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
There are conflicting data regarding the benefit of intravascular ultrasound (IVUS)–guided percutaneous coronary intervention (PCI) over angiography-guided PCI. Since the last meta-analysis was ...published, several new studies have been reported. We performed a comprehensive meta-analysis to evaluate the clinical impact of IVUS-guided PCI with drug-eluting stent compared with conventional angiography-guided PCI. This meta-analysis included 26,503 patients from 3 randomized and 14 observational studies; 12,499 patients underwent IVUS-guided PCI and 14,004 underwent angiography-guided PCI. Main outcome measures were total mortality, myocardial infarction (MI), stent thrombosis, and target lesion revascularization (TLR). IVUS-guided PCI was significantly associated with more stents, longer stents, and larger stents. Regarding clinical outcomes, IVUS-guided PCI was associated with a significantly lower risk of TLR (odds ratio OR 0.81, 95% confidence interval CI 0.66 to 1.00, p = 0.046). In addition, the risk of death (OR 0.61, 95% CI 0.48 to 0.79, p <0.001), MI (OR 0.57, 95% CI 0.44 to 0.75, p <0.001), and stent thrombosis (OR 0.59, 95% CI 0.47 to 0.75, p <0.001) were also decreased. In conclusion, our meta-analysis demonstrated that IVUS-guided PCI was associated with lower risk of death, MI, TLR, and stent thrombosis after drug-eluting stent implantation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Objectives This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions. Background The optimal ...bifurcation stenting technique needs to be evaluated. Methods The trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non–left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis. Results Between the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p = 0.064), comprising 15.1% versus 3.7% for the main branch (p = 0.004) and 2.8% versus 5.6% for the SB (p = 0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p = 0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p = 0.44), comprising 5.2% versus 4.8% for the main branch (p = 0.90) and 3.9% versus 8.3% for the SB (p = 0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p = 0.84). Conclusions Angiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non–left main bifurcation lesions once the procedure was performed successfully.
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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 This study sought to evaluate the intravascular ultrasound (IVUS) minimal lumen area (MLA) for functionally significant left main coronary artery (LMCA) stenosis using fractional ...flow reserve (FFR) as the standard. Background The evaluation of significant LMCA stenosis remains challenging. Methods We identified 112 patients with isolated ostial and shaft intermediate LMCA stenosis (angiographic diameter stenosis of 30% to 80%) who underwent IVUS and FFR measurement. Results The FFR was ≤0.80 in 66 LMCA lesions (59%); these exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter of stenosis, longer lesion length, smaller MLA, larger plaque burden, and more frequent plaque rupture. The independent factors of an FFR of ≤0.80 were plaque rupture (odds ratio OR: 4.47; 95% Confidence Interval (CI): 1.35 to 14.8; p = 0.014); body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001). The optimal IVUS MLA cutoff value for an FFR of ≤0.80 was 4.5 mm2 (77% sensitivity, 82% specificity, 84% positive predictive value, 75% negative predictive value, area under the curve: 0.83, 95% CI: 0.76 to 0.96; p < 0.001) overall and 4.1 to 4.5 mm2 in various subgroups. Adjustment for the body surface area, body mass index, and left ventricular mass did not improve the diagnostic accuracy of the IVUS MLA. Conclusions In patients with isolated ostial and shaft intermediate LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm2 is a useful index of an FFR of ≤0.80.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Left Main Coronary Artery Disease Lee, Pil Hyung, MD; Ahn, Jung-Min, MD; Chang, Mineok, MD ...
Journal of the American College of Cardiology,
09/2016, Volume:
68, Issue:
11
Journal Article
Peer reviewed
Open access
Abstract Left main coronary artery (LMCA) disease is the highest-risk lesion subset of ischemic heart disease, and has traditionally been an indication for coronary artery bypass grafting (CABG). ...Recent evidence suggests comparable clinical outcomes between percutaneous coronary intervention (PCI) and CABG for LMCA disease, with similar rates of mortality and serious composite outcomes, a higher rate of stroke with CABG, and a higher rate of repeat revascularization with PCI. These results have been translated to the current guideline recommendation that PCI is a reasonable alternative to CABG in patients with low to intermediate anatomic complexity. However, how the characteristics, treatment, and clinical outcomes of patients with unprotected LMCA disease have evolved over time has not yet been fully evaluated. We therefore described secular trends in the characteristics and long-term outcomes of unprotected LMCA disease using “real-world” clinical experience from the IRIS-MAIN (Interventional Research Incorporation Society-Left MAIN Revascularization) registry together with a broad review of this topic.
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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 This study describes the characteristics of a real-world Asian patient population treated with transcatheter aortic valve replacement (TAVR) and evaluates their clinical outcomes. ...Background No previously reported randomized or observational studies adequately assess the safety and efficacy of TAVR in an Asian population. Methods The Asian TAVR registry is an international multicenter study that enrolled patients with aortic stenosis who underwent TAVR in Asian countries. Results In total, 848 patients with mean STS score of 5.2 ± 3.8% were enrolled between March 2010 and September 2014 at 11 centers in 5 countries. The Edwards Sapien or Medtronic CoreValve was implanted in 64.7% and 35.3% of patients, respectively. The procedural success rate was 97.5%. The 30-day and 1-year mortality rates were 2.5% and 10.8%, respectively. There was no difference in 1-year mortality between devices (Sapien: 9.4%; CoreValve: 12.2%; log-rank p = 0.40). The rates of stroke, life-threatening bleeding, major vascular complications and acute kidney injury (stage 2 to 3) were 3.8%, 6.4%, 5.0% and 3.3%, respectively. Moderate or severe paravalvular leakage was significantly more common with the CoreValve than Sapien (14.4% vs. 7.3%; p = 0.001). According to the multivariate model, a higher STS score, lower body mass index, New York Heart Association functional class III–IV symptoms, diabetes mellitus, prior cerebrovascular accident, low mean gradient at baseline, and moderate or severe paravalvular leakage were significantly associated with reduced survival. Conclusions Despite anatomical features of concern, the clinical outcomes of TAVR in our Asian population were favorable in comparison with those of previously published trials and observational studies. (The Asian Transcatheter Aortic Valve Replacement Registry Asian TAVR; NCT02308150 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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
Abstract Background How statins alter the natural course of coronary atherosclerosis with compositional changes remains unclear. Objectives This study aimed to determine the effect of statin therapy ...on modifying plaque composition. Methods The STABLE (Statin and Atheroma Vulnerability Evaluation) prospective, single-center, double-blind, randomized study evaluated the effect of statins on functionally insignificant coronary stenoses. We randomly assigned 312 patients with a virtual histology (VH) intravascular ultrasound–defined fibroatheroma-containing index lesion to rosuvastatin 40 mg versus 10 mg (2:1 ratio). In 225 (72%) patients, grayscale- and VH-intravascular ultrasound were completed at baseline and 12 months. The primary endpoint was the change in VH-defined percent compositional volume within the target segment from baseline to follow-up in the per-protocol analysis set. Results Percent necrotic core (NC) volume within the target segment significantly decreased from 21.3 ± 6.8% to 18.0 ± 7.5% during 1-year follow-up, whereas the percent fibrofatty volume increased (11.7 ± 5.8% vs. 14.8 ± 9.3%; all p < 0.001). Percent fibrous (59.4 ± 7.8% vs. 59.2 ± 8.6%) and dense calcium (7.6 ± 5.1% vs. 7.8 ± 5.6%) volumes were unchanged. Frequencies of VH (55% vs. 29%) decreased significantly. Normalized total (202.9 ± 72.3 mm3 vs. 188.5 ± 67.8 mm3 ; p = 0.001) and percent (51.4 ± 8.3% vs. 50.4 ± 8.8%; p = 0.018) atheroma volumes decreased. Independent predictors of percent NC volume change were body mass index (β = 0.37; 95% confidence interval CI: 0.05 to 0.70), high sensitivity C-reactive protein (β = −3.16; 95% CI: −5.64 to −0.69), and baseline percent NC volume (β = −0.44; 95% CI: −0.68 to −0.19; all p < 0.05). VH-defined percent compositional volume changes in the rosuvastatin 40- and 10-mg groups were similar. Conclusions Rosuvastatin reduced NC and plaque volume and decreased thin-cap fibroatheroma rate. There were no significant differences between high- versus moderate-intensity rosuvastatin. (Statin and Atheroma Vulnerability Evaluation STABLE; NCT00997880 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)- ras ...pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. Methods Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10·9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3×3 design; two to six patients for each dose with 12–18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (108 plaque-forming units pfu, 3×108 pfu, 109 pfu, or 3×109 pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov , number NCT00629759. Findings Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5·6 previous treatments, SD 2·8, range 2·0–12·0) and had large tumours (7·0 cm diameter, SD 2·7, range 1·8–10·9). Patients received a mean of 3·4 (SD 2·2, range 1·0–8·0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I–III flu-like symptoms, and four had transient grade I–III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1×109 pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I–III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. Interpretation Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway. Funding Jennerex Biotherapeutics (San Francisco, CA, USA) and Green Cross Corporation (Giheung-Gu, Yongin, South Korea).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The current transcatheter aortic valve implantation (TAVI) devices have been designed to fit Caucasian and Latin American aortic root anatomies. We evaluated the racial differences in aortic root ...anatomy and calcium distribution in patients with aortic stenosis who underwent TAVI. We conducted a multicenter study of 4 centers in Asia and Europe, which includes consecutive patients who underwent TAVI with preprocedural multidetector computed tomography. Quantitative assessment of aortic root dimensions, calcium volume for leaflet, and left ventricular outflow tract were retrospectively performed in a centralized core laboratory. A total of 308 patients (Asian group, n = 202; Caucasian group, n = 106) were analyzed. Compared to Caucasian group, Asian group had smaller annulus area (406.3 ± 69.8 vs 430.0 ± 76.8 mm2 ; p = 0.007) and left coronary cusp diameter (30.2 ± 3.2 vs 31.1 ± 3.4 mm; p = 0.02) and lower height of left coronary artery ostia (12.0 ± 2.5 vs 13.4 ± 3.4 mm; p <0.001). Of baseline anatomic characteristics, body height showed the highest correlation with annulus area (Pearson correlation r = 0.64; p <0.001). Co-existence of lower height of left coronary artery ostia (<12 mm) and small diameter of left coronary cusp (<30 mm) were more frequent in Asian group compared with Caucasian group (35.6% vs 20.8%; p = 0.02). In contrast, there were no differences in calcium volumes of leaflet (367.2 ± 322.5 vs 359.1 ± 325.7 mm3 ; p = 0.84) and left ventricular outflow tract (8.9 ± 23.4 vs 10.1 ± 23.8 mm3 ; p = 0.66) between 2 groups. In conclusion, judicious consideration will be required to perform TAVI for short patients with lower height of left coronary artery ostia and small sinus of Valsalva.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK