I introduce here what we have been and are doing in the Cross-ministerial Strategic Innovation Promotion Program (SIP) "Innovative AI Hospital System" project supported by the Japanese government. This SIP program began in April 2018 as 1 of 12 SIP projects that aim to establish "Society 5.0" in various scientific areas. This AI hospital program is the only one related to the health and medical care field, in which we are attempting to construct a big medical database, to implement many artificial intelligence (AI) tools in hospital systems, and to make the medical care system more effective along with reduction of workload of medical workers. To maintain or improve the quality of the health and medical care system, it is indispensable to share various updated and useful information among healthcare workers as well as the general population. We have been challenging to establish the digitalized medical care system in various aspects. I describe here where we are and the future perspective of the AI-based digital medicine.

Health inequalities are defined as "gaps in health status between groups, which are created by differences in community or socioeconomic status." In response to the General Assembly Resolution (2009) of the World Health Organization, the World Medical Association issued a statement in the same year, and the Japanese health policy "Health Japan 21 (second term) " indicated a "reduction of health inequalities" as the basic direction. In 2000, we described the presence of health inequalities in Japan, which was regarded as a relatively egalitarian country. This was the starting point of the Japan Gerontological Evaluation Study. It was developed into large longitudinal studies that reveal the significance of "social determinants of health" that cause health inequalities. We verified the feasibility and effects of healthy aging policies by fostering social capital through community intervention studies. These findings and knowledge have been translated into municipal and central government policies. Here we review what has been achieved and the remaining challenges in more than 20 years of social epidemiological research.

"Specified expectant mothers" are defined as pregnant women at high risk of needing extra support after birth. To provide them appropriate support, the methods for evaluating specified expectant mothers should be standardized. Thus, in this study, I reviewed the evaluation and multidisciplinary collaboration in some regions reported to be actively supporting specified expectant mothers in Japan. The main items related to "specified expectant mothers" were as follows: (1) mental disorders, (2) younger age, (3) no consultation/late first visit, (4) poverty, and (5) multiple pregnancy. It is important to proactively identify and confirm the problems faced by pregnant women through screening and interviews conducted by the medical staff.

Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum IgG4 levels. In 2003, IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with autoimmune pancreatitis. IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically, IgG4-RD occurs when an autoantigen triggers an immune response characterized by Th2 predominance with increased production of cytokines, such as interleukin 4 (IL-4), IL-5, IL-10, IL-13, and tumor growth factor-β (TGF-β), in the affected organ. IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating IgG4-RD from malignant tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against Rheumatism classification criteria for IgG4-RD have high diagnostic sensitivity and specificity. IgG4-RD generally responds well to treatment with steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of steroids. In Japan, low-dose steroid maintenance therapy is usually given to prevent a relapse. B-cell depletion with rituximab is effective in patients resistant to or dependent on steroids. Most patients with IgG4-RD who receive steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse, fibrosis development, and associated malignancies, have not been clearly defined. Therefore, novel treatment strategies, including rituximab, need to be tested in international randomized controlled clinical trials.

Regenerative medicine is a medical treatment that aims to restore lost human body functions by regenerating missing or dysfunctional organs and tissues using stem cells, etc. There are three major types of stem cells used in regenerative medicine: induced pluripotent stem cells (iPS cells), embryonic stem cells (ES cells), and mesenchymal stem cells (MSCs). MSCs are expected to be widely applied to regenerative medicine because of their ability to differentiate into various types of cells, repair cells and tissues; anti-inflammatory effects; secretion of various growth factors; and resolution of abnormally accumulated protein amyloid. MSCs can be derived from bone marrow, dental pulp, and other sources, but adipose tissue-derived stem cells (ADSCs) may be superior in that they can be harvested with the least amount of invasion, and therefore, a sufficient amount of stem cells can be cultured relatively easily. When MSCs are administered systemically by intravenous infusion, they tend to accumulate at the site of disease, a property known as "homing," which is extremely advantageous for clinical applications. In Japan, stem cell therapy can be performed only after the research or treatment plan has been reviewed and approved by the "Committee for Specific Approval of Regenerative Medicine" and submitted to the Ministry of Health, Labor and Welfare for approval in accordance with the "Act on Securing the Safety of Regenerative Medicine" and after approval by the ethics committee of the facility where the therapy is performed. In this review, the characteristics of MSCs, the actual status of their clinical application, and their future prospects are presented.

Cancer patients in adolescents and young adults (AYA) generation aged 15-39 years have various psychosocial needs during their treatment course such as school enrollment, finding employment, marriage, and fertility. It is difficult for medical professionals to gain experience related to providing medical care and consultation support to these kinds of AYA generation cancer patients. There is a need to provide information and establish both support and medical care systems that are able to meet the diverse needs unique to this generation. This review will explain how to launch an AYA support team (AST).

We have worked and established the AST since 2016, which is medical care teams that provide support according to the life stage of each individual patient and build a multidisciplinary AYA generation patient support system. The team-building process consisted of two main projects: building and enlarging multidisciplinary team and establishing screening process of psychosocial needs of AYA generation patients. Multidisciplinary healthcare professionals got involved in the AST with already-existing patient support functions in our center: the patient support center, which is an outpatient department and the palliative care team, which is an inpatient interdepartmental team. The AST systematically finds patients in need of assistance and offers them support as a multidisciplinary team. The AST also established a procedure that systematically gathers information about the needs of patients by using a screening tool. In addition, the AST provides the following specialized services: reproductive medicine, supporting cancer patients with children, employment support, and peer support. The AST has been established and sophisticatedly worked. It can flexibly provide various psychosocial support services. This review will explain how to launch an AST.

Introduction: In clinical research, ethical review is required prior to conducting the research. A surgical procedure is a complex intervention with properties that make it more difficult to evaluate rigorously and monitor than drug treatments. This study aimed to clarify the current status and issues in the ethical review and monitoring of surgical research.

Methods: We developed a self-administered questionnaire on surgical ethical review. The questionnaire was distributed to university hospitals in Japan and collected from November 2018 to February 2019. The distributed questionnaire consisted of the reviewed items, items with difficulties, and important items on ethical review. Fisher's exact test or the chi-square test was used for analysis.

Results: The questionnaires from 39 medical university hospitals were completed with appropriate answers to all items. "Technical review" was conducted at a significantly lower proportion (n = 30/39, 76.9%, p = 0.002). "Evaluation of the progress and results" was also (n = 22/39, 56.4%, p < 0.001). University hospitals in which "technical aspects and ethical review" was regarded the most important and difficult were higher (n = 24/39, 61.5%; n = 26/39, 66.7%, respectively). Respondents considered not only items written in the study protocol but also those on monitoring or oversight of surgical research as difficult.

Conclusions: Our findings suggest that it is necessary to improve the ethical review system and provide supports to conduct an appropriate review for surgical research, e.g., technical aspect review or study progress/result evaluation.

Introduction: To date, no studies have assessed the prognostic ability of nutritional indicators to predict changes in quadriceps muscle thickness (QMT). Hence, this study aimed to identify the optimal nutritional indicators for predicting the change in QMT during the acute phase in patients with stroke.

Methods: This retrospective cohort study was a post-hoc analysis of a prospective study in a single hospital. The Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), and Mini Nutritional Assessment - Short Form (MNA-SF) were assessed. The primary outcome was the 2-week change in QMT from the time of admission in the paralytic and non-paralytic sides. QMT was evaluated at the rectus femoris and the vastus intermedius in both lower limbs using B-mode ultrasound imaging. The sum of both measurements was defined as QMT. Univariate and multivariate analyses were performed to confirm the effects of nutritional risks assessed by each nutritional indicator on QMT change.

Results: We analyzed 118 patients (mean age, 80.2 ± 8.8 years). No significant difference was found in QMT change in the non-paralytic limbs between the groups stratified based on GNRI and CONUT. However, the difference was significant between the malnourished and normal nutritional status in patients categorized by MNA-SF. After adjusting for potential confounders, a significant association was found between MNA-SF and change in QMT (malnourished vs. normal nutritional status; B = −0.143; 95% confidence interval [CI], −0.254 to −0.031) in the non-paralytic limbs. MNA-SF was not independently associated with change in QMT in the paralytic limb. Furthermore, GNRI and CONUT were not independently associated with change in QMT in both paralytic and non-paralytic limbs.

Conclusions: Although MNA-SF might be useful for predicting the QMT change in non-paralytic limbs, GNRI and CONUT cannot predict the QMT change in either the paralytic or non-paralytic limb.

Introduction: The current guidelines for managing hypertension recommend strict blood pressure (BP) control to prevent bleeding complications in patients with hypertension on antithrombotic therapy. However, the target BP value of <130/80 mmHg is achieved in a small proportion of these patients. This study aimed to examine the factors associated with nonachievement of target BP value (≥130/80 mmHg) in patients on antithrombotic therapy.

Methods: This retrospective study was conducted at an outpatient clinic in 2018. Clinical parameters were obtained from the center's electronic medical database. Office BP was measured once in the sitting position. A target BP value of <130/80 mmHg was defined according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2019.

Results: Of the 26,803 outpatients who had scheduled visits during this time, 2,427 received antithrombotic therapy. Patients with chronic kidney disease stage 5 or on hemodialysis and those with missing data on body mass index were excluded from the study; eventually, 2,201 outpatients met the inclusion criteria. BP values of <140/90 mmHg were observed in 59.2% of these outpatients; however, only 30.6% displayed the target BP value of <130/80 mmHg. Univariate and multivariate logistic regression analyses indicated that male gender and obesity significantly correlated with nonachievement of the target BP (≥130/80 mmHg). However, heart failure and ischemic heart disease were negatively but significantly related to nonachievement of the target BP.

Conclusions: The target BP value was achieved in only a small proportion of the patients treated with antithrombotic drugs. In patients on antithrombotic therapy, obesity appeared to be a modifiable risk factor, whereas cardiovascular comorbidities, such as heart failure, were negative factors contributing to nonachievement of the target BP.

Introduction: Studies on the effect of androgen receptor pathway inhibitors (ARPI), docetaxel (DTX), and radium-223 (Ra-223) after first-line treatment with ARPI in patients with castration-resistant prostate cancer (CRPC) are scarce. This study compared the efficacy of treatment after ARPI for CRPC.

Methods: Patients with CRPC who received ARPI as first-line treatment and different second-line treatments were retrospectively reviewed. Clinicopathological backgrounds and treatment outcomes, including maximum prostate-specific antigen (PSA) decrease, progression-free survival (PFS), and overall survival (OS), were compared between second-line treatments.

Results: In total, 88 patients were enrolled. Forty-one (46.6%), 37 (42.0%), and 10 (11.4%) patients were treated with ARPI, DTX, and Ra-223, respectively. Patients whose PSA levels were not adequately reduced by first-line treatment with ARPI were eventually enrolled in the DTX treatment (P = 0.030). PSA decrease was not significantly different when comparing treatments. PFS in the DTX group was significantly better than in the other two groups (P = 0.023). In multivariate analysis, DTX was an independent prognostic factor for better PFS compared to ARPI (hazard ratio, 95% confidence interval; 0.44, 0.25-0.79, P = 0.006). Subgroup analysis showed a favorable impact of DTX on PFS in patients with Gleason score >8 (interaction P = 0.027) and a PSA decline >50% (interaction P = 0.019) during first-line treatment with ARPI. However, no significant difference in OS was observed between groups of different second-line treatments.

Conclusions: This study suggests that in patients with CRPC, second-line treatment with DTX following progression in patients who received ARPI as first-line treatment is more beneficial compared with second-line treatment with ARPI or Ra-233.

Introduction: Scholarship is an essential component of postgraduate education. This study's objective was to investigate the effect of a new reform requiring research publication experience before taking the pediatric board examination to promote scholarly activities among pediatric residents in Japan.

Methods: We conducted an experimental study from 2015 to 2018 to investigate the effectiveness of this reform for promoting scholarly activities among Japanese pediatric residents.

Results: Of all 2524 participants, the number of examinees before and after the reform was 1580 and 944, respectively. The yearly number of the residents' presentations and publications during their residency was 1.2 (SD 0.9) and 0.06 (SD 0.16), respectively, before the reform and 1.3 (SD 1.0) and 0.21 (SD 0.18), respectively, after the reform. Multiple regression showed the post-reform examinees (β = 0.37, p < 0.01) and the number of research presentations (β = 0.28, p < 0.01) were significantly associated with the number of research publications during the residency. While no contributive variables were found in the institution types, residents in the Kyushu and Okinawa area (i.e., southern island area in Japan) published fewer articles than those in the Tokyo area (β = −0.05, p = 0.03).

Conclusions: The newly implemented policy requiring residents to publish research articles as a board examination prerequisite effectively promotes research activities among pediatric residents.

Introduction: The COVID-19 pandemic has caused stress and anxiety for pregnant women worldwide. We examined the anxiety symptom in Japanese women during pregnancy using a self-administered questionnaire under the COVID-19 pandemic.

Methods: Between April 2020 and March 2021 (2020, the COVID-19 pandemic), we asked 248 Japanese women without history of mental disorders who delivered singleton neonates at 37-41 weeks' gestation to answer the two-item generalized anxiety disorder scale (GAD-2) at first, second, and third trimesters of gestation. We also asked 311 women with the same situation between January 2019 and December 2019 (2019) as control.

Results: The women with anxiety symptom were common during the first trimester of gestation irrespective of COVID-19 pandemic. In 2019, the proportion of the women with anxiety symptom decreased as the trimester of pregnancy progressed (p < 0.01); however, in 2020, the proportion of women with anxiety symptom did not decrease during pregnancy. During the late pregnancy, the proportions of women with anxiety symptom in 2020 were significantly higher than those in 2019 (p < 0.01) regardless of maternal parity or age in Japan.

Conclusion: The COVID-19 pandemic seemed to prevent the decrease in anxiety symptom that should decrease as pregnancy progresses regardless of maternal parity or age in Japan.

Public health centers have played an important role in controlling the spread of COVID-19 in Japan. However, the staff members of 469 centers have been overwhelmed by the huge increase in workload, and some public health centers were obliged to temporarily stop regular HIV testing. With the halting of HIV testing during the COVID-19 crisis, the proportion of "Ikinari-AIDS" or a sudden diagnosis of AIDS without prior knowledge of the HIV infection status is expected to rise. To provide essential public health services, it is time for Japan to focus on delivering public health services beyond the existing public health centers.

Healthcare providers are at risk of exposure to SARS-CoV-2 via droplets, respiratory secretions, and contact with contaminated surfaces. Personal protective equipment (PPE) is necessary for primary reliable prevention to treat patients with coronavirus disease 2019 (COVID-19). However, PPE shortages have had a significant impact on every medical facility, and outpatient clinics are especially vulnerable to shortages of medical supplies. During the first stage of the pandemic, efforts were made to reduce the use of medical supplies. Guidance and strategies were proposed to ration the use of PPE, including reusing it. However, reuse (wash) of isolation gowns has not been practically promoted despite these suggestions. Further, reusable products may have advantages for economic and ecologic reasons. We developed an adult universally sized, long-sleeved, 100% polyester, reusable/washable gown with liquid barrier protection. The isolation gown can be worn repeatedly through washing and subsequent disinfection, and it can withstand washing in 80°C hot water for 10 min and/or immersion in 0.05%-0.1% sodium hypochlorite for 30 min and then dried. This new gown's liquid barrier performance is at Association for the Advancement of Medical Instrumentation level 1, even after 20 repeated uses with low cost. The choice of barrier level for gowns should be made based on the risk of contamination. However, the healthcare setting for COVID-19 patients varies greatly with not fully elucidated transmissibility. The newly made reusable isolation gown can be one option for treating COVID-19 patients especially in low-risk settings with economical advantage. Further, preparedness for reuse may have critical implications in extreme shortage. Reconsideration should be focused on reusable gowns with liquid barrier performance and their appropriate use.

The patient was a 57-year-old man with a 15-year history of diabetes mellitus and a 3-year history of dialysis. He developed a subacute onset of Parkinsonism, including gait disturbance, bradykinesia, cogwheel rigidity, and myoclonus attacks. Magnetic resonance imaging (MRI) of the brain revealed swollen bilateral basal ganglia lesions, which appeared hyperintense with the lentiform fork sign on fluid-attenuated inversion recovery images, indicating vasogenic edematous lesions. He was diagnosed with diabetic uremic syndrome. Dopamine transporter single-photon emission computed tomography revealed no decrease in dopamine transporters. After approximately 4 weeks of continuous hemodialysis, rehabilitation, and supportive therapy, his neurological symptoms and MRI findings markedly improved. Although this disease has been reported in a few cases, its etiology and treatment remain unclear. In this case of diabetic uremic syndrome, dopamine secretion capacity was normal even though the patient had parkinsonian symptoms. This finding might contribute to further elucidation of the pathological mechanism of diabetic uremic syndrome.

We analyzed the clinicopathological characteristics of six patients with duodenal gastrointestinal stromal tumor (dGIST) resected in our hospital between 2005 and 2020. The patients (5 males, 1 female) were aged from 43 to 83 years old (mean: 63.7 years old). With respect to the preoperative diagnosis, one patient was diagnosed with dGIST by a biopsy, and five patients were diagnosed with suspected dGIST by esophagogastroduodenoscopy (EGD). The tumor locations were the third portion in four cases, second portion in one, and fourth portion in one. The pathological stages were I in four patients, II in one, and IIIB in one. All patients were discharged 12.8 days (10-15 days) postoperatively without complications, such as pancreatic fistula or suture deficiency. Regarding the prognosis, all patients are alive without recurrence.

The wedge resection is a reasonable option for resection of dGIST and should be routinely considered if technically feasible.

Salivary duct carcinoma (SDC) is a rare and highly aggressive salivary gland tumor with rapid growth, distant metastasis, and a high recurrence rate. Moreover, the parotid gland is the most common site with a poor prognosis. A lower frequency of distance metastasis to the liver, skin, and brain has also been reported, although the lungs, bones, and lymph nodes are the most common sites of SDC metastasis. We report a case of nonconvulsive status epilepticus (NCSE) in a 73-year-old male comatose patient having SDC of the parotid gland with an unusual metastasis to the skin and brain diagnosed by frequent cerebrospinal fluid examinations. Meningeal carcinomatosis usually has a poor prognosis, and NCSE is a reversible cause of altered mentation. Clinicians should know the unique set of epilepsy etiologies in patients with malignant tumors.

A 68-year-old woman with a history of schizophrenia developed coronavirus disease (COVID) -19 and was transferred to our hospital. Despite treatment, she died of respiratory failure 16 days after the onset. At the time of autopsy, polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA using swabs from the nasopharynx and the lung was positive; however, the cerebrospinal fluid was negative. An autopsy showed diffuse alveolar damage and recent multiple cerebral infarcts. Acute splenitis was observed with thrombi adhering to the vascular endothelium in areas of severe neutrophilic infiltration. Immunohistochemistry using an antibody against the SARS-CoV-2 nucleocapsid showed immunoreactivity along the hyaline membrane of the lung; however, the antibody showed no immunoreactivity in the medulla, the thalamus, the frontal lobe, and the pituitary. Future pathologic studies should clarify the mechanisms involved in a variety of clinical and pathological changes related to COVID-19.

A 39-year-old man presented with worsening fever, cough, and fatigue. He was immediately admitted to the intensive care unit (ICU) and was found to have sepsis, septic pulmonary embolism, right empyema, liver abscess, pyelonephritis, and a prostate abscess, with background diabetes mellitus. While receiving treatment, an ICU nurse noticed that the patient's toe tips were too large to fit the clamp device of pulse oximeters. Thus, we re-examined the patient and confirmed that he had clinical features indicative of acromegaly including bulging eyebrows, enlarged nose and lips, large feet, and prognathism. He and his family had not noticed these features except for his enlarged feet. We evaluated the patient further for acromegaly, and a pituitary mass was detected via contrast-enhanced head magnetic resonance imaging. Whole-body computed tomography also revealed thickened heel pads, cauliflower deformity, frontal sinus enlargement, sella turcica enlargement, and mandibular malocclusion. A 75 g oral glucose tolerance test was performed to investigate abnormal secretion of growth hormone (GH), and the results revealed a paradoxical increase in GH levels. The patient was then diagnosed with acromegaly according to the clinical guidance of the Japan Endocrine Society. Acromegaly develops slowly; thus, to improve patients' prognoses, physicians including internists, family physicians, and endocrinologists should include acromegaly in their differential when signs are apparent.