SCI 발표논문

1. 39882023

   제1저자 김미현 · 교신저자 박준원

   Kim MH, Choi SR, Park JK, Lee EY, Lee EB, Park JW

   Risk of Bloodstream Infection in Patients with Systemic Lupus Erythematosus Exposed to Prolonged Medium-to-High-Dose Glucocorticoids.

   Lupus. 2023;32(5):625-632.

   Abstract

   OBJECTIVES This study aimed to investigate the incidence rate and risk factors of bloodstream infection (BSI) in patients with systemic lupus erythematosus (SLE) exposed to medium to high doses of glucocorticoids.

   METHODS This study included 1109 treatment episodes with prolonged (≥4 weeks) medium-to-high-dose glucocorticoids (≥15 mg/day prednisolone) in 612 patients with SLE for over 14 years. Clinical features regarding systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), immunosuppressant use, and laboratory results were obtained from the electronic medical database. The primary outcome of this study was the 1-year incidence of BSI. The effect of clinical factors on the outcome was investigated using a generalized estimating equation.

   RESULTS During a total of 1078.64 person-years, 30 cases of BSI occurred, with an incidence rate of 2.78 (95% confidence interval (CI) 1.88-3.97) per 100 person-years. Mortality rate of the treatment episodes with BSI was 16.7%, which was significantly higher than that in the other episodes (incidence rate ratio (IRR) 19.59, 95% CI 7.33-52.44). When the incidence rate of BSI was stratified by baseline glucocorticoid dose and SLEDAI-2K score, a higher incidence rate of BSI occurred as disease activity or baseline glucocorticoid dose increased. In the multivariable analysis, SLEDAI-2K ≥20 (adjusted IRR (aIRR) 4.66, 95% CI 2.17-10.00), initial baseline prednisolone ≥ 60 mg/day (aIRR 2.42, 95% CI 1.11-5.32), and cumulative prednisolone dose ≥15 mg/day during the previous 6 months (aIRR 2.13, 95% CI 1.03-4.40) significantly increased the risk of BSI.

   CONCLUSION In patients with SLE exposed to prolonged medium-to-high-dose glucocorticoids, the 1-year incidence rate of BSI was significantly higher than previously reported in the general patients with SLE. Severe disease activity, and high-dose glucocorticoid treatment previously or at baseline increased the risk of BSI.

   PubMed IF 1.8 류마티스내과
2. 39872023

   제1저자 한민주, Young-Ro Lee, 박태영 · 교신저자 이해영

   Han M^*, Lee YR^*, Park T^*, Ihm SH, Pyun WB, Burkard T, Cho MC, Camafort M, Yang E, Stergiou GS, Lee HY, Seo JM, Korean Society of Hypertension

   Feasibility and measurement stability of smartwatch-based cuffless blood pressure monitoring: A real-world prospective observational study.

   Hypertens Res. 2023;46(4):922-931.

   Abstract

   Cuffless wearable devices are currently being developed for long-term monitoring of blood pressure (BP) in patients with hypertension and in apparently healthy people. This study evaluated the feasibility and measurement stability of smartwatch-based cuffless BP monitoring in real-world conditions. Users of the first smartwatch-based cuffless BP monitor approved in Korea (Samsung Galaxy Watch) were invited to upload their data from using the device for 4 weeks post calibration. A total of 760 participants (mean age 43.7 ± 11.9, 80.3% men) provided 35,797 BP readings (average monitoring 22 ± 4 days [SD]; average readings 47 ± 42 per participant [median 36]). Each participant obtained 1.5 ± 1.3 readings/day and 19.7% of the participants obtained measurements every day. BP showed considerable variability, mainly depending on the day and time of the measurement. There was a trend towards higher BP levels on Mondays than on other days of the week and on workdays than in weekends. BP readings taken between 00:00 and 04:00 tended to be the lowest, whereas those between 12:00 and 16:00 the highest. The average pre-post calibration error for systolic BP (difference in 7-day BP before and after calibration), was 6.8 ± 5.6 mmHg, and was increased with higher systolic BP levels before calibration. Smartwatch-based cuffless BP monitoring is feasible for out-of-office monitoring in the real-world setting. The stability of BP measurement post calibration and the standardization and optimal time interval for recalibration need further investigation.

   PubMed IF 5 순환기내과
3. 39862023

   제1저자 이대원, 김범석 · 교신저자 임석아

   Lee DW, Keam B, Lee KS, Ahn JH, Sohn J, Ahn JS, Lee MH, Kim JH, Lee KE, Kim HJ, Kim SY, Park YH, Ock CY, Lee KH, Han SW, Kim SB, Im YH, Chung HC, Oh DY, Im SA

   A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03).

   Cancer Res Treat. 2023;55(2):523-530.

   Abstract

   PURPOSE This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.

   MATERIALS AND METHODS Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient's body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.

   RESULTS A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2-positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).

   CONCLUSION This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

   PubMed IF 4.2 혈액종양내과
4. 39852023

   제1저자 최진호, 조인래 · 교신저자 이상협

   Choi JH, Cho IR, Lee SH, Kim JS, Park N, Lee MW, Jang DK, Paik WH, Ahn DW, Ryu JK, Kim YT, Kim E, Lee J

   Efficacy and safety of novel hemostatic gel in endoscopic sphincterotomy or endoscopic papillectomy: A multicenter, randomized controlled clinical trial.

   Dig Liver Dis. 2023;55(4):527-533.

   Abstract

   BACKGROUND Endoscopists often experience obstacles with traditional hemostasis using the side-viewing duodenoscope for bleeding after endoscopic sphincterotomy (EST) or endoscopic papillectomy (EP).

   AIMS In this randomized controlled trial, we evaluated the efficacy and safety of a novel hemostatic gel for post-EST or post-EP bleeding.

   METHODS A randomized trial was conducted from November 2020 to December 2021 at two tertiary centers in South Korea. Patients who experienced bleeding immediately after EST or EP were enrolled in the study, and primary hemostasis was achieved with either the novel hemostatic gel or epinephrine spray.

   RESULTS A total of 84 patients were enrolled in this study, and 41 patients were finally analyzed in each group. Hemostatic gel was significantly superior to epinephrine spray for successful primary hemostasis (100% vs. 85.4%; P = 0.026). ). In terms of delayed bleeding, no significant difference was observed between the hemostatic gel and epinephrine spray (2.4% vs. 7.3%; P = 0.329). The mean procedural time was significantly higher for the hemostatic gel than epinephrine spray (3.23 ± 1.94 vs. 1.76 ± 0.99 min; P < 0.001), and no differences were observed in the adverse events.

   CONCLUSIONS The novel hemostatic gel is expected to achieve satisfactory results with easier hemostasis for immediate bleeding after EST or EP. (Registered in Clinical Research Information Service: KCT0005607).

   PubMed IF 4.9 소화기내과
5. 39842023

   제1저자 박남영 · 교신저자 백우현, 조재희

   Park N, Jung MK, Kim EJ, Paik WH, Cho JH

   In-stent radiofrequency ablation with uncovered metal stent placement for tumor ingrowth/overgrowth causing self-expandable metal stent occlusion in distal malignant biliary obstruction: multicenter propensity score-matched study.

   Gastrointest Endosc. 2023;97(4):694-703.e2.

   Abstract

   BACKGROUND AND AIMS In patients with unresectable malignant biliary obstruction (MBO), endoscopic drainage with a self-expandable metal stent (SEMS) is a well-established treatment, but stent patency is limited. This study aimed to evaluate the efficacy of in-stent radiofrequency ablation (IS-RFA) followed by uncovered SEMS placement for the management of occluded SEMSs.

   METHODS From 2016 to 2020, 48 patients with recurrent biliary obstruction due to tumor ingrowth or overgrowth after SEMS placement for pancreatobiliary cancer in 3 tertiary hospitals were analyzed. For distal MBO, patients in the RFA group were treated with IS-RFA and uncovered SEMS placement, and those in the control group were treated with uncovered SEMS placement alone. Patients in both groups were matched on the basis of propensity scores in a 1:1 ratio.

   RESULTS The median time to recurrent biliary obstruction (TRBO) was 117 days in the RFA group and 82.5 days in the control group (P = .029). No significant differences in median overall survival were detected between the 2 groups (170 days vs 72 days; P = .902). No significant adverse events were reported after the second SEMS placement in either group, but 2 cases of mild cholangitis were reported in the control group. Ablation was interrupted in 5 patients (35.7%) of the RFA group owing to in-stent contact, but sufficient ablative energy was delivered in the majority of the patients (92.9%) after IS-RFA was repeated in the same session.

   CONCLUSIONS IS-RFA followed by an uncovered SEMS is safe and feasible and may improve TRBO as a stent revision for occluded SEMSs in pancreatobiliary cancer.

   PubMed IF 8 소화기내과
6. 39832023

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

   Sunwoo SH, Cha MJ, Han SI, Kang H, Cho YS, Yeom DH, Park CS, Park NK, Choi SW, Kim SJ, Cha GD, Jung D, Choi S, Oh S, Nam GB, Hyeon T, Kim DH, Lee SP

   Ventricular tachyarrhythmia treatment and prevention by subthreshold stimulation with stretchable epicardial multichannel electrode array.

   Sci Adv. 2023;9(13):eadf6856.

   Abstract

   The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead is incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting in pain, myocardial damage, and recurrences of ventricular tachyarrhythmia (VTA). We present a method for VTA treatment based on subthreshold electrical stimulations using a stretchable epicardial multichannel electrode array, which does not disturb the normal contraction or electrical propagation of the ventricle. In rabbit models with myocardial infarction, the infarction was detected by mapping intracardiac electrograms with the stretchable epicardial multichannel electrode array. Then, VTAs could be terminated by sequential electrical stimuli from the epicardial multichannel electrode array beginning with low-energy subthreshold stimulations. Last, we used these subthreshold stimulations to prevent the occurrence of additional VTAs. The proposed protocol using the stretchable epicardial multichannel electrode array provides opportunities toward the development of innovative methods for painless ICD therapy.

   PubMed IF 13.9 순환기내과
7. 39822023

   제1저자 이찬미, 최평균, 강창경 · 교신저자 박완범, 박상원, 신현무

   Lee CM, Choe PG, Kang CK, Lee E, Song KH, Bang JH, Kim ES, Kim HB, Kim NJ, Kim HR, Kim Y, Lee CH, Shin HM, Park SW, Park WB, Oh MD

   Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

   Front Immunol. 2023;14:1106664.

   Abstract

   BACKGROUND Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19.

   METHODS We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively.

   RESULTS Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19.

   CONCLUSIONS Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

   PubMed IF 7 감염내과
8. 39812023

   제1저자 공성혜, 조애정 · 교신저자 윤지은, 김정희

   Kong SH, Jo AJ, Park CM, Park KI, Yun JE, Kim JH

   Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study.

   Front Endocrinol (Lausanne). 2023;14:1085252.

   Abstract

   INTRODUCTION The study aimed to demonstrate the risk factors for fractures and to develop prediction models for major osteoporotic and hip fractures in osteopenic patients using the nationwide cohort study in South Korea.

   METHODS The study was a retrospective nationwide study using the national screening program for transitional ages from the National Health Insurance Services database in Korea from 2008 to 2019. Primary outcomes were incident fracture events of major osteoporotic and hip fractures. Major osteoporotic and hip fracture events were defined as diagnostic and procedural codes. Patients were followed until the fragility fractures, death, or 2019, whichever came first.

   RESULTS All participants were 66-year-old females, with a mean body mass index was 25.0 ± 3.1 kg/m². During a median follow-up of 10.5 years, 26.9% and 6.7% of participants experienced major osteoporotic and hip fractures. In multivariate analysis, a history of fracture, chronic airway disease, falls, diabetes mellitus and cerebrovascular diseases were significant risk factors for major osteoporotic (hazard ratio [HR] 2.35 for a history of fracture; 1.17 for chronic airway disease; 1.10 for falls; 1.12 for diabetes mellitus; 1.11 for cerebrovascular disease) and hip fractures (HR 1.75 for a history of fracture; 1.54 for diabetes mellitus; 1.27 for cerebrovascular disease; 1.17 for fall; 1.15 for chronic airway disease). The performances of the prediction models were area under the receiver operating curve of 0.73 and 0.75 for major osteoporotic and hip fractures.

   CONCLUSION The study presented prediction models of major osteoporotic and hip fractures for osteopenia patients using simple clinical features.

   PubMed IF 5.7 내분비대사내과
9. 39802023

   제1저자 김휘영, 김다정 · 교신저자 조주연, 김원

   Kim HY, Kim DJ, Lee HA, Cho JY, Kim W

   Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification.

   Metabolites. 2023;13(3):metabo13030444.

   Abstract

   Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463-0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340-0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417-0.779), and tyrosine (OR = 2.743; 95% CI, 1.875-4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.

   PubMed IF 4.5 소화기내과
10. 39792023

    제1저자 조형호 · 교신저자 김나영

    Jo HH, Kim N, Jang J, Choi Y, Park J, Park YM, Ahn S, Yoon H, Shin CM, Park YS, Lee DH, Oh HJ, Lee HS, Park YS, Ahn SH, Suh YS, Park DJ, Kim HH, Kim JW, Kim JW, Lee KW, Chang W, Park JH, Lee YJ, Lee KH, Kim YH

    Impact of Body Mass Index on Survival Depending on Sex in 14,688 Patients with Gastric Cancer in a Tertiary Hospital in South Korea.

    Gut Liver. 2023;17(2):243-258.

    Abstract

    BACKGROUND/AIMS The incidence and prognosis of gastric cancer (GC) shows sex difference. This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex.

    METHODS The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital.

    RESULTS Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%). However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p<0.001). Both sexes had the worst prognosis in the underweight group (p<0.001), and the higher BMI, the better prognosis in males, but not females. Sex differences in prognosis according to BMI tended to be more prominent in males than in females in subgroup analysis of TNM stages I, II, and III and the operative treatment group.

    CONCLUSIONS GC-specific survival was affected by BMI in a sex-dependent manner. These differences may be related to genetic, and environmental, hormonal factors; body composition; and muscle mass (Trial registration number: NCT04973631).

    PubMed IF 4.1 소화기내과
11. 39782023

    제1저자 김형준 · 교신저자 이연주

    Kim HJ, Oh DK, Lim SY, Cho YJ, Park S, Suh GY, Lim CM, Lee YJ

    Antibiogram of Multidrug-Resistant Bacteria Based on Sepsis Onset Location in Korea: A Multicenter Cohort Study.

    J Korean Med Sci. 2023;38(10):e75.

    Abstract

    BACKGROUND Administration of adequate antibiotics is crucial for better outcomes in sepsis. Because no uniform tool can accurately assess the risk of multidrug-resistant (MDR) pathogens, a local antibiogram is necessary. We aimed to describe the antibiogram of MDR bacteria based on locations of sepsis onset in South Korea.

    METHODS We performed a prospective observational study of adult patients diagnosed with sepsis according to Sepsis-3 from 19 institutions (13 tertiary referral and 6 university-affiliated general hospitals) in South Korea. Patients were divided into four groups based on the respective location of sepsis onset: community, nursing home, long-term-care hospital, and hospital. Along with the antibiogram, risk factors of MDR bacteria and drug-bug match of empirical antibiotics were analyzed.

    RESULTS MDR bacteria were detected in 1,596 (22.7%) of 7,024 patients with gram-negative predominance. MDR gram-negative bacteria were more commonly detected in long-term-care hospital- (30.4%) and nursing home-acquired (26.3%) sepsis, whereas MDR gram-positive bacteria were more prevalent in hospital-acquired (10.9%) sepsis. Such findings were consistent regardless of the location and tier of hospitals throughout South Korea. Patients with long-term-care hospital-acquired sepsis had the highest risk of MDR pathogen, which was even higher than those with hospital-acquired sepsis (adjusted odds ratio, 1.42; 95% confidence interval, 1.15-1.75) after adjustment of risk factors. The drug-bug match was lowest in patients with long-term-care hospital-acquired sepsis (66.8%).

    CONCLUSION Gram-negative MDR bacteria were more common in nursing home- and long-term-care hospital-acquired sepsis, whereas gram-positive MDR bacteria were more common in hospital-acquired settings in South Korea. Patients with long-term-care hospital-acquired sepsis had the highest the risk of MDR bacteria but lowest drug-bug match of initial antibiotics. We suggest that initial antibiotics be carefully selected according to the onset location in each patient.

    PubMed IF 3.2 호흡기내과
12. 39772023

    제1저자 김규호 · 교신저자 임수

    Kim K, Moon JH, Ahn CH, Lim S

    Effect of olmesartan and amlodipine on serum angiotensin-(1-7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension.

    Diabetol Metab Syndr. 2023;15(1):43.

    Abstract

    BACKGROUND Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1-7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension.

    METHODS This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1-7) from baseline to week 24.

    RESULTS Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1-7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1-7) levels (r = - 0.252 and r = - 0.299, respectively). The change in Ang-(1-7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1-7) levels were an independent predictor of a reduction in albuminuria.

    CONCLUSIONS These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1-7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease.

    TRIAL REGISTRATION ClinicalTrials.gov NCT05189015.

    PubMed IF 4.9 내분비대사내과
13. 39762023

    제1저자 김효진, 최문기 · 교신저자 박성혁, 오국환

    Kim HJ^*, Choo M^*, Kwon HN, Yoo KD, Kim Y, Tsogbadrakh B, Kang E, Park S, Oh KH

    Metabolomic profiling of overnight peritoneal dialysis effluents predicts the peritoneal equilibration test type.

    Sci Rep. 2023;13(1):3803.

    Abstract

    This study primarily aimed to evaluate whether peritoneal equilibration test (PET) results can be predicted through the metabolomic analysis of overnight peritoneal dialysis (PD) effluents. From a total of 125 patients, overnight PD effluents on the day of the first PET after PD initiation were analyzed. A modified 4.25% dextrose PET was performed, and the PET type was categorized according to the dialysate-to-plasma creatinine ratio at the 4-h dwell time during the PET as follows: high, high average, low average, or low transporter. Nuclear magnetic resonance (NMR)-based metabolomics was used to analyze the effluents and identify the metabolites. The predictive performances derived from the orthogonal projection to latent structure discriminant analysis (OPLS-DA) modeling of the NMR spectrum were estimated by calculating the area under the curve (AUC) using receiver operating characteristic curve analysis. The OPLS-DA score plot indicated significant metabolite differences between high and low PET types. The relative concentrations of alanine and creatinine were greater in the high transporter type than in the low transporter type. The relative concentrations of glucose and lactate were greater in the low transporter type than in the high transporter type. The AUC of a composite of four metabolites was 0.975 in distinguish between high and low PET types. Measured PET results correlated well with the total NMR metabolic profile of overnight PD effluents.

    PubMed IF 4.9 신장내과
14. 39752023

    제1저자 최선미, 모요셉 · 교신저자 강혜련

    Choi SM^*, Mo Y^*, Bang JY, Ko YG, Ahn YH, Kim HY, Koh J, Yim JJ, Kang HR

    Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

    Respir Res. 2023;24(1):68.

    Abstract

    BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis.

    METHODS We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction.

    RESULTS In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C⁺ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs.

    CONCLUSIONS Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

    PubMed IF 5.7 알레르기내과
15. 39742023

    제1저자 정고은, 오소희 · 교신저자 정지봉

    Chung GE^*, Oh S^*, Ahn DW, Kim SH, Jung YJ, Kim JW, Kim BG, Lee KL, Jeong JB

    Effects of additive interactions among obesity, visceral adiposity, and sarcopenia on nonalcoholic fatty liver disease.

    Sci Rep. 2023;13(1):3628.

    Abstract

    Although the association of nonalcoholic fatty liver disease (NAFLD) with obesity or sarcopenia is known, few studies have investigated the combined effect of various body composition parameters on the risk of NAFLD. Thus, the aim of this study was to evaluate effects of interactions between various body composition parameters, including obesity, visceral adiposity, and sarcopenia, on NAFLD. Data of subjects who underwent health checkups between 2010 and December 2020 were retrospectively analyzed. Body composition parameters including appendicular skeletal muscle mass (ASM) and visceral adiposity were assessed using bioelectrical impedance analysis. Sarcopenia was defined as ASM/weight beyond two standard deviations below the gender-specific mean for healthy young adults. NAFLD was diagnosed using hepatic ultrasonography. Interaction analyses, including relative excess risk due to interaction (RERI), synergy index (SI), and attributable proportion due to interaction (AP), were performed. Among a total of 17,540 subjects (mean age: 46.7 years, 49.4% males), the prevalence of NAFLD was 35.9%. The odds ratio (OR) of interaction between obesity and visceral adiposity affecting NAFLD was 9.14 (95% CI: 8.29-10.07). The RERI was 2.63 (95% CI: 1.71-3.55), SI was 1.48 (95% CI: 1.29-1.69) and AP was 29%. The OR of interaction between obesity and sarcopenia affecting NAFLD was 8.46 (95% CI: 7.01-10.21). The RERI was 2.21 (95% CI: 0.51-3.90). SI was 1.42(95% CI: 1.11-1.82) and AP was 26%. The OR of interaction between sarcopenia and visceral adiposity affecting NAFLD was 7.25 (95% CI: 6.04-8.71), however, there was no significant additive interaction with RERI = 0.87 (95% CI: -0.76 to 2.51). Obesity, visceral adiposity, and sarcopenia were found to be positively associated with NAFLD. Obesity, visceral adiposity, and sarcopenia were found to have additive interaction effects on NAFLD.

    PubMed IF 4.9 소화기내과
16. 39732023

    제1저자 류현진 · 교신저자 오국환

    Ryu H, Hong Y, Kang E, Kang M, Kim J, Park HC, Oh YK, Chin HJ, Park SK, Jung JY, Hyun YY, Sung SA, Ahn C, Oh KH, KNOW-CKD Study Group

    Comparison of outcomes of chronic kidney disease based on etiology: a prospective cohort study from KNOW-CKD.

    Sci Rep. 2023;13(1):3570.

    Abstract

    The causes of chronic kidney disease (CKD) affects its outcomes. However, the relative risks for adverse outcomes according to specific causes of CKD is not well established. In a prospective cohort study from KNOW-CKD, a cohort was analyzed using overlap propensity score weighting methods. Patients were grouped into four categories according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), or polycystic kidney disease (PKD). From a total of 2070 patients, the hazard ratio of kidney failure, the composite of cardiovascular disease (CVD) and mortality, and the slope of the estimated glomerular filtration rate (eGFR) decline according to the cause of CKD were compared between causative groups in a pairwise manner. There were 565 cases of kidney failure and 259 cases of composite CVD and death over 6.0 years of follow-up. Patients with PKD had a significantly increased risk for kidney failure compared to those with GN [Hazard ratio (HR) 1.82], HTN (HR 2.23), and DN (HR 1.73). For the composite outcome of CVD and death, the DN group had increased risks compared to the GN (HR 2.07), and HTN (HR 1.73) groups but not to the PKD group. The adjusted annual eGFR change for the DN and PKD groups were - 3.07 and - 3.37 mL/min/1.73 m² per year, respectively, and all of these values were significantly different than those of the GN and HTN groups (- 2.16 and - 1.42 mL/min/1.73 m² per year, respectively). In summary, the risk of kidney disease progression was relatively higher in patients with PKD compared to other causes of CKD. However, the composite of CVD and death was relatively higher in patients with DN-related CKD than in those with GN- and HTN-related CKD.

    PubMed IF 4.9 신장내과
17. 39722023

    제1저자 박지혜, 안홍율 · 교신저자 이은영, 천재희

    Park J^*, An H^*, Lim J, Park IS, Kim MH, Kim JH, Kim SW, Koh YI, Lee EY, Cheon JH

    Interplay between chronic inflammation and clonal haematopoiesis of indeterminate potential in Behçet's disease.

    Arthritis Res Ther. 2023;25(1):33.

    Abstract

    BACKGROUND Clonal haematopoiesis of indeterminate potential (CHIP) is a predisposition to haematological malignancy whose relationship with chronic inflammatory diseases, such as cardiovascular diseases, has been highlighted. Here, we aimed to investigate the CHIP emergence rate and its association with inflammatory markers in Behçet's disease (BD).

    METHODS We performed targeted next-generation sequencing to detect the presence of CHIP using peripheral blood cells from 117 BD patients and 5004 healthy controls between March 2009 and September 2021 and analysed the association between CHIP and inflammatory markers.

    RESULTS CHIP was detected in 13.9% of patients in the control group and 11.1% of patients in the BD group, indicating no significant intergroup difference. Among the BD patients of our cohort, five variants (DNMT3A, TET2, ASXL1, STAG2, and IDH2) were detected. DNMT3A mutations were the most common, followed by TET2 mutations. CHIP carriers with BD had a higher serum platelet count, erythrocyte sedimentation rate, and C-reactive protein level; older age; and lower serum albumin level at diagnosis than non-CHIP carriers with BD. However, the significant association between inflammatory markers and CHIP disappeared after the adjustment for various variables, including age. Moreover, CHIP was not an independent risk factor for poor clinical outcomes in patients with BD.

    CONCLUSIONS Although BD patients did not have higher CHIP emergence rates than the general population, older age and degree of inflammation in BD were associated with CHIP emergence.

    PubMed IF 5.4 류마티스내과
18. 39712023

    제1저자 박우찬, 변자민 · 교신저자 고영일, 윤성수

    Park W, Byun JM, Hong J, Kim I, Shin DY, Park S, Koh Y, Yoon SS

    Comparison of the effect of DLI according to cell sources in relapsed AML after allogeneic stem cell transplantation.

    Ann Hematol. 2023;102(3):629-639.

    Abstract

    For relapsed acute myeloid leukemia (AML) patients who received allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion (DLI) is an effective therapy. However, the cell source of DLI remains a topic of debate. In this study, we aimed to compare the efficacy and safety of G-CSF mobilized cells (G-DLI) with conventionally collected DLI (C-DLI). A total of 81 patients (50 C-DLI vs. 31 G-DLI) were assessed for clinical outcomes. There were no statistically significant differences in the baseline characteristics between the two groups including AML risk, donor types, interval from relapse to DLI, and infused CD3⁺ cell count. Although not statistically significant, complete remission (CR) and chimerism conversion rates were higher in G-DLI than in C-DLI: 51.6% vs. 28.0%, P = 0.057 and 42.3% vs. 28.2%, P = 0.363, respectively. There was no difference in acute graft-versus-host disease (GVHD) incidence and severity of acute GVHD between the two groups. The median overall survival (OS) of the G-DLI and C-DLI groups was 139 days and 106 days, respectively (P = 0.58). In conclusion, G-DLI appears to be a safe and an equally efficacious substitute for C-DLI, which is more readily available.

    PubMed IF 2.3 혈액종양내과
19. 39702023

    제1저자 안현진, 이소령 · 교신저자 최의근

    Ahn HJ, Lee SR, Choi EK, Bae NY, Ahn HJ, Kwon S, Lee SW, Han KD, Oh S, Lip GYH

    Increased risk of incident atrial fibrillation in young adults with mental disorders: A nationwide population-based study.

    Heart Rhythm. 2023;20(3):365-373.

    Abstract

    BACKGROUND Mental disorders and cardiovascular diseases are closely related. However, a paucity of information on the risk of incident atrial fibrillation (AF) in patients with mental disorders exists.

    OBJECTIVE We aimed to assess the association between mental disorders and the risk of AF, particularly in young adults.

    METHODS Using the Korean National Health Insurance Database between 2009 and 2012, we identified adults aged 20-39 years without a history of AF and who have been diagnosed with mental disorders. Mental disorders were defined as having one of the following diagnoses: depression, insomnia, anxiety disorder, bipolar disorder, or schizophrenia. The primary outcome was new-onset AF during follow-up.

    RESULTS A total of 6,576,582 subjects (mean age 30.9 ± 5.0 years; 3,919,339 [59.6%] men) were included. Among the total population, 10% had mental disorders. During the follow-up period, 8932 incident AF events occurred. Patients with mental disorders showed a higher AF incidence than did those without (25.4 per 100,000 person-years vs 17.7 per 100,000 person-years). After multivariable adjustment, mental disorders were associated with a significantly higher risk of AF (adjusted hazard ratio 1.526; 95% confidence interval 1.436-1.621). Patients with bipolar disorder or schizophrenia had a 2-fold higher risk of AF and those with depression, insomnia, and anxiety disorder had a 1.5- to 1.7-fold higher risk of AF than did those without mental disorders.

    CONCLUSION Young adults diagnosed with mental disorders have a higher risk of incident AF. Awareness for AF in high-risk populations should thus be considered.

    PubMed IF 7 순환기내과
20. 39692023

    제1저자 나윤숙 · 교신저자 조수정

    Na YS, Kim SG, Cho SJ

    Risk assessment of metachronous gastric cancer development using OLGA and OLGIM systems after endoscopic submucosal dissection for early gastric cancer: a long-term follow-up study.

    Gastric Cancer. 2023;26(2):298-306.

    Abstract

    BACKGROUND Metachronous gastric cancer (MGC) may develop in patients undergoing curative endoscopic submucosal dissection for early gastric cancer. As gastritis and intestinal metaplasia are notable precursors to gastric cancer, we assessed MGC risk using the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM) systems.

    METHODS This retrospective cohort study classified the OLGA and OLGIM stages for 916 patients who had undergone endoscopic submucosal dissection for early gastric cancer between 2005 and 2015. MGC development was followed up until 2020 and risk factors were evaluated using the Cox proportional hazards regression analysis.

    RESULTS During a median follow-up of 94 months, MGC developed in 120 subjects. OLGA stages II ~ IV were significantly associated with increased MGC risk (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.05-3.19; HR 2.31, 95% CI 1.22-4.38; HR 2.36, 95% CI 1.16-4.78) in multivariable analysis, even after adjusting for the well-known positive predictor of Helicobacter pylori eradication. OLGIM stages II ~ IV also showed significant association (HR 2.86, 95% CI 1.29-6.54; HR 2.94, 95% CI 1.34-6.95; HR 3.64, 95% CI 1.60-8.29). 5-year cumulative incidence increased with each stage. Helicobacter pylori-eradicated patients with OLGIM stages 0 ~ II had significantly less MGC than non-eradicated patients (4.5% vs 11.8%, p = 0.022), which was not observed with OLGIM stages III ~ IV.

    CONCLUSIONS High OLGA and OLGIM stages are independent risk factors for metachronous gastric cancer, with the OLGIM staging system being a better predictor. Patients with OLGIM stages 0 ~ II are a subgroup that may benefit more from Helicobacter pylori eradication.

    PubMed IF 6.1 소화기내과
21. 39682023

    제1저자 Rismiati H · 교신저자 이해영

    Rismiati H, Lee KS, Kang J, Cho HJ, Lee HY

    The role of discharge checklist in guideline-directed medical therapy for heart failure patients.

    Korean J Intern Med. 2023;38(2):195-206.

    Abstract

    BACKGROUND/AIMS Initiation of guideline-directed medical therapy (GDMT) during hospitalization is recommended for patients with heart failure (HF). However, GDMT is underutilized in real-world practice. This study evaluated the role of a discharge checklist on GDMT.

    METHODS This was a single-center, observational study. The study included all patients hospitalized for HF between 2021 and 2022. The clinical data were retrieved from the electronic medical records and discharge checklist published by the Korean Society of Heart Failure. The adequacy of GDMT prescriptions was evaluated in three ways: the total number of GDMT drug classes and two types of adequacy scores. The primary endpoint was the incidence of all-cause mortality or rehospitalization due to HF within 2 months of discharge.

    RESULTS Overall, the checklist was completed by 244 patients (checklist group) and was not completed in 171 patients (non-checklist group). The baseline characteristics were comparable between two groups. At discharge, a higher proportion of patients in the checklist group received GDMT than in the non-checklist group (67.6% vs. 50.9%, p = 0.001). The incidence of primary endpoint was lower in the checklist group compared to the non-checklist group (5.3% vs. 11.7%, p = 0.018). The use of the discharge checklist was associated with significantly lower risk of death and rehospitalization in the multivariable analysis (hazard ratio, 0.45; 95% confidence interval, 0.23-0.92; p = 0.028).

    CONCLUSION Discharge checklist usage is a simple but effective strategy for GDMT initiation during hospitalization. The discharge checklist was associated with better outcome in patients with HF.

    PubMed IF 2.2 순환기내과
22. 39672023

    제1저자 김수환, 김은란 · 교신저자 장현주

    Kim SH, Kim ER, Park JJ, Kim ES, Goong HJ, Kim KO, Nam JH, Park Y, Lee SP, Jang HJ, KSGE, Research Group of Capsule Endoscopy and Artificial Intelligence in Imaging

    Cancer risk in patients with Peutz-Jeghers syndrome in Korea: a retrospective multi-center study.

    Korean J Intern Med. 2023;38(2):176-185.

    Abstract

    BACKGROUND/AIMS There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate.

    METHODS Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method.

    RESULTS A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60.

    CONCLUSION PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.

    PubMed IF 2.2 소화기내과
23. 39662023

    제1저자 이재민, 한경도 · 교신저자 이상협, 박진명

    Lee JM, Han KD, Lee SH, Park JM, Park N, Jeon H, Kim HJ, Ryu JK, Kim YT

    The association between smoking, changes in smoking behavior, and acute pancreatitis: A population-based cohort study in Korea.

    J Gastroenterol Hepatol. 2023;38(3):451-459.

    Abstract

    BACKGROUND AND AIMS In the Asian population, existing studies regarding the association between smoking and acute pancreatitis are few in number. The aim of this study was to investigate the incidence of acute pancreatitis according to smoking habits and smoking habit changes of the Korean population.

    METHODS We used clinical data from individuals (aged 20 years or older) who received health examinations arranged by the Korean National Health Insurance Service in 2009 (n = 4 238 822) or in 2009 and 2011 (n = 2 617 306). The incidence of acute pancreatitis was analyzed according to smoking status or smoking habit change reported by individuals during their health examination. Newly diagnosed acute pancreatitis was identified using claims data from baseline to the date of diagnosis or until December 31, 2018.

    RESULTS The risk of acute pancreatitis was significantly higher in current smokers compared with never-smokers regardless of age or sex. The adjusted hazard ratio (HR) of acute pancreatitis in current smokers increased according to the amount of smoking (HR 1.28; 95% confidence interval [CI], 1.12-1.45 in <10 cigarettes/day, HR 1.4; CI, 1.3-1.52 in 10-19 cigarettes/day, HR 1.66; CI, 1.55-1.78 in ≥20 cigarettes/day). The adjusted HR of acute pancreatitis in continuous smokers was 1.66 (CI, 1.53-1.8) compared with never-smokers and was higher than smokers who quit smoking (HR 1.34; CI, 1.17-1.54).

    CONCLUSIONS In this Korean population-based cohort study, smoking increased the incidence of acute pancreatitis in a dose-dependent manner, and smoking cessation helped decrease the incidence of acute pancreatitis.

    PubMed IF 3.5 소화기내과
24. 39652023

    제1저자 김학령 · 교신저자 김학령

    Kim HL, Joh HS, Lim WH, Seo JB, Kim SH, Zo JH, Kim MA

    One-month changes in blood pressure-adjusted pulse wave velocity for predicting long-term cardiovascular outcomes in patients undergoing percutaneous coronary intervention.

    J Hypertens. 2023;41(3):437-442.

    Abstract

    OBJECTIVE The prognostic value of changes in arterial stiffness has not been well evaluated. This study was conducted to investigate whether the change in arterial stiffness one month after percutaneous coronary intervention (PCI) affects the long-term cardiovascular prognosis.

    METHODS A total of 405 patients (mean age, 62.0 ± 11.0 years; female sex, 27.7%) who underwent PCI with drug-eluting stent (DES) implantation was prospectively enrolled. The measurement of brachial-ankle pulse wave velocity (baPWV) was taken in all the study patient at the time of admission for index PCI. Major adverse cardiovascular event (MACE), a composite of cardiac death, nonfatal myocardial infarction, coronary revascularization and ischemic stroke, was assessed during clinical follow-up after index PCI.

    RESULTS During the median follow-up duration of 5.3 years (interquartile range. 2.9-7.9 years), there was 65 MACE (16.0%). There was no significant difference in clinical characteristics between patients with and without MACE except for higher prevalence of triple vessel disease in those with MACE. The baPWV value decreased at one month after index PCI (1560 ± 305 to 1530 ± 318 cm, P < 0.001). In multivariable cox regression analysis, the change of baPWV at one month was not associated with MACE occurrence ( P > 0.05). However, the change in systolic blood pressure (SBP)-adjusted baPWV (baPWV/SBP) at one month (increased vs . decreased) was significantly associated with MACE occurrence even after controlling for potential confounders (hazard ratio, 2.25; 95% confidence interval, 1.37-3.69; P = 0.001).

    CONCLUSION The baPWV/SBP change at one month was associated with long-term MACE in patients undergoing DES implantation. The results of this study suggest that baPWV/SBP changes at one month may be helpful in risk stratification of patients at a high coronary risk.

    PubMed IF 5.6 내분비대사내과
25. 39642023

    제1저자 이소령 · 교신저자 최의근

    Lee SR, Choi EK, Park SH, Han KD, Oh S, Abdelgawwad K, Lip GYH

    Renal outcomes of rivaroxaban compared with warfarin in Asian patients with nonvalvular atrial fibrillation: A nationwide population-based cohort study.

    Front Cardiovasc Med. 2023;10:1040834.

    Abstract

    BACKGROUND Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians.

    OBJECTIVES To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients.

    METHODS Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m² at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population.

    RESULTS We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA₂DS₂-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23-2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300-0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m², rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713-0.892, p < 0.001).

    CONCLUSION Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF.

    PubMed IF 3 순환기내과
26. 39632023

    제1저자 이선영, 선충현 · 교신저자 변자민, 윤홍식

    Lee S^*, Sun CH^*, Jang H, Kim D, Yoon SS, Koh Y, Na SC, Cho SI, Kim MJ, Seong MW, Byun JM, Yun H

    ITDetect: a method to detect internal tandem duplication of FMS-like tyrosine kinase (FLT3) from next-generation sequencing data with high sensitivity and clinical application.

    BMC Bioinformatics. 2023;24(1):62.

    Abstract

    Internal tandem duplication (ITD) of the FMS-like tyrosine kinase (FLT3) gene is associated with poor clinical outcomes in patients with acute myeloid leukemia. Although recent methods for detecting FLT3-ITD from next-generation sequencing (NGS) data have replaced traditional ITD detection approaches such as conventional PCR or fragment analysis, their use in the clinical field is still limited and requires further information. Here, we introduce ITDetect, an efficient FLT3-ITD detection approach that uses NGS data. Our proposed method allows for more precise detection and provides more detailed information than existing in silico methods. Further, it enables FLT3-ITD detection from exome sequencing or targeted panel sequencing data, thereby improving its clinical application. We validated the performance of ITDetect using NGS-based and experimental ITD detection methods and successfully demonstrated that ITDetect provides the highest concordance with the experimental methods. The program and data underlying this study are available in a public repository.

    PubMed IF 4.4 혈액종양내과
27. 39622023

    제1저자 최진아 · 교신저자 김나영

    Choi J, Kim N, Nam RH, Kim JW, Song CH, Na HY, Kang GH

    Influence of location-dependent sex difference on PD-L1, MMR/MSI, and EGFR in colorectal carcinogenesis.

    PLoS One. 2023;18(2):e0282017.

    Abstract

    BACKGROUND The incidence and mortality rates of colorectal cancer (CRC) has been reported to be strongly associated to sex/gender difference. CRC shows sexual dimorphism, and sex hormones have been shown to affect the tumor immune microenvironment. This study aimed to investigate location-dependent sex differences in tumorigenic molecular characteristics in patients with colorectal tumors, including adenoma and CRC.

    METHODS A total of 231 participants, including 138 patients with CRC, 55 patients with colorectal adenoma, and 38 healthy controls, were recruited between 2015 and 2021 at Seoul National University Bundang Hospital. All patients underwent colonoscopy and acquired tumor lesion samples were further analyzed for programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) expression, deficient mismatch repair (dMMR), and microsatellite instability (MSI) status. This study was registered with ClinicalTrial.gov, number NCT05638542.

    RESULTS The average of combined positive score (CPS) was higher in serrated lesions and polyps (lesions/polyps) compared to conventional adenomas (5.73 and 1.41, respectively, P < 0.001). No significant correlation was found between sex and PD-L1 expression within the groups, regardless of histopathological diagnosis. In multivariate analysis where each sex was further stratified by tumor location due to their interaction in CRC, PD-L1 expression was inversely correlated with males having proximal CRC with a CPS cutoff of 1 (Odds ratio (OR) 0.28, P = 0.034). Females with proximal CRC showed a significant association with dMMR/MSI-high (OR 14.93, P = 0.032) and high EGFR expression (OR 4.17, P = 0.017).

    CONCLUSION Sex and tumor location influenced molecular features such as PD-L1, MMR/MSI status and EGFR expression in CRC, suggesting a possible underlying mechanism of sex-specific colorectal carcinogenesis.

    PubMed IF 2.8 소화기내과
28. 39612023

    제1저자 양한모, 이주은 · 교신저자 김효수

    Yang HM^*, Lee JE^*, Kim JY, You J, Kim J, Lee HS, Yoo HM, Kong MG, Han JK, Cho HJ, Park KW, Kang HJ, Koo BK, Park YB, Kim HS

    Identification of cell-biologic mechanisms of coronary artery spasm and its ex vivo diagnosis using peripheral blood-derived iPSCs.

    Biomater Res. 2023;27(1):16.

    Abstract

    BACKGROUND Although vasospastic angina (VSA) is known to be caused by coronary artery spasm, no study has fully elucidated the exact underlying mechanism. Moreover, in order to confirm VSA, patients should undergo invasive coronary angiography with spasm provocation test. Herein, we investigated the pathophysiology of VSA using peripheral blood-derived induced pluripotent stem cells (iPSCs) and developed an ex vivo diagnostic method for VSA.

    METHODS AND RESULTS With 10 mL of peripheral blood from patients with VSA, we generated iPSCs and differentiated these iPSCs into target cells. As compared with vascular smooth muscle cells (VSMCs) differentiated from iPSCs of normal subjects with negative provocation test, VSA patient-specific iPSCs-derived VSMCs showed very strong contraction in response to stimulants. Moreover, VSA patient-specific VSMCs exhibited a significant increase in stimulation-induced intracellular calcium efflux (Changes in the relative fluorescence unit [ΔF/F]; Control group vs. VSA group, 2.89 ± 0.34 vs. 10.32 ± 0.51, p < 0.01), and exclusively induced a secondary or tertiary peak of calcium efflux, suggesting that those findings could be diagnostic cut-off values for VSA. The observed hyperreactivity of VSA patient-specific VSMCs were caused by the upregulation of sarco/endoplasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) due to its enhanced small ubiquitin-related modifier (SUMO)ylation. This increased activity of SERCA2a was reversed by treatment with ginkgolic acid, an inhibitor of SUMOylated E1 molecules (pi/µg protein; VSA group vs. VSA + ginkgolic acid, 52.36 ± 0.71 vs. 31.93 ± 1.13, p < 0.01).

    CONCLUSIONS Our findings showed that abnormal calcium handling in sarco/endoplasmic reticulum could be induced by the enhanced SERCA2a activity in patients with VSA, leading to spasm. Such novel mechanisms of coronary artery spasm could be useful for drug development and diagnosis of VSA.

    PubMed IF 9.8 순환기내과
29. 39602023

    제1저자 이현우, 양현준 · 교신저자 진광남

    Lee HW^*, Yang HJ^*, Kim H, Kim UH, Kim DH, Yoon SH, Ham SY, Nam BD, Chae KJ, Lee D, Yoo JY, Bak SH, Kim JY, Kim JH, Kim KB, Jung JI, Lim JK, Lee JE, Chung MJ, Lee YK, Kim YS, Lee SM, Kwon W, Park CM, Kim YH, Jeong YJ, Jin KN, Goo JM

    Deep Learning With Chest Radiographs for Making Prognoses in Patients With COVID-19: Retrospective Cohort Study.

    J Med Internet Res. 2023;25:e42717.

    Abstract

    BACKGROUND An artificial intelligence (AI) model using chest radiography (CXR) may provide good performance in making prognoses for COVID-19.

    OBJECTIVE We aimed to develop and validate a prediction model using CXR based on an AI model and clinical variables to predict clinical outcomes in patients with COVID-19.

    METHODS This retrospective longitudinal study included patients hospitalized for COVID-19 at multiple COVID-19 medical centers between February 2020 and October 2020. Patients at Boramae Medical Center were randomly classified into training, validation, and internal testing sets (at a ratio of 8:1:1, respectively). An AI model using initial CXR images as input, a logistic regression model using clinical information, and a combined model using the output of the AI model (as CXR score) and clinical information were developed and trained to predict hospital length of stay (LOS) ≤2 weeks, need for oxygen supplementation, and acute respiratory distress syndrome (ARDS). The models were externally validated in the Korean Imaging Cohort of COVID-19 data set for discrimination and calibration.

    RESULTS The AI model using CXR and the logistic regression model using clinical variables were suboptimal to predict hospital LOS ≤2 weeks or the need for oxygen supplementation but performed acceptably in the prediction of ARDS (AI model area under the curve [AUC] 0.782, 95% CI 0.720-0.845; logistic regression model AUC 0.878, 95% CI 0.838-0.919). The combined model performed better in predicting the need for oxygen supplementation (AUC 0.704, 95% CI 0.646-0.762) and ARDS (AUC 0.890, 95% CI 0.853-0.928) compared to the CXR score alone. Both the AI and combined models showed good calibration for predicting ARDS (P=.079 and P=.859).

    CONCLUSIONS The combined prediction model, comprising the CXR score and clinical information, was externally validated as having acceptable performance in predicting severe illness and excellent performance in predicting ARDS in patients with COVID-19.

    PubMed IF 8.2 호흡기내과
30. 39592023

    제1저자 조인래 · 교신저자 이상협

    Cho IR, Lee SH, Choi JH, Park N, Lee MW, Kim JS, Jeong S, Lee DH, Jeong TW, Ki BY, Paik WH, Ryu JK, Kim YT

    Development of novel biliary metal stent with coil-spring structure and its application in vivo swine biliary stricture model.

    Front Oncol. 2023;13:1103217.

    Abstract

    BACKGROUND As of date, endoscopic biliary stenting with plastic stent (PS) and self-expandable metal stent (SEMS) have been widely used for the palliation of biliary tract strictures. However, these two stents have several limitations regarding the management of biliary strictures caused by intrahepatic and hilar cholangiocarcinoma. PS has short patency and also risks bile duct injury and bowel perforation. SEMS is difficult to revise when occluded by tumor overgrowth. To compensate for such shortcomings, we developed a novel biliary metal stent with coil-spring structure. The aim of this study was to investigate the feasibility and efficacy of the novel stent in a swine model.

    METHODS The biliary stricture model was prepared in six mini-pigs using endobiliary radiofrequency ablation. Conventional PS (n=2) and novel stents (n=4) were deployed endoscopically. Technical success was defined as successful stent placement and clinical success was defined as >50% reduction of serum bilirubin level. Adverse events, stent migration, and endoscopic removability for one month after stenting were also assessed.

    RESULTS The biliary stricture was successfully created in all animals. The technical success rate was 100 %, and the clinical success rate was 50% in the PS group and 75% in the novel stent group. In the novel stent group, the median pre- and post-treatment serum bilirubin levels were 3.94 and 0.3 mg/dL. Stent migration occurred in two pigs and two stents were removed by endoscopy. There was no stent-related mortality.

    CONCLUSIONS The newly designed biliary metal stent was feasible and effective in a swine biliary stricture model. Further studies are needed to verify the usefulness of the novel stent in the management of biliary strictures.

    PubMed IF 3.4 소화기내과

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