SCI 발표논문

1. 1452022

   제1저자 강창경 · 교신저자 박완범

   Kang CK, Chang E, Jung J, Lee E, Song KH, Choe PG, Bang JH, Kim ES, Park SW, Kim HB, Kim NJ, Park WB, Oh MD

   Different levels of humoral and cellular immunity to varicella-zoster virus in seropositive healthcare workers.

   J Infect Public Health. 2022;15(7):734-738.

   Abstract

   BACKGROUND There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination.

   METHODS Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4⁺ or CD8⁺ T cells.

   RESULTS A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4⁺ T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group.

   CONCLUSION Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions.

   PubMed IF 4.8 감염내과
2. 1442022

   제1저자 강승경, 박미래 · 교신저자 조수정

   Kang S^*, Park M^*, Cho JY, Ahn SJ, Yoon C, Kim SG, Cho SJ

   Tumorigenic mechanisms of estrogen and Helicobacter pylori cytotoxin-associated gene A in estrogen receptor α-positive diffuse-type gastric adenocarcinoma.

   Gastric Cancer. 2022;25(4):678-696.

   Abstract

   BACKGROUND Diffuse-type gastric cancer (DGC), for which Helicobacter pylori infection is a causal factor, is associated with poor prognosis among young women, possibly due to female hormones such as estrogen. We aimed to identify the carcinogenesis induced by estrogen and H. pylori in DGC.

   METHODS We screened and selected estrogen receptor alpha (ERα)-positive (MKN45) and ERα-negative (SNU5) DGC cell lines. H. pylori strain 60190 and its isogenic mutant strain lacking cytotoxin-associated gene A (60190ΔCagA) were used to infect MKN45 cells. And the cytotoxin-related gene A (CagA) cDNA which was cloned into pSP65-SR-HA (cagA-pSP65SRa) vector was used to transfect MKN45 cells. Tumor samples were used for DGC organoid culture.

   RESULTS In MKN45 cells, we found that estradiol promotes epithelial-mesenchymal transition (EMT) and stemness phenotypes via HOTAIR expression. These effects were further enhanced by the addition of CagA secreted by H. pylori but were reversed by co-treatment with fulvestrant (ICI 182,780), a selective ER degrader. We also validated the effect of estrogen on DGC organoids. ERα expression was associated with tumor invasion and HOTAIR expression in DGC patients with overt H. pylori infection.

   CONCLUSIONS These findings may explain the rapid DGC progression in young women with physiologically high levels of estrogen and suggest that fulvestrant with ovarian function suppression could serve as a tumor-suppressive agent in premenopausal patients with DGC.

   PubMed IF 6.1 소화기내과
3. 1432022

   제1저자 정석송 · 교신저자 김원, 박상민

   Jeong S, Oh YH, Choi S, Chang J, Kim SM, Son JS, Lee G, Ahn JC, Lee DH, Koo BK, Kim W, Park SM

   Association of non-alcoholic fatty liver disease with incident dementia later in life among elder adults.

   Clin Mol Hepatol. 2022;28(3):510-521.

   Abstract

   BACKGROUND/AIMS Accumulating evidence suggests a link between non-alcoholic fatty liver disease (NAFLD) and brain health. However, population-based evidence on the association between NAFLD and dementia remains unclear. This study was conducted to determine the association between NAFLD and incident dementia.

   METHODS The study population included 608,994 adults aged ≥60 years who underwent health examinations between 2009 and 2010. Data were collected from the Korean National Health Insurance Service database. NAFLD was assessed using the fatty liver index (FLI). A Cox proportional hazards regression model was used to determine the association between NAFLD and dementia.

   RESULTS During the 6,495,352 person-years of follow-up, 48,538 participants (8.0%) developed incident dementia. The participants were classified into low (FLI <30), intermediate (FLI ≥30 and <60), and high (FLI ≥60) groups. In the overall study population, the FLI groups were associated with a risk of dementia (P for trend <0.001). After propensity score matching, a low FLI was associated with a reduced risk of dementia (adjusted hazard ration [aHR], 0.96; 95% confidence interval [CI], 0.93-0.98; P=0.002), whereas a high FLI (NAFLD) was associated with an increased risk of dementia (aHR, 1.05; 95% CI, 1.02-1.08; P=0.001). A higher risk of dementia in the high FLI group than in the intermediate FLI group was attributed to Alzheimer's disease (aHR, 1.04; 95% CI, 1.01-1.07; P=0.004) rather than vascular dementia (aHR, 0.94; 95% CI, 0.75-1.18; P=0.602).

   CONCLUSION NAFLD was associated with an increased risk of dementia, which was attributed to an increased risk of Alzheimer's disease.

   PubMed IF 21.7 소화기내과
4. 1422022

   제1저자 황보율, 최준영 · 교신저자 이은경, 문재훈

   Hwangbo Y, Choi JY, Lee EK, Ryu CH, Cho SW, Chung EJ, Hah JH, Jeong WJ, Park SK, Jung YS, Kim JH, Kim MJ, Kim SJ, Kim YK, Lee CY, Lee JY, Lee YJ, Yu HW, Park DJ, Ryu J, Park YJ, Lee KE, Moon JH

   A Cross-Sectional Survey of Patient Treatment Choice in a Multicenter Prospective Cohort Study on Active Surveillance of Papillary Thyroid Microcarcinoma (MAeSTro).

   Thyroid. 2022;32(7):772-780.

   Abstract

   Background: Active surveillance (AS) is offered as a choice to patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to identify patient and physician factors associated with the choice of AS. Methods: We conducted a cross-sectional survey of patients with low-risk PTMC who were enrolled in a prospective study comparing outcomes following AS and surgery. Patients completed a questionnaire to assess their prior knowledge of the disease, considerations in the decision-making process, and reasons for choosing the treatment. We also surveyed 19 physician investigators about their disease management preferences. Variables affecting the patients' choice of AS, including patients' characteristics and their decision-making process, were analyzed in a multivariable analysis. Results: The response rate of the patient survey was 72.8% (857/1177). Among the patients who responded to the survey, 554 patients (128 male; mean age 49.4 ± 11.6 years; response rate 73.4%) with low-risk PTMC chose AS (AS group), whereas 303 patients (55 male; 46.6 ± 10.7 years; 71.8%) chose immediate surgery (iOP group). In the AS group, 424 patients (76.5%) used a decision aid, and 144 (47.5%) used it in the iOP group. The choice of AS was associated with the following variables: patient age >50 years (odds ratio 1.713 [confidence interval, CI 1.090-2.690], p = 0.020), primary tumor size ≤5 mm (odds ratio 1.960 [CI 1.137-3.379], p = 0.015), and consulting an endocrinologist (odds ratio 114.960 [CI 48.756-271.057], p < 0.001), and use of a decision aid (odds ratio 2.469 [CI 1.320-4.616], p = 0.005). The proportion of patients who were aware of AS before their initial consultation for treatment decision was higher in the AS group than in the iOP group (64.6% vs. 56.8%). Family members were reported to have influenced the treatment decisions more in the iOP group (p = 0.025), whereas the AS group was more influenced by information from the media (p = 0.017). Physicians' attitudes regarding AS of low-risk PTMC tended to be more favorable among endocrinologists than surgeons and all became more favorable as the study progressed. Conclusions: Emerging evidence suggests that physicians' attitudes and communication tools influence the treatment decision of low-risk PTMC patients. Support is needed for patient-centered decision making. (Clinical trial No: NCT02938702).

   PubMed IF 6.6 내분비대사내과
5. 1412022

   제1저자 박혜인조 · 교신저자 오윤규

   Park HC, Hong Y, Yeon JH, Ryu H, Kim YC, Lee J, Kim YH, Chae DW, Chung W, Ahn C, Oh KH, Oh YK

   Mayo imaging classification is a good predictor of rapid progress among Korean patients with autosomal dominant polycystic kidney disease: results from the KNOW-CKD study.

   Kidney Res Clin Pract. 2022;41(4):432-441.

   Abstract

   BACKGROUND Mayo imaging classification (MIC) is a useful biomarker to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to validate MIC in the prediction of renal outcome in a prospective Korean ADPKD cohort and evaluate clinical parameters associated with rapid disease progression.

   METHODS A total of 178 ADPKD patients were enrolled and prospectively observed for an average duration of 6.2 ± 1.9 years. Rapid progressor was defined as MIC 1C through 1E while slow progressor was defined as 1A through 1B. Renal composite outcome (doubling of serum creatinine, 50% decline of estimated glomerular filtration rate [eGFR], or initiation of renal replacement therapy) as well as the annual percent change of height-adjusted total kidney volume (mHTKV-α), and eGFR decline (mGFR-α) were compared between groups.

   RESULTS A total of 110 patients (61.8%) were classified as rapid progressors. These patients were younger and showed a higher proportion of male patients. Rapid progressor was an independent predictor for renal outcome (hazard ratio, 4.09; 95% confidence interval, 1.23-13.54; p = 0.02). The mGFR-α was greater in rapid progressors (-3.58 mL/min per year in 1C, -3.7 in 1D, and -4.52 in 1E) compared with that in slow progressors (-1.54 in 1A and -2.06 in 1B). The mHTKV-α was faster in rapid progressors (5.3% per year in 1C, 9.4% in 1D, and 11.7% in 1E) compared with that in slow progressors (1.2% in 1A and 3.8% in 1B).

   CONCLUSION MIC is a good predictive tool to define rapid progressors in Korean ADPKD patients.

   PubMed IF 3.5 신장내과
6. 1402022

   제1저자 Mariam T. Nawas, 이정옥 · 교신저자 Roni Tamari

   Nawas MT^*, Lee JO^*, Flynn J, Maloy M, Jakubowski AA, Papadopoulos EB, Cho C, Ponce DM, Sauter CS, Perales MA, Devlin S, Giralt SA, Castro-Malaspina HR, Tamari R

   CD34+ -selected hematopoietic stem cell transplant conditioned with a myeloablative regimen in patients with advanced myelofibrosis.

   Bone Marrow Transplant. 2022;57(7):1101-1107.

   Abstract

   Allogeneic hematopoietic stem cell transplantation (Allo-HCT) remains the only curative treatment for myelofibrosis (MF). Transplantation in patients with MF is mostly done using a reduced intensity conditioning regimen with calcineurin inhibitors for graft versus host disease (GVHD) prophylaxis. Here we sought to evaluate outcomes of patients who underwent an ex vivo CD34+ -selected allo-HCT using myeloablative conditioning (MAC). Twenty-seven patients were included in this retrospective analysis. All patients were conditioned with busulfan, melphalan and fludarabine and antithymocyte globulin to prevent graft rejection. G-CSF mobilized peripheral blood stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection by CliniMACS device. Median follow-up among survivors was 50.6 months. The estimated 3-year overall survival, relapse free survival and the combined endpoint of GVHD/relapse free survival were 88% (95% CI, 75-100%), 80% (95% CI, 66-98%) and 74% (95% CI, 59-93%), respectively. The cumulative incidence of grade II-IV acute GVHD at day 100 was 33.3% (95% CI 16.4-51.3%), and two patients suffered chronic GVHD. There were no cases of primary graft failure. However, delayed graft failure occurred in two patients. We conclude that CD34+ selected allo-HCT with a MAC resulted in high survival rates in this cohort of patients with MF.

   PubMed IF 5.1 혈액종양내과
7. 1392022

   제1저자 김정한, 김택수 · 교신저자 박완범, 김인호

   Kim JH, Kim TS, Chang E, Kang CK, Choe PG, Kim NJ, Oh MD, Park WB, Kim I

   Effectiveness of antimicrobial stewardship programmes based on rapid antibiotic susceptibility testing of haematological patients having high-risk factors for bacteraemia-related mortality: a post-hoc analysis of a randomised controlled trial.

   Int J Antimicrob Agents. 2022;60(1):106604.

   Abstract

   A randomised controlled trial showed that rapid phenotypic antibiotic susceptibility testing (AST) with antimicrobial stewardship programme (ASP) increases the proportion of haematological patients with bacteraemia receiving optimal targeted therapy within 72 h of blood culture collection. This post-hoc analysis aimed to evaluate the effects of rapid phenotypic AST intervention in haematological patients at high risk of a poor outcome from bacteraemia. Haematological patients with bacteraemia (n = 116) were assigned randomly to a conventional AST group or a rapid AST group. The two outcome measures were the proportion of patients receiving optimal targeted therapy at 72 h post blood culture collection and the time to optimal targeted therapy; subgroup analysis was conducted based on baseline demographics (age, sex) and prognostic (Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score, appropriateness of empirical antibiotic therapy and multidrug-resistant organism) indicators. The interaction effect between the intervention and subgroup factors was examined using regression model analysis. Age, sex, Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score and appropriateness of empirical antibiotic therapy had no significant interaction effects on the proportion of patients receiving optimal targeted therapy (P = 0.129-0.826). However, infection by a multidrug-resistant organism did have a significant interaction effect (P = 0.042). Regarding time to optimal targeted therapy, there were no significant interaction effects between the intervention and subgroup factors (P = 0.156-0.848). In conclusion, rapid phenotypic AST with ASP intervention may accelerate early optimal targeted antimicrobial treatment of haematological patients, even those in high-risk subgroups with bacteraemia.

   PubMed IF 5 감염내과
8. 1382022

   제1저자 최유정 · 교신저자 이승표

   Choi YJ, Koh Y, Lee HJ, Hwang IC, Park JB, Yoon YE, Kim HL, Kim HK, Kim YJ, Cho GY, Sohn DW, Paeng JC, Lee SP

   Independent Prognostic Utility of 11C-Pittsburgh Compound B PET in Patients with Light-Chain Cardiac Amyloidosis.

   J Nucl Med. 2022;63(7):1064-1069.

   Abstract

   ¹¹C-Pittsburgh compound B (PiB) PET/CT visualizes the amount of myocardial amyloid deposit and can be used to prognosticate patients with amyloid light-chain (AL) cardiac amyloidosis (CA). However, whether ¹¹C-PiB PET/CT has any independent additional prognostic value beyond the commonly used biomarkers remains unknown. Methods: This prospective study was on a cohort of 58 consecutive patients with AL CA who underwent ¹¹C-PiB PET/CT. The patients were stratified into 2 groups on the basis of a visual assessment of whether there was myocardial ¹¹C-PiB uptake on PET/CT. The primary endpoint was 1-y overall mortality. The independent prognostic utility of ¹¹C-PiB PET/CT was analyzed using net reclassification improvement and integrated discrimination improvement. Results: Among the 58 patients enrolled, 35 were positive for myocardial ¹¹C-PiB uptake on PET/CT. Patients with myocardial ¹¹C-PiB PET uptake had a worse 1-y overall survival rate than those without (81.8% vs. 45.5%, P = 0.003 by log-rank test). In the multivariate analysis, positivity for myocardial ¹¹C-PiB uptake on PET/CT was an independent predictor of 1-y mortality (adjusted hazard ratio, 3.382; 95% CI, 1.011-11.316; P = 0.048). In analysis of 3 subgroups of patients-those with a troponin I level of at least 0.1 ng/mL, those with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of at least 1,800 pg/mL, and those with a difference of at least 180 mg/L between free light chains (the 3 commonly used biomarkers and their thresholds for staging in AL amyloidosis)-Kaplan-Meier curves showed for all 3 subgroups that patients positive for myocardial ¹¹C-PiB uptake on PET/CT had a worse prognosis than those who were negative. Additionally, when the results of ¹¹C-PiB PET/CT were added to these 3 biomarkers, the performance of 1-y mortality prediction significantly improved by net reclassification improvement (troponin I, 0.861; NT-proBNP, 0.914; difference between free light chains, 0.987) and by integrated discrimination improvement (0.200, 0.156, and 0.108, respectively). Conclusion:¹¹C-PiB PET/CT is a strong independent predictor of 1-y overall mortality and provides incremental prognostic benefits beyond the 3 commonly used biomarkers of AL amyloidosis staging. Considering the recent development of numerous amyloid-targeting molecular imaging agents, further investigations are warranted on whether PET/CT should be included in risk stratification for patients with AL CA.

   PubMed IF 9.6 순환기내과
9. 1372022

   제1저자 황영재, 최용훈 · 교신저자 김나영

   Hwang YJ^*, Choi Y^*, Kim N, Lee HS, Yoon H, Shin CM, Park YS, Lee DH

   The Difference of Endoscopic and Histologic Improvements of Atrophic Gastritis and Intestinal Metaplasia After Helicobacter pylori Eradication.

   Dig Dis Sci. 2022;67(7):3055-3066.

   Abstract

   BACKGROUND/AIMS Helicobacter pylori (H. pylori) is an important risk factor of atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC). However, no report to date has described the endoscopic improvement of AG and IM after H. pylori eradication. Thus, the aim of this study was to evaluate the improvement of AG and IM after H. pylori eradication using endoscopic and histologic analyses.

   METHODS A total of 380 subjects were prospectively enrolled for up to 12 years and grouped by their H. pylori infection status: negative, non-eradicated, and eradicated. Endoscopic and histologic analyses of AG and IM were performed in the antrum and the corpus, by annual follow-up endoscopy.

   RESULTS Endoscopic AG and IM in the antrum and corpus in the eradicated group improved compared to that in the non-eradicated group (AG, P = 0.002 and P = 0.005; IM, P = 0.038 and P = 0.048, respectively). Histologic AG and IM in the antrum and corpus in the eradicated group also improved compared to that in the non-eradicated group (all P < 0.001). Time taken to the endoscopic improvement of AG and IM after H. pylori eradication was significantly longer than time taken to the histologic improvement in the antrum and corpus (AG in antrum: 3.47 ± 2.60 vs. 2.34 ± 1.71 years, P = 0.004; AG in corpus: 3.19 ± 2.30 vs. 1.87 ± 1.48 years, P = 0.002; IM in antrum: 4.40 ± 2.38 vs. 3.62 ± 2.35 years, P = 0.043; and IM in corpus: 4.82 ± 1.08 vs. 3.61 ± 2.22 years, P = 0.007, respectively).

   CONCLUSIONS Both endoscopic and histologic improvements of AG and IM were observed after H. pylori eradication, while endoscopic improvement took significantly longer time than histologic improvement.

   PubMed IF 2.8 소화기내과
10. 1362022

    제1저자 신동훈 · 교신저자 김홍빈

    Shin DH, Kim HS, Heo E, Shin MJ, Kim NH, Lee H, Park JS, Park KU, Jung J, Song KH, Kang M, Jung J, Kim ES, Kim HB

    Stepwise Expansion of Antimicrobial Stewardship Programs and Its Impact on Antibiotic Use and Resistance Rates at a Tertiary Care Hospital in Korea.

    Microbiol Spectr. 2022;10(3):e0033522.

    Abstract

    To optimize antibiotic use, the US CDC has outlined core elements of antimicrobial stewardship programs (ASP). However, they are difficult to implement in limited-resource settings. We report on the successful implementation of a series of ASP with insufficient number of infectious diseases specialists. We retrospectively collected data regarding antibiotic administration and culture results of all patients admitted to a tertiary care teaching hospital, Seoul National University Bundang Hospital (SNUBH), from January 2010 to December 2019. Trends of antibiotic use and antibiotic resistance rates were compared with those from Korean national data. Trend analyses were performed using nonparametric, two-sided, correlated seasonal Mann-Kendall tests. Total antibiotic agent usage has significantly decreased with ASP implementation at SNUBH since 2010. National claim data from tertiary care hospitals have revealed an increase in the use of all broad-spectrum antibiotics except for third-generation cephalosporins (3GC). In contrast, at SNUBH, glycopeptide and fluoroquinolone use gradually decreased, and 3GC and carbapenem use did not significantly change. Furthermore, the rate of colonization with methicillin-resistant Staphylococcus aureus showed a consistently decreasing trend, while that with 3GC- and fluoroquinolone-resistant Escherichia coli significantly increased. Unlike the national rate, the rate of colonization with antibiotic resistant-Klebsiella pneumoniae did not increase and that of 3GC- and fluoroquinolone-resistant Pseudomonas aeruginosa significantly decreased. Stepwise implementation of core ASP elements was effective in reducing antibiotic use despite a lack of sufficient manpower. Long-term multidisciplinary teamwork is necessary for successful and sustainable ASP implementation. IMPORTANCE Antimicrobial stewardship programs aimed to optimize antibiotic use are difficult to implement in limited-resource settings. Our study indicates that stepwise implementation of core antimicrobial stewardship program elements was effective in reducing antibiotic use in a tertiary care hospital despite the lack of sufficient manpower.

    PubMed IF 4.1 감염내과
11. 1352022

    제1저자 이희선 · 교신저자 김형관

    Lee H, Kim HK, Kim B, Han K, Park JB, Hwang IC, Yoon YE, Park HE, Choi SY, Kim YJ, Cho GY

    Augmented risk of dementia in hypertrophic cardiomyopathy: A propensity score matching analysis using the nationwide cohort.

    PLoS One. 2022;17(6):e0269911.

    Abstract

    BACKGROUND Dementia is a big medical and socioeconomic problem on aging society, and cardiac diseases have already shown a significant contribution to developing dementia. However, the risk of dementia related to hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has never been evaluated.

    METHODS In a large-scale longitudinal cohort using National Health Insurance database, 4,645 subjects with HCM aged ≥50 years between 2010 and 2016 were collected and matched with 13,935 controls, based on propensity scores (1:3). We investigated the incidence and risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) between groups.

    RESULTS During follow-up (median 3.9 years after 1-year lag), incident dementia occurred in 739 subjects (4.0%): 78.2% for AD and 13.0% for VaD. The incidence of dementia, AD, and VaD were 23.0, 18.0, and 2.9/1,000 person-years, respectively, and was generally more prevalent in HCM. HCM group had a 50% increased risk of dementia, particularly AD, whereas there was no difference in the risk of VaD. The impact of HCM on AD (HR 1.52, 95% CI 1.26-1.84, p<0.001) was comparable with that of diabetes mellitus and smoking. Increased risk of AD in relation to HCM was consistent in various subgroups including younger healthier population.

    CONCLUSIONS This is the first to demonstrate the increased risk of dementia, mainly AD rather than VaD, in subjects with HCM. Early surveillance and active prevention for cognitive impairment could help for a better quality of life in an era that HCM is considered a chronic manageable disease with low mortality.

    PubMed IF 2.8 순환기내과
12. 1342022

    제1저자 김민주 · 교신저자 조선욱

    Kim MJ, Cho SW, Kim YA, Choi HS, Park YJ, Park DJ, Cho BY

    Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves' Disease.

    Endocrinol Metab (Seoul). 2022;37(3):524-532.

    Abstract

    BACKGRUOUND Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves' disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves' disease.

    METHODS Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.

    RESULTS The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.

    CONCLUSION Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

    PubMed IF 5.1 내분비대사내과
13. 1332022

    제1저자 김율담, 방지영 · 교신저자 강혜련

    Kim RL^*, Bang JY^*, Kim J, Mo Y, Kim Y, Lee CG, Elias JA, Kim HY, Kang HR

    Mesenchymal stem cells exert their anti-asthmatic effects through macrophage modulation in a murine chronic asthma model.

    Sci Rep. 2022;12(1):9811.

    Abstract

    Despite numerous previous studies, the full action mechanism of the pathogenesis of asthma remains undiscovered, and the need for further investigation is increasing in order to identify more effective target molecules. Recent attempts to develop more efficacious treatments for asthma have incorporated mesenchymal stem cell (MSC)-based cell therapies. This study aimed to evaluate the anti-asthmatic effects of MSCs primed with Liproxstatin-1, a potent ferroptosis inhibitor. In addition, we sought to examine the changes within macrophage populations and their characteristics in asthmatic conditions. Seven-week-old transgenic mice, constitutively overexpressing lung-specific interleukin (IL)-13, were used to simulate chronic asthma. Human umbilical cord-derived MSCs (hUC-MSCs) primed with Liproxstatin-1 were intratracheally administered four days prior to sampling. IL-13 transgenic mice demonstrated phenotypes of chronic asthma, including severe inflammation, goblet cell hyperplasia, and subepithelial fibrosis. Ly6C⁺M2 macrophages, found within the pro-inflammatory CD11c⁺CD11b⁺ macrophages, were upregulated and showed a strong correlation with lung eosinophil counts. Liproxstatin-1-primed hUC-MSCs showed enhanced ability to downregulate the activation of T helper type 2 cells compared to naïve MSCs in vitro and reduced airway inflammation, particularly Ly6C⁺M2 macrophages population, and fibrosis in vivo. In conclusion, intratracheal administration is an effective method of MSC delivery, and macrophages hold great potential as an additional therapeutic target for asthma.

    PubMed IF 4.9 알레르기내과
14. 1322022

    제1저자 이태민, 이소령 · 교신저자 최의근

    Rhee TM, Lee SR, Choi EK, Oh S, Lip GYH

    Efficacy and Safety of Oral Anticoagulants for Atrial Fibrillation Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

    Front Cardiovasc Med. 2022;9:885548.

    Abstract

    BACKGROUND Data on different direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with renal impairment are insufficient. We aimed to perform pairwise and network meta-analysis comparing oral anticoagulants (OACs) in AF patients with renal impairment, including advanced chronic kidney disease (CKD) with creatinine clearance <30 mL/min.

    METHODS PubMed, Embase, Cochrane Database, and references of related articles were searched up to April 2021. We included randomized trials and non-randomized studies using propensity-score or multivariable-model adjustments that compared clinical outcomes among OACs. Hazard ratios (HRs) for stroke or thromboembolism, major bleeding, and all-cause death were pooled using random-effects model.

    RESULTS From 19 studies, 124,628 patients were included. In patients with AF and CKD, DOACs presented significantly lower risks of stroke or thromboembolism [HR_pooled = 0.78, 95% confidence interval (CI) = 0.73-0.85, I² = 16.6%] and major bleeding [HR_pooled = 0.76 (0.64-0.89), I² = 85.7%] when compared with warfarin, regardless of the severity of renal impairment. Results were consistent in advanced CKD patients for stroke or thromboembolism [HR_pooled = 0.60 (0.43-0.85), I² = 0.0%] and major bleeding [HR_pooled = 0.74 (0.59-0.93), I² = 30.4%]. In the network meta-analysis, edoxaban and apixaban presented the highest rank probability to reduce the risk of stroke or thromboembolism (edoxaban, P-score = 94.5%) and major bleeding (apixaban, P-score = 95.8%), respectively. Apixaban remained the safest OAC with the highest rank probability for major bleeding (P-score = 96.9%) in patients with advanced CKD.

    CONCLUSION DOACs, particularly apixaban and edoxaban, presented superior efficacy and safety than warfarin in AF patients with CKD. Apixaban was associated with the lowest risk of major bleeding among OACs for patients with advanced CKD.

    SYSTEMATIC REVIEW REGISTRATION [PROSPERO], identifier [CRD42021241718].

    PubMed IF 3 순환기내과
15. 1312022

    제1저자 김소연 · 교신저자 이현우

    Kim SY, Lee HJ, Lee JK, Park TY, Heo EY, Kim DK, Chung HS, Lee HW

    Association between oxygen saturation level during bronchoscopy and post-bronchoscopy adverse events: a retrospective cohort study.

    Respir Res. 2022;23(1):144.

    Abstract

    BACKGROUND Flexible bronchoscopy is widely used to diagnose and treat various respiratory diseases. However, caution is warranted for post-bronchoscopy adverse events. Although desaturation frequently occurs during bronchoscopy, its clinical impact and the optimal oxygen saturation level during the procedure remain unclear. This study aimed to investigate whether the percutaneous oxygen saturation (SpO₂) level during bronchoscopy is associated with the development of post-bronchoscopy respiratory adverse events.

    METHODS In this single-center retrospective cohort study conducted from March 2020 to February 2021, 569 patients were classified into high or low oxygen saturation groups based on the SpO₂ level during bronchoscopy. The primary outcome was post-bronchoscopy respiratory adverse events, and secondary outcomes were other post-bronchoscopy adverse events and clinical outcomes.

    RESULTS Among 569 patients, 458 and 111 patients were classified into the high oxygen saturation (SpO₂ > 96%) and low oxygen saturation (SpO₂ ≤ 94%) groups, respectively. After propensity score matching, the low oxygen saturation group had more post-bronchoscopy respiratory and febrile adverse events than the high oxygen saturation group. In the multivariable regression analysis, low SpO₂ level during bronchoscopy was an independent risk factor for post-bronchoscopy respiratory adverse events (odds ratio = 3.16 [95% confidence interval 1.37-7.30]). In the low oxygen saturation group, the high-risk subgroups for post-bronchoscopy respiratory adverse events were the elderly, women, current smokers, and patients with chronic obstructive pulmonary disease or acute decompensated heart failure before bronchoscopy. There was no significant difference in the length of hospital stay, intensive care unit admission, or mortality between the high and low oxygen saturation groups.

    CONCLUSIONS Close monitoring is recommended for patients with SpO₂ ≤ 94% during bronchoscopy due to the increased risk of respiratory adverse events after the procedure.

    PubMed IF 5.7 호흡기내과
16. 1302022

    제1저자 장의진 · 교신저자 박경운, 김남중

    Chang E, Chang HE, Shin IS, Oh YR, Kang CK, Choe PG, Park WB, Choi EH, Oh MD, Park KU, Kim NJ

    Investigation on the transmission rate of carbapenemase-producing carbapenem-resistant Enterobacterales among exposed persons in a tertiary hospital using whole-genome sequencing.

    J Hosp Infect. 2022;124:1-8.

    Abstract

    BACKGROUND To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE), screening is recommended for patients sharing rooms with CP-CRE-detected patients and healthcare workers caring for them.

    AIM The aim of this study was to investigate the transmission rate of CP-CRE among exposed people in a tertiary hospital using whole-genome sequencing.

    METHODS This study was conducted in a 1751-bed tertiary teaching hospital from January 2017 to December 2019. Index patients were defined as those with positive results in CP-CRE tests during hospitalization. When an index patient was detected in a shared room, we performed CRE screening tests for patients whose stay overlapped with an index patient's stay for at least one day. Where a second case was found, healthcare worker contacts were also screened. CP-CRE were confirmed, and the carbapenemase type identified, by PCR. Whole-genome sequencing was used to compare isolates from index and exposed patients.

    RESULTS During the study period, 47 index patients were identified, and they had been in contact with 152 patients in shared rooms and 54 healthcare workers. None of the healthcare workers had CRE. Among the 152 exposed patients, four patients had the same type of carbapenemases as their CP-CRE index patients and all of them were KPC. Whole-genome sequencing revealed that three of these four pairs showed genotypic accordance between the index and the exposed.

    CONCLUSION The CP-CRE transmission rate among the exposed patients was calculated as 2.0% (= 3/152).

    PubMed IF 3.4 감염내과
17. 1292022

    제1저자 양석훈 · 교신저자 구본권

    Yang S, Koo BK, Narula J

    Interactions Between Morphological Plaque Characteristics and Coronary Physiology: From Pathophysiological Basis to Clinical Implications.

    JACC Cardiovasc Imaging. 2022;15(6):1139-1151.

    Abstract

    High-risk coronary plaque refers to a distinct set of plaque characteristics prone to future coronary events. Coronary physiology represents a group of indexes reflective of the local physiological environment and hemodynamic changes in the macrovascular and microvascular system. Although a large body of evidence has supported the clinical relevance of these 2 factors, currently, identifying plaque morphology cannot reliably capture the lesion subset that causes hard events. Also, the guideline-directed approach based on physiological indexes cannot fully predict and prevent clinical events. In parallel, there is accumulating evidence that these 2 aspects of coronary artery disease influence each other with significant clinical implications, despite traditionally being considered to have separate effects on significances, treatments, and outcomes. In this state-of-the-art review, the authors explore the clinical evidence of pathophysiological interplay of physiological indexes related to local hemodynamics, epicardial stenosis, and microvascular dysfunction with plaque morphological characteristics that provide a better understanding of the nature of coronary events. Furthermore, the authors examine the emerging data on the complementary role between plaque morphology and coronary physiology in prognostication and how to apply this concept to overcome the limitations of individual assessment alone. Finally, they propose the potential benefit of integrative assessment of coronary anatomy, plaque quantity and quality, and physiological aspects of a target lesion and vessels for personalized risk profiling and optimized treatment strategy.

    PubMed IF 19 순환기내과
18. 1282022

    제1저자 최유정, 박재민 · 교신저자 이승표, 임선희

    Choi YJ, Park J, Hwang D, Kook W, Kim YJ, Tanaka H, Hozumi T, Yuasa T, Ling LH, Yu CM, Park SW, Ha JW, Otsuji Y, Song JK, Sohn DW, Lim SH, Lee SP

    Network Analysis of Cardiac Remodeling by Primary Mitral Regurgitation Emphasizes the Role of Diastolic Function.

    JACC Cardiovasc Imaging. 2022;15(6):974-986.

    Abstract

    BACKGROUND Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics.

    OBJECTIVES The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data.

    METHODS Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups.

    RESULTS The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003).

    CONCLUSIONS The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR.

    PubMed IF 19 순환기내과
19. 1272022

    제1저자 장희준, 윤준식, 박수영, 이한아 · 교신저자 이정훈

    Jang H, Yoon JS, Park SY, Lee HA, Jang MJ, Kim SU, Sinn DH, Seo YS, Kim HY, Kim SE, Jun DW, Yoon EL, Sohn JH, Ahn SB, Shim JJ, Jeong SW, Cho YK, Kim HS, Nam JY, Lee YB, Kim YJ, Yoon JH, Zoulim F, Lampertico P, Dalekos GN, Idilman R, Sypsa V, Berg T, Buti M, Calleja JL, Goulis J, Manolakopoulos S, Janssen H, Papatheodoridis GV, Lee JH

    Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B.

    Clin Gastroenterol Hepatol. 2022;20(6):1343-1353.e16.

    Abstract

    BACKGROUND & AIMS Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC.

    METHODS The incidence of HCC was evaluated in Korean patients with chronic hepatitis B who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort.

    RESULTS A total of 9143 Korean patients (mean age, 49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median, 5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.26-0.66), propensity score-matching (aHR, 0.46; 95% CI, 0.28-0.76), and inverse probability weighting analyses (aHR, 0.44; 95% CI, 0.28-0.70). In the Caucasian cohort (n = 719; mean age, 51.8 years; HBeAg-positive, 20.3%; cirrhosis, 34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR, 0.21; 95% CI, 0.00-1.67).

    CONCLUSIONS This multinational cohort study implies that HBeAg positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.

    PubMed IF 16.2 소화기내과
20. 1262022

    제1저자 배재현, 최훈지 · 교신저자 임수

    Bae JH^*, Choe HJ^*, Holick MF, Lim S

    Association of vitamin D status with COVID-19 and its severity : Vitamin D and COVID-19: a narrative review.

    Rev Endocr Metab Disord. 2022;23(3):579-599.

    Abstract

    Vitamin D is associated with biological activities of the innate and adaptive immune systems, as well as inflammation. In observational studies, an inverse relationship has been found between serum 25-hydroxyvitamin D (25(OH)D) concentrations and the risk or severity of coronavirus disease 2019 (COVID-19). Several mechanisms have been proposed for the role of vitamin D in COVID-19, including modulation of immune and inflammatory responses, regulation of the renin-angiotensin-aldosterone system, and involvement in glucose metabolism and cardiovascular system. Low 25(OH)D concentrations might predispose patients with COVID-19 to severe outcomes not only via the associated hyperinflammatory syndrome but also by worsening preexisting impaired glucose metabolism and cardiovascular diseases. Some randomized controlled trials have shown that vitamin D supplementation is beneficial for reducing severe acute respiratory syndrome coronavirus 2 RNA positivity but not for reducing intensive care unit admission or all-cause mortality in patients with moderate-to-severe COVID-19. Current evidence suggests that taking a vitamin D supplement to maintain a serum concentration of 25(OH)D of at least 30 ng/mL (preferred range 40-60 ng/mL), can help reduce the risk of COVID-19 and its severe outcomes, including mortality. Although further well designed studies are warranted, it is prudent to recommend vitamin D supplements to people with vitamin D deficiency/insufficiency during the COVID-19 pandemic according to international guidelines.

    PubMed IF 8.7 내분비대사내과
21. 1252022

    제1저자 박세윤 · 교신저자 김태형, 김홍빈

    Park SY, Moon SM, Kim B, Lee MJ, Park JY, Hwang S, Yu SN, Lee YM, Lee HJ, Hong KW, Park KH, Kwak YG, Moon C, Jeon MH, Park SH, Kim YK, Song KH, Kim ES, Kim TH, Kim HB, Korea Study Group for Antimicrobial Stewardship (KOSGAP)

    Appropriateness of antibiotic prescriptions during hospitalization and ambulatory care: a multicentre prevalence survey in Korea.

    J Glob Antimicrob Resist. 2022;29:253-258.

    Abstract

    OBJECTIVES Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea.

    METHODS The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated.

    RESULTS The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699).

    CONCLUSION This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

    PubMed IF 3.7 감염내과
22. 1242022

    제1저자 김경식, 최준영 · 교신저자 조선욱, 박수경

    Kim K, Choi JY, Kim SJ, Lee EK, Lee YK, Ryu JS, Lee KE, Moon JH, Park YJ, Cho SW, Park SK

    Active Surveillance Versus Immediate Surgery for Low-Risk Papillary Thyroid Microcarcinoma Patients in South Korea: A Cost-Minimization Analysis from the MAeSTro Study.

    Thyroid. 2022;32(6):648-656.

    Abstract

    Background: Active surveillance (AS) has been established as an alternative to immediate surgery for low-risk papillary thyroid microcarcinoma (PTMC). Nonetheless, it remains difficult to decide between AS and immediate surgery, since limited objective evidence exists regarding risks and benefits. The aim of study is to compare the cumulative costs of AS and immediate surgery. Methods: To estimate cumulative costs, a hypothetical model is simulated based on the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Micro-Carcinoma (MAeSTro) study, a multicenter prospective cohort study of AS for PTMC. Direct and indirect costs are estimated from diagnosis to the treatment decision and follow-up for 10 years and a longer period. In the case of the scenarios, AS, AS to surgery due to changing their mind, and lobectomy (analyzed regardless of levothyroxine [LT4] treatment, as well as subdivided into lobectomy/LT4[-] and lobectomy/LT4[+]) are considered. A sensitivity analysis is performed using different discount rates to address uncertainties in future time costs. To compare the cumulative costs, we referred to previous research conducted in Hong Kong, the United States, and Japan. Results: The initial cost of AS is estimated to be 5.6 times lower than that of lobectomy (regardless of LT4 use), while the 10-year cumulative costs of AS ($2545) and lobectomy regardless of LT4 ($3045) are similar under a discount rate of 3%. However, in the long-term follow-up period, immediate surgery is going to be estimated more economical than AS. The costs of the two management approaches are similar in Hong Kong, but substantially different in the United States and Japan, implying that it could be affected by each country's national health insurance coverage and the thyroid ultrasound interval during follow-up. Conclusion: Considering both direct and indirect costs, the cumulative costs of AS and immediate surgery in low-risk PTMC patients are similar during 10 years, and surgery could be more economical for patients with a life expectancy in long-term follow-up. However, careful interpretation is needed for long-term follow-up and the country's health care system and environment. Nevertheless, considering the representative protocols and objective costs in South Korea, it is expected to be a key to suggest the appropriate treatment for PTMC patients.

    PubMed IF 6.6 내분비대사내과
23. 1232022

    제1저자 문준성 · 교신저자 임수, Nauck MA

    Moon JS, Hong JH, Jung YJ, Ferrannini E, Nauck MA, Lim S

    SGLT-2 inhibitors and GLP-1 receptor agonists in metabolic dysfunction-associated fatty liver disease.

    Trends Endocrinol Metab. 2022;33(6):424-442.

    Abstract

    Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition that affects nearly one billion people globally, characterized by triacylglycerol accumulation in the liver as a consequence of metabolic abnormalities (obesity and impaired glucose regulation). Low-grade inflammation, oxidative stress, mitochondrial dysfunction, and dysbiosis in gut microbiota are involved in the etiology of MAFLD, and both cardiovascular events and hepatic complications are the long-term consequences. In the absence of approved therapies for this condition, sodium-glucose cotransporter 2 inhibitors (SGLT-2 Is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have the specific advantage of lowering body weight and providing cardiovascular benefits. Here, we discuss potential roles for SGLT-2 Is and GLP-1 RAs in the prevention and treatment of intrahepatic triacylglycerol accumulation and associated inflammation and/or fibrosis.

    PubMed IF 20.1 내분비대사내과
24. 1222022

    제1저자 이희진, 이소령 · 교신저자 최의근

    Lee HJ, Lee SR, Choi EK, Park SH, Chung JW, Choi JM, Han MJ, Jung JH, Han KD, Oh S, Lip GYH

    Risk of Dementia After Smoking Cessation in Patients With Newly Diagnosed Atrial Fibrillation.

    JAMA Netw Open. 2022;5(6):e2217132.

    Abstract

    IMPORTANCE Incident atrial fibrillation (AF) is associated with an increased risk of dementia. However, data on the association between smoking cessation after AF diagnosis and dementia risk are limited.

    OBJECTIVE To evaluate the association between changes in smoking status after AF diagnosis and dementia risk.

    DESIGN, SETTING, AND PARTICIPANTS This nationwide cohort study with 126 252 patients used data from the Korean National Health Insurance Service database, including patients who had a national health checkup examination within 2 years before and after AF diagnosis between January 1, 2010, and December 31, 2016. Based on their smoking status, participants were classified as never smokers, ex-smokers, quit smokers, and current smokers. Ex-smokers were defined as those who had quit smoking before the first examination and remained quit until the second examination. Patients who were current smokers at the first health examination but had quit smoking before the second examination were classed as quit smokers. The index date was the second health examination. Patients were followed up until dementia, death, or the study period ended (December 31, 2017), whichever occurred first. Data were analyzed from January 13, 2020, to March 29, 2022.

    EXPOSURES Smoking cessation after newly diagnosed AF.

    MAIN OUTCOMES AND MEASURES Dementia, including Alzheimer disease and vascular dementia, was the primary outcome. Cox proportional hazards regression model was used to estimate hazard ratios.

    RESULTS A total of 126 252 patients (mean [SD] age, 62.6 [12.0] years; 61.9% men) were included in the analysis. The mean (SD) CHA2DS2-VASc score, which measures the risk of ischemic stroke, was 2.7 (1.7). Smoking status of the total study population was as follows: 65 579 never smokers (51.9%), 34 670 ex-smokers (27.5%), 8919 quit smokers (7.1%), and 17 084 current smokers (13.5%). During a median of 3 years of follow-up, dementia occurred in 5925 patients (1.11 per 1000 person-years). After multivariable adjustment, the risk of quit smokers was significantly lower than that of current smokers (hazard ratio, 0.83 [95% CI, 0.72-0.95]).

    CONCLUSIONS AND RELEVANCE The findings of this cohort study suggest that all types of smoking were associated with a significantly higher risk of dementia in patients with new-onset AF. Smoking cessation after AF diagnosis was associated with a lower risk of dementia than among current smokers. These findings may support promoting smoking cessation to reduce dementia risk in patients with new-onset AF.

    PubMed IF 11.7 순환기내과
25. 1212022

    제1저자 오도연 · 교신저자 오도연

    Oh DY, Lee KH, Lee DW, Yoon J, Kim TY, Bang JH, Nam AR, Oh KS, Kim JM, Lee Y, Guthrie V, McCoon P, Li W, Wu S, Zhang Q, Rebelatto MC, Kim JW

    Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study.

    Lancet Gastroenterol Hepatol. 2022;7(6):522-532.

    Abstract

    BACKGROUND Immunotherapies have shown clinical activity in patients with advanced biliary tract cancer, for which outcomes remain poor despite standard of care treatment with gemcitabine and cisplatin. We aimed to evaluate gemcitabine and cisplatin plus durvalumab with or without tremelimumab as first-line treatment in patients with advanced biliary tract cancer.

    METHODS This open-label, single-centre, phase 2 study was conducted at Seoul National University Hospital. Eligible patients were treatment-naïve adults aged 18 years or older with histologically proven unresectable or recurrent biliary tract cancer, at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (version 1.1), an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 12 weeks or longer, and adequate healthy organ and bone marrow function. Initially, all patients received one 3-week cycle of gemcitabine (1000 mg/m²) and cisplatin (25 mg/m²) on day 1 and 8 followed by gemcitabine and cisplatin plus durvalumab (1120 mg) and tremelimumab (75 mg) on day 1 of each cycle, starting with the second cycle (chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group). Following protocol amendment, patients were recruited to receive gemcitabine and cisplatin plus durvalumab, starting on day 1 of the first cycle (chemotherapy plus durvalumab group) or gemcitabine and cisplatin plus durvalumab and tremelimumab also from day 1 of the first cycle (chemotherapy plus durvalumab and tremelimumab group) in parallel and allocated using a random block method. Assessors and patients were not masked to the treatment group. The primary endpoint was objective response rate, assessed in the efficacy population (ie, patients who were treated at least until the first tumour response assessment). This study is registered with ClinicalTrials.gov, NCT03046862 (active).

    FINDINGS Between March 2, 2017, and Feb 13, 2020, 128 patients were enrolled (32 in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, 49 in the chemotherapy plus durvalumab group, and 47 in the chemotherapy plus durvalumab and tremelimumab group). Four patients (two in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group and two in the chemotherapy plus durvalumab group) were excluded and 124 were evaluable for tumour response. The median duration of follow-up was 48·2 months (IQR 41·5-49·4) for the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, 26·6 months (19·0-27·9) for the chemotherapy plus durvalumab group, and 24·2 months (20·7-31·7) for the chemotherapy plus durvalumab and tremelimumab group. 82 (66%) of 124 patients achieved an objective response (15 [50%] of 30 in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, 34 [72%] of 47 in the chemotherapy plus durvalumab group, and 33 [70%] of 47 in the chemotherapy plus durvalumab and tremelimumab group). The most common grade 3 and 4 adverse events were decreased neutrophil count (67 [53%] of 126), anaemia (50 [40%]), and decreased platelet count (24 [19%]), with no unexpected safety events. No adverse events leading to discontinuation or death occurred.

    INTERPRETATION Gemcitabine and cisplatin plus immunotherapy showed promising efficacy and acceptable safety in patients with biliary tract cancer. Gemcitabine and cisplatin plus durvalumab are being evaluated in the phase 3, TOPAZ-1 study (NCT03875235) as first-line treatment in patients with advanced biliary tract cancer.

    FUNDING AstraZeneca; National Research Foundation of Korea (Grant No. 2021R1A2C2007430).

    PubMed IF 45.042 혈액종양내과
26. 1202022

    제1저자 김주성 · 교신저자 이상협

    Kim JS, Lee SH, Park N, Huh G, Chun JW, Choi JH, Cho IR, Paik WH, Ryu JK, Kim YT

    The effect of nafamostat mesilate infusion after ERCP for post-ERCP pancreatitis.

    BMC Gastroenterol. 2022;22(1):271.

    Abstract

    BACKGROUND Nafamostat mesilate decreases the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, no studies have administered nafamostat mesilate after ERCP. So we investigated if the infusion of nafamostat mesilate after ERCP can affect the post-ERCP pancreatitis (PEP) in high-risk patients.

    METHODS In a tertiary hospital, 350 high-risk patients of PEP were reviewed retrospectively. Among them, 201 patients received nafamostat mesilate after ERCP. Patient-related and procedure-related risk factors for PEP were collected. We performed a propensity score matching to adjust for the significant different baseline characteristics. The incidence and severity of PEP were evaluated according to the infusion of nafamostat mesilate. The risk factors of PEP were also analyzed by multivariate logistic regression.

    RESULTS The baseline characteristics were not different after the matching. The PEP rate (17.4% vs. 10.3%, P = 0.141) was insignificant. Among the PEP patients, mild PEP was significantly higher in the nafamostat mesilate group (85.7% vs. 45.5%, P = 0.021). Only one patient in the nafamostat mesilate group developed severe PEP. Although young age (odds ratio [OR] 3.60, 95% CI 1.09-11.85, P = 0.035) was a risk factor, nafamostat mesilate (odds ratio [OR] 0.30, 95% CI 0.09-0.98, P = 0.047) was a protective factor for moderate to severe PEP.

    CONCLUSIONS The administration of nafamostat mesilate after ERCP in high-risk patients was not effective in preventing PEP, but may attenuate the severity of PEP.

    PubMed IF 3.2 소화기내과
27. 1192022

    제1저자 강병근 · 교신저자 성노현, 김원

    Kang B, Kang B, Roh TY, Seong RH, Kim W

    The Chromatin Accessibility Landscape of Nonalcoholic Fatty Liver Disease Progression.

    Mol Cells. 2022;45(5):343-352.

    Abstract

    The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the generegulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

    PubMed IF 8.2 소화기내과
28. 1182022

    제1저자 이태민 · 교신저자 최의근

    Rhee TM, Choi EK, Han KD, Ahn HJ, Lee SR, Oh S, Lip GYH

    Type and Severity of Migraine Determines Risk of Atrial Fibrillation in Women.

    Front Cardiovasc Med. 2022;9:910225.

    Abstract

    OBJECTIVE To evaluate sex differences in the risk of atrial fibrillation (AF) according to the type and severity of migraine.

    METHODS We analyzed the nationwide health screening recipients in 2009 without previous AF diagnosis from the Korean National Health Insurance Service data. The diagnosis, type, and severity of migraine were determined using claims data. Newly developed AF was identified during a 10-year follow-up. Sex-difference in the effect of migraine on AF was evaluated.

    RESULTS A total of 4,020,488 subjects were enrolled from January 1, to December 31, 2009 and followed-up through December 31, 2018; 4,986 subjects had migraine with aura (age 50.6 ± 14.0 years, men 29.3%); and 105,029 had migraine without aura (age 51.6 ± 14.3 years, men 30.9%). Risk of AF in a mild degree of migraine was similar to that in the control group, regardless of sex or the presence of aura. Severe migraine without aura modestly but significantly increased the risk of AF in both men and women compared to controls, with increase in AF risk being most prominent in women who had severe migraine with aura [incidence rate (IR) = 3.39, hazard ratio (HR)_adjust = 1.48, 95% confidence intervals (CI) = 1.18-1.85]. No significant association according to aura was observed in men with severe migraines (p for interaction 0.011).

    CONCLUSION Severe migraine with aura significantly increased the risk of incident AF in women, but not in men. Surveillance for incident AF and prompt lifestyle modification may be beneficial, particularly for young women suffering from severe migraine with aura.

    PubMed IF 3 순환기내과
29. 1172022

    제1저자 이찬미, 김영준 · 교신저자 박경화, 송경호

    Lee CM^*, Kim YJ^*, Jung SI, Kim SE, Park WB, Choe PG, Kim ES, Kim CJ, Choi HJ, Lee S, Lee SH, Jung Y, Bang JH, Cheon S, Kwak YG, Kang YM, Park KH^*, Song KH^*, Kim HB, Korea INfectious Diseases (KIND) Study Group

    Different clinical characteristics and impact of carbapenem-resistance on outcomes between Acinetobacter baumannii and Pseudomonas aeruginosa bacteraemia: a prospective observational study.

    Sci Rep. 2022;12(1):8527.

    Abstract

    This study aimed to evaluate the differences in clinical characteristics and impact of carbapenem resistance (CR) on outcomes between Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) bacteraemia. We prospectively identified all patients with Ab and Pa bacteraemia in 10 hospitals over 1 year. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrent bacteraemia within 30 days. We included 304 Ab and 241 Pa bacteraemia cases. CR was detected in 216 patients (71%) with Ab bacteraemia and 55 patients (23%) with Pa bacteraemia. Treatment failure was significantly higher in CR-Ab than in CR-Pa (60.6% vs. 34.5%, P = 0.001). In Ab, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. In Pa, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in Ab for treatment failure in both groups, but not in Pa bacteraemia. We demonstrated significant differences in clinical characteristics and impact of CR on clinical outcomes between Ab and Pa bacteraemia, suggesting that different treatment approaches may be needed.

    PubMed IF 4.9 감염내과
30. 1162022

    제1저자 신동우,박재원 · 교신저자 황진혁,김용훈

    Shin DW, Park J, Lee JC, Kim J, Kim YH, Hwang JH

    Multi-Phase, Contrast-Enhanced Computed Tomography-Based Radiomic Prognostic Marker of Non-Metastatic Pancreatic Ductal Adenocarcinoma.

    Cancers (Basel). 2022;14(10):cancers14102476.

    Abstract

    Background/Aim: This study investigated the predictive ability of intra-tumor enhancement on computed tomography (CT) for the outcomes of patients with pancreatic ductal adenocarcinoma (PDA). Methods: Multi-phase, contrast-enhanced CT (including unenhanced, pancreatic parenchymal phase (PPP) and portal venous phase (PVP)) images of patients diagnosed with non-metastatic PDA were analyzed to investigate prognostic factors. Results: Two hundred ninety-eight patients with PDA (159 with resectable pancreatic cancer (RPC) and 139 with borderline resectable pancreatic cancer (BRPC)/locally advanced pancreatic cancer (LAPC)) were included. The attenuation values of PDA during the PPP (94.5 vs. 60.7 HU; p <0.001) and PVP (101.5 vs. 75.5 HU; p <0.001) were higher in patients with RPC than in those with BRPC/LAPC. Well-enhanced PDA during the PPP was associated with longer overall survival in the RPC group (27.9 vs. 15.4 months; p <0.001) and the BRPC/LAPC group (22.7 vs. 13.6 months; p = 0.024). Patients with BRPC/LAPC who underwent neoadjuvant treatment and had well-enhanced PDA during the PPP were more likely to undergo resection. Although tumor size was also an independent prognostic factor, it was not correlated with intra-tumoral enhancement during the PPP. Conclusions: Intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.

    PubMed IF 4.8 소화기내과

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