SCI 발표논문

전체 4,588편

35982021

제1저자 임승균 · 교신저자 김정희, 이영아

, , , , , , ,
Long-Term Health Outcomes of Korean Adults With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.
Front Endocrinol (Lausanne). 2021;12:761258.

Abstract
There is a lack of studies regarding the long-term outcomes of Asian adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. We hypothesized that adults with CAH are at higher metabolic risk than their age-, and sex-matched controls. We further investigated the long-term health outcome-related factors in adults with CAH. We compared metabolic risk between adults with CAH (71 men, 93 women) and age-, and sex-matched controls (190 men, 261 women) from the Korean National Health and Nutrition Examination Survey data. The presence of obesity, testicular adrenal rest tumors (TARTs), and menstrual irregularity was assessed. Hormone status and treatment regimens were compared according to the presence of adverse outcomes. The median age was 27.0 y and 28.0 y for men and women, respectively. Adults with CAH had a higher waist circumference (88.0 vs. 82.3 cm in men, and 83.5 vs. 72.3 cm in women), and blood pressure (125.0 vs. 113.0 mmHg in men, and 120.0 vs. 104.0 mmHg in women) than age- and sex-matched controls (P<0.05 for all). The 2.7-fold increased risk for hypertension (men) and 2.0-fold increased risk for obesity (women) was significant in patients with CAH (P<0.05 for both). Obese adults with CAH showed significantly higher adrenal limb thicknesses (men) and 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels (women) (P<0.05 for both). TARTs occurred in 58.1% of men and did not differ by hormone or treatment regimen. Irregular menstruation was observed in 57.1% of women, with higher dehydroepiandrosterone sulfate levels in those with irregular periods. Adults with CAH had a higher metabolic risk than the general population. Poor disease control may increase their risk of metabolic morbidity and menstrual irregularity.
PubMed IF 5.7 내분비대사내과
35972021

제1저자 이윤석 · 교신저자 황진혁

, , , ,
Pharmacoethnicity of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer: a systematic review and meta-analysis.
Sci Rep. 2021;11(1):20152.

Abstract
Treatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line chemotherapy regimens for metastatic pancreatic cancer (PC) were assessed according to ethnic groups categorized as Western or Asian subgroups. PubMed, EMBASE, and Cochrane library were searched. Thirteen studies were eligible in this meta-analysis. Overall survival was not significantly different between FOLFIRINOX and GNP (HR 1.00, 95% CI 0.83-1.20, P = 0.990). However, the Western subgroup showed a higher survival benefit for FOLFIRINOX over GNP (HR 0.84, 95% CI 0.74-0.95, P = 0.006) whereas the Asian subgroup showed the survival benefit for GNP over FOLFIRINOX (HR 1.29, 95% CI 1.03-1.60, P = 0.030). Progression free survival was not significantly different between the two regimens in the Western subgroup (HR 1.01, 95% CI 0.84-1.20, P = 0.950) and the Asian subgroup (HR 1.13, 95% CI 0.97-1.33, P = 0.110). Occurrence of febrile neutropenia was significantly higher in FOLFIRINOX at both ethnic subgroups; however, that of peripheral neuropathy was significantly higher only in GNP of the Asian subgroup. Therefore, pharmacoethnicity might be a factor worth considering when deciding on a frontline chemotherapeutic regimen although the overall survival was not significantly different between FOLFIRINOX and GNP for metastatic PCs.
PubMed IF 4.9 소화기내과
35962021

제1저자 강민구 · 교신저자 김광일

, , , , , ,
Accuracy and Diversity of Wearable Device-Based Gait Speed Measurement Among Older Men: Observational Study.
J Med Internet Res. 2021;23(10):e29884.

Abstract
BACKGROUND Gait speed measurements are widely used in clinical practice, as slow gait is a major predictor of frailty and a diagnostic criterion for sarcopenia. With the development of wearable devices, it is possible to estimate the gait speed in daily life by simply wearing the device.
OBJECTIVE This study aims to accurately determine the characteristics of daily life gait speed and analyze their association with sarcopenia.
METHODS We invited community-dwelling men aged >50 years who had visited the outpatient clinic at a tertiary university hospital to participate in the study. Daily life gait speed was assessed using a wearable smart belt (WELT) for a period of 4 weeks. Data from participants who wore the smart belt for at least 10 days during this period were included. After 4 weeks, data from a survey about medical and social history, usual gait speed measurements, handgrip strength measurements, and dual-energy x-ray absorptiometry were analyzed.
RESULTS A total of 217,578 daily life gait speed measurements from 106 participants (mean age 71.1, SD 7.6 years) were analyzed. The mean daily life gait speed was 1.23 (SD 0.26) m/s. The daily life gait speed of the participants varied according to the time of the day and day of the week. Daily life gait speed significantly slowed down with age (P<.001). Participants with sarcopenia had significantly lower mean daily life gait speed (mean 1.12, SD 0.11 m/s) than participants without sarcopenia (mean 1.23, SD 0.08 m/s; P<.001). Analysis of factors related to mean daily life gait speed showed that age and skeletal muscle mass of the lower limbs were significantly associated characteristics.
CONCLUSIONS More diverse and accurate information about gait speed can be obtained by measuring daily life gait speed using a wearable device over an appropriate period, compared with one-time measurements performed in a laboratory setting. Importantly, in addition to age, daily life gait speed is significantly associated with skeletal muscle mass of the lower limbs.
PubMed IF 8.2 노인병내과
35952021

제1저자 김경아, 최광현 · 교신저자 정숙향

, , , , , , , , , ,
Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.
Epidemiol Health. 2021;43:e2021077.

Abstract
OBJECTIVES Injection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data on this topic are available in Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).
METHODS We used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of a questionnaire survey on lifetime risk factors for HCV infection were analyzed according to a self-reported history of injection drug use (PWID vs. non-PWID group).
RESULTS Among the 2,468 patients, 166 (6.7%) were in the PWID group, which contained younger patients (50.6±8.2 vs. 58.2±13.1 years) and a higher proportion of male (81.9 vs. 48.8%) than the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not significantly differ between the groups.
CONCLUSIONS As of 2019, PWID constituted a minority of HCV-infected people in Korea. The epidemiological characteristics, but not treatment uptake and outcomes, were different between the PWID and non-PWID groups. Therefore, active HCV screening and treatment should be offered to PWID in Korea.
PubMed IF 2.4 소화기내과
35942021

제1저자 황성혜 · 교신저자 전누리, 김세중

, , , , , , , ,
Role of Human Primary Renal Fibroblast in TGF-β1-Mediated Fibrosis-Mimicking Devices.
Int J Mol Sci. 2021;22(19):ijms221910758.

Abstract
Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-β (TGF-β) and TGF-β inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-β1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-β-treated group and TGF-β-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-β-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-β1, TGF-β2, and TGF-β3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.
PubMed IF 5.924 신장내과
35932021

제1저자 정고은, 조은주 · 교신저자 신동욱, 유수종

, , , , , , , , ,
Nonalcoholic fatty liver disease increases the risk of diabetes in young adults: A nationwide population-based study in Korea.
Metabolism. 2021;123:154866.

Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes but has been rarely investigated in young adults. In this study, we investigated the relationship between NAFLD and incident diabetes risk in young adults using nationwide Korean population data.
METHODS This population-based cohort study from the Korean National Health Insurance Service included adults aged 20 through 39 years who underwent a health examination from 2009 to 2012. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of alcohol consumption of ≥30 g/day. Newly diagnosed diabetes during follow-up was identified using claims data. Cox regression was used to calculate the hazard ratio for incident diabetes after adjusting for classical confounders.
FINDINGS Among the 5,254,786 participants, 9.3% had an FLI ≥60. During the median follow-up of 8.6 years, 91,885 cases of incident diabetes occurred. In multivariable analysis, the risk of incident diabetes was significantly higher in the NAFLD group than the control group (adjusted hazard ratio = 4.97, 95% confidence interval, 4.90-5.05). Stratified analyses showed higher associations in those who were ≥30 years, male, obese, smokers, alcohol consumers, and did not regularly exercise (all P < 0.001).
CONCLUSIONS NAFLD is associated with a five-fold increased risk of incident diabetes in young adults. These results suggest an independent high risk for incident diabetes in young adults and underscore the importance of paying early attention to patients who develop NAFLD before middle age.
PubMed IF 16.7 소화기내과
35922021

제1저자 공성혜 · 교신저자 김상완

, , , ,
Epidemiology and prognosis of parathyroid carcinoma: real-world data using nationwide cohort.
J Cancer Res Clin Oncol. 2021;147(10):3091-3097.

Abstract
PURPOSE Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy with a poor prognosis. Due to the rarity, the natural course and prognostic factors of the disease are yet unclear. Therefore, we aimed to identify the incidence, prognosis, and prognostic factors of PC in the nationwide cohort study.
METHODS The study is a nationwide study using the National Health Insurance Services database in Korea from 2002 to 2017. PC was defined as patients with ICD-10 code of PC and a procedural code for parathyroidectomy.
RESULTS From 2002 to 2017, 255 patients were diagnosed with PC whose mean age was 53.2 years, and 155 (60.2%) were women. The crude and age-standardized incidence were 10.2 and 6.6/10,000,000 person-year in 2016, rising from 4.1 and 3.8/10,000,000 person-year in 2003 (p < 0.001), respectively. The 5- and 10-year survival rates were 86.5 and 72.9%, respectively. In survival analysis, age over 50 years, thyroidectomy at the initial surgery, and reoperation had increased risk of mortality with HRs of 4.83 (95% CI 1.47-15.90), and 4.21 (95% CI 1.60-11.08), and 1.05 (95% CI 1.02-1.08) in multivariate analysis, respectively.
CONCLUSION Incidence of PC has been rising over time, similar to the trends in Western countries. The prognostic factors for mortality were old age, parathyroidectomy alone, and recurrence, emphasizing the importance of preoperative suspicion of the disease. The study is clinically meaningful in the first Asian nationwide study to reveal the natural course of PC.
PubMed IF 3.3 내분비대사내과
35912021

제1저자 최성미 · 교신저자 강혜련, 이하나

, , , , , , , , ,
Lung virome: New potential biomarkers for asthma severity and exacerbation.
J Allergy Clin Immunol. 2021;148(4):1007-1015.e9.

Abstract
BACKGROUND Although some respiratory virus infections are known to contribute to the development and exacerbation of asthma, commensal viromes in airway have not been extensively studied due to technical challenges.
OBJECTIVES This study investigated the characteristics of the virome in asthmatic airways.
METHODS Both the bacteriome and virome profiles in sputum from 12 healthy individuals, 15 patients with nonsevere asthma, and 15 patients with severe asthma were analyzed and assessed for the association with clinical characteristics such as severity, exacerbation, Asthma Control Test (ACT), and lung function.
RESULTS While analysis of the 16S ribosomal RNA bacteriome in the airway showed no differences, clear contrasts in the diversity and composition of airway viromes were observed between healthy controls and patients with asthma. Herpesviruses were the most abundant type of virus in the asthma group (44.6 ± 4.6%), mainly with cytomegalovirus (CMV) and EBV accounting for 24.5 ± 3.3% and 16.9 ± 3.5%, respectively, in contrast to those in the healthy controls (5.4 ± 2.5% and 7.1 ± 3.0%, respectively). CMV and EBV were more abundant in patients with asthma who experienced exacerbation, and their abundance showed correlation with more severe asthma, lower ACT score, and lower lung function. On the contrary, bacteriophage that is abundant in healthy controls was severely reduced in patients with asthma in the order of nonsevere and severe asthma and presented significant positive correlation with ACT and FEV₁/forced vital capacity.
CONCLUSIONS Lung viromes, especially, CMV, EBV, and bacteriophage may be potential biomarkers of asthma severity and exacerbation.
PubMed IF 11.2 알레르기내과
35902021

제1저자 박지혜 · 교신저자 김원, 김원호

, , , ,
Histological severity of nonalcoholic fatty liver disease is associated with 10-year risk for atherosclerotic cardiovascular disease.
Hepatol Int. 2021;15(5):1148-1159.

Abstract
BACKGROUND AND AIM Nonalcoholic fatty liver disease (NAFLD) is associated with atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated the association between the histological severity of NAFLD and ASCVD. Therefore, we investigated whether the histological severity of NAFLD is associated with ASCVD risk.
METHODS We performed cross-sectional analysis of prospectively enrolled, biopsy-proven NAFLD patients. The 10-year ASCVD risk was assessed using the Korean Risk Prediction Model. The histological spectrum of NAFLD was classified by the nonalcoholic steatohepatitis (NASH) clinical research network histological scoring system. The association between each histological subgroup and ASCVD risk was analyzed using logistic regression analysis.
RESULTS This study included 398 Korean subjects (mean age, 57.9 years; male, 44.2%) with biopsy-proven NAFLD and 102 no-NALFD controls. Subjects with ASCVD risk ≥ 10% showed more severe grades of hepatocellular ballooning and more advanced stages of fibrosis when compared with subjects with ASCVD risk < 10% (p < 0.05 for each). The presence of NASH (odds ratio [OR] 4.07; 95% confidence interval [CI] 1.40-11.88) or advanced fibrosis (OR 8.11; 95% CI 1.83-35.98) was independently associated with a higher risk of ASCVD even after adjustment for age, sex, body mass index, blood pressure, lipids, liver enzymes, systemic inflammation, and insulin resistance.
CONCLUSIONS Patients with NASH or advanced fibrosis are at an increased risk of developing ASCVD compared with no-NAFLD controls or subjects with NAFL, independent of conventional metabolic risk factors for CVD. Histological information on NAFLD may be helpful to promote our understanding of extrahepatic complications, such as ASCVD, resulting from NAFLD progression.
PubMed IF 7.8 소화기내과
35892021

제1저자 박지명 · 교신저자 임재준

, , , , ,
Radiographic severity and treatment outcome of Mycobacterium abscessus complex pulmonary disease.
Respir Med. 2021;187:106549.

Abstract
INTRODUCTION The lack of reliable predictors for the treatment response complicates decisions to initiate treatment in patients with Mycobacterium abscessus complex pulmonary disease (MABC-PD). We aimed to investigate whether baseline radiographic disease severity is associated with treatment outcome in MABC-PD.
METHOD We retrospectively analyzed 101 patients with MABC-PD (54 with M. abscessus-PD and 47 with M. massiliense-PD) treated in a tertiary referral hospital between January 2006 and December 2019. Using chest computed tomography images, baseline radiographic disease severity was quantitatively scored according to five categories of radiographic lesions (bronchiectasis, bronchiolitis, cavities, nodules, and consolidation).
RESULTS Treatment success was achieved in 53.7% of patients with M. abscessus-PD and 85.1% of patients with M. massiliense-PD. Higher overall scores for baseline radiographic disease severity were associated with treatment failure in patients with M. massiliense-PD (aOR 1.35, 95% CI 1.02-1.79 for each 1-point increase in severity score), as well as in patients with M. abscessus-PD (aOR 1.15, 95% CI 1.00-1.33). This was particularly prominent in patients with overall severity score of ≥14 (aOR 31.16, 95% CI 1.12-868.95 for M. massiliense-PD and aOR 3.55, 95% CI 1.01-12.45 for M. abscessus-PD). Among variable radiographic abnormalities, the score for cavitary lesion severity was associated with treatment failure in patients with M. abscessus-PD (aOR 1.26, 95% CI 1.01-1.56), but not in patients with M. massiliense-PD.
CONCLUSIONS Given the association between baseline radiographic disease severity and treatment outcome, initiating treatment should be actively considered before significant progression of radiographic lesions in patients with MABC-PD.
PubMed IF 3.3 호흡기내과
35882021

제1저자 이정원 · 교신저자 김나영

, , , , ,
Favorable outcomes of rescue second- or third-line culture-based Helicobacter pylori eradication treatment in areas of high antimicrobial resistance.
Helicobacter. 2021;26(5):e12844.

Abstract
BACKGROUND Failure of second or third-line eradication treatment against Helicobacter pylori (H. pylori) is principally caused by antimicrobial resistance and reduced treatment adherence.
AIMS To evaluate the efficacy and safety of culture-based rescue eradication treatments in patients who have previously experienced failed eradication treatment.
METHODS Patients who had persistent H. pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14-day administration of clarithromycin-containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes.
RESULTS A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n = 11), MEA (n = 15), quadruple (n = 53), or RLA triple (n = 5) therapy group. The eradication rates in the intention-to-treat and per-protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%).
CONCLUSIONS As a rescue therapy, culture-based susceptibility-guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance.
PubMed IF 4.6 소화기내과
35872021

제1저자 강은주 · 교신저자 김범석

, , , , , , , , , , , ,
Randomized Phase II Study of Axitinib versus Observation in Patients with Recurred or Metastatic Adenoid Cystic Carcinoma.
Clin Cancer Res. 2021;27(19):5272-5279.

Abstract
PURPOSE The role of chemotherapy in adenoid cystic carcinoma (ACC) is controversial because ACC is usually stable without chemotherapy and the lack of randomized trials. Here, we conducted the first randomized trial to evaluate the efficacy of axitinib as compared with observation in ACC.
PATIENTS AND METHODS In this multicenter, prospective phase II trial, we enrolled patients with recurrent or metastatic ACC whose cancer had progressed within the past 9 months. Patients were randomly assigned to either axitinib (5 mg twice daily) or observation at a 1:1 ratio. Crossover from observation to axitinib was permitted after progression. The primary endpoint was a 6-month progression-free survival (PFS) rate. The secondary endpoints included objective response rate (ORR), overall survival (OS), PFS, duration of response, and adverse events.
RESULTS Sixty patients were allocated to the axitinib or observation group, with response evaluation conducted in 54 patients. With a median follow-up of 25.4 months, the 6-month PFS rate was 73.0% with axitinib and 23.0% with observation. Median PFS was longer in the axitinib arm (10.8 months vs. 2.8 months, P < 0.001). The ORR of axitinib was 0.0%, but the disease control rate was 100.0% with axitinib and 51.9% with observation. Median OS was not reached with axitinib, but was 27.2 months with observation (P = 0.226). The most frequently reported adverse events for axitinib were oral mucositis and fatigue.
CONCLUSIONS In this first randomized trial in patients with ACC, axitinib significantly increased the 6-month PFS rate as compared with observation. (ClinicalTrials.gov number, NCT02859012).
PubMed IF 10.9 혈액종양내과
35862021

제1저자 나지은 · 교신저자 신동현, 이정훈

, , , , , , , , , , , , , ,
Efficacy of entecavir versus tenofovir in preventing hepatocellular carcinoma in patients with chronic hepatitis B with maintained virologic response.
J Viral Hepat. 2021;28(10):1392-1399.

Abstract
BACKGROUND & AIMS Several studies suggested that efficacy of tenofovir in reducing the risk of the development of hepatocellular carcinoma (HCC) might be better than that of entecavir. It remains unknown whether a change in therapy can further reduce the risk of HCC in patients receiving entecavir therapy and achieved goal of antiviral therapy, a maintained undetectable hepatitis B virus (HBV) DNA level in the serum.
METHODS A total of 1336 treatment-naïve chronic HBV mono-infected adult patients, who started entecavir or tenofovir treatment and achieved a maintained virologic response during follow-up were analysed.
RESULTS During a median 4.4 years of follow-up (range, 1.0-7.4 years) after achieving virologic response, 99 patients developed HCC. The 5-year cumulative HCC incidence rate was 7.3% and 6.3% for the entecavir and tenofovir groups, respectively, with similar risk of HCC between the two groups (adjusted HR, 0.82; 95% CI, 0.52-1.29; p = 0.3). The risk of HCC was similar in the propensity score-matched cohort (HR, 1.02; 95% CI, 0.68-1.52; p = 0.94) and inverse probability treatment weighting analysis (HR, 1.11; 95% CI, 0.74-1.66; p = 0.62). In the subgroup analysis, HCC risk was similar between the two drugs in both patients with and without cirrhosis.
DISCUSSION In patients showing maintained virologic response, no difference in the risk of HCC between entecavir and tenofovir was observed. This indicates entecavir might be as effective as tenofovir in the prevention of HCC among those patients and suggest that a change in therapy in anticipation of further reducing the risk of HCC might not be necessary for patients receiving entecavir and showing virologic response.
PubMed IF 2.3 소화기내과
35852021

제1저자 박세훈 · 교신저자 한경도, 김동기

, , , , , , , , , , , , ,
The Prognostic Significance of Body Mass Index and Metabolic Parameter Variabilities in Predialysis CKD: A Nationwide Observational Cohort Study.
J Am Soc Nephrol. 2021;32(10):2595-2612.

Abstract
BACKGROUND The association between variabilities in body mass index (BMI) or metabolic parameters and prognosis of patients with CKD has rarely been studied.
METHODS In this retrospective observational study on the basis of South Korea's national health screening database, we identified individuals who received ≥3 health screenings, including those with persistent predialysis CKD (eGFR <60 ml/min per 1.73 m² or dipstick albuminuria ≥1). The study exposure was variability in BMI or metabolic parameters until baseline assessment, calculated as the variation independent of the mean and stratified into quartiles (with Q4 the highest quartile and Q1 the lowest). We used Cox regression adjusted for various clinical characteristics to analyze risks of all-cause mortality and incident myocardial infarction, stroke, and KRT.
RESULTS The study included 84,636 patients with predialysis CKD. Comparing Q4 versus Q1, higher BMI variability was significantly associated with higher risks of all-cause mortality (hazard ratio [HR], 1.66; 95% confidence interval [95% CI], 1.53 to 1.81), P [for trend] <0.001), KRT (HR, 1.20; 95% CI, 1.09 to 1.33; P<0.001), myocardial infarction (HR, 1.19; 95% CI, 1.05 to 1.36, P=0.003), and stroke (HR, 1.19; 95% CI, 1.07 to 1.33, P=0.01). The results were similar in the subgroups divided according to positive or negative trends in BMI during the exposure assessment period. Variabilities in certain metabolic syndrome components (e.g., fasting blood glucose) also were significantly associated with prognosis of patients with predialysis CKD. Those with a higher number of metabolic syndrome components with high variability had a worse prognosis.
CONCLUSIONS Higher variabilities in BMI and certain metabolic syndrome components are significantly associated with a worse prognosis in patients with predialysis CKD.
PubMed IF 9.7 신장내과
35842021

제1저자 박세훈, 강성진 · 교신저자 임예지, 이하정

, , , , , , , , , ,
Association between early post-transplant hypertension or related antihypertensive use and prognosis of kidney transplant recipients: a nationwide observational study.
J Nephrol. 2021;34(5):1457-1465.

Abstract
BACKGROUND Additional research is warranted for the clinical significance of post-transplant hypertension and related antihypertensive medication use in kidney transplant (KT) recipients.
METHODS This observational study included nationwide KT recipients who maintained a functioning graft for at least 1 year after KT in South Korea, observed between 2008 and 2017. The use of antihypertensive medications lasting between 6 months and 1 year was the main exposure, and those who had inconsistent/transient use of antihypertensive drugs were excluded. The prognostic outcome included death-censored graft failure (DCGF), death-with functioning graft (DWFG), and major adverse cerebrocardiovascular events (MACCEs).
RESULTS We included 8,014 patients without post-transplant hypertension and 6,114 recipients who received treatment for hypertension in the post-transplant period. Those with post-transplant hypertension had a significantly higher risk of DCGF than those without [adjusted hazard ratio (HR) 1.27 (1.09-1.48)]. Post-transplant hypertension patients who required multiple drugs showed a significantly higher risk of DWFG [HR 1.57 (1.17-2.10)] and MACCE [HR 1.35 (1.01-1.81)] than the controls. Among the single-agent users, those who received beta-blockers showed a significantly higher risk of DCGF, although the risks of DWFG or MACCE were similar between the types of antihypertensive agents. Among the multiple agent users, the prognosis was similar, regardless of the prescribed types of antihypertensive agents.
CONCLUSION Post-transplant hypertension was associated with poor post-transplant prognosis, particularly when multiple types of medications were required for treatment. During initial prescription of antihypertensive medication, clinicians may consider that beta-blockers were associated with a higher risk of DCGF in the single-agent users.
PubMed IF 2.6 신장내과
35832021

제1저자 이창훈 · 교신저자 곽민선

, , ,
Synergistic harmful interaction between sustained physical inactivity and hypertension/diabetes mellitus on the risk of all-cause mortality: a retrospective observational cohort study.
J Hypertens. 2021;39(10):2058-2066.

Abstract
OBJECTIVE Hypertension, diabetes mellitus and physical inactivity can cause cardiovascular complications or premature death. However, it has not been clarified whether those major comorbidities and physical activity interact in affecting health outcomes. The aim of this study is to evaluate the potential interaction between temporal physical activity profiles and hypertension or diabetes mellitus on the risk for all-cause mortality.
METHODS This study used Korea National Health Insurance Service (KNHIS) database and included about 6.5 million participants who underwent health screening in 2009 and 2011. Physical activity was evaluated as 2-year change based on self-reported survey using 7-day recall method, and grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Participants were categorized into groups according to the presence of hypertension/diabetes mellitus. Outcome included all-cause mortality.
RESULTS In total, 6 554 082 participants (48.4 ± 13.3 years; 56.7% men) were included. During a median 6.4-year follow-up, 83 241 deaths occurred. Compared with the 'remained active' group, other groups had a higher mortality risk after adjustment for covariates [adjusted hazard ratio (aHR) 1.17, 95% CI 1.13-1.21 in the 'inactive-to-active' group, aHR 1.28, 95% CI 1.24-1.32 in the 'active-to-inactive' group, aHR 1.52, 95% CI 1.48-1.57 in the 'remained inactive' group). Hypertension and diabetes mellitus were significant effect modifiers in the association between physical activity and the risk of all-cause mortality (P for interaction <0.001). The harmful effects of persistent physical inactivity on all-cause mortality were the most obvious in those with both hypertension and diabetes mellitus among groups.
CONCLUSION Sustained physical inactivity was associated with increased risk of all-cause mortality in those with hypertension or diabetes mellitus more strongly than in those without. Physicians should emphasize sustained physical activity even more in patients with hypertension or diabetes mellitus.
PubMed IF 5.6 소화기내과
35822021

제1저자 이해영 · 교신저자 김철호

, , , , , , , , , , , , , , , , , , , , , , ,
A Randomized, Double-blind, Active-controlled, Two Parallel-Group, Optional Titration, Multicenter, Phase IIIb Study to Evaluate the Efficacy and Safety of Fimasartan Versus Perindopril Monotherapy With and Without a Diuretic Combination in Elderly Patients With Essential Hypertension.
Clin Ther. 2021;43(10):1746-1756.

Abstract
PURPOSE The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg).
METHODS This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks.
FINDINGS At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period.
IMPLICATIONS In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555.
PubMed IF 3.7 순환기내과
35812021

제1저자 김화정, 김유정 · 교신저자 권정혜

, , , , , , ,
Current Status and Cardinal Features of Patient Autonomy after Enactment of the Life-Sustaining Treatment Decisions Act in Korea.
Cancer Res Treat. 2021;53(4):917-925.

Abstract
PURPOSE The main purpose of the Life-Sustaining Treatment Decisions Act recently enacted in Korea is to respect the patient's self-determination. We aimed to investigate the current status and features of patient self-determination after implementation of the law.
MATERIALS AND METHODS Between February 2018 and January 2019, 54,635 cancer deaths were identified from the National Health Insurance Service (NHIS) database. We analyzed the characteristics of decedents who complied with the law process by self-determination compared with decedents with family determination and with decedents who did not comply with the law process.
RESULTS In multivariable analysis, patients with self-determination were younger, were less likely to live in rural areas, were less likely to belong to the highest income quintile, were less likely to be treated in general hospitals, and were more likely to show a longer time from cancer diagnosis compared with patients with family determination. Compared with patients who did not comply with the law process, patients with self-determination were younger, lived in Seoul or capital area, were less likely to belong to the highest income quintile, were treated in general hospitals, were less likely to have genitourinary or hematologic malignancies, scored higher on the Charlson comorbidity index, and showed a longer time from cancer diagnosis. Patients with self-determination were more likely to use hospice and less likely to use intensive care units (ICUs) at the end-of-life (EOL).
CONCLUSION Decedents with self-determination were more likely to be younger, reside in the Seoul or capital area, show a longer time from cancer diagnosis, and were less likely to belong to the highest income quintile. They utilized hospice more frequently, and received less ICU care at the EOL.
PubMed IF 4.2 혈액종양내과
35802021

제1저자 정석송, 조유리 · 교신저자 박상민, 김원

, , ,
Differential Effectiveness of Tenofovir and Entecavir for Prophylaxis of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Depending on Coexisting Cirrhosis and Prior Exposure to Antiviral Therapy: A Systematic Review and Meta-analysis.
J Clin Gastroenterol. 2021;55(9):e77-e86.

Abstract
GOALS This meta-analysis evaluated the comparative effectiveness of tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC).
BACKGROUND It is unclear whether TDF or ETV is more effective in reducing the risk of HCC in chronic hepatitis B (CHB) patients with or without underlying cirrhosis.
METHODS We searched the MEDLINE database through April 13, 2020, for studies involving CHB treated with TDF and/or ETV. Primary and secondary outcomes were the incidence of HCC and overall survival, respectively, calculated as risk ratios (RRs). Adjusted results were further evaluated by pooling propensity score matched cohorts.
RESULTS Of the 229 records identified, 17 studies were included in the quantitative analysis. TDF treatment was associated with a significantly lower risk of HCC development [RR, 0.63; 95% confidence interval (CI), 0.43-0.93; P=0.024] and mortality (RR, 0.69; 95% CI, 0.57-0.84; P=0.003) than ETV treatment. Moreover, TDF significantly lowered HCC risk in patients with cirrhosis (RR, 0.69; 95% CI, 0.56-0.84) and antiviral treatment-naive patients (RR, 0.59; 95% CI, 0.35-0.98) compared with ETV. Among treatment-naive patients, TDF significantly prolonged survival compared with ETV (RR, 0.69; 95% CI, 0.52-0.91).
CONCLUSIONS TDF likely confers a lower risk of HCC development and longer survival in patients with CHB, especially among treatment-naive patients and those with underlying cirrhosis, than ETV.
PubMed IF 2.7 소화기내과
35792021

제1저자 김연욱 · 교신저자 이춘택

, , , , , , , , , , ,
Lung cancer probability and clinical outcomes of baseline and new subsolid nodules detected on low-dose CT screening.
Thorax. 2021;76(10):980-988.

Abstract
BACKGROUND Limited data are available regarding the management of subsolid nodules detected on lung cancer screening with low-dose CT (LDCT). We aimed to determine the characteristics of screen-detected subsolid nodules, and to evaluate the probability of lung cancer and the clinical course of subsolid nodules detected at baseline and during follow-up screening.
METHODS We evaluated 50 132 asymptomatic adults (22 631 never-smokers and 27 501 ever-smokers) who underwent LDCT screening for lung cancer between May 2003 and June 2019 at a tertiary centre in South Korea. The incidence, characteristics and clinical outcomes of the baseline and new screen-detected subsolid nodules were determined.
RESULTS A total of 6725 subsolid nodules (5116 pure ground glass opacity nodules and 1609 part-solid nodules) were detected in 4545 participants (1484 new subsolid nodules detected in 937 (1.9%) participants; the overall incidence of subsolid nodules: 10.7% in never-smokers and 7.7% in ever-smokers, p<0.001). Among 4918 subsolid nodules that underwent follow-up with CT scans (the mean number of CT scans, including the baseline LDCT scan: 4.6), 2116 nodules (30.0% of baseline subsolid nodules and 78.9% of new subsolid nodules) resolved spontaneously. Among 293 biopsied subsolid nodules, 227 (77.5%) nodules were diagnosed as lung cancer, of which 226 (99.6%) were adenocarcinomas. No significant difference was observed in pathological invasiveness or the initial stage between the baseline and new cancerous subsolid nodules. Multivariable analyses revealed that new detection at follow-up screening was significantly associated with a lower probability of lung cancer (OR 0.26, 95% CI 0.14 to 0.49) and overall growth (OR 0.39, 95% CI 0.26 to 0.59), but with a higher probability of resolution (OR 6.30, 95% CI 5.09 to 7.81).
CONCLUSIONS LDCT screening led to a considerably high rate of subsolid nodule detection, particularly in never-smokers. Compared with the baseline subsolid nodules, the new subsolid nodules were associated with a lower probability of lung cancer and higher probability of spontaneous resolution, indicating their more inflammatory nature. Less aggressive follow-up may be allowed for new subsolid nodules, particularly in screening programmes for Asian populations.
PubMed IF 9.1 호흡기내과
35782021

제1저자 김세훈 · 교신저자 김태범

, , , , , , , , , , , , , , , , , , ,
Pragmatic Randomized Controlled Trial for Stepping Down Asthma Controller Treatment in Patients Controlled with Low-Dose Inhaled Corticosteroid and Long-Acting β2-Agonist: Step-Down of Intervention and Grade in Moderate Asthma Study.
J Allergy Clin Immunol Pract. 2021;9(10):3638-3646.e3.

Abstract
BACKGROUND Current asthma guidelines recommend stepping down controller treatment when the condition is well-controlled for a certain time. However, the optimal step-down strategy for well-controlled patients receiving a low-dose inhaled corticosteroid (ICS) with a long-acting β₂-agonist (LABA) remains unclear.
OBJECTIVE This study was a randomized, open-label, three-arm, parallel pragmatic trial comparing two kinds of step-down approaches for maintaining treatment.
METHODS Adults with asthma who were aged 18 years or older, and who had been stable with low-dose ICS/LABA for at least 3 months, were enrolled. Subjects (n = 225) were randomly allocated into one of three groups (maintaining low-dose ICS/LABA [G1], discontinuing LABA [G2], and reducing ICS/LABA to once daily [G3]), and were observed for 6 months. The primary end point was a change in Asthma Control Test (ACT) scores between randomization and the final 6-month follow-up.
RESULTS The change in ACT was analyzed in the per-protocol population; noninferiority was not demonstrated in either step-down group compared with the maintenance group (95% confidence interval of the difference, G2 vs G1 = -1.40-0.55; G3 vs G1 = -1.19-0.77). Although over 90% of patients were fine, higher rates of treatment failure were observed in step-down groups (G1: 0%; G2: 9.46%; and G3: 9.09%; P = .027). There were no significant differences between step-down approaches in terms of ACT change or treatment failure.
CONCLUSIONS Both step-down methods were not noninferior to maintenance of treatment. Step-down therapy can be attempted when patients are stable, but appropriate monitoring and supervision are necessary with precautions regarding loss of disease control.
PubMed IF 6.6 알레르기내과
35772021

제1저자 차명진 · 교신저자 김효수

, , , , , , , , , , ,
Time Course and Risk Factors of New-Onset Complete Atrioventricular Block After Transcatheter Aortic Valve Implantation.
Int Heart J. 2021;62(5):988-996.

Abstract
In this study, we aimed to investigate the time course of new-onset complete atrioventricular block (CAVB) and its reversibility after transcatheter aortic valve implantation (TAVI). We analyzed 206 consecutive patients without baseline CAVB who underwent successful TAVI. The incidence of new-onset CAVB was determined to be 12.6% (26/206). Among these patients, 14 recovered from CAVB within 2 weeks (6.8%, 14/206), while the remaining 12 (5.8%, 12/206) underwent permanent pacemaker (PPM) insertion. Among the 12 patients who received the PPM, 4 were able to recover from CAVB within 4 months. Thus, only 8 among 206 patients (3.8%) showed persistent CAVB. Early-onset CAVB on the day of the procedure was the strongest predictor of PPM implantation (OR = 127). The electrocardiographic changes that occurred after TAVI were mostly recovered after 1 month. The most critical procedural factor that predicts CAVB and PPM insertion is the deep implantation (>4 mm) of a big valve (oversizing index >5.9%). In conclusion, the incidence of CAVB after TAVI was estimated to be at 12.6%. Two-thirds of these patients recovered from CAVB within 3 days, resulting in a final rate of persistent CAVB of 4%. To prevent CAVB, we have to implant an appropriate valve type with an optimal size and depth.
PubMed IF 1.4 순환기내과
35762021

제1저자 Enerelt Natsagdorj · 교신저자 김상균

, , , , , , ,
Clinical Outcomes of Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients with Comorbidities.
J Gastric Cancer. 2021;21(3):258-267.

Abstract
PURPOSE As the rate of endoscopic resection for early gastric cancer (EGC) has increased in patients with comorbid diseases, it is necessary to elucidate the efficacy of endoscopic submucosal dissection (ESD) for EGC in patients with comorbidities. This study aimed to analyze the clinical outcomes of ESD for EGC in patients with comorbidities.
MATERIALS AND METHODS A total of 969 patients with 1,015 lesions who underwent ESD for EGC at Seoul National University Hospital between 2010 and 2014 were analyzed. The short- and long-term clinical outcomes were evaluated according to the comorbidity status.
RESULTS Comorbidities were observed in 558 patients (57.6%). The comorbidity group had a higher proportion of patients using antithrombotic agents (29.5% vs. 0.9%; P<0.0001). Although procedure-related complications (bleeding and perforation) were not significantly different between the two groups, the length of hospital stay was significantly longer (1.8 vs. 1.4 days, P=0.023), while survival was significantly shorter in the comorbidity group (5-year overall survival rate: 90.5% vs. 97.2%, P<0.0001; 5-year disease-specific survival rate: 97.9% vs. 100%, P=0.018; 5-year disease-free survival rate: 83.4% vs. 89.2%, P=0.007).
CONCLUSIONS Gastric ESD can be performed in patients with comorbidities without increasing the risk of complications.
PubMed IF 5.1 소화기내과
35752021

제1저자 남아롱, 윤지선 · 교신저자 오도연

, , , , , , , ,
ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer.
Cancer Lett. 2021;516:38-47.

Abstract
Olaparib, a potent PARP inhibitor, has been shown to have great anti-tumor effects in some tumor types. Although biliary tract cancer (BTC) is a good candidate for DNA damage response (DDR)-targeted agents, targeted DDR inhibitors, including olaparib, are currently rarely evaluated in BTC. In our project, a total of ten BTC cell lines were used to assess the efficacy of olaparib. Olaparib alone showed moderate anti-proliferative effects in BTC cells and increased p-ATR and PD-L1 expression levels. In combination with an ATR inhibitor (AZD6738, ceralasertib) showed synergistic anti-proliferative effects and increased DNA strand breaks in vitro. PD-L1 induced by olaparib was also downregulated by ceralasertib through p-STAT-3 and YAP reduction with or without human primary peripheral blood mononuclear cells. In SNU478-xenograft models, the combination treatment significantly suppressed tumor growth. PD-L1 and YAP were strongly downregulated, similar to in vitro conditions, and expression of CXCR2 and CXCR4 was further reduced. In the current ongoing clinical trial (NCT04298021), BTC patients treated with olaparib and ceralasertib combination have shown tumor response. In conclusion, co-targeting of PARP and ATR might be a potential therapeutic approach for patients with BTC.
PubMed IF 11.8 혈액종양내과
35742021

제1저자 최진우, 이송이, 조은주 · 교신저자 김효철, 조현종

, , , , , ,
Gas generating microspheres for immediate release of Hsp90 inhibitor aiming at postembolization hypoxia in transarterial chemoembolization therapy of hepatocellular carcinoma.
Int J Pharm. 2021;607:120988.

Abstract
CO₂ gas generating poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) was designed for rapid release of tanespimycin (17-AAG) in transarterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC). As poorly water-soluble drug is generally released from PLGA MS in a sustained manner, the drug release profile should be controlled according to its clinical indications. In current study, responding to immediate increase in hypoxia inducible factor-1α (HIF-1α) level under hypoxia state followed by embolization of tumor feeding arteries, sodium bicarbonate (NaHCO₃) was added to PLGA/17-AAG MS for fast drug release by CO₂ gas generation in slightly acidic tumor microenvironment. With the aid of NaHCO₃, initial burst release of 17-AAG was available without losing the micron-size and spherical shape of designed MS for embolization of artery. Acid-responsive CO₂ gas generation and subsequent immediate release of 17-AAG from MS were successfully verified. PLGA/17-AAG/NaHCO₃ MS-treated group exhibited higher antiproliferation and apoptosis induction efficacies in McA-RH7777 and SNU-761 cells. McA-RH7777 tumor-implanted rats treated by TACE using PLGA/17-AAG/NaHCO₃ MS presented a complete therapeutic response. All these findings suggest that developed tumor microenvironment-responsive gas-generating MS can be efficiently applied to TACE therapy of HCC.
PubMed IF 6 소화기내과
35732021

제1저자 김학령 · 교신저자 조상호

,
Current Evidence on Long-Term Prognostic Factors in Vasospastic Angina.
J Clin Med. 2021;10(18):jcm10184270.

Abstract
Vasospastic angina (VSA) is characterized by a reversible spasm of the coronary arteries and is more prevalent in Asians. Vasodilators, such as calcium channel blockers, are effective in relieving coronary spasms and preventing clinical events. Therefore, the prognosis of VSA is generally known to be better than for significant organic stenosis caused by atherosclerosis. However, coronary vasospasm is sometimes associated with fatal complications such as sudden death, ventricular arrhythmia, and myocardial infarction. Thus, it is very important to identify and actively treat high-risk patients to prevent VSA complications. Here, we will review clinical factors associated with long-term prognosis in patients with VSA.
PubMed IF 3.3 순환기내과
35722021

제1저자 이소령 · 교신저자 최의근

, , , , , ,
Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation.
Eur Heart J Cardiovasc Pharmacother. 2021;7(5):415-423.

Abstract
AIMS To compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with atrial fibrillation (AF).
METHODS AND RESULTS Using the Korean nationwide claims database, we identified patients who were prescribed apixaban and did not fulfil the dose reduction criteria for apixaban between January 2015 and December 2017. A multivariable Cox hazard regression model was performed, and hazard ratios (HRs) for ischaemic stroke, major bleeding (MB), all-cause death, and composite outcome were analysed. Compared to patients prescribed on-label standard dose apixaban (n = 4194), patients prescribed off-label underdosed apixaban (n = 2890) showed a higher risk of ischaemic stroke [adjusted HR (aHR) 1.38, 95% confidence interval (CI) 1.06-1.81], all-cause death (aHR 1.19, 95% CI 1.01-1.39), and the composite outcome (aHR 1.17, 95% CI 1.03-1.34), but with no significant differences in MB between the two groups. Among the patients who did not meet any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischaemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% CI 1.25-2.73). Among the patients who met a single dose reduction criterion, off-label underdosed apixaban use was associated with a higher risk of all-cause death than on-label standard dose apixaban (aHR 1.32, 95% CI 1.07-1.64).
CONCLUSION The off-label underdosed apixaban group showed higher risks of ischaemic stroke, all-cause death, and composite clinical outcomes than the on-label standard dose apixaban group, but both showed comparable risks of MB. Label adherence to apixaban dosing should be emphasized to achieve the best clinical outcomes for Asian patients with AF.
PubMed IF 8.2 순환기내과
35712021

제1저자 김정희, 이형철 · 교신저자 김수진

, , , , , , , , , , , ,
Perioperative hemodynamic instability in pheochromocytoma and sympathetic paraganglioma patients.
Sci Rep. 2021;11(1):18574.

Abstract
For pheochromocytoma and sympathetic paraganglioma (PPGL), surgery can be used as a curative treatment; however, the life-threatening risk of perioperative hemodynamic instability (HI) presents challenges. This study aimed to analyze the incidence and predictive factors of perioperative HI. The electronic medical records of 114 consecutive patients who underwent surgery for PPGLs at our institution were retrospectively reviewed. HI was defined as one or more episodes of systolic blood pressure > 200 mmHg or mean blood pressure < 60 mmHg during surgery. The factors predictive of perioperative HI were determined using both univariate and multivariate analyses. Intraoperative HI occurred in 79 (69.3%) patients. In multivariate analysis, α-adrenergic receptor blocker duration (days) (odds ratio, 1.015; 95% confidence interval, 1.001-1.029) was a predictor for intraoperative HI. Postoperative hypotension occurred in 36 (31.6%) patients. Higher urine epinephrine levels, and greater preoperative highest heart rate (HR) were predictive factors for postoperative hypotension in PPGL patients. Caution should be taken in perioperative management for PPGL, especially with long duration of α-adrenergic receptor blocker use, higher urine epinephrine levels, and greater preoperative highest HR.
PubMed IF 4.9 내분비대사내과
35702021

제1저자 이진우, 허진, 권유욱, 채정환 · 교신저자 김효수

, , , , , , , , , , , , , , , ,
KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.
J Hematol Oncol. 2021;14(1):148.

Abstract
BACKGROUND Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance.
METHODS Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo.
RESULTS KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo.
CONCLUSIONS KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.
PubMed IF 47.8 순환기내과
35692021

제1저자 이영아, 이현정 · 교신저자 박영주, 김종일

, , , , , , , , , , , , , , , , , , , ,
NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake.
J Clin Invest. 2021;131(18):e144847.

Abstract
BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).
PubMed IF 14.3 내분비대사내과

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