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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

Background: The timed up and go (TUG) test assesses balance and mobility performance., Aim: This study aims to investigate the association between TUG time and mortality in Japanese older persons and to clarify possible moderation effects on mortality and TUG time., Methods: In all, 874 participants who were ≥ 65 years of age completed the TUG test and had their anthropometric parameters and physical functions measured. We investigated the association between all-cause mortality and TUG using a Cox regression model that included confounders, and explored the time associated with mortality using a restricted cubic spline. We also performed subgroup analyses to explore whether age, sex, and body mass index (BMI) affected the relationship between TUG time and mortality., Results: The median age and mean follow-up period were 74 and 8.5 years, respectively. Median TUG time was 7.4 s and the prevalence of mortality was 25.7%. TUG time in one second was positively associated with an increased risk of total mortality [hazard ratio (HR): 1.054 (1.016-1.093); P = 0.005] in the Cox regression model. The positive association of mortality and TUG time was present when the TUG was over 10.5 s in the restricted cubic spline curve. Older age (75 years or older) moderated the relationship between TUG time and mortality [P interaction  = 0.096]., Conclusion: This study demonstrates that TUG time is associated with all-cause mortality in Japanese older adults., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Background and Aim: Disability is an important health problem among older individuals, prompting the need for long-term care. Age-related disability is usually associated with mobility; however, little is known about the association between mobility and long-term care. Therefore, this study aimed to clarify the association between the timed up and go (TUG) test measuring mobility and long-term care eligibility., Patients and Methods: We analyzed follow-up data of 489 community-dwelling healthy older adults (≥ 65 years) who participated in a prospective observational study. They were divided into certified (59 participants) and uncertified (430 participants) groups based on long-term care eligibility. Anthropometric and physical functioning measures included the TUG test and hand grip strength (HGS), among others. These measures were compared between groups and a multivariate logistic regression analysis evaluated the association between the TUG test times and long-term care eligibility., Results: Participants' minimum follow-up period was 4 years. TUG times were significantly slower (median time: 7.4 vs. 8.3 s, p < 0.001) and HGS and knee-extension strength significantly lower in the certified group than in the uncertified group. The logistic regression analysis showed that TUG times were significantly associated with long-term care eligibility after adjusting for potential covariates. In addition, mediation analysis showed that 53.1% of the association between HGS and long-term care eligibility was mediated through TUG times., Conclusion: The TUG test was associated with long-term care eligibility among healthy older adults, implying that the test may be helpful as a predictor for the early determination of dependence in old age.

The aim of this study was to investigate factors associated with sarcopenia among elderly patients with poorly controlled diabetes mellitus (DM). We retrospectively analyzed 41 patients with type 2 DM, aged ≥65 years who required diabetes education hospitalization. Patients were classified into two groups according to the presence or absence of a weakened hand grip, and clinical characteristics were compared. Patients with a weakened hand grip ( n = 21) scored worse on a mini-mental state examination (24.3 vs. 26.5, p = 0.04), showed a higher prevalence of diabetic peripheral neuropathy (76% vs. 40%, p = 0.03), and had a higher serum phosphorus concentration (3.8 vs. 3.3 mg/dL, p < 0.01) compared to those without a weakened hand grip ( n = 20). The serum phosphorus concentration was inversely correlated to hand grip strength ( r = -0.501, p < 0.001) among the total of 41 patients. This inverse association was also confirmed after adjusting the effects of estimated glomerular filtration rate, age, and glycated hemoglobin. Thus, cognitive impairment, diabetic peripheral neuropathy, and high serum phosphorus concentrations are associated with hand grip weakness in elderly patients with type 2 DM.

Hyponatremia associated with low-dose trimethoprim in patients on concomitant systemic corticosteroid therapy has rarely been reported. Here, we describe a 57-year-old woman with a history of diabetes mellitus and hypertension treated with telmisartan, who presented with progressive visual impairment of the left eye due to anti-aquaporin-4 antibody-positive optic neuritis. The patient received pulsed intravenous methylprednisolone followed by oral prednisolone at 30 mg/day and trimethoprim-sulfamethoxazole prophylaxis (160 mg and 800 mg daily). Her serum sodium level steadily decreased, and the potassium level was slightly elevated despite well-preserved renal function. This state persisted even after telmisartan discontinuation. In addition to hypotonic hyponatremia (125 mEq/L) with natriuresis, hyperkalemic renal tubular acidosis was diagnosed based on normal anion gap metabolic acidosis and hyperkalemia with low urinary potassium excretion. After trimethoprim-sulfamethoxazole cessation, electrolytes and acid-base imbalances swiftly recovered. We can conclude that caution must be exercised when treating such patients, because even low-dose trimethoprim may cause hyponatremia concomitant with hyperkalemic renal tubular acidosis, despite the mineralocorticoid effects of systemic corticosteroids.

Background: The programmed cell death 1 (PD-1) inhibitor pembrolizumab is a promising agent for treatment of several different malignancies, but as with all immunotherapy there is a potential risk of immune-related adverse events. Adrenocorticotropic hormone (ACTH) deficiency and hypophysitis have been reported in patients treated with a different PD-1 inhibitor, nivolumab. However, clinical characteristics of these side effects associated with pembrolizumab have yet to be described in detail., Case Presentation: An 85-year-old Japanese woman was diagnosed with advanced squamous cell lung cancer. The patient was treated with 200 mg pembrolizumab every three weeks as first-line therapy. Routine examination including thyroid function, complete blood count, serum cortisol and sodium levels before each pembrolizumab infusion had shown no significant changes up to the eighth cycle. However, 8 days after the eighth cycle of single-agent pembrolizumab, she presented with rapidly worsening general fatigue and appetite loss over two days. Laboratory data revealed a low serum cortisol level (0.92 μg/dL) with inappropriately low ACTH (8.3 pg/mL), hyponatremia (122 mmol/L) and hypoglycemia (68 mg/dL). Standard-dose short ACTH testing showed an unsatisfactory cortisol response, indicating adrenal insufficiency. Pituitary magnetic resonance imaging showed diffuse substantial gadolinium enhancement, T2 hyperintensity, loss of pituitary bright spot, but no pituitary enlargement. Serum cortisol and ACTH levels were low throughout the day, and urinary free cortisol excretion fell below the lower normal limit. There was no ACTH and cortisol response in the corticotropin-releasing hormone test, despite significant responses of other anterior pituitary hormones to their corresponding challenge tests. Thus, isolated ACTH deficiency was diagnosed, and hypophysitis was suspected as the etiology. After administration of 15 mg/day hydrocortisone, the patient's debilitation, hyponatremia, and hypoglycemia swiftly disappeared., Conclusion: This is a case of isolated ACTH deficiency possibly due to hypophysitis in a patient with advanced lung cancer, in whom recent routine examinations had shown unremarkable results. We therefore conclude that isolated ACTH deficiency can suddenly arise during pembrolizumab monotherapy, albeit probably only rarely. Caution should be exercised to make sure that adrenal insufficiency is recognized immediately in order to achieve swift recovery by steroid replacement., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease characterized by progressive muscle weakness and myotonia along with multiple organ system involvements. Overall, DM1 patients show reduced life expectancy, mainly due to respiratory or cardiac abnormalities. Chronic respiratory impairment is associated with increased morbidity in DM1. The main ventilatory dysfunction etiology in DM1 is complex, consisting of both peripheral respiratory dysfunction and central respiratory drive dysfunction as well as upper airway muscle dysfunction leading to obstructive sleep apnea syndrome (SAS) and aspiration. Advancements in early diagnosis of DM1 and management with non-invasive therapeutic tools have improved life expectancy for DM1 patients. We present herein two siblings with DM1, a thin elder brother and an obese younger sister with visceral fat accumulation. Although neither had voluntary symptoms related to respiratory dysfunction, their apnea-hypopnea indices revealed severe SAS and subsequent arterial blood gases studies showed hypercapnia as well as hypoxia, suggesting central nervous system involvement with peripheral respiratory dysfunction. Non-invasive positive pressure ventilation during sleep was started following pulmonary assessment. Respiratory function should be assessed in DM1 patients, even those free of respiratory symptoms, because respiratory muscle weakness occurs in a high percentage of these patients and will shorten their lives.

Transient photoluminescence (PL) characteristics and localization phenomena in InGaN/GaN core-shell nanorods (NRs) were investigated from 6 K up to 285 K. The NRs exhibit three well-defined PL bands in the near-UV, blue, and green range ascribed to the emission of quantum well (QW) areas situated at the (1.00) sidewalls, (10.1) top facets, and (00.1) tip, respectively. At low temperature, time-resolved PL shows a fast decay time of about 0.5 ns for the semi- and non-polar QWs, while the polar QWs exhibit at least a twice-longer time. Rapid delocalization of carriers above 50 K indicates shallow potential fluctuations in the QWs. At room temperature, the characteristic fast PL decay time of the three QW bands stabilizes around 300 ps. The slow decaying PL components have different characteristic decay times that are explained by additional localization at basal stacking faults (BSFs), taking into account the quantum confined Stark effect. In addition, narrow excitonic luminescence lines are observed in the BSF-enriched polar QWs, providing direct evidence of the impact of the BSF/QW crossings on the optical properties of the NRs. A PL rise time of about 100 ps does not show any deviation between bands. These findings are suggestive of similar transport mechanisms in temperature equilibrium without inter-facet transport between different QWs. We believe that predictable transient characteristics can play a key role in creating uniform NR ensembles for device applications.