SCI 발표논문

2021년 358편

2382021

제1저자 김학령 · 교신저자 김학령

, , , , , ,
Association between household income and pulse pressure: data from the Korean National Health and Nutrition Examination Survey.
Blood Press. 2021;30(4):258-264.

Abstract
PURPOSE There has been limited evidence for the association between socioeconomic status (SES) and arterial stiffness. This study was performed to investigate the association between household income and brachial pulse pressure (PP) in the general Korean population.
MATERIALS AND METHODS This study was based on data acquired in the 2018 Korea National Health and Nutrition Examination Survey (2018 KNHANES). A total of 13004 subjects at the age of 20 years or older analysed. The information on monthly household income was obtained through the questionnaire, and was stratified into 5 groups for each quintile. Brachial blood pressure (BP) was measured 3 times, and the average of the second and third measured BPs were used. PP was calculated as the difference between systolic and diastolic BPs.
RESULTS A lower household income was associated with a higher prevalence of cardiovascular risk factors. As household income increased, PP decreased proportionally (p < .001). In multiple linear regression analysis, household income (per quintile) was independently associated with PP even after controlling for potential confounders (β = -.125, p < .001). Multiple binary logistic regression analysis showed that the increased household income level was significantly associated lower probability having higher PP (≥ 43.5 mmHg) even after controlling for multiple covariates (the lowest vs. the highest household income; odds ratio, 0.48; 95% confidence interval, .41-.55; p < .001).
CONCLUSION Low household income was associated with higher PP. This provides additional evidence for the association between low SES and high arterial stiffness.
PubMed IF 2.8 순환기내과
2372021

제1저자 최슬기, 강병주 · 교신저자 이은영

, , , , , ,
Association of first, second, and third-line bDMARDs and tsDMARD with drug survival among seropositive rheumatoid arthritis patients: Cohort study in A real world setting.
Semin Arthritis Rheum. 2021;51(4):685-691.

Abstract
OBJECTIVES To determine the association of first, second, and third-line biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among seropositive rheumatoid arthritis (RA) patients.
METHODS The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date.
RESULTS Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69-0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25-0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19-0.63) was associated with lower drug failure risk compared to third TNFi users.
CONCLUSION First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third-line use of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among seropositive RA patients.
PubMed IF 3.8 류마티스내과
2362021

제1저자 임성윤 · 교신저자 김세중

,
Pathophysiology of Cardiorenal Syndrome and Use of Diuretics and Ultrafiltration as Volume Control.
Korean Circ J. 2021;51(8):656-667.

Abstract
Acute or chronic dysfunction of the heart or kidneys can cause dysfunction of other organs. This interaction between the heart and kidneys is characterized as cardiorenal syndrome (CRS). Recently, a preponderance of data indicated that venous congestion plays an important role in the combination of renal and cardiac diseases. This review aims to focus on the pathophysiology of venous congestion that leads to renal impairment in heart failure and the use of diuretics or ultrafiltration as decongestive therapy in CRS. We found that although clinical studies have confirmed that decongestive therapy has a definite role in decreasing volume overload and the consequent symptom improvement in patients with CRS, the impact of diuretics or ultrafiltration on the improvement of kidney function or mortality remains uncertain. A precise assessment of volume status is required to determine the adequacy of decongestion. Objective measures of renal venous congestion may be a future metric to assess the adequacy of the diuretic response in patients and guide therapeutic decision making.
PubMed IF 3.4 신장내과
2352021

제1저자 손경희 · 교신저자 강혜련

, , , ,
Finding the Optimal Alternative for Immediate Hypersensitivity to Low-Osmolar Iodinated Contrast.
Invest Radiol. 2021;56(8):480-485.

Abstract
OBJECTIVES Avoiding culprit agents is recommended for subjects who have had previous hypersensitivity reaction (HSR) to low-osmolar contrast media (LOCM). However, the guidelines for choosing optimal alternatives have not been determined. We investigated the outcomes of reexposure in patients with previous immediate HSRs to provide a safe option.
MATERIALS AND METHODS The outcomes of reexposure were assessed in a cohort with previous LOCM-associated HSR based on skin testing results and the presence of a common N-(2,3-dihydroxypropyl) carbamoyl side chain.
RESULTS Among 482 skin tests, 38.7% (31/80), 45.8% (99/216), and 64.0% (119/186) of mild, moderate, and severe index HSRs showed positivity to at least 1 LOCM, of which 62.8% showed positivity to at least 2 different LOCM. The overall recurrent HSRs were reduced from 43.8% upon reexposure to the culprit LOCM to 12.3% upon using nonculprit skin test negative LOCM (P = 0.004); those with severe index HSRs exhibited a significant reduction (11.3% vs 100%), but those with non-severe HSRs to LOCM did not. In subjects with severe index HSRs, the skin test cross-reactivity between LOCM was associated with sharing the common side chain (20.7% vs 11.5%, P = 0.003), and the recurrence rate of HSRs was effectively reduced by avoiding the common side chain (24.0% vs 7.8%, P = 0.039). However, these differences were not observed in those with non-severe index HSRs.
CONCLUSIONS In patients who experienced a severe index HSR to LOCM, skin test negative LOCM without a common side chain could be suggested as an option for safe reexposure.
PubMed IF 7.9 알레르기내과
2342021

제1저자 박진주 · 교신저자 최동주

, , , , , , , , , , ,
Heart failure and atrial fibrillation: tachycardia-mediated acute decompensation.
ESC Heart Fail. 2021;8(4):2816-2825.

Abstract
AIMS Tachycardia is a reversible event that may cause hemodynamic decompensation but may not necessarily cause direct damages to the myocardium. To evaluate the clinical outcomes of patients with heart failure (HF) and atrial fibrillation (AF), whose acute decompensation was tachycardia mediated.
METHODS AND RESULTS The Korean Acute Heart Failure registry was a prospective registry that consecutively enrolled 5625 patients with acute HF. Patients were classified into three groups according to the rhythm and aggravating factor: (i) 3664 (65.1%) patients with sinus rhythm (SR), (ii) 1033 (18.4%) patients with AF whose decompensation was tachycardia-mediated, AF-TM (+), and (iii) N = 928 (16.5%) patients with AF whose decompensation was not tachycardia-mediated, AF-TM (-). The primary outcomes were in-hospital and post-discharge 1 year all-cause mortality. At admission, the mean heart rate was 90.8 ± 23.4, 86.8 ± 26.8, and 106.3 ± 29.7 beats per minute for the SR, AF-TM (-), and AF-TM (+) groups, respectively. The AF-TM (+) group had more favourable characteristics such as de novo onset HF, less diabetes, ischaemic heart disease, and higher blood pressure than the AF-TM (-) group. In-hospital mortality rates were 5.1%, 6.5%, and 1.7% for SR, AF-TM (-), and AF-TM (+) groups, respectively. In logistic regression analysis, the AF-TM (+) group had lower in-hospital mortality after adjusting the significant covariates (odds ratio, 0.49; 95% confidence interval, 0.26-0.93). The mortality rate did not differ between SR and AF-TM (-) groups. During 1 year follow-up, 990 (18.5%) patients died. In univariate and multivariate Cox proportional regression analyses, there was no difference in 1-year all-cause mortality between the three groups.
CONCLUSIONS In patients with HF and AF, patients whose acute decompensation is tachycardia-mediated have better in-hospital, but similar post-discharge outcomes compared with those with SR or those with AF whose decompensation is not tachycardia-mediated.
CLINICAL TRIAL REGISTRATION ClinicalTrial.gov NCT01389843.
PubMed IF 3.8 순환기내과
2332021

제1저자 조인래 · 교신저자 조재희

, , , , ,
Comparison of contrast-enhanced versus conventional EUS-guided FNA/fine-needle biopsy in diagnosis of solid pancreatic lesions: a randomized controlled trial.
Gastrointest Endosc. 2021;94(2):303-310.

Abstract
BACKGROUND AND AIMS Contrast-enhanced harmonic EUS (CEH-EUS) is useful in the differential diagnosis of solid pancreatic lesions (SPLs). However, there is lack of verification about the usefulness of CEH-EUS-guided FNA/fine-needle biopsy (FNB) sampling. This study aimed to investigate the usefulness of CEH-EUS-guided FNA/FNB sampling without on-site cytopathology.
METHODS Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to 2 parallel groups, the interventional group (CEH-EUS) or the control group (conventional EUS). The diagnostic sensitivity and optimal number of needle passes for pathologic diagnosis were investigated and compared between groups.
RESULTS Two hundred forty patients were enrolled from March 2016 to September 2019, with 120 patients assigned to each group. Pancreatic malignancies and neuroendocrine tumors were found in 202 (90.83%) and 9 (3.75%) patients, respectively. There was no statistically significant difference between the groups in terms of age, sex, lesion size (30.96 ± 12.09 mm in the CEH-EUS group vs 33.09 ± 16.39 mm in the conventional EUS group; P = .252), lesion location, adverse event rate, and disease distribution. The diagnostic sensitivity values in the CEH-EUS and conventional EUS groups were 85.8% and 88.3%, respectively (P = .564). All patients in the conventional EUS group and most in the CEH-EUS group received a pathologic diagnosis within 3 needle passes.
CONCLUSIONS Diagnostic sensitivity for SPLs was not different between the CEH-EUS and conventional EUS groups, and no independent factors were found that could improve diagnostic sensitivity. CEH-EUS-guided FNA/FNB sampling does not need to be used routinely and may be selectively considered for small, indeterminate lesions. (Clinical trial registration number: KCT 0001840.).
PubMed IF 8 소화기내과
2322021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Atrial fibrillation and kidney function: a bidirectional Mendelian randomization study.
Eur Heart J. 2021;42(29):2816-2823.

Abstract
AIMS The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function.
METHODS AND RESULTS We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530].
CONCLUSIONS Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study.
PubMed IF 45.3 신장내과
2312021

제1저자 조재호 · 교신저자 김선욱

, , , , , , , , , ,
A Smart Diaper System Using Bluetooth and Smartphones to Automatically Detect Urination and Volume of Voiding: Prospective Observational Pilot Study in an Acute Care Hospital.
J Med Internet Res. 2021;23(7):e29979.

Abstract
BACKGROUND Caregivers of patients who wear conventional diapers are required to check for voiding every hour because prolonged wearing of wet diapers causes health problems including diaper dermatitis and urinary tract infections. However, frequent checking is labor intensive and disturbs patients' and caregivers' sleep. Furthermore, assessing patients' urine output with diapers in an acute care setting is difficult. Recently, a smart diaper system with wetness detection technology was developed to solve these issues.
OBJECTIVE We aimed to evaluate the applicability of the smart diaper system for urinary detection, its accuracy in measuring voiding volume, and its effect on incontinence-associated dermatitis (IAD) occurrence in an acute care hospital.
METHODS This prospective, observational, single-arm pilot study was conducted at a single tertiary hospital. We recruited 35 participants aged ≥50 years who were wearing diapers due to incontinence between August and November 2020. When the smart diaper becomes wet, the smart diaper system notifies the caregiver to change the diaper and measures voiding volume automatically. Caregivers were instructed to record the weight of wet diapers on frequency volume charts (FVCs). We determined the voiding detection rate of the smart diaper system and compared the urine volume as automatically calculated by the smart diaper system with the volume recorded on FVCs. Agreement between the two measurements was estimated using a Bland-Altman plot. We also checked for the occurrence or aggravation of IAD and bed sores.
RESULTS A total of 30 participants completed the protocol and 390 episodes of urination were recorded. There were 108 records (27.7%) on both the FVCs and the smart diaper system, 258 (66.2%) on the FVCs alone, 18 (4.6%) on the smart diaper system alone, and 6 (1.5%) on the FVCs with sensing device lost. The detection rate of the smart diaper system was 32.8% (126/384). When analyzing records concurrently listed in both the FVCs and the smart diaper system, linear regression showed a strong correlation between the two measurements (R²=0.88, P<.001). The Bland-Altman assessment showed good agreement between the two measurements, with a mean difference of -4.2 mL and 95% limits of agreement of -96.7 mL and 88.3 mL. New occurrence and aggravation of IAD and bed sores were not observed. Bed sores improved in one participant.
CONCLUSIONS The smart diaper system showed acceptable accuracy for measuring urine volume and it could replace conventional FVCs in acute setting hospitals. Furthermore, the smart diaper system has the potential advantage of preventing IAD development and bed sore worsening. However, the detection rate of the smart diaper system was lower than expected. Detection rate polarization among participants was observed, and improvements in the user interface and convenience are needed for older individuals who are unfamiliar with the smart diaper system.
PubMed IF 8.2 노인병내과
2302021

제1저자 윤기철 · 교신저자 김나영

,
Roles of Sex Hormones and Gender in the Gut Microbiota.
J Neurogastroenterol Motil. 2021;27(3):314-325.

Abstract
The distribution of gut microbiota varies according to age (childhood, puberty, pregnancy, menopause, and old age) and sex. Gut microbiota are known to contribute to gastrointestinal (GI) diseases such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer; however, the exact etiology remains elusive. Recently, sex and gender differences in GI diseases and their relation to gut microbiota has been suggested. Furthermore, the metabolism of estrogen and androgen was reported to be related to the gut microbiome. As gut microbiome is involved in the excretion and circulation process of sex hormones, the concept of "microgenderome" indicating the role of sex hormone on the gut microbiota has been suggested. However, further research is needed for this concept to be universally accepted. In this review, we summarize sex- and gender-differences in gut microbiota and the interplay of microbiota and GI diseases, focusing on sex hormones. We also describe the metabolic role of the microbiota in this regard. Finally, current subjects, such as medication including probiotics, are briefly discussed.
PubMed IF 3.7 소화기내과
2292021

제1저자 박세훈 · 교신저자 김동기

, , , , , , , , , , , , ,
Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
PLoS One. 2021;16(7):e0254649.

Abstract
As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40-69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.
PubMed IF 2.8 신장내과
2282021

제1저자 윤혁 · 교신저자 Siddharth Singh

, , , , , , ,
Histologic Remission Is Associated With Lower Risk of Treatment Failure in Patients With Crohn Disease in Endoscopic Remission.
Inflamm Bowel Dis. 2021;27(8):1277-1284.

Abstract
BACKGROUND Although achieving histologic remission in ulcerative colitis is established, the incremental benefit of achieving histologic remission in patients with Crohn disease (CD) treated to a target of endoscopic remission is unclear. We evaluated the risk of treatment failure in patients with CD in clinical and endoscopic remission by histologic activity status.
METHODS In a single-center retrospective cohort study, we identified adults with active CD who achieved clinical and endoscopic remission through treatment optimization. We evaluated the risk of treatment failure (composite of clinical flare requiring treatment modification, hospitalization, and/or surgery) in patients who achieved histologic remission vs persistent histologic activity through Cox proportional hazard analysis.
RESULTS Of 470 patients with active CD, 260 (55%) achieved clinical and endoscopic remission with treatment optimization; 215 patients with histology were included (median age, 33 years; 46% males). Overall, 132 patients (61%) achieved histologic remission. No baseline demographic, disease, or treatment factor was associated with achieving histologic remission. Over a 2-year follow-up, patients with CD in clinical and endoscopic remission who achieved histologic remission experienced a 43% lower risk of treatment failure (1-year cumulative risk: 12.9% vs 18.2%; adjusted hazard ratio, 0.57 [95% confidence interval, 0.35-0.94]) as compared with persistent histologic activity.
CONCLUSIONS Approximately 61% of patients with active CD who achieved clinical and endoscopic remission with treatment optimization simultaneously achieved histologic remission, which was associated with a lower risk of treatment failure. Whether histologic remission should be a treatment target in CD requires evaluation in randomized trials.
PubMed IF 5.5 소화기내과
2272021

제1저자 공병수 · 교신저자 이장한, 조영민

, , ,
Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.
Cell Rep. 2021;36(4):109447.

Abstract
Mitochondria are principal metabolic organelles that are increasingly unveiled as immune regulators. However, it is currently not known whether mitochondrial-encoded peptides modulate T cells to induce changes in phenotype and function. In this study, we found that MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) prevented autoimmune β cell destruction by targeting T cells in non-obese diabetic (NOD) mice. MOTS-c ameliorated the development of hyperglycemia and reduced islet-infiltrating immune cells. Furthermore, adoptive transfer of T cells from MOTS-c-treated NOD mice significantly decreased the incidence of diabetes in NOD-severe combined immunodeficiency (SCID) mice. Metabolic and genomic analyses revealed that MOTS-c modulated T cell phenotype and function by regulating T cell receptor (TCR)/mTOR complex 1 (mTORC1) signaling. Type 1 diabetes (T1D) patients had a lower serum MOTS-c level than did healthy controls. Furthermore, MOTS-c reduced T cell activation by alleviating T cells from the glycolytic stress in T1D patients, suggesting therapeutic potential. Our findings indicate that MOTS-c regulates the T cell phenotype and suppresses autoimmune diabetes.
PubMed IF 7.7 내분비대사내과
2262021

제1저자 서인호, 은혁수, 김자경, 신의철 · 교신저자 김원, 박수형, 신의철

, , , , , , , , , , , , ,
IL-15 enhances CCR5-mediated migration of memory CD8+ T cells by upregulating CCR5 expression in the absence of TCR stimulation.
Cell Rep. 2021;36(4):109438.

Abstract
During microbial infection, bystander CD8⁺ T cells that are not specific to infecting pathogens can be activated by interleukin (IL)-15. However, the tissue-homing properties of bystander-activated CD8⁺ T cells have not been elucidated. Here, we examine the effects of IL-15 on the expression of chemokine receptors on CD8⁺ T cells and their migration. IL-15 upregulates CCR5 in memory CD8⁺ T cells in the absence of T cell receptor (TCR) stimulation and enhances CCR5-dependent migration. IL-15-induced CCR5 upregulation is abrogated by TCR stimulation, indicating that CCR5 is upregulated in bystander-activated CD8⁺ T cells. Moreover, CCR5 signals increase proliferation and cytotoxic protein expression in IL-15-treated memory CD8⁺ T cells, although the increase has a small extent. CCR5 upregulation in bystander-activated CD8⁺ T cells is associated with severe liver injury in patients with acute hepatitis A. Altogether, the results indicate that CCR5 upregulation by IL-15 mediates the migration of bystander-activated CD8⁺ T cells.
PubMed IF 7.7 소화기내과
2252021

제1저자 김학령 · 교신저자 김학령

, , , , ,
Improved Prognostic Value in Predicting Long-Term Cardiovascular Events by a Combination of High-Sensitivity C-Reactive Protein and Brachial-Ankle Pulse Wave Velocity.
J Clin Med. 2021;10(15):jcm10153291.

Abstract
BACKGROUND Both C-reactive protein (CRP) and arterial stiffness are associated with the development of cardiovascular disease (CVD). This study was performed to investigate whether a combination of these two measurements could improve cardiovascular risk stratification.
METHODS A total of 6572 consecutive subjects (mean age, 60.8 ± 11.8 years; female, 44.2%) who underwent both high-sensitivity CRP (hs-CRP) and brachial-ankle pulse wave velocity (baPWV) measurement within 1 week were retrospectively analyzed. Major adverse cardiovascular events (MACE), including cardiovascular death, acute myocardial infarction, coronary revascularization, and stroke were assessed during the clinical follow-up.
RESULTS During a mean follow-up period of 3.75 years (interquartile range, 1.78-5.31 years), there were 182 cases of MACE (2.8%). The elevated baPWV (≥1505 cm/s) (hazard ratio (HR), 4.21; 95% confidence interval (CI), 2.73-6.48; p < 0.001) and hs-CRP (≥3 mg/L) (HR, 1.57; 95% CI, 1.12-2.21; p < 0.001) levels were associated with MACE even after controlling for potential confounders. The combination of baPWV and hs-CRP further stratified the subjects' risk (subjects with low baPWV and hs-CRP vs. subjects with high baPWV and hs-CRP; HR, 7.08; 95% CI, 3.76-13.30; p < 0.001). Adding baPWV information to clinical factors and hs-CRP had an incremental prognostic value (global Chi-square score, from 126 to 167, p < 0.001).
CONCLUSIONS The combination of hs-CRP and baPWV provided a better prediction of future CVD than either one by itself. Taking these two simple measurements simultaneously is clinically useful in cardiovascular risk stratification.
PubMed IF 3.3 순환기내과
2242021

제1저자 고성준, 최선미 · 교신저자 이진우

, , , ,
All-cause mortality of patients with idiopathic pulmonary fibrosis: a nationwide population-based cohort study in Korea.
Sci Rep. 2021;11(1):15145.

Abstract
Most epidemiologic studies of patients with idiopathic pulmonary fibrosis (IPF) have been conducted in North America and Europe. Moreover, there are limited data concerning the cause of death and cause-specific mortality rate of IPF patients in population-based studies. We analyzed information from the Korean National Health Insurance Service database from 2006 to 2016. Patients with a diagnosis code of IPF were extracted from the database and we included those who satisfied the narrow definition of IPF diagnosis. Age- and sex-matched controls were randomly selected at a case-to-control rate of 1:3. We included 42,777 patients newly diagnosed with IPF during the study period. Their mean age was 64.6 years, and 65.4% were male. The age-standardized mortality rates were 85.66 (95% confidence interval [CI] 84.45-86.89) per 1000 person-years. The survival rates of IPF patients 1, 2, 3, 5, and 10 years after IPF diagnosis were 84.5%, 77.4%, 71.9%, 62.9%, and 48.4%, respectively. The standardized mortality ratio of IPF patients compared to that of the normal population was 4.66. The leading cause of death in IPF patients was respiratory causes, followed by cancer. Patients with IPF in Korea showed significantly higher mortality compared to the general population.
PubMed IF 4.9 호흡기내과
2232021

제1저자 김학령 · 교신저자 김상현

, , , , , , ,
Prognostic value of serum soluble ST2 in stable coronary artery disease: a prospective observational study.
Sci Rep. 2021;11(1):15203.

Abstract
The role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80-104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.
PubMed IF 4.9 순환기내과
2222021

제1저자 김유진, 박영수 · 교신저자 신철민, 한경도

, , , , , , ,
Risk of Heart Disease after Cholecystectomy: A Nationwide Population-Based Cohort Study in South Korea.
J Clin Med. 2021;10(15):jcm10153253.

Abstract
The aim of the study is to evaluate the risk of heart disease in individuals who underwent cholecystectomy. This was a retrospective cohort study using the National Health Insurance Service database of South Korea. A total of 146,928 patients who underwent cholecystectomy and 268,502 age- and sex-matched controls were compared. Multivariate Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for heart disease after cholecystectomy. In results, a previous history of cholecystectomy increased the risk of heart disease (congestive heart failure [CHF], myocardial infarction [MI], atrial fibrillation [AF]) (adjusted HR [aHR]: 1.40, 95% CI: [1.36-1.44]). The increased risk was particularly seen for CHF (1.22 [1.16-1.29]) but not for MI and AF (p > 0.05). In the subgroup analyses, cholecystectomy was associated with an increased risk of MI in patients aged <65 years (1.49 [1.16-1.92] and 1.18 [1.05-1.35] in patients aged 40-49 and 50-64 years, respectively), but not in those aged ≥ 65 years (0.932 [0.838-1.037]). Moreover, the risk of MI was increased in patients without diabetes mellitus (DM) (1.16 [1.06-1.27]); however, it was decreased in patients with DM (0.83 [0.72-0.97]). In contrast, cholecystectomy did not modify the risk of AF in the subgroup analyses (all p > 0.05). In conclusion, a history of cholecystectomy is associated with an increased risk of CHF. Cholecystectomy may increase the risk of MI in the younger population without DM. These findings suggest that the alteration of bile metabolism and homeostasis might be potentially associated with the development of some heart diseases.
PubMed IF 3.3 소화기내과
2212021

제1저자 최광현 · 교신저자 정숙향

, , ,
Prognostic role of plasma level of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor in hepatocellular carcinoma.
World J Gastroenterol. 2021;27(27):4453-4467.

Abstract
BACKGROUND Most hepatocellular carcinomas (HCCs) are hypervascular, with characteristic features of hepatic arterial supply to the tumor. The factors involved in tumor angiogenesis include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF).
AIM To investigate the profiles of plasma levels of angiogenesis markers in patients with HCC and evaluate their roles in predicting overall survival (OS) and progression-free survival (PFS).
METHODS Plasma samples from 240 prospectively enrolled HCC patients in the very early to advanced stages were used to measure the levels of Ang-1, Ang-2, and VEGF. Their associations with clinical characteristics, OS, and PFS were analyzed.
RESULTS The median plasma levels of Ang-1, Ang-2, and VEGF were 3216 pg/mL, 1684 pg/mL, and 26.5 pg/mL, respectively. The plasma level of Ang-2 showed a significant increase from early stage [Barcelona clinic liver cancer (BCLC) A] to intermediate (BCLC B) and advanced stage HCC (BCLC C/D), whereas Ang-1, VEGF, and alpha-fetoprotein (AFP) levels in the plasma did not show any such changes. Multivariable analysis, propensity score-matched analysis, and time-dependent receiver operating curve analysis revealed that Ang-2 levels had the highest predictive power for OS and PFS. Neither Ang-1 nor VEGF was significantly associated with OS or PFS. The neutrophil-to-lymphocyte ratio was an independent factor for OS and PFS.
CONCLUSION The plasma levels of Ang-2 correlated with liver function, tumor stage, and tumor invasiveness, showing better performance in predicting OS and PFS than AFP, Ang-1, or VEGF.
PubMed IF 7.7 소화기내과
2202021

제1저자 주이진, 곽민선 · 교신저자 윤순호

, , ,
Fully automated waist circumference measurement on abdominal CT: Comparison with manual measurements and potential value for identifying overweight and obesity as an adjunct output of CT scan.
PLoS One. 2021;16(7):e0254704.

Abstract
OBJECTIVE Waist circumference (WC) is a widely accepted anthropometric parameter of central obesity. We investigated a fully automated body segmentation algorithm for measuring WC on abdominal computed tomography (CT) in comparison to manual WC measurements (WC-manual) and evaluated the performance of CT-measured WC for identifying overweight/obesity.
MATERIALS AND METHODS This retrospective study included consecutive adults who underwent both abdominal CT scans and manual WC measurements at a health check-up between January 2013 and November 2019. Mid-waist WCs were automatically measured on noncontrast axial CT images using a deep learning-based body segmentation algorithm. The associations between CT-measured WC and WC-manual was assessed by Pearson correlation analysis and their agreement was assessed through Bland-Altman analysis. The performance of these WC measurements for identifying overweight/obesity (i.e., body mass index [BMI] ≥25 kg/m2) was evaluated using receiver operating characteristics (ROC) curve analysis.
RESULTS Among 763 subjects whose abdominal CT scans were analyzed using a fully automated body segmentation algorithm, CT-measured WCs were successfully obtained in 757 adults (326 women; mean age, 54.3 years; 64 women and 182 men with overweight/obesity). CT-measured WC was strongly correlated with WC-manual (r = 0.919, p < 0.001), and showed a mean difference of 6.1 cm with limits of agreement between -1.8 cm and 14.0 cm in comparison to WC-manual. For identifying overweight/obesity, CT-measured WC showed excellent performance, with areas under the ROC curve (AUCs) of 0.960 (95% CI, 0.933-0.979) in women and 0.909 (95% CI, 0.878-0.935) in men, which were comparable to WC-manual (AUCs of 0.965 [95% CI, 0.938-0.982] and 0.916 [95% CI, 0.886-0.941]; p = 0.735 and 0.437, respectively).
CONCLUSION CT-measured WC using a fully automated body segmentation algorithm was closely correlated with manually-measured WC. While radiation issue may limit its general use, it can serve as an adjunctive output of abdominal CT scans to identify overweight/obesity.
PubMed IF 2.8 소화기내과
2192021

제1저자 임재현, 이소령 · 교신저자 최의근

, , , , , , , , ,
Exercise and the Risk of Dementia in Patients with Newly Diagnosed Atrial Fibrillation: A Nationwide Population-Based Study.
J Clin Med. 2021;10(14):jcm10143126.

Abstract
BACKGROUND It is unclear whether exercise would reduce dementia in patients with a new diagnosis of atrial fibrillation (AF). Therefore, we aimed to evaluate the association between the change in physical activity (PA) before and after new-onset AF and the risk of incident dementia.
METHODS Using the Korean National Health Insurance Service database, we enrolled a total of 126,555 patients with newly diagnosed AF between 2010 and 2016, who underwent health examinations within two years before and after their diagnosis of AF. The patients were divided into four groups: persistent non-exercisers, exercise starters, exercise quitters, and exercise maintainers.
RESULTS Based on a total of 396,503 person-years of follow-up, 5943 patients were diagnosed with dementia. Compared to persistent non-exercisers, exercise starters (adjusted hazard ratio (aHR) 0.87; 95% confidence interval (CI) 0.81-0.94), and exercise maintainers (aHR 0.66; 95% CI 0.61-0.72) showed a lower risk of incident dementia; however, the risk was similar in exercise quitters (aHR 0.98; 95% CI 0.92-1.05) (p-trend < 0.001). There was a J-shaped relationship between the dose of exercise and the risk of dementia, with the risk reduction maximized at 5-6 times per week of moderate-to-vigorous PA among exercise starters.
CONCLUSION Patients who initiated or continued regular exercise after diagnosis of AF were associated with a lower risk of dementia than persistent non-exercisers, with no risk reduction associated with exercise cessation. Our findings may provide evidence for the benefit of exercise prescription to patients with new-onset AF to prevent incident dementia regardless of their current exercise status.
PubMed IF 3.3 순환기내과
2182021

제1저자 신동우 · 교신저자 황진혁

, , , ,
Maintenance of skeletal muscle mass during FOLFIRINOX is a favorable prognostic factor in pancreatic cancer patients.
BMC Res Notes. 2021;14(1):272.

Abstract
OBJECTIVE The study aimed to investigate the effect of body composition changes during chemotherapy on clinical outcomes in patients with pancreatic cancer.
RESULTS In patients with locally advanced pancreatic cancer (LAPC), the cross-sectional area of skeletal muscle (SM) and adipose tissue (AT) at the level of third lumbar vertebra was measured. The SM and AT ratios indicated the changes during chemotherapy. The patients were classified into three groups based on these ratios: group 1, ≥ 1.00; group 2, 0.85-0.99; group 3, < 0.85. The overall survival (OS) and surgical resection rates were estimated. Fifty-eight patients with LAPC who received first-line FOLFIRINOX were analyzed. Fifteen (25.9%) patients who underwent resection showed maintained BMI, SM, and AT as compared to the patients who did not undergo resection. As the SM ratio decreased, the risk for death increased significantly. Further, the resection rate was significantly higher in patients with maintained SM compared to those with low SM ratio. On the contrary, the change in AT ratio was not associated with OS and resection rate; however, significant decrease in AT more than 15% showed poor clinical outcomes. Maintenance of SM during chemotherapy is a reliable prognostic factor indicating longer OS and higher resection rate.
PubMed IF 1.7 소화기내과
2172021

제1저자 강창희, 송진희 · 교신저자 김나영

, , , , , , , , , , ,
The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer.
Front Oncol. 2021;11:679324.

Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17β-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. One week after the AOM injection, mice were administered with DSS in drinking water for seven days; daily E2 injections were intraperitoneally administered during this period. The mice were sacrificed 16 weeks after AOM injection and analyzed for PD-L1 expression in the distal colon tissues using Western blotting and immunohistochemistry (IHC). Based on Western blotting results, PD-L1 expression was reduced in Nrf2 knockout (KO) female and E2-treated male mice when compared with their wild-type counterparts, following AOM/DSS treatment; this supports the association of PD-L1 expression with tumor progression. Additionally, this finding was in good agreement with the IHC results for PD-L1. Furthermore, we observed that PD-L1 is predominantly expressed in stromal cells rather than on epithelial cells in the colon. Western blotting revealed that PD-L1 expression in the colon positively correlates with expressions of inducible nitric oxide synthase (iNOS) (male, P = 0.002; female, P <0.001) and cyclooxygenase-2 (COX-2) (male, P <0.001; female, P <0.001). Collectively, our findings indicate that estrogen ameliorates the immune microenvironment represented by PD-L1 expression and enhances its effect in the absence of Nrf2.
PubMed IF 3.4 소화기내과
2162021

제1저자 박재형 · 교신저자 조구영

, , , ,
Left Atrial Strain to Predict Stroke in Patients With Acute Heart Failure and Sinus Rhythm.
J Am Heart Assoc. 2021;10(13):e020414.

Abstract
Background Stroke is a major comorbidity in patients with heart failure (HF), especially in those with decreased left atrial (LA) function, and thus, identifying patients highly at risk of stroke can prevent its occurrence. We evaluated the predictive value of global longitudinal strain of LA (LAGLS) in patients with acute HF and sinus rhythm. Methods and Results In this retrospective study, 2461 patients (53.3% men, 69.7±14.4 years old) with sinus rhythm and LAGLS among 4312 consecutive patients with acute HF from 3 tertiary hospitals were included. HF phenotypes were defined as HF with reduced ejection fraction (EF) (left ventricular EF ≤40%), HF with midrange EF (40% <left ventricular EF <50%), and HF with preserved ejection fraction (left ventricular EF ≥50%). Primary outcome was new-onset stroke. The mean left ventricular EF was 39.4%±15.6%. Moreover, 1388 (57.5%), 342 (14.2%), and 682 (28.3%) were classified with HF with reduced EF, HF with midrange EF, and HF with preserved EF, retrospectively. LAGLS was 17.2%±10.4%. During the follow-up duration (mean: 30.3±25.4 months), 100 patients experienced stroke. Patients with stroke had higher LA diameter (P=0.031) and lower LAGLS (P=0.010) than those without stroke. In the univariate analysis, age, diabetes mellitus, LA diameter, LA volume index, and LAGLS were significant risk factors for stroke. In the multivariate analysis, each 1% decrease in LAGLS was associated with a 3.8% increased risk for stroke (hazard ratio [HR], 1.038; 95% CI, 1.013-1.065; P=0.003). When applying a LAGLS cutoff point of 14.5%, patients with LAGLS <14.5% had approximately twice the risk for stroke after adjusting other significant variables (HR, 1.940; 95% CI, 1.269-2.965; P=0.002). Conclusions In patients with acute HF and sinus rhythm, decreased LAGLS (<14.5%) was associated with an increased risk for stroke, with an annual incidence of 2.38%.
PubMed IF 6 순환기내과
2152021

제1저자 박진균 · 교신저자 송영욱

, , , , , , , , , , ,
Inhibition of histone deacetylase 6 suppresses inflammatory responses and invasiveness of fibroblast-like-synoviocytes in inflammatory arthritis.
Arthritis Res Ther. 2021;23(1):177.

Abstract
BACKGROUND To investigate the effects of inhibiting histone deacetylase (HDAC) 6 on inflammatory responses and tissue-destructive functions of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA).
METHODS FLS from RA patients were activated with interleukin (IL)-1β in the presence of increasing concentrations of M808, a novel specific HDAC6 inhibitor. Production of ILs, chemokines, and metalloproteinases (MMPs) was measured in ELISAs. Acetylation of tubulin and expression of ICAM-1 and VCAM-1 were assessed by Western blotting. Wound healing and adhesion assays were performed. Cytoskeletal organization was visualized by immunofluorescence. Finally, the impact of HDAC6 inhibition on the severity of arthritis and joint histology was examined in a murine model of adjuvant-induced arthritis (AIA).
RESULTS HDAC6 was selectively inhibited by M808. The HDAC6 inhibitor suppressed the production of MMP-1, MMP-3, IL-6, CCL2, CXCL8, and CXCL10 by RA-FLS in response to IL-1β. Increased acetylation of tubulin was associated with decreased migration of RA-FLS. Inhibiting HDAC6 induced cytoskeletal reorganization in RA-FLS by suppressing the formation of invadopodia following activation with IL-1β. In addition, M808 tended to decrease the expression of ICAM-1 and VCAM-1. In the AIA arthritis model, M808 improved the clinical arthritis score in a dose-dependent manner. Also, HDAC6 inhibition was associated with less severe synovial inflammation and joint destruction.
CONCLUSION Inhibiting HDAC6 dampens the inflammatory and destructive activity of RA-FLS and reduces the severity of arthritis. Thus, targeting HDAC6 has therapeutic potential.
PubMed IF 5.4 류마티스내과
2142021

제1저자 한미연 · 교신저자 오국환

, , , , , , , ,
Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study.
BMC Nephrol. 2021;22(1):247.

Abstract
BACKGROUND Although uric acid (UA) is regarded as a risk factor for cardiovascular disease, whether UA is an independent risk factor contributing to coronary artery calcification in chronic kidney disease (CKD) is not well known. We evaluated whether UA level is associated with coronary artery calcium (CAC) score in a predialysis CKD cohort.
METHODS A total of 1,350 subjects who underwent coronary computed tomography as part of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease were analysed. We conducted a logistic regression analysis to evaluate the association between UA and the presence of CAC.
RESULTS CAC was detected in 705 (52.2 %) patients, and the level of UA was significantly higher in CAC > 0 patients. UA showed a positive relationship with CAC > 0 in age- and sex-adjusted logistic regression analysis (Odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.04-1.19, P = 0.003). However, UA showed no association with CAC > 0 in multivariate analysis. Further analysis showed that UA showed a positive association with CAC > 0 only in estimated glomerual filtration rate (eGFR) > 60 ml/min/1.73 m² (OR 1.23, 95 % CI 1.02-1.49, P = 0.036) but not in eGFR 30-59 ml/min/1.73 m² (OR 0.92, 95 % CI 0.78-1.08, P = 0.309) or < 30 ml/min/1.73 m² (OR 0.92, 95 % CI 0.79-1.08, P = 0.426).
CONCLUSIONS UA level was significantly associated with CAC in early CKD, but not in advanced CKD.
PubMed IF 2.9 신장내과
2132021

제1저자 이태민 · 교신저자 김학령

, , , , , ,
Age-specific association between invasively measured central blood pressure and left ventricular mass index.
Clin Exp Hypertens. 2021;43(5):419-427.

Abstract
Background: The impact of age on the association between central aortic hemodynamics and left ventricular (LV) remodeling has not been well elucidated. We compared the relationship between measurements of central blood pressure (CBP) and LV mass index (LVMI) according to their ages (<50 years versus ≥50 years). Methods: A total of 305 consecutive subjects (64.4 ± 10.9 years, 60.7% males) who underwent invasive coronary angiography (ICA) for the evaluation of coronary artery disease were prospectively enrolled. Just before ICA, CBP was measured at the aortic root using a pig-tail catheter, and CBP indices, including aortic systolic blood pressure (aSBP), aortic pulse pressure (aPP), aortic fractional pulse pressure (=aPP/mean aortic pressure), and aortic pulsatility index (=aPP/diastolic aortic pressure), were recorded. All subjects underwent transthoracic echocardiography, and LVMI was measured on the same day of ICA. Results: In simple linear correlation analyses, LVMI was associated with all CBP indices in subjects aged <50 years (n = 29) (P < .05 for each), but not in those aged ≥50 years (n = 276) (P > .05 for each). In the younger age group (≤50 years), multivariable analysis showed that aSBP (β= 0.457, P= .021) and aPP (β= 0.610, P= .006) had a significant association with LVMI after adjusting for possible confounding factors. The results remained consistent even when analyzed in a 1:1 propensity score-matched cohort. In conclusion, invasively measured aPP showed the closest association with LVMI in subjects aged <50 years, but not those aged ≥50 years. Conclusion: Aortic pulsatile hemodynamic status appears to have a greater effect on LV remodeling in younger people than in older people.
PubMed IF 6.8 순환기내과
2122021

제1저자 강창경, 김민지 · 교신저자 김항래, 오명돈

, , , , , , , , , , , , ,
Longitudinal Analysis of Human Memory T-Cell Response According to the Severity of Illness up to 8 Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
J Infect Dis. 2021;224(1):39-48.

Abstract
BACKGROUND Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post-symptom onset (PSO) according to the severity of illness is unknown.
METHODS We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis.
RESULTS A total of 24 patients (7 asymptomatic, 9 with mild disease, and 8 with severe disease) and 6 healthy volunteers were analyzed. SARS-CoV-2-specific OX40+CD137+CD4+ T cells and CD69+CD137+CD8+ T cells persisted at 8 months PSO. Also, antigen-specific cytokine-producing or polyfunctional CD4+ T cells were maintained for up to 8 months PSO. Memory CD4+ T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease.
CONCLUSIONS Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.
PubMed IF 4.1 감염내과
2112021

제1저자 김아이린, 박효민 · 교신저자 이은주, 김효수

, , , , , ,
Discovery of chemerin as the new chemoattractant of human mesenchymal stem cells.
Cell Biosci. 2021;11(1):120.

Abstract
BACKGROUND The homing capacity of human mesenchymal stem cells (hMSCs) to the injured sites enables systemic administration of hMSCs in clinical practice. In reality, only a small proportion of MSCs are detected in the target tissue, which is a major bottleneck for MSC-based therapies. We still don't know the mechanism how MSCs are chemo-attracted to certain target organ and engrafted through trans-endothelial migration. In this study, we aimed to determine the mechanism how the circulating hMSCs home to the injured liver.
METHODS AND RESULTS When we compare the cytokine array between normal and injured mouse liver at 1-day thioacetamide (TAA)-treatment, we found that chemerin, CXCL2, and CXCL10 were higher in the injured liver than normal one. Among three, only chemerin was the chemoattractant of hMSCs in 2D- and 3D-migration assay. Analysis of the signal transduction pathways in hMSCs showed that chemerin activated the phosphorylation of JNK1/2, ERK1/2 and p38, and finally upregulated CD44, ITGA4, and MMP-2 that are involved in the transendothelial migration and extravasation of MSCs. Upstream transcription regulators of CD44, ITGA4, and MMP-2 after chemerin treatment were MZF1, GATA3, STAT3, and STAT5A. To develop chemerin as a chemoattractant tool, we cloned gene encoding the active chemerin under the CMV promoter (CMV-aChemerin). We analyzed the migration of hMSCs in the 3D model for space of the Disse, which mimics transmigration of hMSCs in the liver. CMV-aChemerin-transfected hepatocytes were more effective to attract hMSC than control hepatocytes, leading to the enhanced transendothelial migration and homing of hMSCs to liver. The homing efficiency of the intravascularly-delivered hMSCs to liver was evaluated after systemic introduction of the CMV-aChemerin plasmid packed in liposome-vitamin A conjugates which target liver. CMV-aChemerin plasmid targeting liver significantly enhanced homing efficiency of hMSCs to liver compared with control plasmid vector.
CONCLUSIONS Chemerin is the newly found chemoattractant of hMSCs and may be a useful tool to manipulate the homing of the intravascularly-administered hMSC to the specific target organ.
PubMed IF 6.5 순환기내과
2102021

제1저자 서경진, 윤성혜 · 교신저자 김진원

, , , , , , , , ,
A single-arm feasibility study of gradual dose de-escalation of antiemetic dexamethasone for older patients receiving chemotherapy.
J Geriatr Oncol. 2021;12(6):922-929.

Abstract
OBJECTIVES To investigate whether discontinuation of prophylactic dexamethasone by gradual dose de-escalation is practicable in older patients with cancer undergoing moderately emetogenic chemotherapy.
MATERIALS AND METHODS This single-arm, feasibility study prospectively enrolled 40 patients (≥70 years old) with colorectal cancer, who were scheduled to undergo adjuvant FOLFOX chemotherapy, and ten patients ≤60 years old to serve as a control group for pharmacokinetic study. All patients received an antiemetic regimen consisting of intravenous dexamethasone 8 mg and palonosetron at day 1 of the first cycle and underwent phone interviews using symptom questionnaires at day 7 of each cycle. Dexamethasone was tapered off through gradual de-escalation by 2 mg per cycle, when complete response (CR; no emesis and no rescue therapy) was achieved. Primary endpoint was the proportion of patients who discontinued dexamethasone completely.
RESULTS The median age of the patient was 74 years, and 50% were male. Of the 40 patients, 36 completed twelve cycles of chemotherapy, and 73% (N = 29) were able to discontinue dexamethasone completely. The mean (±SD) dose of dexamethasone per cycle was 3.0 mg (±2.4 mg), which was reduced to 37.5% of the initial dose level. The severity of patient-reported nausea did not significantly change over chemotherapy cycle. Geriatric assessment revealed no decline in any domain and fasting blood glucose and hemoglobin A1c levels were not elevated after twelve cycles of chemotherapy, compared to the baseline.
CONCLUSION Gradual dose de-escalation and discontinuation of prophylactic dexamethasone is feasible without compromising its antiemetic effect in older patients undergoing chemotherapy.
PubMed IF 2.9 혈액종양내과
2092021

제1저자 김정현 · 교신저자 김세훈

, , , , , , ,
Pharmacological prevention of delayed hypersensitivity reactions caused by iodinated contrast media.
World Allergy Organ J. 2021;14(7):100561.

Abstract
BACKGROUND Delayed hypersensitivity reactions (DHRs) to radiocontrast media (RCM) occur in approximately 0.5-23.0% of patients and are thought to be caused by T cell-mediated mechanisms. However, an optimal pharmacological preventive strategy is not yet established in patients with histories of delayed reactions to RCM.
OBJECTIVE We aimed to evaluate the efficacy of pharmacological prevention in patients with histories of delayed reactions to non-ionic low-osmolar RCM when re-exposed to RCM.
METHODS A retrospective review of electronic medical records of 117 patients with previous histories of DHRs to RCM who visited an allergy clinic for the prevention of reactions after the re-exposure to RCM was conducted. The effects of pharmacological prevention were compared according to the symptom scores of previous reactions based on their intensities and durations with electronic medical records (EMRs).
RESULTS Of the 117 patients who experienced DHRs after RCM injection, we confirmed the outcomes of RCM re-exposure in 101 patients. For pharmacological prevention, 92 patients (91.1%) received steroids before RCM injection and among them, 50 patients (49.5%) received additional steroids after RCM injection. With this pharmacological prevention, patients of symptoms improved or no recurrence, recurrence of similar previous symptoms, and recurrence of worse symptoms were 98 (97.0%), 2 (2.0%), and 1 (1.0%), respectively. The proportions of no recurrence after pharmacological prevention were lower in patients with severe reactions and higher symptom scores.
CONCLUSION Pharmacological prevention showed a beneficial effect in most patients with delayed hypersensitivity to RCM. Further investigations are needed to establish an effective protocol for the prevention of delayed reactions to RCM.
PubMed IF 4 알레르기내과

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