Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice.

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.

Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.

Targeting Innate Immunity in Glioma Therapy.

Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a deeper understanding of the molecular and cellular mechanisms that cause resistance to immunotherapy. Further insights into the innate immune response are crucial for developing more potent treatments for brain tumors. Our review provides a brief overview of innate immunity. In addition, we provide a discussion of current therapies aimed at boosting the innate immunity in gliomas. These approaches encompass strategies to activate Toll-like receptors, induce stress responses, enhance the innate immune response, leverage interferon type-I therapy, therapeutic antibodies, immune checkpoint antibodies, natural killer (NK) cells, and oncolytic virotherapy, and manipulate the microbiome. Both preclinical and clinical studies indicate that a better understanding of the mechanisms governing the innate immune response in GBM could enhance immunotherapy and reinforce the effects of chemotherapy and radiotherapy. Consequently, a more comprehensive understanding of the innate immune response against cancer should lead to better prognoses and increased overall survival for GBM patients.

Evaluation of Commercial Corrosion Sensors for Real-Time Monitoring of Pipe Wall Thickness under Various Operational Conditions.

In this study, we investigated the performance and reliability of commercial corrosion sensors for monitoring the integrity of piping systems in various fluid environments as an alternative to ultrasonic transducers. To this end, we investigated pipes' wall-thinning using commercial electrical resistance (ER), linear polarization resistance (LPR), and ultrasonic transducer (UT) sensors under various operating environments. A pilot-scale closed-loop test bed was built to simulate a real pipeline flow situation, from which the sensor data were collected and analyzed. Experimental results indicate that, in the case of the LPR sensor, it is challenging to accurately measure the corrosion rate when a specific measure exceeds the threshold in a severe corrosion environment. In contrast, the ER sensor could measure metal loss under all conditions and reflect the corresponding characteristics. The metal loss (about 0.25 mm) of the real pipe after the experiment was confirmed to be equal to the metal loss (0.254 mm) measured by the sensor. Furthermore, the regression analysis revealed a high correlation between the results obtained from the ER and UT sensors. Thus, evaluating the remaining thickness of the piping system using the commercial ER sensor is deemed to be effective and reliable.

Atomic layer deposited Al2O3passivation layer for few-layer WS2field effect transistors.

We have investigated the effect of an Al2O3passivation layer on the performance of few-layer WS2FETs. While the performance of WS2FETs is often limited by a substantial decrease in carrier mobility owing to charged impurities and a Schottky barrier between the WS2and metal electrodes, the introduction of an Al2O3overlayer by atomic layer deposition (ALD) suppressed the influence of charged impurities by high-κdielectric screening effect and reduced the effective Schottky barrier height. We argue that n-doping of WS2, induced by positive fixed charges formed at Al2O3/WS2interface during the ALD process, is responsible for the reduction of the effective Schottky barrier height in the devices. In addition, the Al2O3passivation layer protected the device from oxidation, and maintained stable electrical performance of the WS2FETs over 57 d. Thus, the ALD of Al2O3overlayer provides a facile method to enhance the performance of WS2FETs and to ensure ambient stability.

Impact of PRECISE-DAPT and DAPT Scores on Dual Antiplatelet Therapy Duration After 2nd Generation Drug-Eluting Stent Implantation.

PURPOSE: Determining the optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an important clinical issue. We evaluated the effects of ischemia (by DAPT score) and bleeding (by PRECISE-DAPT score), as well as the impact of DAPT duration, on clinical outcomes. METHODS: From pooled analysis of four randomized clinical trials, 5131 patients undergoing second-generation DES implantation were randomized to short-duration (n = 2575; ≤ 6 months) or standard-duration (n = 2556; ≥ 12 months) DAPT groups. This population was further divided into four subgroups according to PRECISE-DAPT (high bleeding risk ≥ 25) and DAPT (high ischemic risk ≥ 2) scores. RESULTS: Net clinical outcomes (1.3% vs. 1.3%; p = 0.89) and ischemic events (5.0% vs. 4.5%; p = 0.44) did not differ between the two duration groups, although bleeding events were more frequent in patients with standard-duration DAPT (0.4% vs. 0.9%; p = 0.04). Standard-duration DAPT was associated with fewer ischemic events (6.9% vs. 4.0%; p = 0.02) and no increase in bleeding events only among patients at low bleeding risk and high ischemic risk. The other groups show no differences in net clinical outcomes, ischemic events, or bleeding events according to DAPT duration. CONCLUSION: Compared with short-duration DAPT, standard-duration DAPT was associated with similar net clinical outcomes and ischemic events, but more bleeding events at 12 months after second-generation DES implantation. However, standard-duration DAPT reduced ischemic events without increasing bleeding events among patients at low bleeding and high ischemic risk. When determining DAPT duration, considering both ischemic and bleeding risk can help optimize patient benefits. CLINICAL TRIAL REGISTRATION: EXCELLENT (NCT00698607), RESET (NCT01145079), IVUS-XPL (NCT01308281), OPTIMA-C (NCT03056118).

Design Study of a Round Window Piezoelectric Transducer for Active Middle Ear Implants.

This report describes the design of a new piezoelectric transducer for round window (RW)-driven middle ear implants. The transducer consists of a piezoelectric element, gold-coated copper bellows, silicone elastomer (polydimethylsiloxane, PDMS), metal cylinder (tungsten), and titanium housing. The piezoelectric element is fixed to the titanium housing and mechanical resonance is generated by the interaction of the bellows, PDMS, and tungsten cylinder. The dimensions of PDMS and the tungsten cylinder with output characteristics suitable for compensation of sensorineural hearing loss were derived by mechanical vibrational analysis (equivalent mechanical model and finite element analysis (FEA)). Based on the results of FEA, the RW piezoelectric transducer was implemented, and bench tests were performed under no-load conditions to confirm the output characteristics. The transducer generates an average displacement of 219.6 nm in the flat band (0.1-1 kHz); the resonance frequency is 2.3 kHz. To evaluate the output characteristics, the response was compared to that of an earlier transducer. When driven by the same voltage (6 Vp), the flat band displacement averaged 30 nm larger than that of the other transducer, and no anti-resonance was noted. Therefore, we expect that the new transducer can serve as an output device for hearing aids, and that it will improve speech recognition and treat high-frequency sensorineural hearing loss more effectively.

Newly designed Protein Transduction Domain (PTD)-mediated BMP-7 is a potential therapeutic for peritoneal fibrosis.

While the bone morphogenetic protein-7 (BMP-7) is a well-known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half-life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein-7 (BMP-7). This study aims at evaluating the therapeutic effects of PTD-BMP-7 consisted of PTD and full-length BMP-7 on epithelial-mesenchymal transition (EMT)-related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF-ß1 or TGF-ß1 + PTD-BMP-7. Peritoneal dialysis (PD) catheters were inserted into Sprague-Dawley rats, and these rats were infused intra-peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD-BMP-7. In vitro, TGF-ß1 treatment significantly increased fibronectin, type I collagen, α-SMA and Snail expression, while reducing E-cadherin expression in HPMCs (P < .001). PTD-BMP-7 treatment ameliorated TGF-ß1-induced fibronectin, type I collagen, α-SMA and Snail expression, and restored E-cadherin expression in HPMCs (P < .001). In vivo, the expressions of EMT-related molecules and the thickness of the sub-mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra-peritoneal administration of PTD-BMP-7. PTD-BMP-7 treatment significantly inhibited the progression of established PD fibrosis. These findings suggest that PTD-BMP-7, as a prodrug of BMP-7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.

Optimal Duration for Dual Antiplatelet Therapy After Left Main Coronary Artery Stenting.

BACKGROUND: Coronary interventions using drug-eluting stents (DESs) of left main coronary artery (LMCA) lesions have shown favorable clinical outcomes. However, duration of dual antiplatelet therapy (DAPT) after LMCA interventions has not yet been investigated.Methods and Results:From a multicenter Korean Multicenter Angioplasty Team (KOMATE) registry, 1,004 patients who received DES implantations for LMCA lesions and did not experience major adverse cardiovascular events (including major bleeding) for 1 year after coronary intervention were analyzed. Patients were divided into 2 groups; DAPT ≤12 (n=503) and >12 months (n=501). The primary endpoint was number of net clinical adverse events (NACEs), composite of cardiac deaths, myocardial infarctions, stent thrombosis and major bleeding events. During a 4.5-year follow-up period after LMCA interventions, the DAPT >12 months group showed a lower NACE rate than the DAPT ≤12 months group (adjusted-HR 0.53 [0.29-0.99], P=0.045). For patients who maintained DAPT >12 months, rate of cardiac deaths, myocardial infarctions, and stent thrombosis events were lower than in patients who had DAPT ≤12 months (adjusted-HR 0.35 [0.17-0.73], P=0.005) without increased major bleeding (P=0.402). CONCLUSIONS: For patients who can continue DAPT without major bleeding events, prolonged DAPT (>12 months) after LMCA stenting demonstrated better long-term efficacy outcomes than DAPT ≤12 months with comparable safety.

Efficacy and Safety of Guideline-Recommended Risk Score-Directed Dual Antiplatelet Therapy After 2nd-Generation Drug-Eluting Stents.

BACKGROUND: Evaluate the safety and efficacy of guideline-recommended risk score-directed dual antiplatelet therapy (GD-DAPT) based on THE PRECISE-DAPT score after 2nd-generation drug-eluting stent (DES) implantation.Methods and Results:We analyzed 5,131 patients pooled from 4 clinical trials. Patients were divided into 3 groups according to current recommendations on the duration of DAPT and their actual DAPT duration: GD-DAPT (n=2,183), shorter DAPT (n=1,540), longer DAPT (n=1,408). The primary endpoint was the rate of net adverse clinical events (NACE) during the first 12 months. The secondary endpoints were ischemic or bleeding events. Overall, GD-DAPT did not affect NACE (1.2% vs. 1.2% for shorter DAPT and 1.7% for longer DAPT) or bleeding events (0.6% vs. 0.5% and 0.9%), and there were fewer ischemic events (2.8% vs. 4.4% and 4.0%, P=0.03) than with shorter DAPT. Especially in acute coronary syndrome (ACS) patients, GD-DAPT had fewer NACE (1.5% vs. 1.4% and 4.2%; P=0.006) and bleeding events (0.8% vs. 0.5% and 2.8%; P=0.001) than longer DAPT as well as fewer ischemic events (2.8% vs. 4.4% and 4.7%; P=0.03) than shorter DAPT. CONCLUSIONS: GD-DAPT did not affect NACE or bleeding events and reduced the number of ischemic events at 12 months compared with shorter DAPT. For ACS, GD-DAPT was associated with favorable outcomes compared with non-GD-DAPT. Therefore, GD-DAPT may optimize efficacy and safety.

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial.

Importance: Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively evaluated in patients with acute coronary syndromes (ACS). Objective: To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents. Design, Setting, and Participants: A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019. Interventions: Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). Main Outcomes and Measures: The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. Results: Among 3056 patients who were randomized (mean age, 61 years; 628 women [20%]; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, -1.98% [95% CI, -3.50% to -0.45%]; hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.92]; P = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 [95% CI, 0.34 to 0.91]; P = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 [95% CI, 0.45 to 1.06]; P = .09). Conclusions and Relevance: Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02494895.

Randomized evaluation of ticagrelor monotherapy after 3-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with new-generation sirolimus-eluting stents: TICO trial rationale and design.

BACKGROUND: Ticagrelor monotherapy after short-term dual-antiplatelet therapy (DAPT) may optimize ischemic and bleeding risks, particularly for acute coronary syndrome (ACS) patients, because its strategy is less potent than ticagrelor-based DAPT but more potent than aspirin or clopidogrel monotherapy. METHODS: The TICO randomized open-label trial will evaluate whether ticagrelor monotherapy following 3-month DAPT is superior to 12-month ticagrelor-based DAPT in terms of net adverse clinical events (NACE) including efficacy and safety in ACS patients treated with ultrathin bioresorbable polymer sirolimus-eluting stents (BP-SES). Patients undergoing BP-SES implantation for ACS treatment will be randomized in a 1:1 fashion to the (1) ticagrelor monotherapy group after 3-month DAPT; or the (2) 12-month DAPT group. The primary endpoint is NACE within 12 months of percutaneous coronary intervention, which includes major adverse cardiac and cerebrovascular events (MACCE) plus major bleeding as defined by Thrombolysis in Myocardial Infarction. MACCE includes the composite of all-cause death, myocardial infarction, stent thrombosis, stroke, and target vessel revascularization. Secondary endpoints included each component of the primary endpoint. CONCLUSIONS: The TICO trial is an ongoing trial evaluating the efficacy and safety of ticagrelor monotherapy following 3-month DAPT exclusively in ACS patients treated with uniform BP-SES. It may provide novel insights regarding the need for adjusted use of DAPT for rebalancing risk-benefit in current practice and changing from the conventional concept of aspirin maintenance to a ticagrelor-based regimen in the management of ACS.

Two-year outcomes of statin therapy in patients with acute myocardial infarction with or without dyslipidemia after percutaneous coronary intervention in the era of new-generation drug-eluting stents within Korean population: Data from the Korea Acute Myocardial Infarction Registry.

BACKGROUND: Limited studies focused on long-term outcomes of statin therapy in patients with acute myocardial infarction (AMI) with or without dyslipidemia after percutaneous coronary intervention (PCI) in the era of new-generation drug-eluting stents (DES). We thought to investigate 2-year clinical outcomes of statin therapy in these patients. METHODS: A total of 18,137 eligible AMI patients (from the Korea AMI Registry [KAMIR]) were finally enrolled and divided into four groups according to the presence or absence of dyslipidemia and statin therapy (dyslipidemia+/statin- [group A, 309 patients], dyslipidemia+/statin+ [group B, 2094 patients], dyslipidemia-/statin- [group C, 672 patients], dyslipidemia-/statin+ [group D, 15062 patients]). The primary outcome was major adverse cardiac event (MACE) defined as all-cause death, myocardial infarction (MI) and revascularization. RESULTS: During the 2-year follow-up period, the cumulative incidence of MACE in the group A was higher than the group B (adjusted hazard ratio [HR], 2.207; 95% confidence interval (CI), 1.098-3.743; p = .024) and the group D (adjusted HR, 2.110; 95% CI, 1.240-3.593, p = .006). This significantly increased incidence of MACE caused by the higher cumulative incidences of all-cause death and cardiac death (CD) in the group A compared with groups B and D. However, the cumulative incidences of MI and revascularization were not significantly different among these four groups. CONCLUSION: Statin therapy demonstrated significantly reduced incidences of MACE, all-cause death and CD compared with non-users after PCI in AMI patients with or without dyslipidemia during 2-year follow-up period in the era of new-generation DES.

Comparison Between Beta-Blockers with Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers with Angiotensin II Type I Receptor Blockers in ST-Segment Elevation Myocardial Infarction After Successful Percutaneous Coronary Intervention with Drug-Eluting Stents.

BACKGROUND/AIMS: Limited comparative data concerning long-term clinical outcomes of combination therapy between beta-blockers (BB) with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) therapy in patients with ST-segment elevation myocardial infarction (STEMI) are available. We thought to compare 2-year major clinical outcomes between BB with ACEI and BB with ARB therapy in patients with STEMI after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: 13,873 STEMI patients who underwent successful PCI with DES were enrolled and divided into two groups as the BB with ACEI group (n = 10,393) and the BB with ARB group (n = 3480). The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, cardiac death (CD), recurrent myocardial infarction (re-MI), total coronary revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], non-TVR) during the 2-year follow-up period. RESULTS: After propensity score-matched (PSM) analysis, two PSM groups (3296 pairs, n = 6592, C-statistic = 0.675) were generated. Although the incidences of re-MI, TLR, and TVR were similar, the incidences of MACE (8.3% vs. 6.8%, log-rank p = 0.038, hazard ratio [HR] 1.210, 95% confidence interval [CI] 1.010-1.451, p = 0.039), all-cause death, CD, total revascularization, and non-TVR of the BB with ARB group were significantly higher than the BB with ACEI group after PSM. In addition, diabetes and multivessel disease were significant predictors for non-TVR. CONCLUSIONS: The combination BB with ACEI may be beneficial for reducing MACE in STEMI patients after successful PCI with DES than the BB with ARB.

Two-year clinical outcomes of zotarolimus- and everolimus-eluting durable-polymer-coated stents versus biolimus-eluting biodegradable-polymer-coated stent in patients with acute myocardial infarction with dyslipidemia after percutaneous coronary intervention: data from the KAMIR.

There are limited data comparing the clinical outcomes among new-generation drug-eluting stents (DES) in acute myocardial infarction (AMI) patients with dyslipidemia after percutaneous coronary intervention (PCI). We thought to investigate 2-year clinical outcomes among durable-polymer (DP)-coated stents [zotarolimus eluting (ZES) and everolimus eluting (EES)] and biodegradable-polymer (BP)-coated biolimus-eluting stent (BES) in dyslipidemic AMI patients after PCI. Finally, a total 2403 enrolled patients were divided into ZES (n = 953), EES (n = 1145) or BES (n = 305) group. The primary endpoint was major adverse cardiac events (MACE) defined as total death (TD), cardiac death (CD), myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and non-TVR. The secondary endpoint was the incidence of definite or probable stent thrombosis (ST). The 2-year adjusted hazard ratio (HR) of MACE for ZES vs. EES [HR, 1.066; 95% confidence interval (CI) 0.752-1.511; p = 0.720], ZES vs. BES (HR 0.933; 95% CI 0.565-1.541; p = 0.786), EES vs. BES (HR 1.876; 95% CI 0.535-1.436; p = 0.600) and ZES/EES vs. BES (HR 0.929; 95% CI 0.591-1.462; p = 0.751) was similar. The cumulative incidences of ST were comparable (ZES vs. EES vs. BES = 1.1% vs. 0.9% vs. 1.1%, p = 0.675) and adjusted HR was not different. In addition, the 2-year adjusted HR of TD, CD, MI, TLR, TVR, and non-TVR was similar. The AMI patients with dyslipidemia receiving ZES, EES, or BES after PCI showed comparable safety and efficacy during 2-year follow-up periods. Therefore, DP-DES or BP-DES is equally acceptable in dyslipidemic AMI patients during PCI.

Risk Factors for Restenosis after Drug-coated Balloon Angioplasty for Complex Femoropopliteal Arterial Occlusive Disease.

BACKGROUND: Currently, there exist limited data on patient outcomes following the use of drug-coated balloons (DCBs) to treat complex femoropopliteal arterial occlusive lesions. The aim of the this study is to investigate the outcomes of patient treated with DCBs and to identify the predictors of restenosis. METHODS: We retrospectively investigated medical records from 120 patients (137 limbs) treated with DCBs for femoropopliteal lesions at a single center between 2013 and 2016. Primary patency, target lesion revascularization (TLR), and risk factors of restenosis were analyzed. RESULTS: There were 80 de novo and 57 in-stent restenosis lesions. Mean lesion length was 22.2 ± 11.6 cm. The clinical primary patency was 85.2% at 1 year and 65.3% after 2 years. The TLR-free survival rate was 93.0% at 1 year and 87.1% after 2 years. Critical limb ischemia (CLI; hazard ratio [HR] 5.80, 95% confidence interval [CI] 1.26-26.68, P = 0.024) and hypercholesterolemia (HR 4.66, 95% CI 1.30-16.76, P = 0.018) were identified as independent predictors of restenosis. In addition, nonuse of cilostazol and popliteal artery involvement showed trends toward an increased risk of restenosis. CONCLUSIONS: Treatment with DCBs showed excellent primary patency and TLR-free survival at 1 year after the procedure. However, the primary patency continuously deteriorated beyond 1 year, suggesting a late catch-up phenomenon. The risk of restenosis after treatment with DCBs was significantly associated with CLI and hypercholesterolemia.

A Vibro-Acoustic Hybrid Implantable Microphone for Middle Ear Hearing Aids and Cochlear Implants.

To develop totally implantable middle ear and cochlear implants, a miniature microphone that is surgically easy to implant and has a high sensitivity in a sufficient range of audio frequencies is needed. Of the various implantable acoustic sensors under development, only micro electro-mechanical system-type acoustic sensors, which attach to the umbo of the tympanic membrane, meet these requirements. We describe a new vibro-acoustic hybrid implantable microphone (VAHIM) that combines acceleration and sound pressure sensors. Each sensor can collect the vibration of the umbo and sound pressure of the middle ear cavity. The fabricated sensor was implanted into a human temporal bone and the noise level and sensitivity were measured. From the experimental results, it is shown that the proposed method is able to provide a wider-frequency band than conventional implantable acoustic sensors.

Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease.

OBJECTIVE: Buerger disease is a rare inflammatory vasculopathy presenting with severe claudication or critical limb ischemia. In this study, we sought to evaluate the feasibility and clinical outcomes of endovascular therapy for Buerger disease involving arteries in the lower extremities. METHODS: Between January 2006 and May 2016, there were 44 Buerger disease patients (43 men; mean age, 40.4 ± 9.6 years) with 50 target limbs treated by endovascular therapy at the Severance Cardiovascular Hospital. Baseline characteristics as well as both immediate and late clinical outcomes were retrospectively analyzed. RESULTS: The majority (86.4%) of patients presented with critical limb ischemia. A total of 88 target lesions in 50 limbs were treated with endovascular procedures. All limbs showed infrapopliteal artery occlusions, and multilevel diseases involving the iliac or femoropopliteal artery were found in 31 patients (62%). Technical success was achieved in 80% of subjects. We found that a lower serum level of C-reactive protein, specifically the log C-reactive protein value (odds ratio, 0.03; 95% confidence interval [CI], 0.00-0.71; P = .030), was an independent predictor of technical failure. The median follow-up duration was 29 months. Major adverse limb event-free survival and reintervention- and amputation-free survival were 83.3% and 67.9% at 3 years, respectively. In a multivariate Cox proportional hazards analysis, previous endovascular treatment (hazard ratio, 3.70; 95% CI, 1.20-11.31; P = .022) and previous amputation (hazard ratio, 4.68; 95% CI, 1.37-15.96; P = .014) were identified as independent risk factors for reintervention- and amputation-free survival. CONCLUSIONS: In patients with Buerger disease, endovascular treatment achieved technical success in the majority of the cases and was associated with favorable immediate and late clinical outcomes. These findings indicate that endovascular therapy may be considered a first-line treatment option for severe symptomatic patients with Buerger disease.

Piezoelectric Actuator with Frequency Characteristics for a Middle-Ear Implant.

The design and implementation of a novel piezoelectric-based actuator for an implantable middle-ear hearing aid is described in this paper. The proposed actuator has excellent low-frequency output characteristics, and can generate high output in a specific frequency band by adjusting the mechanical resonance. The actuator consists of a piezoelectric element, a miniature bellows, a cantilever membrane, a metal ring support, a ceramic tip, and titanium housing. The optimal structure of the cantilever-membrane design, which determines the frequency characteristics of the piezoelectric actuator, was derived through finite element analysis. Based on the results, the piezoelectric actuator was implemented, and its performance was verified through a cadaveric experiment. It was confirmed that the proposed actuator provides better performance than currently used actuators, in terms of frequency characteristics.

Development of limited-view and three-dimensional reconstruction method for analysis of electrohydrodynamic jetting behavior.

For an electrohydrodynamic (EHD) jet, variables such as the direction of the meniscus and the ejection stability need to be analyzed. Thus, the EHD jet should be observed three-dimensionally (3D) because the variables can only be obtained in the 3D field, especially in unstable modes. However, if the 3D field is reconstructed from multi-directional binary images, eliminating reconstruction errors caused by invisible areas is almost impossible, even when using a tomographic technique. To solve this problem, a new 3D reconstruction method including an ellipse estimation was developed in this study. The method was verified by numerical simulation and applied to estimate the jetting flow rate and the direction of an ethanol droplet ejected from a nozzle according to a voltage.