Development of Prediction Model Using Machine-Learning Algorithms for Nonsteroidal Anti-inflammatory Drug-Induced Gastric Ulcer in Osteoarthritis Patients: Retrospective Cohort Study of a Nationwide South Korean Cohort.

Background: Nonsteroidal anti-inflammatory drugs (NSAID) are currently among the most prescribed medications worldwide to relieve pain and reduce inflammation, especially in patients suffering osteoarthritis (OA). However, NSAIDs are known to have adverse effects on the gastrointestinal system. If a gastric ulcer occurs, planned OA treatment needs to be changed, incurring additional treatment costs and causing discomfort for both patients and clinicians. Therefore, it is necessary to create a gastric ulcer prediction model that can reflect the detailed health status of each individual and to use it when making treatment plans. Methods: Using sample cohort data from 2008 to 2013 from the National Health Insurance Service in South Korea, we developed a prediction model for NSAID-induced gastric ulcers using machine-learning algorithms and investigated new risk factors associated with medication and comorbidities. Results: The population of the study consisted of 30,808 patients with OA who were treated with NSAIDs between 2008 and 2013. After a 2-year follow-up, these patients were divided into two groups: without gastric ulcer (n=29,579) and with gastric ulcer (n=1,229). Five machine-learning algorithms were used to develop the prediction model, and a gradient boosting machine (GBM) was selected as the model with the best performance (area under the curve, 0.896; 95% confidence interval, 0.883-0.909). The GBM identified 5 medications (loxoprofen, aceclofenac, talniflumate, meloxicam, and dexibuprofen) and 2 comorbidities (acute upper respiratory tract infection [AURI] and gastroesophageal reflux disease) as important features. AURI did not have a dose-response relationship, so it could not be interpreted as a significant risk factor even though it was initially detected as an important feature and improved the prediction performance. Conclusions: We obtained a prediction model for NSAID-induced gastric ulcers using the GBM method. Since personal prescription period and the severity of comorbidities were considered numerically, individual patients' risk could be well reflected. The prediction model showed high performance and interpretability, so it is meaningful to both clinicians and NSAID users.

Pulmonary pleomorphic carcinoma presenting as undifferentiated non-small cell carcinoma with giant cells: A case report and review of literature.

Pulmonary pleomorphic carcinoma (PPC) is a poorly differentiated non-small cell lung carcinoma, including squamous cell carcinoma, adenocarcinoma, or undifferentiated non-small cell lung carcinoma with at least 10% spindle and/or giant cells. Here, we report a case of PPC showing undifferentiated non-small cell lung carcinoma with giant cells. A 71-year-old man with dyspnea underwent right lobectomy because of a mass in the right upper lobe of the lung. A 5.0 × 3.0 × 1.5 cm-sized tumor was identified; microscopically, the tumor composed of undifferentiated large sized tumor cells admixed with syncytial tumor giant cells and emperipoletic giant cells. Immunohistochemically, the tumor cells were reactive for pan-cytokeratin, but negative for P40, thyroid transcription factor 1 (TTF-1), and vimentin. The tumor cells were also positive for 3 clones of programmed death-ligand 1 (PD-L1). The clinical and histologic findings supported the diagnosis of an undifferentiated non-small cell lung carcinoma with giant cells, which is a subtype of pulmonary pleomorphic carcinoma. Unfortunately, after surgery, multifocal lymph node metastasis was identified in radiologic examination. Only palliative chemotherapy was administered to the patient, although he was indicated for immunochemotherapy. Pulmonary pleomorphic carcinoma is known to have a poor prognosis, even in early stages of the disease, therefore, we should be careful in the diagnosis to ensure optimal treatment.

Diagnostic Roles of Immunohistochemistry in Thymic Tumors: Differentiation between Thymic Carcinoma and Thymoma.

Background: The present study aims to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in thymic tumors, including thymic carcinoma (TC) and thymoma (TM). Methods: Eligible studies were obtained by searching the PubMed databases and screening the searched articles. Thirty-eight articles were used in the present meta-analysis and included 636 TCs and 1861 TMs. Besides, for IHC markers with statistical significance, a diagnostic test accuracy review was performed. Results: The comparison of various IHC expressions between TC and TM was performed for 32 IHC markers. Among these IHC markers, there were significant differences between TC and TM for beta-5t, B-cell lymphoma 2 (Bcl-2), calretinin, CD1a, CD5, carcinoembryonic antigen (CEA), cytokeratin19 (CK19), CD117, glucose transporter 1 (Glut-1), insulin-like growth factor 1 receptor (IGF-1R), mesothelin, MOC31, mucin1 (MUC1), p21, and terminal deoxynucleotidyl transferase (TdT). Markers with higher expressions in TCs were Bcl-2, calretinin, CD5, CEA, CD117, Glut-1, IGF-1R, mesothelin, MOC31, MUC1, and p21. Among these markers, there were no significant differences between TC and TM type B3 in immunohistochemistries for Bcl-2 and CK19. On the other hand, ß-catenin and CD205 showed a considerable difference in IHC expressions between TC and TM type B3, but not between TC and overall TM. In diagnostic test accuracy review, MUC1 and beta-5t were the most useful markers for TC and TM, respectively. Conclusions: Taken together, our results showed that the expression rates for various IHC markers significantly differed between TC and TM. The IHC panel can be useful for differentiation from limited biopsied specimens in daily practice.

The Burden and Risk Factors for Infection of Transvenous Cardiovascular Implantable Electronic Device: a Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: There are limited published data on the incidence and cost associated with cardiac implantable electrical device (CIED) infection for Asian patients. We analyzed the infection burden associated with the implantation of CIEDs in Korea. METHODS: In the Health Insurance Review & Assessment Service (HIRA) database during the period from January 1, 2014 to December 31, 2016, we identified 16,908 patients with CIED implantation. CIED infection was defined as either: 1) Infection-related diagnosis code by the Korean Standard Classification of Diseases after any CIED procedure; or 2) CIED removal along with systemic infection. RESULTS: The proportions of first implantation and replacement were 77.6% and 22.4%, respectively. During the follow-up period of 17.1±10.6 months, a total of 462 patients had CIED infection with incidence of 1.95 per 100 person-years with higher infection rate in replacement than first implantation (3.97 vs. 1.4 per 100 person-years, p<0.001). The average cost per person was US$ 16,584 (pacemaker, $13,736; implantable cardioverter defibrillator, $28,402; cardiac resynchronization therapy, $29,674). The risk factors of CIED infection were generator replacement (adjusted hazard ratio [aHR], 3.14; 95% confidence interval [CI], 2.60-3.78), diabetes mellitus (aHR, 1.94; 95% CI, 1.58-2.38), and congestive heart failure (aHR, 1.86; 95% CI, 1.51-2.28). CONCLUSIONS: The rate of CIED infection in Korea was 1.95 per 100 person-years with average cost of US$ 16,584. The most important risk factor was generator replacement. This result suggests that generator replacement should be performed cautiously to avoid CIED infection.

Temporal Trends of Cardiac Implantable Electronic Device Implantations: a Nationwide Population-based Study.

BACKGROUND AND OBJECTIVES: Implantation of cardiac implantable electronic devices (CIED), including permanent pacemakers (PM), implantable cardioverter-defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices, has increased significantly over the past several years. However, limited data exists regarding temporal trends of CIED implantations in Asian population. This study aimed to investigate temporal trends of CIED treatment in Korea. METHODS: Using the National Health Insurance Service database of the entire Korean adult population, temporal trends of CIED procedures between 2009 and 2016 were evaluated. Additionally, temporal changes in the prevalence of patients' comorbidities were evaluated. RESULTS: A total of 35,421 CIED procedures (new implantations: 27,771, replacements: 7,650) were performed during the study period. The mean age of new CIED recipients and the prevalence of comorbidities, including hypertension, diabetes mellitus, heart failure, stroke, and atrial fibrillation, increased substantially with time. Compared to 2009, the number of new implantations of PM, ICD, and CRT devices increased by 2.0 (1,977 to 3,910), 3.6 (230 to 822), and 4.9 (44 to 217) times in 2016, respectively. The annual new implantation rate of CIED also increased accordingly (5.1 to 9.3 for PM, 0.6 to 1.9 for ICD, and 0.1 to 0.5 for CRT devices, per 100,000 persons). CONCLUSIONS: The number of CIED implantation increased substantially from 2009 to 2016 in Korea. Also, the patients with CIED have been changed to be older and have more comorbidities. Therefore, the burden of health care cost in patients with CIED would be expected to increase in the future.

Toward Security Enhanced Provisioning in Industrial IoT Systems.

Through the active development of industrial internet of things (IIoT) technology, there has been a rapid increase in the number of different industrial wireless sensor networks (IWSNs). Accordingly, the security of IWSNs is also of importance, as many security problems related to IWSN protocols have been raised and various studies have been conducted to solve these problems. However, the provisioning process is the first step in introducing a new device into the IIoT network and a starting point for IIoT security. Therefore, leakage of security information in the provisioning process makes exposure of secret keys and all subsequent security measures meaningless. In addition, using the exploited secret keys, the attacker can send false command to the node or send false data to the network manager and it can cause serious damage to industrial infrastructure depending on the IWSN. Nevertheless, a security study on the provisioning process has not been actively carried out, resulting in a provisioning process without guaranteed security. Therefore, in this paper, we analyzed security issues of the provisioning process in IWSN by researching prominent IWSN standards, including ISA 100.11a, WirelessHART, and Zigbee, and also an ISA 100.11a-certified device and provisioning process-related studies. Then, we verified the security issues of the provisioning process through testing and analyzing the provisioning process using the ISA 100.11a standard-implemented devices and ISA 100.11a-certified devices. Finally, we discuss security considerations and the direction of future research on provisioning security for IWSN in the IIoT era.

Cardiac resynchronization therapy using a dual chamber pacemaker in patients with severe left ventricular dysfunction and a left bundle branch block.

Through the use of a dual chamber (DDD) pacemaker, we achieved a cardiac resynchronization effect in a 51-year-old female patient who was transferred to our hospital from another hospital for an operation for three-vessel coronary artery disease. Her electrocardiogram showed a left bundle branch block (LBBB) and a prolonged QRS interval of 166 milliseconds. Severe left ventricle (LV) dysfunction was diagnosed via echocardiography. Coronary artery bypass grafting (CABG) was then performed. In order to accelerate left atrial activation and reduce the conduction defect, DDD pacing using right atrial and left and right ventricular pacing wires was initiated postoperatively. The cardiac output was measured immediately, and one and twelve hours after arrival in the intensive care unit. The cardiac output changed from 2.8, 2.4, and 3.6 L/min without pacing to 3.5, 3.4, and 3.5 L/min on initiation of pacing. The biventricular synchronization using DDD pacing was turned off 18 hours after surgery. She was transferred to a general ward with a cardiac output of 3.9 L/min. In patients with coronary artery disease, severe LV dysfunction, and LBBB, cardiac resynchronization therapy can be achieved through DDD pacing after CABG.

A hybrid procedure for atrial fibrillation using total thoracoscopic ablation and post-procedural electrophysiological confirmation of ablation lines.

Atrial fibrillation (AF) is the most common chronic arrhythmia in the world, and it is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality. To overcome the limitations of transvenous radiofrequency (RF) ablation for AF, total thoracoscopic ablation (TTA) has evolved as a new technique. TTA has several advantages over transvenous RF ablation and is known to produce better outcomes, especially in patients with persistent AF. Herein, we report 2 cases of successful TTA followed by an electrophysiological study confirming satisfactory ablation lines; the first such procedure reported in Korea.

Surgical experience of ascending aorta and aortic valve replacement in patient with calcified aorta.

BACKGROUND: The conventional method of aortic cross-clamping is very difficult and increases the risk of cerebral infarct due to embolism of the calcified aorta in these patients. Accordingly, we analyzed our experience with 11 cases of ascending aorta and aortic valve replacement with hypothermic circulatory arrest. MATERIALS AND METHODS: From January 2002 to December 2009, 11 patients had ascending aorta and aortic valve replacement with hypothermic arrest at our hospital. We performed a retrospective study. RESULTS: There were 5 males and 6 females, with a mean age of 68 years (range, 44 to 82 years). Eight patients had aortic stenosis, and 3 patients had aortic regurgitation. An aortic cannula was inserted into the right axillary artery in 3 patients and ascending aorta in 6 patients. Two patients with aortic regurgitation had a remote access perfusion catheter inserted though the right femoral artery. The mean cardiopulmonary bypass time was 180 minutes (range, 110 to 306 minutes) and mean hypothermic circulatory arrest time was 30 minutes (range, 20 to 48 minutes). The mean rectal temperature during hypothermic circulatory arrest was 21℃ (range, 19℃ to 23℃). No patient had any new onset of cerebral infarct or cardiovascular accident after surgery. There was no hospital mortality. Early complications occurred in 1 patient who needed reoperation due to postoperative bleeding. Late complications occurred in 1 patient who underwent a Bentall operation due to prosthetic valve endocarditis. The mean follow-up duration was 32 months (range, 1 month to 8 years) and 1 patient died suddenly due to unknown causes after 5 years. CONCLUSION: Patients with a calcified aorta can be safely treated with a technique based on aorta and aortic valve replacement under hypothermic circulatory arrest.

Anti-inflammatory effects of ethanol extract from Orostachys japonicus on modulation of signal pathways in LPS-stimulated RAW 264.7 cells.

In this study, powder of Orostachys japonicus A. Berger (O. japonicus) was extracted with 95% ethyl alcohol and fractionated using a series of organic solvents, including n-hexane (hexane), dichloromethane (DCM), ethylacetate (EtOAc), n-butanol (BuOH), and water (H(2)O). We investigated the anti-inflammatory effects of these O. japonicus extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Their effects on the expression of inflammatory mediators and transcription factors were analyzed by Western blotting. DCM fraction significantly inhibited formation of reactive oxygen species (ROS) as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Phosphorylation of the pro-inflammatory transcription factor complex nuclear factor-kappa B (NF-κB) p65 and expression of inducible nitric oxide synthase (iNOS), one of its downstream proteins, were also suppressed by DCM fraction. These effects were regulated by upsteam proteins in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways. Taken together, our data suggest that O. japonicus could be used as a potential source for anti-inflammatory agents.

Stimulation of activity and expression of antioxidant enzymes by solvent fractions and isolated compound from Cedrela sinensis leaves in HepG2 cells.

Cedrela sinensis has been widely used in traditional Oriental medicine to treat a variety of diseases. However, little is known about the cellular actions by which this plant mediates its antioxidant effects. In this study, activity-guided fractionations of C. sinensis leaves were performed using column chromatographic techniques as well as biological assays with HepG2 cells. The ethanol (95%) extract of C. sinensis leaves was sequentially extracted with hexane, chloroform, ethyl acetate (EtOAc), butanol, and water, and the fractions were screened for their antioxidant potentials for scavenging radicals as well as inducing antioxidant enzyme activity and expression. The most potent antioxidant EtOAc fraction was further separated using chromatographic techniques including open column and high-performance liquid chromatography. Compound 1 from the EtOAc fraction showed strong radical scavenging activity with a 50% scavenging concentration value close to that of ascorbic acid and induced both the activity and expressions of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Inhibitory effects on the phosphorylations of upstream mitogen-activated protein kinases such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 were also observed after treatments with compound 1. Compound 1 was identified as quercitrin by (1)H- and (13)C-nuclear magnetic resonance techniques. Taken together, our findings demonstrated for the first time that C. sinensis leaves appear to be a useful source of a cytoprotective and chemopreventive agent that can stimulate the activity and expression of crucial antioxidant enzymes in cells.