SCI 발표논문

2021년 358편

282021

제1저자 송지은 · 교신저자 이은영

, , , , , ,
Role of Synovial Exosomes in Osteoclast Differentiation in Inflammatory Arthritis.
Cells. 2021;10(1):cells10010120.

Abstract
This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA (p = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA (p = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific "synovial signature of osteoclastogenesis."
PubMed IF 6 류마티스내과
272021

제1저자 김예림 · 교신저자 김세중, 한승석

, , , , , , , , , ,
Target value of mean arterial pressure in patients undergoing continuous renal replacement therapy due to acute kidney injury.
BMC Nephrol. 2021;22(1):20.

Abstract
BACKGROUND Although patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI) frequently have instability in mean arterial pressure (MAP), no consensus exists on the target value of MAP related to high mortality after CRRT.
METHODS A total of 2,292 patients who underwent CRRT due to AKI in three referral hospitals were retrospectively reviewed. The MAPs were divided into tertiles, and the 3^rd tertile group served as a reference in the analyses. The major outcome was all-cause mortality during the intensive care unit period. The odds ratio (OR) of mortality was calculated using logistic regression after adjustment for multiple covariates. The nonlinear relationship regression model was applied to determine the threshold value of MAP related to increasing mortality.
RESULTS The mean value of MAP was 80.7 ± 17.3 mmHg at the time of CRRT initiation. The median intensive care unit stay was 5 days (interquartile range, 2-12 days), and during this time, 1,227 (55.5%) patients died. The 1^st tertile group of MAP showed an elevated risk of mortality compared with the 3^rd tertile group (adjusted OR, 1.28 [1.03-1.60]; P = 0.029). In the nonlinear regression analysis, the threshold value of MAP was calculated as 82.7 mmHg. Patients with MAP < 82.7 mmHg had a higher mortality rate than those with ≥ 82.7 mmHg (adjusted OR, 1.21 [1.01-1.45]; P = 0.037).
CONCLUSIONS Low MAP at CRRT initiation is associated with a high risk of mortality, particularly when it is < 82.7 mmHg. This value may be used for risk classification and as a potential therapeutic target.
PubMed IF 2.9 신장내과
262021

제1저자 권순일, 이소령 · 교신저자 최의근

, , , , , , , ,
Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Prior Gastrointestinal Bleeding.
Stroke. 2021;52(2):511-520.

Abstract
BACKGROUND AND PURPOSE Limited data support the benefits of non-vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB.
METHODS Oral anticoagulant-naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes.
RESULTS A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA₂DS₂-VASc score, 3.7). Lower risks of ischemic stroke, major bleeding, and the composite outcome were associated with NOAC use than with warfarin use (weighted hazard ratio, 0.608 [95% CI, 0.543-0.680]; hazard ratio, 0.731 [95% CI, 0.642-0.832]; and hazard ratio, 0.661 [95% CI, 0.606-0.721], respectively). For all secondary outcomes, NOACs showed greater risk reductions compared with warfarin.
CONCLUSIONS NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.
PubMed IF 11.1 순환기내과
252021

제1저자 황인주 · 교신저자 김효수, 이은주

, , , ,
Retinol from hepatic stellate cells via STRA6 induces lipogenesis on hepatocytes during fibrosis.
Cell Biosci. 2021;11(1):3.

Abstract
BACKGROUND Hepatic stellate cells (HSCs) are activated in response to liver injury with TIF1γ-suppression, leading to liver fibrosis. Here, we examined the mechanism how reduction of TIF1γ in HSCs induces damage on hepatocytes and liver fibrosis.
METHOD Lrat:Cas9-ERT2:sgTif1γ mice were treated Tamoxifen (TMX) or wild-type mice were treated Thioacetamide (TAA). HSCs were isolated from mice liver and analyzed role of Tif1γ. HepG2 were treated retinol with/without siRNA for Stimulated by retinoic acid 6 (STRA6) or Retinoic acid receptor(RAR)-antagonist, and LX2 were treated siTIF1γ and/or siSTRA6. TAA treated mice were used for evaluation of siSTRA6 effect in liver fibrosis.
RESULTS When we blocked the Tif1γ in HSCs using Lrat:Cas9-ERT2:sgTif1γ mice, retinol is distributed into hepatocytes. Retinol influx was confirmed using HepG2, and the increased intracellular retinol led to the upregulation of lipogenesis-related-genes and triglyceride. This effect was inhibited by a RAR-antagonist or knock-down of STRA6. In the LX2, TIF1γ-suppression resulted in upregulation of STRA6 and retinol release, which was inhibited by STRA6 knock-down. The role of STRA6-mediated retinol transfer from HSCs to hepatocytes in liver fibrosis was demonstrated by in vivo experiments where blocking of STRA6 reduced fibrosis.
CONCLUSIONS Retinol from HSCs via STRA6 in response to injury with TIF1γ-reduction is taken up by hepatocytes via STRA6, leading to fat-deposition and damage, and liver fibrosis.
PubMed IF 6.5 순환기내과
242021

제1저자 박혜인조 · 교신저자 오윤규

, , , , , , , , , , , , , , , , , ,
Genetic identification of inherited cystic kidney diseases for implementing precision medicine: a study protocol for a 3-year prospective multicenter cohort study.
BMC Nephrol. 2021;22(1):2.

Abstract
BACKGROUND Inherited cystic kidney disease is a spectrum of disorders in which clusters of renal cysts develop as the result of genetic mutation. The exact methods and pipelines for defining genetic mutations of inherited cystic kidney disease are not clear at this point. This 3-year, prospective, multicenter, cohort study was designed to set up a cohort of Korean patients with inherited cystic kidney disease, establish a customized genetic analysis pipeline for each disease subtype, and identify modifying genes associated with the severity of the disease phenotype.
METHODS/DESIGN From May 2020 to May 2022, we aim to recruit 800 patients and their family members to identify pathogenic mutations. Patients with more than 3 renal cysts in both kidneys are eligible to be enrolled. Cases of simple renal cysts and acquired cystic kidney disease that involve cyst formation as the result of renal failure will be excluded from this study. Demographic, laboratory, and imaging data as well as family pedigree will be collected at baseline. Renal function and changes in total kidney volume will be monitored during the follow-up period. Genetic identification of each case of inherited cystic kidney disease will be performed using a targeted gene panel of cystogenesis-related genes, whole exome sequencing (WES) and/or family segregation studies. Genotype-phenotype correlation analysis will be performed to elucidate the genetic effect on the severity of the disease phenotype.
DISCUSSION This is the first nationwide cohort study on patients with inherited cystic kidney disease in Korea. We will build a multicenter cohort to describe the clinical characteristics of Korean patients with inherited cystic kidney disease, elucidate the genotype of each disease, and demonstrate the genetic effects on the severity of the disease phenotype.
TRIAL REGISTRATION This cohort study was retrospectively registered at the Clinical Research Information Service ( KCT0005580 ) operated by the Korean Center for Disease Control and Prevention on November 5th, 2020.
PubMed IF 2.9 신장내과
232021

제1저자 김치훈, 이태민 · 교신저자 박경우

, , , , , , , , ,
Association Between Low Muscle Mass and Prognosis of Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.
J Am Heart Assoc. 2021;10(1):e018554.

Abstract
Background Low muscle mass has been associated with poor prognosis in certain chronic diseases, but its clinical significance in patients with coronary artery disease is unclear. We assessed the clinical significance of 2 easily measured surrogate markers of low muscle mass: the ratio of serum creatinine to serum cystatin C (Scr/Scys), and the ratio of estimated glomerular filtration rate by Scys to Scr (eGFRcys/eGFRcr). Methods and Results Patients with coronary artery disease undergoing percutaneous coronary intervention were prospectively enrolled from a single tertiary center, and Scr and Scys levels were simultaneously measured at admission. Best cut-off values for Scr/Scys and eGFRcys/eGFRcr to discriminate 3-year mortality were determined; 1.0 for men and 0.8 for women in Scr/Scys, and 1.1 for men and 1.0 for women in eGFRcys/eGFRcr. The prognostic values on 3-year mortality and the additive values of 2 markers on the predictive model were compared. In 1928 patients enrolled (mean age 65.2±9.9 years, 70.8% men), the risk of 3-year mortality increased proportionally according to the decrease of the surrogate markers. Both Scr/Scys- and eGFRcys/eGFRcr-based low muscle mass groups showed significantly higher risk of death, after adjusting for possible confounders. They also increased predictive power of the mortality prediction model. Low Scr/Scys values were associated with high mortality rate in patients who were ≥65 years, nonobese, male, had renal dysfunction at baseline, and presented with acute myocardial infarction. Conclusions Serum surrogate markers of muscle mass, Scr/Scys, and eGFRcys/eGFRcr may have clinical significance for detecting patients with coronary artery disease at high risk for long-term mortality.
PubMed IF 6 순환기내과
222021

제1저자 한석문, 문인기 · 교신저자 최의근

, , , , , , , , , , , ,
Increased atrial fibrillation risk in Parkinson's disease: A nationwide population-based study.
Ann Clin Transl Neurol. 2021;8(1):238-246.

Abstract
OBJECTIVE Parkinson's disease (PD) is the second most common neurodegenerative disorder associated with various morbidities. Although the relationship between cardiovascular disease and PD has been studied, a paucity of information on PD and atrial fibrillation (AF) association exists. Thus, we aimed to investigate whether patients with PD have an increased risk of AF.
METHODS This study included 57,585 patients with newly diagnosed PD (≥40-year-old, mean age 69.7 years, men 40.2%) and without a history of AF from the Korean National Health Insurance Service (NHIS) database between 2010 and 2015. Furthermore, an equal number of age- and sex-matched subjects without PD were selected for comparison. The primary outcome was new-onset AF.
RESULTS During the mean follow-up period of 3.4 ± 1.8 years, AF was newly diagnosed in 3,665 patients. A significantly higher incidence rate of AF was noted among patients with PD than among patients without PD (10.75 and 7.86 per 1000 person-year, respectively). Multivariate Cox-regression analysis revealed that PD was an independent risk factor for AF (hazard ratio [HR]: 1.27, 95% confidence interval [CI]: 1.18-1.36). Furthermore, subgroup analyses revealed that AF risk was higher in the younger age subgroups, and compared with the non-PD group, the youngest PD group (age: 40-49 years) had a threefold increased risk of AF (HR: 3.06, 95% CI: 1.20-7.77).
INTERPRETATION Patients with PD, especially the younger age subgroups, have an increased risk of AF. Active surveillance and management of AF should be considered to prevent further complications.
PubMed IF 3.9 순환기내과
212021

제1저자 최영훈, 이윤석, 이상협 · 교신저자 백우현

, , , , , ,
Role of EUS at high risk for choledocholithiasis without severe cholangitis and visible stone on cross-sectional imaging: A multicenter randomized clinical trial.
Endosc Ultrasound. 2021;10(6):455-462.

Abstract
BACKGROUND AND OBJECTIVES The prevalence of choledocholithiasis in the high-risk group of choledocholithiasis has been reported to be slightly more than 50% when there is no definite cholangitis. Replacement of diagnostic endoscopic retrograde cholangiography (ERC) with an EUS-first approach may be beneficial in these patients.
MATERIALS AND METHODS In this prospective, multicenter study, patients with dilated common bile duct and serum total bilirubin levels of 1.8-4 mg/dL were randomly allocated to undergo either EUS first, followed by subsequent ERC if necessary (EUS group) or ERC only (ERC group). The primary endpoint was the incidence of negative outcomes associated with a false-negative diagnosis of the choledocholithiasis or the endoscopic procedure. The secondary endpoints were the rate of diagnostic ERC and hospital stay length related to the endoscopic procedure.
RESULTS Of 90 patients who were randomly assigned, the final analysis involved 42 in the EUS group and 44 in the ERC group. The negative outcomes were not significantly different between the EUS and ERC groups (2.4% vs. 6.8%; P = 0.62). The rate of diagnostic ERC was significantly lower in the EUS group (2.4% vs. 47.7%; P < 0.001). The hospital stay length related to the endoscopic procedure was significantly shorter in the EUS group (1.8 ± 1.0 vs. 2.5 ± 1.2 days; P = 0.001).
CONCLUSION In selected high-risk choledocholithiasis patients, an EUS-first strategy significantly decreased the rate of diagnostic ERC and hospital stay but did not achieve a significant reduction in negative endoscopic procedure outcomes.
PubMed IF 4.7 소화기내과
202021

제1저자 조재철 · 교신저자 윤성수, 이원식

, , , , , , , , , , ,
Busulfan, etoposide, cytarabine, and melphalan as a high-dose regimen for autologous stem cell transplantation in peripheral T-cell lymphomas.
Ann Hematol. 2021;100(1):189-196.

Abstract
Given the unsatisfactory survival in patients who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for peripheral T-cell lymphomas (PTCLs), we conducted a prospective trial of busulfan (Bu), etoposide (E), cytarabine (A), and melphalan (M) (BuEAM), including IV Bu instead of carmustine (BCNU) as in standard BEAM, as a high-dose regimen in such patients. This study evaluated the efficacy and toxicity of BuEAM as a high-dose regimen for ASCT in patients with T-cell lymphomas. The high-dose chemotherapy at seven centers in Korea included Bu (3.2 mg/kg IV qd from day 6 to day 5), E (200 mg/m² IV bid on day 4 and day 3), A (1 g/m² IV qd on day 4 and day 3), and M (140 mg/m² IV qd on day 2). Eighty-one patients were enrolled in this study. The main subtypes were peripheral T-cell lymphoma, not other specified (n = 32, 39.5%), NK/T-cell lymphoma (n = 22, 27.5%), and angioimmunoblastic T-cell lymphoma (n = 12, 14.8%). Upfront and salvage ASCTs were performed in 65 (80.2%) and 16 (19.8%) patients, respectively. The disease status of the patients before ASCT was 54 patients (66.7%) with complete response and 27 patients (33.3%) with partial response. The common grade-III toxicities were anorexia (8.6%), diarrhea (7.4%), and stomatitis (4.9%). No veno-occlusive disorder was noted. Fifty-six (69.1%) and seven (8.6%) patients achieved complete and partial response, respectively, after ASCT, although 17 patients (21.0%) showed progressive disease. At a median follow-up duration of 49.3 months, the estimated 3-year progression-free survival and overall survival were 55.2% and 68.2% in all patients. The BuEAM high-dose regimen for ASCT was well tolerated and seemed to be effective in patients with T-cell lymphomas.
PubMed IF 2.3 혈액종양내과
192021

제1저자 임수 · 교신저자 임수

, , ,
COVID-19 and diabetes mellitus: from pathophysiology to clinical management.
Nat Rev Endocrinol. 2021;17(1):11-30.

Abstract
Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium-glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.
PubMed IF 39.1 내분비대사내과
182021

제1저자 백선하 · 교신저자 김세중

, , , , , ,
Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial.
JAMA Intern Med. 2021;181(1):81-92.

Abstract
IMPORTANCE Few high-quality studies have clarified whether hypertonic saline is best administered as slow continuous infusion (SCI) therapy or rapid intermittent bolus (RIB) therapy for symptomatic severe hyponatremia.
OBJECTIVE To compare the risk of overcorrection in RIB and SCI with hypertonic saline in patients with symptomatic hyponatremia.
DESIGN, SETTING, AND PARTICIPANTS This prospective, investigator-initiated, multicenter, open-label, randomized clinical trial enrolled 178 patients older than 18 years with moderately severe to severe hyponatremia and glucose-corrected serum sodium (sNa) levels of 125 mmol/L or less. Recruitment took place from August 24, 2016, until August 21, 2019, across emergency departments and wards of 3 general hospitals in the Republic of Korea.
INTERVENTIONS Either RIB or SCI of hypertonic saline, 3%, for 24 to 48 hours stratified by the severity of clinical symptoms.
MAIN OUTCOME AND MEASURES The primary outcome was overcorrection at any given period, defined as increase in the sNa level by greater than 12 or 18 mmol/L within 24 or 48 hours, respectively. Secondary and post hoc outcomes included efficacy and safety of the treatment approaches. The sNa concentrations were measured every 6 hours for 2 days.
RESULTS The 178 patients (mean [SD] age, 73.1 [12.2] years; 80 (44.9%) male; mean [SD] sNa concentrations, 118.2 [5.0] mmol/L) were randomly assigned to the RIB group (n = 87) or the SCI group (n = 91). Overcorrection occurred in 15 of 87 (17.2%) and 22 of 91 (24.2%) patients in the RIB and SCI groups, respectively (absolute risk difference, -6.9% [95% CI, -18.8% to 4.9%]; P = .26). The RIB group showed lower incidence of relowering treatment than the SCI group (36 of 87 [41.4%] vs 52 of 91 [57.1%] patients, respectively; absolute risk difference, -15.8% [95% CI, -30.3% to -1.3%]; P = .04; number needed to treat, 6.3). Groups did not differ in terms of efficacy in increasing sNa concentrations nor improving symptoms, but RIB, when compared with SCI, showed better efficacy in achieving target correction rate within 1 hour (intention-to-treat analysis: 28 of 87 (32.2%) vs 16 of 91 (17.6%) patients, respectively; absolute risk difference, 14.6% [95% CI, 2%-27.2%]; P = .02; number needed to treat, 6.8; per-protocol analysis: 21 of 72 (29.2%) vs 12 of 73 (16.4%) patients, respectively; absolute risk difference, 12.7% [95% CI, -0.8% to 26.2%]; P = .07). The statistical significance of the intention-to-treat and per-protocol analyses were similar for all outcomes except for achieving the target correction rate within 1 hour.
CONCLUSIONS AND RELEVANCE This randomized clinical trial found that both RIB and SIC therapies of hypertonic saline for treating hyponatremia were effective and safe, with no difference in the overcorrection risk. However, RIB had a lower incidence of therapeutic relowering treatment and tended to have a better efficacy in achieving sNa within 1 hour than SCI. RIB could be suggested as the preferred treatment of symptomatic hyponatremia, which is consistent with the current consensus guidelines.
TRIAL REGISTRATION ClinicalTrials.org Identifier: NCT02887469.
PubMed IF 26.3 신장내과
172021

제1저자 양효준 · 교신저자 김상균, 장재영

, , , , , , , , , , , , , , , , , ,
Risk factors of lymph node metastasis after non-curative endoscopic resection of undifferentiated-type early gastric cancer.
Gastric Cancer. 2021;24(1):168-178.

Abstract
BACKGROUND This study aimed to investigate risk factors for lymph node (LN) or distant metastasis after non-curative endoscopic resection (ER) of undifferentiated-type early gastric cancer (EGC).
METHODS Of 1124 patients who underwent ER for undifferentiated-type gastric cancer at 18 tertiary hospitals across six geographic areas in Korea between 2005 and 2014, 634 with non-curative ER beyond the expanded criteria were retrospectively enrolled. According to the treatment after ER, patients were divided into additional surgery (n = 270) and follow-up (n = 364) groups. The median follow-up duration was 59 months for recurrence and 84 months for mortality.
RESULTS LN metastasis was found in 6.7% (18/270) of patients at surgery. Ulcer [odds ratio (OR) 3.83; 95% confidence interval (CI) 1.21-12.13; p = 0.022] and submucosal invasion (OR 10.35; 95% CI 1.35-79.48; p = 0.025) were independent risk factors. In the follow-up group, seven patients (1.9%) developed LN or distant recurrence. Ulcer [hazard ratio (HR) 7.60; 95% CI 1.39-35.74; p = 0.018], LVI (HR 6.80; 95% CI 1.07-42.99; p = 0.042), and positive vertical margin (HR 6.71; 95% CI 1.28-35.19; p = 0.024) were independent risk factors. In the overall cohort, LN metastasis rates were 9.6% in patients with two or more risk factors and 1.2% in those with no or one risk factor.
CONCLUSIONS LVI, ulcer, submucosal invasion, and positive vertical margin are independently associated with LN or distant metastasis after non-curative ER of undifferentiated-type EGC. Surgical resection is strongly recommended for patients with two or more risk factors.
PubMed IF 6.1 소화기내과
162021

제1저자 고성준 · 교신저자 이진우

, , , , , , , ,
Phase Angle and Frailty Are Important Prognostic Factors in Critically Ill Medical Patients: A Prospective Cohort Study.
J Nutr Health Aging. 2021;25(2):218-223.

Abstract
OBJECTIVES To investigate whether phase angle (PhA) measured by bioelectrical impedance analysis (BIA) and frailty are associated with the outcomes of critical illnesses.
DESIGN A single-center prospective cohort study.
SETTING Medical intensive care unit (ICU) in Seoul National University Hospital, Seoul, Republic of Korea.
PARTICIPANTS 97 patients who were admitted to the medical ICU.
MEASUREMENTS On admission, PhA was measured by BIA, and frailty was assessed by the Korean Modified Barthel Index (KMBI) scoring system. Patients were classified according to PhA and KMBI scores, and their impact on the outcomes of critical illnesses was evaluated.
RESULTS The patients' mean age was 62.4 ± 16.4 years, and 56 of the patients (57.7%) were men. Having a high PhA above 3.5 at the time of ICU admission was associated with lower in-hospital mortality (adjusted OR 0.42, p = .042), and a shorter duration of ICU stay (5.6 days vs. 9.8 days, p = .016) compared to those with a low PhA. Other indices measured by BIA were not significantly associated with outcomes of critical illnesses. Frailty (KMBI > 60) was associated with more mechanical ventilation days (2.3 days vs. 7.1 days; p = .018).
CONCLUSION Both PhA and frailty are important prognostic factors predicting the outcomes of critical illnesses. Low PhA scores were associated with increased mortality and a longer duration of ICU stay, and frailty was associated with more mechanical ventilation days.
PubMed IF 5 호흡기내과
152021

제1저자 이경희 · 교신저자 유철규

, , , ,
Cigarette smoke extract decreased basal and lipopolysaccharide-induced expression of MARCO via degradation of p300.
Respirology. 2021;26(1):102-111.

Abstract
BACKGROUND AND OBJECTIVE Alveolar macrophages of patients with COPD display impaired cytokine release and diminished phagocytosis. COPD exacerbations exhibit immune dysfunction towards the respiratory pathogens. CS and CSE were reported to aggravate bacterial infections in COPD patients.
METHODS MARCO is highly expressed in lungs and is involved in pathogen clearance. We investigated the effect of CSE on MARCO expression and its regulatory mechanisms. After relevant siRNA transfection and treatment with CSE and/or LPS, we measured the levels of MARCO by q-RT PCR, immunoblotting and flow cytometry. Immunofluorescence staining and immunoprecipitation were used to evaluate the mechanism.
RESULTS CSE decreased LPS-induced expression of MARCO mRNA and protein. Upregulation of MARCO by LPS was Nrf2-dependent. Nrf2 knockdown significantly suppressed LPS-induced increase in MARCO transcripts. CSE did not block nuclear translocation of Nrf2 in LPS-treated cells, but rather CSE itself strongly accumulated Nrf2 in the nucleus through the degradation of its cytoplasmic inhibitor, KEAP1. However, CSE markedly suppressed LPS-induced Nrf2 acetylation. Histone acetyltransferase p300/CBP directly acetylates Nrf2, which augments promoter-specific DNA binding of Nrf2. Our results reveal CSE-induced polyubiquitinylation and subsequent degradation of p300 via the proteasome. Pretreatment with proteasome inhibitors completely blocked CSE-induced degradation of p300 and suppression of MARCO expression.
CONCLUSION These findings suggest that CSE decreases MARCO expression via the proteasomal degradation of p300 in macrophages, which may be in part responsible for impaired bacterial phagocytosis.
PubMed IF 7.2 호흡기내과
142021

제1저자 최평균, 강창경 · 교신저자 박완범, 오명돈

, , , , , , , , , , ,
Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection.
Emerg Infect Dis. 2021;27(1):327-9.

Abstract
We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.
PubMed IF 7.9 감염내과
132021

제1저자 김정한, 김인호 · 교신저자 박완범, 김택수

, , , , , , , , , , , , , , , , , ,
Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.
Clin Microbiol Infect. 2021;27(1):69-75.

Abstract
OBJECTIVES Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia.
METHODS This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture.
RESULTS The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr).
DISCUSSION ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.
PubMed IF 8.7 감염내과
122021

제1저자 오미진 · 교신저자 변자민

, , , , , ,
A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Intermediated-risk Acute Myeloid Leukemia Patients.
In Vivo. 2021;35(1):617-622.

Abstract
BACKGROUND/AIM For intermediate risk acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation (alloSCT) and chemotherapy are equally recommended as consolidation after first complete remission (CR1). In real-world, alloSCT might not be readily available, but there is paucity of data on the optimal timing of alloSCT for these patients.
PATIENTS AND METHODS In this pilot study, we compared the outcomes of 13 patients undergoing alloSCT in CR1 with 13 patients undergoing alloSCT after relapse (non-CR1) to examine whether upfront alloSCT yields a better prognosis.
RESULTS There were no differences between the two groups with regards to relapse-free survival (p=0.507) and overall survival (p=0.798). There were more chronic graft-versus-host-disease (GVHD) in the CR1 group compared to the non-CR group (p=0.001), but no difference in acute GVHD.
CONCLUSION The outcome of alloSCT after relapse is not inferior to that of alloSCT in CR1, supporting the role of alloSCT after relapse in the setting of limited donors and resources.
PubMed IF 1.8 혈액종양내과
112021

제1저자 정은희 · 교신저자 변자민

, , , , , ,
Identification of an Optimal Population for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Mature T and NK Cell Neoplasms.
In Vivo. 2021;35(4):2379-2390.

Abstract
BACKGROUND/AIM The prognosis of mature T and natural killer (NK) cell neoplasms still remains dismal, despite the advancements in the understanding of the heterogeneous features of these diseases. As allogeneic stem cell transplantation (alloSCT) is an attractive salvage option for relapsed/refractory patients, we conducted this study to identify those who might benefit the most from alloSCT.
PATIENTS AND METHODS This was a retrospective, single-center, longitudinal cohort study of patients who received alloSCT between December 2019 and January 2000.
RESULTS The median relapse-free survival and overall survival were 4.4 and 10.0 months, respectively. Disease control status at alloSCT and number of previous treatments were associated with survival outcomes. The conditioning intensity did not significantly alter survival.
CONCLUSION AlloSCT offers a cure chance for selected relapsed or refractory T and NK cell neoplasms, especially when used early and the disease is well controlled prior to transplantation.
PubMed IF 1.8 혈액종양내과
102021

제1저자 임주현 · 교신저자 김영선

, , , , , , ,
Dietary pattern and its association with right-colonic diverticulosis.
J Gastroenterol Hepatol. 2021;36(1):144-150.

Abstract
BACKGROUND AND AIM In East Asia, colonic diverticulosis develops most commonly in the right colon and is known to have different characteristics compared with left-sided one. This study was designed to investigate whether right-colonic diverticulosis is associated with posteriori dietary patterns.
METHODS We retrospectively reviewed medical records of prospectively collected cohort that received health check-up in Korea between May 2011 and January 2012. Their anthropometric data, biochemical results, medication history, underlying diseases, colonoscopic findings, and dietary data obtained from semi-quantitative food-frequency questionnaire were analyzed. Three dietary patterns were identified using factor analysis: healthy dietary pattern (vegetables, fish, seaweed, fruits, and beans), meat dietary pattern (red meat, processed meat/fish, fried noodle, poultry, and cephalopods), and snack dietary pattern (bread, sweets, dairy products, nuts, and rice cake).
RESULTS Out of the total 1911 patients, 203 (10.6%) had right-colonic diverticulosis, 21 (1.1%) had pan-colonic diverticulosis, and 12 (0.6%) had left-colonic diverticulosis. Among the total, none of the three patterns were associated with right-colonic diverticulosis, under adjustment with age, gender, body mass index, metabolic syndrome, and total energy intake. However, among women, meat dietary pattern was positively associated with right-colonic diverticulosis (odds ratio 1.866, 95% confidence interval: 1.0983-3.173, P = 0.021).
CONCLUSION This study demonstrated that meat dietary pattern is positively associated with right-colonic diverticulosis among women.
PubMed IF 3.5 소화기내과
92021

제1저자 송경호, 김동민 · 교신저자 김의석

, , , , , , , , , , , , , ,
Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19.
Korean J Intern Med. 2021;36(1):11-14.

Abstract
Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARS-CoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results. The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.
PubMed IF 2.2 감염내과
82021

제1저자 강승주 · 교신저자 신철민

, , ,
Association Between ALDH2 Polymorphism and Gastric Cancer Risk in Terms of Alcohol Consumption: A Meta-Analysis.
Alcohol Clin Exp Res. 2021;45(1):6-14.

Abstract
BACKGROUND Alcohol may increase gastric cancer risk. Alcohol can be more carcinogenic in persons who possess inactive ALDH2. The aim of this meta-analysis was to evaluate whether ALDH2 polymorphism can affect alcohol-induced gastric carcinogenesis.
METHODS We searched the PubMed, EMBASE, and Cochrane databases to identify relevant articles published between January 2000 and September 2019. Eligible articles were selected according to inclusion and exclusion criteria. The data were analyzed using Review Manager 5.3.
RESULTS A total of 7 case-control studies on ALDH2 rs671 polymorphism consisting of 3,251 gastric cancer cases and 4,943 controls were included in the analysis. Inactive ALDH2 genotypes (G/A or A/A) were associated with an increased risk of gastric cancer (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.04 to 1.52, p = 0.02, I² = 64%), compared with active ALDH2 (G/G genotype). Subgroup analysis by alcohol consumption showed that inactive ALDH2 increased risk for gastric cancer in moderate to heavy drinkers (OR = 1.85, 95% CI: 1.52 to 2.25, p < 0.01, I² = 6%) more than in nondrinkers or mild drinkers (OR = 1.19; 95% CI: 1.05 to 1.36, p < 0.01, I² = 6%). Moderate/heavy alcohol consumption increased gastric cancer risk in individuals with inactive ALDH2 (OR = 2.23, 95% CI: 1.63 to 3.05, p < 0.01, I² = 30%) more than those with active ALDH2 (OR = 1.40, 95% CI: 0.98 to 2.01, p = 0.07, I² = 85%).
CONCLUSIONS The ALDH2 polymorphism modifies the risk of gastric cancer. Moderate/heavy drinkers are more susceptible to gastric cancer than non-drinkers or light drinkers with inactive ALDH2.
PubMed IF 3.455 소화기내과
72021

제1저자 박우찬 · 교신저자 오도연

, , , , , , , ,
Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients.
Cancer Res Treat. 2021;53(1):199-206.

Abstract
PURPOSE The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC).
MATERIALS AND METHODS We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics.
RESULTS The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman's rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline.
CONCLUSION sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.
PubMed IF 4.2 혈액종양내과
62021

제1저자 최미홍 · 교신저자 이경훈

, , , , , , , , , , , ,
Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients.
Cancer Res Treat. 2021;53(1):65-76.

Abstract
PURPOSE This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
MATERIALS AND METHODS We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
RESULTS Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
CONCLUSION Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.
PubMed IF 4.2 혈액종양내과
52021

제1저자 이진호 · 교신저자 오국환

, , , , , , , ,
Klotho ameliorates diabetic nephropathy via LKB1-AMPK-PGC1α-mediated renal mitochondrial protection.
Biochem Biophys Res Commun. 2021;534:1040-1046.

Abstract
Diabetic nephropathy (DN) is associated with renal mitochondrial injury and decreased renal klotho expression. Klotho is known as an aging suppressor, and mitochondrial dysfunction is the hallmark of aging. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a master regulator of mitochondrial biogenesis, and adenosine monophosphate-activated protein kinase (AMPK) is known as a guardian of mitochondria. Here, we report that recombinant soluble klotho protein (rKL) protects against DN in db/db mice via PGC1α-AMPK-mediated mitochondrial recovery in the kidney. We injected rKL into db/db and db/m mice for 8 weeks and collected the serum and kidney tissue. We treated murine renal tubular cells with rKL in vitro, with and without exposure to 30 mM high glucose (HG). rKL treatment ameliorated major disorders from diabetes, such as obesity, hyperglycemia, and intrarenal reactive oxygen species (ROS) generation, in db/db mice. rKL also diminished albuminuria, recovered renal proximal tubular mitochondria, increased renal p-AMPK and PGC1α, and down-regulated mTOR/TGF-β in db/db mice. In S1 mouse proximal tubular cells, rKL treatment ameliorated HG-mediated cellular and mitochondrial damage and enhanced oxidative phosphorylation, with an increase in PGC1α-AMPK-induced mitochondrial recovery. Our data suggest that klotho exerts a mitochondrial protective effect in diabetic kidney disease by inducing AMPK-PGC1α expression.
PubMed IF 2.5 신장내과
42021

제1저자 장은선 · 교신저자 정숙향

, , ,
Effectiveness of 4-Week Oral Taurine Treatment for Muscle Cramps in Patients with Liver Cirrhosis: A Single-Arm Pilot Study.
Yonsei Med J. 2021;62(1):21-28.

Abstract
PURPOSE Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available. This pilot study aimed to evaluate whether taurine supplementation improves muscle cramps in Korean cirrhotic patients.
MATERIALS AND METHODS Ten cirrhotic patients who experienced muscle cramps one or more times/week were enrolled in this prospective single-arm study and administered with an oral taurine solution (1 g/50 mL) thrice a day for 4 weeks. Taurine was discontinued for the subsequent 4 weeks. The frequency and intensity of muscle cramps were evaluated using a questionnaire at weeks 0, 2, 4, 6, and 8 after the start of treatment.
RESULTS At baseline, the median frequency of muscle cramps was six times/week, and all patients had severe pain. Muscle cramp scores (frequency×intensity) decreased in seven patients by weeks 4 and 8 after treatment initiation. Compared to baseline muscle cramp scores [median 21, interquartile range (IQR): 8-84], median muscle cramp scores were lower at week 4 (6.5, IQR: 3-12, p=0.126) and week 8 (5, IQR: 1.5-56, p=0.066). All five patients whose baseline plasma taurine levels were below the normal limit showed increased taurine levels at week 4; 60% of them experienced improvements in their muscle cramps. Of the five patients with normal or higher taurine levels, 80% experienced an improvement in symptoms at week 4. The safety and tolerability of the 4-week taurine therapy were excellent.
CONCLUSION Oral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients.
PubMed IF 3.1 소화기내과
32021

제1저자 정수지 · 교신저자 박흥우

, , , ,
Incidence rates of severe cutaneous adverse reactions due to antiseizure medication: A nationwide study using health claims data in Korea.
Epilepsia. 2021;62(1):250-257.

Abstract
OBJECTIVE Antiseizure medications (ASMs) can rarely result in severe, sometimes fatal, cutaneous adverse reactions. To date, few studies have reported on the incidence rates (IRs) of severe cutaneous adverse reactions (SCARs) due to ASM use. This study aimed to determine the IRs of SCAR resulting from the use of seven commonly prescribed ASMs, carbamazepine (CBZ), phenytoin (PHT), oxcarbazepine (OXC), lamotrigine (LMT), zonisamide (ZNS), levetiracetam (LVT), and topiramate (TPM), and to compare the associated risks among the drugs.
METHODS Using a nationwide health claims database, we selected all the patients prescribed with one of the target ASMs. We defined a SCAR case as the first hospitalization with one of three specific codes provided by the International Classification of Diseases, 10th revision (L511, L512, and L27). We then calculated the IR of SCARs according to each target ASM.
RESULTS The IR of SCARs for each ASM was as follows: 870/1 000 000 person-years (PYs) for CBZ, 5750/1 000 000 PYs for PHT, 1490/1 000 000 PYs for OXC, 3860/1 000 000 PYs for LMT, 1540/1 000 000 PYs for ZNS, 830/1 000 000 PYs for LVT, and 400/1 000 000 PYs for TPM. Concomitant use of antibiotics and nonsteroidal anti-inflammatory drugs significantly increased the risk of SCARs with OXC, LVT, or TPM use. Comorbid skin disease was associated with a significantly higher IR of SCARs from CBZ, PHT, OXC, LMT, or LVT use.
SIGNIFICANCE This is the first study in Asia to determine the IRs of SCARs for various ASMs and compare the rates across drugs using a large dataset. The results from this study should help clinicians select safer ASMs in practice.
PubMed IF 5.6 알레르기내과
22021

제1저자 이소희 · 교신저자 박흥우

, , , ,
Blood Eosinophil Count as a Predictor of Lung Function Decline in Healthy Individuals.
J Allergy Clin Immunol Pract. 2021;9(1):394-399.e1.

Abstract
BACKGROUND Little is known about the effect of blood eosinophil count (BEC) on a decline in lung function in healthy individuals.
OBJECTIVE Using a well-established health screening database, we assessed the associations between BEC and a decline in lung function, measured as the forced expiratory volume in 1 second (FEV₁).
METHODS Serial BEC and FEV₁ data were analyzed using linear mixed models adjusted for gender, height, and smoking status. The association between BEC consistency and a decline in FEV₁ was evaluated in subpopulation analyses.
RESULTS A total of 4634 individuals were enrolled. The mean number of health screenings was 7.49 over an average of 11.74 years of observation. A higher log2-transformed BEC was significantly associated with a greater decline in FEV₁ that was stronger in nonsmokers (P = 8.56 × 10^-8) than in smokers (P = 1.52 × 10^-3). In subpopulation analyses of 2018 individuals with consistent BECs, those with BECs consistently ≥100/μL (P = 4.58 × 10^-6), ≥200/μL (P = 3.53 × 10^-7), and ≥300/μL (P = 1.12 × 10^-3) had a significantly higher dose-dependent FEV₁ decline than those with BECs consistently <100/μL. A BEC threshold of 100/μL in nonsmokers and 200/μL in smokers may predict an accelerated decline in FEV₁.
CONCLUSIONS BEC is associated with a decline in FEV₁, and a consistently high BEC is an independent risk factor for an accelerated decline in FEV₁. These results suggest the use of the BEC to identify healthy individuals at high risk for developing chronic lung disease, which in turn may enable a tailored preventive strategy.
PubMed IF 6.6 알레르기내과
12021

제1저자 김민관 · 교신저자 이승표

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Impact of age on coronary artery plaque progression and clinical outcome: A PARADIGM substudy.
J Cardiovasc Comput Tomogr. 2021;15(3):232-239.

Abstract
BACKGROUND The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).
METHODS From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.
RESULTS With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm³/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm³/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.
CONCLUSIONS The rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411.
PubMed IF 5.4 순환기내과

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