In a randomized trial of imaging-guided or angiography-guided PCI for complex coronary lesion revascularization procedures, imaging-guided PCI led to a lower risk of target-vessel failure than ...angiography-guided PCI.
This study sought to determine whether intravascular ultrasound (IVUS) guidance compared with angiographic guidance reduces long-term risk of cardiac death in patients undergoing complex percutaneous ...coronary intervention (PCI).
Although IVUS is a useful tool for accurate assessment of lesion profiles and optimal stent implantation, there are limited data on long-term clinical outcomes between IVUS-guided and angiography-guided PCI for patients with complex lesions.
From March 2003 through December 2015, a total of 6,005 patients undergoing PCI for complex lesions with drug-eluting stents were enrolled from a prospective institutional registry. All enrolled subjects had at least 1 complex lesion (defined as bifurcation, chronic total occlusion, left main disease, long lesion, multivessel PCI, multiple stent implantation, in-stent restenosis, or heavily calcified lesion). Patients were classified according to use of IVUS or not. Multiple sensitivity analyses, including multivariable adjustment, propensity-score matching, and inverse-probability-weighted method, were performed to adjust baseline differences.
Among the study population, IVUS was used in 1,674 patients (27.9%) during complex PCI. The IVUS-guided PCI group had a significantly larger mean stent diameter (3.2 ± 0.4 vs. 3.0 ± 0.4; p < 0.001), and more frequent use of post-dilatation (49.0% vs. 17.9%; p < 0.001) compared with the angiography-guided PCI group. IVUS-guided PCI was associated with a significantly lower risk of cardiac death during 64 months of median follow-up compared with angiography-guided PCI (10.2% vs. 16.9%; hazard ratio: 0.573; 95% confidence interval: 0.460 to 0.714; p < 0.001). Results were consistent after multivariable regression, propensity-score matching, and inverse-probability-weighted method. The risks of all-cause death, myocardial infarction, stent thrombosis, ischemia-driven target lesion revascularization, and major adverse cardiac events were also significantly lower in the IVUS-guided PCI group.
Among patients with complex coronary artery lesion, IVUS-guided PCI was associated with the lower long-term risk of cardiac death and adverse cardiac events compared with angiography-guided PCI. Use of IVUS should be actively considered for complex PCI.
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IMPORTANCE: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited. OBJECTIVE: To determine ...whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI. DESIGN, SETTING, AND PARTICIPANTS: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018. INTERVENTIONS: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498). MAIN OUTCOMES AND MEASURES: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%. RESULTS: Among 2993 patients who were randomized (mean age, 64 years; 795 women 26.6%), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% 1-sided 95% CI, –∞% to 1.3%; P = .007 for noninferiority). There were no significant differences in all-cause death (21 1.4% vs 18 1.2%; hazard ratio HR, 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 0.8% vs 17 1.2%; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 0.8% vs 5 0.3%; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02). CONCLUSIONS AND RELEVANCE: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194
In addition to laser photocoagulation, therapeutic interventions for diabetic retinopathy (DR) have heretofore consisted of anti-VEGF drugs, which, besides drawbacks inherent to the treatments ...themselves, are limited in scope and may not fully address the condition's complex pathophysiology. This is because DR is a multifactorial condition, meaning a gene therapy focused on a target with broader effects, such as the mechanistic target of rapamycin (mTOR), may prove to be the solution in overcoming these concerns. Having previously demonstrated the potential of a mTOR-inhibiting shRNA packaged in a recombinant adeno-associated virus to address a variety of angiogenic retinal diseases, here we explore the effects of rAAV2-shmTOR-SD in a streptozotocin-induced diabetic mouse model. Delivered via intravitreal injection, the therapeutic efficacy of the virus vector upon early DR processes was examined. rAAV2-shmTOR-SD effectively transduced mouse retinas and therein downregulated mTOR expression, which was elevated in sham-treated and control shRNA-injected (rAAV2-shCon-SD) control groups. mTOR inhibition additionally led to marked reductions in pericyte loss, acellular capillary formation, vascular permeability, and retinal cell layer thinning, processes that contribute to DR progression. Immunohistochemistry showed that rAAV2-shmTOR-SD decreased ganglion cell loss and pathogenic Müller cell activation and proliferation, while also having anti-apoptotic activity, with these effects suggesting the therapeutic virus vector may be neuroprotective. Taken together, these results build upon our previous work to demonstrate the broad ability of rAAV2-shmTOR-SD to address aspects of DR pathophysiology further evidencing its potential as a human gene therapeutic strategy for DR.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary ...syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population.
We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2–5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453.
Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 2·6% patients vs 39 2·9%; hazard ratio HR 0·90 95% CI 0·57–1·42; p=0·90) and neither did stroke (11 0·8% patients vs 12 0·9%; 0·92 0·41–2·08; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 1·8% patients vs ten 0·8%; 2·41 1·15–5·05; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 95% CI 0·68–3·35; p=0·32). The rate of BARC type 2–5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 95% CI 0·45–1·05; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis.
The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care.
Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.
Background In patients with ST-segment-elevation myocardial infarction, timely reperfusion therapy with door-to-balloon (D2B) time <90 minutes is recommended by the current guidelines. However, ...whether further shortening of symptom onset-to-door (O2D) time or D2B time would enhance survival of patients with ST-segment-elevation myocardial infarction remains unclear. Therefore, the current study aimed to evaluate the prognostic impact of O2D or D2B time in patients with ST-segment-elevation myocardial infarction who underwent primary percutaneous coronary intervention. Methods and Results We analyzed 5243 patients with ST-segment-elevation myocardial infarction were treated at 20 tertiary hospitals capable of primary percutaneous coronary intervention in Korea. The association between O2D or D2B time with all-cause mortality at 1 year was evaluated. The median O2D time was 2.0 hours, and the median D2B time was 59 minutes. A total of 92.2% of the total population showed D2B time ≤90 minutes. In univariable analysis, 1-hour delay of D2B time was associated with a 55% increased 1-year mortality, whereas 1-hour delay of O2D time was associated with a 4% increased 1-year mortality. In multivariable analysis, D2B time showed an independent association with mortality (adjusted hazard ratio, 1.90; 95% CI , 1.51-2.39; P<0.001). Reducing D2B time within 45 minutes showed further decreased risk of mortality compared with D2B time >90 minutes (adjusted hazard ratio, 0.30; 95% CI , 0.19-0.42; P<0.001). Every reduction of D2B time by 30 minutes showed continuous reduction of 1-year mortality (90 to 60 minutes: absolute risk reduction, 2.4%; number needed to treat, 41.9; 60 to 30 minutes: absolute risk reduction, 2.0%; number needed to treat, 49.2). Conclusions Shortening D2B time was significantly associated with survival benefit, and the survival benefit of shortening D2B time was consistently observed, even <60 to 90 minutes.
Zinc and apolipoprotein E (apoE) are reportedly involved in the pathology of Alzheimer's disease. To investigate the associative interaction among zinc, apoE, and amyloid-β (Aβ) and its role in ...amyloid pathogenesis, we performed various biochemical and immunoreactive analyses using brain tissues of Tg2576 mice and synthetic Aβ and apoE peptides. On amyloid plaques or in brain lysates of Tg2576 mice, apoE and Aβ immunoreactivities increased after zinc chelation and were restored by its subsequent replacement. Zinc depletion dissociated apoE/Aβ complexes or larger-molecular sizes of Aβ oligomers/aggregates into smaller-molecular sizes of apoE and/or Aβ monomers/complexes. In the presence of zinc, synthetic apoE and/or Aβ peptides aggregated into larger-molecular sizes of oligomers or complexes. Endogenous proteases or plasmin in brain lysates degraded apoE and/or Aβ complexes, and their proteolytic activity increased with zinc depletion. These biochemical findings suggest that zinc associates with apoE and Aβ to encourage the formation of apoE/Aβ complexes or large aggregates, raising the deposition of zinc-rich amyloid plaques. In turn, the presence of abundant zinc around and within apoE/Aβ complexes may block the access or activity of Aβ-degrading antibodies or proteases. These results support the plausibility of chelation strategy aiming at reducing amyloid pathology in Alzheimer's disease.
An ultrahigh sensitive capacitive pressure sensor based on a porous pyramid dielectric layer (PPDL) is reported. Compared to that of the conventional pyramid dielectric layer, the sensitivity was ...drastically increased to 44.5 kPa–1 in the pressure range <100 Pa, an unprecedented sensitivity for capacitive pressure sensors. The enhanced sensitivity is attributed to a lower compressive modulus and larger change in an effective dielectric constant under pressure. By placing the pressure sensors on islands of hard elastomer embedded in a soft elastomer substrate, the sensors exhibited insensitivity to strain. The pressure sensors were also nonresponsive to temperature. Finally, a contact resistance-based pressure sensor is also demonstrated by chemically grafting PPDL with a conductive polymer, which also showed drastically enhanced sensitivity.
The objectives of this study were to develop a real-time tillage depth measurement system for agricultural tractor performance analysis and then to validate these configured systems through soil ...non-penetration tests and field experiment during plow tillage. The real-time tillage depth measurement system was developed by using a sensor fusion method, consisting of a linear potentiometer, inclinometer, and optical distance sensor to measure the vertical penetration depth of the attached implement. In addition, a draft force measurement system was developed using six-component load cells, and an accuracy of 98.9% was verified through a static load test. As a result of the soil non-penetration tests, it was confirmed that sensor fusion type A, consisting of a linear potentiometer and inclinometer, was 6.34-11.76% more accurate than sensor fusion type B, consisting of an optical distance sensor and inclinometer. Therefore, sensor fusion type A was used during field testing as it was found to be more suitable for use in severe working environments. To verify the accuracy of the real-time tillage depth measurement system, a linear regression analysis was performed between the measured draft and the predicted values calculated using the American Society of Agricultural and Biological Engineers (ASABE) standards-based equation. Experimental data such as traveling speed and draft force showed that it was significantly affected by tillage depth, and the coefficient of determination value at M3-Low was 0.847, which is relatively higher than M3-High. In addition, the regression analysis of the integrated data showed an R-square value of 0.715, which is an improvement compared to the accuracy of the ASABE standard prediction formula. In conclusion, the effect of tillage depth on draft force of agricultural tractors during plow tillage was analyzed by the simultaneous operation of the proposed real-time tillage depth measurement system and draft force measurement system. In addition, system accuracy is higher than the predicted accuracy of ±40% based on the ASABE standard equation, which is considered to be useful for various agricultural machinery research fields. In future studies, real-time tillage depth measurement systems can be used in tractor power train design and to ensure component reliability, in accordance with agricultural working conditions, by predicting draft force and axle loads depending on the tillage depth during tillage operations.
Background:Although there is an increase in the use of mechanical circulatory support devices to rescue patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock ...(CS), the optimal timing of the application remains controversial. Therefore, this study aimed to compare the clinical outcomes between venoarterial-extracorporeal membrane oxygenation (VA-ECMO) insertion before and after coronary revascularization in AMI patients with refractory CS.Methods and Results:A total of 253 patients with AMI who underwent revascularization therapy with VA-ECMO were included. The study population was stratified into extracorporeal cardiopulmonary resuscitation (E-CPR) before revascularization (N=106, reference cohort) and refractory CS without E-CPR before revascularization (n=147, comparison cohort). Patients with refractory CS but without E-CPR before revascularization were further divided into VA-ECMO before revascularization (N=50) and VA-ECMO after revascularization (n=97). The primary endpoint was a composite of in-hospital mortality, left ventricular assist device implantation, and heart transplantation. The primary endpoint occurred in 60 patients (40.8%) of the comparison cohort and 51 patients (48.1%) of the reference cohort. Among the comparison cohort, the primary endpoint was significantly lower in VA-ECMO before revascularization than in VA-ECMO after revascularization (32.0% vs. 49.5%, OR 0.480, 95% CI 0.235–0.982, P=0.045). A similar trend was observed after a 1-year follow up.Conclusions:Early initiation of VA-ECMO before revascularization therapy might improve clinical outcomes in patients with AMI complicated by refractory CS.
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