After I graduated from Juntendo University in 1985, I joined the Department of Collagen Disease and was assigned to the Hematology Group. At that time, bone marrow transplantation was being developed as a groundbreaking treatment. Juntendo hospitals were also conducting bone marrow transplantation. Vitamin D₃ inhibits clonal growth of myeloid leukemia, another cancer, and this finding needs further study in animals before clinical trials can be considered. Loss of a whole chromosome 7 (-7), or the long arm of chromosome 7 del (7q) occurs frequently in myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). We identified the smallest commonly deleted regions to as 7q31.1 (D7S486) and 7q33-34 (D7S498, D7S505), suggesting that alterations of a tumor suppressor genes in each region play an important role in de novo AML. We found that the ratio of CD4⁺ to CD8⁺ T cells (CD4/CD8 ratio) was decreased in patients with multiple myeloma (MM). The serum level of interleukin-16 (IL-16) was significantly higher in stage III patients, which is produced by activated CD8⁺ T cell and can induce CD4⁺ T cell activation.

I would like to express my deep gratitude to CEO Hideoki Ogawa and the many other people at Juntendo University for giving me the opportunity to work at a university that is experiencing such incredible growth.

Throughout my research career, I have focused on understanding the extracellular matrix (ECM) and its roles in disease pathogenesis and the aging process. My initial interest in muscular dystrophies gradually expanded to include various organs and systems, including the kidneys, brain, cartilage, skin, and eyes. During my tenure at the National Institutes of Health (NIH), I made substantial contributions to generating and analyzing conditional knockout mouse models for key ECM molecules, including laminin α1 and perlecan. These studies elucidated the roles of ECM components in hereditary diseases, embryonic development, and the functionality of the neuromuscular junction. Upon returning to Japan, I transitioned this foundational expertise into translational research across multiple fields, benefiting from a collaborative environment that bridges basic and clinical sciences. My recent work examines the impact of glycosylation on ECM remodeling. Reflecting on this scientific journey, I emphasize the importance of ECM as a structural component and as a dynamic regulator of cellular behavior. As I retire from active academic life, I aspire to support the next generation of scientists in exploring the extracellular space, an area rich with potential therapeutic opportunities.

After graduating from Juntendo University in 1984, I joined the First Department of Surgery at Juntendo University in 1986 after two years of surgical training. When I started my career as a gastrointestinal surgeon, the only surgical treatment approach was the “open abdominal method”, which involves making a large incision in the abdomen. At that time, I did not anticipate the development of new techniques. In the late 1980s, “laparoscopic surgery” using a laparoscope and endoscopic forceps with a small wound through a port was introduced. At our hospital, laparoscopic surgery for cholelithiasis and colorectal cancer was introduced in 1991 and 1993, respectively. Laparoscopic cholecystectomy has rapidly become popular worldwide and has become the gold standard surgical procedure in Japan. With improvements in laparoscopic surgical techniques, laparoscopic surgery for colorectal cancer has evolved into a less invasive technique (reduced port surgery) and more complicated procedure.

While one would think there would be no further procedural changes in surgical treatment, another wave emerged, that of robotic surgery. A surgically assisted robotic system was approved by the Food and Drug Administration (FDA) in 2001. In Japan, the use of this system was covered by government insurance in 2012 for prostatectomy. Robotic surgery for prostatectomies was initiated at our hospital in 2013. The use of robotic surgery for colorectal cancer surgery was initiated as a clinical trial in 2015. It was covered by government insurance in 2018, and by Mar. 2025, we had performed approximately 270 robotic surgeries. It has been a great asset and very valuable experience for me to be involved in the launch of two minimally invasive surgical techniques, “laparoscopic surgery” and “robotic surgery,” during my 41 years of practice as a surgeon in Juntendo, from the time when only “open surgery” was available.

Teleconsultation in Japan was initially introduced as a doctor-to-doctor or dentist-to-dentist (D-to-D) service, restricted to non-emergency, follow-up consultations for patients already under medical care and in stable condition. Following the onset of COVID-19 in February 2020 and the resulting restrictions on international travel, demand increased not only for first-time doctor-to-patient (D-to-P) consultations within Japan but also for cross-border teleconsultations. This study aimed to examine the regulatory evolution and implementation challenges of cross-border teleconsultation in Japan. While cross-border teleconsultation offers accessible and convenient care for international patients, broader implementation remains limited due to challenges such as inadequate international patient support systems and the absence of consistent international legal frameworks. The findings highlight the need to develop standardized international telemedicine frameworks and to establish robust communication channels among governments.

Artificial intelligence (AI) is rapidly transforming internal medicine by enhancing diagnostic accuracy, enabling personalized treatment, and optimizing patient management. As of August 2024, the U.S. Food and Drug Administration has authorized nearly 950 AI/ML-enabled medical devices, while an American Medical Association survey reported that 66% of physicians already incorporate AI into clinical practice. This review provides a comprehensive overview of AI’s expanding role across internal medicine, highlighting its applications in medical interviews, text-based communication, and the interpretation of core diagnostic modalities such as electrocardiography, chest X-ray, and auscultation. While several FDA-approved AI tools are already integrated into clinical workflows, many technologies remain at the research or proof-of-concept stage, with validation often limited to retrospective or controlled trial settings.

The transformative potential of AI is particularly relevant in urban healthcare, where population density, limited resources, and disproportionate burdens of chronic and lifestyle-related diseases underscore the need for innovative solutions. AI can mitigate physician shortages, streamline care in overburdened systems, and support equitable access to diagnostics and treatment in metropolitan areas. Key technologies, including machine learning, deep learning, and large language models, are critically examined, along with emerging innovations such as EHR-based foundation models.

Despite its promise, AI integration raises ethical, legal, social, and regulatory challenges, including algorithmic bias, data privacy, validation standards, and workforce adaptation. This paper explores these multifaceted aspects, emphasizing the importance of collaborative efforts to ensure responsible and equitable implementation, ultimately aiming to improve patient outcomes and public health in the digital era.

Heat-related illness (HRI) represents a growing public health challenge in the context of global warming. Ranging from mild symptoms such as heat cramps to life-threatening heatstroke, HRI requires prompt recognition and appropriate management to reduce morbidity and mortality. The diagnosis of HRI is primarily based on clinical symptoms but is supported by laboratory evaluation, especially in severe cases. Heatstroke, the most critical form, is defined by core body temperature ≥ 40°C and central nervous system dysfunction. In addition to conventional laboratory markers, recent advances in molecular biology have identified several biomarkers, such as heat shock proteins, HMGB1 (High Mobility Group Box 1), and mitochondrial DNA, which may improve early and accurate detection and prognostication. This review summarizes the diagnostic approach to HRI, highlighting key clinical findings, laboratory assessments, and emerging molecular markers.

Despite significant advances in antimicrobial therapy and supportive intensive care, mortality in septic shock remains unacceptably high. Hemoadsorption therapies have emerged as adjunctive strategies designed to remove circulating mediators that propagate the dysregulated host response. Among these, polymyxin B hemoperfusion (PMX-HP) represents the most extensively studied extracorporeal modality, specifically targeting circulating endotoxin. Over three decades of investigation have produced a complex body of evidence, ranging from early promising results in small, open-label studies to large randomized trials with inconsistent outcomes. Recent findings from the TIGRIS trial, employing Bayesian design and biomarker-guided patient selection, provide compelling support for a survival benefit in a well-defined subgroup of septic shock patients with intermediate endotoxin activity. This review synthesizes the evolution of PMX-HP research, from EUPHAS through EUPHRATES and TIGRIS, highlighting lessons learned in trial design, biomarker utilization, and patient stratification. These experiences underscore the potential of precision-based extracorporeal interventions in sepsis while outlining the critical methodological and regulatory challenges that remain.

Cognitive impairments tend to persist among survivors of sepsis long after discharge, and may involve memory, attention, and executive function. These deficits are driven by chronic sequelae of neuroinflammation, blood-brain barrier breakdown, and an extended period of delirium in critical illness. Although post-intensive care syndrome is increasingly acknowledged, cognitive recovery is not systematically assessed during follow-up. This Perspective emphasises the crucial importance of early recognition of cognitive impairment, the use of multidisciplinary rehabilitation, and the incorporation of screening for cognitive dysfunction in post-ICU care to ensure that sepsis care becomes concerned not only with survival but also with the restoration of neurocognitive well-being.

Objectives To measure neurocognitive abilities, psychological well-being, and quality of life (QOL) in survivors of adult sepsis post-intensive care unit (ICU) discharge in Pakistan and to establish clinical and demographic predictors of post-ICU outcomes.

Design A cross-sectional study at tertiary care hospitals in Islamabad, Pakistan.

Methods Structured questionnaires were used to evaluate 500 adult survivors of sepsis, 4-8 weeks after ICU discharge. Mini-Mental State Examination (MMSE) was used to measure cognitive functioning, Hospital Anxiety and Depression Scale (HADS) to measure psychological symptoms, and the Short Form-36 (SF-36) to measure QOL. Hospital records provided demographic and clinical information. Statistical procedures involved chi-square tests, Mann-Whitney U tests, Kruskal-Wallis tests, Spearman correlations, and multiple regression tests.

Results Among 500 participants, 284 (57%) were cognitively impaired (MMSE < 24), 300 (60%) reported borderline-to-clinical anxiety, and 250 (50%) were depressed. The QOL was low, with the mean SF-36 score being 35/100 (SD ± 12). The longer the ICU stay, the poorer the cognition, the more anxiety, and the lower the quality of life (p < 0.001). Poorer outcomes were also predicted by older age (> 60 years, n = 150; 30%) and female sex (n = 180; 36%).

Conclusion In Pakistan, cognitive impairment, psychological distress, and poor quality of life among sepsis survivors are high within weeks of ICU discharge. Longer ICU stay, comorbidities, female sex, and older age predict poorer outcomes. Early follow-up and organised rehabilitation measures are acutely required to enhance survivorship.

Objectives To assess the effect of unilateral and bilateral hand movements on interhemispheric inhibition (IHI), which was assessed with transcranial magnetic stimulation and compared between healthy volunteers and patients with stroke.

Methods Eleven patients with chronic hemiparetic stroke performed paretic and bilateral hand tasks, and six healthy volunteers performed right-hand and bilateral hand tasks. IHI between the hemispheres was assessed using transcranial magnetic stimulation before and 0, 10, and 30 min after both tasks.

Results IHI from contralesional to ipsilesional motor cortex (M1) after the bilateral hand task was disinhibited more strongly and for a longer time than that after the paretic hand task in stroke patients. IHI from ipsilesional to contralesional M1 in stroke patients was significantly disinhibited with the bilateral hand task and inhibited with the paretic hand task 10 min after the tasks. Task and time had no significant effects on IHI in both tasks in healthy volunteers.

Conclusions Inter-hemispheric inhibitory interneurons were modified differently by unilateral and bilateral hand movements. Bilateral hand movement might have a stronger effect on IHI than paretic hand movement.

Background Pandemics and natural disasters have historically disrupted research ecosystems worldwide. In India, for example, the COVID-19 epidemic, the 2004 Indian Ocean tsunami, and the 1918 influenza pandemic have not only impacted education systems but also research-related activities. Early-career scholars were disproportionately affected by the severe disruptions to research activity induced by the COVID-19 Pandemic.

Aim To determine and examine the difficulties PhD research scholars encountered in India during the COVID-19 Pandemic and to understand coping mechanisms used to minimise uncertainties.

Methods Among full-time PhD scholars at a tertiary healthcare institution in India, we conducted a sequential explanatory mixed-methods study. A pre-validated online questionnaire was used to gather quantitative data, and focus group discussions (FGDs) were held to examine problems and potential solutions further. Descriptive statistics, thematic analysis, and triangulation of questionnaire and FGD results were used to examine the data.

Results 16 scholars participated in FGDs, and 41 scholars completed the questionnaire. Administrative barriers, logistical obstacles, time limits from pandemic-related tasks, participant recruitment issues, infrastructure closures, and missed opportunities for collaboration were the six thematic domains of difficulty that surfaced. Five types of coping techniques were identified: emotion-focused, meaning-focused, problem-focused, problem-avoidance, and social-focused coping. Adaptive measures, such as local material sourcing, skill development through online platforms, and alternative data collection, were used by scholars.

Conclusion Natural calamities and pandemics have a systemic impact on research, particularly for early-career researchers. Flexible deadlines, emergency funding, streamlined teamwork, and crisis-adaptive ethics review procedures were among the few recommendations.

Objectives Problematic smartphone use (PSU) is widespread among medical students and might be associated with visual, musculoskeletal, and neurological complaints. In this study, we investigated the relationship between PSU and oculomotor strain, cervical disability, and the impact of headaches.

Materials and Methods The present study was conducted through a cross-sectional survey among 498 medical students in Lahore, Pakistan. PSU was assessed using the Smartphone Addiction Scale-Short Version (SAS-SV), oculomotor strain with the Computer Vision Syndrome Questionnaire (CVS-Q), cervical disability with the Neck Disability Index (NDI), and headache impact using the HIT-6. Data were assessed using Pearson's correlations, t-test, ANOVA, and multivariate regression in SPSS v.26.

Results The average SAS-SV score was 32.1 ± 4.9. PSU was associated with CVS (r = 0.229), NDI (r = 0.147), and HIT-6 (r =  0.088). Scores for all measures were higher among female students (p < 0.001). The youngest students presented with higher PSU; the CVS was more intense in 21-23 years of age, and older students had a greater cervical disability. Predictors of CVS, cervical disability, and headache impact were PSU, gender (female), younger age, low physical activity status, and comorbidities according to the regression models.

Conclusion PSU is associated with increased oculomotor strain, neck disability, and headache burden in medical students, especially for females, younger-aged students, and those having low activity or comorbidities. Preventive strategies that promote digital well-being and healthy behaviours are advised.

Introduction Laparoscopic proximal gastrectomy (LPG) with esophagogastrostomy (EG) and double-tract reconstruction (DTR) for early gastric cancer of the upper stomach is a function-preserving surgery that retains oncological curative capability. However, direct comprehensive comparative analyses on the clinical outcomes of EG and DTR as reconstructive techniques following LPG are lacking. Therefore, this study investigated the short- and long-term clinical outcomes of EG and DTR following LPG.

Materials and Methods A retrospective comparative analysis was conducted based on a dataset compiled from two institutions. LPG cases for gastric cancer meeting eligibility criteria were divided into an EG group and a DTR group, and clinicopathological characteristics, perioperative outcomes, nutritional status, 3-year overall survival (OS), and cancer-specific survival (CSS) were analyzed. Furthermore, univariate and multivariate analyses were performed to identify risk factors for complications following LPG.

Result Among the 1198 patients, 104 received LPG, of whom 49 underwent EG and 41 underwent DTR. The DTR was significantly more frequently selected in patients with advanced cancer, while no significant differences were found in the other preoperative clinical factors. No significant differences were observed in perioperative outcomes, including postoperative complications, nutritional parameters, 3-year OS, and CSS. Multivariate analysis identified cardiac disease as a risk factor for postoperative complications following LPG.

Conclusion Short- and long-term clinical outcomes following LPG are equivalent between EG and DTR. For gastric cancer patients with cardiac disease undergoing LPG, careful attention is required for perioperative management.