1.DNA methylome analysis reveals epigenetic alteration of complement genes in advanced metabolic dysfunction-associated steatotic liver disease
Amal MAGDY ; Hee-Jin KIM ; Hanyong GO ; Jun Min LEE ; Hyun Ahm SOHN ; Keeok HAAM ; Hyo-Jung JUNG ; Jong-Lyul PARK ; Taekyeong YOO ; Eun-Soo KWON ; Dong Hyeon LEE ; Murim CHOI ; Keon Wook KANG ; Won KIM ; Mirang KIM ;
Clinical and Molecular Hepatology 2024;30(4):824-844
Background/Aims:
Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD.
Methods:
Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing.
Results:
Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data.
Conclusions
Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.
2.Clinical Relevance of Enlarged Perivascular Spaces in Neurodegenerative Disease
Yu-Ri JE ; Hong-Gi HAM ; Yu-Hyun PARK ; Tae-Yun KIM ; Min-su GO ; Hye-In LEE ; Da Eun KIM ; Na-Yeon JUNG ; Myung Jun LEE ; Sang-Won SEO ; Eun-Joo KIM
Journal of the Korean Neurological Association 2023;41(4):281-292
Background:
Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology.
Methods:
We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured.
Results:
There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336).
Conclusions
Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.
3.Reference diameter and characteristics of the distal radial artery based on ultrasonographic assessment
Jun-Won LEE ; Jung-Woo SON ; Tae-Hwa GO ; Dae Ryong KANG ; Sang Jun LEE ; Se Eun KIM ; Dong-Hyuk CHO ; Young Jun PARK ; Young Jin YOUN ; Min-Soo AHN ; Sung Gyun AHN ; Jang-Young KIM ; Byung-Su YOO ; Junghan YOON ; Seung-Hwan LEE
The Korean Journal of Internal Medicine 2022;37(1):109-118
Background/Aims:
While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm.
Methods:
The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath.
Results:
The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm.
Conclusions
We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.
4.Epidural hematoma treated by aspiration after transforaminal epidural steroid injection - A case report -
Go Eun KIM ; Sung Jun HONG ; Sang Soo KANG ; Ho Joon KI ; Jae Hyun PARK
Anesthesia and Pain Medicine 2021;16(2):184-190
Background:
Spinal epidural hematoma is rare condition that can rapidly develop into severe neurologic deficits. The pathophysiology of this development remains unclear. There are several case reports of emergency hematoma evacuations after epidural steroid injection. Case: We report on two patients who developed acute, large amounts of epidural hematoma without neurological deficits after transforaminal epidural steroid injection. After fluoroscopy guided aspiration for epidural hematoma was performed, neurological defects did not progress and the hematoma was shown to be absorbed on magnetic resonance imaging.
Conclusions
These reports are believed to be the first of treating epidural hematoma occurring after transforaminal epidural steroid injection through non-surgical hematoma aspiration. If large amounts of epidural hematoma are not causing neurological issues, it can be aspirated until it is absorbed.
5.Empty Sella Syndrome Associated with Growth Hormone Deficiency:the First Case Report of WeissKruszka Syndrome
Jisun PARK ; Dong Jun HA ; Go Hun SEO ; Seri MAENG ; Sung Mo KANG ; Sujin KIM ; Ji Eun LEE
Journal of Korean Medical Science 2021;36(18):e133-
Weiss-Kruszka syndrome (WSKA), caused by heterozygous loss-of-function variants in ZNF462 gene, is a recently described and extremely rare genetic disorder. The main phenotypes include characteristic craniofacial features, ptosis, dysgenesis of the corpus callosum, and neurodevelopmental impairment. We report the first Korean boy with molecularly confirmed WSKA presenting with an atypical manifestation. A 16-year-old boy with a history of bilateral ptosis surgery presented with short stature (−3.49 standard deviation score) and delayed puberty. The patient showed characteristic craniofacial features including an inverted triangular-shaped head, exaggerated Cupid's bow, arched eyebrows, down-slanting palpebral fissures, and poorly expressive face. He had a mild degree of intellectual disability and mild hypotonia. Endocrine studies in the patient demonstrated complete growth hormone deficiency (GHD) associated with empty sella syndrome (ESS), based on a magnetic resonance imaging study for the brain that showed a flattened pituitary gland and cerebrospinal fluid space herniated into the sella turcica. To identify the genetic cause, we performed whole exome sequencing (WES). Through WES, a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462 was identified. This is the first case of WSKA accompanied by primary ESS associated with GHD. More clinical and functional studies are needed to elucidate this association.
6.Evaluation of Adherence to Guideline for Heart Failure with Reduced Ejection Fraction in Heart Failure with Preserved Ejection Fraction and with or without Atrial Fibrillation
Min-Soo AHN ; Byung-Su YOO ; Jung-Woo SON ; Young Jun PARK ; Hae-Young LEE ; Eun-Seok JEON ; Seok-Min KANG ; Dong-Ju CHOI ; Kye Hun KIM ; Myeong-Chan CHO ; Seong Yoon KIM ; Dae Ryong KANG ; Tae-Hwa GO
Journal of Korean Medical Science 2021;36(40):e252-
Background:
This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF).
Methods:
We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group.
Results:
Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01–3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27–0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day rehospitalization (wHR, 0.60; 95% CI, 0.37–0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48–0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59–0.99; P = 0.041).
Conclusion
Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.
7.Measuring the Burden of Disease in Korea, 2008-2018
Yoon-Sun JUNG ; Young-Eun KIM ; Hyesook PARK ; In-Hwan OH ; Min-Woo JO ; Minsu OCK ; Dun-Sol GO ; Seok-Jun YOON
Journal of Preventive Medicine and Public Health 2021;54(5):293-300
The study aims to examine the current status and differences in the burden of disease in Korea during 2008-2018. We calculated the burden of disease for Koreans from 2008 to 2018 using an incidence-based approach. Disability adjusted life years (DALYs) were expressed in units per 100 000 population by adding years of life lost (YLLs) and years lived with disability (YLDs). DALY calculation results were presented by gender, age group, disease, region, and income level. To explore differences in DALYs by region and income level, we used administrative district and insurance premium information from the National Health Insurance Service claims data. The burden of disease among Koreans showed an increasing trend from 2008 to 2018. By 2017, the burden of disease among men was higher than that among women. Diabetes mellitus, low back pain, and chronic lower respiratory disease were ranked high in the burden of disease; the sum of DALY rates for these diseases accounted for 18.4% of the total burden of disease among Koreans in 2018. The top leading causes associated with a high burden of disease differed slightly according to gender, age group, and income level. In this study, we measured the health status of Koreans and differences in the population health level according to gender, age group, region, and income level. This data can be used as an indicator of health equity, and the results derived from this study can be used to guide community-centered (or customized) health promotion policies and projects, and for setting national health policy goals.
8.A study on the predictive indicators for the recovery of spontaneous circulation in the early arterial blood gas analysis of cardiac arrest in the elderly
Hyun Joon LIM ; Jun Hwi CHO ; Joong Bum MOON ; Chan Woo PARK ; Myoung Cheol SHIN ; Ka Eul KIM ; Yoon Soo PARK ; Go Eun YANG ; Taek Geun OHK
Journal of the Korean Society of Emergency Medicine 2021;32(2):103-111
Objective:
The number of elderly patients in Korea has been on the rise recently, and hence the number of out-of-hospital cardiac arrest (OHCA) elderly patients is also rising. The causes of cardiac arrest for the elderly vary, and, it is difficult to predict the recovery of spontaneous circulation (ROSC) in OHCA patients. Therefore, the purpose of this study was to ascertain the predictive value of arterial blood gas analysis (ABGA) results in achieving ROSC in the elderly.
Methods:
A retrospective analysis of emergency department patients with OHCA was performed at the Kangwon National University Hospital, Korea from 1 January 2016 to 31 December 2019. The initial ABGA results were compared between two patient groups, those who had achieved a return of spontaneous circulation and those who had not. Univariate and multivariable analyses were performed to elucidate the factors associated with ROSC.
Results:
Overall, 229 OHCA patients were included in the final analysis. The lactate level was independently related to ROSC. A receiver operating characteristics (ROC) curve was plotted to obtain the best cutoff value. The lactate level <9.85 mmol/L showed the largest area under the ROC curve (AUC) to predict ROSC (AUC, 0.666; 95% confidence interval, 0.588-0.743). Multiple regression analysis was performed using the cutoff value, which was a lactate level of 9.85 (odds ratio, 2.907; 95% confidence interval, 1.432-5.902; P=0.003).
Conclusion
The ABGA results during the cardiopulmonary resuscitation of OHCA patients, showed that the lactate level was an independent factor associated with ROSC. The lactate cutoff value was 9.85 mmol/L.
9.Effect of estimating equations for glomerular filtration rate on novel surrogate markers for renal outcome
Kipyo KIM ; Eunji BAEK ; Suryeong GO ; Hyung-Eun SON ; Ji-Young RYU ; Yongjin YI ; Jong Cheol JEONG ; Sejoong KIM ; Ho Jun CHIN
Kidney Research and Clinical Practice 2021;40(2):220-230
Background:
s: Recently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown.
Methods:
We retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels. We compared the effectiveness of eGFR percentage change or slope to estimate end-stage renal disease (ESRD) risk according to two estimating equations (modified Modification of Diet in Renal Disease equation [eGFRm] and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation [eGFRc]) for GFR.
Results:
In the YR1 and YR3 groups, 9,971 and 10,171 candidates were enrolled and ESRD incidence during follow-up was 0.26% and 0.19%, respectively. The eGFR percentage change was more effective than eGFR slope in estimating ESRD risk, regardless of the method of estimation. A 40% of decline in eGFR was better than 30%, and a 3-year baseline period was better than a 1-year period for prediction accuracy. Although some diagnostic indices from the CKD-EPI equation were better, we found no significant differences in the discriminative ability and hazard ratios for incident ESRD between eGFRc and eGFRm in either eGFR percentage change or eGFR slope.
Conclusion
There were no significant differences in the prediction accuracy of GFR percentage change or eGFR slope between eGFRc and eGFRm in the general population.
10.Epidural hematoma treated by aspiration after transforaminal epidural steroid injection - A case report -
Go Eun KIM ; Sung Jun HONG ; Sang Soo KANG ; Ho Joon KI ; Jae Hyun PARK
Anesthesia and Pain Medicine 2021;16(2):184-190
Background:
Spinal epidural hematoma is rare condition that can rapidly develop into severe neurologic deficits. The pathophysiology of this development remains unclear. There are several case reports of emergency hematoma evacuations after epidural steroid injection. Case: We report on two patients who developed acute, large amounts of epidural hematoma without neurological deficits after transforaminal epidural steroid injection. After fluoroscopy guided aspiration for epidural hematoma was performed, neurological defects did not progress and the hematoma was shown to be absorbed on magnetic resonance imaging.
Conclusions
These reports are believed to be the first of treating epidural hematoma occurring after transforaminal epidural steroid injection through non-surgical hematoma aspiration. If large amounts of epidural hematoma are not causing neurological issues, it can be aspirated until it is absorbed.

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