBDS may increase the risk of PEP compared with ERCP for currently symptomatic patients. Thus, ERCP should be performed before patients become asymptomatic using conservative treatments if patients can tolerate ERCP procedures.

Introduction: Allergic diseases affect both children and adults, but generation-specific prevalence rates are unclear.

Methods: An online questionnaire was used from December 2021 to January 2022 to survey the prevalence of allergic diseases among staff and their families of designated allergic disease medical hospitals in Japan. In this study, bronchial asthma (BA), atopic dermatitis (AD), food allergies (FAs), allergic rhinitis (AR), allergic conjunctivitis (AC), metal allergies (MAs), and drug allergies (DAs) were the allergic diseases surveyed.

Results: In total, 18,706 individuals were surveyed (median age, 36 years; quartile range, 18-50). Allergic disease was reported in 62.2% of respondents. Across all ages, prevalence rates were as follows: BA (14.7%), AD (15.6%), FAs (15.2%), AR (47.4%), AC (19.5%), MAs (1.9%), and DAs (4.6%). The prevalence of BA and AR was higher in male children, whereas that of FAs and AC was higher in adult females. The prevalence of MAs and DAs peaked during adulthood and predominated among females.

Conclusions: Our results suggest that approximately two-thirds of the Japanese population may have an allergic disease, with AR being the most prevalent.

Introduction: Blood gas analysis is an important test for making quick and important clinical decisions, and it is recommended that a dedicated syringe that contains heparin be used to measure blood gas. We hypothesized that a plastic syringe could be used as a less-expensive substitute for a dedicated syringe, given that the test is performed immediately after collection.

Methods: This single-center, prospective, observational study involved patients admitted to the Kanoya Medical Center (Kagoshima, Japan) between July 2020 and March 2021, who were requiring blood gas analysis using a dedicated syringe under arterial line (A-line) monitoring. There were no exclusion criteria. Two samples were collected from each patient using a dedicated syringe, and one sample was collected using a plastic syringe. To determine clinical substitutability, Bland-Altman analysis was performed.

Results: A total of 60 samples from 20 consecutive patients were collected and assayed. The mean patient age was 72 years, and 75% patients were men. The 95% limit of agreement for pH, PCO₂, PO₂, Na, K, Ca, and SO₂ were similar for both dedicated and plastic syringes. HCO₃ and BE were significantly higher in the samples taken with plastic syringes, whereas Hb and Ht could not be measured accurately with any syringe.

Conclusions: The use of plastic syringes in place of dedicated syringes is generally considered acceptable for most items considering that measurement is performed within 3 min of collection, and the cost of medical materials may be reduced. Regardless of the type of syringe, caution should be exercised in interpreting the results of measuring Hb and Ht using a blood gas analyzer.

Introduction: To date, the appropriate epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients aged ≥75 years with advanced EGFR mutation-positive, nonsmall cell lung cancer remain unknown.

Methods: This study included a total of 89 patients aged ≥75 years who were diagnosed with EGFR mutation-positive, nonsmall cell lung cancer and treated with EGFR-TKIs at the Tokyo Metropolitan Geriatric Hospital and Nihon University ITABASHI Hospital from 2009 to 2020. The patients were classified into five groups based on their treatment: gefitinib (n = 23), erlotinib (n = 4), afatinib (n = 3), first-line osimertinib (n = 23), and TKI to TKI (n = 36). The efficacy and safety of each EGFR-TKI were analyzed.

Results: No significant differences in the overall survival and progression-free survival were observed among the groups. However, a significantly higher incidence of drug-induced interstitial lung disease (ILD) was detected with osimertinib than with the first-generation EGFR-TKIs (p= 0.008).

Conclusions: In older patients with EGFR mutation-positive lung cancer, the incidence of drug-induced ILD was significantly increased during osimertinib treatment. This outcome should be noted when treating older patients with osimertinib who may not always want to live longer but want to live better.

Medical devices provide important infrastructural support in modern healthcare systems. However, in low- and middle-income countries (LMICs), inadequate maintenance and management of devices due to a shortage of healthcare personnel (not only doctors and nurses but also other professionals including biomedical engineers [BMEs]) has resulted in inefficient and weak healthcare systems. High-income countries, including Japan, have resolved these problems by developing human resources and technologies to maintain and manage these systems. In this paper, we discuss the possibility of mitigating these problems in LMICs through human resource development and technology, based on lessons from Japan's experience. The problem of medical device management in LMICs stems from the fact that there are few professionals, such as BMEs, in charge of the management of medical devices and that clinical engineering departments in charge of device management have not been established. Since the 1980s, Japan has introduced a licensing system for BMEs, establishing operational guidelines to clarify their responsibilities within hospitals and using technology to utilize data and reduce workloads. Nevertheless, workload problems and high costs required to introduce computerized management systems persist. Moreover, it would be difficult to implement the same measures as those adopted in Japan in LMICs where there is an overwhelming shortage of medical personnel. It may be necessary to further reduce workloads for data entry and device management; use up-to-date, inexpensive, and user-friendly technology; and train non-BME personnel to operate and maintain equipment.

There was a global shortage of nab-paclitaxel (Abraxane^®), a major antineoplastic agent, for a long period (from October 2021 to June 2022) because of manufacturing problems. Japan was one of the first affected countries by the depletion, and the medical institutes started to save the use of the drug in August 2021; numerous patients with gastric, breast, and lung cancer who potentially could receive benefits failed to be treated with the antineoplastic agent; thus, they opted for alternative treatments. Meanwhile, the hospitals in the United States and some countries continued to consume nab-paclitaxel at a regular pace as usual and then the worldwide depletion occurred in October 2021. Early communications about the drug shortage between authorities worldwide might have soothed the depletion; effective platforms for global information sharing would be necessary in order to secure the access to anticancer agents.

Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disorder, resulting from MEN1 gene abnormalities, which causes tumors mainly in the endocrine glands. We experienced a sporadic case of MEN1 complicated with papillary thyroid carcinoma (PTC) and found a novel missense mutation in the patient's MEN1 gene. Her older sister, who showed no typical symptom of MEN1, had a history of PTC, suggesting the presence of another genetic factor involved in PTC development. This case suggests the importance of an individual's genetic background in the development of MEN1 complications.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease that is characterized by predominant upper lobe fibrosis and pleural thickening. In this report, we present an unusual case of idiopathic PPFE with left vocal cord paralysis that developed repeated aspiration pneumonia. Vocal cord paralysis is a rare complication of PPFE, and two mechanisms can be proposed: 1) Fibrous adhesion of the recurrent laryngeal nerve to the chest wall can cause stretching of the nerve. 2) Traction or compression of the recurrent laryngeal nerve due to the distortion of the tracheobronchial tree can cause paralysis of the vocal cord. Finally, to reduce the risk of aspiration pneumonia, laryngoscopic evaluation of the vocal cord is recommended in patients with PPFE with hoarseness and dysphagia for early intervention.

Vertical transmission of the herpes simplex virus (HSV) in the preclinical phase of the disease progression is rare. Here, we present a case of perinatal-acquired herpes from an asymptomatic mother. Our findings suggest that clinicians should consider screening predisposed mothers for HSV as part of prenatal care to identify asymptomatic primary genital HSV infections.

Intracranial germ cell tumors are uncommon brain tumors; germinoma is the most common tumor in children and young adults, and the most common regions affected are pineal gland and suprasellar region. Germinomas of the suprasellar region are accompanied by endocrine alterations, with adipsia being a rare presentation. Here, we present the case of a patient with an extensive intracranial germinoma whose initial presentation was adipsia, without any other endocrinological alteration, with development of severe hypernatremia and unusual manifestations derived from it, such as deep vein thrombosis, myopathy with rhabdomyolysis, and neurological axonal damage.