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In both 5- and 15-min data, FI was significantly higher in malignant tissues than in benign tissues. The diagnostic accuracy was similar at 5 and 15 min. Therefore, the 5-min FI was enough applying in the further analyses.

Background and purpose:Oscillatory shear stress could not be directly measured in consideration of direction, although cerebrospinal fluid has repetitive movements synchronized with heartbeat. Our aim was to evaluate the important of oscillatory shear stress in the cerebral aqueduct and foramen magnum in idiopathic normal pressure hydrocephalus by comparing it with wall shear stress and the oscillatory shear index in patients with idiopathic normal pressure hydrocephalus., Materials and methods:By means of the 4D flow application, oscillatory shear stress, wall shear stress, and the oscillatory shear index were measured in 41 patients with idiopathic normal pressure hydrocephalus, 23 with co-occurrence of idiopathic normal pressure hydrocephalus and Alzheimer-type dementia, and 9 age-matched controls. These shear stress parameters at the cerebral aqueduct were compared with apertures and stroke volumes at the foramen of Magendie and cerebral aqueduct., Results:Two wall shear stress magnitude peaks during a heartbeat were changed to periodic oscillation by converting oscillatory shear stress. The mean oscillatory shear stress amplitude and time-averaged wall shear stress values at the dorsal and ventral regions of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus groups were significantly higher than those in controls. Furthermore, those at the ventral region of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus group were also significantly higher than those in the co-occurrence of idiopathic normal pressure hydrocephalus with Alzheimer-type dementia group. The oscillatory shear stress amplitude at the dorsal region of the cerebral aqueduct was significantly associated with foramen of Magendie diameters, whereas it was strongly associated with the stroke volume at the upper end of the cerebral aqueduct rather than that at the foramen of Magendie., Conclusions:Oscillatory shear stress, which reflects wall shear stress vector changes better than the conventional wall shear stress magnitude and the oscillatory shear index, can be directly measured on 4D flow MR imaging. Oscillatory shear stress at the cerebral aqueduct was considerably higher in patients with idiopathic normal pressure hydrocephalus.

While single-junction solar cells may be capable of attaining AM1.5 efficiencies of up to 29%, multi-junction (MJ, Tandem) III–V compound solar cells appear capable of realistic efficiencies of up to 50% and are promising for space and terrestrial applications. In fact, the InGaP/GaAs/Ge 3-junction solar cells have been widely used for space applications since 1997. In addition, industrialization of concentrator solar cell modules using III–V compound MJ solar cells has been announced by some companies. This chapter presents principles and key issues for realizing high-efficiency MJ solar cells, issues relating to development and manufacturing, and applications for space and terrestrial uses.

Background Several patients with persistent atrial fibrillation (per-AF) suffer from recurrence after pulmonary vein isolation (PVI). Various methods to predict the recurrence were tried, but deep learning on 12-leads electrocardiography (ECG) after PVI was not studied. Purpose To elucidate diagnostic performance of deep learning on 12-leads ECG after PVI in patients with per-AF Methods We enrolled consecutive 109 patients with per-AF who underwent PVI (68.8±10.0 years, 83 males) excluding failure cases. We defined recurrence in 3–12 months after PVI. From the ECG just after PVI, five beats of each lead were sampled separately. Deep learning (convolutional neural network on bitmap ECG image) was performed by transfer learning of Inception-Resnet-V2 model. Gradient weighted class activation color mapping (GradCam) was performed to detect convolutional importance in the lead. Results Thirty-six patients showed recurrence in the period. Lead II (accuracy 0.701), aVR (0.690) were the top 2 leads of prediction, which showed larger accuracy than statistical accuracies of Non PV foci = SVC (accuracy = 0.541) and left atrial diameter >50mm (0.596). In lead II, GradCam spotlighted strong convolution of latter half of P wave in recurrent case, and former half of P wave and T wave in no-recurrent case. Conclusions Deep learning on ECG was a powerful tool to predict recurrence of per-AF after PVI. Funding Acknowledgement Type of funding sources: None. Results of deep learningResults of GradCam

Background The usefulness of computed tomography myocardial perfusion (CTP) to assess hemodynamically significant coronary artery lesions has been previously reported. However, the diagnostic value of quantitative evaluation of regional absolute coronary flow by CTP to detect microvascular dysfunction remains unknown. Purpose The aim of study is to assess the diagnostic value of preprocedural CTP to detect coexisting microvascular dysfunction with functionally significant epicardial stenosis in patients with chronic coronary syndromes. Methods and results Thirty-three chronic coronary syndrome patients with de novo single functionally significant stenosis (Fractional flow reserve [FFR] The determinants of coexistence of microvascular dysfunction and functional epicardial stenosis were determined. In invasive wire-based analysis, FFR, coronary flow reserve (CFRwire) and IMR were 0.68 (0.57–0.72), 1.61 (1.00–1.98), and 26.7 (19.3–39.4) respectively. In CTP analysis, rest and hyperemic-MBF and CFR derived from CTP (CFRCTP; calculated as hyperemic-MBF/rest-MBF) were 2.00 (1.31–2.35) ml/min/g, 4.03 (2.11–5.44) ml/min/g, and 2.09 (1.49–2.09) respectively. In the lesions with IMR>25, hyperemic-MBF was significantly lower than that in IMR25 showed area under the curve of 0.72 (0.54–0.90), sensitivity of 47% and specificity of 94%. Conclusion Quantitative assessment of absolute coronary flow by CTP may help detect coexisting microvascular dysfunction in patients with significant epicardial stenotic lesions. Funding Acknowledgement Type of funding source: None

Background Peri-coronary adipose tissue attenuation expressed by fat attenuation index (FAI) on coronary CT angiography (CCTA) reflects peri-coronary inflammation and is associated with cardiac mortality. CCTA also provides two-dimensional and three-dimensional quantification of the individual component of atherosclerotic plaque and entire vessel. The atherosclerotic burden or disease extent in entire epicardial coronary arteries provides prognostic information in patients with coronary artery disease. Purpose This study sought to explore the prognostic significance of FAI values and whole vessel and lesion plaque quantification on CCTA in stable patients with intermediate epicardial stenosis evaluated by fractional flow reserve (FFR). Methods A total of 277 patients (277 lesions) with intermediate coronary stenosis who underwent FFR measurement and CCTA were studied. FAI was assessed by the crude analysis of the mean CT attenuation value (−190 to −30 Hounsfield units; higher values indicating inflammation) on CCTA. CT findings including whole vessel and lesion plaque quantification, and target vessel myocardial mass were investigated. Major adverse cardiovascular outcome (MACE) was defined as all cause death, cardiac death, myocardial infarction, unplanned revascularization, and heart failure requiring admission. Survivals from MACE were assessed. Results The mean FAI and the median FFR values were −71.6 and 0.77, respectively. FFR values were weakly albeit significantly correlated with FAI values. (r=−0.016, P=0.008.) MACE was occurred 43 (15.5%) patients during 5 years F-up. ROC analyses revealed that best cut-off value of FAI to predict MACE was −73.1. Kaplan-Meier analysis revealed that lesions with FAI ≥−73.1 had a significantly higher risk of MACE. (Chi-square 5.5, P=0.019) FFR values and the percutaneous coronary intervention were not predictive of MACE. Multivariate COX proportional hazards regression analysis revealed that age, remodeling index, and lesions with FAI ≥−73.1 were independent predictors of MACE. Conclusion The peri-coronary inflammation evaluated by FAI and CT remodeling index enhances cardiac risk prediction in chronic coronary syndrome patients with intermediate lesions. Non-invasive comprehensive CT assessment may help identify high risk patients of subsequent clinical events and provide enhanced patient management. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): This study was supported in part by an unrestricted research grant from St. Jude Medical (Abbot Vascular, Santa Clara, CA, USA). The company had no role in study design, conduct, data analysis or manuscript preparation.

Benign metastasizing leiomyoma (BML) is a rare disease associated with a history of uterine surgery leiomyomas. BML is often seen in the lungs. Symptomatic patients with BML are usually treated with surgical resection or medical castration. Here, we report three patients diagnosed with BML. A 58-year-old patient presented with back pain. Magnetic resonance imaging (MRI) and positron emission tomography – computed tomography (PET/CT) showed a tumor of 3 cm in diameter in the L2/L3 vertebrae with Fluorine-18 deoxyglucose (FDG) accumulation. Histopathology of CT-guided biopsy was smooth muscle tumor, which was compatible with the specimen obtained by hysterectomy for leiomyoma five years before. After administration of letrozole for one month, her back pain improved. Letrozole was used for 5 years, and the size of the tumor remained stable. A 38-year-old patient presented with abdominal distension. CT demonstrated multiple abdominal and subcutaneous tumors and uterine leiomyomas. She had myomectomy and complete surgical resection of the multiple tumor, and was diagnosed with BML. Six years later, she presented with slight cough, and CT showed multiple small nodules in the lungs. Because her symptom diminished spontaneously, she was followed without treatment. Her lung tumors gradually increased without symptoms. A 45-year-old patient with a past history of myomectomy twice presented with Raynaud symptom. CT showed multiple small nodules in the lung which showed no accumulation of 18-FDG. Histopathology of CT-guided biopsy was well-differentiated smooth muscle tumors, and she was diagnosed with BML. Because she had no symptoms, she was followed conservatively without treatment.

Background Cardiac magnetic resonance (CMR) imaging is a useful instrument for the assessment of pathological and functional conditions without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Both unrecognized myocardial infarction (UMI) and impaired global myocardial blood flow (g-MBF) have been reported to be strongly associated with worse outcome in patients with cardiovascular disease. However, their combined efficacy remains undetermined. Purpose We sought to assess the prognostic value of the presence of UMI and pre-procedural hyperemic g-MBF evaluated by phase-contrast cine magnetic resonance imaging (PC-CMR) in patients with chronic coronary syndrome who underwent elective percutaneous coronary intervention (PCI). Methods A total of 177 patients with de novo functionally significant stenosis who underwent pre-PCI CMR and PCI between September, 2016 and March, 2019 were retrospectively studied. UMI was defined as a scar detected by late gadolinium enhancement (LGE) without previously diagnosed MI. g-MBF was assessed by quantifying coronary sinus flow using PC-CMR at rest and hyperemic state. The predictors of major adverse cardiac events (MACE; cardiac death, nonfatal myocardial infarction, clinically driven unplanned revascularization, or hospitalization for congestive heart failure) during follow-up were investigated. Results UMI was detected in 40 (27.7%) patients and rest and maximal hyperemic g-MBF evaluated by the coronary sinus flow obtained by PC-CMR were 0.95 ml/min/g and 2.26 ml/min/g, respectively. During the median follow-up of 26 months, cardiovascular death occurred in 1 patient (0.6%), nonfatal myocardial infarction occurred in 4 patients (2.3%), and clinically driven revascularization and hospitalization due to congestive heart failure occurred in 25 patients (14.1%) and 3 patients (1.7%) patients, respectively. In patients with MACE, hyperemic g-MBF was significantly lower and the prevalence of UMI were significantly higher compared with those without MACE (1.94 ml/min/g vs 2.36 ml/min/g P=0.014; 48.3% vs 23.6%, P=0.011). Cox proportional hazards model indicated that impaired hyperemic g-MBF ( Conclusion In patients with chronic coronary syndrome undergoing elective PCI, the combined assessment of UMI and hyperemic g-MBF obtained by preprocedural noninvasive CMR may provide significant prognostic information. Funding Acknowledgement Type of funding source: None

Background Recent studies reported the association between elevated fat attenuation index (FAI) of pericoronary adipose tissue (PCAT) on coronary computed tomography angiography (CTA) and worse cardiac outcomes. Purpose We investigated the prognostic value of increased FAI-defined coronary inflammation status in patients with coronary artery disease. Methods Three-hundred fifty-eight patients (127 acute coronary syndromes [ACS], 231 stable coronary artery disease) with left anterior descending artery (LAD) as a culprit vessel who underwent coronary CTA were retrospectively studied. The FAI defined as the mean CT attenuation value of PCAT (−190 to −30 Hounsfield Unit [HU]) was measured at the proximal 40-mm segment of LAD. All subjects were divided into two groups according to the median value of FAI in the LAD. The association between the incidence of major adverse cardiac events (MACE) including all-cause death, myocardial infarction, heart failure, target and non-target vessel revascularization were evaluated. Results In a total of 358 patients, median FAI values surrounding the LAD was −71.46 (interquartile range, −77.10 to −66.34) HU. Thirty-eight patients (10.6%) experienced MACE during the follow-up period (median, 818 days). Kaplan-Meier analysis revealed that high FAI-LAD (>−71.46 HU [median]) was significantly associated with the incidence of MACE (log-rank test, chi-square = 4.183, P=0.041) (Figure). Conclusions In patients with coronary artery disease with culprit LAD lesions, elevated FAI of PCAT surrounding the LAD was associated with worse clinical outcomes. Assessment of FAI may have a potential for potential for non-invasive risk-stratification by coronary CTA. Kaplan-Meier analysis for MACE Funding Acknowledgement Type of funding source: None

Background A recent study has shown that lipid-rich plaque (LRP) detected by near-infrared spectroscopy (NIRS) is a significant predictor of future adverse events. Pericoronary adipose tissue inflammation (FAI; fat attenuation index) evaluated by computed tomography angiography (CTA) has also been reported to be linked with cardiac events. The relationship between NIRS-defined LRP and FAI remains to be determined. Methods A total of 82 de novo culprit lesions in 82 patients with chronic coronary syndromes (CCS) who underwent perprocedural CTA and NIRS was retrospectively studied. FAI was assessed by the crude analysis of the mean CT attenuation value (−190 to −30 Hounsfield units; higher values indicating inflammation) of pericoronary adipose tissue. Plaque morphology was assessed by coronary CTA and grey-scale intravascular ultrasound (IVUS). NIRS-defined LRP was defined as a maximum lipid core burden index (LCBI) in 4 mm ≥400. Relationship between NIRS-defined LRP, CTA/grey-scale IVUS findings, and FAI was assessed. Univariate and multivariate logistic regression analyses were performed to determine the predictors for NIRS-derived LRP. Results NIRS-defined LRP was observed in 35 (42.6%) patients. Maximum LCBI showed modest correlations both with FAI (r=0.29, p-value=0.007) and CT-derived remodeling index (r=0.51, p Conclusions FAI of the culprit lesion in CCS was an independent predictor of NIRS-defined LRP, supporting the notion that local pericoronary adipose tissue inflammation may correlate to the presence of LRP. Comprehensive assessment of coronary CTA including FAI evaluation may provide a highly accurate information with high sensitivity and specificity for identifying high risk lesions potentially leading to future cardiac events. Funding Acknowledgement Type of funding source: None

Background The concept of coronary flow capacity (CFC) originated from positron emission tomography has been reported to provide prognostic information. Phase contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying global coronary sinus flow (CSF) and global coronary flow reserve (g-CFR) without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Purpose We evaluated the prognostic value of postprocedural CFC by quantifying CSF using PC-CMR in patients with acute coronary syndrome (ACS) treated with primary or urgent percutaneous coronary intervention (PCI). Methods This study prospectively but nonconsecutively enrolled 569 ACS patients who underwent uncomplicated primary (for ST-segment elevation myocardial infarction (STEMI)) or urgent PCI within 48 hours of symptom onset (for non-ST elevation acute coronary syndrome (NSTE-ACS)). Breath-hold PC-CMR images of CS were acquired to assess absolute CSF at rest and during maximum hyperemia within 30 days after culprit lesion PCI and revascularization of functionally significant non-culprit lesions. The entire cohort was stratified by the CFC according to the thresholds of hyperemic CSF and g-CFR. Impaired CFC was defined as a severely-reduced CFC in the present study. The association of CFC and baseline clinical characteristics with major adverse cardiac events (all-cause death, nonfatal myocardial infarction, hospitalization for congestive heart failure or stroke) was investigated. Results In the final analysis of 502 patients (Male 417 (83.1%), mean age was 67 [58, 73]) and 310 patients (82.3%) with STEMI and 192 patients (38.2%) with NSTE-ACS were studied. In a total cohort, rest and maximal hyperemic CSF and corrected G-CFR were 0.93 [0.68, 1.24] ml/min/g, 2.08 [1.44, 2.77] ml/min/g, and 2.21 [1.58, 3.05], respectively. During a median follow-up of 28 months, MACE occurred in 53 patients (all-cause death: 19, nonfatal myocardial infarction: 16, late revascularization: 59, hospitalization for congestive heart failure: 9, stroke: 9). Cox proportional hazards analysis showed that corrected G-CFR and impaired CFC were both independent predictors of MACE. (hazard ratio (HR), 0.61, 95% confidence interval (CI): 0.45–0.82, p=0.001; HR, 3.51, 95% CI: 1.79–6.86, p≤0.001, respectively). Cardiac event-free survival was significantly worse in patients with impaired CFC (log-rank χ2=22.9, P Conclusions In ACS patients successfully revascularized with primary or urgent PCI, CFC categorization stratified by noninvasive PC-CMR provided significant prognostic information independent of infarction size, conventional risk factors and g-CFR. Funding Acknowledgement Type of funding source: None

Background Aortic valve calcification (AVC) has been known as an independent predictor for adverse cardiovascular events and all-cause mortality. Previous studies demonstrated that AVC was associated with aortic valve inflammation and atherosclerosis. However, the relationship between the progression of AVC and pericoronary inflammation remains undetermined. Purpose The purpose of this study was to evaluate the impact of the pericoronary inflammation on the progression of AVC. Methods A total of 107 patients with suspected or known chronic coronary syndromes who underwent clinically indicated serial 320-slice coronary computed tomography angiography (CTA) at Tsuchiura Kyodo General Hospital from January 2011 to June 2019 were retrospectively studied. Pericoronary inflammation was assessed by pericoronary adipose tissue attenuation (PCATA) defined as the mean CT attenuation value of PCATA (−190 to −30 Hounsfield units [HU]) on proximal 40 mm segments of coronary arteries. AVC was quantified by Agatston score on CTA. The mean aortic attenuation (HU Aorta) and the standard deviation (SD) in the region of interest at the level of the sinotubular junction was measured. AVC was defined as the threshold for calcium detection (mean HU Aorta + 2SD). AVC index was calculated as follows: (follow-up/baseline) AVC divided by follow-up period. AVC progression was defined as newly-developed AVC at follow-up or an increased AVC index during follow-up. All patients were divided into two groups according to the presence or absence of AVC progression, and clinical characteristics and CT findings were compared between these two groups. Results AVC progression was observed in 26 patients (24.3%) between 2 serial CT examinations (median, 34 months). There was no significant difference in age, gender and the prevalence of other cardiovascular risk factors between the 2 groups. Patients in AVC progression group were associated with higher prevalence of elevated PCATA-LAD, higher LV mass index at baseline and the initial AVC presence. Receiver-operating characteristic curve analysis revealed that the optimal cut off value of PCATA-LAD for predicting AVC progression was −68.26 HU (area under the curve 0.605; 95% confidence interval [CI], 0.465–0.745). Multivariable logistic regression analysis revealed that baseline PCATA-LAD ≥−68.26 HU (odds ratio [OR], 3.12; 95% CI, 1.04–9.35, p=0.042) and the presence of baseline positive AVC (OR, 6.84; 95% CI, 2.34–20.0, p=0.0004) were independent predictors of AVC progression. Conclusions The increased pericoronary inflammation and the presence of AVC may help identify patients with high risk for future AVC progression. Funding Acknowledgement Type of funding source: None

Background Recent studies have reported the association between periaortic adipose tissue volumes identified by multi-detector computed tomography (MDCT) and the periaortic adipose tissue inflammation (PATI) identified by positron emission tomography, which may suggest the link between perivascular inflammation and aortic dilation. However, clinical significance of the PATI identified by MDCT remains elusive in patients with asymptomatic abdominal aortic aneurysm (AAA). Methods A total of 77 patients with AAA (diameter >30mm) who underwent the initial and follow-up MDCT examinations were studied retrospectively. PATI was assessed by the crude analysis of the mean CT attenuation value (−190 to −30 Hounsfield units; higher values indicating inflammation). The AAA progression (AP) was defined as the growth of AAA diameter >5.0mm/year from the initial to follow-up. Univariate and multivariate logistic regression analysis were performed to determine the predictors for AP. Results AP was observed in 19 (24.7%) patient, the median initial AAA diameter was 38.9 (32.7–42.9) mm, and the median progression of AAA diameter was 3.1 (1.5–4.9) mm/year. The initial AAA diameter (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.05–1.28; p-value=0.001) and the initial PATI (OR: 1.12; 95% CI: 1.05–1.20; p-value=0.004) were independent predictors of AP. PATI of −71.08 at initial MDCT and the initial AAA diameter of 37.7mm were the best cut-off value to predict AP. Receiver operating characteristic curve analysis revealed that the best cut-off values of PATI at initial MDCT and the initial AAA diameter for predicting AP were −71.08 (AUC: 0.68, 95% CI: 0.50–0.82) and 37.7 (AUC: 0.71, 95% CI: 0.59–0.84), respectively. Addition of the initial AAA diameter to PATI at initial MDCT significantly increased the accuracy for discriminating AP (net reclassification improvement; 95% CI: 0.67 [0.17–1.17]; p-value = 0.007, integrated discrimination improvement; 95% CI: 0.14 [0.04–0.24]; p-value =0.007). Conclusions PATI was an independent and significant predictor of aortic dilation, supporting the notion that local adipose tissue inflammation may contribute to aortic remodeling. Comprehensive assessment of MDCT including PATI evaluation may provide a highly accurate information for identifying high risk lesions potentially leading to future AAA rupture. Funding Acknowledgement Type of funding source: None

Background Despite the reduction in late thrombotic events with newer generation coronary stents, late stent failure remains a concern following stent implantation. Neoatherosclerosis (NA) is a cause of in-stent restenosis and acute thrombotic occlusion originating from the stented segment by disruption of the in-stent atheroma. Although the clinical impact of NA at 1 year has been reported, clinical significance of NA observed at very later phase remains to be determined. We sought to investigate the association between optical coherence tomography (OCT) findings at very late phase after stenting and subsequent clinical outcomes. Methods A total of 195 patients with 316 stents (including 74 bare metal stents, 48 first-generation DES, and 194 second-generation DES) without stent failure who underwent OCT examination at >3 years (4.9 [3.9- 5.8] years) after stent implantation according to the prespecified protocol were investigated. OCT analysis included the presence of lipid-laden neointima, macrophage, malapposition, thrombus, and plaque rupture within the stents. NA was defined as having lipid-laden neointima. The criteria for the diagnosis of NA were signal-poor region in continuous flames, lipid length longer than 0.3 mm, and invisible stent strut at NA site. Quantitative OCT measurement included lipid length (LL), lipid arc, minimum lumen area (MLA) at the stented segment and minimum stent area (MSA). Major adverse cardiac events (MACE) including all-cause death, non-fatal myocardial infarction, and clinically driven revascularization were assessed. MACE-free survival rate was compared between patients with stent showing NA (NA group) and those without NA (non-NA group). Furthermore, in per-stent basis analysis, stent failure including remote revascularization and stent thrombosis of the stent after follow-up OCT examination was assessed. Results NA was identified in 50 stents (15.8%) in 38 patients (19.5%). During the median follow-up period of 2.1 [1.0- 2.8] years after OCT examination, 15 MACEs (7.7%) were captured in the total cohort, of which stent failure was observed in 5 stents (5/316, 1.6%). In patient-based analysis, patients with NA had more frequent MACE than those without (18.0% vs 5.1%, p=0.01). Kaplan-Meier analysis revealed that significantly higher MACE rate was detected in NA group than in non-NA group (χ2=5.4, Log-rank p=0.02). In stent-based analysis, NA stents had more frequent stent failure than those without (8.0% vs 0.4%, p=0.002) Conclusions NA observed by OCT at >3 years after implantation were associated with subsequent worse clinical outcomes in both patient and stent-based analysis. NA at the very late phase after stenting might be the therapeutic target of secondary prevention and OCT examination at very late phase after stenting may help identify high risk patients of subsequent MACE. Funding Acknowledgement Type of funding source: None

Summary Background & aims The associations between dietary magnesium intake and stroke and coronary heart disease (CHD) incidences are inconsistent and not established in Asian. We aimed to determine the association between dietary magnesium intake and the risk of stroke and CHD in a Japanese population. Subjects/Methods We studied 85,293 Japanese subjects by questionnaire at baseline (age 45–74 years, without cardiovascular disease or cancer in 1995 and 1998 for Cohorts I and II, respectively). The participants were followed until the end of 2009 and 2010 in Cohorts I and II, respectively. Dietary magnesium intake was estimated from a self-administered 138-item food-frequency questionnaire. Results After 1,305,738 person-years of follow-up, 4110 strokes and 1283 cases of CHD were documented. The multivariable-adjusted hazard ratios (HRs, 95% confidence intervals, 95%CIs) of CHD for the fourth and fifth quintiles of dietary magnesium intake were 0.70 (0.50–0.99) and 0.66 (0.44–0.97) in men (P for trend = 0.036), respectively, and third quintile of dietary magnesium intake was 0.61 (0.39–0.96) in women (P for trend = 0.241), compared with the lowest quintile in men and women. We observed no decreased risks of incident stroke in men or women with higher dietary magnesium intakes. Conclusions Higher dietary magnesium intake was associated with a reduced risk of CHD in Japanese men.

A finding between dietary pattern and cancer may provide visions beyond the assessment of individual foods or nutrients. We examined the influence of dietary pattern with colorectal cancer (CRC) among a Japanese population.A total of 93,062 subjects (43,591 men, 49,471 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2012, during which 2482 cases of CRC (1514 men, 968 women) were newly identified. Dietary data was obtained from a validated food-frequency questionnaire between 1995 and 1998.Three dietary pattern was derived from principal components factor: prudent, westernized, and traditional pattern. After controlled for potential confounders, the prudent pattern showed a decreased association of CRC risk in men (HR for highest quintile vs lowest: 0.85; 95% CI: 0.72-1.00; P trend0.05), slightly more strongly with distal colon cancer (P trend0.05); but an increased risk of rectal cancer in women (P trend0.05). The westernized pattern showed a significant positive linear trend for colon (P trend0.05) and distal cancer (P trend0.05) in women. There was no apparent association of traditional Japanese dietary pattern on the overall or any specific sites risk of CRC.A prudent dietary pattern showed an inverse association with CRC risk in men, and a westernized pattern was related with a higher risk of colon and distal cancer in women.

Background The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. Patients and methods Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m2 each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. Results Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade ≥3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade ≥3 or treatment-related death did not occur. Conclusions This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed., Highlights • This is the first prospective study evaluating gefitinib induction followed by CRT in EGFR-mutated, locally advanced NSCLC. • The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. • The objective response rate throughout the treatment protocol was 85.0% (17 of 20). • The safety findings were consistent with the known safety profiles of all agents administered. • Our results might raise a critical point that needs to be evaluated in further studies to improve the cure rate.

Backgrounds Near-infrared spectroscopy (NIRS) has been implicated to assess the composition of the atherosclerotic plaques in native coronary arteries. However, little has been reported about the assessment of neoatherosclerosis within stents by NIRS. Optical coherence tomography (OCT) is one of the current clinical standard modalities to identify neoatherosclerosis. We sought to compare NIRS and OCT assessments in the detection and evaluation of in-stent neoatherosclerosis. Methods We retrospectively analyzed 54 in-stent lesions in 52 patients who underwent both NIRS and OCT examinations before percutaneous coronary intervention (PCI). All stented segment in both PCI target and non-target lesions were investigated. NIRS analysis included lipid core burden index (LCBI)4mm. NIRS-derived lipid-rich plaque (NIRS-lipid) is defined as LCBI4mm more than 400 according to the previous studies. OCT-derived lipid-laden neointima (OCT-lipid) was defined as having a signal-poor region with diffuse border precluding visualization of stent struts of more than 90 degrees and 1mm in longitudinal length. OCT analysis included the presence or absence of lipid-laden neointima, calcification, ruptured plaque, thrombus, heterogeneous neointima and measurement of lipid length and lipid arc. Lipid volume index (LVI) was defined by OCT as the averaged lipid arc multiplied by lipid length. Max LCBI4mm were compared in lesions with co-registered OCT findings and correlations between max LCBI4mm and LVI were determined. Additionally, OCT findings predicting max LCBI4mm more than 400 were determined. Results Max LCBI4mm was 202 (7.5-460). OCT-lipid was observed in 31 (57.4%) lesions. LVI was 1283 (475-4725). Lesions with OCT-lipid has significantly higher LCBI than those without OCT-lipid (343 [106-593] vs 42 [0-260], p = 0.003). On the other hand, max LCBI were not significantly different according to the presence or absence of calcification, ruptured plaque, thrombus and heterogeneous neointima (60 [39-537] vs 227 [6-451], p = 0.913; 441 [43-547] vs 202 [6-435], p = 0.328; 245 [10-548] vs 251 [42-446], p = 0.990; 202 [40-440] vs 235 [3-471], p = 0.970, respectively). Linear regression analysis showed significant correlation between LVI and max LCBI4mm (P Conclusion There is good agreement between NIRS and OCT for detection of neoatherosclerosis in stented lesions. In the in-stent lesions, the cut-off value of max LCBI for predicting OCT-lipid was smaller than the previously reported value in de novo lesions. Application of different cut-off value may be considered in in-stent lesions.

Introduction/Background The appropriate operative method for patients with early-staged endometrial cancer remains controversial. The aim of the present study was to assess the recurrence rate of the vaginal stump after modified radical hysterectomy for patients with endometrial cancer. Methodology Medical records of the patients with FIGO stages I, II, and III endometrial cancer treated with modified radical hysterectomy and pelvic lymph nodes dissection at Kumamoto University Hospital between 2006 and 2014 were analyzed retrospectively. The patients who had been histologically diagnosed with carcinosarcoma or sarcoma were excluded. The recurrence site, FIGO stage, and histological type were analyzed in patients with recurrent disease within 5 years after the initial treatment. Results Two hundred-nine patients with endometrial cancer underwent modified radical hysterectomy during an observational period, and 22 patients (10.5%) had an initial relapse within 5 years. The sites of initial recurrence included the vaginal stump, the urinary bladder, the vaginal inlet, the perineum, the spleen, the adrenal gland, the pelvic and paraaortic lymph nodes, the lung, and the brain in 6 patients with stage I and 16 patients with stage 3. Although the recurrence of the vaginal stump was confirmed in 2 patients with stage III, there was no recurrence of the vaginal stump in 135 patients with stage I and 16 patients with stage II. The recurrence rate of the vaginal stump was 0.9% (2/209) in all patients including stages I, II, and III. Conclusion Modified radical hysterectomy with sufficient resection margins of the vagina and the parametrium may decrease the postoperative recurrent rate of the vagina for patients with stage I and stage II endometrial cancer. Disclosure Nothing to disclose.

Background Impaired global coronary flow reserve (G-CFR) is known to predict worse outcomes in patients with coronary artery disease. Phase contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying coronary sinus flow (CSF) and G-CFR without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Although G-CFR impairment is previously reported to be linked with endothelium dysfunction and progression of atherosclerosis, the association of perivascular adipose tissue inflammation with myocardial coronary flow remains to be determined. Purpose We evaluated the association between G-CFR by quantifying CSF using PC-CMR and the extent of coronary inflammation evaluated by perivascular adipose tissue inflammatory status using CT to assess if coronary inflammation is linked with G-CFR in patients with stable angina pectoris (SAP) treated with elective percutaneous coronary intervention (PCI). Methods The study enrolled 74 SAP patients with single denovo lesion who underwent coronary CT angiography and PC-CMR within 90 days before coronary intervention. Proximal 40-mm segments of all three major epicardial coronary vessels were traced and examined. Coronary inflammation was assessed by the CT fat attenuation index of perivascular adipose tissue (FAI-PVAT) defined as the mean attenuation of the perivascular adipose tissue (−190 to −30 Hounsfield units (HU)) in a layer of tissue within a radial distance from the outer coronary artery wall equal to the diameter of the vessel. CMR images were also acquired to assess absolute CSF at rest and during maximum hyperemia before elective PCI. The patients were divided into 4 groups according to the number of inflamed vessels as defined by showing FAI ≥−70.1 HU. Results In the final analysis of 69 patients (mean age 67, Male 45 (65.2%)), 18, 19, 20, 12 patients exhibited none, 1, 2, 3 inflamed vessels with FAI ≥−70.1 HU, respectively. Rest and maximal hyperemic CSF and corrected G-CFR were 1.28 [0.76,1.55] vs 1.47 [1.11, 1.81] vs 1.30 [0.94, 1.64] vs 1.27 [1.11, 2.00] ml/min/g; P=0.49, 3.50 [2.84, 5.25] vs 3.28 [2.62, 4.31] vs 3.11 [2.16, 3.63] vs 2.37 [1.40, 2.98] ml/min/g; P=0.049, 3.57 [2.17, 4.54] vs 2.25 [1.73, 3.49] vs 2.26 [1.64, 3.38] vs 1.89 [0.89, 2.32]; P=0.023, respectively. G-CFR and hyperemic CSF were both significantly lower in the group with larger number of inflamed vessels. Conclusions In SAP patients with significant coronary artery stenosis, G-CFR obtained by PC-CMR significantly associated with the prevalence of inflamed vessels detected by coronary CT. The extent of coronary inflammation may influence global coronary endothelium dysfunction, resulting in decreased G-CFR.

Background Unrecognized myocardial infarction (UMI) has been reported to be strongly associated with worse outcome in patients with cardiovascular disease. Cardiac magnetic resonance (CMR) imaging is a useful instrument for the assessment of pathological and functional conditions. Purpose This study sought to evaluate the prognostic value of the presence of unrecognized non-infarct-related late gadolinium enhancement (non-IR LGE) evaluated by cardiac magnetic resonance imaging in patients presenting with a first acute myocardial infarction (AMI). Methods We studied 311 AMI patients including 213 STEMI and 98 NSTEMI patients without the history of prior MI who underwent uncomplicated primary or emergent PCI within 48 hours of symptom onset between October, 2012 and June, 2017. CMR images were acquired at 28 [21, 32] days after primary/emergent PCI. UMI was defined as having LGE separately in the different and remote area from the perfused territory by infarct-related artery. In case of multiple LGE areas of infarction, the coronary angiography findings were used to support identification of the area corresponding to the culprit artery of AMI. The association of CMR variables and other clinical characteristics with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, nonfatal stroke) were investigated. Results Forty-six patients (14.8%) showed UMI defined by the presence of non-IR LGE (27 STEMI and 19 NSTEMI). During the follow up for 830 [385, 1309] days, cardiovascular death occurred in 7 patients (2.3%), and non-fatal MI and non-fatal stroke occurred in 10 and 1 patients, respectively (3.2%, 0.3%, respectively). There was no significant difference in the prevalence of UMI and incidence of MACE between the patients with STEMI and NSTEMI (p=0.13, p=0.11, respectively). Event-free survival was significantly worse in patients with UMI (log-rank χ2=16.3, P=0.001) in a total cohort. Cox proportional hazards analysis showed that UMI was independent predictors of adverse cardiac events during follow-up in patients with first MI (hazard ratio, 7.60, 95% confidence interval, 2.78–20.8, p=0.0001). Conclusions In first AMI patients, UMI defined by non-IR LGE obtained by noninvasive CMR provides significant prognostic information. Early detection of UMI by CMR may help risk stratification of patients with AMI and support adjunctive aggressive patient management such as strong statin therapy and life style intervention.

Background Quantitative flow ratio (QFR) is a novel three-dimensional quantitative coronary angiography (QCA)-based computational index that can estimate fractional flow reserve (FFR) without pharmacologically induced hyperemia or the use of a pressure wire. Purpose We aimed to evaluate the determinants of visual-functional mismatches between conventional two-dimensional QCA and QFR. Methods A total of 504 de novo intermediate-to-severe lesions from 504 patients with stable angina who underwent angiographical and physiological assessments were analyzed. All lesions were divided into four groups based on the significance of visual (QCA-diameter stenosis [DS] >50% and ≤50%) and functional (QFR Results Among 504 lesions, 153 lesions (30.4%) showed concordantly negative (DS ≤50% and QFR >0.80) and 170 lesions (33.7%) showed concordantly positive (DS >50% and QFR ≤0.80) visual and functional assessments. Among 181 lesions (35.9%) with discordant results, 75 lesions (14.9%) showed a mismatch (DS >50% and QFR >0.80) and 106 lesions (21.0%) showed a reverse mismatch (DS ≤50% and QFR ≤0.80), respectively. Reverse mismatch was associated with smaller reference diameter (odds ratio [OR] 0.561; P=0.036), greater DS (OR 1.039, P=0.013), lower coronary flow reserve (CFR) (OR 0.571, P Conclusions There was a high prevalence of visual-functional mismatches between QCA-DS and QFR, and CFR was an important functional factor of mismatches. Our results suggested the difference between predictors of reported visual-functional mismatches of QCA/FFR and those of QCA/QFR.

Background Measurement of the fractional flow reserve (FFR) has become a standard practice for revascularization decision-making in evaluating the functional significance of angiographically intermediate epicardial coronary stenosis. The quantitative flow ratio (QFR) is a novel method for rapid computational estimation of FFR without pressure wire and vasodilator drugs. Purpose Nevertheless, the evidence was shown the clinical better outcome of coronary revascularization stratified by FFR, the adoption of FFR remains low. We hypothesized that combined QFR and FFR hybrid strategy could improve the physiological assessment without pressure wire and drugs. Methods and results We performed a post-hocanalysis of 549 vessels with angiographically intermediate stenosis in 549 patients who underwent measurement of FFR. The median FFR and QFR values were 0.81 (0.73–0.87) and 0.79 (0.74–0.87), respectively.The ischemic threshold was defined as 0.80 for both QFR and FFR measures. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the QFR for predicting an FFR of ≤0.80 were 86.2%, 71.9%, 78.9%, 74.5%, and 84.5%, respectively. The area under the receiver operating characteristic curve using the cut-off threshold of ≤0.80 for the FFR was 0.85 (95% confidence interval [CI], 0.81–0.88) for the QFR.In total, 433 (78.9%) and 116 (21.1%) lesions showed concordant and discordant FFR and QFR functional classifications, respectively. A hybrid QFR-FFR strategy was developed, by allowing deferral when QFR values providing negative predictive value greater than 90% and treat others when QFR values greater than that showing 90% positive predictive value, with adenosine being given only to patients with QFR in between those values. For the FFR cut-off (0.8), an QFR of 0.83 could be used to defer revascularization (NPV of 90.0%). When QFR values fall between 0.73 and 0.84, adenosine is given for hyperemic induction and the FFR cut-off of 0.8 is used to guide revascularization. This hybrid QFR-FFR approach has a 95% agreement with an FFR-only decision making, and 285 lesions (51.9%) would have obviated the need of a pressure wire and adenosine. Hybrid QFR-FFR strategy Conclusions A hybrid QFR-FFR strategy for coronary revascularization could reduce the need of a pressure wire and vasodilator drugs, which may increase the penetration of functional assessment of coronary lesions.

Background Previous reports showed all diastolic resting indexes tested were virtually identical to the instantaneous wave-free ratio (iFR). Although RFR has been also reported to be diagnostically equivalent to iFR, no comparisons have been reported about the prevalence and characteristics of discordance in diagnosis between diastolic pressure ratio (dPR) and resting full-cycle ratio (RFR). Purpose This study sought to determine the coronary pressure characteristics of lesions classified as discordant between dPR and RFR in angiographically intermediate stenoses. Methods We recruited 532 patients with 668 intermediate (angiographically stenosis between 30% to 70% severity) coronary lesions undergoing FFR assessment and analyzed DICOM pressure tracings of resting state (dPR and RFR) using a fully automated off-line software algorithm in a blind fashion. Diagnostic performance of dPR and RFR was evaluated using FFR as a reference. Furthermore, we investigated similarity and difference between dPR and RFR. Results Median FFR was 0.81 with an interquartile range of 0.74 to 0.87. RFR was highly correlated to dPR (R2=0.94, p0.80 and the FFR values were significantly lower in RFR+/dPR– than in RFR-/dPR-, and significantly higher in RFR+/dPR– than in RFR+/dPR+. (P Conclusion Significant difference in FFR values was observed according to dPR/RFR agreement and disagreement. Revascularization decision making might defer according to the resting index used. Compared with RFR, lesions might be more frequently deferred when dPR was used to assess physiological significance. Acknowledgement/Funding None

Background Phase contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying global coronary sinus flow (CSF) and global coronary flow reserve (G-CFR) without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Purpose We evaluated the prognostic value of G-CFR by quantifying CSF using PC-CMR in patients with ACS treated with primary or emergent percutaneous coronary intervention (PCI). Methods The study prospectively enrolled 387 ACS patients who underwent uncomplicated primary or emergent PCI within 48 hours of symptom onset. Breath-hold PC-CMR images of CS were acquired to assess absolute CSF at rest and during maximum hyperemia within 30 days after primary PCI and revascularization of functionally significant non-culprit lesions of ACS. The association of G-CFR and baseline clinical characteristics with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for congestive heart failure) was investigated. Results In the final analysis of 366 patients (Male 294 (80.3%), mean age 65) including 233 patients (63.7%) with ST-segment elevation myocardial infarction (STEMI) and 133 patients (36.3%) with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), rest and maximal hyperemic CSF and corrected G-CFR were 1.24 [0.83, 1.71] ml/min/g, 2.56 [1.87, 3.66] ml/min/g, and 2.20 [1.53, 3.17], respectively. During a median follow-up of 16 months, MACE occurred in 84 patients (cardiac death: 9, nonfatal myocardial infarction: 11, late revascularization: 59, hospitalization for congestive heart failure: 5). Cardiac event-free survival was significantly worse in patients with a corrected G-CFR Conclusions In ACS patients successfully revascularized within 48 hours of onset, G-CFR obtained by noninvasive PC-CMR provided significant prognostic information independent of infarction size and conventional risk scores.

Background Fractional flow reserve (FFR) is the current standard for determining severity of epicardial stenosis and indication for percutaneous coronary intervention (PCI). However in practice, FFR is not enough robust to select lesions that will truly benefit from PCI. Coronary flow capacity (CFC) provides integrated information of coronary flow reserve (CFR) and coronary flow during hyperemia that is useful for identifying flow-limiting stenosis considering both epicardial and microvascular conditions. Objective We hypothesized that the effect of FFR-guided PCI would be enhanced by further consideration of CFC. This study aimed to investigate the prognostic effect of PCI according to CFC status of the stable lesions, using pressure-temperature sensor-tipped wire for FFR and CFC evaluation. Methods From a global, multicenter registry of comprehensive physiological assessment, a total of 1397 patients (1694 vessels) were enrolled. Three patients/vessels were excluded due to lost follow-up. Low CFC was defined for lesions with reduced CFR and the corresponding inverse of thermodilution-derived mean transit time under hyperemia, which represents hyperemic coronary flow. The effect of FFR-guided PCI on vessel-oriented composite outcomes (VOCO) was assessed by multivariate marginal COX proportional regression model with or without the interaction term between PCI and CFC, using the CFC definition with the CFR threshold of 2.0 (Figure: red + green area showing low CFC). Using the same model, variously defined CFC was tested to determine the optimal thresholds (Figure: red only area ∼ red + green + blue area). Results During the 5-year follow-up period, VOCO was identified for a total of 113 vessels. In the multivariate model, the HR of PCI was 0.963 (95% CI: 0.538–1.723). When the interaction was added to the model, the effect of PCI on VOCO incidence was significantly different according to CFC status (p=0.069 for interaction). The optimal criterion of CFC was made where Akaike Information Criterion of the model was minimized (CFR threshold of 2.9 for the CFC definition), where PCI had HR of 0.443 (95% CI: 0.196–0.999) and 1.521 (95% CI: 0.828–2.796) for lesions low and high CFC, respectively. CFR had no significant interaction with PCI (p=0.26). CFC Map Conclusion The effect of PCI on VOCO was significantly different according to CFC status. PCI to lesions with low CFC was prognostically beneficial. Our results suggested the potential of CFC for optimizing PCI benefit in stable lesions after FFR assessment.

Background Inflammation is linked with progression of coronary atherosclerosis. Recent studies have reported the association between elevated perivascular fat attenuation index (FAI) on computed tomography (CT) and worse cardiac outcomes in patients with coronary artery disease. Purpose We aimed to investigate the differences in FAI-defined peri-coronary inflammation status between the culprit and non-culprit vessels in patients with acute coronary syndromes (ACS). Methods A total of 78 ACS patients with left anterior descending coronary arteries (LAD) as a culprit vessel who underwent coronary CT angiography and invasive coronary angiography were studied. Proximal 40-mm segments of the LAD and the right coronary artery (RCA) were traced. Coronary inflammation was assessed by the FAI defined as the mean CT attenuation value of perivascular adipose tissue (−190 to −30 Hounsfield units [HU]) in a layer of tissue within a radial distance from the outer coronary artery wall equal to the diameter of the vessel. All patients were divided into two groups according to the values of FAI in the LAD: high FAI group (FAI-LAD > median; n=39) and low FAI group (FAI-LAD ≤ median; n=39). Patient characteristics, angiographic and CT findings were compared between the two groups. Results In a total of 78 patients, median FAI in the LAD was −70.20 (interquartile range, −74.81 to −64.58) HU. High FAI group was associated with male sex and lower left ventricular ejection fraction compared with Low FAI group. Minimal lumen diameter, reference diameter, diameter stenosis, and lesion length on quantitative coronary angiography analysis and coronary artery calcium score on CT was not different between the groups. FAI in the RCA was also higher in High FAI group than that in Low FAI group (−67.64±8.31 vs. −76.47±6.25 HU, P Conclusions In ACS patients with culprit LAD lesions, FAI-defined peri-coronary inflammation status is higher in the culprit vessel than in the non-culprit vessel.

Background Impaired global coronary flow reserve (G-CFR) is known to predict worse outcomes in patients with coronary artery disease. Phase contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying coronary sinus flow (CSF) and global coronary flow reserve (G-CFR) without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Although G-CFR impairment has been previously reported to be linked with endothelium dysfunction and subsequent atherosclerosis, the relationship between coronary inflammation and absolute coronary blood flow volume or coronary flow reserve remains elusive. Purpose We evaluated the association between G-CFR by quantifying CSF using PC-CMR and the extent of coronary inflammation in patients with ACS treated with emergent percutaneous coronary intervention (PCI). Methods The study enrolled 107 ACS patients who underwent uncomplicated emergent PCI within 48 hours of symptom onset and coronary CT angiography were performed before PCI. Proximal 40-mm segments of all three major epicardial coronary vessels were examined. Coronary inflammation was assessed by the CT fat attenuation index of perivascular adipose tissue (FAI−PVAT) defined as the mean attenuation of the perivascular adipose tissue (−190 to −30 Hounsfield units (HU)) in a layer of tissue within a radial distance from the outer coronary artery wall equal to the diameter of the vessel, as previously reported. CMR images were acquired to assess absolute CSF at rest and during maximum hyperemia within 30 days after emergent PCI and revascularization of non-culprit significant lesions. The patients were divided into 4 groups according to the number of inflamed vessels (defined as 0, 1, 2, 3 vessels with FAI ≥−70.1 HU). Results In the final analysis of 102 patients (mean age 64, Male 65 (63.7%)) including 77 patients with non-ST-segment elevation myocardial infarction (NSTEMI) (75.5%) and 25 patients with unstable angina pectoris (UAP), 25, 30, 26, 21 patients exhibited none, 1, 2, 3 inflamed vessels with FAI ≥−70.1 HU, respectively. Rest and maximal hyperemic CSF and corrected G-CFR were 1.17 [0.63, 1.71] vs 1.36 [1.05, 1.67] vs 1.21 [0.83, 1.94] vs 1.35 [0.96, 1.67] ml/min/g; P=0.61, 3.26 [2.62, 2.99] vs 3.50 [2.60, 4.03] vs 3.34 [1.78, 4.20] vs 2.48 [1.54, 3.43]; P=0.061, 2.95 [2.05, 4.30] vs 2.63 [1.80, 3.56] vs 2.15 [1.37, 2.91] vs 2.18 [1.46, 2.42]; P=0.018, respectively. G-CFR was significantly lower in group with increased number of inflamed vessels. Conclusions In ACS patients successfully revascularized within 48 hours of onset, G-CFR obtained by noninvasive PC-CMR significantly associated with the prevalence of inflamed vessels detected by coronary CT. Further large population study is warranted to test the hypothesis that the extent of coronary inflammation before coronary revascularization in patients with ACS might provide prognostic information.

Background The fractional flow reserve (FFR) becomes a standard practice for revascularization decision-making in evaluating the functional significance of angiographically intermediate epicardial coronary stenosis. The quantitative flow ratio (QFR) is a novel method for rapid computational estimation of FFR without pressure wire and hyperemic induction. FFR has been reported to be associated with not only epicardial stenosis but also subtended myocardial mass (Vsub). In contrast, the relationship between QFR and Vsub has not been clarified. Purpose We sought to examine if subtended myocardial mass (Vsub) assessed by coronary computed tomography showed a significant relationship with QFR in comparison with FFR. Methods and results We performed a post-hoc analysis of 152 territories (LAD 116, RCA 25 and LCX 11 lesions) with angiographically intermediate-to-severe stenosis in 152 patients who underwent FFR assessment. The median FFR and QFR values were 0.76 (0.64–0.84) and 0.76 (0.72–0.83), respectively. The median diameter stenosis (%DS) and minimum lumen diameter (MLD) were 54.5 (43.9–64.2) and 1.2 (0.9–1.6), respectively. In total, 123 (80.9%) and 29 (19.1%) lesions showed concordant and discordant FFR and QFR functional classifications, respectively. The ability of Vsub/MLD2 to discriminate lesions with FFR≤0.80 and QFR≤0.80 was assessed compared with QCA data. FFR values were associated with Vsub (R=0.37, P Conclusions Subtended cardiac mass volume derived from CT segmentation improved the diagnostic performance of angiography-derived parameters to identify ischemia-producing lesions when FFR used as a reference standard, whereas QFR showed non-significant relationship with subtended cardiac mass.

Background Studies of sex differences in fractional flow reserve (FFR) measurements have shown that in comparison with men, angiographic lesions of similar visual severity are less likely to be ischemia producing in women. Gender specific differences may influence revascularization decision making and prognosis after deferred revascularization following FFR measurement. Purpose This study sought to investigate the gender difference in long-term prognosis of patients of deferred revascularization following FFR assessment. Methods A total of 879 patients (879 vessels) with deferred revascularization with FFR >0.75 who underwent FFR and CFR measurements were enrolled from 3 countries (Korea, Japan, and Spain). Long-term outcomes were assessed in 649 men and 230 women by the patient-oriented composite outcome (POCO, a composite of any death, any myocardial infarction [MI], and any revascularization). We applied inverse-probability weighting (IPW) based on propensity scores to account for differences at baseline between women and men (age, hypertension, hyperlipidemia, diabetes mellitus, lesion location, clinical status, FFR, Reference diameter, Diameter stenosis, lesion length). The median follow-up duration was 1855 days (745–1855 days). Results Median FFR values were 0.88 (0.83–0.93) in men and 0.89 (0.85–0.94) in women, respectively. The occurrences of POCO were significantly high in men compared with that in women (10.5% vs 4.2%, P=0.007). Kaplan–Meier analysis revealed that women had a significantly lower risk of POCO (χ2=7.2, P=0.007). Multivariate COX regression analysis revealed that age, male, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve were independent predictors of POCO. After applying IPW, the hazard ratio of male for POCO was 2.20 (95% confidence interval: 1.12 to 4.33, P=0.023). Conclusion This large multinational study reveals that long-term outcome differs between women and men in favour of women after FFR-guided revascularization deferral. Acknowledgement/Funding None

Background:Skin rashes as a side effect of Tocilizumab therapy (TCZ- Tx) has not been paid much attention, because the incidence was only 1~2% in the drug information sheets. However, we experienced several RA cases with development of various skin rashes associated with neutrophil activation after TCZ-Tx. On the other hand, it is well known that the neutrophil counts in peripheral blood decreases after TCZ-Tx, whereas it does not affect the rate of serious infections. The detailed mechanism is still unclear.Objectives:To detect the characteristics of the changes in gene expressions of peripheral blood associated with TCZ-Tx and the development of skin rashes as its side effect.Methods:Total of 14 RA patients with TCZ-Tx were included. Among them, 4 patients developed TCZ-related rashes (group S) and 10 patients did not show any side effects (group C). Peripheral whole blood at just before (pre) and 3 months after (post) TCZ-Tx from each patient were subjected to the analysis. Total RNAs were extracted with PAXgene miRNA kit and analyzed with next-generation sequencing. First, group C was investigated for the normal response to TCZ-Tx. Differentially expressed genes (DEGs) were selected by paired comparison (post vs. pre). And then, enrichment analysis using gene ontology (GO) terms were performed. Second, to explore the characteristics of group S, all expressed genes in 14 cases at just before TCZ-Tx were subjected to a hierarchical clustering analysis. The DEGs (group S vs. C and post vs. pre) were also investigated with weighted gene co-expression network analysis (WGCNA) and GO analysis. Meanwhile, the total eigengene expressions of the important modules identified by WGCNA in each cases were also calculated.Results:Surprisingly, 8 out of the top 10 enriched GO terms in the up-regulated genes were relevant to leukocyte activation such as ‘neutrophil migration” by the analysis of DEGs (post vs. pre) in group C. The cluster analysis of ‘pre’ genes confirmed that the patterns of gene expression between group S and C was different. WGCNA analysis of DEGs (group S vs. C) revealed that genes related to acute inflammation such as ‘leukocyte mediated immunity’ were activated in group S. Interestingly, it was not correlated with disease activity score (DAS) of RA. By the analysis of DEGs (post vs. pre) of upregulated genes, we found that the total eigengene expressions of the module enriched with genes related to ‘cell adhesion’ or ‘leukocyte migration’ were significantly increased in all cases of group S.Conclusion:This is the first evidence that the genes associated with neutrophil migration is significantly activated after TCZ-Tx. It is noteworthy that the gene activation was observed in cases without any side effects. The decreased neutrophil counts in peripheral blood have been known after initiation of TCZ-Tx, which did not affect the rate of serious infections. Recently, It was reported that TCZ affects neutrophil trafficking to the bone marrow1). Our findings will provide a rationale for its cause. On the other hand, we experienced several RA cases with development of various skin rashes associated with neutrophil activation after TCZ-Tx. However, majority of patients do not develop the side effect, even though genes related to ‘neutrophil migration’ are activated. In group S, our findings indicate that the genes related to ‘leukocyte mediated immunity’ was already activated at the initiation of treatment without correlating to DAS of RA, furthermore, the gene upregulation related to ‘leukocyte migration’ was more prominent after TCZ-Tx. Although it is difficult to predict the patients developing skin rashes before TCZ-Tx, we do not recommend to use TCZ for the patients with neutrophilic dermatosis which is often associated with RA.References: :[1]Lok LSCet al.,Eur J Clin Invest. 47(10):736-745 (2017).Disclosure of Interests: :Moe Sakamoto: None declared, Akemi Senoh: None declared, Yoshiharu Sato: None declared, Hiroshi Iijima: None declared, Mari Yamaguchi: None declared, Toshie Higuchi: None declared, Yoshinobu Koyama Grant/research support from: Eli-Lilly and Mochida., Speakers bureau: BMS, Ayumi, Chugai, Ono, Mitsubishi Tanabe, Abbvie and Eisai.

Background CLEOPATRA study demonstrated the efficacy and safety of pertuzumab (P) + trastuzumab (T) + docetaxel (D) but efficacy results of Japanese subgroup weren't consistent with the whole study results. A phase IV, multicenter, prospective, COMACHI study was conducted in Japan to re-confirm the efficacy and safety of P+T+D demonstrated in the CLEOPATRA study. Methods Patients (pts) with HER2-positive breast cancer who were diagnosed as Stage IV or recurred more than a year after (neo)adjuvant taxane chemotherapy completion were enrolled. Pts were administered study drugs intravenously every 3 weeks. Discontinuation of D was allowed after cycle 6. After discontinuation of D, pts were given maintenance by T+P, however not allowed to receive hormonal therapy for HR positive pts. We defined PFS as the primary endpoint. To demonstrate a median PFS of 12.4 months (mos) or more, which was observed in the placebo arm in the CLEOPATRA study. Results From November 2013 to September 2015, 132 pts were enrolled and all pts were treated with T+P at least once. The median age was 56.5 years old and 102 pts (77.3%) had not received prior HER2 therapy. Median cycles of T and P were both 24.0 (range 2.0-71.0) and that of D was 6.0 (range 0.0-65.0). Pts characteristics and subgroup analysis results are shown in the Table below.Table353PTableNameLevelPatientsEventsTime to event[n (%)][n (%)][Median (95% CI)]Alln/a132 (100.0%)66 (50.0%)22.8 (16.9, 34.8)Prior (neo) adjuvant therapy(Excluding hormone therapy)YES38 ( 28.8%)18 (47.4%)27.7 (12.4, NE )NO94 ( 71.2%)48 (51.1%)20.8 (16.9, 38.8)Age - 6536 ( 27.3%)17 (47.2%)33.1 (18.7, NE )Disease Type at ScreeningVISCERAL DISEASE81 ( 61.4%)49 (60.5%)18.4 (13.8, 33.7)NON-VISCERAL DISEASE51 ( 38.6%)17 (33.3%)NE (20.7, NE )ER/PgR StatusPOSITIVE72 ( 54.5%)39 (54.2%)18.9 (14.7, 33.1)NEGATIVE60 ( 45.5%)27 (45.0%)33.7 (20.6, NE )HER2 Status IHC/ISHIHC Median PFS was 22.8 mos [95% CI, 16.9-34.8], and thereby a median PFS of 12.4 mos or more was confirmed. The incidence of typical Grade 3/4 adverse events were febrile neutropenia (31.1%), neutropenia (24.2%), leukopenia (10.6%), and diarrhea (4.5%), and these findings are consistent with the CLEOPATRA study except for febrile neutropenia. Febrile neutropenia lead to only one case of treatment discontinuation and it was manageable. Conclusions The efficacy and safety of P+T+D in Japanese pts were consistent with those of the CLEOPATRA study and we confirmed this treatment as a standard care at 1st line therapy for HER2-positive metastatic breast cancer. Legal entity responsible for the study Chugai Pharmaceutical Co., Ltd. Funding Chugai Pharmaceutical Co., Ltd. Disclosure N. Masuda: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Kyowa-Kirin; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Officer / Board of Directors: Japan Breast Cancer Research Group Association. S. Ohtani: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: AstraZeneca. S. Nagai: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli-Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd. Y. Komoike: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, the publisher, for writing atricle: Nikkei Business Publications, Inc. Y. Ito: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self): Eisai; Research grant / Funding (institution): Covance; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): A2healthcare; Research grant / Funding (institution): Parexel; Research grant / Funding (institution): Kyowa-Kirin. M. Ikeda: Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Asahi Kasei Pharma Corporation; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Mundipharma; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Nippon Kayaku; Research grant / Funding (institution): Hisamitsu; Officer / Board of Directors, engaged in the project of medical practice guidline: Japanese Breast cancer society; Officer / Board of Directors, the leader of clinical trial comittee: Setouchi Breast Project Comprehensive Support Organization. K. Ishida: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Nippon Kayaku. T. Nakayama: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Novartis. T. Takashima: Speaker Bureau / Expert testimony, Officer / Board of Directors: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Officer / Board of Directors: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Eli-Lilly. T. Asakawa: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. S. Matsumoto: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. D. Shimizu: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. M. Takahashi: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa-Kirin; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Daiichi Sankyo; Speaker Bureau / Expert testimony: Allergan; Speaker Bureau / Expert testimony, Research grant / Funding (institution): FUJIFILM Toyama Chemical; Speaker Bureau / Expert testimony: Nihon Medi-Physics; Honoraria (self), for wrtitin article: The Asahi Shimbun Company. All other authors have declared no conflicts of interest.

Aims Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. Methods and results The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000–04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50–79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality. The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73–1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55–0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64–0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01–4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07–11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03–1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40–0.99), respectively. Conclusion An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

We report on investigations of the quantum Hall chiral edge states using a near-field scanning optical microscope that enables us to irradiate circularly polarized light from the probe tip with spatial resolution below the diffraction limit. We have found a clear evidence for the formation of spin-split incompressible strips near the edge of a two-dimensional electron system in high magnetic fields.