Gachon University Gil Medical Center

BackgroundDespite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited.MethodsIn this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years. Safety was also assessed.ResultsOf 3048 patients who underwent randomization, 1526 were assigned to the intensive-targeting group and 1522 to the conventional-targeting group. The median follow-up was 3.0 years. The median LDL cholesterol level during the trial was 56 mg per deciliter (1.4 mmol per liter) in the intensive-targeting group and 66 mg per deciliter (1.7 mmol per liter) in the conventional-targeting group. A primary end-point event occurred in 100 patients (Kaplan–Meier estimate of cumulative incidence, 6.6%) in the intensive-targeting group and in 147 patients (Kaplan–Meier estimate of cumulative incidence, 9.7%) in the conventional-targeting group (hazard ratio, 0.67; 95% confidence interval, 0.52 to 0.86; P=0.002). The incidence of prespecified safety end points was similar in the two trial groups, except for a lower incidence of creatinine elevation in the intensive-targeting group.ConclusionsAmong patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter. (Funded by the Cardiovascular Research Center and Yuhan; Ez-PAVE ClinicalTrials.gov number, NCT04626973.)

Interferon regulatory factor 3 (IRF3) is classically recognized for antiviral immunity, yet emerging evidence implicates it in sterile inflammation. This study investigated whether IRF3 regulates macrophage-stromal signaling driving corneal pathology and evaluated the therapeutic potential of targeting IRF3. In vitro assays utilized human macrophages stimulated with lipopolysaccharide (LPS) and interferon-γ (IFNγ) to generate an inflammatory macrophage population (Mϕ-LPS/IFNγ cells), along with primary human corneal stromal fibroblasts (HCFs) stimulated with LPS. IRF3 was silenced by small interfering RNA (siRNA), and inflammatory mediators and toll-like receptor 4 (TLR4)/MyD88 transcripts were quantified. Macrophage-HCF interactions were assessed in Transwell cocultures. In vivo, Irf3-/- and wild-type mice underwent corneal epithelial debridement followed by topical LPS to evaluate corneal opacity, fibrotic markers, cytokine expression, and myeloid-cell subsets. Piceatannol, a stilbenoid compound known to inhibit IRF3, was tested in vitro and as topical eye drops. IRF3 expression was upregulated in both macrophages and HCFs under inflammatory conditions. Silencing IRF3 significantly reduced inflammatory cytokines, including CXCL10, and decreased TLR4-associated transcripts in HCFs. In cocultures, IRF3-silenced macrophages partially attenuated HCF activation. In vivo, Irf3 deficiency markedly reduced LPS-induced corneal opacity, stromal inflammatory transcripts, monocyte recruitment, and macrophage-associated markers. Piceatannol suppressed IRF3-dependent inflammatory responses in vitro and, when applied topically, reduced corneal Irf3 expression and myeloid/inflammatory signatures. IRF3 is a pivotal regulator of innate immune-driven stromal inflammation and opacity. Both genetic and pharmacologic inhibition of IRF3 attenuated cytokine and myeloid responses, suggesting that targeting IRF3, potentially via piceatannol (PIC), offers a therapeutic strategy for preserving corneal transparency.

The relationship between body mass index (BMI) and cardiovascular outcomes in chronic kidney disease (CKD) remains controversial. While the obesity paradox has been observed in this population, the impact of longitudinal BMI patterns over time is not well established. In this study, we investigated the association between BMI trajectories and the risk of cardiovascular events (CVEs) using data from 1061 patients enrolled in the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). BMI was categorized as high (≥ 23 kg/m2) or low (< 23 kg/m2), and assessed at three time points over a 7-year period. We applied targeted maximum likelihood estimation (TMLE) and marginal structural models (MSMs) to adjust for time-varying covariates, including estimated glomerular filtration rate, blood pressure, hemoglobin, albumin, and C-reactive protein, as well as baseline demographic and clinical characteristics. Patients with persistently high BMI had a significantly reduced risk of CVEs (relative risk 0.279; 95% CI 0.143–0.546; P < 0.001) compared to those with consistently low BMI. Transient increases or decreases in BMI did not show the same benefit. Our findings suggest that sustained high BMI may be protective against cardiovascular events in patients with CKD, challenging current weight management recommendations and supporting individualized approaches based on long-term risk profiles.

Background: In cancer surgery, resection of the primary tumor and regional lymph nodes (LNs) is critical. Adequate LN examination is essential to detect metastasis, which determines the cancer stage. Fluorescence emission allows for visual differentiation and rapid monitoring of LNs. Methods: Cancer tissue is stained with a fluorescent dye (indocyanine green, ICG) to identify LNs. Fluorescence is induced from the stained LNs using LED light, and a photosensor coupled with a speaker detects the fluorescence signal and triggers an audible alarm. Filters are applied to prevent false alarms. Results: Upon LN detection, an alarm is emitted from the speaker, and the results are recorded using the LED and a digital multimeter (DMM). In clinical trials, ICG is injected to induce LN fluorescence staining, followed by LED irradiation to induce the fluorescent wavelength and verify LN imaging. Discussion: In clinical trials, ICG stains both LNs and blood vessels, which may lead to false positives. To address this limitation, artificial intelligence algorithms can be trained to specifically identify LNs. Conclusions: Detection of fluorescence wavelengths via photosensors allows for rapid identification of LNs, confirmed through an audible alarm, thereby reducing surgical time. This method shows potential for broad application in cancer surgery.

Atopic dermatitis (AD), allergic rhinitis (AR), and asthma are typical allergic diseases, with a common pathogenesis involving increased type 2 immunity. Despite numerous studies, the association between these diseases and metabolic syndrome (MetS) remains controversial. This study aimed to explore relationships between AD, AR, and asthma both to MetS and to each of its components. Population-based, cross-sectional data were obtained from the Korean National Health and Nutrition Examination Survey from 2019 to 2020. Multiple logistic regression analyses were conducted to evaluate the association between allergic diseases and MetS. The results were compared with those of previous studies of the association between MetS and allergic diseases, identified in a literature review following a search of PubMed and the Cochrane Library. Based on assessments of 1,329, 4,824, and 1,172 patients with AD, AR, and asthma, respectively, negative associations between both AD and AR and MetS were determined, after adjusting for confounding factors. By contrast, asthma was positively associated with MetS (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.50-0.67; OR 0.73, 95% CI 0.67-0.78; OR 1.70, 95% CI 1.51-1.92, respectively). The heterogeneous findings highlight the need for further investigation of associations between the studied allergic diseases and MetS as well as each of its components.

Maternal smoking during pregnancy is associated with adverse outcomes, but its relationship with childhood seizures remains unclear. Previous studies have produced inconsistent findings regarding the link between maternal smoking during pregnancy and seizure risk in offspring. We aim to investigate the association between maternal smoking during pregnancy and seizures in offspring through systematic review and meta-analysis. We conducted a search across multiple electronic databases such as PubMed, Embase, ScienceDirect, Scopus, and Web of Science. The search was performed on May 12, 2025. Papers reporting seizure frequency according to maternal smoking or odds ratios for seizure in offspring were selected. Dose-response analysis was performed based on restricted cubic spline analysis between the number of cigarettes per day and the effect estimate. The meta-analysis was performed using Review Manager version 5.4.1, and the dose-response analysis was conducted using STATA version 13 software. Among the 1,128 articles initially identified, 14 studies involving 12,887,398 subjects were included. Offspring exposed to maternal smoking during pregnancy exhibited an increased association with seizures (odds ratio 1.49, 95% confidence interval 1.21–1.84) compared to those whose mothers did not smoke during pregnancy. Subgroup analysis revealed a significantly heightened association in febrile convulsion, epilepsy, and neonatal seizure. Dose-response analysis shows a linear increase in childhood epilepsy with maternal smoking, where each additional daily cigarette raises the odds ratio by 1.7%. Our study establishes a significant association between maternal smoking during pregnancy and seizures in offspring. These findings highlight the importance of public health efforts to reduce maternal smoking and highlight the potential impact on childhood health outcomes. CRD42023416464

BackgroundAntipsychotics are frequently prescribed off-label to manage behavioral and psychological symptoms of dementia but pose safety risks in older adults, including a 1.5–2.0-fold increased risk of mortality. The coronavirus disease (COVID-19) pandemic disrupted dementia care, increasing reliance on pharmacologic treatments.ObjectiveThis study aimed to evaluate whether the COVID-19 pandemic was associated with changes in the prevalence of antipsychotic prescribing among patients with dementia.MethodsUsing the Korean National Health Insurance Database, this study analyzed a random 50% sample of eligible individuals aged ≥60 years diagnosed with dementia between 2016 and 2021 (n = 876,158; 9.8 million person-observations). Outcomes included the likelihood, duration, and number of antipsychotic prescriptions issued, characterizing pharmacologic management of dementia. Interrupted time series analysis assessed associations between the pandemic and relative changes in these outcomes, adjusting for demographic factors, comorbid burden, and seasonality.ResultsAfter the pandemic onset, there were relative slope increases per quarter of 1.5%, 3.2%, and 0.4% in the likelihood, duration, and number of prescriptions, respectively (all p < 0.001; pre-pandemic levels: 0.172 patients prescribed, 12.97 days, and 18.10 prescriptions per person-quarter). Antipsychotic prescriptions decreased by 1.6% (p < 0.001) during the first quarter after the outbreak but subsequently showed a progressive increase, reflecting prolonged care disruption after initial access barriers.ConclusionsThe COVID-19 pandemic was associated with increased antipsychotic prescribing among patients with dementia. To mitigate similar effects in future public health crises, governments and healthcare providers should strengthen mental health support, non-pharmacological interventions, telehealth continuity, and tailored prescribing guidelines.