Purpose: Claudins are a type of tight junction proteins in human endothelia and epithelia. Ozone brings about oxidative stress and lung inflammation in humans and experimental models. However, the impact of ozone on claudins in subjects with asthma remains poorly understood. The aim of this study was to find variations in the tight junction proteins claudin-4 and claudin-5 in subjects with asthma in relation to ambient ozone concentration. Methods: We previously recruited 50 patients with stable/exacerbated asthmatics and 25 controls. Furthermore, to examine the influence of ozone concentration, we reanalyzed 18 patients with stable or exacerbated asthma and 3 controls. The plasma claudin-4 and claudin-5 levels in response to high concentrations of ozone were compared to stable/exacerbated asthma, and controls. Results: The lung functions were significantly lower in subjects with asthma than those in controls. Blood eosinophil proportions were significantly higher in exacerbated asthmatics than in subjects with stable asthma. In high concentration period of ozone, plasma claudin-4 levels were significantly higher in subjects with exacerbated asthma (0.44 ± 0.30 ng/mL, P = 0.005) or stable asthma (0.38± 0.31 ng/mL, P= 0.009) compared to those in control subjects (0.16± 0.1 ng/mL). Plasma claudin-5 levels were lower in subjects with stable asthma (2.97 ± 1.38 ng/mL, P = 0.011) than in control subjects (6.92 ± 3.9 ng/mL), and higher in subjects with exacerbated asthma (7.49 ± 4.23 ng/mL, P < 0.001) than those with stable asthma. Conclusion These results reveal that claudins be changed in patients with asthma following ozone exposure in subjects with asthma.

OBJECTIVES: The escalating burden of cardiovascular disease (CVD) is a critical public health issue worldwide. CVD, especially acute myocardial infarction (AMI) and stroke, is the leading contributor to morbidity and mortality in Korea. We aimed to develop algorithms for identifying AMI and stroke events from the National Health Insurance Service (NHIS) database and validate these algorithms through medical record review. METHODS: We first established a concept and definition of “hospitalization episode,” taking into account the unique features of health claims-based NHIS database. We then developed first and recurrent event identification algorithms, separately for AMI and stroke, to determine whether each hospitalization episode represents a true incident case of AMI or stroke. Finally, we assessed our algorithms’ accuracy by calculating their positive predictive values (PPVs) based on medical records of algorithm- identified events. RESULTS: We developed identification algorithms for both AMI and stroke. To validate them, we conducted retrospective review of medical records for 3,140 algorithm-identified events (1,399 AMI and 1,741 stroke events) across 24 hospitals throughout Korea. The overall PPVs for the first and recurrent AMI events were around 92% and 78%, respectively, while those for the first and recurrent stroke events were around 88% and 81%, respectively. CONCLUSIONS We successfully developed algorithms for identifying AMI and stroke events. The algorithms demonstrated high accuracy, with PPVs of approximately 90% for first events and 80% for recurrent events. These findings indicate that our algorithms hold promise as an instrumental tool for the consistent and reliable production of national CVD statistics in Korea.

OBJECTIVES: Stroke remains the second leading cause of death in Korea. This study was designed to estimate the crude, age-adjusted and age-specific incidence rates, as well as the case fatality rate of stroke, in Korea from 2011 to 2020. METHODS: We utilized data from the National Health Insurance Services from January 1, 2002 to December 31, 2020, to calculate incidence rates and 30-day and 1-year case fatality rates of stroke. Additionally, we determined sex and age-specific incidence rates and computed age-standardized incidence rates by direct standardization to the 2005 population. RESULTS: The crude incidence rate of stroke hovered around 200 (per 100,000 person-years) from 2011 to 2015, then surged to 218.4 in 2019, before marginally declining to 208.0 in 2020. Conversely, the age-standardized incidence rate consistently decreased by 25% between 2011 and 2020. When stratified by sex, the crude incidence rate increased between 2011 and 2019 for both sexes, followed by a decrease in 2020. Age-standardized incidence rates displayed a downward trend throughout the study period for both sexes. Across all age groups, the 30-day and 1-year case fatality rates of stroke consistently decreased from 2011 to 2019, only to increase in 2020. CONCLUSIONS Despite a decrease in the age-standardized incidence rate, the total number of stroke events in Korea continues to rise due to the rapidly aging population. Moreover, 2020 witnessed a decrease in incidence but an increase in case fatality rates.

OBJECTIVES: Cardiovascular diseases are a leading cause of mortality worldwide, and acute myocardial infarction (AMI) is particularly fatal condition. We evaluated the incidence and case fatality rates of AMI in Korea from 2011 to 2020. METHODS: We utilized data from the National Health Insurance Services to calculate crude, age-standardized, and age-specific incidence rates, along with 30-day and 1-year case fatality rates, of AMI from 2011 to 2020. Age-standardized incidence rates were determined using direct standardization to the 2005 population. RESULTS: The crude incidence rate of AMI per 100,000 person-years consistently increased from 44.7 in 2011 to 68.3 in 2019, before decreasing slightly to 66.2 in 2020. The age-standardized incidence rate of AMI displayed a 19% rise from 2011 to 2019, followed by a slight decline in 2020. The increasing trend for AMI incidence was more pronounced in males than in females. Both 30-day and 1-year case fatality rates remained stable among younger individuals but showed a decrease among older individuals. There was a minor surge in case fatality in 2020, particularly among recurrent AMI cases. CONCLUSIONS Over the past decade, the AMI incidence rate in Korea has consistently increased, with a slight downturn in 2020. The case fatality rate has remained relatively stable except for a minor increase in 2020. This study provides data for continuous surveillance, the implementation of targeted interventions, and the advancement of research aimed at AMI in Korea.

Background/Aims: Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods: Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results: Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

Background: Myringotomy with tympanostomy tube insertion (MTI) is a superficial surgical procedure used to prevent hearing loss in children with serous otitis media. Intravenous anesthesia, often ketamine, is preferred for this procedure because of its ability to induce sedation without compromising airway reflexes. However, ketamine alone may be insufficient and potentially lead to spontaneous movement during surgery. This study evaluated the effectiveness of midazolam and fentanyl as adjuvants to ketamine in reducing spontaneous movement during MTI and enhancing the quality of recovery. Methods: This study involved two groups of 30 patients each: one group received intravenous ketamine (1.5 mg/kg) with an equal volume of normal saline (K group), while the other received a combination of midazolam, fentanyl, and ketamine (0.05 mg/kg, 1 μg/kg, and 1.5 mg/kg, respectively; MFK group). We assessed side effects, intraoperative patient movement, surgeon satisfaction, and emergence agitation scores. Results: The MFK group exhibited significantly lower scores for patient movement (p<0.01) and emergence agitation (p<0.01) and markedly higher surgeon satisfaction scores (p<0.01) than the K group. Conclusion Administering a midazolam-fentanyl-ketamine combination effectively reduced spontaneous movement during surgery and emergence agitation during recovery without prolonging discharge times in children undergoing MTI.

Background: Direct immunofluorescence (DIF) is a histochemical technique used to detect tissue-bound autoantibodies and diagnose various immune-mediated skin diseases. Objective: This study aimed to evaluate the sensitivity of DIF for each disorder, and the consistency between clinical, histopathological, and DIF results. Methods: A retrospective study was conducted in 194 patients who underwent skin biopsy and DIF testing at our hospital between January 2011 and December 2021. An antibody panel against immunoglobulin G (IgG), IgA, IgM, C3, C1q, and fibrinogen was used. The concordance rate and κ-coefficient between the clinical, histopathological, and DIF results were evaluated. Results: DIF was observed to be positive in 87 cases; 51 cases of immune-mediated bullous diseases, seven cases of connective tissue diseases (CTDs), 25 cases of vasculitis, and four cases of other diseases. The overall sensitivity of DIF for immune-mediated bullous diseases was 71.8%, which was higher than that of histopathology (64.8%). In CTDs and vasculitis, the overall sensitivities of DIF were 30.4% and 65.8%, respectively, which were lower than those of histopathology (73.9% and 84.2%, respectively). In addition, good concordance among the clinical, histological, and DIF results was observed. Conclusion DIF is a useful diagnostic method, especially for immune-mediated bullous diseases, lupus erythematosus, and Henoch-Schonlein purpura. However, in other CTDs and vasculitis cases, the sensitivity of DIF is relatively low. Therefore, the diagnostic value of DIF along with clinical and histopathological findings will be maximized only when the DIF test is performed for appropriate diseases.

Eosinophilic dermatosis of hematological malignancy (EDHM) is a rare condition associated with various hematologic malignancies, characterized by pruritic skin eruptions. We present a case of a 66-year-old woman with follicular lymphoma who developed urticarial and vesicular lesions indicative of EDHM following chemotherapy.The diagnosis was confirmed through histological analysis, revealing eosinophilic infiltration. Treatment included additional chemotherapy sessions and topical corticosteroids, resulting in complete resolution of skin lesions and lymphoma. EDHM requires careful differentiation based on clinical and histological findings. The pathogenesis remains unclear, but addressing underlying hematologic malignancies appears crucial in management. Early recognition of EDHM is essential for appropriate intervention due to its limited therapeutic options.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Background and Objectives: Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Recent advances in PAH-specific drugs have improved its outcomes, although the healthcare burden of novel therapeutics may lead to a discrepancy in outcomes between developing and developed countries. We analyzed how the epidemiology and clinical features of PAH has changed through the rapidly advancing healthcare infrastructure in South Korea. Methods: PAH was defined according to a newly devised 3-component algorithm. Using a nationwide health insurance claims database, we delineated annual trends in the prevalence, incidence, medication prescription pattern, and 5-year survival of PAH in Korea. Cumulative survival and potential predictors of mortality were also assessed among 2,151 incident PAH cases. Results: Between 2002 or 2004 and 2018, the prevalence and incidence of PAH increased 75-fold (0.4 to 29.9 per million people) and 12-fold (0.5 to 6.3 per million person-years), respectively. The proportion of patients on combination PAH-specific drug therapy has also steadily increased up to 29.0% in 2018. Among 2,151 incident PAH cases (median [interquartile range] age, 50 [37–62] years; 67.2% female), the 5-year survival rate and median survival duration were 71.8% and 13.1 years, respectively. Independent predictors of mortality were age, sex, etiology of PAH, diabetes, dyslipidemia, and chronic kidney disease. Conclusions This nationwide study delineated that the prevalence and incidence of PAH have grown rapidly in Korea since the early 2000s. The use of combination therapy has also increased, and the 5-year survival rate of PAH in Korea was similar to those in western countries.