Abstract Objectives This study investigated the role of fractional myocardial mass (FMM), a vessel-specific myocardial mass, in the evaluation of physiological severity of stenosis. Using computed ...tomography angiography, the study investigated fractional myocardial mass, a concept of myocardial mass subtended by specific vessel, which could reduce anatomical-physiological mismatch. Background Discordance between anatomical stenosis and physiological severity is common but remains poorly understood. Methods This multicenter study enrolled 463 patients with 724 lesions, who underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography with fractional flow reserve (FFR) measurement. FMM was assessed by allometric scaling analysis of arterial tree length and myocardial mass from CCTA. Results FFR <0.80, a criteria for vessel-specific physiological stenosis, was found in 281 vessels (39%). FMM decreased consistently according to the vessel downstream (p < 0.001, all). The frequency of FFR <0.80 increased in proportion to FMM and inverse proportion to angiographic minimal luminal diameter (MLD) (p < 0.001). In per-vessel analysis, FMM per MLD (FMM/MLD) showed good correlation with FFR (r = 0.61) and was superior to diameter stenosis (DS) for FFR <0.80 by receiver operating characteristic and reclassification analysis (C-statistics = 0.84 versus 0.74, net reclassification improvement NRI = 0.63, integrated discrimination improvement IDI = 0.18; p < 0.001, all). The optimal cutoff of FMM/MLD was 29 g/mm, with sensitivity = 75%, specificity = 77%, positive predictive value = 68%, negative predictive value = 83%, and accuracy = 77%. Addition of FMM/MLD to DS could further discriminate vessels with FFR <0.80 (C-statistic = 0.86 vs. 0.84, NRI = 0.34, IDI = 0.03; p < 0.005, all). In per-range classification analysis, agreement between FFR and FMM/MLD maintained >80% when the severity of disease was away from cutoff. Conclusions FMM/MLD could find physiological severity of coronary artery with higher accuracy than anatomical stenosis. FMM may explain the anatomical-physiological discordance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Renal infarction is a rare condition resulting from an acute disruption of renal blood flow, and the cause and outcome of renal infarction are not well established. Study Design Case ...series. Setting & Participants 438 patients with renal infarction in January 1993 to December 2013 at 9 hospitals in Korea were included. Renal infarction was defined by radiologic findings that included single or multiple wedge-shaped parenchymal perfusion defects in the kidney. Predictor Causes of renal infarction included cardiogenic (n = 244 55.7%), renal artery injury (n = 33 7.5%), hypercoagulable (n = 29 6.6%), and idiopathic (n = 132 30.1%) factors. Outcomes We used recurrence, acute kidney injury (AKI; defined as creatinine level increase ≥ 0.3 mg/dL within 48 hours or an increase to 150% of baseline level within 7 days during the sentinel hospitalization), new-onset estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (for >3 months after renal infarction in the absence of a history of decreased eGFR), end-stage renal disease (ESRD; receiving hemodialysis or peritoneal dialysis because of irreversible kidney damage), and mortality as outcome metrics. Results Treatment included urokinase (n = 19), heparin (n = 342), warfarin (n = 330), and antiplatelet agents (n = 157). 5% of patients died during the initial hospitalization. During the median 20.0 (range, 1-223) months of follow-up, 2.8% of patients had recurrent infarction, 20.1% of patients developed AKI, 10.9% of patients developed new-onset eGFR < 60 mL/min/1.73 m2 , and 2.1% of patients progressed to ESRD. Limitations This was a retrospective study; it cannot clearly determine the specific causal mechanism for certain patients or provide information about the causes of mortality. 16 patients were excluded from the prognostic analysis. Conclusions Cardiogenic origins were the most important causes of renal infarction. Despite aggressive treatment, renal infarction can lead to AKI, new-onset eGFR < 60 mL/min/1.73 m2 , ESRD, and death.
Background Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic ...dermatitis (AD) risk remains poorly understood. Objective We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species. Methods Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases COCOA) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children PSKC) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11β-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured. Results In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 95% CI, 1.02-1.69; hazard ratio for anxiety, 1.41 95% CI, 1.06-1.89) and PSKC (odds ratio for distress, 1.85 95% CI, 1.06-3.25). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD ( P < .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios ( P = .037) and, especially in those who later had AD, decreased placental 11β-hydroxysteroid dehydrogenase type 2 levels ( P = .010) and increased IgE levels at 1 year of age ( P = .005). Conclusion Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objectives The goal of this study was to identify clinical and lesion-specific local factors affecting visual-functional mismatch. Background Although lesion severity determined by coronary ...angiography has not been well correlated with physiological significance, the mechanism of the discordance remains poorly understood. Methods The authors assessed quantitative coronary angiography, intravascular ultrasound (IVUS), and fractional flow reserve (FFR) in a prospective cohort of 1,000 patients with 1,129 coronary lesions. Three-dimensional computational simulation studies were performed. Results Lesions with angiographic diameter stenosis (DS) ≥50% and FFR >0.80 (“mismatches”) were seen in 57% of non–left main lesions and in 35% of the left main lesions, respectively (p = 0.032). Conversely, among the lesions with DS <50% and FFR <0.80 (“reverse mismatches”) 16% were found in the non–left main lesions and 40% in the left main lesions (p < 0.001). The independent predictors for mismatch were advanced age, non–left anterior descending artery location, absence of plaque rupture, short lesion length, large minimal lumen area, smaller plaque burden, and greater minimal lumen diameter. Conversely, reverse mismatch was independently associated with younger age, left anterior descending artery location, the presence of plaque rupture, a smaller minimal lumen area, and larger plaque burden. In a computational simulation study, FFR was influenced by DS, lesion length, different lesion shape, plaque eccentricity, surface roughness, and various shapes of plaque rupture. Conclusions There were high frequencies of visual-functional mismatch between angiography and FFR. The discrepancy was related to the clinical and lesion-specific factors frequently unrecognizable by angiography, thus suggesting that coronary angiography cannot accurately predict FFR. (Natural History of FFR-Guided Deferred Coronary Lesions IRIS FFR-DEFER; NCT01366404 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objectives The authors sought to identify whether a coronary side branch (SB) is supplying a myocardial mass that may benefit from revascularization. Background The amount of subtending ...myocardium and physiological stenosis is frequently different between the main vessel (MV) and SB. Methods In this multicenter registry, 482 patients who underwent coronary computed tomography angiography and fractional flow reserve (FFR) measurement were enrolled. The % fractional myocardial mass (FMM), the ratio of vessel-specific myocardial mass to whole myocardium, was assessed in 5,860 MV or SB consisting of 2,930 bifurcations. Physiological stenosis was defined by fractional flow reserve (FFR) <0.80. Myocardial mass that may benefit from revascularization was defined by %FMM ≥10%. Results In per-bifurcation analysis, MV supplied a 1.5- to 9-fold larger myocardial mass compared with SB. Unlike left main bifurcation (n = 482), only 1 of every 5 non-left main SB (n = 2,448) supplied %FMM ≥10% (97% vs. 21%; p < 0.001). SB length ≥73 mm could estimate %FMM ≥10% (c-statistic = 0.85; p < 0.001). In 604 vessels interrogated by FFR, diameter stenosis was similar (p = NS), but %FMM ≥10%, FMM/minimal luminal diameter, and frequency of FFR <0.80 was higher in MV compared with SB (p < 0.001, all). Generalized estimating equations modeling demonstrate that vessel diameter, left myocardial mass, and FFR were not (p = NS), but SB length ≥73 mm and left main bifurcation were significant predictors for %FMM ≥10% (p < 0.001). Conclusions Compared with MV, SB supplies a smaller myocardial mass and showed less physiological severity despite similar stenosis severity. SB supplying a myocardial mass of %FMM≥10%, which may benefit revascularization could be identified by vessel length ≥73 mm. Pre-procedural recognition of these findings may guide optimal revascularization strategy for bifurcation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in ...immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. Study Design Prospective, randomized, controlled, open-label trial. Setting & Participants Septic patients with AKI receiving CVVHDF for AKI. Intervention Conventional (40 mL/kg/h) and high (80 mL/kg/h) doses of CVVHDF for the duration of CRRT. Outcomes Patient and kidney survival at 28 and 90 days, circulating cytokine levels. Results 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P = 0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P = 0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. Limitations Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. Conclusions High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.
Abstract Purpose The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for ...a future single-pill combination formulation. Methods This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure SiDBP between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. Findings 420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, –6.0 (8.5) mm Hg; amlodipine 5 mg, –10.6 (9.2) mm Hg; amlodipine 10 mg, –15.9 (7.2) mm Hg; fimasartan 30 mg, –10.1 (9.1) mm Hg; fimasartan 60 mg, –13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, –16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, –19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, –16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, –21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups ( P = 0.0884). The most common AE was headache (12 patients 2.9%), followed by dizziness (11 patients 2.6%) and elevated blood creatine phosphokinase levels (6 patients 1.4%). Implications Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background No reported prospective, randomized study has evaluated the impact of an endoscopy nurse participating as a second observer during colonoscopy. Objective To determine whether the ...participation of an endoscopy nurse enhanced the polyp detection rate (PDR) and adenoma detection rate (ADR) during screening colonoscopy. Design Multicenter, prospective, randomized study. Setting Academic hospitals. Patients A total of 844 consecutive patients undergoing screening colonoscopy. Interventions Single observation by colonoscopist or dual observation by colonoscopist and endoscopy nurse during colonoscope withdrawal. Main Outcome Measurements PDR and ADR. Results No significant difference in patient demographic data, adequacy of bowel preparation, or mean withdrawal time was observed between the 2 groups. In total, 1153 polyps, including 762 adenomas, were detected in 791 patients. Seven nonpolypoid, depressed neoplastic lesions (0-IIc or combined types) were only detected in the dual observation group. A multivariate analysis revealed that experienced (≥2 years) endoscopy nurse participation significantly increased the PDR and ADR compared with those in the single observation group by a colonoscopist alone (adjusted odds ratio OR 1.58 95% CI, 1.07-2.32; adjusted OR 1.47 95% CI, 1.01-2.12, respectively). Additionally, the PDR was significantly higher in the dual-observation group with fellows (<500 colonoscopies) and an experienced endoscopy nurse versus that in the single observation group (adjusted OR 2.07 95% CI, 1.15-3.74). There was no significant benefit of experienced nurse participation in the subgroup with experienced colonoscopists. Limitations Absence of colonoscopist blinding. Conclusions Experienced endoscopy nurse participation increased the PDR and ADR during screening colonoscopy. However, the benefit of participation by experienced nurses appears to be exclusively with inexperienced colonoscopists. (Clinical trial registration number: NCT01124266 .)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives This study sought to test the noninferiority of triple antiplatelet therapy (TAT) versus double-dose clopidogrel dual antiplatelet therapy (DDAT) in patients undergoing percutaneous ...coronary intervention (PCI). Background Antiplatelet regimen is an integral component of medical therapy after PCI. A 1-week duration of doubling the dose of clopidogrel was shown to improve outcome at 1 month compared with the conventional dose in patients with acute coronary syndrome undergoing PCI. Yet in Asia, the addition of cilostazol is used more commonly than DDAT in high-risk patients. Methods We randomly assigned 3,755 all-comers undergoing PCI to either TAT or DDAT, which was continued for 1 month, to test the noninferiority of TAT versus DDAT. The primary outcome was the cumulative incidence of net clinical outcome at 1 month post-PCI defined as the composite of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO (Platelet Inhibition and Patient Outcomes) major bleeding. Results TAT was noninferior to DDAT with respect to the primary outcome, which occurred in 1.2% and 1.4% of patients, respectively (−0.22% absolute difference, 0.34% 1-sided 97.5% confidence interval, p = 0.0007 for noninferiority; hazard ratio: 0.85; 95% confidence interval: 0.49 to 1.48; p = 0.558 for superiority). The individual risks of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO major bleeding did not differ significantly between the 2 groups. There were no significant between-group differences in the treatment effect with regard to the rate of the primary outcome. Conclusions The adjunctive use of cilostazol was noninferior to doubling the dose of clopidogrel for 1 month in all-comers undergoing PCI with exclusively drug-eluting stents. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis–SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen HOST-ASSURE; NCT01267734 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective To identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome. Methods A total of 3169 rheumatoid arthritis (RA) patients were recruited ...as part of the Korean Observational Study Network for Arthritis, the nationwide cohort of South Korea. Patients were stratified according to age at disease onset: <40 years (younger age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n = 1516), and ≥60 years (EORA, n = 486). To evaluate the significance of differences in clinical features among these 3 groups, we performed analysis of variance ( anova ) and the χ2 test. We used multivariable logistic regression analysis to examine the association of onset age with functional disability measured with Health Assessment Questionnaire-Disability Index (HAQDI). Results EORA patients were associated with high HAQDI (≥1) in bivariable analysis odds ratio (OR) 1.36, confidence interval (CI) 1.04-1.77. However, in multivariable analysis, not elderly onset but patients' age, female gender, high disease activity, disease duration over 10 years, and comorbidity with cardiovascular disease were associated with high HAQDI. Only in a predefined subgroup with disease duration <10 years, elderly onset was an independent influencing factor for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease duration of <5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years). Conclusions Disease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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