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Purpose@#Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. @*Methods@#Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. @*Results@#The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. @*Conclusion@#While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.
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Purpose@#Total colonoscopy is recommended if colorectal polyps are clinically suspected.This study aimed to investigate the performance status of pediatric colonoscopic polypectomy in Korea. @*Methods@#We surveyed pediatric endoscopic specialists who perform colonoscopic polypectomy in Korea using a questionnaire of 13 questions on pediatric colonoscopic polypectomy performance status. @*Results@#The survey was conducted at 45 institutions, and 32 specialists (71.1%) responded.Among the respondents, 31.2% (10/32) said colonoscopy was performed in all age groups, while 12.5% (4/32) said sigmoidoscopy was performed in all age groups. Meanwhile, 56.2% (18/32) said that sigmoidoscopy was performed in young children, while colonoscopy was performed in older children. Among them, 38.9% (7/18) believe that 4–6 years were young, and 44.5% (8/18) believe that 7–9 years were young. Regarding surveillance examinations, 21.9% (7/32) said they would perform a surveillance colonoscopy or sigmoidoscopy in the future if less than five juvenile polyps were found in the colon. Meanwhile, if less than five adenomatous polyps were found in the colon, 93.8% (30/32) said they would perform surveillance colonoscopy or sigmoidoscopy in the future. @*Conclusion@#More than half of the pediatric endoscopic specialists in Korea choose between a colonoscopy and sigmoidoscopy depending on the patient’s age, contrary to the generally accepted recommendation of total colonoscopy if colorectal polyps are suspected in children and adolescents. In this survey, most pediatric endoscopists used the age range of 4–9 years as the reference age.
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Purpose@#We aimed to investigate factors that correlate with fecal calprotectin (FC) levels in children and adolescents with colorectal polyps. @*Methods@#Pediatric patients aged <19 years who underwent colonoscopic polypectomy for a juvenile polyps (JPs) and FC tests were simultaneously conducted in a multicenter, retrospective study. Baseline demographics, colonoscopic and histological findings, and laboratory tests, including FC levels, were investigated. Correlations between the factors were investigated, and linear regression analysis revealed factors that correlated with FC levels. FC levels measured after polypectomies were investigated and the FC levels pre- and post-polypectomies were compared. @*Results@#A total of 33 patients were included in the study. According to Pearson correlation analysis, the polyp size was the only factor that showed a statistically significant correlation with FC levels (r=0.75, p<0.001). Furthermore, according to the multivariate linear regression analysis, polyp size was the only factor that showed a statistically significant correlation with FC levels (adjusted R2=0.5718, β=73.62, p<0.001). The median FC level was 400 mg/ kg (interquartile range [IQR], 141.6–1,000 mg/kg), and the median polyp size was 14 mm (IQR, 9–20 mm). Nineteen patients underwent post-polypectomy FC tests. FC levels showed a significant decrease after polypectomy from a median of 445.2 mg/kg (IQR, 225–1,000) to 26.5 mg/kg (11.5–51) ( p<0.001). @*Conclusion@#FC levels significantly correlated with polyp size in children and adolescents with JPs.
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Background@#Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. @*Methods@#This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. @*Results@#In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). @*Conclusions@#There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.
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In mid-2022, as the wave of pediatric coronavirus disease 2019 (COVID-19) cases escalated in South Korea, a public-private partnership was made to establish a Pediatric COVID-19 Module Clinic (PMC). We describe the utilization of the first prototype children’s modular clinic in Korea University Anam Hospital functioning as the COVID-19 PMC. Between August 1 and September 30, 2022, a total of 766 children visited COVID-19 PMC. Daily number of patient visits to the COVID-19 PMC ranged between 10 and 47 in August; and less than 13 patients per day in September 2022. Not only the model provided timely care for the COVID-19 pediatric patients, but it also enabled safe and efficacious care for the non-COVID-19 patients in the main hospital building while minimizing exposure risk to severe acute respiratory syndrome coronavirus 2 transmission. Current description highlights the importance of spatial measures for mitigating in-hospital transmission of COVID-19, in specifically on pediatric care.
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Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.
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Purpose@#This study aimed to investigate the characteristics of elderly patients who visited a non-regional trauma center to examine the effects of old age on the clinical outcomes of patients. @*Methods@#The medical charts of 159 patients with trauma who visited the National Health Insurance Service Ilsan Hospital between March 2020 and February 2022 were retrospectively analyzed. @*Results@#Of the 159 patients, 41 were assigned to the elderly patient group (EPG) and 118 were assigned to the non-elderly patient group (NEPG). The average age of patients in each group was 75.5 and 38.2 years in the EPG and the NEPG, respectively. Comparing the injury mechanism between the two groups, pedestrian traffic accidents (TA) were the most common (24.4%), followed by slipping (19.5%), motorcycle TA, and bicycle TA (14.6%) in EPG. In the NEPG, motorcycle TA (28.0%) was the most common, followed by car TA (27.1%), and fall injury (16.9%), with a significant difference between the two groups (p < 0.001). The significant differences between the two groups were the injury severity score (ISS; p = 0.004), severe trauma (p = 0.045), intensive care unit admission (p = 0.028), emergency operation (p = 0.034), and mortality (p = 0.013). The statistically significant risk factors for mortality were old age (p = 0.024) and chest injury (p = 0.013). @*Conclusion@#Patients in the EPG compared with the NEPG group showed different injury mechanisms. The EPG has a higher severity and mortality rate than the NEPG.
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γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.
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Background/Aims@#Endoscopic submucosal dissection is a widely used treatment for gastric epithelial neoplasms. Accurate delineation of the horizontal margins is necessary for the complete resection of gastric epithelial neoplasms. Recently, image-enhanced endoscopy has been used to evaluate horizontal margins of gastric epithelial neoplasms. The aim of this study was to investigate whether I-SCAN-optical enhancement (I-SCAN-OE) is superior to chromoendoscopy in evaluating the horizontal margin of gastric epithelial neoplasms. @*Methods@#This was a multicenter, prospective, and randomized trial. The participants were divided into two groups: I-SCAN-OE and chromoendoscopy. For both groups, we first evaluated the horizontal margins of early gastric cancer or high-grade dysplasia using white-light imaging, and then evaluated, the horizontal margins using I-SCAN-OE or chromoendoscopy. We devised a unique scoring method based on the pathological results obtained after endoscopic submucosal dissection to accurately evaluate the horizontal margins of gastric epithelial neoplasms. The delineation scores of both groups were compared, as were the ratios of positiveegative horizontal margins. @*Results@#In total, 124 patients were evaluated for gastric epithelial neoplasms, of whom 112 were enrolled in the study. A total of 112 patients participated in the study, and 56 were assigned to each group (1:1). There was no statistically significant difference in the delineation scores between the groups (chromoendoscopy, 7.80±1.94; I-SCAN-OE, 8.23±2.24; p=0.342). @*Conclusions@#I-SCAN-OE did not show superiority over chromoendoscopy in delineating horizontal margins of gastric epithelial neoplasms.
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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.
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Objectives@# This study evaluated usual dietary intakes of total fat and fatty acids among the Korean population based on the revised Dietary Reference Intakes for Koreans 2020 (2020 KDRIs). @*Methods@# This study utilized data from the eighth Korea National Health and Nutrition Examination Survey (KNHANES 2019–2021). We included 18,895 individuals aged 1 year and above whose 1-day 24-hour dietary recall data were available. To calculate the external variability using the National Cancer Institute 1-day method, data from the U.S. NHANES 2017-March 2020 Pre-pandemic dataset were employed. The total fat and fatty acid intake were evaluated based on the Acceptable Macronutrient Distribution Ranges (AMDRs) and Adequate intake (AI) of 2020 KDRIs for each sex and age groups. @*Results@# Approximately 86% of the Korean population obtained an adequate amount of energy from total fat consumption (within the AMDRs), indicating an appropriate level of intake. However, the percentage of individuals consuming saturated fatty acids below the AMDR was low, with only 12% among those under 19 years of age and 52% aged 19 years and older. On a positive note, approximately 70% of the population showed adequate consumption of essential fatty acids, exceeding the AI. Nevertheless, monitoring the intake ratio of omega 3 (n-3) to omega 6 (n-6) fatty acids is essential to ensure an optimum balance. @*Conclusions@# This study explored the possibility of estimating the distribution of nutrient intake in a population by applying the external variability ratio. Therefore, if future KNHANES conduct multiple 24-hour recalls every few years-similar to the U.S. NHANESeven for a subset of participants, this may aid in the accurate assessment of the nutritional status of the population.
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Purpose@#: This study aimed to identify and describe the leadership experience of advanced practice nurses (APN). @*Methods@#: Data were collected through five focus group interviews in 2022 with a total of 24 APNs in groups of 4-6 participants. All interviews were recorded, transcribed, and data were analyzed using qualitative content analysis. @*Results@#: Nine categories emerged from three main themes. First, “Roles of APN leadership” comprised a trusted clinical expert, a moderator for the entire team, a resource person for nurturing the next generation, and a change agent for improving clinical practice. Second, “Facilitators and barriers to APN leadership” included ambiguity of APN role, support system, and institutional backing. Third, “Strategies for strengthening APN leadership competencies” comprised systematic leadership education and speaking up for APNs. @*Conclusion@#: APNs are passionate about their expertise and practice, but lack the legal and organizational authority and support to provide successive leadership. Systematic education including leadership and organizational advocacy will enable APN to provide leadership that benefits patients, institutions, and the wider healthcare system.
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Purpose@#In this study, we investigated the prognostic implications of focal breast edema on preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer. @*Methods@#Data of 899 patients with breast cancer at a single institution were retrospectively analyzed. The patients were divided into an edema-positive group (EPG) and an edemanegative group (ENG) based on the presence of peritumoral, prepectoral, or subcutaneous edema. Two radiologists evaluated the presence or absence of focal edema and its subtypes on preoperative breast MRI. Clinicopathologic characteristics and survival outcomes were compared between the two groups and among the three subtypes using Pearson’s χ2 test, Kaplan–Meier estimator, and Cox proportional hazards model. @*Results@#There were 399 (44.4%) and 500 (55.6%) patients in the EPG and ENG, respectively.The EPG showed significantly higher rates of axillary lymph node metastasis (55.6% vs.19.2%, p < 0.001) and lymphovascular invasion (LVI) (57.9% vs. 12.6%, p < 0.001) than the ENG. Patients in the EPG showed significantly worse overall survival (OS) rate (log-rank p < 0.001; hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56–9.11) and recurrencefree survival rate (log-rank p < 0.001; HR, 3.00; 95% CI, 1.94–4.63) than those in the ENG.After adjusting for other variables, focal breast edema remained a significant factor affecting the OS rate, regardless of the edema type. Specifically, the presence of subcutaneous edema emerged as the strongest predictor for OS with the highest HR (p < 0.001; HR, 9.10; 95% CI, 3.05–27.15). @*Conclusion@#Focal breast edema on preoperative breast MRI implies a higher possibility of LVI and axillary lymph node metastasis, which can lead to a poor prognosis. A detailed description of focal breast edema, especially subcutaneous edema, on preoperative breast MRI may provide prognostic predictions. More intensive surveillance is required for patients with breast cancer and focal preoperative breast edema.
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Purpose@#A nationwide study (2012-2017) of preventable trauma death rates (PTDR) showed a 15.3% decrease after Regional Trauma centers were initiated. However, in non-trauma centers with an Emergency Department there is limited data of preventable mortality in trauma patients. Therefore, the purpose of this retrospective study was to investigate preventable mortality in trauma patients in a nonregional trauma center and determine the effect of initiating a Trauma Team. @*Methods@#There were 46 deaths of trauma patients recorded in the National Health Insurance service Ilsan Hospital (NHISIH) in South Korea from January 2019 to December 2021. These patients’ preventable deaths were analyzed by an expert panel review considering the implementation of the Trauma Team in April 2020. @*Results@#All deaths were attributable to blunt trauma with an average Injury Severity Score of 26.0 ± 19.2, Revised Trauma Score of 5.05 ± 3.20 and Trauma and Injury Score of 56.6 ± 41.3. The most frequent cause of death was traumatic brain injury followed by respiratory arrest. The most frequent error was delayed transfusion followed by delayed treatment of bleeding. Treatment errors occurred the most in the Emergency Room followed by the Intensive Care Unit. The PTDR of patients before the involvement of a Trauma Team (January 2019 to March 2020) and after the Trauma Team was initiated in April 2020 decreased from 27.27% to 4.27%, respectively (p = 0.021). @*Conclusion@#The introduction of a dedicated Trauma Team in a non-regional trauma center significantly reduced the overall PTDR in trauma patients.
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Background/Aims@#A full colonoscopy is currently required in children and adolescents with colorectal polyps, because of their potential of neoplastic transformation and complications such as intussusception. We aimed to analyze the associations of polyp characteristics in children and adolescents with colorectal polyps. Based on these findings, we also aimed to reevaluate the necessity of conducting a full colonoscopy. @*Methods@#Pediatric patients <18 years of age who had undergone a colonoscopic polypectomy and those with <5 colorectal polyps were included in this multicenter, retrospective study. Baseline clinicodemographics, colonoscopic and histologic findings were investigated. @*Results@#A total of 91 patients were included. Multivariate logistic regression analysis showed that polyp size was the only factor associated with the presence of any polyps located proximal to the splenic flexure (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.28 to 4.28; p=0.007). Furthermore, polyp location proximal to the splenic flexure and sessile morphology were associated with the presence of any adenomatous polyp (OR, 8.51; 95% CI, 1.43 to 68.65; p=0.023; OR, 18.41; 95% CI, 3.45 to 173.81; p=0.002, respectively). @*Conclusions@#In children and adolescents presenting with <5 colorectal polyps, polyp size and the presence of any adenomatous polyp were positively associated with polyp location proximal to the splenic flexure. This finding supports the necessity of a full colonoscopic exam in pediatric patients with colorectal polyps for the detection of polyps before the occurrence of complications such as intussusception or neoplastic transformation.
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Purpose@#This study aimed to compare the intraoperative and postoperative outcomes between robotic and laparoscopic transperitoneal adrenalectomies. @*Methods@#In this retrospective study, 93 patients underwent adrenalectomy using 2 surgical modalities: 45 patients underwent adrenalectomy using the da Vinci Xi system (robotic group), and 48 patients using laparoscopic devices (laparoscopic group). We compared the operation time, intraoperative bleeding, and hospital stay according to the surgical modality and tumor characteristics. @*Results@#There were no significant differences in the operative time (P = 0.827), hospital stay (P = 0.177), and intraoperative bleeding (P = 0.174) between the groups. However, the robotic group showed a lower coefficient of variation in total operative time than that of the laparoscopic group (100.6 ± 23.3 minutes vs. 101.9±32.7 minutes, 0.230 vs. 0.321). When divided into 2 subgroups based on the tumor size (3 cm had a shorter operative time than that of the laparoscopic group (P = 0.032). The robotic group also had fewer cases of intraoperative bleeding (P = 0.034). @*Conclusions@#Compared to the laparoscopic transperitoneal adrenalectomy, the robotic one achieved a lower deviation in total operative time and showed less bleeding and a shorter operative time, especially for tumors sized >3 cm.
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Rubinstein-Taybi syndrome (RSTS) is an extremely rare genetic disorder affecting multi-organ systems. A tendency to form keloid is one of the common dermatologic manifestations.We describe a 23-year-old female presented with extensive keloids which developed spontaneously. She had typical facial features, broad thumbs, and dental defects, which were suspicious features of genetic syndrome. Direct sequencing for cyclic-AMP-regulated enhancer binding protein revealed a novel mutation. So far, 23 cases of RSTS have been reported in Korean literature. To the best of our knowledge, this is the first report in Korea to describe confirmed case of RSTS with extensive keloids as a chief manifestation.
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Background@#Pitavastatin is a cholesterol-lowering drug and is widely used clinically. In addition to this effect, pitavastatin has shown the potential to induce apoptosis in cutaneous squamous cell carcinoma (SCC) cells. @*Objective@#The purpose of this study is to investigate the effects and possible action mechanisms of pitavastatin. @*Methods@#SCC cells (SCC12 and SCC13 cells) were treated with pitavastatin, and induction of apoptosis was confirmed by Western blot. To examine whether pitavastatin-induced apoptosis is related to a decrease in the amount of intermediate mediators in the cholesterol synthesis pathway, the changes in pitavastatin-induced apoptosis after supplementation with mevalonate, squalene, geranylgeranyl pyrophosphate (GGPP) and dolichol were investigated. @*Results@#Pitavastatin dose-dependently induced apoptosis of cutaneous SCC cells, but the viability of normal keratinocytes was not affected by pitavastatin at the same concentrations. In supplementation experiments, pitavastatin-induced apoptosis was inhibited by the addition of mevalonate or downstream metabolite GGPP. As a result of examining the effect on intracellular signaling, pitavastatin decreased Yes1 associated transcriptional regulator and Ras homolog family member A and increased Rac family small GTPase 1 and c-Jun Nterminal kinase (JNK) activity. All these effects of pitavastatin on signaling molecules were restored when supplemented with either mevalonate or GGPP. Furthermore, pitavastatininduced apoptosis of cutaneous SCC cells was inhibited by a JNK inhibitor. @*Conclusion@#These results suggest that pitavastatin induces apoptosis of cutaneous SCC cells through GGPP-dependent JNK activation.
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Epiphora is a symptom in which tears overflow onto the face, with its most common cause being the obstruction of the nasolacrimal system. As a cause of nasolacrimal system obstruction, nasolacrimal duct tumors are very rare. Angioleiomyoma, which is a benign tumor, arises from vascular smooth muscle, occurs in the nasolacrimal duct, and is extremely rare. With the development of endoscopic intranasal approach for the treatment of nasolacrimal duct obstruction, there is increased importance for the consideration of otorhinolaryngological evaluation and treatment as well as dacryocystorhinostomy by conventional external approach. In this article, we introduce a case in which angioleiomyoma in the nasolacrimal duct was detected by nasal endoscopy and was successfully treated with endoscopic surgery.
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Purpose@#This article aimed to investigate 1) whether electronic cigarette (EC) users are more likely to experience asthma attacks or emergency room (ER) visits due to asthma than non-users and 2) how age and smoking behaviors moderate the effect size of the association. @*Materials and Methods@#We used National Health Interview Survey data from 2016–2019. Multiple logistic regression analysis was performed to identify the association between current EC use and having an asthma attack and ER visitation due to asthma. Interaction terms were included to explore the moderation effects of age and cigarette smoking status. Subgroup analysis was conducted according to age group. @*Results@#Of the 218911 participants, 2.0% of them experienced an asthma attack, and 0.5% visited the ER due to asthma. Current EC use was associated with higher odds of having an asthma attack. In interaction analysis, age and smoking status were identified as a moderator in the relationship between EC use and asthma attacks. Participants in their 20s or 30s showed the highest interaction effect. @*Conclusion@#Our analysis indicates the potential impact of EC use on public health and the moderating effects of smoking behavior.