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Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07.
Kim, ST, Kim, SY, Lee, J, Yun, SH, Kim, HC, Lee, WY, Kim, TW, Hong, YS, Lim, SB, Baek, JY, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022;(33):3868-3877
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Abstract
PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).
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The effect of weight loss interventions in truck drivers: Systematic review.
Pritchard, EK, Kim, HC, Nguyen, N, van Vreden, C, Xia, T, Iles, R
PloS one. 2022;(2):e0262893
Abstract
INTRODUCTION Truck driving is the most common vocation among males internationally with a high proportion overweight/obese due to a combination of work and lifestyle factors leading to health complications. With limited studies in this area, this systematic review aimed to identify and describe interventions addressing weight reduction in truck drivers. METHODS Five electronic databases were searched, January 2000 to June 2020 (CINAHL, Cochrane Library, Embase, Ovid MEDLINE, Scopus). Inclusion criteria: experimental primary studies, long-distance (≥500 kms) truck drivers, peer reviewed publications in English. Weight loss interventions included physical activity, diet, behavioral therapy, or health promotion/education programs. Exclusions: non-interventional studies, medications or surgical interventions. Two independent researchers completed screening, risk of bias (RoB) and data extraction with discrepancies managed by a third. Study descriptors, intervention details and outcomes were extracted. RESULTS Seven studies (two RCTs, five non-RCTs,) from three countries were included. Six provided either counselling/coaching or motivational interviewing in combination with other components e.g. written resources, online training, provision of exercise equipment. Four studies demonstrated significant effects with a combined approach, however, three had small sample sizes (<29). The effect sizes for 5/7 studies were medium to large size (5/7 studies), indicating likely clinical significance. RoB assessment revealed some concerns (RCTs), and for non-RCTs; one moderate, two serious and two with critical concerns. Based on the small number of RCTs and the biases they contain, the overall level of evidence in this topic is weak. CONCLUSION Interventions that include a combination of coaching and other resources may provide successful weight reduction for truck drivers and holds clinical significance in guiding the development of future interventions in this industry. However, additional trials across varied contexts with larger sample populations are needed.
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Chronic cough is associated with depressive mood in women regardless of smoking status and lung function.
Heo, IR, Kim, JY, Go, SI, Kim, TH, Ju, S, Yoo, JW, Lee, SJ, Cho, YJ, Jeong, YY, Lee, JD, et al
The clinical respiratory journal. 2021;(7):753-760
Abstract
BACKGROUND Chronic cough is a common respiratory symptom, and, if persistent, the patient's quality of life can worsen and result in a depressive mood, or vice versa. Although previous reports suggest a relationship between chronic cough and depression, we further investigated this relationship according to smoking status and lung function. METHODS This observational study used cross-sectional data from the 6th Korean National Health and Nutrition Examination Survey (2014 and 2016). Propensity score matching using age, sex, smoking status, and lung function was performed for participants with and without chronic cough to reduce the confounding effects associated with depressive mood. Questionnaires recorded coughs persisting for >3 months and the Patient Health Questionnaire-9 (PHQ-9) assessed the severity of depressive mood. RESULTS Among 12 494 participants who were >18 years old, 226 with chronic cough were matched with 226 with non-chronic cough. Overall, chronic cough participants showed higher PHQ-9 scores than the non-chronic cough participants (4.29 ± 5.23 vs. 2.63 ± 3.38, P < .001). When stratified by sex, the difference remained significant in women (5.69 ± 5.96 vs. 3.05 ± 3.97, P < .001) but not in men (3.18 ± 4.27 vs. 2.31 ± 3.65, P = .092). When stratified by lung function status, the difference remained significant for those with normal lung function (4.32 ± 5.32 vs. 2.78 ± 3.86, P = .003) and reduced lung function (4.19 ± 4.93 vs. 2.11 ± 3.55, P ≤ 0.001). Multivariate logistic regression analysis revealed that chronic cough was associated with PHQ-9 score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.014-1.27, P = .014), chronic obstructive pulmonary disease (OR, 4.87; 95% CI, 1.041-22.86, P = .044) and physician-diagnosed bronchial asthma (OR, 2.93; 95% CI, 1.162-7.435, P = .023). CONCLUSIONS Depressive mood is significantly correlated with chronic cough in females.
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Association between physical activity and inflammatory markers in community-dwelling, middle-aged adults.
Cho, SMJ, Lee, H, Shim, JS, Jeon, JY, Kim, HC
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(7):828-836
Abstract
Physical activity has been known to deter inflammatory process; yet, the evidence is scarce in healthy, middle-aged population. We assessed the association between physical activity and inflammatory biomarkers, including high sensitivity (hs) C-reactive protein, interleukin (IL)-1α, -1β, and -6, tumor necrosis factor (TNF) -α and -β, and monocyte chemotactic protein (MCP) -1 and -3. Functional and leisure-time physical activity was assessed by the International Physical Activity Questionnaire. Inflammatory biomarkers were measured by multiplex enzyme-linked immunosorbent assay. Compared with highly physically active participants based on total metabolic equivalent of task, the most sedentary group had significantly higher odds ratio and [95% confidence interval] for ≥75th percentile of TNF-α (1.64 [1.10-2.44]), TNF-β (1.50 [1.09-2.07]), IL-1β (2.14 [1.49-3.09]), hsIL-1β (1.72 [1.15-2.58]), IL-6 (1.84 [1.24-1.73]), hsIL-6 (2.05 [1.35-3.12]), and MCP-1 (1.91 [1.28-2.87]) levels. Results for IL-1α and MCP-3 were inconsistent, as the least active group had lower odds for above the median IL-1α (0.65 [0.49-0.95]) and MCP-3 (0.71 [0.54-0.93]) yet higher odds for ≥75th percentile IL-1α (2.36 [1.63-3.42]) and MCP-3 (2.44 [1.63-3.64]) levels. Based on duration of moderate-to-vigorous physical activity, sedentary participants had significantly higher odds for above median (1.40 [1.13-1.73]) and ≥75th percentile (1.33 [1.00-1.77]) IL-1β compared with those fulfilling the guideline recommendation. Subgroup analyses showed minimal sex differences. Routine inflammatory assessment may help to achieve primordial prevention of cardiovascular and metabolic diseases. Novelty: Healthy, middle-aged adults with physically active lifestyle were generally at lower odds for elevated inflammatory status. The associations persisted regardless of sex, age, comorbidities, adiposity, and diet.
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Modifiable Risk Factors for Cardiovascular Disease in Korea and Japan.
Arafa, A, Lee, HH, Eshak, ES, Shirai, K, Liu, K, Li, J, Anni, NS, Shim, SY, Kim, HC, Iso, H
Korean circulation journal. 2021;(8):643-655
Abstract
Cardiovascular disease (CVD) is the leading cause of death and a major contributor to disability worldwide. Since the majority of cardiovascular events are preventable, identification of modifiable CVD risk factors and implementation of primordial prevention strategies should be a public health priority. In this aspect, the American Heart Association declared a strategic goal to reduce total CVD mortality in the US by 20% within 10 years via eliminating 7 major CVD risk factors (hypertension, diabetes, dyslipidemia, cigarette smoking, physical inactivity, obesity, and poor-quality diet) in 2010, and their strategy has been achieving. However, the applicability of similar metrics to prevent CVD among East Asians requires an in-depth investigation of the modifiable CVD risk factors based on national and regional evidence-based findings. Herein, this review article aims to discuss several modifiable risk factors for CVDs, using epidemiological evidence from cohort studies and nationally representative data of 2 East Asian countries: Korea and Japan.
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Clinical Impact of Supplementation of Vitamins B1 and C on Patients with Sepsis-Related Acute Respiratory Distress Syndrome.
Yoo, JW, Kim, RB, Ju, S, Lee, SJ, Cho, YJ, Jeong, YY, Lee, JD, Kim, HC
Tuberculosis and respiratory diseases. 2020;83(3):248-254
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Acute respiratory distress syndrome (ARDS) is a life-threatening condition that commonly develops in patients with sepsis. Patients with ARDS require admission to intensive care and invasive mechanical ventilation. Vitamin B1 and C deficiencies have been reported in critically ill patients with sepsis. Vitamin B1 is involved in aerobic metabolism, and vitamin C has anti-inflammatory and anti-oxidative effects. The aim of this Korean retrospective cohort study was to evaluate the clinical impact of vitamin B1 and C supplementation in patients with sepsis-related ARDS. Patients with ARDS requiring invasive mechanical ventilation, admitted to an intensive care unit (ICU) were included in this study. Clinical outcomes were compared between patients administered with vitamin B1 (200 mg/day) and C (2 g/day) between June 2018-May 2019 (the supplementation group) and those who did not receive vitamin B1 and C administration between June 2017-May 2018 (the control group). Seventy-nine patients were included. Thirty-three patients received vitamin B1 and C, and 46 patients did not. There were no significant differences in the number of deaths between the patients who received vitamin B1 and C and those who did not. The mean number of days not requiring ICU admission or ventilation was greater in patients supplemented with vitamin B1 and C than that in the control patients, but the difference was not statistically significant. Steroid administration was more frequent in patients receiving vitamin B1 and C supplementation than in those without it. The authors concluded that Vitamin B1 and C supplementation at the doses used in this study did not reduce the death rates in ARDS patients.
Abstract
BACKGROUND Although few studies have reported improved clinical outcomes with the administration of vitamin B1 and C in critically ill patients with septic shock or severe pneumonia, its clinical impact on patients with sepsis-related acute respiratory distress syndrome (ARDS) remains unclear. The purpose of this study was to evaluate the association with vitamin B and C supplementation and clinical outcomes in patients with ARDS. METHODS Patients with ARDS requiring invasive mechanical ventilation, admitted to the medical intensive care unit (ICU) were included in this study. Clinical outcomes were compared between patients administered with vitamin B1 (200 mg/day) and C (2 g/day) June 2018-May 2019 (the supplementation group) and those who did not receive vitamin B1 and C administration June 2017-May 2018 (the control group). RESULTS Seventy-nine patients were included. Thirty-three patients received vitamin B1 and C whereas 46 patients did not. Steroid administration was more frequent in patients receiving vitamin B1 and C supplementation than in those without it. There were no significant differences in the mortality between the patients who received vitamin B1 and C and those who did not. There were not significant differences in ventilator and ICU-free days between each of the 21 matched patients. CONCLUSION Vitamin B1 and C supplementation was not associated with reduced mortality rates, and ventilator and ICU-free days in patients with sepsis-related ARDS requiring invasive mechanical ventilation.
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Effect of Smartphone-Based Lifestyle Coaching App on Community-Dwelling Population With Moderate Metabolic Abnormalities: Randomized Controlled Trial.
Cho, SMJ, Lee, JH, Shim, JS, Yeom, H, Lee, SJ, Jeon, YW, Kim, HC
Journal of medical Internet research. 2020;22(10):e17435
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Metabolic disorders are established precursors to cardiovascular disease. The aim of the study was to evaluate the longitudinal effect of smartphone-based health care app on metabolic parameters in a sample of the general population with moderate metabolic abnormalities. The study is a single-blind 3-arm parallel-design randomized controlled trial delivering a 6-month primary prevention program via mobile app. One hundred twenty-nine smartphone users, aged between 30-59 years with at least 2 metabolic abnormalities, have been recruited. Results showed that the simultaneous diet/exercise logging and lifestyle coaching yielded greater body weight reduction, specifically via body fat mass reduction. On the other hand, the systolic blood pressure did not change notably between the 3 groups at any follow-up examinations. Authors conclude that future studies focusing on comparative effectiveness using alternative study designs are needed to integrate these apps in everyday lives and clinic practice.
Abstract
BACKGROUND Metabolic disorders are established precursors to cardiovascular diseases, yet they can be readily prevented with sustained lifestyle modifications. OBJECTIVE We assessed the effectiveness of a smartphone-based weight management app on metabolic parameters in adults at high-risk, yet without physician diagnosis nor pharmacological treatment for metabolic syndrome, in a community setting. METHODS In this 3-arm parallel-group, single-blind, randomized controlled trial, we recruited participants aged 30 to 59 years with at least 2 conditions defined by the Third Report of the National Cholesterol Education Program expert panel (abdominal obesity, high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, and high fasting glucose level). Participants were randomly assigned (1:1:1) by block randomization to either the nonuser group (control), the app-based diet and exercise self-logging group (app only), or the app-based self-logging and personalized coaching from professional dieticians and exercise coordinators group (app with personalized coaching). Assessments were performed at baseline, week 6, week 12, and week 24. The primary outcome was change in systolic blood pressure (between baseline and follow-up assessments). Secondary outcomes were changes in diastolic blood pressure, body weight, body fat mass, waist circumference, homeostatic model of assessment of insulin resistance, triglyceride level, and high-density lipoprotein cholesterol level between baseline and follow-up assessments. Analysis was performed using intention-to-treat. RESULTS Between October 28, 2017 and May 28, 2018, 160 participants participated in the baseline screening examination. Participants (129/160, 80.6%) who satisfied the eligibility criteria were assigned to control (n=41), app only (n=45), or app with personalized coaching (n=43) group. In each group, systolic blood pressure showed decreasing trends from baseline (control: mean -10.95, SD 2.09 mmHg; app only: mean -7.29, SD 1.83 mmHg; app with personalized coaching: mean -7.19, SD 1.66 mmHg), yet without significant difference among the groups (app only: P=.19; app with personalized coaching: P=.16). Instead, those in the app with personalized coaching group had greater body weight reductions (control: mean -0.12, SD 0.30 kg; app only: mean -0.35, SD 0.36 kg, P=.67; app with personalized coaching: mean -0.96, SD 0.37 kg; P=.08), specifically by body fat mass reduction (control: mean -0.13, SD 0.34 kg; app only: mean -0.64, SD 0.38 kg, P=.22; app with personalized coaching: mean -0.79, SD 0.38 kg; P=.08). CONCLUSIONS Simultaneous diet and exercise self-logging and persistent lifestyle modification coaching were ineffective in lowering systolic blood pressure but effective in losing weight and reducing body fat mass. These results warrant future implementation studies of similar models of care on a broader scale in the context of primary prevention. TRIAL REGISTRATION ClinicalTrials.gov NCT03300271; http://clinicaltrials.gov/ct2/show/NCT03300271.
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2018 Guidelines for the Management of Dyslipidemia in Korea.
Rhee, EJ, Kim, HC, Kim, JH, Lee, EY, Kim, BJ, Kim, EM, Song, Y, Lim, JH, Kim, HJ, Choi, S, et al
Journal of lipid and atherosclerosis. 2019;(2):78-131
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Three-dimensional analysis of morphologic changes and visual outcomes in diabetic macular edema.
Lee, H, Kang, KE, Chung, H, Kim, HC
Japanese journal of ophthalmology. 2019;(3):234-242
Abstract
PURPOSE To investigate the association of retinal fluid volume with the visual and anatomic outcomes of patients with diabetic macular edema (DME) after treatment with bevacizumab. STUDY DESIGN Retrospective observational study. METHODS We retrospectively analyzed 65 eyes of 58 DME patients treated with bevacizumab. The volumes of the inner intraretinal fluid (IRF) in the inner nuclear layer (INL), outer IRF in the outer plexiform layer (OPL)/outer nuclear layer (ONL), and subretinal fluid (SRF) were calculated. The correlations between the baseline fluid volumes and best-corrected visual acuity (BCVA), area of disorganization of the retinal inner layers (DRIL), disrupted external limiting membrane (ELM), and disrupted ellipsoid zone (EZ) at 12 months after treatment were assessed. RESULTS The baseline volume of the inner IRF correlated with poor BCVA at the final visit (r = 0.52, P < .001) whereas the baseline volume of the outer IRF and SRF volume did not show a significant correlation with BCVA at the final visit (P = .07 and P = .61, respectively). The improvement in BCVA correlated with the reduction in the baseline volume of the inner IRF and outer IRF (r = 0.25, P = .04 and r = 0.36, P = .003), but not with the SRF volume (P = .59). The baseline volume of the inner IRF correlated positively with the area of DRIL and the disrupted ELM at the final visit (r = 0.56, P < .001 and r = 0.25, P = .04, respectively). Such relationship remained in each quadrant of the macula (P < .005 for all quadrants). CONCLUSION The baseline volume of the inner IRF correlated with a poor visual outcome, an increased DRIL area, and a more disrupted ELM area in patients with DME after treatment with bevacizumab.
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Buffering of cytosolic calcium plays a neuroprotective role by preserving the autophagy-lysosome pathway during MPP+-induced neuronal death.
Jung, S, Chung, Y, Lee, Y, Lee, Y, Cho, JW, Shin, EJ, Kim, HC, Oh, YJ
Cell death discovery. 2019;:130
Abstract
Parkinson's disease (PD) is a chronic neurodegenerative disease with no cure. Calbindin, a Ca2+-buffering protein, has been suggested to have a neuroprotective effect in the brain tissues of PD patients and in experimental models of PD. However, the underlying mechanisms remain elusive. Here, we report that in 1-methyl-4-phenylpyridinium (MPP+)-induced culture models of PD, the buffering of cytosolic Ca2+ by calbindin-D28 overexpression or treatment with a chemical Ca2+ chelator reversed impaired autophagic flux, protecting cells against MPP+-mediated neurotoxicity. When cytosolic Ca2+ overload caused by MPP+ was ameliorated, the MPP+-induced accumulation of autophagosomes decreased and the autophagic flux significantly increased. In addition, the accumulation of damaged mitochondria and p62-positive ubiquitinated protein aggregates, following MPP+ intoxication, was alleviated by cytosolic Ca2+ buffering. We showed that MPP+ treatment suppressed autophagic degradation via raising the lysosomal pH and therefore reducing cytosolic Ca2+ elevation restored the lysosomal pH acidity and normal autophagic flux. These results support the notion that functional lysosomes are required for Ca2+-mediated cell protection against MPP+-mediated neurotoxicity. Thus, our data suggest a novel process in which the modulation of Ca2+ confers neuroprotection via the autophagy-lysosome pathway. This may have implications for the pathogenesis and future therapeutic targets of PD.
