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Effects of Phytoncide Fragrance on Resting-State Brain Activity in Mild Cognitive Impairment: A Randomized Double-Blind Controlled Study.
Kim, J, Park, S, Kim, H, Roh, D, Kim, DH
Journal of integrative and complementary medicine. 2024
Abstract
Introduction: The therapeutic potential of phytoncide fragrances may be optimal for patients with mild cognitive impairment (MCI) that display complex symptomatology. This study aimed to explore the clinical value of phytoncide by evaluating its electrophysiological effects in patients with MCI. Materials and Methods: This was a double-blind, randomized controlled trial. A total of 24 community-dwelling patients were randomly assigned to either a phytoncide or no-odor group. Participants wore a dental mask, for 30 min at rest that had either the fragrance stimulus or water added to it. The quantitative electroencephalography (EEG) during the resting state was recorded before and after a single intervention. Results: There were significant interaction effects in absolute EEG-power values in the occipital (F = 6.52, p = 0.018) and parietal (F = 5.41, p = 0.030) left hemisphere at β frequency. Phytoncide odor significantly decreased low and high β activity in the occipital (corrected p = 0.009) and parietal (corrected p = 0.047) left hemisphere, respectively. In source localization, phytoncide odor significantly decreased deep source activation in the left inferior and middle frontal gyri at β 2 frequency band compared with the no-odor group (threshold = 4.25, p < 0.05). Conclusions: Reductions in β, indicative of anxiety, depression, and stress, suggest relief from emotion-related symptoms that are common in patients with MCI. Trial Registration: Clinical Trials Registry Korea (registration: KCT0007317).
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Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.
Chung, MK, Kim, DH, Park, JI, Lee, S, Park, HC, Kim, K, Kang, YS, Ko, K, Kim, J, Koo, H, et al
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2024;(1):47-57
Abstract
OBJECTIVE This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS Meal intervention statistically significantly stabilized serum phosphorus level (β = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.
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Frailty as an Effect Modifier in Randomized Controlled Trials: A Systematic Review.
Yao, A, Gao, L, Zhang, J, Cheng, JM, Kim, DH
Journal of general internal medicine. 2024
Abstract
BACKGROUND The effect of clinical interventions may vary by patients' frailty status. Understanding treatment effect heterogeneity by frailty could lead to frailty-guided treatment strategies and reduce overtreatment and undertreatment. This systematic review aimed to examine the effect modification by frailty in randomized controlled trials (RCTs) that evaluate pharmacological, non-pharmacological, and multicomponent interventions. METHODS We searched PubMed, Web of Science, EMBASE, and ClinicalTrial.gov, from their inception to 8 December 2023. Two reviewers independently extracted trial data and examined the study quality with senior authors. RESULTS Sixty-one RCTs that evaluated the interaction between frailty and treatment effects in older adults were included. Frailty was evaluated using different tools such as the deficit accumulation frailty index, frailty phenotype, and other methods. The effect of several pharmacological interventions (e.g., edoxaban, sacubitril/valsartan, prasugrel, and chemotherapy) varied according to the degree of frailty, whereas other treatments (e.g., antihypertensives, vaccinations, osteoporosis medications, and androgen medications) demonstrated consistent benefits across different frailty levels. Some non-pharmacological interventions had greater benefits in patients with higher (e.g., chair yoga, functional walking, physical rehabilitation, and higher dose exercise program) or lower (e.g., intensive lifestyle intervention, psychosocial intervention) levels of frailty, while others (e.g., resistance-type exercise training, moderate-intensive physical activity, walking and nutrition or walking) produced similar intervention effects. Specific combined interventions (e.g., hospital-based disease management programs) demonstrated inconsistent effects across different frailty levels. DISCUSSION The efficacy of clinical interventions often varied by frailty levels, suggesting that frailty is an important factor to consider in recommending clinical interventions in older adults. REGISTRATION PROSPERO registration number CRD42021283051.
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Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.
Kim, JY, Kim, J, Park, SJ, Park, KM, Kim, JS, Kim, SH, Shim, J, Choi, EK, Kim, DH, Oh, IY, et al
Journal of Korean medical science. 2024;(8):e72
Abstract
BACKGROUND In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04096547.
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Protocol of BEYOND trial: Clinical BEnefit of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in rhYthm cONtrol of atrial fibrillation in patients with diabetes mellitus.
Lee, K, Lee, SK, Lee, J, Jeon, BK, Kim, TH, Yu, HT, Lee, JM, Park, JK, Baek, YS, Kim, DH, et al
PloS one. 2023;(1):e0280359
Abstract
SGLT-2 inhibitor, traditionally used for glycemic control, has several beneficial effects that can help manage heart failure (HF). SGLT-2 inhibitors reduce the risk of cardiovascular mortality in patients with HF. As atrial fibrillation (AF) is closely associated with HF and diabetes mellitus (DM) is a risk factor for AF, we assume that SGLT-2 inhibitors will also show therapeutic benefits regarding AF, especially for rhythm control. This trial has a multicenter, prospective, open, blinded endpoint design. It is a 1:1 randomized and controlled study. A total of 716 patients who are newly diagnosed of AF and DM within 1 year will be enrolled from 7 tertiary medical centers. The trial is designed to compare the effects of SGLT-2 inhibitors and other oral hypoglycemic agents on atrial rhythm control in patients with AF and DM. The primary outcome is the recurrence of AF within a year (including post-antiarrhythmic drugs (AAD) or ablation). The secondary outcomes are the ablation rate within a year, change in AF burden, size of the left atrium, NT-proBNP, the AF symptom score, and the quality of life. This trial will prospectively evaluate the effect and safety of SGLT-2 inhibitors on AF rhythm control in patients with DM. It will provide an invaluable dataset on rhythm control in AF with DM for future studies and offer novel information to assist in clinical decisions. (BEYOND trial, ClinicalTrials.gov number: NCT05029115. https://clinicaltrials.gov/ct2/show/NCT05029115).
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.
Fernandez-Rozadilla, C, Timofeeva, M, Chen, Z, Law, P, Thomas, M, Schmit, S, Díez-Obrero, V, Hsu, L, Fernandez-Tajes, J, Palles, C, et al
Nature genetics. 2023;(1):89-99
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Abstract
Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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Disruption of IL-18 signaling via engineered IL-18BP biologics alleviates experimental cholestatic liver disease.
Kim, DH, Lee, KJ, Park, J, Chi, S, Han, J, Bang, Y, Kim, SM, Kang, SG, Cha, SH, Han, YH
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;:115587
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis around intrahepatic and extrahepatic bile ducts leading to severe hepatic cirrhosis and high mortality. Although there is an urgent clinical unmet need for PSC, no effective medical therapy has been developed to delay the disease progression until today. IL-18 binding protein (IL-18BP) is well-known to be a natural negative feedback regulator for IL-18, and we have developed a recombinant long-acting IL-18BP referred to as APB-R3 as a therapeutic agent to treat IL-18-related inflammatory diseases. Here, we aimed to study whether disrupted IL-18 signaling by APB-R3 treatment can inhibit PSC injuries in the experimental DDC diet-induced PSC rodent model. First, we found that the amounts of free IL-18 are augmented under PSC condition with increased expression of biliary IL-18 receptors. Administration of APB-R3 effectively attenuated key diagnostic parameters of PSC such as plasma ALP and GGT levels as well as bile acids levels. We also observed that blockade of IL-18 suppressed ductular reactive and proliferative phenotypes of cholangiocytes. Additionally, APB-R3 significantly ameliorated DDC diet-induced periductal fibrosis and transcriptional expressions of pro-fibrotic marker genes. Enhanced senescence associated secretory phenotype (SASP) markers in cholestatic liver disease were diminished by APB-R3 treatment. Our findings clearly demonstrate that the administration of IL-18BP biologics, APB-R3, effectively alleviates DDC diet-induced biliary injuries in rodent PSC model, implying APB-R3 can be a promising therapeutic reagent which warrants clinical human trials as new therapeutic options.
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Interaction of drugs with gut microbiota modulators.
Kim, DH
Drug metabolism reviews. 2023;(3):181-194
Abstract
Orally administered drugs undergo four stages of absorption, distribution, metabolism, and excretion in the body. However, before being absorbed into the body, orally administered drugs contact with gut microbiota, which catalyze their metabolic reactions such as reduction, hydroxylation (including deconjugation), dehydrogenation, acetylation, etc. Although these metabolic reactions typically inactivate drugs (ranitidine, digoxin, and amlodipine), some activate them (sulfasalazine). The composition and quantity of gut microbiota are variable across individuals and fluctuated by gut microbiota modulators such as diets, drugs (antibiotics), probiotics, prebiotics, pathogen infections, and stressors. Gut microbiota-involved metabolisms of drugs in the gastrointestinal tract are dependent on the composition and quantity of gut microbiota. Therefore, the bioavailability of orally administered drugs is significantly affected by gut microbiota modulators. This review describes gut microbiota modulator-drug interactions.
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Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.
Lee, SA, Hong, SJ, Sung, JH, Kim, KS, Kim, SH, Cho, JM, Chun, SW, Lee, SR, Kim, CS, Kim, TN, et al
Medicine. 2023;(47):e36122
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Abstract
BACKGROUND We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.
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Current Research on the Influence of Statin Treatment on Rotator Cuff Healing.
Yoon, JP, Park, SJ, Kim, DH, Shim, BJ, Chung, SW
Clinics in orthopedic surgery. 2023;(6):873-879
Abstract
Rotator cuff tears are a condition characterized by damage to the muscles and tendons that connect the scapula and humerus, which are responsible for shoulder rotation and arm lifting. Metabolic factors such as diabetes, thyroid disease, high cholesterol, vitamin D deficiency, obesity, and smoking have been associated with an increased risk of rotator cuff tears. Interestingly, patients with hyperlipidemia, a condition characterized by high levels of cholesterol and other fats in the blood, have been found to have a higher incidence of rotator cuff tears and breakdown of tendon matrix. As a result, statin therapy, which is commonly used to lower cholesterol levels in hyperlipidemia, has been explored as a potential treatment to improve clinical outcomes in rotator cuff tears. However, the results of preclinical and clinical studies on the effects of statins on tendon healing in rotator cuff tears are limited and not well-defined. Moreover, since hyperlipidemia and rotator cuff tears are more prevalent in older individuals, a literature review on the efficacy and safety of statin therapy in this population is needed.