SCI 발표논문

2021년 358편

3582021

제1저자 손민지 · 교신저자 임수

, , , , ,
Efficacy and Safety of Lactobacillus plantarum K50 on Lipids in Koreans With Obesity: A Randomized, Double-Blind Controlled Clinical Trial.
Front Endocrinol (Lausanne). 2021;12:790046.

Abstract
BACKGROUND Only few studies have investigated the role of probiotics in the development of obesity. We aimed to determine the efficacy and safety of an intake of Lactobacillus plantarum K50 (LPK) on body fat and lipid profiles in people with obesity.
METHODS This randomized, double-blind, placebo-controlled, clinical trial involved 81 adults with a body mass index of 25-30 kg/m² who were assigned randomly to a diet including 4 × 10⁹ colony-forming unit of LPK or a placebo. Changes in body fat, anthropometric parameters, and biomarkers of obesity were compared using a linear mixed-effect model.
RESULTS After 12 weeks of treatment, body weight, fat mass, and abdominal fat area did not change significantly in the two groups. However, total cholesterol levels decreased from 209.4 ± 34.4 mg/dL to 203.5 ± 30.9 mg/dL in the LPK group, but increased from 194.7 ± 37.5 mg/dL to 199.9 ± 30.7 mg/dL in the placebo group (P = 0.037). Similarly, triglyceride levels decreased from 135.4 ± 115.8 mg/dL to 114.5 ± 65.9 mg/dL in the LPK group, with a significant difference between groups. LPK supplementation also tended to decrease leptin levels compared with placebo. It also changed the distribution of gut microbiota significantly, with an increase in L. plantarum and a decrease in Actinobacteria, both of whose changes in abundance were correlated with changes in visceral adiposity, with borderline significance.
CONCLUSION A 12-week consumption of LPK reduced the total cholesterol and triglyceride levels significantly with favorable alterations in microbiota, suggesting potential benefits for controlling blood lipid profiles.
PubMed IF 5.7 내분비대사내과
3572021

제1저자 김수환 · 교신저자 김지원

,
Small Bowel Malignancies in Patients Undergoing Capsule Endoscopy for Iron Deficiency Anemia.
Diagnostics (Basel). 2021;12(1):diagnostics12010091.

Abstract
Small bowel malignancies are rare and usually asymptomatic or symptoms are nonspecific. Therefore, small bowel tumors are difficult to diagnose. In patients with iron deficiency anemia (IDA) who have negative bidirectional endoscopy results, the small bowel may be considered the source of bleeding. However, in asymptomatic IDA patients with negative bidirectional endoscopy results, evidence supporting the routine use of capsule endoscopy (CE) is insufficient. CE can be considered in selected patients with recurrent or persistent IDA. The frequency of small bowel malignancies is low in patients undergoing CE for IDA, but the usefulness of CE for the diagnosis of small bowel malignancies in younger age groups with IDA has been reported. For patients with risk factors for small bowel malignancy, investigation of the small bowel should be considered. Efforts should be made to prevent adverse events, such as capsule retention or capsule aspiration, through meticulous history taking and endoscopic capsule delivery as necessary.
PubMed IF 3.8 소화기내과
3562021

제1저자 장우영, 김봉영 · 교신저자 김홍빈

, , , , , , , , , ,
Are the Current Guidelines Sufficient to Establish Infection Control Strategies for COVID-19 Related Issues in Hospitals?
J Korean Med Sci. 2021;36(50):e343.

Abstract
As hospitals cater to elderly and vulnerable patients, a high mortality rate is expected if a coronavirus disease 2019 (COVID-19) outbreak occurs. Consequently, policies to prevent the spread of COVID-19 in hospital settings are essential. This study was conducted to investigate how effectively national and international guidelines provide recommendations for infection control issues in hospitals. After selecting important issues in infection control, we performed a systematic review and analysis of recommendations and guidelines for preventing COVID-19 transmission within medical institutions at national and international levels. We analyzed guidelines from the World Health Organization, Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control, and Korea Disease Control and Prevention Agency. Recent guidelines do not provide specific solutions to infection control issues. Therefore, efforts need to be made to devise consistent advice and guidelines for COVID-19 control.
PubMed IF 3.2 감염내과
3552021

제1저자 정고은, 장영 · 교신저자 신동욱, 유수종

, , , , , , , , , ,
The Change in Metabolic Syndrome Status and the Risk of Nonviral Liver Cirrhosis.
Biomedicines. 2021;9(12):biomedicines9121948.

Abstract
BACKGROUND Nonalcoholic fatty liver disease is considered to be the hepatic component of metabolic syndrome (MetS). However, the association between changes in MetS status and the risk of liver cirrhosis (LC) has not been investigated to date. This study assessed the association between changes in MetS and subsequent nonviral LC development.
METHODS Data were obtained from the Korean National Health Insurance Service. Individuals who participated in health screenings from both 2009 to 2010 and 2011 to 2012 were included. The primary outcome was LC development according to the static and dynamic MetS status. Subjects were stratified into four groups according to the change in MetS status observed from the two-year interval screening (2009-2011). Cox regression analysis was used to examine the hazard ratios of LC.
RESULTS During a median of 7.3 years of follow-up, 24,923 incident LC cases developed among 5,975,308 individuals. After adjusting for age, sex, smoking, alcohol, regular exercise, and body mass index, the adjusted hazard ratios (95% confidence intervals) for LC development were 1.39 (1.33-1.44) for the MetS-Developed group, 1.32 (1.26-1.37) for the MetS-Recovered group, and 1.51 (1.45-1.56) for the MetS-Sustained group, relative to the MetS-Free group. Stratified analyses according to age, sex, smoking, alcohol intake, exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease showed similar results.
CONCLUSIONS Both static and dynamic MetS status are independent risk factors for LC development. The risk of LC was the highest in people with sustained MetS and was lower in the MetS-Recovered group than in the MetS-Sustained group. These results suggest that improving a person's MetS status may be helpful in preventing LC.
PubMed IF 4.5 소화기내과
3542021

제1저자 서정민 · 교신저자 변자민, 홍준식

, , , , , ,
Association between preconditioning absolute lymphocyte count and transplant outcomes in patients undergoing matched unrelated donor allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and anti-thymocyte globulin.
Ther Adv Hematol. 2021;12:20406207211063783.

Abstract
BACKGROUND Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft-versus-host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome.
METHODS The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7.
RESULTS Patients with preconditioning ALC <500/μl were associated with shorter overall survival (OS) and higher infectious mortality. The incidence of acute GVHD and moderate-severe chronic GVHD as well as relapse rates did not differ according to preconditioning ALC. In multivariate analyses, low preconditioning ALC was recognized as an independent adverse prognostic factor for OS.
CONCLUSION Patients with lower ALC are exposed to excessive dose of ATG, leading to profound T-cell depletion that results in higher infectious mortality and shorter OS. Our results call for the implementation of more creative dosing regimens for patients with low preconditioning ALC.
PubMed IF 2.8 혈액종양내과
3532021

제1저자 이소령 · 교신저자 최의근

, , , , ,
Lower risk of stroke after alcohol abstinence in patients with incident atrial fibrillation: a nationwide population-based cohort study.
Eur Heart J. 2021;42(46):4759-4768.

Abstract
AIMS The aim of this study was to evaluate the association between alcohol consumption status (and its changes) after newly diagnosed atrial fibrillation (AF) and the risk of ischaemic stroke.
METHODS AND RESULTS Using the Korean nationwide claims and health examination database, we included subjects who were newly diagnosed with AF between 2010 and 2016. Patients were categorized into three groups according to the status of alcohol consumption before and after AF diagnosis: non-drinkers; abstainers from alcohol after AF diagnosis; and current drinkers. The primary outcome was incident ischaemic stroke during follow-up. Non-drinkers, abstainers, and current drinkers were compared using incidence rate differences after the inverse probability of treatment weighting (IPTW). Among a total of 97 869 newly diagnosed AF patients, 51% were non-drinkers, 13% were abstainers, and 36% were current drinkers. During 310 926 person-years of follow-up, 3120 patients were diagnosed with incident ischaemic stroke (10.0 per 1000 person-years). At 5-year follow-up, abstainers and non-drinkers were associated with a lower risk for stroke than current drinkers (incidence rate differences after IPTW, -2.03 [-3.25, -0.82] for abstainers and -2.98 [-3.81, -2.15] for non-drinkers, per 1000 person-years, respectively; and incidence rate ratios after IPTW, 0.75 [0.70, 0.81] for non-drinkers and 0.83 [0.74, 0.93] for abstainers, respectively).
CONCLUSION Current alcohol consumption was associated with an increased risk of ischaemic stroke in patients with newly diagnosed AF, and alcohol abstinence after AF diagnosis could reduce the risk of ischaemic stroke. Lifestyle intervention, including attention to alcohol consumption, should be encouraged as part of a comprehensive approach to AF management to improve clinical outcomes.
PubMed IF 45.3 순환기내과
3522021

제1저자 김민석 · 교신저자 김윤준

, , , , , , , , , , ,
Yttrium-90 Radioembolization Is Associated with Better Clinical Outcomes in Patients with Hepatocellular Carcinoma Compared with Conventional Chemoembolization: A Propensity Score-Matched Study.
J Hepatocell Carcinoma. 2021;8:1565-1577.

Abstract
BACKGROUND Both trans-arterial radioembolization (TARE) and conventional trans-arterial chemoembolization (TACE) can effectively control hepatocellular carcinoma (HCC) in patients who are not suitable for curative resection. This study compared the effectiveness of TARE and conventional TACE as the initial trans-arterial treatment for hepatocellular carcinoma (HCC) assessed by tumor response and clinical outcomes.
MATERIAL AND METHODS Data were retrospectively analyzed the propensity score-matched cohort for overall survival (OS), progression-free survival (PFS), and intrahepatic PFS in patients who have received TARE or TACE as the first HCC treatment from March 2012 to December 2017.
RESULTS A total of 138 patients initially treated with TARE (n = 54) or TACE (n = 84) was included in this study. Of 138 patients, median age was 59 years and the mean follow-up period was 27.6 months. TARE showed better OS (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.31-0.92, log-rank P = 0.02), better PFS (HR = 0.51, 95% CI = 0.36-0.97, log-rank P = 0.04), and better intrahepatic PFS (HR = 0.51, 95% CI = 0.30-0.88, log-rank P = 0.01) compared with TACE. TARE was an independent prognostic factor for OS (adjusted HR [aHR] = 0.52, 95% CI = 0.30-0.90, P = 0.02), PFS (aHR = 0.57, 95% CI = 0.35-0.94, P = 0.03), and intrahepatic PFS (aHR = 0.49, 95% CI = 0.28-0.84, P = 0.01).
CONCLUSION TARE as initial trans-arterial treatment is associated with better clinical outcomes such as longer OS compared with TACE in patients with HCC.
PubMed IF 3.9 소화기내과
3512021

제1저자 장인순, 김수진 · 교신저자 이규언, 김정희

, , , , , , , , ,
Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients.
Endocrinol Metab (Seoul). 2021;36(6):1287-1297.

Abstract
BACKGROUND An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea.
METHODS We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.
RESULTS The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis.
CONCLUSION The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.
PubMed IF 5.1 내분비대사내과
3502021

제1저자 박한기, 이소희 · 교신저자 박흥우

, , , ,
Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals.
J Cachexia Sarcopenia Muscle. 2021;12(6):2145-2153.

Abstract
BACKGROUND The associations between long-term changes in body mass composition and decline in lung function in healthy adults are unknown.
METHODS Using a well-defined health check-up database, we first assessed individual longitudinal changes in muscle mass (MM) and fat mass (FM) measured via bioelectrical impedance analyses. Then we classified the enrolled individuals into five body composition groups according to their MM index (MMI) [MM (kg)/height (m)² ] or FM index (FMI) [FM (kg)/height (m)² ] change rate quartiles. Linear mixed models adjusted for age, smoking status, height, and body mass index were used to analyse the rate of forced expiratory volume in 1 s (FEV1) decline and body composition groups.
RESULTS A total of 15 476 middle-aged individuals (6088 women [mean age ± standard deviation: 50.74 ± 7.44] and 9388 men [mean age ± standard deviation: 49.36 ± 6.99]) were enrolled. The mean number of measurements was 6.96 (interquartile range [IQR]: 5-9) over an average follow-up period of 8.95 years (IQR: 6.73-11.10). Decrease in MMI was significantly associated with accelerated FEV1 decline in men only (P = 1.7 × 10^-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10^-10 and P < 2.0 × 10^-16 respectively). Linear mixed model analyses indicated that annual increase of 0.1 kg/m² in MMI was related to accelerated FEV1 decline by 30.79 mL/year (95% confidence interval [CI]: 26.10 to 35.48 mL/year) in men. Annual increase of 0.1 kg/m² in FMI was related to accelerated FEV1 decline by 59.65 mL/year in men (95% CI: 56.84 to 62.28 mL/year) and by 22.84 mL/year in women (95% CI: 18.95 to 26.74 mL/year). In body composition analysis, we found increase in MMI was significantly associated with attenuated FEV1 decline in men only (P = 1.7 × 10^-9 ), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10^-10 and P < 2.0 × 10^-16 respectively). Individuals characterized with gain MM combined with loss of FM were associated with the most favourable outcome (i.e. the smallest rate of decline in FEV1) in both women and men. In men, loss of FM over time is more closely related with attenuated FEV1 decline than change in MM (gain or loss).
CONCLUSIONS Change in body composition over time can be used to identify healthy middle-aged individuals at high risk for rapid FEV1 decline.
PubMed IF 9.9 알레르기내과
3492021

제1저자 윤지완 · 교신저자 곽민선

, , , , , , ,
Hepatic fibrosis is associated with an increased rate of decline in bone mineral density in men with nonalcoholic fatty liver disease.
Hepatol Int. 2021;15(6):1347-1355.

Abstract
BACKGROUND There is still controversy about the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). The aim of this study was to clarify the association between NAFLD and the decline in BMD in healthcare examinees.
METHODS Participants who underwent regular health check-ups with BMD and hepatic ultrasonography from 2006 to 2015 with more than one follow-up until 2020 were included. Propensity score matching was performed between the NAFLD group and the control group, and mixed linear regression models were used for the longitudinal analysis.
RESULTS Of 2623 eligible participants (mean age 58.7 ± 7.3 years; males 31.3%), 888 (33.9%) had NAFLD. At baseline, the NAFLD group had a higher total hip BMD than the non-NAFLD group in men (0.988 vs. 1.015 g/cm², p = 0.007); however, there was no difference in baseline BMD in women (p = 0.253). In longitudinal analysis during a follow-up period of 7.1 years, there was no significant difference in the BMD decline rate between the two groups in the PS-matched cohort (p = 0.816 in men and p = 0.827 in women). However, among men with NAFLD, those with a high and intermediate probability of advanced fibrosis by the FIB-4 showed a significantly increased rate of decline in total hip BMD compared to those with low scores (0.01 vs. - 0.19% change/year, p = 0.011).
CONCLUSIONS NAFLD was not associated with the total hip BMD decline rate. However, hepatic fibrosis was significantly associated with an increased rate of decline in total hip BMD in men with NAFLD.
CLINICAL TRIAL REGISTRATION This study is a retrospective observational study and is not a drug trial. There was no need for clinical trial registration.
PubMed IF 7.8 내분비대사내과
3482021

제1저자 김범석 · 교신저자 박영석

, , , , , , , , , , , , , ,
A phase I study of IMC-001, a PD-L1 blocker, in patients with metastatic or locally advanced solid tumors.
Invest New Drugs. 2021;39(6):1624-1632.

Abstract
Introduction IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 (programmed death-ligand 1). This study evaluated the safety, pharmacokinetics, and pharmacodynamics of IMC-001 in patients with advanced solid tumors. Materials and Methods This open-labeled phase I study used a standard 3 + 3 dose-escalation design, with doses ranging from 2 to 20 mg/kg. IMC-001 was administered intravenously every 2 weeks until disease progression or unacceptable toxicity. The dose-limiting toxicity window was defined as 21 days from the first dose. Results Fifteen subjects were included in 5 dose-escalation cohorts. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common adverse events (AEs) were general weakness, decreased appetite, fever, and cough. No grade 4 or 5 treatment emergent AEs were reported during the study. One subject in the 2 mg/kg cohort showed grade 2 immune-induced thyroiditis and diabetes mellitus suspected to be related to IMC-001. Over the dose range of 2-20 mg/kg IMC-001, the AUC_0-14d, AUC_0-∞, and C_max generally increased in a dose-proportional manner for each step of dose escalation. Of the 15 enrolled patients, 1 subject with rectal cancer showed a partial response, and the disease control rate was 33.3%. Conclusions IMC-001 demonstrated a favorable safety profile up to 20 mg/kg administered intravenously every 2 weeks and showed preliminary efficacy in patients with advanced solid tumors. Based on pharmacokinetic and pharmacodynamic data, 20 mg/kg was selected as the recommended phase II dose. Clinical trial identification NCT03644056 (date of registration: August 23, 2018).
PubMed IF 3.4 혈액종양내과
3472021

제1저자 백진혁, 강성일, 류지원 · 교신저자 김세중

, , , , , , , , , , ,
Renal outcomes of laparoscopic versus open surgery in patients with rectal cancer: a propensity score analysis.
Kidney Res Clin Pract. 2021;40(4):634-644.

Abstract
BACKGROUND A laparoscopic approach is widely used in abdominal surgery. Although several studies have compared surgical and oncological outcomes between laparoscopic surgery (LS) and open surgery (OS) in rectal cancer patients, there have been few studies on postoperative renal outcomes.
METHODS We conducted a retrospective cohort study involving 1,633 patients who underwent rectal cancer surgery between 2003 and 2017. Postoperative acute kidney injury (AKI) was diagnosed according to the serum creatinine criteria of the Kidney Disease: Improving Global Outcomes classification.
RESULTS Among the 1,633 patients, 1,072 (65.6%) underwent LS. After matching propensity scores, 395 patients were included in each group. The incidence of postoperative AKI in the LS group was significantly lower than in the OS group (9.9% vs. 15.9%; p = 0.01). Operation time, estimated blood loss, and incidence of transfusion in the LS group were significantly lower than those in the OS group. Cox proportional hazard models revealed that LS was associated with decreased risk of postoperative AKI (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.402-0.893; p = 0.01) and postoperative transfusion was associated with increased risk of AKI (HR, 2.495; 95% CI, 1.529-4.072; p < 0.001). In the subgroup analysis, the incidence of postoperative AKI in patients with middle or high rectal cancer who underwent LS was much lower than in those who underwent OS (HR, 0.373; 95% CI, 0.197-0.705; p = 0.002).
CONCLUSION This study showed that LS may have a favorable effect on the development of postoperative AKI in patients with rectal cancer.
PubMed IF 3.5 신장내과
3462021

제1저자 정영애, 구보경 · 교신저자 김원, 황금숙

, , , , , , , , , , , , , , , ,
Association between circulating bile acid alterations and nonalcoholic steatohepatitis independent of obesity and diabetes mellitus.
Liver Int. 2021;41(12):2892-2902.

Abstract
BACKGROUND AND AIMS Bile acid (BA) dysregulation is related to not only metabolic diseases but also nonalcoholic fatty liver disease (NAFLD). We investigated whether circulating BA levels are altered according to the histological severity of NAFLD independent of metabolic derangements.
METHODS Global metabolic profiling and targeted BA analysis using sera collected from biopsy-proven no-NAFLD (n = 67), nonalcoholic fatty liver (NAFL) (n = 99), and nonalcoholic steatohepatitis (NASH, n = 75) subjects were performed sequentially. Circulating metabolome analysis integrated with the hepatic transcriptome was performed to elucidate the mechanistic basis of altered circulating BA profiles after stratification by obesity (body mass index ≤ 25 kg/m² ). Circulating BA alterations were also validated in an independent validation cohort (29 no-NAFLD, 70 NAFL and 37 NASH).
RESULTS Global profiling analysis showed that BA was the metabolite significantly altered in NASH compared to NAFL. Targeted BA analysis demonstrated that glyco-/tauro-conjugated primary BAs were commonly increased in nonobese and obese NASH, while unconjugated primary BAs increased only in nonobese NASH. These characteristic primary BA level changes were maintained even after stratification according to diabetes status and were replicated in the independent validation cohort. Compared to nonobese NAFL patients, nonobese NASH patients exhibited upregulated hepatic expression of CYP8B1.
CONCLUSIONS BA metabolism is dysregulated as the histological severity of NAFLD worsens, independent of obesity and diabetes status; dysregulation is more prominent in nonobese NAFLD patients. Metabolome-driven omics approach provides new insight into our understanding of altered BA metabolism associated with individual phenotypes of NAFLD.
PubMed IF 6.2 소화기내과
3452021

제1저자 김영찬, 김정현 · 교신저자 강혜련

, , , , , , ,
Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 via alveolar macrophage modulation.
Exp Lung Res. 2021;47(10):465-475.

Abstract
Transforming growth factor beta 1 (TGF-β1) induces pulmonary fibrosis by enhancing epithelial apoptosis and affects the enzymatic activity of transglutaminase 2 (TG2). The aim of this study was to determine the role of TG2 in TGF-β1-induced lung remodeling and alveolar macrophage modulation. We characterized the in vivo effects of TGF-β1 and TG2 on lung inflammation, fibrosis, and macrophage activity using transgenic C57BL/6 mice with wild and null TG2 loci. The effect of TG2 inhibition on in vitro TGF-β1-stimulated alveolar macrophages was assessed through mRNA analysis. TG2 was remarkably upregulated in the lungs of TGF-β1 transgenic (TGF-β1 Tg) mice, especially in alveolar macrophages and epithelial cells. In the absence of TG2, TGF-β1-induced inflammation was suppressed, decreasing the number of macrophages in the bronchoalveolar lavage fluid. In addition, the alveolar destruction and peribronchial fibrosis induced by TGF-β1 overexpression were significantly reduced, which correlated with decreases in the expression of fibroblast growth factor and matrix metallopeptidase 12, respectively. However, TG2 deficiency did not compromise the phagocytic activity of alveolar macrophages in TGF-β1 Tg mice. At the same time, TG2 contributed to the regulation of TGF-β1-induced macrophage activation. Inhibition of TG2 did not affect the TGF-β1-induced expression of CD86, an M1 marker, in macrophages, but it did reverse the TGF-β1-induced expression of CD206. This result suggests that TG2 mediates TGF-β1-induced M2-like polarization but does not contribute to TGF-β1-induced M1 polarization. In conclusion, TG2 regulates macrophage modulation and plays an important role in TGF-β1-induced lung inflammation, destruction, and fibrosis.
PubMed IF 1.9 알레르기내과
3442021

제1저자 임영효,윤지현 · 교신저자 김효수,박준규

, , , , , ,
A First-in-Man Clinical Evaluation of Sirolimus and Ascorbic Acid-Eluting Stent Systems: a Multicenter, Subject-Blinded, Randomized Study.
Korean Circ J. 2021;51(12):1001-1014.

Abstract
BACKGROUND AND OBJECTIVES This clinical trial was conducted to evaluate the safety and efficacy of D+Storm™ drug-eluting stent (DES) and BioMatrix Flex™ DES.
METHODS This study was a multicenter, subject-single-blind, randomized, and confirmed comparative clinical trial. According to the inclusion criteria, those diagnosed with stable angina, unstable angina, silent ischemia, or non-ST-segment myocardial infarction were selected among patients with coronary artery stenosis as subjects. Among the subjects with 50% stenosis on coronary angiography, the experiment was performed on those who had a lesion with reference vessel 2.5-4.0 mm in diameter and ≤40 mm in length. The primary endpoint was an in-segment late loss and the secondary endpoints were in-stent late lumen loss, stent malapposition, the incidence of mortality, myocardial infarction, reoperation, and stent thrombosis at 36 weeks.
RESULTS 57 patients in the D+Storm™ DES group and 55 patients in the BioMatrix Flex™ DES group were enrolled in the study. Fifty-seven patients in the D+Storm™ DES group and Fifty-five patients in the BioMatrix Flex™ DES group were enrolled in the study. An average of in-segment late lumen loss was 0.08±0.13 mm in the D+Storm™ DES group and 0.14±0.32 mm in the BioMatrix Flex™ DES group with no significant difference between the 2 groups (p=0.879). In addition, there was no significant difference in adverse events between D+Storm™ DES and BioMatrix Flex™ DES.
CONCLUSIONS This study demonstrated the clinical effectiveness and safety of D+Storm™ DES implantation in patients with coronary artery disease over a 36-week follow-up period.
PubMed IF 3.4 순환기내과
3432021

제1저자 김범석 · 교신저자 김범석

, , , , , , , , , , , , , , , , , , , , , , , ,
Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck.
ESMO Open. 2021;6(6):100309.

Abstract
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.
PubMed IF 10.6 혈액종양내과
3422021

제1저자 Rismiati H · 교신저자 이해영

,
Hypertensive Heart Failure in Asia.
Pulse (Basel). 2021;9(3-4):47-56.

Abstract
Hypertension (HT) is an important risk factor for heart failure (HF). The prevalence of HT among the HF population is higher in Asia than in other regions around the world. In Asia, HT is the most common cause of HF after ischemic heart disease. Hypertensive HF (HHF) results from structural and functional adaptations of the heart, which lead to left ventricular (LV) hypertrophy (LVH). Hypertensive LVH can cause ventricular diastolic dysfunction and becomes a risk factor for myocardial infarction, which is a well-known cause of LV systolic dysfunction. Asymptomatic systolic and diastolic LV dysfunction easily progress to clinically overt HF with other precipitating factors. Although the precise pathophysiology of HHF is still unclear, we have known that HHF can be reversed by effective control of blood pressure (BP). Thus, HT control is essential not only for primary prevention but also for the secondary prevention of HF. Here, we reviewed the epidemiology, pathophysiology, outcome, and implication of BP management in HHF patients, especially in the Asian population.
PubMed IF 3.4 순환기내과
3412021

제1저자 정종탁 · 교신저자 송경호

, , , , ,
Are coveralls required as personal protective equipment during the management of COVID-19 patients?
Antimicrob Resist Infect Control. 2021;10(1):164.

Abstract
OBJECTIVES Few studies have investigated the contamination of personal protective equipment (PPE) during the management of patients with severe-to-critical coronavirus disease (COVID-19). This study aimed to determine the necessity of coveralls and foot covers for body protection during the management of COVID-19 patients.
METHODS PPE samples were collected from the coveralls of physicians exiting a room after the management of a patient with severe-to-critical COVID-19 within 14 days after the patient's symptom onset. The surface of coveralls was categorized into coverall-only parts (frontal surface of the head, anterior neck, dorsal surface of the foot cover, and back and hip) and gown-covered parts (the anterior side of the forearm and the abdomen). Sampling of the high-contact surfaces in the patient's environment was performed. We attempted to identify significant differences in contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between the coverall-only and gown-covered parts.
RESULTS A total of 105 swabs from PPEs and 28 swabs from patient rooms were collected. Of the PPE swabs, only three (2.8%) swabs from the gown-covered parts were contaminated with SARS-CoV-2. However, 23 of the 28 sites (82.1%) from patient rooms were contaminated. There was a significant difference in the contamination of PPE between the coverall-only and gown-covered parts (0.0 vs 10.0%, p = 0.022).
CONCLUSIONS Coverall contamination rarely occurred while managing severe-to-critical COVID-19 patients housed in negative pressure rooms in the early stages of the illness. Long-sleeved gowns may be used in the management of COVID-19 patients.
PubMed IF 5.2 감염내과
3402021

제1저자 장동기, 안동원 · 교신저자 정지봉

, , , , , , , , , ,
Impacts of body composition parameters and liver cirrhosis on the severity of alcoholic acute pancreatitis.
PLoS One. 2021;16(11):e0260309.

Abstract
AIM Liver cirrhosis and features of muscle or adipose tissues may affect the severity of acute pancreatitis (AP). We aimed to evaluate the impact of body composition parameters and liver cirrhosis on the severity of AP in patients with alcohol-induced AP (AAP).
METHODS Patients with presumed AAP who underwent CT within one week after admission were retrospectively enrolled. L3 sectional areas of abdominal fat and muscle, and mean muscle attenuations (MMAs) were quantified. The presence of liver cirrhosis was determined using clinical and CT findings. Factors potentially associated with moderately severe or severe AP were included in the multivariable logistic regression analysis.
RESULTS A total of 242 patients (47.0 ± 12.6 years, 215 males) with presumed AAP were included. The mild and moderately severe/severe (MSS) groups included 137 (56.6%) and 105 patients (43.4%), respectively. Patients in the MSS group had higher rates of liver cirrhosis, organ failure, and local complications. Among body composition parameters, mean MMA (33.4 vs 36.8 HU, P<0.0001) and abdominal muscle mass (126.5 vs 135.1 cm2, P = 0.029) were significantly lower in the MSS group. The presence of liver cirrhosis (OR, 4.192; 95% CI, 1.620-10.848) was found to be a significant risk factor for moderately severe or severe AP by multivariable analysis.
CONCLUSION The results of this study suggest that liver cirrhosis has a significant impact on the severity of AAP. Of the body composition parameters examined, MMA and abdominal muscle mass showed potential as promising predictors.
PubMed IF 2.8 소화기내과
3392021

제1저자 김율 · 교신저자 이지영, 신철민

, , , ,
Cholecystectomy and subsequent risk of Parkinson's disease: a nationwide retrospective cohort study.
NPJ Parkinsons Dis. 2021;7(1):100.

Abstract
Growing evidence has suggested that the gut-brain axis plays an important role in the pathogenesis of Parkinson's disease (PD), and that this role is mediated by the interactions between bile acids (BAs) and intestinal microbiota. Given that cholecystectomy can lead to alterations in BAs and gut microbiota, we investigated whether cholecystectomy is linked to a higher risk of PD. We constructed a cohort of patients with an operation code of cholecystectomy from 2010 to 2015 (n = 161,838) and age- and sex-matched control subjects without cholecystectomy (n = 286,135) using the National Health Insurance Service database. Incident PD was traced over a maximum observation period of 7 years. We identified 1404 incident PD cases during 1,631,265 person-years of follow-up. The cholecystectomy group showed an elevated risk of PD compared to the control group, even after adjusting for potential confounding factors (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.02-1.27). When the data were split by sex, the risk elevation was significant in men (adjusted HR 1.22, 95% CI 1.06-1.41), but not in women (adjusted HR 1.03, 95% CI 0.88-1.22). Our results provide evidence that cholecystectomy is associated with an increased risk of developing PD. This association differed between men and women, suggesting sex-specific effects of cholecystectomy on the risk of PD.
PubMed IF 8.5 소화기내과
3382021

제1저자 김정석, 윤혁 · 교신저자 박동일, 예병덕

, , , , , , , , , , , , , , , , ,
Clinical Outcomes and Response Predictors of Vedolizumab Induction Treatment for Korean Patients With Inflammatory Bowel Diseases Who Failed Anti-TNF Therapy: A KASID Prospective Multicenter Cohort Study.
Inflamm Bowel Dis. 2021;27(12):1931-1941.

Abstract
BACKGROUND We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed.
METHODS Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission.
RESULTS Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event.
CONCLUSIONS Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy.
PubMed IF 5.5 소화기내과
3372021

제1저자 허건, 이희승, 최진호 · 교신저자 이상협

, , , , , , , ,
Gemcitabine plus Nab-paclitaxel as a second-line treatment following FOLFIRINOX failure in advanced pancreatic cancer: a multicenter, single-arm, open-label, phase 2 trial.
Ther Adv Med Oncol. 2021;13:17588359211056179.

Abstract
BACKGROUND The aim of this study was to evaluate the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) as second-line chemotherapy following first-line FOLFIRINOX treatment failure in advanced pancreatic cancer.
METHODS This was a multicenter, single-arm, open-label, phase 2 trial done at three tertiary centers in South Korea from May 2018 to December 2019. Eligible patients were aged 20 years or older, had histologically confirmed advanced pancreatic ductal adenocarcinoma, and disease progression after receiving first-line FOLFIRINOX. Patients received a second-line GnP regimen as intravenous nab-paclitaxel at a dose of 125 mg/m² and gemcitabine at a dose of 1000 mg/m², on days 1, 8, and 15 every 4 weeks until disease progression or unacceptable toxicity. The primary outcome was survival rate at 6 months and the secondary outcomes were median progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events. This study is registered with Clinicaltrials.gov. (NCT03401827).
RESULTS Forty patients were enrolled in the study. The survival rate at 6 months was 72.5% [95% confidence interval (CI), 59.9-87.7], achieving superiority over prespecified assumed 6-month OS rate of 20% for best supportive care only (p < 0.001). The median PFS and OS were 5.8 months (95% CI, 4.3-8.7) and 9.9 months (95% CI, 7.5-12.4), respectively. DCR was 87.5% with six partial responses and 29 stable diseases. Grade 3 or higher treatment-related adverse events occurred in 25 (62.5%) patients with the most common being thrombocytopenia, anemia, neutropenia, peripheral neuropathy, and peripheral edema.
CONCLUSION GnP demonstrated favorable efficacy with acceptable toxicity in patients with advanced pancreatic ductal adenocarcinoma after FOLFIRINOX failure.
PubMed IF 4.1 소화기내과
3362021

제1저자 이정훈 · 교신저자 김윤준

, , , , ,
Entecavir Plus Pegylated Interferon and Sequential Hepatitis B Virus Vaccination Increases Hepatitis B Surface Antigen Seroclearance: A Randomized Controlled Proof-of-Concept Study.
Clin Infect Dis. 2021;73(9):e3308-e3316.

Abstract
BACKGROUND Hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure for patients with chronic hepatitis B, but is rarely achievable with oral nucleos(t)ide analogues alone. We conducted a randomized controlled proof-of-concept trial to evaluate the impact of adding pegylated interferon (peg-IFN) alfa-2a plus sequential or concomitant hepatitis B virus (HBV) vaccination.
METHODS A total of 111 patients who achieved serum HBV DNA <20 IU/mL and quantitative HBsAg <3000 IU/mL with entecavir were randomly assigned (1:1:1) to the E + sVIP group (entecavir + peg-IFN alfa-2a [180 µg every week over 48 weeks] plus sequential HBV vaccination [20 µg of HBsAg on weeks 52, 56, 60, and 76]), the E + cVIP group (entecavir + peg-IFN alfa-2a + concomitant HBV vaccination [weeks 4, 8, 12, and 28]), or the control group (entecavir only). The primary endpoint was HBsAg seroclearance at week 100, and secondary endpoints included safety.
RESULTS No differences in baseline quantitative HBsAg were observed among the groups. The E + sVIP group in the intention-to-treat analysis showed a significantly higher chance of HBsAg seroclearance during week 100 than the control group (16.2% vs 0%; P = .025), but the E + cVIP group (5.4%) failed to reach a significant difference (P = .54). Adverse events were significantly more frequent in the E + sVIP (81.1%) and E + cVIP group (70.3%) than the control group (2.7%) (both P < .0001). However, the frequency of serious adverse events did not differ significantly among the 3 groups (2.7%, 5.4%, and 2.7%, respectively; P = 1.00).
CONCLUSIONS Entecavir plus an additional peg-IFN alfa-2a treatment followed by sequential HBV vaccination under an intensified schedule significantly increases the chance of HBsAg seroclearance compared to entecavir alone.
CLINICAL TRIALS REGISTRATION NCT02097004.
PubMed IF 8.3 소화기내과
3352021

제1저자 김연욱 · 교신저자 이춘택

, , , , , , , , , , ,
Differences in detection patterns, characteristics, and outcomes of central and peripheral lung cancers in low-dose computed tomography screening.
Transl Lung Cancer Res. 2021;10(11):4185-4199.

Abstract
BACKGROUND Although low-dose computed tomography (LDCT) screening is known to be effective for the detection of lung cancers localized in peripheral lung regions at a curable stage, limited data is available regarding the characteristics and outcomes of central lung cancers diagnosed in a screening cohort. This study aimed to determine whether LDCT screening could effectively detect central lung cancers at an early stage and offer survival benefits.
METHODS We analyzed 52,615 adults who underwent lung cancer screening with LDCT between May 2003 and Dec 2019 at a tertiary center in South Korea. Characteristics and outcomes of those diagnosed with lung cancer, stratified by screen-detection status and cancer location, were evaluated.
RESULTS A total of 352 individuals (281 screen-detected, 71 non-screen-detected) were diagnosed with lung cancer. Compared to screen-detected cancers, non-screen-detected cancers tended to be centrally-located (11.4% vs. 64.8%, P<0.001). Most non-screen-detected central cancers (89.1%) had a negative result on prior LDCT screening. Multivariable regression analyses revealed that for peripheral cancers, screen-detection was associated with a significantly lower probability of diagnosis at an advanced stage [III/IV, odds ratio (OR) =0.15, 95% confidence interval (CI): 0.05-0.45] and mortality [hazard ratio (HR) =0.33, 95% CI: 0.13-0.84]; however, the association was insignificant for central cancers. For screen-detected cancers, central location, compared to peripheral location, was significantly associated with a higher risk of diagnosis at an advanced stage (OR =20.83, 95% CI: 6.67-64.98) and mortality (HR =4.98, 95% CI: 2.26-10.97).
CONCLUSIONS Unlike for peripheral cancers, LDCT screening did not demonstrate an improvement in outcomes of central lung cancers, indicating an important limitation of LDCT screening and the need for developing novel modalities to screen and treat central lung cancer.
PubMed IF 3.4 호흡기내과
3342021

제1저자 A Maxim Bax · 교신저자 윤연이

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Plaque Character and Progression According to the Location of Coronary Atherosclerotic Plaque.
Am J Cardiol. 2021;158:15-22.

Abstract
Although acute coronary syndrome culprit lesions occur more frequently in the proximal coronary artery, whether the proximal clustering of high-risk plaque is reflected in earlier-stage atherosclerosis remains unclarified. We evaluated the longitudinal distribution of stable atherosclerotic lesions on coronary computed tomography angiography (CCTA) in 1,478 patients (mean age, 61 years; men, 58%) enrolled from a prospective multinational registry of consecutive patients undergoing serial CCTA. Of 3,202 coronary artery lesions identified, 2,140 left lesions were classified (based on the minimal lumen diameter location) into left main (LM, n = 128), proximal (n = 739), and other (n = 1,273), and 1,062 right lesions were classified into proximal (n = 355) and other (n = 707). Plaque volume (PV) was the highest in proximal lesions (median, 26.1 mm³), followed by LM (20.6 mm³) and other lesions (15.0 mm³, p <0.001), for left lesions, and was lager in proximal (25.8 mm³) than in other lesions (15.2 mm³, p <0.001) for right lesions. On both sides, proximally located lesions tended to have greater necrotic core and fibrofatty components than other lesions (left: LM, 10.6%; proximal, 5.8%; other, 3.4% of the total PV, p <0.001; right: proximal, 8.4%; other 3.1%, p <0.001), with less calcified plaque component (left: LM, 18.3%; proximal, 30.3%; other, 37.7%, p <0.001; right: proximal, 23.3%, other, 36.6%, p <0.001), and tended to progress rapidly (adjusted odds ratios: left: LM, reference; proximal, 0.95, p = 0.803; other, 0.64, p = 0.017; right: proximal, reference; other, 0.52, p <0.001). Proximally located plaques were larger, with more risky composition, and progressed more rapidly.
PubMed IF 2.5 순환기내과
3332021

제1저자 박하람 · 교신저자 김태민

, , , , , , , , , ,
Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors in Patients With De Novo EGFRT790M-Mutant NSCLC.
J Thorac Oncol. 2021;16(11):1859-1871.

Abstract
INTRODUCTION EGFR^T790M mostly exists subclonally and is acquired as the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, because de novo EGFR^T790M-mutant NSCLC is rare, little is known on acquired resistance mechanisms to third-generation EGFR TKIs.
METHODS Acquired resistance mechanisms were analyzed using tumor and plasma samples before and after third-generation EGFR TKI treatment in four patients with de novo EGFR^T790M-mutant NSCLC. Genetic alterations were analyzed by whole-exome sequencing, targeted sequencing, fluorescence in situ hybridization, and droplet digital PCR. MTOR^L1433S, confirmed for oncogenicity using the Ba/F3 system, was reproduced in H1975 cell lines using CRISPR/Cas9-RNP.
RESULTS Of seven patients with NSCLC with de novo EGFR^T790M/L858R mutation, four (LC1-4) who received third-generation EGFR TKIs acquired resistance after achieving a partial response (median = 27 mo, range: 17-48 mo). Novel MTOR^L1433S and EGFR^C797S/L798I mutations in cis, MET amplification, and EGFR^C797S mutation were identified as acquired resistance mechanisms to third-generation EGFR TKIs. The MTOR^L1433S mutation was oncogenic in Ba/F3 models and revealed resistance to osimertinib through AKT signaling activation in NCI-H1975 cells harboring the MTOR^L1433S mutation edited by CRISPR/Cas9 (half-maximal inhibitory concentration, 800 ± 67 nM). Osimertinib in combination with mTOR inhibitors abrogated acquired resistance to osimertinib.
CONCLUSIONS Activation of bypass pathways and the EGFR^C797S or EGFR^C797S/L798I mutation were identified as acquired resistance mechanisms to third-generation EGFR TKIs in patients with NSCLC with de novo EGFR^T790M mutation. In addition, MTOR^L1433S- and EGFR^L858R/T790M-mutant NSCLC cells were sensitive to osimertinib plus mTOR inhibitors.
PubMed IF 23.3 혈액종양내과
3322021

제1저자 박세훈 · 교신저자 이하정

, , , , , , , , ,
Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study.
Am J Transplant. 2021;21(11):3629-3639.

Abstract
Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88-6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73-1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24-4.39]) and death-censored graft failure (HR 2.26 [1.39-3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.
PubMed IF 8.1 신장내과
3312021

제1저자 김미나, 문준호 · 교신저자 조영민

, ,
Sodium-glucose cotransporter-2 inhibition reduces cellular senescence in the diabetic kidney by promoting ketone body-induced NRF2 activation.
Diabetes Obes Metab. 2021;23(11):2561-2571.

Abstract
AIMS To evaluate whether sodium-glucose cotransporter-2 (SGLT2) inhibition reduces cellular senescence in the kidney and to investigate the molecular pathways involved in the renoprotective effect.
MATERIALS AND METHODS Dapagliflozin (1 mg/kg), glimepiride (2.5 mg/kg) or vehicle was administered daily via oral gavage for 8 weeks in db/db mice. Expression levels of ageing marker genes (p21, p16, and p53) and oxidative stress were measured in the kidney using real-time RT-PCR, immunohistochemistry, and Western blot analysis. For in vitro analysis, HK-2 cells, a human renal tubular epithelial cell line, were pretreated with H₂ O₂ to induce cellular senescence, and the levels of ageing markers were measured after treatment with β-hydroxybutyrate (β-HB) or NRF2-specific siRNA.
RESULTS Expression levels of ageing marker genes (p21, p16 and p53) and senescence-associated secretory phenotypes of the kidney were increased in the vehicle-treated db/db (db/db + vehicle) group compared with the db/+ group, and this increase was markedly reversed in the dapagliflozin-treated db/db (db/db + SGLT2 inhibitor) group, but not in the glimepiride-treated db/db (db/db + sulphonylurea [SU]) group. In the kidneys of mice in the db/db + SGLT2 inhibitor group, oxidative stress and DNA damage were also reduced compared with those of mice in the db/db + vehicle and db/db + SU groups. Dapagliflozin increased plasma β-HB, which reduced H₂ O₂ -induced DNA damage and senescence in HK-2 cells. β-HB-induced NRF2 nuclear translocation mediated anti-senescent effects by inducing antioxidant pathways.
CONCLUSIONS Dapagliflozin prevented the progression of diabetic kidney disease by inhibiting cellular senescence and oxidative stress via ketone-induced NRF2 activation.
PubMed IF 6.1 내분비대사내과
3302021

제1저자 최광준 · 교신저자 김세중

, , , , , , ,
Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2Vaccination in Patient with Multiple Myeloma.
Emerg Infect Dis. 2021;27(11):2973-2975.

Abstract
A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.
PubMed IF 7.9 신장내과
3292021

제1저자 박지은, 이경희 · 교신저자 허정배, 유철규

, , , , , , ,
The impact of organic extracts of seasonal PM2.5 on primary human lung epithelial cells and their chemical characterization.
Environ Sci Pollut Res Int. 2021;28(42):59868-59880.

Abstract
Lung epithelial cells serve as the first line of defense against various inhaled pollutant particles. To investigate the adverse health effects of organic components of fine particulate matter (PM_2.5) collected in Seoul, South Korea, we selected 12 PM_2.5 samples from May 2016 to January 2017 and evaluated the effects of organic compounds of PM_2.5 on inflammation, cellular aging, and macroautophagy in human lung epithelial cells isolated directly from healthy donors. Organic extracts of PM_2.5 specifically induced neutrophilic chemokine and interleukin-8 expression via extracellular signal-regulated kinase activation. Moreover, PM_2.5 significantly increased the expression of aging markers (p16, p21, and p27) and activated macroautophagy. Average mass concentrations of organic and elemental carbon had no significant correlations with PM_2.5 effects. However, polycyclic aromatic hydrocarbons and n-alkanes were the most relevant components of PM_2.5 that correlated with neutrophilic inflammation. Vegetative detritus and residential bituminous coal combustion sources strongly correlated with neutrophilic inflammation, aging, and macroautophagy activation. These data suggest that the chemical composition of PM_2.5 is important for determining the adverse health effects of PM_2.5. Our study provides encouraging evidence to regulate the harmful components of PM_2.5 in Seoul.
PubMed IF 4.223 호흡기내과

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