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Insights from the COCOA birth cohort: The origins of childhood allergic diseases and future perspectives.
Lee, E, Lee, SY, Kim, HB, Yang, SI, Yoon, J, Suh, DI, Oh, HY, Ahn, K, Kim, KW, Shin, YH, et al
Allergology international : official journal of the Japanese Society of Allergology. 2024;(1):3-12
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Abstract
The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches-proteomics, transcriptomics, and metabolomics-we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.
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The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis.
Suh, SW, Lim, E, Burm, SY, Lee, H, Bae, JB, Han, JW, Kim, KW
BMC medicine. 2024;(1):109
Abstract
BACKGROUND Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia. METHODS We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals. RESULTS The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low. CONCLUSIONS Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.
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Comments on Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Kim, KW
Gut and liver. 2023;(6):954-955
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Systolic blood pressure, low-density lipoprotein cholesterol levels, and adverse kidney outcome: results from KNOW-CKD.
Kim, KW, Koh, HB, Kim, HW, Park, JT, Yoo, TH, Kang, SW, Oh, KH, Hyun, YY, Jung, JY, Sung, SA, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2023;(6):1395-1406
Abstract
It is unknown whether intensive control of blood pressure (BP) and lipids can delay the progression of chronic kidney disease (CKD). This study examined the combined association of strict targets of systolic BP (SBP) and low-density lipoprotein cholesterol (LDL-C) levels with adverse kidney outcomes. In total, 2012 patients from the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD) were classified into four groups according to SBP of 120 mmHg and LDL-C of 70 mg/dl: group 1, <120 and <70; group 2, <120 and ≥70; group 3, ≥120 and <70; group 4, ≥120 and ≥70. We constructed time-varying models treating two variables as time-varying exposures. The primary outcome was the progression of CKD, defined as a ≥50% decrease in estimated glomerular filtration rate from the baseline or the onset of kidney failure requiring replacement therapy. The primary outcome events occurred in 27.9%, 26.7%, 40.3%, and 39.1% from groups 1 to 4. In the time-varying model, the hazard ratios (95% confidence intervals) for the primary outcome were 0.48 (0.33-0.69), 0.78 (0.63-0.96), and 0.96 (0.74-1.23) for groups 1 to 3, respectively, compared with group 4. When less stringent cut-offs of SBP of 130 mmHg and LDL-C of 100 mg/dl were used, this graded association was lost, while only SBP was associated with adverse kidney outcomes. In this study, the lower targets of SBP of <120 mmHg and LDL-C < 70 mg/dl were synergistically associated with a lower risk of adverse kidney outcomes.
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Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer: The Phase 2b NIFTY Randomized Clinical Trial.
Hyung, J, Kim, I, Kim, KP, Ryoo, BY, Jeong, JH, Kang, MJ, Cheon, J, Kang, BW, Ryu, H, Lee, JS, et al
JAMA oncology. 2023;(5):692-699
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Abstract
IMPORTANCE The NIFTY trial demonstrated the benefit of treatment with second-line liposomal irinotecan (nal-IRI) plus fluorouracil (FU) and leucovorin (LV) for patients with advanced biliary tract cancer (BTC). OBJECTIVE To report the updated efficacy outcomes from the NIFTY trial with extended follow-up of 1.3 years with reperformed masked independent central review (MICR) with 3 newly invited radiologists. DESIGN, SETTING, AND PARTICIPANTS The NIFTY trial was a randomized, multicenter, open-label, phase 2b clinical trial conducted between September 5, 2018, and December 31, 2021, at 5 tertiary referral centers in South Korea. Patients with advanced BTC whose disease progressed while receiving first-line gemcitabine plus cisplatin with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1, were eligible. Data analysis was completed on May 9, 2022. INTERVENTIONS Patients were randomized 1:1 to receive LV, 400 mg/m2, bolus and FU, 2400 mg/m2, for a 46-hour infusion intravenously every 2 weeks with or without nal-IRI, 70 mg/m2, before LV intravenously. Patients were treated until disease progression or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES Primary end point was progression-free survival (PFS) as assessed by MICR. Secondary end points were PFS as assessed by the investigator, overall survival, and objective response rate. RESULTS A total of 178 patients (75 women [42.1%]; median [IQR] age, 64 [38-84] years) were randomly assigned, and 174 patients were included in the full analysis set (88 patients [50.6%] in the nal-IRI plus FU/LV group vs 86 patients [49.4%] in the FU/LV alone group). In this updated analysis, the median MICR-assessed PFS was 4.2 months (95% CI, 2.8-5.3) for the nal-IRI plus FU/LV group and 1.7 months (95% CI, 1.4-2.6) for the FU/LV alone group (hazard ratio, 0.61; 95% CI, 0.44-0.86; P = .004), in contrast to the 7.1 and 1.4 months reported in the previous study, respectively. The discordance rate for tumor progression date between the MICR and investigators was 17.8% (vs 30% in the previous study). CONCLUSIONS AND RELEVANCE The NIFTY randomized clinical trial demonstrated significant improvement in PFS with treatment with nal-IRI plus FU/LV compared with FU/LV alone for patients with advanced BTC after progression to gemcitabine plus cisplatin. The combination of nal-IRI plus FU/LV could be considered as a second-line treatment option for patients with previously treated advanced BTC. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT03524508.
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Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.
Mahalingam, G, Samtani, S, Lam, BCP, Lipnicki, DM, Lima-Costa, MF, Blay, SL, Castro-Costa, E, Shifu, X, Guerchet, M, Preux, PM, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023;(11):5114-5128
Abstract
INTRODUCTION Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS We used individual participant data (N = 39271, Mage = 70.67 (40-102), 58.86% female, Meducation = 8.43 years, Mfollow-up = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.
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Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal epithelial cells.
Nguyen, HP, Shin, S, Shin, KJ, Tran, PH, Park, H, De Tran, Q, No, MH, Sun, JS, Kim, KW, Kwak, HB, et al
Biochimica et biophysica acta. Molecular cell research. 2023;(1):119384
Abstract
Adverse effects of spaceflight on the human body are attritubuted to microgravity and space radiation. One of the most sensitive organs affected by them is the eye, particularly the retina. The conditions that astronauts suffer, such as visual acuity, is collectively called a spaceflight-associated neuro-ocular syndrome (SANS); however, the underlying molecular mechanism of the microgravity-induced ocular pathogenesis is not clearly understood. The current study explored how microgravity affects the retina function in ARPE19 cells in vitro under time-averaged simulated microgravity (μG) generated by clinostat. We found multicellular spheroid (MCS) formation and a significantly decreased cell migration potency under μG conditions compared to 1G in ARPE19 cells. We also observed that μG increases intracellular reactive oxygen species (ROS) and causes mitochondrial dysfunction in ARPE19 cells. Subsequently, we showed that μG activates autophagic pathways and ciliogenesis. Furthermore, we demonstrated that mitophagy activation is triggered via the mTOR-ULK1-BNIP3 signaling axis. Finally, we validated the effectiveness of TPP-Niacin in mitigating μG-induced oxidative stress and mitochondrial dysfunction in vitro, which provides the first experimental evidence for TPP-Niacin as a potential therapeutic agent to ameliorate the cellular phenotypes caused by μG in ARPE19 cells. Further investigations are, however, required to determine its physiological functions and biological efficacies in primary human retinal cells, in vivo models, and target identification.
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Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.
Lennon, MJ, Lam, BCP, Lipnicki, DM, Crawford, JD, Peters, R, Schutte, AE, Brodaty, H, Thalamuthu, A, Rydberg-Sterner, T, Najar, J, et al
JAMA network open. 2023;(9):e2333353
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IMPORTANCE The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. OBJECTIVES To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. DATA SOURCE AND STUDY SELECTION Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). DATA EXTRACTION AND SYNTHESIS Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. MAIN OUTCOMES AND MEASURES The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. RESULTS The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. CONCLUSIONS AND RELEVANCE This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.
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Associations between social connections and cognition: a global collaborative individual participant data meta-analysis.
Samtani, S, Mahalingam, G, Lam, BCP, Lipnicki, DM, Lima-Costa, MF, Blay, SL, Castro-Costa, E, Shifu, X, Guerchet, M, Preux, PM, et al
The lancet. Healthy longevity. 2022;(11):e740-e753
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BACKGROUND Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. METHODS We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. FINDINGS Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=37·54-72·19%), suggesting robust results across studies. INTERPRETATION Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline. FUNDING EU Joint Programme-Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health.
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Lifestyle interventions after colorectal cancer surgery using a mobile digital device: A study protocol for a randomized controlled trial.
Kim, YI, Park, IJ, Kim, CW, Yoon, YS, Lim, SB, Yu, CS, Kim, JC, Lee, Y, Kim, H, Chung, S, et al
Medicine. 2022;(41):e31264
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BACKGROUND In treating colorectal cancer, surgical techniques and adjuvant treatments have advanced over the past century, but relatively less attention has been given to improve health-related quality of life (HRQOL). Recent studies report a significant association between cancer recurrence and patient lifestyle after surgery, hence emphasizing the need to assist patients to reduce this risk through appropriate lifestyle choices. The proposed study will evaluate the effects of digital interventions on lifestyle after surgery for colorectal cancer using mobile applications. METHODS A randomized controlled trial design was proposed. A total of 320 patients diagnosed with colorectal cancer aged between 20 and 70 years were to be enrolled and randomized in equal numbers into 4 groups (3 groups assigned to different mobile applications and a control group). Surveys that evaluate HRQOL, physical measurements, and metabolic parameters (fasting glucose, hemoglobin A1C, triglyceride, high-density lipoprotein cholesterol), and fat/muscle mass measurements by abdominal computed tomography (CT), will be conducted prior to surgery and every 6 months post-surgery for 18 months. Statistical analysis will be used to compare the outcomes between groups. DISCUSSION Results from this study could provide evidence that easily accessible mobile applications can influence patient lifestyles. Results showing minimal effects of such applications could also be constructive for improving healthcare-related applications.