Purpose: The incidence and prognostic implications of atrial fibrillation (AF) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are controversial, especially for Korean patients. Furthermore, the pattern of antithrombotic therapy for these patients is unknown. The present study sought to identify the impact of AF on Korean patients undergoing TAVI and demonstrate the status of antithrombotic therapy for these patients. Materials and Methods: A total of 660 patients who underwent TAVI for severe AS were recruited from the nationwide K-TAVI registry in Korea. The enrolled patients were stratified into sinus rhythm (SR) and AF groups. The primary endpoint was all-cause death at 1-year. Results: AF was recorded in 135 patients [pre-existing AF 108 (16.4%) and new-onset AF 27 (4.1%)]. The rate of all-cause death at 1 year was significantly higher in patients with AF than in those with SR [16.2% vs. 6.4%, adjusted hazard ratio (HR): 2.207, 95% confidence interval (CI): 1.182–4.120, p=0.013], regardless of the onset timing of AF. The rate of new pacemaker insertion at 1 year was also significantly higher in patients with AF than in those with SR (14.0% vs. 5.5%, adjusted HR: 3.137, 95%CI: 1.621–6.071, p=0.001).Among AF patients, substantial number of patients received the combination of multiple antithrombotic agents (77.8%), and the most common combination was that of aspirin and clopidogrel (38.1%). Conclusion AF was an independent predictor of 1-year mortality and new pacemaker insertion in Korean patients undergoing TAVI.

Two open-label, randomized, two-period crossover studies were conducted to investigate the pharmacokinetic (PK) properties, safety, and bioequivalence of the test formulation (KD4004), a new fixed-dose combination (FDC) formulation of dapagliflozin and metformin extended release (XR) tablets, relative to the reference formulation (10 mg dapagliflozin/1,000 mg metformin XR FDC tablet) in healthy subjects under fasting (Part A) and fed (Part B) conditions. After giving the dose, serial blood samples were collected for a period of 48 hours. Primary PK parameters (AUC 0-t and C max ) were used to assess bioequivalence between two dapagliflozin/metformin XR (10/1,000 mg) FDC formulations under fed and fasting conditions. Safety and tolerability were also evaluated. Part A and Part B were completed by 32 and 37 subjects, respectively. Bioequivalence of the two FDC formulations of dapagliflozin and metformin XR tablets was established in both the fasted and the fed conditions as the 90% confidence interval of the ratios of adjusted geometric means for AUC 0-t and C max were contained within the predefined range of 0.800–1.250 bioequivalence criteria. Single-dose administration of dapagliflozin and metformin XR was safe and well tolerated as the two FDC formulations. In conclusion, both FDC formulations of dapagliflozin and metformin XR tablets were bioequivalent in fed and fasted subjects. All treatments were well tolerated.

Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients’ characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients’ behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https:/hiss.nhis.or.kr).

Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients’ characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients’ behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https:/hiss.nhis.or.kr).

Background: Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a ‘cytokine storm’ is involved in the pathogenesis of severe illness.However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC). Methods: A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/ moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the proinflammatory cytokines/chemokines. Results: Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV2 significantly increased proinflammatory cytokines/chemokines and S100A9 in human primary PBMCs. Conclusion These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

Peutz-Jeghers syndrome is an autosomal dominant inherited disease that manifests as a combination of mucocutaneous pigmentation and gastrointestinal hamartomatous polyps that usually cause intussusception and intestinal hemorrhage. We report the case of a 40-year-old male patient who was diagnosed 20 years ago and had previously undergone 3 intestinal resection surgeries. This time, with the use of combined operative and endoscopic polypectomy, more than 100 polyps were removed. This technique is useful for providing a "clean" small intestine that allows the patient a long interval between laparotomies and reduces the complications associated with multiple laparotomies and resections.
Adult ; Endoscopy ; Hemorrhage ; Humans ; Intestine, Small ; Intussusception ; Laparotomy ; Male ; Peutz-Jeghers Syndrome* ; Pigmentation ; Polyps*

PURPOSE: The purpose of this study was to compare the diagnostic performance of ultrasound (US) elastography and conventional B-mode US for discrimination between benign and malignant breast lesions. MATERIALS AND METHODS: During a 13-month period, 277 women with 335 sonographically visible breast lesions who were scheduled to undergo biopsy were examined with US elastography. Elastographic findings were classified as benign or malignant based on the area ratio, with 1.00 as the threshold. Findings on conventional B-mode US were classified according to the BI-RADS category, as follows: lesions of BI-RADS categories 2 and 3 were considered benign, while those in categories 4 and 5 were considered malignant. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and ROC curve analysis for comparison of the diagnostic performance of US elastography and conventional B-mode US. RESULTS: Of the 335 breast lesions, 85 (25.4%) showed malignancy on pathology. Findings on B-mode US showed malignancy in 264 (78.8%) and elastographic findings showed malignancy in 102 (30.4%). The sensitivity, specificity, PPV, NPV, and accuracy of B-mode US and elastography were 98.8%, 28.0%, 31.8%, 98.6%, and 79.4% and 69.4%, 81.2%, 57.8%, 88.8%, and 79.4%, respectively. Elastography showed significantly higher specificity and PPV and lower sensitivity and NPV, compared with B-mode US (p < 0.001). The area under the ROC curve (AUC value) was 0.761 for elastography, and 0.634 for B-mode US (p < 0.001). CONCLUSIONS: US elastography can improve specificity and PPV of B-mode US, but with significant sacrifice of sensitivity and NPV. Therefore, US elastography may complement B-mode US for differentiation of breast masses.
Biopsy ; Breast ; Complement System Proteins ; Discrimination (Psychology) ; Elasticity Imaging Techniques ; Female ; Humans ; ROC Curve ; Sensitivity and Specificity

OBJECTIVE: To evaluate the incidence, predictive factors, and clinical outcomes of angiographically negative acute arterial upper and lower gastrointestinal (GI) bleeding. MATERIALS AND METHODS:From 2001 to 2008, 143 consecutive patients who underwent an angiography for acute arterial upper or lower GI bleeding were examined. RESULTS: The angiographies revealed a negative bleeding focus in 75 of 143 (52%) patients. The incidence of an angiographically negative outcome was significantly higher in patients with a stable hemodynamic status (p < 0.001), or in patients with lower GI bleeding (p = 0.032). A follow-up of the 75 patients (range: 0-72 months, mean: 8 +/- 14 months) revealed that 60 of the 75 (80%) patients with a negative bleeding focus underwent conservative management only, and acute bleeding was controlled without rebleeding. Three of the 75 (4%) patients underwent exploratory surgery due to prolonged bleeding; however, no bleeding focus was detected. Rebleeding occurred in 12 of 75 (16%) patients. Of these, six patients experienced massive rebleeding and died of disseminated intravascular coagulation within four to nine hours after the rebleeding episode. Four of the 16 patients underwent a repeat angiography and the two remaining patients underwent a surgical intervention to control the bleeding. CONCLUSION: Angiographically negative results are relatively common in patients with acute GI bleeding, especially in patients with a stable hemodynamic status or lower GI bleeding. Most patients with a negative bleeding focus have experienced spontaneous resolution of their condition.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Angiography ; Arteries ; Disseminated Intravascular Coagulation/etiology ; Embolization, Therapeutic ; Female ; Gastrointestinal Hemorrhage/*radiography/surgery ; Hemodynamics ; Humans ; Male ; Middle Aged ; Recurrence

Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity that's characterized by headache, confusion, seizure and frequent visual disturbances. It is associated with certain neuro-radiological findings, and predominantly white matter abnormalities of the parieto-occipital lobes. RPLS has been identified mostly in patients with malignant hypertension, pre-eclampsia and renal insufficiency and in those patients who are using immunosuppressive agents or cytotoxic drugs. We report here on a case of RPLS in a patient who was undergoing chemotherapy. A 49-year-old woman presented with abrupt mental changes and visual disturbances five days after the administration of a chemotherapeutic agent. MRI showed hyper-intense signals on the magnetic resonance (MR) diffusion images in the bilateral temporal, parietal and occipital lobes. The clinical manifestations completely resolved after one week of treatment that consisted of blood pressure control, a negative intake-output balance and the best supportive care. These radiological changes and the reversible clinical manifestations were consistent with RPLS.
Antineoplastic Combined Chemotherapy Protocols ; Blood Pressure ; Cisplatin ; Cytarabine ; Diffusion ; Etoposide ; Female ; Headache ; Hodgkin Disease ; Humans ; Hypertension, Malignant ; Immunosuppressive Agents ; Magnetic Resonance Spectroscopy ; Middle Aged ; Occipital Lobe ; Posterior Leukoencephalopathy Syndrome ; Pre-Eclampsia ; Prednisone ; Renal Insufficiency ; Seizures