• Korean Journal of Radiology
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• v.21 no.11
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• pp.1256-1264
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• 2020

Objective: Lung segmentation using volumetric quantitative computed tomography (CT) analysis may help predict outcomes of patients with coronavirus disease (COVID-19). The aim of this study was to investigate the relationship between CT volumetric quantitative analysis and prognosis in patients with COVID-19. Materials and Methods: CT images from patients diagnosed with COVID-19 from February 18 to April 15, 2020 were retrospectively analyzed. CT with a negative finding, failure of quantitative analysis, or poor image quality was excluded. CT volumetric quantitative analysis was performed by automated volumetric methods. Patients were stratified into two risk groups according to CURB-65: mild (score of 0-1) and severe (2-5) pneumonia. Outcomes were evaluated according to the critical event-free survival (CEFS). The critical events were defined as mechanical ventilator care, ICU admission, or death. Multivariable Cox proportional hazards analyses were used to evaluate the relationship between the variables and prognosis. Results: Eighty-two patients (mean age, 63.1 ± 14.5 years; 42 females) were included. In the total cohort, male sex (hazard ratio [HR], 9.264; 95% confidence interval [CI], 2.021-42.457; p = 0.004), C-reactive protein (CRP) (HR, 1.080 per mg/dL; 95% CI, 1.010-1.156; p = 0.025), and COVID-affected lung proportion (CALP) (HR, 1.067 per percentage; 95% CI, 1.033-1.101; p < 0.001) were significantly associated with CEFS. CRP (HR, 1.164 per mg/dL; 95% CI, 1.006-1.347; p = 0.041) was independently associated with CEFS in the mild pneumonia group (n = 54). Normally aerated lung proportion (NALP) (HR, 0.872 per percentage; 95% CI, 0.794-0.957; p = 0.004) and NALP volume (NALPV) (HR, 1.002 per mL; 95% CI, 1.000-1.004; p = 0.019) were associated with a lower risk of critical events in the severe pneumonia group (n = 28). Conclusion: CRP in the mild pneumonia group; NALP and NALPV in the severe pneumonia group; and sex, CRP, and CALP in the total cohort were independently associated with CEFS in patients with COVID-19.

• Korean Journal of Radiology
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• v.21 no.8
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• pp.1007-1017
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• 2020

Objective: The purpose of our study was to investigate the predictive abilities of clinical and computed tomography (CT) features for outcome prediction in patients with coronavirus disease (COVID-19). Materials and Methods: The clinical and CT data of 238 patients with laboratory-confirmed COVID-19 in our two hospitals were retrospectively analyzed. One hundred sixty-six patients (103 males; age 43.8 ± 12.3 years) were allocated in the training cohort and 72 patients (38 males; age 45.1 ± 15.8 years) from another independent hospital were assigned in the validation cohort. The primary composite endpoint was admission to an intensive care unit, use of mechanical ventilation, or death. Univariate and multivariate Cox proportional hazard analyses were performed to identify independent predictors. A nomogram was constructed based on the combination of clinical and CT features, and its prognostic performance was externally tested in the validation group. The predictive value of the combined model was compared with models built on the clinical and radiological attributes alone. Results: Overall, 35 infected patients (21.1%) in the training cohort and 10 patients (13.9%) in the validation cohort experienced adverse outcomes. Underlying comorbidity (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.67-6.71; p < 0.001), lymphocyte count (HR, 0.12; 95% CI, 0.04-0.38; p < 0.001) and crazy-paving sign (HR, 2.15; 95% CI, 1.03-4.48; p = 0.042) were the independent factors. The nomogram displayed a concordance index (C-index) of 0.82 (95% CI, 0.76-0.88), and its prognostic value was confirmed in the validation cohort with a C-index of 0.89 (95% CI, 0.82-0.96). The combined model provided the best performance over the clinical or radiological model (p < 0.050). Conclusion: Underlying comorbidity, lymphocyte count and crazy-paving sign were independent predictors of adverse outcomes. The prognostic nomogram based on the combination of clinical and CT features could be a useful tool for predicting adverse outcomes of patients with COVID-19.

• Korean Journal of Radiology
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• v.21 no.9
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• pp.1065-1076
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• 2020

Objective: To determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared with pathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserver agreement for evaluating mrTRG. Materials and Methods: Between 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; mean age, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologists independently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologists graded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models were used for survival analysis. Cohen's kappa analysis was used to determine interobserver agreement. Results: According to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5. By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantly different according to the 5-point grading mrTRG (p = 0.024) and pTRG (p = 0.038). The 5-year disease-free survival (DFS) was significantly different among the five mrTRG groups (p = 0.039), but not among the five pTRG groups (p = 0.072). OS and DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio = 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, k value between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI. Conclusion: mrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weighted MRI may improve interobserver agreement on mrTRG.

• Korean Journal of Radiology
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• v.21 no.6
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• pp.736-745
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• 2020

Objective: To identify the initial chest computed tomography (CT) findings and clinical characteristics associated with the course of coronavirus disease 2019 (COVID-19) pneumonia. Materials and Methods: Baseline CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia (39 men, 46.2 ± 15.9 years) were retrospectively analyzed. Baseline CT findings including lobar distribution, presence of ground glass opacities, consolidation, linear opacities, and lung severity score were evaluated. The outcome event was recovery with hospital discharge. The time from symptom onset to discharge or the end of follow-up (for those remained hospitalized) was recorded. Data were censored in events such as death or discharge without recovery. Multivariable Cox proportional hazard regression was used to explore the association between initial CT, clinical or laboratory findings, and discharge with recovery, whereby hazard ratio (HR) values < 1 indicated a lower rate of discharge at four weeks and longer time until discharge. Results: Thirty-two patients recovered and were discharged during the study period with a median length of admission of 16 days (range, 9 to 25 days), while the rest remained hospitalized at the end of this study (median, 17.5 days; range, 4 to 27 days). None died during the study period. After controlling for age, onset time, lesion characteristics, number of lung lobes affected, and bilateral involvement, the lung severity score on baseline CT (> 4 vs. ≤ 4 [reference]: adjusted HR = 0.41 [95% confidence interval, CI = 0.18-0.92], p = 0.031) and initial lymphocyte count (reduced vs. normal or elevated [reference]: adjusted HR = 0.14 [95% CI = 0.03-0.60], p = 0.008) were two significant independent factors that influenced recovery and discharge. Conclusion: Lung severity score > 4 and reduced lymphocyte count at initial evaluation were independently associated with a significantly lower rate of recovery and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia.

• Journal of Nutrition and Health
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• v.57 no.2
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• pp.211-227
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• 2024

Introduction: Seaweed is a sustainable and underexplored source of bioactive compounds with potent anti-inflammatory activities. However, studies on the interaction between seaweed and genes on inflammation are limited. Purpose: We aimed to evaluate the relationships between seaweed consumption and the polygenic risk scores (PRS) and their interactions with high-sensitivity C-reactive protein (hs-CRP) levels. Methods: Information on seaweed consumption was collected using a food frequency questionnaire, which included laver, kelp, and sea mustard among the items consumed. A total of 31 hs-CRP-related single nucleotide polymorphisms (SNPs) were selected using genome-wide association studies and clumping analysis, and the individual PRS were calculated by weighting the effect size of each allele in the selected SNPs of 39,369 middle-aged (≥40 years) Koreans using the Korean Genome and Epidemiology Study (KoGES)-Health Examinees (HEXA) cohort data. To investigate the interaction between seaweed intake and the PRS on hs-CRP levels >1 mg/L, hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed using multivariable Cox proportional hazards models. Results: During a mean follow-up period of 4.8 years, we recorded 436 patients with elevated hs-CRP levels. Women in the highest tertile of the PRS with the lowest quartile of seaweed intake had an increased incidence of elevated hs-CRP levels compared with women in the lowest tertile of the PRS with the lowest seaweed intake quartile (HR 2.34, 95% CI 1.23-4.45). No significant association was observed among the men. Conclusion: In conclusion, we identified a new interaction between the PRS, seaweed intake, and inflammation in Korean women, and this study suggests that the interaction between the identification of genetic predisposition and dietary seaweed intake may have an impact on determining the risk of developing hyperinflammation in the future.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.213-220
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• 2023

The most common skin disease, acne, often occurs in adolescence, but it is also detected/observed in adults due to air pollution and drug abuse. One of the causative agents of acne, Cutibacterium acnes (C. acnes) plays a role in the development of skin acne by inducing inflammatory mediators. Torreya nucifera (TN) is an evergreen tree of the family Taxaceae, having well reported antioxidant, anti-proliferative, liver protection, and nerve protection properties. Improvement of these bioactive properties of natural products is one of the purposes of natural product chemistry and pharmaceuticals. We believe biorenovation could be one improvement strategy that utilizes microbial metabolism to produce unique derivatives having enhanced bioactivity. Therefore, in this study, the C. acnes-induced RAW264.7 inflammation model was used to evaluate the anti-inflammatory activity of the biorenovated Torreya nucifera product (TNB). The results showed improved viability of TNB-treated cells compared to TN-treated cells in the concentration range of 50, 100, and 200 ㎍/mL. At non-toxic concentrations, TNB inhibited the production of nitric oxide and prostaglandin E2 by suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. TNB also attenuated the expression of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α induced by C. acnes. Furthermore, TNB inhibited the nuclear factor-κB signaling pathway, a transcription factor known to regulate inflammatory mediators. Based on these results, this study suggests the potential of using TNB as natural material for the treatment of acnes and thus, supporting our postulation of biorenovation as an bioactivity improvement strategy.

• Tuberculosis and Respiratory Diseases
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• v.87 no.2
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• pp.176-184
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• 2024

Background: Results of studies investigating the association between body mass index (BMI) and mortality in patients with coronavirus disease-2019 (COVID-19) have been conflicting. Methods: This multicenter, retrospective observational study, conducted between January 2020 and August 2021, evaluated the impact of obesity on outcomes in patients with severe COVID-19 in a Korean national cohort. A total of 1,114 patients were enrolled from 22 tertiary referral hospitals or university-affiliated hospitals, of whom 1,099 were included in the analysis, excluding 15 with unavailable height and weight information. The effect(s) of BMI on patients with severe COVID-19 were analyzed. Results: According to the World Health Organization BMI classification, 59 patients were underweight, 541 were normal, 389 were overweight, and 110 were obese. The overall 28-day mortality rate was 15.3%, and there was no significant difference according to BMI. Univariate Cox analysis revealed that BMI was associated with 28-day mortality (hazard ratio, 0.96; p=0.045), but not in the multivariate analysis. Additionally, patients were divided into two groups based on BMI ≥25 kg/m² and underwent propensity score matching analysis, in which the two groups exhibited no significant difference in mortality at 28 days. The median (interquartile range) clinical frailty scale score at discharge was higher in nonobese patients (3 [3 to 5] vs. 4 [3 to 6], p<0.001). The proportion of frail patients at discharge was significantly higher in the nonobese group (28.1% vs. 46.8%, p<0.001). Conclusion: The obesity paradox was not evident in this cohort of patients with severe COVID-19. However, functional outcomes at discharge were better in the obese group.

• Journal of Preventive Medicine and Public Health
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• v.57 no.4
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• pp.327-338
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• 2024

Objectives: Estimating the number of deaths caused by smoking is crucial for developing and evaluating tobacco control and smoking cessation policies. This study aimed to determine smoking-attributable mortality (SAM) in Korea in 2020. Methods: Four large-scale cohorts from Korea were analyzed. A Cox proportional-hazards model was used to determine the hazard ratios (HRs) of smoking-related death. By conducting a meta-analysis of these HRs, the pooled HRs of smoking-related death for 41 diseases were estimated. Population-attributable fractions (PAFs) were calculated based on the smoking prevalence for 1995 in conjunction with the pooled HRs. Subsequently, SAM was derived using the PAF and the number of deaths recorded for each disease in 2020. Results: The pooled HR for all-cause mortality attributable to smoking was 1.73 for current men smokers (95% confidence interval [CI], 1.53 to 1.95) and 1.63 for current women smokers (95% CI, 1.37 to 1.94). Smoking accounted for 33.2% of all-cause deaths in men and 4.6% in women. Additionally, it was a factor in 71.8% of men lung cancer deaths and 11.9% of women lung cancer deaths. In 2020, smoking was responsible for 53 930 men deaths and 6283 women deaths, totaling 60 213 deaths. Conclusions: Cigarette smoking was responsible for a significant number of deaths in Korea in 2020. Monitoring the impact and societal burden of smoking is essential for effective tobacco control and harm prevention policies.

• Oncology Letters
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• v.42 no.1
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• pp.453-460
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• 2019

The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancer-specific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. Kaplan-Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan-Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein-coupled receptor 149 (GPR149), was significantly associated with shorter time-to-progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.

• Hip & pelvis
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• v.34 no.1
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• pp.25-34
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• 2022

Purpose: Mortality rates following hip fracture surgery have been well-studied. This study was conducted to examine mortality rates in asymptomatic patients presenting for treatment of acute hip fractures with concurrent positive COVID-19(+) tests compared to those with negative COVID-19(-) tests. Materials and Methods: A total of 149 consecutive patients undergoing hip fracture surgery during the COVID-19 pandemic at two academic medical centers were reviewed retrospectively. Patients were divided into two groups for comparative analysis: one group included asymptomatic patients with COVID-19+ tests versus COVID-19- tests. The primary outcome was mortality at 30-days and 90-days. Results: COVID-19+ patients had a higher mortality rate than COVID-19- patients at 30-days (26.7% vs 6.0%, P=0.005) and 90-days (41.7% vs 17.2%, P=0.046) and trended towards an increased length of hospital stay (10.1±6.2 vs 6.8±3.8 days, P=0.06). COVID-19+ patients had more pre-existing respiratory disease (46.7% vs 11.2%, P=0.0002). Results of a Cox regression analysis showed an increased risk of mortality at 30-days and 90-days from COVID-19+ status alone without an increased risk of death in patients with pre-existing chronic respiratory disease. Conclusion: Factors including time to surgery, age, preexisting comorbidities, and postoperative ambulatory status have been proven to affect mortality and complications in hip fracture patients; however, a positive COVID-19 test result adds another variable to this process. Implementation of protocols that will promote prompt orthogeriatric assessments, expedite patient transfer, limit operating room traffic, and optimize anesthesia time can preserve the standard of care in this unique patient population.