Chung-Ang University Hospital

Potassium-competitive acid blockers (P-CABs) are newly introduced gastrointestinal protectants, but their interaction with clopidogrel remains uncharacterized. Proton pump inhibitors (PPIs) are often coprescribed with clopidogrel, despite potential pharmacodynamic interactions. This study evaluated the effectiveness and safety of P-CAB and PPI coadministered with clopidogrel in patients with ischemic stroke. This population-based, longitudinal, retrospective cohort study used the Korean National Health Insurance Service database, covering 51.4 million individuals (≈97% of the Korean population) from 2016 to 2022. Patients with incident ischemic stroke were identified using predefined criteria. Propensity score matching compared the 6-month incidence of major adverse cardiovascular events (including myocardial infarction, stroke recurrence, and all-cause mortality) and gastrointestinal bleeding among 3 cohorts: clopidogrel alone, clopidogrel+P-CAB, and clopidogrel+PPI. Between 2017 and 2021, 40 752 of 65 180 patients with incident stroke (62.5%) received clopidogrel. A total of 6680 patients (16.4%) formed the clopidogrel-alone cohort, 578 (1.4%) the clopidogrel+P-CAB cohort, and 8806 (21.6%) the clopidogrel+PPI cohort. During the follow-up period, stroke recurred in 268 patients (4.0%) receiving clopidogrel alone, 26 patients (4.5%) receiving clopidogrel+P-CAB, and 431 patients (4.9%) receiving clopidogrel+PPI. After propensity score matching, the clopidogrel+P-CAB cohort showed a higher risk of major adverse cardiovascular events (hazard ratio [HR], 2.40 [95% CI, 1.18-4.85]) and stroke recurrence (HR, 2.64 [95% CI, 1.27-5.47]) than the clopidogrel-alone cohort. The clopidogrel+PPI cohort also had an increased risk of major adverse cardiovascular events (HR, 1.38 [95% CI, 1.17-1.63]) and stroke recurrence (HR, 1.41 [95% CI, 1.20-1.67]) relative to clopidogrel alone. Among PPIs, esomeprazole was associated with a higher risk of major adverse cardiovascular events (HR, 1.46 [95% CI, 1.10-1.92]) and stroke recurrence (HR, 1.50 [95% CI, 1.13-2.00]). Gastrointestinal bleeding did not differ significantly among the clopidogrel-alone, clopidogrel+P-CAB, and clopidogrel+PPI cohorts. Concomitant use of P-CABs or PPIs with clopidogrel was associated with an increased risk of ischemic events in patients with stroke. P-CABs or PPIs should, therefore, be prescribed cautiously for patients with stroke treated with clopidogrel.

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.

Postoperative pain management after lumbar spine surgery often involves modest to high doses of opioids, which can contribute to the risk of dependence. Epidural analgesia has emerged as a promising opioid-sparing alternative, but its efficacy compared with conventional opioid-based intravenous patient-controlled analgesia (IV-PCA) in a randomized trial has not been established in these patients. We asked whether an opioid-sparing protocol, compared with conventional opioid-based IV-PCA, (1) provides superior pain control, (2) reduces opioid consumption, and (3) lowers the frequency of opioid-related adverse events. In this multicenter, randomized, double-blind, parallel-group trial, we enrolled 98 patients undergoing single-level lumbar fusion or decompression. Eligible participants were adults age 20 to 80 years diagnosed with lumbar spinal stenosis or spondylolisthesis. Exclusion criteria included history of prior lumbar surgery, coagulation disorders, or opioid dependence. Patients were randomized to either the epidural opioid-free IV-PCA group (intraoperative single-shot epidural ropivacaine injection with opioid-free IV-PCA; epidural group) or the conventional opioid-based IV-PCA group (fentanyl-based IV-PCA; control group). In the epidural opioid-free group, fentanyl was administered solely as a rescue analgesic for breakthrough pain. All patients and outcome assessors were blinded to group allocation. In the fusion arm, 25 patients were randomized to the epidural group and 25 to the control group; data from all randomized patients (n = 25 in each group) were fully analyzed. In the decompression arm, 24 were randomized to the epidural group and 24 to the control group; data from all randomized patients (n = 24 in each group) were fully analyzed. Three patients (one in the fusion arm and two in the decompression arm) discontinued the intervention because of severe postoperative nausea and vomiting but were included in the final analysis based on the intention-to-treat principle, preventing differential loss to follow-up bias. There were no important differences between treatment and control groups in terms of baseline demographic or clinical data in either study arm. The minimum clinically important difference (MCID) for the numeric rating scale (NRS) pain score was defined as 2 points. The sample size was calculated to detect a 15% reduction in NRS scores (0.9 points), ensuring sensitivity to differences smaller than the MCID of 2 points. Secondary outcomes included total fentanyl consumption, rescue analgesic demand, and opioid-related adverse events. There were no clinically important differences between the epidural and control groups in either the decompression or the fusion arms of the study in terms of NRS pain scores at any time point (the largest difference was seen at 24 hours in the fusion group, but it was not clinically important: mean ± SD 2.7 ± 1.5 versus 4.4 ± 1.5 points of 10 total, mean difference -1.8 points [95% confidence interval (CI) -2.6 to -0.9]; p = 0.04). However, despite no important differences in pain control, fentanyl consumption was lower in the epidural groups than the control groups of both the fusion arm (122 ± 140 versus 1467 ± 481 µg, mean difference -1345 µg [95% CI -1550 to -1140]; p < 0.001) and the decompression arm (41 ± 51 versus 1046 ± 451 µg, mean difference -1005 µg [95% CI -1196 to -813]; p < 0.001). In the fusion arm of the study, postoperative urinary retention was less common in the epidural group (4% [1 of 25] versus 32% [8 of 25], relative risk 0.13 [95% CI 0.02 to 0.93]; p = 0.02); there were no differences in complications between the epidural and control groups in the decompression arm of the study. A single epidural ropivacaine injection with opioid-free IV-PCA provided effective pain control, reduced opioid consumption, and decreased urinary retention risk after single-level lumbar spine surgery. This protocol is a viable and effective opioid-sparing strategy. Level I, therapeutic study.

ObjectiveTo evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines.Materials and MethodsThis multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022.ResultsA total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018.ConclusionThe revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Lip augmentation is a common cosmetic procedure that requires an objective and validated scale to assess treatment outcomes. Existing lip fullness scales may not be universally applicable across ethnic groups. This study aimed to develop and validate the Humedix Lip Fullness Scale and assess its agreement with the Allergan Lip Fullness Scale. A total of 53 females were photographed under standardized conditions. Five dermatologists independently evaluated lip fullness using the Humedix scale and analyzed intra- and inter-rater reliability using Cohen's and Fleiss' Kappa, respectively. The same evaluators reassessed the images using the Allergan scale after 6 months, and agreement between the scales was analyzed using Cohen's Kappa. Intra-rater reliability was perfect (Cohen's Kappa = 1.0000), and inter-rater reliability was high (0.9682, 95% confidence interval: 0.9377-0.9987). Agreement between the Humedix and Allergan scales was strong (Cohen's Kappa = 0.8456, weighted Kappa = 0.9056). The Humedix Lip Fullness Scale demonstrated excellent reliability and strong agreement with the Allergan scale, validating its use as an objective tool for assessing lip volume.

<title>Abstract</title> Background Failure to anticipate difficult direct laryngoscopy (DDL) leads to catastrophic airway events. While Western algorithms exist, evidence from Southeast Asia—particularly in settings with high volumes of head-and-neck pathology—is limited. We investigated DDL prevalence and validated a simplified cumulative risk score in a Cambodian tertiary center. Methods We conducted a retrospective cohort study of 3,080 adults undergoing elective surgery with planned Macintosh laryngoscopy (January–June 2023) at Preah Ang Duong Hospital, Phnom Penh. DDL was defined as Cormack–Lehane grade III/IV or ≥ 3 attempts. Seven bedside predictors were analyzed using multivariable logistic regression. A composite risk score (range 0–3) was derived from the strongest independent predictors. Results DDL prevalence was 9.0% (278/3,080), rising to 13.5% in maxillofacial and 11.3% in ENT procedures ¹ . Independent predictors included Mallampati class III–IV (Adjusted Odds Ratio [AOR] 4.14), limited neck mobility (AOR 2.18), Thyromental Distance (TMD) ≤ 6.5 cm (AOR 1.95), and obesity (BMI ≥ 27.5 kg/m²; AOR 1.86) ² . The Upper Lip Bite Test was not predictive (p = 0.21) ³ . A simplified composite score (Mallampati + BMI + TMD) demonstrated superior discrimination (AUC 0.76) compared to single predictors. At a cutoff of ≥ 1, the score yielded a sensitivity of 71% and specificity of 87% Conclusions DDL affects nearly 1 in 11 elective surgical patients in this cohort, driven by a complex case-mix. A simple, three-point composite score offers a zero-cost tool to enhance preoperative risk stratification in resource-limited settings where advanced airway equipment may be scarce.

Background/Objectives: Growing concerns about antibiotic-associated adverse events, including Clostridioides difficile infection, prompted implementation of an antibiotic stewardship program (ASP) in South Korea in November 2024. One year post-implementation, we evaluated changes in antibiotic consumption and C. difficile infection incidence. Methods: This study was conducted at Chung-Ang University Gwangmyeong Hospital, South Korea. Segmented regression and interrupted time series analyses were performed using weekly data on antibiotic use (days of therapy [DOT] per 1000 patient-days) and C. difficile infection or colonization (cases per 1000 patient-days) over 157 weeks (November 2022-October 2025). Weeks 1-105 defined the pre-ASP period, and weeks 106-157 the post-ASP period. A 4-week lag between antibiotic use and subsequent C. difficile infection was hypothesized. Results: Before ASP, weekly total antibiotic use increased (β1 = 1.14, 95% CI, 0.76 to 1.51, p < 0.001). After ASP, the slope decreased significantly (β3 = -1.50, 95% CI -2.62 to -0.39, p = 0.009), consistent across anti-pseudomonal penicillins and cephalosporins and fluoroquinolones. Pre-ASP C. difficile incidence increased (α1 = 0.01, 95% CI, 0.01 to 0.02, p < 0.001); the upward trend attenuated post-ASP, though slope change was not significant (α3 = -0.01, 95% CI, -0.03 to 0.004, p = 0.13). An increase of 1 DOT per 1000 patient-days was associated with a 0.005-case increase in C. difficile infection incidence after 4 weeks. Conclusions: The observed effects of proactive ASP strategies underscore the importance of maintaining stewardship in clinical practice. Further studies are warranted to assess the sustainability of these findings and evaluate additional factors influencing C. difficile infection incidence.