Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background/Aims: Functional dyspepsia (FD) has long been regarded as a syndrome because its pathophysiology is multifactorial. However, recent reports have provided evidence that changes in the duodenal ecosystem may be the key. This study aimed to identify several gastrointestinal factors and biomarkers associated with FD, specifically changes in the duodenal ecosystem that may be key to understanding its pathophysiology. Methods: In this case-control study, 28 participants (12 with FD and 16 healthy control individuals) were assessed for dietary nutrients, gastrointestinal symptom severity, immunological status of the duodenal mucosa, and microbiome composition from oral, duodenal, and fecal samples. Integrated data were analyzed using immunohistochemistry, real-time polymerase chain reaction, 16S rRNA sequencing, and network analysis. Results: Duodenal mucosal inflammation and impaired expression of tight junction proteins were confirmed in patients with FD. The relative abundance of duodenal Streptococcus (p=0.014) and reductions in stool Butyricicoccus (p=0.047) were confirmed. These changes in the gut microbiota were both correlated with symptom severity. Changes in dietary micronutrients, such as higher intake of valine, were associated with improved intestinal barrier function and microbiota. Conclusions This study emphasizes the relationships among dietary nutrition, oral and gut microbiota, symptoms of FD, impaired function of the duodenal barrier, and inflammation. Assessing low-grade inflammation or increased permeability in the duodenal mucosa, along with changes in the abundance of stool Butyricicoccus, is anticipated to serve as effective biomarkers for enhancing the objectivity of FD diagnosis and monitoring.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D).In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Objectives: This study aimed to investigate the relationship between adult attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms. Methods: A total of 52 patients diagnosed with adult ADHD completed self-report assessment scales. The clinical features of ADHD were assessed using the Adult ADHD Self-Report Scale (ASRS) and Korean Adult ADHD Rating Scale (K-AARS). The State-Trait Anxiety Inventory (STAI) was used to assess anxiety-related symptoms. Correlation and linear regression analyses were conducted to examine the relationships between the diagnostic scales of adult ADHD and anxiety. Results: Higher scores on the ASRS were related to higher scores on the STAI-S (r=0.482) and STAI-T (r=0.573), which assess state anxiety and trait anxiety, respectively. Subscales of inattention (STAI-S, r=0.485; STAI-T, r=0.648), impulsivity (STAI-S, r=0.404; STAI-T, r=0.491), emotional dysregulation (STAI-S, r=0.498; STAI-T, r=0.639), disorganization (STAI-S, r=0.427; STAI-T, r=0.545) on the KAARS, and the subtotal of K-AARS clinical subscales (STAI-S, r=0.517; STAI-T, r=0.540) had significant correlations with both STAI-S and STAI-T scores. After adjusting for demographic characteristics, there were significant associations between ASRS total scores (β= 0.299) and STAI-S scores, and between inattention (β=0.297), impulsivity (β=0.560), emotional dysregulation (β=0.393), disorganization (β=0.817), subtotal scores on the K-AARS subscales (β=0.114), and STAI-S scores. The multivariate regression analysis also showed significant associations between ASRS total scores (β=0.409) and STAI-T scores. Associations between K-AARS subscales of inattention (β=0.468), impulsivity (β=0.817), emotional dysregulation (β=0.598), disorganization (β=1.120), subtotal scores on the K-AARS subscales (β=0.134), and STAI-T scores remained significant after adjusting demographic variables. Conclusion Comprehensive assessment of ADHD symptoms related to anxiety would be important for the evaluation and treatment of anxiety in adult ADHD patients.

Objective: In Korea, radiology has been positioned towards the early adoption of artificial intelligence-based software as medical devices (AI-SaMDs); however, little is known about the current usage, implementation, and future needs of AI-SaMDs.We surveyed the current trends and expectations for AI-SaMDs among members of the Korean Society of Radiology (KSR). Materials and Methods: An anonymous and voluntary online survey was open to all KSR members between April 17 and May 15, 2023. The survey was focused on the experiences of using AI-SaMDs, patterns of usage, levels of satisfaction, and expectations regarding the use of AI-SaMDs, including the roles of the industry, government, and KSR regarding the clinical use of AI-SaMDs. Results: Among the 370 respondents (response rate: 7.7% [370/4792]; 340 board-certified radiologists; 210 from academic institutions), 60.3% (223/370) had experience using AI-SaMDs. The two most common use-case of AI-SaMDs among the respondents were lesion detection (82.1%, 183/223), lesion diagnosis/classification (55.2%, 123/223), with the target imaging modalities being plain radiography (62.3%, 139/223), CT (42.6%, 95/223), mammography (29.1%, 65/223), and MRI (28.7%, 64/223). Most users were satisfied with AI-SaMDs (67.6% [115/170, for improvement of patient management] to 85.1% [189/222, for performance]). Regarding the expansion of clinical applications, most respondents expressed a preference for AI-SaMDs to assist in detection/diagnosis (77.0%, 285/370) and to perform automated measurement/quantification (63.5%, 235/370). Most respondents indicated that future development of AI-SaMDs should focus on improving practice efficiency (81.9%, 303/370) and quality (71.4%, 264/370). Overall, 91.9% of the respondents (340/370) agreed that there is a need for education or guidelines driven by the KSR regarding the use of AI-SaMDs. Conclusion The penetration rate of AI-SaMDs in clinical practice and the corresponding satisfaction levels were high among members of the KSR. Most AI-SaMDs have been used for lesion detection, diagnosis, and classification. Most respondents requested KSR-driven education or guidelines on the use of AI-SaMDs.

Background: Transient receptor potential canonical (TRPC) channels are non-selective cationic channels with perme‑ ability to ­Ca2+ and ­Na+ . Despite their importance, there are currently few studies on TRPC in the periodontal ligament (PDL) and bone cells in the dental field. To provide biological information regarding TRPC in PDL cells and periodontal tissue, we evaluated TRPC channels expression in the osteoblast differentiation of PDL cells and periodontitis-induced tissue. Human PDL cells were cultured in osteogenic differentiation media for 28 days, and the expression of Runx2, osteocalcin (OCN), and TRPC1, 3, 4, and 6 was evaluated by real-time PCR. In ligature-induced periodontitis mice, the alveolar bone and osteoid areas, the osteoclast number, and the expression of Runx2, OCN, TRPC3, and TRPC6 was evaluated by H&E staining, TRAP staining, and immunohistochemistry, respectively. Results: In the PDL cell differentiation group, TRPC6 expression peaked on day 7 and TRPC3 expression generally increased during differentiation. During the 28 days of periodontitis progression, alveolar bone loss and osteoclast numbers increased compared to the control group during the experimental period and the osteoid area increased from day 14. TRPC6 expression in the periodontitis group increased in the PDL area and in the osteoblasts compared to the control group, whereas TRPC3 expression increased only in the PDL area on days 7 and 28. Conclusions These results indicate changes of TRPC3 and TRPC6 expression in PDL cells that were differentiating into osteoblasts and in periodontitis-induced tissue, suggesting the need for research on the role of TRPC in osteo‑ blast differentiation or periodontitis progression.

Objective: Little is known about the effects of using different expert-determined reference standards when evaluating the performance of deep learning-based automatic detection (DLAD) models and their added value to radiologists. We assessed the concordance of expert-determined standards with a clinical gold standard (herein, pathological confirmation) and the effects of different expert-determined reference standards on the estimates of radiologists’ diagnostic performance to detect malignant pulmonary nodules on chest radiographs with and without the assistance of a DLAD model. Materials and Methods: This study included chest radiographs from 50 patients with pathologically proven lung cancer and 50 controls. Five expert-determined standards were constructed using the interpretations of 10 experts: individual judgment by the most experienced expert, majority vote, consensus judgments of two and three experts, and a latent class analysis (LCA) model. In separate reader tests, additional 10 radiologists independently interpreted the radiographs and then assisted with the DLAD model. Their diagnostic performance was estimated using the clinical gold standard and various expertdetermined standards as the reference standard, and the results were compared using the t test with Bonferroni correction. Results: The LCA model (sensitivity, 72.6%; specificity, 100%) was most similar to the clinical gold standard. When expertdetermined standards were used, the sensitivities of radiologists and DLAD model alone were overestimated, and their specificities were underestimated (all p-values < 0.05). DLAD assistance diminished the overestimation of sensitivity but exaggerated the underestimation of specificity (all p-values < 0.001). The DLAD model improved sensitivity and specificity to a greater extent when using the clinical gold standard than when using the expert-determined standards (all p-values < 0.001), except for sensitivity with the LCA model (p = 0.094). Conclusion The LCA model was most similar to the clinical gold standard for malignant pulmonary nodule detection on chest radiographs. Expert-determined standards caused bias in measuring the diagnostic performance of the artificial intelligence model.

Background/Aims: Esophageal perforation is associated with high mortality and morbidity in patients presenting to the emergency department (ED) with esophageal injury. We investigated the effectiveness of initial CT scan in patients with esophageal injury to determine the risk factors for complications. Methods: Patients admitted through the ED for evaluation of esophageal injuries between January 2001 and May 2020, were investigated. Demographic data, etiological factors, comorbidities, treatment administered, and outcomes were collected. Esophageal injury was graded based on the following CT criteria: (a) normal, (b) pneumomediastinum, (c) mediastinitis, fluid collection, abscess, or overt esophageal wall injury, and (d) pleural effusion, subcutaneous emphysema, or pneumothorax. Grade 2 was defined as microperforation and grades 3 and 4 as overt perforation. Results: Of 281 patients with esophageal injury, 38 had CT-documented overt perforations and 20 had microperforations. Foreign body-induced injury (n=37), Boerhaave syndrome (n=12), and chemical injury (n=3) were common causes of esophageal injury. Complications occurred in 24 (8.5%) patients. Risk factors for complications were age ≥65 years (OR 4.14, 95% CI 1.18~14.56, P=0.027), cerebrovascular disease (OR 8.58, 95% CI 1.13~65.19, P=0.038), Boerhaave syndrome (OR 12.52, 95% CI 2.07~75.68, P=0.006), chemical injury (OR 15.72, 95% CI 3.67~67.28, P<0.001), and CT-documented grade 4 perforation (OR 15.75, 95% CI 4.39~56.55, P<0.001). Conclusions Initial CT-based grading in the ED are useful for predicting potential complications and for managing patients with esophageal injury and suspected perforation.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization.However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccineinduced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARSCoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins.Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein.The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.