SCI 발표논문
2022년 265편
- 852022
제1저자 이현정 · 교신저자 김형관
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Impact of diabetes mellitus on the outcomes of subjects with hypertrophic cardiomyopathy: A nationwide cohort study.Diabetes Res Clin Pract. 2022;186:109838.
PubMed IF 4.6 순환기내과Abstract
AIMS Diabetes mellitus (DM) often coexists in elderly hypertrophic cardiomyopathy (HCM) patients; however, its impact on clinical outcomes is unclear.
METHODS We compared clinical outcomes according to the presence of DM in a nationwide HCM cohort.
RESULTS In 9,883 HCM subjects (mean age 58.5 ± 13.1, men 71.7%), 1,327 (13.4%) had DM. During follow-up (mean 5.9 ± 2.5 years), end-stage renal disease (ESRD) progression, coronary events (myocardial infarction, coronary revascularization), heart failure (HF), cardiovascular mortality, and all-cause mortality occurred in 80 (0.8%), 365 (3.7%), 1,558 (15.8%), 354 (3.6%), and 877 (8.9%) subjects, respectively. DM HCM subjects had significantly higher risks of ESRD progression (HR 3.49, 95% CI 2.20-5.54) and HF (HR 1.15, 95% CI 1.01-1.32) compared to non-DM HCM subjects, independent of age, sex, ischemic heart disease, atrial fibrillation, and other comorbidities. There was a tendency for greater risk of ESRD progression, HF, and all-cause death in subjects with more advanced stage of DM (p-for-trend < 0.05 for all). Insulin-treated DM was associated with the highest risk.
CONCLUSIONS DM HCM subjects have higher risk of ESRD progression and HF. Considering the extended life expectancy of HCM and increasing number of elderly HCM subjects, active surveillance and management of DM-related outcomes should be highlighted.
- 842022
제1저자 송미경 · 교신저자 김형관, 배은정
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Relationship between life-threatening events and electromechanical window in patients with hypertrophic cardiomyopathy: A novel parameter for risk stratification of sudden cardiac death.Heart Rhythm. 2022;19(4):588-594.
PubMed IF 7 순환기내과Abstract
BACKGROUND Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young individuals, largely due to ventricular arrhythmias, which may be associated with electrical disturbances from pathologic myocardial changes.
OBJECTIVES The purpose of this study was to investigate electromechanical mismatches in patients with HCM and the relationship between electromechanical mismatches and life-threatening events (LTEs).
METHODS We performed a retrospective review of patients (age 1-80 years) diagnosed with HCM. Electromechanical mismatch was evaluated using the electromechanical window (EMW), defined as the interval between the Q wave and aortic valve closure minus the QT interval.
RESULTS We enrolled 458 patients (mean age 52.4 ± 18.8 years). When the EMW of patients with HCM was compared to that of age-/sex-matched normal controls, EMW was more negative in patients with HCM than in normal controls (-51 ± 35 ms vs 7 ± 19 ms; P <.001). LTEs occurred in 25 patients (5.5%). EMW was more negative in patients with LTEs than in those without (-77 ± 33 ms vs -42 ± 31 ms; P <.001). The cutoff value of EMW to identify patients with LTEs was -54 ms, and the c-index of EMW was 0.726. EMW less than -54 ms, unexplained syncope, pediatric onset, and extreme left ventricular hypertrophy were significant risk factors for LTEs on multivariate analysis.
CONCLUSION EMW was more negative in patients with HCM than in healthy individuals, and profound EMW negativity was an independent risk factor for LTEs. EMW can be useful for risk stratification of SCD in patients with HCM.
- 832022
제1저자 임수 · 교신저자 Ferrannini E
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Initial combination of metformin, sitagliptin, and empagliflozin in drug-naïve patients with type 2 diabetes: Safety and metabolic effects.Diabetes Obes Metab. 2022;24(4):757-762.
- 822022
제1저자 Subbiah V · 교신저자 김범석
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Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study.Ann Oncol. 2022;33(4):406-415.
PubMed IF 80.4 혈액종양내과Abstract
BACKGROUND Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with ∼4 years of additional study follow-up.
PATIENTS AND METHODS ROAR (NCT02034110) is an open-label, nonrandomized, phase II basket study evaluating dabrafenib plus trametinib in BRAF V600E-mutant rare cancers. The ATC cohort comprised 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS At data cutoff (14 September 2020), median follow-up was 11.1 months (range, 0.9-76.6 months). The investigator-assessed ORR was 56% (95% confidence interval, 38.1% to 72.1%), including three complete responses; the 12-month DOR rate was 50%. Median PFS and OS were 6.7 and 14.5 months, respectively. The respective 12-month PFS and OS rates were 43.2% and 51.7%, and the 24-month OS rate was 31.5%. No new safety signals were identified with additional follow-up, and adverse events were consistent with the established tolerability of dabrafenib plus trametinib.
CONCLUSIONS These updated results confirm the substantial clinical benefit and manageable toxicity of dabrafenib plus trametinib in BRAF V600E-mutant ATC. Dabrafenib plus trametinib notably improved long-term survival and represents a meaningful treatment option for this rare, aggressive cancer.
- 812022
제1저자 강한빛, 방지영 · 교신저자 김혜영, 강혜련
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Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation.Clin Exp Allergy. 2022;52(4):518-529.
PubMed IF 5 알레르기내과Abstract
BACKGROUND Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation.
METHODS Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH-S) treated with or without A. lwoffii before IL-13 stimulation were analysed by quantitative RT-PCR.
RESULTS In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+ M2a and CD11b+ M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+ M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down-regulated the expression of M2 markers related but up-regulated those related to M2b macrophages.
CONCLUSIONS AND CLINICAL RELEVANCE Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.
- 802022
제1저자 기유정, 이봉기 · 교신저자 박경우
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Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI.Korean Circ J. 2022;52(4):304-319.
PubMed IF 3.4 순환기내과Abstract
BACKGROUND AND OBJECTIVES De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-ST-segment elevation ACS (NSTE-ACS).
METHODS This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year.
RESULTS Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48-0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48-2.26; p=0.915; p for interaction=0.271).
CONCLUSIONS Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.
- 792022
제1저자 김정선, 서경진 · 교신저자 이대원, 임석아
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A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer.Cancer Res Treat. 2022;54(2):488-496.
PubMed IF 4.2 혈액종양내과Abstract
PURPOSE We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
MATERIALS AND METHODS This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
RESULTS A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2-positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
CONCLUSION This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.
- 782022
제1저자 서혜림 · 교신저자 오도연
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Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer.Cancer Res Treat. 2022;54(2):541-553.
PubMed IF 4.2 혈액종양내과Abstract
PURPOSE Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
MATERIALS AND METHODS We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
RESULTS In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
CONCLUSION This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.
- 772022
제1저자 김유정, Hiratsuka Y · 교신저자 서상연
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A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients.Cancer Res Treat. 2022;54(2):621-629.
PubMed IF 4.2 혈액종양내과Abstract
PURPOSE We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.
MATERIALS AND METHODS In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.
RESULTS The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88.
CONCLUSION The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.
- 762022
제1저자 이동현 · 교신저자 김원
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A sequential approach using the age-adjusted fibrosis-4 index and vibration-controlled transient elastography to detect advanced fibrosis in Korean patients with non-alcoholic fatty liver disease.Aliment Pharmacol Ther. 2022;55(8):994-1007.
PubMed IF 6.8 소화기내과Abstract
BACKGROUND AND AIMS Vibration-controlled transient elastography (VCTE) has shown good diagnostic performance in predicting fibrosis stages in patients with non-alcoholic fatty liver disease (NAFLD). However, an optimal diagnostic approach to detect advanced fibrosis in patients with NAFLD has not been established.
APPROACH AND RESULTS We prospectively collected data from 539 subjects who underwent liver biopsy at a single centre between January 2014 and December 2019. Diagnostic performance was estimated using the area under the receiver-operating characteristic curve (AUROC). Several models combining the fibrosis 4 index (FIB-4) score and liver stiffness measurement (LSM) were analysed to reduce the need for unnecessary liver biopsies. We observed significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) in 173 (32.1%), 74 (13.7%) and 46 subjects (8.5%), respectively. The AUROCs (95% CI) for LSMs to diagnose ≥F2, ≥F3 and F4 were 0.82 (0.78-0.85), 0.92 (0.89-0.94) and 0.95 (0.93-0.97), respectively. Optimal LSM cut-off values were 6.7 (≥F2), 8.3 (≥F3) and 9.8 (F4) kPa. LSMs were affected by waist circumference, serum albumin and fibrosis stage (R2 = 0.315). Abdominal obesity, elevated transaminase, diabetes mellitus and high IQR/Median were associated with the discordance of ≥2 fibrosis stages between LSMs and histologic data. The sequential use of the age-adjusted FIB-4 and LSMs yielded the least uncertainty (5.3%) in classifying disease severity with the highest diagnostic accuracy (81%) among a variety of non-invasive test combinations.
CONCLUSIONS The sequential approach of age-adjusted FIB-4 and VCTE could represent a practical diagnostic strategy to detect advanced fibrosis in NAFLD (ClinicalTrials.gov #NCT02206841).
- 752022
제1저자 박지석 · 교신저자 조구영
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Feasibility of the contraction-relaxation coupling index in outcome prediction for patients with acute heart failure.ESC Heart Fail. 2022;9(2):1228-1238.
PubMed IF 3.8 순환기내과Abstract
AIMS Contemporary heart failure (HF) classification based on left ventricular (LV) ejection fraction is limited for comprehensive assessment of LV function. We aimed to validate the feasibility of the contraction-relaxation coupling index (CRC) as a novel predictor for clinical outcomes in patients with acute HF.
METHODS AND RESULTS A total of 3266 consecutive patients (median age: 74 years, 53% male) with acute HF were included. CRC was defined as the ratio of end-diastolic elastance (LV end-diastolic pressure/stroke volume) to end-systolic elastance (LV end-systolic pressure/end-systolic volume). The risk for 1 year composite endpoint of all-cause mortality or hospitalization for HF (primary outcome) was compared after group categorization using CRC tertiles (Tertile 1: CRC ≤ 0.17, Tertile 2: 0.17 < CRC ≤ 0.40, and Tertile 3: 0.40 < CRC). The median CRC was 0.3 and the median LVEF was 42%. After adjustment for clinical and echocardiographic covariates, CRC was an independent predictor for the primary outcome (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.47-2.07 in Tertile 3 and HR: 1.21, 95% CI: 1.02-1.44 in Tertile 2 when compared with Tertile 1; HR: 1.23, 95% CI: 1.14-1.33 per one-standard deviation increment in CRC). The risk model with CRC showed better performance in outcome discrimination than the model with LVEF (c-statistic 0.701 vs. 0.699, P for difference <0.001). Patients with higher CRC demonstrated better effectiveness of neurohormonal blockade for the primary outcome compared with those with lower CRC (HR: 0.38, 95% CI: 0.29-0.50 in Tertile 3 and HR: 0.67, 95% CI: 0.52-0.89 in Tertile 1).
CONCLUSIONS CRC provides an independent value for outcome prediction in patients with acute HF. CRC would be a sensitive indicator for prognostic risk stratification and for predicting treatment response to the neurohormonal blockade.
- 742022
제1저자 이승훈 · 교신저자 고정민, 김정희
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Indices of ACTH-stimulated adrenal venous sampling as predictors of postsurgical outcomes in primary aldosteronism.Clin Endocrinol (Oxf). 2022;96(4):521-530.
PubMed IF 2.8 내분비대사내과Abstract
OBJECTIVE This study aimed to investigate the impact of indices of adrenal venous sampling (AVS) on postsurgical outcomes in patients with primary aldosteronism (PA).
DESIGN AND PATIENTS This retrospective study determined biochemical and clinical outcomes based on ACTH-stimulated AVS parameters (lateralisation index [LI], contralateral ratio [CLR], and ipsilateral ratio [ILR]) in 251 patients with PA at 3 months after surgery.
RESULTS Modified complete biochemical success was achieved in 8 of 12 (66.7%) patients with LI = 3-4, 39 of 47 (83.0%) with LI = 4-10, and 155 of 169 (91.7%) with LI ≥ 10 (p = .004 for trend). Modified complete biochemical success was achieved in 29 of 38 (76.3%) patients with CLR ≥ 1 and ILR ≤ 2, 73 of 86 (84.9%) with CLR = 0.25-1 and ILR > 2, and 100 of 104 (96.2%) with CLR < 0.25 and ILR > 2 (p = .001 for trend). After adjusting for confounders, modified complete biochemical success was associated with an LI ≥ 10 (odds ratio [OR] = 6.32; 95% confidence interval [CI] = 1.33-29.93) using LI = 3-4 as a reference and combined CLR < 0.25 and ILR > 2 (OR = 11.49; 95% confidence interval [CI] = 2.49-53.01) using combined CLR ≥ 1 and ILR ≤ 2 as a reference. Using combined CLR ≥ 1 and ILR ≤ 2 as a reference, complete clinical success was associated with combined CLR < 0.25 and ILR > 2 (OR = 3.10; 95% CI = 1.03-9.28) and combined CLR = 0.25-1 and ILR > 2 (OR = 4.92; 95% CI = 1.64-14.76).
CONCLUSION LI ≥ 10 may be appropriate for achieving biochemical success. With ILR > 2, CLR < 0.25, and CLR < 1 may be appropriate for achieving biochemical and clinical success, respectively.
- 732022
제1저자 조인래 · 교신저자 이상욱
, , ,
Comparison of Risk Factors for Cholangiocarcinoma and Hepatocellular Carcinoma: A Prospective Cohort Study in Korean Adults.Cancers (Basel). 2022;14(7):cancers14071709.
PubMed IF 4.8 소화기내과Abstract
Cholangiocarcinoma (CCA), especially intrahepatic CCA, is known to share several risk factors with hepatocellular carcinoma (HCC) and liver cirrhosis has been proposed as a common pathogenic factor. We aimed to identify the risk factors of CCA and to examine differences in risk factors between CCA and HCC. We followed 510,217 Korean adults who underwent health checkups during 2002−2003 until 2013 via linkage to national hospital discharge records. Hazard ratios (HRs) were calculated after adjustment for confounders. During the mean follow-up of 10.5 years, 1388 and 2920 individuals were diagnosed with CCA and HCC, respectively. Choledocholithiasis (HR = 13.7; 95% confidence interval (CI) = 7.58−24.88) was the strongest risk factor for CCA, followed by cholelithiasis (HR = 2.94) and hepatitis B virus (HBV) infection (HR = 2.71). Two of the strongest risk factors for HCC—liver cirrhosis (HR = 1.29; 95% CI = 0.48−3.45) and hepatitis C virus infection (HR = 1.89; 95% CI = 0.49−7.63)—were not significantly associated with the risk of CCA. HBV infection and diabetes increased the risk of both HCC and CCA, but the HRs were lower for CCA than for HCC (Pheterogeneity < 0.001 for HBV; Pheterogeneity = 0.001 for diabetes). The magnitudes of the effects of age, sex, obesity, alcohol consumption, and smoking on the development of both cancers were different (Pheterogeneity < 0.05 for each variable). In conclusion, choledocholithiasis, cholelithiasis, HBV, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors of CCA. Liver cirrhosis did not increase the risk of CCA. The magnitudes of the potential effects of common risk factors were generally different between CCA and HCC.
- 722022
제1저자 이창훈 · 교신저자 곽민선
, , ,
Continuing regular physical activity and maintaining body weight have a synergistic interaction in improving survival: a population-based cohort study including 6.5 million people.Eur J Prev Cardiol. 2022;29(3):547-555.
PubMed IF 10 순환기내과Abstract
AIMS Continuing physical activity (PA) and maintaining body weight are tightly intertwined; however, no study investigated whether these two factors have interactions in terms of the mortality. The aim of this study is to elucidate whether continuing regular PA and maintaining body weight have interactions in terms of all-cause mortality risk.
METHODS AND RESULTS Participants with health screening from both 2009 and 2011 without underlying cancer or cardiovascular disease were included. Physical activity change was grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Body weight change was categorized as stable (weight change < 5%), weight gain, or loss. Outcome included all-cause mortality. Of 6 572 984 total participants, 91 347 deaths occurred during a median 7.4-year follow-up. Compared with the remained active and stable weight group, most other groups had a higher mortality risk. The weight loss and remained inactive group [adjusted hazard ratio (aHR), 2.30; 95% confidence interval (CI), 2.22-2.38] and the weight gain and remained inactive group (aHR, 2.17; 95% CI, 2.09-2.25) showed the highest mortality risks. Among stable weight participants, the ranking of the groups from highest to lowest in terms of mortality risk was as follows: remained inactive (aHR, 1.46; 95% CI, 1.41-1.50), active-to-inactive (aHR, 1.24; 95% CI, 1.19-1.29), inactive-to-active (aHR, 1.15; 95% CI, 1.11-1.20), and remained active (reference). Remaining active and maintaining a stable body weight had a synergistic interaction on decreasing all-cause mortality risk (multiplicative P for interaction < 0.001; relative excess risk due to interaction, 0.38; 95% CI, 0.31-0.46; attributable proportion, 0.18; 95% CI, 0.15-0.22).
CONCLUSIONS Continuing regular PA as recommended and maintaining body weight have multiplicative and additive interactions on reducing all-cause mortality. Healthcare providers should emphasize the importance of both regular PA and body weight maintenance for the general public.
- 712022
제1저자 최정민, 이소령 · 교신저자 최의근
, , , , , , , , , , , ,
Non-alcoholic Fatty Liver Disease and the Risk of Incident Atrial Fibrillation in Young Adults: A Nationwide Population-Based Cohort Study.Front Cardiovasc Med. 2022;9:832023.
PubMed IF 3 순환기내과Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease including cardiovascular. However, the association between NAFLD and the risk of incident atrial fibrillation (AF), especially in young adults, remains unclear. We aimed to evaluate the association between NAFLD as assessed by the fatty liver index (FLI) and the risk of AF in young adults.
METHODS We identified individuals aged 20-39 years who underwent health examinations conducted by the Korean National Health Insurance Corporation between January 2009 and December 2012. Individuals with significant liver disease, heavy alcohol consumption, or prevalent AF were excluded. We categorized based on FLI: <30, 30 to <60, and ≥60. Incident AF was evaluated as the primary outcome.
RESULTS We included 5,333,907 subjects (mean age, 31 ± 5 years; men, 57%). During a mean follow-up of 7.4 ± 1.1 years, 12,096 patients had newly diagnosed AF (incidence rate 0.31 per 1,000 person-years). After adjustment, subjects with FLI 30 to <60 and FLI ≥60 showed a higher risk of AF compared to those with FLI <30 (hazard ratio [HR] 1.21, 95% confidence interval [CI, 1.15-1.27] and HR 1.47, 95% CI [1.39-1.55], p < 0.001, respectively). In women, the increased AF risk was accentuated in the higher FLI group than in the individuals with FLI <30, compared with men (p-for-interaction = 0.023). A higher incident AF risk in the higher FLI groups was consistently observed in various subgroups.
CONCLUSION Among young adults, NAFLD assessed using FLI was positively correlated with the AF risk. These findings support the evidence of AF screening in young adults with high FLI scores.
- 702022
제1저자 강창경, 김민지, 홍지수 · 교신저자 박완범, 이창한, 김항래
, , , , , , , , , , , , , , , , ,
Distinct Immune Response at 1 Year Post-COVID-19 According to Disease Severity.Front Immunol. 2022;13:830433.
PubMed IF 7 감염내과Abstract
BACKGROUND Despite the fact of ongoing worldwide vaccination programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding longevity, breadth, and type of immune response to coronavirus disease-19 (COVID-19) is still important to optimize the vaccination strategy and estimate the risk of reinfection. Therefore, we performed thorough immunological assessments 1 year post-COVID-19 with different severity.
METHODS We analyzed peripheral blood mononuclear cells and plasma samples at 1 year post-COVID-19 in patients who experienced asymptomatic, mild, and severe illness to assess titers of various isotypes of antibodies (Abs) against SARS-CoV-2 antigens, phagocytic capability, and memory B- and T-cell responses.
FINDINGS A total of 24 patients (7, 9, and 8 asymptomatic, mild, and severe patients, respectively) and eight healthy volunteers were included in this study. We firstly showed that disease severity is correlated with parameters of immune responses at 1 year post-COVID-19 that play an important role in protecting against reinfection with SARS-CoV-2, namely, the phagocytic capacity of Abs and memory B-cell responses.
INTERPRETATION Various immune responses at 1 year post-COVID-19, particularly the phagocytic capacity and memory B-cell responses, were dependent on the severity of the prior COVID-19. Our data could provide a clue for a tailored vaccination strategy after natural infection according to the severity of COVID-19.
- 692022
제1저자 원호륜, 전언주 · 교신저자 박영주, 구본석
, , , , , , , , , , ,
Is Maintaining Thyroid-Stimulating Hormone Effective in Patients Undergoing Thyroid Lobectomy for Low-Risk Differentiated Thyroid Cancer? A Systematic Review and Meta-Analysis.Cancers (Basel). 2022;14(6):cancers14061470.
PubMed IF 4.8 내분비대사내과Abstract
There is no clear evidence that post-operative maintenance of thyroid-stimulating hormone (TSH) in the mid to lower reference range (0.5-2 mU/L) improves prognosis in patients undergoing thyroid lobectomy for low-risk differentiated thyroid cancer (DTC). The purpose of this systematic review and meta-analysis was to compare and analyze the recurrence rate according to whether the serum TSH level was maintained below 2 mU/L in patients who underwent thyroid lobectomy for low-risk DTC. Clinical data and outcomes were collected from MEDLINE, Embase, and the Cochrane Database of Systematic Reviews. The inclusion criteria were related studies on TSH maintenance or serum TSH concentration after surgery for DTC. Seven observational studies with a total of 3974 patients were included in this study. In the patients who received TSH maintenance less than 2 mU/L, the recurrence rate during the follow-up period was 2.3%. A subgroup analysis of five studies showed that the odds ratio for recurrence in patients who received TSH maintenance was 1.45 (p-value = 0.45) compared to patients who did not receive TSH maintenance. In conclusion, the evidence for the effectiveness of post-operative TSH maintenance less than 2 mU/L in patients undergoing thyroid lobectomy for low-risk DTC is insufficient.
- 682022
제1저자 장한나 · 교신저자 김정희
, ,
Diabetes Mellitus Predicts Weight Gain After Surgery in Patients With Acromegaly.Front Endocrinol (Lausanne). 2022;13:854931.
PubMed IF 5.7 내분비대사내과Abstract
OBJECTIVE Metabolic complications are common in patients with acromegaly. However, this occasionally does not improve post-surgery and may be related to postoperative weight gain. We aimed to investigate the postoperative weight change and factors associated with postoperative weight gain in patients with acromegaly.
DESIGN AND METHODS Overall, 113 consecutive patients with body weight records pre- and 3-6 months post-surgery between October 2009 and March 2021 were enrolled. Patients were divided into three groups: weight loss (weight decrease ≥3%), stable, and weight gain (weight increase ≥3%). Hormone status, metabolic comorbidities, and anthropometric parameters were compared between the groups.
RESULTS Among 113 patients, 29 (25.7%) and 26 (23.0%) patients lost and gained weight, respectively, post-surgery. There were no significant differences in baseline characteristics, including age at diagnosis, sex, body mass index, and growth hormone levels among the three groups. The prevalence of diabetes mellitus at diagnosis was significantly higher in the weight gain group than in the other groups. Patients with diabetes (n=22) had a 5.2-fold higher risk of postoperative weight gain than those with normal glucose tolerance (n=37) (P=0.006). In the diabetes mellitus group, the percentage lean mass decreased (-4.5 [-6.6-2.0]%, P=0.002), and the percentage fat mass significantly increased post-surgery (18.0 [4.6-36.6]%, P=0.003), whereas the normal glucose tolerance group did not show body composition changes post-surgery.
CONCLUSION In patients with acromegaly, 23% experienced ≥3% weight gain post-surgery. Diabetes mellitus at diagnosis is a significant predictor of weight and fat gain post-surgery.
- 672022
제1저자 이동호 · 교신저자 김정희
, , , , , , ,
Association of androgen excess and bone mineral density in women with classical congenital adrenal hyperplasia with 21-hydroxylase deficiency.Arch Osteoporos. 2022;17(1):45.
PubMed IF 2.7 내분비대사내과Abstract
UNLABELLED The relationship between androgen excess and bone health in patients with congenital adrenal hyperplasia (CAH) with 21-hydroxylase (21-OH) deficiency is not fully understood. This study demonstrated positive correlations between androgen hormones and bone mineral density (BMD) in CAH women with 21-OH deficiency.
PURPOSE This study aims to assess BMD and its association with androgen excess in women with CAH.
METHODS We enrolled 92 women with CAH with 21-OH deficiency and retrospectively reviewed their clinical features, hormone concentrations, body composition, glucocorticoid (GC) dose, and BMD.
RESULTS BMD was not different according to the subtypes of CAH. BMD at the lumbar spine was lower in women with CAH with regular menstruation than those with irregular menstruation (1.081 vs. 1.165 g/cm2, P < 0.05). BMD was lower in women with CAH with 17-hydroxyprogesterone (17-OHP) < 10 ng/mL than in those with ≥ 10 ng/mL (lumbar spine, 1.019 vs. 1.150 g/cm2; femur neck, 0.806 vs. 0.899 g/cm2; total hip, 0.795 vs. 0.943 g/cm2; all P < 0.05). After adjusting for age and BMI in correlation analyses, testosterone concentrations were positively correlated with lumbar spine, femur neck, and total hip BMD (r = 0.46, r = 0.38, and r = 0.35, respectively; all P < 0.05), while 17-OHP was positively correlated with lumbar spine BMD (r = 0.38, P < 0.01). In subgroup analysis, 17-OHP was positively correlated with BMD (lumbar spine, r = 0.22; femur neck, r = 0.22; total hip, r = 0.24; all P < 0.05) only in the group with a total cumulative dose of GC ≥ 156.0 g/m2.
CONCLUSION Androgen excess may have a protective effect on BMD in women with classic CAH and high cumulative doses of GC.
- 662022
제1저자 최용훈 · 교신저자 김나영
, , , , , , , , , , , , , , , , , , , , , , ,
Sex-based differences in histology, staging, and prognosis among 2983 gastric cancer surgery patients.World J Gastroenterol. 2022;28(9):933-947.
PubMed IF 7.7 소화기내과Abstract
BACKGROUND Few studies have been conducted on sex differences in the incidence, pathophysiology, and prognosis of gastric cancer (GC).
AIM To analyze the differences in GC characteristics according to sex in patients who underwent surgical treatment for GC.
METHODS A total of 2983 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital between 2003 and 2017 were included. Baseline clinicopathological characteristics, histologic type of GC, overall and GC-specific survival rates, and associated risk factors were analyzed.
RESULTS Among the 2983 patients, 2005 (67.2%) and 978 (32.8%) were males and females, respectively. The average age of the female group (59.36 years) was significantly younger than that of the male group (61.66 years; P < 0.001). Cancer of the gastric body (P < 0.001) and diffuse-type histology (P < 0.001) were more common in females than in males. This trend was more prominent in females younger than 60 years of age, with a significantly higher proportion of diffuse-type cancer than in the male group. Regardless of sex, diffuse-type GC was more common in younger patients, and the proportion of intestinal-type GC increased with age. The overall survival rate was significantly higher in females (P < 0.001). However, this difference disappeared for GC-specific survival (P = 0.168), except for the poor GC-specific survival rate in advanced-stage cancer (stage III or above) in females (P = 0.045). The risk factors for GC-related mortality were older age, upper location of GC, and diffuse- or mixed-type histology. In terms of comorbidities, more males died from diseases other than GC, including other malignancies such as lung cancer, hepatocellular carcinoma, and pancreatic cancer, and respiratory diseases such as interstitial lung disease and chronic obstructive pulmonary disease, while there were relatively more cardiovascular or cerebrovascular deaths in females.
CONCLUSION Sex-based differences in GC were observed in clinicopathological features, including age at diagnosis, tumor location, histologic type, survival rate, and comorbidities.
- 652022
제1저자 최유정 · 교신저자 김형관
, , , , , , , ,
Emergency department utilization in patients with hypertrophic cardiomyopathy: a nationwide population-based study.Sci Rep. 2022;12(1):3534.
PubMed IF 4.9 순환기내과Abstract
Despite the increasing burden of hypertrophic cardiomyopathy (HCM) on healthcare resources, data on emergency department (ED) utilization in HCM are lacking. This nationwide population-based study extracted 14,542 HCM patients from the National Health Insurance Service database between 2015-2016, and investigated their ED utilization during a one-year period. The reason for ED utilization was defined as the primary diagnosis upon discharge from EDs. The clinical outcome was defined as hospitalization or all-cause mortality within 90 days after the ED visits. A total of 3209 (22.1%) HCM patients visited EDs within a one-year period (mean age, 66.8 ± 13.8 years; male, 57.4%). The majority (71.1%) of HCM patients who visited the EDs were aged ≥ 60 years. The ED utilization rate was higher in women than in men (26.3% versus 19.7%, P < 0.001). Cardiovascular diseases were the most common reason for ED visits (n = 1333, 41.5%). Among HCM patients who visited EDs, 1195 (37.2%) were hospitalized, and 231 (7.2%) died within 90 days. ED visits for cardiovascular disease was associated with a higher 90-day all-cause mortality (adjusted odds ratio, 2.72; 95% confidence interval 1.79-4.12). These findings would serve as a basis for future research to establish medical policies on ED utilization in HCM.
- 642022
제1저자 이현승 · 교신저자 박흥우
,
Role of mTOR in the Development of Asthma in Mice With Cigarette Smoke-Induced Cellular Senescence.J Gerontol A Biol Sci Med Sci. 2022;77(3):433-442.
PubMed IF 4.6 알레르기내과Abstract
The role of cellular senescence in the development of asthma is not well known. We aimed to evaluate the susceptibility of mice with cellular senescence to asthma development and determine whether the mTOR pathway played an important role in this process. Cellular senescence was induced in mice by intranasal instillation of 2% cigarette smoke extract (CSE). Subsequently, a low dose (0.1 μg) of house dust mite (HDM) allergens, which cause no inflammation and airway hyperresponsiveness (AHR) in mice without cellular senescence, was administered intranasally. To evaluate the role of the mTOR pathway in this model, rapamycin (TORC1 inhibitor) was injected intraperitoneally before CSE instillation. CSE significantly increased senescence-associated β-gal activity in lung homogenate and S100A8/9+ p-mTOR+ population in lung cells. Moreover, S100A8/9+ or HMGB1+ populations in airway epithelial cells with p-mTOR activity increased remarkably. Rapamycin attenuated all changes. Subsequent administration of low-dose HDM allergen induced murine asthma characterized by increased AHR, serum HDM-specific immunoglobulin E, and eosinophilic airway inflammation; these asthma characteristics disappeared after rapamycin injection. In vitro experiments showed significant activation of bone marrow-derived cells cocultured with S100A9 or HMGB1 overexpressing MLE-12 cells treated with HDM allergen, compared to those treated with HDM allergen only. CSE increased the levels of senescence markers (S100A8/9 and HMGB1) in airway epithelial cells, making the mice susceptible to asthma development due to low-dose HDM allergens by activating dendritic cells. Because rapamycin significantly attenuated asthma characteristics, the mTOR pathway may be important in this murine model.
- 632022
제1저자 윤혁 · 교신저자 이동호
, , , ,
Total polyp number may be more important than size and histology of polyps for prediction of metachronous high-risk colorectal neoplasms.BMC Gastroenterol. 2022;22(1):91.
PubMed IF 3.2 소화기내과Abstract
BACKGROUND To evaluate whether the risk of metachronous high-risk colorectal neoplasm (HR-CRN) differs according to the indication for surveillance colonoscopy.
METHODS Patients who underwent polypectomy or endoscopic resection of colorectal neoplasms were enrolled and classified into three groups according to the indication for surveillance colonoscopy: advanced colorectal neoplasm (ACRN: adenoma ≥ 10 mm, adenoma with high-degree dysplasia and/or villous component), advanced serrated polyps (ASP: hyperplastic polyp or sessile serrated lesion ≥ 10 mm, traditional serrated polyp), and high-risk polyps (HRP: 3 or more adenomas or serrated polyps). The primary outcome was the development of metachronous HR-CRN, defined as ACRN, ASP, or HRP at the first follow-up colonoscopy.
RESULTS In total, 367 patients were enrolled (ACRN group: N = 264; ASP group: N = 33; HRP group: N = 70). Among the 160 patients who underwent follow-up colonoscopy, 28 (18%) had HR-CRN. In univariable analysis, indication for surveillance colonoscopy was not found to be associated with the development of metachronous HR-CRN. Instead, the total polyp number at index colonoscopy showed a positive association with the risk of metachronous HR-CRN in trend analysis (p = 0.001). In multivariable analysis, the presence of 5 or more polyps at index colonoscopy was found to be associated with the risk of metachronous HR-CRN (OR, 2.575, p = 0.049) after adjusting for risk factors, such as obesity, diabetes, and smoking.
CONCLUSIONS The risk of metachronous HR-CRN did not differ according to the main indications for surveillance colonoscopy. The presence of 5 or more polyps at index colonoscopy was the only risk factor for metachronous HR-CRN.
- 622022
제1저자 Kadowaki T · 교신저자 임수
, , , , , , , , ,
Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial.Lancet Diabetes Endocrinol. 2022;10(3):193-206.
PubMed IF 36.3 내분비대사내과Abstract
BACKGROUND Semaglutide 2·4 mg once weekly has been investigated for weight management in global populations. Differences exist between Asian and non-Asian populations in terms of body composition and definitions of obesity. In the Semaglutide Treatment Effect in People with obesity (STEP) 6 trial, we assessed the effect of semaglutide versus placebo for weight management in adults from east Asia with obesity, with or without type 2 diabetes.
METHODS This randomised, double-blind, double-dummy, placebo-controlled, phase 3a superiority trial was done at 28 outpatient clinics in Japan and South Korea. Eligible participants were adults (aged ≥18 years in South Korea; ≥20 years in Japan) with a BMI of at least 27·0 kg/m2 with two or more weight-related comorbidities or a BMI of 35·0 kg/m2 or more with one or more weight-related comorbidity (one comorbidity had to be either hypertension, dyslipidaemia, or, in Japan only, type 2 diabetes) who had at least one self-reported unsuccessful dietary attempt to lose bodyweight. Participants were randomly assigned (4:1:2:1) to once-weekly subcutaneous semaglutide 2·4 mg or matching placebo, or semaglutide 1·7 mg or matching placebo, plus lifestyle recommendations for 68 weeks. Data for the placebo groups were pooled in statistical analyses. The primary endpoints were percentage change in bodyweight from baseline at week 68 and the proportion of participants who had achieved a reduction of at least 5% of baseline bodyweight at week 68. Change in abdominal visceral fat area was assessed as a supportive secondary endpoint using computed tomography scanning in a subset of participants. Efficacy outcomes were assessed in the full analysis set, which included all randomly assigned participants according to the intention-to-treat principle. Safety was assessed in all participants who received at least one dose of the study drug. This trial was registered with ClinicalTrials.gov, NCT03811574.
FINDINGS Between Jan 21, 2019 and June 4, 2019, 437 participants were screened, of whom 401 were randomly assigned to semaglutide 2·4 mg (n=199), semaglutide 1·7 mg (n=101), or placebo (n=101) and included in the intention-to-treat analysis. Estimated mean change in bodyweight from baseline to week 68 was -13·2% (SEM 0·5) in the semaglutide 2·4 mg group and -9·6% (0·8) in the semaglutide 1·7 mg group versus -2·1% (0·8) in the placebo group (estimated treatment difference [ETD] -11·1 percentage points [95% CI -12·9 to -9·2] for semaglutide 2·4 mg vs placebo; -7·5 percentage points [95% CI -9·6 to -5·4] for semaglutide 1·7 mg vs placebo; both p<0·0001). At week 68, a larger proportion of participants had achieved a 5% or higher reduction in baseline bodyweight in the semaglutide 2·4 mg group (160 [83%] of 193 participants) and semaglutide 1·7 mg group (71 [72%] of 98 participants) than in the placebo group (21 [21%] of 100 participants); odds ratio [OR] 21·7 [95% CI 11·3 to 41·9] for semaglutide 2·4 mg vs placebo; OR 11·1 [95% CI 5·5 to 22·2] for semaglutide 1·7 mg vs placebo; both p<0·0001). Abdominal visceral fat area was reduced by 40·0% (SEM 2·6) among participants in the semaglutide 2·4 mg group and 22·2% (3·7) among participants in the semaglutide 1·7 mg group versus 6·9% (3·8) in the placebo group (ETD -33·2% [95% CI -42·1 to -24·2] for semaglutide 2·4 mg vs placebo; -15·3% [95% CI -25·6 to -4·9] for semaglutide 1·7 mg vs placebo). 171 (86%) of 199 participants in the semaglutide 2·4 mg group, 82 (82%) of 100 participants in the semaglutide 1·7 mg group, and 80 (79%) of 101 participants in the placebo group reported adverse events. Gastrointestinal disorders, which were mostly mild to moderate, were reported in 118 (59%) of 199 participants in the semaglutide 2·4 mg group, 64 (64%) of 100 participants in the semaglutide 1·7 mg group, and 30 (30%) of 101 participants in the placebo group. Adverse events leading to trial product discontinuation occurred in five (3%) of 199 participants in the semaglutide 2·4 mg group, three (3%) of 100 participants in the semaglutide 1·7 mg group, and one (1%) of 101 participants in the placebo group.
INTERPRETATION Adults from east Asia with obesity, with or without type 2 diabetes, given semaglutide 2·4 mg once a week had superior and clinically meaningful reductions in bodyweight, and greater reductions in abdominal visceral fat area compared with placebo, representing a promising treatment option for weight management in this population.
FUNDING Novo Nordisk.
TRANSLATIONS For the Korean and Japanese translations of the abstract see Supplementary Materials section.
- 612022
제1저자 권순일, 이소령 · 교신저자 최의근
, , , , , ,
Hypertension control and end-stage renal disease in atrial fibrillation: a nationwide population-based cohort study.Clin Res Cardiol. 2022;111(3):284-293.
PubMed IF 3.4 순환기내과Abstract
BACKGROUND The impact of hypertension control on the risk of end-stage renal disease (ESRD) in patients newly diagnosed with atrial fibrillation (AF) is unknown. This study aimed to investigate the impact of hypertension control on incident ESRD among AF patients.
METHODS From the National Health Information database of Korea, we identified ESRD-free patients who were newly diagnosed with AF during 2010 and 2016. The patients were divided into four groups (NN, NH, HN, and HH) according to combinations of dichotomous blood pressure status [normotensive (N) or hypertensive (H)] of two consecutive check-ups. The primary outcome was incident ESRD. Cox proportional hazard regression analysis evaluated ESRD risks across the groups. The association between ESRD risks and changes in blood pressures was also evaluated.
RESULTS During the mean follow-up duration of 3.2 ± 1.9 years, 130,259 ESRD-free patients with AF (mean age 63.1 ± 12.1 years, male 61.2%) were evaluated. Compared to NN, other patient groups showed higher ESRD risks [hazard ratio (95% confidence interval) = 1.43 (1.08-1.89), 1.39 (1.08-1.79), and 2.03 (1.55-2.65) for NH, HN, and HH, respectively]. There was a significant trend of decreasing risks of ESRD in patients with greater reductions in systolic blood pressure after AF diagnosis (p for-trend < 0.001). The association between hypertension control and the ESRD risk was more accentuated in patients with chronic kidney disease.
CONCLUSION Uncontrolled hypertension was associated with an increased risk of incident ESRD in patients with newly diagnosed AF. This study emphasizes the importance of blood pressure control once patients are diagnosed with AF to prevent ESRD.
- 602022
제1저자 정종탁 · 교신저자 최평균
, , , , , , , , , , ,
Reduction in the acquisition rate of carbapenem-resistant Acinetobacter baumannii (CRAB) after room privatization in an intensive care unit.J Hosp Infect. 2022;121:14-21.
PubMed IF 3.4 감염내과Abstract
BACKGROUND Acinetobacter baumannii is one of the major pathogens responsible for healthcare-associated infections, especially in intensive care units (ICUs).
AIM To evaluate the effect of room privatization in an ICU on the acquisition of carbapenem-resistant A. baumannii (CRAB).
METHODS Between March and August 2017, a medical ICU was renovated from a multi-bed bay room to single rooms. Acquisition of CRAB was compared between patients admitted to the ICU over 18 months pre-renovation (September 2015 to February 2017) and post-renovation (September 2017 to February 2019). A Cox proportional hazard model was used with adjustment for demographics and comorbidities.
FINDINGS Of the 901 patients, who contributed 8276 patient-days, 95 (10.5%) acquired CRAB during their ICU stay. The CRAB acquisition rate was significantly higher during the pre-renovation period (1.87 per 100 patient-days) than during the post-renovation period (0.39 per 100 patient-days) (P<0.001). In the multi-variable Cox regression model, CRAB acquisition was significantly associated with the presence of a feeding tube (adjusted hazard ratio (aHR), 6.08; 95% confidence interval (CI), 2.46-15.06; P<0.001), continuous renal replacement therapy (aHR, 1.66; 95% CI, 1.09-2.53; P=0.019) and admission after renovation of the ICU to single rooms (aHR, 0.23; 95% CI, 0.12-0.41; P<0.001).
CONCLUSIONS Renovation of ICUs to single rooms is an efficient strategy to prevent transmission of multi-drug-resistant organisms and hospital-acquired infections.
- 592022
제1저자 최평균, 정세임 · 교신저자 김남중
, , , , , , , , , , ,
Exploration for the effect of renal function and renal replacement therapy on pharmacokinetics of remdesivir and GS-441524 in patients with COVID-19: A limited case series.Clin Transl Sci. 2022;15(3):732-740.
PubMed IF 4.3 감염내과Abstract
Remdesivir, an antiviral agent for the treatment of coronavirus disease 2019 (COVID-19), is metabolized intracellularly, with these metabolites eliminated predominantly in urine. Because of a lack of safety and pharmacokinetic (PK) data, remdesivir is not currently recommended for patients with estimated glomerular filtration rate less than 30 ml/min/1.73 m2 and those on hemodialysis. This study evaluated the PKs of remdesivir and its metabolite, GS-441524, in patients with COVID-19 who were and were not receiving renal replacement therapy (RRT). This study enrolled two patients with normal renal function, two with impaired renal function not receiving RRT, two receiving continuous RRT (CRRT), and three undergoing intermittent hemodialysis (IHD). Patients were administered 200 mg remdesivir on the first day, followed by 100 mg/day for 5-10 days. Serial blood samples were collected for PK analysis, and PK parameters were assessed by a noncompartmental method. Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving CRRT than in patients with normal renal function, but was similar in patients undergoing IHD and those with normal renal function. By contrast, systemic exposure to GS-441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function. The PK profiles of remdesivir and GS-441524 varied according to renal function and RRT. The impact of PK changes of remdesivir and its metabolite on safety and efficacy should be considered when administering remdesivir to patients with COVID-19 with renal impairment.
- 582022
제1저자 문서일, 정고은 · 교신저자 구보경, 김원
, , , , , , ,
A PNPLA3 Polymorphism Confers Lower Susceptibility to Incident Diabetes Mellitus in Subjects With Nonalcoholic Fatty Liver Disease.Clin Gastroenterol Hepatol. 2022;20(3):682-691.e8.
PubMed IF 16.2 소화기내과Abstract
BACKGROUND AND AIMS We investigated the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genotype and the risk of diabetes mellitus (DM) using a biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) cohort and a longitudinal observational cohort.
METHODS Associations between genotypes and the prevalence of DM were evaluated with stratification according to the histological severity of NAFLD in the Boramae cohort (n = 706). A longitudinal cohort consisting of nondiabetic individuals with ≥2 health checkups was then selected to investigate the risk of incident DM according to the genotype (the GENIE cohort; n = 4998).
RESULTS Among subjects with NAFLD in the Boramae cohort, the G allele was independently associated with a lower prevalence of DM in both NAFL (odds ratio [OR] per 1 allele, 0.66; 95% confidence interval [CI], 0.46-0.97) and nonalcoholic steatohepatitis (OR per 1 allele, 0.59; 95% CI, 0.38-0.92). This result was replicated in the longitudinal GENIE cohort. The G allele was associated with a lower risk of incident DM during the median follow-up of 60 months in subjects with NAFLD (hazard ratio, 0.65; 95% CI, 0.45-0.93). In contrast, G allele carriers without NAFLD showed higher odds for DM in the context of the Boramae cohort (OR, 2.44; 95% CI, 1.00-5.95).
CONCLUSIONS These findings clarify conflicting results regarding the association between the PNPLA3 rs738409 genotype and the risk of DM, demonstrating a clear difference between subjects with and without NAFLD; this difference might be explained by the low metabolic risk in genetic NAFLD.
- 572022
제1저자 정고은, 조은주 · 교신저자 신동욱, 유수종
, , , , , , , , , , , ,
Young adults with nonalcoholic fatty liver disease, defined using the fatty liver index, can be at increased risk of myocardial infarction or stroke.Diabetes Obes Metab. 2022;24(3):465-472.
PubMed IF 6.1 소화기내과Abstract
AIM To investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and cardiovascular events among a nationally representative sample of young adults in Korea.
METHODS AND RESULTS This population-based cohort study from the Korean National Health Insurance Service included adults who were aged 20 to 39 years when they underwent a health examination between 2009 and 2012. NAFLD was defined as a fatty liver index (FLI) ≥60, and participants were divided into three groups according to FLI (<30, 30-59 and ≥60) to investigate the dose-dependent effect of FLI score. Among 5 324 410 participants, 9.8% had an FLI ≥60. There were 13 051 myocardial infarctions (MIs; 0.39%) and 8573 strokes (0.26%) during a median follow-up of 8.4 years. In multivariable analysis, NAFLD was associated with a higher risk of MI and stroke (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.61-1.77 and HR 1.73, 95% CI 1.63-1.84, respectively). MI and stroke had dose-dependent relationships with FLI (HR 1.28 in participants with FLI 30-59 and 1.73 in those with FLI ≥60 for MI and HR 1.18 in participants with FLI 30-59 and 1.41 in those with FLI ≥60 for stroke, respectively).
CONCLUSIONS Nonalcholic fatty liver disease was an independent predictor of MI and stroke in young adults. These results suggest that primary prevention of cardiovascular disease should be emphasized in young adults with NAFLD.
- 562022
제1저자 허기영 · 교신저자 조영민, 이형기
, , , , , , ,
A double-blind, placebo-controlled, single-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects.Diabetes Obes Metab. 2022;24(3):411-420.
PubMed IF 6.1 내분비대사내과Abstract
AIM To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue under development, in healthy males and females presenting with no childbearing potential.
MATERIALS AND METHODS A randomized, double-blind, placebo-controlled, single-ascending dose study was conducted in 56 subjects who randomly received a single subcutaneous dose of HM15136 or its matching placebo at a ratio of 6:2 at 10, 20, 30, 50, 80, 100, and 120 μg/kg.
RESULTS All adverse events were mild and transient. Neither serious adverse events nor discontinuation as a result of adverse events occurred. The most frequent adverse drug reaction was nausea (5.3%, only in the 100- and 120-μg/kg groups). HM15136, particularly at doses of 50 μg/kg or higher, increased fasting blood glucose, with a maximum increase and area under the curve of 1.5 mmol/L at day 10 (P = .006) and 166.3 day·mmol/L (P = .022) at the dose of 80 μg/kg, while suppressing the secretion of endogenous glucagon, which continued until day 17. HM15136 also significantly reduced gluconeogenic and ketogenic amino acids. Compensatory changes in endogenous insulin and incretin hormones by HM15136 were not apparent. HM15136 was slowly but steadily absorbed and reached a peak concentration at 46-68 hours after a single subcutaneous injection. HM15136 was eliminated with a terminal phase half-life of 77.1-101.1 hours.
CONCLUSIONS A single subcutaneous dose of HM15136 at 10-120 μg/kg was safe and well tolerated. The long half-life of HM15136, coupled with an increase in blood glucose for ~2 weeks, may warrant a weekly dosing regimen.
서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.