1.Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles
Myeongjin SONG ; Kyung Min LIM ; Kwonwoo SONG ; Geun-Ho KANG ; Se Jong KIM ; Youngseo LEE ; Sujin YU ; Ki-Heon JEONG ; Ssang-Goo CHO
International Journal of Stem Cells 2024;17(4):407-417
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton’s jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJMSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
2.Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles
Myeongjin SONG ; Kyung Min LIM ; Kwonwoo SONG ; Geun-Ho KANG ; Se Jong KIM ; Youngseo LEE ; Sujin YU ; Ki-Heon JEONG ; Ssang-Goo CHO
International Journal of Stem Cells 2024;17(4):407-417
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton’s jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJMSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
3.Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles
Myeongjin SONG ; Kyung Min LIM ; Kwonwoo SONG ; Geun-Ho KANG ; Se Jong KIM ; Youngseo LEE ; Sujin YU ; Ki-Heon JEONG ; Ssang-Goo CHO
International Journal of Stem Cells 2024;17(4):407-417
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton’s jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJMSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
4.Fecal Calprotectin at Postinduction Is Capable of Predicting Persistent Remission and Endoscopic Healing after 1 Year of Treatment with Infliximab in Pediatric Patients with Crohn’s Disease
Yoo Min LEE ; Eun Sil KIM ; Sujin CHOI ; Hyo-Jeong JANG ; Yu Bin KIM ; So Yoon CHOI ; Byung-Ho CHOE ; Ben KANG
Gut and Liver 2024;18(3):498-508
Background/Aims:
The recent update on Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added a decrease in fecal calprotectin (FC) to an acceptable range as an intermediate target for Crohn’s disease (CD). We aimed to investigate whether postinduction FC could predict future persistent remission (PR) and endoscopic healing (EH) after 1 year of treatment with infliximab (IFX) in pediatric patients with CD.
Methods:
This multicenter retrospective observational study included pediatric patients with CD who were followed up for at least 1 year after starting IFX. The association of postinduction FC with PR and EH was investigated.
Results:
A total of 132 patients were included in this study. PR and EH were observed in 71.2% (94/132) and 73.9% (82/111) of the patients, respectively. In multivariate logistic regression analysis, only the postinduction FC level was associated with PR (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08 to 0.66; p=0.009). The FC levels at initiation of IFX and postinduction were significantly associated with EH (OR, 0.73; 95% CI, 0.53 to 0.99; p=0.044 and OR, 0.20; 95% CI, 0.06 to 0.49; p=0.002, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level for postinduction FC associated with PR was 122 mg/kg, and that associated with EH was 377 mg/kg.
Conclusions
Postinduction FC was associated with PR and EH after 1 year of treatment with IFX in pediatric patients with CD. Our findings emphasize the importance of FC as an intermediate target in the treat-to-target era.
5.Psychometric Properties of the Fall Risk Perception Questionnaire-Short Version for Inpatients in Acute Care Hospitals
Jeeeun CHOI ; Sujin LEE ; Eunjin PARK ; Sangha KU ; Sunhwa KIM ; Wonhye YU ; Eunmi JEONG ; Sukhee PARK ; Yusun PARK ; Hye Young KIM ; Sung Reul KIM
Journal of Korean Academy of Nursing 2024;54(2):151-161
Purpose:
Patients’ perception of fall risk is a promising new indicator for fall prevention. Therefore, a fall risk perception questionnaire that can be used rapidly and repeatedly in acute care settings is required. This study aimed to develop a short version of the fall risk perception questionnaire (Short-FRPQ) for inpatients.
Methods:
For the psychometric measurements, 246 inpatients were recruited from an acute care hospital. The construct (using confirmatory factor analysis and discriminant validity of each item), convergent, and known-group validities were tested to determine the validity of the Short-FRPQ. McDonald’s omega coefficient was used to examine the internal consistency of reliability.
Results:
In the confirmatory factor analysis, the fit indices of the Short-FRPQ, comprising 14 items and three factors, appeared to be satisfactory. The Short-FRPQ had a significantly positive correlation with the original scale, the Korean Falls Efficacy Scale-International, and the Morse Fall Scale. The risk of falls group, assessed using the Morse Fall Scale, had a higher score on the Short-FRPQ. McDonald’s omega coefficient was .90.
Conclusion
The Short-FRPQ presents good reliability and validity. As patient participation is essential in fall interventions, evaluating the fall risk perception of inpatients quickly and repeatedly using scales of acceptable validity and reliability is necessary.
6.Associations of Polyp Characteristics in Children and Adolescents Presenting with Less Than Five Colorectal Polyps: A Full Colonoscopy Is Still Required
Ju Young KIM ; Yu Bin KIM ; Sujin CHOI ; Yoo Min LEE ; Hyun Jin KIM ; Soon Chul KIM ; Hyo-Jeong JANG ; So Yoon CHOI ; Dae Yong YI ; Yoon LEE ; You Jin CHOI ; Yunkoo KANG ; Kyung Jae LEE ; Suk Jin HONG ; Jun Hyun HWANG ; Sanggyu KWAK ; Byung-Ho CHOE ; Ben KANG
Gut and Liver 2023;17(3):441-448
Background/Aims:
A full colonoscopy is currently required in children and adolescents with colorectal polyps, because of their potential of neoplastic transformation and complications such as intussusception. We aimed to analyze the associations of polyp characteristics in children and adolescents with colorectal polyps. Based on these findings, we also aimed to reevaluate the necessity of conducting a full colonoscopy.
Methods:
Pediatric patients <18 years of age who had undergone a colonoscopic polypectomy and those with <5 colorectal polyps were included in this multicenter, retrospective study. Baseline clinicodemographics, colonoscopic and histologic findings were investigated.
Results:
A total of 91 patients were included. Multivariate logistic regression analysis showed that polyp size was the only factor associated with the presence of any polyps located proximal to the splenic flexure (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.28 to 4.28; p=0.007). Furthermore, polyp location proximal to the splenic flexure and sessile morphology were associated with the presence of any adenomatous polyp (OR, 8.51; 95% CI, 1.43 to 68.65; p=0.023; OR, 18.41; 95% CI, 3.45 to 173.81; p=0.002, respectively).
Conclusions
In children and adolescents presenting with <5 colorectal polyps, polyp size and the presence of any adenomatous polyp were positively associated with polyp location proximal to the splenic flexure. This finding supports the necessity of a full colonoscopic exam in pediatric patients with colorectal polyps for the detection of polyps before the occurrence of complications such as intussusception or neoplastic transformation.
7.Fecal Calprotectin Levels Significantly Correlate with Polyp Size in Children and Adolescents with Juvenile Colorectal Polyps
Yu Bin KIM ; Ju Young KIM ; Sujin CHOI ; Yoo Min LEE ; So Yoon CHOI ; Soon Chul KIM ; Hyo-Jeong JANG ; Yoon LEE ; In Sook JEONG ; Dae Yong YI ; Yunkoo KANG ; Kyung Jae LEE ; Byung-Ho CHOE ; Ben KANG
Pediatric Gastroenterology, Hepatology & Nutrition 2023;26(1):34-42
Purpose:
We aimed to investigate factors that correlate with fecal calprotectin (FC) levels in children and adolescents with colorectal polyps.
Methods:
Pediatric patients aged <19 years who underwent colonoscopic polypectomy for a juvenile polyps (JPs) and FC tests were simultaneously conducted in a multicenter, retrospective study. Baseline demographics, colonoscopic and histological findings, and laboratory tests, including FC levels, were investigated. Correlations between the factors were investigated, and linear regression analysis revealed factors that correlated with FC levels. FC levels measured after polypectomies were investigated and the FC levels pre- and post-polypectomies were compared.
Results:
A total of 33 patients were included in the study. According to Pearson correlation analysis, the polyp size was the only factor that showed a statistically significant correlation with FC levels (r=0.75, p<0.001). Furthermore, according to the multivariate linear regression analysis, polyp size was the only factor that showed a statistically significant correlation with FC levels (adjusted R2=0.5718, β=73.62, p<0.001). The median FC level was 400 mg/ kg (interquartile range [IQR], 141.6–1,000 mg/kg), and the median polyp size was 14 mm (IQR, 9–20 mm). Nineteen patients underwent post-polypectomy FC tests. FC levels showed a significant decrease after polypectomy from a median of 445.2 mg/kg (IQR, 225–1,000) to 26.5 mg/kg (11.5–51) ( p<0.001).
Conclusion
FC levels significantly correlated with polyp size in children and adolescents with JPs.
8.Potential Utility of Fecal Calprotectin in Discriminating Colorectal Polyps From Other Major Etiologies in Children Presenting With Isolated Hematochezia
Yu Bin KIM ; Ju Young KIM ; Sujin CHOI ; Hyun Jin KIM ; Yoo Min LEE ; Yoon LEE ; Hyo-Jeong JANG ; Eun Hye LEE ; Kyung Jae LEE ; Soon Chul KIM ; So Yoon CHOI ; Yunkoo KANG ; Dae Yong YI ; You Jin CHOI ; Byung-Ho CHOE ; Ben KANG
Journal of Korean Medical Science 2022;37(9):e72-
Background:
Colorectal polyps are the most common cause of isolated hematochezia in children, which requires a colonoscopy for diagnosis. We aimed to investigate the potential utility of fecal calprotectin (FC) in assessing colorectal polyps detected by colonoscopy among children presenting with isolated hematochezia.
Methods:
Pediatric patients of the age of < 18 years who had undergone both colonoscopy and FC tests for isolated hematochezia from June 2016 to May 2020 were included in the present multicenter, retrospective, cross-sectional study. Comparative analysis was conducted between major causes of isolated hematochezia and FC cut-offs for discriminating colorectal polyps were explored.
Results:
A total 127 patients were included. Thirty-five patients (27.6%) had colorectal polyps, followed by anal fissure (14.2%), ulcerative colitis (UC; 12.6%), and others. A significant difference in FC levels was observed between patients with colorectal polyps (median, 278.7 mg/kg), anal fissures (median, 42.2 mg/kg), and UC (median, 981 mg/ kg) (P < 0.001). According to receiver operating characteristic curve analysis, among patients diagnosed with colorectal polyp or anal fissure, the most accurate FC cut-off for discriminating colorectal polyps from anal fissures on colonoscopy was 225 mg/kg (sensitivity, 59.4%; specificity, 94.4%; positive predictive value [PPV], 95.0%; negativepredictive value [NPV], 56.7%; area under the curve [AUC], 0.8; 95% confidence interval [CI], 0.678–0.923; P < 0.001), while among patients diagnosed with colorectal polyp or UC, the most accurate FC cut-off for discriminating colorectal polyps from UC on colonoscopy was 879 mg/kg (sensitivity, 81.2%; specificity, 56.2%; PPV, 78.8%; NPV, 60.0%; AUC, 0.687; 95% CI, 0.521–0.852; P < 0.001).
Conclusion
FC may assist in assessing the cause of lower gastrointestinal tract bleeding in children who present with isolated hematochezia.
9.Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era
So Yoon CHOI ; Sujin CHOI ; Ben KANG ; Byung-Ho CHOE ; Yeoun Joo LEE ; Jae Hong PARK ; Yu Bin KIM ; Jae Young KIM ; Kunsong LEE ; Kyung Jae LEE ; Ki Soo KANG ; Yoo Min LEE ; Hyun Jin KIM ; Yunkoo KANG ; Hyo-Jeong JANG ; Dae Yong YI ; Suk Jin HONG ; You Jin CHOI ; Jeana HONG ; Soon Chul KIM
Journal of Korean Medical Science 2022;37(37):e279-
Background:
Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19).
Methods:
This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021.
Results:
A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn’s disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset 1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn’s disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020).
Conclusion
Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.
10.Preparation and Practice of the Necessary Documents in Hospital for the “Act on Decision of Life-Sustaining Treatment for Patients at the End-of-Life”
Sun Kyung BAEK ; Hwa Jung KIM ; Jung Hye KWON ; Ha Yeon LEE ; Young-Woong WON ; Yu Jung KIM ; Sujin BAIK ; Hyewon RYU
Cancer Research and Treatment 2021;53(4):926-934
Purpose:
Six forms relating to decisions on life-sustaining treatment (LST) for patients at the end-of-life (EOL) in hospital are required by the “Act on Decision of LST for Patients at the EOL.” We investigated the preparation and creation status of these documents from the database of the National Agency for Management of LST.
Materials and Methods:
We analyzed the contents and details of each document necessary for decisions on LST, and the creation status of forms. We defined patients completing form 1 as “self-determined” of LST, and those whose family members had completed form 11/12 as “family decision” of LST. According to the determination subject, we compared the four items of LST on form 13 (the paper of implementation of LST) and the documentation time interval between forms.
Results:
The six forms require information about the patient, doctor, specialized doctor, family members, institution, decision for LST, and intention to use hospice services. Of 44,381 who had completed at least one document, 36,693 patients had form 13. Among them, 11,531, 10,976, and 12,551 people completed forms 1, 11, and 12, respectively. The documentation time interval from forms 1, 11, or 12 to form 13 was 8.6±13.6 days, 1.0±9.5 days, and 1.5±9.7 days, respectively.
Conclusion
The self-determination rate of LST was 31% and the mean time interval from self-determination to implementation of LST was 8.6 days. The creation of these forms still takes place when the patients are close to death.

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