SCI 발표논문

전체 4,588편

40182023

제1저자 손희준, 구보경 · 교신저자 김원

, , , , , , , ,
PNPLA3 genotypes modify the adverse effect of the total energy intake on high-risk nonalcoholic steatohepatitis development.
Am J Clin Nutr. 2023;117(5):910-917.

Abstract
BACKGROUND The relationship between diet and risk genotypes in nonalcoholic steatohepatitis (NASH) development and fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear.
OBJECTIVE We aimed to investigate the effects of diet on NASH development and fibrosis progression in patients with NAFLD stratified by the PNPLA3 genotype.
METHODS We performed a prospective study in a cohort of patients with biopsy-confirmed NAFLD. Histologic deterioration was obtained using serial transient elastography at every 1 or 2 y. The primary outcome was fibrosis progression, and the secondary outcome was development of high-risk NASH, defined as FibroScan-aspartate aminotransferase score ≥0.67 during the follow-up of patients with nonalcoholic fatty liver at the baseline. Dietary intake was evaluated using a semiquantitative food frequency questionnaire.
RESULTS The primary outcome was observed in 42 (29.0%) of the 145 patients during a median follow-up of 49 mo; neither the total energy intake nor each macronutrient intake significantly affected the primary outcome occurrence. Conversely, the total energy intake (HR per 1-SD: 3.03; 95% CI: 1.31, 7.01) and the PNPLA3 rs738409 genotype [HR per 1 risk allele (G): 2.06; 95% CI: 1.11, 3.83)] were independent risk factors for high-risk NASH. The significant interaction between the total energy intake and PNPLA3 genotype was noted in developing high-risk NASH (P = 0.044). As the number of PNPLA3 risk alleles decreased, the effect of the total energy intake on high-risk NASH increased; the HR per 1-SD increment in total energy intake was 1.52 (95% CI: 0.42, 5.42), 3.54 (95% CI: 1.23, 10.18), and 8.27 (95% CI: 1.20, 57.23) for the GG, CG, and CC genotypes, respectively.
CONCLUSIONS The total energy intake adversely affected the development of high-risk NASH in patients with biopsy-confirmed NAFLD. The effect was more prominent in patients without the PNPLA3 risk allele, highlighting the importance of personalized dietary interventions in NAFLD treatment.
PubMed IF 6.9 소화기내과
40172023

제1저자 이현덕 · 교신저자 조수정

, , , , , , ,
A Randomized Controlled Trial of Fibrin Glue to Prevent Bleeding After Gastric Endoscopic Submucosal Dissection.
Am J Gastroenterol. 2023;118(5):892-899.

Abstract
INTRODUCTION This study evaluated the efficacy of fibrin glue for preventing postendoscopic submucosal dissection (ESD) bleeding in high-risk patients for bleeding (expected iatrogenic ulcer size ≥40 mm or receiving antithrombotic therapy).
METHODS A multicenter, open-label, randomized controlled trial was performed at 4 tertiary medical centers in South Korea between July 1, 2020, and June 22, 2022. Patients with gastric neoplasm and a high risk of post-ESD bleeding were enrolled and allocated at 1:1 to a control group (standard ESD) or a fibrin glue group (fibrin glue applied to iatrogenic ulcers after standard ESD). The primary outcome was overall bleeding events within 4 weeks. The secondary outcomes were acute bleeding (within 48 hours post-ESD) and delayed bleeding (48 hours to 4 weeks post-ESD).
RESULTS In total, 254 patients were randomized, and 247 patients were included in the modified intention-to-treat population (125 patients in the fibrin glue group and 122 patients in the control group). Overall bleeding events occurred in 12.0% (15/125) of the fibrin glue group and 13.1% (16/122) of the control group ( P = 0.791). Acute bleeding events were significantly less common in the fibrin glue group than in the control group (1/125 vs 7/122, P = 0.034). Delayed bleeding events occurred in 11.2% (14/125) in the fibrin glue group and 7.3% (9/122) in the control group ( P = 0.301).
DISCUSSION This trial failed to show a preventive effect of fibrin glue on overall post-ESD bleeding in high-risk patients. However, the secondary outcomes suggest a potential sealing effect of fibrin glue during the acute period.
PubMed IF 7.6 소화기내과
40162023

제1저자 곽순구 · 교신저자 박준빈

, , , , , , , , , , , , , , ,
Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance.
JACC Cardiovasc Imaging. 2023;16(5):575-587.

Abstract
BACKGROUND Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR).
OBJECTIVES The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications.
METHODS The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR.
RESULTS Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm²; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001).
CONCLUSIONS In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.
PubMed IF 19 순환기내과
40152023

제1저자 김동완 · 교신저자 김동완

, , , , , , , , , , , , , , ,
CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report.
J Thorac Oncol. 2023;18(5):650-656.

Abstract
INTRODUCTION CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.
METHODS Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations after progression on a first- or second-generation EGFR TKI and were osimertinib naive. They received osimertinib 80 mg orally once daily plus oleclumab 1500 mg (dose level 1 [DL1]) or 3000 mg (DL2) intravenously every 2 weeks. Primary end points included safety and objective response rate by Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS By July 9, 2021, five patients received DL1 and 21 received DL2. Of these patients, 60.0% and 85.7% had any-grade treatment-related adverse events (TRAEs) and 20.0% and 14.3% had grade 3 TRAEs, respectively. No dose-limiting toxicities, serious TRAEs, or deaths occurred. Four patients were T790M positive on retrospective circulating tumor DNA (ctDNA) testing; three had objective partial responses. In patients who were T790M negative in tumor and ctDNA, objective response rate was 25.0% at DL1 and 11.8% at DL2 (all partial responses); response durations at DL2 were 14.8 and 16.6 months. In patients receiving DL2, excluding those who were T790M positive by ctDNA, median progression-free survival was 7.4 months, and median overall survival was 24.8 months. DL2 was the recommended phase 2 dose.
CONCLUSIONS Oleclumab plus osimertinib was found to have moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.
PubMed IF 23.3 혈액종양내과
40142023

제1저자 이현우, 진광남, 김은영 · 교신저자 조영준

, , , , , , , , , , , ,
Artificial Intelligence Solution for Chest Radiographs in Respiratory Outpatient Clinics: Multicenter Prospective Randomized Clinical Trial.
Ann Am Thorac Soc. 2023;20(5):660-667.

Abstract
Rationale: Artificial intelligence (AI)-assisted diagnosis imparts high accuracy to chest radiography (CXR) interpretation; however, its benefit for nonradiologist physicians in detecting lung lesions on CXR remains unclear. Objectives: To investigate whether AI assistance improves the diagnostic performance of physicians for CXR interpretation and affects their clinical decisions in clinical practice. Methods: We randomly allocated eligible patients who visited an outpatient clinic to the intervention (with AI-assisted interpretation) and control (without AI-assisted interpretation) groups. Lung lesions on CXR were recorded by seven nonradiologists with or without AI assistance. The reference standard for lung lesions was established by three radiologists. The primary and secondary endpoints were the physicians' diagnostic accuracy and clinical decision, respectively. Results: Between October 2020 and May 2021, 162 and 161 patients were assigned to the intervention and control groups, respectively. The area under the receiver operating characteristic curve was significantly larger in the intervention group than in the control group for the CXR level (0.840 [95% confidence interval (CI), 0.778-0.903] vs. 0.718 [95% CI, 0.640-0.796]; P = 0.017) and lung lesion level (0.800 [95% CI, 0.740-0.861] vs. 0.677 [95% CI, 0.605-0.750]; P = 0.011). The intervention group had higher sensitivity in terms of both CXR and lung lesion level and a lower false referral rate for the lung lesion level. AI-assisted CXR interpretation did not affect the physicians' clinical decisions. Conclusions: AI-assisted CXR interpretation improves the diagnostic performance of nonradiologist physicians in detecting abnormal lung findings. Clinical trial registered with Clinical Research Information Service of the Republic of Korea (KCT 0005466).
PubMed IF 6 호흡기내과
40132023

제1저자 이우진, 정근화 · 교신저자 최수연, 박경일

, , , , , , ,
Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume.
CNS Neurosci Ther. 2023;29(5):1243-1253.

Abstract
BACKGROUND Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity.
METHODS From an institutional cohort of a routine health check-up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions.
RESULTS Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log-transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log-transformed total WMH and the lower log-transformed periventricular WMH volume, but not with the log-transformed subcortical WMH volumes.
CONCLUSIONS Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.
PubMed IF 6.6 순환기내과
40122023

제1저자 심지수, 이현승 · 교신저자 박흥우

, , , , ,
Inhibition of glutaminase 1 activity reverses airway hyperresponsiveness and decreases IL-1β+ M1s and IL-17 producing ILC3s in high-fat diet-fed obese mice.
Am J Physiol Lung Cell Mol Physiol. 2023;324(5):L625-L638.

Abstract
In obesity, disturbed glutamine metabolism contributes to enhanced inflammation by inducing alterations in immune cells. As macrophages and innate lymphoid cells (ILCs) are known to be involved in the pathogenesis of obesity-related asthma, we tested our hypothesis that altered glutamine metabolism may link obesity to airway hyperresponsivenss (AHR), a cardinal feature of asthma, focusing on these innate immune cells. Four-week-old male C57BL/6 mice were fed a high-fat diet (HFD) for 13 wk in the presence or absence of BPTES [Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, a selective inhibitor of glutaminase 1 which converts glutamine to glutamate] and their blood, lung, and adipose tissues were analyzed. We then conducted in vitro experiments using bone marrow-derived macrophages (BMDMs) and mouse alveolar macrophage cell line. Furthermore, we investigated plasma glutamine and glutamate levels in obese and nonobese asthmatics. BPTES treatment prevented HFD-induced AHR and significantly decreased IL-1β⁺ classically activated macrophages (M1s) and type 3 ILCs (ILC3s) which increased in the lungs of HFD-fed obese mice. In in vitro experiments, BPTES treatment or glutamine supplement significantly reduced the proportion of IL-1β⁺NLRP3⁺ M1s in lipopolysaccharide-stimulated BMDMs and mouse alveolar macrophage cell line. BPTES treatment also significantly reduced the IL-17 producing ILC3s differentiated from ILCs in naïve mouse lung. In addition, plasma glutamate/glutamine ratios were significantly higher in obese asthmatics compared to nonobese asthmatics. Inhibition of glutaminolysis reverses AHR in HFD-induced obese mice and decreases IL-1β⁺NLRP3⁺ M1s and IL-17 producing ILC3s, which suggests altered glutamine metabolism may have a role in the pathogenesis of obesity-related AHR.
PubMed IF 3.8 알레르기내과
40112023

제1저자 한미연, 문성지 · 교신저자 오국환, 박수경

, , , , , , , , , , , , , , , , , ,
Novel Genetic Variants Associated with Chronic Kidney Disease Progression.
J Am Soc Nephrol. 2023;34(5):857-875.

Abstract
SIGNIFICANCE STATEMENT eGFR slope has been used as a surrogate outcome for progression of CKD. However, genetic markers associated with eGFR slope among patients with CKD were unknown. We aimed to identify genetic susceptibility loci associated with eGFR slope. A two-phase genome-wide association study identified single nucleotide polymorphisms (SNPs) in TPPP and FAT1-LINC02374 , and 22 of them were used to derive polygenic risk scores that mark the decline of eGFR by disrupting binding of nearby transcription factors. This work is the first to identify the impact of TPPP and FAT1-LINC02374 on CKD progression, providing predictive markers for the decline of eGFR in patients with CKD.
BACKGROUND The incidence of CKD is associated with genetic factors. However, genetic markers associated with the progression of CKD have not been fully elucidated.
METHODS We conducted a genome-wide association study among 1738 patients with CKD, mainly from the KoreaN cohort study for Outcomes in patients With CKD. The outcome was eGFR slope. We performed a replication study for discovered single nucleotide polymorphisms (SNPs) with P <10 -6 in 2498 patients with CKD from the Chronic Renal Insufficiency Cohort study. Several expression quantitative trait loci (eQTL) studies, pathway enrichment analyses, exploration of epigenetic architecture, and predicting disruption of transcription factor (TF) binding sites explored potential biological implications of the loci. We developed and evaluated the effect of polygenic risk scores (PRS) on incident CKD outcomes.
RESULTS SNPs in two novel loci, TPPP and FAT1-LINC02374 , were replicated (rs59402340 in TPPP , Pdiscovery =7.11×10 -7 , PCRIC =8.13×10 -4 , Pmeta =7.23×10 -8 ; rs28629773 in FAT1-LINC02374 , Pdiscovery =6.08×10 -7 , PCRIC =4.33×10 -2 , Pmeta =1.87×10 -7 ). The eQTL studies revealed that the replicated SNPs regulated the expression level of nearby genes associated with kidney function. Furthermore, these SNPs were near gene enhancer regions and predicted to disrupt the binding of TFs. PRS based on the independently significant top 22 SNPs were significantly associated with CKD outcomes.
CONCLUSIONS This study demonstrates that SNP markers in the TPPP and FAT1-LINC02374 loci could be predictive markers for the decline of eGFR in patients with CKD.
PubMed IF 9.7 신장내과
40102023

제1저자 최유정 · 교신저자 김형관

, , , , , , , , , ,
Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction.
Heart. 2023;109(10):771-778.

Abstract
OBJECTIVE To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model.
METHODS This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved (≥60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death.
RESULTS During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death.
CONCLUSIONS Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM.
PubMed IF 4.4 순환기내과
40092023

제1저자 선우성혁, 한상인, 정동준 · 교신저자 이승표, 현택환, 김대형

, , , , , , , , , , , , , ,
Stretchable Low-Impedance Conductor with Ag-Au-Pt Core-Shell-Shell Nanowires and in Situ Formed Pt Nanoparticles for Wearable and Implantable Device.
ACS Nano. 2023;17(8):7550-7561.

Abstract
Mechanically soft metallic nanocomposites have gained much attention as a key material for intrinsically stretchable biointegrated devices. However, it has been challenging to develop a stretchable conductive nanocomposite with all the desired material characteristics including high conductivity, high stretchability, low cytotoxicity, and low impedance. Here, we present a material strategy for the stretchable conductive nanocomposite, particularly emphasizing low impedance, by combining silver-gold-platinum core-shell-shell nanowires and homogeneously dispersed in situ synthesized platinum nanoparticles (Pt NPs). The highly embossed structure of the outermost Pt shell, together with the intrinsic electrical property of Pt, contributes to minimizing the impedance. The gold-platinum double-layer sheath prevents leaching of cytotoxic Ag ions, thus improving biocompatibility. Homogeneously dispersed Pt NPs, synthesized in situ during fabrication of the nanocomposite, simultaneously enhance conductivity, reduce impedance, and improve stretchability by supporting the percolation network formation. This intrinsically stretchable nanocomposite conductor can be applied to wearable and implantable bioelectronics for recording biosignals and delivering electrical stimulations in vivo.
PubMed IF 17.3 순환기내과
40082023

제1저자 김낙현 · 교신저자 박완범, 김홍빈

, , , , , , , , ,
Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes of Staphylococcus aureus Bacteremia.
J Korean Med Sci. 2023;38(16):e129.

Abstract
BACKGROUND Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB.
METHODS Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction.
RESULTS Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020).
CONCLUSION The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.
PubMed IF 3.2 감염내과
40072023

제1저자 이태민 · 교신저자 김형관

, , , , , , , , , ,
Impact of coronary artery revascularization on long-term outcome in hypertrophic cardiomyopathy patients: a nationwide population-based cohort study.
Sci Rep. 2023;13(1):6412.

Abstract
Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63-3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55-3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD.
PubMed IF 4.9 순환기내과
40062023

제1저자 김선미 · 교신저자 오국환

, , , , , , , , ,
Association of Chronic Kidney Disease With Atrial Fibrillation in the General Adult Population: A Nationwide Population-Based Study.
J Am Heart Assoc. 2023;12(8):e028496.

Abstract
Background The incidences of atrial fibrillation (AF) and chronic kidney disease (CKD) are increasing, and AF is prevalent in patients with CKD. However, few studies have investigated the incidence or association of AF in a large CKD population from a longitudinal study. Methods and Results From a nationwide cohort, a total of 4 827 987 Korean individuals without prior AF, who received biennial health checkups provided by the National Health Insurance Service between 2009 and 2012 in Korea, were analyzed. Incidence of AF was ascertained through the end of 2018. During a median follow-up of 8.1 years, the annual incidence rate of AF was 1.17 per 1000 person-years among subjects without CKD, 1.55 for stage 1 CKD, 1.86 for stage 2 CKD, 2.1 for stage 3 CKD, and 4.33 for stage 4 CKD. In Fine-Gray regression models, CKD was associated with an increased risk of AF; the adjusted hazard ratios and 95% CIs of AF occurrence were 1.77 (1.69-1.85), 1.85 (1.80-1.91), 1.99 (1.95-2.04), and 4.04 (3.07-5.33) in individuals with CKD stages 1, 2, 3, and 4, respectively, compared with non-CKD. The association between CKD and incident AF remained statistically significant after adjustment for multiple confounding factors and was consistent across subgroups stratified by sex and age. Conclusions CKD is associated with an increased incidence of AF. Even mild CKD is associated with incident AF, and there was a stepwise increase in the risk of incident AF with a decrease in renal function.
PubMed IF 6 신장내과
40052023

제1저자 신은석 · 교신저자 김효수

, , , , , , , , , , ,
Association of Clinical Outcomes With Sex in Patients Receiving Chronic Maintenance Antiplatelet Monotherapy After Percutaneous Coronary Intervention: A Post Hoc Gender Analysis of the HOST-EXAM Study.
J Am Heart Assoc. 2023;12(8):e026770.

Abstract
Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P=0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P=0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P=0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P=0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.
PubMed IF 6 순환기내과
40042023

제1저자 강지훈 · 교신저자 박경우

, , , , , , , , , , , , , , , , ,
Dual antiplatelet therapy de-escalation in acute coronary syndrome: an individual patient meta-analysis.
Eur Heart J. 2023;44(15):1360-1370.

Abstract
AIMS Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS.
METHODS AND RESULTS Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints.
CONCLUSION In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy.
STUDY REGISTRATION NUMBER This study was registered in the PROSPERO (ID: CRD42021245477).
PubMed IF 45.3 순환기내과
40032023

제1저자 오도연 · 교신저자 오도연

, , , , , , , , , , , , , , , ,
Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.
Cancer. 2023;129(8):1195-1204.

Abstract
BACKGROUND The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers.
METHODS Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review.
RESULTS A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%).
CONCLUSIONS Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.
PubMed IF 5.6 혈액종양내과
40022023

제1저자 정재원, 정경연 · 교신저자 조선욱, 안화영

, , , , , , ,
Efficacy of selenium supplementation for mild-to-moderate Graves' ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial.
Trials. 2023;24(1):272.

Abstract
BACKGROUND The therapeutic effect of selenium has been demonstrated in mild Graves' ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea.
METHODS The SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19 years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6 months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6 months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3 months, clinical activity of GO at 3 and 6 months, thyroid autoantibody titers at 3 and 6 months, and the response rate at 3 and 6 months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6.
DISCUSSION The SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO.
TRIAL REGISTRATION KCT0004040. Retrospectively registered on 5 June 2019. https://cris.nih.go.kr/cris/search/detailSearch.do/14160 .
PubMed IF 2.1 내분비대사내과
40012023

제1저자 이규선, 박근호 · 교신저자 박경우

, , , , , , , , , , , , , , , , , , , , ,
Prasugrel dose de-escalation in diabetic patients with acute coronary syndrome receiving percutaneous coronary intervention: results from the HOST-REDUCE-POLYTECH-ACS trial.
Eur Heart J Cardiovasc Pharmacother. 2023;9(3):262-270.

Abstract
AIMS The aim of this study was to evaluate the efficacy and safety of prasugrel dose de-escalation therapy in patients with diabetes mellitus (DM)-acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).
METHODS AND RESULTS This was a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) randomized trial. The efficacy and safety of prasugrel dose de-escalation therapy (prasugrel 5 mg daily) were compared with conventional therapy (prasugrel 10 mg daily) in patients with DM. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and Bleeding Academic Research Consortium (BARC) class ≥2 bleeding events. The secondary ischaemic outcome was major adverse cardiovascular and cerebrovascular events, defined as the composite of cardiac death, non-fatal MI, ST, or ischaemic stroke. Of 2338 patients randomized, 990 had DM. The primary endpoint of NACE occurred in 38 patients (7.6%) receiving prasugrel dose de-escalation and in 53 patients (11.3%) receiving conventional therapy among patients with DM [hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.43-0.99; P = 0.049]. Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischaemic events (HR 1.03; 95% CI 0.56-1.88; P = 0.927) but decreased BARC class ≥2 bleeding in patients with DM (HR 0.44; 95% CI 0.23-0.84; P = 0.012).
CONCLUSION Prasugrel dose de-escalation compared with conventional therapy may reduce the risk of net clinical outcomes, mostly driven by a reduction in bleeding without an increase in ischaemic events in patients with DM. Trial Registration: HOST-REDUCE-POLYTECH-ACS, NCT02193971, https://clinicaltrials.gov/ct2/show/NCT02193971.
PubMed IF 8.2 순환기내과
40002023

제1저자 김병욱 · 교신저자 송경호, 윤성혜

, , , , , , , , , , , , ,
Evaluation of Vancomycin TDM Strategies: Prediction and Prevention of Kidney Injuries Based on Vancomycin TDM Results.
J Korean Med Sci. 2023;38(14):e101.

Abstract
The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC_0-24) of 400 to 600 mg*h/L for serious methicillin-resistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC_0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC_0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC_0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.
PubMed IF 3.2 감염내과
39992023

제1저자 공성혜, 이준협 · 교신저자 한도현, 김정희

, , , , , , , , , , , ,
In-depth proteomic signature of parathyroid carcinoma.
Eur J Endocrinol. 2023;188(4):385-394.

Abstract
OBJECTIVE Diagnosing parathyroid carcinoma (PC) is complicated and controversial that early diagnosis and intervention are often difficult. Therefore, we aimed to elucidate the protein signatures of PC through quantitative proteomic analyses to aid in the early and accurate diagnosis of PC.
DESIGN We conducted a retrospective cohort study.
METHODS We performed liquid chromatography with tandem mass spectrometry using formalin-fixed paraffin-embedded samples. For the analyses, 23 PC and 15 parathyroid adenoma (PA) tissues were collected from 6 tertiary hospitals in South Korea.
RESULTS The mean age of the patients was 52 years, and 63% were women. Proteomic expression profiling revealed 304 differentially expressed proteins (DEPs) with a cut-off of P < .05 and fold change >1.5. Among DEPs, we identified a set of 5 proteins that can discriminate PC from PA: carbonic anhydrase 4 (CA4), alpha/beta hydrolase domain-containing protein 14B (ABHD14B), laminin subunit beta-2 (LAMB2), CD44 antigen (CD44), and alpha-1-acid glycoprotein 1 (ORM1) that exhibited the highest area under the curve of 0.991 in neural network model. The nuclear percentage of CA4 and LAMB2 in immunohistochemistry was significantly lower in PC tissue than in the PA (CA4: 2.77 ± 1.96%, 26.2 ± 3.45%, P < .001; LAMB2: 6.86 ± 3.46%, 38.54 ± 4.13%, P < .001). The most enriched canonical pathways in PC included glycoprotein-6 signaling and mammalian target of rapamycin (mTOR).
CONCLUSIONS We identified key proteins differentially expressed between PC and PA using proteomic analyses of parathyroid neoplasms. These findings may help to diagnose PC accurately and elucidate potential therapeutic targets.
PubMed IF 6.7 내분비대사내과
39982023

제1저자 이찬미, 김민지 · 교신저자 박완범, 김항래, 신현무

, , , , , , , , , ,
Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19.
Front Immunol. 2023;14:1110874.

Abstract
INTRODUCTION Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.
METHODS We prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.
RESULTS A total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14⁺CD16⁺), IFN-γ⁺ CD4⁺ or CD8⁺ T cells, and HLA-DR⁺PD-1⁺ CD4⁺ T cells were higher in the high IL-6 group than in the low IL-6 group.
CONCLUSION There were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.
PubMed IF 7 감염내과
39972023

제1저자 박지혜, 천재영 · 교신저자 윤혁, 천재희

, , ,
Feasibility of a Clinical Decision Support Tool for Ustekinumab to Predict Clinical Remission and Relapse in Patients With Crohn's Disease: A Multicenter Observational Study.
Inflamm Bowel Dis. 2023;29(4):548-554.

Abstract
BACKGROUND Ustekinumab was recently approved for the treatment of moderate to severe Crohn's disease (CD). Although the ustekinumab Clinical Decision Support Tool (UST-CDST) was able to predict ustekinumab responsiveness in a clinical trial, it is not clear whether UST-CDST can also predict a future clinical relapse following ustekinumab therapy in the real-life setting.
METHODS We enrolled patients with moderate to severe CD who were refractory to conventional therapies and who showed a clinical response after induction therapy with ustekinumab and monitored them until the relapse. We performed a Cox proportional hazard analysis to investigate the predictive capability of UST-CDST for a clinical disease relapse.
RESULTS Clinical remission rates at week 20 were 25.0% for low-probability responders, 66.7% for intermediate-probability responders, and 75.0% for high-probability responders. The high-probability responders were more likely to achieve clinical remission at week 20 compared with the low-probability responders. Among 99 patients with moderate to severe CD, 37 (37.4%) experienced a clinical relapse during the median follow-up period of 18.0 months of ustekinumab treatment. The cumulative relapse rates were 70.0% in the low-probability responders, 35.9% in the intermediate-probability responders, and 22.5% in the high-probability responders (P = .001). In a multivariable Cox proportional hazard analysis, the high-probability responders and intermediate-probability responders had a lower risk of clinical relapse than the low-probability responders. Receiver operating characteristic analysis using UST-CDST to predict relapse revealed an area under the curve of 0.698.
CONCLUSIONS The UST-CDST can predict clinical relapse in patients with moderate to severe CD subjected to ustekinumab therapy.
PubMed IF 5.5 소화기내과
39962023

제1저자 김보경 · 교신저자 조수정

, , , , , , ,
Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study.
J Korean Med Sci. 2023;38(13):e99.

Abstract
BACKGROUND This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19).
METHODS We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration.
RESULTS Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74-0.98) and PPI users (OR, 0.62; 95% CI, 0.52-0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52-1.54) or PPI users (OR, 1.22; 95% CI, 0.60-2.51).
CONCLUSION H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.
PubMed IF 3.2 소화기내과
39952023

제1저자 송명진 · 교신저자 정세영, 임성윤

, , , , , ,
Association of Dexmedetomidine With New-Onset Atrial Fibrillation in Patients With Critical Illness.
JAMA Netw Open. 2023;6(4):e239955.

Abstract
IMPORTANCE Dexmedetomidine is a widely used sedative in the intensive care unit (ICU) and has unique properties that may be associated with reduced occurrence of new-onset atrial fibrillation (NOAF).
OBJECTIVE To investigate whether the use of dexmedetomidine is associated with the incidence of NOAF in patients with critical illness.
DESIGN, SETTING, AND PARTICIPANTS This propensity score-matched cohort study was conducted using the Medical Information Mart for Intensive Care-IV database, which includes records of patients admitted to the ICU at Beth Israel Deaconess Medical Center in Boston dating 2008 through 2019. Included patients were those aged 18 years or older and hospitalized in the ICU. Data were analyzed from March through May 2022.
EXPOSURE Patients were divided into 2 groups according to dexmedetomidine exposure: those who received dexmedetomidine within 48 hours after ICU admission (dexmedetomidine group) and those who never received dexmedetomidine (no dexmedetomidine group).
MAIN OUTCOMES AND MEASURES The primary outcome was the occurrence of NOAF within 7 days of ICU admission, as defined by the nurse-recorded rhythm status. Secondary outcomes were ICU length of stay, hospital length of stay, and in-hospital mortality.
RESULTS This study included 22 237 patients before matching (mean [SD] age, 65.9 [16.7] years; 12 350 male patients [55.5%]). After 1:3 propensity score matching, the cohort included 8015 patients (mean [SD] age, 61.0 [17.1] years; 5240 males [65.4%]), among whom 2106 and 5909 patients were in the dexmedetomidine and no dexmedetomidine groups, respectively. Use of dexmedetomidine was associated with a decreased risk of NOAF (371 patients [17.6%] vs 1323 patients [22.4%]; hazard ratio, 0.80; 95% CI, 0.71-0.90). Although patients in the dexmedetomidine group had longer median (IQR) length of stays in the ICU (4.0 [2.7-6.9] days vs 3.5 [2.5-5.9] days; P < .001) and hospital (10.0 [6.6-16.3] days vs 8.8 [5.9-14.0] days; P < .001), dexmedetomidine was associated with decreased risk of in-hospital mortality (132 deaths [6.3%] vs 758 deaths [12.8%]; hazard ratio, 0.43; 95% CI, 0.36-0.52).
CONCLUSIONS AND RELEVANCE This study found that dexmedetomidine was associated with decreased risk of NOAF in patients with critical illness, suggesting that it may be necessary and warranted to evaluate this association in future clinical trials.
PubMed IF 11.7 호흡기내과
39942023

제1저자 정은희, 변자민 · 교신저자 윤성수

, , , , , ,
Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study (KMM122).
Cancer Med. 2023;12(8):9186-9193.

Abstract
BACKGROUND Current guidelines recommend using filgrastim or tbo-filgrastim to mobilize hematopoietic progenitor cells in an autologous setting. However, previous studies have suggested other forms of granulocyte colony-stimulating factor (G-CSF) are equally efficacious, possibly with fewer leukaphereses required. Thus, we prospectively studied the efficacy of lenograstim, a glycosylated recombinant form of G-CSF, in multiple myeloma (MM) patients.
METHODS From November 2011 to January 2020, 98 MM patients undergoing autologous stem cell transplant (ASCT) from five academic centers in Korea were enrolled. Patients were mobilized with subcutaneous lenograstim (Neutrogin®) with fixed doses of 10 μg/kg for 4 days.
RESULTS Most of the patients ( N = 90, 91.8%) achieved at least the targets of 2 × 10⁶ CD34+ cells/kg body weight, and more than half of MM patients ( N = 57, 58.2%) reached a target of 5 × 10⁶ CD34+ cells/kg body weight. The mobilization failure rate was 8.2% ( N = 8). The median number of CD34 + cell/kg using G-CSF only was 5.25 × 10⁶ /kg (range 0.49-13.47). Adverse events included transfusion (TF, N = 53, 54.1%), bone pain ( N = 6, 6.1%), fever ( N = 2, 2.0%), and gastrointestinal troubles ( N = 2, 2.0%). There were no grade 3 or 4 adverse events during mobilization. Body surface area (BSA) at mobilization and platelet TF were factors associated with CD34+ collection. Most patients achieved neutrophil ( N = 93, 98.9%) and platelet ( N = 89, 95.7%) engraftment.
CONCLUSION Lenograstim can safely and effectively mobilize stem cells in MM autologous settings.
PubMed IF 3.5 혈액종양내과
39932023

제1저자 이승미, 조금준 · 교신저자 김원, 박중신

, , , , , , , , , , , , ,
Metabolic dysfunction-associated fatty liver disease as a risk factor for adverse outcomes in subsequent pregnancy: a nationwide cohort study.
Hepatol Int. 2023;17(2):367-376.

Abstract
BACKGROUND AND PURPOSE A recent international expert consensus opinion suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) replaces nonalcoholic fatty liver disease (NAFLD), since MAFLD is a better predictor of cardiovascular disease. We estimated the prevalence of FLD in fertile females and evaluated the clinical impact of either NAFLD or MAFLD on maternal and fetal outcomes during subsequent pregnancy.
METHODS The study population included fertile females who underwent health examinations and became pregnant within 1 year of health examination. Hepatic steatosis was defined as a fatty liver index of ≥ 30. The fertile females were divided into four groups: neither-FLD, NAFLD-only, MAFLD-only, and both-FLDs. During subsequent pregnancy, the risks of adverse pregnancy outcomes, including gestational diabetes, pregnancy-associated hypertension, preterm birth, and low birthweight, were compared among the four groups.
RESULTS The study population comprised 762,401 females, including 720,606 with neither-FLD, 318 with NAFLD-only, 14,371 with MAFLD-only, and 27,106 with both-FLDs. Compared to females with neither-FLD, the risk of adverse pregnancy outcomes was higher in females with any FLD, with an adjusted OR of 1.73 (95% CI 1.25-2.41) in the NALFD-only group, 2.65 (2.53-2.77) in the MAFLD-only group, and 2.39 (2.31-2.48) in the both-FLDs group. Pregnancy outcomes (cesarean delivery, gestational diabetes, and low birthweight) were worse in females with MAFLD compared with NAFLD.
CONCLUSION Any form of FLD is a risk factor for adverse pregnancy outcomes. These data suggest that MAFLD is associated with a higher risk of adverse pregnancy outcomes for both mother and fetus than NAFLD.
PubMed IF 7.8 소화기내과
39922023

제1저자 구보경 · 교신저자 김원

, , , , , ,
Long-Term Effect of PNPLA3 on the Aggravation of Nonalcoholic Fatty Liver Disease in a Biopsy-Proven Cohort.
Clin Gastroenterol Hepatol. 2023;21(4):1105-1107.e3.

Abstract
The PNPLA3 rs738409 G allele increases the risk of not only nonalcoholic fatty liver disease (NAFLD) but also nonalcoholic steatohepatitis (NASH) or fibrosis.¹ It also affects the prognosis of patients with NAFLD in specific conditions. After liver transplantation, patients with NAFLD carrying the rs738409 GG genotype have a higher risk of graft steatosis² or development of hepatocellular carcinoma.³ In addition, rs738409 modifies the effects of medical intervention: patients with NAFLD carrying the GG genotype showed a lower effect of omega-3 polyunsaturated fatty acid treatment on the reduction of liver fat;⁴ in contrast, they were more sensitive to the beneficial effects of lifestyle modifications.^5,6.
PubMed IF 16.2 소화기내과
39912023

제1저자 박진명, 박남영 · 교신저자 이상협, 한경도

, , , , , , , ,
A population-based cohort study on risk factors for acute pancreatitis: A comparison by age group.
Pancreatology. 2023;23(3):321-329.

Abstract
BACKGROUND /objectives: Acute pancreatitis (AP) is an acute inflammatory disorder that can occur in all age groups. The risk of AP has been shown to increase with age. However, no study has compared risk factors for AP according to age group yet. Thus, the aim of this study was to perform such comparison.
METHODS Clinical data from individuals 20 years of age and older who received a health examination arranged by the Korean national health insurance program in 2009 (n = 4,238,822) were used. First-attack AP was identified using claims data from baseline to December 2018. Incidence and risk factors of AP were analyzed for young (20-39 years old), middle-aged (40-64 years old), and old (over 65 years old) groups.
RESULTS Incidences of AP in young, middle-aged, and old groups were 16.30, 27.85, and 57.19 per 100,000 person-years, respectively. Smoking, alcohol drinking, diabetes, gallstone, and chronic pancreatitis were associated with increased risk of AP in all age groups. Meanwhile, male, older age, and higher waist circumference were associated with increased risk of AP in middle-aged and old groups. In young and middle-aged groups, risk of AP was increased in the presence of hypertension and dyslipidemia. However, high income was associated with decreased risk of AP in these groups.
CONCLUSIONS In this population-based cohort study, incidences and risk factors for AP differed according to age group. Thus, a tailored strategy might be needed to prevent AP according to age group.
PubMed IF 3.9 소화기내과
39902023

제1저자 김경아, 이세준 · 교신저자 정숙향, 김승택

, , , , , , , , , , , ,
Next-generation sequencing analysis of hepatitis C virus resistance-associated substitutions in direct-acting antiviral failure in South Korea.
Clin Mol Hepatol. 2023;29(2):496-509.

Abstract
BACKGROUND/AIMS We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea.
METHODS Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS.
RESULTS RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate.
CONCLUSION NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.
PubMed IF 21.7 소화기내과
39892023

제1저자 황도연, 김희림 · 교신저자 이태진, 김효수

, , , , , , , , , , , , , , , , ,
Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study.
JACC Asia. 2023;3(2):198-207.

Abstract
BACKGROUND The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease-Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI).
OBJECTIVES The goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy.
METHODS A Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country.
RESULTS From the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively.
CONCLUSIONS Based on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).
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