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Masao Yamaguchi,1 Yoshihiro Nishimura,2 Yuko Takumi,3 Nobuya Hayashi,4 Kei Sakamoto,3 Yuji Tohda5 1Division of Respiratory Medicine, Third Department of Medicine, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan; 2Kita-Harima Medical Center, Ono, Hyogo, Japan; 3Patient Safety Division, Research and Development, AstraZeneca K.K., Osaka, Japan; 4Data Science and Innovation Division, Research and Development, AstraZeneca K.K., Osaka, Japan; 5Department of Respiratory Medicine and Allergology, Kindai University School of Medicine, Osaka-Sayama, Osaka, JapanCorrespondence: Masao Yamaguchi, Division of Respiratory Medicine, Third Department of Medicine, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan, Tel +81-436-62-1211, Fax +81-436-62-7340, Email myama@med.teikyo-u.ac.jpIntroduction: This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan.Methods: This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥ 1.5 were defined as having severe uncontrolled asthma.Results: In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by − 1.16 (1.40 [− 1.36, − 0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics.Conclusion: No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.Keywords: benralizumab, severe uncontrolled asthma, anti-interleukin-5 receptor α monoclonal antibody, eosinophils, exacerbation, asthma control, quality of life

The domestic silkworm (Bombyx mori) is reared under controlled environments. Therefore, silkworms may be exposed at night to light used by humans working or living nearby. Artificial light at night (LAN) disturbs natural lighting cycles and negatively affects insect physiology, behavior, and ecology in the field. However, the effects of dim LAN on domestic silkworms have not been assessed in detail. The present study investigated the effects of night lighting on diapause regulation in Bombyx mori, with a focus on light sensitivity. The silkworm larvae were exposed to LAN at intensity varying from 0.1-100 lux under a short-day photoperiod that should induce diapauses, and then the incidence of diapause in eggs laid by resultant moths was evaluated. The incidence of diapause was 100 % in control (without night lighting) silkworms, but the incidence in those exposed to LAN = 0.1 lux was < 2 %. These results showed that exposing larvae to night lighting at 0.1 lux under a short-day photoperiod substantially inhibited diapause induction in the next generation. [ABSTRACT FROM AUTHOR]

Jun Aoki,1 Kazuhiro Sakamoto,1 Rina Takahashi,1 Koichiro Niwa,1 Shun Ishiyama,1 Kiichi Sugimoto,1 Hirohiko Kamiyama,1 Makoto Takahashi,1 Yutaka Kojima,1 Michitoshi Goto,1 Yuichi Tomiki,1 Toshiaki Iba21Department of Coloproctological Surgery, Juntendo University, Faculty of Medicine, Tokyo, Japan; 2Department of Emergency and Disaster Medicine, Juntendo University, Faculty of Medicine, Tokyo, JapanBackground: There is a high incidence of venous thromboembolism (VTE) during the perioperative period for cancer. Therefore, there is an urgent need to elucidate the perioperative onset and appropriate prophylaxis for VTE.Purpose: VTE during the perioperative period for colorectal cancer was evaluated by lower limb venous ultrasonic examinations (lower limb echo) under enoxaparin prophylaxis. We also examined the relationship between hemorrhagic adverse events and anti-Xa factor activity.Patients and methods: Eighty-three subjects who underwent lower limb echo during the perioperative period for colorectal cancer were prospectively included. Enoxaparin was administered for 5 days, from day 1 to day 5 after surgery. Lower limb echo was performed before surgery and on day 5 after surgery. The activated partial thromboplastin time, D-dimer levels, and anti-Xa factor activity were measured before surgery and on days 1, 3, 5, 7, and 9 after surgery.Results: VTEs before surgery were observed on lower limb echo for 16 patients (19.2%). Three patients (3.6%) had a new thrombus during the perioperative period. The preoperative D-dimer level was an independent prognostic factor for newly formed postoperative VTEs (p=0.0036; odds ratio, 19.37). Three patients (3.6%) had hemorrhagic events; however, there was no significant trend for anti-Xa factor activity.Conclusion: VTE prevention using enoxaparin was relatively safe, and D-dimer measurements before surgery were useful for predicting perioperative VTE.Keywords: postoperative complications, pulmonary thromboembolism, deep vein thrombosis, D-dimer, anti-Xa factor activity

Shunta Hori, Tatsuki Miyamoto, Keiichi Sakamoto, Takuto Shimizu, Kazuki Ichikawa, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Makito Miyake, Tatsuo Yoneda, Nobumichi Tanaka, Katsunori Yoshida, Kiyohide Fujimoto Department of Urology, Nara Medical University, Kashihara, Nara 634-8522, Japan Background: Transplant renal vein thrombosis (TRVT) is a severe vascular complication and is caused by various factors, including recipient factors, donor factors, immunosuppression regimens, and surgical techniques. Despite adequate interventions, including thrombolytic therapy or surgical thrombectomy, successful salvage of the allograft is often difficult. We observed a case of TRVT induced by compression of the renal vein immediately after intraoperative abdominal closure.Case presentation: A 41-year-old male underwent ABO-compatible living kidney transplantation. The donor was his 45-year-old sister, and her right kidney was donated. The allograft had a single artery and vein. One of the preoperative recipient problems was obesity (body mass index, 33.4 kg/m2). Intraoperative Doppler ultrasonography (US) revealed sufficient blood flow throughout the allograft, and urine output was also observed. After surgery, hematuria was observed; the urine output decreased and serum creatinine levels increased to 7.0 mg/dL. Doppler US showed a decrease in diastolic flow and an elevated resistive index, which were similar findings to those noted in acute rejection. Although steroid pulse therapy was initiated, allograft dysfunction was worsening. On postoperative day 4, surgical exploration revealed TRVT; consequently, thrombectomy was performed. The urine output increased, and serum creatinine levels decreased to 1.8 mg/dL. The cause of TRVT development may be that the transplant renal vein was relatively short, due to the right kidney being compressed by surrounding tissues after abdominal closure, and that TRVT was gradually developing due to stagnant blood flow.Conclusion: Although TRVT is induced by multiple factors, an accurate diagnosis is often difficult. Understanding these factors, including obesity, and considering TRVT as a cause of allograft dysfunction are important during the pre-, peri-, and postoperative periods. Knowledge of TRVT can lead to early and accurate diagnosis and intervention, resulting in better outcomes for the patients with allograft dysfunction. Keywords: kidney transplantation, surgical exploration, transplant renal vein thrombosis, thrombectomy

Norihito Omote, Naozumi Hashimoto, Masahiro Morise, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Yoshio Nakahara, Yoshinori Hasegawa Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan Background: Non-small cell lung cancer (NSCLC) is the predominant cause of death in patients with COPD, and the severity of COPD in NSCLC patients is classified mainly as mild to moderate. Most advanced NSCLC patients with mild to moderate COPD are treated with chemotherapy; however, the feasibility for and prognosis after chemotherapy of these patients are not well understood. The aim of this study was to elucidate the impact of mild to moderate COPD on the feasibility for and prognosis after chemotherapy in NSCLC patients.Patients and methods: A retrospective review was performed on 268 NSCLC patients who received first-line chemotherapy from 2009 to 2014 in our institution. Finally, 85 evaluable patients were included in this study. The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients with mild to moderate COPD and those without COPD (non-COPD).Results: Forty-three patients were classified as COPD (27 cases mild and 16 cases moderate) and 42 patients as non-COPD. The COPD group were older and had fewer never-smokers than the non-COPD group. The objective response rate did not differ between groups (p=0.14). There was no significant difference in overall survival between COPD and non-COPD groups (15.0 and 17.0 months, log-rank test p=0.57). In the multivariate Cox’s proportional hazard model, the adjusted hazard ratio (HRadj) was statistically significant for male sex (HRadj =5.382, 95% CI: 1.496–19.359; p=0.010), pathological diagnosis of adenocarcinoma (HRadj =0.460, 95% CI: 0.223–0.948; p=0.035), and epithelial growth factor receptor negative mutation (HRadj =6.040, 95% CI: 1.158–31.497; p=0.033), but not for the presence of COPD (HRadj =0.661, 95% CI: 0.330–1.325; p=0.24). Toxicity profile in COPD group was favorable, as in the non-COPD group.Conclusion: Mild to moderate COPD did not have a significant deleterious impact on toxicity and prognosis in NSCLC patients. Keywords: toxicity, survival, prognostic factors

The impact of resolving western boundary currents and mesoscale eddies on a carbon circulation simulation for the North Pacific Ocean is investigated to evaluate the merits of using high‐resolution ocean biogeochemical models for climate projections. Simulations by a 100‐km resolution global ocean biogeochemical model with and without embedding a 10‐km resolution model in the North Pacific Ocean are compared. The major improvement in the high‐resolution simulation is the representation of the Kuroshio, its extension current, and the recirculation gyres formed to its south and north, resulting in a proper representation of the North Pacific subtropical mode water (STMW) and an increase in storage of the anthropogenic CO2 (Canth) in STMW by about two‐thirds. The larger storage rate in STMW is caused by supply of a larger amount of warm surface water containing rich Canth to the formation region by the intensified Kuroshio. A huge buoyancy loss from this warm water results in the increased formation of STMW that occupies a vast area in the western subtropical gyre. The surface uptake of Canth in the formation region of STMW is slightly increased but is largely comparable to that of the low‐resolution model. Moreover, there is no structural difference in Canth uptake in other parts of the subtropical region. Thus, the improvement of Canth distribution can be understood as a redistribution of water mass in the subtropical gyre by the improved circulation. The present assessment motivates the use of a high horizontal resolution ocean model in next‐generation projection experiments with carbon cycles. Plain Language Summary: Accurately representing absorption and accumulation of anthropogenic CO2 (Canth) by the ocean in Earth system models is important to reliably project future climate change. This study investigates the impact of realistically expressing the Kuroshio, which is not expressed adequately in the majority of current Earth system models, on a carbon circulation simulation for the North Pacific Ocean. Two simulations differing in the horizontal grid spacing, about 100 and 10 km, are compared. The intensified Kuroshio in the fine resolution model results in an improved oceanic structure for the upper 500‐m depths in the western North Pacific Ocean, and more Canth is accumulated there, which is closer to observations. Budget analysis suggests that source for the increased Canth accumulation is not local surface flux but a supply of Canth‐rich surface water from low latitudes by the intensified Kuroshio. Such improvements would give more fidelity to projections of regional subsurface water acidification rate. Overall, the use of a fine horizontal resolution ocean model can be recommended in next‐generation projection experiments with carbon cycles for the North Pacific Ocean. Key Points: Storage of anthropogenic carbon in the western North Pacific Ocean is improved by using a 10‐km horizontal resolution ocean modelImprovement in the formation and distribution of the North Pacific subtropical mode water is a keyUse of 10‐km class high horizontal resolution ocean models is recommended as part of Earth system models with carbon cycles [ABSTRACT FROM AUTHOR]

Kazuo Sakamoto, Masatsugu Nozoe, Yoshitomo Tsutsui, Nobuhiro Suematsu, Toru Kubota, Masanori Okabe, Yusuke Yamamoto Division of Cardiology, Cardiovascular and Aortic Center, Saiseikai Fukuoka General Hospital, Fukuoka, Japan Abstract: Cardiac magnetic resonance imaging (MRI) is a useful tool for detecting the arrhythmogenic substrate in cardiac sarcoidosis. We herein present a case of bipolar radiofrequency catheter ablation for ventricular tachycardia (VT) complicated with cardiac sarcoidosis, guided by pre-procedural cardiac MRI. Neither echocardiography nor endocardial voltage mapping suggested a septal VT substrate. However, MRI alone detected intramural lesions in the septum. Although application of endocardial energy failed to treat the VT, bipolar ablation targeting the potential substrate identified by MRI successfully eliminated the VT. Even when no abnormalities are depicted on echocardiography and endocardial voltage mapping, intramural scar tissue identified by cardiac MRI could be critical for VT. Keywords: cardiac sarcoidosis, VT, MRI, bipolar ablation

Koji Ishikawa,1 Takashi Nagai,1 Keizo Sakamoto,1 Kenji Ohara,2 Takeshi Eguro,1,2 Hiroshi Ito,1 Yoichi Toyoshima,1 Akatsuki Kokaze,3 Tomoaki Toyone,1 Katsunori Inagaki1 1Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, 2Department of Orthopaedic Surgery, Yamanashi Red Cross Hospital, Yamanashi, 3Department of Public Health, Showa University School of Medicine, Tokyo, Japan Abstract: Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P76.5 µg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P

Masushi Kohta,1 Kazumi Sakamoto,2 Yasuhiro Kawachi,3 Tsunao Oh-i4 1Medical Engineering Laboratory, ALCARE Co, Ltd, Tokyo, 2Department of Nursing, 3Department of Dermatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, 4Department of Dermatology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan Purpose: There have been previous clinical studies regarding the impact of dressings on the prevention of pressure ulcer development. However, it remains unclear whether one type of dressing is better than any other type for preventing ulcer development during surgery. Therefore, we compared the effects of ceramide 2-containing hydrocolloid dressing with film dressings in high-risk patients with regard to reducing the incidence of pressure ulcer development during surgery. Patients and methods: A prospective, randomized, open-label, clinical trial was conducted involving patients who were at a high risk of developing pressure ulcers at a Japanese hospital. The intervention group received ceramide 2-containing hydrocolloid dressings (n=66), and the control group received film dressings (n=64). The primary end point was the incidence rate of pressure ulcer development in both groups; skin damage, such as blanchable erythema, skin discoloration, contact dermatitis, and stripped skin, was recorded as the secondary end point. The relative risk (RR) and 95% confidence interval (CI) were assessed to compare the probability ratios of pressure ulcer development between the groups. Results: There were significantly fewer patients who developed pressure ulcers in the intervention group than in the control group (RR, 0.37; 95% CI, 0.05–0.99; P=0.04). In the post hoc subgroup analysis, the superiority of the intervention group was more marked when patients had a lower body mass index (P=0.02), lower albumin values (P=0.07), and operation time of 3 hours or more and less than 6 hours (P=0.03). There was no evidence of any statistically significant differences in the types of skin damage reported. Conclusion: Application of ceramide 2-containing hydrocolloid dressing reduced the risk of pressure ulcer development in patients who were at a high risk during surgery compared with film dressings. Keywords: operating room, wound dressing, friction, skin protection, shear

Masushi Kohta,1 Kazumi Sakamoto,2 Tsunao Oh-i31Medical Engineering Laboratory, ALCARE Co, Ltd, Sumida-ku, Tokyo, 2Department of Nursing, 3Department of Dermatology, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, JapanBackground: Numerous clinical challenges regarding adhesive dressings have shown that using an adhesive dressing could minimize or prevent superficial skin loss in patients at risk of developing pressure ulcers. However, evidence that polyurethane film dressings and ceramide 2-containing hydrocolloid dressing can reduce the risk of pressure ulcer development in high-risk patients undergoing surgery is limited. Therefore, we assessed the effects of application of these dressings for reducing the risk of pressure ulcer development in these patients and identified other risk factors.Methods: A matched case-control study was conducted involving 254 patients at high risk for pressure ulcer development at one acute care hospital in Japan. No patients in this study had a pressure ulcer at the start of the study. Thirty-one patients developed a pressure ulcer during surgery, and these patients were defined as cases. Controls were randomly matched for sex and age (±4 years), from which 62 patients were selected. Medical records were obtained for preoperative factors, including age, sex, body mass index, diabetes mellitus, albumin, total protein, C-reactive protein, white cell count, red cell count, and hemoglobin, and for intraoperative factors, including dressing application, operation time, body position, and surgery type. The odds ratio (OR) and 95% confidence interval (CI) were determined to identify risk factors for pressure ulcer development in patients undergoing surgery.Results: By multiple logistic regression analysis, there was a significantly reduced risk of pressure ulcer development for patients who had dressing applications as compared with those without dressing applications (OR 0.063; 95% CI 0.012–0.343; P=0.001). Prone position (OR 8.791; 95% CI 1.630–47.400; P=0.01), prolonged operation time (OR 1.684; 95% CI 1.189–2.385, P=0.003), and reduced body mass index (OR 0.774; 95% CI 0.584–0.948; P=0.02) were also significant predictive risk factors for development of a pressure ulcer.Conclusion: Application of film dressing and ceramide 2-containing hydrocolloid dressing reduced the risk of pressure ulcer development in high-risk patients undergoing surgery.Keywords: pressure ulcer prevention, operating room, wound dressing, friction

Tsuyoto Harada, Ken Inada, Kazuo Yamada, Kaoru Sakamoto, Jun Ishigooka Department of Psychiatry, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan Objective: Patients often develop neuropsychiatric symptoms such as anxiety and agitation after they have started taking an antidepressant, and this is thought to be associated with a potentially increased risk of suicide. However, the incidence of antidepressant-induced jitteriness/anxiety syndrome has not been fully investigated, and little has been reported on its predictors. The aim of this study was to survey the incidence of antidepressant-induced jitteriness/anxiety syndrome and clarify its predictors in a natural clinical setting.Materials and methods: Between January 2009 and July 2012, we prospectively surveyed 301 patients who had not taken any antidepressants for 1 month before presentation, and who were prescribed antidepressants for 1 month after their initial visit. Patients were classified as developing antidepressant-induced jitteriness/anxiety syndrome if they experienced any symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania during the first month.Results: Among the 301 patients, 21 (7.0%) developed antidepressant-induced jitteriness/anxiety syndrome. Major depressive disorder and a diagnosis of mood disorder in first-degree relatives of patients were significantly associated with induction of antidepressant-induced jitteriness/anxiety syndrome (odds ratio 10.2, P=0.001; odds ratio 4.65, P=0.02; respectively). However, there was no such relationship for sex, age, class of antidepressant, combined use of benzodiazepines, or diagnosis of anxiety disorder.Conclusion: The findings of this study suggest that major depressive disorder and a diagnosis of mood disorder in first-degree relatives may be clinical predictors of antidepressant-induced jitteriness/anxiety syndrome.Keywords: side effects, antidepressants, selective serotonin-reuptake inhibitors, tricyclic antidepressive agents, suicide