SCI 발표논문

2021년 358편

2682021

제1저자 김주리 · 교신저자 김상균

, , , , ,
Long-term natural history after endoscopic resection for gastric dysplasia.
Surg Endosc. 2021;35(9):5247-5255.

Abstract
BACKGROUND AND STUDY AIMS Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm.
METHODS A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated.
RESULTS Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients (12.2%) during the mean follow-up duration of 63.6 months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1 months. While age (P < 0.001) and mucosal atrophy (P = 0.09) of index cases were associated with the development of synchronous neoplasm, age (P = 0.017), incomplete resection (P = 0.025), and intestinal metaplasia (P = 0.017) of background mucosa of index cases were significantly related to the development of metachronous neoplasm in multivariate analysis. Cumulative incidence of SMN was not significantly different among H. pylori negative, eradicated, and persistent group.
CONCLUSIONS Age, incomplete ER, and background intestinal metaplasia of index gastric dysplasia were significantly associated with metachronous recurrence. Endoscopic surveillance for metachronous recurrence after ER for gastric dysplasia is mandatory for longer than 10 years.
PubMed IF 3.3 소화기내과
2672021

제1저자 송명진 · 교신저자 이연주

,
Strategies for successful implementation and permanent maintenance of a rapid response system.
Korean J Intern Med. 2021;36(5):1031-1039.

Abstract
Rapid response systems (RRSs) have been introduced to intervene with patients experiencing non-code medical emergencies and operate widely around the world. An RRS has four components: an afferent limb, an efferent limb, quality improvement, and administration. A proper triggering system, a hospital culture that embraces the RRS from the afferent limb, experienced primary responders, and dedicated physicians from the efferent limb are key for successful implementation. After initial implementation, quality improvement through objective outcome measures and self-evaluation are crucial, which lead to a better outcome when this process is well performed. Furthermore, better outcomes lead to more investment, which is essential for effective development of the system. The RRS is successfully maintained when these four components are closely interconnected.
PubMed IF 2.2 호흡기내과
2662021

제1저자 고수령, 김세중 · 교신저자 백선하

, , , , , , , , ,
Association between copeptin levels and treatment responses to hypertonic saline infusion in patients with symptomatic hyponatremia: a prospective cohort study.
Kidney Res Clin Pract. 2021;40(3):371-382.

Abstract
BACKGROUND Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients.
METHODS We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24-48 hours and copeptin levels at baseline/24 hours were analyzed.
RESULTS Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02).
CONCLUSION There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.
PubMed IF 3.5 신장내과
2652021

제1저자 Kristianne Rachel P Medina-Liabres · 교신저자 김세중

, , , , , , ,
Mortality predictors in critically ill patients with acute kidney injury requiring continuous renal replacement therapy.
Kidney Res Clin Pract. 2021;40(3):401-410.

Abstract
BACKGROUND Because of high cost of continuous renal replacement therapy (CRRT) and the high mortality rate among severe acute kidney injury patients, careful identification of patients who will benefit from CRRT is warranted. This study determined factors associated with mortality among critically ill patients requiring CRRT.
METHODS This was a retrospective observational study of 414 patients admitted to the intensive care unit of four hospitals in South Korea who received CRRT from June 2017 to September 2018. Patients were divided according to degree of fluid overload (FO) and disease severity. The Cox proportional hazards model was used to explore the effect of relevant variables on mortality.
RESULTS In-hospital mortality rate was 57.2%. Ninety-day mortality rate was 58.5%. Lower creatinine and blood pH were significant predictors of mortality. A one-unit increase in the Sequential Organ Failure Assessment (SOFA) score was associated with increased risk of and 90-day mortality (hazard ratio [HR], 1.07; p < 0.001). The risk of 90-day mortality in FO patients was 57.2% (p < 0.001) higher than in those without FO. High SOFA score was associated with increased risk for 90-day mortality (HR, 1.79; p = 0.03 and HR, 3.05; p = 0.001) in patients without FO and with FO ≤ 10%, respectively. The highest mortality rates were in patients with FO > 10%, independent of disease severity.
CONCLUSION FO increases the risk of mortality independent of other factors, including severity of acute illness. Prevention of FO should be a priority, especially when managing the critically ill.
PubMed IF 3.5 신장내과
2642021

제1저자 권순일, 이현정 · 교신저자 김형관, Steve R. Ommen

, , , , , , , , , , , , , ,
Association of physical activity with all-cause and cardiovascular mortality in 7666 adults with hypertrophic cardiomyopathy (HCM): more physical activity is better.
Br J Sports Med. 2021;55(18):1034-1040.

Abstract
OBJECTIVES Recommendations on physical activity (PA) for adults with hypertrophic cardiomyopathy (HCM) are not well established. We investigated the association of PA intensity with mortality in the general adult HCM population.
METHODS A nationwide population-based cohort of individuals with HCM who underwent health check-ups including questionnaires on PA levels were identified from the years 2009 to 2016 in the National Health Insurance Service database. Subjects who reported no PA at baseline were excluded. To estimate each individual's PA level, the PA score (PAS) was calculated based on the self-reported questionnaires, and the study population was categorised into three groups according to tertiles of PAS. The associations of PAS with all-cause and cardiovascular mortality were analysed.
RESULTS A total of 7666 participants (mean age 59.5 years, 29.9% were women) were followed up for a mean 5.3±2.0 years. All-cause and cardiovascular mortality progressively decreased from the lowest to the highest tertiles of PA intensity: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively (p-for-trend=0.0144 and 0.0023, respectively). Of note, compared with the middle PA group, the highest PA group did not have an increased risk of all-cause and cardiovascular mortality (HR 0.78, (95% CI 0.63 to 0.95) and HR 0.75 (95% CI 0.54 to 1.03), respectively). All subgroup and sensitivity analyses consistently showed that all-cause and cardiovascular mortality did not increase with higher PA levels.
CONCLUSIONS Moderate-to-vigorous-intensity PA, in a middle-aged population of patients with HCM, was associated with progressive reduction of all-cause and cardiovascular mortality. The impact of vigorous-intensity PA on a younger age group requires further investigation.
PubMed IF 15.5 순환기내과
2632021

제1저자 유태경 · 교신저자 김원, 최무림

, , , , , , , , , , , , , , , , ,
Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease.
J Hepatol. 2021;75(3):514-523.

Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) poses an increasing clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype.
METHODS We recruited 125 Korean patients (83 with biopsy-proven NAFLD and 42 without NAFLD) and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed single nucleotide polymorphisms. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean individuals with NAFLD was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models.
RESULTS The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in patients with NAFLD homozygous for the non-reference allele of rs2291702, compared to no-NAFLD individuals with the same genotype (p = 4.79 × 10^-6). This change was replicated in an additional 162 individuals, yielding a combined p value of 8.05 × 10^-8 from a total of 245 patients with NAFLD and 42 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing endoplasmic reticulum stress, and exacerbated NAFLD diet-induced liver fibrosis in mice, while overexpression of AGXT2 attenuated liver fibrosis and steatosis.
CONCLUSIONS We identified a new molecular role for AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD.
LAY SUMMARY Elucidating causal genes for non-alcoholic fatty liver disease (NAFLD) has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 Korean individuals (83 with NAFLD and 42 without NAFLD), we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of causal genes that act on the basis of genotype.
PubMed IF 40.1 소화기내과
2622021

제1저자 이경희 · 교신저자 유철규

, , , ,
Cigarette smoke extract-induced downregulation of p300 is responsible for the impaired inflammatory cytokine response of macrophages.
Cell Signal. 2021;85:110050.

Abstract
Patients with chronic obstructive pulmonary disease (COPD) are susceptible to infection owing to the impaired immune function of alveolar macrophages. This is presumed to be caused, at least partially, by cigarette smoke (CS), which is a major risk factor for COPD. Although CS has been reported to inhibit Toll-like receptor (TLR) function and phagocytosis in macrophages, the molecular mechanism of CS-mediated impairment of macrophage immune function has not been completely elucidated. We investigated the effects of CS extracts (CSE) on macrophage immune function and its molecular mechanism. We assessed lipopolysaccharide (LPS, TLR4 ligand)-, Pam3CSK4 (TLR2 ligand)-, or CpG-oligodeoxynucleotide (TLR9 ligand)-induced IL-6, TNF-α, and IL-1β production in macrophages. Upregulation of IL-6, TNF-α, and IL-1β mRNA and protein by TLR ligands was suppressed on treatment with CSE. However, LPS-induced MAP kinase activation, IκBα degradation, and nuclear translocation of NF-κB were not impeded by CSE. In contrast, CSE significantly suppressed NF-κB transcriptional activity in the nucleus. We found that p300, which acetylates RelA/p65 at lysine 310, and acetyl-p65 (K310) were downregulated upon CSE treatment. Knock-down of p300 suppressed LPS-induced acetylation of NF-κB p65 and production of inflammatory cytokine. To summarize, these results suggest that CSE impair cytokine response by decreasing the expression levels of p300.
PubMed IF 4.7 호흡기내과
2612021

제1저자 이현승 · 교신저자 강혜련

, , , , , , , ,
Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages.
Immun Inflamm Dis. 2021;9(3):871-882.

Abstract
BACKGROUND Transglutaminase 2 (TG2), a multifunctional calcium-dependent acyltransferase, is upregulated in asthmatic airways and reported to play a role in the pathogenesis of allergic asthma. However, the underlying mechanism is not fully understood.
OBJECTIVE To investigate the role of TG2 in alternative activation of alveolar macrophages by using murine asthma model.
METHODS TG2 expression was assessed in induced sputum of 21 asthma patients and 19 healthy controls, and lung tissue of ovalbumin (OVA)-induced murine asthma model. To evaluate the role of TG2 in asthma, we developed an OVA asthma model in both TG2 null and wild-type mice. The expression of M2 macrophage markers was measured by fluorescence-activated cell sorting (FACS) after OVA sensitization and challenge. To evaluate the effect of TG2 inhibition in vitro, interleukin 4 (IL-4) or IL-13-stimulated expression of M2 macrophage markers was measured in CRL-2456 cells in the presence and absence of a TG2 inhibitor.
RESULTS The expression of both TG2 and M2 markers was increased in the sputum of asthmatics compared with that of healthy controls. The expression of TG2 was increased in macrophages of OVA mice. Airway hyperresponsiveness, and the number of inflammatory cells, including eosinophils, was significantly reduced in TG2 null mice compared with wild-type mice. Enhanced expression of M2 markers in OVA mice was normalized by TG2 knockout. IL-4 or IL-13-stimulated expression of M2 markers in alveolar macrophages was also attenuated by TG2 inhibitor treatment in vitro.
CONCLUSION Our results suggest that TG2-mediated modulation of alveolar macrophage polarization plays important roles in the pathogenesis of asthma.
PubMed IF 3.5 알레르기내과
2602021

제1저자 오지현 · 교신저자 강혜련

, , , , , , , ,
Reintroduction of Antituberculous Drugs in Patients with Antituberculous Drug-Related Drug Reaction with Eosinophilia and Systemic Symptoms.
J Allergy Clin Immunol Pract. 2021;9(9):3442-3449.e3.

Abstract
BACKGROUND Patients who suffered drug reaction with eosinophilia and systemic symptom (DRESS) during the treatment of tuberculosis (TB) commonly experience multidrug hypersensitivity reactions resulting in limited anti-TB drug choices. Therefore, reintroduction based on a desensitization protocol may be an option to resume anti-TB medication.
OBJECTIVE To evaluate the outcomes and safety of resuming anti-TB drugs according to reintroduction methods in patients with anti-TB drug-related DRESS.
METHODS A retrospective cohort of patients who had experienced anti-TB drug-related severe cutaneous adverse reactions from 2011 to 2017 was established from separate 5 institutions.
RESULTS Anti-TB medication was resumed in 27 of 29 patients with anti-TB drug-related DRESS through complete changing regimen (n = 9), reintroduction by a graded challenge (n = 5), or reintroduction using a desensitization protocol (n = 13). Nine patients completely changed their anti-TB regimen to second-line TB drugs, but only 1 (11.1%) succeeded in maintaining new anti-TB drugs. The other 8 failed to take drugs due to the occurrence of hypersensitivity reactions to the newly introduced anti-TB drugs. Two (40.0%) of 5 patients who underwent graded rechallenges successfully completed anti-TB drugs, whereas 3 (60%) failed to resume anti-TB drugs due to the recurrence of hypersensitivity reactions. In 13 patients who resumed anti-TB drugs using a desensitization protocol, no one who underwent desensitization developed recurrence of DRESS; 11 (84.6%) eventually completed anti-TB treatment and 2 eventually failed to complete anti-TB treatment due to late-onset itching and drug-induced liver injury.
CONCLUSIONS Resuming anti-TB medication based on desensitization protocols may be a safe and effective option for those with anti-TB drug-related DRESS.
PubMed IF 6.6 알레르기내과
2592021

제1저자 최유정 · 교신저자 최의근

, , , , , , , , ,
Increased Risk of Atrial Fibrillation in Patients with Atopic Triad: A Nationwide Population-Based Study.
J Allergy Clin Immunol Pract. 2021;9(9):3422-3430.e5.

Abstract
BACKGROUND Despite a sharp increase in the global prevalence of allergy over the past decade, the relation between multiple atopic conditions and atrial fibrillation (AF) has not been fully elucidated.
OBJECTIVE To determine whether there is an association between atopic diseases and AF and to examine the effect of multiple atopic diseases on the incidence of AF.
METHODS This retrospective population-based study used the database from the 2009 National Health Insurance Services-Health Screening Cohort in Korea. A total of 6,748,564‬ subjects without a previous history of AF were included in the final analysis and observed until 2017. The atopic triad included asthma, allergic rhinitis, and atopic dermatitis. A total of 1,168,196‬ subjects (17.3%) with at least one atopic disease were classified as the atopic group. The primary outcome was new-onset AF.
RESULTS During a median 7.2 ± 1.0 years of follow-up, 136,253‬ subjects were given the new diagnosis of AF (30,300 in the atopic group and 105,953 in the nonatopic group). The incidence of AF was 3.63/1000 person-years in the atopic group and 2.64/1000 person-years in the nonatopic group. The risk for AF showed a positive correlation with the number of diseases in the atopic triad (adjusted hazard ratio [aHR], 95% confidence interval [CI]: one disease: aHR = 1.15, CI, 1.14-1.17; two diseases: aHR = 1.34, CI, 1.31-1.38; and three diseases: aHR = 1.35, CI, 1.11-1.66; P for trend < .001).
CONCLUSIONS The atopic triad of asthma, allergic rhinitis, and atopic dermatitis was associated with an increased risk for AF. Moreover, multiple atopic conditions have a higher risk for AF.
PubMed IF 6.6 순환기내과
2582021

제1저자 김유형, 김용휘 · 교신저자 임환섭, 김정희

, , , , ,
Changes in copeptin levels before and 3 months after transsphenoidal surgery according to the presence of postoperative central diabetes insipidus.
Sci Rep. 2021;11(1):17240.

Abstract
Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P < 0.001, percentage difference = - 42.2%) and also in the transient CDI group (P = 0.002, - 27.2%). Three months postoperative copeptin level < 1.9 pmol/L under normal serum sodium levels was the optimal cutoff value for diagnosing permanent CDI with an accuracy of 81.8%, while 3-month postoperative copeptin level ≥ 3.5 pmol/L excluded the CDI with a negative predictive value of 100%. Conclusively, 3 months postoperative copeptin levels significantly decreased from preoperative levels in the transient CDI group as well as the permanent CDI group. Three-month postoperative copeptin levels ≥ 3.5 pmol/L under normal serum sodium levels may be diagnostic for excluding postoperative CDI.
PubMed IF 4.9 내분비대사내과
2572021

제1저자 김형준,전경만 · 교신저자 이연주

, , , , , , , , , , ,
Relationship between the presence of dedicated doctors in rapid response systems and patient outcome: a multicenter retrospective cohort study.
Respir Res. 2021;22(1):236.

Abstract
BACKGROUND Rapid response systems (RRSs) improve patients' safety, but the role of dedicated doctors within these systems remains controversial. We aimed to evaluate patient survival rates and differences in types of interventions performed depending on the presence of dedicated doctors in the RRS.
METHODS Patients managed by the RRSs of 9 centers in South Korea from January 1, 2016, through December 31, 2017, were included retrospectively. We used propensity score-matched analysis to balance patients according to the presence of dedicated doctors in the RRS. The primary outcome was in-hospital survival. The secondary outcomes were the incidence of interventions performed. A sensitivity analysis was performed with the subgroup of patients diagnosed with sepsis or septic shock.
RESULTS After propensity score matching, 2981 patients were included per group according to the presence of dedicated doctors in the RRS. The presence of the dedicated doctors was not associated with patients' overall likelihood of survival (hazard ratio for death 1.05, 95% confidence interval [CI] 0.93‒1.20). Interventions, such as arterial line insertion (odds ratio [OR] 25.33, 95% CI 15.12‒42.44) and kidney replacement therapy (OR 10.77, 95% CI 6.10‒19.01), were more commonly performed for patients detected using RRS with dedicated doctors. The presence of dedicated doctors in the RRS was associated with better survival of patients with sepsis or septic shock (hazard ratio for death 0.62, 95% CI 0.39‒0.98) and lower intensive care unit admission rates (OR 0.53, 95% CI 0.37‒0.75).
CONCLUSIONS The presence of dedicated doctors within the RRS was not associated with better survival in the overall population but with better survival and lower intensive care unit admission rates for patients with sepsis or septic shock.
PubMed IF 5.7 호흡기내과
2562021

제1저자 이정석, Grace-Hyun J Kim · 교신저자 이은영

, , , , , ,
The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores.
J Clin Med. 2021;10(17):jcm10173812.

Abstract
We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n = 26) had matched PFT results and prospective cohort 2 (n = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation-the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = -0.433, p = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, p = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.
PubMed IF 3.3 류마티스내과
2552021

제1저자 강민우 · 교신저자 한승석

, , , , , , ,
Machine learning model to predict hypotension after starting continuous renal replacement therapy.
Sci Rep. 2021;11(1):17169.

Abstract
Hypotension after starting continuous renal replacement therapy (CRRT) is associated with worse outcomes compared with normotension, but it is difficult to predict because several factors have interactive and complex effects on the risk. The present study applied machine learning algorithms to develop models to predict hypotension after initiating CRRT. Among 2349 adult patients who started CRRT due to acute kidney injury, 70% and 30% were randomly assigned into the training and testing sets, respectively. Hypotension was defined as a reduction in mean arterial pressure (MAP) ≥ 20 mmHg from the initial value within 6 h. The area under the receiver operating characteristic curves (AUROCs) in machine learning models, such as support vector machine (SVM), deep neural network (DNN), light gradient boosting machine (LGBM), and extreme gradient boosting machine (XGB) were compared with those in disease-severity scores such as the Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II. The XGB model showed the highest AUROC (0.828 [0.796-0.861]), and the DNN and LGBM models followed with AUROCs of 0.822 (0.789-0.856) and 0.813 (0.780-0.847), respectively; all machine learning AUROC values were higher than those obtained from disease-severity scores (AUROCs < 0.6). Although other definitions of hypotension were used such as a reduction of MAP ≥ 30 mmHg or a reduction occurring within 1 h, the AUROCs of machine learning models were higher than those of disease-severity scores. Machine learning models successfully predict hypotension after starting CRRT and can serve as the basis of systems to predict hypotension before starting CRRT.
PubMed IF 4.9 신장내과
2542021

제1저자 윤연이 · 교신저자 윤연이

, , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Differential progression of coronary atherosclerosis according to plaque composition: a cluster analysis of PARADIGM registry data.
Sci Rep. 2021;11(1):17121.

Abstract
Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm³), with necrotic core and fibro-fatty PV regression (- 5.7 mm³ and - 5.6 mm³, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (- 2.4 mm³). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm³). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm³), predominantly increasing in calcified PV (+ 35.9 mm³). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.
PubMed IF 4.9 순환기내과
2532021

제1저자 이서영, 이소령 · 교신저자 최의근

, , , , , , , , , , , , ,
Association Between Change in Metabolic Syndrome Status and Risk of Incident Atrial Fibrillation: A Nationwide Population-Based Study.
J Am Heart Assoc. 2021;10(16):e020901.

Abstract
Backgroud There is a paucity of information on whether changes in metabolic syndrome (MetS) status affect the risk of new-onset atrial fibrillation (AF). We aimed to evaluate whether changes in MetS status and components of MetS affect AF risk using data from a nationwide observational cohort. Methods and Results A total of 7 565 531 adults without prevalent AF (mean age, 47±14 years) who underwent 2 serial health examinations by the Korean National Health Insurance Cooperation were identified. The patients were categorized into 4 groups according to the change in MetS status in serial evaluations, as follows: patients with persistent MetS (n=1 388 850), healthy patients newly diagnosed with MetS in the second evaluation (n=608 158), patients with MetS who were healthy in the second evaluation (n=798 555), and persistently healthy individuals (n=4 769 968). During a mean 7.9-year follow-up, incident AF was diagnosed in 139 305 (1.8%) patients. After multivariable adjustment, the AF risk was higher by 31% in the patients with persistent MetS , 26% in the patients with MetS who were healthy in the second evaluation, and 16% in the healthy patients newly diagnosed with MetS in the second evaluation compared with the persistently healthy individuals. Regardless of the MetS component type, the AF risk correlated with changes in the number of components. The risk of AF was strongly correlated with MetS status changes in the young and middle-age groups (20-39 years and 40-64 years, respectively) than in the elderly group (≥65 years). Conclusions Dynamic changes in MetS status and persistent MetS were associated with an increased risk of AF in a large-scale Asian population.
PubMed IF 6 순환기내과
2522021

제1저자 김수환, 강현우 · 교신저자 정지봉

, , , , , , , , , ,
Association of obesity, visceral adiposity, and sarcopenia with an increased risk of metabolic syndrome: A retrospective study.
PLoS One. 2021;16(8):e0256083.

Abstract
AIMS Metabolic syndrome (MS) is a global health problem associated with an increased risk of diabetes mellitus (DM), cardiovascular disease (CVD), and cancer. Body composition parameters, including obesity, visceral adiposity, and sarcopenia contribute to the development of MS and CVD. Previous studies have investigated the association of individual body composition parameters with MS. Studies analyzing the association between multiple body composition parameters and MS have been rare. We aimed to investigate the association between MS and multiple body composition parameters, including obesity, visceral adiposity, and sarcopenia.
METHODS A total of 13,620 subjects who underwent voluntary routine checkups at the Health Care Center of our institution between October 2014 and December 2019 were enrolled. Only data from the first examination of subjects who underwent repeated checkups were included. Clinical and laboratory data were collected. Skeletal muscle mass and visceral fat area (VFA) were measured using bioelectrical impedance analysis. Appendicular skeletal muscle mass (ASM) was divided by body weight (in kg) and expressed as a percentage (calculated as, ASM% = ASM × 100/Weight). Data were compared between the groups based on obesity, VFA, and ASM%. Logistic regression analysis was performed to determine the risk of MS in each group.
RESULTS Body mass index and VFA were significantly higher in subjects with MS than in those without MS. ASM% was significantly lower in subjects with MS than in those without MS. Subjects with obesity, visceral adiposity, or sarcopenia had a higher prevalence of MS than those without. As the number of metabolic components increased from 0 to 5, we identified a decreasing trend of ASM% and an increasing trend of VFA and BMI (P for trend < 0.001 for all). In the paired analyses, all the three body composition parameters showed additive effects in predicting MS. In the logistic regression analysis, the three parameters were associated with an increased risk of MS after adjustment for age, sex, hypertension, DM, dyslipidemia, smoking, alcohol intake, and C-reactive protein.
CONCLUSIONS Obesity, visceral adiposity, and sarcopenia showed additive effects on MS prediction. Subjects with obesity, visceral adiposity, or sarcopenia were significantly associated with the increased risk of MS after adjustment for multiple confounders. Increasing skeletal muscle and reducing visceral fat may be strategies for the prevention or treatment of MS.
PubMed IF 2.8 소화기내과
2512021

제1저자 김세훈, 지은정 · 교신저자 안소연, 장윤석

, , , , , ,
Association of asthma comorbidity with poor prognosis of coronavirus disease 2019.
World Allergy Organ J. 2021;14(8):100576.

Abstract
BACKGROUND While global health agencies have listed asthma as a vulnerability for severe cases of coronavirus disease 2019 (COVID-19), the evidence supporting this is scarce.
METHODS A nationwide cohort study was conducted using the validated Korean national health insurance claim data of patients diagnosed with COVID-19 between January 1 and April 8, 2020. Asthma comorbidity was determined using a diagnosis code assigned by the physician and the prescription of asthma-related medications. The clinical course of COVID-19 was classified into 3 severity grades according to the requirements for oxygen supply and mechanical ventilation. We also evaluated the association of asthma with overall and in-hospital mortality of COVID-19.
RESULTS Asthma morbidity was a significant risk factor for severe COVID-19 (grade 2 requiring oxygen supply) (adjusted odds ratio [aOR] = 1.341, 95% confidence interval [CI], 1.051-1.711, P = 0.018) and grade 3 requiring mechanical ventilation or leading to death (aOR = 1.723, 95% CI: 1.230-2.412, P = 0.002) multinomial logistic regression adjusting co-risk factors. Asthma was also significantly associated with mortality of COVID-19 (aOR = 1.453, 95% CI: 1.015-2.080, P = 0.041) and was revealed to have a shorter time to in-hospital mortality of COVID-19 (P < 0.001). Patients with recent asthma exacerbation showed more severe COVID-19 of grade 3 (OR = 7.371, 95% CI: 2.018-26.924, P = 0.003) and higher mortality (OR = 9.208, 95% CI: 2.597-32.646, P < 0.001) in univariable analysis, but the statistical significance was not found in multivariable analysis.
CONCLUSION Asthma morbidity was associated with severity and mortality of COVID-19. Patients with asthma should pay more attention to avoid worsening of COVID-19.
PubMed IF 4 알레르기내과
2502021

제1저자 문선준, 장한나 · 교신저자 문민경

, , ,
Lipid Profiles in Primary Aldosteronism Compared with Essential Hypertension: Propensity-Score Matching Study.
Endocrinol Metab (Seoul). 2021;36(4):885-894.

Abstract
BACKGROUND There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function.
METHODS Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively.
RESULTS Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed.
CONCLUSION PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.
PubMed IF 5.1 내분비대사내과
2492021

제1저자 곽순구 · 교신저자 이승표, Marc R Dweck

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.
J Am Coll Cardiol. 2021;78(6):545-558.

Abstract
BACKGROUND Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined.
OBJECTIVES Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality.
METHODS Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome.
RESULTS There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m²) and small (LVEDVi ≤55 mL/m²) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort.
CONCLUSIONS Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.
PubMed IF 22.3 순환기내과
2482021

제1저자 이연희 · 교신저자 곽철, 김세중, 한승석

, , , , , , , , , , , , , , ,
Machine learning-based prediction of acute kidney injury after nephrectomy in patients with renal cell carcinoma.
Sci Rep. 2021;11(1):15704.

Abstract
The precise prediction of acute kidney injury (AKI) after nephrectomy for renal cell carcinoma (RCC) is an important issue because of its relationship with subsequent kidney dysfunction and high mortality. Herein we addressed whether machine learning (ML) algorithms could predict postoperative AKI risk better than conventional logistic regression (LR) models. A total of 4104 RCC patients who had undergone unilateral nephrectomy from January 2003 to December 2017 were reviewed. ML models such as support vector machine, random forest, extreme gradient boosting, and light gradient boosting machine (LightGBM) were developed, and their performance based on the area under the receiver operating characteristic curve, accuracy, and F1 score was compared with that of the LR-based scoring model. Postoperative AKI developed in 1167 patients (28.4%). All the ML models had higher performance index values than the LR-based scoring model. Among them, the LightGBM model had the highest value of 0.810 (0.783-0.837). The decision curve analysis demonstrated a greater net benefit of the ML models than the LR-based scoring model over all the ranges of threshold probabilities. The application of ML algorithms improves the predictability of AKI after nephrectomy for RCC, and these models perform better than conventional LR-based models.
PubMed IF 4.9 신장내과
2472021

제1저자 장한나, 문선준 · 교신저자 김정희, 한도현

, , , , , ,
Mass Spectrometry-Based Proteomic Discovery of Prognostic Biomarkers in Adrenal Cortical Carcinoma.
Cancers (Basel). 2021;13(15):cancers13153890.

Abstract
Adrenal cortical carcinoma (ACC) is an extremely rare disease with a variable prognosis. Current prognostic markers have limitations in identifying patients with a poor prognosis. Herein, we aimed to investigate the prognostic protein biomarkers of ACC using mass-spectrometry-based proteomics. We performed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) using formalin-fixed paraffin-embedded (FFPE) tissues of 45 adrenal tumors. Then, we selected 117 differentially expressed proteins (DEPs) among tumors with different stages using the machine learning algorithm. Next, we conducted a survival analysis to assess whether the levels of DEPs were related to survival. Among 117 DEPs, HNRNPA1, C8A, CHMP6, LTBP4, SPR, NCEH1, MRPS23, POLDIP2, and WBSCR16 were significantly correlated with the survival of ACC. In age- and stage-adjusted Cox proportional hazard regression models, only HNRNPA1, LTBP4, MRPS23, POLDIP2, and WBSCR16 expression remained significant. These five proteins were also validated in TCGA data as the prognostic biomarkers. In this study, we found that HNRNPA1, LTBP4, MRPS23, POLDIP2, and WBSCR16 were protein biomarkers for predicting the prognosis of ACC.
PubMed IF 4.8 내분비대사내과
2462021

제1저자 김미소 · 교신저자 김태민

, , , , , , , , ,
A phase II study of brentuximab vedotin in patients with relapsed or refractory Epstein-Barr virus-positive and CD30-positive lymphomas.
Haematologica. 2021;106(8):2277-2280.

PubMed IF 8.2 혈액종양내과
2452021

제1저자 김원세, 박진주 · 교신저자 국웅, 최동주

, , , , , , , , , , , , ,
Predicting survival in heart failure: a risk score based on machine-learning and change point algorithm.
Clin Res Cardiol. 2021;110(8):1321-1333.

Abstract
OBJECTIVE Machine learning (ML) algorithm can improve risk prediction because ML can select features and segment continuous variables effectively unbiased. We generated a risk score model for mortality with ML algorithms in East-Asian patients with heart failure (HF).
METHODS From the Korean Acute Heart Failure (KorAHF) registry, we used the data of 3683 patients with 27 continuous and 44 categorical variables. Grouped Lasso algorithm was used for the feature selection, and a novel continuous variable segmentation algorithm which is based on change-point analysis was developed for effectively segmenting the ranges of the continuous variables. Then, a risk score was assigned to each feature reflecting nonlinear relationship between features and survival times, and an integer score of maximum 100 was calculated for each patient.
RESULTS During 3-year follow-up time, 32.8% patients died. Using grouped Lasso, we identified 15 highly significant independent clinical features. The calculated risk score of each patient ranged between 1 and 71 points with a median of 36 (interquartile range: 27-45). The 3-year survival differed according to the quintiles of the risk score, being 80% and 17% in the 1st and 5th quintile, respectively. In addition, ML risk score had higher AUCs than MAGGIC-HF score to predict 1-year mortality (0.751 vs. 0.711, P < 0.001).
CONCLUSIONS In East-Asian patients with HF, a novel risk score model based on ML and the new continuous variable segmentation algorithm performs better for mortality prediction than conventional prediction models.
CLINICAL TRIAL REGISTRATION Unique identifier: INCT01389843 https://clinicaltrials.gov/ct2/show/NCT01389843 .
PubMed IF 3.4 순환기내과
2442021

제1저자 박진주 · 교신저자 조구영, 배희준

, , , , , , , , ,
Heart failure and atrial fibrillation in patients with an interatrial shunt.
Clin Res Cardiol. 2021;110(8):1270-1279.

Abstract
OBJECTIVE Congenital interatrial shunt can unload the left atrium (LA) and may lower the risk of new-onset heart failure (HF) or atrial fibrillation (AF). We evaluated the risk of new-onset HF or AF in patients with and without interatrial shunt.
METHODS We enrolled 2660 consecutive patients with acute stroke or transient ischemic attack (TIA) who underwent transesophageal echocardiography at Seoul National University Bundang Hospital from January 1, 2006 to December 31, 2018. The primary outcomes were 10-year new-onset HF, new-onset AF, and new-onset HF or AF composite.
RESULTS Overall, 466 (17.5%) patients with an interatrial shunt had smaller E velocity (0.66 ± 0.21 vs. 0.69 ± 0.22 m/s, P = 0.037) and smaller E/e' (9.1 ± 4.0 vs. 10.0 ± 5.0, P = 0.001) than 2194 (82.5%) patients without an interatrial shunt. The 10-year incidence of AF, HF, and AF or HF composite was lower in patients with an interatrial shunt (10-year AF, 11.2 vs. 17.8%, P < 0.001; 10-year HF, 6.2 vs. 10.4%, P = 0.005; 10-year AF or HF composite, 16.5 vs. 23.4%, P = 0.001). In multivariable analysis, the presence of an interatrial shunt was associated with a 38% (HR 0.62, 95% CI 0.40-0.96), 40% (HR 0.60; 95% CI 0.39-0.93), and 26% (HR 0.74; 95% CI 0.57-0.96) reduced risk for new-onset HF, AF, and new-onset HF or AF composite, respectively.
CONCLUSION In patients with interatrial shunt, the risk of AF and HF was lower. Interatrial shunt may be beneficial, and the closure of an interatrial shunt should be performed only in carefully selected patients. An interatrial shunt can unload the left atrium. In patients with stroke or TIA, the presence of an interatrial shunt was associated with a reduced risk for new-onset HF and AF. AF atrial fibrillation, HF heart failure, HR hazard ratio, LA left atrium.
PubMed IF 3.4 순환기내과
2432021

제1저자 문준호 · 교신저자 구보경, 김원

, ,
Non-alcoholic fatty liver disease and sarcopenia additively increase mortality: a Korean nationwide survey.
J Cachexia Sarcopenia Muscle. 2021;12(4):964-972.

Abstract
BACKGROUND Sarcopenia is an independent risk factor not only for advanced-stage non-alcoholic fatty liver disease (NAFLD) but also for mortality. We investigated the association of sarcopenia and/or NAFLD with mortality among the Korean general population.
METHODS Individuals aged 35-75 years without any history of cancer, ischaemic heart disease, ischaemic stroke, or secondary causes of chronic liver disease were selected from the Korean National Health and Nutrition Examination Surveys from 2008 to 2015. Their mortality data until December 2018 were retrieved from the National Death Registry. NAFLD and sarcopenia were defined by hepatic steatosis index and appendicular skeletal muscle mass divided by body mass index (BMI), respectively.
RESULTS A total of 28 060 subjects were analysed [mean age, 50.6 (standard error, 0.1) years, 48.2 (0.3) % men]; the median follow-up duration was of 6.8 (interquartile range, 4.8, 8.4) years. NAFLD predicted mortality after adjustment for age, sex, BMI, hypertension, dyslipidaemia, and smoking (HR 1.32, 95% CI 1.03-1.70), but this prediction lost its statistical significance after additional adjustment for diabetes mellitus. In contrast, NAFLD with advanced fibrosis independently increased the risk of mortality after adjustment for all covariates (HR 1.68, 95% CI 1.02-2.79). Stratified analysis revealed that NAFLD and sarcopenia additively increased the risk of mortality as an ordinal scale (HR 1.46, 95% CI 1.18-1.81, P for trend = 0.001). The coexistence of NAFLD and sarcopenia increased the risk of mortality by almost twice as much, even after adjustment for advanced fibrosis (HR 2.18, 95% CI 1.38-3.44).
CONCLUSIONS Concurrent NAFLD and sarcopenia conferred a two-fold higher risk of mortality. The observation that NAFLD and sarcopenia additively increase mortality suggests that risk stratification would be helpful in predicting mortality among those with metabolic derangement.
PubMed IF 9.9 소화기내과
2422021

제1저자 김예림 · 교신저자 김동기

, , , , , , , , , , , , , , , , ,
Predictive value of triglyceride/high-density lipoprotein cholesterol for major clinical outcomes in advanced chronic kidney disease: a nationwide population-based study.
Clin Kidney J. 2021;14(8):1961-1968.

Abstract
BACKGROUND Dyslipidemia is an essential parameter in the prediction of cardiovascular disease (CVD). We aimed to explore whether lipid profiles could predict major outcomes in patients with advanced chronic kidney disease (CKD).
METHODS We retrospectively reviewed the National Health Insurance Service database for people who received nationwide health screening in 2009. All subjects exposed to a lipid-lowering agent before screening were excluded. The population was divided into control, early [estimated glomerular filtration rate (eGFR) 45-59 mL/min/1.73 m²] and advanced (eGFR <45 mL/min/1.73 m²) CKD groups. The hazard ratios (HRs) of outcomes were calculated using multivariate Cox regression models.
RESULTS A total of 3 634 873 participants were included in this study, with 404 298 (11.1%) and 66 805 (1.8%) having early and advanced CKD, respectively. For all populations, levels of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) showed a linear association with major cardiovascular and cerebrovascular events (MACCEs) and all-cause mortality, while low-density lipoprotein cholesterol (LDL-C) showed a different pattern of association with MACCEs (linear association) from all-cause mortality (U-shaped association). The significance between the levels of LDL-C and outcomes was attenuated in the advanced CKD group. For TG/HDL-C, although the significance was decreased, the linear patterns with both MACCEs and all-cause mortality were maintained in the advanced CKD group.
CONCLUSIONS The pattern and significance of lipid profiles were different according to the grade of kidney function. TG/HDL-C should be additionally considered as a predictive marker for CVD and mortality along with LDL-C in patients with CKD.
PubMed IF 5.3 신장내과
2412021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Causal effects of education on chronic kidney disease: a Mendelian randomization study.
Clin Kidney J. 2021;14(8):1932-1938.

Abstract
BACKGROUND Poor socio-economic status, including low education attainment, has been reported in chronic kidney disease (CKD) patients. We aimed to investigate the causal effects of education attainment on the risk of CKD.
METHODS The study was an observational cohort study including Mendelian randomization (MR) analysis. First, the clinical association between education attainment years as the exposure and prevalent CKD Stages 3-5 as the outcome was investigated by multivariable logistic regression in 308 741 individuals 40-69 years of age from the UK Biobank. MR analysis was performed with a previously reported genetic instrument from a genome-wide association meta-analysis of education attainment. Two-sample MR was performed with summary statistics for CKD in 567 460 individuals with European ancestry in the CKDGen genome-wide association meta-analysis. The findings were replicated by allele score-based MR in 321 260 individuals of white British ancestry in the UK Biobank with quality-controlled genetic data.
RESULTS Higher education attainment was significantly associated with lower adjusted odds for CKD in the clinical analysis {>17 years versus <16 years, adjusted odds ratio [OR] 0.910 [95% confidence interval (CI) 0.849-0.975]}. The causal estimates obtained by the inverse variance method in the two-sample MR indicated that higher genetically predicted education attainment causally reduced the risk of CKD [OR 0.934 (95% CI 0.873-0.999)]. Allele score-based MR also supported that higher education attainment was causally linked to a decreased risk of CKD [adjusted OR 0.944 (95% CI 0.922-0.966)].
CONCLUSION The study suggests that higher education attainment causally reduces the risk of CKD development in the general population.
PubMed IF 5.3 신장내과
2402021

제1저자 함종호 · 교신저자 강혜련, 김혜영

, , , , , , , , , , , , , ,
Interactions between NCR+ILC3s and the Microbiome in the Airways Shape Asthma Severity.
Immune Netw. 2021;21(4):e25.

Abstract
Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)⁺ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR⁺ILC3 frequencies and microbial diversity in the lung. Sputum NCR⁺ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR⁺ILC3s may contribute to a healthy commensal diversity and normal lung function.
PubMed IF 5.9 알레르기내과
2392021

제1저자 황인주 · 교신저자 이은주, 김효수

, , , , , , , , , , ,
Endothelin-1 enhances the regenerative capability of human bone marrow-derived mesenchymal stem cells in a sciatic nerve injury mouse model.
Biomaterials. 2021;275:120980.

Abstract
We expanded the application of endothelin-1 (EDN1) by treating human mesenchymal stem cell (hMSC) organotypic spinal cord slice cultures with EDN1. EDN1-treated hMSCs significantly enhanced neuronal outgrowth. The underlying mechanism of this effect was evaluated via whole-genome methylation. EDN1 increased whole-genome demethylation and euchromatin. To observe demethylation downstream of EDN1, deaminases and glycosylases were screened, and APOBEC1 was found to cause global demethylation and OCT4 gene activation. The sequence of methyl-CpG-binding domain showed similar patterns between EDN1- and APOBEC1-induced demethylation. SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 4 (SMARC A4) and SMARC subfamily D, member 2 (SMARC D2) were screened via methyl-CpG-binding domain sequencing as a modulator in response to EDN1. Chromatin immunoprecipitation of the H3K9me3, H3K27me3, and H3K4me4 binding sequences on the APOBEC1 promoter was analyzed following treatment with or without siSMARC A4 or siSMARC D2. The results suggested that SMARC A4 and SMARC D2 induced a transition from H3K9me3 to H3K4me3 in the APOBEC1 promoter region following EDN1 treatment. Correlations between EDN1 pathways and therapeutic efficacy in hBM-MSCs were determined in a sciatic nerve injury mouse model. Thus, EDN1 may be a useful novel-concept bioactive peptide and biomaterial component for improving hMSC regenerative capability.
PubMed IF 13.6 순환기내과

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