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Yuntae Kim,1,2 Shun Yamamoto,1 Ken Kato1 1Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; 2Department of Gastroenterology, St. Luke International Hospital, Tokyo, JapanCorrespondence: Ken Kato, Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, Tel +81-3-3542-2511, Fax +81-3-3542-3815, Email kenkato@ncc.go.jpAbstract: Esophageal cancer (EC) is the seventh most common malignancy globally. There are two main histological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. ESCC is the predominant histological type of esophageal cancer worldwide and has worse prognosis than esophageal adenocarcinoma. However, effective treatment for patients with ESCC remains limited. Moreover, the risk of recurrence remains high in patients with resectable ESCC even with perioperative multidisciplinary treatment, such as chemoradiotherapy or chemotherapy. Nivolumab, a human monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein 1, has recently been identified as a potential treatment for patients with metastatic esophageal cancer based on the results of the ATTRACTION-3 and CheckMate 648 trials. The CheckMate 577 trial showed survival benefits of postoperative nivolumab monotherapy compared with placebo in patients with resectable locally advanced esophageal cancer who did not achieve a pathological complete response after preoperative chemoradiotherapy. In this review, we discuss the data on the efficacy and safety of postoperative nivolumab and share future perspectives on immune checkpoint inhibitors as perioperative therapy for patients with locally advanced ESCC.Keywords: esophageal squamous cell carcinoma, immune checkpoint inhibitor, nivolumab, postoperative treatment

Akihiro Shiroshita,1– 3 Shungo Yamamoto,4 Keisuke Anan,3,5 Hokuto Suzuki,1 Masafumi Takeshita,1 Yuki Kataoka3,6– 8 1Department of Respiratory Medicine, Ichinomiyanishi Hospital, Ichinomiya, Japan; 2Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA; 3Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan; 4Department of Infectious Disease, Kyoto City Hospital, Kyoto, Japan; 5Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan; 6Department of Internal Medicine, Kyoto Min-Iren Asukai Hospital, Kyoto, 606-8226, Japan; 7Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan; 8Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/Public Health, Kyoto, 606-8501, JapanCorrespondence: Akihiro Shiroshita, Department of Respiratory Medicine, Ichinomiyanishi Hospital, 1 Kaimeihira, Ichinomiya, Aichi Prefecture, 494-0001, Japan, Tel +81-80-3807-4960, Fax +81-586-48-0055, Email akihirokun8@gmail.comPurpose: Whether the empirical use of anti-pseudomonal antibiotics actually improves patient outcomes is unclear. Hence, we aimed to determine whether empirical anti-pseudomonal antibiotics are better than anti-pseudomonal antibiotics in treating patients with recurrent lower respiratory tract infections (LRTIs).Patients and Methods: We extracted data from the Japanese nationwide database of the Real World Data Co., Ltd. Our target population was patients with LRTIs, defined as chronic obstructive pulmonary disease exacerbation and pneumonia. We included patients aged ≥ 40 years who were admitted for lower respiratory tract infections ≥ 2 times within 90 days. We excluded patients who had an event (death or transfer) within 24 h after admission. We ran a frailty model adjusted for the following confounding factors: number of recurrences, age, body mass index, activities of daily living, Hugh-Johns classification, altered mental status, oxygen use on admission, blood urea nitrogen, and systemic steroid use.Results: We included 893 patients with 1362 observations of recurrent LRTIs. There were 897 (66%) observations in the non-anti-pseudomonal antibiotic group and 465 (34%) in the anti-pseudomonal group; the numbers of in-hospital deaths were 86/897 (10%) and 63/465 (14%), respectively. Our frailty model yielded an adjusted hazard ratio (HR) (anti-pseudomonal group/non-anti-pseudomonal group) of 1.49 (95% confidence interval, 1.03– 2.14).Conclusion: The empirical use of anti-pseudomonal antibiotics was associated with a higher HR of in-hospital mortality than the use of non-anti-pseudomonal antibiotics. Physicians might need to consider limiting the prescription of anti-pseudomonal antibiotics based on background factors such as the patient’s baseline function and disease severity. Further studies are needed to evaluate the causal relationship between empirical anti-pseudomonal antibiotics and mortality, and identify specific patient population who benefit from empirical anti-pseudomonal antibiotics.Keywords: clinical epidemiology, COPD, Emphysema, infection and inflammation, pneumonia

Daichi Tsukakoshi,1 Shuhei Yamamoto,1 Shuhei Takeda,1 Keisuke Furuhashi,1 Masaaki Sato2 1Department of Rehabilitation, Shinshu University Hospital, Matsumoto, Japan; 2Division of Occupational Therapy, School of Health Sciences, Shinshu University, Matsumoto, Nagano, JapanCorrespondence: Shuhei Yamamoto, Department of Rehabilitation, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan, Tel +81-263-37-2836, Fax +81-263-37-2835, Email syamamoto@shinshu-u.ac.jpAbstract: The purpose of this narrative review is to examine rehabilitation modalities for patients with heart failure and Frailty who require comprehensive intervention. Ischemic heart disease is the leading cause of death worldwide, accounting for 16% of global mortality. Due to population growing and aging, the total number of heart failure patients continues to rise, a condition known as the heart failure pandemic. Furthermore, frailty has been associated with an increased risk for heart failure and increased morbidity and mortality. The 2021 update of the 2017 ACC expert consensus decision pathway for optimization of HF treatment has become more concerning, citing frailty as one of the 10 most important issues associated with heart failure with reduced ejection fraction (HFrEF). Frailty and heart failure share common pathological mechanisms and are associated with poor clinical outcomes. Most studies of frailty in patients with heart failure primarily focus on physical frailty, and associations between psycho-psychological and social factors such as cognitive dysfunction and social isolation have also been reported. These results suggest that a more comprehensive assessment of frailty is important to determine the risk in patients with heart failure. Therefore, mechanisms of the three domains, including not only physical frailty but also cognitive, psychological, spiritual, and social aspects, should be understood. In addition to interventions in these three domains, nutritional and pharmacological interventions are also important and require tailor-made interventions for the widely varied conditions associated with heart failure and frailty. Although several studies have shown a relationship between frailty and prognosis in patients with heart failure, interventions to improve the prognosis have not yet been established. Further information is needed on frailty intervention by a multidisciplinary team to improve the prognosis.Keywords: frailty, heart failure, rehabilitation, cardiovascular diseases

Mizue Ichinose,1,2 Itaru Miura,1 Sho Horikoshi,1,3 Shinnosuke Yamamoto,1,4 Keiko Kanno-Nozaki,1 Kenya Watanabe,5 Hirooki Yabe1 1Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan; 2Department of Neuropsychiatry, Hoshigaoka Hospital, Koriyama, Japan; 3Department of Psychiatry, Horikoshi Psychosomatic Clinic, Fukushima, Japan; 4Department of Psychiatry, Fukushima Red Cross Hospital, Fukushima, Japan; 5Department of Pharmacy, Fukushima Medical University Hospital, Fukushima, JapanCorrespondence: Itaru MiuraDepartment of Neuropsychiatry, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, 960-1295, JapanTel +81-24-547-1331Fax +81-24-548-6735Email itaru@fmu.ac.jpObjective: Although switching antipsychotics is a common strategy in the treatment of schizophrenia, caution is needed because of the risk of worsening of psychosis, particularly when switching to a dopamine D2 partial agonist. Homovanillic acid (HVA), a dopamine metabolite, is thought to be a possible indicator of the response to antipsychotics. We examined the effects of switching to brexpiprazole monotherapy from other antipsychotics on plasma HVA levels and side effects during maintenance treatment of schizophrenia.Methods: The antipsychotics of 37 Japanese patients with schizophrenia or schizoaffective disorder were switched to brexpiprazole for the improvement of side effects. We evaluated clinical symptoms and extrapyramidal symptoms (EPS) and took fasting blood samples at baseline and endpoint (eight weeks after completing the switch) to measure plasma levels of HVA, prolactin, and metabolic parameters.Results: Switching to brexpiprazole significantly decreased the Drug-Induced Extrapyramidal Symptoms Scale total score (p=0.008), prolactin levels (p< 0.001), body weight (p=0.046), and body-mass index (p=0.034), and increased HDL cholesterol (p=0.008). On the other hand, switching to brexpiprazole did not change plasma levels of HVA or Positive and Negative Syndrome Scale scores.Conclusion: Switching to brexpiprazole significantly improved EPS, high prolactin levels, and metabolic side effects without elevating plasma HVA levels. Brexpiprazole may stabilize dopaminergic neural transmission and could be a useful strategy to decrease the burden in patients with schizophrenia during the maintenance phase. Because of the small sample size, further studies with larger sample sizes are needed to confirm and extend our results.Keywords: brexpiprazole, extrapyramidal symptoms, EPS, homovanillic acid, prolactin, schizophrenia, switching

Mikio Momoeda,1 Sayako Akiyama,2 Shigetomo Yamamoto,3 Masami Kondo,4 Takeshi Fukai4 1Department of Integrated Women’s Health, St Luke’s International Hospital, Tokyo, Japan; 2Market Access, Bayer Yakuhin Ltd., Tokyo, Japan; 3Medical Affairs, Bayer Yakuhin Ltd., Osaka, Japan; 4Product Development, Bayer Yakuhin Ltd., Osaka, JapanCorrespondence: Mikio Momoeda 9-1 Akashicho, Chuo-ku, Tokyo 104-8560, JapanTel +81-3-3541-5151Fax +81-3-5550-2605Email momoeda-tky@umin.ac.jpPurpose: Dysmenorrhea negatively affects women’s quality of life and poses a considerable economic burden. A recent study in Japanese patients with dysmenorrhea (NCT01892904) reported a significant reduction in the number of days with menstrual pain after treatment with a flexible extended regimen of ethinylestradiol (EE)/drospirenone (DRSP) compared with a cyclic regimen. However, individual patients’ menstrual pain patterns and intensities were not indicated. Heatmapping was used to visualize menstrual pain patterns and intensities by re-evaluating the previously published data from NCT01892904.Patients and Methods: NCT01892904 was a Phase III, multicenter, randomized, open-label, active-control study of 212 women aged ≥ 20 years randomized 1:1 to receive flexible extended or 28-day cyclic EE/DRSP treatment. Daily pain levels were recorded in patient diaries, and menstrual pain patterns and intensities were visualized using heatmapping. Patients were stratified by baseline dysmenorrhea scores and primary or secondary dysmenorrhea.Results: The heatmap data demonstrated that EE/DRSP reduced the degree of menstrual pain. Regular peaks of menstrual pain were alleviated in the extended regimen group but were still observed in the cyclic regimen group. While a decrease in the days with menstrual pain was observed in patients with higher baseline dysmenorrhea scores (5– 6), those with lower baseline scores (3– 4) were more likely to experience lower intensities of menstrual pain. Although pain relief was less likely in patients with secondary dysmenorrhea, those who had lower baseline dysmenorrhea scores (3– 4) and received the flexible extended regimen experienced a greater reduction in the number of days with menstrual pain than those who received the cyclic regimen.Conclusion: Heatmapping effectively visualized the daily burden of menstrual pain in Japanese patients with dysmenorrhea. The analysis using heatmaps suggested that the flexible extended EE/DRSP treatment regimen was more likely to alleviate the regular occurrence of menstrual pain peaks compared with the cyclic regimen.Keywords: dysmenorrhea, ethinylestradiol, pain measurement, patient-reported outcomes

Kentaro Inamura,1,2 Gulanbar Amori,1,2 Takeshi Yuasa,3 Shinya Yamamoto,3 Junji Yonese,3 Yuichi Ishikawa1,21Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; 3Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, JapanBackground: B7-H3 (CD276), an immune checkpoint molecule, regulates the tumor-immune microenvironment and controls the aggressiveness of various tumors. Although B7-H3 expression has been associated with the number of tumor-infiltrating FOXP3+ regulatory T cells, little information is available about this association in clear cell renal cell carcinoma (ccRCC).Methods: Using 252 consecutive cases of ccRCC, we examined the association of B7-H3 expression in both the tumor cells and tumor vasculature with the number of tumor-infiltrating FOXP3+ cells and assessed whether the effects of B7-H3 expression on survival differ according to FOXP3+ cell number.Results: High B7-H3 expression was observed in the tumor cells and tumor vasculature in 15% and 54% of ccRCC cases, respectively. High FOXP3+ cell number was positively associated with B7-H3 expression in both the tumor cells (odds ratio [OR] =2.93; P=0.0041) and tumor vasculature (OR=2.45; P=0.0007). Tumor cell B7-H3 expression was associated with increased disease-specific mortality in high FOXP3+ cell number group (hazard ratio [HR] =2.98; P=0.017), but not in low FOXP3+ group (P=0.71). Tumor vasculature B7-H3 expression was also associated with increased disease-specific mortality in high FOXP3+ cell number group (HR=4.86; P=0.0025), but not in low FOXP3+ group (P=0.48).Conclusion: We demonstrate that B7-H3 expression in both tumor cells and the tumor vasculature is positively associated with FOXP3+ cell number. Such expression is also associated with increased mortality in high FOXP3+ cell number group, but not in low FOXP3+ cell number group. These findings suggest that B7-H3-expressing ccRCCs may exert tumor-promoting immunity by interacting with FOXP3+ regulatory T cells in the tumor microenvironment.Keywords: immune checkpoint inhibitor, immunotherapy, prognosis, renal cancer, TIL

Saki Yamamoto,1 Akira Iwata,1 Yuki Yano,1 Toshimitsu Ohmine,1 Keisuke Honma,1 Kazuma Senzaki,1 Minami Fujiwara,1 Takayuki Murakami,1 Junji Inoue,1 Yuki Sano,2 Shuji Okagawa,3 Yuta Otsuki,4 Hideyuki Wanaka,5 Masataka Kataoka,1 Hiroshi Iwata61Department of Physical Therapy, Faculty of Comprehensive Rehabilitation, Osaka Prefecture University, Habikino, Osaka, Japan; 2Department of Rehabilitation, Osaka General Medical Center, Osaka, Osaka, Japan; 3Department of Rehabilitation, Tatsumi Hospital, Ikeda, Osaka, Japan; 4Department of Rehabilitation, Kisei Hospital, Osaka, Osaka, Japan; 5Department of Rehabilitation, Kobe Rosai Hospital, Kobe, Hyogo, Japan; 6Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, JapanPurpose: Movement velocity of the limbs or trunk plays an important determinant of gait speed in older adults. Movement velocity-focused training of the lower limbs or trunk has recently been shown to be an effective intervention to improve gait ability. Because movement velocities of various body regions are significantly correlated, movement velocity training of the upper limbs may also be effective for improving gait speed. Therefore, the purpose of this study was to investigate whether movement velocity training of the upper limbs in a seated position is effective for improving gait ability.Patients and methods: This study was a nonrandomized controlled trial. The participants were older adults residing in geriatric health service facilities. They were assigned to the movement velocity training of the upper limbs group (n=26) or control group (n=15). The participants in the training group performed exercises (three times per week for 10 weeks) to move the upper limbs as quickly as possible. The outcomes were gait speed, movement velocity, and quadriceps strength. These measurements were performed preintervention and 4, 8, and 10 weeks after intervention.Results: A significant time–group interaction was found for maximum gait speed and movement velocity of the upper limbs. Bonferroni post-hoc test showed significant improvement in gait speed between preintervention and 10 weeks after intervention in the training group. The movement velocity of the upper limbs was significantly improved between preintervention and 4, 8, and 10 weeks after intervention.Conclusion: Movement velocity training of the upper limbs showed significant and clinically relevant improvements in maximum gait speed at 10 weeks after intervention. This training is a potentially useful intervention and can be safely performed.Keywords: older people, movement velocity training, arm, gait speed, seated position

Guzel Bikbova,1,2 Toshiyuki Oshitari,1 Takayuki Baba,1 Mukharram Bikbov,2 Shuichi Yamamoto1 1Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan; 2Cornea and Refractive Surgery Department, Ufa Eye Research Institute, Ufa, Russia Abstract: Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy. Keywords: diabetes mellitus, cornea, innervation, neuroprotective therapy

Ryuichi Hirano,1,2 Yuichi Sakamoto,3 Junichi Kitazawa,3 Shoji Yamamoto,1 Hiroyuki Kayaba2 1Department of Pharmacy, Aomori Prefectural Central Hospital, Aomori, Japan; 2Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Laboratory Medicine, Aomori Prefectural Central Hospital, Aomori, Japan Background: Candidemia is associated with high mortality, and its prognostic factors need to be examined in more detail in order to improve its management. A case of breakthrough (BT) candidemia is defined as the development of candidemia during antifungal therapy. The microbiological characteristics of and appropriate clinical practices for BT candidemia remain unclear. Objectives: The primary objective of the present study was to identify the prognostic factors of candidemia, while the secondary objective was to elucidate the microbiological characteristics of patients with BT candidemia. Materials and methods: A total of 121 patients diagnosed with candidemia between January 2007 and December 2016 were enrolled in this study. The primary outcome was the 30-day mortality rate. Results: The overall incidence of candidemia was 0.056 cases/1000 inpatients. Among the 126 Candida isolated, C. albicans accounted for 36%, C. parapsilosis 26%, C. glabrata 12%, C. ­guilliermondii 14%, C. tropicalis 3%, C. pelliculos 1%, and other unidentifiable Candida ­species 8%. The 30-day mortality rate was 33%. In a multivariate Cox hazard analysis, C. albicans, the absence of antifungal therapy, age, lung disease, and mechanical ventilation were associated with a high mortality rate, whereas C. parapsilosis, the removal of a central venous catheter, and surgical wards were associated with a lower mortality rate. Fourteen patients had BT candidemia. A significant difference was observed in the proportion of C. guilliermondii and other Candida species exhibiting resistance to fluconazole and voriconazole, between patients with and without BT candidemia. Resistance to fluconazole was prominent in patients that developed candidemia with a history of azole antifungal agents. Conclusion: The prompt initiation of antifungal therapy and removal of central venous ­catheter were essential for better outcomes. A class switch to other antifungal agents needs to be considered in empirical antifungal therapy for BT candidemia with a history of exposure to azole antifungal agents. Keywords: antifungal stewardship, breakthrough candidemia, candidemia, Japan

Mitsuru Yashiro,1 Masaki Ohya,1 Toru Mima,1 Yumi Ueda,2 Yuri Nakashima,1 Kazuki Kawakami,1 Yohei Ishizawa,2 Shuto Yamamoto,1 Sou Kobayashi,1 Takurou Yano,1 Yusuke Tanaka,1 Kouji Okuda,1 Tomohiro Sonou,1 Tomohiro Shoshihara,1 Yuko Iwashita,1 Yu Iwashita,1 Kouichi Tatsuta,1 Ryo Matoba,2 Shigeo Negi,1 Takashi Shigematsu1 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2DNA Chip Research Inc., Minato, Japan Background: FGF23 plays an important role in calcium–phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium–phosphorus metabolism. Methods: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. Results: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. Conclusion: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells. Keywords: FGF23, STAT1, PPARγ, DNA microarray, bioinformatics analysis, nonprotein-coding gene

Gen Miura, Takayuki Baba, Toshiyuki Oshitari, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan Purpose: The aim of this study is to determine the effect of pupil size of eyes with cataracts on the flicker electroretinograms (ERGs) elicited and recorded with the RETeval system.Patients and methods: Forty-one eyes of 41 patients (mean age, 76.5±7.3 years) that had grade 2 nuclear or cortical cataract without any other abnormalities were studied. Flicker ERGs were recorded before and after mydriatic drops instillation. The ERGs were elicited by the white light delivered at the frequency of 28.3 Hz and intensities of 2, 8, and 32 Td-s. The amplitudes and the implicit times of the flicker ERGs before and after mydriasis were compared.Results: There were no significant differences between the amplitudes before and after mydriasis (P=0.35, 2 Td-s; P=0.31, 8 Td-s; P=0.50, 32 Td-s). There were also no significant differences between the implicit times before and after mydriasis (P=0.86, 2 Td-s; P=0.98, 8 Td-s; P=0.95, 32 Td-s). The mean amplitudes and implicit times of the nuclear and cortical cataracts groups before the mydriasis were also not significantly different from those after mydriasis for all stimulus intensities.Conclusion: The lack of significant differences in the amplitudes and the implicit times of the flicker ERG of cataractous eyes before and after mydriasis indicated that the RETeval flicker ERGs in cataractous eyes is less affected by the pupil diameter. With our earlier study, it was assumed that the effect of cataracts on the RETeval flicker ERGs was due to the opacity of the crystalline lens, and the influence of the cataract would not be reduced or increased by mydriasis. Keywords: electroretinogram, ERG, flicker ERG, cataract, RETeval

Junji Katsuhira,1,2 Sumiko Yamamoto,3 Nodoka Machida,4 Yuji Ohmura,5 Masako Fuchi,6 Mizuho Ohta,7 Setsuro Ibayashi,7 Arito Yozu,8 Ko Matsudaira2 1Department of Prosthetics and Orthotics and Assistive Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, 2Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 3Graduate School of International University of Health and Welfare, Tokyo, 4International University of Health and Welfare, School of Health Sciences at Narita, Department of Physical Therapy, Chiba, 5International University of Health and Welfare, School of Health Sciences at Odawara, Department of Physical Therapy, Kanagawa, 6Department of Occupational Therapy, Kyusyu Nutrition Welfare University, Fukuoka, 7Seiai Rehabilitation Hospital, Fukuoka, 8Center for Medical Sciences, Ibaraki Prefectural University of Health Science, Ibaraki, Japan Purpose: The synergistic effects of a trunk orthosis and an ankle–foot orthosis (AFO) in stroke patients with a hemiplegic gait are unclear. We previously developed a trunk orthosis with joints providing resistive force (TORF) to modify malalignment of the trunk and pelvis and confirmed its positive effects in stroke patients during level walking without an AFO. The aim of the present study was to determine if this trunk orthosis and an AFO have synergistic effects during level walking in community-dwelling patients with chronic stroke. Methods: Twenty-eight community-dwelling stroke patients performed level walking at a self-selected speed with an AFO and again while wearing a TORF (TORF group) or a corset (control group). Spatiotemporal, kinematic, and kinetic data were recorded using a three-dimensional motion analysis system. Results: When compared with the control group, the TORF group showed significant increases in walking speed, number of steps on the paretic leg per minute, and peak ankle plantar flexion moment during the single stance phase. Conclusion: The TORF increased the ankle joint plantar flexion moment at the end of the single stance phase during level walking in stroke patients, leading to an increase in their gait speed because of the modified trunk and pelvis alignment. Keywords: biomechanics, orthosis, gait, stroke, joint moment, motion analysis

Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan Background: Various biomarkers have been shown to predict prognosis in various types of cancers. However, these biomarkers have not been studied in advanced small cell lung cancer (SCLC). The modified Glasgow prognostic score (mGPS) is based on serum albumin level and C-reactive protein (CRP). The prognostic nutritional index (PNI) is a combination of serum albumin level and absolute lymphocyte count. This study aimed to evaluate the prognostic value of mGPS and PNI in SCLC.Methods: We retrospectively reviewed and calculated mGPS and PNI for patients with stage IIIB or IV SCLC who initiated platinum-based combination chemotherapy between November 2007 and June 2016. We compared overall survival (OS) and progression-free survival (PFS) between high and low groups of these two biomarkers. Univariate and multivariate Cox hazard analyses assessed the prognostic value of these biomarkers.Results: We reviewed 97 SCLC patients. The OS of patients with mGPS 0–1 and higher PNI was significantly longer than that of those with mGPS 2 and lower PNI. The PFS of mGPS 0–1 was significantly longer than that of mGPS 2, while there was no significant difference in PFS according to PNI. Multivariate analyses found mGPS 0–1 (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.27–4.31, P

Tomohiro Nizawa, Takayuki Baba, Masayasu Kitahashi, Toshiyuki Oshitari, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan Purpose: To determine the differences in the retinal sensitivities obtained by microperimetry with a single cross or a circular fixation target in normal individuals.Methods: Thirty-two eyes of 16 healthy volunteers (mean age 28.9±1.4 years, range 24–44 years) were studied. The retinal sensitivity of the central 0 degrees and of the mean central 2 degrees consisting of 8 points were determined independently using the two different fixation targets with Microperimeter 3. The Goldmann III stimulus with a luminance of 1.0 cd/m2 was presented for 200 ms on a white background.Results: The retinal sensitivity of the central 0 degrees was significantly better with the circular target than that with the cross target (P=0.003, right eyes; P=0.001, left eyes). The mean retinal sensitivity in the central 2 degrees was not significantly different between the cross and circular fixation targets. (P=0.07, right eyes; P=0.08, left eyes).Conclusion: These results indicate that the circular fixation target is a better target to use to evaluate the central retinal sensitivity. The difference in the retinal sensitivity is most likely due to the cross fixation target overlapping the test stimulus target. Keywords: microperimetry, retinal sensitivity, fixation targets, stimuli

Shoichiro Yamamoto,1 Seigo Miyoshi,1 Hitoshi Katayama,1 Mikio Okazaki,2 Hisayuki Shigematsu,2 Yoshifumi Sano,2 Minoru Matsubara,3 Naohiko Hamaguchi,1 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension, and Nephrology, 2Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, 3Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama, Japan Purpose: Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices.Patients and methods: Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland–Altman analysis.Results: Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P0.8 and P

Mikio Momoeda,1 Masami Kondo,2 Joerg Elliesen,3 Masanobu Yasuda,2 Shigetomo Yamamoto,4 Tasuku Harada5 1Department of Integrated Women’s Health, St Luke’s International Hospital, Tokyo, 2Product Development, Bayer Yakuhin Ltd, Osaka, Japan; 3Global Clinical Development, Bayer AG, Berlin, Germany; 4Medical Affairs, Bayer Yakuhin Ltd, Osaka, 5Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Tottori, Japan Background: Dysmenorrhea is a common condition in women, which is characterized by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic regimen of ethinylestradiol/drospirenone (28d regimen) is approved for this indication in Japan. Aim: The aim of this study was to assess the safety and efficacy of a flexible extended regimen of ethinylestradiol/drospirenone (flexible regimen) in Japanese women with dysmenorrhea. Methods: This multicenter, open-label study was performed in Japanese women with dysmenorrhea who, after a baseline observational phase, were randomized to receive ethinylestradiol 20 µg/drospirenone 3 mg in a flexible regimen (one tablet each day for 24–120 days followed by a 4-day tablet-free interval) or in the standard 28d regimen (one tablet each day for 24 days, followed by 4 days of placebo tablets for six cycles). The primary endpoint was the number of days with dysmenorrhea of at least mild intensity over a 140-day evaluation period. Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were also assessed. Results: A total of 216 women (mean age 29.7 years) were randomized to the flexible regimen (n=108) or 28d regimen (n=108) and 212 were included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107). Women in the flexible-regimen group reported a mean of 3.4 fewer days with dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in disease severity reported in both treatment groups. According to the investigators, 64.8% and 59.4% of women in the flexible-regimen and 28d-regimen treatment groups had “very much improved” or “much improved” disease, while 54.3% and 50.9% of patients reported being “very much satisfied” or “much satisfied” with their treatment, respectively. Conclusion: In Japanese women with dysmenorrhea, a flexible extended regimen of ethinylestradiol/drospirenone decreased the number of days with dysmenorrheic pain versus the traditional 28d regimen. Keywords: oral contraceptive, dysmenorrhea, ethinylestradiol/drospirenone, flexible extended regimen, pain relief

Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan Background: Pulmonary adenocarcinoma, recently benefited by new cytotoxic and molecularly targeted drugs, has been classified by driver mutations, such as EGFR mutations. The aim of this study was to research the proportions of patients treated with first- to third-line chemotherapy and to find influential factors for the introduction of chemotherapy and survival benefit from chemotherapy.Materials and methods: Data were collected retrospectively on patients who met the following criteria: adenocarcinoma, diagnosed between June 2007 and March 2015 at our hospital, stage IIIB or IV, and EGFR wild type. A nonchemotherapy group of patients who did not receive chemotherapy was compared with a chemotherapy group of patients who received it. The patients who had received first- to third-line chemotherapy between June 2007 and November 2015 at our hospital were also analyzed.Results: During the study period, 46 patients did not receive chemotherapy, while 148, 89, and 48 received first-, second- and third-line chemotherapy, respectively. As predictive factors for unlikely chemotherapy, multivariate logistic analysis detected Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, hemoglobin

Ryuichi Hirano,1 Yuichi Sakamoto,2 Junichi Kitazawa,2 Shoji Yamamoto,1 Naoki Tachibana2 1Department of Pharmacy, 2Laboratory Medicine and Blood Transfusion, Aomori Prefectural Central Hospital, Aomori-shi, Japan Background: Vancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Materials and methods: The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the ­concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated. Results: Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate. Conclusion: Our ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections. Keywords: antimicrobial stewardship, prospective audit and feedback, therapeutic drug monitoring, vancomycin

Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan Background: Pulmonary squamous cell carcinoma has not benefited from improvements in chemotherapy over the past decade, compared with non-squamous non-small-cell lung cancer. Nowadays, treatment strategies differ between squamous and non-squamous non-small-cell lung cancers. This study aimed to investigate the percentage of patients treated with first-, second-, or third-line chemotherapy and the characteristics of patients for whom chemotherapy has been beneficial. Method: Data on patients with stage IIIB or IV squamous cell carcinoma diagnosed between June 2007 and March 2015, and on patients who had received first-, second-, or third-line chemotherapy between June 2007 and November 2015 at our hospital, were retrospectively extracted from our institutional medical charts. We also compared patients who were treated with chemotherapy (chemotherapy group) and patients who were not (non-chemotherapy group) using multivariate logistic regression and multivariate Cox hazard analyses, respectively. Results: During the study period, 103, 63, and 32 patients received first-, second-, and third-line chemotherapy, respectively. Fifty-one patients did not receive chemotherapy. Factors predicting unlikely chemotherapy included age ≥75 years, Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≥2, Charlson comorbidity index ≥2, hemoglobin

As a measure for contrasting pine wilt disease, which caused serious damage in Japanese black pine (Pinus thunbergii Parl.) by the pine wood nematode (Bursaphelenchus xylophilus (Steiner et Buhrer) Nickle), resistant trees have been widely planted in Japan. The propagation of resistant trees using cuttings obtained from healthy stock plants and inoculated with pine wood nematode is expected to further increase in the next future. To improve the cutting propagation of Japanese black pine trees resistant to pine wilt disease, the factors associated with rooting and root volume were investigated. The type of cutting and the crown position of stock plants from which cuttings were taken, were markedly associated with rooting. The crown position did not show significant interactions with any other investigated factor, while fresh weight of cuttings and their number of winter buds did not affect rooting. The rooting percentage was markedly higher for cuttings taken from the lower crown than for those from the upper crown, as already reported for other coniferous tree species. The length of the longest needle was significantly correlated with the root volume of cuttings, and showed significantly interactions with crown position and fresh weight of cuttings. Such correlation suggests that the growth of needles can be considered a useful predictor in the assessment of the root volume of cuttings during the propagation period, allowing growers to transplant rooted cuttings at the appropriate time without excavating or uprooting. These findings may contribute to the improvement of cutting propagation of Japanese black pine.

Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan Background: Small-cell lung cancer (SCLC) is responsive to initial chemotherapy but becomes resistant to cytotoxic drugs. The aim of this study was to evaluate what proportion of patients with SCLC had received the first- and further-line chemotherapy and which patients had benefited from chemotherapy. Methods: We retrospectively reviewed medical records of patients with SCLC who had been treated with the best supportive care alone and the first-, second-, or third-line chemotherapy at the Osaka Police Hospital from June 2007 until March 2015. Results: Among 145 patients diagnosed with SCLC and eligible for analysis, 118 patients received chemotherapy. We added five patients who initiated the second-line chemotherapy during the study period at our institution. Sixty-five and 31 patients received the second- and third-line chemotherapies, respectively. Multivariate logistic regression analysis detected age ≥75 years (odds ratio, 2.80; 95% confidence interval, 1.01–7.75; P=0.047) and European Clinical Oncology Group Performance Status (ECOG PS) 3–4 (14.3; 4.86–41.9; P

Toshiyuki Oshitari, Sakiko Nonomura, Miyuki Arai, Yoko Takatsuna, Eiju Sato, Takayuki Baba, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan Purpose: To compare the effects of sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of STTA injection combined with microaneurysm photocoagulation (MAPC; STTA + MAPC) on eyes with diabetic macular edema (DME). Patients and methods: The medical records of 138 eyes of 138 patients with DME treated by either STTA or STTA + MAPC were reviewed. The degree of DME was determined by the optical coherence tomographic features: patients with serous retinal detachment (SRD+; 38 eyes) and patients without SRD (non-SRD; 100 eyes). The central macular thickness (CMT) and the best-corrected visual acuity (BCVA) were measured periodically for 6 months after the treatments. Results: The BCVA was significantly improved in the non-SRD group after STTA + MAPC. The CMT was significantly improved in all groups and improved considerably more in the non-SRD group than in the SRD+ group after STTA + MAPC. Conclusion: Our findings indicate that MAPC has an additive effect in the non-SRD type. Keywords: diabetic macular edema, sub-Tenon's triamcinolone acetonide injection, microaneurysm photocoagulation, best-corrected visual acuity, central macular thickness

Seigo Minami, Yoshitaka Ogata, Suguru Yamamoto, Kiyoshi Komuta Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan Background: Advanced non-small-cell lung cancer (NSCLC) eventually progresses after first-line chemotherapy, and usually requires salvage treatment. Although neither gemcitabine nor vinorelbine is approved as a candidate drug in the second- or further-line for NSCLC, they can be alternative drugs in terms of anti-tumor effects and toxicities. Actually, in our institution, we often use a combination of these two anti-tumor drugs in our daily practice. Methods: We retrospectively reviewed 85 patients with advanced NSCLC who had received combination chemotherapy of gemcitabine and vinorelbine after a platinum-based regimen from June 2007 to June 2014 in Osaka Police Hospital, and performed Cox proportional hazard analyses in order to detect predictive factors for progression-free survival (PFS). Results: Patient characteristics included a mean age of 65.5 years, 56 males, 54 adenocarcinoma, 53 European Clinical Oncology Group performance status 0–1. Thirteen and 35 patients received the study treatment as the second- and third-line treatment, respectively. The overall response rate, disease control rate, PFS, and overall survival were 4.7% (95% confidence interval 1.3%–11.6%), 30.6% (21.0%–41.5%), 2.1 months (1.7–2.8 months), and 6.9 months (5.0–11.0 months). Twenty-one and six patients experienced grade 4 neutropenia and febrile neutropenia, respectively. European Clinical Oncology Group performance status 0–1 was detected as a factor predicting longer PFS by univariate (hazard ratio, 1.63; 95% confidence interval, 1.28–2.08; P

Nana Furuya, Toshiyuki Oshitari, Jiro Yotsukura, Takayuki Baba, Shuichi Yamamoto Department of Ophthalmology and Visual Science, Chiba University, Graduate School of Medicine, Chuo-ku, Chiba, Japan Abstract: We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation. Keywords: relapsing polychondritis, scleritis, oral prednisolone, ocular cellulitis

Yu Nishijima,1,* Seigo Minami,1,* Suguru Yamamoto,1 Yoshitaka Ogata,1 Taro Koba,1,2 Shinji Futami,1 Kiyoshi Komuta1 1Department of Respiratory Medicine, Osaka Police Hospital, Tennoji-ku, Osaka, Japan; 2Department of Internal Medicine, National Hospital Organization, Kinki-Chuo Chest Medical Center, Kita-ku, Sakai, Osaka, Japan *These authors contributed equally to this work Background: Indacaterol, a once-daily, long-acting ß2-agonist, may improve not only respiratory function, dyspnea symptoms, and quality of life, but also physical activity for patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the effect of 12-week indacaterol therapy on daytime physical activity in patients with untreated COPD. Methods: The subjects were stable and untreated COPD outpatients with a percent predicted forced expiratory volume in 1 second (%FEV1) below 80%. Baseline assessments included clinical assessment, respiratory function testing, arterial blood gas analysis, the COPD assessment test (CAT™), and the Medical Outcomes Study 36-Item Short-Form Health Survey, Japanese version 2 (SF-36v2®). Patients underwent monitoring by uniaxial accelerometer before and after 12 weeks once-daily inhalation of indacaterol 150 µg/day. Results: Eighteen patients were evaluable. Patient characteristics included a mean age of 74.2 years, and three patients were current smokers. Indacaterol improved mean (± standard deviation [SD]) %FEV1 from 55.2% (±17.9%) to 61.0% (±17.3%) (P=0.003), CAT scores from 16.4 (±10.2) points to 12.4 (±8.2) points (P=0.04), some scales of the SF-36v2 (physical component summary, 41.6±9.7 points to 45.1±7.9 points, P=0.03), and number of daily steps (3,311.5±2,103.3 steps/day to 3,841.8±2,096.8 steps/day, P=0.02), but did not affect daily energy expenditure (85.0±77.2 kcal change to 90.9±56.8 kcal, P=0.29) or exercise duration of an intensity of level 1 or more (36.4±23.9 minutes increase to 40.8±21.6 minutes, P=0.12). Conclusion: Twelve weeks of indacaterol improved respiratory function and quality of life, but did not significantly affect physical activity in patients with moderate-to-severe COPD. Keywords: indacaterol, long-acting ß2-agonist, chronic obstructive pulmonary disease, physical activity, uniaxial accelerometer

Minoru Tomizawa,1 Fuminobu Shinozaki,2 Yasufumi Motoyoshi,3 Takao Sugiyama,4 Shigenori Yamamoto,5 Makoto Sueishi41Department of Gastroenterology, 2Department of Radiology, 3Department of Neurology, 4Department of Rheumatology, 5Department of Pediatrics, Shimoshizu Hospital, National Hospital Organization, Yotsukaido, JapanAbstract: The aim of this study was to evaluate the association between juxtapapillary diverticulum (JD) and acute cholangitis (AC), and to analyze laboratory data to reveal the underlying mechanism. We conducted a retrospective review of 139 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between April 2008 and March 2013 for diagnosis or treatment of biliary tract conditions. The Wilcoxon signed-rank test was used for comparison of variables between patients with or without JD. The χ2 test was used to analyze the association between JD and AC duct dilatation. Logistic regression analysis was performed to identify variables with strong correlation with AC. ERCP was attempted in 139 patients, but in one patient the endoscope did not reach the papilla of Vater because of a partial gastrectomy, and in two patients evaluation for JD was not possible because of duodenal or papilla of Vater cancer. Therefore, 136 patients were included in this study. JD was significantly associated with AC (P

Sakiko Nonomura, Toshiyuki Oshitari, Miyuki Arai, Eiju Sato, Yoko Takatsuna, Takayuki Baba, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To compare the effect of posterior sub-Tenon’s capsule triamcinolone acetonide (STTA) injection to that of pars plana vitrectomy (PPV) for diabetic macular edema (DME).Patients and methods: The medical records of 50 patients (52 eyes) with DME were reviewed. Twenty-six eyes underwent STTA (20 mg) and the other 26 eyes underwent vitrectomy combined with cataract surgery. The central macular thickness (CMT), measured by optical coherence tomography, and best-corrected visual acuity (BCVA) were determined before and 1, 3, and 6 months after treatment.Results: The differences in the BCVA and the CMT between the STTA group and the PPV group were not significant before or at any time after the treatment. In both the STTA and PPV groups, there were significant differences between the pre-treatment CMT and BCVA at any time after treatment.Conclusion: We recommend STTA injection for the treatment of DME.Keywords: diabetic macular edema, posterior sub-Tenon’s capsule triamcinolone acetonide injection, pars plana vitrectomy, central macular thickness

Masayasu Kitahashi,1 Takayuki Baba,1 Madoka Sakurai,1 Hirotaka Yokouchi,1 Mariko Kubota-Taniai,1 Yoshinori Mitamura,2 Shuichi Yamamoto1 1Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, 2Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan Background: The purpose of this study was to compare the effectiveness of pneumatic displacement combined with intravitreal bevacizumab (IVB) with that of pneumatic displacement (PD) alone to treat massive submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). Methods: Thirty-two eyes of 32 patients with massive SMH secondary to PCV were studied. Twenty-two eyes were treated with a combination of PD and 1.25 mg of intravitreal bevacizumab (PD + IVB group), and ten eyes with pneumatic displacement alone (PD group). Results: Pretreatment, the differences in best-corrected visual acuity and size of the SMH between the two groups were not significant (P=0.59 and P=0.72, respectively). Complete displacement of the hemorrhage from under the fovea was achieved in 19 of 22 eyes (86.4%) in the PD + IVB group and in five of ten eyes (50%) in the PD group. The best-corrected visual acuity in the PD + IVB group was significantly better than that in the PD group at one, 3, and 6 months after treatment (P0.3 logMAR units was obtained in 18 eyes (81.8%) in the PD + IVB group and two eyes (20%) in the PD group (P

Madoka Sakurai, Takayuki Baba, Masayasu Kitahashi, Hirotaka Yokouchi, Mariko Kubota-Taniai, Guzel Bikbova, Toshiyuki Oshitari, Shuichi YamamotoDepartment of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, JapanPurpose: To compare the 1-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy (RF-PDT) to intravitreal ranibizumab (IVR) alone for eyes with polypoidal choroidal vasculopathy (PCV).Methods: We reviewed the medical records from 47 consecutive patients with PCV (47 naïve eyes). Seventeen eyes from 17 patients had one IVR treatment combined with RF-PDT followed by two additional IVR treatments (combined group), and 30 eyes from 30 patients were treated with 3 monthly IVR treatments (IVR group). All eyes had a follow-up period of at least 12 months.Results: At 12 months, the mean logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) significantly improved from 0.55 to 0.38 logMAR units in the combined group (P=0.041) but did not change significantly in the IVR group (P=0.371). The central foveal thickness (CFT) was significantly thinner in both groups at 6 months (P

Minoru Tomizawa,1 Fuminobu Shinozaki,2 Aika Ozaki,2 Akira Baba,2 Yoshiya Fukamizu,2 Futoshi Matsunaga,2 Takao Sugiyama,3 Shigenori Yamamoto,4 Makoto Sueishi,3 Takanobu Yoshida51Department of Gastroenterology, 2Department of Radiology, 3Department of Rheumatology, 4Department of Pediatrics, 5Department of Internal Medicine, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, JapanPurpose: Information on the extent or structure of esophageal cancer (ESC) is necessary for identifying whether the carcinoma is localized or resectable. Diffusion-weighted imaging (DWI) and diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) are useful for this purpose.Patients and methods: One case of ESC with dysphagia presented at our hospital. Endoscopic examination revealed an elevated lesion with an ulcer, and stenosis was detected. DWI showed a high-intensity signal extending from the proximal to the distal ends of the carcinoma and extending to the tunica adventitia. A strong signal was also observed using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). DWIBS clearly revealed ESC, and these findings, along with those from DWI, suggested that our case had stage-T3 ESC. FDG-PET did not reveal the detailed structure of the ESC. DWIBS, on the other hand, showed that the signal extended to the tunica adventitia and the lumen of the esophagus.Conclusion: These findings suggest that DWI and DWIBS are useful for the detection and assessment of ESC.Keywords: positron emission tomography, endoscopy, computed tomography, cross section, squamous cell carcinoma

Yu Monden,1 Shohaku Yamamoto,1 Ryoji Yamakawa,1 Atsuko Sunada,2 Seishi Asari,3 Koichi Makimura,4 Yoshitsugu Inoue5 1Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, 2Laboratory for Clinical Investigation, 3Department of Infection Control and Prevention, Osaka University Hospital, Osaka, 4Teikyo University Institute of Medical Mycology, Tokyo, 5Division of Ophthalmology and Visual Sciences, Tottori University Faculty of Medicine, Tottori, Japan Purpose: To report the isolation of Pestalotiopsis clavispora from the cornea of a patient with recurrent keratitis. Case report: A 73-year-old male gardener presented with conjunctival injection and an oval infiltrate with feathery margins in the temporal half of the cornea in the right eye. His ocular history in the right eye included cataract surgery, five episodes of herpes simplex keratitis, three glaucoma surgeries, and bullous keratopathy. He had been treated with corticosteroids for years. Light microscopy of corneal scrapings revealed a filamentous fungus, and fungal keratitis was diagnosed. Treatment with topical voriconazole and pimaricin ointment was commenced. One month later, the infiltrate resolved. The antifungal agents were discontinued 7 months later, and keratitis relapsed 4 days after the discontinuation. The fungus was isolated and identified by molecular techniques as P. clavispora. Based on the results of antifungal susceptibility testing, treatment with topical and intravenous micafungin was initiated. The corneal infiltrate resolved 1 month after the relapse. Conclusion: Molecular identification of the pathogen, and antifungal susceptibility testing, are useful in treating patients with fungal keratitis caused by a rare human pathogen. Keywords: fungal keratitis, Pestalotiopsis clavispora, plant pathogen, molecular identification, antifungal susceptibility test

Yosuke Yamada,1,2 Daichi Yamashita,2,3 Shinji Yamamoto,2,3 Tomoyuki Matsui,4 Kazuya Seo,4 Yoshikazu Azuma,4 Yoshikazu Kida,5 Toru Morihara,5 Misaka Kimura1 1Laboratory of Sports and Health Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan; 3Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan; 4Department of Rehabilitation, Graduate School of Medical Science, Kyoto, Prefectural University of Medicine, Kyoto, Japan; 5Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Abstract: The aim of the study was to examine the relationship between pitching ball velocity and segmental (trunk, upper arm, forearm, upper leg, and lower leg) and whole-body muscle volume (MV) in high school baseball pitchers. Forty-seven male high school pitchers (40 right-handers and seven left-handers; age, 16.2 ± 0.7 years; stature, 173.6 ± 4.9 cm; mass, 65.0 ± 6.8 kg, years of baseball experience, 7.5 ± 1.8 years; maximum pitching ball velocity, 119.0 ± 9.0 km/hour) participated in the study. Segmental and whole-body MV were measured using segmental bioelectrical impedance analysis. Maximum ball velocity was measured with a sports radar gun. The MV of the dominant arm was significantly larger than the MV of the non-dominant arm (P < 0.001). There was no difference in MV between the dominant and non-dominant legs. Whole-body MV was significantly correlated with ball velocity (r = 0.412, P < 0.01). Trunk MV was not correlated with ball velocity, but the MV for both lower legs, and the dominant upper leg, upper arm, and forearm were significantly correlated with ball velocity (P < 0.05). The results were not affected by age or years of baseball experience. Whole-body and segmental MV are associated with ball velocity in high school baseball pitchers. However, the contribution of the muscle mass on pitching ball velocity is limited, thus other fundamental factors (ie, pitching skill) are also important. Keywords: pitching, ball velocity, muscle volume, body composition, trunk, upper and lower extremities