Academic literature on the topic 'Takeda, Izumo'

This study explores the character of Takezo the ronin in Musashi by Eiji Yoshikawa through the psychological perspective of aggression. This research specifically aims to (a) explore Takezo's psychology of aggression as a ronin and (b) the impact of Takezo's aggression on others. The approaches used in this research are the psychology of literacy and the psychology of aggression. The method used is qualitative; it uses data exposure and interpretation. The data source is the novel Musashi by Eiji Yoshikawa (translated version in Indonesian). The data used is in the form of text that is relevant to Takezo's psychology of aggression. The data analysis techniques are carried out in five stages, (1) identifying data related to Takezo's psychology of aggression, (2) data classification related to Takezo's psychology of aggression, (3) data presentation related to Takezo's psychology of aggression, and (4) summarizing data related to Takezo's psychology of aggression. The results showed that Takezo's aggressions are represented in the form of thoughts and behaviour. Takezo's aggressive thoughts are wanting to defeat and kill his enemies. Takezo's aggressive behaviour is killing his enemies, who are samurai. Takezo's aggressions cause the impact of physical category, and they are death and disability on the defeated samurai. Besides, in the psychological category, Takezo's aggressions cause fear and hatred in society. It is concluded that Takezo represents ronin, which desires destructive aggression that has a physical and psychological impact on others.

Background:Medical image analysis using deep learning (DL) has been attracting attention. In previous research, we proposed a DL method for detection of joint region and evaluation for bone destruction at a single point in time in hand X-rays of patients with rheumatoid arthritis (RA) [1-2]. However, in the score of van der Heijde-modified total Sharp scores (mTSS) in X-rays, it is difficult to apply the method as it is. In mTSS, score difference between 2-time points is important, and there is a problem that the score at each time varies depending on the doctor who evaluates.Objectives:We aimed at developing an mTSS scoring method considering 2-time-point difference with a DL method.Methods:A total of 104 X-ray image sets of both hands at two time points with an interval of ≥1 year were randomly obtained from patients with RA who had visited our clinic in 2015. Well-trained doctors determined the erosion scores of MP and PIP/IP joints of each hand in X-rays according to mTSS. These evaluations of hand joints were performed using our developed annotation software tool. In the learning phase, joint images were randomly divided into five sets for 5-fold cross-validation. We utilized a convolutional neural network model, such as SSD [3], for detecting joint regions and classifying the scores (Fig 1).Figure1.The models for classification were designed in consideration of the difference in erosion scores of each patient between the 2-time points of X-rays. The loss function of the DL model was defined bellow;SCE: softmax cross entropyMSE: mean squared errort: training datay: output of DL model0: the former time point1: the latter time pointT: transpose of matrixHere, the coefficient γ is designed to reduce the error for another set of scores with equal differences. The first term of the loss function works to optimize the score at each time point, and the second term works to optimize the score difference at both time points. Thus, our method can be trained without being affected by characteristic training data.Results:The number of joints with differences in erosion score between the former and latter time points was 1 (-2 points), 9 (-1), 2015 (0), 32 (+1), 17 (+2), and 6 (+3). There were no joints with score changes of -5, -4, -3, +4, and +5 points.As a performance of predicting the difference in erosion score between the 2-time points of each patient’s X-ray, our models presented a mean error of 0.412 per each joint in one set for 5-cross validation as compared with physicians’ evaluation (Fig 2).Figure 2.Conclusion:Our DL-based models to predict hand joint erosion scores in X-rays were developed with relatively small samples. This suggests that the predictive performance may increase by collecting more training dataset. Next, we will apply our method to the prediction of joint space narrowing score.References:[1]Izumi K, Hashimoto M, Suzuki K, et al. Detecting Hand Joint Ankylosis in Radiographic Images Using Deep Learning: A Step in Developing Automatic Radiographic Scoring System for Bone Destruction.Arthritis Rheumatol2018;70 (suppl 10).[2]Izumi K, Suzuki K, Hashimoto M, et al. SAT0543 AUTOMATIC DETECTION OF HAND JOINT REGION, ANKYLOSIS AND SUBLUXATION IN RADIOGRAPHIC IMAGES USING DEEP LEARNING: DEVELOPMENT OF ARTIFICIAL INTELLIGENCE-BASED RADIOGRAPHIC EVALUATION SYSTEM FOR BONE DESTRUCTION.Annals of the Rheumatic Diseases2019;78 (suppl 2), pp. 1364-1364.[3]Liu W, Anguelov D, Szgedy C, et al. SSD: single shot multibox detector.European Conference on Computer Vision (ECCV) 2016.Acknowledgments:Izumi and Suzuki are contributed equally.Disclosure of Interests:Keisuke Izumi Grant/research support from: Asahi Kasei Pharma, Takeda Pharmaceutical Co., Ltd., Speakers bureau: Asahi Kasei Pharma Corp, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Kanata Suzuki Employee of: Fujitsu Laboratories Ltd., Masahiro Hashimoto: None declared, Toshio Endoh Employee of: Fujitsu Laboratories Ltd., Kentaro Doi Employee of: Fujitsu Ltd., Yuki Iwai Employee of: Fujitsu Ltd., Yuko Kaneko Speakers bureau: AbbVie, Eisai Pharmaceutical, Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K., Santen Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co. Ltd. and UCB Japan Co. Ltd., Masahiro Jinzaki: None declared, Shigeru Ko Grant/research support from: Fujitsu Ltd., Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Teijin, Consultant of: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan

Background:Symptoms in patients with rheumatoid arthritis (RA) are potentially influenced by exercise load and meteorological change, and often vary from day to day, especially in unstable condition of RA. Patients with RA not infrequently experience worsening of joint symptoms when the load on the joint, such as walking and doing housework, exceeds a moderate range. However, the worsening of joint symptoms is often not observed in the midst of the loading of the joint, but often becomes apparent after a few hours or days.Objectives:To elucidate the relationship between smartphone- and smartwatch-acquired daily objective data (barometric pressures, steps, and activity) and daily subjective patient reported outcomes of RA.Methods:A smartphone (iPhone 8) and a wristband-type smartwatch (Fitbit Versa 2) were lent to each patient for free. A mobile app was developed and installed into the smartphones to collect patients’ daily subjective RA symptoms including Pt-P-VAS (patient-pain-visual analogue scale), Pt-G-VAS (pt-general-VAS), PtTJCount(68)(patient self-determined tender joint count among 68 joints), PtTJCount(28), PtSJCount(66)(patient self-determined swollen joint count among 66 joints), PtSJCount(28). Also, the smartwatch data and physicians’ assessment were collected from the same subject. Physicians’ and patients’ assessment of TJC, SJC, and G-VAS was independently performed without seeing each other’s assessment.We conducted a simple linear regression analysis with outcome variables of Pt-P-VAS, Pt-G-VAS, PtTJCount(68), PtTJCount(28), PtSJCount(66), and PtSJCount(28). The independent variables included smartphone-acquired daily steps and barometric pressure of the reported day and the previous day, and smartwatch-acquired minutes of “lightly active (1-3 METs equivalent)”, “fairly active(3-6 METs equivalent)”, and “very active(>6 METs equivalent)” of the reported day and previous day. We defined low barometric pressure as below 1000 hPa. The level of activity was measured by the smartwatch. Patients were blinded to daily barometric pressure data and their daily active time when the patients answered daily symptom questions on the smartphones.Results:A total of five patients were enrolled. At baseline, mean (± standard deviation (SD)) age was 50.8±14.8 years; all patients were females; mean disease duration was 6.6±4.9 years; mean SDAI was 18.6±25.5; mean DAS28-CRP was 3.23±1.85; mean morning stiffness was 134±116 min; mean HAQ-DI was 0.7±0.9. Mean observation period was 77.8 days. Because of the missing data, the sample size (N) for the regression analysis varies with the outcomes: Pt-P-VAS and Pt-G-VAS are 250 while PtTJCount and PtSJCount are 260.The table 1 showed that the patients’ assessment of TJC, SCJ, and G-VAS was correlated well with the physicians’ assessment.Table 1.Evaluation itemCorrelation between physicians and patients (ρ)Tender Joint Count (68)0.909Tender Joint Count(28)0.913Swollen Joint Count(66)0.896Swollen Joint Count(28)0.890General VAS0.688The figure 1 showed the change associated with one SD increment in each independent variable with 90% confidence intervals. Low barometric pressure was associated with bad health conditions (high Pt-G-VAS, Pt-P-VAS, and SJCount). Moreover, longer very active time in the previous day (“veryactive_1” in the Figure 1) was associated with bad health condition (high SJCount). Many steps were associated with good health conditions (low Pt-G-VAS, Pt-P-VAS, and SJCount).Figure 1.Conclusion:High barometric pressure was associated with good health conditions, and longer very active time in the previous day was associated with bad health condition. Barometric pressure data and physical activity data acquired by mobile digital devices may predict the change in RA symptoms. Further investigation in larger patient numbers is warranted.Acknowledgements:The authors would like to thank Harumi Kondo for her assistance.Disclosure of Interests:Keisuke Izumi Speakers bureau: Abbvie, Asahi Kasei Pharma, Bristol Myers Squibb, Chugai Pharmaceutical, Eli-Lily, Mochida Pharmaceutical, Ono Pharmaceutical, Grant/research support from: Abbvie, Asahi Kasei Pharma, Daisuke Moriwaki Employee of: CyberAgent, Inc., Takamichi Toda Employee of: AI Shift, Inc., Misako Higashida-Konishi: None declared, Manami Koyama: None declared, Hisaji Oshima: None declared, yutaka okano Speakers bureau: Asahi Kasei Pharma, Yuko Kaneko Speakers bureau: AbbVie, Astellas, Ayumi, Bristol–Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Kirin, Novartis, Pfizer, Sanofi, Takeda, Taisho, Tanabe-Mitsubishi, and UCB, Shigeru Ko: None declared, Tsutomu Takeuchi Speakers bureau: Abbott Japan Co, Ltd, Bristol–Myers KK, Chugai Pharmaceutical Co, Ltd, Eisai Co, Ltd, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Co, Pfizer Japan Inc, Takeda Pharmaceutical Co, Ltd, Astellas Pharma and Daiichi Sankyo Co, Ltd., Consultant of: Astra Zeneca KK, Eli Lilly Japan KK, Novartis Pharma KK, Mitsubishi Tanabe Pharma Co, Asahi Kasei Medical KK, Abbvie GK and Daiichi Sankyo Co, Ltd., Grant/research support from: Abbott Japan Co, Ltd, Astellas Pharma, Bristol-Myers KK, Chugai Pharmaceutical Co, Ltd, Daiichi Sankyo Co, Ltd, Eisai Co, Ltd, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Co, Pfizer Japan Inc, Sanofi–Aventis KK, Santen Pharmaceutical Co, Ltd, Takeda Pharmaceutical Co, Ltd, Teijin Pharma Ltd, Abbvie GK, Asahikasei Pharma Corp and Taisho Toyama Pharmaceutical Co, Ltd.

Background:ANCA-associated vasculitis sometimes presents mononeuritis multiplex which worsens the prognosis and activity of daily living in patients.Objectives:This study aimed to determine the clinical feature of mononeuritis multiplex associated with AAV.Methods:Consecutive patients with AAV who visited Tokyo Medical Center between April 2006 and December 2019 were included in this study. We examined the following clinical features: prevalence of neuropathy, age of onset, sex, the worst blood test values before the initial therapy (white blood cell count (WBC), eosinophil count (Eo), MPO-ANCA, PR3-ANCA, and C-reactive protein(CRP) levels), manual muscle testing (MMT)score of 20 muscles (Max 100 points), and time (days) from the initial symptoms to the initial induction therapies.Results:A total of 89 patients with AAV were identified. Among them, 19 patients had eosinophilic granulomatosis with polyangiitis (EGPA) (8 males and 11 females, mean age 63.3 ± 2.7), 9 patients had granulomatosis with polyangiitis (GPA) (0 males, 9 females, mean age 75.6 ± 3.9), and 61 patients had microscopic polyangiitis (MPA) (17 males, 44 females, mean age 78.2 ± 1.5). Of the 89 AAV patients, 26 had sensory neuropathy (15/19 EGPA (78.9%), 11/61 MPA (18.0%), and 0/9 GPA (0%)). Motor neuropathy was observed in 19 patients (EGPA 14/19 (73.7%), MPA 5/61 (8.2%), GPA 0/9 (0%)). 15 patients had both sensory and motor neuropathies (EGPA 12/19 (63.2%), MPA 3/61 (4.9%), GPA 0 (0%)). In patients with both sensory and motor neuropathy, sensory impairment preceded in all cases. Among patients with neuropathy, the time from initial symptoms to initial induction therapy in patients with and without motor neuropathy was 34 ± 10.1 days and 30 ± 10.8 days (p = 0.776), respectively. Also, when comparing those who were treated within 7 days from the onset of movement disorders with those who were treated later, MMT score two weeks after the start of treatment were 92.15 ± 1.47 vs. 91.25 ± 2.65 (p = 0.77).Between the patients with EGPA with and without sensory neuropathy, there were no significant differences in the following: highest WBC(19620.0 ± 2082.6 vs. 19350.0 ± 4033.5 cells/uL (p = 0.953)), highest Eo(10790.6 ± 1774.8 vs 12440.8 ± 3436.9 cells/uL (p = 0.6750)), and highest CRP levels (4.467 ± 0.96 vs 2.70 ± 1.85 mg/dL (p = 0.41)) before the initial therapy. On the other hand, comparing the EGPA patients with and without motor neuron disorder, CRP levels were significantly higher in those with motor impairment than those without(WBC 20978.6 ± 2049.8 vs. 15600.0 ± 3429.9 cells/uL (p = 0.20); Eo 12213.4 ± 1775.5 vs. 8127.0 ± 2971.0 cells/uL (p = 0.25); CRP 5.13 ± 0.89 vs. 1.20 ± 1.48 mg/dL (p = 0.04)). And in patients with motor neuropathy, the decrease in MMT score was significantly correlated with the worst levels of CRP(p = 0.001)while the decrease was not correlated with the other blood tests. ANCA levels were not associated with sensory or motor neuropathy. In similar analyses of patients with MPA and GPA, there were no significant findings.Conclusion:Worst CRP levels before the initial therapy can be a poor prognosis factor for motor neuropathy in patients with EGPA. Therefore, EGPA patients with high CRP levels need to be paid more attention to because of possible development of motor neuropathy.Disclosure of Interests:satoshi hama: None declared, Yutaro Hayashi: None declared, Keisuke Izumi Grant/research support from: Asahi Kasei Pharma, Takeda Pharmaceutical Co., Ltd., Speakers bureau: Asahi Kasei Pharma Corp, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Misako Higashida-Konishi: None declared, mari ushikubo: None declared, kumiko akiya: None declared, yutaka okano: None declared, Hisaji Oshima: None declared

Aggressive B-cell lymphomas are genetically and clinically heterogeneous. Standard clinical trial designs do not efficiently evaluate the safety and efficacy of multiple drug combinations within the context of underlying molecular biology. The rapid identification of oncogenic driver pathways and development of multiple targeted drugs in lymphomas create many potential combinations. To address this need, we developed a Phase 1 master protocol termed PRISM (NCT03527147) to evaluate multiple targeted therapies alone or in combination for the treatment of relapsed/refractory (R/R) aggressive B-cell lymphoma. Each study arm is conducted in a predefined disease subset with the aim of addressing clinical and translational questions within an overarching protocol. All study arms are open label and not randomized. Enrolment of subjects into a given study arm is based on meeting inclusion/exclusion criteria and available slots. Pertinent inclusion criteria for the master protocol are: (a) a diagnosis of R/R non-Hodgkin lymphoma based on established World Health Organization criteria; (b) ≥1 prior line of therapy for the treatment of current histology, no known curative treatment options available, or the subject is ineligible for potential curative options; (c) the presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy and; (d) an ECOG performance status ≤2. Exclusion criteria for the master protocol include: (a) a history of prior malignancy, severe or uncontrolled disease or conditions; (b) use of anti-lymphoma therapy within 14 days of the first dose of study drug and; (c) a requirement for ongoing immunosuppressive therapy. Treatment-specific inclusion/exclusion criteria are also provided (see www.clinicaltrials.gov). As PRISM has multiple study arms, subjects can be simultaneously screened for multiple arms. In each arm, a safety review for dose-limiting toxicity (DLT) is performed after 6 subjects have completed the protocol-defined DLT window. Further enrolment will only proceed in that arm if ≤1 subject experiences a DLT (Figure 1). The sample size for each respective arm is determined based on prior clinical/experimental data on anticipated/clinically meaningful activity of each drug combination. This determines a minimally acceptable response and a desirable response. For each arm, a futility analysis occurs after approximately 10 sequentially enrolled subjects. An arm is considered futile if there is <10% probability for the overall response rate (ORR) to be above the desirable response. A final analysis after approximately 21 enrolled subjects will determine whether the treatment should be studied further. The primary criterion for success is set as having >80% chance for the response rate to be above the minimally acceptable response. The study endpoints include safety, ORR, duration of response, progression-free survival, overall survival, and standard pharmacokinetic parameters. Exploratory analyses include in depth translational studies employing peripheral blood and tumor tissue collected at screening and during treatment. These investigations aim to discover predictive biomarkers, identify the molecular correlates of response based on known genetic subtypes, investigate pharmacodynamic and pathway changes and define the depth of response using assays for measurable residual disease (MRD). Exploratory translational endpoints may inform additional biomarker selection strategies for future arms of the PRISM study. All study arms within PRISM to date have combined acalabrutinib, a highly selective BTK inhibitor, with additional targeted agents in subjects with R/R diffuse large B-cell lymphoma. The mechanism of action of the drugs combined with acalabrutinib are as follows: 1. AZD9150 is a 16-nucleotide antisense oligonucleotide designed to target and down-regulate expression of human STAT3 mRNA; administered intravenously. 2. AZD6738 is an inhibitor of ATR; administered orally. 3. Hu5F9-G4 is an anti-CD47 antibody and rituximab is an anti-CD20 antibody; both administered intravenously. 4. AZD5153 is a BRD4 inhibitor; administered orally. In summary, PRISM is a unique platform protocol designed to efficiently evaluate targeted agents in R/R aggressive B-cell lymphoma with an emphasis on comprehensive translational and molecular investigations. Disclosures Izumi: AstraZeneca: Equity Ownership; Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acalabrutinib patents. Hamdy:AstraZeneca: Equity Ownership; Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acalabrutinib patents. Arkenau:Acerta Pharma: Research Funding. de Vos:Portola Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Verastem: Consultancy. Reagan:Kite, A Gilead Company: Consultancy; Curis: Consultancy; Seattle Genetics: Research Funding. Zinzani:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Davies:BioInvent: Research Funding; ADCT Therapeutics: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Pfizer: Honoraria, Research Funding; Acerta Pharma: Honoraria, Research Funding; MorphoSys AG: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pagel:AstraZeneca: Consultancy; Pharmacyclics, Inc.: Consultancy. Vose:Legend Pharmaceuticals: Honoraria; Acerta Pharma: Honoraria, Other: Grants, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Celgene Corporation: Research Funding; Incyte Corporation: Research Funding; Kite Pharma: Honoraria, Other: Grants, Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; AbbVie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria. Bitman:Acerta Pharma: Employment; AstraZeneca: Equity Ownership. Brock:Acerta Pharma: Employment; AstraZeneca: Equity Ownership. Clark:AstraZeneca: Employment, Equity Ownership. Frigault:Acerta Pharma: Employment; AstraZeneca: Employment, Equity Ownership. Ware:Acerta Pharma: Employment; Astrazeneca: Employment, Equity Ownership. Yang:Acerta Pharma: Employment; AstraZeneca: Equity Ownership. Staudt:Nanostring: Patents & Royalties. Flinn:TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals: Research Funding; AbbVie, Seattle Genetics, TG Therapeutics, Verastem: Consultancy; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding. OffLabel Disclosure: acalabrutinib in DLBCL

Background:In the case of seronegative arthritis, it was difficult to make a differential diagnosis between remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) and seronegative rheumatoid arthritis (seronegative RA) because the distribution of affected joints was similar and the patients with RS3PE or seronegative RA may have edema.Objectives:To compare the clinical characteristics of RS3PE and seronegative RAMethods:We retrospectively examine consecutive patients diagnosed with RS3PE or seronegative RA in our hospital from 2007 to 2019. Patients in whom both ACPA and RF were negative were included. The patients with RS3PE met the criteria of McCarty et al.: (1) pitting edema of the dorsum of both hands and both feet, (2) sudden onset of polyarthritis, (3) seronegative for ACPA and RF. (4)no radiologically evident erosions developed. The patients with seronegative RA met the EULAR/ACR 2010 criteria. The patients who were diagnosed with RS3PE at first and then diagnosed with seronegative RA afterward were included in seronegative RA group. The first analysis was performed on the affected joints, CRP, ESR, Hb, LDH, edema, the history of malignancy 2 years before and after the diagnosis, treatment, and the history of infection requiring hospitalization after the start of treatment. The affected joints were shoulders, elbows, wrists, finger joints (the MCP, and PIP joints), hips, knees, ankles, and toe joints (the MTP and PIP joints). The secondary analysis was performed on the above evaluations with a propensity score (PS) matching for age.Results:In the first analysis, 20 patients with RS3PE and 122 patients with seronegative RA were enrolled. The mean ages (RS3PE, seronegative RA) were 81.1, 67.4 years old. Females were 60.0%, 63.1%. The mean observation period was 25.4, 63.6 months. The proportion of affected joints were shoulders (25.0%, 42.6%), elbows (10.0%, 29.5%: p=0.06), wrists (85.0%, 73.8%), finger joints (80.0%, 95.1%: p=0.01), hips (0%, 9.8%), knees (40.0%, 37.7%), ankles (65.0%, 39.3%: p=0.03) and toe joints (40.0%, 32.8%). Edema at diganosis was observed in 100%, 17.21% (p <0.0001). The mean levels of the following blood tests at diagnosis were noted: CRP, 9.0 and 4.8 mg/dL (p=0.02); ESR, 87.6 and 60.7 mm/1h (p=0.003); Hb, 10.4 and 11.8 mg/dl (p=0.001); LDH, 198.3 and 177.9 U/L (p = 0.12); MMP-3, 742.5 and 633.8 ng/mL (p = 0.14). The proportion of patients with high LDH levels (>222 U/L) was 13.6% and 9.0% (p=0.0269). The proportion of patients having the history of malignancy was 20.0%, 8.2% (p=0.10). The patient treated with prednisolone as the initial treatment was 100% and 41.0%; the mean dose was 14.3 and 9.9 mg/d. After the start of treatment, the proportion of infection requiring hospitalization was 20.0 and 3.28% (p=0.002).In the secondary analysis with PS, 17 patients with RS3PE and 17 patients with seronegative RA were enrolled. The mean ages were 80.4, 78.9 years old. Females were 52.9, 76.4%. The affected joints with difference were elbows (11.8, 35.3%: p=0.10), wrists (82.4, 100%: p=0.06), and finger joints (82.4, 100%: p=0.06). The mean levels of Hb at diagnosis was 10.4, 11.4 mg/dL (p=0.01). The proportion of patients having the history of malignancy was 23.5% and 0% (p=0.03). After the start of treatment, the proportion of infection requiring hospitalization was 23.5% and 0% (p=0.03).Conclusion:When the ankles are affected and edema is observed, RS3PE is more likely than seronegative RA. RS3PE had higher levels of CRP, ESR, and LDH. The proportion of anemia was higher in RS3PE. The proportions of infection requiring hospitalization and the history of malignancy were higher in RS3PE.References:[1]McCarty DJ, O’Duffy JD et al. Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE Syndrome). JAMA 1985; 254: 2763–2767. DOI:10.1001/jama.1985.03360190069027Disclosure of Interests:Misako Higashida-Konishi: None declared, Keisuke Izumi Grant/research support from: Asahi Kasei Pharma, Takeda Pharmaceutical Co., Ltd., Speakers bureau: Asahi Kasei Pharma Corp, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Satoshi Hama: None declared, Yutaro Hayashi: None declared, Yutaka Okano: None declared, Hisaji Oshima: None declared

Introdução: A queilite actínica (QA) é uma desordem potencialmente maligna associada à exposição crônica à luz solar como principal fator etiológico. A QA tem como principal sítio de acometimento o vermelhão do lábio inferior, apresentando características clínicas marcantes. Porém, a análise histopatológica desta lesão merece um enfoque especial pelas características bastante expressivas para o potencial de malignidade. Assim, para essa análise, são elencados dois sistemas principais: o sistema da Organização Mundial da Saúde (OMS), e o binário. Objetivo: Realizar uma revisão da literatura para demonstrar os pontos avaliados e o valor preditivo dos sistemas de gradação histológica em QA. Metodologia: Trata-se de um estudo de revisão bibliográfica, utilizando artigos da base de dados da SCIELO e PUBMED, encontrados com o uso dos descritores: “actinic cheilitis”, “WHO system”, “binary system”, “oral potentially malignant disorders”, “histological features in actinic cheilitis”, fazendo uso do operador booleano “AND”. Conclusão: Diante da revisão realizada, percebeu-se a importância da adoção dos sistemas de gradação histológica da OMS, e o binário para uma análise minuciosa de lesões de QA, que apresentam potencial de malignidade. Ademais, constatou-se o favorecimento do sistema binário na redução da subjetividade entre os patologistas quanto à gradação das avaliações histopatológicas. Descritores: Queilite; Patologia Bucal; Neoplasias Labiais; Classificação; Diagnóstico. Referências Lopes MLDS, Silva Junior FLS, Lima KC, Oliveira PT, Silveira EJD. Clinicopathological profile and management of 161 cases of actinic cheilitis. An Bras Dermatol. 2015;90(4):347-50. 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Dancyger A, Heard V, Huang B, Suley C, Tang D, Ariyawardana A. Malignant transformation of actinic cheilitis: A systematic review of observational studies. J Investig Clin Dent. 2018; 9(4):e12343. de Santana Sarmento DJ, da Costa Miguel MC, Queiroz LM, Godoy GP, da Silveira EJ. Actinic cheilitis: clinicopathologic profile and association with degree of dysplasia. Int J Dermatol. 2014; 53(4):466-72. Wood NH, Khammissa R, Meyerov R, Lemmer J, Feller L. Actinic cheilitis: a case report and a review of the literature. Eur J Dent. 2011; 5(1):101-6. Mello FW, Melo G, Modolo F, Rivero ER. Actinic cheilitis and lip squamous cell carcinoma: Literature review and new data from Brazil. J Clin Exp Dent. 2019;11(1):e62-9. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36(10):575-80. Paiva MAF, Soares MSM, Figueiredo CRLV, Luna AH, Oliveira VEN, Brasil Júnior O. Associação entre displasia e inflamação em queilite actínica. J Bras Patol Med Lab. 2012; 48(6):455-58. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37(3):127-33. Câmara PR, Dutra SN, Takahama Júnior A, Fontes K, Azevedo RS. A comparative study using WHO and binary oral epithelial dysplasia grading systems in actinic cheilitis. Oral Dis. 2016; 22(6):523-9. Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42(10):987-93. Nagata G, Santana T, Queiroz A, Caramez RH, Trierveiler M. Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site. J Cutan Pathol. 2018. doi: 10.1111/cup.13270. Mello FW, Miguel AFP, Dutra KL, Porporatti AL, Warnakulasuriya S, Guerra ENS, Rivero ERC. Prevalence of oral potentially malignant disorders: A systematic review and meta-analysis. J Oral Pathol Med. 2018;47(7):633-40. Izumo T. Oral premalignant lesions: from the pathological viewpoint. Int J Clin Oncol. 2011;16(1):15-26. Kujan O, Khattab A, Oliver RJ, Roberts SA, Thakker N, Sloan P. Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation. Oral Oncol. 2007; 43(3):224-31. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. World Health Organization Classification of Head and Neck Tumours. WHO/IARC Classification of Tumours 2017; 4th ed. Lyon, France: IARC Press. R SA, B N P, Hegde U, K U, G S, G K, Sil S. Inter- and Intra-Observer Variability in Diagnosis of Oral Dysplasia. Asian Pac J Cancer Prev. 2017;18(12):3251-54. Olinici D, Cotrutz CE, Mihali CV, Grecu VB, Botez EA, Stoica L, Onofrei P, Condurache O, Dimitriu DC. The ultrastructural features of the premalignant oral lesions. Rom J Morphol Embryol. 2018;59(1):243-48.

Kuwako has worked extensively in Japan to apply his expertise in environmental ethics to the resolution of practical environmental problems. The Ohashi River, which runs through Matsue City in the Izumo region and feeds the Hii River, has recently undergone extensive modification for flood control. This controversial project has been politically polarizing because of the tensions between human welfare, traditional cultural beliefs, sustainability, and environmental aesthetics. Changing the spatial structure of a community is both a cultural and a historical project that must take into account traditional beliefs about the relationship between human beings and the environment. The decision-making process for the development of social infrastructure should be grounded in meaningful citizen participation and should reflect the environmental values of the people.

This chapter assesses the degree of continuity of the nohkan that is illustrated in three contemporary Noh play adaptations of William Butler Yeats's At the Hawk's Well by nohkan performers of the Issō School. It looks at interviews conducted with nohkan performers and a composer. It also highlights the nohkan's traditional role in contemporary and English-language Noh that allows variations and embellishments by performers, which demonstrate musical continuity in the context of experimentation. The chapter discusses a number of shinsaku Noh that have been successful and performed more frequently. It describes the performance of Yokomichi Mario's Taka no Izumi and Takahime, including the English-language Noh production of At the Hawk's Well by Theatre Nohgaku.