KEIO JOURNAL OF MEDICINE最新文献

Inflammatory bowel diseases (IBD) are currently recognized to involve chronic intestinal inflammation in genetically susceptible individuals. Patients with IBD mainly develop gastrointestinal inflammation, but it is sometimes accompanied by extraintestinal manifestations such as arthritis, erythema nodosum, episcleritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis. These clinical aspects imply the importance of interorgan networks in IBD. In the gastrointestinal tract, immune cells are influenced by multiple local environmental factors including microbiota, dietary environment, and intercellular networks, which further alter molecular networks in immune cells. Therefore, deciphering networks at interorgan, intercellular, and intracellular levels should help to obtain a comprehensive understanding of IBD. This review focuses on the intestinal immune system, which governs the physiological and pathological functions of the digestive system in harmony with the other organs.

Patients with tracheostomy who undergo a full sternotomy have an increased risk of mediastinitis and sternal infection. This report describes a reoperative aortic valve replacement (re-AVR) for structural valve deterioration (SVD) through a lower hemisternotomy. This procedure was performed on a 71-year-old man with a tracheostomy who had previously undergone a Bentall procedure with a bioprosthetic valve to replace an enlarged ascending aortic aneurysm. Comorbidities included chronic renal failure requiring hemodialysis. Fourteen months after the Bentall procedure, the patient presented with sudden dyspnea and was transferred to another hospital. Upon suffering acute heart failure, the patient required mechanical ventilation and was transferred to our hospital for intubation. The patient subsequently developed severe pneumonia. As a result of prolonged ventilation, the patient underwent tracheostomy and was administered antibiotic medication (piperacillin/tazobactam) for pneumonia. Echocardiography revealed severe aortic regurgitation caused by SVD. There was a risk that a full sternotomy in a patient with tracheostomy could cause mediastinitis; therefore, we performed a re-AVR through a lower hemisternotomy (second T incision). The re-AVR surgery proceeded without complications, and the bioprosthetic valve was removed while preserving the vascular graft from the previous Bentall procedure. The postoperative course was uneventful, and the patient was discharged from hospital 31 days after the tracheostomy was closed. The success of this procedure demonstrates the viability of re-AVR through a lower hemisternotomy in patients with SVD who are at risk of additional surgical complications.

Food protein-induced enterocolitis syndrome (FPIES) is a type of non-IgE-mediated gastrointestinal food allergy. FPIES is characterized by repetitive vomiting without classic IgE-mediated allergic skin or respiratory symptoms 1-4 h after causative food ingestion. The condition may be classified as acute or chronic, typical or atypical, and liquid or solid according to the course of symptoms, presence of IgE antibodies, and causative food, respectively. Since the development of international consensus guidelines in 2017, epidemiological studies have been conducted in many countries. FPIES is a relatively rare disease, with a prevalence of 0.015%-0.7%. However, the number of patients has been increasing in recent years. Most patients develop the disease in infancy. The natural history of FPIES is generally favorable, with most FPIES cases resolving before school age. FPIES is diagnosed using symptoms such as vomiting or diarrhea, or via an oral food challenge (OFC). Currently, no validated biomarker is available for diagnosis, and the mechanisms related to gastrointestinal manifestations and immune system involved in the development of FPIES have not yet been elucidated. Treatment with intravenous fluids and ondansetron is recommended in the acute phase. Long-term management consists of complete causative food elimination and periodic OFC to confirm tolerance. Given that many diagnoses are delayed because of a lack of awareness of the condition, FPIES must be widely recognized by healthcare providers. In the future, it is expected that FPIES pathogenesis will be further clarified, and more objective diagnostic criteria will be developed.

This study investigated lifestyle changes and the self-reported mental health status of Japanese community residents during the COVID-19 pandemic. Differences in demography, daily lifestyle changes, and approaches to problem solving were analyzed in two age cohorts (<60 vs ≥60 years). The prevalence of moderate/increased psychological distress was 31.7%, with no significant difference between the cohorts. Compared with the pre-COVID-19 era, more than 80% of the participants stopped eating out and spent more time at home, and more than 70% used public transport less frequently. There were significant differences between the cohorts for the time spent at home, opportunities to eat meals outside of home, and shopping in stores. Participants aged under 60 years were less likely to use television and newspapers or to consult a family doctor. Those aged over 60 years were less likely to consult friends/colleagues or to use the Internet/social networking services. Identifying the risk factors for psychological distress is warranted for implementing measures to maintain and improve the physical and mental health of residents.

Emerging infections are caused when microorganisms that are maintained in a reservoir where they cause no harm, transmit from the reservoir to a new host. I have been studying the replication, molecular basis for pathogenesis, and host responses to emerging viruses, including influenza virus, Ebola virus, and SARS-CoV-2, and using the knowledge gained from these studies to develop antivirals and vaccines.Influenza viruses cause epidemics every winter, but occasionally new influenza viruses emerge and spread worldwide (pandemic). We established a technique that allows us to make influenza viruses artificially. This technique is now widely used for basic research and for the development of vaccines against highly pathogenic avian influenza virus for pandemic preparedness and live attenuated influenza vaccines. Using this technique, we elucidated the mechanisms of emergence of pandemic viruses, viral replication, and the molecular mechanism of pathogenesis.Ebola virus causes severe disease with a mortality rate of up to 90%. In 2013, a major outbreak of Ebola virus began in West Africa that led to nearly 30,000 people being infected and a death toll of over 10,000 people. During the outbreak, we established a laboratory in Sierra Leone and used samples from Ebola patients to study host responses and identify biomarkers for severe infection. We also established a technology to artificially make Ebola virus and used this technology to make an Ebola virus that grows only in a particular cell line. Using this virus, we produced an inactivated Ebola vaccine, which was shown to be safe and effective in a Phase I clinical trial.Late in 2019, SARS-CoV-2 emerged in Wuhan, China and has since caused unprecedented damage globally. In our laboratory, we established an animal model for this infection and have used it to evaluate pathogenicity, efficacy of therapeutic monoclonal antibodies and antivirals, and to develop vaccines.In my presentation, I will discuss our findings regarding these emerging viral infections.

Virtual reality (VR) is emerging as a groundbreaking tool in the treatment of congenital heart diseases. This innovative technology offers a transformative approach by creating immersive, interactive, and personalized environments for both patients and healthcare professionals. In the pediatric cardiology institute in Safra Children's hospital in Sheba Medical Center in Israel, VR is being utilized for patient education, pre-operative planning, and intraoperative guidance. Patients can explore 3D visualizations of their own hearts, gaining a better understanding of their condition and proposed treatments. Surgeons and medical teams benefit from VR simulations that enhance their surgical planning and decision-making processes observing complex cases and evaluating printed models. Furthermore, Augmented reality AR can be employed in the operating room for observing the rib cage and reviewing the patient anatomy. The 3D visualization program is led by the Engineering in Medicine (EiM) tech-lab which cooperates with different specialties in the hospital including plastic surgery, ENT, ObGyn and more. The most critical topic addressed by the lab, cooperating with engineers from the Israeli Institute of technology deals with registration of the holographic image on the real patient body allowing intra-operative guidance. (Presented at the 2008th Meeting, September 27, 2023).

Patients with spinal deformities, both adolescents and adults, often experience pulmonary symptoms such as shortness of breath during physical exertion and reduced exercise tolerance. These symptoms significantly affect their daily functioning, and recent research by Van Kempen et al. (2022) involving 8,723 AIS patients found that declines in pulmonary function tests (PFTs) were linked to the severity of their spinal deformities.However, these clinically relevant pulmonary symptoms are not routinely monitored, which could have health implications as patients age, given the gradual deterioration of pulmonary function associated with the severity of their spinal deformities. PFTs have been used to quantify these symptoms, but a discrepancy exists between these objective measurements and the subjective experiences of patients, reducing their clinical value. To address this gap, patient-reported outcome measures (PROMs) capturing the patient's perspective are needed but are currently lacking.The presentation outlines ongoing efforts to rectify this situation, with a focus on measuring pulmonary function and exercise tolerance through structured patient interviews, the use of smart vests with sensors, and the development of a patient-reported outcome measure (PROM). These endeavors aim to improve the monitoring and management of pulmonary symptoms in spinal deformity patients, ultimately enhancing their quality of life and long-term health. (Presented at the 2009st Meeting, November 8, 2023).

The quest to cure cancer has been one of the Holy Grails of medicine. The discovery I am going to share with you, CAR T cells, is a promising new form of therapy of cancer that offers the prospect of curing cancer using the immune system. CAR T cells are the first form of synthetic biology to enter the practice of medicine. The notion of using the immune system to fight cancer is an old idea. Over a century ago, bacteria were ground up and injected into patients with late-stage cancers, and occasionally the cancer would disappear. However, we now have precise tools for genetic editing and gene insertion like CRISPR/Cas9 to rewrite the DNA code, offering the possibility to improve the immune system over what has evolved in a Darwinian fashion. In 2017 for the first time, CAR T cells were approved for the treatment of cancer. Today they are used worldwide in more than 15,000 patients and they offer the promise to move beyond cancer to other fields of medicine such as autoimmune disease and heart disease. Here I will discuss the promises and challenges faced by the evolving CAR T cell industry.

Our understanding of the biology of the intestinal epithelium has advanced since the establishment of an organoid culture system. Although organoids have enabled investigation of the mechanism of self-renewal of human intestinal stem cells in vitro, it remains difficult to clarify the behavior of human normal and diseased intestinal epithelium in vivo. Recently, we developed a xenotransplantation system in which human intestinal organoids are engrafted onto epithelium-depleted mouse colons. This xenograft recapitulated the original tissue structures. Upon xenotransplantation, normal colon organoids developed normal colon crypt structures without tumorigenesis, whereas tumor-derived organoids formed colonic tumors resembling the original tumors. The non-tumorigenicity of human intestinal organoids highlights the safety of organoid-based regenerative medicine. As an example of regenerative medicine for short bowel syndrome, we devised a unique organ-repurposing approach to convert colons into small intestines by organoid transplantation. In this approach, the transplanted rat small intestinal organoids not only engrafted onto the rat colons but also remodeled the colon subepithelial structures into a small intestine-like conformation. Luminal flow accelerated the maturation of villi in the small intestine, which promoted the formation of a lymphovascular network mimicking lacteals. In this review, we provide an overview of recent advances in gastrointestinal organoid transplantation and share our understanding of human disease biology and regenerative medicine derived from these studies.

Because recovery from upper limb paralysis after stroke is challenging, compensatory approaches have been the main focus of upper limb rehabilitation. However, based on fundamental and clinical research indicating that the brain has a far greater potential for plastic change than previously thought, functional restorative approaches have become increasingly common. Among such interventions, constraint-induced movement therapy, task-specific training, robotic therapy, neuromuscular electrical stimulation (NMES), mental practice, mirror therapy, and bilateral arm training are recommended in recently published stroke guidelines. For severe upper limb paralysis, however, no effective therapy has yet been established. Against this background, there is growing interest in applying brain-machine interface (BMI) technologies to upper limb rehabilitation. Increasing numbers of randomized controlled trials have demonstrated the effectiveness of BMI neurorehabilitation, and several meta-analyses have shown medium to large effect sizes with BMI therapy. Subgroup analyses indicate higher intervention effects in the subacute group than the chronic group, when using movement attempts as the BMI-training trigger task rather than using motor imagery, and using NMES as the external device compared with using other devices. The Keio BMI team has developed an electroencephalography-based neurorehabilitation system and has published clinical and basic studies demonstrating its effectiveness and neurophysiological mechanisms. For its wider clinical application, the positioning of BMI therapy in upper limb rehabilitation needs to be clarified, BMI needs to be commercialized as an easy-to-use and cost-effective medical device, and training systems for rehabilitation professionals need to be developed. A technological breakthrough enabling selective modulation of neural circuits is also needed.