SCI 발표논문

2021년 358편

1482021

제1저자 김예림 · 교신저자 김동기, 한경도

, , , , , , , , , , , , , , , , ,
The minimum-mortality estimated glomerular filtration rate percentile shifts upward in the aged population: a nationwide population-based study.
Clin Kidney J. 2021;14(5):1356-1363.

Abstract
BACKGROUND The estimated glomerular filtration rate (eGFR) is a biomarker not only for kidney function, but also for major clinical outcomes. We aimed to evaluate the patterns of mortality across the entire eGFR percentile spectrum using a population-based dataset.
METHODS We retrospectively reviewed the National Health Insurance Service (NHIS) database for people who received nationwide health check-ups from 2009 to 2012. Subjects who were ≥45 years old and had one or more serum creatinine values available were included in the study. The primary outcome was all-cause mortality as a function of eGFR percentile.
RESULTS The middle-aged group (45-64 years) showed a U-shaped pattern of association between eGFR percentile and all-cause mortality. The minimum-mortality eGFR percentile was shifted upward in the elderly group (≥65 years). Specifically, the minimum-mortality eGFR percentiles were the 28th percentile (83.8 mL/min/1.73 m²) for middle-aged males, the 63rd percentile (86.2 mL/min/1.73 m²) for elderly males, the 42nd percentile (102.8 mL/min/1.73 m²) for middle-aged females and the 75th percentile (90.1 mL/min/1.73 m²) for elderly females. Diabetes and hypertension shifted the minimum-mortality eGFR percentile upward in the middle-aged group. This pattern was attenuated in the elderly group.
CONCLUSIONS The eGFR percentile showing minimum mortality moves upward in the aged population as well as patients with diabetes and hypertension, which might reduce the clinical significance of hyperfiltration. Risk stratification for mortality should be approached differently according to the specific conditions of the patient group.
PubMed IF 5.3 신장내과
1472021

제1저자 전준영, 송경호 · 교신저자 김의석

, , , , , , , , , , , , , , , , , , ,
Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity.
Int J Med Inform. 2021;149:104403.

Abstract
BACKGROUND A vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose.
METHODS We describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital's electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose.
RESULTS After implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity.
CONCLUSION Introduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.
PubMed IF 5 감염내과
1462021

제1저자 신유진 · 교신저자 임수

, ,
Comparison betweeen dapagliflozin add-on therapy and insulin dose escalation in patients with uncontrolled type 2 diabetes treated with insulin: DVI study.
Diabetes Res Clin Pract. 2021;175:108843.

Abstract
AIM To assess the efficacy and tolerability of adjunct therapy with a sodium-glucose cotransporter-2 inhibitor, dapagliflozin, compared with insulin escalation for patients with uncontrolled type 2 diabetes on current insulin therapy.
METHODS A 12-month retrospective case-control study of patients with glycated hemoglobin (HbA1c) > 7% on insulin therapy. The study group received add-on therapy with dapagliflozin (10 mg once daily); the control group received titrated increases of their existing insulin dose by a mean of 21.6% from baseline. The primary endpoint was the change in HbA1c after 12 months. Secondary outcomes included changes in fasting plasma glucose, postprandial 2-h glucose levels, insulin requirements, and body weight.
RESULTS After 12 months, the reduction in HbA1c was significantly greater in the dapagliflozin group than in the control group (from 8.9 ± 1.2% to 8.0 ± 1.0% vs 9.1 ± 1.2% to 8.7 ± 1.5%, respectively). Results for fasting plasma glucose and postprandial 2-h glucose were similar. Dapagliflozin therapy decreased systolic blood pressure (-4.7 mmHg) and body weight (-1.4 kg) significantly, whereas body weight increased by 0.6 kg in the control group. The dapagliflozin group showed significantly fewer hypoglycemic events than the control group (18.5% vs 32.6%, respectively). Daily insulin dose increased by 5.4 ± 6.1 U (21.6%) in the control group but decreased by 1.9 ± 5.3 U (-4.5%) in the dapagliflozin group (p < 0.001).
CONCLUSION As an adjunct to insulin therapy, dapagliflozin therapy significantly improved glycemic control, with the clinical advantages of weight loss, insulin sparing, and less hypoglycemia.
PubMed IF 4.6 내분비대사내과
1452021

제1저자 권순일, 김태정 · 교신저자 최의근, 고상배

, , , , , , , ,
Predictors of ischemic stroke for low-risk patients with atrial fibrillation: A matched case-control study.
Heart Rhythm. 2021;18(5):702-708.

Abstract
BACKGROUND The predictors of ischemic stroke in "low-risk" patients with atrial fibrillation (AF) (CHA₂DS₂-VASc score 0 in men or 1 in women) are debated.
OBJECTIVE This study aimed to investigate the factors associated with ischemic stroke in low-risk patients with AF. Imaging characteristics of their ischemic strokes were also evaluated.
METHODS This was a matched case-control study conducted at a single tertiary institution. We identified 44 patients with de novo ischemic stroke and incidentally found AF with a low-risk CHA₂DS₂-VASc score. A 1:5 age- and sex-matched control group was selected for patients with AF and a low-risk CHA₂DS₂-VASc score but without ischemic stroke and oral anticoagulant therapy. Conditional multivariate logistic regression analysis was performed to identify the predictors.
RESULTS There were no significant differences in age, sex, body mass index, comorbidities, left atrial size, and left ventricular ejection fraction. Smokers were more prevalent in the stroke group than in the nonstroke group (24 of 44 [54.5%] vs 22 of 220 [10.0%]; P < .001). Additionally, the mean white blood cell count was significantly higher in the stroke group (P = .019). In conditional univariate logistic regression analysis, smoking and white blood cell count were significant predictors of stroke. In multivariate analysis, smoking was the only significantly associated factor (matched odds ratio 9.10; 95% confidence interval 2.48-33.42). In the stroke group, 14 of 44 patients (31.8%) had multiple vascular territory infarcts.
CONCLUSION Smoking was the predictor associated with ischemic stroke in patients with AF and a low-risk CHA₂DS₂-VASc score.
PubMed IF 7 순환기내과
1442021

제1저자 김선웅, 윤준식 · 교신저자 이정훈

, , , , , , , , , , , , , , , , , , , , , , , , ,
Empirical Treatment With Carbapenem vs Third-generation Cephalosporin for Treatment of Spontaneous Bacterial Peritonitis.
Clin Gastroenterol Hepatol. 2021;19(5):976-986.e5.

Abstract
BACKGROUND & AIMS Third-generation cephalosporins (TGCs) are recommended as first-line antibiotics for treatment of spontaneous bacterial peritonitis (SBP). However, antibiotics against multidrug-resistant organisms (such as carbapenems) might be necessary. We aimed to evaluate whether carbapenems are superior to TGC for treatment of SBP.
METHODS We performed a retrospective study of 865 consecutive patients with a first presentation of SBP (275 culture positive; 103 with TGC-resistant bacterial infections) treated at 7 referral centers in Korea, from September 2013 through January 2018. The primary outcome was in-hospital mortality. We made all comparisons using data from patients whose baseline characteristics were balanced by inverse probability of treatment weighting.
RESULTS Of patients who initially received empirical treatment with antibiotics, 95 (11.0%) received carbapenems and 655 (75.7%) received TGCs. Among the entire study cohort, there was no significant difference in in-hospital mortality between the carbapenem (25.8%) and TGC (25.3%) groups (adjusted odds ratio [aOR], 0.97; 95% CI, 0.85-1.11; P = .66). In the subgroup of patients with high chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores (score of 7 or greater, n = 314), carbapenem treatment was associated with lower in-hospital mortality (23.1%) than in the TGC group (38.8%) (aOR, 0.84; 95% CI, 0.75-0.94; P=.002). In contrast, among patients with lower CLIF-SOFA scores (n = 436), in-hospital mortality did not differ significantly between the carbapenem group (24.7%) and the TGC group (16.0%) (aOR, 1.06; 95% CI, 0.85-1.32; P = .58).
CONCLUSIONS For patients with a first presentation of SBP, empirical treatment with carbapenem does not reduce in-hospital mortality compared to treatment with TGCs. However, among critically ill patients (CLIF-SOFA scores ≥7), empirical carbapenem treatment was significantly associated with lower in-hospital mortality than TGCs.
PubMed IF 16.2 소화기내과
1432021

제1저자 한정규, 신영철, 손민환 · 교신저자 김효수

, , , , , , , ,
Direct conversion of adult human fibroblasts into functional endothelial cells using defined factors.
Biomaterials. 2021;272:120781.

Abstract
We aimed to directly convert adult human dermal fibroblasts (aHDFs) into functional endothelial cells (ECs). Lentiviral vectors encoding endothelial transcription factors (TFs) were constructed. We examined whether five TFs (FOXO1, ER71, KLF2, TAL1, and LMO2) used for the generation of mouse induced ECs (iECs) could convert the aHDFs into human iECs. Twenty-eight days after transduction with lentiviral constructs, 32.1 ± 5.1% cells expressed vascular endothelial (VE)-cadherin. Factor screening revealed that only three factors (3F: ER71, KLF2, and TAL1) were necessary to induce VE-cadherin (+) cells (49.4 ± 3.5%). However, whole transcriptome sequencing showed that VE-cadherin (+) cells were not completely reprogrammed. Mature iECs double-positive for VE-cadherin/Pecam1 (DP cells) with a cobblestone appearance were obtained at a frequency of only 5.1 ± 0.6%. Using whole transcriptome analysis, the potential factors that could block the conversion were screened. Among candidates TWIST1-knockdown enhanced efficiency of conversion. Rosiglitazone, an inhibitor of epithelial-mesenchymal transition (EMT), also improved the conversion efficiency. Moreover, a 2nd second-stage conversion process, in which VE-cadherin (+) cells were incubated for additional two weeks, further enhanced the efficiency. The final protocol for 6 weeks yielded a conversion rate of 19.6 ± 3.0% iECs, defined by DP cells depicting the nature of mature ECs in various analyses. Further analyses revealed that the genetic and epigenetic profiles of iECs resembled those of functional ECs. Collectively, aHDFs can be converted into functional ECs through the transduction of ER71, KLF2, and TAL1, combined with two EMT inhibitors (siTWIST1 and rosiglitazone), followed by 2nd stage conversion.
PubMed IF 13.6 순환기내과
1422021

제1저자 최진호 · 교신저자 이상협

, , , , ,
Ursodeoxycholic acid for the prevention of gallstone and subsequent cholecystectomy following gastric surgery: A systematic review and meta-analysis.
J Hepatobiliary Pancreat Sci. 2021;28(5):409-418.

Abstract
BACKGROUND/PURPOSE Patients who undergo gastric surgery are prone to form postsurgical gallstones. Debates still exist about the need for prevention and the selection of preventive methods. No studies had been reported comparing the efficacy of prophylactic ursodeoxycholic acid (UDCA) and prophylactic cholecystectomy (PC) for lowering postsurgical gallstone formation and subsequent cholecystectomy (SC) in patients who have undergone gastric surgery.
METHODS We did a systematic review to identify studies from PUBMED, EMBASE, and the Cochrane database through 30 June 2020. We conducted direct and indirect comparisons of each prophylaxis using conventional and network meta-analysis. Studies with patients who have no history of cholecystectomy and who have not had preoperative gallstone were included.
RESULTS The excellent preventive effects of PC and UDCA were demonstrated for gallstone formation (odds ratio [OR] 0.05, [95% CI 0.01, 0.22] and 0.20, [95% CI 0.16, 0.24], respectively) and the need for SC (OR 0.10, [95% CI 0.02, 0.57] and OR 0.22, [95% CI 0.14, 0.35], respectively) than control group. The UDCA group showed a tendency to generate more gallstones (OR 3.74, [95% CI 0.88, 15.82]) and a greater need for SC (OR 2.19, [95% CI 0.47-10.14]) than did the PC group without statistical significance.
CONCLUSIONS Prophylaxis for gallstone formation may be needed for patients who undergo gastric surgery to reduce troublesome morbidities. Prophylactic UDCA seems to be a reasonable preventive method for postsurgical gallstone formation to ensure clinical benefit while reducing the burden of subsequent cholecystectomy for the patient as compared to a PC.
PubMed IF 2.5 소화기내과
1412021

제1저자 유정주, 조은주 · 교신저자 신동욱, 유수종

, , , , , ,
Glucose Variability and Risk of Hepatocellular Carcinoma in Patients with Diabetes: A Nationwide Population-Based Study.
Cancer Epidemiol Biomarkers Prev. 2021;30(5):974-981.

Abstract
BACKGROUND Although diabetes is a well-known risk factor for hepatocellular carcinoma, exactly which metabolic parameters of diabetes are associated with hepatocellular carcinoma remain unexplored. In this study, we investigated the relationship between glucose variability (GV) and hepatocellular carcinoma in patients with diabetes through a nationwide population-based study.
METHODS A population-based cohort study including 674,178 diabetic subjects participating in more than three health examinations within 5 years from the index year (2009 and 2010) were followed until the end of 2017. The coefficient of variation, SD, variability independent of the mean, and average real variability were calculated as GV indices.
RESULTS During a median follow-up of 6.7 years, there were 5,494 cases of hepatocellular carcinoma. When groups were classified according to glucose level, the highest risk for hepatocellular carcinoma was observed when the basal blood glucose level was 180 mg/dL or greater [adjusted HR (aHR), 1.19; 95% confidence interval (CI), 1.08-1.31]. We observed increasing trends for the relationship between GV and hepatocellular carcinoma in multivariable Cox proportional analyses. The risk of hepatocellular carcinoma increased by 27% (aHR, 1.27; 95% CI, 1.17-1.38) for the highest quartile of GV relative to the lowest quartile. These findings were consistent regardless of the presence of chronic viral hepatitis or cirrhosis, alcohol consumption, or body mass index.
CONCLUSIONS GV was an independent predictor of hepatocellular carcinoma, even after adjusting for confounding factors. There was a linear relationship between increase in GV and prevalence of hepatocellular carcinoma.
IMPACT Visit-to-visit GV might be helpful for identifying patients with diabetes at high risk of hepatocellular carcinoma.
PubMed IF 3.7 소화기내과
1402021

제1저자 장한나, 김사홍 · 교신저자 박도중

, , ,
Bariatric Surgery for Cowden Syndrome with PTEN Mutation: a Case Report.
Obes Surg. 2021;31(5):2316-2318.

PubMed IF 3.4 내분비대사내과
1392021

제1저자 김정현 · 교신저자 이진우

, , , , , , ,
Dexmedetomidine versus midazolam for sedation during endobronchial ultrasound-guided transbronchial needle aspiration: A randomised controlled trial.
Eur J Anaesthesiol. 2021;38(5):534-540.

Abstract
BACKGROUND Desaturation is a common complication of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Dexmedetomidine (DEX), a commonly used sedative in intensive care, is associated with less respiratory depression compared with other sedatives.
OBJECTIVE We compared DEX with midazolam (MDZ) when used as a sedative during EBUS-TBNA.
DESIGN A randomised, parallel, double-blinded trial.
SETTING A university-affiliated teaching hospital between June 2014 and July 2015.
PATIENTS A total of 102 patients who underwent EBUS-TBNA were randomly allocated to two groups (48 DEX group, 54 MDZ group).
INTERVENTIONS DEX group received 0.25 to 0.75 μg kg-1 h-1 (start with 0.5 μg kg-1 h-1, modulated in three steps from 0.25 to 0.75 μg kg-1 h-1) of DEX after a loading dose of 0.25 μg kg-1 h-1 for 10 min to maintain a Ramsay Sedation Scale (RSS) of 3 to 5. If the patient was agitated, 1 mg of MDZ bolus was used as a rescue drug. Patients in the MDZ group initially received 0.05 mg kg-1 of MDZ as a bolus. For maintenance and rescue, 1 mg of MDZ bolus was used.
MAIN OUTCOME MEASURES The primary outcome was the presence of oxygen desaturation. Secondary outcomes were level of sedation (Ramsay Sedation Scale score), cough score, sedation and procedure satisfaction score.
RESULTS The baseline characteristics of the patients, duration of EBUS-TBNA procedures and the use of rescue MDZ were not different between the groups. There was no significant difference in desaturation events between the DEX and MDZ groups (56.3 and 68.5%, respectively; P = 0.20). The level of sedation and the sedation satisfaction scores were similar between the two groups. However, cough score was significantly lower in the DEX group (41.9 vs. 53.4; P = 0.02).
CONCLUSION The use of DEX during EBUS-TBNA was not superior to MDZ in terms of oxygen desaturation.
TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT02157818.
PubMed IF 7.8 호흡기내과
1382021

제1저자 권순일, 정진형 · 교신저자 최의근

, , , , , , , , , ,
Impact of Non-Vitamin K Antagonist Oral Anticoagulants on the Change of Antithrombotic Regimens in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.
Korean Circ J. 2021;51(5):409-422.

Abstract
BACKGROUND AND OBJECTIVES Antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) has changed in recent years with new data from large randomized trials and updates to clinical guidelines. This study aimed to investigate the trends in periprocedural antithrombotic regimens in Korean patients with AF undergoing PCI with non-vitamin K antagonist oral anticoagulants (NOACs).
METHODS Using the claims database of the Health Insurance Review and Assessment during 2013-2018, 27,594 patients with AF undergoing PCI were identified. The annual prevalence of PCI and prescriptions of each antithrombotic agent, including antiplatelet agents and oral anticoagulants, within 30 days after PCI were investigated.
RESULTS During 2013-2018, the number of patients with AF undergoing PCI increased up to 1.3-fold (from 3,913 to 5,075 patients per year). After the introduction of NOACs, the proportion of dual antiplatelet therapy (DAPT) decreased from 71.9% to 49.8% but still occupied the largest proportion among antithrombotic regimens. Triple antithrombotic therapy (TAT) use increased from 25.4% to 46.0%, and NOAC has rapidly replaced warfarin as the oral anticoagulant of choice. TAT was preferred to DAPT for patients with CHA₂DS₂-VASc score ≥2. Among various factors, prior intracranial hemorrhage was the most powerful predictor of favoring DAPT use over TAT.
CONCLUSION Since the introduction of NOACs, the patterns of periprocedural antithrombotic regimens have changed rapidly toward more use of TAT, specifically with NOAC-based regimen. Appropriate stroke prevention with oral anticoagulants is still underutilized in patients with AF undergoing PCI in Korea.
PubMed IF 3.4 순환기내과
1372021

제1저자 이현우 · 교신저자 이창훈

, , ,
Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis.
Thorax. 2021;76(5):479-486.

Abstract
BACKGROUND The association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.
METHODS We searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.
RESULTS ACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I²=95%, low certainty of evidence).
CONCLUSIONS ACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.
PubMed IF 9.1 호흡기내과
1362021

제1저자 권순일, 이소령 · 교신저자 최의근

, , , , , ,
Validation of Adhesive Single-Lead ECG Device Compared with Holter Monitoring among Non-Atrial Fibrillation Patients.
Sensors (Basel). 2021;21(9):s21093122.

Abstract
There are few reports on head-to-head comparisons of electrocardiogram (ECG) monitoring between adhesive single-lead and Holter devices for arrhythmias other than atrial fibrillation (AF). This study aimed to compare 24 h ECG monitoring between the two devices in patients with general arrhythmia. Twenty-nine non-AF patients with a workup of pre-diagnosed arrhythmias or suspicious arrhythmic episodes were evaluated. Each participant wore both devices simultaneously, and the cardiac rhythm was monitored for 24 h. Selective ECG parameters were compared between the two devices. Two cardiologists independently compared the diagnoses of each device. The two most frequent monitoring indications were workup of premature atrial contractions (41.4%) and suspicious arrhythmia-related symptoms (37.9%). The single-lead device had a higher noise burden than the Holter device (0.04 ± 0.05% vs. 0.01 ± 0.01%, p = 0.024). The number of total QRS complexes, ventricular ectopic beats, and supraventricular ectopic beats showed an excellent degree of agreement between the two devices (intraclass correlation coefficients = 0.991, 1.000, and 0.987, respectively). In addition, the minimum/average/maximum heart rates showed an excellent degree of agreement. The two cardiologists made coherent diagnoses for all 29 participants using both monitoring methods. In conclusion, the single-lead adhesive device could be an acceptable alternative for ambulatory ECG monitoring in patients with general arrhythmia.
PubMed IF 4 순환기내과
1352021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study.
Nutrients. 2021;13(5):nu13051490.

Abstract
We aimed to investigate the causal effects of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) through Mendelian randomization (MR) analysis. This MR study utilized a genetic instrument developed from previous genome-wide association studies for various serum n-3 and n-6 PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data (N = 337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD (N = 184,305). Higher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the pleiotropy-robust MR methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid showed significant causal estimates for a higher risk of CAD. This study supports the causal effects of certain n-3 and n-6 PUFA types on the risk of CAD.
PubMed IF 5.8 신장내과
1342021

제1저자 윤동환 · 교신저자 임춘수

, , , , ,
Can sodium fluorescein cause contrast-induced nephropathy?
Nephrol Dial Transplant. 2021;36(5):819-825.

Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury (AKI), and can be diagnosed when the etiology of AKI is unclear other than via a contrast agent. Fluorescent angiography (FAG) with fluorescein sodium dye is generally considered to be safe for patients with kidney diseases. However, it remains unresolved whether or not FAG can induce CIN.
METHODS Patients from two tertiary hospitals who underwent FAG and had serum creatinine results within 4 weeks before FAG and 3 days after FAG between 2001 and 2017 were retrieved. Cases with concurrent iodinated contrast imaging or undergoing dialysis were excluded from the analysis. CIN was defined by two criteria: CIN criteria as >0.5 mg/dL or >25% increase in serum creatinine (sCr) level within 3 days after FAG, and contrast-induced acute kidney injury (CIAKI) criteria as ≥0.3 mg/dL increase within 2 days or ≥50% increase within 7 days after FAG.
RESULTS A total of 979 patients were screened, and we found 124 patients with AKI after FAG. After excluding 32 patients with clear causes of AKI other than FAG, the incidence rates of CIN were 7.3% by CIN criteria and 6.4% by CIAKI criteria. CIN incidence had a U-shaped distribution according to chronic kidney disease (CKD) stages in CIN criteria, while linear association between CIN incidence and CKD stages were found in CIAKI criteria. Kaplan-Meier curves showed the CIN group was significantly associated with end-stage renal disease (ESRD) progression (log-rank P < 0.001, in both CIN criteria and CIAKI criteria), and adjusted hazard ratios by multivariable Cox regression were 2.23 [95% confidence interval (CI) 1.468-3.378] in CIN criteria and 2.17 (95% CI 1.462-3.232) in CIAKI criteria.
CONCLUSIONS According to CIN and CIAKI criteria, FAG may cause CIN and appeared to be a possible risk factor for ESRD progression. However, CIN or CIAKI criteria themselves may overestimate AKI and require meticulous attention to the interpretation of results.
PubMed IF 8.3 신장내과
1332021

제1저자 변자민 · 교신저자 이정옥

, , , , , , ,
Should patients receive consolidation chemotherapy before reduced intensity allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in first complete remission?
Ther Adv Hematol. 2021;12:20406207211001135.

Abstract
BACKGROUND For acute myeloid leukemia (AML) patients, the role of bridging consolidation chemotherapy after achieving first complete remission (CR1) in the transplant setting is a frequently debated issue. The lack of data from Asian patients led us to conduct this study.
METHODS We retrospectively studied outcomes of 106 patients in CR1 undergoing allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning (RIC) based on their exposure to pre-transplant consolidation chemotherapy. There were 35 in the no consolidation group versus 71 in the consolidation group.
RESULTS The median relapse free survival (RFS) was 9 months for the no consolidation group and 51 months for consolidation group (p = 0.023). The median overall survival was 32 months for the no consolidation group and not reached for the consolidation group (p = 0.034). Multivariate analysis recognized consolidation and poor cytogenetics as adverse prognostic factors for RFS. Moreover, RFS was better in patients with a shorter time lapse between last chemotherapy and alloSCT in both the no consolidation group and the consolidation group. Consolidation chemotherapy did not negatively affect neutrophil and platelet engraftment, infection rates, or acute graft-versus-host disease (GVHD) incidence. On the other hand, patients undergoing consolidation chemotherapy showed trends towards a more severe degree of chronic GVHD.
CONCLUSION The exposure to consolidation chemotherapy in CR1 prior to alloSCT with RIC conditioning did not negatively impact the outcomes in Korean AML patients, for whom a suitable donor is rarely immediately available. Therefore, post-remission consolidation chemotherapy is a reasonable option if required.
PubMed IF 2.8 혈액종양내과
1322021

제1저자 박찬순 · 교신저자 양한모

, , , , , , , , , , , , , ,
Left Ventricular Ejection Fraction 1 Year After Acute Myocardial Infarction Identifies the Benefits of the Long-Term Use of β-Blockers: Analysis of Data From the KAMIR-NIH Registry.
Circ Cardiovasc Interv. 2021;14(4):e010159.

Abstract
[Figure: see text].
PubMed IF 7.2 순환기내과
1312021

제1저자 박남영 · 교신저자 이상협

, , , , , , , , ,
Optimal timing of endoscopic retrograde cholangiopancreatography for acute cholangitis associated with distal malignant biliary obstruction.
BMC Gastroenterol. 2021;21(1):175.

Abstract
BACKGROUND There is a lack of studies regarding the optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with cholangitis caused by distal malignant biliary obstruction (MBO). This study aims to investigate the optimal timing of ERCP in patients with acute cholangitis associated with distal MBO with a naïve papilla.
METHODS A total of 421 patients with acute cholangitis, associated with distal MBO, were enrolled for this study. An urgent ERCP was defined as being an ERCP performed within 24 h following emergency room (ER) arrival, and early ERCP was defined as an ERCP performed between 24 and 48 h following ER arrival. We evaluated both 30-day and 180-day mortality as primary outcomes, according to the timing of the ERCP.
RESULTS The urgent ERCP group showed the lowest 30-day mortality rate (2.2%), as compared to the early and delayed ERCP groups (4.3% and 13.5%) (P < 0.001). The 180-day mortality rate was lowest in the urgent ERCP group, followed by early ERCP and delayed ERCP groups (39.4%, 44.8%, 60.8%; P = 0.006). A subgroup analysis showed that in both the primary distal MBO group, as well as in the moderate-to-severe cholangitis group, the urgent ERCP had significantly improved in both 30-day and 180-day mortality rates. However, in the secondary MBO and mild cholangitis groups, the difference in mortality rate between urgent, early, and delayed ERCP groups was not significant.
CONCLUSIONS In patients with acute cholangitis associated with distal MBO, urgent ERCP might be helpful in improving the prognosis, especially in patients with primary distal MBO or moderate-to-severe cholangitis.
PubMed IF 3.2 소화기내과
1302021

제1저자 김기표, 양현식 · 교신저자 김세중

, , , , , , , , , , ,
Real-Time Clinical Decision Support Based on Recurrent Neural Networks for In-Hospital Acute Kidney Injury: External Validation and Model Interpretation.
J Med Internet Res. 2021;23(4):e24120.

Abstract
BACKGROUND Acute kidney injury (AKI) is commonly encountered in clinical practice and is associated with poor patient outcomes and increased health care costs. Despite it posing significant challenges for clinicians, effective measures for AKI prediction and prevention are lacking. Previously published AKI prediction models mostly have a simple design without external validation. Furthermore, little is known about the process of linking model output and clinical decisions due to the black-box nature of neural network models.
OBJECTIVE We aimed to present an externally validated recurrent neural network (RNN)-based continuous prediction model for in-hospital AKI and show applicable model interpretations in relation to clinical decision support.
METHODS Study populations were all patients aged 18 years or older who were hospitalized for more than 48 hours between 2013 and 2017 in 2 tertiary hospitals in Korea (Seoul National University Bundang Hospital and Seoul National University Hospital). All demographic data, laboratory values, vital signs, and clinical conditions of patients were obtained from electronic health records of each hospital. We developed 2-stage hierarchical prediction models (model 1 and model 2) using RNN algorithms. The outcome variable for model 1 was the occurrence of AKI within 7 days from the present. Model 2 predicted the future trajectory of creatinine values up to 72 hours. The performance of each developed model was evaluated using the internal and external validation data sets. For the explainability of our models, different model-agnostic interpretation methods were used, including Shapley Additive Explanations, partial dependence plots, individual conditional expectation, and accumulated local effects plots.
RESULTS We included 69,081 patients in the training, 7675 in the internal validation, and 72,352 in the external validation cohorts for model development after excluding cases with missing data and those with an estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or end-stage kidney disease. Model 1 predicted any AKI development with an area under the receiver operating characteristic curve (AUC) of 0.88 (internal validation) and 0.84 (external validation), and stage 2 or higher AKI development with an AUC of 0.93 (internal validation) and 0.90 (external validation). Model 2 predicted the future creatinine values within 3 days with mean-squared errors of 0.04-0.09 for patients with higher risks of AKI and 0.03-0.08 for those with lower risks. Based on the developed models, we showed AKI probability according to feature values in total patients and each individual with partial dependence, accumulated local effects, and individual conditional expectation plots. We also estimated the effects of feature modifications such as nephrotoxic drug discontinuation on future creatinine levels.
CONCLUSIONS We developed and externally validated a continuous AKI prediction model using RNN algorithms. Our model could provide real-time assessment of future AKI occurrences and individualized risk factors for AKI in general inpatient cohorts; thus, we suggest approaches to support clinical decisions based on prediction models for in-hospital AKI.
PubMed IF 8.2 신장내과
1292021

제1저자 최유정 · 교신저자 박준빈

, , , , , , , , ,
Prognostic implications of left ventricular mass-geometry in patients with no or nonobstructive coronary artery disease.
BMC Cardiovasc Disord. 2021;21(1):187.

Abstract
BACKGROUND Coronary computed tomography angiography (CCTA) is widely used as a first-line noninvasive modality that frequently exhibits no or nonobstructive coronary artery disease (CAD) in clinical practice, along with abnormal left ventricular (LV) geometry on echocardiography. However, the combined prognostic value of these findings has not been well elucidated. Therefore, we aimed to evaluate the prognostic implications of abnormal LV geometry in individuals with no or nonobstructive CAD.
METHODS A total of 5806 subjects with no CAD or nonobstructive CAD (luminal narrowing < 50%) on CCTA were included in the study. The major exclusion criteria were structural heart disease and a history of myocardial infarction or coronary revascularization. Abnormal LV geometry on echocardiography was defined as LV mass index > 95 g/m² in women and > 115 g/m² in men, and/or relative wall thickness > 0.42. The primary outcome was all-cause mortality.
RESULTS A total of 5803 subjects without significant obstructive CAD (age, 56.6 ± 8.87 years; men, 3884 [66.9%]). Of them, 4045 (69.7%) subjects had normal LV geometry and 1758 (30.3%) had abnormal LV geometry respectively. During a mean follow-up of 6.2 ± 1.48 years, 84 (1.44%) subjects died in the study population. Of these, 56 subjects were from the normal LV geometry group (1.24%) and 28 were from the abnormal LV geometry group (2.32%). Subjects with abnormal LV geometry had significantly worse survival rates (log-rank, p < 0.001). After adjustment for confounding factors, abnormal LV geometry was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.64; 95% confidence interval, 1.04-2.58; p = 0.034). Moreover, abnormal LV geometry was significantly worse in survival when classified as those with no CAD (log-rank, p = 0.024) and nonobstructive CAD (Log-rank, p < 0.001).
CONCLUSIONS Abnormal LV geometry portends a worse prognosis in subjects with no or nonobstructive CAD. These findings suggest that LV geometry assessment can help improve the stratification of individuals with these CCTA findings.
PubMed IF 3.1 순환기내과
1282021

제1저자 이은영, 송경호 · 교신저자 진범식, 박진균

, , , , , , , , , , ,
Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis.
Sci Rep. 2021;11(1):8080.

Abstract
The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.
PubMed IF 4.9 류마티스내과
1272021

제1저자 이춘수 · 교신저자 김효수

, , , , ,
Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK.
Stem Cell Reports. 2021;16(4):868-882.

Abstract
Identifying lineage-specific markers is pivotal for understanding developmental processes and developing cell therapies. Here, we investigated the functioning of a cardiomyogenic cell-surface marker, latrophilin-2 (LPHN2), an adhesion G-protein-coupled receptor, in cardiac differentiation. LPHN2 was selectively expressed in cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs) during mouse and human pluripotent stem cell (PSC) differentiation; cell sorting with an anti-LPHN2 antibody promoted the isolation of populations highly enriched in CPCs and CMCs. Lphn2 knockdown or knockout PSCs did not express cardiac genes. We used the Phospho Explorer Antibody Array, which encompasses nearly all known signaling pathways, to assess molecular mechanisms underlying LPHN2-induced cardiac differentiation. LPHN2-dependent phosphorylation was the strongest for cyclin-dependent kinase 5 (CDK5) at Tyr15. We identified CDK5, Src, and P38MAPK as key downstream molecules of LPHN2 signaling. These findings provide a valuable strategy for isolating CPCs and CMCs from PSCs and insights into the still-unknown cardiac differentiation mechanisms.
PubMed IF 5.6 순환기내과
1262021

제1저자 오상민 · 교신저자 김남중

, , , , , , , , ,
Clinical Application of the Standard Q COVID-19 Ag Test for the Detection of SARS-CoV-2 Infection.
J Korean Med Sci. 2021;36(14):e101.

Abstract
We evaluated the Standard Q COVID-19 Ag test for the diagnosis of coronavirus disease 2019 (COVID-19) compared to the reverse transcription-polymerase chain reaction (RT-PCR) test. We applied both tests to patients who were about to be hospitalized, had visited an emergency room, or had been admitted due to COVID-19 confirmed by RT-PCR. Two nasopharyngeal swabs were obtained; one was tested by RT-PCR and the other by the Standard Q COVID-19 Ag test. A total of 118 pairs of tests from 98 patients were performed between January 5 and 11, 2021. The overall sensitivity and specificity for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the Standard Q COVID-19 Ag test compared to RT-PCR were 17.5% (95% confidence interval [CI], 8.8-32.0%) and 100% (95% CI, 95.3-100.0%). Analysis of the results using RT-PCR cycle thresholds of ≤ 30 or ≤ 25 increased the sensitivity to 26.9% (95% CI, 13.7-46.1%), and 41.1% (95% CI, 21.6-64.0%), respectively.
PubMed IF 3.2 감염내과
1252021

제1저자 조성우, 김동영 · 교신저자 강혜련, 이하나

, , , , ,
Microbiome profiling of uncinate tissue and nasal polyps in patients with chronic rhinosinusitis using swab and tissue biopsy.
PLoS One. 2021;16(4):e0249688.

Abstract
Chronic rhinosinusitis (CRS) is characterized according to the presence or absence of nasal polyps (NPs) and displays nasal microbiota dysbiosis. However, optimal sampling methods of the nasal microbiome in CRS have not been identified. We aimed to assess the microbial composition in patients with CRS, comparing different sampling methods (swab and tissue biopsy), tissue types (uncinate tissue and NP), and disease subtypes. Samples were obtained by swabbing the middle meatus and taking a biopsy of uncinate tissue (UT) in patients with CRS with (CRSwNP, N = 8) or without NP (CRSsNP, N = 6) and controls (N = 8). NPs were also harvested in CRSwNP. DNAs were extracted from fifty-two samples and analyzed by 16S rRNA gene amplicon sequencing. As a result, a great interpersonal variance was observed in nasal swabs, while UT samples presented distinct microbiome with low inter-personal differences. Moreover, the UT microbiomes were further differentiated into three clusters which are associated with disease status (control, CRSsNP, and CRSwNP). Compared to UT, NP revealed a unique microbiome profile with significantly less bacterial diversity. Prevotella was the genus whose abundance was negatively correlated with disease severity in NP. In conclusion, tissue samples are better specimens than nasal swabs for assessing the microbiomes of CRS patients. Several bacteria in UT and NP tissues revealed an association with clinical severity of CRSwNP.
PubMed IF 2.8 알레르기내과
1242021

제1저자 최정연, 김진각 · 교신저자 김광일

, , , , ,
How does the multidimensional frailty score compare with grip strength for predicting outcomes after hip fracture surgery in older patients? A retrospective cohort study.
BMC Geriatr. 2021;21(1):234.

Abstract
BACKGROUND Frailty and low handgrip strength (HGS) are associated with adverse outcomes after hip fracture (HF) surgery. We aimed to compare the predictive role of frailty and HGS for adverse outcome in HF patients.
METHODS We included older patients (age ≥ 65 years) who underwent HF surgery to compare the predictive role of HGS and hip-multidimensional frailty score (Hip-MFS) for postoperative complications and mortality. The Hip-MFS was calculated based on comprehensive geriatric assessment (CGA), and HGS was measured with a hand dynamometer. The primary outcome was a composite of postoperative complications (e.g., pneumonia, urinary tract infection, delirium, acute pulmonary thromboembolism, and unplanned intensive care unit admission). The secondary outcomes were 6-month mortality and mortality at the end of follow-up.
RESULTS The median observation time was 620.5 days (interquartile range: 367.0-784.8 days). Among the 242 patients (mean age: 81.5 ± 6.7 years, 73.1% women), 106 (43.8%) experienced postoperative complications. The 6-month mortality and mortality at the end of follow-up were 7.4% (n = 18) and 20.7% (n = 50), respectively. The Hip-MFS (odds ratio [OR], 1.250; 95% confidence interval [CI], 1.092-1.432) and HGS (OR, 1.147; 95% CI, 1.082-1.215) could predict postoperative complications. The Hip-MFS could predict both 6-month mortality (hazard ratio [HR], 1.403; 95% CI, 1.027-1.917) and mortality at the end of follow-up (HR, 1.493; 95% CI, 1.249-1.769) after adjustment, while HGS was only associated with mortality at the end of follow-up (HR, 1.080; 95% CI, 1.024-1.139). For mortality at the end of follow-up, predictive models with the Hip-MFS were superior to those with HGS in the time-dependent receiver-operating curve analysis after adjustment (p = 0.017). Furthermore, the addition of Hip-MFS or HGS to the American Society of Anesthesiologists (ASA) classification improved its prognostic ability.
CONCLUSIONS Both the Hip-MFS and HGS could predict postoperative complications and improve prognostic utility when combined with the ASA classification. The Hip-MFS was a stronger predictor of mortality than HGS after HF surgery. HGS could be a useful pre-screening tool to identify patients at a high risk of postoperative complications and those who may benefit from further CGA.
PubMed IF 4.5 노인병내과
1232021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Causal effects of relative fat, protein, and carbohydrate intake on chronic kidney disease: a Mendelian randomization study.
Am J Clin Nutr. 2021;113(4):1023-1031.

Abstract
BACKGROUND The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes.
OBJECTIVES We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis.
METHODS The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition-that is, the number of calories from each macronutrient divided by total calorie intake-of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR.
RESULTS The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: -0.036; 95% CI: -0.048, -0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)].
CONCLUSIONS A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population.
PubMed IF 6.9 신장내과
1222021

제1저자 공성혜 · 교신저자 신찬수

, , ,
Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume.
Endocrinol Metab (Seoul). 2021;36(2):351-358.

Abstract
BACKGROUND We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.
METHODS The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.
RESULTS Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.
CONCLUSION Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.
PubMed IF 5.1 내분비대사내과
1212021

제1저자 이은영 · 교신저자 윤성수

, , , ,
Recent Clinical Update of Acute Myeloid Leukemia: Focus on Epigenetic Therapies.
J Korean Med Sci. 2021;36(13):e85.

Abstract
Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that are essential for normal cell biology, including DNA methylation and histone acetylation, have been identified. As epigenetic dysregulation is an important carcinogenic mechanism and some epigenetic changes are reversible, these epigenetic alterations have become targets for novel drug development against AML. This review summarizes the recent advances in epigenetic therapies for AML and discusses future research directions.
PubMed IF 3.2 혈액종양내과
1202021

제1저자 박지석, 정진형 · 교신저자 최의근

, , , , , , , , , ,
Longitudinal Patterns in Antithrombotic Therapy in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention in the Non-Vitamin K Oral Anticoagulant Era: A Nationwide Population-Based Study.
J Clin Med. 2021;10(7):jcm10071505.

Abstract
We investigated whether longitudinal patterns in antithrombotic therapy have changed after the introduction of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI). Using a claims database of the Korean AF population who underwent PCI between 2012 and 2016 (n = 18,691), we analyzed prescription records of oral anticoagulants (OACs) and antiplatelets at 3-month intervals over 2 years after PCI. The study population was stratified (pre-NOAC, transition, and NOAC era) using time-periods of NOAC introduction in Korea and an expansion of reimbursement for NOAC in AF as indicators. The overall rates of OAC were low at baseline (24.9%, 26.9%, and 35.2% in pre-NOAC, transition, and NOAC era, respectively), contrary to high rates of dual antiplatelet therapy (DAPT) (73.3%, 71.4%, and 63.6%). However, OAC prescription rates were increased at 1-year (18.5%, 22.5%, and 31.6%), and 2-year follow-up (17.8%, 24.2%, and 31.8%) from pre-NOAC to NOAC era. In NOAC era, 63.5% of baseline OAC prescriptions comprised NOAC, of which 96.4% included triple therapy with DAPT. Over 2 years, we observed increasing rates of double therapy with a single antiplatelet (18.3% and 20.0% at 1- and 2-year follow-up) and OAC monotherapy (2.7% and 8.9% at 1- and 2-year follow-up).
PubMed IF 3.3 순환기내과
1192021

제1저자 장영, 유정주 · 교신저자 신동욱, 유수종

, , , , , , , , ,
Weight fluctuation and risk of hepatocellular carcinoma: a nationwide population-based 8-million-subject study.
Hepatol Int. 2021;15(2):482-492.

Abstract
BACKGROUND/AIM The importance of hepatocellular carcinoma (HCC) caused by obesity has been emphasized. Many studies have shown that weight fluctuations as well as high BMI are associated with various adverse outcomes. In this study, we investigated the relationship between weight fluctuation and HCC in general populations drawn from a nationwide population-based cohort.
METHOD A population-based cohort study including 8,001,829 subjects participating in more than three health examinations within 5 years from the index year were followed until the end of 2017. The degree of weight fluctuation and incidence of HCC during the period were evaluated.
RESULTS When we classified groups according to baseline body mass index (BMI) level, the highest risk for HCC was observed in subjects with BMI of 30 or greater (adjusted hazard ratio [aHR] 1.40, 95% confidence interval [CI] 1.27-1.54). Also, increasing trends for the relationship between weight fluctuation and HCC were observed in multivariable Cox proportional analyses. The risk of HCC increased by 16% (aHR 1.16, 95% CI 1.12-1.20) for the highest quartile of weight fluctuation relative to the lowest quartile. These findings were consistent regardless of the baseline BMI or other metabolic factors. However, these effects of weight fluctuation on HCC were not observed in liver cirrhosis or viral hepatitis subgroups.
CONCLUSION Weight fluctuation is an independent predictor of HCC. In the absence of liver cirrhosis or chronic hepatitis, the impact of weight fluctuation on HCC is further emphasized. These results suggest maintaining steady weight is recommended to reduce the risk of HCC.
PubMed IF 7.8 소화기내과

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