First-in-Human Evaluation of a Polymer-Free Everolimus-Eluting Stent Using a Titanium Dioxide Film.

BACKGROUND: In patients with coronary artery disease treated with permanent polymer-coated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 µm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer. METHODS: A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months. RESULTS: Twenty patients with 20 lesions were treated with TIGERevolutioN®. At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months. CONCLUSION: The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up. TRIAL REGISTRATION: Trial Registration: Clinical Research Information Service Identifier: KCT0005699.

Synthesis and evaluation of 68 Ga-HBED-CC-EDBE-folate for positron-emission tomography imaging of overexpressed folate receptors on CT26 tumor cells.

The 68 Ga is a positron-emitting radionuclide that can be combined with bifunctional chelating agents and bioactive substances for use as positron-emission tomography (PET) diagnostic agents. The HBED-CC is an acyclic chelating agent that is rapidly labeled with 68 Ga under mild conditions. To target cancer cells, bioactive substances can be conjugated to the carboxyl terminus of HBED-CC. Because folic acid strongly binds to folate receptors that are overexpressed on the surfaces of many types of cancer cells, it was coupled with HBED-CC through a small polyethylene glycol-based linker (EDBE) to generate an active, receptor-selective targeting system. The HBED-CC-EDBE-folate (HCEF) precursor was readily labeled with 68 Ga in 5 minutes at room temperature (98% radiochemical yield; 99% radiochemical purity after isolation). In cellular uptake tests, higher uptakes of 68 Ga-HCEF were observed for the CT26 and KB cell lines (which express folate receptors) than for the A549 cell line (which does not). Finally, in vivo micro-PET measurements over 2 hours of binding in BALB/c mice into which CT26 tumors had been transplanted showed the selective accumulation of 68 Ga-HCEF in the folate receptor-expressing CT26 tumors. These results confirmed the potential of 68 Ga-HCEF as a PET diagnostic agent for tumors that express folate receptors.

Comparison of optimal bowel cleansing effects of 1L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate: A randomized controlled study.

Various low-volume bowel cleansing formulations that improve compliance have been approved and are being used in clinical practice. This study aimed to compare the effectiveness of 1 L polyethylene glycol (PEG) with ascorbic acid with that of sodium picosulfate (PICO) with magnesium citrate. This was a multicenter, randomized controlled, non-inferiority study. Patients were randomized into a 1 L PEG with ascorbic acid group and a PICO with magnesium citrate group according to the bowel cleansing agent used. Colonoscopy was performed as a single-blind study wherein the endoscopist had no information about any bowel preparation agent. The efficacy of bowel cleansing was assessed using the Harefield Cleansing Scale (HCS), and adverse events, preferences, and satisfaction were evaluated using a patient-reported questionnaire before colonoscopy. A total of 254 participants were randomly assigned to two groups: 115 in the 1 L PEG with ascorbic acid group and 113 in the PICO with magnesium citrate group. Overall bowel cleansing success was not statistically different between the two groups (97.4 vs. 97.3%), confirming that 1 L PEG with ascorbic acid was not inferior to PICO with magnesium citrate (lower confidence limit, -4.15%; p = 1.00). High-quality bowel cleansing was achieved in 87% of the 1 L PEG with ascorbic acid group and 77% of the PICO with magnesium citrate group (Lower confidence limit, 1.29%, p = 0.05). In terms of patient satisfaction, PICO with magnesium citrate was better, but compliance and side effects were similar in both groups. The 1 L PEG with ascorbic acid showed similar efficacy and adverse events as PICO with magnesium citrate. Although 1 L PEG with ascorbic acid is very effective in bowel preparation despite its small volume, it is necessary to increase satisfaction such as taste and feeling.

The effects of barrier materials on reduction of pericardial adhesion formation in rabbits: a comparative study of a hyaluronan-based solution and a temperature sensitive poloxamer solution/gel material.

OBJECTIVE: This study was performed to examine the efficacy and safety of a hyaluronan solution (Guardix-SL) and a temperature sensitive poloxamer solution/gel material (Guardix-SG) on the prevention of pericardial adhesion in rabbits. METHODS: A total of 60 rabbits were divided into three groups according to material applied after epicardial abrasion: the control group (group CO), the Guardix SL group (group SL), and the Guardix SG group (group SG). The ejection fraction and the presence of pericardial effusion were evaluated by echocardiograms at the immediate postoperative period and 2 wk after the surgery. The adhesion was evaluated macroscopically and microscopically 2 wk after the surgery. RESULTS: In the group SG, mild pericardial effusions were observed only at the immediate postoperative period in 10 out of 20 rabbits with an insignificant reduction of the ejection fraction. Group CO had a significantly higher macroscopic adhesion and fibrosis score than did groups SL and SG (P < 0.001), and group SL had a significantly higher adhesion score than did group SG (P = 0.045). Inflammation score and the expression of anti-macrophage antibody in group CO were higher than those in groups SL and SG, although the differences were not significant. CONCLUSIONS: Guardix-SL and Guardix-SG effectively reduced the adhesion formation, and Guardix-SG is more effective than Guardix-SL for preventing adhesion. However, Guardix-SG showed a potential disadvantage of decreasing the ejection fraction, although this was statistically insignificant. Further study to verify the appropriate dosage to maximize the therapeutic effect without decreasing the heart function is needed.

Predictors of Favorable Angiographic Outcomes After Drug-Coated Balloon Use for de novo Small Vessel Coronary Disease (DCB-ONLY).

We evaluated the angiographic parameter and clinical outcomes of drug-coated balloon (DCB) to assess the optimal angiographic criteria in de novo small vessel disease (SVD). Patients (n = 424, mean age: 64.4 ± 11.2 years, men: 69.8%) at 20 sites in Korea were prospectively enrolled. The primary end point was late luminal loss (LLL) at 9-month follow-up angiography. Secondary end points included restenosis rates, target lesion failure (TLF), and DCB-related thrombosis during the 12-month follow-up period. We included 403 patients for analysis excluding 21 patients who required bailout stenting. Baseline mean reference vessel .diameter was 2.52 ± 0.39 mm and mean minimal luminal diameter (MLD) was 0.71 ± 0.40 mm. The mean MLD was 1.54 ± 0.37 mm after DCB. Late luminal loss was -0.01 ± 0.43 mm and restenosis was noted in 26 patients (12.2%). Minimal luminal diameter >1.6 mm and %diameter stenosis (DS) <45% after DCB was associated maintenance of MLD without LLL at 9-months. Multivariate analysis demonstrated that %DS at baseline and post-MLD was associated with the restenosis. During 12-month follow-up, TLF was 2.6% including 1 cardiac death, 1 myocardial infarction, and 10 ischemia-driven target lesion revascularizations. Drug-coated balloon showed a low restenosis and lower LLL despite high in-segment DS. Post-MLD and % DS may be helpful to get optimal results in de novo SVD after DCB.

Efficacy and tolerability of pegylated interferon-alpha2a plus ribavirin versus pegylated interferon-alpha2b plus ribavirin in treatment-naive chronic hepatitis C patients.

OBJECTIVES: The authors compared the efficacies and tolerabilities of pegylated interferon-alpha2a (PEG-IFN-alpha2a) + ribavirin and pegylated interferon-alpha2b (PEG-IFN-alpha2b) + ribavirin for the initial treatment of chronic hepatitis C. METHODS: A total of 126 treatment-naive patients (29.4% genotype 1, 70.6% genotype non-1) were treated with PEG-IFN-alpha2a 180 microg/week (group A, n = 79) or PEG-IFN-alpha2b 1.5 microg/kg/week (group B, n = 47) with ribavirin (800 mg/day for genotype non-1 or 1,000-1,200 mg/day for genotype 1) for 24 (genotype non-1) or 48 weeks (genotype 1). RESULTS: End-of-treatment virologic response, sustained virologic response, and biochemical response were not significantly different in groups A and B (84.8 vs. 89.4%, 70.9 vs. 72.3%, and 70.9 vs. 74.5%, respectively; p > 0.05). In patients with the HCV genotype 1 or non-1, treatment responses were not significantly different. Multivariate analysis showed that HCV genotype only was an independent factor that affected sustained virologic response (p = 0.048). The proportions of treatment discontinuations in groups A and B were similar (10.1 vs. 10.6%; p = 1.000). CONCLUSIONS: PEG-IFN-alpha2a or PEG-IFN-alpha2b + ribavirin combination therapies showed similar efficacies and tolerabilities as initial treatments for chronic hepatitis C.

Predicting sleep apnea responses to oral appliance therapy using polysomnographic airflow.

STUDY OBJECTIVES: Oral appliance therapy is an increasingly common option for treating obstructive sleep apnea (OSA) in patients who are intolerant to continuous positive airway pressure (CPAP). Clinically applicable tools to identify patients who could respond to oral appliance therapy are limited. METHODS: Data from three studies (N = 81) were compiled, which included two sleep study nights, on and off oral appliance treatment. Along with clinical variables, airflow features were computed that included the average drop in airflow during respiratory events (event depth) and flow shape features, which, from previous work, indicates the mechanism of pharyngeal collapse. A model was developed to predict oral appliance treatment response (>50% reduction in apnea-hypopnea index [AHI] from baseline plus a treatment AHI <10 events/h). Model performance was quantified using (1) accuracy and (2) the difference in oral appliance treatment efficacy (percent reduction in AHI) and treatment AHI between predicted responders and nonresponders. RESULTS: In addition to age and body mass index (BMI), event depth and expiratory "pinching" (validated to reflect palatal prolapse) were the airflow features selected by the model. Nonresponders had deeper events, "pinched" expiratory flow shape (i.e. associated with palatal collapse), were older, and had a higher BMI. Prediction accuracy was 74% and treatment AHI was lower in predicted responders compared to nonresponders by a clinically meaningful margin (8.0 [5.1 to 11.6] vs. 20.0 [12.2 to 29.5] events/h, p < 0.001). CONCLUSIONS: A model developed with airflow features calculated from routine polysomnography, combined with age and BMI, identified oral appliance treatment responders from nonresponders. This research represents an important application of phenotyping to identify alternative treatments for personalized OSA management.

An omentum-cultured 3D-printed artificial trachea: in vivo bioreactor.

The purpose of this study was to evaluate whether the prior implantation of a 3D-printed polycaprolactone (PCL) artificial trachea in the omentum is beneficial for revascularization of the scaffold and reduces associated complications in the reconstruction of a circumferential tracheal defect. Ten New Zealand rabbits were divided into 2 groups: (1) PCL-OC group (PCL scaffold cultured in omentum for 2 weeks before transplantation) and (2) PCL group. In the PCL-OC group, newly formed connective tissue completely covered the luminal surface of the scaffold with mild inflammation at 2 weeks postoperatively; a minor degree of stenosis was noted at 8 weeks postoperatively. The PCL group showed scaffold exposure without any tissue regeneration at 2 weeks postoperatively, and a moderate degree of luminal stenosis 6 weeks after implantation. Histology revealed highly organized regenerated tissue composed of ciliated respiratory epithelium, and submucosal layer in the PCL-OC group. Neo-cartilage regeneration was noted in part of the regenerated tissue. The PCL group demonstrated severe inflammation and an unorganized structure compared to that of the PCL-OC group. In vivo omentum culture of the tracheal scaffold before transplantation is beneficial for rapid re-epithelialization and revascularization of the scaffold. It also prevents postoperative luminal stenosis.

Meta-analysis of angiographic versus intravascular ultrasound parameters of drug-eluting stent efficacy (from TAXUS IV, V, and VI).

Both quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) are currently used to assess in-stent restenosis. This study aimed to use standardized imaging and clinical follow-up to compare QCA parameters with several IVUS parameters to evaluate their strengths and weaknesses for detecting in-stent restenosis in a drug-eluting stent population. A subset of patients from the TAXUS IV, V, and VI studies was evaluated. The subset, which included 216 TAXUS-treated patients and 191 bare-metal stent-treated patients, had complete IVUS and QCA performed at baseline and follow-up. As expected, all QCA and IVUS parameters were consistent with less intimal hyperplasia in TAXUS patients than controls. The overall incidence of QCA binary restenosis was 14.0%, which was 9.3% in TAXUS-treated patients and 19% in bare-metal stent-treated patients (p = 0.0008). Regression analysis showed that QCA late lumen loss and percentage of diameter stenosis correlated only moderately with the various IVUS measures of neointimal hyperplasia for the combined group of patients (TAXUS + bare-metal stent), as well as for the TAXUS-treated and bare-metal stent-treated patients separately. However, in general, correlations within the control (bare-metal stent) group tended to be stronger than within the TAXUS group. The strongest correlation was between QCA percentage of diameter stenosis and IVUS percentage of intimal hyperplasia in the overall group and the control group. The strongest IVUS predictor of QCA binary restenosis at 9 months was maximum percentage of intimal hyperplasia, with an overall C = 0.91 and p <0.001. In conclusion, the QCA and IVUS parameters used to evaluate drug-eluting stent efficacy showed a moderate correlation with IVUS percentage of intimal hyperplasia, reliably predicting QCA binary in-stent restenosis.

Versatile PEG-derivatized phosphine oxide ligands for water-dispersible metal oxide nanocrystals.

We report the simple synthesis of poly(ethylene glycol)(PEG)-derivatized phosphine oxide ligands for water-dispersible metal oxide nanocrystals.

Bifidus fermentation increases hypolipidemic and hypoglycemic effects of red ginseng.

Antihyperlipidemic and antihyperglycemic effects of Red Ginseng (RG, steamed and dried root of Panax ginseng C. A. Meyer, family Araliaceae), major component of which is ginsenoside Rg3, and Bifidodoterium-fermented RG (FRG), major component of which is ginsenoside Rh2, were investigated. Orally administered RG and FRG potently reduced the serum triglyceride levels in corn-oil-induced hypertriglycemidemic mice as well as total cholesterol and triglyceride levels in Triton WR-1339-induced hyperlipidemic mice. Of the saponin and polysaccharide fractions of RG and FRG, the polysaccharide fraction inhibited postprandial blood glucose elevation of maltose- or starch-loaded mice and reduced the blood triglyceride levels in corn-oil-induced hypertriglycemidemic mice. The saponin fraction and its ginsenosides Rg3 and Rh2 reduced blood triglyceride and total cholesterol levels in Triton WR1339-induced hyperlipidemic mice. The inhibitory effect of FRG and its main constituents against hyperlipidemia and hyperglycemia in mice were more potent than those of RG. These findings suggest that hypolipidemic and hypoglycemic effects of RG can be enforced by Bifidus fermentation and FRG may improve hyperlipidemia and hyperglycemia.

Clinical outcomes of biodegradable polymer biolimus-eluting BioMatrix stents versus durable polymer everolimus-eluting Xience stents.

There are limited data about clinical outcomes of biodegradable polymer biolimus-eluting BioMatrix stents (BP-BES) and durable polymer everolimus-eluting Xience stents (DP-EES) in real world practice. We sought to compare the clinical outcomes of BP-BES and DP-EES in real world cohorts of patients undergoing percutaneous coronary intervention. A prospective multicenter registry enrolled 999 patients treated with BP-BES and 1,000 patients treated with DP-EES. The primary outcome was target lesion failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization. Definite or probable stent thrombosis was also compared in total and propensity score-matched cohorts. The median follow-up duration was 24 months, and mean age was 65 years (interquartile range, 56-72 years). Patients receiving BP-BES had a lower prevalence of acute coronary syndrome, prior myocardial infarction, multi-vessel disease, bifurcation lesions, and left anterior descending artery lesions than those receiving DP-EES. After propensity score matching (692 pairs), target lesion failure occurred in 22 patients receiving BP-BES and in 25 patients receiving DP-EES (3.2% versus 3.6%; adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.53 to 1.60; p = 0.77). The risk of definite or probable stent thrombosis did not differ between the 2 groups (0.4% versus 0.4%; adjusted HR, 1.03; 95% CI, 0.21 to 4.98; p = 0.97). The results were consistent across various subgroups. In the propensity score-matched analysis of real world cohorts, BP-BES showed similar clinical outcomes compared to DP-EES. We need to investigate about whether differences in clinical outcome emerge during long-term follow-up.

Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery.

OBJECTIVE: We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM) in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model. METHODS: A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25) and saline as the control group (group CO; n = 25). In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery. RESULTS: In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001). Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002) and fibrosis score (P = .018) than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant. CONCLUSIONS: In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required.

Efficient hybrid solar cells using PbS(x)Se(1-x) quantum dots and nanorods for broad-range photon absorption and well-assembled charge transfer networks.

We present hybrid solar cells with high efficiency utilizing a novel donor-acceptor combination of poly[2,6-(4,4'-bis-(2-ethylhexyl)dithieno[3,2-b:2',3'-d]silole)-alt-4,7(2,1,3-benzothiadiazole)] (PSBTBT) and a PbSxSe1-x inorganic semiconductor. Several nanocomposite parameters are evaluated in order to improve the hybrid device efficiency, including donor-acceptor materials, surface modification of the inorganic semiconductor, and mixture of quantum dots (QDs) and nanorods (NRs) in the polymer matrix. A high power conversion efficiency (PCE) of ~3.4% is attained from the optimal device with a PbS0.7Se0.3 QD : NR blending ratio of 0.3 : 0.7 (wt/wt) under air mass (AM) 1.5 solar illumination, which is attributed to the broad-range absorption of the solar energies and the efficient charge separation and transport dynamics. The optoelectronic and nanomorphological properties of these novel hybrid solar cells are described.

Fabrication of CuInTe2 and CuInTe(2-x)Se(x) ternary gradient quantum dots and their application to solar cells.

We report the first synthesis of colloidal CuInTe2, CuInTe2-xSex gradient alloyed quantum dots (QDs) through a simple hot injection method. We confirmed the composition of synthesized QDs to cationic rich phase of CuIn1.5Te2.5 and Cu0.23In0.36Te0.19Se0.22 with XPS and ICP analysis, and we have also found that the gradient alloyed Cu0.23In0.36Te0.19Se0.22 QDs exhibit greatly improved stability over the CuIn1.5Te2.5 QDs. The solution-processed solar cell based on the gradient alloyed Cu0.23In0.36Te0.19Se0.22 QDs exhibited 17.4 mA/cm(2) of short circuit current density (Jsc), 0.40 V of open circuit voltage (Voc), 44.1% of fill factor (FF), and 3.1% of overall power conversion efficiency at 100 mW/cm(2) AM 1.5G illumination.

Advantages of glove finger-coated polyvinyl acetate pack in endoscopic sinus surgery.

BACKGROUND: This study investigated the efficacy of glove finger-coated polyvinyl acetate (PA) pack on hemostasis, pain levels, and wound healing after endoscopic sinus surgery (ESS). METHODS: A prospective, randomized, double-blinded controlled study was performed in 30 patients who underwent bilateral ESS for chronic rhinosinusitis. Fifteen patients (control group) had both nasal cavities packed with PA pack (Merocel; Medtronic Xomed, Jacksonville, FL) and another 15 subjects (experimental group) had their nasal cavities packed with PA in a glove finger. Pain levels were assessed by patients on a visual analog scale 12 hours after surgery and at the time of packing removal. The amount of bleeding on removal were quantified by weighing it after removal. Lund-Kennedy score and synechiae formation were assessed at 4, 8, and 12 weeks after surgery. The use of analgesics and oral steroid was compared between the two groups. RESULTS: The experimental group showed lower levels of pain and lessened bleeding during packing removal than the control group. There were no differences in pain levels at 12 hours after surgery, use of analgesics and oral steroid between the two groups. One (6%) of each group had postoperative bleeding and required additional packing for hemostasis. Lower Lund-Kennedy score at postoperative 4 weeks was documented in the experimental group. In addition, two (13%) control subjects developed a synechiae between the middle turbinate and the lateral wall. CONCLUSION: PA packing in a glove finger is advantageous in terms of pain, bleeding on packing removal, and postoperative wound healing, compared with PA pack only.

Journey of a swallowed toothbrush to the colon.

Toothbrush swallowing is a rare event. Because no cases of spontaneous passage have been reported, prompt removal is recommended to prevent the development of complications. Most swallowed toothbrushes have been found in the esophagus or the stomach of affected patients, and there has been no previously reported case of a toothbrush in the colon. Here, we report a case of a swallowed toothbrush found in the ascending colon that caused a fistula between the right colon and the liver, with a complicating small hepatic abscess. This patient was successfully managed using exploratory laparotomy. To our knowledge, this is the first documented case of a swallowed toothbrush found in the colon.

In-situ encapsulation of quantum dots into polymer microspheres.

We have incorporated fluorescent quantum dots (QDs) into polystyrene microspheres using functionalized oligomeric phosphine (OP) ligands. We find that a uniform distribution of quantum dots is loaded inside each polymer bead. Some local close-packing of quantum dots in the beads is attributed to the self-polymerization of the functionalized ligands. The presence of quantum dots disturbs the nucleation and growth processes during the formation of polymer microspheres and results in a wider size distribution of the quantum dot-embedded polystyrene beads than for the control without dots. The change in quantum efficiency of the quantum dots before (approximately 20%) and after (12%) loading into the beads substantiates the protection of oligomeric phosphine ligands yet indicates that the properties of these quantum dots are still affected during processing.

Size series of small indium arsenide-zinc selenide core-shell nanocrystals and their application to in vivo imaging.

We have developed a size series of unusually small, water-soluble (InAs)ZnSe (core)shell quantum dots (QDs) that emit in the near-infrared and exhibit new behavior in vivo, including multiple sequential lymph node mapping and extravasation from the vasculature. The biological utility of these fluorescent probes resulted from our intentional choice to match the semiconductor material and water-soluble ligand with a desired final hydrodynamic diameter and emission wavelength.

Phosphine oxide polymer for water-soluble nanoparticles.

A phosphine oxide polymer was developed using bis(dichlorophosphino)ethane and poly(ethylene glycol). This polymer system was used to transfer various nanoparticles from organic solvents to water, retaining their physical properties and reactivities.