1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.Orthognathic surgery with removal of lipoma in the asymmetric mandibular prognathism of a patient with a mandibular bone defect due to intramuscular lipoma on the medial aspect of the ramus: a case report
Yoon Ju NAM ; Min Seong KANG ; Jung Han LEE ; Bok Joo KIM ; Jung Han KIM ; Chul Hoon KIM
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2024;50(4):235-240
Lipomas, the most common soft-tissue mesenchymal neoplasms in adults, are characterized by the proliferation of mature white adipocytes without cytologic atypia. Lipomas are rarely observed in the head and neck region. We present a case of resection and orthognathic surgical removal of an intramuscular lipoma of the mandible with involvement of the mandibular ramus and condylar head and neck. An 18-year-old female patient was referred to our hospital for orthognathic surgery for the management of facial asymmetry and mandibular prognathism. The patient did not present with facial swelling, pain, or temporomandibular dysfunction; however, on radiographic examination, including cone-beam computed tomography and magnetic resonance imaging, an infiltrative fatty lesion was observed in the masticator space inside the right mandible, and the adjacent mandible exhibited bone thinning and deformity. Resection of the lipoma was performed along with orthognathic surgery, including a Le Fort I osteotomy for the maxilla and bilateral sagittal split ramus osteotomy (BSSRO). In this case, because the ramus was split using BSSRO, accessing the lipoma intraorally was easy.Consequently, aesthetic scarring was avoided, and no complications, such as unfavorable splitting or pathologic fracture, occurred. Although recurrence has not been observed about 1 year, long-term follow-up should be performed.
3.Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET
Jin-Young LEE ; Bok Yun KANG ; Sang-Jin JUNG ; Ah-Won KWAK ; Seung-On LEE ; Jin Woo PARK ; Sang Hoon JOO ; Goo YOON ; Mee-Hyun LEE ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2023;31(2):200-209
Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.
4.The Sagittal Balance of Cervical Spine : Comprehensive Review of Recent Update
Sang Hoon LEE ; Tae Hwan KIM ; Seok Woo KIM ; Hyun Take RIM ; Heui Seung LEE ; Ji Hee KIM ; In Bok CHANG ; Joon Ho SONG ; Yong Kil HONG ; Jae Keun OH
Journal of Korean Neurosurgical Society 2023;66(6):611-617
The cervical spine plays a critical role in supporting the skull, maintaining horizontal gaze, and facilitating walking. Its unique characteristics, including the widest range of motion among spinal segments, have led to extensive research on cervical sagittal alignment. Various parameters have been proposed to evaluate cervical alignment, with studies investigating their clinical significance, correlation with symptoms, and implications for surgical interventions. Recent findings suggest that cervical sagittal alignment not only impacts the cervical spine but also influences global spine-pelvic alignment through compensatory mechanisms. This comprehensive review examines classical and new parameters of cervical sagittal alignment and considers the dynamic and muscular factors associated with it.
5.Distant Metastatic Microcystic Adnexal Carcinoma
Se Hoon LEE ; So Yeon YUN ; Dong Soo YU ; Young Bok LEE
Annals of Dermatology 2023;35(Suppl2):S215-S218
Microcystic adnexal carcinoma (MAC) is a rare malignant neoplasm of ductal origin. MAC is a clinically aggressive, locally destructive tumor with a high rate of recurrence, but distant metastasis is rare. A 55-year-old male who had been taking immunosuppressants for 2 years after a liver transplantation due to hepatocellular carcinoma presented with a dermal nodule on the sole. He visited the clinic because the nodule, discovered 3 months ago, continued to increase in size. The histopathologic findings from the lesion were consistent with MAC.The patient underwent wide local excision and confirmed a histologically negative margin.After 11 months, the patient revisited with multiple skin nodules on the buttock, back, and right forearm that were distant from the primary tumor site. The lesions were histologically confirmed as MAC. We report a rare case of MAC with distant metastasis.
6.Workload in Emergency Rooms among Clinical Specialties and Overburdened Neurologists
Daeyoung KIM ; Nathan JO ; Jae-Kwan CHA ; Hojin CHOI ; Sang Wuk JEONG ; Im Seok KOH ; Kwang Ik YANG ; Kwang-Yeol PARK ; Kyung-Bok LEE ; Woong-woo LEE ; Dong Hoon SHIN ; Dong Jin SHIN
Journal of the Korean Neurological Association 2022;40(2):127-136
Background:
To evaluate workload in emergency rooms (ERs) among clinical specialties including neurology and investigate characteristics of neurological consultations in ER.
Methods:
A nationwide survey was conducted to evaluate the number of specialists, resident physicians/surgeons, and emergency consultations of each clinical specialty in Korean tertiary referral hospitals from 2018 to 2019. Characteristics of neurological emergency consultations during the same period were investigated in one of the hospitals that participated.
Results:
A total of 23 hospitals were included. Four irrelevant clinical specialties were excluded. The number of neurology specialists and resident physicians were 12.5/hospital (4.1% of all specialists) and 6.4/hospital (3.4% of all resident physicians/surgeons), respectively, while the mean numbers of specialists and resident physicians or surgeons per clinical specialty were 13.7/hospital and 8.6/hospital, respectively. Neurological consultations accounted for 11.0% of all ER consultations for severe patients (Korean Triage and Acuity Scale level 1-3). Annual ER consultations for severe patients per neurology specialist was 274.1, which was only second to pediatrics (290.0). Annual ER consultations for severe patients per resident physician was 406.6 which was 1.6 times higher than the second highest (internal medicine, 247.0). Frequent conditions for neurological ER consultation were dizziness (24.8%), motor weakness (23.9%), headache (10.6%), dysarthria (9.9%), and seizures (7.7%). Frequent primary diagnoses were cerebrovascular diseases (29.0%) and episodic and paroxysmal disorders (24.9%).
Conclusions
Workloads of neurology specialists for ER consultation were significantly heavy, and the workload of neurology resident physicians was the heaviest among all specialties. This should be considered in health care policies.
7.Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity
You Hoon JEON ; Kangmo AHN ; Jihyun KIM ; Meeyong SHIN ; Soo-Jong HONG ; So-Yeon LEE ; Bok Yang PYUN ; Taek Ki MIN ; Minyoung JUNG ; Jeongmin LEE ; Tae Won SONG ; Hye-Young KIM ; Sooyoung LEE ; Kyunguk JEONG ; Yoonha HWANG ; Minji KIM ; Yong Ju LEE ; Min Jung KIM ; Ji Young LEE ; Hye Yung YUM ; Gwang Cheon JANG ; Young A PARK ; Jeong Hee KIM ;
Journal of Korean Medical Science 2022;37(4):e30-
Background:
Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea.
Methods:
AD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed.The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites,treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschoolonset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups.
Results:
A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancyonset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group.
Conclusion
This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.
8.The Investigation on the Burden of Neurology Residents to Manage the Patient who Received Thrombolytic Treatment in the Emergency Department with Hyperacute Stroke
Hyun Joon LEE ; Dong Hoon SHIN ; Kwang Ik YANG ; Im-Seok KOH ; Kyung Bok LEE ; Woong-Woo LEE ; Daeyoung KIM ; Kwang-Yeol PARK ; Sang Wuk JEONG ; Hojin CHOI ; Jae-Kwan CHA ; Dong Jin SHIN
Journal of the Korean Neurological Association 2021;39(4):305-311
Background:
Because Korea is the fastest aging country, the stroke incidence is increasing rapidly. We investigate the trend of the number of patients with acute stroke in recent years and estimate the burden of the neurologist to treat the acute stroke patient visited the emergency department.
Methods:
We requested a questionnaire survey to all teaching hospitals on the number of hospital beds, the number of stroke patients who visited the emergency department, the number of stroke patients in charge of the neurologist, and the number of days on duty of residents from 2016 to 2019.
Results:
Of 69 teaching hospitals, 41 hospitals answered the survey. The average hospital beds per hospital were increased annually from 909 to 916. The average patients who visited the emergency department with stroke and were in charged to neurologists were rapidly increased from 799 to 867 per hospital. In particular, the number of patients with hyperacute cerebral infarction requiring the thrombolytic administration or mechanical thrombectomy were rapidly increased from 105 to 131. On the other hand, the average number of residents per hospital was decreased from 5.1 to 4.8. Therefore, the days on duty per resident were increased from 74 to 77.
Conclusions
The number of acute stroke patients, especially, hyperacute stroke required the rapid cooperation and high labor were increasing rapidly in recent years. However, because the number of residents were decreased, the burden was increasing. To improve the quality of acute stroke treatment, it is necessary to increase the number of residents.
9.Risk Factors of Unfavorable Outcomes, Major Bleeding, and All-Cause Mortality in Patients with Venous Thromboembolism
Han Young LEE ; Tae Hoon YEO ; Tae Kyung HEO ; Young Gyu CHO ; Dong Hui CHO ; Kyung Bok LEE
Vascular Specialist International 2021;37(4):46-
Purpose:
This study aimed to analyze the clinical outcomes of venous thromboembolism (VTE) patients and identify the risk factors for VTE-related unfavorable outcomes, major bleeding, and 30-day all-cause mortality.
Materials and Methods:
From January 2016 to December 2020, 198 patients with confirmed VTE were enrolled. Potential risk factors for unfavorable outcomes, major bleeding, and all-cause mortality were analyzed.
Results:
VTE-related unfavorable outcomes developed in 13.1%, while 30-day all-cause mortality was 8.6%. In the multivariate analysis, a pulse ≥110/min and respiratory rate ≥30/min were statistically significant predictors for VTE-related unfavorable outcomes. Diabetes was a significant risk factor for major bleeding. In addition, a history of malignancy, no anticoagulation treatment, and need for mechanical ventilation were significant predictors of all-cause mortality.
Conclusion
VTE-related mortality and morbidity rates remained high. In cases of tachycardia and tachypnea, early aggressive treatment is needed to prevent unfavorable outcomes. Patients with risk factors should be closely monitored.
10.The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management
Woo-Jung SONG ; Mira CHOI ; Dong Hun LEE ; Jae-Woo KWON ; Gun-Woo KIM ; Myung Hwa KIM ; Mi-Ae KIM ; Min-Hye KIM ; Byung-Keun KIM ; Sujeong KIM ; Joung Soo KIM ; Jung Eun KIM ; Ju-Young KIM ; Joo-Hee KIM ; Hyun Jung KIM ; Hye One KIM ; Hyo-Bin KIM ; Joo Young ROH ; Kyung Hee PARK ; Kui Young PARK ; Han-Ki PARK ; Hyunsun PARK ; Jung Min BAE ; Ji Yeon BYUN ; Dae Jin SONG ; Young Min AHN ; Seung Eun LEE ; Young Bok LEE ; Joong Sun LEE ; Ji Hyun LEE ; Kyung-Hwan LIM ; Young-Min YE ; Yoon-Seok CHANG ; You Hoon JEON ; Jiehyun JEON ; Mihn-Sook JUE ; Sun Hee CHOI ; Jeong-Hee CHOI ; Gyu-Young HUR ; Young Min PARK ; Dae Hyun LIM ; Sang Woong YOUN
Allergy, Asthma & Immunology Research 2020;12(4):563-578
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

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