1.Serum Krebs von den Lungen-6 Level as a Reflecting Biomarker in Patients with Interstitial Lung Abnormalities
Hyung Koo KANG ; Sung Jun CHUNG ; Jiyeon KANG ; Hyeon-Kyoung KOO ; Sung-Soon LEE ; Jae-Woo JUNG ; Jae-Chol CHOI ; Jae Yeol KIM ; Jong Wook SHIN
Tuberculosis and Respiratory Diseases 2026;89(2):266-274
Background:
Research on the relationship between the progression of interstitial lung abnormalities (ILA) and serum biomarkers, including white blood cell differential counts and Krebs von den Lungen-6 (KL-6), is limited. This study aimed to examine the clinical characteristics of patients with ILA and evaluate the association between disease progression and serum biomarkers.
Methods:
This retrospective cohort study analyzed data from 159 patients (63 with ILA and 74 with interstitial lung diseases) between October 2021 and September 2022. Data collected included clinical characteristics, pulmonary function tests, chest computed tomography (CT), complete blood cell counts, and KL-6 levels. In 52 of these patients who had previously undergone chest CT, the utility of serum biomarkers in reflecting radiologic progression was assessed using receiver operating characteristic curve analysis.
Results:
Patients with ILA exhibited clinical characteristics similar to those with idiopathic pulmonary fibrosis. Serum KL-6 levels did not correlate with forced vital capacity or diffusing capacity of the lung for carbon monoxide in patients with ILA. Among the 52 patients with ILA, 13 demonstrated radiologic progression. Serum KL-6 displayed moderate predictive performance, with area under the curves ranging from 0.57 to 0.89 (p=0.014) for radiologic progression. Levels of KL-6 greater than 400 U/mL were more frequently observed in patients with radiologic progression (61.5% vs. 20.5%, p=0.006). In multivariate analysis, age and KL-6 were independently associated with radiologic progression in patients with ILA.
Conclusion
Serum KL-6 levels may serve as a potential indicator of ILA progression in asymptomatic patients. Those with KL-6 levels exceeding 400 U/mL should be closely monitored for radiologic progression.
2.Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea
Eui-Soon KIM ; Sun-Kyeong PARK ; Jong-Chan YOUN ; Hye Sun LEE ; Hae-Young LEE ; Hyun-Jai CHO ; Jin-Oh CHOI ; Eun-Seok JEON ; Sang Eun LEE ; Min-Seok KIM ; Jae-Joong KIM ; Kyung-Kuk HWANG ; Myeong-Chan CHO ; Shung Chull CHAE ; Seok-Min KANG ; Jin Joo PARK ; Dong-Ju CHOI ; Byung-Su YOO ; Jae Yeong CHO ; Kye Hun KIM ; Byung-Hee OH ; Barry GREENBERG ; Sang Hong BAEK
Journal of Korean Medical Science 2024;39(1):e8-
Background:
The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry.
Methods:
A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY).
Results:
Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY).
Conclusion
There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.
3.Sex Differences in Chronic Cough Epidemiology: The Korean Cough Study Group
Jiyeon KANG ; Woo Jung SEO ; Jieun KANG ; Jung Gon KIM ; Sung Jun CHUNG ; Hyung Koo KANG ; Sung-Soon LEE ; Tai Joon AN ; Hyonsoo JOO ; Hyun LEE ; Youlim KIM ; Ina JEONG ; Jinkyeong PARK ; Sung-Kyoung KIM ; Jong-Wook SHIN ; Chin Kook RHEE ; Yee Hyung KIM ; Kyung Hoon MIN ; Ji-Yong MOON ; Deog Kyeom KIM ; Seung Hun JANG ; Kwang Ha YOO ; Jin Woo KIM ; Hyoung Kyu YOON ; Hyeon-Kyoung KOO
Journal of Korean Medical Science 2024;39(38):e273-
Background:
Chronic cough is a common symptom encountered by healthcare practitioners.The global prevalence of chronic cough is 9.6%, with a female predominance. The aim of our study is to reveal the sex differences in prevalence and severity of chronic cough in South Korea, stratified by age and etiology.
Methods:
This study included adult patients with chronic cough who were recruited from 19 respiratory centers in South Korea. Patients completed the cough numeric rating scale (NRS) and COugh Assessment Test (COAT) questionnaire to assess the severity and multidimensional impact of cough.
Results:
Among the 625 patients, 419 (67.0%) were females, with a male-to-female ratio of 1:2.03. The mean age was 49.4 years, and the median duration of cough was 12 weeks. The mean NRS and COAT scores were 5.5 ± 1.8 and 9.5 ± 3.6, respectively. Female patients were older (45.3 ± 15.4 vs. 51.6 ± 15.2, P < 0.001) and more likely to have asthma/cough variant asthma (CVA) (26.7% vs. 40.8%, P = 0.001) than male patients. There was no difference in the duration or severity of cough between sexes, regardless of the cause. The male-tofemale ratio was lower for upper airway cough syndrome (UACS), asthma/CVA, and gastroesophageal reflux disease (GERD), but not for eosinophilic bronchitis (EB) or unexplained cough. The mean age of female patients was higher in UACS and asthma/CVA, but not in EB, GERD, or unexplained cough. The majority (24.2%) fell within the age category of 50s. The proportion of females with cough increased with age, with a significant rise in the 50s, 60s, and 70–89 age groups. The severity of cough decreased in the 50s, 60s, and 70–89 age groups, with no significant sex differences within the same age group.
Conclusion
The sex disparities in prevalence and severity of cough varied significantly depending on the age category and etiology. Understanding the specific sex-based difference could enhance comprehension of cough-related pathophysiology and treatment strategies.
4.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
5.Comparison of Frequency and Stay Time between Normal and Abnormal Elimination Behavior of Cats Using a Litter Box with Automatic Sensor
Ji-Woo SHIN ; Sun-Woo HAN ; Soon-Hak KWEON ; Myungseok KANG ; Jong-Hyuk KIM ; Chung-Gwang CHOI ; Joon-Seok CHAE
Journal of Veterinary Clinics 2024;41(2):71-78
Changes in elimination behavior, including urination and defecation, are common clinical signs of numerous disorders in cats. Therefore, this study attempted to automatically measure the elimination behavior of cats using the litter box and develop an early warning system for the guardian in case of abnormalities. To construct an early warning system for abnormal changes through cat elimination behavior, it consisted of a litter box, an automatic sensor for data collection and data wifi transmission, a server for data analysis, and a mobile phone app for result transmission and early warning. To establish the reference interval (RI), the elimination behavior was monitored for more than 2 weeks using a motion sensor within a litter box in 37 healthy cats and 19 diseased cats.The data were expressed as daily total visits, daily total stay duration, average stay duration per elimination, weekly total visits, and weekly total stay duration.Healthy cats showed median daily total visits of 3 times/day (RI 1.0-7.0) and daily total stay duration of 192 s/day (RI 8.0-452.0). For weekly data, the median total visits were 20 times/week (RI 3.0-35.25) and the median total stay duration was 1,147 s/week (RI 80.0-2,249.5). The average stay duration per elimination was 59 s/elimination (RI 4.67-132.0). Diseased cats showed more frequent elimination behavior than healthy cats (p < 0.001). Otherwise, for each elimination, diseased cats had shorter stay durations than healthy cats (p < 0.001). This study established the RIs of elimination behavior parameters (frequency and duration) in healthy cats. The present study might help guardians and veterinarians detect changes in elimination behaviors in diseased cats at an early stage.
6.Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke
Boyoung KIM ; Ji Sung LEE ; Hong-Kyun PARK ; Young Bok YUNG ; Ki Chang OH ; Jeong Joo PARK ; Yong-Jin CHO ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Hee-Joon BAE ; Tai Hwan PARK ; Sang-Soon PARK ; Kyung Bok LEE ; Jun LEE ; Byung-Chul LEE ; Minwoo LEE ; Joon-Tae KIM ; Kang-Ho CHOI ; Dong-Eog KIM ; Jay Chol CHOI ; Dong-Ick SHIN ; Jee-Hyun KWON ; Wook-Joo KIM ; Sung Il SOHN ; Jeong-Ho HONG ; Hyung Jong PARK ; Seong-Hwa JANG ; Kwang-Yeol PARK ; Sang-Hwa LEE ; Jong-Moo PARK ; Keun-Sik HONG
Journal of the Korean Neurological Association 2023;41(2):112-120
Background:
For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients.
Methods:
Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927).
Results:
The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]).
Conclusions
In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.
7.KAAACI Allergic Rhinitis Guidelines: Part 2. Update in nonpharmacotherapy
Sang Chul PARK ; Soo Jie CHUNG ; Jeong-Hee CHOI ; Yong Ju LEE ; Hyeon-Jong YANG ; Do-Yang PARK ; Dong-Kyu KIM ; Il Hwan LEE ; Soo Whan KIM ; Do Hyun KIM ; Young Joon JUN ; Song-I YANG ; Minji KIM ; Gwanghui RYU ; Sung-Yoon KANG ; Sang Min LEE ; Mi-Ae KIM ; Hyun-Jung KIM ; Gil-Soon CHOI ; Hyun Jong LEE ; Hyo-Bin KIM ; Bong-Seong KIM
Allergy, Asthma & Respiratory Disease 2023;11(3):126-134
Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and nonmedical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the “KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy” in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on nonpharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.
8.KAAACI Allergic Rhinitis Guidelines: Part 1. Update in pharmacotherapy
Minji KIM ; Sung-Yoon KANG ; Song-I YANG ; Il Hwan LEE ; Gwanghui RYU ; Mi-Ae KIM ; Sang Min LEE ; Hyun-Jung KIM ; Do-Yang PARK ; Yong Ju LEE ; Dong-Kyu KIM ; Do Hyun KIM ; Young Joon JUN ; Sang Chul PARK ; Bong-Seong KIM ; Soojie CHUNG ; Hyun Jong LEE ; Hyo-Bin KIM ; Jeong-Hee CHOI ; Gil-Soon CHOI ; Hyeon-Jong YANG ; Soo Whan KIM
Allergy, Asthma & Respiratory Disease 2023;11(3):117-125
The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines for AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and a systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.
9.Clinical Practice Guidelines for Oropharyngeal Dysphagia
Seoyon YANG ; Jin-Woo PARK ; Kyunghoon MIN ; Yoon Se LEE ; Young-Jin SONG ; Seong Hee CHOI ; Doo Young KIM ; Seung Hak LEE ; Hee Seung YANG ; Wonjae CHA ; Ji Won KIM ; Byung-Mo OH ; Han Gil SEO ; Min-Wook KIM ; Hee-Soon WOO ; Sung-Jong PARK ; Sungju JEE ; Ju Sun OH ; Ki Deok PARK ; Young Ju JIN ; Sungjun HAN ; DooHan YOO ; Bo Hae KIM ; Hyun Haeng LEE ; Yeo Hyung KIM ; Min-Gu KANG ; Eun-Jae CHUNG ; Bo Ryun KIM ; Tae-Woo KIM ; Eun Jae KO ; Young Min PARK ; Hanaro PARK ; Min-Su KIM ; Jungirl SEOK ; Sun IM ; Sung-Hwa KO ; Seong Hoon LIM ; Kee Wook JUNG ; Tae Hee LEE ; Bo Young HONG ; Woojeong KIM ; Weon-Sun SHIN ; Young Chan LEE ; Sung Joon PARK ; Jeonghyun LIM ; Youngkook KIM ; Jung Hwan LEE ; Kang-Min AHN ; Jun-Young PAENG ; JeongYun PARK ; Young Ae SONG ; Kyung Cheon SEO ; Chang Hwan RYU ; Jae-Keun CHO ; Jee-Ho LEE ; Kyoung Hyo CHOI
Journal of the Korean Dysphagia Society 2023;13(2):77-106
Objective:
Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia.
Methods:
Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology.
Results:
Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended.
Conclusion
This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.
10.Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models
Seong Hee KANG ; Hyung Joon YIM ; Ji-won HWANG ; Mi-jung KIM ; Young-Sun LEE ; Young Kul JUNG ; Hyungshin YIM ; Baek-Hui KIM ; Hae-Chul PARK ; Yeon Seok SEO ; Ji Hoon KIM ; Jong Eun YEON ; Soon Ho UM ; Kwan Soo BYUN
The Korean Journal of Internal Medicine 2022;37(4):745-756
Background/Aims:
Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects.
Methods:
The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis.
Results:
The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2.
Conclusions
The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

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