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Objective There are growing interests on suicide risk screening in clinical settings and classifying high-risk groups of suicide with suicidal ideation is crucial for a more effective suicide preventive intervention. Previous statistical techniques were limited because they tried to predict suicide risk using a simple algorithm. Machine learning differs from the traditional statistical techniques in that it generates the most optimal algorithm from various predictors.Methods We aim to analyze the Personality Assessment Inventory (PAI) profiles of child and adolescent patients who received outpatient psychiatric care using machine learning techniques, such as logistic regression (LR), random forest (RF), artificial neural network (ANN), support vector machine (SVM), and extreme gradient boosting (XGB), to develop and validate a classification model for individuals with high suicide risk.Results We developed prediction models using seven relevant features calculated by Boruta algorithm and subsequently tested all models using the testing dataset. The area under the ROC curve of these models were above 0.9 and the RF model exhibited the best performance.Conclusion Suicide must be assessed based on multiple aspects, and although Personality Assessment Inventory for Adolescent assess an array of domains, further research is needed for predicting high suicide risk groups.

Introduction Leakage is a serious and potentially fatal complication of gastrectomy for gastric cancer. However, comprehensive reports regarding leakage after gastrectomy remain limited. We aimed to evaluate the incidence and treatment outcomes of leakage after gastrectomy for cancer. Methods We reviewed the prospectively collected data of 14,075 Patients who underwent gastrectomy for gastric cancer between 2005 and 2017. Outcomes included incidence, risk factors of leakage, and leakage treatment outcomes. Results The median day of leakage detection was postoperative day 7 (range 1–29days). The overall leakage incidence was 1.51% (213/14,075), and the most frequent location was the oesophagojejunostomy (2.07%). Leakage after total gastrectomy was more frequent with minimally invasive surgery (open:1.64%, laparoscopic:3.56%, robotic:5.83%; P Conclusions Leakage after gastric cancer surgery is associated with high mortality. Improved surgeon experience using minimally invasive techniques is required to reduce the risk of leakage. Surgery is an effective treatment for early leakage, although further studies are needed to establish the most appropriate treatment strategies.

Background: Muscle undergoes change continuously with aging. Sarcopenia, in which muscle mass decrease with aging, is associated with various diseases, the risk of falling, and the deterioration of quality of life. Obesity and sarcopenia also have a synergy effect on the disease of the older adults. Objects: This study examined the risk factors for sarcopenia, sarcopenic obesity, and sarcopenia without obesity and developed prediction models. Methods: This machine-learning study used the 2008–2011 Korea National Health and Nutrition Examination Surveys in the analysis. After data curation, 5,563 older participants were selected, of whom 1,169 had sarcopenia, 538 had sarcopenic obesity, and 631 had sarcopenia without obesity; the remaining 4,394 were normal. Decision tree and random forest models were used to identify risk factors. Results: The risk factors for sarcopenia chosen by both methods were body mass index (BMI) and duration of moderate physical activity; those for sarcopenic obesity were sex, BMI, and duration of moderate physical activity; and those for sarcopenia without obesity were BMI and sex. The areas under the receiver operating characteristic curves of all prediction models exceeded 0.75. BMI could predict sarcopenia-related disease. Conclusion: Risk factors for sarcopenia-related diseases should be identified and programs for sarcopenia-related disease prevention should be developed. Data-mining research using population data should be conducted to enhance the effectiveness of early treatment for people with sarcopenia-related diseases through predictive models.

Background: Postural control deficit is a major characteristic in patients with chronic ankle instability (CAI). Elastic ankle tapings are commonly used to facilitate postural control in patients with CAI as well as prevent relapse of a lateral ankle sprain. However, equivocal evidence exists concerning the effect of elastic ankle taping on postural control. Objects: This study aimed to evaluate the effects of elastic ankle tapings using kinesio taping (KT) and dynamic taping (DT) on static and dynamic postural control in patients with CAI. Methods: Fifteen subjects with CAI were participated in this study. The participants performed tests under three conditions (barefoot, KT, and DT). Static postural control was evaluated using the one-leg standing test (OLST) and dynamic postural control using the modified Star Excursion Balance Test (mSEBT). One-way repeated-measures analysis of variance was used to compare center of pressure (CoP) data and normalized mSEBT reach distances among the three conditions (with α = 0.05). Results: The CoP parameters (path length, ellipse area, and mean velocity) of the OLST significantly decreased on applying KT and DT compared with those when barefoot. The normalized reach distances in the anteromedial (AM), medial (M), and posteromedial (PM) directions of the mSEBT significantly increased with DT compared to that in the control condition. Further, the higher reach distances with KT compared with those in the control condition were obtained in the M and PM directions of the mSEBT. No significant differences were identified in any of the OLST and SEBT parameters between the two different taping applications. Conclusion: KT and DT improved static postural control during the OLST compared with the control condition. Moreover, these tapes improved dynamic postural control during the mSEBT compared to the control. Therefore, elastic ankle tapings are useful prophylactic devices for the prevention and treatment of ankle sprain in people with CAI.

PURPOSE We propose a deep learning method that classifies focal liver lesions (FLLs) into cysts, hemangiomas, and metastases from portal phase abdominal CT images. We propose a synthetic data augmentation process to alleviate the class imbalance and the Lesion INformation Augmented (LINA) patch to improve the learning efficiency. METHODS A dataset of 502 portal phase CT scans of 1,290 FLLs was used. First, to alleviate the class imbalance and to diversify the training data patterns, we suggest synthetic training data augmentation using DCGAN-based lesion mask synthesis and pix2pix-based mask-to-image translation. Second, to improve the learning efficiency of convolutional neural networks (CNNs) for the small lesions, we propose a novel type of input patch termed the LINA patch to emphasize the lesion texture information while also maintaining the lesion boundary information in the patches. Third, we construct a multi-scale CNN through a model ensemble of ResNet-18 CNNs trained on LINA patches of various mini-patch sizes. RESULTS The experiments demonstrate that (a) synthetic data augmentation method shows characteristics different but complementary to those in conventional real data augmentation in augmenting data distributions, (b) the proposed LINA patches improve classification performance compared to those by existing types of CNN input patches due to the enhanced texture and boundary information in the small lesions, and (c) through an ensemble of LINA patch-trained CNNs with different mini-patch sizes, the multi-scale CNN further improves overall classification performance. As a result, the proposed method achieved an accuracy of 87.30%, showing improvements of 10.81%p and 15.0%p compared to the conventional image patch-trained CNN and texture feature-trained SVM, respectively. CONCLUSIONS The proposed synthetic data augmentation method shows promising results in improving the data diversity and class imbalance, and the proposed LINA patches enhance the learning efficiency compared to the existing input image patches.

Impacted mandibular third molars (M3M) are associated with the occurrence of distal caries on the adjacent mandibular second molars (DCM2M). In this study, we aimed to develop and validate five machine learning (ML) models designed to predict the occurrence of DCM2Ms due to the proximity with M3Ms and determine the relative importance of predictive variables for DCM2Ms that are important for clinical decision making. A total of 2642 mandibular second molars adjacent to M3Ms were analyzed and DCM2Ms were identified in 322 cases (12.2%). The models were trained using logistic regression, random forest, support vector machine, artificial neural network, and extreme gradient boosting ML methods and were subsequently validated using testing datasets. The performance of the ML models was significantly superior to that of single predictors. The area under the receiver operating characteristic curve of the machine learning models ranged from 0.88 to 0.89. Six features (sex, age, contact point at the cementoenamel junction, angulation of M3Ms, Winter's classification, and Pell and Gregory classification) were identified as relevant predictors. These prediction models could be used to detect patients at a high risk of developing DCM2M and ultimately contribute to caries prevention and treatment decision-making for impacted M3Ms.

Background/Aims Previous studies have investigated the relationship between visceral obesity and the risk of colorectal tumors. Visceral obesity may affect the outcome of colorectal cancer (CRC), including survival and metastasis. We investigated the associations between visceral adipose tissue and oncologic outcomes in stage III CRC. Methods Four hundred seventy-two patients with stage III CRC were identified. Subcutaneous and visceral adipose tissue areas were measured volumetrically via computed tomography for each patient at different levels of the lumbar spine. After adjusting for age, sex, and other clinical factors, the effects of visceral adipose tissue area on mortality and recurrence were assessed using Cox proportional hazard regression. Results In univariate and multivariate analyses, a higher visceral adipose tissue to total adipose tissue (VT) ratio (hazard ratio [HR], 1.041; 95% CI, 1.008 to 1.075; p=0.015) and higher visceral adipose tissue to subcutaneous adipose tissue (VS) ratio (HR, 1.016; 95% CI, 1.005 to 1.028; p=0.006) were both associated with poor CRC-specific survival. Interestingly, in the evaluation of each site of recurrence, a higher VT ratio (HR, 1.069; 95% CI, 1.010 to 1.131; p=0.020) and higher VS ratio (HR, 1.024; 95% CI, 1.003 to 1.045; p=0.023) were both related to a higher risk of peritoneal seeding and tumor recurrence. The VT ratio at the L3-L4 level was significantly associated with a higher risk of peritoneal seeding and tumor recurrence (HR, 4.969; 95% CI, 1.303 to 18.949; p=0.019), while other levels showed no such relationship. Conclusions Visceral obesity is closely related to increased risks of CRC-specific mortality and peritoneal seeding metastasis in stage III CRC patients.

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT‐P17 to United States‐licensed adalimumab (US‐adalimumab) and European Union‐approved adalimumab (EU‐adalimumab). This double‐blind, parallel‐group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT‐P17, US‐adalimumab, or EU‐adalimumab. Primary end points were PK equivalence in terms of: area under the concentration–time curve from time zero to infinity (AUC0–inf); AUC from time zero to the last quantifiable concentration (AUC0–last); and maximum serum concentration (Cmax). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80–125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT‐P17; 103 US‐adalimumab; 106 EU‐adalimumab), 308 subjects received study drug. AUC0–inf, AUC0–last, and Cmax were equivalent among CT‐P17, US‐adalimumab, and EU‐adalimumab, because 90% CIs for the ratios of GLSMs were within the 80–125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single‐dose administration of CT‐P17, EU‐adalimumab, and US‐adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.

Background: Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients. Methods: The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases—Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS. The primary end point was a patient-oriented composite outcome (a composite of all-cause death, nonfatal myocardial infarction, and any repeat revascularization) at 12 months. The key secondary end point was device-oriented composite outcome (a composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) at 12 months. Results: A total of 3413 patients were randomized to receive the DP-DES (1713 patients) and BP-DES (1700 patients). At 12 months, patient-oriented composite outcome occurred in 5.2% in the DP-DES group and 6.4% in the BP-DES group (absolute risk difference, –1.2%; P non inferiority P =0.038), mostly because of a reduction in target lesion revascularization. The rate of spontaneous nonfatal myocardial infarction and stent thrombosis were extremely low, with no significant difference between the 2 groups (0.6% versus 0.8%; P =0.513 and 0.1% versus 0.4%; P =0.174, respectively). Conclusions: In ACS patients receiving percutaneous coronary intervention, DP-DES was noninferior to BP-DES with regard to patient-oriented composite outcomes at 12 months after index percutaneous coronary intervention. Registration: URL: https://wwwclinicaltrials.gov ; Unique identifier: NCT02193971.

Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, it may prolong the QTc interval. Furthermore, when hydroxychloroquine is administered concomitantly with other drugs, it can exacerbate the risk of QT prolongation. Nevertheless, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and concomitant medications has not yet been identified. To evaluate the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice, we analyzed the electrocardiogram results obtained for 447,632 patients and their relevant electronic health records in a tertiary teaching hospital in Korea from 1996 to 2018. We repeated the case–control analysis for each drug. In each analysis, we performed multiple logistic regression and calculated the odds ratio (OR) for each target drug, hydroxychloroquine, and the interaction terms between those two drugs. The DDIs were observed in 12 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, cyclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, isoniazid, clarithromycin, and furosemide), all with a p value of

Background: Paclitaxel is a microtubule stabilizing anticancer therapy used to treat multiple cancers including breast cancer. DHP107 is an oral paclitaxel solubilized in lipid components using DaeHwa-Lipid bAsed Self-Emulsifying Drug delivery system (DH-LASED) technology. It demonstrated comparable efficacy and safety to IV paclitaxel in a phase 3 study for patients with advanced gastric cancer (Ann Oncol 2018) leading to regulatory approval in Korea, and also met the primary endpoint (ORR 54.5%) as first-line therapy (ESMO 2019) in the OPTIMAL Phase II study in patients with HER2 negative metastatic breast cancer (MBC). The confirmatory OPTIMAL Phase III study is ongoing in Asia and Europe. The OPERA Phase II study was designed as multinational, multicenter, randomized, open-label study to establish pharmacokinetic (PK) profile and efficacy of DHP107 in patients with MBC in the U.S. Method: A total of 72 patients with metastatic HER2 negative (HR+/HER2- or triple-negative breast cancer (TNBC)) will be randomized in a 2:1 fashion to receive DHP107 (200mg/m2 orally twice a day on Days 1, 8, and 15 in a 28-day cycle) or IV paclitaxel (80 mg/m2 on Days 1, 8, and 15 in a 28-day cycle) until disease progression or unacceptable toxicity. Tumor assessments are performed every 8 weeks. PK analyses were performed in a subset of patients receiving DHP107. A total of 103 blood samples were collected on Day 1 of Cycle 1 at predose and 1, 2, 3, 4, 6, and 10 hours post dose (before the 2nd dose administration on Day 1), and at predose on Day 8 of Cycle 1. All PK parameters were calculated by non-compartmental analysis using Phoenix WinNonlin version® 8.1. Results: A total of 13 subjects were enrolled in the PK substudy, All 13 patients were female and of Caucasian, non-Hispanic, ethnicity. Median Tmax was 2.17 h (range 1.92-4.08). Mean Cmax and AUC0-10h and their coefficient of variations (CV) were 330 ng/mL (31.1%) and 1233 ng·h/mL (30.3%), respectively (Table 1). The PK parameters of DHP107 were similar to those in a previous Phase I study in Korean cancer patients where Cmax and AUC0-48h were 235 ng/mL (43.9%) and 1348 ng·h/mL (19.7%) (Invest New Drugs 2012). Conclusion: PK profiles were well characterized from plasma concentrations in 13 Caucasian patients with MBC up to 10 hours after oral 200mg/m2 BID administration. DHP107 was rapidly absorbed and eliminated and inter-individual variability in exposure such as Cmax and AUClast was considered low. Compared to previous phase I PK results in Korean patients, Cmax and AUC parameters were similar after dosing with DHP107, demonstrating no clinically significant differences between Asian and Caucasian patients. Safety and efficacy will be evaluated in the ongoing OPERA and OPTIMAL studies. Table 1StatisticTmax(h)Cmax(ng/mL)AUClast, 0-10h(ngh/mL)AUCinf(ngh/mL)N13131311Mean(SD)330(103)1233(374)1462(411)CV%31.130.328.1Median[Min-Max]2.17[1.92-4.08] Citation Format: Hope S Rugo, Timothy J Pluard, Priyanka Sharma, Michelle Melisko, Ghassan Al-Jazayrly, Neelima Vidula, Yan Ji, David Weng, Hyeong-Seok Lim, Koung Eun Yoon, Hyun Ju Cho. Pharmacokinetic evaluation of an oral paclitaxel DHP107 (Liporaxel®) in patients with recurrent or metastatic breast cancer (MBC): Phase II study (OPERA, NCT03326102) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-16.

Purpose Previous estimates of the cause- and age-specific frequency of pediatric meningitis in Korea were mainly derived from single- and multi-center studies. Herein, we used data on the number of cases of bacterial and viral meningitis from the Health Insurance Review and Assessment Service database to examine time- and sex-related trends. Methods We extracted data on meningitis diagnoses registered in the Health Insurance Review and Assessment Service from 2009 to 2017, using Korean Standard Classification of Disease and Cause of Death codes. Information on 202,254 children aged 0 to 18 years was extracted. Detailed demographic and disease information was available for 84,543 children who underwent hospitalization. Results Among all hospitalized patients, 2166, 36,155, and 46,192 children were diagnosed with bacterial, viral, or other types of meningitis, respectively. There were 30 cases of fungal meningitis and another 30 cases of meningitis attributable to other pathogens. The number of cases of bacterial and viral meningitis was highest among infants (1,087 [50.2%]) and patients in their early childhood (12,949 [35.9%]), respectively. Meningitis outbreaks were most likely to occur during the summer, and boys were more susceptible to meningitis than girls. The following pathogens most commonly caused infant meningitis: group B Streptococcus, Escherichia coli, and type B Haemophilus influenzae. Conclusion This study reports the number of pediatric meningitis cases, stratified by age, disease type, and month/year. The present findings contribute to a better understanding of pediatric meningitis in Korea and provide a foundation for future research to identify the risk factors for this disease.

Deep learning has recently attracted widespread interest as a means of reducing noise in low-dose CT (LDCT) images. Deep convolutional neural networks (CNNs) are typically trained to transfer high-quality image features of normal-dose CT (NDCT) images to LDCT images. However, existing deep learning approaches for denoising LDCT images often overlook the statistical property of CT images. In this paper, we propose an approach to statistical image restoration for LDCT using deep learning. We introduce a loss function to incorporate the noise property in image domain derived from the noise statistics in sinogram domain. In order to capture the spatially-varying statistics of CT images, we increase the receptive fields of the neural network to cover full-size CT slices. In addition, the proposed network utilizes $z$ -directional correlation by taking multiple consecutive CT slices as input. For performance evaluation, the proposed networks are trained and validated with a public dataset consisting of LDCT-NDCT image pairs. We also perform a retrospective study by testing the networks with clinical LDCT images. The experimental results show that the denoising networks successfully reduce the noise level and restore the image details without adding artifacts. This study demonstrates that the statistical deep learning approach can restore the image quality of LDCT without loss of anatomical information.

The epidemiology of demyelinating diseases in the Korean pediatric population has not been reported to date. This study aimed to identify the epidemiology of demyelinating diseases in Korean children by using big data. The subjects were children (0-17 years old) diagnosed with acute-disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica, and Guillain-Barré syndrome enrolled in the Korean Health Insurance Review and Assessment Service (HIRA) from January 2010 to December 2017.Of 1722 enrolled children, 553 (32.1%) had acute-disseminated encephalomyelitis, 170 (9.9%) had multiple sclerosis, 68 (3.9%) had neuromyelitis optica, and 931 (54.1%) had Guillain-Barré syndrome. The male-female ratios were 1.47:1 in acute-disseminated encephalomyelitis, 1.43:1 in Guillain-Barré syndrome, 1:1.66 in multiple sclerosis, and 1:1.62 in neuromyelitis optica. Demyelinating diseases were most prevalent in summer. The prevalence differed by region, with 545 (31.6%) in Seoul and 298 (17.3%) in Gyeonggi. This study is the first to identify the incidence of demyelinating diseases in South Korea.

Objectives To design and evaluate 3D‐printed nasal swabs for collection of samples for SARS‐CoV‐2 testing. Design An iterative design process was employed. Laboratory evaluation included in vitro assessment of mock nasopharyngeal samples spiked with two different concentrations of gamma‐irradiated SARS‐CoV‐2. A prospective clinical study compared SARS‐CoV‐2 and human cellular material recovery by 3D‐printed swabs and standard nasopharyngeal swabs. Setting, participants Royal Melbourne Hospital, May 2020. Participants in the clinical evaluation were 50 hospital staff members attending a COVID‐19 screening clinic and two inpatients with laboratory‐confirmed COVID‐19. Intervention In the clinical evaluation, a flocked nasopharyngeal swab sample was collected with the Copan ESwab and a mid‐nasal sample from the other nostril was collected with the 3D‐printed swab. Results In the laboratory evaluation, qualitative agreement with regard to SARS‐CoV‐2 detection in mock samples collected with 3D‐printed swabs and two standard swabs was complete. In the clinical evaluation, qualitative agreement with regard to RNase P detection (a surrogate measure of adequate collection of human cellular material) in samples collected from 50 hospital staff members with standard and 3D‐printed swabs was complete. Qualitative agreement with regard to SARS‐CoV‐2 detection in three pairs of 3D‐printed mid‐nasal and standard swab samples from two inpatients with laboratory‐confirmed SARS‐CoV‐2 was also complete. Conclusions Using 3D‐printed swabs to collect nasal samples for SARS‐CoV‐2 testing is feasible, acceptable to patients and health carers, and convenient.

Background Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor has therapeutic potential for acute ischemic stroke by suppressing microglial activation and facilitating neuroprotection. In this first-in-human study, we investigate the safety, tolerability and pharmacokinetics (PK) of JPI-289 in healthy male volunteers. Subjects and methods In single ascending dose (SAD) study, 35, 75, 150, 300, 600 mg JPI-289 or placebo was infused intravenously over 30 minutes to 40 subjects. In multiple ascending dose (MAD) study, 150, 300, 450 mg JPI-289 or placebo was infused over 1 hour every 12 hours to each of 24 subjects for 3.5 days (7 times). The plasma and urine concentrations of JPI-289 and its metabolites were determined. Results In the SAD study, AUClast and Cmax tended to increase supra-proportionally especially at higher doses in SAD study. However, Cmax showed dose-proportionality in the range of 75-600mg. JPI-289 reached a mean Tmax within 0.50 hour after dosing and a mean elimination half-life (t1/2) was 2.18 to 3.21 hours. In the MAD study, observed accumulation index ranged from 1.52 to 1.76. The effective half-life of JPI-289 was 1.88 to 3.05 hours, indicating that the plasma JPI-289 concentration rapidly reaches steady state. % recovered of JPI-289 measured in urine was 1.59-9.05%. In both studies, concentration of metabolites was less than 10% of JPI-289. Adverse events reported in the study were all mild in intensity and resolved without any sequelae. Conclusion The tolerable dose ranges and pharmacokinetic characteristics of JPI-289 evaluated in these studies will be useful in further clinical development of JPI-289.

The burden of coronary artery disease has been assessed by various semi-quantitative angiographic scores, which are frequently different each other. A non-invasive and quantitative modality may substitute angiographic sores for prognostic implication and decision of revascularization strategy. We compared fractional myocardial mass (FMM) with angiographic scores for predicting myocardial ischemia.In this multicenter registry, 411 patients who underwent coronary computed tomography angiography (CCTA) were followed by invasive coronary angiography and fractional flow reserve (FFR) measurement. CCTA-derived %FMM with diameter stenosis≥70% (%FMM-70) or ≥50% (%FMM-50) were compared with 9 angiographic scores (APPROACH, Duke Jeopardy, BARI, CASS, SYNTAX, Jenkins, BCIS-1, Leaman, Modified Duke) and were tested regarding their performance for predicting FFR≤0.80.The performance of %FMM-70 and %FMM-50 were similar to most angiographic scores (%FMM-70, c-statistics = 0.74; %FMM-50, 0.73; angiographic scores, 0.68-0.77). The frequency of FFR≤0.80 increased consistently according to %FMM-70, %FMM-50, and all angiographic scores (p 0.001, all). The optimal cutoff of %FMM-50 and %FMM-70 for FFR≤0.80 were ≥36.3% and ≥8.7%, respectively. Using these cutoffs, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of %FMM-50 were 81%, 55%, 3%, 67%, 71%, and of %FMM-70 were 67%, 78%, 82%, 61%, 71%.%FMM was comparable to angiographic scores for prediction of functional stenosis defined by FFR≤0.80. The integration of the severity of stenosis and the amount of subtended myocardium may improve the detection of the functional significance of vessel.

The purpose of this study was to evaluate the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) in patients with both chronic liver disease and a history of extrahepatic malignancy. This retrospective study included 59 hepatocellular carcinomas (HCCs) and 45 metastases pathologically confirmed between 2008 and 2017 in 104 patients with chronic liver disease (cirrhosis or chronic hepatitis B) and a history of extrahepatic malignancy. Two radiologists blinded to the final diagnosis independently reviewed MRI (95 patients) or CT (9 patients) images, and their consensus data were used to calculate the diagnostic performance of LI-RADS categories. Serum tumor markers, tumor multiplicity, and suspected metastatic lymph nodes were also evaluated. The sensitivity, specificity, and accuracy of LR-5 for diagnosing HCC were 69% (95% confidence intervals [CI] 56–81), 98% (95% CI 88–99), and 82% (95% CI 73–89), respectively, and those of LR-M for diagnosing metastasis were 89% (95% CI 76–96), 88% (95% CI 77–95), and 88% (95% CI 81–94), respectively. Elevation of serum carcinoembryonic antigen (P = 0.01) or carbohydrate antigen 19–9 levels (P = 0.02) and tumor multiplicity (P = 0.004) were more frequently observed in metastasis than in HCC. Three of four metastases categorized as LR-4 or LR-5 were smaller than 2 cm. The LI-RADS provides high specificity (98%) for differentiating HCC from metastases in patients with both chronic liver disease and a history of extrahepatic malignancy.

Contrast-induced acute kidney injury (CI-AKI) is one of the leading causes of new-onset renal failure in hospitalized patients. Statin has been evaluated for its protective effect against CI-AKI but rarely in patients receiving intravenous (IV) administrations of iodine-based contrast media for enhanced computed tomography (CT). In total, 12,371 patients who underwent contrast-enhanced abdominopelvic CT were retrospectively reviewed and stratified into statin users and statin nonusers. Subgroup analyses comparing high-intensity statins with low- to moderate-intensity statins were conducted within statin users and similar comparisons were performed within statin users stratified based on baseline eGFR. Overall, CI-AKI events did not occur less in statin users compared with non-statin users (p = 0.342). Within statin users, CI-AKI events did not decrease in high-intensity statin users compared with low- to moderate-intensity statin users (p = 0.355). Moreover, no significant difference in CI-AKI events was found between high-intensity statin users and low- to moderate-intensity statin users even after stratifying the patients with baseline eGFR. Collectively, statin was not significantly associated with the risk of CI-AKI events in patients undergoing contrast-enhanced abdominopelvic CT and high-intensity statins did not show significant association with CI-AKI over low- to moderate-intensity statins in the subgroup analysis. • Statin is not associated with risk of CI-AKI events in patients undergoing intravenous administration of contrast-enhanced CT. • CI-AKI incidence among high-intensity statin users was not significantly different from that of low- to moderate-intensity statin users.

To evaluate the diagnostic performance of LR-M criteria for differentiating hepatocellular carcinoma, intrahepatic mass-forming cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma and to compare the imaging features of each type. In this retrospective study, 110 patients were surgically diagnosed with cholangiocarcinoma (n = 67) and combined hepatocellular-cholangiocarcinoma (n = 43) at a single tertiary hospital between 2013 and 2018. Among them, those with risk factors were enrolled (16 cholangiocarcinomas and 33 combined hepatocellular-cholangiocarcinomas). Forty-nine other patients with size-matched hepatocellular carcinoma were selected as a control group. Two independent readers evaluated the imaging findings of the preoperative MRIs based on LI-RADS version 2018 and assigned an LI-RADS category. The diagnostic performance of the LR-M criteria for diagnosing cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma was evaluated, and the imaging features were compared. The imaging findings of the tumors in patients without risk factors (51 cholangiocarcinomas and 10 combined hepatocellular-cholangiocarcinomas) were evaluated for subgroup analysis. In the non-hepatocellular carcinoma group, 33 patients were categorized into LR-M and 14 patients into LR-5 (67.3% and 28.6%, respectively), while 5 patients with hepatocellular carcinoma were categorized into LR-M and 38 patients into LR-5 (10.2% and 77.6%, respectively). Sensitivity and specificity of the LR-M criteria were 67.3% and 89.8%, respectively. When more than two LR-M features were present, cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma were suggested with a specificity of 95.9%. The diagnostic performance of the LR-M criteria is acceptable with moderate sensitivity and high specificity for both cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma. Imaging findings of primary hepatic carcinomas should be understood as a spectrum.

Background To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets. Methods Five previously published prognostic models (ATRIA, CHADS2, CHADS2VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites. Results The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57–0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation. Conclusion This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.

Introduction This study characterized the pharmacokinetics (PKs) of a donepezil patch formulation currently under development, using mixed effect modeling analysis, and explored optimal patch dosing regimens in comparison with the donepezil oral formulation. Methods PK data used in this analysis were from 60 healthy Korean male subjects participating in two Phase I studies, where subjects received single or multiple doses of donepezil of 43.75, 87.5, and 175 mg via patches, and 12 of them received a single oral dose of 10 mg of donepezil, followed by a single dose of donepezil via a patch. Donepezil PKs were analyzed by nonlinear mixed effect modeling using NONMEM software. Results A well-stirred model with two-compartment distribution and delayed absorption was chosen as the best model for the oral formulation. The PKs of donepezil after the patch applications were best described by a two-compartment linear model with zero-order absorption (D2) and absorption delay. The relative bioavailability (BA) of donepezil after the patch application compared with oral dosing was described to be affected by the duration of patch application. Conclusion PK simulations based on the chosen PK models suggested that, overall, donepezil exposure in plasma is similar whether with 10 mg of oral donepezil every 24 h or a 175 mg patch every 72 h, and likewise with 5 mg of oral donepezil every 24 h or an 87.5 mg patch every 72 h.

Background Preoperative chemoradiotherapy (PCRT) followed by surgery and adjuvant chemotherapy is the current standard treatment for stage II/III rectal cancer. However, radiotherapy in the pelvic area is commonly associated with complications such as anastomotic leakage, sexual dysfunction, and fecal incontinence. Recently, the MERCURY study showed that preoperative high-resolution magnetic resonance imaging (MRI) helped to selectively avoid PCRT. It remains unclear whether PCRT is necessary in patients who can achieve a negative circumferential resection margin (CRM) with surgery alone and in patients with cT1–2N1 or cT3N0 without CRM involvement and lateral lymph node metastasis. This study aims to evaluate the efficacy of upfront radical surgery with total mesorectal excision (TME) followed by adjuvant chemotherapy with folinic acid (or leucovorin), fluorouracil, and oxaliplatin (FOLFOX) versus the current standard treatment in patients with surgically resectable, locally advanced rectal cancer. Methods This study, named TME-FOLFOX, is a prospective, open-label, multicenter, phase II randomized trial. Patients with locally advanced rectal cancer will be randomized to receive PCRT followed by TME and adjuvant chemotherapy (arm A) or upfront radical surgery with TME followed by adjuvant FOLFOX chemotherapy (arm B). Clinical stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis will be defined using preoperative MRI. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints include 5-year DFS, local recurrence rate, systemic recurrence rate, cost-effectiveness, and overall survival. We hypothesized that our experimental group (arm B) will have a 3-year DFS of 75% and a non-inferiority margin of 15%. Discussion Identifying whether patients require PCRT is one of the critical issues in locally advanced rectal cancer. This study aims to elucidate whether PCRT may not be required for all patients with stage II/III rectal cancer, especially for the MRI-based intermediate-risk group (with cT1–2N1 or cT3N0) without CRM involvement and lateral lymph node metastasis. If the findings indicate that our proposed treatment, which omits PCRT, is non-inferior to the standard treatment, then patients may avoid unnecessary radiation-related toxicity, have a shorter treatment duration, and save on medical costs. Trial registration ClinicalTrials.gov, NCT02167321. Registered on 19 June 2014.

Whether part of the blood pressure lowering effects of glyceryl trinitrate (GTN) is the result of centrally mediated reduction in sympathetic activity is debated. In humans, baroreflex activity potentially obscures the central sympatholytic effects of GTN. We examined this in a routine clinical tilt test in a patient with baroreflex failure secondary to previous neck radiotherapy. With reduced baroreflex function we observed an exaggerated fall in blood pressure and reduced sympathetic activity with GTN, supporting a peripheral vasodilation and central sympatholytic effect.

Background The characteristics of human parainfluenza virus type 4 (hPIV4) infection are not thoroughly understood. We therefore clarified the characteristics of hPIV4 in Korea. Method From January 2013 to December 2017, children admitted with respiratory tract infection at the Department of Pediatrics in Chung‐Ang University Hospital were enrolled in the study. Nasopharyngeal aspirate specimens were obtained from patients and tested for hPIV types by multiplex reverse transcription polymerase chain reaction. We retrospectively reviewed subject medical records, focusing on epidemiological and clinical characteristics. Results Of the 12 423 NPA specimens, 8,406 were positive by multiplex reverse transcription polymerase chain reaction for nine respiratory viruses, and 1,018 were positive for one of the four types of hPIV: 1,018 specimens led to the detection of 1,029 hPIVs; 3ss (31.3%) were positive for hPIV1, 120 (11.7%) were positive for hPIV2, 356 (34.6%) were positive for hPIV3, and 231 (22.4%) were positive for hPIV4. Of the hPIV‐positive patients, the mean age was 2.3 years (range, 0.1–12.7 years), 225 (97.4%) had no underlying disease, and 178 (77.1%) had a fever with a duration of 4.1 ± 2.3 days and a peak temperature of 39.0 ± 0.7 ℃. The most common diagnosis in hPIV4 infection was pneumonia (44.2%), followed by bronchiolitis (26.0%) and upper respiratory tract infection (24.3%). Only 2.2% of patients were diagnosed with croup. Although the most prevalent overall type of hPIV was hPIV3, hPIV4 generally caused acute respiratory tract infection in summer and early fall in an irregular annual pattern. Conclusions Human parainfluenza virus type 4 is an important common pathogen of respiratory tract infections in pediatric patients in Korea.

Objective The aim of this study is to develop a nomogram for prediction of pathologic complete remission (pCR) after preoperative chemoradiotherapy (CRT) for rectal cancer. Methods mRNA expression levels of seven molecular markers [p53, p21, Ki-67, vascular endothelial growth factor (VEGF), CD133, CD24, CD44] were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 120 rectal cancers. Endoscopic findings of clinical complete remission (cCR) and biologic variables were used to construct nomogram in the training group (n=80), which was validated in the validation group (n=40). Results mRNA expression levels of four markers (p53, p21, Ki67, CD133) correlated with pCR (24/80, 30.0%) in the training group. Low expression of p53 and/or high expression of p21, Ki67 and CD133 showed greater pCR rate. pCR was shown in 18 (69.2%) of 26 cases showing endoscopic cCR in the training group. Higher pCR rate was demonstrated in lower tumor location than middle tumor (19/49, 38.8% vs. 5/31, 16.1%). A nomogram for prediction of pCR was developed from the multivariate prediction model using these six variables, which showed good discrimination ability in the training group [area under the curve (AUC)=0.945] and validation group (AUC=0.922). The calibration plot showed good agreement between actual and predicted pCR in both patient groups. Conclusions Nomogram for assessment of pCR can be useful for making treatment decisions after CRT according to predicted responses.

Please see the Editorial Comment by Tyler J. Fraum discussing this article. Background: Long acquisition times for breath-hold contrast-enhanced T1-weighted (CE-T1W) imaging in MR enterography (MRE) protocols result in reduced image quality. Objective: To compare CE-T1W imaging performed using sensitivity encoding (SENSE) and compressed-sensing SENSE (CS-SENSE) in terms of image quality and diagnostic performance for active inflammation in Crohn disease (CD). Methods: This retrospective study included 41 patients (31 men, 10 women; mean age, 34±12 years) who underwent MRE for known or suspected CD between June 2020 and September 2020. MRE was performed in one of two scanning rooms based on scheduling availability. Per institutional protocol, in one room, the enteric phase was acquired using SENSE (acceleration factor 3), and the portal phase was acquired using CS-SENSE (acceleration factor 5); this order was reversed in the other room. Two radiologists independently assessed sequences for subjective image quality measures at the patient level and for active inflammation at the bowel-segment level. Mean image quality scores between readers were computed. Diagnostic performance for active inflammation was compared using generalized estimating equations; a separate experienced radiologist reviewed the full MRE protocol to establish the reference standard. Results: The mean acquisition time of CE-T1W imaging was 17.2 ± 1.1 seconds for SENSE versus 11.5 ± 0.8 seconds for CS-SENSE (P .05). For reader 1, CS-SENSE, compared with SENSE, demonstrated sensitivity of 86% versus 81% (P=.09), specificity of 88% versus 83% (P=.08), and accuracy of 87% versus 82% (P=.56). For reader 2, CS-SENSE, compared with SENSE, demonstrated sensitivity of 92% versus 80% (P=.006), specificity of 91% versus 98% (P=.16), and accuracy of 91% versus 86% (P=.002). Conclusion: Use of CS-SENSE for CE-T1W imaging in MRE protocols results in reduced scan times with reduced artifact and improved image quality. Clinical impact: The benefits of CS-SENSE in MRE protocols may improve the diagnostic performance for active inflammation in CD.

Most electronic medical records, such as free-text radiological reports, are unstructured; however, the methodological approaches to analyzing these accumulating unstructured records are limited. This article proposes a deep-transfer-learning-based natural language processing model that analyzes serial magnetic resonance imaging reports of rectal cancer patients and predicts their overall survival. To evaluate the model, a retrospective cohort study of 4,338 rectal cancer patients was conducted. The experimental results revealed that the proposed model utilizing pre-trained clinical linguistic knowledge could predict the overall survival of patients without any structured information and was superior to the carcinoembryonic antigen in predicting survival. The deep-transfer-learning model using free-text radiological reports can predict the survival of patients with rectal cancer, thereby increasing the utility of unstructured medical big data.

Assessment of magnetic resonance imaging (MRI) after neoadjuvant chemoradiation therapy (nCRT) is essential in rectal cancer staging and treatment planning. However, when predicting the pathologic complete response (pCR) after nCRT for rectal cancer, existing works either rely on simple quantitative evaluation based on radiomics features or partially analyze multi-parametric MRI. We propose an effective pCR prediction method based on novel multi-parametric MRI embedding. We first seek to extract volumetric features of tumors that can be found only by analyzing multiple MRI sequences jointly. Specifically, we encapsulate multiple MRI sequences into multi-sequence fusion images (MSFI) and generate MSFI embedding. We merge radiomics features, which capture important characteristics of tumors, with MSFI embedding to generate multi-parametric MRI embedding and then use it to predict pCR using a random forest classifier. Our extensive experiments demonstrate that using all given MRI sequences is the most effective regardless of the dimension reduction method. The proposed method outperformed any variants with different combinations of feature vectors and dimension reduction methods or different classification models. Comparative experiments demonstrate that it outperformed four competing baselines in terms of the AUC and F1-score. We use MRI sequences from 912 patients with rectal cancer, a much larger sample than in any existing work.

Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by progressive cognitive impairment. The deposition of amyloid beta (Aβ) and hyperphosphorylated tau is considered the hallmark of AD pathology. Many therapeutic approaches such as Food and Drug Administration-approved cholinesterase inhibitors and N–methyl–D–aspartate receptor antagonists have been used to intervene in AD pathology. However, current therapies only provide limited symptomatic relief and are ineffective in preventing AD progression. Cannabidiol (CBD), a phytocannabinoid devoid of psychoactive responses, provides neuroprotective effects through both cannabinoid and noncannabinoid receptors. Recent studies using an AD mouse model have suggested that CBD can reverse cognitive deficits along with Aβ-induced neuroinflammatory, oxidative responses, and neuronal death. Furthermore, CBD can reduce the accumulation of Aβ and hyperphosphorylation of tau, suggesting the possibility of delaying AD progression. Particularly, the noncannabinoid receptor, peroxisome proliferator-activated receptor gamma, has been suggested to be involved in multiple functions of CBD. Therefore, understanding the underlying mechanisms of CBD is necessary for intervening in AD pathology in depth and for the translation of preclinical studies into clinical settings. In this review, we summarize recent studies on the effect of CBD in AD and suggest problems to be overcome for the therapeutic use of CBD.

Background: Over one billion adults have hypertension globally, of whom 70% cannot achieve hypertension control goal with monotherapy alone. Data are lacking on patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Methods: Using eleven electronic health record databases that 118 million patients across eight countries/regions, we characterized the initiation of antihypertensive dual combination therapies for patients with hypertension. In each database, we first constructed cohorts of patients who newly initiate dual combination therapy of the four most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEi] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; beta-blocker; and thiazide diuretic) after escalating from monotherapy, and then described treatment utilization using these cohorts. Findings: We identified 980,648 patients with hypertension who newly initiated dual combination therapy: 12,541 from Australia, 6,980 from South Korea, 2,096 from Singapore, 7,008 from China, 16,663 from Taiwan, 103,994 from France, 76,082 from Italy, and 754,137 from the United States (US). Significant variations in treatment utilization existed across databases and patient subgroups. In Australia and Singapore databases, starting an ACEi/ARB monotherapy followed by a CCB was most common while in South Korea, China and Taiwan databases, starting a CCB monotherapy followed by an ACEi/ARB was most common. In Italy, France, and US databases, sequential use of an ACEi/ARB monotherapy followed by a diuretic was most common. Younger patients were more likely to be prescribed ACEi/ARB then a CCB or a diuretic compared with older patients. Women were more likely to be prescribed diuretics then an ACEi/ARB or a CCB compared with men. Interpretation: Large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic groups. These results highlight the need for future research to identify which dual combination therapy is most effective in practice. Funding: This study was supported by the National Research Foundation Singapore under its AI Singapore Programme (Award Number: AISG-GC-2019-002), National Medical Research Council (NMRC) under the Open Fund - Large Collaborative Grant (OF-LCG) - NMRC/OFLCG/001/2017 and Center Grant (CG) schemes - NMRC/CG/C016/2017, the Bio Industrial Strategic Technology Development Program (20003883, 20005021), the Ministry of Trade, Industry & Energy (MOTIE, Korea), a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health &Welfare, Republic of Korea (grant number: HR16C0001), the Australian Government National Health and Medical Research Council (NHMRC Grant Number: APP1192469). Declaration of Interest: JL, XW, CR MVZ are employees of IQVIA. YL reports grants from the National Heart, Lung, and Blood Institute (K12HL138037) and the Yale Center for Implementation Science. She was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion. HMK received expenses and/or personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He was a co-founder of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, Medtronic, the U.S. Food and Drug Administration, Johnson & Johnson, and the Shenzhen Center for Health Information. MAS reports grants from US National Science Foundation, grants from US National Institutes of Health, grants from the US Department of Veterans Affairs, grants from IQVIA, and personal fees from Janssen Research & Development and Private Health Management. SCY reports grants from Korean Ministry of Health & Welfare, grants from Korean Ministry of Trade, Industry & Energy. RWP reports grants from Korean Ministry of Health & Welfare, grants from Korean Ministry of Trade, Industry & Energy. The other co-authors report no potential competing interests. Ethical Approval: Use of TMUCRD data has been approved by theTMU-Joint Institutional Review Board (Project number: TMU-JIRB N202011003).

A d-starlike tree (or a d-quasistar ) is a subdivision of a star tree of degree d . A family of hypercube-like interconnection networks, called restricted hypercube-like graphs , includes most non-bipartite hypercube-like networks found in the literature such as twisted cubes, crossed cubes, Mobius cubes, recursive circulant G ( 2 m , 4 ) of odd m , etc. In this paper, we prove that given an arbitrary fault-free vertex r in an m -dimensional restricted hypercube-like graph with a set F of faults (vertex and/or edge faults) and d positive integers, l 1 , l 2 , … , l d , whose sum is equal to the number of fault-free vertices minus one, there exists a d -starlike tree rooted at r , each of whose subtrees forms a fault-free path on l i vertices for i ∈ { 1 , 2 , … , d } , provided | F | ≤ m − 2 and | F | + d ≤ m . The bounds on | F | and | F | + d are the maximum possible.

Background and purpose To evaluate the safety and efficacy of preoperative chemotherapy (CTx) followed by chemoradiotherapy (CCRT) for high-risk gastric cancer (GC). Methods and materials The inclusion criteria were as follows: (1) Borrmann type 4; (2) large Borrmann type 3 (≥8 cm); (3) single bulky (≥3 cm × 1) or multiple lymph nodes (≥1.5 cm × 3). Patients received two 21-day courses of induction CTx of TS-1 (35 mg/m2, p.o, twice daily on days 1–14), docetaxel (30 mg/m2, i.v., days 1 and 8), and cisplatin (30 mg/m2, i.v., days 1 and 8) followed by CCRT (two courses of TS-1 and cisplatin in combination with 45 Gy radiation). Results Forty-two patients were enrolled between March 2014 and February 2016, and 39 of these completed sequential CTx and CCRT. Among the 33 patients who underwent R0 resection, the pathologic response rate was 39.4% [no residual carcinoma (n = 5, 15.2%), with 1–10% residual carcinoma (n = 8, 24.2%)]. Overall, 4 patients (12.1%) were pathologic stage 0, 7 (21.2%) were stage I, 10 (30.3%) were stage II, and 12 (36.4%) were stage III. The overall survival rate at 3 years was 77.9% for stages 0 and I, 66.8% for stages II–III, and 33.3% for unresectable cases (P = 0.001). Toxicity was mild to moderate with grade 4 neutropenia (n = 1) and neutropenic fever (n = 1) as the most prominent side-effects. Conclusions Sequential CTx and CCRT prior to surgery are feasible and effective for high-risk GC. Trial registration number: NCT02495493.

BackgroundAmbroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD.MethodsABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed.ResultsEnhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2–8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events.ConclusionsLong-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.

Highlights • Febrile seizures were reported to be associated with seasonal viral epidemics. • The seasonal distribution of febrile seizures was high from late spring to summer. • Influenza virus and enterovirus was most frequently associated with febrile seizure., Purpose The seasonal distribution patterns of febrile seizures and of respiratory and enteric viral pathogens are similar. In this study, we analyzed trends in febrile seizures and viral infection in Korean children, using big data from the Korean Health Insurance Review and Assessment Service (HIRA). Methods We analyzed children younger than 6 years who visited the hospital and were diagnosed with febrile seizures from 2009 to 2016, using medical records in the HIRA database. A total of 666,136 medical records of children with a main or subdiagnosis of febrile seizure from 2008 to 2016 were included. Of these records, patients younger than 1 month and records before 2009 were excluded. Finally, 558,130 records were extracted. Results The medical records included 315,774 male children and 242,356 (43.4%) female children, with a mean age of 2.31 ± 1.31 years. The annual incidence of febrile seizure was 25.4 per 1000 person-years (27.9 for boys and 22.7 for girls). The ratio of male to female children was 1.30: 1, and records of 1-year-old children comprised the highest proportion (n = 210,400, 33.70%). The total monthly number of patients was highest in May (n = 64,969, 11.6%), and peaks were formed from April to July. The fewest patients were seen in October (n = 34,424, 6.17%). The most common viral pathogens were influenza in April and enterovirus during May–July. Conclusion The seasonal distribution of febrile seizures was high from late spring to summer, and influenza virus and enterovirus were most frequently associated.

Objective. Patients with diabetes have higher mortality rate than patients without diabetes after ST-segment elevated myocardial infarction (STEMI). Prognosis of patients with new onset diabetes (N...

Background Tegoprazan (CJ-12420) is a potassium-competitive acid blocker (P-CAB) with therapeutic potential for gastro-oesophageal reflux disease (GERD) by reversibly suppressing gastric H+ /K+ -ATPase. Aims To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of tegoprazan METHODS: A phase I, randomised, double-blind and placebo-controlled clinical trial was conducted in 56 healthy male subjects without Helicobacter pylori infection. In the single ascending dose study, 50, 100, 200 and 400 mg tegoprazan were administered to 32 subjects. In the multiple ascending dose study, 100 and 200 mg tegoprazan were administered every 24 hours to each of the eight subjects for 7 days. In the comparative pharmacodynamics study, 40 mg esomeprazole was administered to eight subjects every 24 hours for 7 days. The assessment included safety, tolerability, pharmacodynamics through monitoring of 24-hour gastric pH and pharmacokinetics of tegoprazan in plasma and urine. Results Tegoprazan was generally well tolerated. Most adverse events reported in the study were mild in intensity and resolved without any sequelae. Exposure to tegoprazan increased in a dose-proportional manner. Multiple dosing with tegoprazan showed no accumulation in plasma on day 7. The pharmacodynamic analysis revealed that tegoprazan showed rapid, dose-dependent gastric acid suppression. Conclusions Tegoprazan was well tolerated and showed rapid and potent gastric acid suppression. This supports the further development of tegoprazan as a treatment for acid-related disorders.

Cilostazol is a selective inhibitor of phosphodiesterase III (PDE III), which is prescribed for patients with peripheral arterial disease, especially intermittent claudication. The purpose of the study was to investigate the pharmacokinetic (PK) of cilostazol and its metabolites on the immediate (IR) formulation of cilostazol in healthy Korean male volunteers by population PK modeling analysis implemented using NONMEM software.A 2 × 2 crossover study comparing multiple oral doses of IR and SR formulations of cilostazol were conducted. Serial plasma concentrations of cilostazol and its active metabolites were used in this analysis.The PK was best depicted by one-compartment model, with absorption kinetics of cilostazol having mixed first- and zero-order kinetics with a time delay at the beginning of absorption. The introduction of interoccasion variabilities into zero-order (D1), first-order (Ka), and relative bioavailability (F1) significantly improved the model fit, and total body water (TBW) was identified as a significant covariate positively affecting the clearance of cilostazol. The model validation suggested that the model constructed in this study predicted the plasma concentration of cilostazol and its two active metabolites reasonably well.The PK model we developed explored the PK characteristics of cilostazol in Korean male subjects, and may be useful for identifying optimal individual dosing regimens of cilostazol.

Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.

MINI: A risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer was developed. The low-risk group showed an extremely rare extragastirc recurrence and higher extragastric recurrence-free survival than the high-risk group. Postsurgical computed tomography surveillance may be unnecessary in the low-risk group after curative resection of early gastric cancer. OBJECTIVE To stratify the postsurgical computed tomography (CT) surveillance based on a risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer (EGC). SUMMARY OF BACKGROUND DATA Postsurgical CT surveillance should not be routinely performed in all patients because of the low incidence of extragastric recurrence and potential risk of radiation exposure. METHODS Data from 3162 patients who underwent surgical resection for EGC were reviewed to develop a risk-scoring system to predict extragastric recurrence. Risk scores were based on the predictive factors for extragastric recurrence, which were determined using Cox proportional hazard regression model. The risk-scoring system was validated by Uno censoring adjusted C-index. External validation was performed using an independent dataset (n = 430). RESULTS The overall incidence of extragastric recurrence was 1.4% (44/3162). Five risk factors (lymph node metastasis, indications for endoscopic resection, male sex, positive lymphovascular invasion, and elevated macroscopic type), which were significantly associated with extragastric recurrence, were incorporated into the risk-scoring system, and the patients were categorized into 2 risk groups. The 10-year extragastric recurrence-free survival differed significantly between low- and high-risk groups (99.7% vs 96.5%; P < 0.001). The predictive accuracy of the risk-scoring system in the development cohort was 0.870 [Uno C-index; 95% confidence interval (95% CI), 0.800-0.939]. Discrimination was good after internal (0.859) and external validation (0.782, 0.549-1.000). CONCLUSION This risk-scoring system might be useful to predict extragastric recurrence of EGC after curative surgical resection. We suggest that postsurgical CT surveillance to detect extragastric recurrence should be avoided in the low-risk group.