In a depopulating society, it is difficult to ensure sufficient resources and finances for health and health care. Thus, effective management of the reform of the healthcare system by visualizing the quality, efficiency, and equity of health care is imperative. This article presents an overview of the studies conducted by my team in this area over the past 35 years, covering the following four sections: (1) visualization of healthcare system using individual-level data, (2) healthcare system at the organizational level, (3) healthcare system at the national and regional levels, and (4) creation of a social system for health.

To improve the quality, efficiency, and equity of the healthcare system as well as the social system for people's health, it is necessary to visualize the actual situation and share this information with all stakeholders to contribute to the joint management of healthcare system. On this basis, from the perspectives of each region and the nation, it is important to visualize and grasp various wider determinants of people's health and healthcare performance and to improve health care and social systems.

Background: The possibility of developing a severe coronavirus infectious (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased, particularly in patients with hematological malignancies. These patients are more likely to produce less antibody protection due to the immunocompromised nature of the disease and the anticancer treatments. Therefore, the present systematic review intended to evaluate the seroconversion rate of COVID-19 vaccines in patients with hematological malignancies compared with healthy controls.

Methods: A comprehensive systematic search was conducted in Medline via PubMed, EMBASE, and the World Health Organization COVID-19 Research Database, as well as other searches (i.e., reference list from article search and manual searches), from December 2020 to May 2022. The outcome of interest included estimating the seroconversion rates following COVID-19 vaccination in patients with hematological malignancies and comparing them with those in healthy controls. After two-step screening, the data were extracted and the summary measures were calculated using a random-effects model.

Results: A total of 39 articles regarding patients with hematological malignancies were included in the present review. After the first vaccine dose, these patients had considerably lower antibody response rates (37.0%) compared with healthy controls (74.5%). Following the second vaccine dose, the seroconversion rate in patients reached 66.8%, whereas it peaked at 97.9% in the healthy controls following complete immunization. Notably, the BNT162b2 and ChAdOx1 vaccine combination achieved the highest seropositivity rate of approximately 70%. Multiple myeloma, chronic lymphocytic leukemia, and lymphoma were the cancers of interest in most of the studies.

Conclusions: The results of the present study highlighted the comparatively low seropositivity rates in patients with hematological malignancies, with substantial variations in rates across disease groups. The findings emphasize the possibility of additional booster doses for these individuals to enhance their immunity against SARS-CoV-2.

Adipose tissues, such as white, brown, and beige tissues, play pivotal roles in maintaining energy balance and metabolic health. Whereas white adipocytes store energy, brown and beige adipocytes exhibit high energy expenditure owing to their distinct mitochondrial density and UCP1 expression. Dysfunction in these tissues contributes to metabolic disorders such as type 2 diabetes and cardiovascular diseases. Adipose tissue expansion through cell enlargement or increased cell numbers caused by excess energy storage in white adipocytes substantially influences metabolic health. In obesity, hypertrophic adipocytes trigger inflammation, fibrosis, and hypoxia, whereas smaller adipocytes exert favorable metabolic effects, contributing to insulin sensitivity.

Brown and beige adipocytes consume energy for thermogenesis to maintain body temperature, contributing to metabolic homeostasis. The intricate interactions between brown adipose tissues and various organs, such as the liver and heart, highlight the systemic implications of adipose tissue functions. Understanding the complex underlying mechanisms may lead to the development of innovative therapies targeting metabolic disorders by modulating the functions of brown adipose tissue and its interactions with other physiological systems. In this review, we discuss insights into the mechanisms underlying the dysregulation of metabolism owing to abnormalities in adipose tissue remodeling. We focus on the endocrine functions of thermogenic brown and beige adipocytes and explore the interorgan interactions that influence whole-body metabolism.

Background: This study aimed to assess the conclusiveness of Cochrane Reviews (CRs) in oncology nursing.

Methods: We searched systematically for all CRs published in the Cochrane Library in the oncology nursing field between January 2014 and April 2023. We analyzed the difference between conclusive and inconclusive outcomes using the χ² and Mann-Whitney U-tests and identified 430 articles. However, we excluded 385 articles after reviewing their titles and abstracts. We assessed 45 full-text articles for eligibility and identified 32 articles. Of the 32 articles, we extracted 19 interventions.

Results: The overall outcomes were 182 cases, with 51.6% (n = 94) and 48.4% (n = 88) demonstrating conclusiveness and inconclusiveness, respectively. Regarding conclusiveness, 28.0% (n = 51) and 23.6% (n = 43) reported that the studied interventions were effective and ineffective, respectively. We found that studies on interventions related to physical activity and yoga had significantly high rates of conclusive. Compared with inconclusiveness outcomes, conclusive outcomes involved significantly more studies (p < 0.001) and patients (p < 0.001).

Conclusions: Ultimately, these findings reveal that in the oncology nursing field, only 51% of the main outcomes of each nursing intervention in CRs were conclusive.

The dynamics of neurite extension and synaptic connections are central issues in neural circuit research. The development of technologies for labeling purified cytoskeletal proteins with fluorescent dyes and introducing them into living neurons using microinjection greatly facilitated our understanding of cytoskeletal dynamics in neuronal axons. Imaging data showed that the cytoskeleton repeatedly polymerized and depolymerized within the axon, and elongation was driven by the new cytoskeleton formed at the axon tip. This finding significantly revised previously proposed models that explained slow axonal transport.

After the discovery of green fluorescent protein (GFP), its potential application to the live imaging of neurons was recognized in the 1990s, and a new method for visualizing synapses using GFP-tagged postsynaptic scaffolding molecules was established. This method revealed the continuous turnover of synapses during development, which overturned the established theory that synapses are highly stable once they are formed. Live imaging of synapses also demonstrated that the molecular composition of synapses changes rapidly, driven by the rapid replacement of synaptic molecules. Fluorescence measurement of single GFP molecules enabled estimation of the absolute number of postsynaptic molecules in a single synapse. Furthermore, in multiple mouse models of autism spectrum disorders (ASDs), enhanced synapse turnover was detected as a common circuit-level phenotype. This study provides solid experimental evidence that an increase in synapse dynamics underlies the pathophysiology in mouse models of ASDs.

The introduction of fluorescence imaging in neurobiology revealed that the neuronal cytoskeleton and synaptic structure are not static but dynamic cellular components. Imaging technology is expected to further advance our understanding of the dynamic properties of neurons and neural circuits.

Due to the difficulty of finding brain-dead donors, in October 1998, I performed the first living-donor lobar lung transplantation (LDLLT) for a ventilator-dependent 24-year-old female patient with bronchiectasis using lobes from her parents. The patient is still alive and in good health 25 years after the transplantation. Over time, the indications for LDLLT have expanded to include pulmonary hypertension, pulmonary fibrosis, congenital genetic diseases, pulmonary complications after stem cell transplantation, and, more recently, severe lung injury due to COVID-19 infection. In 2022, we successfully performed an ABO-incompatible LDLLT. To address size mismatches, we have developed new LDLLT techniques, such as right-to-left inverted transplantation, upper lobe-sparing transplantation, and segmental lung transplantation. Our published studies cover a range of topics, encompassing both basic and clinical research. Of particular significance is the observation that LDLLT offers immunological advantages over cadaveric lung transplantation (CLT). Having conducted 353 cases of lung transplantation, including 161 LDLLTs and 192 CLTs, our 5-year survival rates were 83% after LDLLT and 74% after CLT, surpassing the 55% 5-year survival rate reported by the International Society for Heart and Lung Transplantation. We have hosted numerous observers and research fellows from 15 countries. In addition, I have contributed to LDLLT procedures not only in Japan but also abroad. It brings me great satisfaction to think that my educational efforts may ultimately lead to saving the lives of those suffering from end-stage respiratory failure around the world.

With the prevalence of psychiatric disorders and the limitations of the diagnostic scheme and treatment options of these disorders, magnetic resonance imaging (MRI) studies play a significant role in uncovering the pathological basis of psychiatric disorders and potentially using biological markers in clinical settings. The use of MRI in clinical research has grown over the past three decades, and current MRI research continues to provide an avenue to guide the development of diagnostic approaches and therapeutic solutions. However, the current shortcomings of MRI studies derive not only from technical limitations (i.e., the range of contrasts that MRI probes or sensors can create) but also from confounding factors in the current methodological approaches of case-control studies for psychiatric disorders. Thus, by reviewing the recent literature on MRI research on psychiatric disorders, we explain the current progress and limitations of brain MRI methodologies used to study psychiatric disorders. We consider the growing use of cross-disorder methods to identify shared and disease-specific pathological features across psychiatric disorders. In addition, we need to outline healthy developmental and aging changes of the brain and investigate the disorder difference as a deviation of the trajectory. Although these methods have provided us with new insights, the demarcation between psychiatric disorders based on a definitive set of pathologies remains limited. This challenge of disease stratification is further complicated by the presence of multiple different sets of disorder pathologies within a single disorder and the different progressive timelines of different disorders. As such, we introduce the ongoing research projects in Japan, namely, the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) and the Strategic International Brain Science Research Promotion Program (Brain/MINDS Beyond). These collaborative research initiatives across Japan use neuroimaging and travel-subject harmonization to conduct nationwide MRI studies capable of providing large-scale coherent results, which may address the current limitations of MRI psychiatric disorder research.

Introduction: Even though an MEK inhibitor has been recently launched, neurofibroma still negatively affects the well-being of patients with neurofibromatosis type 1 (NF1). The coronavirus disease 2019 (COVID-19) pandemic resulted in restricted access to medical care. The present study was conducted to investigate the real-world settings of patients with NF1 who underwent surgery with or without restricted medical access during the COVID-19 pandemic.

Methods: Based on data obtained from medical records, the present study examined 123 and 260 patients who underwent surgery for neurofibromas with and without restricted medical access, respectively.

Results: The mean numbers of surgeries performed during the periods with and without restricted medical access were 5.8 and 9.8 per month, respectively, and there were 1.18- and 1.46-fold more female patients than male patients for each group, respectively. Regardless of whether medical access was restricted, the majority of patients who underwent surgery were middle-aged females with multiple or severe neurofibromas and mild extracutaneous symptoms. Tumor burden was the most common reason for surgery. However, cutaneous neurofibromas were more likely to be treated than plexiform neurofibromas under restricted medical access.

Conclusions: Patients with NF1, particularly middle-aged females with severe cutaneous manifestations and mild extracutaneous manifestations, still underwent surgery for neurofibromas regardless of whether medical access was restricted.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic may have led to an increase in home deaths due to hospital bed shortage and hospital visitation restrictions. This study aimed to examine changes in the proportion of home deaths before and after the COVID-19 pandemic and identify associated factors.

Methods: We used publicly available nationwide data to describe the proportion of home deaths among total deaths from 2015 to 2021. Furthermore, we used municipal-level data to examine the factors associated with the increase in the proportion of home deaths from 2019 to 2021. The dependent variable was the absolute change in the proportion of home deaths from 2019 to 2021. The independent variables included each municipality's 2019 home death percentage, medical and long-term care (LTC) resources divided by the population of older people, population density, and cumulative number of COVID-19 cases. A multivariable linear regression analysis was conducted after the standardization of each variable.

Results: The proportions of home deaths in 2015, 2019, and 2021 were 12.7%, 13.6%, and 17.2%, respectively, indicating a sharp increase in home death rate after the COVID-19 pandemic. In the multivariable linear regression analysis that included 1,696 municipalities, conventional home care support clinics and hospitals (HCSCs) (coefficient [95% confidence intervals (CIs) ], 0.19 [0.01-0.37]), enhanced HCSCs (0.53 [0.34-0.71]), home-visiting nurses (0.26 [0.06-0.46]), population density (0.44 [0.21-0.67]), and cumulative COVID-19 cases (0.49 [0.27-0.70]) were positively associated with the increase in home deaths, whereas beds of LTC welfare facilities (−0.55 [−0.74-−0.37]) and the proportion of home deaths in 2019 (−1.24 [−1.44-−1.05]) were negatively associated with the increase.

Conclusions: During the COVID-19 pandemic, home deaths significantly increased, particularly in densely populated areas with high cumulative COVID-19 cases. HCSCs, especially enhanced HCSCs, are crucial for meeting the demand for home-based end-of-life care.

Introduction: The clinical benefit of hemostasis molecular indicators such as thrombin-antithrombin complex (TAT), soluble fibrin (SF), and prothrombin fragment 1 + 2 (F1+2) for the diagnosis of disseminated intravascular coagulation (DIC) is reported. Recently, novel DIC diagnostic criteria that adopt them were proposed in Japan. Despite the theoretical understanding of their function, the practical use of these markers remains unclear. The present study aimed to provide a descriptive overview of current clinical practice regarding the measurement of hemostasis markers in sepsis management in Japan.

Methods: This retrospective observational analysis used the Japanese Diagnosis Procedure Combination inpatient database containing data from more than 1500 acute-care hospitals in Japan. We identified adult patients hospitalized for sepsis between April 2018 and March 2021. Descriptive statistics for measuring several hemostasis laboratory markers were summarized using patient disease characteristics, hospital characteristic, and geographical location.

Results: This study included 153,474 adult sepsis patients. Crude in-hospital mortality was 30.0%. Frequency of measurement of fibrinogen, fibrin degradation products (FDP), and D-dimer in sepsis patients on admission was 43.2%, 36.1%, and 46.4%, respectively. Novel and specific hemostasis molecular markers such as TAT, SF, and F1+2 were seldom measured (1.9%, 1.7%, and 0.02%, respectively). Hemostasis molecular markers were more frequently measured with progression of thrombocytopenia. Measurement of these clinically favorite hemostasis markers was influenced not only by disease characteristics but also hospital characteristic or geographical location.

Conclusions: Hemostasis molecular markers such as TAT, SF, and F1+2 were rarely measured in clinical settings. Although adopted by several DIC scoring systems, neither fibrinogen, FDP, nor D-dimer was routinely measured.

Introduction: Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC.

Methods: In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver.

Results: The patients were divided into two grades (high donor LISI, >−1.23 [n = 43]; and low donor LISI, ≤−1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02).

Conclusions: This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies.

Introduction: Health literacy (HL) is a crucial indicator for health promotion and diabetes care improvement, but the available measurements are mostly in English. This study aimed to translate and validate the 14-item Health Literacy Scale (HLS-14) questionnaire from English to Vietnamese for patients with diabetes in Vietnam.

Methods: We translated HLS-14 into Vietnamese in accordance with the World Health Organization guidelines and conducted a cross-sectional survey among 571 outpatients with type 2 diabetes using the HLS-14 Vietnamese version (HLS-14 VN). The reliability and validity of the tool were assessed using Cronbach's alpha, composite reliability (CR), average variance extracted (AVE), and maximum shared variance (MSV), and confirmatory analysis was conducted.

Results: Cronbach's alpha coefficients for the three subscales as in the original version were 0.931, 0.810, and 0.928 for functional HL, communicative HL, and critical HL, respectively. However, AVE for critical HL was 0.488, which improved to 0.516 after the removal of one item in the communicative HL. For all subscales in the revised 13-item version (HLS-13 VN), CR was above 0.8, AVE was above 0.5, and MSV was less than AVE. Confirmatory analysis of HLS-13 VN revealed an acceptable fit with comparative fit index of 0.983, goodness-of-fit index of 0.963, and root mean squared error of approximation of 0.058.

Conclusions: The reliability and validity of HLS-13 VN were confirmed. The tool is suitable for use in clinical settings in Vietnam to assess multidimensional HL in patients with type 2 diabetes.

Introduction: Thyroglobulin (Tg) is a very sensitive and specific marker in patients who have undergone total thyroidectomy for papillary thyroid carcinoma (PTC). However, the presence of a Tg antibody (TgAb) interferes with Tg immunometric assays, making Tg levels unreliable indicators. There are currently no other tumor markers to monitor in patients with PTC whose serum is TgAb-positive. Thus, we investigated whether carbohydrate antigen 19-9 (CA19-9) can be used as a tumor marker for PTC.

Methods: We retrospectively analyzed 196 consecutive patients with PTC (maximum diameter ≥ 2 cm). The serum CA19-9 and Tg values of each patient were obtained before and 0.5-1 month postsurgery. Immunohistochemical staining for PTC was performed using an antibody against CA19-9.

Results: High pre-surgery serum levels of CA19-9 were observed in 6.1% of the patients. Postsurgery, serum CA19-9 levels in all 196 patients decreased considerably and were within the normal range. CA19-9 expression was detected in 28 of 62 PTCs (45.2%) and was detected at various degrees and ranges in conventional PTC histology.

Conclusions: Although further studies with longer follow-ups are necessary, serum CA19-9 levels may serve as a surrogate tumor marker for PTC in place of serum Tg levels sin some patients.

Introduction: In Japan, insurance began covering two cancer gene panel tests in 2019. However, the availability of these tests remains limited to 247 facilities (as of October 2023). This survey-based study assessed the knowledge and recognition of cancer genomic medicine by physicians involved in cancer treatment.

Methods: Written requests for participation in a web-based questionnaire survey were sent to 14,579 affiliated general clinical oncologists certified by the Japanese Board of Cancer Therapy. The survey was conducted from July 1 to 31st, 2021. Data between physicians affiliated with cancer genome hospitals and noncancer genome hospitals and between regions of Japan were compared.

Results: In total, 2,402 valid responses were analyzed. Of the respondents, 1,296 and 1,106 were physicians working at cancer and noncancer genome hospitals, respectively. Physicians working at cancer genome hospitals showed significantly higher results for both knowledge of cancer genomic medicine and experience in cancer gene panel test performance compared with those working at noncancer genome hospitals. There were no significant regional differences in the percentage of physicians who reported having performed cancer gene panel tests.

Conclusions: The survey results suggest a disparity in the knowledge of cancer genomic medicine between physicians working at cancer genome hospitals and those working at noncancer genome hospitals; this disparity should be addressed by stakeholders. Closer collaboration between these facilities may be necessary to achieve national dissemination of cancer genomic medicine.

Introduction: We examined the risk factors for fourth-degree perineal lacerations (intrapartum anorectal mucosal lacerations) and rectovaginal fistulas as one of the later complications.

Methods: We reviewed the obstetric records of all singleton vaginal deliveries after 22 weeks of gestation at our institute between January 2006 and December 2018 (n = 19,370).

Results: Of the 19,370 deliveries, 61 had fourth-degree perineal lacerations (0.31%). Of the 61 women, 5 (8.2%) developed rectovaginal fistulas 2-3 weeks after their deliveries. Upon multivariate analysis, nulliparity (Adjusted odds ratios (OR) 3.58, 95% confidence interval (CI) 1.6-8.1, p < 0.01), midline episiotomy (Adjusted OR 2.10, 95% CI 1.0-4.2, p = 0.03), vacuum extraction (Adjusted OR 7.01, 95% CI 3.5-14, p < 0.01), and forceps delivery (Adjusted OR 22.0, 95% CI 7.8-61, p < 0.01) were independently associated with fourth-degree perineal lacerations, while mediolateral episiotomy (Adjusted OR infinity, 95% CI 2.1-infinity, p = 0.03) and forceps delivery (Adjusted OR infinity, 95% CI 14.5-infinity, p = 0.01) were independently associated with rectovaginal fistulas. In addition, in the women with fourth-degree perineal lacerations, mediolateral episiotomy was associated with rectovaginal fistulas (OR infinity, 95% CI 1.8-infinity, p = 0.04).

Conclusions: Midline episiotomy and instrument-assisted delivery are independent risk factors for fourth-degree perineal lacerations after vaginal delivery. Mediolateral episiotomy and forceps delivery were independently associated with rectovaginal fistulas. Once fourth-degree perineal lacerations occurred, women with mediolateral episiotomies were more likely to develop rectovaginal fistulas.

Clinical doctors with overwhelming workloads at university or center hospitals may not have sufficient time to allocate for each patient or to consider each patient's personal condition. Retirement may be a good chance to make a new start by becoming a clinical doctor in a smaller institute. Becoming a clinical doctor in a smaller institute may give you satisfaction and happiness different from being a university clinical doctor. I believe that after retirement from a university or big hospital, older clinical doctors should continue to participate in clinical practice for as long as they wish. This may be one of the solutions for providing clinical doctors in the current and coming super-aged Japan.

A manuscript written not adhering to the fundamentals of academic writing (so-called paper-writing rules) may be rejected before the significance of the study is recognized. Submitting authors, especially those with little experience, may neglect such fundamentals. A simple checklist, which would enable the authors to check whether a manuscript for submission adheres to such fundamentals, should appear at the beginning of the Author Guidelines of medical journal. This checklist may contribute to writing a manuscript following the fundamentals of academic writing, thereby preventing rejection based solely on the writing style.

Galantamine is a cholinesterase inhibitor employed in Alzheimer's disease management. Cholinesterase inhibitors are associated with potential cholinergic side effects that, when severe, can result in cholinergic crises. Although crises induced by other cholinesterase inhibitors, such as distigmine and rivastigmine, have been reported, cases of galantamine-induced cholinergic crises remain undocumented. This study presents a case of cholinergic crisis triggered by galantamine overdose in an 89-year-old woman weighing 37 kg with Alzheimer's disease history, even though her serum cholinesterase levels were normal. The patient overdosed on 264 mg of galantamine, leading to rapid deterioration, marked by restlessness, tremors, sweating, diarrhea, pharyngeal gurgling, and severe hypoxia. Upon arrival at the emergency department, the patient exhibited pinpoint pupils, compromised airway, and low oxygen saturation, necessitating immediate intubation and transfer to the intensive care unit. After 72 h, the patient successfully recovered and was weaned off mechanical ventilation, maintaining normal serum cholinesterase levels. Animal studies suggest a lethal galantamine threshold of 3 to 6 mg/kg in humans. Unlike other cholinesterase inhibitors that typically reduce serum cholinesterase levels during cholinergic crises, galantamine appears to selectively inhibit acetylcholinesterase, possibly sparing butyrylcholinesterase. This selectivity may explain the normal serum cholinesterase levels.