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Introduction: The comprehension of musical tonal structure may rely on executive functions, such as cognitive control and working memory updating, to orient the listener to a tonal context and guid...

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Funding Acknowledgements Type of funding sources: None. Background Quantification of left ventricular (LV) dyssynchrony is of great interest for resynchronization therapy (CRT). Recently, cardiac computed tomography (CCT) is feasible for evaluation of dyssynchrony. Our aim was to assess a novel simplified approach using CCT to quantify LV dyssynchrony. Methods We studied 346 consecutive patients with a wide range of QRS width and ejection fractions (EF). Electrocardiogram-gated contrast-enhanced 256-slice multidetector CT (Brilliance 256 iCT, Philips Medical Systems) was performed before CRT. After CCT scan, the LV endocardial boundaries from short-axis images reconstructed at 5% increments of cardiac cycle were automatically detected, and a time from R-wave to maximal wall motion was calculated for each of the 16 standardized segments for all slices using software "Myocardial Contraction Map" (Argus, Inc Ehime, Japan). The standard deviation of all segments modified by mean heart rate (%SD) was respectively calculated as the global parameter of dyssynchrony. LVEF was also measured using MDCT. Results %SD was feasible in all patients, respectably. %SD was significantly different between the different QRS duration groups; narrow QRS (150 ms): 14 ± 7% (p Conclusion This novel simplified approach by CCT can quantify dyssynchrony in different QRS duration and morphology groups. This method has promise for clinical applications to the evaluation of patients for CRT. Abstract Figure.

Background It has been reported that low voltage areas and conduction abnormalities detected by electrophysiology catheters in the left atrium (LA) represent regional degeneration and fibrosis of the atrium and are related to a poor atrial fibrillation (AF) ablation outcome. Assessment of the local atrial function is clinically useful because atrial degeneration does not occur uniformly throughout the atrium. Though evaluating the global atrial function using speckle tracking imaging (STI) by transthoracic echocardiography (TTE) has been attempted, TTE does not have a sufficient image quality to assess local atrial STI. Purpose To evaluate the local atrial function by STI using intracardiac echocardiography (ICE) and to elucidate the characteristics of the STI in normal and abnormal voltage regions in the LA. Methods We included 9 patients undergoing AF ablation with written informed consent for this prospective observational study. After pulmonary vein isolation, we performed voltage mapping of the LA in sinus rhythm using a CARTO system (Biosense). Abnormal regions and normal regions were defined as those with low voltage areas ( Results Among the study population, 5 patients had low voltage areas in the LA. We evaluated the STI at 26 normal regions and 44 abnormal regions. The typical regional speckle tracking waveform in the normal region was similar to a jugular vein pressure waveform (right figure). There was a difference in the amplitude of the Sct between the groups; it was significantly smaller in the abnormal regions (normal and abnormal regions, 9.8±5.0% and 5.6±3.8%, p=0.0001). The duration of the Sct was significantly more prolonged in the abnormal regions than normal regions (98.8±26.3ms and 118.2±33.9ms, p=0.015). Conclusions This pilot study demonstrated that the local atrial function was evaluable by STI using ICE and that the regional strain tracking waveform during the atrial contraction phase in abnormal voltage regions was smaller and more prolonged than that in normal regions. An evaluation of the regional STI with an ICE may be useful to detect regional abnormalities of the atrium. Representative case Funding Acknowledgement Type of funding source: None

Background Diagnosing heart failure with preserved ejection fraction (HFpEF) still remains challenging, and simple and reliable diagnostic tools have been required. Recently, novel and evidence-based diagnostic algorithms for HFpEF were proposed, such as H2FPEF score (Circulation. 2018) and HFA-PEFF score (Eur Heart J 2019), and their accuracy was validated in the outside patient group. However, there are regional and ethnic variations in patient characteristics of HFpEF, particularly between Western and Asian countries, and it is not elucidated whether these diagnostic scores are useful in Asian population. Purpose To investigate the validity of the HFA-PEFF- and H2FPEF score in Japanese patients with HFpEF. Methods We calculated H2FPEF score and the second step of HFA-PEFF score among the registered patients in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for HFpEF. The obtained scores were compared with the scores of the HFpEF cohort in the previous validation studies. We followed the study patients for median of 360 days (IQR 237–630 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We enrolled 757 patients hospitalized for HFpEF between June 2016 and August 2019 for the present study. H2FPEF score was obtained in 588 (77.7%) patients among them. Compared with the HFpEF cohorts in the previously reported sub-analysis of TOPCAT trial, the PURSUIT-HFpEF cohort had lower mean value of HFpEF score (4.0±1.8 points vs. 6.0±2.0 points in Americans or 5.3±1.9 points in Russians). It had significantly higher proportion (40.3%, p HFA-PEFF score was obtained in 615 (81.2%) patients, though global longitudinal strain was not available. The mean value of HFA-PEFF score was 5.0±0.8, and all patients had ≥2 points. The proportion of patients in the high likelihood of HFpEF category (5–6 points) was 88.3%, which was significantly higher (p Conclusion The HFA-PEFF score could be more useful for the diagnosis and risk stratification for HFpEF than the H2PEF score in the Japanese cohort. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

Background The degree of mechanical dyssynchrony has been suggested as a predictor for long-term survival after cardiac resynchronization therapy (CRT). There have been little reports of dyssynchrony assessment with the use of cardiac computed tomography (CCT). Methods We studied 35 heart failure (HF) patients (average age 67±10 years) referred for CRT with NYHA III-IV heart failure, left ventricular (LV) ejection fraction (EF) 20±10% (all ≤35%), and QRS duration 156±22 ms (all ≥120ms). Electrocardiogram-gated contrast-enhanced 256-slice multidetector CT was performed before CRT. Based on CCT, the LV endocardial boundaries from short-axis images reconstructed at 5% increments of cardiac cycle were automatically detected, and the time from R-wave to maximal wall motion was calculated for each of the 16 standardized segments for all slices using software “Myocardial Contraction Map”. The standard deviation modified by mean heart rate (%SD) was respectively calculated as the global parameter of dyssynchrony. LVEF was also measured using MDCT. The predefined primary end-point was the first HF hospitalization or death over 2 years. Results %SD was feasible in all patients, respectably. There were 16 events over 2 years; 11 HF hospitalizations and 5 deaths. Patients with %SD ≥22% (optimal cutoff for outcome by ROC curve analysis) had a better clinical outcome than patients with %SD Conclusion Patients who had %SD ≥22% assessed by MDCT had a particularly favorable event-free survival following CRT, and this appears to be an important prognostic marker. Funding Acknowledgement Type of funding source: None

Background Preoperative left atrial (LA) function is associated with paroxysmal atrial fibrillation (PAF) ablation outcome. The presence of left atrial low voltage zone (LVZ) is also associated with recurrence. We hypothesized that reduced pre-ablation LA function reflects the presence of LVZ. Purpose We investigated the association between baseline LA function and the presence of LVZ in patients undergoing initial PAF ablation. Further, we sought to create the new predictive scoring for the presence of LVZ. Methods Consecutive 305 patients who underwent LA voltage mapping during initial PAF ablation from January 2017 to October 2019 in our institute were retrospectively analyzed. We performed 256-slice MDCT at baseline. As the representative of LA function, we calculated LA emptying fraction (LAEF), where LAEF = {[(maximum LAV) − (minimum LAV)]/(maximum LAV)} x 100. LVZ was defined as regions where bipolar peak-to-peak voltage was Results Out of 305 pts, 56 pts (18%) had LVZ in LA. In univariate analysis, low body mass index, higher percentage of female sex, higher age, higher E/e', larger maximum LA volume and lower LAEF (29.3±11.8% vs. 41.2±9.7, P Conclusions In PAF patients, preoperative LAEF was strongly associated with the presence of LVZ. LVZ might reflect the myocardial injury causing LA dysfunction. OLAF-LVZ predictive score: combination of Old age (≥65), Female sex, and LAEF (≤31%) could be useful to stratify the risk of the presence of LVZ. Funding Acknowledgement Type of funding source: None

Introduction Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes. Purpose To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: 87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident. Results The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p Conclusions Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

Introduction Structural remodeling is an important aspect of pathophysiology of heart failure (HF). The compensatory mechanism against diastolic dysfunction would be more obvious on the left atrium rather than left ventricle in HF with preserved ejection fraction (HFpEF). Purpose To investigate the impact of left atrial (LA) and left ventricular (LV) remodeling on clinical outcomes in HFpEF patients. Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute HF (diagnosed by using Framingham criteria) met the inclusion criteria: a LV ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 381 patients (age, 82±9 years; men, 45%; atrial fibrillation (AF), 34%) whose follow-up data after survival discharge were available and whose LA volume index (LAVI) and left ventricular end-diastolic volume index (LVEDVI) at discharge were measured by the biplane Simpson's method using echocardiography. The primary endpoint was defined as the composite of death, re-hospitalization for HF, and cerebrovascular accident. Results The LAVI and LVEDVI at discharge was 54±25 ml/m2 and 55±21 ml/m2, respectively (r2=0.014, p=0.021). When patients were classified into the LAVI tertiles groups (T1: 60ml/m2 (n=130)), there was a positive correlation between the prevalence of diastolic dysfunction and the LAVI tertiles (T1, 21.0%; T2, 48.8%; T3, 51.5%; p Conclusions Increased LAVI at discharge, which was associated with diastolic dysfunction, related to unfavorable prognosis in patients with HFpEF. However, LAVI was no more a predictor for the adverse outcomes but LVEDVI was in the AF subgroup. The clinical significance of atrial and ventricular remodeling may differ between sinus rhythm and AF rhythm in HFpEF population. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

Background While multiple catheter ablation for recurrent atrial fibrillation (AF) is effective for the maintenance of sinus rhythm, some of patients have ablation-refractory AF. Left atrial (LA) dysfunction and the presence of low voltage zone (LVZ) are associated with recurrence after AF ablation. The association between recurrence and LA dysfunction/ LVZ among patients undergoing multiple AF ablation remains unclear. Purpose We aimed to compare (i)LA function, (ii)the prevalence of LVZ among patients undergoing first, second and third or more AF ablation procedures. Further, we investigated whether LA dysfunction and LVZ are associated with recurrence after multiple procedures. Methods We retrospectively analyzed 460 patients undergoing AF ablation procedures including first, second and third or more sessions from January 2017 to October 2019 in our institute. Before each session, 256-slice MDCT was performed under sinus rhythm to measure pre-ablation LA emptying fraction (LAEF) as the representative of LA function. At the end of each session, we checked the presence of LVZ, which was defined as regions where bipolar peak-to-peak voltage was Results Out of 460 sessions, 295 were first (follow-up years: 1.5 [0.8, 2.0]), 134 were second (1.0 [0.5, 1.8]), and 31 were third or more sessions (1.2 [0.7, 2.0]). As the number of sessions increased, the recurrence rate was increased (19% vs. 31% vs. 61%, first vs. second vs. ≥third, P Conclusions As the number of sessions increased, the recurrence rate was increased. The prevalence of LA dysfunction and LVZ was high in patients requiring multiple ablation procedure. LA dysfunction and LVZ possibly reflect arrhytmogenic substrate causing recurrence of ablation-refractory AF. We should carefully consider repeated AF ablation in patients with severe LA dysfunction and extensive LVZ. Figure 1 Funding Acknowledgement Type of funding source: None

Background Catheter ablation of atrial fibrillation (AF) is effective, but certain patients experience AF recurrences. Obstructive sleep apnea (OSA) is a risk factor for AF recurrence. Watch peripheral arterial tonometry (WP) has a good correlation with polysomnography (PSG) in terms of the apnea-hypopnea index (AHI) and is easier to perform than PSG. Patients in AF have a high prevalence of OSA. Whether all patients with AF should be evaluated for OSA before catheter ablation is still controversial. Purpose To elucidate the prevalence and predictors of OSA using WP as a home sleep apnea test in AF patients before catheter ablation. Methods This study was conducted under a retrospective, single-center, observational design. Patients who received AF ablation without a prior diagnosis of sleep apnea and assessment of their AHI using WP were included in this analysis. The patients were mounted with a WP device by themselves at their own home. Twenty-two patients who were already diagnosed with OSA were excluded. Results Seven hundred seventy-four (65±11 years, 567 males, 440 paroxysmal AF) out of 776 patients were successfully mounted with WP devices on their own and underwent an OSA assessment. Their mean body mass index (BMI) was 24.1±3.5 kg/m2. The mean AHI was 20.1±15.6. Only 88 (11.4%) patients had a normal AHI (AHI Conclusion Almost All patients successfully underwent WP to diagnose OSA. AF patients had a high prevalence of OSA, and screening OSA would be important in AF patients receiving ablation even if patients do not have sleepiness or are obese. We cannot deny OSA in AF patients before catheter ablation without performing screening tests for OSA. Funding Acknowledgement Type of funding source: None

Background Psoriatic arthritis (PsA) is a chronic and debilitating disease that can be managed by different clinical specialists. Objectives The objective of theLOOPstudy was to evaluate the impact of clinical specialty setting on the time to diagnosis and treatment of patients with PsA. Clinical disease activity and disease burden were also compared between clinical settings. Methods LOOPwas a cross-sectional, multicentre, observational study conducted in 17 countries in Western and Eastern Europe, the Middle East, Latin America and Asia. Adult patients (>= 18 years) with a suspected or established diagnosis of PsA who were routinely visiting a rheumatologist, dermatologist or non-rheumatology/non-dermatology physician were enrolled. All patients were assessed by both a rheumatologist and a dermatologist. Results Of 1483 enrolled patients, a total of 1273 had a confirmed diagnosis of PsA. There was no significant difference in the median time from onset of inflammatory musculoskeletal symptoms to PsA diagnosis between patients enrolled by rheumatologists and dermatologists (6.0 vs. 3.9 months). However, the median time from diagnosis to first treatment with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) was significantly shorter in the rheumatology setting compared with the dermatology setting (0 vs. 2.0 months;P < 0.001). In addition, disease activity was significantly higher in the dermatology setting compared with the rheumatology setting. Conclusions Differences in the management and clinical status of patients with PsA were observed between the rheumatology and dermatology settings. Importantly, median time from diagnosis to first csDMARDwas significantly shorter in the rheumatology setting, and patients in the dermatology setting had higher disease activity. These data show the importance of improved collaboration between rheumatologists and dermatologists. AbbVie

Objective To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. Methods Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). Results The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. Conclusion Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.

Static encephalopathy of childhood with neurodegeneration in adulthood (SENDA) or β-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA), causing abnormal iron accumulation in the globus pallidus and substantia nigra through autophagic dysfunction due to WDR45 mutations.1,2 SENDA/BPAN is often difficult to diagnose because brain MRI does not detect the characteristic findings in childhood. We found transient hyperintensity and swelling in the globus pallidus and substantia nigra due to infections during childhood as characteristic findings.

This chapter focuses on the possibility that music training could serve as a type of cognitive training. Music is an interesting potential avenue for cognitive training not only because music learning and processing are likely to draw heavily on executive function abilities, but also because musical experience has its own intrinsic rewards. This suggests that music training might serve as a particularly enjoyable and rewarding route to cognitive training. The authors describe some theoretical reasons to expect a strong relationship between executive function and music, describe the small body of work that has experimentally assessed the possibility that musical experience might transfer to executive function abilities, and finally recommend ways in which a music training program might strengthen cognitive abilities.

Background Successful restoration of sinus rhythm (SR) by catheter ablation (CA) for persistent atrial fibrillation (AF) improves cardiac function, resulting in decrease of plasma brain natriuretic peptide (BNP) level. The exact significance and prognostic implications of this change have yet to be determined. Purpose To examine the impact of pre- and post-procedural BNP level on the clinical outcome after CA in patients with persistent AF and reduced left ventricular ejection fraction (LVEF). Methods Out of 242 patients with LVEF Results All patients successfully restored SR at the end of CA. Within 3 months of a blanking period (BP), improvement of LVEF (from 39±10% to 65±12%, p55.5 pg/ml (n=50) than the others (50% vs. 29%; HR, 3.99; 95% CI, 2.07–7.68; p Conclusions Not pre-procedural but post-procedural BNP level early after CA predicted the future clinical outcome in patients with persistent AF and reduced LVEF. Decreased but still elevated BNP level after restoration of SR would identify the residual risk for developing unfavorable outcome.

Background The strategy of intravascular ultrasound (IVUS)-guided wiring for CTO PCI, that is, leading the second guidewire into the true lumen under observing by IVUS from subintimal space, is the last resort. We developed the angiography-based 3D wiring method. During establishment of the angiography-based 3D wiring method, we deduced that observation of the guidewire tip as well as the shaft named “The tip detection method” simplifies and facilitates 3D wiring under IVUS-guided wiring. Therefore, we produced New CTO IVUS which is the upgraded version of Navifocus WR IVUS by adding the pull-back transducer system. This pull-back system enables us to detect the tip as well as the shaft of the second guidewire in real time (tip detection method), which facilitates the 3D wiring technique under IVUS-guided wiring. Objective We evaluated the efficacy of the tip detection method during 3D wiring for CTO PCI with New CTO IVUS. Method We created a target pinpoint penetration model and performed the procedures using an experimental heartbeat model. The target (a tube with a lumen 0.6 mm in diameter) was placed in the distal part of a CTO 20 mm in length made of 2.5% agar. After the second guidewire (Conquest-12g) was advanced into the CTO lesion to within 5mm of the target using the angiography-based wiring, IVUS-guided wiring was performed by using Navifocus WR or New CTO IVUS each five times. Result The frequency of the puncture time was reduced using the new CTO IVUS compared to the Navifocus WR (1.7±0.8 vs. 28.8±23.2, p=0.17). The procedure time was significantly shorter using the new CTO IVUS compared to the Navifocus WR (103±61 vs. 459±373 seconds, p=0.04). Conclusion The tip detection method during 3D wiring with the new short tip IVUS with the pull-back system enables us to easily perform 3D wiring and will change the CTO PCI strategy.

Background Serum Brain Natriuretic Peptide (BNP) level is associated with various cardiovascular events. Because elevated BNP level reflects increased left ventricular end-diastolic pressure and LA pressure promoting left atrial (LA) remodeling, BNP level might be associated with the extent of arrhythmogenic substrate in patients with atrial fibrillation (AF). We hypothesized that elevated BNP level has impact on outcome after catheter ablation (CA) for AF. Purpose We investigated the impact of baseline BNP level on outcome after multiple CA for paroxysmal atrial fibrillation (PAF), and assessed the association between baseline BNP level and extent of LA remodeling. Methods This was a retrospective, single-center observational study. A total of 287 patients who underwent CA for PAF in our institute from March 2012 to March 2014. All patients had dataset of baseline BNP level and LA volume measured by multi-detector computed tomography (MDCT) in sinus rhythm. First we performed receiver operating characteristic (ROC) analysis for recurrence after multiple CA and obtained the best cut-off value of BNP. Patients were divided into Low BNP and High BNP group based on BNP cut-off value, and AF-free survival was analyzed with log-rank test. To assess the impact of BNP level on recurrence, multivariate Cox regression model were performed. Finally, we assessed the extent of baseline LA remodeling in low BNP and high BNP group. Results During follow-up period, AF recurred in 65/287 patients (26.2%) after multiple CA procedure (follow up 3.4 [2.2, 4.0] years, total number of sessions: 1.39±0.63). Patients with recurrence had greater baseline BNP than those without recurrence (99.8 pg/mL [30.0, 128] vs. 60.7 pg/mL [17.3, 80.8], recurrence vs. no-recurrence, P Conclusion Baseline serum BNP level was associated with recurrence after multiple procedures for PAF. The baseline extent of LA remodeling was greater in High BNP than in Low BNP. Elevated BNP level might reflect the severe LA remodeling causing ablation-refractory AF even after multiple CA. The preoperative assessment of BNP might be helpful for prediction of multiple CA outcome.

The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm

Background Increasing incidence of syphilis in the United States and penicillin shortages internationally call for research on alternative treatment options. In this randomized, multisite, open-label, non-comparative clinical trial, we are evaluating the efficacy of cefixime as treatment of early syphilis. Methods Eligible participants are 18 years or older, have laboratory confirmed early syphilis (new Rapid Plasma Reagin [RPR] titer ≥1:8 or 4-fold titer rise in past 12 months), and no concomitant antibiotic use. Patients with HIV infection must have undetectable viral load in the past 12 months and CD4+ count ≥350 cells/μl. Participants were randomized to receive either 2.4M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day, for ten days. Participants return for follow-up at 3, 6, and 12 months post-treatment for laboratory testing. The main outcome is a 4-fold RPR titer decrease at 6 months post-treatment. Results To date, 27 participants (15 penicillin, 12 cefixime) are enrolled. The majority of the study population is men (26/27), Latino (15/27), and HIV-infected (25/27). Eight participants completed their 3-month follow up (4 cefixime/4 penicillin). In the cefixime arm, 3/4 participants had an equal or greater than four-fold decrease in the RPR titer, and 1/4 had a two-fold decrease. In the penicillin arm, 2/4 participants had an equal or greater than 4-fold decrease in the RPR titer, 1/4 had a two-fold decrease, and 1/4 is missing data. Conclusion Enrollment is still open and data collection ongoing. Initial results are encouraging. Disclosure No significant relationships.

Background:Hydroxychloroquine (HCQ) is an essential drug for systemic lupus erythematosus. But in Japan, chloroquine and HCQ remain unavailable until mid 2015 because of a series of lawsuits about its retinal toxicity in the 1970s. There is insufficient knowledge regarding renal protective effect of HCQ.Objectives:We aimed to investigate its efficacy of adding HCQ for Lupus nephritis (LN) as a maintenance-phase therapy.Methods:We conducted an observational retrospective cohort study included patients with LN (n=42) in maintenance-phase in Japan. We reviewed medical records of LN patients aged > 18 years who were initiated HCQ from May 2015 to May 2018. Maintenance phase was defined as stabilization in serum creatinine and urinary segment after induction therapy and who achieved complete or partial remission. The annual change of proteinuria was compared between patients on HCQ who have proteinuria (>0.5g/gCr) or not. Other outcome measures were disease flare, dose of steroids, renal and immunologic features.Results:A total of 42 patients were analyzed and allocated to two groups based on their amount of daily urine protein level: HCQ with proteinuria as group A (>0.5g/gCr, n=14) and HCQ without proteinuria as group B(≦0.5g/gCr, n=28). Both groups were comparable, with mean (SD) age of 36.1 (12.9) years and 37.5 (13.8), female 78.6% and 92.9% in each group, mean (SD) disease duration until HCQ of 3.5 (3.25) and 3.3 (2.9) years in group A and group B, with prednisolone dose at base line of 10.3 (7.1) mg and 7.9 (4.4) mg, respectively. The mean (SD) proteinuria at base line was 1.38 (1.11) g/gCr in group A and 0.20 (0.09) g/gCr in group B and after 12 months, proteinuria decreased in group A (-1.34 g/gCr in group A vs +0.03 g/gCr in group B; pConclusion:In patients with clinically stable LN but with proteinuria, hydroxychloroquine is a good therapeutic option for achievement of complete remission.Disclosure of Interests:None declared

Paddy fields are an important source of atmospheric CH4, the second most important greenhouse gas. There is a strong concern that the increasing atmospheric CO2 concentration ([CO2]) and global warming are further stimulating CH4 emissions, but the magnitude of this stimulation varies substantially by study, and few open-field evaluations have been conducted. Here we report results obtained at a Japanese rice free-air CO2 enrichment (FACE) site under water and soil temperature elevation during two growing seasons. Our objectives were to evaluate the effects of high [CO2] (ambient + 200 μmol mol−1) and elevated soil temperature (+ 2 °C) on CH4 emissions under completely open-field conditions. We found about 80% enhancement in total seasonal emissions by the additive effects of FACE and warming, indicating a strong positive feedback effect of global warming. The enhancement in CH4 emission from the FACE-effect alone (+ 26%) was statistically non-significant (P = 0.19). Nevertheless, observed positive correlations between CH4 emissions and rice biomass agreed well with previous studies, suggesting that higher photosynthesis led to greater rhizodeposition, which then acted as substrates for methanogenesis. Soil warming increased the emission by 44% (P < 0.001), which was equivalent to a Q10 of 5.5. Increased rice biomass by warming could only partly explain the enhanced CH4 emissions, but stoichiometric analysis of the electron budget indicated that even a moderate enhancement in organic matter decomposition due to soil warming can cause a large increase in CH4 production under conditions where Fe(III) reduction, which was little affected by soil warming, dominates electron-accepting processes. At later rice growth stages, advanced root senescence due to elevated temperature probably provided more substrate for methanogenesis. Our stoichiometric evaluation showed that in situ Fe reduction characteristics and root turnover in response to elevated temperature should be understood to correctly predict future CH4 emissions from paddy fields under a changing climate. Challenges remain for determination of in situ root-exudation rate and its response to FACE and warming.

Background Evidence suggests that timely and effective management can improve long-term outcomes in patients (pts) with psoriatic arthritis (PsA); however factors influencing treatment management decisions are not well understood. Objectives To evaluate the association between the clinical specialty setting and time from inflammatory musculoskeletal symptom onset to PsA diagnosis and to different management steps in pts with a diagnosis of PsA. Methods LOOP is a large cross-sectional, multi-centre, observational study conducted in 17 countries across Western and Eastern Europe, Latin America, and Asia. Adult pts (≥18 years) with a suspected or an established diagnosis of PsA routinely visiting a rheumatologist (rheum), dermatologist (derm) or non-rheum/non-derm site were eligible to participate in this study. Each enrolled patient in the study was assessed by both rheum and derm. Main endpoints assessed were time from inflammatory musculoskeletal symptom onset to PsA diagnosis, time from PsA diagnosis to first csDMARD and to first bDMARD, and time from first csDMARD to first bDMARD. Results Of the 1483 pts enrolled in this study, 1273 pts with a confirmed diagnosis of PsA were included in this analysis. A majority of pts were recruited by rheums (671, 52.7%), followed by derms (541, 42.5%), physiatrists (36, 2.8%), and other specialties (25, 2.0%). PsA was first suspected by a rheum in 726 (57.0%) pts and by a derm in 541 pts (42.5%). Pt demographics and disease characteristics were mostly comparable between rheum and derm settings. Current disease activity and disease burden of patients with PsA categorised by clinical specialty are shown in table 1. Disease activity was higher in PsA pts in derm setting compared with rheum setting. The timing of different disease management steps by clinical specialty is reported in table 2. The mean time from symptom onset to PsA diagnosis was 24 months (mo) in rheum setting and 1 mo longer for derms. In rheum and derm settings, the mean time from PsA diagnosis to first csDMARD were 11 and 25 mo, respectively; whereas the mean time to first bDMARD were 52 and 55 mo, respectively. The mean time from first csDMARD to first bDMARD was 42 mo for rheums; while it was 3 months shorter for derms. Conclusions Although the duration from symptom onset to PsA diagnosis was similar between rheum and derm setting, there were differences in the timing of introduction of different DMARD classes. Notably, mean time to first csDMARD was significantly shorter in rheum setting. PsA pts in derm setting had significantly higher disease activity. These data lend further support to the need for rheum-derm collaborative approach to optimise management of pts with PsA. Acknowledgements AbbVie funded the LOOP study, contributed to its design, and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. Medical writing was provided by Deepa Venkitaramani, PhD, of AbbVie. Disclosure of Interest W.-H. Boehncke Grant/research support from: Abbvie, Biogen Idec, Celgene, Covagen, Galderma, Janssen, Leo, Lilly, MSD, Novartis, Pantec Biosolutions, Pfizer, and UCB, Consultant for: Abbvie, Biogen Idec, Celgene, Covagen, Galderma, Janssen, Leo, Lilly, MSD, Novartis, Pantec Biosolutions, Pfizer, and UCB, Speakers bureau: Abbvie, Biogen Idec, Celgene, Covagen, Galderma, Janssen, Leo, Lilly, MSD, Novartis, Pantec Biosolutions, Pfizer, and UCB, R. Horvath Grant/research support from: AbbVie, MSD, Novartis, Pfizer, and UCB, Consultant for: AbbVie, MSD, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, and UCB, E. Dalkilic Grant/research support from: AbbVie, Speakers bureau: AbbVie, MSD, Roche, Pfizer, and UCB, S. Lima Consultant for: Abbive, BMS, and Janssen, Speakers bureau: Abbive, BMS, and Janssen, M. Okada Grant/research support from: AbbVie Japan, Ayumi Pharmaceutical, Eli Lilly and Company, Mitsubishi Tanabe Pharma, and Ono Pharmaceutical, Consultant for: AbbVie Japan, Ayumi Pharmaceutical, Eli Lilly and Company, Mitsubishi Tanabe Pharma, and Ono Pharmaceutical, Speakers bureau: AbbVie Japan, Ayumi Pharmaceutical, Eli Lilly and Company, Mitsubishi Tanabe Pharma, and Ono Pharmaceutical, M. Hojnik Shareholder of: AbbVie, Employee of: AbbVie, F. Ganz Shareholder of: AbbVie, Employee of: AbbVie, E. Lubrano Grant/research support from: AbbVie, Celgene, Janssen, MSD, Novartis, and Pfizer, Consultant for: AbbVie, Celgene, Janssen, MSD, Novartis, and Pfizer, Speakers bureau: AbbVie, Celgene, Janssen, MSD, Novartis, and Pfizer

In this study, we propose a new image display method to obtain high contrast-to-noise ratio (CNR) using energy resolved photon-counting mammography (ERPCM) with a cadmium telluride (CdTe) series detector manufactured by JOB CORPOLATION. The CdTe series detector can detect high-energy photons with high sensitivity, enabling users to image with high-energy X-rays. Using this detector, it is possible to reduce the dose given to a patient while increasing the CNR. First, the spectrum was divided into three bins and their corresponding linear attenuation coefficients were calculated from input and output photon numbers. Further, absorption vector length (AVL) and average absorption length (AAL) were calculated from the linear attenuation coefficients and from thicknesses of objects after beam-hardening correction. We further compared the CNR between ERPCM and general mammography images under the constant average glandular dose (AGD). We imaged an acrylic plate (1 mm thick) on RMI-156 phantom, determined regions of interest (ROIs) on an acrylic plate and background, and calculated the CNR. Our ERPCM generated two types of images: an AVL image and an AAL image. AMULET Innovality manufactured by FUJIFILM generated an integrated image. MicroDose SI manufactured by Philips generated a count image and removed electrical noise by the photon-counting technique. The four images, in order of decreasing CNR, were the AAL image, AVL image, MicroDose image, and AMULET image. The proposed method using ERPCM generated an image with higher CNR than images using general mammography under the constant AGD.

Background and aims Mizoribine is an inhibitor of inosine monophosphate dehydrogenase, which is widely used for patients with lupus nephritis and also patients after renal transplants. Its anti-cytomegaloviral effect is unique as an immunosuppressant. We examined the efficacy and safety of early sequential combination of mizoribine and tacrolimus in lupus nephritis. Methods Retrospective review of electric medical record was performed for all the 65 patients who received the combination therapy of mizoribine and tacrolimus and corticosteroids for induction or maintenance of lupus nephritis at St. Luke’s International Hospital, Tokyo, Japan. For efficacy analysis, we extracted a series of change in serum creatinine, serum complement level, urine protein creatinine ratio, dose of corticosteroid. We further reviewed safety profile such as adverse events occurred during the use of multi-target therapy, drug survival rate, or reasons for discontinue multi-target therapy in all patients. Complete remission of lupus nephritis was defined as a value of proteinuria Results Fifty six out of the sixty three patients (female:male=59:4, average age 37.4 years old) achieved complete remission in 6 months and there were only two relapses and both of them had Class V nephritis. At four month, the average urine protein creatinine ratio was 0.36 g/gCr, and the average dose of prednisolone was 9.9 mg/day. There were only three episodes of infections which required antibiotics administrations. Conclusions Early sequential combination of mizoribine and tacrolimus seems to be effective and safe for lupus nephritis.

Background Hydroxychloroquine (HCQ) has been widely used in the world. However, due to the problem of retinopathy caused by chloroquine, it had not been approved in Japan until 2015, although it has been used for limited number of patients in some institutions. The primary purpose of our study is to collect the data on adverse effect of HCQ among Japanese patients with systemic lupus erythematosus. We also assessed the efficacy of our methods to improve the tolerability in cases with gastrointestinal and dermatological side effects of HCQ. Method We retrospectively collected the data of all the 174 lupus patients treated with HCQ from the electric medical record of St Luke’s International Hospital, Tokyo, Japan. We extracted the following parameters during the period between April 2008 and June 2017; patients’ baseline characteristics, side effects and duration of using HCQ, and reasons of discontinuation. As for dermatological side effects, some of the patients underwent oral desensitisation; HCQ was once stopped, and after confirming negative DLST and obtaining consent from patients, it was resumed with the 36 days-desensitisation protocol. For patients with gastrointestinal side effects, some of the patients were prescribed Hangeshashinto, a traditional herbal medicine for gastrointestinal discomfort, in addition to HCQ. Result During the period, the mean age of the patients was 41.8. 161 patients (92.5%) were female and 152 patients (87.4%) were treated with steroids. The average duration of using HCQ was 582.4 days. 21 patients (12.0%) had side effects and 14 patients (8.0%) discontinued HCQ. 10 patients had skin side effects, 7 were performed DLST, 7 were negative, and 2 resumed HCQ. 5 patients had gastrointestinal side effects, 2 were prescribed Hangeshashinto. 2 patients were possible retinopathy and stopped HCQ. Conclusion This is one of the largest studies which reported well tolerability of HCQ in Japanese real world practice. Despite the concern of retinopathy, there were only 2 cases who stopped HCQ due to possible retinopathy in this study. In addition, our methods may help continuing HCQ in patients with skin or gastrointestinal side effects. Further larger study is needed to confirm these results.

Temperature dependence of the reverse transformation induced by shot-peening has been investigated for austenitic stainless steel (SUS 304) containing large amount of strain-induced martensite (α’). When the SUS 304 specimen is shot-peened under higher temperature than 100 o C, the volume fraction of austenite (γ) on the peened surface is increased. This indicates that the reverse transformation is occurred by the shot-peening. Furthermore, the amount of the γ generated by the reverse transformation is increased as the processing temperature increases. Hence, it is found that the reverse transformation behavior of the SUS 304 steel by the shot-peening depends on the processing temperature.

Background Central nervous system involvement is one of the most serious complications in Behcet9s disease (BD). This condition is referred to as neuro-Behcet9s disease (NB) and can be classified into acute type (ANB) and chronic progressive type (CPNB) based upon differences in the clinical course and responses to corticosteroid treatment. Diagnostic criteria were generated in 2013 based on a multicenter clinical survey performed by the Behcet9s Disease Research Committee of the Ministry of Health, Labor and Welfare of the Japanese Government. Although “Guidelines for Treatment of NB” was also proposed based on the survey, it is still preliminary. Objectives The aim of the current study is to develop evidence-based recommendations for the management of NB supplemented by expert opinions where necessary. Methods First, clinical questions (CQs) on NB were extracted from a literature search for problem areas and related keywords, and draft CQs and a flow chart were prepared. The expert committee, a task force of the research subcommittee for NB, consisted of 7 board-certified rheumatologists (one was also a board-certified neurologist) and 3 board-certified neurologists. A systematic literature search was performed using Medline and the Japan Medical Abstract Society databases from 1997 to 2016. A total of 15 initial CQs were generated. These yielded the final recommendations developed from 3 blind Delphi rounds, in which the rate of agreement scores on CQs (range 1 [disagree]–5 [strongly agree]) was determined though voting by the whole committee. Results Thirteen recommendations were developed for the management of NB (general 1, ANB 7, CPNB 5). The strength of each recommendation was established based on the evidence level as well as rate of agreement. There was excellent concordance between the level of agreement of rheumatologists and that of neurologists. Based on these recommendations, a flow chart was established for the management for ANB and CPNB (Figure). Conclusions The recommendations generated in this study are mainly based not only on expert opinions but on the results of uncontrolled evidence from open trials and retrospective cohort studies. Guidelines that can be used for international studies are needed, for which verification by further properly designed controlled clinical trials is required. Disclosure of Interest None declared