Purpose: This study evaluated the therapeutic efficacy of intravitreal methotrexate (MTX) injections in patients diagnosed with intraocular lymphoma via vitrectomy and immunocytochemical staining. Methods: In a retrospective analysis of medical records, we reviewed data from four patients (six eyes) diagnosed with intraocular lymphoma cytologically after undergoing vitrectomy at our hospital between December 2021 and December 2023. Each case was followed for a minimum of 6 months after treatment, with comparisons made between pre- and post-treatment observations Results: The mean age of the patients was 63.5 ± 9.8 years, with an average interval of 29.3 ± 32.0 months from initial symptom onset to intraocular lymphoma diagnosis. Diagnosis was confirmed through cytological and immunocytochemical analysis of vitreous specimens, identifying diffuse large B-cell lymphoma in four eyes and atypical lymphoid cells in two eyes. On average, 14.0 ± 1.7 intravitreal MTX injections were administered per eye. The mean best-corrected visual acuity improved from 1.18 ± 0.90 pre-treatment to 0.37 ± 0.70 post-treatment. Ophthalmic complications included toxic keratopathy in three eyes and retinal hemorrhage in one eye. Additionally, nasal cavity lymphoma was diagnosed in two patients. Conclusions Diagnostic vitrectomy combined with cytology and immunocytochemical staining is essential for the early diagnosis of intraocular lymphoma and differentiation from inflammatory diseases, such as uveitis. Intravitreal MTX injections can induce clinical remission in intraocular lymphoma cases.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Purpose: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.