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Taiju Miyagami,1 Satoshi Teranaka,2 Yuichiro Mine,1 Tomohiro Matsumoto,3 Yuki Yoshimatsu,4,5 Shinichi Matsumoto,6 Kohei Yamaguchi,7 Toru Morikawa8,9 1Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 2Department of Physical Medicine and Rehabilitation, Japanese Red Cross Ashikaga Hospital, Tochigi, Japan; 3Division of General Medicine, Nerima Hikarigaoka Hospital, Tokyo, Japan; 4Elderly Care, Queen Elizabeth Hospital, Lewisham and Greenwich NHS Trust, London, UK; 5Centre for Exercise Activity and Rehabilitation, School of Human Sciences, University of Greenwich, London, UK; 6Yushoukai Home Care Clinic Katsushika, Tokyo, Japan; 7Department of Dysphagia Rehabilitation, Tokyo Medical and Dental University, Tokyo, Japan; 8Department of General Medicine, Nara City Hospital, Nara, Japan; 9Department of Clinical Epidemiology, Hyogo Medical University, Nishinomiya, JapanCorrespondence: Taiju Miyagami, Department of General Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo Bunkyo-Ku, Tokyo, 113-8431, Japan, Tel +81-3-3813-3111, Fax +81-3-5802-1190, Email tmiyaga@juntendo.ac.jpAbstract: This opinion paper addresses the challenges and future directions for preventing aspiration pneumonia in Japan’s rapidly aging population. It highlights the increasing proportion of elderly individuals and the associated rise in health issues like decreased swallowing function, a risk factor for aspiration pneumonia. The paper emphasizes the effectiveness of dentist-provided oral care in preventing this condition but notes the lack of collaboration between dentists and physicians in Japan’s clinical practice. Key challenges identified include the scarcity of full-time hospital dentists, insufficient communication between physicians and dentists, limited patient understanding and motivation regarding oral care, and a lack of training in geriatric dentistry. The paper advocates for enhanced awareness among healthcare professionals and patients, increased hospital dentists, and improved collaboration mechanisms, particularly in light of recent positive changes in insurance reimbursement policies for elderly oral care.Keywords: dentist, aging, aspiration pneumonia, oral care

Atsushi Kimura,1 Kohei Yamaguchi,2 Haruka Tohara,2 Yusuke Sato,3 Naoko Sawada,3 Yasuhide Nakagawa,3 Yukako Matsuda,4,5 Motoharu Inoue,5 Yuji Wada,6 Kazuhiro Tamaki3,4 1College of Risk Management, Nihon University, Tokyo, Japan; 2Department of Dysphagia Rehabilitation, Tokyo Medical and Dental University, Tokyo, Japan; 3Geriatric Health Services Facility Nanohana, Medical Corporation Kanjinkai, Tokyo, Japan; 4Nanohana Dentistry Clinic, Medical Corporation Kanjinkai, Tokyo, Japan; 5Department of Dysphagia Rehabilitation, Nihon University of Dentistry, Tokyo, Japan; 6College of Gastronomy Management, Ritsumeikan University, Shiga, JapanCorrespondence: Atsushi Kimura, College of Risk Management, Nihon University, Setagaya-ku, Tokyo, 1548513, Japan, Tel +81 3 6453 1600, Fax +81 3 6453 1630, Email kimura.atsushi@nihon-u.ac.jp Kazuhiro Tamaki, Geriatric Health Services Facility Nanohana, Medical Corporation Kanjinkai, Nishitama-Gun, Tokyo, 1901212, Japan, Tel +81 42 568 5111, Fax +81 42 568 5127, Email tamakikazuhiro@g.kanjinkai.netPurpose: Past research has shown that exposure to the image of a slim person reduces food consumption among young adults. However, it remains unknown whether this paradigm could be adapted and applied to increase food intake among older adults with dementia by exposing them to the image of a higher-weight person to mitigate weight loss and malnutrition. The present study explored whether weight-related visual cues affect the amount of food consumed by older adults with dementia.Participants and Methods: In the experiment, twenty-one elderly people with dementia living in a nursing home were visually exposed to one of four conditions (a cartoon image of a normal-weight chef, a higher-weight chef, a flower or no image) during real-life daily lunch situations over the course of four weeks, during which each condition was presented for one week.Results: Results demonstrate that participants finished their meals more frequently when they were exposed to the image of the higher-weight chef than when they were not exposed to any images.Conclusion: These results suggest that exposure to a cartoon chef character representing a stereotyped social group related to body weight activates the stereotype and increases stereotype-consistent behavior in older adults with dementia. The present findings will contribute to understanding the effect of visual information on eating behavior and to designing eating environments which facilitate sufficient nutrition intake among older adults with dementia.Keywords: nudge, body weight, dementia, food consumption, dining environment

Kazuharu Nakagawa, Kanako Yoshimi, Akira Yoshizawa, Kota Aritaki, Kohei Yamaguchi, Ayako Nakane, Haruka Tohara Department of Dysphagia Rehabilitation, Division of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanCorrespondence: Kanako Yoshimi, Department of Dysphagia Rehabilitation, Division of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan, Tel/Fax +81 3-5803-5560, Email k.yoshimi.gerd@tmd.ac.jpPurpose: Oral rehydration solutions (ORSs) are effective in replacing fluids and electrolytes and are widely used. OS-1 Jelly (Otsuka Pharmaceutical Factory, Tokushima, Japan) is a jelly drink corresponding to code 2-1 of the 2021 Japanese Dysphagia Diet. Although jelly drinks are less likely to be aspirated than liquids, their physical properties vary depending on the product. Therefore, the severity of dysphagia may affect intake status. This study aimed to investigate the association between the intake status of ORS jelly and swallowing function.Patients and Methods: Thirty-six patients with dysphagia who required videoendoscopic swallowing evaluation at our university hospital were enrolled. Videoendoscopic swallowing evaluation was performed, and each participant swallowed 5 mL of OS-1 Jelly or thickened water modified to International Dysphagia Diet Standardization Initiative (IDDSI) level 2 three times. Statistical analysis was performed to determine the difference in the number of swallows, time until the swallowing reflex, position for inducing the swallowing reflex, presence of pharyngeal residue, penetration, or aspiration between ORS jelly and thickened water.Results: The time until the swallowing reflex was induced and the position of the swallowing reflex triggered were significantly earlier for ORS jelly (p=0.012, p=0.001). The incidence of pharyngeal residue was significantly lower with ORS jelly (p=0.002). The Penetration-Aspiration Scale score was similar for both samples (p=0.062), and no aspiration was observed in either sample.Conclusion: Patients with dysphagia who can swallow thickened water modified to IDDSI level 2 can consume ORS jelly. ORS jelly, which requires no thickening and can be easily and safely consumed, is effective for water and electrolyte intake in patients with dysphagia.Keywords: oral rehydration solutions, swallowing function, fluid intake, electrolyte supply

Yu Nakanishi,1 Hiroshi Iwamoto,1 Shintaro Miyamoto,1 Satoshi Nakao,1 Naoko Higaki,1 Kakuhiro Yamaguchi,1 Shinjiro Sakamoto,1 Yasushi Horimasu,1 Takeshi Masuda,1 Naoko Matsumoto,2 Taku Nakashima,1 Yojiro Onari,3 Kazunori Fujitaka,1 Yoshinori Haruta,4 Hironobu Hamada,5 Soichiro Hozawa,6 Noboru Hattori1 1Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 2Department of Respiratory Medicine, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan; 3Department of Respiratory Medicine, Hiroshima Mazda Hospital, Hiroshima, Japan; 4Haruta Respiratory Clinic, Hiroshima, Japan; 5Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences Hiroshima University, Hiroshima, Japan; 6Hiroshima Allergy and Respiratory Clinic, Hiroshima, JapanCorrespondence: Hiroshi Iwamoto, Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan, Tel +81-82-257-5196, Email iwamotohiroshig@gmail.comPurpose: Asthma guidelines recommend considering the patient preference to optimize medication choices. Patient preference for inhaler medication may affect asthma outcomes, but evidence regarding this is lacking. This study investigated the associations between patient preference for inhaler medications and asthma outcomes.Patients and Methods: A multicenter questionnaire survey was conducted among 351 adult patients with asthma treated with regular inhaled corticosteroids. Agreement between patients’ preferences and current medication was evaluated using two questions: matched preference was defined as patients answering that the current inhaler medication was the most preferred treatment and they were satisfied with it. Mismatched preference was defined as when patients reported that the current inhaler medication was not the most preferred treatment and/or they were not satisfied with it. We investigated the factors associated with patient preference for asthma inhaler medications.Results: In total, 269 (76.6%) patients were classified into the matched preference group and 82 (23.4%) patients into the mismatched preference group. Multivariate analyses showed that matched preference was independently associated with higher asthma control test scores (P< 0.001), fewer exacerbations (P=0.009), less regular oral corticosteroid use (P=0.009), and better inhaler adherence (P=0.006) than the mismatched preference group. In subgroup analysis, younger age was associated with matched preference in patients using dry powder inhalers but not in those using pressurized metered dose inhalers.Conclusion: The use of preference-matched inhaler medication was associated with better asthma outcomes. Evaluation of patients’ preference for inhaler medication might provide useful information for individualized treatment with asthma inhaler medications.Keywords: patient preference, asthma control, inhaled corticosteroids, inhaler adherence, shared decision-making

Asami Nagaoka-Takatori,1 Madoka Ishii,1 Koremasa Hayama,1 Daisuke Obinata,2 Kenya Yamaguchi,2 Satoru Takahashi,2 Hideki Fujita1 1Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, 173-8610, Japan; 2Department of Urology, Nihon University School of Medicine, Tokyo, 173-8610, JapanCorrespondence: Hideki FujitaDivision of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, JapanTel +81-3-3972-8111 (ext. 2502)Fax +81-3-5995-9841Email fujita.hideki@nihon-u.ac.jpAbstract: A 50-year-old Japanese woman presented with a 4-day history of multiple purpura on her extremities and myalgia. She had been receiving nivolumab therapy for stage IV renal cell carcinoma for 18 months. Nivolumab was temporarily discontinued due to liver dysfunction and resumed 3 months before. Biopsy specimen revealed leukocytoclastic vasculitis, and direct immunofluorescence showed deposition of IgA and C3 in the vessel walls of the upper dermis. Based on these findings, a diagnosis of IgA vasculitis was made. She was treated with 20 mg/day of oral prednisolone, which resulted in the complete disappearance of purpura and myalgia. Although the patient needed temporary cessation of nivolumab therapy, she experienced no recurrence of purpura or myalgia, and the dose of prednisolone was gradually tapered to 5 mg/day. Although nivolumab can lead to various immune-related adverse events, vasculitis is rare. To the best of our knowledge, this is the second case of IgA vasculitis during nivolumab therapy.Keywords: immune checkpoint inhibitors, leukocytoclastic vasculitis, PD-1, purpura

Yoshiko Hara,1 Ayako Nakane,2 Haruka Tohara,2 Kazumasa Kubota,1 Kazuharu Nakagawa,2 Koji Hara,2 Kohei Yamaguchi,2 Kanako Yoshimi,2 Shunsuke Minakuchi1 1Department of Gerodontology and Oral Rehabilitation, Division of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Dysphagia Rehabilitation, Division of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanCorrespondence: Ayako NakaneDepartment of Dysphagia Rehabilitation, Division of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, JapanTel/Fax +81-3-5803-5562Email fujigerd@tmd.ac.jpPurpose: We aimed to determine the efficacy of interferential current transcutaneous electrical sensory stimulation (IFC-TESS) in patients with dementia who were being treated for dysphagia in nursing homes under normal living conditions.Patients and Methods: This study recruited 54 nursing home residents (13 males, 41 females; mean age, 84.5 ± 10.7 years) with dysphagia and dementia. IFC-TESS was performed with Gentle Stim® (Careido Co. Ltd., Kanagawa, Japan) for 15 minutes. Two sessions per day were administered 5 days per week, for 3 weeks. The outcomes included the improvement of the patients’ cough reflexes and nutritional states across the 3 weeks of intervention; the former was evaluated with the cough test based on the changes in cough latency time and cough frequency, while the latter was assessed based on changes in the functional oral intake scale (FOIS) score and oral calorie intake.Results: The cough latency times before and after the 3-week intervention were 15.8 (7.0– 60.0) and 6.7 (3.6– 30.7) s/min, respectively; the cough frequencies were 5.0 (0.0– 5.0) and 5.0 (5.0– 5.0) t/min, respectively; the FOIS scores were 5.0 (5.0– 6.0) and 5.0 (5.0– 6.0), respectively; and oral calorie intakes were 1300.0 (862.5– 1420.0) and 1300.0 (1005.0– 1462.5) kcal/day, respectively. All parameters significantly improved across the intervention (p < 0.05). When the results were adjusted for age, sex, body mass index, mini nutritional assessment results, Barthel index, and mini-mental state examination scores, IFC-TESS improved the cough reflex and oral calorie intake in older nursing home residents with dementia.Conclusion: Cervical IFC-TESS can improve the cough reflexes and nutritional states of patients with dysphagia and dementia in nursing homes. As it has previously been difficult to perform active rehabilitation with dementia patients, IFC-TESS may be effective and practicable for the rehabilitation of this patient population.Keywords: cough frequency, cough latency time, FOIS, IFC-TESS, oral calorie intake

Ayana Goto, Nobuhisa Matsuhashi, Takao Takahashi, Toshiyuki Tanahashi, Satoshi Matsui, Hisashi Imai, Yoshihiro Tanaka, Kazuya Yamaguchi, Kazuhiro Yoshida Department of Surgical Oncology, Gifu University School of Medicine, Gifu City 501-1194, JapanCorrespondence: Nobuhisa MatsuhashiDepartment of Surgical Oncology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, JapanTel +81-58-230-6233Fax +81-58-230-1074Email nobuhisa517@hotmail.comIntroduction: The abdominal desmoid tumor shows invasive development and high local recurrence rate. The primary treatment method is complete removal of the tumor because of the high recurrence rate; however, the problem for the surgeon is the reconstruction of the abdominal wall after resection of the abdominal desmoid tumor.Case Presentation: A 63-year-old man underwent open drainage and ileostomy for the perforation of ileocecal tumor. After 3 months, he underwent right hemicolectomy and ileostomy closure. Pathological examination revealed no malignancy, and the ileocecal tumor showed the presence of abscess. He noticed a palpable mass in the left abdomen. Enhanced abdominal computed tomography (CT) revealed a large abdominal incisional hernia and an enhanced mass of 40 mm in the left rectus muscle. Needle biopsy was performed and the diagnosis was desmoid tumor. He underwent resection of the desmoid tumor and repair of hernia. We performed wide local resection, with a 2-cm surgical margin. The hernia was repaired by simple closure, and the defect in the left abdomen was repaired with reconstruction using the fascia lata patch through plastic surgery.Conclusion: We encountered a case of abdominal wall desmoid tumor combined with a large abdominal incisional hernia. We selected the use of autologous fascia based on the risk of recurrence. The patient has not shown recurrence of incisional hernia or desmoid tumor 22 months after surgery. The use of fascia lata patch can be considered as a satisfactory alternative for such reconstruction cases.Keywords: abdominal desmoid tumor, incisional hernia, abdominal wall reconstruction, autologous fascia

Atsushi Kimura,1 Kohei Yamaguchi,2,3 Haruka Tohara,3 Yusuke Sato,4 Naoko Sawada,4 Yasuhide Nakagawa,4 Yukako Matsuda,2,5 Motoharu Inoue,2,5 Kazuhiro Tamaki2,4 1College of Risk Management, Nihon University, Setagaya-ku, Tokyo, Japan; 2Dentistry Nanohana Clinic, Medical Corporation Kanjinkai, Nishitama-gun, Tokyo, Japan; 3Department of Gerodontology and Oral Rehabilitation, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan; 4Geriatric Health Services Facility Nanohana, Medical Corporation Kanjinkai, Nishitama-gun, Tokyo, Japan; 5Department of Dysphasia Rehabilitation, Nihon University of Dentistry, Chiyoda-Ku, Tokyo, JapanCorrespondence: Atsushi KimuraCollege of Risk Management, Nihon University, 3-34-1 Shimouma, Setagaya-ku, Tokyo 154-8513, JapanTel +81 3 6453 1600Fax +81 3 6453 1630Email kimura.atsushi@nihon-u.ac.jpKazuhiro TamakiGeriatric Health Services Facility Nanohana, Medical Corporation Kanjinkai, 454 Tonogaya, Mizuho-machi, Nishitama-gun, Tokyo 190-1212, JapanTel +81 42 568 5111Fax +81 42 568 5127Email tamakikazuhiro@g.kanjinkai.netPurpose: The previous study demonstrated that the addition of a sauce is an effective means of influencing the consumption of finger foods among French elderly people with dementia. However, it is unclear the relative importance of low-level sensory factors such as flavor and a semi-solid nature and high-level cognitive factors such as memory stimulation and familiarity to the effect of the addition of sauce on food intake. The present study investigated whether the addition of sauce affects finger-snack intake among Japanese elderly people with dementia who were not familiar with sauce dipping.Patients And Methods: A total of 21 patients with dementia who were recruited in a nursing home in Tokyo received a plate of cut baumkuchen (a very thinly layered German roll cake), which had pieces of baumkuchen both with and without sauce, at their afternoon snack time. The amount of food intake and the first choice between options were measured for each participant. We used chocolate (in Experiment 1, n = 21) and agave (Experiment 2, n =14) syrups as sauce samples.Results: Results of both experiments demonstrate that snack consumption was greater for the with-sauce options than for the without-sauce options. A 90.5% of the participants in Experiment 1 and 64.3% of participants in Experiment 2 ate more snacks with sauce than without sauce.Conclusion: These findings imply that low-level sensory factors such as flavor and a semi-solid nature contribute relatively more strongly to the enhancement of food consumption with the addition of sauce than do high-level cognitive factors such as memory stimulation and familiarity, because Japanese elderly people are not always familiar with the custom of wiping up the sauce with food.Keywords: food consumption, dementia, under nutrition, food improvement, sauce

Kazuyoshi Kawakami,1 Takeru Wakatsuki,2 Azusa Soejima,1 Kazuo Kobayashi,1 Takashi Yokokawa,1 Takeshi Aoyama,1 Kenichi Suzuki,1 Mitsukuni Suenaga,2 Kensei Yamaguchi,2 Ayaka Inoue,3 Yoshiaki Machida,3 Toshihiro Hama1 1Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo 135-8550, Japan; 2Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo 135-8550, Japan; 3Section for Practical Education, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-Ku, Tokyo 142-8501, JapanCorrespondence: Kazuyoshi KawakamiThe Japanese Foundation for Cancer Research, Cancer Institute Hospital, Depatment of Pharmacy, 3-8-31 Ariake Koto-ku, Tokyo 135-8550, JapanEmail kazu.kawakami@jfcr.or.jpIntroduction: Regorafenib is an oral multikinase inhibitor for the treatment of metastatic colorectal cancer (mCRC). The clinical factors that may affect adherence to regorafenib remain unclear. The aim of this study was to evaluate adherence to regorafenib with mCRC and to identify factors that might affect adherence to regorafenib.Methods: A total of 108 consecutively enrolled Japanese patients with mCRC received regorafenib. Adherence was measured by pharmacists using pill counts and a self-reported treatment diary for patients at a pharmaceutical outpatient clinic. The median relative dose intensities of regorafenib and the factors adversely affecting adherence were retrospectively surveyed. Logistic regression analysis was then performed using patient socio-demographic factors and clinical factors.Results: A total of 96 patients were included in the analysis. The median adherence rate was 61.7% in the first cycle. The median relative dose intensity was 57.1%. The most common reason for non-adherence was a hand-foot-skin reaction (35.6%). On multivariate analysis, increased non-adherence to regorafenib was significantly associated with sex (female) [odds ratio (OR) = 4.36; 95% confidence interval (CI): 1.43–13.22, p = 0.01].Discussion: Hand-foot-skin reactions and female sex were associated with lower adherence to regorafenib. Since these factors could be associated with lower adherence to regorafenib, it would be useful to consider these factors when assessing adherence.Keywords: adherence, regorafenib, colorectal cancer, hand-foot-skin reactions

Hiroyoshi Taketani,1,* Taichiro Nishikawa,1,* Hisakazu Nakajima,2 Kazuki Kodo,2 Satoru Sugimoto,2 Wataru Aoi,3 Shin-ichi Horike,4 Makiko Meguro-Horike,4 Hiroshi Ishiba,1 Yuya Seko,1 Atsushi Umemura,1 Kanji Yamaguchi,1 Michihisa Moriguchi,1 Kohichiroh Yasui,1 Yoshito Itoh11Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan; 4Advanced Science Research Center, Kanazawa University, Kanazawa, Japan*These authors contributed equally to this workCorrespondence: Taichiro NishikawaKyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachidouri Hirokouji Agaru, Kamigyo-ku, Kyoto 602-8566, JapanTel +81 75 251 5519Fax +81 75 251 1017Email taichi@koto.kpu-m.ac.jpBackground and aims: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome, and its progression is associated with aging-associated impairment in metabolic homeostasis. Recently, energy metabolism in adipose tissue has been the subject of renewed interest, because significant energy expenditure can be induced in cells derived from white adipose tissue progenitors, in addition to brown adipose tissue (BAT). Here we evaluated whether aging-associated change in various adipose tissue depots affects the progression of NAFLD.Methods: Six-week-old male C57BL/6NCrSlc mice were fed control chow (C) or high-fat diet (60% fat; HF) for 12 or 24 weeks (12w/C, 12w/HF, 24w/C and 24w/HF groups, respectively) or switched from C to HF diet at 18 weeks of age (24w/C/HF group) and fed for a further 24 weeks. Some 24w/HF mice received a subcutaneous transplantation of adipose progenitors (106, cells/mouse) from young donor mice. Basal energy expenditure, glucose tolerance, and liver and adipose tissue histology were then evaluated. In addition, features of senescence and the capacity of adipose progenitors to “brown” were compared in mice of various ages.Results: 12w/HF mice demonstrated compensation in the forms of hypertrophy of interscapular classical BAT and the appearance of subcutaneous beige adipocytes, consistent with improved metabolic homeostasis. In contrast, 24w/HF and 24w/C/HF mice developed obesity, glucose intolerance, and severe NAFLD, with accelerated senescence and loss of adipose progenitors in subcutaneous fat tissues. Recruitment of adipose progenitors ameliorated these findings in 24w/HF mice.Conclusion: Impaired metabolic compensation in adipose tissue resulted in the progression of NAFLD, which was associated with aging-related deterioration in adipose progenitors. A new approach targeting adipose tissue progenitors might represent a potential strategy for the prevention of NAFLD.Keywords: nonalcoholic fatty liver disease, obesity, scenescence, brown adipocyte, mesenchymal stem cells, cell transplantation

Yusuke Kitagawa, Hiroki Osumi, Eiji Shinozaki, Yumiko Ota, Izuma Nakayama, Takeshi Suzuki, Takeru Wakatsuki, Takashi Ichimura, Mariko Ogura, Akira Ooki, Daisuke Takahari, Mitsukuni Suenaga, Keisho Chin, Kensei YamaguchiDepartment of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, JapanPurpose: Patients with gastrointestinal neuroendocrine carcinoma (GI-NEC) have poor prognoses. Although platinum-based combination chemotherapy is commonly used as first-line treatment, the benefit of amrubicin (AMR) and salvage chemotherapy in those who develop platinum-refractory GI-NEC remains unknown. This study aimed to evaluate the efficacy and safety of AMR monotherapy in patients with platinum-refractory GI-NEC.Patients and methods: Platinum-refractory GI-NEC patients who received AMR monotherapy between April 2012 and September 2017 were retrospectively analyzed. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. PFS and OS were estimated using Kaplan-Meier methods and compared using log-rank tests.Results: In total, 16 patients were enrolled. Of them, 13 (81.3%), 1 (6.2%), and 2 (12.5%) received cisplatin plus irinotecan, cisplatin plus etoposide, and fluoropyrimidine plus platinum, respectively, before AMR monotherapy. The primary sites of NEC included the esophagus (N=3, 18.8%), stomach (N=10, 62.5%), duodenum (N=1, 6.2%) and colorectum (N=2, 12.5%). Patients were administered a median of 3 (range, 1–15) cycles of AMR. The ORR was 6.3%, and the median PFS and OS were 2.9 months (95% CI: 1.7–7.4) and 13.8 months (95% CI: 7.9–23.5), respectively. Neutropenia was the most serious adverse event. Grade 3 or higher neutropenia and febrile neutropenia occurred in 50.0% and 6.2% of patients, respectively. Other nonhematological toxicities were not severe, and no treatment-related deaths occurred. The 10 patients who received subsequent chemotherapy after AMR had significantly longer OS than those who did not (17.3 months vs 8.9 months; p=0.018). The median PFS of those who received organ-specific subsequent chemotherapy after AMR was 3.8 months, which was longer than that of those who received prior AMR.Conclusion: AMR is feasible with minimal side effects for platinum-refractory GI-NEC. Organ-specific subsequent chemotherapy after AMR may improve patient survival.Keywords: amrubicin monotherapy, platinum refractory, gastrointestinal neuroendocrine carcinoma

Chizuru Namiki,1 Koji Hara,1 Haruka Tohara,1 Kenichiro Kobayashi,2 Ariya Chantaramanee,1 Kazuharu Nakagawa,1 Takayuki Saitou,2 Kohei Yamaguchi,1 Kanako Yoshimi,1 Ayako Nakane,1 Shunsuke Minakuchi1 1Department of Gerodontology, Division of Gerontology and Gerodontology, Tokyo Medical and Dental University, Tokyo, Japan; 2Kobayashi Dental Clinic, Tokyo, Japan Purpose: Producing tongue pressure (TP) by pushing the tongue against the palate consists of lifting the tongue muscles and elevating the floor of the mouth via suprahyoid muscle contraction. Though studies have shown that tongue-pressure resistance training (TPRT) increases tongue function, none have focused on suprahyoid muscle function enhancements. Our study aimed to verify whether TPRT improves both tongue function and hyoid movement during swallowing.Materials and methods: Eighteen patients (mean age: 76.8±6.2 years) with presbyphagia presenting with symptoms such as coughing and choking were enrolled. All patients performed daily living activities independently. None of the participants had diseases causing dysphagia or previous oral or pharyngeal surgery. Participants were instructed to push their tongues against the palate as hard as possible with their mouths closed for 10 seconds, and then resting for 10 seconds. A set consisted of five consecutive exercise and resting periods; two sets per day were performed for a month. TP and the oral diadochokinetic rate (ODKR), measured by repetitions of the syllables /ta/ and /ka/, assessed tongue function. The extent of anterior and superior hyoid movement and parameters related to swallowing, including the penetration aspiration scale (PAS) and the normalized residue ratio scale (NRRS) in the valleculae (NRRSv) and piriform sinus (NRRSp), were evaluated based on videofluoroscopic data.Results: The anterior (P=0.031) and superior hyoid movement (P=0.012), TP (P=0.002), ODKR/ta/ (P=0.034), ODKR/ka/ (P=0.009), and the width of the upper esophageal sphincter (P=0.001) were larger at follow-up than at baseline. NRRSp (P=0.022), PAS (P=0.016), and pharyngeal transit times (P=0.004) were smaller at follow-up than at baseline.Conclusion: TPRT improved tongue strength, dexterity, both anterior and superior hyoid elevation, and swallowing functions. Therefore, TPRT could improve tongue function and suprahyoid muscle function simultaneously and contribute to prevention of sarcopenic dysphagia. Keywords: sarcopenic dysphagia, swallowing muscle, tongue function, suprahyoid muscle

Yuya Seko,1 Taichiro Nishikawa,1 Atsushi Umemura,1 Kanji Yamaguchi,1 Michihisa Moriguchi,1 Kohichiroh Yasui,1 Mayumi Kimura,2 Hiroaki Iijima,3 Toshio Hashimoto,3 Yoshio Sumida,4 Takeshi Okanoue,5 Yoshito Itoh1 1Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan; 3Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan; 4Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan; 5Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan Aim: Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is known to be associated with type 2 diabetes mellitus (T2DM) in high rate. The improvement in hepatic function due to sodium-glucose co-transporter 2 (SGLT2) inhibitors has been reported in T2DM patients with and without NAFLD. However, only a few studies have attempted to evaluate the role of SGLT2 inhibitors in T2DM patients with biopsy-proven NASH, and no detailed prospective studies including the individual hepatic fibrosis stage have been reported. Therefore, we investigated the effect of canagliflozin on hepatic function in T2DM patients with biopsy-confirmed NASH. Methods: T2DM patients with NASH (hepatic fibrosis stage 1–3 confirmed via liver biopsy, n=10) were enrolled and received canagliflozin (100 mg) once a day for 12 weeks. The primary end point was change in serum alanine aminotransferase (ALT) levels from baseline to week 12. Secondary end points were liver function/fibrosis markers, metabolic parameters, and safety. Results: The change in ALT from baseline to week 12 was -23.9 U/L (95% CI –48.1 to 0.3, P=0.0526). Significant improvements in several hepatic function/fibrosis markers, such as aspartate aminotransferase, fibrosis-4 index, and FM-fibro index, and metabolic parameters including hemoglobin A1c and body weight were found. No serious or liver-related adverse events were reported. Regarding individual patients, different trends in ALT-lowering effects between stage 1 and stage 2/3 subjects were observed; the degree of ALT-lowering effect tended to be greater in the stage 1 group than in the stage 2/3 group. Conclusion: Our results suggest that canagliflozin is effective and well-tolerated in patients with T2DM and NASH. Canagliflozin may be useful for the treatment of T2DM patients with NASH, especially those in early stages of NASH. Keywords: canagliflozin, Japanese, NASH, fibrosis stages, SGLT2 inhibitor, type 2 diabetes mellitus

Hiroki Osumi, Daisuke Takahari, Keisho Chin, Mariko Ogura, Takashi Ichimura, Takeru Wakatsuki, Takeshi Suzuki, Yumiko Ota, Izuma Nakayama, Akira Ooki, Mitsukuni Suenaga, Eiji Shinozaki, Kensei Yamaguchi Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan Background: Oral fluoropyrimidine plus platinum is a standard first-line treatment for advanced gastric cancer (AGC). However, this treatment is problematic for AGC patients with massive ascites or inadequate oral intake. This study aimed at evaluating the efficacy and safety of modified oxaliplatin (L-OHP) with l-leucovorin (l-LV) and bolus/continuous infusion of 5-fluorouracil (5-FU) (mFOLFOX6) regimen for patients with massive ascites or inadequate oral intake.Methods: This retrospective study was conducted at a single Japanese institute from November 2015 to May 2018. The mFOLFOX6 regimen consisted of 85 mg/m2 L-OHP, 400 mg/m2 bolus of 5-FU, and 400 mg/m2 1-LV on the first day, followed by 2,400 mg/m2 of 5-FU as a continuous infusion in 46 hours for first-line treatment. The definition of inadequate oral intake was the need for total parenteral nutrition (TPN). Massive ascites was defined as continuous ascites from the pelvic cavity to the upper abdomen. Improvement in oral intake was defined as no TPN for more than 7 days, and improvement in ascites was defined as a decrease in ascites of more than one grade defined by the Japan Clinical Oncology Study Group trial (JCOG0106).Results: Among the 364 patients with AGC who received first-line chemotherapy, 17 patients (13 [76.5%] had inadequate oral intake, and four [23.5%] had massive ascites) were enrolled in this study. Median time to treatment failure and overall survival were 4.8 (95% CI=1.5–7.5) and 8.8 months (95% CI=2.3–not available), respectively. Objective improvements in oral intake and ascites were seen in 11 of 13 patients (84.6%) and 6 of 12 patients (50%), respectively. The major grade 3 or 4 adverse events were neutropenia (35.3%), febrile neutropenia (5.9%), fatigue (5.9%), anorexia (5.9%), and infection (5.9%). No treatment-related deaths occurred.Conclusion: We found that mFOLFOX6 can be a novel treatment option as the first-line treatment for AGC patients with massive ascites or inadequate oral intake. Keywords: advanced gastric cancer, FOLFOX, massive ascites, inadequate oral intake

Izuma Nakayama, Keisho Chin, Daisuke Takahari, Mariko Ogura, Takashi Ichimura, Takeru Wakatsuki, Hiroki Osumi, Yumiko Ota, Takeshi Suzuki, Mitsukuni Suenaga, Eiji Shinozaki, Kensei Yamaguchi Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Purpose: Gastric cancer in young adults (GCYA) is known to have distinct clinicopathological features, including a female predominance and diffuse-type histology. Previous reports have focused on patients who had undergone gastrectomy with curative intent. Information concerning the treatment of unresectable advanced- or recurrent-stage GCYA is lacking. Therefore, we aimed to investigate whether the distinct clinicopathological features of GCYA affect the outcome of systemic chemotherapy.Patients and methods: We conducted a retrospective cohort study at a single institution in Japan. GCYA was classified as a disease in individuals who were

Yasuhiro Yamazaki, Haruka Tohara, Koji Hara, Ayako Nakane, Yoko Wakasugi, Kohei Yamaguchi, Shunsuke Minakuchi Department of Gerodontology, Tokyo Medical and Dental University, Tokyo, Japan Purpose: This study aimed to determine whether excessive neck muscle tone affects hyoid bone kinetics during swallowing using videofluorography (VF) in an unnatural posture in healthy individuals. Subjects and methods: Subjects were 28 healthy adults (12 men, 16 women; mean age, 39.75±9.50 years) without any history or present complaints of swallowing disorders. We first established the participant’s posture a reclining wheelchair that was adjusted to a 30-degree angle with the headrest (without excessive neck muscle tone) or without headrest (with excessive neck muscle tone), used an electromyogram above the mylohyoid muscle to represent the suprahyoid muscles and above the sternohyoid muscle to represent the infrahyoid muscles to confirm neck muscle tone, and then conducted VF of swallowing measurements. Videofluorographic images were obtained when 5 mL of 50% (w/v) barium sulfate was being swallowed, and hyoid bone coordinate (the resting position and the elevated position), extent of horizontal and vertical hyoid bone elevation, as well as duration and velocity of hyoid bone elevation were evaluated (x-axis and y-axis coordinates for the resting position of hyoid bone are referred to as Xr and Yr, respectively; those for the elevated hyoid bone position induced during swallowing are referred to as Xs and Ys, respectively). Results: In the resting position of the hyoid bone, the Yr coordinates in those with excessive neck muscle tone were significantly lower than in those without excessive neck muscle tone. Vertical hyoid bone elevation and hyoid bone elevation velocity were significantly higher with excessive neck muscle tone than without excessive neck muscle tone, whereas horizontal elevation showed no significant differences. Conclusion: Our findings suggest that the generation of neck muscle tone due to inappropriate posture may encourage hyoid depression and increase the extent of hyoid bone elevation, thereby increasing the risk of aspiration. Keywords: dysphagia, swallow, muscle tone, hyoid bone, infrahyoid muscles, suprahyoid muscles

Shusuke Yagi,1 Akira Takashima,1 Minoru Mitsugi,2 Toshihiro Wada,2 Junko Hotchi,1 Ken-ichi Aihara,3 Tomoya Hara,1 Masayoshi Ishida,1 Daiju Fukuda,4 Takayuki Ise,1 Koji Yamaguchi,1 Takeshi Tobiume,1 Takashi Iwase,1 Hirotsugu Yamada,1 Takeshi Soeki,1 Tetsuzo Wakatsuki,1 Michio Shimabukuro,4 Masashi Akaike,5 Masataka Sata11Department of Cardiovascular Medicine, Graduate School of Health Biosciences, University of Tokushima, Tokushima, 2Department of Internal Medicine, Shikoku Central Hospital, Shikokuchuo, 3Department of Medicine and Bioregulatory Sciences, 4Department of Cardio-Diabetes Medicine, 5Department of Medical Education, Graduate School of Health Biosciences, University of Tokushima, Tokushima, JapanBackground: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease.Methods: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.Results: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate.Conclusion: The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.Keywords: blood pressure, combination tablet, uric acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol

Second harmonic generation (SHG) spectroscopy in the visible and infrared regions has been a useful tool to selectively probe electronic properties at surfaces and interfaces. By examining variation of SHG under a magnetic field, one can also evaluate magnetic properties at the surfaces/interfaces. When multiple elements are involved in SHG, however, it is difficult to separate their contributions. In order to meet the demand of studying increasingly complex magnetic multilayer materials, element selectivity is desired. Here, using an Fe-based multilayer sample with broken inversion symmetry, we present observation of magnetization-induced SHG in the soft x-ray regime around the Fe M-shell absorption edge. Significant variation of SHG signal was captured depending on the direction of the magnetic moment, assuring sensitivity of the measurement likely enhanced by the Fe M-edge inner-shell resonance. The present methodology paves the way for element specific studies of magnetic properties at buried interfaces. [ABSTRACT FROM AUTHOR]