1.Prevalence and Risk Factors of COVID-19 Reinfection in Patients with Rheumatoid Arthritis:A Retrospective Observational Study
Young-Eun KIM ; Soo Min AHN ; Ji Seon OH ; Seokchan HONG ; Chang‑Keun LEE ; Bin YOO ; Yong‑Gil KIM
Yonsei Medical Journal 2024;65(11):645-650
Purpose:
To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA).
Materials and Methods:
This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection.
Results:
Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0–66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1–1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years.The median time interval between infections was 0.8 (IQR, 0.6–1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057–8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9– 2.8); post-reinfection median, 2.3 (IQR, 1.8–2.6), p for change=0.895].
Conclusion
In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection.
2.Development of a multi-analysis model using an epithelial-fibroblast co-culture system as an alternative to animal testing
Min-Ju KIM ; Hee-Sung HWANG ; Jee Hoon CHOI ; Eun-Seon YOO ; Mi-Im JANG ; Juhee LEE ; Seung Min OH
Environmental Analysis Health and Toxicology 2024;39(3):e2024024-
The evaluation of respiratory chemical substances has been mostly performed in animal tests (OECD TG 403, TG 412, TG 413, etc.). However, there have been ongoing discussions about the limited use of these inhalation toxicity tests due to differences in the anatomical structure of the respiratory tract, difficulty in exposure, laborious processes, and ethical reasons. Alternative animal testing methods that mimic in vivo testing are required. Therefore, in this study, we established a co-culture system composed of differentiated epithelial cells under an air-liquid interface (ALI) system in the apical part and fibroblasts in the basal part. This system was designed to mimic the wound-healing mechanism in the respiratory system. In addition, we developed a multi-analysis system that simultaneously performs toxicological and functional evaluations. Several individual assays were used sequentially in a multi-analysis model for pulmonary toxicity. Briefly, cytokine analysis, histology, and cilia motility were measured in the apical part, and cell migration and gel contraction assay were performed by exposing MRC-5 cells to the basal culture. First, human airway epithelial cells from bronchial (hAECB) were cultured under air-liquid interface (ALI) system conditions and validated pseudostratified epithelium by detecting differentiation-related epithelial markers using Transepithelial Electrical Resistance (TEER) measurement, Hematoxylin and Eosin (H&E) staining, and immunocytochemistry (ICC) staining. Afterward, the co-culture cells exposed to Transforming growth factor-beta 1 (TGF-β1), a key mediator of pulmonary fibrosis, induced significant toxicological responses such as cytotoxicity, cell migration, and gel contraction, which are wound-healing markers. In addition, cilia motility in epithelial cells was significantly decreased compared to control. Therefore, the multi-analysis model with a 3D epithelial-fibroblast co-culture system is expected to be useful in predicting pulmonary toxicity as a simple and efficient high-throughput screening method and as an alternative to animal testing.
3.Prevalence and Risk Factors of COVID-19 Reinfection in Patients with Rheumatoid Arthritis:A Retrospective Observational Study
Young-Eun KIM ; Soo Min AHN ; Ji Seon OH ; Seokchan HONG ; Chang‑Keun LEE ; Bin YOO ; Yong‑Gil KIM
Yonsei Medical Journal 2024;65(11):645-650
Purpose:
To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA).
Materials and Methods:
This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection.
Results:
Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0–66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1–1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years.The median time interval between infections was 0.8 (IQR, 0.6–1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057–8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9– 2.8); post-reinfection median, 2.3 (IQR, 1.8–2.6), p for change=0.895].
Conclusion
In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection.
4.Development of a multi-analysis model using an epithelial-fibroblast co-culture system as an alternative to animal testing
Min-Ju KIM ; Hee-Sung HWANG ; Jee Hoon CHOI ; Eun-Seon YOO ; Mi-Im JANG ; Juhee LEE ; Seung Min OH
Environmental Analysis Health and Toxicology 2024;39(3):e2024024-
The evaluation of respiratory chemical substances has been mostly performed in animal tests (OECD TG 403, TG 412, TG 413, etc.). However, there have been ongoing discussions about the limited use of these inhalation toxicity tests due to differences in the anatomical structure of the respiratory tract, difficulty in exposure, laborious processes, and ethical reasons. Alternative animal testing methods that mimic in vivo testing are required. Therefore, in this study, we established a co-culture system composed of differentiated epithelial cells under an air-liquid interface (ALI) system in the apical part and fibroblasts in the basal part. This system was designed to mimic the wound-healing mechanism in the respiratory system. In addition, we developed a multi-analysis system that simultaneously performs toxicological and functional evaluations. Several individual assays were used sequentially in a multi-analysis model for pulmonary toxicity. Briefly, cytokine analysis, histology, and cilia motility were measured in the apical part, and cell migration and gel contraction assay were performed by exposing MRC-5 cells to the basal culture. First, human airway epithelial cells from bronchial (hAECB) were cultured under air-liquid interface (ALI) system conditions and validated pseudostratified epithelium by detecting differentiation-related epithelial markers using Transepithelial Electrical Resistance (TEER) measurement, Hematoxylin and Eosin (H&E) staining, and immunocytochemistry (ICC) staining. Afterward, the co-culture cells exposed to Transforming growth factor-beta 1 (TGF-β1), a key mediator of pulmonary fibrosis, induced significant toxicological responses such as cytotoxicity, cell migration, and gel contraction, which are wound-healing markers. In addition, cilia motility in epithelial cells was significantly decreased compared to control. Therefore, the multi-analysis model with a 3D epithelial-fibroblast co-culture system is expected to be useful in predicting pulmonary toxicity as a simple and efficient high-throughput screening method and as an alternative to animal testing.
5.Development of a multi-analysis model using an epithelial-fibroblast co-culture system as an alternative to animal testing
Min-Ju KIM ; Hee-Sung HWANG ; Jee Hoon CHOI ; Eun-Seon YOO ; Mi-Im JANG ; Juhee LEE ; Seung Min OH
Environmental Analysis Health and Toxicology 2024;39(3):e2024024-
The evaluation of respiratory chemical substances has been mostly performed in animal tests (OECD TG 403, TG 412, TG 413, etc.). However, there have been ongoing discussions about the limited use of these inhalation toxicity tests due to differences in the anatomical structure of the respiratory tract, difficulty in exposure, laborious processes, and ethical reasons. Alternative animal testing methods that mimic in vivo testing are required. Therefore, in this study, we established a co-culture system composed of differentiated epithelial cells under an air-liquid interface (ALI) system in the apical part and fibroblasts in the basal part. This system was designed to mimic the wound-healing mechanism in the respiratory system. In addition, we developed a multi-analysis system that simultaneously performs toxicological and functional evaluations. Several individual assays were used sequentially in a multi-analysis model for pulmonary toxicity. Briefly, cytokine analysis, histology, and cilia motility were measured in the apical part, and cell migration and gel contraction assay were performed by exposing MRC-5 cells to the basal culture. First, human airway epithelial cells from bronchial (hAECB) were cultured under air-liquid interface (ALI) system conditions and validated pseudostratified epithelium by detecting differentiation-related epithelial markers using Transepithelial Electrical Resistance (TEER) measurement, Hematoxylin and Eosin (H&E) staining, and immunocytochemistry (ICC) staining. Afterward, the co-culture cells exposed to Transforming growth factor-beta 1 (TGF-β1), a key mediator of pulmonary fibrosis, induced significant toxicological responses such as cytotoxicity, cell migration, and gel contraction, which are wound-healing markers. In addition, cilia motility in epithelial cells was significantly decreased compared to control. Therefore, the multi-analysis model with a 3D epithelial-fibroblast co-culture system is expected to be useful in predicting pulmonary toxicity as a simple and efficient high-throughput screening method and as an alternative to animal testing.
6.Prevalence and Risk Factors of COVID-19 Reinfection in Patients with Rheumatoid Arthritis:A Retrospective Observational Study
Young-Eun KIM ; Soo Min AHN ; Ji Seon OH ; Seokchan HONG ; Chang‑Keun LEE ; Bin YOO ; Yong‑Gil KIM
Yonsei Medical Journal 2024;65(11):645-650
Purpose:
To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA).
Materials and Methods:
This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection.
Results:
Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0–66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1–1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years.The median time interval between infections was 0.8 (IQR, 0.6–1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057–8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9– 2.8); post-reinfection median, 2.3 (IQR, 1.8–2.6), p for change=0.895].
Conclusion
In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection.
7.The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for sublingual immunotherapy
Gwanghui RYU ; Hye Mi JEE ; Hwa Young LEE ; Sung-Yoon KANG ; Kyunghoon KIM ; Ju Hee KIM ; Kyung Hee PARK ; So-Young PARK ; Myong Soon SUNG ; Youngsoo LEE ; Eun-Ae YANG ; Jin-Young MIN ; Eun Kyo HA ; Sang Min LEE ; Yong Won LEE ; Eun Hee CHUNG ; Sun Hee CHOI ; Young-Il KOH ; Seon Tae KIM ; Dong-Ho NAHM ; Jung Won PARK ; Jung Yeon SHIM ; Young Min AN ; Man Yong HAN ; Jeong-Hee CHOI ; Yoo Seob SHIN ; Doo Hee HAN ;
Allergy, Asthma & Respiratory Disease 2024;12(3):125-133
Allergen immunotherapy (AIT) has been used for over a century and has been demonstrated to be effective in treating patients with various allergic diseases. AIT allergens can be administered through various routes, including subcutaneous, sublingual, intralymphatic, oral, or epicutaneous routes. Sublingual immunotherapy (SLIT) has recently gained clinical interest, and it is considered an alternative treatment for allergic rhinitis (AR) and asthma. This review provides an overview of the current evidence-based studies that address the use of SLIT for treating AR, including (1) mechanisms of action, (2) appropriate patient selection for SLIT, (3) the current available SLIT products in Korea, and (4) updated information on its efficacy and safety. Finally, this guideline aims to provide the clinician with practical considerations for SLIT.
8.The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for allergen immunotherapy
Hwa Young LEE ; Sung-Yoon KANG ; Kyunghoon KIM ; Ju Hee KIM ; Gwanghui RYU ; Jin-Young MIN ; Kyung Hee PARK ; So-Young PARK ; Myongsoon SUNG ; Youngsoo LEE ; Eun-Ae YANG ; Hye Mi JEE ; Eun Kyo HA ; Yoo Seob SHIN ; Sang Min LEE ; Eun Hee CHUNG ; Sun Hee CHOI ; Young-Il KOH ; Seon Tae KIM ; Dong-Ho NAHM ; Jung Won PARK ; Jung Yeon SHIM ; Young Min AN ; Doo Hee HAN ; Man Yong HAN ; Yong Won LEE ; Jeong-Hee CHOI ;
Allergy, Asthma & Respiratory Disease 2024;12(3):102-124
Allergen immunotherapy (AIT) is a causative treatment of allergic diseases in which allergen extracts are regularly administered in a gradually escalated doses, leading to immune tolerance and consequent alleviation of allergic diseases. The need for uniform practice guidelines in AIT is continuously growing as the number of potential candidates for AIT increases and new therapeutic approaches are tried. This updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT, published in 2010, proposes an expert opinion by specialists in allergy, pediatrics, and otorhinolaryngology. This guideline deals with the basic knowledge of AIT, including mechanisms, clinical efficacy, allergen standardization, important allergens in Korea, and special consideration in pediatrics. The article also covers the methodological aspects of AIT, including patient selection, allergen selection, schedule and doses, follow-up care, efficacy measurements, and management of adverse reactions. Although this guideline suggests the optimal dosing schedule, an individualized approach and modifications are recommended considering the situation for each patient and clinic.
9.Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment
Do Seon SONG ; Hee Yeon KIM ; Young Kul JUNG ; Tae Hyung KIM ; Hyung Joon YIM ; Eileen L YOON ; Ki Tae SUK ; Jeong-ju YOO ; Sang Gyune KIM ; Moon Young KIM ; Young CHANG ; Soung Won JEONG ; Jae Young JANG ; Sung-Eun KIM ; Jung-Hee KIM ; Jung Gil PARK ; Won KIM ; Jin Mo YANG ; Dong Joon KIM ; ; Ashok Kumar CHOUDHURY ; Vinod ARORA ; Shiv Kumar SARIN ;
Clinical and Molecular Hepatology 2024;30(3):388-405
Background/Aims:
Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF).
Methods:
We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high.
Results:
Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353–5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484– 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC).
Conclusions
Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.
10.Perceptions of and Practices for the Management of Constipation: Results of a Korean National Survey
Young Sin CHO ; Seon-Young PARK ; Jeong Eun SHIN ; Kyung Sik PARK ; Jung-Wook KIM ; Tae Hee LEE ; Seong-Eun KIM ; Yoo Jin LEE ; Han Seung RYU ;
Gut and Liver 2024;18(2):275-282
Background/Aims:
Although guidelines exist regarding the evaluation and management of patients with chronic constipation (CC), little is known about real-world clinical practice patterns. This study aimed to evaluate the various practices used to manage CC patients in various clinical settings in South Korea.
Methods:
A nationwide web-based survey was conducted, randomly selecting gastroenterologists and non-gastroenterologists. The 25-item questionnaire included physicians’ perceptions and practices regarding the available options for diagnosing and managing CC patients in Korea.
Results:
The study participants comprised 193 physicians (86 gastroenterologists, 44.6%) involved in the clinical management of CC patients. The mean clinical experience was 12 years. Only 21 of 193 respondents (10.9%) used the Rome criteria when diagnosing CC. The Bristol Stool Form Scale was used by 29% of the respondents (56/193), while the digital rectal examination was performed by 11.9% of the respondents (23/193). Laboratory testing and colonoscopies were performed more frequently by gastroenterologists than by non-gastroenterologists (both p=0.001). Physiologic testing was used more frequently by gastroenterologists (p=0.046), phy-sicians at teaching hospitals, and physicians with clinical experience ≤10 years (both p<0.05). There were also significant differences in the preference for laxatives depending on the type of hospital.
Conclusions
There were discrepancies in the diagnosis and management of CC patients depending on the clinical setting. The utilization rates of the Bristol Stool Form Scale and digital rectal examination by physicians are low in real-world clinical practice. These results imply the need for better and more practical training of physicians in the assessment and management of CC.

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