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.

Objective: This study aimed to investigate the prevalence and characteristics of impacted teeth (ITs) in orthodontic patients at university dental hospitals in Korea. Methods: This study included 14,774 patients who visited the Department of Orthodontics at 10 university dental hospitals in Korea between 2020 and 2022 and underwent orthodontic diagnosis. The prevalence and characteristics of ITs were investigated using orthodontic diagnostic records, radiographs, and diagnostic casts. Results: The prevalence of ITs, excluding third molar impaction, in Korean orthodontic patients was 13.6% (n = 2,014).The prevalence of ITs in pediatric orthodontic patients was 24.5% (n = 1,614).Of these patients, 68.2% had one IT, 27.5% had two ITs, 24.3% had bilateral IT, and 75.7% had unilateral IT. The most frequent IT was the maxillary canine (50.1%), followed by the mandibular second molar (11.7%), and maxillary second premolar (9.6%). An abnormal eruption path (46.5%) was the most frequent etiology. Orthodontic traction after surgical exposure (70.6%) was the most frequent treatment option. Among the patients with ITs, 29.8% had other dental anomalies, such as tooth agenesis (8.7%), microdontia (8.0%), and supernumerary teeth (5.1%). Furthermore, 50.8% had complications such as cystic lesions (18.3%), transposition (17.7%), and root resorption (14.8%).Among the patients with maxillary canine impaction, 62.2% had labial maxillary canine impaction and 21.1% had palatal maxillary canine impaction. Conclusions The prevalence of ITs in Korean orthodontic patients at university dental hospitals was high, particularly in pediatric orthodontic patients.

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Background: This study aimed to identify the clinical characteristics of multidrug-resistant/ rifampicin-resistant tuberculosis (MDR/RR-TB) in the Republic of Korea. Methods: Data of notified people with tuberculosis between July 2018 and December 2021 were retrieved from the Korea Tuberculosis Cohort database. MDR/RR-TB was further categorized according to isoniazid susceptibility as follows: multidrug-resistant tuberculosis (MDR-TB), rifampicin-monoresistant tuberculosis (RMR-TB), and RR-TB if susceptibility to isoniazid was unknown. Multivariable logistic regression analysis was conducted to identify the factors associated with MDR/RR-TB. Results: Between 2018 and 2021, the proportion of MDR/RR-TB cases among all TB cases and TB cases with known drug susceptibility test results was 2.1% (502/24,447). The proportions of MDR/RR-TB and MDR-TB cases among TB cases with known drug susceptibility test results were 3.3% (502/15,071) and 1.9% (292/15,071), respectively. Among all cases of rifampicin resistance, 31.7% (159/502) were RMR-TB and 10.2% (51/502) were RR-TB. Multivariable logistic regression analyses revealed that younger age, foreigners, and prior tuberculosis history were significantly associated with MDR/ RR-TB. Conclusion Rapid identification of rifampicin resistance targeting the high-risk populations, such as younger generations, foreign-born individuals, and previously treated patients are necessary for patient-centered care.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Background: This study aimed to identify the clinical characteristics of multidrug-resistant/ rifampicin-resistant tuberculosis (MDR/RR-TB) in the Republic of Korea. Methods: Data of notified people with tuberculosis between July 2018 and December 2021 were retrieved from the Korea Tuberculosis Cohort database. MDR/RR-TB was further categorized according to isoniazid susceptibility as follows: multidrug-resistant tuberculosis (MDR-TB), rifampicin-monoresistant tuberculosis (RMR-TB), and RR-TB if susceptibility to isoniazid was unknown. Multivariable logistic regression analysis was conducted to identify the factors associated with MDR/RR-TB. Results: Between 2018 and 2021, the proportion of MDR/RR-TB cases among all TB cases and TB cases with known drug susceptibility test results was 2.1% (502/24,447). The proportions of MDR/RR-TB and MDR-TB cases among TB cases with known drug susceptibility test results were 3.3% (502/15,071) and 1.9% (292/15,071), respectively. Among all cases of rifampicin resistance, 31.7% (159/502) were RMR-TB and 10.2% (51/502) were RR-TB. Multivariable logistic regression analyses revealed that younger age, foreigners, and prior tuberculosis history were significantly associated with MDR/ RR-TB. Conclusion Rapid identification of rifampicin resistance targeting the high-risk populations, such as younger generations, foreign-born individuals, and previously treated patients are necessary for patient-centered care.

Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.