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Background A non-negligible proportion of myocardial infarction (MI) is not clinically recognized and unrecognized myocardial infarction (UMI) is associated with adverse outcomes. Purpose To determine the prevalence and prognostic significance of UMI by delayed-enhancement cardiac magnetic resonance (DE-CMR) before elective percutaneous coronary intervention (PCI). Methods In this prospective, single-center study, 236 patients with stable coronary artery disease undergoing elective and uncomplicated PCI were studied. All patients underwent DE-CMR before PCI. The prevalence of UMI was evaluated and the association of clinical and CMR-derived variables with primary MACE, defined as cardiovascular death, nonfatal MI, hospitalization for heart failure, unplanned late revascularization, and ischemic stroke was investigated. Results In the final analysis of 213 patients, 63 patients (29.6%) showed UMI. Target territory UMI was observed in 38 (17.8% of total, 60.3% of patients with UMI). UMI was significantly associated with sex, diabetes mellitus, left ventricular ejection fraction, SYNTAX score and fractional flow reserve in target vessels. During follow-up periods (median, 23 months), MACE was observed in 17 (27.0%) of patients with UMI, and 17 (11.3%) without (P=0.001). In a multivariable model, UMI (hazard ratio [HR] 2.18, 95% confidential interval, 1.10–4.33, P=0.001) remained as an independent predictor of MACE. Kaplan–Meier analysis indicated that the presence of UMI was significantly associated with higher incidence of MACE. Conclusions The prevalence of UMI in patients undergoing elective PCI was 29.6%. UMI was independently associated with an increased risk of MACE after successful PCI. Given the non-negligible prevalence and potential clinical significance of UMI, clinical studies comparing PCI and guideline directed medical therapy (GDMT) versus GDMT only strategy might have to take the presence of UMI into consideration. Funding Acknowledgement Type of funding sources: None.

Backgrounds Coronary pressure indices such as fractional flow reserve (FFR) are standard in guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization, especially in terms of the impact on prognosis. We aimed to investigate the potentially differential prognostic associations of elective PCI according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC) and baseline CFC (bCFC). Methods From the Inclusive invasive physiological assessment in angina syndromes (ILIAS) registry composed of 16 hospitals globally from 7 countries, patients with obstructive coronary artery disease who underwent invasive coronary physiological assessment were included (N=2370 vessels). We assessed effect measure modifications of the association of PCI and 5-year target vessel failure (TVF) according to CFR, CFC and bCFC either assessed by Doppler-technique or thermodilution-method in three models: conditional logistic regression, marginal structural model, and COX proportional hazard model. Reduced CFR, CFC and bCFC were defined as CFR17.0 cm/s in Doppler-technique, respectively (Figure 1), and the corresponding percentiles in thermodilution-methods. All models were adjusted for FFR, the interaction between PCI and FFR, and other confounders. Results The mean age of the population was 63.3 years and there were 1322 (73.6%) males. Median FFR was 0.85 and PCI was performed in 600 (25.3%) vessels. Reduced CFR, CFC, and abnormal bCFC were defined in 988 (41.7%), 542 (22.9%), and 600 (25.3%) vessels, respectively. There were little overlaps in vessels with reduced CFC and abnormal bCFC. In univariate analyses, vessels with reduced CFC had worse outcomes compared with those with normal CFC if deferred (13.4% vs. 6.6%), whereas reduced CFC was associated with better prognosis if treated by PCI (9.5% vs. 11.3%). Significant effect measure modifications were observed by CFC either in odds ratio (P=0.0018), additive (P=0.029), and hazard ratio scale (P=0.0002) (Figure 2). Vessels with reduced CFC had, compared with those with normal CFC, higher adjusted absolute risk of 5-year TVF by 5.9 [0.1, 12] percent if deferred, but lower risk by 1.8 [−1.7, 5.3] percent if treated by PCI. CFR and bCFC were not significant effect modifiers in any scales. Similar associations were observed in per-patient analyses, whereas the findings were less robust. Conclusions We observed a beneficial impact of PCI on absolute risk of 5-year clinical outcomes in vessels with reduced CFC, and a detrimental effect in those with normal CFC. CFR and bCFC were not robust effect modifiers of PCI. Therefore, CFC, combined with FFR, could be potentially used to optimize the patient selection for elective PCI treatment. Funding Acknowledgement Type of funding sources: None.

Background An incidence of cardiovascular events increases with age in women. The relationship between cardiovascular risk factors, and the underlying pathology and the prevalence of lipid plaques has not been systematically studied in different age groups in women presented with acute coronary syndromes (ACS). Purpose We investigated the underlying pathology and the prevalence of lipid plaques in culprit lesions by optical coherence tomography (OCT) in women with different risk factors. Methods A total of 382 women who underwent pre-intervention OCT imaging were included. The underlying pathology and the prevalence of lipid plaques in the culprit lesion was compared between women with and without cardiovascular risk factors (i.e. hypertension, smoking, hyperlipidemia, diabetes mellitus, family history and chronic kidney disease) in three different age groups (70 yr). Results The relative prevalence of plaque erosion was higher in younger women ( Conclusion The prevalence of plaque erosion was higher in younger women ( Funding Acknowledgement Type of funding sources: Foundation.

Background Prognostic value of unrecognized non-infarct-related territory (non-IR) myocardial infarction (UMI) in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) remains to be elucidated. Purpose This study sought to evaluate the prevalence of non-IR UMI and its prognostic value in patients with first NSTE-ACS presentation. Methods This retrospective single-center analysis was conducted in patients with NSTE-ACS without prior history of coronary artery disease, who underwent uncomplicated urgent percutaneous coronary intervention (PCI) within 48 hours of admission between August 2014 and January 2018. All patients underwent postprocedural cardiac magnetic resonance imaging (CMR) within 30 days after PCI. Non-IR UMI was defined as the presence of non-IR delayed gadolinium enhancement with an ischemic distribution pattern. We investigated the association of non-IR UMI, other CMR findings and baseline clinical characteristics with major adverse cardiac events (MACE), defined as all-cause death, non-fatal myocardial infarction, ischemic stroke, late revascularization and hospitalization for congestive heart failure. Results A total of 168 NSTE-ACS patients were included (124 males (73.8%); 66±11 years). Non-IR UMI was detected in 28 patients (16.7%). During a median follow-up of 32 months (15–58), MACE occurred in 10 (35.7%) patients with non-IR UMI, and 20 (14.3%) patients without (P=0.013). Patients with MACE showed higher frequency of non-IR UMI in RCA territory and multi vessel disease, higher level of NT-proBNP at admission, higher Genisini score, and greater extent of UMI. Cox's proportional hazards analysis showed that the presence of non-IR UMI was an independent predictor of MACE (HR 2.34, 95% CI 1.02–5.37, P=0.045), after adjusting confounding factors, such as multi vessel disease and serum levels of NT-proBNP at admission. The discriminant efficacy (IDI and NRI) of predicting MACE was significantly improved when the presence of non-IR UMI added to the reference clinical risk model. Kaplan-Meier analysis revealed that patients with non-IR UMI were significantly associated with poor prognosis. (Figure 1). Conclusions In patients with NSTE-ACS undergoing urgent PCI, the prevalence of non-IR UMI was 16.7%. Non-IR UMI provided prognostic information independent of conventional risk factors. Funding Acknowledgement Type of funding sources: None.

Background Vascular inflammation has been recognized as one of the key factors in the pathogenesis of acute coronary syndromes (ACS). Peri-coronary adipose tissue (PCAT) attenuation by computed tomography angiography (CTA) has emerged as a marker specific for coronary artery inflammation. We examined the relationship between clinical presentation and coronary artery inflammation assessed by PCAT attenuation and coronary plaque characteristics. Methods Patients with ACS or stable angina pectoris (SAP) who underwent pre-intervention coronary CTA and optical coherence tomography (OCT) were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries. PCAT attenuation and OCT findings were compared between patients with ACS versus SAP. Results Among 471 patients (ACS: 198, SAP: 273), PCAT attenuation was higher in ACS patients than in SAP patients both at the culprit plaque level (−67.5±9.6 Hounsfield unit [HU] vs. −71.5±11.0 HU, p Conclusions PCAT attenuation at culprit plaque, culprit vessel, and pan-coronary levels was higher in ACS patients than in SAP patients. Vascular inflammation appears to play a crucial role in the development of ACS. Funding Acknowledgement Type of funding sources: None.

Background The presence of layered plaque is suggestive of recurrent thrombotic events. However, the impact of layered plaque detected by optical coherence tomography (OCT) on coronary inflammation and coronary flow reserve remains unclear. Purpose We aimed to investigate the association of OCT-derived layered plaque with pericoronary adipose tissue inflammation assessed by coronary computed tomography angiography (cCTA) and global coronary flow reserve (G-CFR) assessed by cardiac magnetic resonance imaging (CMR) in patients with acute coronary syndrome (ACS). Methods We investigated 88 patients with first ACS who underwent preprocedural cCTA and OCT imaging of the culprit lesion, and CMR after percutaneous coronary intervention (PCI). All patients were divided into four groups according to the OCT-derived culprit plaque characteristics: layered vs. non-layered plaque; and plaque rupture vs. plaque erosion. Coronary inflammation was assessed by the mean value of pericoronary adipose tissue (PCAT) attenuation (−190 to −30 HU) of the three major coronary vessels. G-CFR was obtained by quantifying absolute coronary sinus flow at rest and during maximum hyperemia. CCTA and CMR findings were compared between the groups. Results In a total of 88 patients, layered plaque [L] with plaque rupture [PR] was observed in 25 patients, layered plaque with plaque erosion [PE] was observed in 26 patients, non-layered plaque [NL] with PR was observed in 23 patients, and non-layered plaque with PE was observed in 14 patients, respectively. Three-vessel-PCAT attenuation value (L-PR vs. L-PE vs. NL-PR vs. NL-PE; −68.13±6.18 vs. −69.01±6.72 vs. −69.76±4.04 vs. −74.61±5.63 HU, P=0.009) and culprit vessel PCAT attenuation value (L-PR vs. L-PE vs. NL-PR vs. NL-PE; −66.39±7.38 vs. −68.94±8.06 vs. −70.01±5.76 vs. −75.45±6.60 HU, P=0.003) showed the graded difference between the four groups. G-CFR value also showed the graded difference between the four groups (L-PR vs. L-PE vs. NL-PR vs. NL-PE; 2.26 [1.80–2.87] vs. 2.24 [1.72–3.13] vs. 2.97 [2.24–3.83] vs. 3.18 [2.67–4.08], P=0.022). Conclusions The presence of layered plaque at the culprit lesion was associated with high PCATA and low G-CFR in patients with ACS. Detection of layered plaque may indicate increased pericoronary inflammation and impaired coronary flow reserve, potentially providing the risk stratification in patients with ACS. Funding Acknowledgement Type of funding sources: None.

Objectives This study sought to assess the predictors of coherence tomography (OCT) and coronary computed tomography angiographic (CCTA) findings for non-infarct-related (non-IR) territory unrecognized myocardial infarction (UMI) in patients with first non-ST-elevation acute coronary syndrome (NSTE-ACS) presentation. Background UMI detected by cardiac magnetic resonance (CMR) is associated with adverse outcomes in patients with both acute coronary syndrome and chronic coronary syndrome. However, the association between the presence of UMI and findings of multimodality coronary imaging remains unknown. Methods We investigated 69 patients with a first clinical episode of NSTE-ACS, who underwent pre-PCI 320-slice CCTA, uncomplicated urgent percutaneous coronary intervention (PCI) with OCT assessment within 48 hours of admission, and post-PCI CMR. UMI was assessed on late gadolinium enhancement (LGE-CMR) by identifying regions of hyperenhancement with an ischemic distribution pattern in non-IR territories (non-IR UMI). Results Non-IR UMI was detected in 11 patients (15.9%). ROC analysis revealed the optimal cut-off value of PCATA in culprit vessel for predicting the presence of non-IR UMI were −71.3. Lower ejection fraction, higher Gensini score, high pericoronary inflammation (>−71.3), OCT-defined culprit lesion plaque rupture (OCT-PR), and OCT-defined culprit lesion cholesterol crystal (OCT-CC) were significantly associated with the presence of non-IR UMI (Figure 1A). OCT findings are shown in Figure 1B. Patients with non-IR UMI had a higher prevalence of OCT-PR and OCT-CC than those without. Compared with patients without non-IR UMI, the prevalence of high pericoronary inflammation was higher in patients with non-IR UMI (Figure 1C). When the total cohort was divided into four groups according to the numbers of aforementioned OCT-derived risk factors and PCATA, patients with all of these UMI risk factors showed 46.2% (6/13) prevalence of non-IR UMI, whereas none of 15 patients without these factors showed non-IR UMI (Figure 1D). Conclusions When culprit lesion showed OCT-PR, OCT-CC, and high PCATA, about half of these patients are likely to have non-IR UMI. The integrated CCTA and OCT assessment may help identify the presence of non-IR UMI, potentially providing prognostic information in first NSTE-ACS patients. Funding Acknowledgement Type of funding sources: None.

Background Evidence regarding the use of pressure indices for the assessment of coronary stenoses in patients with chronic kidney disease (CKD) is scarce. Methods We assessed the relation between eGFR, FFR and resting Pd/Pa in 1147 consecutive patients (1316 vessels) included in the International Collaboration of Comprehensive Physiologic Assessment Study. We also compared FFR and Pd/Pa against a standardized cut-off of coronary flow reserve (CFR Results FFR increases as renal function worsens (beta −10.5, 95% CI −20.0 to −11.03, p=0.030), a relation that was not seen with resting Pd/Pa (beta −6.14, 95% CI −19.9 to 6.78, p=0.351). Both indices had similar diagnostic accuracies for the detection of a CFR CFR decreased linearly with deteriorating eGFR, and this was mainly driven by higher resting coronary flow in CKD patients (p=0.026), while hyperaemic coronary flow remained similar (p=0.403). IMR did not change significantly with eGFR (beta −0.02, 95% −0.09 to 0.05, p=0.557). The incidence of VOCO was higher in patients with CKD and FFR>0.80 when compared to non-CKD patients and FFR>0.80 (12.7% vs 6.90%, p=0.062). Prognosis was worse for those with CKD, negative FFR and CFR Conclusions The assessment of a given coronary stenosis in patients with CKD with either FFR or resting Pd/Pa is equivalent when compared to underlying coronary flow. In CKD, impaired CFR is caused by a state of increased resting flow. The assessment of CFR on top of standard pressure wire examination significantly improves prognostic stratification in CKD patients. Funding Acknowledgement Type of funding sources: None.

Background CAC evaluated by non-contrast computed tomography is a marker of atherosclerosis. However, the characteristic features of CCTA and optical coherence tomography (OCT) of culprit lesions in patients with NSTE-ACS showing zero CAC remain unknown. Objectives This study aimed to assess the prevalence and characteristic features of culprit lesions on coronary CT angiography (CCTA) and optical coherence tomography (OCT) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) showing zero coronary artery calcium (CAC). Methods A total of 176 consecutive patients with NSTE-ACS who underwent preprocedural CCTA and OCT were studied. Patients were divided into two groups according to their CAC (zero-CAC and non-zero-CAC groups). Baseline characteristics, CCTA and OCT findings were compared between these two groups. Results The prevalence of patients with zero-CACS was 15.9% (28/176). Patients in zero CAC group were younger (mean age, 55 vs. 65 years, P Conclusions Zero CAC NSTE-ACS was not rare. Zero-CAC NSTE-ACS was characterized by specific phenotypes defined by the combined assessment of CCTA and OCT. Further studies are warranted if these characteristics of NSTE-ACS on preprocedural imaging studies provide prognostic information or guidance of a specific therapeutic approach. Funding Acknowledgement Type of funding sources: None.

Background The frequent pathological cause of acute coronary thrombosis is plaque rupture or erosion. A previous CT angiographic study failed to discriminate OCT-defined intact fibrous cap culprit lesions (IFC lesions) from those with ruptured fibrous cap (RFC group) in patients with acute coronary syndrome (ACS) and chronic coronary syndrome. Objectives This study aimed to evaluate the diagnostic efficacy of preprocedural coronary CT imaging to identify optical coherence tomography (OCT)-defined plaque rupture or erosion at culprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods Consecutive patients with suspected NSTE-ACS who underwent preprocedural non-contrast CT and CT angiography (CCTA) were studied. Patients with at least one lesion with more than 50% stenosis at the proximal segment on CCTA were subsequently assessed by invasive coronary angiography and OCT. ALL CT and OCT examination were performed within 24 hours from presentation. The diagnosis of intact fibrous cap or ruptured fibrous cap was made by OCT for the angiographically most severely stenosed lesion. Cases of ambiguous OCT diagnosis such as massive thrombosis or calcified nodule precluding the fibrous cap assessment were excluded from the final analysis. Results In the final analysis of 176 patients, OCT identified 87 RFC plaques and 89 IFC plaques for the culprit lesions, respectively. In IFC group, lower prevalence of diabetes mellitus (24.7% vs. 41.4%, P=0.025) and lower peak cardiac marker elevation (CPK, 159 vs. 272 U/L, P Conclusions Preprocedural comprehensive CT imaging including CAC and pericoronary adipose tissue inflammation could identify IFC or RFC culprit lesions defined by OCT. Further studies are needed to confirm our preliminary results and if CT imaging in NSTE-ACS provides prognostic information or specific therapeutic approach such as conservative therapy or non-stenting strategy before invasive angiography. Funding Acknowledgement Type of funding sources: None.

Background Index of microcirculatory resistance (IMR) has been used as a clinical measure of microvascular function. Transthoracic Doppler echocardiography (TDE) can provide information on the functional status of coronary artery circulation. This study aims to assess the diagnostic value of left-anterior-descending artery (LAD) flow velocity by TDE for microvascular dysfunction. Methods Consecutive patients who were scheduled for elective percutaneous coronary intervention (PCI) for LAD lesions were prospectively enrolled in the single tertiary-care center between April 2020 and July 2021. Pre-PCI LAD diastolic peak velocity (DPV) by TDE at rest and hyperemia were measured. By invasive coronary angiography, quantitative coronary angiography and invasive wire-based physiological indices including fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were measured. Results A total of 104 patients were studied. Median FFR and IMR values were 0.70 (0.60–0.74) and 20.68 (14.92–31.69), respectively. No significant relationship was observed between FFR and IMR. The prevalence of microvascular dysfunction defined as IMR≥25 was 39.4%. Basal DPV was 25 (20–33) cm/sec, and hyperemic DPV was 51 (41–67) cm/sec. In lesions with IMR≥25, reference diameter (RD) was significantly greater [2.63 (2.22–3.19) mm vs 2.39 (2.09–2.66) mm, p=0.019], basal DPV was lower [26 (18–29) cm/sec vs 29 (22–37) cm/sec, p=0.022)] and hyperemic DPV was lower [49 (19–54) cm/sec vs 56 (42–70) cm/sec, p=0.023] compared to lesions with IMR2.84mm are independent predictors for IMR≥25 [Odds ratio: 3.08 (1.22–7.78), p=0.017; odds ratio 4.40 (1.55–12.50), p=0.005]. Conclusion Basal DPV by non-invasive pre-PCI TDE and reference diameter can predict lesions with coexisting microvascular dysfunction in LAD territory with functionally significant lesions without the need of vasodilator-induced hyperemia and a wire-based invasive physiological measurement. Funding Acknowledgement Type of funding sources: None.

Introduction Guideline-directed management of chronic coronary syndrome (CCS) remains focused on obstructive causes of angina, and is based on established therapies derived from studies predominantly including men. This occurs despite documented higher mortality from cardiovascular causes in women compared to men, which is hypothesized to be related to a higher prevalence of coronary microvascular dysfunction (CMD) in women. However, data on the relationship between sex, the different endotypes of CCS, and related sex-specific clinical outcomes are limited. Purpose This study aimed to investigate the relationship between sex and the different endotypes of CCS, as well as sex-specific clinical outcomes of CCS endotypes. Method In patients with stable angina undergoing coronary angiography, the following invasive coronary hemodynamics were characterized: fractional flow reserve (FFR; 2.5mmHg/cm/sec or index of microvascular resistance >25 considered abnormal). Patients were stratified into three groups: 1) hemodynamically significant obstructive coronary artery disease (oCAD) (FFR abnormal or a severe coronary stenosis requiring revascularization), 2) no-obstructive coronary artery disease but with CMD (FFR normal, but abnormal CFR and/or MR), or 3) no-obstructive coronary artery disease and no CMD (FFR normal, and normal CFR and MR). We assessed the prevalence of the CCS endotypes across sex, and sex-specific cardiovascular outcomes over a follow-up of 7 years defined as the composite endpoint of death or acute myocardial infarction. Results Amongst a total of 1987 included patients, 1435 (72.2%) were men and 552 (27.8%) were women. oCAD occurred in 904 (45.5%) patients, which was significantly more prevalent in men (48.9% (701/1435) of men vs. 36.8% (203/552) of women, p Conclusion In patients evaluated for CCS who underwent clinically indicated coronary angiography and physiological assessment, men were more likely to have oCAD and women were more likely to be classified as CMD. There were no sex-related differences in the prognosis associated with the individual CCS endotypes. Therefore, pathophysiological changes in the coronary circulation potentially underlying angina pectoris are similarly prevalent in men and women, but the high incidence of CMD in women makes women prone to underdiagnosis if no additional physiological measurements are assessed. Funding Acknowledgement Type of funding sources: None.

Importance: Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. Objective: To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime. Design, Setting, and Participants: Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months. Interventions: Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. Main Outcomes and Measures: The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause. Results: A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. Conclusions and Relevance: These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF. Trial registration: ClinicalTrials.gov Identifier: NCT03036124.

Background: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. Methods: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. Results: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p >.05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p =.004; RFS: 68.8% vs. 77.3%, p =.005) and multivariable analysis (OS: HR: 1.52, p =.019; RFS: HR: 1.32, p =.05). Conclusions: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location. © 2020 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC

Vitamin K is considered to be involved in the pathological mechanisms of coronary artery calcification (CAC). Correlation between CAC and plasma vitamin K levels was studied. A total of 103 patients, with at least one coronary risk factor, were studied. CAC was measured using 64-slice multislice computed tomography (MSCT) and divided into three groups: none (CAC score = 0; n 25), mild to moderate (0 n 52) and severe (CAC score > 400; n 26). Phylloquinone (PK) and menaquinone (MK)-4 and MK-7 were measured by HPLC-tandem MS. Mean age of patients was 64 (sd 13) years, of which 57 % were male. Median CAC score was 57·2. Median levels of PK, MK-4 and MK-7 were 1·33, 0 and 6·99 ng/ml, showing that MK-7 was the dominant vitamin K in this population. MK-7 showed a significant inverse correlation with uncarboxylated osteocalcin (ucOC, P = 0·014), protein induced by vitamin K absence of antagonist-2 (PIVKA-2, P = 0·013), intact parathyroid hormone (P = 0·007) and bone-specific alkaline phosphatase (P = 0·018). CAC showed an inverse correlation with total circulating uncarboxylated matrix Gla protein (t-ucMGP, P = 0·018) and Hb (P = 0·05), and a positive correlation with age (P P = 0·03), pulse wave velocity (P P

Radioluminescence were measured in several ceramics materials under irradiation in {sup 60}Co gamma-ray irradiation facility using the fused silica core fiber. Aluminum oxide (Al{sub 2}O{sub 3}), europium oxide (Eu{sub 2}O{sub 3}), and gadolinium oxide (Gd{sub 2}O{sub 3}) had luminescent peaks. These peaks had the linearity to the gamma-ray dose rate under 6.3 Gy/s.

The atmosphere detritiation system (ADS) for ITER, which is a system provided to remove tritium in building and confinement atmospheres to secure the tritium safety for workers and public in both normal and off-normal conditions based on the ALARA principle, has been designed. In normal condition including maintenance activities, the ADS removes tritium in effluent gas and secondary confinement atmosphere. In the event of off-normal tritium release, the ADS, as a whole, maintains the tritium safety by mitigating the effect of the tritium release according to the operation scenario established based on the present design.

In this design work, a combination of the hydrogen pumps in charge of the function of hydrogen isotopes recovery and the oxygen pump was adopted to the blanket tritium recovery system for the prototype fusion reactor designed by Japan Atomic Energy Research Institute (JAERI). The main functions of this system are described below. 1) Transport of tritium with helium purge gas: tritium released from ceramic breeding material in the blanket is transported to the tritium recovery system by the helium purge gas which contains a small amount of hydrogen gas. 2) Steam electrolysis and removal of oxygen gas: the oxygen pump with electrolyte of oxygen ionic conductors electrolyzes the steam (H 2 O and HTO) contained in the purge gas into hydrogen isotopes and oxygen, and simultaneously removes impurity of oxygen by electrical membrane permeation. 3) Recovery of hydrogen isotopes: the hydrogen pump with electrolyte of protonic conductors electrically recovers the pure hydrogen isotopes (HT and H 2 ) from the purge gas. Based on the experimental data obtained by feasibility study and the present design effort, it was revealed that the simple and continuous tritium recovery system for gaseous stream is possible and attractive for fusion power reactors.

The purpose of this study is to develop a radiation distribution monitor using a normal plastic optical fiber. The monitor has a long operating length and can obtain continuous radiation distributions. A principle of;the position sensing is based on a time-of-flight technique. The monitor is sensitive to beta rays or charged particles, gamma rays, and fast neutrons. The spatial resolutions for beta rays (/sup 90/Sr-/sup 90/Y), gamma rays (/sup 137/Cs) and D-T neutrons are 30 cm, 37 cm and 13 cm, respectively. The detection efficiencies for the beta rays, the gamma rays and D-T neutrons are 0.11%, 1.6/spl times/10/sup -5/% and 1.2/spl times/10/sup -4/%, respectively. The effective attenuation length of the detection efficiency is 18 m. In this paper, we describe the basic characteristics of this monitor.

Electrochemical properties of the ceramic protonic conductor cell were investigated to evaluate its feasibility of hydrogen pumping for the purpose of tritium extraction in fusion fuel system. Expe...

In order to improve the safe handling and control of tritium for the ITER fuel cycle, effective in situ tritium accounting methods have been developed at the Tritium Process Laboratory in the Japan Atomic Energy Research Institute under one of the ITER-EDA R&D tasks. The remote and multilocation analysis of process gases by an application of laser Raman spectroscopy developed and tested could provide a measurement of hydrogen isotope gases with a detection limit of 0.3 kPa analytical periods of 120 s. An in situ tritium inventory measurement by application of a `self-assaying' storage bed with 25 g tritium capacity could provide a measurement with the required detection limit of less than 1% and a design proof of a bed with 100 g tritium capacity.

A system composed of a palladium diffuser and an electrolytic reactor has been proposed and then developed for the fuel cleanup system of ITER. The performance of the system has been studied in detail in a stand-alone test. A fuel simulation loop of ITER was constructed by connecting the fuel cleanup and hydrogen isotope separation systems developed; and the function of each system in the loop has been demonstrated. For tritium recovery from the exhaust gas during helium glow discharge cleaning of the vacuum chamber of ITER, a cryogenic molecular sieve bed system has been proposed and demonstrated.

An integrated fusion fuel loop was constructed. A palladium diffuser first treated a simulated plasma exhaust gas, that is a mixture of hydrogen isotopes and impurities such as helium and methane. ...

Membrane detritiation processes using gas permeation membrane have the advantages of being simple in system configuration and compact in size compared to conventional oxidation followed by adsorpti...

BACKGROUND In de novo human atherosclerosis, compensatory vessel enlargement limits the effect of intimal plaque formation on lumen narrowing. We hypothesized that arterial remodeling may also play an important role in determining the chronic lumen size after angioplasty and tested this hypothesis using the hypercholesterolemic rabbit iliac artery angioplasty model. METHODS AND RESULTS Morphometric analysis of histological cross-sectional areas of vessels from animals killed immediately after angioplasty (acute group, n = 11) were compared with the same areas from animals killed 4 weeks after the procedure (chronic group, n = 37), when restenosis occurs in this model. The area circumscribed by the internal elastic lamina (IEL) increased by 20% from acute to 4 week follow-up after angioplasty (acute group, 2.36 +/- 0.45 mm2, chronic group, 2.84 +/- 0.89 mm2). Over the same time period, intimal area increased by 0.82 mm2. Despite this increase in intimal area, lumen area decreased by only 0.34 mm2 because of the compensatory enlargement of the IEL area. In the chronic group, polynomial regression analysis revealed a quadratic relation between intimal area and lumen area (R2 = .35, P < .001). A lumen area of 0.45 mm2 (the nadir of the quadratic relation) was used to divide the chronic group into two subgroups: restenotic (n = 21; lumen area, < 0.45 mm2) and nonrestenotic (n = 16; lumen area, > 0.45 mm2). By definition, there was a significant difference in lumen area between the two subgroups (0.15 +/- 0.15 mm2 for restenotic; 0.73 +/- 0.18 mm2 for nonrestenotic). Surprisingly, the intimal areas in the two subgroups were virtually identical (2.41 +/- 0.92 mm2 for restenotic, 2.49 +/- 0.69 mm2 for nonrestenotic, P = NS). The difference in the lumen area between restenotic and nonrestenotic vessels was a result of the significantly greater IEL area in the nonrestenotic subgroup (3.22 +/- 0.83 mm2 for nonrestenotic, 2.56 +/- 0.84 mm2 for restenotic, P < .05). In both restenotic and nonrestenotic vessels, the IEL area increased with increases in intimal area. In the restenotic arteries, the slope of this correlation was < 1, showing inadequate compensatory enlargement for the intimal plaque. In the nonrestenotic vessels, the slope was > 1, limiting the effect of intimal plaque on luminal narrowing. CONCLUSIONS These data indicate that the iliac artery in an atherosclerotic rabbit model compensates for intimal formation after angioplasty by vessel enlargement. Furthermore, the degree of vessel enlargement is more important than intimal area in determining the chronic lumen size.

Secondary lithium batteries using electrochemically-doped poly(N-vinyl-carbazole) (PVCz) deposited on a Pt plate or gauze, and doped PVCz-graphite as cathodes exhibit flat discharge voltages and good cyclability with high coulombic efficiencies.

New strategies in the treatment of acute coronary syndromes have focused on the potential for blocking platelet aggregation through the use of platelet surface membrane glycoprotein (GP) IIb/IIIa receptor inhibitors. The benefits of GPIIb/IIIa inhibition in preventing ischemic complications of interventional treatment have been well defined in patients with unstable angina. In the future, major therapeutic applications for this class of agents may include the stabilization of patients with unstable angina and potentially as single medical therapy, as several recently completed trials have suggested. This article attempts to review recently published clinical trials regarding the use of GPIIb/IIIa receptor inhibitors, and clarify current problems in the use of this agent and directions for future investigation.

Radiation effects on key components of diagnostic systems expected to be subjected to high neutron and gamma fluxes and fluences are being examined in irradiation tests to evaluate and establish an ITER-relevant database to support the design. A comprehensive irradiation database has been accumulated and permits conclusions to be drawn on the application of these components in ITER. The design studies on prototypical assemblies of diagnostic components are continuing based on the irradiation data bases, neutronics calculations for evaluating irradiation environment of diagnostic components and required specification of diagnostic systems. These studies will aid the recognition of detailed requirements of diagnostic systems leading to more specific irradiation tests on diagnostic components.

A Nuclear Pumped Laser (NPL) using 3He/Ne/Ar gas mixture is investigated for a purpose of applying to an optical self‐powered neutron detector. Reactor experiments and simulations on lasing mechanism have been made to estimate the best gas pressure and mixture ratios on the threshold input power density (or thermal neutron flux) in 3He/Ne/Ar mixture. Calculational results show that the best mixture pressure is 3He/Ne/Ar=2280/60/100 Torr and thermal neutron flux threshold 5×1012 n/cm2 sec, while the reactor experiments made in the research reactor ‘‘YAYOI’’ of the University of Tokyo and ‘‘JRR‐4’’ of JAERI also demonstrate that excitational efficiency is maximized in a similar gas mixture predicted by the calculation.

In calculation of an uptake coefficient (UC), proportional to the glomerular filtration rate for renal dynamic images with 99mTc diethyl triamine pentaacetate (DTPA), by the graphic method proposed by Rutland. We developed a new method of estimating input and output functions, by applying a factor analysis method to the renal dynamic images. The purposes of this paper are to describe the results obtained through phantom experiments and its clinical application. In the phantom experiments, a hemofilter was used as a method for real kidney and the filtration rate was changed to estimate the reproducibility of UCs. the UCs were estimated by trying different input functions; abdominal aorta curve, renal artery curve and intrarenal artery curve. The UCs estimated by using the intrarenal artery curve as an input function showed the best correlation with the pre-determined filtration rate. In clinical applications 8 normal subjects, 3 patients with acute renal failure, 11 donors and 22 recipients were studied. The USs obtained were compared with clinical data of renal function. A group of subjects having with both kidneys in the normal body space were classified as Cluster 1, another group of transplant recipients were classified as Cluster 2. In Cluster 1 the UCs showed a good correlation with Ccr (r = 0.909), and effective renal plasma flow (r = 0.798), and an inverse correlation between UCs and serum creatinine values (r = 0.747). The median value of UCs in 11 donors at pretransplantation were 0.30, which increased to 0.46 at 3 weeks after transplantation. Cluster 2 has many risk factors (to be abnormal space, rejection, toxicity of Cyclosporin and immuno suppression) compared to Cluster 1, but in Cluster 2 the UCs showed a good correlation with Ccr (r = 0.955), and effective renal plasma flow (r = 0.653), and an inverse correlation between UCs and serum creatinine values (r = 0.857). Cluster 1 and Cluster 2 showed the same correlations with Ccr and UCs. But Cluster 1 is a different group from Cluster 2. The results of the study showed that the modified Rutland's analy analytical method can estimate the renal filtration rate accurately, evaluate the residual renal function in donors quantitatively and be a useful parameter for monitoring renal graft function.

In Zambia, theileriosis manifests itself in the form of Corridor disease (CD), caused by Theileria parva lawrencei, and East Coast fever (ECF), caused by T. parva parva. Of the approximately 3 million cattle in Zambia, 1.4 million are at risk to theileriosis. ECF is found in the Northern and Eastern provinces of the country, while CD appears in Southern, Central, Lusaka and Copperbelt provinces. Theileriosis is a major constraint to the development of the livestock industry in Zambia, with losses of about 10,000 cattle per annum. The disease is spreading at a very fast rate, over-flowing its original borders. The epidemiology is complicated by, among other factors, the wide distribution of the tick vector, Rhipicephalus appendiculatus, which is found all over the country. The current strategy of relying on tick control and therapeutic drugs as a way of controlling the disease is becoming increasingly difficult for Zambia. This is because both curative drugs and acaricides are very costly. Immunization against theileriosis using the infection and treatment method as a way of controlling the disease is becoming increasingly accepted, provided local Theileria stocks are used. This paper reviews the incidence of theileriosis in the last 2 years, 1991 and 1992. It also gives a historical perspective of the disease, epidemiology and control measures presently in use.

An uptake coefficient (UC) is estimated with applying the method proposed by Rutland to the renal dynamic images with 99mTc-diethyltriamine pentaacetate (DTPA). UC estimated with this method is proportional to glomerular filtration rate in the original Rutland's method the cardiac and renal time-activity curves (TAC) were used for input and output functions, respectively. In this paper, our method of estimating an input and output function by applying factor analysis method to renal dynamic images and it's clinical application are presented. In 11 patients, U"s estimated by this modified method revealed good correlations between the UCs and CCr (r = 0.75), between UCs and effective renal plasma flow (r = 0.67), and inverse correlations between UCs and serum creatinine values (r = 0.65). The results showed that UC in this method can be a useful parameter for grafted renal function. This method is simple in technique and applicable for the evaluation of split renal function in renal transplant donors.

Objective —To investigate the effects of heart rate on the Doppler measurements of left ventricular function and to determine the normal pattern of rate dependency. Setting —University hospital specialising in internal medicine. Participants —14 healthy male volunteers 10 of whom were studied. Intervention : Transoesophageal atrial pacing. Main outcome measures —At paced rates of 70, 80, and 90 ppm the ratio of early to late peak transmitral flow velocity (E/A) was 1·97 (0·28), 1·49 (0·21), and 0·95 (0·11) respectively; the ratio of early to late time-velocity integrals of transmitral flow (Ei/Ai) was 3·03 (0·51), 2·11 (0·24), and 1·14 (0·30) respectively; and the atrial filling fraction (AFF) was 0·17 (0·03), 0·21, (0·04), and 0·24 (0·04) (mean (SD)). Results —Heart rate showed a linear correlation with E/A (r 2 = 0·806), Ei/Ai (r 2 = 0·838), and AFF (r 2 = 0·343). Neither the peak aortic flow velocity or the mean aortic flow acceleration showed significant changes during pacing at rates of 70, 80, 90, and 100 ppm. Conclusions —E/A and Ei/Ai can be expected to decrease by 0·5 and 0·9 for each increase of 10 beats/min in heart rate. Knowledge of this relation may be useful for the development of algorithms to correct for heart rate when diastolic function is assessed.