1.Clinical Usefulness of a Cell-based Assay for Detecting Myelin Oligodendrocyte Glycoprotein Antibodies in Central Nervous System Inflammatory Disorders
Jin Myoung SEOK ; Patrick WATERS ; Mi Young JEON ; Hye Lim LEE ; Seol-Hee BAEK ; Jin-Sung PARK ; Sa-Yoon KANG ; Ohyun KWON ; Jeeyoung OH ; Byung-Jo KIM ; Kyung-Ah PARK ; Sei Yeul OH ; Byoung Joon KIM ; Ju-Hong MIN
Annals of Laboratory Medicine 2024;44(1):56-63
Background:
The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients’ clinical characteristics.
Methods:
We established the CBA using HEK 293 cells transiently overexpressing fulllength human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD).
Results:
Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ = 0.883, P < 0.001); two patients (2/166, 1.2%) were only positive in our in-house CBA, and the CBA scores of the two laboratories correlated well (r = 0.663, P < 0.001). The commercial MOG-Ab CBA kit showed one falsenegative and three false-positive results. The clinical presentation at disease onset differed between MOGAD and NMOSD; ON was the most frequent manifestation in MOGAD, and transverse myelitis was most frequent in NMOSD.
Conclusions
The in-house CBA for MOG-Abs demonstrated reliable results and can potentially be used to evaluate CNS inflammatory disorders. A comprehensive, long-term study with a large patient population would clarify the clinical significance of MOG-Abs.
2.Gut microbiome and metabolome signatures in liver cirrhosis-related complications
Satya Priya SHARMA ; Haripriya GUPTA ; Goo-Hyun KWON ; Sang Yoon LEE ; Seol Hee SONG ; Jeoung Su KIM ; Jeong Ha PARK ; Min Ju KIM ; Dong-Hoon YANG ; Hyunjoon PARK ; Sung-Min WON ; Jin-Ju JEONG ; Ki-Kwang OH ; Jung A EOM ; Kyeong Jin LEE ; Sang Jun YOON ; Young Lim HAM ; Gwang Ho BAIK ; Dong Joon KIM ; Ki Tae SUK
Clinical and Molecular Hepatology 2024;30(4):845-862
Background/Aims:
Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis.
Methods:
Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased).
Results:
Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites.
Conclusions
Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.
3.Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study
Hee Jo HAN ; Seung Woo KIM ; Hyunjin KIM ; Jungmin SO ; Eun-Jae LEE ; Young-Min LIM ; Jung Hwan LEE ; Myung Ah LEE ; Byung-Jo KIM ; Seol-Hee BAEK ; Hyung-Soo LEE ; Eunhee SOHN ; Sooyoung KIM ; Jin-Sung PARK ; Minsung KANG ; Hyung Jun PARK ; Byeol-A YOON ; Jong Kuk KIM ; Hung Youl SEOK ; Sohyeon KIM ; Ju-Hong MIN ; Yeon Hak CHUNG ; Jeong Hee CHO ; Jee-Eun KIM ; Seong-il OH ; Ha Young SHIN
Journal of Korean Medical Science 2024;39(18):e150-
Background:
During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea.
Methods:
This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients.
Results:
Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients.
Conclusion
This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
4.Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration
Min-Gul KIM ; Suin KIM ; Ji-Young JEON ; Seol Ju MOON ; Yong-Geun KWAK ; Joo Young NA ; SeungHwan LEE ; Kyung-Mi PARK ; Hyo-Jin KIM ; Sang-Min LEE ; Seo-Yeon CHOI ; Kwang-Hee SHIN
The Korean Journal of Physiology and Pharmacology 2024;28(2):153-164
This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control.Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5–6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.
5.Effective Timing of Introducing an Inpatient Smoking Cessation Program to Cancer Patients
Yu-Ri CHOE ; Ji-Won CHOI ; Ju-Ri JEONG ; Hye-Mi DOH ; Mi-Lee KIM ; Min-Seol NAM ; Hee-Ji KHO ; Ha-Young PARK ; Hye-Ran AHN ; Sun-Seog KWEON ; Yu-Il KIM ; In-Jae OH
Yonsei Medical Journal 2023;64(4):251-258
Purpose:
We aimed to identify factors influencing smoking cessation success among cancer patients registered in an inpatient smoking cessation program at a single cancer center.
Materials and Methods:
The electronic medical records of enrolled patients with solid cancer were retrospectively reviewed. We evaluated factors associated with 6-month smoking cessation.
Results:
A total of 458 patients with cancer were included in this study. Their mean age was 62.9±10.3 years, and 56.3% of the participants had lung cancer. 193 (42.1%) had not yet begun their main treatment. The mean number of counseling sessions for the participants was 8.4±3.5, and 46 (10.0%) patients were prescribed smoking cessation medications. The 6-month smoking cessation success rate was 48.0%. Multivariate analysis showed that younger age (<65 years), cohabited status, early stage, and the number of counseling sessions were statistically significant factors affecting 6-month smoking cessation success (p<0.05). Initiation of a cessation program before cancer treatment was significantly associated with cessation success (odds ratio, 1.66; 95% confidence interval, 1.02–2.70; p=0.040).
Conclusion
Smoking cessation intervention must be considered when establishing a treatment plan immediately after a cancer diagnosis among smokers.
6.Analysis of clinical risk factors of failed electrical cardioversion in patients with persistent atrial fibrillation or atrial flutter
Ki‑Hun KIM ; Ha‑Young CHOI ; Jino PARK ; Yeo‑Jeong SONG ; Seunghwan KIM ; Dong‑Kie KIM ; Sang‑Hoon SEOL ; Doo‑Il KIM ; Pil‑Sung YANG ; Hong Euy LIM ; Junbeum PARK ; Jae‑Min SHIM ; Jinhee AHN ; Sung Ho LEE ; Sung Il IM ; Ju Youn KIM
International Journal of Arrhythmia 2023;24(3):17-
Background:
Although rhythm control could be the best for symptomatic atrial fibrillation (AF), some patients fail to achieve sinus rhythm (SR). This study aimed to identify clinical risk factors of failed electrical cardioversion (ECV).
Methods:
A total of 248 patients who received ECV for persistent AF or atrial flutter (AFL) were retrospectivelyreviewed. Patients were divided into three groups: Group 1 maintained SR for > 1 year, group 2 maintained SR ≤ 1 yearafter ECV, and group 3 failed ECV. SR maintenance was assessed using regular electrocardiography or Holter monitoring.
Results:
Patients were divided into group 1 (73, 29%), group 2 (146, 59%), and group 3 (29, 12%). The mean ageof patients was 60 ± 10 years, and 197 (79%) were male. Age, sex, and baseline characteristics were similar amonggroups. However, increased cardiac size, digoxin use, heart failure (HF), and decreased left ventricular ejection frac‑ tion (LVEF) were more common in group 3. Univariate analysis of clinical risk factors for failed ECV was increasedcardiac size [hazard ratio (HR) 2.14 (95% confidence interval [CI], 1.06–4.34, p = 0.030)], digoxin use [HR 2.66 (95% CI, 1.15–6.14), p = 0.027], HF [HR 2.60 (95% CI, 1.32–5.09), p = 0.005], LVEF < 40% [HR 3.45 (95% CI, 1.00–11.85), p = 0.038], and decreased LVEF [HR 2.49 (95% CI, 1.18–5.25), p = 0.012]. Among them, HF showed clinical significance only by multivariate analysis [HR 3.01 (95% CI, 1.13–7.99), p = 0.027].
Conclusions
Increased cardiac size, digoxin use, HF, LVEF < 40%, and decreased LVEF were related to failed ECV for persistent AF or AFL. Among these, HF was the most important risk factor. Further multi-center studies including greater number of participants are planned.
7.Improvement of the intestinal epithelial barrier during laxative effects of phlorotannin in loperamide‑induced constipation of SD rats
Ji Eun KIM ; Hee Jin SONG ; Yun Ju CHOI ; You Jeong JIN ; Yu Jeong ROH ; Ayun SEOL ; So Hae PARK ; Ju Min PARK ; Hyun Gu KANG ; Dae Youn HWANG
Laboratory Animal Research 2023;39(1):1-11
Background:
Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment.
Results:
The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats.
Conclusions
These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.
8.Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample
Jina HAN ; Hye Jin BAEK ; Eunbi NOH ; Kyuhyun YOON ; Jung Ae KIM ; Sukhyun RYU ; Kay O LEE ; No Yai PARK ; Eunok JUNG ; Sangil KIM ; Hyukmin LEE ; Yoo-Sung HWANG ; Jaehun JUNG ; Hun Jae LEE ; Sung-il CHO ; Sangcheol OH ; Migyeong KIM ; Chang-Mo OH ; Byengchul YU ; Young-Seoub HONG ; Keonyeop KIM ; Sunjae JUNG ; Mi Ah HAN ; Moo-Sik LEE ; Jung-Jeung LEE ; Young HWANGBO ; Hyeon Woo YIM ; Yu-Mi KIM ; Joongyub LEE ; Weon-Young LEE ; Jae-Hyun PARK ; Sungsoo OH ; Heui Sug JO ; Hyeongsu KIM ; Gilwon KANG ; Hae-Sung NAM ; Ju-Hyung LEE ; Gyung-Jae OH ; Min-Ho SHIN ; Soyeon RYU ; Tae-Yoon HWANG ; Soon-Woo PARK ; Sang Kyu KIM ; Roma SEOL ; Ki-Soo PARK ; Su Young KIM ; Jun-wook KWON ; Sung Soon KIM ; Byoungguk KIM ; June-Woo LEE ; Eun Young JANG ; Ah-Ra KIM ; Jeonghyun NAM ; ; Soon Young LEE ; Dong-Hyun KIM
Epidemiology and Health 2023;45(1):e2023075-
OBJECTIVES:
We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea.
METHODS:
In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022.
RESULTS:
In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%.
CONCLUSIONS
The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.
9.Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer with Brain Metastasis : The Role of Gamma Knife Radiosurgery
Min Ho LEE ; Kyung-Rae CHO ; Jung Won CHOI ; Doo-Sik KONG ; Ho Jun SEOL ; Do-Hyun NAM ; Hyun Ae JUNG ; Jong-Mu SUN ; Se-Hoon LEE ; Jin Seok AHN ; Myung-Ju AHN ; Keunchil PARK ; Jung-Il LEE
Journal of Korean Neurosurgical Society 2021;64(2):271-281
: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1–77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5–27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.
10.Feline adipose tissue-derived mesenchymal stem cells pretreated with IFN-γ enhance immunomodulatory effects through the PGE 2 pathway
Seol-Gi PARK ; Ju-Hyun AN ; Qiang LI ; Hyung-Kyu CHAE ; Su-Min PARK ; Jeong-Hwa LEE ; Jin-Ok AHN ; Woo-Jin SONG ; Hwa-Young YOUN
Journal of Veterinary Science 2021;22(2):e16-
Background:
Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells.
Objectives:
This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ).
Methods:
To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs.
Results:
Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factorbeta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E 2 (PGE 2 ) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE 2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ.
Conclusions
IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE 2 , which induces macrophage polarization and increases regulatory T-cell numbers.

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