Drug delivery systems for wound healing treatment of upper airway injury.

INTRODUCTION: Endotracheal intubation is a common procedure to maintain an open airway with risks for traumatic injury. Pathological changes resulting from intubation can cause upper airway complications, including vocal fold scarring, laryngotracheal stenosis, and granulomas and present with symptoms such as dysphonia, dysphagia, and dyspnea. Current intubation-related laryngotracheal injury treatment approaches lack standardized guidelines, relying on individual clinician experience, and surgical and medical interventions have limitations and carry risks. AREAS COVERED: The clinical and preclinical therapeutics for wound healing in the upper airway are described. This review discusses the current developments on local drug delivery systems in the upper airway utilizing particle-based delivery systems, including nanoparticles and microparticles, and bulk-based delivery systems, encompassing hydrogels and polymer-based approaches. EXPERT OPINION: Complex laryngotracheal diseases pose challenges for effective treatment, struggling due to the intricate anatomy, limited access, and recurrence. Symptomatic management often requires invasive surgical procedures or medications that are unable to achieve lasting effects. Recent advances in nanotechnology and biocompatible materials provide potential solutions, enabling precise drug delivery, personalization, and extended treatment efficacy. Combining these technologies could lead to groundbreaking treatments for upper airways diseases, significantly improving patients' quality of life. Research and innovation in this field are crucial for further advancements.

The Effects of ROCK Inhibitor on Prevention of Dexamethasone-Induced Glaucoma Phenotype in Human Trabecular Meshwork Cells.

Purpose: This study investigated the effects of dexamethasone (Dex) on human trabecular meshwork (TM) cells, a model of glucocorticoid-induced glaucoma, and evaluated the impact of ripasudil (Rip) as a co-delivery or sequential dosing strategy. Methods: In vitro experiments were conducted to assess the effects of Dex and Rip on TM cells. Confocal microscopy was used to evaluate the impact of Dex and Rip on F-actin staining signals. Contractility of the TM cells upon Dex and Rip treatment mimicking co-delivery and sequential delivery was quantified using collagen gel contraction assay. Transepithelial electrical resistance (TEER) values and fluorescein isothiocyanate (FITC)-dextran permeability were also measured to assess the impact of Dex and Rip on TM cells. Results: Dex and Rip did not exhibit cytotoxicity at the maximum tested concentration (20 µM). Dex-treated TM cells exhibited higher F-actin staining signals compared to controls, which were reduced when co-treated with Rip. Rip inhibited Dex-induced collagen gel contraction activity in both co-delivery and sequential treatments. Dex resulted in increased TEER values as the dose increased, whereas TEER values were maintained when co-treated with Rip. Conclusions: Co-delivery of Rip has the potential to prevent glaucoma symptoms when patients are treated with Dex. This study highlights the importance of identifying strategies to reduce the side effects of prolonged use of glucocorticoids, such as Dex, in the treatment of various diseases. Translational Relevance: This study demonstrates the potential of co-delivering ripasudil with dexamethasone to mitigate glucocorticoid-induced ocular hypertension and a secondary glaucoma that resembles primary open-angle glaucoma, providing insights for the development of novel preventive strategies in clinical care.

Janus USPION modular platform (JUMP) for theranostic ultrasound-mediated targeted intratumoral microvascular imaging and DNA/miRNA delivery.

Rationale: High mortality in pancreatic cancer (PDAC) and triple negative breast cancer (TNBC) highlight the need to capitalize on nanoscale-design advantages for multifunctional diagnostics and therapies. DNA/RNA-therapies can provide potential breakthroughs, however, to date, there is no FDA-approved systemic delivery system to solid tumors. Methods: Here, we report a Janus-nanoparticle (jNP)-system with modular targeting, payload-delivery, and targeted-imaging capabilities. Our jNP-system consists of 10 nm ultrasmall superparamagnetic iron oxide nanoparticles (USPION) with opposing antibody-targeting and DNA/RNA payload-protecting faces, directionally self-assembled with commercially available zwitterionic microbubbles (MBs) and DNA/RNA payloads. Results: Sonoporation of targeted jNP-payload-MBs delivers functional reporter-DNA imparting tumor-fluorescence, and micro-RNA126 reducing non-druggable KRAS in PDAC-Panc1 and TNBC-MB231 xenografted tumors. The targeting jNP-system enhances ultrasound-imaging of intra-tumoral microvasculature using less MBs/body weight (BW). The jNP-design enhances USPION's T2*-magnetic resonance (MR) and MR-imaging of PDAC-peritoneal metastases using less Fe/BW. Conclusion: Altogether, data advance the asymmetric jNP-design as a potential theranostic Janus-USPION Modular Platform - a JUMP forward.

Application of Nanoparticles: Diagnosis, Therapeutics, and Delivery of Insulin/Anti-Diabetic Drugs to Enhance the Therapeutic Efficacy of Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic metabolic disorder of carbohydrates, lipids, and proteins due to a deficiency of insulin secretion or failure to respond to insulin secreted from pancreatic cells, which leads to high blood glucose levels. DM is one of the top four noncommunicable diseases and causes of death worldwide. Even though great achievements were made in the management and treatment of DM, there are still certain limitations, mainly related to the early diagnosis, and lack of appropriate delivery of insulin and other anti-diabetic agents. Nanotechnology is an emerging field in the area of nanomedicine and NP based anti-diabetic agent delivery is reported to enhance efficacy by increasing bioavailability and target site accumulation. Moreover, theranostic NPs can be used as diagnostic tools for the early detection and prevention of diseases owing to their unique biological, physiochemical, and magnetic properties. NPs have been synthesized from a variety of organic and inorganic materials including polysaccharides, dendrimers, proteins, lipids, DNA, carbon nanotubes, quantum dots, and mesoporous materials within the nanoscale size. This review focuses on the role of NPs, derived from organic and inorganic materials, in the diagnosis and treatment of DM.

Long-Term Antibody Release Polycaprolactone Capsule and the Release Kinetics in Natural and Accelerated Degradation.

Although therapy using monoclonal antibodies (mAbs) has been steadily successful over the last 20 years, the means of delivery of mAbs has not been optimized, especially for long-term delivery. Frequent injections or infusions have been the current standard of care. In this study, we have developed a long-term antibody biodegradable implant using a porous polycaprolactone (PCL) capsule. It released bevacizumab (Bev) slowly for 8 months to date. The Bev release kinetics fit a drug release model with experimental data of the diffusion coefficient and partition coefficient through the polymer capsule. Since screening drug release profiles for the long term (>6 months) is time consuming, an accelerated degradation method was used after validating the characteristics of the PCL capsule in natural and accelerated degradation conditions. The correlation of the time period between natural and accelerated degradation was determined. Overall, the study suggests that mAbs can be released from a porous PCL capsule without an effect of the polymer degradation over a long period (∼6 months) and the long-term release kinetics can be determined by the accelerated degradation within 14 days.

Repetitive drug delivery using Light-Activated liposomes for potential antimicrobial therapies.

Overuse or misuse of antibiotics and their residues in the environment results in the emergence and prevalence of drug-resistant bacteria and leads to serious health problems. Notable progress in liposome research has been made in drug delivery and several liposomal drugs have been approved for clinical use owing to its biocompatibility and improved efficacy. Recently, liposomes have been engineered further to release encapsulated drugs on the target of interest in a dose-controlled fashion in response to external stimuli such as light, pH, and heat. Among those, light-activated liposomal drug delivery gained a lot of attention because drug release at the targeted sites can be precisely controlled by varying laser/light duration, energy and beam area. We envision potential applications of the light-activated liposomal delivery systems for effective drug-resistant antimicrobial therapies. The use of light-activated liposomes will be widely spread in antimicrobial therapies if the amount of drug is precisely controlled for a prolonged time at a target location. In this review, we discussed the breadth and depth of various light-activated liposomal drug delivery technology. Emphasis was given to repetitive release mechanism and applications of light-activated liposomes because the repeatability provides stability and precise control of the drug delivery system to prevent overdose of antimicrobials and treat with minimal doses. We described limitations on translation from pre-clinical to clinical settings and strategies to overcome the limitations. Careful consideration of light-responsive materials, lipid composition, laser parameters and laser safety is important when selecting and designing the drug delivery system for successful applications.

Effect of Cholesterol on Nano-Structural Alteration of Light-Activatable Liposomes via Laser Irradiation: Small Angle Neutron Scattering Study.

Although the light-activated liposomes have been extensively studied for drug delivery applications, the fundamental mechanism of the drug release based on lipid compositions has not been fully understood. Especially, despite the extensive use of cholesterol in the lipid composition, the role of cholesterol in the light-activated drug release has not been studied. In this study, the influence of cholesterol on drug release from light-responsive drug-encapsulated liposomes after activated by near infrared (NIR) laser was investigated. We prepared methotrexate (MTX)-encapsulated DSPC liposomes consisting of 0 mol% (-Chol) or 35 mol% cholesterol (+Chol), with (+Au) or without gold nanorods (-Au) on the lipid bilayer to compare drug release, morphological changes, and nanostructures after laser irradiations. Transmission electron microscopy (TEM) and small angel neutron scattering (SANS) data revealed that only +Chol +Au liposomes showed partial aggregation of the liposomes after laser irradiation. Similar trends on the drug release and structural change were observed when the liposomes were heated to above chain-transition temperature. Overall, we have found that (1) inclusion of 35 mol% cholesterol enhanced the permeability of lipid bilayers above Tc; (2) the mechanism of laser-activated liposomal drug delivery is disrupting lipid bilayer membranes by the photothermal effect in the presence of plasmonic materials. By understanding the fundamentals of the technology, precise controlled drug release at a targeted site with great stability and repeatability is anticipated.

Increased Cardiac Arrhythmia After Pregnancy-Induced Hypertension: A South Korean Nationwide Database Study.

Background Although pregnancy-induced hypertension (PIH) is associated with an elevated cardiovascular risk, long-term studies or prepregnancy baseline data are scarce. Therefore, using a large nationwide cohort with prepregnancy periodic health screening data, we investigated whether clinically significant arrhythmia incidence increases after PIH. Methods and Results Data were extracted from the Korea National Health Insurance database and combined with the National Health Screening Examination database; women who gave birth between 2007 and 2015 and underwent the national health screening test within a year before pregnancy were followed up until 2016. We excluded women who had a diagnosis of arrhythmia within 1 year before pregnancy. The primary outcome was significant arrhythmia during the year after delivery. Secondary analysis included only specific diagnostic codes of arrhythmia with clinical significance. Additionally, the risk of arrhythmia was stratified by the use of magnesium sulfate. Of 2 035 684 women (PIH; n=37 297 versus normotensive pregnancy; n=1 998 387), the PIH group had a higher prepregnancy risk profile and showed a higher incidence of arrhythmia than women with normotensive pregnancies within 1 year. Women with PIH had a significantly higher risk of atrial flutter/fibrillation and atrioventricular block, but not lethal arrhythmias. Other predictors of arrhythmia development included advanced maternal age and cesarean section. Stratified analysis showed a higher risk of arrhythmia with magnesium sulfate use. Conclusions PIH was significantly associated with the development of arrhythmia within 1 year after delivery. Nevertheless, the incidence of lethal arrhythmias was not increased by PIH. Arrhythmia, especially atrial fibrillation, may largely contribute to increasing the future cardiovascular risk in women with a PIH history.

Clinical outcome in patients with end-stage heart failure who underwent continuous-flow left ventricular assist devices in a single center.

BACKGROUND/AIMS: The continuous flow left ventricular assist device (cf-LVAD) has improved the survival of chronic end-stage heart failure (HF) patients. Here we describe our clinical experience of the initial 50 LVAD patients from a single center. METHODS: A total of 50 patients underwent LVAD implantation as bridge to transplantation (BTT; n = 28, 56%), bridge to candidacy (BTC; n = 2, 4%), or as destination therapy (DT; n = 20, 40%) from 2012 to 2019. Pre-implant characteristics and clinical outcomes were compared between BTT/BTC and DT. RESULTS: The median age of patients was 67 years (range, 59 to 73). Men were more likely to receive LVAD (76% vs. 24%) than women. DT patients were older, had smaller body surface area, and worse laboratory profiles than BTT/BTC patients. There was no in-hospital mortality. During an average of 14 months (range, 8 to 23), the all-cause mortality was 22%. The first-year survival was 86 and 90% in BTT/BTC and DT groups, respectively. Hemorrhagic stroke was the most common cause (27%) of death. In the BTT/BTC group, 22 patients successfully underwent heart transplantation during median duration of 10 months (range, 7 to 14). The most common post-LVAD complication during the first year of LVAD implantation was major bleeding (44%). A significant proportion (76%) of patients experienced rehospitalization with gastrointestinal bleeding as the most common cause. CONCLUSION: We describe short-term clinical outcome of LVAD patients from a single center for the first time in Korea. With the newer generation LVAD and a dedicated team approach, improved clinical outcomes of LVAD for end-stage HF are expected.

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation.

BACKGROUND: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. METHODS: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. RESULTS: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04-1.34], P=0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6-65.7], P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P<0.001; net reclassification index 1.05, P<0.001; integrated discrimination index 0.20, P<0.001). CONCLUSIONS: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02798731.

Repetitive drug releases from light-activatable micron-sized liposomes.

In this work, a novel light activatable micron-sized liposomal drug carrier that has a unique capability to release drug repetitively in proportion to the cycle number of short irradiation (5 s) of near-infrared (NIR) pulsed laser is reported. We synthesized methotrexate (MTX)-loaded liposomes based on a modified reverse-phase evaporation method. Gold nanorods (AuNR) were attached to the liposomal surfaces, enabling the liposomes to release drug under short NIR irradiation via the photothermal effect. The concentrations of methotrexate (MTX) released from the liposomes were 10.6, 29.8, 43.7 and 65.9 µg/mL after one, two, three or four NIR laser cycles (1.1 W at 1064 nm, 5 s per cycle), respectively. The current finding will provide possible solution to the previously reported inconsistency in drug release from light activatable liposomal drug carriers at each activation cycle. The repeatability of drug release described in this work is believed to be due to reversible nature of the liposomes. The liposomes release drug via lipid bilayer melting when irradiated by laser due to gold nanorods' plasmonic heat on the lipid bilayer surface and quickly regain their original structure once the laser source is removed. We provided evidence of the reversible liposomal structures by monitoring the change of number densities of liposomes using a microelectrode sensor with different laser irradiation durations and powers. We also assessed the micron-sized liposome with respect to long-term stability, drug encapsulation efficiency, and drug-releasing efficiency, demonstrating the possibility of utilizing these liposomes as long-term drug delivery vehicles for various drugs.

Prognostic Implication of RV Coupling to Pulmonary Circulation for Successful Weaning From Extracorporeal Membrane Oxygenation.

OBJECTIVES: The aim of this study was to explore if right ventricular (RV) contractile function and its coupling to pulmonary circulation (PC) were associated with successful weaning from venoarterial-extracorporeal membrane oxygenation (VA-ECMO) at maintenance of pump flow. BACKGROUND: Limited data are available on predictors of successful weaning from VA-ECMO. METHODS: A total of 79 patients with cardiogenic shock underwent transthoracic echocardiography to evaluate weaning from ECMO and were prospectively enrolled between 2016 and 2019. The noninvasively measured RV-PC coupling index was acquired by indexing tricuspid annular S' velocity, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and RV free-wall longitudinal strain (FWLS) to right ventricular systolic pressure (RVSP). RESULTS: Transthoracic echocardiography was performed at a median 3.0 days (range 1 to 6 days) after ECMO initiation at a median ECMO flow of 3.2 l/min (range 3.0 to 3.6 l/min). The RV-PC coupling matrix, tricuspid annular S'/RVSP, TAPSE/RVSP, and RV FWLS/RVSP exhibited satisfactory predictive performances for predicting successful weaning from ECMO. Using the best cutoff values derived from the area under the receiver-operator characteristic curve, tricuspid annular S'/RVSP demonstrated a significantly better predictive performance than conventional echocardiographic parameters (left ventricular ejection fraction >20%, left ventricular outflow tract time-velocity integral ≥10 cm, and mitral annular S' ≥6 cm/s). CONCLUSIONS: Echocardiographic RV-PC coupling metrics exhibited a significantly better performance for predicting successful weaning from VA ECMO compared with conventional echocardiographic criteria at maintenance of pump flow.

New onset diabetes mellitus and cardiovascular events in Korean patients with acute myocardial infarction receiving high-intensity statins.

BACKGROUND: High-intensity statin therapy is typically used in patients with acute myocardial infarction (AMI) for secondary prevention. However, there have been consistent concerns regarding its association with diabetes mellitus. We investigated the effect of high-intensity atorvastatin and rosuvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes over a 3-year follow-up period. METHODS: Data from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 patients with AMI were enrolled from major cardiovascular centers. Among them, 2221 patients without diabetes who had been administered with high-intensity atorvastatin (40-80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were evaluated for the incidence of NODM and major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization cases in the following 3 years. RESULTS: Baseline characteristics were comparable between the two groups. Event-free survival rate of NODM was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank P-value = 0.662). Multivariate Cox analysis revealed that statin type was not a prognostic factor in the development of NODM and MACE. CONCLUSIONS: Administering high-intensity atorvastatin and rosuvastatin in patients with AMI produced comparable effects on NODM and clinical outcomes, suggesting their clinical equivalence in secondary prevention.

Laser-Activated Drug Implant for Controlled Release to the Posterior Segment of the Eye.

To treat chronic posterior eye diseases, frequent intravitreal injections or sustained-release drug implants are the current standard of care. Sustained-release drug implants often involve burst release of the drugs and the dosage from the implants cannot be controlled after implantation, which may lead to local side effects. The present study attempts to develop a dosage-controllable drug delivery implant that consists of a nanoporous biodegradable PLGA capsule and light-activated liposomes. Controllable drug release from the implant was achieved using a pulsed near-infrared (NIR) laser both in vitro and in vivo. The in vitro drug release kinetics from two different initial dose implants, 1000 and 500 µg, was analyzed by fitting zero-order and first-order kinetics, as well as the Korsmeyer-Peppas and Higuchi models. The 1000 and 500 µg implants fit the first-order and zero-order kinetics model, respectively, the best. The multiple drug releases in the vitreous were determined by an in vivo fluorimeter, which was consistent with the in vitro data. The dose released was also clinically relevant. Histology and optical and ultrasound imaging data showed no abnormality in the eyes received implant treatment, suggesting that the drug delivery system was safe to the retina. This on-demand dose-controllable drug delivery system could be potentially used for long-term posterior eye disease treatment to avoid frequent invasive injections.

Impact of Catheter Ablation on Sleep Quality and Relationship Between Sleep Stability and Recurrence of Paroxysmal Atrial Fibrillation After Successful Ablation: 24-Hour Holter-Based Cardiopulmonary Coupling Analysis.

Background Sleep fragmentation and sleep apnea are common in patients with atrial fibrillation (AF). We investigated the impact of radio-frequency catheter ablation (RFCA) on sleep quality in patients with paroxysmal AF and the effect of a change in sleep quality on recurrence of AF. Methods and Results Of 445 patients who underwent RFCA for paroxysmal AF between October 2007 and January 2017, we analyzed 225 patients who had a 24-hour Holter test within 6 months before RFCA. Sleep quality was assessed by cardiopulmonary coupling analysis using 24-hour Holter data. We compared cardiopulmonary coupling parameters (high-frequency coupling, low-frequency coupling, very-low-frequency coupling) before and after RFCA. Six months after RFCA, the high-frequency coupling (marker of stable sleep) and very-low-frequency coupling (rapid eye movement/wake marker) was significantly increased (29.84%-36.15%; P<0.001; and 26.20%-28.76%; P=0.002, respectively) while low-frequency coupling (unstable sleep marker) was decreased (41.25%-32.13%; P<0.001). We divided patients into 3 tertiles according to sleep quality before RFCA, and the risk of AF recurrence in each group was compared. The second tertile was used as a reference; patients with unstable sleep (Tertile 3) had a significantly lower risk of AF recurrence (hazard ratio [HR], 0.32; 95% CI, 0.12-0.83 for high-frequency coupling; and HR, 0.22; 95% CI, 0.09-0.58 for low-frequency coupling). Conclusions Sleep quality improved after RFCA in patients with paroxysmal AF. The recurrence rate was significantly lower in patients who had unstable sleep before RFCA. These results suggest that RFCA can influence sleep quality, and sleep quality assessment before RFCA may provide a risk marker for recurrence after RFCA in patients with paroxysmal AF.

Cardiovascular and Bleeding Risks Associated With Nonsteroidal Anti-Inflammatory Drugs After Myocardial Infarction.

BACKGROUND: Limited data are available regarding the risk for adverse clinical events with concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment after myocardial infarction (MI). OBJECTIVES: The aim of this study was to investigate the risk for cardiovascular and bleeding events according to groups of antithrombotic medications and subtypes of NSAIDs in patients with MI. METHODS: This was a nationwide cohort study to enroll a study population from the Health Insurance Review and Assessment Service database in Korea between 2009 and 2013. Patients were divided into groups on the basis of the prescribed antithrombotic medications. The primary and secondary outcomes were thromboembolic cardiovascular and clinically relevant bleeding events. The risk for adverse clinical events was assessed by ongoing NSAID treatment and subtypes of NSAIDs. RESULTS: In total, 108,232 patients (mean age 64.2 ± 12.8 years, 72.1% men, mean follow-up duration 2.3 ± 1.8 years) with first diagnosed MI were enrolled. Concomitant NSAID treatment significantly increased the risk for cardiovascular events (hazard ratio [HR]: 6.96; 95% confidence interval [CI]: 6.24 to 6.77; p < 0.001) and bleeding events (HR: 4.08; 95% CI: 3.51 to 4.73; p < 0.001) compared with no NSAID treatment. Among NSAID subtypes, the risk for cardiovascular and bleeding events was lowest with the use of celecoxib (HR: 4.65; 95% CI: 3.17 to 6.82; p < 0.001, and 3.44; 95% CI: 2.20 to 5.39; p < 0.001, respectively) and meloxicam (HR: 3.03; 95% CI: 1.68 to 5.47; p < 0.001, and 2.80; 95% CI: 1.40 to 5.60; p < 0.001, respectively). CONCLUSIONS: Concomitant NSAID treatment significantly increased the risk for cardiovascular and bleeding events after MI. Although NSAID treatment should be avoided after MI, celecoxib and meloxicam could be considered as alternative options in cases in which NSAID use is unavoidable.

Comparison of the Major Clinical Outcomes for the Use of Endeavor® and Resolute Integrity® Zotarolimus-Eluting Stents During a Three-Year Follow-up.

Background: Endeavor®-zotarolimus-eluting stent (E-ZES) was the first ZES to be developed, and Resolute integrity®-ZES (I-ZES) has been developed more recently. Comparative studies on long-term usage of these two ZESs have been rare. Objectives: The aim of this study was to compare the efficacy and safety of E-ZES and I-ZES during a long-term follow-up of patients who underwent percutaneous coronary intervention (PCI). Methods: A total of 767 patients who underwent PCI with E-ZES or I-ZES were eligible for this study. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any repeat revascularization. The secondary endpoint was stent thrombosis (ST). Results: After propensity score-matched (PSM) analysis, two PSM groups (193 pairs, n = 386, C-statistic = 0.824) were generated. During the 3-year follow-up period, the cumulative incidence of MACEs (hazard ratio [HR], 0.837; 95% confidence interval [CI], 0.464-1.508; p = 0.553) and ST (HR, 0.398; 95% CI, 0.077-2.052; p = 0.271) was similar for the E-ZES and I-ZES groups. Additionally, the cumulative incidences of all-cause death, cardiac death, non-fatal MI, and any repeat revascularization were not significantly different between the two groups. Conclusions: Although I-ZES utilizes a more advanced stent platform, stent design, and polymer system than E-ZES, both the ZESs showed comparable efficacy and safety during the 3-year follow-up period in this single-center, all-comers registry. However, further large-scaled, randomized, well-controlled trials with long-term follow-up are needed to verify these results.

Validation of FRIEND and ACSM Equations for Cardiorespiratory Fitness: Comparison to Direct Measurement in CAD Patients.

The regression equation of the American College of Sports Medicine (ACSM) was a preferred method for estimating maximal oxygen consumption (VO2max). Recently, a more precise equation from the fitness registry and the importance of exercise national database (FRIEND) for healthy people was developed. This study compared VO2max estimated by the ACSM and FRIEND equations to VO2max directly measured in coronary artery disease (CAD) patients. Overall, 293 CAD patients who participated in cardiac rehabilitation between June 2015 and December 2018 were analyzed. Directly measured VO2max values were compared to the ACSM and FRIEND equations. The directly measured VO2max was significantly different from the estimated VO2max by ACSM equation (24.16 vs. 28.7 mL/kg/min, p < 0.001), which was overestimated by 20% in men and 16% in women. However, there was no statistically significant difference between the directly measured VO2max and the estimated VO2max by the FRIEND equation. (24.16 vs. 24.15 mL/kg/min, p = 0.986). In CAD patients, the estimated VO2max from the ACSM equation was significantly higher than the directly measured VO2max. In addition, estimated cardiorespiratory fitness (CRF) by the FRIEND equation showed similar results with directly measured CRF. As a result, the FRIEND equation can predict CRF more accurately than the ACSM.

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

BACKGROUND AND PURPOSE: Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. METHODS: A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. RESULT: Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). CONCLUSIONS: SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.

Comparison of 3-year clinical outcomes between Endeavor Resolute® and Resolute Integrity® zotarolimus-eluting stents in an Asian population.

OBJECTIVE: There is a scarcity of comparative studies between Endeavor Resolute®-zotarolimus-eluting stent (R-ZES) and Resolute Integrity®-ZES (I-ZES) during long-term follow-up periods. Although the stent alloy and the polymer of these two ZESs are similar, the platform and the design of these two stents are different. This study was conducted to compare the efficacy and safety of these two different ZESs in the all-comer Korean patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period. METHODS: This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In this single-center, retrospective, and all-comer patients' cohort study, a total of 889 patients who underwent PCI with R-ZES (n=394) or I-ZES (n=495) were enrolled. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, nonfatal myocardial infarction (MI), any repeat revascularization including target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR, and the secondary endpoint was stent thrombosis (ST) at 3 years. RESULTS: To adjust for any potential confounders, the propensity score-adjusted multivariable analysis was performed using the logistic regression model (C-statistics=0.689). The cumulative incidence rates of MACEs [adjusted hazard ratio (aHR), 1.341; 95% confidence interval (CI), 0.615-2.922; p=0.461], all-cause death, nonfatal MI, any repeat revascularization, and ST (aHR, 2.090; 95% CI, 0.163-26.77; p=0.571) were similar between the two groups during the 3-year follow-up period. CONCLUSION: R-ZES and I-ZES demonstrated comparable efficacy and safety after PCI during a 3-year follow-up period. However, these results can perhaps be more precisely defined by other large and long-term follow-up studies in the future. (Anatol J Cardiol 2020; 23: 268-76).