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Background Although regular physical activity has beneficial cardiovascular effects, exercise can trigger sudden cardiac arrest (SCA). Coronary artery disease (CAD) was identified as the most common cause of an exercise-related out-of-hospital cardiac arrest (OHCA). Regular exercise has been reported to reduce the risk of plaque rupture in animal studies and basic research. Therefore, we compared the coronary artery findings in CAD-OHCA patients with and without habitual exercise. There have been few reports on whether regular exercise changes the prognosis in OHCA due to CAD (CAD-OHCA). We investigated the association between the better clinical outcome and the regular exercise in patients with CAD-OHCA. Methods This is a single-center retrospective analysis from 2006 to 2019. The consecutive 397 patients with OHCA due to myocardial ischemia underwent coronary angiography (CAG). After excluding 73 patients with vasospastic angina, the remaining 324 patients with CAD were enrolled in this study. We divided these patients into two groups according to whether they were habitually exercising (Exercise group: N=37) or not/unknown (Non-Exercise group: N=287). Clinical outcome was a 30-day survival with minimal neurologic impairment represented by a Glasgow-Pittsburgh Cerebral Performance Categories Scale value 1 or 2. Results The patients in the Exercise Group were significantly younger (exercise vs. non-exercise, 57±12 vs. 64±12 years; P Conclusions The patients with habitual exercise had less plaque rupture, less coronary thrombosis than non-exercise. The patients with regular exercise had better clinical outcomes than non-exercise after CAD-OHCA. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Tokyo Metropolitan Goverment Figure 1. Findings of the culprit lesion in coronar arteriesFigure 2. Kaplan-Meier analysis

BackgroundIn clinical practice for systemic lupus erythematosus (SLE), the concept of “treat to target” has been introduced with an established goal of reducing glucocorticoid dose as much as possible while controlling disease activity. Although it has been shown that various personality characteristics of patients with SLE affect their disease activity and damage, it is not clear whether the personality characteristics of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait characterized by perseverance and passion for achieving long-term goals.ObjectivesThis study aims to evaluate the relationship between attending physicians’ grit personality characteristics and treatment goal achievements in patients with SLE.MethodsA cross-sectional study was conducted on 386 patients with SLE in five referral hospitals in Japan. The main exposure was the “perseverance” and “consistency” (scores 1-5) of the attending physicians, as measured by the Short Grit Scale, and the primary outcome was the achievement of the Lupus Low Disease Activity Score (LLDAS). Considering the clustering of achievement of LLDAS by each attending physician, the association between attending physician’s personality and LLDAS was analyzed by logistic regression with cluster robust variance estimation. Odds ratios to assess the relationship between perseverance and consistency and LLDAS were estimated with adjustment for confounders (age, sex, disease duration, hydroxychloroquine use, immunosuppressant use, and Systemic Lupus International Collaborating Clinics-Damage Index). We used multiple imputation to handle the uncertainty caused by missing values of potential confounders on the assumption of missing at random.ResultsThe median age of the patients was 45 years (interquartile range[IQR],36-56), 88% were female, and the median disease duration was 152 months(IQR, 80-240). Thirty-seven doctors were in charge of the patients (1-79 patients/each doctor). The median age of the attending physicians was 40 years (IQR, 35-43), and 19% were female. The median perseverance and consistency scores of attending physicians were 3.1 (IQR, 3.0-3.5) and 3.3 (IQR, 2.8-3.8), respectively. Of the enrolled patients, 154 (40%) had achieved LLDAS. The attending physicians with a lower consistency score of ConclusionThe grit personality characteristics of the attending physician may affect the achievement of treatment goals in patients with SLE.Disclosure of InterestsKEN-EI SADA Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., Grant/research support from: I received a research grant from Pfizer Inc., Yoshia Miyawaki: None declared, Kenta Shidahara: None declared, Shoichi Nawachi: None declared, Yu Katayama: None declared, Yosuke ASANO: None declared, Keigo Hayashi: None declared, Keiji Ohashi: None declared, Eri Katsuyama: None declared, Takayuki Katsuyama: None declared, Mariko Narazaki: None declared, Yoshinori Matsumoto: None declared, Nao Oguro: None declared, Yuichi Ishikawa: None declared, Natsuki Sakurai: None declared, Chiharu Hidekawa: None declared, Ryusuke Yoshimi: None declared, Takanori Ichikawa: None declared, Dai Kishida: None declared, Yasuhiro Shimojima: None declared, Noriaki Kurita: None declared, Nobuyuki Yajima: None declared

BackgroundThe minimally important difference (MID) required to interpret the magnitude of changes in lupus patient-reported outcome (LupusPRO), which is a widely used outcome measure of quality of life in SLE patients, remains unclear.ObjectivesWe report preliminary results of an ongoing prospective observational study that assesses the MID as the interpretability of emotional health (EH) domain in Japanese version of LupusPRO.MethodsWe recruited subjects at three university hospitals in Japan participating in an ongoing multidisciplinary cohort study (the Lupus registry of Nationwide institutions (LUNA). Of a total of 210 SLE patients enrolled during the 17-month recruitment period, patients with low disease activity, defined as SLE Disease Activity Index 2000 (SLEDAI-2K) ≤ 4, and who were seen at least twice of three months’ duration and responded to both the LupusPRO and health status change questions were included in this subcohort. The second questionnaire was given an allowance period of 30 days before or after the ​three months from starting date. Descriptive statistics were presented as means and standard deviations (SD) or counts and percentages (%). The emotional health score ranges from 0 to 100; a higher score indicates less frequent presence of symptoms. The change in health status was assessed using the 7-point Global Rating of Change 1), and the score = 0 and the score ≥ +1 were considered in the ‘unchanged’ and the minimal ‘improved’ category, respectively. MID was mainly estimated using the mean change of the groups with the score ≥ +1 as the anchor-based method, and the area under the curve (AUC) was also calculated as a sensitivity analysis to estimate MID thresholds 2) and 95% confidence intervals (CI) were constructed using 1000 bootstrapping.ResultsThe mean age of the 24 eligible patients was 48 (SD 14), and 88% were female. The glucocorticoid dose, SLEDAI-2K, and Systemic Lupus International Collaborating Clinics /American College of Rheumatology Damage Index were 3.4 (2.1) mg, 1.0 (1.1) and 1.1 (1.9), respectively. The mean EH score was 67.5 (30.3), five patients (21%) had the maximum EH score at baseline, 73.4 (25.0) after three months, 7.2 (18.0) for the change in EH. The correlation coefficient and the AUC for the change in health status and the EH were 0.23 and 0.60. The mean changes were 4.1 (18.4) of the groups with ‘unchanged’ health status and 12.3 (17.1) of the groups with ‘improved’ health status. The MID for improvement was estimated at 12.3 using the anchor-based method, and the cutoff point corresponded to 9.3 [95%CI -6.7 to 25.3]) of the EH change score by the receiver operating curve method.ConclusionIn this study, the MID (3 months) for the EH domain in the Japanese version of LupusPRO was estimated to be between 9 and 12, which was similar to the results of the previous cross-sectional study 3). The challenge in estimating the MID in our setting was the low correlation with external anchors, even though the study population was limited to patients with low disease activity, because disease activity at baseline can generally influence ‘improved’ health status.References[1]Kamper SJ, Maher CG, Mackay G. Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther. 2009;17(3):163.[2]Froud R, Abel G. Using ROC curves to choose minimally important change thresholds when sensitivity and specificity are valued equally: the forgotten lesson of pythagoras. theoretical considerations and an example application of change in health status. PLoS One. 2014;9(12):e114468.[3]Miyawaki Y, Shimizu S, Ogawa Y, et al. Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study. Arthritis Res Ther. 2021;23(1):79.AcknowledgementsThe authors thank Yuka Nakanou for her significant assistance in data management and Kikuko Miyazaki for her expert assistance on this topic.Disclosure of InterestsYoshia Miyawaki: None declared, Kenta Shidahara: None declared, Shoichi Nawachi: None declared, Yosuke ASANO: None declared, Yu Katayama: None declared, Keiji Ohashi: None declared, Eri Katsuyama: None declared, Takayuki Katsuyama: None declared, Mariko Narazaki: None declared, Yoshinori Matsumoto Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., KEN-EI SADA Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., Ryo Yanai: None declared, Nobuyuki Yajima: None declared, Ayuko Takatani: None declared, Kunihiro Ichinose: None declared, Jun Wada Speakers bureau: Jun Wada receives speaker honoraria from Astra Zeneca, Daiichi Sankyo, Novartis, Novo Nordisk Pharma, Tanabe Mitsubishi and receives grant support from Astellas, Baxter, Bayer, Chugai, Dainippon Sumitomo, Kyowa Kirin, Novo Nordisk Pharma, Ono, Otsuka, Tanabe Mitsubishi, and Teijin.

Background and purpose Many reports have examined electrocardiographic (ECG) changes after subarachnoid hemorrhage from long ago; however, there are few reports on the prognosis of patients who have an ECG abnormality. Therefore, in this study, the prognoses of patients with subarachnoid hemorrhage showing abnormal ECG findings were retrospectively analyzed. Methods Over 30 months from January 2014 to June 2016, 199 patients (mean age, 61.1±17.0 years; 46.7% male) admitted with a subarachnoid hemorrhage (SAH) were enrolled. To assess the mechanism underlying abnormal ECG in the SAH, predictor variables, such as demographics (age, sex, and body surface area), hemodynamics (heart rate and systolic blood pressure), blood biochemical results, neurological assessments (Glasgow Coma Scale), and computed tomography (CT) severity classification (World Federation of Neurosurgical Societies classification) were recorded. The subarachnoid hemorrhage was classified into either the cerebral aneurysm rupture group (N=132) or traumatic subarachnoid hemorrhage group (N=67) and analyzed. Results In the cerebral aneurysm rupture group, the QT prolongation was significantly increased compared with the traumatic subarachnoid hemorrhage group (424.8±87.7 ms vs. 400.5±95.8 ms, P Conclusions Significantly prolonged QT and ST changes are noted in patients with severe aneurysmal subarachnoid hemorrhage. The cause of the ECG abnormality in subarachnoid hemorrhage patients is not yet understood. A small number of experimental animal models have shown that electrocardiogram abnormalities associated with subarachnoid hemorrhage develop in the brain stem, and an autonomic nerve abnormality may also be involved. A D-dimer is positively correlated with both aneurysm trauma and traumatic subarachnoid hemorrhage and may be used for auxiliary diagnosis of a subarachnoid hemorrhage.

In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists.

Objective Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [18F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain. Method A randomized controlled trial comparing 5-day bright light exposure + environmental light (bright light exposure group) with environmental light alone (no intervention group) was performed for 55 participants in a university hospital. The uptake of [18F]FDG in olfactory bulb and hippocampus using FDG positron emission tomography was compared between two groups. Results There was a significant increase of uptake in both right and left olfactory bulb for bright light exposure group vs. no intervention group. After adjustment of log-transformed illuminance, there remained a significant increase of uptake in the right olfactory bulb. Conclusion The present findings suggest a possibility that 5-day bright light exposure may increase [18F]FDG in the right olfactory bulb of the human brain, suggesting a possibility of neurogenesis. Further studies are warranted to directly confirm this possibility.

Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance.

We implemented an antimicrobial stewardship (AS) program whereby pharmacists sought appropriate use of antimicrobial agents in January 2012. At that time, we targeted anti-methicillin-resistant Staphylococcus aureus (MRSA) agents and carbapenems; however, in January 2014, we added tazobactam/piperacillin (TAZ/PIPC). We evaluated outcomes using multilateral analyses. The average one-day dosage of carbapenems increased; however, the duration of administration and number of recipient patients decreased significantly (P0.01). Moreover, the percentage of patients receiving meropenem (MEPM), for whom the time above minimal inhibitory concentration (MIC) was 40% or higher increased (P0.01). In contrast, patient utilization of TAZ/PIPC increased significantly after targeting of carbapenems as specific antibacterial agents. However, after TAZ/PIPC was targeted as a specific antibacterial agent, the number of TAZ/PIPC administrations decreased significantly (P0.01). The duration of hospitalization and mortality rate in patients receiving specific antibacterial agents significantly decreased after implementation of the AS program (P0.01). In conclusion, pharmacist's interventions to provide AS and patient follow-up reduced improper use and promoted proper administration of antibacterial agents. Furthermore, AS was effective in improving patient prognoses and suppressing drug-resistant strains, as well as promoting effective treatment.

Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is essential for cell proliferation and differentiation. Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections. Because patients with GATA-2 deficiency syndrome could retain a wild-type copy of GATA-2, boosting residual wild-type GATA-2 activity may represent a novel therapeutic strategy for the disease. Here, we sought to establish a screening system to identify GATA-2 activators using human U937 monocytic cells as a potential model of the DC progenitor. Enforced GATA-2 expression in U937 cells induces CD205 expression, a marker of DC differentiation, indicating U937 cells as a surrogate of human primary DC progenitors. Transient luciferase reporter assays in U937 cells reveals a high promoter activity of the -0.5 kb GATA-2 hematopoietic-specific promoter (1S promoter) fused with two tandemly connected GATA-2 +9.9 kb intronic enhancers. We thus established U937-derived cell lines stably expressing tandem +9.9 kb/-0.5 kb 1S-luciferase. Importantly, forced GATA-1 expression, a repressor for GATA-2 expression, in the stable clones caused significant decreases in the luciferase activities. In conclusion, our system represents a potential tool for identifying novel regulators of GATA-2, thereby contributing to the development of novel therapeutic approaches.

Background and aims To investigate relationship between cystatin C (Cys)/creatinine ratio and disease activity of systemic lupus erythematosus (SLE). Methods Clinical and laboratory data were collected from 52 patients with SLE who had been examined their Cys at least once. Female rate was 96.2% and the average age±standard deviation was 47.9±13.2 years old. Estimated GFR (eGFR) was calculated based on Cys (eGFRcys) and creatinine (eGFRcre). Shrunken pore syndrome (SPS) was defined as eGFRcys/eGFRcre Results Comparing 20 patients with Cys Conclusions SLE patients with increased ratio of Cys to creatinine had high disease activity, and organ involvements were found with high frequency in patients with SPS.

A middle-aged woman who had undergone autologous hematopoietic stem cell transplantation (HSCT) 1 month previously suffered severe epigastralgia and relapse of lymphoma. The epigastralgia was not relieved by chemotherapy. Thereafter, her pancreatic and hepatic enzyme levels were markedly elevated and disseminated varicella emerged. Despite acyclovir administration, her general condition deteriorated rapidly and she died. Serum varicella zoster virus (VZV) DNA level was shown to be elevated and a diagnosis of disseminated VZV infection was established postmortem. In patients with severe abdominal pain following HSCT, early suspicion and therapeutic intervention for VZV are important, even in the absence of skin lesions.

Madagascar periwinkle plants containing physiologically active indole alkaloids were grown hydroponically under red light (R) from red Light-Emitting Diodes (LEDs; 660nm peak wavelength) or white light (FL) from fluorescent lamps in the enclosed artificial lighting plant factory. The effects of light quality on growth and vindoline (VIN) and catharanthine (CAT) accumulation per plant were investigated. Total leaf fresh weight and dry weight were greater in the R-grown plants than in the FL-grown plants. This increase of leaf biomass was caused by an increase of individual leaf fresh weight rather than an increase of leaf number per plant. At 77 d after germination the VIN and CAT accumulations per plant were 1.7 times and 1.4 times higher in the R-grown plants than in the FL-grown plants, respectively. Both the increase in the total leaf dry weight and the increase in the VIN and CAT concentrations in the total leaves contributed to the enhancement of alkaloids accumulation under R conditions. Cultivation under the red light using red LEDs for more than two and a half months was more effective than FL-based white light to produce VDL and CAT in the Madagascar periwinkle.

The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n=2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1–2 or 3–4 acute GVHD was significantly associated with a lower relapse rate. Grade 3–4 acute GVHD was associated with a higher risk of non-relapse and overall mortality than no acute GVHD, whereas grade 1–2 acute GVHD was associated with a lower risk of non-relapse and overall mortality than no acute GVHD. Limited or extensive chronic GVHD was significantly associated with a lower relapse rate. Limited chronic GVHD was associated with a lower overall and non-relapse mortality than no chronic GVHD. In conclusion, mild acute or chronic GVHD was associated not only with a low risk of relapse but also with a low risk of non-relapse mortality, and provides a survival benefit in UCBT.

Inappropriate antimicrobial treatment could adversely affect the recovery of patients with aspiration pneumonia. We attempted to identify inappropriate antibacterial treatment and to determine the standard use of anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs in aspiration pneumonia patients with MRSA-positive in sputum. Aspiration pneumonia patients with MRSA-positive sputum treated between January 2013 and May 2013 were included in this study to determine the risk factors for death during hospitalization. The relationship between anti-MRSA medicine use and death during hospitalization was also investigated. More than 10⁷ MRSA colony-forming units in sputum culture, creatinine clearance of less than 30 mL/min, and quinolone use were found to be risk factors for death during hospitalization. The death rate during hospitalization was significantly lower in cases a Geckler classification of 4 or 5 when anti-MRSA treatment was initiated soon after the culture was obtained. Therefore, we concluded that the use of quinolones as antibacterial treatment in aspiration pneumonia patients with MRSA-positive sputum should be avoided and that anti-MRSA treatment should be started in cases with good quality sputum cultures.

The loss energy density (AC loss) in cylindrical superconductor with ripple current based on Irie-Yamafuji model in which the magnetic fiel dependence of critical current density is taken into account is theoretically calculated for design of DC transmission cable system. It is confirme that the AC loss does not changed for the cases with and without DC current when the critical current does not depend on magnetic fiel which is corresponding to Bean-London model. On the contrary, it is found that there is current region where the AC loss becomes smaller than that for the case without DC current. The AC loss of ripple current is seems to be enough small in layered structure of DC transmission cable made by thin tape superconductor., Proceedings of the 24th International Symposium on Superconductivity (ISS 2011), October 24-26, 2011, Tokyo, Japan