1.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
2.Monitoring the Outcomes of Systemic Chemotherapy Including Immune Checkpoint Inhibitor for HER2-Positive Metastatic Gastric Cancer by Liquid Biopsy
Seung-Hyun JUNG ; Choong-kun LEE ; Woo Sun KWON ; Sujin YUN ; Minkyu JUNG ; Hyo Song KIM ; Hyun Cheol CHUNG ; Yeun-Jun CHUNG ; Sun Young RHA
Yonsei Medical Journal 2023;64(9):531-540
Purpose:
For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers.
Materials and Methods:
To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment.
Results:
In the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in wellknown cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2–42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging.
Conclusion
Our data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier:NCT02901301).
3.Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort
Jin Young LEE ; Jean Kyung BAK ; Mina KIM ; Ho-Gyun SHIN ; Kyun-Ik PARK ; Seung-Pyo LEE ; Hee-Sun LEE ; Ju-Yeun LEE ; Kwang-il KIM ; Si-Hyuck KANG ; Jang Hoon LEE ; Se Yong JANG ; Ju-Hee LEE ; Kye Hun KIM ; Jae Yeong CHO ; Jae-Hyeong PARK ; Sue K. PARK ; Hae-Young LEE
The Korean Journal of Internal Medicine 2023;38(1):56-67
Background/Aims:
This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension.
Methods:
The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension.
Results:
The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events.
Conclusions
This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.
4.2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon HA ; Jung Hwan PARK ; Kyoung Jin KIM ; Jung Hee KIM ; Kyong Yeun JUNG ; Jeongmin LEE ; Jong Han CHOI ; Seung Hun LEE ; Namki HONG ; Jung Soo LIM ; Byung Kwan PARK ; Jung-Han KIM ; Kyeong Cheon JUNG ; Jooyoung CHO ; Mi-kyung KIM ; Choon Hee CHUNG ; ;
Endocrinology and Metabolism 2023;38(6):597-618
Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.
5.The Effects of Grit and Nursing Work Environment of Nurses in Tertiary Hospitals on Nursing Performance and Retention Intention:Mediating Effect of Compassionate Rationalism Leadership
Yeun Hee KWAK ; In Sil JANG ; Won LEE ; Seung Ju BAEK ; Seok Kyung HYUN ; Sun Man KIM
Journal of Korean Clinical Nursing Research 2023;29(2):163-174
Purpose:
To identify the effect of a new leadership type by confirming the effect of clinical nurses' grit and nursing work environment on nursing performance and retention intention with the mediating effect of compassionate rationalism leadership in the process.
Methods:
A proportional stratified sampling method was used with 45 tertiary general hospitals nationwide as the sampling unit. An online survey targeting nurses who have been working continuously for more than one year was conducted from October 14 to November 9, 2022. The final analysis included 1,256 questionnaires. The correlation between the participants' variables was analyzed using Pearson's correlation coefficients. The mediating effect was confirmed using a regression analysis, and bootstrapping.
Results:
The compassionate rationalism leadership had a mediating effect on the relationship between grit and nursing performance (F=203.21, p<.001), nursing work environment and nursing performance (F=109.48, p<.001), grit and retention intention (F=149.90, p<.001), and nursing work environment and retention intention (F=25.14, p<.001).
Conclusion
The compassionate rationalism leadership of nursing managers had a positive effect on nursing performance and retention intention.Therefore, with the development and application of educational programs of compassionate rationalism leadership, it can be used to improve nursing performance and operate an efficient nursing organization.
6.Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort
Hwa Kyung BYUN ; Seung Yeun CHUNG ; Kyoung-Jin KIM ; Jinsil SEONG
Cancer Research and Treatment 2021;53(4):962-972
Purpose:
Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia.
Materials and Methods:
A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively.
Results:
Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. –0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months.
Conclusion
IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.
7.A Boy with X-Linked Inhibitor of Apoptosis Protein (XIAP) Deficiency as the Initial Presentation of Pure Red Cell Aplasia
Soo Yeun SIM ; Hye Yeon CHOI ; Seung Bum HAN ; Nack Gyun CHUNG ; Bin CHO ; MyungShin KIM ; Dae Chul JEONG
Clinical Pediatric Hematology-Oncology 2021;28(2):84-88
X-linked inhibitor of apoptosis protein (XIAP) deficiency is a rare immunodeficiency disorder. A 13-month-old boy was diagnosed with pure red cell aplasia (PRCA) and treated with steroid and cyclosporine. Bone marrow showed diminished erythroid precursors, and positive results for Parvovirus B19 and Cytomegalovirus (CMV) infection. A genetic study of Diamond-Blackfan anemia was negative. Five months later, he was admitted due to fever and lymphadenopathy. PCR showed still positive for the Parvovirus, CMV, and Epstein-Barr virus (EBV). He was diagnosed with diffuse large B-cell lymphoma that was positive for EBV. The patient received chemotherapy with R-CHOP, and achieved complete remission. Immunoglobulin (Ig) levels were within an age-matched normal range until the completion of chemotherapy. Subsequently, he was admitted nine times due to recurrent pneumonia and acute otitis media between two and eight years old. We reanalyzed the Ig levels and lymphocyte subsets: IgG, IgA, and IgM were 30 mg/dL, below 1.0 mg/dL, and 36 mg/dL, respectively. Lymphocyte subsets showed nearly absent CD19 (+) cells, but T- and NK cell counts were within normal ranges. A genetic study showed a hemizygous inframe deletion mutation in exon 4 of the IAP gene without the SH2D1A mutation, consistent with a XIAP deficiency. Therefore, he was diagnosed with XIAP deficiency. Genetic analysis of his mother, aunt and elder sister showed that they were carriers of the same gene mutation. He receives intravenous Ig regularly with follow-up, and still requires a low dose steroid to maintain hemoglobin level. We report XIAP deficiency as initial presentation of PRCA.
8.Development of an RNA sequencing panel to detect gene fusions in thyroid cancer
Dongmoung KIM ; Seung-Hyun JUNG ; Yeun-Jun CHUNG
Genomics & Informatics 2021;19(4):e41-
In addition to mutations and copy number alterations, gene fusions are commonly identified in cancers. In thyroid cancer, fusions of important cancer-related genes have been commonly reported; however, extant panels do not cover all clinically important gene fusions. In this study, we aimed to develop a custom RNA-based sequencing panel to identify the key fusions in thyroid cancer. Our ThyChase panel was designed to detect 87 types of gene fusion. As quality control of RNA sequencing, five housekeeping genes were included in this panel. When we applied this panel for the analysis of fusions containing reference RNA (HD796), three expected fusions (EML4-ALK, CCDC6-RET, and TPM3-NTRK1) were successfully identified. We confirmed the fusion breakpoint sequences of the three fusions from HD796 by Sanger sequencing. Regarding the limit of detection, this panel could detect the target fusions from a tumor sample containing a 1% fusion-positive tumor cellular fraction. Taken together, our ThyChase panel would be useful to identify gene fusions in the clinical field.
9.PAIVS: prediction of avian influenza virus subtype
Hyeon-Chun PARK ; Juyoun SHIN ; Sung-Min CHO ; Shinseok KANG ; Yeun-Jun CHUNG ; Seung-Hyun JUNG
Genomics & Informatics 2020;18(1):e5-
Highly pathogenic avian influenza (HPAI) viruses have caused severe respiratory disease and death in poultry and human beings. Although most of the avian influenza viruses (AIVs) are of low pathogenicity and cause mild infections in birds, some subtypes including hemagglutinin H5 and H7 subtype cause HPAI. Therefore, sensitive and accurate subtyping of AIV is important to prepare and prevent for the spread of HPAI. Next-generation sequencing (NGS) can analyze the full-length sequence information of entire AIV genome at once, so this technology is becoming a more common in detecting AIVs and predicting subtypes. However, an analysis pipeline of NGS-based AIV sequencing data, including AIV subtyping, has not yet been established. Here, in order to support the pre-processing of NGS data and its interpretation, we developed a user-friendly tool, named prediction of avian influenza virus subtype (PAIVS). PAIVS has multiple functions that support the pre-processing of NGS data, reference-guided AIV subtyping, de novo assembly, variant calling and identifying the closest full-length sequences by BLAST, and provide the graphical summary to the end users.
10.Treatment outcome of anaplastic ependymoma under the age of 3 treated by intensity-modulated radiotherapy
Joongyo LEE ; Seung Yeun CHUNG ; Jung Woo HAN ; Dong-Seok KIM ; Jina KIM ; Jin Young MOON ; Hong In YOON ; Chang-Ok SUH
Radiation Oncology Journal 2020;38(1):26-34
Purpose:
Intensity-modulated radiotherapy (IMRT) allows for more precise treatment, reducing unwanted radiation to nearby structures. We investigated the safety and feasibility of IMRT for anaplastic ependymoma patients below 3 years of age.
Materials and Methods:
A total of 9 anaplastic ependymoma patients below 3 years of age, who received IMRT between October 2011 and December 2017 were retrospectively reviewed. The median equivalent dose in 2 Gy fractions was 52.0 Gy (range, 48.0 to 60.0 Gy). Treatment outcomes and neurologic morbidities were reviewed in detail.
Results:
The median patient age was 20.9 months (range, 12.1 to 31.2 months). All patients underwent surgery. The rates of 5-year overall survival, freedom from local recurrence, and progression-free survival were 40.6%, 53.3%, and 26.7%, respectively. Of the 9 patients, 5 experienced recurrences (3 had local recurrence, 1 had both local recurrence and cerebrospinal fluid [CSF] seeding, and 1 had CSF seeding alone). Five patients died because of disease progression. Assessment of neurologic morbidity revealed motor dysfunction in 3 patients, all of whom presented with hydrocephalus at initial diagnosis because of the location of the tumor and already had neurologic deficits before radiotherapy (RT).
Conclusion
Neurologic morbidity is not caused by RT alone but may result from mass effects of the tumor and surgical sequelae. Administration of IMRT to anaplastic ependymoma patients below 3 years of age yielded encouraging local control and tolerable morbidities. High-precision modern RT such as IMRT can be considered for very young patients with anaplastic ependymoma.

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