1.Practice guidelines for managing extrahepatic biliary tract cancers
Hyung Sun KIM ; Mee Joo KANG ; Jingu KANG ; Kyubo KIM ; Bohyun KIM ; Seong-Hun KIM ; Soo Jin KIM ; Yong-Il KIM ; Joo Young KIM ; Jin Sil KIM ; Haeryoung KIM ; Hyo Jung KIM ; Ji Hae NAHM ; Won Suk PARK ; Eunkyu PARK ; Joo Kyung PARK ; Jin Myung PARK ; Byeong Jun SONG ; Yong Chan SHIN ; Keun Soo AHN ; Sang Myung WOO ; Jeong Il YU ; Changhoon YOO ; Kyoungbun LEE ; Dong Ho LEE ; Myung Ah LEE ; Seung Eun LEE ; Ik Jae LEE ; Huisong LEE ; Jung Ho IM ; Kee-Taek JANG ; Hye Young JANG ; Sun-Young JUN ; Hong Jae CHON ; Min Kyu JUNG ; Yong Eun CHUNG ; Jae Uk CHONG ; Eunae CHO ; Eui Kyu CHIE ; Sae Byeol CHOI ; Seo-Yeon CHOI ; Seong Ji CHOI ; Joon Young CHOI ; Hye-Jeong CHOI ; Seung-Mo HONG ; Ji Hyung HONG ; Tae Ho HONG ; Shin Hye HWANG ; In Gyu HWANG ; Joon Seong PARK
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):161-202
		                        		
		                        			 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. 
		                        		
		                        		
		                        		
		                        	
2.Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis
Taewoong CHOI ; Simyoung RYU ; Jun-Sang BAE ; Shin Hyuk YOO ; Ji-Hun MO
Journal of Rhinology 2024;31(2):67-77
		                        		
		                        			
		                        			 Chronic rhinosinusitis (CRS) is characterized by prolonged inflammation of the nasal and paranasal sinus mucosa lasting over 12 weeks. CRS is divided into two main types based on the presence of nasal polyps: CRS without nasal polyps and CRS with nasal polyps. The condition is further classified into endotypes based on type 1, type 2, and type 3 inflammatory signatures, with differences in terms of disease severity, prognosis, and treatment response. Recent studies have emphasized the importance of the epithelial-mesenchymal transition (EMT) in CRS progression. In CRS, the EMT can be triggered by infections, allergens, hypoxia, and environmental pollutants. Specifically, EMT induction proceeds through the following mechanisms: viral and bacterial infections disrupt the epithelial barrier, house dust mites and other allergens activate the TGF-β and EGFR signaling pathways, hypoxia increases HIF-1α and other mesenchymal markers, and diesel exhaust particles and particulate matter cause oxidative stress. Maintaining the integrity of the epithelial barrier is essential for nasal mucosa homeostasis. In CRS, barrier damage activates repair processes that trigger the EMT, resulting in barrier dysfunction and tissue remodeling. Epithelial barrier dysfunction allows antigens and pathogens to penetrate, perpetuating inflammation and promoting the EMT. This disruption is a hallmark of CRS, emphasizing the importance of barrier integrity in the development of the disease. Key signaling pathways regulating the EMT in CRS include TGF-β, Wnt, HMGB1, AGE/ERK, TNF-α, and various miRNAs. These signaling pathways connect to various downstream pathways, such as the Smad2/3, GSK-3β/β-catenin, RAGE, and NF-κB pathways. This review focuses on the complex mechanisms of the EMT in CRS, emphasizing the role of epithelial barrier dysfunction and subsequent EMT processes in driving the disease’s development and progression. A deeper understanding of these EMT-driven mechanisms will help identify the potential therapeutic targets aimed at restoring epithelial integrity and reversing the EMT. 
		                        		
		                        		
		                        		
		                        	
3.Peripapillary Perfusion Analysis Using Optical Coherence Tomography Angiography in Patients with Normal Tension Glaucoma
Do Young KIM ; Soojin KIM ; Sang Ah KIM ; Jun Mo LEE ; Ji Hyun KIM
Korean Journal of Ophthalmology 2024;38(1):51-63
		                        		
		                        			 Purpose:
		                        			This study aimed to assess the difference in the vascular parameters of perfusion in the optic nerve head in normal tension glaucoma (NTG) across disease stages using optical coherence tomography angiography and its correlation with peripapillary retinal nerve fiber layer (RNFL) thickness. 
		                        		
		                        			Methods:
		                        			In this retrospective study, 83 eyes with varying stages of NTG (25 mild, 31 moderate, and 27 severe) and 90 healthy eyes were enrolled. The perfusion density (PD) and flux index (FI) of the optic nerve head divided into four sectors were determined. We compared the vascular, structural, and functional parameters between normal and glaucomatous eyes and performed a subgroup analysis among the NTG stages. Pearson correlation coefficient was used to assess the topographic correlation between vascular parameters and RNFL thickness. 
		                        		
		                        			Results:
		                        			PD and FI were significantly decreased in the NTG group. Subgroup analysis revealed a significant decrease in vascular parameters in most regions in the NTG group, except for the nasal PD and temporal FI. Post hoc analysis showed a significant decrease in PD in the inferior region across all severity levels (mild vs. moderate, p = 0.012; moderate vs. severe, p = 0.012; mild vs. severe, p < 0.001). PD and FI were strongly correlated with RNFL thickness in all quadrants (all p < 0.001), with the strongest correlation observed in the inferior region. 
		                        		
		                        			Conclusions
		                        			Vascular parameters were significantly decreased in glaucomatous eyes, and the degree of decrease in vascular parameters was proportional to glaucoma severity. Peripapillary perfusion analysis using optical coherence tomography angiography may complement other measurements used for glaucoma diagnosis. 
		                        		
		                        		
		                        		
		                        	
4.Analysis of Clinical Characteristics and Post-Treatment Prognosis of Eosinophilic and Neutrophilic Chronic Rhinosinusitis With Nasal Polyps in Korean Patients
Chae-Young KIM ; Kwang-Hyun BYUN ; Jun-Sang BAE ; Eun-Hee KIM ; Shin-Hyuk YOO ; Ji-Hun MO
Korean Journal of Otolaryngology - Head and Neck Surgery 2024;67(6):328-335
		                        		
		                        			 Background and Objectives:
		                        			The aim of this study was to examine the clinical characteristics and prognosis of chronic rhinosinusitis with nasal polyps (CRSwNP) following endoscopic sinus surgery (ESS), focusing on distinct histological endotypes characterized by eosinophil and neutrophil infiltration.Subjects and Method A total of 207 patients diagnosed with CRSwNP who underwent ESS between August 2014 and September 2018 were included in the study. Patients were categorized into different groups based on eosinophil and neutrophil counts in the tissues. The demographic data, Lund-Mackay score, Lund-Kennedy (L-K) endoscopic score, Sino-Nasal Outcome Test-22 and Kaplan-Meier estimation were analyzed according to different histologic endotypes. 
		                        		
		                        			Results:
		                        			The histologic types were divided into four groups: the eosinophilic polyp (EP)+ neutrophlic polyp (NP) group, the EP group, the NP group, and the nonEP+nonNP group. Among the groups, the highest level of inflammation (L-K score, p<0.05) was observed in the EP+NP group, and the worst prognosis was observed in the EP+NP group according to the results of the Kaplan-Meier analysis (p<0.001). 
		                        		
		                        			Conclusion
		                        			Compared to non-neutrophil-infiltration polyps, neutrophil infiltration was associated with worse outcome when it was accompanied with eosinophilic infiltration. This discovery underlines how crucial it is to take neutrophils in nasal polyps into account in order to better understand their clinical behavior and maybe design customized treatments for better patient outcomes. 
		                        		
		                        		
		                        		
		                        	
5.No Change in Complications Following Thyroidectomy Despite Increase in Thyroid Cancer Surgeries: A Meta-Regression Analysis
Jun Sung LEE ; Jin Seok LEE ; Hyeok Jun YUN ; Seok-Mo KIM ; Hojin CHANG ; Yong Sang LEE ; Juyeon YANG ; Hye Sun LEE ; Hang-Seok CHANG
Yonsei Medical Journal 2024;65(6):348-355
		                        		
		                        			 Purpose:
		                        			The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. 
		                        		
		                        			Materials and Methods:
		                        			PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords “thyroidectomy” and “complication.” A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. 
		                        		
		                        			Results:
		                        			This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). 
		                        		
		                        			Conclusion
		                        			Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase. 
		                        		
		                        		
		                        		
		                        	
6.The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea
Dong-gon HYUN ; Jee Hwan AHN ; Ha-Yeong GIL ; Chung Mo NAM ; Choa YUN ; Jae-Myeong LEE ; Jae Hun KIM ; Dong-Hyun LEE ; Ki Hoon KIM ; Dong Jung KIM ; Sang-Min LEE ; Ho-Geol RYU ; Suk-Kyung HONG ; Jae-Bum KIM ; Eun Young CHOI ; JongHyun BAEK ; Jeoungmin KIM ; Eun Jin KIM ; Tae Yun PARK ; Je Hyeong KIM ; Sunghoon PARK ; Chi-Min PARK ; Won Jai JUNG ; Nak-Jun CHOI ; Hang-Jea JANG ; Su Hwan LEE ; Young Seok LEE ; Gee Young SUH ; Woo-Sung CHOI ; Keu Sung LEE ; Hyung Won KIM ; Young-Gi MIN ; Seok Jeong LEE ; Chae-Man LIM
Journal of Korean Medical Science 2023;38(19):e141-
		                        		
		                        			 Background:
		                        			Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. 
		                        		
		                        			Methods:
		                        			From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. 
		                        		
		                        			Results:
		                        			Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). 
		                        		
		                        			Conclusion
		                        			In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death. 
		                        		
		                        		
		                        		
		                        	
7.Evaluation of public’s perception of scar cosmesis after thyroidectomy: results of a survey of Turkish versus South Korean individuals
Erman ALCI ; Soo Young KIM ; Hyeok Jun YUN ; Seda GOZENER ; Murat OZDEMIR ; Yigit TURK ; Hur HASSOY ; Yong Sang LEE ; Seok-Mo KIM ; Gokhan ICOZ ; Hang-Seok CHANG ; Ozer MAKAY
Annals of Surgical Treatment and Research 2023;105(3):119-125
		                        		
		                        			 Purpose:
		                        			Visible scars on the neck caused by thyroid surgery give rise to significant aesthetic, functional, and psychosocial problems. The objective of this study is to comparatively investigate the public perception of neck scar cosmesis in Turkish and South Korean populations. 
		                        		
		                        			Methods:
		                        			This survey was prepared to collect participants’ demographic and socioeconomic data and determine their perception of scar cosmesis on the neck and consisted of 15 questions. One thousand thirty-nine individuals who did not undergo thyroid surgery completed the survey. The P-values of <0.05 were deemed to indicate statistical significance. 
		                        		
		                        			Results:
		                        			There were 1,039 respondents, of whom 525 (50.5%) were Turkish and 514 (49.5%) were South Korean. South Korean respondents stated that they would be significantly more uncomfortable with the thought of having a scar due to thyroid surgery, compared to the Turkish respondents (P < 0.001). The South Korean respondents stated that they would be significantly more concerned about the scar’s length, thickness, and darkening color, compared to the Turkish respondents (P < 0.001 for all cases). 
		                        		
		                        			Conclusion
		                        			Patients’ expectations, which are affected by various sociodemographic factors and cultural characteristics, are as important as the medical condition when deciding on the type of thyroid surgery. The study findings clearly indicated that the South Korean population would be significantly more uncomfortable with having a scar on the neck, compared to the Turkish population. Therefore, in selected cases, a scarless thyroidectomy approach, such as transoral endoscopic thyroidectomy, vestibular approach may be preferable for societies like South Korea. 
		                        		
		                        		
		                        		
		                        	
8.Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection
Dong-Hoon LIM ; Hyunseok YOON ; Kyu-pyo KIM ; Baek-Yeol RYOO ; Sang Soo LEE ; Do Hyun PARK ; Tae Jun SONG ; Dae Wook HWANG ; Jae Hoon LEE ; Ki Byung SONG ; Song Cheol KIM ; Seung-Mo HONG ; Jaewon HYUNG ; Changhoon YOO
Cancer Research and Treatment 2023;55(4):1313-1320
		                        		
		                        			 Purpose:
		                        			There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). 
		                        		
		                        			Materials and Methods:
		                        			Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. 
		                        		
		                        			Results:
		                        			Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. 
		                        		
		                        			Conclusion
		                        			Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker. 
		                        		
		                        		
		                        		
		                        	
9.Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample
Jina HAN ; Hye Jin BAEK ; Eunbi NOH ; Kyuhyun YOON ; Jung Ae KIM ; Sukhyun RYU ; Kay O LEE ; No Yai PARK ; Eunok JUNG ; Sangil KIM ; Hyukmin LEE ; Yoo-Sung HWANG ; Jaehun JUNG ; Hun Jae LEE ; Sung-il CHO ; Sangcheol OH ; Migyeong KIM ; Chang-Mo OH ; Byengchul YU ; Young-Seoub HONG ; Keonyeop KIM ; Sunjae JUNG ; Mi Ah HAN ; Moo-Sik LEE ; Jung-Jeung LEE ; Young HWANGBO ; Hyeon Woo YIM ; Yu-Mi KIM ; Joongyub LEE ; Weon-Young LEE ; Jae-Hyun PARK ; Sungsoo OH ; Heui Sug JO ; Hyeongsu KIM ; Gilwon KANG ; Hae-Sung NAM ; Ju-Hyung LEE ; Gyung-Jae OH ; Min-Ho SHIN ; Soyeon RYU ; Tae-Yoon HWANG ; Soon-Woo PARK ; Sang Kyu KIM ; Roma SEOL ; Ki-Soo PARK ; Su Young KIM ; Jun-wook KWON ; Sung Soon KIM ; Byoungguk KIM ; June-Woo LEE ; Eun Young JANG ; Ah-Ra KIM ; Jeonghyun NAM ; ; Soon Young LEE ; Dong-Hyun KIM
Epidemiology and Health 2023;45(1):e2023075-
		                        		
		                        			 OBJECTIVES:
		                        			We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. 
		                        		
		                        			METHODS:
		                        			In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. 
		                        		
		                        			RESULTS:
		                        			In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. 
		                        		
		                        			CONCLUSIONS
		                        			The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19. 
		                        		
		                        		
		                        		
		                        	
10.Protective Efficacy and Immunogenicity of Rv0351/Rv3628 Subunit Vaccine Formulated in Different Adjuvants Against Mycobacterium tuberculosis Infection
Kee Woong KWON ; Tae Gun KANG ; Ara LEE ; Seung Mo JIN ; Yong Taik LIM ; Sung Jae SHIN ; Sang-Jun HA
Immune Network 2023;23(2):e16-
		                        		
		                        			
		                        			 Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4 + T cells coexpressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response. 
		                        		
		                        		
		                        		
		                        	
            
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