Anticoagulants are a risk factor for delayed bleeding after colorectal endoscopic submucosal dissection: A HASID multicenter study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3 %). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96-1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Self-clustered GAN for precipitation nowcasting.

This paper proposes a novel GAN framework with self-clustering approach for precipitation nowcasting (ClusterCast). Previous studies have primarily captured the motion vector using only a single latent space, making the models difficult to adapt to disparate space-time distribution of precipitation. Environmental factors (e.g., regional characteristics and precipitation scale) have an impact on precipitation systems and can cause non-stationary distribution. To tackle this problem, our key idea is to train a generator network to predict future radar frames by learning a sub-network that automatically labels precipitation types from a generative model. The training process consists of (i) clustering the hierarchical features derived from the generator stem using a sub-network and (ii) predicting future radar frames according to the self-supervised labels, enabling heterogeneous latent representation. Additionally, we attempt an ensemble forecast that prescribes random perturbations to improve performance. With the flexibility of representation learning, ClusterCast enables the model to learn precipitation distribution more accurately. Results indicate that our method generates non-blurry future frames by preventing mode collapse, and the proposed method demonstrates robustness across various precipitation scenarios. Extensive experiments demonstrate that our method outperforms four benchmarks on a 2-h prediction basis with a mean squared error (MSE) of 8.9% on unseen datasets.

Predictive factors associated with technical difficulty in colorectal endoscopic submucosal dissection: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.

Outcomes of Colorectal Endoscopic Submucosal Dissection for Elderly Patients: A Multicenter Study by the Honam Association for the Study of Intestinal Disease (HASID).

BACKGROUND/AIM: The aging population has been growing gradually; therefore, the proportion of elderly patients undergoing colorectal endoscopic submucosal dissection (ESD) has also been increasing. However, there is a lack of large-scale studies on the efficacy and safety of colorectal ESD in elderly patients. PATIENTS AND METHODS: This retrospective analysis evaluated colorectal ESDs performed at five tertiary medical institutions between January 2015 and December 2020. Patients were categorized into the following four age groups: Middle-aged (<65 years), young-elderly (≥65 to <75 years), mid-elderly (≥75 to <85 years), and very elderly (≥85 years). Of the 1,446 patients included, 668 (46.2%), 466 (32.2%), 293 (20.3%), and 19 (1.3%) were in the middle-aged, young-elderly, mid-elderly, and very-elderly groups, respectively. RESULTS: Compared to younger patients, more older patients used aspirin, clopidogrel, and anti-thrombotic agents. Additionally, the Charlson comorbidity index increased significantly with increasing age. However, no significant differences were observed in the complete resection rates nor the rates of complications, such as perforation, bleeding, and post-ESD coagulation syndrome, among the different age groups. A restricted cubic spline curve was used to construct predictive models for complete resection and major complications based on age and showed that the need for complete resection did not decrease with increasing age. Furthermore, major complications did not significantly differ with age progression. CONCLUSION: Colorectal ESD should be actively considered as a relatively safe and effective treatment method for elderly patients.

Conversion of single-energy CT to parametric maps of dual-energy CT using convolutional neural network.

OBJECTIVES: We propose a deep learning (DL) multitask learning framework using convolutional neural network for a direct conversion of single-energy CT (SECT) to 3 different parametric maps of dual-energy CT (DECT): virtual-monochromatic image (VMI), effective atomic number (EAN), and relative electron density (RED). METHODS: We propose VMI-Net for conversion of SECT to 70, 120, and 200 keV VMIs. In addition, EAN-Net and RED-Net were also developed to convert SECT to EAN and RED. We trained and validated our model using 67 patients collected between 2019 and 2020. Single-layer CT images with 120 kVp acquired by the DECT (IQon spectral CT; Philips Healthcare, Amsterdam, Netherlands) were used as input, while the VMIs, EAN, and RED acquired by the same device were used as target. The performance of the DL framework was evaluated by absolute difference (AD) and relative difference (RD). RESULTS: The VMI-Net converted 120 kVp SECT to the VMIs with AD of 9.02 Hounsfield Unit, and RD of 0.41% compared to the ground truth VMIs. The ADs of the converted EAN and RED were 0.29 and 0.96, respectively, while the RDs were 1.99% and 0.50% for the converted EAN and RED, respectively. CONCLUSIONS: SECT images were directly converted to the 3 parametric maps of DECT (ie, VMIs, EAN, and RED). By using this model, one can generate the parametric information from SECT images without DECT device. Our model can help investigate the parametric information from SECT retrospectively. ADVANCES IN KNOWLEDGE: DL framework enables converting SECT to various high-quality parametric maps of DECT.

C-Axis Aligned Composite InZnO via Thermal Atomic Layer Deposition for 3D Nanostructured Semiconductor.

Amorphous oxide semiconductors have been widely studied for various applications, including thin-film transistors (TFTs) for display backplanes and semiconductor memories. However, the inherent instability, limited mobility, and complexity of multicomponent oxide semiconductors for achieving high aspect ratios and conformality of cation distribution remain challenging. Indium-zinc oxide (IZO), known for its high mobility, also faces obstacles in instability resulting from high carrier doping density and low ionization energy. To address these issues and attain a balance between mobility and stability, adopting a highly aligned structure such as a c-axis aligned crystalline IGZO could be advantageous. However, limited studies have reported enhanced electrical performance using crystalline IZO, likely attributed to the high thermal stability of the individual components (In2O3 and ZnO). Here, we first propose a c-axis aligned composite (CAAC) IZO with superior TFT properties, including a remarkable performance of field-effect mobility (µFE) of 55.8 cm2/(V s) and positive-bias-temperature-stress stability of +0.16 V (2 MV/cm, 60 °C, 1 h), as well as a low subthreshold swing of 0.18 V/decade and hysteresis as 0.01 V, which could be obtained through optimization of growth temperature and composition using thermal atomic layer deposition. These results surpass those of TFTs based on nanocrystalline/polycrystalline/amorphous-IZO. We conducted a thorough investigation of CAAC-IZO and revealed that the growth temperature and cation distribution profoundly influence the crystal structure and device properties. Finally, we observed excellent compositional conformality and 97% step coverage of IZO on a high-aspect-ratio (HAR) structure with an aspect ratio reaching 40:1, which is highly promising for future applications. Our results include a detailed investigation of the influence of the crystal structure of IZO on the film and TFT performance and suggest an approach for future applications.

Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound.

BACKGROUND: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have shown comparable outcomes in guiding percutaneous coronary intervention (PCI). However, their comparative effectiveness in complex coronary artery lesions remains unclear. OBJECTIVES: This study compared the effectiveness and safety of OCT-guided vs IVUS-guided PCI for complex coronary artery lesions. METHODS: This was a prespecified, main subgroup analysis of complex coronary artery lesions in the OCTIVUS (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention) trial, which included unprotected left main disease, bifurcation disease, an aorto-ostial lesion, a chronic total occlusion, a severely calcified lesion, an in-stent restenotic lesion, a diffuse long lesion, or multivessel PCI. The primary endpoint was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization. RESULTS: In 2,008 randomized patients, 1,475 (73.5%) underwent imaging-guided PCI for complex coronary artery lesions; 719 (48.7%) received OCT-guided and 756 (51.3%) IVUS-guided PCI. At a median follow-up of 2.0 years, primary endpoint event had occurred in 47 patients (6.5%) in the OCT-guided group and in 56 patients (7.4%) in the IVUS-guided group (HR: 0.87; 95% CI: 0.59-1.29; P = 0.50). These findings were consistent in adjusted analyses. The incidence of contrast-induced nephropathy was similar between the 2 groups (1.9% vs 1.5%; P = 0.46). The incidence of major procedural complications was lower in the OCT-guided group than in the IVUS-guided group (1.7% vs 3.4%; P = 0.03). CONCLUSIONS: Among patients with complex coronary artery lesions, OCT-guided PCI showed a similar risk of primary composite event of death from cardiac causes, target vessel-related myocardial infarction, or target vessel revascularization as compared with IVUS-guided PCI. (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention [OCTIVUS]; NCT03394079).

Colloidal InSb Quantum Dots for 1500 nm SWIR Photodetector with Antioxidation of Surface.

III-V quantum dots (QDs) have emerged as significant alternatives to Cd- and Pb-based QDs, garnering notable attention over the past two decades. However, the understanding of III-V QDs, particularly in the short wave-infrared (SWIR) region, remains limited. InAs QDs are widely recognized as the most prominent SWIR QDs, but their absorption beyond 1400 nm presents various challenges. Consequently, InSb QDs with relatively narrower bandgaps have been investigated; however, research on their device applications is lacking. In this study, InSb QDs are synthesized with absorption ranging from 1000 to 1700 nm by introducing Cl- ions to enhance QD surface stability during synthesis. Additionally, it coated InAs and ZnSe shells onto the InSb QDs to validate photoluminescence in the SWIR region and improve photostability. Subsequently, these QDs are employed in the fabrication of photodetector devices, resulting in photodetection above 1500 nm using Pb-free QDs. The photodetection device exhibited an external quantum efficiency (EQE) of 11.4% at 1370 nm and 6.3% at 1520 nm for InSb core QDs, and 4.6% at 1520 nm for InSb/InAs core/shell QDs, marking the successful implementation of such a device. In detail, the 1520 nm for InSb core device showed a dark current density(JD ) value of: 1.46 × 10-9 A/cm2 , responsivity(R): 0.078 A/W, and specific detectivity based on the shot noise(Dsh *): 3.6 × 1012 Jones at 0 V.

Enhanced Stability and Highly Bright Electroluminescence of AgInZnS/CdS/ZnS Quantum Dots through Complete Isolation of Core and Shell via a CdS Interlayer.

An approach for synthesizing AgInZnS/CdS/ZnS core-shell-shell quantum dots (QDs) that demonstrate exceptional stability and electroluminescence (EL) performance is introduced. This approach involves incorporating a cadmium sulfide (CdS) interlayer between an AgInZnS (AIZS) core and a zinc sulfide (ZnS) shell to prevent the diffusion of Zn ions into the AIZS core and the cation exchange at the core-shell interface. Consequently, a uniform and thick ZnS shell, with a thickness of 2.9 nm, is formed, which significantly enhances the stability and increases the photoluminescence quantum yield (87.5%) of the QDs. The potential for AIZS/CdS/ZnS QDs in electroluminescent devices is evaluated, and an external quantum efficiency of 9.6% in the 645 nm is achieved. These findings highlight the importance of uniform and thick ZnS shells in improving the stability and EL performance of QDs.

Questionnaire-Based Survey of Diabetes Self-Care Activities and Barriers among Young Korean Adults with Early-Onset Diabetes.

PURPOSE: Self-management of diabetes is a significant challenge. This study aimed to assess diabetes self-care activities and barriers among Korean young adults with diabetes mellitus. MATERIALS AND METHODS: This study recruited 209 Korean adults with diabetes, with an onset age of 20-39 years, from four university hospitals. Demographic characteristics and the Summary of Diabetes Self-Care Activities (SDSCA) measure and Diabetes Self-Care Barriers Assessment Scale for Older Adults (DSCB-OA) scores were assessed using questionnaires. RESULTS: The average age of study participants was 32.9±6.1 years. Their self-care activities, including adherence to recommended diabetes medication (5.6±2.4) and number of diabetes pills (5.5±2.3) in the SDSCA measure, were the most well-performed activities among all domains. Responses to inspection of the inside of shoes in the foot care activity (0.8±1.5) and specific exercise sessions in the exercise activity (1.6±1.9) reflected poor levels of compliance. According to the DSCB-OA questionnaire, the mean diabetes self-care barrier of DSCB-OA was 20.6±5.0 of total score 45. The greater perceived barriers to self-care on the DSCB-OA were having difficulty exercising regularly (1.9±0.7) and eating three meals and snacks leading to weight gain (1.9±0.8). CONCLUSION: Young adults with early-onset diabetes showed a greater barrier to regular exercise and poor compliance with foot care and blood sugar testing. Healthcare providers must strengthen their relationship with young adults with diabetes to provide more education and guidelines for lifestyle modification focused on exercise and to promote higher compliance with diabetic self-care activities for improving clinical outcomes.

Mechanistic insights into the anti-restenotic effects of HSP27 and HO1 modulated by reconstituted HDL on neointimal hyperplasia.

High-density lipoprotein (HDL) therapy has demonstrated beneficial effects in acute stroke and acute myocardial infarction models by reducing infarct size. In this study, we investigated the inhibitory effects of reconstituted HDL (rHDL) on neointimal hyperplasia and elucidated its underlying mechanism using a balloon injury rat model. Our finding revealed a significant 37% reduction in the intima to media ratio in the arteries treated with 80 mg/kg rHDL compared to those subjected to injury alone (p < 0.05), indicating a specific inhibition of neointimal hyperplasia. In vivo analysis further supported the positive effects of rHDL by demonstrating a reduction in smooth muscle cell (SMC) proliferation and an increase in endothelial cell (EC) proliferation. Additionally, rHDL treatment led to decreased infiltration of leukocytes and downregulated the expression of matrix metallopeptidase 9 (MMP9) in the neointimal area. Notably, rHDL administration resulted in decreased expression of VCAM1 and HIF1α, alongside increased expression of heme oxygenase 1 (HO1) and heat shock protein 27 (HSP27). Overexpression of HSP27 and HO1 effectively inhibited SMC proliferation. Moreover, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HSP27. Interestingly, HSP27 and HO1 had varying effects on the expression of chemokine receptors and rHDL did not exert significant effect on chemokine receptor expression in THP1 cells. These findings underscore the distinct roles of HSP27 and HO1 as potential regulatory factors in the progression of restenosis. Collectively, our study demonstrates that rHDL exerts a potent anti-neointimal hyperplasia effect by reducing leukocytes infiltration and SMC proliferation while promoting EC proliferation.

Performance Evaluation of Three Antibody Binding Assays, a Neutralizing Antibody Assay, and an Interferon-Gamma Release Assay for SARS-CoV-2 According to Vaccine Type in Vaccinated Group.

We evaluated the performance of SARS-CoV-2 assays in the vaccinated group using receptor-binding domain antibody assays (RBD Ab assay), neutralizing antibody assay (nAb assay), and interferon-gamma release assay (IGR assay). We also compared the performance of the SARS-CoV-2 assays based on vaccine type in a large population. We collected 1851 samples from vaccinated individuals with vector, mix-and-match (MM), and mRNA vaccines. The performance of the RBD Ab assays was assessed by SARS-CoV-2 IgG II Quant (Abbott Laboratories, Sligo, Ireland), SARS-CoV-2 IgG (Beckman Coulter, CA, USA), and anti-SARS-CoV-2 S (Roche Diagnostics GmbH, Mannheim, Germany). The nAb assay was assessed by cPass SARS-CoV-2 neutralization antibody detection kits (GenScript, NJ, USA). The IGR assay was assessed by QuantiFERON (Qiagen, Venlo, The Netherlands). Median values of the RBD Ab assays and nAb assay sequentially increased after the first and second vaccinations. RBD Ab assays and nAb assay showed very strong correlations. The median values of the RBD Ab, nAb, and IGR were higher in the mRNA vaccine group than in the vector and MM vaccine groups. The agreement and correlation among the RBD Ab assays, nAb assay, and IGR assay were higher in the mRNA vaccine group than in the vector and MM vaccine groups. We compared the performance of the RBD Ab assay, nAb assay, and IGR assay based on the vaccine types using the RBD Ab, nAb, and IGR assays. This study provides a better understanding of the assessment of humoral and cellular immune responses after vaccination.

Effectiveness and Safety of Endoscopic Submucosal Dissection for Colorectal Neoplasm in Patients with High Charlson Comorbidity Index Score: A HASID Multicenter Study.

Endoscopic submucosal dissection (ESD) is an effective method for removing early colorectal lesions. However, research on the safety and efficacy of ESD in patients with various underlying conditions remains limited. This study retrospectively examined ESD outcomes in colorectal neoplasm patients from five tertiary medical centers. The Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) were analyzed, and the differences in complete resection and complication rates were analyzed. The CCI, ACCI, and complication rates tended to gradually increase proportionally, and the complication resection rate increased from CCI 2 to ACCI 4 as the starting point, followed by a decreasing trend. Of these, 140 patients (9.7%) had a CCI score of 3 or higher. The high CCI group was older (70.6% vs. 64.7%, p < 0.01) and had a higher proportion of men (70.7% vs. 58.7%, p < 0.01) than the low CCI group. The high CCI group had a higher incidence of cancer than the low CCI group (77.9% vs. 65.2%, p < 0.01). The en bloc resection rate (90.0% vs. 89.3%, p = 0.79) and complete resection rate (75.7% vs. 81.2%, p = 0.12) were not significantly different between the two groups. Colorectal ESD can be safely and effectively performed in patients with various underlying medical conditions.

Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: The OCTIVUS Randomized Clinical Trial.

BACKGROUND: Intravascular imaging-guided percutaneous coronary intervention (PCI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) showed superior clinical outcomes compared with angiography-guided PCI. However, the comparative effectiveness of OCT-guided and IVUS-guided PCI regarding clinical outcomes is unknown. METHODS: In this prospective, multicenter, open-label, pragmatic trial, we randomly assigned 2008 patients with significant coronary artery lesions undergoing PCI in a 1:1 ratio to undergo either an OCT-guided or IVUS-guided PCI. The primary end point was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year, which was powered for noninferiority of the OCT group compared with the IVUS group. Safety outcomes were also assessed. RESULTS: At 1 year, primary end point events occurred in 25 of 1005 patients (Kaplan-Meier estimate, 2.5%) in the OCT group and in 31 of 1003 patients (Kaplan-Meier estimate, 3.1%) in the IVUS group (absolute difference, -0.6 percentage points; upper boundary of one-sided 97.5% CI, 0.97 percentage points; P<0.001 for noninferiority). The incidence of contrast-induced nephropathy was similar (14 patients [1.4%] in the OCT group versus 15 patients [1.5%] in the IVUS group; P=0.85). The incidence of major procedural complications was lower in the OCT group than in the IVUS group (22 [2.2%] versus 37 [3.7%]; P=0.047), although imaging procedure-related complications were not observed. CONCLUSIONS: In patients with significant coronary artery lesions, OCT-guided PCI was noninferior to IVUS-guided PCI with respect to the incidence of a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year. The selected study population and lower-than-expected event rates should be considered in interpreting the trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique number: NCT03394079.

HDAC inhibitor SB939 potentiates TRAIL-induced apoptosis in colorectal cancer cells.

Colorectal cancer (CRC) displays noticeable resistance to chemotherapeutic drugs or innovative tumor cell apoptosis-inducing agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Thus, sensitizers are needed to enhance the effects of TRAIL-based cancer therapies. Elevated tumor cell death has been reported when various HDAC inhibitors are administered with TRAIL in various human cancers; however, SB939-TRAIL combined treatment has not been reported. In this study, we determined the ability of SB939 and TRAIL, as single agents or in combination, to inhibit the growth and survival of colorectal cancer cells. Our results demonstrated the effects of SB939 and TRAIL on cell viability, apoptosis, and morphological changes in HT-29 cells. SB939 treatment induces hyper-acetylation of histones and death receptors (DR) by activating MAPK proteins in a dose- and time-dependent manner. The ability of SB939 to sensitize HT-29 cells suggests that SB939 can induce essential changes in cell signaling pathways. Thus, the pan-HDAC inhibitor SB939 sensitizes TRAIL-induced apoptosis via up-regulation of DR5, and SB939-TRAIL combined treatment may target the MAPK pathways and serve as an effective therapeutic strategy against CRC.