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Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

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Purpose@#In the era of minimally invasive surgery (MIS), robotic pancreatoduodenectomy (PD) is actively performed, and clinical fellows need to thoroughly prepare for MIS-PD during the training process. Although pancreaticojejunostomy (PJ) is a difficult anastomosis that requires repeated practice, there are obstacles preventing its practice that concerns patient safety and limited time in the actual operating room. This study evaluated the efficacy of simulation-based training of robotic duct-to-mucosa PJ using pancreatic and intestinal silicone models using a scoring system. @*Methods@#Three pancreatobiliary clinical fellows who had never performed a real robotic PJ participated in this study. Each trainee, who was well acquainted with master’s video created by a senor surgeon, performed the robotic PJ procedures 9 times, and 3 independent pancreatobiliary surgeons assessed the videos and analyzed the scores using a blind method. @*Results@#The mean robotic PJ times for the 3 trainees were 42.8 and 29.1 minutes for the first and 9th videos, respectively.The mean score was 13.8 (range, 6–17) for the first video and 17.7 (range, 15–19) for the 9th video. When comparing earlier and later attempts, the PJ time decreased significantly (2,201.67 seconds vs. 2,045.50 seconds, P = 0.007), whereas test scores increased significantly (total score 14.22 vs. 16.89, P = 0.011). @*Conclusion@#This robotic education system will help pancreatobiliary trainees overcome the learning curves efficiently and quickly without raising ethical concerns associated with animal models or direct practice with human subjects. This will be of practical assistance to trainees preparing for MIS-PD.

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Although the importance of health promotion for nurses is increasing, there is a lack of meta-analyses targeting nurses in the world. This study aimed to identify the effect sizes between the health-promoting behaviors and related variables of nurses working in Korea. Methods: Systematic review and meta-analysis were conducted according to the PRISMA and MOOSE guidelines. The literature included in this meta-analysis was published between 1994 and 2022 in core databases such as KMbase, KISS, KoreaMed, ScienceON, DBpia, NAL, RISS, CINAHL, CENTRAL, WoS, PubMed, and hand searched. In this study, the PICO-SD framework was applied with Participants being nurses actively working in various healthcare settings across Korea, and for a more comprehensive search, intervention and comparisons were not set. The outcomes measured were nurses' health-promoting behaviors, assessed using structured tools. The study design included observational studies. The Comprehensive Meta-Analysis and the R software program were used for meta-analysis. Results: In total, 50 articles were selected for the systematic review and meta-analysis. The total effect size of the 50 articles was moderate (correlation effect size [ESr] = 0.30). The individual variables presented in the 50 articles were classified into nine sub-categories according to Pender's Health Promotion Model (HPM). Among them, situational influences demonstrated the largest effect size (ESr = 0.44, number of studies [k] = 2), followed by perceived self-efficacy (ESr = 0.39, k = 10) and activity-related affect (ESr = 0.32, k = 12). Conclusions: To achieve the optimal health status of nurses through health promotion intervention programs, these effective variables – situational influences, perceived self-efficacy, and activity-related affect – should be considered when developing the intervention program for nurses.

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Purpose@#The incidence of early-onset colorectal cancer (EoCRC) is increasing worldwide. The association between hypertriglyceridemia (HTG) and EoCRC risk remains unclear. @*Materials and Methods@#We conducted a nationwide cohort study of 3,340,635 individuals aged 20-49 years who underwent health checkups between 2009 and 2011 under the Korean National Health Insurance Service. HTG was defined as serum triglyceride (TG) level ≥ 150 mg/dL. According to the change in TG status, participants were categorized into persistent normotriglyceridemia (NTG; group 1), NTG to HTG (group 2), HTG to NTG (group 3), and persistent HTG (group 4) groups. The EoCRC incidence was followed up until 2019. @*Results@#In total, 7,492 EoCRC cases developed after a mean of 6.05 years of follow-up. Group 4 had the highest risk of EoCRC (adjusted hazard ratio [aHR], 1.097; 95% confidence interval [CI], 1.025 to 1.174). While the risk of rectal cancer was significantly increased in groups 3 and 4 (aHR [95% CI], 1.236 [1.076 to 1.419] and 1.175 [1.042-1.325], respectively), no significant risk differences were observed in right colon cancer. In group 4, male sex and diabetes were associated with a further increased risk of EoCRC (aHR [95% CI], 1.149 [1.082 to 1.221] and 1.409 [1.169 to 1.699], respectively). In addition, there was a dose-response relationship between serum TG levels and the risk of EoCRC (p for trends < 0.0001). @*Conclusion@#Persistent HTG increased the risk of EoCRC, which was significantly higher only for rectal cancer and marginally higher for other colonic subsites.

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Tyrosine kinase (TK) inhibitors are most common used to treat chronic myeloid leukemia (CML). Several studies describe a range of adverse effects of TK inhibitors on the kidney in adult patients, including nephrotic syndrome. However, there are only a few pediatric case reports on TK inhibitor-associated nephrotic syndrome. We report a case of nephrotic syndrome associated with dasatinib, a type of TK inhibitor, in a child who suffered from both the underlying idiopathic nephrotic syndrome and CML. A 14-year-old Korean boy was diagnosed with steroid dependent nephrotic syndrome at 4 years old and CML at 11 years old. He developed a relapse of nephrotic syndrome after treatment with TK inhibitors, especially dasatinib, which he used for four months. Despite receiving steroid pulse therapy due to his underlying steroid dependent nephrotic syndrome, his proteinuria did not respond. He discontinued dasatinib medication due to the possibility to dasatinib induced nephrotic syndrome.After one week, his nephrotic syndrome improved. The case is important because if a CML patient that has been on a TK inhibitor develops a newly onset nephrotic range proteinuria, TK inhibitor-induced nephrotic syndrome should be included in the differential diagnosis.

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Background@#and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. @*Methods@#This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. @*Results@#The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). @*Conclusions@#Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

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Background@#and Purpose Despite the growing demands and challenges faced by patients with amyotrophic lateral sclerosis (ALS) in accessing healthcare services, our understanding of this access remains poor. This study aimed to investigate the healthcare utilization patterns and timing of nutritional and respiration support in patients with ALS in South Korea. @*Methods@#A retrospective cohort study was conducted on patients diagnosed with ALS at a single tertiary hospital between 2016 and 2019 and followed up for 2 years. We evaluated patient characteristics, healthcare utilization (hospital admissions, outpatient visits, and emergency department [ED] visits), and the timing of nutritional and respiration support (noninvasive positive pressure ventilation [NIPPV], tracheostomy, gastrostomy, and nasogastric tube) at 6-month intervals from the first outpatient visit. @*Results@#Among the 143 included patients, 73.4% were admitted at least once, 18.9% experienced unplanned admissions, and 30.1% visited the ED at least once during the study period.The most-common reason for ED visits was neurological symptoms during the first 6 months (59.1%), followed by respiratory symptoms. One fifth of patients who visited the ED underwent tracheostomy (20.9%) or NIPPV (20.9%). Two years after the first visit, 32.2% used a ventilator, and 13.3%, 26.6%, and 6.3% had undergone tracheostomy, gastrostomy, and nasogastric tube insertion, respectively. @*Conclusions@#During the 2 years following their first outpatient visit, 20% of patients with ALS experienced unplanned admissions and 30% visited the ED. An active and prompt supportivecare program should be implemented to ensure timely functional support in order to reduce these risks of unplanned admissions.

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Background/Aims@#To evaluate the efficacy of quadruple-coated probiotics (gQlab) in patients with irritable bowel syndrome (IBS), focusing on sex differences and IBS subtypes. @*Methods@#One hundred and nine Rome III-diagnosed IBS patients were randomized into either a gQlab or placebo group and received either gQlab or a placebo for 4 weeks. Participants replied to questionnaires assessing compliance, symptoms, and safety. Fecal samples were collected at 0 and 4 weeks to measure the probiotic levels using real-time quantitative polymerase chain reaction (qPCR) and to perform metagenomic analysis via 16S ribosomal DNA sequencing. The primary endpoint was the change in the overall IBS symptoms after 4 weeks of treatment. @*Results@#Ninety-two subjects (47 and 45 in the gQlab and placebo groups, respectively) completed the study protocol. At week 4, there was a higher relief of the overall IBS symptoms in the gQlab group (P = 0.005). The overall IBS symptom improvement was statistically significant (P = 0.017) in female patients of the gQlab group compared with the placebo group. Among the IBS subtypes, constipation-predominant IBS patients showed significant relief of the overall IBS symptoms (P = 0.002). At week 4, the fecal microbiome profiles between the 2 groups did not differ, but the qPCR levels of Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus helveticus, Bifidobacterium longum, and Bifidobacterium breve were increased in the gQlab group (P < 0.05 by repeated measures ANOVA). @*Conclusions@#gQlab administration can improve the overall IBS symptoms, especially in female and constipation-predominant IBS patients. Further research is necessary to clarify the pathophysiology behind sex-related treatment responses in IBS patients.

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Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disorder associated with fibroinflammatory conditions that can affect multiple organs. Hallmark histopathological findings of IgG4-RD include lymphocytic infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. However, little is known about central nervous system involvement of IgG4-RD.Hypertrophic pachymeningitis (HP) has recently been reported as a manifestation of IgG4-RD, which may have previously been demonstrated in a significant percentage of idiopathic cases. Herein, we report a rare case of a 63-year-old male who presented with a scalp mass that mimicked a brain tumor. He was diagnosed with IgG4-related HP (IgG4-RP) after surgery. This case suggests that awareness of a possibility of IgG4-RP in patients with isolated scalp masses, even in the absence of systemic symptoms, is crucial. A combination of careful history taking, evaluation of serum IgG4-levels and imaging as an initial work-up, followed by tissue biopsy, is important for the differential diagnosis of IgG4-RP, malignancy, and other infectious diseases.

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Food addiction refers to a condition in which individuals exhibit addictive-like behaviors toward food, like those observed in substance abuse. Although still debated, evidence supporting the validity and usefulness of the concept of food addiction is growing.Food addiction is particularly associated with obesity and eating disorders involving binge eating. This study discusses the cases of two adolescent patients who presented with anorexia nervosa. During the recovery phase of anorexia nervosa, binge eating was observed, and the patterns of binge eating significantly differed between patients, with and without food addiction. Therefore, healthcare professionals treating eating disorders should be aware of food addiction and modify their treatment strategies accordingly.

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Autism spectrum disorder (ASD) can be associated with eating problems. However, currently, there is a lack of established guidelines for assessing and addressing eating behaviors in individuals with ASD. This gap in research exists due to the challenges associated with using traditional assessment methods, which may lead to discrepancies in responses and unintentional potential biases from caregivers. In this review, we provided a comprehensive overview of various eating behaviors commonly observed in individuals with ASD. These behaviors include 1) food neophobia, 2) selective eating, 3) binge eating, 4) food avoidance, 5) chewing and swallowing problems, 6) pica, 7) rumination, 8) rituals, and 9) problematic behaviors. Furthermore, we provide a perspective of utilizing digital tools: 1) augmentative and alternative communication; 2) ecological momentary assessment; and 3) video analysis, behavioral analysis, and facial expression analysis. This review explores existing assessment methods and suggests novel assessment aiding together.

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Nivolumab is a checkpoint inhibitor monoclonal antibody, designed to interact with the programmed death cell receptor-1, preventing the inhibitory signaling on cytotoxic T cells. Immune checkpoint inhibitors can lead to severe cutaneous immune-related adverse events (irAEs). A 54-year-old female with a breast cancer metastasis was referred to our clinic due to diffuse cutaneous lesions of crusted erythematous patches and multiple blisters for 2 weeks. Five months before presentation, she started nivolumab/eribulin immunotherapy. Skin biopsy showed subepidermal blistering with perivascular lymphohistiocytic infiltration with eosinophils. Direct immunofluorescence showed linear deposition of immunoglobulin G and C3 along the dermoepidermal junction, consistent with bullous pemphigoid.Temporal relationship between initiation of nivolumab and skin lesion suggested the diagnosis of nivolumab-induced bullous pemphigoid. Dermatologic toxicity is the most common irAEs associated with nivolumab, but nivolumab-induced bullous pemphigoid is rare. Given the widespread use of immunotherapy, it is important to document this case to develop proper management strategies.

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Nontuberculous mycobacterial infections, which are often acquired from environmental sources such as water and soil, exhibit a variety of cutaneous manifestations that frequently lead to misdiagnoses and delays in treatment. A 77-year-old woman presented with multiple skin lesions in a sporotricoid distribution on her right leg, which persisted despite standard antibiotic treatments. Based on the skin biopsy, revealing granulomatous inflammation with acid-fast bacilli, and PCR testing, a nontuberculous mycobacterial infection was diagnosed. Antimycobacterial drug combinations, including clarithromycin, isoniazid, and rifampicin for 4 months, complete the skin lesion's clearance. This case underscores the need for heightened suspicion and the use of appropriate diagnostic techniques, including tissue biopsies and molecular methods such as PCR.

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Purpose@#This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer. @*Materials and Methods@#Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis. @*Results@#The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02). @*Conclusion@#Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient’s age at IBC diagnosis, income level, and a receipt of systemic treatments.

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Objective@#Discharge against medical advice (DAMA) from emergency departments (EDs) accounts for 0.1% to 2.7%. DAMA carries a risk of increased mortality and readmissions, and higher medical nationwide cost. Our aim was to investigate the general characteristics of DAMA patients from ED and discover for methods to reduce DAMA. @*Methods@#In this study, we collected and analyzed the medical records of patients who visited the ED of a general hospital from 2015 to 2020. The subjects were categorized into a DAMA group and a non-DAMA group. We compared these groups with respect to gender, age, duration of ED stay, way to visit, the reason for the visit, insurance type, accompanied by guardian, and severity classification. In addition, the factors related to ED revisits or hospitalization within one month after DAMA were analyzed. @*Results@#Of the 209,076 patients, 1,982 were subject to DAMA from ED. The DAMA group had a higher ratio of visits to ED by ambulance (53.2% vs. 21.4%, P<0.001), critically ill patients (74.1% vs. 51.7%, P<0.001), and medical aid type 1 (7.7% vs. 3.4%, P<0.001). The factors for the high ratio of ED revisit within one month after DAMA were as follows: critically ill patients (odds ratio [OR], 1.916; 95% confidence interval [CI], 1.305-2.814), accompanied by a guardian (OR, 1.525; 95% CI, 1.105-2.105), and medical aid type 1 (OR, 2.025; 95% CI, 1.358-3.02). @*Conclusion@#Developing a manual on DAMA procedures and a system that can provide economic and social support to patients is to be established to reduce DAMA from ED.

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Merkel cell carcinoma (MCC), a rare cutaneous neuroendocrine carcinoma, is most common in sun-exposed areas of aged individuals. Merkel cell polyomavirus (MCPyV) is one causative agent of MCC. Cases of MCC concurrent with other skin tumors, especially squamous cell carcinoma, are rarely reported. Immunohistochemical staining is performed using antibodies to the MCPyV large-T antigen (CM2B4) only in select cases. To date, no cases of MCPyV have been reported in Korea. Here we report a case of MCC concurrent with squamous cell carcinoma in an aged man and discuss the pathogenesis of the case through CM2B4 staining.

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The depressor anguli oris (DAO) muscle is a thin, superficial muscle located below the corner of the mouth. It is the target for botulinum neurotoxin (BoNT) injection therapy, aimed at treating drooping mouth corners. Hyperactivity of the DAO muscle can lead to a sad, tired, or angry appearance in some patients. However, it is difficult to inject BoNT into the DAO muscle because its medial border overlaps with the depressor labii inferioris and its lateral border is adjacent to the risorius, zygomaticus major, and platysma muscles. Moreover, a lack of knowledge of the anatomy of the DAO muscle and the properties of BoNT can lead to side effects, such as asymmetrical smiles. Anatomical-based injection sites were provided for the DAO muscle, and the proper injection technique was reviewed. We proposed optimal injection sites based on the external anatomical landmarks of the face. The aim of these guidelines is to standardize the procedure and maximize the effects of BoNT injections while minimizing adverse events, all by reducing the dose unit and injection points.

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Purpose@#There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. @*Materials and Methods@#Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. @*Results@#193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. @*Conclusion@#Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

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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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This article provides an annual update of Korean breast cancer statistics, including the incidence, tumor stage, type of surgical treatment, and mortality. The data was collected from the Korean Breast Cancer Society registry system and Korean Central Cancer Registry.In 2019, 29,729 women were newly diagnosed with breast cancer. Breast cancer has continued to increase in incidence since 2002 and been the most common cancer in Korean women since 2019. Of the newly diagnosed cases in 2019, 24,820 (83.5%) were of invasive carcinomas, and 4,909 (16.5%) were of carcinoma in situ. The median age of women with breast cancer was 52.8 years, and breast cancer was most commonly diagnosed in the age group of 40–49 years. The number of patients who have undergone breast conserving surgery has continued to increase since 2016, with 68.6% of patients undergoing breast conserving surgery in 2019. The incidence of early-stage breast cancer continues to increase, with stage 0 or I breast cancer accounting for 61.6% of cases. The most common subtype of breast cancer is the hormone receptor-positive human epidermal growth factor receptor 2-negative subtype (63.1%). The 5-year relative survival rate of patients with breast cancer from 2015 to 2019 was 93.6%, with an increase of 14.3% compared to that from 1993 to 1995. This report improves our understanding of breast cancer characteristics in South Korea.