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Midori Fujishiro,1,2 Sho Tanaka,1,3 Kentaro Watanabe,1 Kazuhiro Imatake,4 Yasuyuki Suzuki,4– 6 Hisamitsu Ishihara,1 Shigemasa Tani4– 6 1Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 2Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan; 3Amemiya Internal Medicine Clinic, Kanagawa, Japan; 4Department of Health Planning Center, Nihon University Hospital, Tokyo, Japan; 5Department of Cardiology, Nihon University Hospital, Tokyo, Japan; 6Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondence: Sho Tanaka, Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan, Tel +81-3-3972-8111, Fax +81-3-3959-9775, Email tanaka.sho@nihon-u.ac.jpPurpose: Chewing problems are associated with increased mortality, geriatric syndromes and poor activities of daily living. Starting in 2018, in Japan, a self-reported questionnaire investigating chewing status was implemented in the annual health checkup program. Considering the bidirectional association between hyperglycemia and poor oral health, it is hypothesized that people with self-reported chewing problems will have relatively poor glycemic profiles. We investigated the metabolic characteristics of elderly community dwellers with self-reported chewing problems, as well as the association between the problems and HbA1c levels.Patients and Methods: This was a retrospective, cross-sectional study. We reviewed the data of 1018 adults ≥ 65 years of age who had undergone an annual health checkup at Nihon University Hospital during the period from January 2019 through December 2019. The presence of chewing problems was investigated using a self-reported questionnaire constructed based on guidance provided by the Japanese government.Results: In the 1018 participants, the overall prevalence of chewing problems was 10.4%. Participants with chewing problems showed significantly higher levels and worse categories of HbA1c than those without such problems (HbA1c < 6.0%, 42.5% vs 54.8%; HbA1c 6.0– 6.9%, 41.5% vs 37.0%; HbA1c ≥ 7.0%, 16.0% vs 8.2%, p = 0.008). Participants with HbA1c ≥ 7.0% have a significantly increased risk of chewing problems as compared to those with HbA1c < 6.0% (odds ratio 2.76, p = 0.002), even after adjusting for the effects of age, sex, body mass index, eating behaviors, and history of diabetes mellitus.Conclusion: HbA1c ≥ 7.0% is associated with self-reported chewing problems in elderly Japanese community-dwellers. We thus recommend a proactive assessment of oral conditions for this population.Keywords: chewing, community dwellers, diabetes mellitus, elderly, glycated hemoglobin

Sho Tanaka,1,2 Midori Fujishiro,1,2 Kazuhiro Imatake,3 Yasuyuki Suzuki,3– 5 Hisamitsu Ishihara,2 Shigemasa Tani3– 5 1Department of Internal Medicine, Nihon University Hospital, Tokyo, 101-8309, Japan; 2Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, 173-8610, Japan; 3Department of Health Planning Center, Nihon University Hospital, Tokyo, 101-8309, Japan; 4Department of Cardiology, Nihon University Hospital, Tokyo, 101-8309, Japan; 5Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, 173-8610, JapanCorrespondence: Midori FujishiroDepartment of Internal Medicine, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo, 101-8309, Japan, Tel +81-3-3972-8111, Fax +81-3-3959-9775, Email fujishiro.midori@nihon-u.ac.jpPurpose: Older individuals are at high risk for hypernatremia. However, actual data on serum sodium levels and differences between the sexes remain unclear in the older Japanese population. This study aimed to describe the data regarding serum sodium level and hypernatremia prevalence and to investigate whether female sex is associated with an increased risk of hypernatremia.Patients and Methods: We retrospectively analyzed the data of adults aged ≥ 65 years without severely reduced kidney function who underwent an annual health checkup in 2019. Serum sodium levels were investigated as the outcome and corrected for glucose, if necessary. Clinical characteristics were compared between women and men.Results: In the 903 participants consisting of 273 women and 630 men who were enrolled in this study, the overall prevalence of hypernatremia, defined as a serum sodium level ≥ 145 mmol/L, was 12.5%. Female participants showed significantly more frequent hypernatremia than male participants (17.6% vs 10.3%, p = 0.003) and higher serum sodium levels (median [interquartile range]; 143.0 [142.0, 144.0] vs 142.4 [141.5, 144.0], p < 0.001). Serum creatinine (sCr), but not estimated glomerular filtration rate (eGFR), was correlated with serum sodium levels (rs = − 0.108, p = 0.001). In the binary logistic regression analysis, female sex was significantly associated with hypernatremia (odds ratio, 1.89; 95% confidence interval, 1.23– 2.89; p = 0.004) even after adjusting for age, alcohol use, antihypertensive agent use, body mass index, and winter season. The association between female sex was reduced and no longer significant after adjusting for sCr, although the association remained unchanged after adjustment for eGFR.Conclusion: One-eighth of the older community dwellers in Japan exhibits hypernatremia after an overnight fast, and female sex is a significant risk factor. Since sCr is a surrogate of muscle mass, smaller muscle mass possibly mediates the association between female sex and hypernatremia.Keywords: elderly, sex, sodium, water, community dwellers

Chikako Ichikawa,1 Sho Tanaka,2,3 Masahiro Takubo,1,3 Masaru Kushimoto,3 Jin Ikeda,3 Katsuhiko Ogawa,3,4 Ichiro Tsujino,3,5 Yutaka Suzuki,3,4 Masanori Abe,2 Hisamitsu Ishihara,1 Midori Fujishiro1,3 1Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 2Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 3Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan; 4Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; 5Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondence: Sho TanakaDivision of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, JapanTel +81-3-3972-8111Fax +81-3-3972-8311Email tanakasho13@gmail.comMidori FujishiroDivision of Diabetes and Metabolic Diseases Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, JapanTel +81-3-3972-8111Fax +81-3-3972-8199Email fujishiro.midori@nihon-u.ac.jpAbstract: The standard six-month tuberculosis (TB) treatment comprises an intensive phase lasting two months, followed by a continuation phase lasting four months. Meanwhile, the nine-month regimen, which has a prolonged continuation phase, is indicated for patients with complicated diabetes mellitus (DM) because of their poor response to treatment. A 61-year-old Japanese man with poorly controlled DM for five years presented with bilateral scrotal swelling noticed two weeks ago. He had a history of pleuritis, pericarditis, and peritonitis two years ago. These symptoms led to the diagnosis of culture-negative extrapulmonary TB. He received the nine-month chemotherapy regimen (isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for seven months), and his symptoms significantly improved. The swollen scrotum was accompanied by mild tenderness and pus discharge from a fistula. Imaging study revealed bilaterally diffusely enlarged epididymis. However, the acid-fast bacilli smear and culture and polymerase chain reaction using urine and pus discharge tested negative. Bilateral epididymectomy was performed. Although the acid-fast bacilli smear was negative, the pathology demonstrated granuloma formation and acid-fast bacilli tissue culture confirmed multi-drug resistant Mycobacterium tuberculosis. The optimal treatment regimen and duration for extrapulmonary TB with unknown drug susceptibility are debatable. The nine-month regimen can be insufficient in some cases. Thus, detailed follow-up is essential, and TB relapse should be thoroughly monitored.Keywords: chemotherapy, diabetes mellitus, tuberculosis, epididymitis

Sho Tanaka,1,2 Masanori Abe,1 Genta Kohno,3 Masaru Kushimoto,2 Jin Ikeda,2 Katsuhiko Ogawa,2,4 Yutaka Suzuki,2,4 Hisamitsu Ishihara,3 Midori Fujishiro2,3 1Division of Nephrology, Hypertension, and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 2Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan; 3Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; 4Division of Neurology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondence: Midori FujishiroDivision of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, JapanTel +81 3 3972 8111Fax +81 3 3972 8199Email fujishiro.midori@nihon-u.ac.jpAbstract: A 65-year-old woman without a history of diabetes mellitus was admitted for elective total knee arthroplasty for osteoarthrosis. There were no specific complaints except for knee flexion contractures, and the results of preoperative tests were unremarkable. On the day of surgery, the patient suffered from a hypoglycemic attack (52 mg/dL) after preoperative overnight fasting. A dextrose infusion immediately corrected the hypoglycemia, and a total knee arthroplasty was then performed. Although a hypoglycemic attack did not recur, further evaluation was required because of nausea that persisted after surgery. The morning serum cortisol level was 0.15 μg/dL with undetectable adrenocorticotropic hormone (ACTH), and the insulin-like growth factor-1 level was 9 ng/mL. An empty sella and bilateral adrenal atrophy were evident in imaging studies. ACTH and growth hormone (GH) did not respond to testing with corticotropin-releasing hormone and GH–releasing peptide-2, respectively. While serum cortisol did not increase on a rapid ACTH stimulation test, urinary free cortisol excretion responded to a prolonged ACTH stimulation test. Finally, the patient was diagnosed as having empty sella syndrome with ACTH and GH deficiencies. After the administration of hydrocortisone as maintenance replacement therapy, the patient’s prolonged postoperative nausea disappeared. Adrenal insufficiency is latent in patients with hypoglycemia episodes. Because patients with adrenal insufficiency require appropriate perioperative corticosteroid supplementation, clinicians should give priority to identifying the underlying etiology of hypoglycemia over non-urgent elective surgery when these co-occur.Keywords: adrenal insufficiency, glucocorticoids, hypoglycemia, hypopituitarism, surgery

Hitoki Saito,1 Momoko Ebashi,2 Masaru Kushimoto,3 Jin Ikeda,3 Fujiko Egashira,1 Suguru Yamaguchi,1 Kentaro Watanabe1 Katsuhiko Ogawa,2,4 Yutaka Suzuki,3,4 Hisamitsu Ishihara,1 Midori Fujishiro1,4 1Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo, Japan; 2Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; 3Division of General Medicine, Department of Internal Medicine, Nihon University, Tokyo, Japan; 4Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan Abstract: Patients with diabetes mellitus (DM) are at increased risk of infections, with the urinary tract being the most frequent infection site. Incomplete bladder emptying, frequent urination and abdominal distension are typical symptoms of urinary tract infections (UTIs). A 68-year-old female with a long history of poorly controlled type 2 DM (T2DM) visited our hospital complaining of urinary retention, which was initially diagnosed as cystitis by another doctor. The urologist at our hospital identified a skin rash extending from the left hip to her genital area. A dermatologist was consulted. She was clinically diagnosed with herpes zoster (HZ) involving the left sacral dermatome area. As Elsberg syndrome (ES) was suspected, a lumbar puncture was performed, revealing aseptic meningitis associated with varicella zoster virus (VZV) infection. Intravenous acyclovir with urinary catheterization in combination with methylprednisolone pulse therapy resulted in a good clinical course. HZ very uncommonly involves sacral dermatomes, but it can develop in patients with prolonged poorly controlled DM. Furthermore, early diagnosis can be difficult when patients have diabetic peripheral neuropathy, which may mask symptoms related to skin lesions. Because this disease is potentially severe, detailed examination is important for clinicians managing patients with DM who have complaints indicative of urinary tract disorders. Keywords: herpes zoster, urinary retention, diabetic neuropathy

Yuji Uchio,1 Hiroyuki Enomoto,2 Levent Alev,2 Yuki Kato,3 Hiroyuki Ishihara,3 Toshinaga Tsuji,4 Toshimitsu Ochiai,5 Shinichi Konno6 1Department of Orthopaedic Surgery, Shimane University School of Medicine, Shimane, Japan; 2Bio-Medicine, Medicines Development Unit, Eli Lilly Japan K.K., Kobe, Japan; 3Clinical Development Department, Shionogi & Co., Ltd., Osaka, Japan; 4Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan; 5Biostatistics Department, Shionogi & Co., Ltd., Osaka, Japan; 6Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan Purpose: To examine the efficacy and safety of duloxetine in Japanese patients with knee pain due to osteoarthritis. Patients and methods: Patients were randomized to receive duloxetine 60 mg/day or placebo for 14 weeks in a double-blind manner (ClinicalTrials.gov Identifier: NCT02248480). The primary efficacy endpoint was mean change in Brief Pain Inventory pain severity (BPI-Severity) average pain. Secondary endpoints included improvement in other BPI-Severity scales, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, health-related quality of life (HRQoL) scales, range of motion of the knee joint, safety and tolerability, and structural changes on X-ray images. Results: Of the 354 randomized patients, 161 in the duloxetine group and 162 in the placebo group completed the study. BPI-Severity average pain improved significantly with duloxetine vs. placebo (−2.57 vs. −1.80; adjusted mean difference: −0.77; 95% CI: −1.11 to −0.43; P

We theoretically propose one-dimensional composite photonic structures for high-resolution THz spectroanalysis. We compare the performance of two GaAs/AlAs composite photonic-structure devices, one with usual 1/4-wavelength layers of distributed Bragg reflectors (DBRs), and the other with the designed DBRs. The device with designed DBRs shows the optical-to-terahertz conversion efficiency up to 10−5 and wide frequency tunability ranging from sub-THz to 3 THz. We found that the composite photonic structure allows us to control photonic modes with a high degree of freedom by flexible structure designs. This device achieve a cw THz source with a highly narrow bandwidth operating at room temperature.