Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Successful emergency medical service training with virtual field trips using video during the COVID-19 pandemic: the Official Development Assistance Project in Uzbekistan / 한국의학교육

Purpose@#The coronavirus disease 2019 pandemic saw many restrictions on the provision of emergency medical service (EMS) training through actual field trips (AFTs), requiring a search for alternatives. This study aimed to assess trainees’ reactions to virtual field trips (VFTs) and determine the characteristics of instructional design for successful VFTs using edited videos and expert interviews. @*Methods@#This study evaluated Uzbekistan trainees’ reactions to the VFT of EMS training using questionnaires in three categories: satisfaction, relevance, and engagement. Factors of satisfaction and dissatisfaction were identified through open-ended questions. @*Results@#A total of 286 trainees responded to the survey during 15 educational sessions conducted from 2020 to 2022. The trainees’ responses to the VFT were positive. Overall mean scores were 4.65±0.49, 4.63±0.50, and 4.63±0.50 out of 5 points for satisfaction, relevance, and engagement, respectively. The trainees reported that the most interesting and helpful videos concerned the introduction of an EMS training curriculum and the observation of training facilities, such as the simulation centers of educational institutes. The leading causes of satisfaction were (1) authenticity of the VFTs, (2) easy-to-understand content, and (3) relevance to the job. The trainees suggested that Uzbek or Russian voice-overs would be better than subtitles in the video clip for focusing on VFT. @*Conclusion@#In situations where AFTs are not available, VFTs using edited videos and expert interviews are a good alternative to EMS education. Based on these results, it is possible that AFTs could be replaced by VFTs using qualified videos with designed instructions as a distance learning method under specific conditions.

Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

Successful Aging Transition and Its Impact on Self-Rated Health and Life Satisfaction: Findings from the Korean Longitudinal Study of Aging (2006-2018)

Background@#The concept of successful aging (SA) is becoming more emphasized. Since this status can change over time, it is necessary to evaluate the pattern of change and its effect on subjective well-being. @*Methods@#In this study, the participants aged 65 or older in the Korean longitudinal study of aging (KLoSA) were divided into four groups based on the change in SA (2006-2018), and its relationships with self-rated health and life satisfaction were evaluated. @*Results@#Compared to the non-SA (NSA)→NSA group, the odds ratio for positive self-rated health was 4.30 (95% confidence interval [CI], 1.64-11.31) in the SA→SA group, 3.92 (95% CI, 1.94-7.95) in the NSA→SA group, and 1.79 (95% CI, 1.28-2.50) in the SA→NSA group. High life satisfaction was 2.42 (95% CI, 1.19-4.94) in the SA→SA group and 2.50 (95% CI, 1.36-4.59) in the NSA→SA group. @*Conclusions@#Maintenance or improvements of a SA state has a significant association with positive self-rated health and high life satisfaction.

Current Status of Physical Activity in South Korea / 가정의학회지

The health benefits of physical activity have been well established. However, more than a quarter of the adult population in the world is insufficiently active (not performing at least 150 minutes of moderate-intensity physical activity per week, 75 minutes of vigorous-intensity physical activity per week, or any equivalent combination of the two), and there has been little improvement since 2001. In South Korea, the prevalence of insufficient physical activity was 54.4% in adults and 94.1% in adolescents in 2020. There was continuous decrease in the prevalence of sufficient aerobic physical activity, from 58.3% in 2014 to 45.6% in 2020. However, daily duration of sedentary behavior increased from 7.5 to 8.6 hours in the same period. Interventions to promote physical activity are necessary in various fields including clinical and policy approaches. As physical activity has decreased during the coronavirus disease 2019 pandemic, safer and more effective strategies to promote physical activity are required.

Predicting Symptomatic and Functional Improvements over 1 Year in Patients with First-Episode Psychosis Using Resting-State Electroencephalography

OBJECTIVE: Although early intervention from the beginning of a psychotic episode is essential for a better prognosis, biomarkers predictive of symptomatic and functional improvement in early psychotic disorders are lacking. This study aimed to investigate whether the spectral power of resting-state electroencephalography (EEG) can be used as a predictive marker of the 1-year prognosis in patients with first-episode psychosis (FEP). METHODS: Twenty-four patients with FEP and matched healthy control (HC) subjects were examined with resting-state EEG at baseline. The symptomatic severity and functional status of FEP patients were assessed at baseline and reassessed after 1 year of usual treatment. Repeated measures analysis of variance was conducted to compare EEG spectral powers across the groups. Multiple regression analysis revealed EEG spectral powers predictive of symptomatic and functional improvement in FEP patients at the 1-year follow-up. RESULTS: Delta band power in the frontal and posterior regions was significantly higher in patients with FEP than in HCs. Higher delta band power in the posterior region predicted later improvement of positive symptoms and general functional status. Lower delta band power in the frontal region predicted improvement of negative symptoms and general functioning after 1 year. CONCLUSION: These results suggest that increased delta absolute power is observed from the beginning of psychotic disorders. Furthermore, decreased delta power in the frontal region and increased delta power in the posterior region might be used as a predictive marker of a better prognosis of FEP, which would aid early intervention in clinical practice.

A Systematic Review and Meta-Analysis of Applicability of Web-Based Interventions for Individuals with Depression and Quality of Life Impairment

OBJECTIVE: The purpose of this meta-analysis was to determine the applicability of web-based treatment programs for individuals with depression and quality of life impairments. METHODS: We conducted database and manual searches using imprecise search-term strategy and inclusion criteria. Research published from 2005 to December 2015 was included in this study. Upon review, a total of 12 published papers on web-based intervention for individuals with depression were assessed eligible for this meta-analysis. Effect sizes were estimated for depression and quality of life. RESULTS: The mean effect size of web-based treatment on depressive symptoms was 0.72. However, unlike the result showing medium to large effect size, the analysis on the quality of life did not yield adequate effects of web-based interventions. CONCLUSION: Our results suggest robust benefits of employing web-based treatments for depressive symptoms. However, the adequacy of these relatively new intervention tools for individuals who suffer severe impairments of quality of life was found insufficient. The current study demonstrates the need to further develop web-based intervention techniques to improve overall functioning, as well as the clinical symptoms of patients with mental disorders.

Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review

OBJECTIVE: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique increasingly used to relieve symptoms of psychiatric disorders. Electrophysiologic markers, such as electroencephalography (EEG) and event-related potentials (ERP), have high temporal resolution sensitive to detect plastic changes of the brain associated with symptomatic improvement following tDCS application. METHODS: We performed systematic review to identify electrophysiological markers that reflect tDCS effects on plastic brain changes in psychiatric disorders. A total of 638 studies were identified by searching PubMed, Embase, psychINFPO. Of these, 21 full-text articles were assessed eligible and included in the review. RESULTS: Although the reviewed studies were heterogeneous in their choices of tDCS protocols, targeted electrophysiological markers, and disease entities, their results strongly support EEG/ERPs to sensitively reflect plastic brain changes and the associated symptomatic improvement following tDCS. CONCLUSION: EEG/ERPs may serve a potent tool in revealing the mechanisms underlying psychiatric symptoms, as well as in localizing the brain area targeted for stimulation. Future studies in each disease entities employing consistent tDCS protocols and electrophysiological markers would be necessary in order to substantiate and further elaborate the findings of studies included in the present systematic review.

Clinical assessment after human adipose stem cell transplantation into dogs

Adipose tissue-derived stem cell (ASCs) are an attractive source of stem cells with therapeutic applicability in various fields for regenerating damaged tissues because of their stemness characteristics. However, little has reported on evaluating adverse responses caused by human ASC therapy. Therefore, in the present study, a clinical assessment after human ASC transplantation into dogs was undertaken. A total of 12 healthy male dogs were selected and divided into four groups: saline infusion, saline bolus, ASC infusion, and ASC bolus groups. Physical assessment and blood analysis were performed following ASC transplantation, and the concentrations of angiogenic factors, and pro- and anti-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). There were no adverse vital sign responses among the dogs. Blood analyses revealed no remarkable complete blood count or serum chemistry results. ELISA results for angiogenic and anti-inflammatory factors including matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were significantly higher in the two ASCs groups than in the controls. In conclusion, this study demonstrated that transplantation of human ASCs produced no adverse effects and could be used safely in dogs. In addition, human ASCs could be involved in modulating secretions of angiogenic factors including MMP9, VEGF, bFGF, and HGF and anti-inflammatory factor IL-10.

Increased Frontal Gamma and Posterior Delta Powers as Potential Neurophysiological Correlates Differentiating Posttraumatic Stress Disorder from Anxiety Disorders

OBJECTIVE: Posttraumatic stress disorder (PTSD) is distinct from anxiety disorders in its etiology and clinical symptomatology, and was reclassified into trauma- and stressor-related disorders in DSM-5. This study aimed to find neurophysiological correlates differentiating PTSD from anxiety disorders using resting-state quantitative electroencephalography (qEEG). METHODS: Thirty-six patients with either PTSD or acute stress disorder and 79 patients with anxiety disorder were included in the analysis. qEEG data of absolute and relative powers and patients’ medication status on the day of qEEG examination were obtained. Electrodes were grouped into frontal, central, and posterior regions to analyze for regional differences. General linear models were utilized to test for group differences in absolute and relative powers while controlling for medications. RESULTS: PTSD patients differed from those with anxiety disorders in overall absolute powers [F(5,327)=2.601, p=0.025]. Specifically, overall absolute delta powers [F(1,331)=4.363, p=0.037], and overall relative gamma powers [F(1,331)=3.965, p=0.047] were increased in PTSD group compared to anxiety disorder group. Post hoc analysis regarding brain regions showed that the increase in absolute delta powers were localized to the posterior region [F(1,107)=4.001, p=0.048]. Additionally, frontal absolute gamma powers [F(1,107)=4.138, p=0.044] were increased in PTSD group compared to anxiety disorder group. CONCLUSION: Our study suggests increased overall absolute delta powers and relative gamma powers as potential markers that could differentiate PTSD from anxiety disorders. Moreover, increased frontal absolute gamma and posterior delta powers might pose as novel markers of PTSD, which may reflect its distinct symptomatology.

Vaccination guideline for Immigrant in Korea by Korean Society of Infectious Diseases / 감염과화학요법

No abstract available.

Changes in Transepidermal Water Loss and Skin Hydration according to Expression of Aquaporin-3 in Psoriasis

BACKGROUND: Aquaporins (AQPs) are a family of water transporting proteins present in many mammalian epithelial and endothelial cell types. Among the AQPs, AQP3 is known to be a water/glycerol transporter expressed in human skin. OBJECTIVE: The relationship between the expression level of AQP3 and transpidermal water loss (TEWL) in the lesional and peri-lesional skin of psoriasis-affected patients, and skin hydration in the lesional and peri-lesional skin of psoriasis patients, was investigated. METHODS: The expression of AQP3 in psoriasis-affected and healthy control skin was determined using immunohistochemical and immunofluroscence staining. TEWL and skin hydration were measured using a Tewameter(R) TM210 (Courage & Khazaka, Cologne, Germany) and a Corneometer(R) CM 820 (Courage & Khazaka), respectively. RESULTS: AQP3 was mainly expressed in the plasma membrane of stratum corneum and the stratum spinosum in normal epidermis. Unlike the normal epidermis, AQP3 showed decreased expression in the lesional and peri-lesional epidermis of psoriasis. TEWL was increased, and skin hydration was decreased, in the lesional and peri-lesional skin of psoriasis patients, compared with the healthy control sample. CONCLUSION: Although various factors contribute to reduced skin hydration in the lesional and peri-lesional skin of psoriasis, AQP3 appears to be a key factor in the skin dehydration of psoriasis-affected skin.

Measles Outbreaks and Infection Control in a Tertiary Hospital / 병원감염관리

BACKGROUND: Both the Korean Society of Infectious Diseases and The Korean Center for Diseases Control recommended MMR (measles, mumps, rubella) vaccination to health care workers (HCWs) but this had rarely been applied mainly due to economic reasons. In this paper, we report a measles outbreak initiated by two inpatients and then spread to other nine infants and three HCWs. We also report that this outbreak was successfully contained by active infection control measures. METHODS: Measles cases were determined according to CDC clinical criteria and confirmed by the level of the measles-specific IgM antibody. Suspected patients were isolated in aeration-limited areas. After measles cases in HCWs were detected, people in 26 pediatric wards were screened for measles-specific IgG antibody. MMR (measle, rubella, mumps) vaccination was applied to HCWs who were negative for measles-specific antibodies or HCWs who were exposed but not sure of their vaccination status. RESULTS: From April 21 to June 4 in 2007, measles-infected patients consisted of eleven infants (11 months old in median age) and three HCW women. Antibody screening revealed that only 73% (19 out of 26) in pediatric wards were positive for measles-specific IgG. After a medical doctor was confirmed as measles-infected, health care worker exposed to measles patients were all vaccinated without antibody test. CONCLUSION: The precise level of anti-measles antibody in adults has to be revealed by further studies involving multiple organizations. This result could be helpful for establishing a proper health care policy of MMR vaccination.

Three Cases of Allopurinol-induced DRESS Syndrome / 대한피부과학회지

Allopurinol (4-hydroxypyrazolo-[3,4-d]pyrimidine) is an effective and widely used xanthine oxidase inhibitor administered in the treatment of hyperuricemic states such as gout. Allopurinol-induced DRESS (Drug rash with eosinophilia and systemic symptoms) syndrome is characterized by hematologic abnormalities, especially eosinophilia and mononucleosis-like atypical lymphocytosis, skin rash, fever, lymph node enlargement and single or multiple organ involvement, which starts within 8 weeks after the initiation of therapy. We report three cases of allopurinol-induced DRESS syndrome who developed erythematous skin eruption six weeks, nine weeks and seven weeks, respectively, after allopurinol therapy. The clinical, laboratory and histologic findings of these patients were compatible with allopurinol-induced DRESS syndrome.