SCI 발표논문

전체 4,588편

32382020

제1저자 구보경 · 교신저자 김원

, , , , , , , , ,
Association Between a Polymorphism in MBOAT7 and Chronic Kidney Disease in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease.
Clin Gastroenterol Hepatol. 2020;18(12):2837-2839.e2.

Abstract
Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share risk factors, and recent meta-analysis confirmed that NAFLD is an independent risk factor for incident CKD.¹ Genetic variants associated with NAFLD, such as patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409² and transmembrane 6 superfamily member 2 (TM6SF2) rs5854292,² have been reported to be associated with renal function in NAFLD subjects.
PubMed IF 16.2 소화기내과
32372020

제1저자 권순일, 이소령 · 교신저자 최의근

, , , , , , , ,
Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.
Am Heart J. 2020;229:81-91.

Abstract
BACKGROUND The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited.
OBJECTIVES We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years.
METHODS Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated.
RESULTS Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively).
CONCLUSION NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.
PubMed IF 3.4 순환기내과
32362020

제1저자 최용훈 · 교신저자 김나영

, , , , , , , , , , , , , , , , , , ,
Effect of Helicobacter pylori eradication after subtotal gastrectomy on the survival rate of patients with gastric cancer: follow-up for up to 15 years.
Gastric Cancer. 2020;23(6):1051-1063.

Abstract
OBJECTIVE Helicobacter pylori (HP) is known to play an important role in the development of gastric cancer (GC). The aim of this study was to analyze the effect of HP eradication on the survival rate and cancer recurrence in patients who underwent subtotal gastrectomy for GC.
DESIGN Totally 1,031 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital from 2003 to 2017 and positive for HP infection were analyzed. The overall and GC-related survival according to HP eradication were compared; risk factors for GC-specific death and cancer recurrence were analyzed, and propensity score matching (PSM) was performed.
RESULTS Statistically significant benefits of overall and GC-specific survival were observed in the eradicated group compared to the non-eradicated group (P < 0.001), and these benefits were maintained after PSM (P < 0.001) in both of early and advance stage. In Cox proportional hazards multivariate analyses, cancer stage (stage II, adjusted hazard ratio [aHR] = 9.33, P < 0.001; stage III or IV, aHR = 26.17, P < 0.001), and HP positivity (aHR = 3.41, P = 0.001) were independent risk factors for GC-specific death; cancer stage (cancer stage II, aHR = 7.08, P < 0.001; cancer stage III or IV, aHR = 19.64, P < 0.001) and HP positivity (aHR = 2.70; P = 0.005) were independent risk factors for cancer recurrence.
CONCLUSION Our results suggest that HP needed to be conducted more intensively in patients who are surgically treated for GC, regardless of cancer stage.
PubMed IF 6.1 소화기내과
32352020

제1저자 박준빈 · 교신저자 김형관

, , , , , , , , , , ,
Obesity and metabolic health status are determinants for the clinical expression of hypertrophic cardiomyopathy.
Eur J Prev Cardiol. 2020;27(17):1849-1857.

Abstract
AIMS We sought to investigate the association of obesity and metabolic health status with the incidence of clinical hypertrophic cardiomyopathy (HCM) diagnosis in the general population. Our goal was to identify modifiable risk factors to attenuate clinical expression of HCM, enabling management evolution from a mostly passive strategy of risk stratification to a proactive strategy of modifying disease expression.
METHODS Using nationwide population-based data from the Korean National Health Insurance Service, 28,679,891 people who were free of prevalent HCM and who underwent health examinations between 2009 and 2015 were followed until 31 December 2016. The primary outcome was clinical HCM that was defined as incident diagnosis of HCM during the follow-up, after a blanking period of 12 months.
RESULTS Over a median follow-up of 5.2 years, 0.027% (n = 7851) of the study participants were diagnosed as incident HCM. The incidence rate per 1000 person-years was 0.059. A significant association was found between body mass index (BMI) and the incidence of clinical HCM after multivariate adjustment, with a hazard ratio per 1 kg/m² increase in BMI of 1.063 (95% confidence interval 1.051-1.075). Metabolically unhealthy participants had a greater incidence of HCM than metabolically healthy participants, regardless of obesity status. The effect of BMI was more pronounced in several subgroups, including participants with no hypertension, those aged less than 65 years and men.
CONCLUSION We found that individuals with obesity and/or metabolic abnormalities had a significantly higher incidence of clinical HCM diagnosis than their counterparts. Efforts to manage obesity and metabolic abnormalities may be important in modifying clinical expression of HCM.
PubMed IF 10 순환기내과
32342020

제1저자 박세훈, 양승희 · 교신저자 이하정

, , , , , , , ,
RNA-Seq profiling of microdissected glomeruli identifies potential biomarkers for human IgA nephropathy.
Am J Physiol Renal Physiol. 2020;319(5):F809-F821.

Abstract
Few studies have examined gene expression changes occurring in the glomeruli of IgA nephropathy (IgAN) using a sensitive transcriptomic profiling method such as RNA sequencing (RNA-Seq). We collected glomeruli from biopsy specimens from patients with IgAN with relatively preserved kidney function (estimated glomerular filtration rate ≥ 60 mL·min^-1·1.73 m^-2 and urine protein-to-creatinine ratio < 3 g/g) and from normal kidney cortexes by hand microdissection and performed RNA-Seq. Differentially expressed genes were identified, and gene ontology term annotation and pathway analysis were performed. Immunohistochemical labeling and primary mesangial cell cultures were performed to confirm the findings of RNA-Seq analysis. Fourteen patients with IgAN and ten controls were included in this study. Glomerulus-specific genes were highly abundant. Principal component analysis showed clear separation between the IgAN and control groups. There were 2,497 differentially expressed genes, of which 1,380 were upregulated and 1,117 were downregulated (false discovery rate < 0.01). The enriched gene ontology terms included motility/migration, protein/vesicle transport, and immune system, and kinase binding was the molecular function overrepresented in IgAN. B cell signaling, chemokine signal transduction, and Fcγ receptor-mediated phagocytosis were the canonical pathways overrepresented. In vitro experiments confirmed that spleen tyrosine kinase (SYK), reported as upregulated in the IgAN transcriptome, was also upregulated in glomeruli from an independent set of patients with IgAN and that treatment with patient-derived IgA1 increased the expression of SYK in mesangial cells. In conclusion, transcriptomic profiling of the IgAN glomerulus provides insights in the intraglomerular pathophysiology of IgAN before it reaches profound kidney dysfunction. SYK may have a pathogenetic role in IgAN.
PubMed IF 3.6 신장내과
32332020

제1저자 윤준식, 이효영 · 교신저자 김윤준

, , , , , , , , , , ,
Prognostic impact of concurrent nonalcoholic fatty liver disease in patients with chronic hepatitis B-related hepatocellular carcinoma.
J Gastroenterol Hepatol. 2020;35(11):1960-1968.

Abstract
BACKGROUND AND AIM As the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally, patients with both NAFLD and chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is also frequently found. This study aimed to investigate the clinical impact of concurrent NAFLD on the prognosis of patients with CHB-related HCC.
METHODS Patients with CHB-related HCC who underwent surgical resection were consecutively selected from August 2009 to December 2013. The association between histologically proven concurrent NAFLD and clinical outcomes were analyzed. Propensity score (PS) matching was adapted to adjust for baseline characteristics. We also investigated the presence of nonalcoholic steatohepatitis (NASH) among patients with NAFLD and its association with clinical outcomes.
RESULTS Among 338 CHB-related HCC patients selected, 196 patients (58.0%) were diagnosed with concurrent NAFLD. The median follow-up duration was 74.9 months. The patients with NAFLD tended to have better recurrence-free survival (RFS; log-rank, P = 0.16) and had significantly better overall survival (OS; log-rank, P = 0.004) than those without NAFLD. However, the survival benefit of the concurrent NAFLD was not significant in a multivariable Cox analysis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73, P = 0.84) or an analysis after PS matching (log-rank, P = 0.57). Regarding the presence or absence of NASH, no differences in the RFS (log-rank, P = 0.61) and OS (log-rank, P = 0.26) were found.
CONCLUSIONS Concurrent NAFLD was not associated with both RFS and OS in patients with CHB-related HCC after adjusting for baseline characteristics. Moreover, NAFLD patients with NASH did not have significantly different clinical outcomes compared with NAFLD patients without NASH.
PubMed IF 3.5 소화기내과
32322020

제1저자 최윤진 · 교신저자 이동호

, ,
Association between high fatty liver index and development of colorectal cancer: a nationwide cohort study with 21,592,374 Korean.
Korean J Intern Med. 2020;35(6):1354-1363.

Abstract
BACKGROUND/AIMS In Korea, the incidence of colorectal cancer (CRC) and nonalcoholic fatty liver disease (NAFLD) has increased due to a westernized lifestyle. This study investigated whether a high fatty liver index that reflects NAFLD correlates with CRC.
METHODS Data from the National Health Insurance Corporation 2009 to 2012 were analyzed. NAFLD disease was defined as a fatty liver index > 60 in the absence of alcohol consumption of ≥ 30 g/day.
RESULTS NAFLD was identified in 2,543,649 (11.8%) of 21,592,374 participants. CRC was identified in 19,785 (0.8%) of participants with NAFLD (fatty liver index ≥ 60) and in 80,871 (0.6%) participants without NAFLD (fatty liver index < 30). Multivariate logistic regression analysis demonstrated an independent association between NAFLD and CRC after adjusting for other confounders (hazard ratio, 1.13; odds ratio, 1.12 to 1.15). In subgroup analyses, fatty liver index ≥ 60 was associated with CRC regardless of body mass index, but the association was more prominent in persons with a normal index. NAFLD, in the absence of diabetes, hypertension, or dyslipidemia, was more highly associated with CRC than when one or more of these conditions are present.
CONCLUSION CRC should be considered as a possibility in patients with fatty liver index ≥ 60, even in the absence of obesity or other metabolic syndromes.
PubMed IF 2.2 소화기내과
32312020

제1저자 Hailian Quan, 오규철 · 교신저자 석승혁, 이해영

, , ,
Fimasartan, an angiotensin II receptor antagonist, ameliorates an in vivo zebrafish model of heart failure.
Korean J Intern Med. 2020;35(6):1400-1410.

Abstract
BACKGROUND/AIMS Angiotensin II in the failing heart initially helps to maintain cardiac output and blood pressure, but ultimately accelerates its deterioration. In this study, we established a model of arrhythmia-induced heart failure (HF) in zebrafish and investigated the role of renin-angiotensin-aldosterone system (RAAS) modulation by using an angiotensin II type 1 receptor blocker, fimasartan, through the assessment of cellular and physiologic responses, morbidity, and mortality.
METHODS HF was induced in zebrafish larvae by exposure to 20 μM terfenadine. Morphologic, physiologic, and functional parameters were assessed in the presence or absence of fimasartan treatment.
RESULTS Zebrafish exposed to terfenadine showed marked dilatation of the ventricle and reduced systolic function. Treatment with terfenadine was associated with 10-fold higher expression of atrial natriuretic peptide (p < 0.001 vs. vehicle), increased p53 mRNA expression, and chromatin fragmentation in the TUNEL assay, all of which were significantly reduced by fimasartan treatment. Moreover, fimasartan improved fractional shortening (terfenadine + fimasartan 16.9% ± 3.1% vs. terfenadine + vehicle 11.4% ± 5.6%, p < 0.05) and blood flow (terfenadine + fimasartan 479.1 ± 124.1 nL/sec vs. terfenadine + vehicle 273.0 ± 109.0 nL/sec, p < 0.05). Finally, treatment with fimasartan remarkably reduced mortality (terfenadine + fimasartan 36.0% vs. terfenadine + vehicle 96.0%, p < 0.001).
CONCLUSION Fimasartan effectively protected against the progression of HF in zebrafish by improving hemodynamic indices, which improved survival. A reduction in apoptotic cell death and an improvement in hemodynamics may be the mechanisms behind these effects. Further human studies are warranted to evaluate the possible role of fimasartan in the treatment of HF.
PubMed IF 2.2 순환기내과
32302020

제1저자 박세훈 · 교신저자 이하정

, , , , , , , ,
Characteristics of kidney transplantation recipients over time in South Korea.
Korean J Intern Med. 2020;35(6):1457-1467.

Abstract
BACKGROUND/AIMS Detailed nationwide information regarding the recent status and time trends of kidney transplantation (KT) in South Korea is limited.
METHODS We performed a nationwide, population-based cohort study using the national claims database of Korea. We included KT recipients from 2008 to 2016, and their demographic and clinical characteristics were collected. The prognostic outcome was graft failure consisted of patient death and death-censored graft failure (DCGF).
RESULTS We studied 14,601 KT recipients with median follow-up duration of 3.96 years. The median age at the time of transplantation consistently increased from the past, and proportion of underlying diabetes mellitus prominently increased, reaching 35.6% in 2016. The preemptive KT accounted for approximately 30% of the total transplantation cases. The recipients showed a 10-year cumulative graft survival rate of 71.8%, consisting of 10-year DCGF free survival of 77.6% and patient survival of 92.8%. Age ≥ 20 and < 30 years, age ≥ 70 years, underlying history of diabetes, non-preemptive transplantation, and poor compliance on tacrolimus and mycophenolic acid were the significant risk factors associated with worse DCGF outcome. The economic cost of KT showed prominently increasing trends, reaching a total insured fee of > 60,000,000$ in 2016. However, the expansion was mainly burdened by the national insurance service but not by the patients.
CONCLUSION In South Korea, the number of kidney transplantation in elderly or in patients with comorbidities has been increasing. Complex clinical factors were associated with medication compliance and patient prognosis.
PubMed IF 2.2 신장내과
32292020

제1저자 박찬순 · 교신저자 이해영

, , , , , , , , , , , , , , , , , ,
J-curve relationship between corrected QT interval and mortality in acute heart failure patients.
Korean J Intern Med. 2020;35(6):1371-1384.

Abstract
BACKGROUND/AIMS This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex.
METHODS We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex.
RESULTS During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female.
CONCLUSION QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.
PubMed IF 2.2 순환기내과
32282020

제1저자 장경민, 박미리 · 교신저자 김학령

, ,
Time point of blood pressure drop in patients with orthostatic hypotension in the emergency department.
J Hypertens. 2020;38(11):2169-2175.

Abstract
OBJECTIVE The purpose of this study was to identify the time of blood pressure (BP) drop in the orthostatic hypotension test, and to propose a realistic and appropriate duration in the orthostatic hypotension test.
METHODS A total of 879 consecutive patients (61-year-old and 44% women) with positive on the orthostatic hypotension test in the emergency department were retrospectively reviewed. Orthostatic hypotension was defined as drop in standing SBP of at least 20 mmHg or standing DBP of at least 10 mmHg from their supine values after standing for 5 min. BP measurements was made at 1, 3, and 5 min after standing.
RESULTS Six hundred and eighty-four (77.8%), 152 (17.3%) and 43 (4.9%) patients had BP drop meeting orthostatic hypotension criteria at 1, 3, and 5 min, respectively. In multivariable analysis, older age (≥60 years) and higher blood urea nitrogen (BUN) (≥15.5 mg/dl) were independently associated with early BP drop at 1 min, and younger age (<40 years) was independently associated with later BP drop at 5 min even after controlling for potential confounders.
CONCLUSION To measure orthostatic BP for orthostatic hypotension diagnosis at emergency department, older patients (≥60 years) with high BUN (≥15.5 mg/dl) should be monitored carefully as BP can drop quickly within 1 min. On the contrary, in younger people (<40 years), BP drop occurred slowly after 3 min, suggesting that clinicians measure BP for a longer time.
PubMed IF 5.6 순환기내과
32272020

제1저자 김도형, 박지인 · 교신저자 임춘수

, , , , , , , ,
The effects of vascular access types on the survival and quality of life and depression in the incident hemodialysis patients.
Ren Fail. 2020;42(1):30-39.

Abstract
Background: Although arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD), the association between vascular access types and quality of life is not well-known. We investigated the relationships between HD vascular access types and all-cause mortality, health-related quality of life (HRQOL) and the degree of depression in a large prospective cohort.Methods: A total of 1461 patients who newly initiated HD were included. The initial vascular access types were classified into AVF, arteriovenous graft (AVG), and central venous catheter (CVC). The primary outcomes were all-cause mortality and HRQOL and depression. The secondary outcome was all-cause hospitalization. Kidney Disease Quality of Life Short Form 36 (KDQOL-36) and Beck's depression inventory (BDI) scores were measured to assess HRQOL and depression.Results: Among 1461 patients, we identified 314 patients who started HD via AVF, 76 via AVG, and 1071 via CVC. In the survival analysis, patients with AVF showed significantly better survival compared with patients with other accesses (p < .001). The AVF and AVG group had higher KDQOL-36 score and lower BDI score than CVC group at 3 months and 12 months after the initiation of HD. The frequency of hospitalization was higher in patients with AVG compared to those with AVF (AVF 0.7 vs. AVG 1.1 times per year) (p = .024).Conclusions: The patients with AVF had better survival rate and low hospitalization rate, and the patients with AVF or AVG showed both higher HRQOL and lower depression scores than those with CVC.
PubMed IF 3.8 신장내과
32262020

제1저자 정영애, 이민경, 김원 · 교신저자 김원, 황금숙

, , , , , , , , , , , , , , , , ,
Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease.
Aliment Pharmacol Ther. 2020;52(10):1603-1614.

Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear.
AIMS To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach.
METHODS A cross-sectional analysis of 361 subjects with biopsy-proven NAFLD (157 NAFL and 138 NASH) and healthy controls (n = 66) was performed. Individuals were categorised as obese or non-obese based on the Asian cut-off for body mass index. Circulating lipidomic profiling of sera was performed based on the histological severity of NAFLD. Circulating lipidomic alterations were validated with an independent validation set (154 NAFLD subjects [93 NAFL and 61 NASH] and 21 healthy controls).
RESULTS Saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in non-obese NAFLD (SM d38:0; P < 0.001) but not in obese NAFLD. Additionally, SM levels were significantly associated with systemic and adipose tissue insulin resistance (SM d38:0; P = 0.002 and <0.001, respectively). Five potential lipid metabolites for non-obese subjects and seven potential lipids for obese subjects were selected to predict NAFLD and NASH. These lipid combinations showed good diagnostic performance for non-obese (area under the curve [AUC] for NAFLD/NASH = 0.916/0.813) and obese (AUC for NAFLD/NASH = 0.967/0.812) subjects. Moreover, distinctly altered patterns of diacylglycerol (DAG), triacylglycerol (TAG) and SM levels were confirmed in the validation set depending on the histological severity of NAFLD.
CONCLUSION Non-obese and obese NAFLD subjects exhibit unique circulating lipidomic signatures, including DAGs, TAGs and SMs. These lipid combinations may be useful biomarkers for non-obese and obese NAFLD patients.
PubMed IF 6.8 소화기내과
32252020

제1저자 이현정 · 교신저자 김형관

, , , , , , , , , , , ,
Clinical impact of atrial fibrillation in a nationwide cohort of hypertrophic cardiomyopathy patients.
Ann Transl Med. 2020;8(21):1386.

Abstract
BACKGROUND The clinical implications of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients are incompletely characterized. We investigated the impact of AF on stroke and mortality, assessed the performance of the CHA2DS2-VASc score, and explored the predictors of stroke in HCM patients.
METHODS A nationwide cohort of HCM patients (n=8,349, mean age 60.7) identified from 2010 to 2015 from the Korean National Health Insurance database were followed up for occurrence of ischemic stroke or all-cause death.
RESULTS During a mean follow-up of 2.5 years, the incidence rate of stroke was 2.69 and 5.87, and mortality rate was 2.06 and 4.44 per 100 person-years in non-AF and AF patients, respectively. AF was independently associated with a 60% and 50% increased risk for stroke and all-cause mortality, respectively. The AF-associated increase in risk of stroke was more prominent in HCM patients with no or few risk factors. The CHA2DS2-VASc score showed poor discrimination of stroke risk in HCM patients with AF, mostly due to the high incidence of stroke in patients with scores of 0 or 1. Traditional risk factors were not always associated with stroke in HCM patients with AF; age, heart failure, high blood pressure and GGT were the strongest predictors of stroke in this population. HCM patients without AF also showed increased incidence of stroke at CHA2DS2-VASc ≥1.
CONCLUSIONS AF was independently associated with increased risks for stroke and all-cause mortality in patients with HCM. The CHA2DS2-VASc score showed poor discrimination of stroke risk in HCM patients with AF.
PubMed IF 3.297 순환기내과
32242020

제1저자 이종찬 · 교신저자 황진혁

, , , , , , ,
Tolerability and safety of EUS-injected adenovirus-mediated double-suicide gene therapy with chemotherapy in locally advanced pancreatic cancer: a phase 1 trial.
Gastrointest Endosc. 2020;92(5):1044-1052.e1.

Abstract
BACKGROUND AND AIMS Locally advanced pancreatic cancer (LAPC) is challenging. Here, we aimed to evaluate the tolerability and safety of Ad5-yCD/mutTK(SR39)rep-ADP (Ad5-DS), a replication-competent adenovirus-mediated double-suicide gene therapy in combination with gemcitabine in patients with LAPC.
METHODS Patients with newly diagnosed LAPC were enrolled in this single-center, open-label, 3 + 3 dose-escalation phase 1 trial. Ad5-DS was injected into the pancreatic mass with EUS-guided fine needles combined with oral 5-fluorocytosine and valganciclovir, and a standard dose of intravenous gemcitabine. The doses of Ad5-DS in cohorts 1 to 3 were 1 × 10¹¹, 3 × 10¹¹, and 1 × 10¹² viral particles (vp)/mL, respectively. Patients were observed for dose-limiting toxicity (DLT) for 8 weeks after Ad5-DS injection. Toxicity within 12 weeks, tumor response in 12 weeks, disease progression in 6.5 months, and detection of adenoviral DNA particles in 8 weeks were also assessed.
RESULTS Among the 11 enrolled patients, 9 completed the evaluation period and 2 withdrew their consent. No DLT was reported; thus, the maximum tolerated dose was not reached. No additional toxicity was reported in 9 to 12 weeks. One patient showed a partial response and 8 showed stable disease at 12 weeks. Two patients showed disease progression at 6.5 months (median progression-free survival, 11.4 months). At 8 weeks, serum adenoviral DNA particles were detected in 4 patients (median, 55 days).
CONCLUSION A combination of intratumoral Ad5-DS and gemcitabine is safe and well tolerated in patients with LAPC. This warrants further investigation in a larger clinical trial. (Clinical trial registration number: NCT02894944.).
PubMed IF 8 소화기내과
32232020

제1저자 최정연 · 교신저자 김광일, 김철호

, , , ,
CHA2DS2-VASc score, cerebral small vessel disease, and frailty in older patients with atrial fibrillation.
Sci Rep. 2020;10(1):18765.

Abstract
The CHA₂DS₂-VASc score is a validated predictor of ischemic stroke in atrial fibrillation (AF) patients. However, data are limited on whether the CHA₂DS₂-VASc score is associated with subclinical brain structural changes or physical frailty among older AF patients. We assessed the relationship between CHA₂DS₂-VASc scores and brain structural changes or physical frailty in AF patients without history of stroke. Overall, 117 patients completed a comprehensive geriatric assessment for physical frailty. In brain magnetic resonance imaging sub-study (n = 49), brain volume and white matter hyperintensity lesion burden were automatically quantified using the LESIONQUANT software program. Patients with high risk of CHA₂DS₂-VASc scores (≥ 2 in men or ≥ 3 in women) tended to be older and had more comorbidities, higher frailty index, and slower gait speed. Total white matter hyperintensity lesion burden was higher in those with high risk of CHA₂DS₂-VASc score than in those with intermediate risk (score of 1 in men or 2 in women) of CHA₂DS₂-VASc score (1.67 [interquartile range: 0.70-3.45] vs. 0.64 [0.19-1.44], p = 0.036). Cognitive function was associated with brain volume, but gait speed was related with white matter hyperintensity lesion burden. In conclusion, we showed a positive relationship between CHA₂DS₂-VASc scores, white matter hyperintensity lesion burden, and physical frailty in older AF patients. Subclinical brain changes associated with high CHA₂DS₂-VASc scores may predict physical frailty risk.
PubMed IF 4.9 노인병내과
32222020

제1저자 조재호 · 교신저자 이동호

, , , , ,
Efficacy of DA-5204 (Stillen 2X) for patients with gastroesophageal reflux disease: A randomized, double-blind, placebo-controlled pilot study.
Medicine (Baltimore). 2020;99(44):e22729.

Abstract
BACKGROUND/AIM Proton pump inhibitor (PPI) alone is not satisfactory for the treatment of gastroesophageal reflux disease (GERD). Therefore, we investigated the efficacy of DA-5204 (Stillen 2X, 90 mg of Artemisia asiatica 95% ethanol extract per tablet) and PPI combination therapy on GERD in comparison to PPI alone.
METHODS This randomized, double-blind, placebo-controlled study randomly assigned 70 patients with endoscopically proven esophageal mucosal injury (Los Angeles classification grade A or B) into 2 groups: pantoprazole 40 mg once daily with DA-5204 twice daily (DA-5204 group) or pantoprazole 40 mg once daily with placebo twice daily (placebo group) for 4 weeks. The primary endpoint was endoscopic healing rate. The secondary endpoint was sufficient relief (≥50% reduction) of symptoms using GERD Questionnaire.
RESULTS Final analyses included 29 patients with the DA-5204 group and 30 patients with the placebo group. At weeks 4, there was no significant difference in the endoscopic healing rate between the 2 groups (DA-5204 vs placebo; 96.6% vs 93.3%; P = 1.000). However, the rate of residual minimal change was significantly lower in the DA-5204 group (5/28, 17.9%) than in the placebo group (17/28, 60.7%) (P < .001). The rates of symptom relief were not different between the DA-5204 group and the placebo group (all P > .05).
CONCLUSION Combined therapy with PPI and DA-5204 has no additional effect on the endoscopic healing rate compared to PPI alone. However, it may be beneficial in resolving minimal change.
PubMed IF 2 소화기내과
32212020

제1저자 정재협 · 교신저자 이종찬, 황진혁

, , , ,
Primary Granulocyte Colony-Stimulating Factor Prophylaxis in Metastatic Pancreatic Cancer Patients Treated with FOLFIRINOX as the First-Line Treatment.
Cancers (Basel). 2020;12(11):cancers12113137.

Abstract
Although FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) has been proven efficacious in metastatic pancreatic cancer (MPC), physicians hesitate to administer it due to its hematologic toxicities. We investigated the usefulness of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. We reviewed electronic medical records of MPC patients with good performance status who were administered FOLFIRINOX as the first-line treatment from 2011 to 2017. The patients were divided into primary G-CSF prophylaxis users (group A) and non-users or therapeutic/secondary users (group B). Cumulative relative dose (cRDI), adverse effects (AEs), and overall survival (OS) were compared. A total of 165 patients (group A (57) vs. group B (108)) were investigated. Intergroup differences in baseline characteristics were not significant, although the cRDI and the number of treatment cycles were both higher in group A than in group B (cRDI: 80.6% vs. 73.9%, p = 0.007; 9 vs. 6 cycles, p = 0.004). Primary G-CSF prophylaxis reduced the risk of neutropenia (55.6% to 31.6%, p = 0.003) and febrile neutropenia (18.5% to 1.8%, p = 0.002) and improved OS (8.8 to 14.7 months; hazard ratio [HR]: 1.766, 95% CI: 1.257-2.481, p = 0.001). When administering FOLFIRINOX for MPC, primary G-CSF prophylaxis could be rationalized to reduced AEs and improve survival; more prospective studies are needed.
PubMed IF 4.8 소화기내과
32202020

제1저자 이홍열 · 교신저자 최선미

, , , , , , , , ,
Prognostic impact of malignant diseases in idiopathic pulmonary fibrosis.
Sci Rep. 2020;10(1):18260.

Abstract
No studies on idiopathic pulmonary fibrosis (IPF) have investigated the prognostic impact of extrapulmonary cancers in patients with IPF. We aimed to determine the prognostic impact of malignancies in patients with IPF. We retrospectively reviewed the medical records of patients diagnosed with IPF between 2001 and 2015. Patients were divided into three groups: IPF without cancer (n = 440), IPF with lung cancer (n = 69), and IPF with extrapulmonary cancer (n = 70). Of the 579 patients with IPF, 139 (24%) had cancer; the three most common types were lung (11.9%), gastric (2.4%), and colorectal (1.9%). Survival was significantly worse in patients with lung cancer than in those without cancer (hazard ratio [HR] = 1.83, 95% confidence interval [CI], 1.35-2.48) or those with extrapulmonary cancer (HR = 1.70, 95% CI, 1.14-2.54). The rate of hospitalisation for cancer-related complications was significantly higher in IPF patients with lung cancer than in those with extrapulmonary cancer. The annual rates of decline in percent predicted forced vital capacity and diffusion capacity for carbon monoxide did not differ among the groups. Physicians should pay attention to the development and progression of cancer and its prognostic impact in patients with IPF.
PubMed IF 4.9 호흡기내과
32192020

제1저자 김학령, 김혜미 · 교신저자 박성하, 성기철

, , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Blood pressure levels and cardiovascular risk according to age in patients with diabetes mellitus: a nationwide population-based cohort study.
Cardiovasc Diabetol. 2020;19(1):181.

Abstract
BACKGROUND Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age.
METHODS Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke.
RESULTS Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of < 70 years, the risk of cardiovascular events was lower in patients with BP < 120/70 mmHg than in those with BP 130-139/80-89 mmHg. At the age of ≥ 70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130-139/80-89 mmHg and BP < 120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130-139/80-89 mmHg and BP 120-129/70-79 mmHg, and it was significantly higher in those with BP ≥ 140/90 mmHg than in those with BP 130-139/80-89 mmHg at all ages.
CONCLUSIONS In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of < 70. However, low BP < 130-139/80-89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130-139/80-89 mmHg at the age of ≥ 70.
PubMed IF 15.6 순환기내과
32182020

제1저자 최정연 · 교신저자 김광일

, , , , , , , ,
Validation of an integrated service model, Health-RESPECT, for older patients in long-term care institution using information and communication technologies: protocol of a cluster randomised controlled trial.
BMJ Open. 2020;10(10):e038598.

Abstract
INTRODUCTION There is an increased healthcare need to manage institutionalised older patients owing to the ageing population. To overcome substantial future challenges, the Health-RESPECT (caRE Systems for Patients/Elderly with Coordinated care using icT), a new information and communication technologies based integrated management service model, was developed to provide effective management, enable consultation with distant professionals and share medical information between acute care hospitals and long-term care institutions.
METHODS AND ANALYSIS A cluster randomised controlled trial will be conducted to examine the effectiveness of the Health-RESPECT in older patients with chronic diseases and their medical staff in charge. Intervention involves registration with simple comprehensive geriatric assessment, establishment of an individualised care plan for three chronic diseases (hypertension, diabetes and heart failure), medication and rehabilitation management, periodic video-conference and in-system assessment after intervention period. Primary outcomes are control levels of the three chronic diseases, adequacy of drug management and overall functional status. Patients will be assessed at before and after study period and 3 months after study ended. Analysis will be carried out with an intention-to-treat principle. In addition to evaluate intervention effects, clinical usability and economic evaluation will be assessed.
ETHICS AND DISSEMINATION The study protocol was reviewed and approved by the Seoul National University Bundang Hospital Institutional Review Board. Study findings will be published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER KCT0004360.
PubMed IF 2.5 노인병내과
32172020

제1저자 김효수, 강지훈 · 교신저자 박경우

, , , , , , , , , , , , , ,
Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial.
Lancet. 2020;396(10257):1079-1089.

Abstract
BACKGROUND A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy.
METHODS HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971.
RESULTS From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference -2·9%, p_{non-inferiority}<0·0001; hazard ratio 0·70 [95% CI 0·52-0·92], p_equivalence=0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40-1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32-0·73]; p=0·0007).
INTERPRETATION In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia.
FUNDING Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio.
PubMed IF 109 순환기내과
32162020

제1저자 윤유나 · 교신저자 김재형, 황진혁

, , , ,
Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells.
Sci Rep. 2020;10(1):16518.

Abstract
Cell division cycle 6 (Cdc6) plays key roles in regulating DNA replication, and activation and maintenance of cell cycle check points. In addition, Cdc6 exerts oncogenic properties via genomic instability associated with incomplete DNA replication. This study aimed to examine the effects of Cdc6 on pancreatic cancer (PC) cells. Our results showed that Cdc6 expression was higher in clinical PC specimens (based on analysis of the GEPIA database) and cell lines, and the high Cdc6 expression was associated with poorer survival in The Cancer Genome Atlas-PC cohort. In addition, Cdc6-depleted PC cells significantly inhibited cell proliferation and colony formation, delayed G₂/M cell cycle progression, and increased expression of p-histone H3 and cyclin A2 levels. These observations could be explained by Cdc6 depletion leading to multipolar and split spindles via centrosome amplification and microtubule disorganization which eventually increases chromosome missegregation. Furthermore, Cdc6-depleted PC cells showed significantly increased apoptosis, which was consistent with increased caspase-9 and caspase-3 activation. Collectively, our results demonstrated that Cdc6-depleted PC cells are arrested in mitosis and eventually undergo cell death by induced multipolar spindles, centrosome aberrations, microtubule disorganization, and chromosome instability. In conclusion, Cdc6 may be a potential biomarker and therapeutic target for PC.
PubMed IF 4.9 소화기내과
32152020

제1저자 이길재, 유현주 · 교신저자 김원, 고광표

, , , , , , , , , , , ,
Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD.
Nat Commun. 2020;11(1):4982.

Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.
PubMed IF 18.1 소화기내과
32142020

제1저자 박지인 · 교신저자 이하정, 김봉수

, , , , , , , , , ,
Comparative analysis of the tonsillar microbiota in IgA nephropathy and other glomerular diseases.
Sci Rep. 2020;10(1):16206.

Abstract
Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n = 21) and other glomerular diseases (n = 36) as well as, healthy controls (n = 23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p < 0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.
PubMed IF 4.9 신장내과
32132020

제1저자 박진주, 박재형 · 교신저자 조구영

, , , , ,
Left Atrial Strain as a Predictor of New-Onset Atrial Fibrillation in Patients With Heart Failure.
JACC Cardiovasc Imaging. 2020;13(10):2071-2081.

Abstract
OBJECTIVES This study sought to identify whether left atrial strain can predict new-onset atrial fibrillation (NOAF) in patients with heart failure (HF) and sinus rhythm.
BACKGROUND Both HF and atrial fibrillation have common risk factors, and HF is a risk factor for the development of atrial fibrillation and vice versa.
METHODS Among 4,312 consecutive patients with acute HF from 3 tertiary hospitals, 2,461 patients with sinus rhythm and peak atrial longitudinal strain (PALS) were included in the study. Reduced PALS was defined as PALS ≤18%, and the primary endpoint was 5-year NOAF.
RESULTS During a 5-year follow-up, 397 (16.1%) patients developed NOAF. Patients with reduced PALS had higher NOAF than their counterparts (18.2% vs. 12.7%; p < 0.001). After adjustment for significant covariates, we identified 6 independent predictors of NOAF, including age >70 years (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.12 to 2.00), hypertension (HR: 1.45; 95% CI: 1.10 to 1.91), left atrial volume index ≥40 ml/m² (HR: 2.03; 95% CI: 1.48 to 2.77), PALS <18% (HR: 1.60; 95% CI: 1.18 to 2.17), HF with preserved ejection fraction (HR: 1.47; 95% CI: 1.11 to 1.95), and no beta-blocker prescription at discharge (HR: 1.48; 95% CI: 1.14 to 1.92). A weighted score based on these variables was used to create a composite score, HAS-BAP (H = hypertension; A = age; S = PALS; B = no beta-blocker prescription at discharge; A = atrial volume index; P = HF with preserved ejection fraction [range 0 to 6] with a median of 3 [interquartile range: 2 to 4]). The probability of NOAF increased with HAS-BAP score.
CONCLUSIONS In patients with HF and sinus rhythm, 16.1% developed NOAF, and PALS could be used to predict the risk for NOAF. The HAS-BAP score allows determination of the risk of NOAF. (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure [STRATS-AHF] Registry; NCT03513653).
PubMed IF 19 순환기내과
32122021

제1저자 김민관 · 교신저자 이승표

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Impact of age on coronary artery plaque progression and clinical outcome: A PARADIGM substudy.
J Cardiovasc Comput Tomogr. 2021;15(3):232-239.

Abstract
BACKGROUND The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).
METHODS From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.
RESULTS With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm³/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm³/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.
CONCLUSIONS The rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411.
PubMed IF 5.4 순환기내과
32112020

제1저자 윤혁 · 교신저자 Siddharth Singh

, , , , , , , ,
Incremental Benefit of Achieving Endoscopic and Histologic Remission in Patients With Ulcerative Colitis: A Systematic Review and Meta-Analysis.
Gastroenterology. 2020;159(4):1262-1275.e7.

Abstract
BACKGROUND & AIMS Clinical remission, defined by a composite of patient reported outcomes and Mayo endoscopy subscore (MES) 0 or 1 is a recommended treatment target in patients with ulcerative colitis (UC). We estimated whether incorporating more rigorous remission definitions, of endoscopic remission (MES 0) and histologic remission, affects risk of relapse.
METHODS Through a systematic review, we identified cohort studies in adults with UC in clinical remission that reported a minimum 12-month risk of clinical relapse, based on MES (0 vs 1) and/or histologic disease activity, in patients with endoscopic remission. Using random effects meta-analysis, we calculated relative and absolute risk of clinical relapse in patients with UC achieving different treatment targets.
RESULTS In a meta-analysis of 17 studies that included 2608 patients with UC in clinical remission, compared to patients achieving MES 1, patients achieving MES 0 had a 52% lower risk of clinical relapse (relative risk, 0.48; 95% CI, 0.37-0.62). The median 12-month risk of clinical relapse in patients with MES 1 was 28.7%; the estimated annual risk of clinical relapse in patients with MES 0 was 13.7% (95% CI, 10.6-17.9). In a meta-analysis of 10 studies in patients in endoscopic remission (MES 0), patients who achieved histologic remission had a 63% lower risk of clinical relapse vs patients with persistent histologic activity (relative risk, 0.37; 95% CI, 0.24-0.56). Estimated annual risk of clinical relapse in who achieved achieving histologic remission was 5.0% (95% CI, 3.3-7.7).
CONCLUSIONS In a systematic review and meta-analysis of patients with UC in clinical remission, we observed that patients achieving more rigorous treatment endpoints (endoscopic and histologic remission) have a substantially lower risk of clinical relapse compared with patients achieving clinical remission.
PubMed IF 29.7 소화기내과
32102020

제1저자 구보경 · 교신저자 김원

, , , , , , , ,
Development and Validation of a Scoring System, Based on Genetic and Clinical Factors, to Determine Risk of Steatohepatitis in Asian Patients with Nonalcoholic Fatty Liver Disease.
Clin Gastroenterol Hepatol. 2020;18(11):2592-2599.e10.

Abstract
BACKGROUND & AIMS There are no biomarkers of nonalcoholic steatohepatitis (NASH) that are ready for routine clinical use. We investigated whether an analysis of PNPLA3 and TM6SF2 genotypes (rs738409 and rs58542926) can be used to identify patients with nonalcoholic fatty liver disease (NAFLD), with and without diabetes, who also have NASH.
METHODS We collected data from the Boramae registry in Korea on 453 patients with biopsy-proven NAFLD with sufficient clinical data for calculating scores. Patients enrolled from February 2014 through March 2016 were assigned to cohort 1 (n = 302; discovery cohort) and patients enrolled thereafter were assigned to cohort 2 (n = 151; validation cohort). DNA samples were obtained from all participants and analyzed for the PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, SREBF2 rs133291 C>T, MBOAT7-TMC4 rs641738 C>T, and HSD17B13 rs72613567 adenine insertion (A-INS) polymorphisms. We used multivariable logistic regression analyses with stepwise backward selection to build a model to determine patients' risk for NASH (NASH PT) using the genotype and clinical data from cohort 1 and tested its accuracy in cohort 2. We used the receiver operating characteristic (ROC) curve to compare the diagnostic performances of the NASH PT and the NASH scoring systems.
RESULTS We developed a NASH PT scoring system based on PNPLA3 and TM6SF2 genotypes, diabetes status, insulin resistance, and levels of aspartate aminotransferase and high-sensitivity C-reactive protein. NASH PT scores identified patients with NASH with an area under the ROC (AUROC) of 0.859 (95% CI, 0.817-0.901) in cohort 1. In cohort 2, NASH PT scores identified patients with NASH with an AUROC of 0.787 (95% CI, 0.715-0.860), which was significantly higher than the AUROC of the NASH score (AUROC, 0.729; 95% CI, 0.647-0.812; P = .007). The AUROC of the NASH PT score for detecting NASH in patients with NAFLD with diabetes was 0.835 (95% CI, 0.776-0.895) and in patients without diabetes was 0.809 (95% CI, 0.757-0.861). The negative predictive value of the NASH PT score <-0.785 for NASH in patients with NAFLD with diabetes reached 0.905.
CONCLUSIONS We developed a scoring system, based on polymorphisms in PNPLA3 and TM6SF2 and clinical factors that identifies patients with NAFLD, with or without diabetes, who have NASH, with an AUROC value of 0.787. This system might help clinicians better identify NAFLD patients at risk for NASH.
PubMed IF 16.2 소화기내과
32092020

제1저자 김학령, 주형준 · 교신저자 임도선, 김명아

, , , , , , ,
Association Between Metabolic Syndrome and Parameters of Subclinical Target Organ Damage in Urban Subjects Without Documented Cardiovascular Disease.
Metab Syndr Relat Disord. 2020;18(8):373-380.

Abstract
Background: Identification of subclinical target organ damage (TOD) at early stage is important for the reduction in cardiovascular risk. This study was performed to assess the association between metabolic syndrome (MetS) and several types of TOD in urban people. Methods: Data from 958 Korean subjects without cardiovascular disease, living in Seoul city (mean age, 55.2 years, 47.6% males), were extracted from the prospective cohort database. All participants underwent extensive evaluation of TOD parameters, including left ventricular mass index (LVMI), E/e', brachial-ankle pulse wave velocity (baPWV), estimated glomerular filtration rate (eGFR), ankle-brachial index (ABI), carotid intima-media thickness (IMT), and obstructive coronary artery disease. Results: MetS and ≥1 TOD were detected in 494 (51.5%) and 329 (34.3%) subjects, respectively. There were no significant differences in the prevalence of ≥1 TOD according to the presence of MetS (P > 0.05). Among MetS components, only high blood pressure was associated with ≥1 TOD (69.6% vs. 59.9%, P = 0.004). There was a positive association between ≥1 TOD and the number of MetS traits (P = 0.034). There were significant linear correlations of Z-score of MetS with baPWV (r = 0.241, P < 0.001) and eGFR (r = -0.173, P < 0.001) but not with LVMI, E/e', ABI, and carotid IMT (P > 0.05 for each). Conclusions: In urban Korean population without cardiovascular disease, TOD is more closely related to the number of risk factors meeting MetS criteria and high blood pressure than the presence of MetS itself.
PubMed IF 1.6 순환기내과

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