1.Complement C5a Receptor Signalingin Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
Eun-Hyeon SHIM ; Sae-Hae KIM ; Doo-Jin KIM ; Yong-Suk JANG
Immune Network 2024;24(4):e24-
		                        		
		                        			
		                        			 Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity. 
		                        		
		                        		
		                        		
		                        	
2.Complement C5a Receptor Signalingin Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
Eun-Hyeon SHIM ; Sae-Hae KIM ; Doo-Jin KIM ; Yong-Suk JANG
Immune Network 2024;24(4):e24-
		                        		
		                        			
		                        			 Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity. 
		                        		
		                        		
		                        		
		                        	
3.Complement C5a Receptor Signalingin Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
Eun-Hyeon SHIM ; Sae-Hae KIM ; Doo-Jin KIM ; Yong-Suk JANG
Immune Network 2024;24(4):e24-
		                        		
		                        			
		                        			 Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity. 
		                        		
		                        		
		                        		
		                        	
4.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. 
		                        		
		                        		
		                        		
		                        	
5.Clinical characteristics and outcomes of COVID-19 in children and adolescents with diabetes in Daegu, South Korea
Na-Won LEE ; You-Min KIM ; Young-Hwan KIM ; Seok-Jin KANG ; Kyung-Mi JANG ; Hae-Sook KIM ; Jung-Eun MOON ; Jin-Kyung KIM
Annals of Pediatric Endocrinology & Metabolism 2024;29(3):167-173
		                        		
		                        			 Purpose:
		                        			Children with comorbidities have a higher risk of severe, coronavirus disease 2019 (COVID-19). This study investigated the clinical features and outcomes of COVID-19 in children and adolescents with diabetes between January and March 2022. 
		                        		
		                        			Methods:
		                        			We retrospectively reviewed the medical records of 123 children and adolescents (73 with type 1 diabetes and 50 with type 2 diabetes, 59 males and 64 females) aged <18 years who had been diagnosed with diabetes. Data were collected from 7 academic medical centers in Daegu, South Korea. 
		                        		
		                        			Results:
		                        			Thirty-five children with diabetes were diagnosed with COVID-19 (18 with type 1 and 17 with type 2 diabetes). Eighteen of the 35 children with diabetes and COVID-19 and 50 of the 88 children with diabetes alone received a COVID-19 vaccination. No significant differences were observed between patients with diabetes and COVID-19 and patients with diabetes alone in the type of diabetes diagnosed, sex, age, body mass index, hemoglobin A1c, or vaccination status. All children with diabetes and COVID-19 had mild clinical features and were safely managed in their homes. Fourteen children had a fever of 38℃ or higher that lasted for more than 2 days, 11 of whom were not vaccinated (p=0.004). None experienced post-COVID-19 conditions. 
		                        		
		                        			Conclusion
		                        			All children and adolescents with pre-existing diabetes had mild symptoms of COVID-19 due to low disease severity, high vaccination rates, uninterrupted access to medical care, and continuous glucose monitoring. Unvaccinated children with diabetes who experienced COVID-19 presented with higher and more frequent fevers compared to vaccinated children. 
		                        		
		                        		
		                        		
		                        	
6.Trends and Clinical Characteristics of Next-Generation Sequencing–Based Genetic Panel Tests: An Analysis of Korean Nationwide Claims Data
Mi JANG ; Hae Yong PAK ; Ja Yoon HEO ; Hyunsun LIM ; Yoon-La CHOI ; Hyo Sup SHIM ; Eun Kyung KIM
Cancer Research and Treatment 2024;56(1):27-36
		                        		
		                        			 Purpose:
		                        			In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea. 
		                        		
		                        			Materials and Methods:
		                        			This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs. 
		                        		
		                        			Results:
		                        			Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020. 
		                        		
		                        			Conclusion
		                        			This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs. 
		                        		
		                        		
		                        		
		                        	
7.Factors Associated with Reaching Mid-Parental Height in Patients Diagnosed with Inflammatory Bowel Disease in Childhood and Adolescent Period
So Yoon CHOI ; Sujin CHOI ; Byung-Ho CHOE ; Jae Hong PARK ; Kwang-Hae CHOI ; Hae Jeong LEE ; Ji Sook PARK ; Ji-Hyun SEO ; Jae Young KIM ; Hyo-Jeong JANG ; Suk Jin HONG ; Eun Young KIM ; Yeoun Joo LEE ; Ben KANG
Gut and Liver 2024;18(1):106-115
		                        		
		                        			 Background/Aims:
		                        			The recent update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added normal growth in children as an intermediate target in Crohn’s disease and ulcerative colitis. We aimed to investigate factors associated with reaching midparental height (MPH) in patients diagnosed with inflammatory bowel disease in childhood and the adolescent period. 
		                        		
		                        			Methods:
		                        			This multicenter retrospective observational study included pediatric patients with inflammatory bowel disease that had reached adult height. Factors associated with reaching MPH were investigated by logistic regression analyses. 
		                        		
		                        			Results:
		                        			A total of 166 patients were included in this study (128 Crohn’s disease and 38 ulcerative colitis). Among them, 54.2% (90/166) had reached their MPH. Multivariable logistic regression analysis revealed that height Z-score at diagnosis and MPH Z-score were independently associated with reaching MPH (odds ratio [OR], 8.45; 95% confidence interval [CI], 4.44 to 17.90;p<0.001 and OR, 0.11; 95% CI, 0.04 to 0.24; p<0.001, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level of "height Z-score at diagnosis minus MPH Z-score" that was associated with reaching MPH was –0.01 with an area under the curve of 0.889 (95% CI [0.835 to 0.944], sensitivity 88.9%, specificity 84.2%, positive predictive value 87.0%, negative predictive value 86.5%, p<0.001). 
		                        		
		                        			Conclusions
		                        			Height Z-score at diagnosis and MPH Z-score were the only factors associated with reaching MPH. Efforts should be made to restore growth in pediatric patients who present with a negative “height Z-score at diagnosis minus MPH Z-score.” 
		                        		
		                        		
		                        		
		                        	
8.A Study on the Characteristics of People With Severe Mental Illness in Seoul
Jiho KIM ; Hae-Woo LEE ; Mi YANG ; Hyo Been LEE ; Yong Lee JANG ; Eun Jin NA
Journal of Korean Neuropsychiatric Association 2024;63(1):49-56
		                        		
		                        			 Objectives:
		                        			Severe mental illness has become one of the leading concerns for the cost of health services. This study analyzed the demographic characteristics and compared the patterns of medical health service use according to the diagnosis of severe mental illness, including schizophrenia spectrum disease, bipolar disease, and major depressive disorder. 
		                        		
		                        			Methods:
		                        			The data from the National Health Insurance Corporation were analyzed, selecting subjects diagnosed at least once for severe mental illness between 2014 and 2019. Severe mental illness included the following: schizophrenia, schizotypal, and delusional disorders (F20– 29); manic episodes and bipolar affective disorder (F30–31); and moderate depressive episodes with psychotic features and recurrent depressive disorder (F32.3–F33). The demographic factors and patterns of medical services, such as outpatient, hospitalization, and re-admission differences, were compared according to the diagnostic categories. 
		                        		
		                        			Results:
		                        			This study included 842459 patients, with 39.6% people in F20–F29, 33.7% in F32.3– F33, and 26.8% in the F30–F31 category. There were significant differences in gender, age, insurance type, Charlson Comorbidity Index score, and economic level according to the diagnostic categories. The engagement of medical health services also showed significant differences among the diagnostic categories. F32.3–F33 showed higher engagement of outpatients than the out-groups, while F20–F29 showed a higher admission rate. The hospitalization duration was significantly longer in F20–F29, and the re-admission rate after discharge within one year was significantly higher in the same group. 
		                        		
		                        			Conclusion
		                        			This paper reviewed the differences in medical care utilization among severe mental illness. The result emphasizes the need for a mental health care system broadening to the community, facilitating psychosocial intervention, and case management. 
		                        		
		                        		
		                        		
		                        	
9.Disease Awareness, Medical Use Behavior, Diagnosis and Treatment Status, Quality of Life and Comorbidities in Primary Cicatricial Alopecia Patients: A Multicenter Survey
Seo Won SONG ; Dong Geon LEE ; Hoon KANG ; Bark-Lynn LEW ; Jee Woong CHOI ; Ohsang KWON ; Yang Won LEE ; Beom Joon KIM ; Young LEE ; Jin PARK ; Moon-Bum KIM ; Do Young KIM ; Sang Seok KIM ; Byung Cheol PARK ; Sang Hoon LEE ; Gwang Seong CHOI ; Hyun-Tae SHIN ; Chang Hun HUH ; Yong Hyun JANG ; Soo Hong SEO ; Jiehyun JEON ; Hyun Sun PARK ; Chong Hyun WON ; Min Sung KIM ; Byung In RO ; Ji Hyun LEE ; Ji Hae LEE ; Dong Soo YU ; Yu Ri WOO ; Hyojin KIM ; Jung Eun KIM
Korean Journal of Dermatology 2024;62(4):206-217
		                        		
		                        			 Background:
		                        			Primary cicatricial alopecia (PCA) is a rare disease that causes irreversible destruction of hair follicles and affects the quality of life (QOL). 
		                        		
		                        			Objective:
		                        			We aimed to investigate the disease awareness, medical use behavior, QOL, and real-world diagnosis and treatment status of patients with PCA. 
		                        		
		                        			Methods:
		                        			A self-administered questionnaire was administered to patients with PCA and their dermatologists. Patients aged between 19 and 75 years who visited one of 27 dermatology departments between September 2021 and September 2022 were included. 
		                        		
		                        			Results:
		                        			In total, 274 patients were included. The male-to-female ratio was 1:1.47, with a mean age of 45.7 years. Patients with neutrophilic and mixed PCA were predominantly male and younger than those with lymphocytic PCA. Among patients with lymphocytic PCA, lichen planopilaris was the most common type, and among those with neutrophilic PCA, folliculitis decalvans was the most common type. Among the total patients, 28.8% were previously diagnosed with PCA, 47.0% were diagnosed with PCA at least 6 months after their first hospital visit, 20.0% received early treatment within 3 months of disease onset, and 54.4% received steady treatment. More than half of the patients had a moderate to severe impairment in QOL. Topical/intralesional steroid injections were the most common treatment. Systemic immunosuppressants were frequently prescribed to patients with lymphocytic PCA, and antibiotics were mostly prescribed to patients with neutrophilic PCA. 
		                        		
		                        			Conclusion
		                        			This study provides information on the disease awareness, medical use behavior, QOL, diagnosis, and treatment status of Korean patients with PCA. This can help dermatologists educate patients with PCA to understand the necessity for early diagnosis and steady treatment. 
		                        		
		                        		
		                        		
		                        	
10.Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Jun-Ook PARK ; Joo Hyun KIM ; Young Hoon JOO ; Sang-Yeon KIM ; Geun-Jeon KIM ; Hyun Bum KIM ; Dong-Hyun LEE ; Hyun Jun HONG ; Young Min PARK ; Eun-Jae CHUNG ; Yong Bae JI ; Kyoung Ho OH ; Hyoung Shin LEE ; Dong Kun LEE ; Ki Nam PARK ; Myung Jin BAN ; Bo Hae KIM ; Do Hun KIM ; Jae-Keun CHO ; Dong Bin AHN ; Min-Su KIM ; Jun Girl SEOK ; Jeon Yeob JANG ; Hyo Geun CHOI ; Hee Jin KIM ; Sung Joon PARK ; Eun Kyung JUNG ; Yeon Soo KIM ; Yong Tae HONG ; Young Chan LEE ; Ho-Ryun WON ; Sung-Chan SHIN ; Seung-Kuk BAEK ; Soon Young KWON
Clinical and Experimental Otorhinolaryngology 2023;16(1):1-19
		                        		
		                        			
		                        			 The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC. 
		                        		
		                        		
		                        		
		                        	
            
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