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Objectives This study sought to evaluate the impact of post-stent optical coherence tomography (OCT) findings, including severe malapposition, on long-term clinical outcomes. Background Suboptimal OCT findings following percutaneous coronary intervention (PCI) are highly prevalent; however, their clinical implications remain controversial. Methods Of the patients registered in the Yonsei OCT registry, a total of 1,290 patients with 1,348 lesions, who underwent OCT immediately post-stenting, were consecutively enrolled for this study. All patients underwent implantation of drug-eluting stents. Post-stent OCT findings were assessed to identify predictors of device-oriented clinical endpoints (DoCE), including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization (TLR). Significant malapposition criteria associated with major safety events (MSE) were also investigated, such as cardiac death, target vessel-related MI, or stent thrombosis. Results The median follow-up period was 43.0 months (interquartile range [IQR] 21.4 to 56.0 months). The incidence rates of stent edge dissection, tissue prolapse, thrombus, and malapposition after intervention were not associated with occurrence of DoCE. However, patients with significant malapposition (total malapposition volume [TMV] ≥7.0 mm3] exhibited more frequent MSE. A smaller minimal stent area (MSA) was identified as an independent predictor for DoCE (hazard ratio [HR]: 1.20 [95% confidence interval [CI]: 1.00 to 1.43]; p = 0.045). Malapposition with TMV ≥7.0 mm3 was found to be an independent predictor of MSE (HR: 6.12 [95% CI: 1.88 to 19.95]; p = 0.003). Follow-up OCT at 3, 6, or 9 months after PCI showed that post-stent TMV ≥7.0 mm3 was related to a greater occurrence of late malapposition and uncovered struts. Conclusions Although most suboptimal OCT findings were not associated with clinical outcomes, a smaller MSA was associated with DoCE, driven mainly by TLR, and significant malapposition with TMV ≥7.0 mm3 was associated with more MSE after PCI. (Yonsei OCT [Optical Coherence Tomography] Registry for Evaluation of Efficacy and Safety of Coronary Stenting; Yonsei OCT registry; NCT02099162 )

This study describes a simple method of inter-fractional photon beam monitoring to measure the entrance dose of radiation treatment using Gafchromic EBT3 film.The film was placed at the center of a 1-cm thick phantom shaped like a block tray and fixed on the accessory tray of the gantry. The entrance dose was measured following the placement of the film in the accessory tray. The dose distribution calculated with the treatment planning system was compared with the dose distribution on the irradiated EBT3 films. The effectiveness of this methodology, as determined by gamma passing rates, was evaluated for the 22 fields of eight three-dimensional conformal radiotherapy (3D-CRT) plans and the 41 fields of nine intensity-modulated radiotherapy (RT) plans. The plans for three-dimensional conformal RT included treatments of the rectum, liver, breast, and head and neck, whereas the plans for intensity-modulated RT included treatments of the liver, brain, and lung.The gamma passing rates for 3D-CRT ranged from 96.4% to 99.5%, with the mean gamma passing rate for 22 fields being 98.0%. The gamma passing rate for intensity-modulated RT ranged from 96.1% to 98.9%, with the mean gamma passing rate for 41 fields being 97.7%. All gamma indices were over the 95% tolerance level.The methodology described in this study, based on Gafchromic EBT3 film, can be utilized for inter-fractional entrance dose monitoring as quality assurance during RT. Clinical application of this method to patients can verify the accuracy of beam delivery in the treatment room.

Background Patient-specific dose prediction improves the efficiency and quality of radiation treatment planning and reduces the time required to find the optimal plan. In this study, a patient-specific dose prediction model was developed for a left-sided breast clinical case using deep learning, and its performance was compared with that of conventional knowledge-based planning using RapidPlan™. Methods Patient-specific dose prediction was performed using a contour image of the planning target volume (PTV) and organs at risk (OARs) with a U-net-based modified dose prediction neural network. A database of 50 volumetric modulated arc therapy (VMAT) plans for left-sided breast cancer patients was utilized to produce training and validation datasets. The dose prediction deep neural network (DpNet) feature weights of the previously learned convolution layers were applied to the test on a cohort of 10 test sets. With the same patient data set, dose prediction was performed for the 10 test sets after training in RapidPlan. The 3D dose distribution, absolute dose difference error, dose-volume histogram, 2D gamma index, and iso-dose dice similarity coefficient were used for quantitative evaluation of the dose prediction. Results The mean absolute error (MAE) and one standard deviation (SD) between the clinical and deep learning dose prediction models were 0.02 ± 0.04%, 0.01 ± 0.83%, 0.16 ± 0.82%, 0.52 ± 0.97, − 0.88 ± 1.83%, − 1.16 ± 2.58%, and − 0.97 ± 1.73% for D95%, Dmean in the PTV, and the OARs of the body, left breast, heart, left lung, and right lung, respectively, and those measured between the clinical and RapidPlan dose prediction models were 0.02 ± 0.14%, 0.87 ± 0.63%, − 0.29 ± 0.98%, 1.30 ± 0.86%, − 0.32 ± 1.10%, 0.12 ± 2.13%, and − 1.74 ± 1.79, respectively. Conclusions In this study, a deep learning method for dose prediction was developed and was demonstrated to accurately predict patient-specific doses for left-sided breast cancer. Using the deep learning framework, the efficiency and accuracy of the dose prediction were compared to those of RapidPlan. The doses predicted by deep learning were superior to the results of the RapidPlan-generated VMAT plan.

The present study verified and evaluated the dosimetric effects of protons scattered from a snout and an aperture in clinical practice, when a range compensator was included. The dose distribution calculated by a treatment planning system (TPS) was compared with the measured dose distribution and the dose distribution calculated by Monte Carlo simulation at several depths. The difference between the measured and calculated results was analyzed using Monte Carlo simulation with filtration of scattering in the snout and aperture. The dependence of the effects of scattered protons on snout size, beam range, and minimum thickness of the range compensator was also investigated using the Monte Carlo simulation. The simulated and measured results showed that the additional dose compared with the results calculated by the TPS at shallow depths was mainly due to protons scattered by the snout and aperture. This additional dose was filtered by the structure of the range compensator so that it was observed under the thin region of the range compensator. The maximum difference was measured at a depth of 16 mm (8.25%), with the difference decreasing with depth. Analysis of protons contributing to the additional dose showed that the contribution of protons scattered from the snout was greater than that of protons scattered from the aperture when a narrow snout was used. In the Monte Carlo simulation, this effect of scattered protons was reduced when wider snouts and longer‐range proton beams were used. This effect was also reduced when thicker range compensator bases were used, even with a narrow snout. This study verified the effect of scattered protons even when a range compensator was included and emphasized the importance of snout‐scattered protons when a narrow snout is used for small fields. It indicated that this additional dose can be reduced by wider snouts, longer range proton beams, and thicker range compensator bases. These results provide a better understanding of the additional dose from scattered protons in clinical practice.

Personal dosimeters are used to measure the amount of radiation exposure in individual radiation workers. We aimed to replace existing personal dosimeters and evaluate a real-time scintillator-based dosimeter by monitoring its radiation dose and checking the location exposed to radiation in the workspace. The developed dosimeter measured the radiation dose based on a scintillating fiber (SF) bundle, and comprised a silicon photomultiplier (SiPM), ultra-wide-band (UWB)-based location detecting system, and Bluetooth system. The SF bundle was exposed to radiation-emitted light, and the photons were amplified and converted to electrical signals through the SiPM. These signals were transferred to the user through the Bluetooth system and monitored. To evaluate the feasibility of this mechanism as a dosimeter, we performed characteristic tests, such as dose linearity, dependence on dose rate, energy, exposed angle, and location coordinate mapping. Also, the dose distribution formed in circles around the iso-center was measured to confirm the feasibility of monitoring the exposure dose and location and to enable the radiation worker to move freely in a workspace. We confirmed dose linearity, independence from energy and angle, and accuracy of location monitoring in our device. The user’s locations were measured with a difference of − 6 cm and − 4.8 cm on the x- and the y-axes, respectively. The measured doses on our developed dosimeter were 62.7, 32.3, 21.0, and 15.4 mSv at distances of 50, 100, 150, and 200 cm from the iso-center. In other words, all measured doses at several points showed an error within 5% as compared to doses provided by the conventional pocket dosimeter. These results show that the developed SF-based dosimeter is advantageous in monitoring the exposure dose and location in real time, and has significant potential as a new personal dosimeter for radiation workers.

Background: Nephrologists commonly engage in decision making regarding the withholding or withdrawal of dialysis and palliative care in patients at end of life (EoL). However, these issues remain an unsolved dilemma for nephrologists. Objective: To explore nephrologists' perceptions on the decision-making process about withholding or withdrawing dialysis and palliative care in Korea. Design: A nationwide 25-item questionnaire online survey via e-mail. Setting/Subjects: A total of 369 Korean nephrologists completed the survey. Results: The proportions of respondents who stated that withholding or withdrawing dialysis at EoL is ethically appropriate were 87.3% and 86.2%, respectively. A total of 72.4% respondents thought that withdrawal of dialysis in a maintenance dialysis patient is ethically appropriate. Responses regarding patient features that should be considered to withhold or withdraw dialysis were as follows: dialysis intolerance (84.3%), poor performance status (74.8%), patient's active request (47.2%), age (28.7%), very severe dementia (27.1%), and several comorbidities (16.5%). Among those nephrologists who responded to the question about the minimum age, at which dialysis should be withheld or withdrawn, most specified an age between 80 and 90 years (94.3%). Fifty-eight percent of respondents stated that terminally ill dialysis patients should be allowed to use palliative care facilities. In addition, a number of nephrologists thought that adequate palliative care facilities, specific treatment guidelines, enough time to manage patients, financial support, and adequate medical experts are necessary. Conclusions: Korean nephrologists thought that withholding or withdrawing dialysis at EoL is ethically appropriate, even in maintenance dialysis patients. Therefore, consensus guidelines for palliative care after withholding or withdrawal of dialysis are needed.

Objectives The aim of this study was to assess whether the effects of ticagrelor monotherapy after 3-month dual-antiplatelet therapy (DAPT) are consistent among patients presenting with ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction, and unstable angina treated with drug-eluting stents. Background Ticagrelor monotherapy after short-term DAPT has not been investigated in patients with STEMI. Methods This was a pre-specified, stratified, subgroup analysis of the STEMI cohort from the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome) trial, which constituted 36% of the total population. The primary outcome was a composite of major bleeding and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, stent thrombosis, stroke, or target vessel revascularization). The secondary outcomes were major bleeding and MACCE. Results The incidence of the primary outcome was 4.4% in patients with STEMI (n = 1,103), 6.0% in those with non–ST-segment elevation myocardial infarction (n = 1,027), and 4.1% in those with unstable angina (n = 926), without statistical significance (p = 0.09). Compared with ticagrelor-based 12-month DAPT, ticagrelor monotherapy after 3-month DAPT showed consistent effects on the primary outcome across clinical presentations (p for interaction [pint] = 0.64). Furthermore, the effect of ticagrelor monotherapy on the reduction of major bleeding was consistent across clinical presentations (pint = 0.36). The effect of ticagrelor monotherapy on MACCE was also consistent in patients with STEMI, without evidence of a higher risk for MACCE (pint = 0.14). Conclusions This pre-specified subgroup analysis revealed no heterogeneity in the effects of ticagrelor monotherapy after 3-month DAPT, compared with 12-month DAPT, for the primary outcome, major bleeding, and MACCE across clinical presentations including STEMI, though larger studies are needed to demonstrate these findings with adequate power. (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome [TICO Study]; NCT02494895 )

The purpose of this study was to investigate the oxygen enhancement ratio (OER) effects on treatment planning for a hypoxic prostate tumor with proton scanning beams. Two different OER-based dose calculation models (the average model and the voxel model) were investigated by using hypoxic tumor models in this simulation study. For the hypoxic tumor model, an oxygen distribution with a range of 2.4–9.4 mmHg was used according to the clinical data. The results given by the average model and the voxel model were compared for 50% and 90% tumor control probabilities with variations in the hypoxic tumor volume and fractionation. Comparison between the treatment plans with OER-based higher predicted dose and with the conventional prescription dose was conducted to investigate the organ-at-risk (OAR) doses for the prostate case. The average model showed a higher calculated dose than the voxel model. The voxel model with a 50% control probability showed good agreement with the current prescription dose. The OER values of the average model ranged from 1.05 to 1.25, which were applied to the whole tumor volume in treatment planning. The voxel-model-based OERs were higher (1.50–1.75) than those of average model, and these OERs should be applied only for the hypoxic boost region. Regarding treatment plans, the doses of the rectum and the bladder were reduced to the tolerable range V80Gy (volume receiving equal to or greater than 80Gy) < 15% and V75Gy (volume receiving equal to or greater than 75Gy) < 15% respectively after an optimization, but the maximum dose to femoral heads was higher than 50 Gy. In conclusion, we investigated the possible ranges of the OER (1.3–1.8) for proton-beam treatment of prostate cases. A dose escalation of up to about 1.8 times can be applied for the small hypoxic region. This result, which was obtained using a model study, should be verified through clinical experiment.

Purpose Obtaining an integral depth-dose (IDD) curve using a recently developed acrylic-disk radiation sensor (ADRS) is time-consuming because its single structure requires point-by-point measurements in a water phantom. The goal of this study was to verify the ability of a newly designed multilayer ADRS, composed of 20 layers, to measure the energy of proton pencil beam scanning (PBS) in patient-specific quality assurance (QA). Materials and methods The multilayer ADRS consisted of a disk-type transmitter, with a diameter of 15 cm and with a thickness of 1 mm, surrounded by a thin optical fiber; this ADRS provided a higher spatial resolution than the single ADRS, which was 2 mm. The dosimetric characteristics of the multilayer ADRS were determined to accurately measure the energy delivered layer-by-layer. We selected five patients to verify the energy measured using the multilayer ADRS from the actual clinical proton therapy plans. The accuracy of the results measured using the multilayer ADRS was compared with that of measurements by a Bragg peak ionization chamber (IC) and that calculated by a Monte Carlo TOPAS simulation. Results The difference between the multilayer ADRS measurements and those of the TOPAS simulation was within 1% for all patients. The ranges, corresponding to the beam energies for each patient, measured using the multilayer ADRS were closer to those calculated using the TOPAS simulation than those measured using the Bragg peak IC. Conclusions The multilayer ADRS is well suited to verifying the energy of a pencil beam. The acrylic materials used in its configuration make this device easier to use and more cost-effective than conventional detectors. This device, with its high extensibility and stability, may be applicable as a new dosimetry tool for PBS.

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

Purpose Imaging, breath‐holding/gating, and fixation devices have been developed to minimize setup errors so that the prescribed dose can be exactly delivered to the target volume in radiotherapy. Despite these efforts, additional patient monitoring devices have been installed in the treatment room to view patients’ whole‐body movement. We developed a facial expression recognition system using deep learning with a convolutional neural network (CNN) to predict patients’ advanced movement, enhancing the stability of the radiation treatment by giving warning signs to radiation therapists. Materials and methods Convolutional neural network model and extended Cohn‐Kanade datasets with 447 facial expressions of source images for training were used. Additionally, a user interface that can be used in the treatment control room was developed to monitor real‐time patient's facial expression in the treatment room, and the entire system was constructed by installing a camera in the treatment room. To predict the possibility of patients' sudden movement, we categorized facial expressions into two groups: (a) uncomfortable expressions and (b) comfortable expressions. We assumed that the warning sign about the sudden movement was given when the uncomfortable expression was recognized. Results We have constructed the facial expression monitoring system, and the training and test accuracy were 100% and 85.6%, respectively. In 10 patients, their emotions were recognized based on their comfortable and uncomfortable expressions with 100% detection rate. The detected various emotions were represented by a heatmap and motion prediction accuracy was analyzed for each patient. Conclusion We developed a system that monitors the patient's facial expressions and predicts patient's advanced movement during the treatment. It was confirmed that our patient monitoring system can be complementarily used with the existing monitoring system. This system will help in maintaining the initial setup and improving the accuracy of radiotherapy for the patients using deep learning in radiotherapy.

Introduction: The PREDICT DNA trial is the first prospective, multi-center study aimed at validating cell-free plasma derived circulating tumor DNA (ctDNA) as a biomarker for treatment response and recurrence in early stage, triple-negative or HER2-positive (any hormone receptor status) breast cancer. Its primary aim is to determine the negative predictive value (NPV) of the absence of ctDNA after neoadjuvant therapy (NAT) for the achievement of pathologic complete response (pCR). This study has met its accrual goals and results of the overall trial are anticipated within the next year. The initial PREDICT DNA study design stipulated that tumor specific mutations (TSMs) to be tracked in blood would be identified by next gen sequencing (NGS) of tumor biopsy tissue. A disadvantage of this design is the dependence on adequate biopsy tissue. Recently, the advent of Safe-SeqS technology has enabled robust detection of rare variants using NGS with a sensitivity of approximately 0.05% mutant allele fraction. We employed these new NGS methods to pilot a novel tissue-independent approach to ctDNA detection and monitoring. Objective: The primary objective of this pilot study was to determine whether ultrasensitive NGS using a targeted cancer mutation panel can identify TSMs in ctDNA of early-stage breast cancer patients without the use of biopsy tissue. Methods: The PREDICT DNA trial enrolled 228 women from 22 sites with stage II/III breast cancer for whom standard neoadjuvant therapy was planned. Of these, 58 patients had matched pre-and post-NAT samples available for analysis at the time of this pilot. All pre-NAT samples were analyzed for the presence of TSMs using Sysmex Inostics’ SafeSEQ. Patients with detectable ctDNA before NAT were also evaluated for residual ctDNA after completion of NAT but prior to surgery. Five samples were also tested by digital PCR (BEAMing) for cross-platform comparison. Results: TSMs in ctDNA were identified in 29 of 58 patients (50%) prior to NAT. Of pre-NAT ctDNA(+) patients, TSMs were detected in TP53 (90%) and PIK3CA (10%); three patients (10%) were found to have 2 TSMs. Concordance between SafeSEQ and BEAMing was 100% in five samples tested [3 ctDNA(+), 2 ctDNA(-)]. Of 29 ctDNA(+) patients, 24 (83%) demonstrated reduction or elimination of detectable ctDNA following neoadjuvant therapy, with 16 (55%) converting to ctDNA(-). Conclusion: Identification of TSMs in the plasma of early-stage breast cancer patients without the need for biopsy tissue is feasible using a SafeSEQ cancer mutation panel. Further measures to improve the sensitivity of pre-treatment TSM analysis, such as increased plasma volume input and comprehensive TP53 mutational analysis are currently under investigation. Correlations between clinicopathologic factors with ctDNA detection and burden, as well as the NPV of post-NAT ctDNA for pCR and residual cancer burden, will be reported at the time of abstract presentation. NH and HP contributed equally to this work. Citation Format: Natasha Hunter, Heather Parsons, Alexander Sherry, Daniel Shinn, Dong Ho Shin, Alex Cole, Giovanni Cragnotti, Taylor Groginski, Margaret Leathers, Andrea L Richardson, Pedram Argani, Antonio Wolff, Leslie Cope, Dan Edelstein, Frank Holtrup, Hilary Sloane, Bapsi Chakravarthy, Vered Stearns, Ben H Park. TBCRC 040: Pathologic response evaluation and detection in circulating tumor DNA (PREDICT DNA): Initial results piloting a tissue-biopsy independent method of identifying and monitoring tumor-specific mutations in early stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-05.

Objective Early warfarin anticoagulation is recommended in patients undergoing surgical bioprosthetic valve implantation or valve repair. It is unclear whether non-vitamin K antagonist oral anticoagulants can be a full alternative to warfarin. This study aimed to compare efficacy and safety of edoxaban with warfarin in patients early after surgical bioprosthetic valve implantation or valve repair. Methods The Explore the Efficacy and Safety of Edoxaban in Patients after Heart Valve Repair or Bioprosthetic Valve Replacement study was a prospective, randomized (1:1), open-label, clinical trial conducted from December 2017 to September 2019. Patients were randomly assigned to receive edoxaban (60 mg or 30 mg once daily) or warfarin for the first 3 months after surgical bioprosthetic valve implantation or valve repair. The primary efficacy outcome was a composite of death, clinical thromboembolic events, or asymptomatic intracardiac thrombosis. The primary safety outcome was the occurrence of major bleeding. Results Of 220 participants, 218 (109 per group) were included in the modified intention-to-treat analysis. The primary efficacy outcome occurred in 4 patients (3.7%) taking warfarin and none taking edoxaban (risk difference, −0.0367; 95% confidence interval, –0.0720 to –0.0014; P Conclusions Edoxaban is noninferior to warfarin for preventing thromboembolism and is potentially comparable for risk of major bleeding during the first 3 months after surgical bioprosthetic valve implantation or valve repair.

Background Phlomis umbrosa Turczaninow has been used as a tradition herbal medicine for treating various inflammatory diseases. Purpose In present study, we explored the effects of P. umbrosa on asthma induced by ovalbumin (OVA) and elucidated the mechanism via in vivo verification and network pharmacology prediction. Methods The animals were intraperitoneally injected OVA on day 1 and 14, followed by OVA inhalation on days 21, 22, and 23. The animals were daily treated P. umbrosa extract (PUE, 20 and 40 mg/kg) by oral gavage from day 18 to day 23. Results PUE significantly decreased airway hyperresponsiveness, eosinophilia, and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with a reduction in airway inflammation and mucus secretion in lung tissue. In network analysis, antiasthmatic effects of PUE were closely related with suppression of mitogen-activated protein kinases and matrix metalloproteinases (MMPs). Consistent with the results from network analysis, PUE suppressed the phosphorylation of ERK and p65, which was accompanied by a decline in MMP-9 expression. Conclusion Administration of PUE effectively reduced allergic responses in asthmatic mice, which was associated with the suppressed phosphorylation of ERK and p65, and expression of MMP-9. These results indicate that PUE has therapeutic potential to treat allergic asthma.

To automatically identify optimal beam angles for proton therapy configured with the double-scattering delivery technique, a beam angle optimization method based on a convolutional neural network (BAODS-Net) is proposed. Fifty liver plans were used for training in BAODS-Net. To generate a sequence of input data, 25 rays on the eye view of the beam were determined per angle. Each ray collects nine features, including the normalized Hounsfield unit and the position information of eight structures per 2° of gantry angle. The outputs are a set of beam angle ranking scores (Sbeam) ranging from 0° to 359°, with a step size of 1°. Based on these input and output designs, BAODS-Net consists of eight convolution layers and four fully connected layers. To evaluate the plan qualities of deep-learning, equi-spaced, and clinical plans, we compared the performances of three types of loss functions and performed K-fold cross-validation (K = 5). For statistical analysis, the volumes V27Gy and V30Gy as well as the mean, minimum, and maximum doses were calculated for organs-at-risk by using a paired-samples t-test. As a result, smooth-L1 loss showed the best optimization performance. At the end of the training procedure, the mean squared errors between the reference and predicted Sbeam were 0.031, 0.011, and 0.004 for L1, L2, and smooth-L1 loss, respectively. In terms of the plan quality, statistically, PlanBAO has no significant difference from PlanClinic (P >.05). In our test, a deep-learning based beam angle optimization method for proton double-scattering treatments was developed and verified. Using Eclipse API and BAODS-Net, a plan with clinically acceptable quality was created within 5 min.

Background Accurate and standardized descriptions of organs at risk (OARs) are essential in radiation therapy for treatment planning and evaluation. Traditionally, physicians have contoured patient images manually, which, is time-consuming and subject to inter-observer variability. This study aims to a) investigate whether customized, deep-learning-based auto-segmentation could overcome the limitations of manual contouring and b) compare its performance against a typical, atlas-based auto-segmentation method organ structures in liver cancer. Methods On-contrast computer tomography image sets of 70 liver cancer patients were used, and four OARs (heart, liver, kidney, and stomach) were manually delineated by three experienced physicians as reference structures. Atlas and deep learning auto-segmentations were respectively performed with MIM Maestro 6.5 (MIM Software Inc., Cleveland, OH) and, with a deep convolution neural network (DCNN). The Hausdorff distance (HD) and, dice similarity coefficient (DSC), volume overlap error (VOE), and relative volume difference (RVD) were used to quantitatively evaluate the four different methods in the case of the reference set of the four OAR structures. Results The atlas-based method yielded the following average DSC and standard deviation values (SD) for the heart, liver, right kidney, left kidney, and stomach: 0.92 ± 0.04 (DSC ± SD), 0.93 ± 0.02, 0.86 ± 0.07, 0.85 ± 0.11, and 0.60 ± 0.13 respectively. The deep-learning-based method yielded corresponding values for the OARs of 0.94 ± 0.01, 0.93 ± 0.01, 0.88 ± 0.03, 0.86 ± 0.03, and 0.73 ± 0.09. The segmentation results show that the deep learning framework is superior to the atlas-based framwork except in the case of the liver. Specifically, in the case of the stomach, the DSC, VOE, and RVD showed a maximum difference of 21.67, 25.11, 28.80% respectively. Conclusions In this study, we demonstrated that a deep learning framework could be used more effectively and efficiently compared to atlas-based auto-segmentation for most OARs in human liver cancer. Extended use of the deep-learning-based framework is anticipated for auto-segmentations of other body sites.

In this research, a multi-slit prompt-gamma camera was developed to locate the distal dose falloff of the proton beam spots in spot scanning proton therapy. To see the performance of the developed camera, therapeutic proton beams were delivered to a solid plate phantom and then the prompt gammas from the phantom were measured using the camera. Our results show that the camera locates the 90% distal dose falloff (= d90%), within about 2–3 mm of error for the spots which are composed 3.8 × 108 protons or more. The measured location of d90% is not very sensitive to the irradiation depth of the proton beam (i.e., the depth of proton beam from the phantom surface toward which the camera is located). Considering the number of protons per spot for the most distal spots in typical treatment cases (i.e., 2 Gy dose divided in 2 fields), the camera can locate d90% only for a fraction of the spots depending on the treatment cases. However, the information of those spots is still valuable in that, in the multi-slit prompt-gamma camera, the distal dose falloff of the spots is located solely based on prompt gamma measurement, i.e., not referring to Monte Carlo simulation. Keywords: Proton therapy, Prompt gamma, Beam range verification, Distal dose falloff

In this study for delivery quality assurance (DQA) of helical tomotherapy, we compared the Delta4 phantom system with the Gafchromic EBT3 film dosimetry system in eight cases and analyzed the global gamma-index passing rate (GPR) of various treatment sites in 109 cases. The mean GPR values for Delta4 and EBT3 film were 98.8% and 97.8%, respectively. GPR values were similar between Delta4 and film dosimetry, with a linear correlation factor of 72.4%. About 70% of the Delta4 cases had GPR values greater than 99%, although the GPR value was highly dependent on the clinical target size; GPR decreased approximately 3.7% when the target size increased by 3 cm. The GPR results show that Delta4 could be a better dosimetry tool than EBT3 film for tomotherapy DQA.

The mechanical-collimation imaging is the most mature technology in prompt gamma (PG) imaging which is considered the most promising technology for beam range verification in proton therapy. The purpose of the present study is to compare the performances of two mechanical-collimation PG cameras, knife-edge (KE) camera and multi-slit (MS) camera. For this, the PG cameras were modeled by Geant4 Monte Carlo code, and the performances of the cameras were compared for imaginary point and line sources and for proton beams incident on a cylindrical PMMA phantom. From the simulation results, the KE camera was found to show higher counting efficiency than the MS camera, being able to estimate the beam range even for 107 protons. Our results, however, confirmed that in order to estimate the beam range correctly, the KE camera should be aligned, at least approximately, to the location of the proton beam range. The MS camera was found to show lower efficiency, being able to estimate the beam range correctly only when the number of the protons is at least 108. For enough number of protons, however, the MS camera estimated the beam range correctly, errors being less than 1.2 mm, regardless of the location of the camera. Keywords: Proton therapy, Beam range verification, Prompt gamma, Knife-edge camera, Multi-slit camera

Ticagrelor has been widely accepted in clinical practice for treatment of acute myocardial infarction (AMI), however its clinical safety and efficacy have not been revealed sufficiently in Asian populations.Among a total 20,270 patients (age75 years) with AMI undergoing percutaneous coronary intervention who received dual antiplatelet therapy for at least 30 days, clinical outcomes at 1 year were assessed from the database of Health Insurance Review and Assessment Service in Korea between 2013 and 2014. Ticagrelor showed a significant effect on reduction of all-cause death [stabilized inverse probability of treatment weighted (sIPTW)-adjusted odds ratio (aOR) 0.57, 95% confidence interval (CI) 0.42-0.77, p0.001]. Stroke was also reduced by using ticagrelor (sIPTW-aOR 0.58, 95% CI 0.41-0.82, p=0.002). Bleeding risk was not increased by ticagrelor use. There were nearly 30% of patients who switched from ticagrelor to different P2Y12 inhibitors. Switching P2Y12 inhibitors was associated with clinical adverse events including MI, stroke, and bleeding.Among patients aged younger than 75 years, ticagrelor was associated with lower incidence of all-cause mortality. Stroke risk was also reduced in patients with a prescription for ticagrelor without an increase in bleeding risk.

Data concerning the clinical impact of combination therapy with β-blockers (BBs) + angiotensin-converting enzyme inhibitors (ACEIs) compared with BBs + angiotensin-receptor blockers (ARBs) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) are limited. We compared the clinical outcomes at 2 years between these two combination therapies. We enrolled 23,978 patients with AMI who underwent successful PCI with DES between January 2005 and June 2015 from the Korea AMI Registry (KAMIR) and divided them into the two groups: BB + ACEI (n = 17,310) and BB + ARB (n = 6668). The primary endpoint was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR. The secondary endpoints were the cumulative incidences of individual components of MACE and target vessel failure (TVF), a composite of death related to the target vessel, re-MI, or clinically driven TVR. The relative risk of MACE was higher in the BB + ARB group than in the BB + ACEI group after propensity score-matched (PSM) analysis (hazard ratio [HR] 1.204; 95% confidence interval [CI] 1.057–1.370; p = 0.005). The relative risks of all-cause death (HR 1.435 [95% CI 1.117–1.845]; p = 0.005), cardiac death (HR 1.733 [95% CI 1.253–2.396]; p = 0.001), TVR (HR 1.437 [95% CI 1.157–1.784]; p = 0.001), and TVF (HR 1.231 [95% CI 1.065–1.424]; p = 0.005) were also higher in the BB + ARB group after PSM. The BB + ACEI group demonstrated reduced cumulative incidences of MACE, all-cause death, cardiac death, TVR, and TVF compared with the BB + ARB group in patients with AMI who underwent successful PCI with DES during a 2-year follow-up period.

Thermal energy storage is an essential technology for using renewable energy to reduce building energy consumption. Among the various energy technologies, much attention has been paid to latent thermal energy storage system using phase change materials because of its large capacity of thermal energy. However, due to the low thermal conductivity of the phase change materials, the system has disadvantages at low charging and discharging rates. To address this issue, a new latent heat thermal energy storage system using a flexible and thin pouch is proposed. The effectively designed pouch arrangement and thin pouch shape provide better heat transfer performance. The real product is tested at various flow rates of heat transfer fluids and the thermal and fluid characteristics of the system are analyzed by the computational fluid dynamics model. As a result, the proposed system has 1.4 times larger amount of discharged energy than that of the water storage system. Moreover, the system can reduce charging, discharging, and total process times by 1.7, 2.5, and 2.2 times, respectively, compared with the conventional sphere capsule piling system.

This study compares the dosimetric characteristics of radiotherapy treatment methods for patients with a vestibular schwannoma. We generated and compared intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO), and proton therapy (Proton) treatment plans among eight patients with a vestibular schwannoma who received stereotactic radiosurgery based on M3 (M3-SRS) treatment. The dose comparison of the planning target volume (PTV) was performed by calculating the homogeneity index (HI), conformity index (CI), coverage index (CVI), and equivalent uniform dose (EUD). A dose comparison for adjacent normal organs was performed by calculating the EUD and the normal tissue complication probability (NTCP). The PTV coverage showed excellent dose homogeneity and conformity on the target volume for M3-SRS treatment. The sparing of the organs at risk (OARs) was excellent in terms of dose delivery to most normal organs away from the target for Proton; however, the other modalities were also within the tolerance dose limit for the OARs. This study further confirmed the possibility of using radiotherapy, along with the use of other treatment methods, for patients with a vestibular schwannoma.

We compared the clinical impact of renin-angiotensin system inhibitors (RASI) on long-term clinical outcomes between ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) after successful percutaneous coronary intervention (PCI) with drug eluting stents (DES) because of the paucity of published data.A total of 24,960 acute myocardial infarction (AMI) patients who underwent PCI with DES and were prescribed the RASI were enrolled and divided into two groups, the STEMI group (n = 14,061) and the NSTEMI group (n = 10,899). The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, cardiac death (CD), recurrent myocardial infarction (re-MI), total coronary revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], non-TVR) during 2 years.After propensity score-matched (PSM) analysis, two PSM groups (6762 pairs, n = 13,524, C-statistic = 0.682) were generated. All-cause death (hazard ratio [HR], 1.386; 95% confidence interval [CI], 1.114-1.725; p = 0.003) and CD (HR, 1.358; 95% CI, 1.041-1.770; p = 0.024) rates were significantly higher in NSTEMI patients. However, the incidence of MACE, re-MI, total revascularization, TLR, TVR, non-TVR was not significantly different between the two groups. In addition, old age (≥65years), decreased left ventricular ejection fraction (50%), hypertension, creatine kinase isoenzyme level, cardiogenic shock, cardiopulmonary resuscitation on admission, and PCI within 24 h were common significant independent risk factors of all-cause death and CD.The mortality reduction capability of RASI was more prominent in the STEMI patients compared with the NSTEMI patients.

Latent heat thermal energy storage (LHTES) affords superior thermal energy capacity and compactness but has limited applications due to the low thermal conductivity of phase change materials (PCMs). Several researches have focused on the improvement of heat transfer and reducing the total melting time of PCMs in LHTES system. Few researches, however, have used flexible PCM containers for this purpose. This study used a flexible elliptical container as a PCM container for improving LHTES heat transfer performance. The effects of the axis ratio (AR) and temperature difference on the thermal charging performance were numerically studied within a single container. Smaller AR values improved the heat transfer performance by promoting heat conduction and natural convection inside the containers. The enhancement rate was increased by 1.1–2.7 times for an AR range of 0.05–0.20 compared to a classic circular container (AR = 1). In addition, the elliptical container showed superior in terms of energy density reduction. Therefore, the elliptical container with optimum AR range (0.05–0.20) can be considered a suitable configuration for effective heat transfer enhancement of PCM containers.

Objectives: This study sought to measure early strut coverage in patients receiving drug-eluting stents (DESs) and to explore the feasibility of short-term dual antiplatelet therapy (DAPT) ...

Background Although antiplatelet therapy (APT) has been recommended to balance ischemic‐bleeding risks, it has been left to an individualized decision‐making based on physicians' perspectives before non‐cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug‐eluting stents. Methods and Results A total of 3582 adult patients undergoing non‐cardiac surgery after percutaneous coronary intervention with second‐generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non‐cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [OR adj ], 1.98; 95% CI, 1.98–3.11), major adverse cardiac event (OR adj , 3.11; 95% CI, 1.31–7.34), and major bleeding (OR adj , 2.34; 95% CI, 1.45–3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT. Conclusions Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03908463.

Background There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation. Methods and Results From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus‐Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate 2 were associated with an increased risk of major bleeding. In contrast, 3‐month aspirin therapy with continued ticagrelor (versus 12‐month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3‐month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39–0.90; P interaction =0.74). Conclusions Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk. Registration URL: https://www.clinicaltrials.gov/ . Unique Identifier: NCT02494895.

Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

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

Immune enhancement of virotherapy by reshaping the tumor immune landscape may improve its success rates. IDO, an IFNγ inducible tryptophan catabolizing enzyme, is upregulated in glioblastoma, correlating with poor prognoses. IDO-mediated tryptophan depletion in the tumor-microenvironment decreases proliferation and induces apoptosis of surrounding effector T-cells. Kynurenine, a metabolite of tryptophan, induces T-cell differentiation into immunosuppressive Tregs. Excess kynurenine elicits AhR-mediated lymphocyte dysfunction and immunosuppression. The immune stimulating effect of oncolytic-virus, Delta-24-RGDOX, triggers IFNγ production contributing to a positive IDO-Kynurenine-AhR feedback loop. We hypothesized that combining Delta-24-RGDOX with IDO inhibitors will synergize to effectively treat glioblastoma. We characterized IDO and AhR in Delta-24-RGDOX infected cancers using immunofluorescence, qRT-PCR, and flow cytometry and found increased expression of both proteins in vitro and in vivo. We also observed induction of AhR in CD4+ and CD8+ T-cells by Delta-24-RGDOX in vivo. Delta-24-RGDOX also increased activity of AhR in cancer cells as indicated by an AhR responsive elements transcription assay. We used a murine glioblastoma model to test the efficacy of combining Delta-24-RGDOX with IDO inhibitor, 1MT/indoximod; the combination produced 30% more long-term survivors compared Delta-24-RGDOX alone (P=0.03), which we showed, through lymphocytic depletion studies, was dependent on CD4+ T-cell activation. We observed 100% survival in the re-challenged long-term glioblastoma survivors, indicating the establishment of immune memory by the combination. Functional studies showed significant increases in anti-tumor activity of splenocytes from combination-treated mice compared to Delta-24-RGDOX-treated mice (P=0.009). Flow cytometry studies revealed that combination-treated mice yielded the highest levels of chronically activated T-cells and lowest levels of Tregs and myeloid derived suppressor cells compared to Delta-24-RGDOX single treatment (P≤0.05). This microenvironment remodeling correlated with complete tumor elimination. Altogether, Delta-24-RGDOX activates the IDO-Kyn-AhR cascade in gliomas, identifying new targets, which when inhibited have the potential to enhance the anti-glioma effect of oncolytic-viruses by reversing tumor immunosuppression.

Background The clinical implications of optical coherence tomography (OCT) assessment following percutaneous coronary intervention are controversial. Purpose We sought to evaluate the impact of post-stent OCT findings, including significant malapposition, on long-term clinical outcomes. Methods A total of 1,290 patients with 1,348 lesions, in which OCT was performed immediately post-stent, were consecutively enrolled in the prospective OCT registry. Post-stent OCT findings were assessed to identify predictors of device-oriented clinical end points (DoCE), including cardiac death, target vessel-related myocardial infarction (MI), stent thrombosis, and target lesion revascularization (TLR). We also looked for significant malapposition criteria that may be associated with thrombotic events such as cardiac death, target vessel-related MI, and stent thrombosis. Results Incidences of stent edge dissection, tissue prolapse, thrombus, and malapposition after intervention were not associated with occurrence of adverse thrombotic events. However, patients with significant malapposition [total malapposition volume (TMV) ≥7.0 mm3 or TMV/stent volume ≥4.1%] exhibited more frequent thrombotic events. In multivariate analysis, smaller minimal stent area (MSA) was identified as an independent predictor for DoCE (hazard ratio [HR], 1.21 [1.01–1.45]; P=0.037). Malapposition with TMV ≥7.0 mm3 was found to be an independent predictor of thrombotic events (HR, 4.62 [1.29–16.47]; P=0.018). Conclusions Although most high-resolution OCT findings were not associated with clinical outcome, smaller MSA was associated with DoCE, driven mainly by TLR, and significant malapposition with TMV ≥7.0 mm3 was associated with more thrombotic events after drug-eluting stent implantation. Kaplan-Meier curve Funding Acknowledgement Type of funding source: None

Background Continuing antiplatelet therapy ( APT ) has been generally recommended during noncardiac surgery, but it is uncertain if preoperative discontinuation of APT has been avoided or harmful in patients with second‐generation drug‐eluting coronary stents. Methods and Results Patients undergoing noncardiac surgery after second‐generation drug‐eluting coronary stent implantation were assessed in a multicenter cohort in Korea. Net adverse clinical events within 30 days postoperatively, defined as all‐cause death, major adverse cardiac events, and major bleeding, were evaluated. Of 3582 eligible patients, 49% patients discontinued APT during noncardiac surgery. The incidence of net adverse clinical events was comparable between patients with continuation versus discontinuation (4.1% versus 3.4%; P =0.257) of APT during noncardiac surgery. Perioperative discontinuation of APT did not impact on net adverse clinical events (adjusted hazard ratio [HR], 1.00; 95% CI, 0.69–1.44; P =0.995). In subgroup analysis, patients undergoing intra‐abdominal surgery were exposed to less risk of major bleeding by discontinuing APT (adjusted HR, 0.26; 95% CI , 0.08–0.91; P =0.035). Prolonged discontinuation of APT for ≥9 days was associated with higher risk of a major adverse cardiac event compared with continuing APT (adjusted HR, 3.38; 95% CI, 1.36–8.38; P =0.009). Conclusions APT was discontinued preoperatively in almost half of patients with second‐generation drug‐eluting coronary stents. Our explorative analysis showed that there was no significant impact of discontinuing APT on the risk of perioperative adverse events except that discontinuing APT may be associated with decreased hemorrhagic risk in patients undergoing intra‐abdominal surgery. Registration URL : https://www.clini​caltr​ials.gov ; Unique identifier: NCT 03908463.

While the bone morphogenetic protein‐7 (BMP‐7) is a well‐known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half‐life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein‐7 (BMP‐7). This study aims at evaluating the therapeutic effects of PTD‐BMP‐7 consisted of PTD and full‐length BMP‐7 on epithelial‐mesenchymal transition (EMT)‐related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF‐β1 or TGF‐β1 + PTD‐BMP‐7. Peritoneal dialysis (PD) catheters were inserted into Sprague‐Dawley rats, and these rats were infused intra‐peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD‐BMP‐7. In vitro, TGF‐β1 treatment significantly increased fibronectin, type I collagen, α‐SMA and Snail expression, while reducing E‐cadherin expression in HPMCs (P

Static intra-access pressure ratio (SIAPR) measurement, using haemodialysis machine transducers, is the vascular access surveillance method in patients undergoing haemodialysis. However, little is known about the relationship between the SIAPR and arterial stiffness, and the clinical usefulness of the SIAPR in predicting cardiovascular events. A total of 209 patients undergoing maintenance haemodialysis were evaluated. The SIAPRs ranged from 0.01 to 0.52 (median: 0.23). When the patients were divided into two groups according to their median of SIAPR, the incidence of previous cardiovascular disease, E/E′ ratio, and brachial-ankle pulse wave velocity were significantly higher in the patients with SIAPRs of ≤0.23 than in those with SIAPRs of >0.23. Conversely, patients with worse comorbid status had a lower SIAPR than patients without it. In the Kaplan-Meier analysis, the cumulative incidence of cardiovascular events was significantly higher in the patients with SIAPRs of ≤0.23 than in those with SIAPRs of >0.23 (P

Microencapsulated phase change slurry (MPCS) is a multiphase fluid with considerable potential to be a next-generation thermal energy transport material because of its high latent heat capacity and heat transfer rate. However, this encapsulated phase change slurry is difficult to transport because of its high viscosity, and its usage with conventional heat exchangers is complex. Therefore, in this study, a new type of thermal energy transport system using a rotary screw fin heat exchanger is developed for the safe and effective transportation of capsules. The long-distance direct PCM transport and MPCMS transport were firstly validated with the new system. The developed system played a role of pumping and heat exchanger has a pipe that rotates and transports MPCS using screw fins and enables the easy flow of water, resulting in enhancement of convective heat transfer. The results indicate that MPCS (

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

PURPOSE Fabricate an acrylic disk radiation sensor (ADRS) and characterize the photoluminescence signal generated from the optical device as basis for the development and evaluation of a new dosimetry system for pencil beam proton therapy. METHODS Based on the characteristics of the proposed optical dosimetry sensor, we established the relation between the photoluminescence output and the applied dose using an ionization chamber. Then, we obtained the relative integral depth dose profiles using the photoluminescence signal generated by pencil beam irradiation at energies of 99.9 and 162.1 MeV, and compared the results with the curve measured using a Bragg peak ionization chamber. RESULTS The relation between the photoluminescence output and applied dose was linear. In addition, the ADRS was dose independent for beam currents up to 6 Gy/min, and the calibration factor for energy was close to 1. Hence, the energy dependence on the optical device can be disregarded. The integral depth dose profiles obtained for the ADRS suitable agreed with the curve measured in the Bragg peak ionization chamber without requiring correction. CONCLUSIONS These results suggest that the ADRS is suitable for dosimetry measurements in pencil beam scanning, and it will be employed as a low-cost and versatile dosimetry sensor in upcoming developments.

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

AIMS We sought to investigate the incidence, predictors, and clinical outcomes of stent optimisation with intravascular ultrasound (IVUS) in long coronary lesions treated with new-generation drug-eluting stents (DESs). METHODS AND RESULTS From four randomised trials comparing IVUS and angiography guidance in long (≥26 mm) or chronic total occlusion coronary lesions, a total of 1,396 patients who underwent IVUS-guided intervention were classified into two groups (stent optimisation and non-optimisation) according to optimisation criteria (minimal stent area [MSA] ≥5.5 mm2 or 80% of mean reference lumen area [MLA]). Major adverse cardiac event (MACE) occurrence, defined as a composite of cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularisation, was compared. Stent optimisation was not met in 578 (41%) patients. Predictors of non-optimisation were older age, longer lesion length, and smaller stent diameter. The MACE rate was significantly higher in the non-optimisation versus the stent optimisation group (4.8% vs 1.9%, log-rank p=0.002; adjusted hazard ratio 2.95, 95% CI: 1.43-6.06). Among possible combinations of absolute and relative expansion criteria, the one best predicting MACE was at least one of MSA ≥5.4 mm2 and/or ≥80% of MLA (Youden index=0.264). CONCLUSIONS Achieving stent optimisation using IVUS evaluation was associated with favourable outcomes in IVUS-guided, new-generation DES implantation for long coronary lesions including CTOs.

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

The aim of the present study was to verify the dosimetric accuracy of two-dimensional (2D) in vivo rectal dosimetry using an endorectal balloon (ERB) with unfoldable EBT3 films for high-dose-rate (HDR) brachytherapy for cervical cancer. The clinical applicability of the technique was discussed.ERB inflation makes the EBT3 films unrolled, whereas its deflation makes them rolled. Patient-specific quality assurance (pQA) tests were performed in 20 patient plans using an Ir-192 remote afterloading system and a water-filled cervical phantom with the ERB. The dose distributions measured in ERBs were compared with those of the treatment plans.The absolute dose profiles measured by the ERBs were in good agreement with those of treatment plans. The global gamma passing rates were 96-100% and 91-100% over 20 pQAs under the criteria of 3%/3 mm and 3%/2 mm, respectively, with a 30% low-dose threshold. Dose-volume histograms of the rectal wall were obtained from the measured dose distributions and showed small volume differences less than 2% on average from the patients' plans over the entire dose interval. The positioning error of the applicator set was detectable with high sensitivity of 12% dose area variation per mm. Additionally, the clinical applicability of the ERB was evaluated in volunteers, and none of them felt any pain when the ERB was inserted or removed.The 2D in vivo rectal dosimetry using the ERB with EBT3 films was effective and might be clinically applicable for HDR brachytherapy for cervical and prostate cancers to monitor treatment accuracy and consistency as well as to predict rectal toxicity.

The vision sensor on a vehicle platform with dynamic motion is affected severely by disturbances that occur owing to vehicle dynamic movement, which results in the degradation of outputs from visio...

Resumen Introduccion y objetivos La vigente guia de practica clinica para el tratamiento de la hipercolesterolemia recomienda mantener la terapia intensiva con estatinas de los pacientes tratados con implante de stent farmacoactivo (SFA). Sin embargo, el tratamiento intensivo con estatinas, una vez estabilizado el paciente, con frecuencia no se lleva a cabo en la practica clinica tras la revascularizacion con SFA. Actualmente se desconoce el impacto de mantener esa terapia intensiva con estatinas en estos pacientes estables. Se estudia la reduccion de eventos adversos en pacientes clinicamente estables en monoterapia con acido acetilsalicilico tras el implante de un SFA segun la terapia de alta o baja intensidad con estatinas. Metodos Se aleatorizo a pacientes estables a los 12 meses del implante de un SFA y en monoterapia con acido acetilsalicilico a recibir terapia de alta intensidad con estatinas (atorvastatina 40 mg; n = 1.000) o terapia de baja intensidad (pravastatina 20 mg; n = 1.000). El objetivo primario fueron los eventos clinicos adversos a los 12 meses de seguimiento (objetivo compuesto de muerte, infarto de miocardio, revascularizacion, trombosis del stent, accidente cerebrovascular, insuficiencia renal, necesidad de intervencion arterial periferica y nuevo ingreso hospitalario por eventos cardiacos). Resultados El objetivo primario a los 12 meses de seguimiento se produjo en 25 pacientes (2,5%) en tratamiento de alta intensidad con estatinas y en 40 (4,1%) en tratamiento de baja intensidad (HR = 0,58; IC95%, 0,36-0,92; p = 0,018). Esta diferencia se debio principalmente a la menor incidencia de muerte cardiaca (0 frente al 0,4%; p = 0,025) y de infarto de miocardio no relacionado con el vaso diana (el 0,1 frente al 0,7%; p = 0,033) en el grupo de tratamiento de alta intensidad con estatinas. Conclusiones Entre los pacientes clinicamente estables en monoterapia con acido acetilsalicilico, el tratamiento de alta intensidad con estatinas redujo la incidencia de eventos comparado con el tratamiento de baja intensidad. Registro de ensayos clinicos: URL: http://www.clinicaltrials.gov . Identificador unico: NCT01557075 .

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

To apply a scintillating fiber dosimetry system to measure the range of a proton therapy beam, a new method was proposed to correct for the quenching effect on measuring an spread out Bragg peak (SOBP) proton beam whose range is modulated by a range modulator wheel. The scintillating fiber dosimetry system was composed of a plastic scintillating fiber (BCF-12), optical fiber (SH 2001), photo multiplier tube (H7546), and data acquisition system (PXI6221 and SCC68). The proton beam was generated by a cyclotron (Proteus-235) in the National Cancer Center in Korea. It operated in the double-scattering mode and the spread out of the Bragg peak was achieved by a spinning range modulation wheel. Bragg peak beams and SOBP beams of various ranges were measured, corrected, and compared to the ion chamber data. For the Bragg peak beam, quenching equation was used to correct the quenching effect. On the proposed process of correcting SOBP beams, the measured data using a scintillating fiber were separated by the Bragg peaks that the SOBP beam contained, and then recomposed again to reconstruct an SOBP after correcting for each Bragg peak. The measured depth-dose curve for the single Bragg peak beam was well corrected by using a simple quenching equation. Correction for SOBP beam was conducted with a newly proposed method. The corrected SOBP signal was in accordance with the results measured with an ion chamber. We propose a new method to correct for the SOBP beam from the quenching effect in a scintillating fiber dosimetry system. This method can be applied to other scintillator dosimetry for radiation beams in which the quenching effect is shown in the scintillator.

Objectives This study sought to evaluate the optimal duration of dual antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES) in elderly patients. Background Qualified studies to evaluate the optimal duration of DAPT in elderly patients have been very limited. Methods Using 6 randomized trials that compared short-term (≤6 months) and long-term (12 months) DAPT, individual participant data meta-analysis was performed in elderly patients (≥65 years of age). The primary study outcome was the 12-month risk of a composite of myocardial infarction, definite or probable stent thrombosis, or stroke. The major secondary outcome was the 12-month risk of major bleeding. Results The primary outcome risk did not significantly differ between patients receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.88 to 1.43; p = 0.3581) in the overall group of study participants. In subgroup analysis, a significant interaction between age and DAPT duration was observed for primary outcome risk (p for interaction = 0.0384). In the subset of younger patients ( Conclusions Short-term DAPT after new-generation DES implantation may be more beneficial in elderly patients than in younger patients.