Purpose: Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib. Materials and Methods: In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes. Results: A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. Conclusion Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

Purpose: This study aimed to examine the relationships between participative decision-making, psychological empowerment, and organizational citizenship behavior of nurses working in hospitals; moreover, we verified the moderated mediating effect of power distance orientation in these relationships. Methods: A total of 201 nurses working at a university hospital in South Korea responded to the survey. Self-report surveys were used to gather data from July 15-August 15, 2021. SPSS 22.0, AMOS 22.0, and SPSS PROCESS macro were used for data analysis. Results: Psychological empowerment significantly mediated the relationship between participative decision making and organizational citizenship behavior. Moreover, the moderating effect of power distance orientation on the relationship between participative decision making and psychological empowerment was also significant when the power distance orientation was at a low and average levels. However, the moderated mediating effect of power distance orientation on the relationship between participative decision making, psychological empowerment, and organizational citizenship behavior was insignificant. Conclusion Involving nurses with lower power distance orientation in decision making is crucial to elicit positive work performance and different strategies are necessary for those with higher power distance orientation. Finally, further studies are needed to understand the power distance orientation and positive work outcomes of nurses.

Background: In psoriasis treatment, not all body regions improve simultaneously after clinical interventions. Objective: This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans. Methods: This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis. Results: The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits. Conclusion We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.

Background: In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). Objective: We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. Methods: We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. Results: We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. Conclusion We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

PURPOSE: This study aimed to evaluate the validity of the Western Ontario and McMaster Universities Arthritis Index Short Form (WOMAC-SF) for the assessment of musculoskeletal disorders. We evaluated whether WOMAC-SF correlated with the World Health Organization Disability Assessment Schedule 12 (WHODAS-12) and Kaigo-Yobo questionnaires for assessing health-outcomes in Korea.MATERIALS AND METHODS: This cross-sectional study used data from the Namgaram-2 cohort. WOMAC, WOMAC-SF, WHODAS-12, and Kaigo-Yobo questionnaires were administered to patients with musculoskeletal disorders, including radiology-confirmed knee osteoarthritis (RKOA), sarcopenia, and osteoporosis. The relationships among WOMAC-SF, WHODAS-12, and Kaigo-Yobo scores were analyzed by stepwise multiple regression analysis.RESULTS: WOMAC-SF was associated with the WOMAC questionnaire. The results of confirmatory factor analysis for the hypothesized model with two latent factors, pain and function, provided satisfactory fit indices. WOMAC-SF pain and function were associated with RKOA. Kaigo-Yobo was associated with WOMAC-SF pain (B=0.140, p=0.001) and WOMAC-SF function (B=0.042, p=0.004). WHODAS-12 was associated with WOMAC-SF pain (B=0.679, p=0.003) and WOMAC-SF function (B=0.804, p<0.001).CONCLUSION: WOMAC-SF was validated for the evaluation of low extremity musculoskeletal disorders and health-related quality of life in a community-based population. Furthermore, we confirmed that WOMAC-SF were reflective of disability and frailty, which affect health outcomes.
Appointments and Schedules ; Arthritis ; Cohort Studies ; Cross-Sectional Studies ; Extremities ; Humans ; Korea ; Ontario ; Osteoarthritis, Knee ; Osteoporosis ; Quality of Life ; Sarcopenia ; World Health Organization

Background: Despite the autologous serum skin test (ASST)and autologous plasma skin test (APST) is widely used test accessingwhether a patient with chronic spontaneous urticaria(CSU) has autoreactivity or not, the clinician often encounterdifficulty making correlation between the test result and clinicalimplications. Objective: This study was aimed to findany clinical and laboratory findings related to the ASST andAPST response. Agreement and correlation between the twotests was also analyzed. Methods: A retrospective study wasconducted on 300 CSU patients who underwent ASST, APST.The subjects were divided into four groups according to theskin test result. Also, the degree of serum and plasma responsewas recorded. Results: Both ASST and APST positivegroup had shorter duration of the disease, higher incidenceof at least one episode of angioedema than negative group.There were no significant differences in the positivity for autoantibodiesincluding antinuclear, ds-DNA, and thyroid-relatedbetween the two groups. The predicted positive rate ofASST and APST according to age showed bimodal peak and decreasing pattern according to disease duration. Predictedpositivity of both tests declined with increase in total immunoglobulineE (IgE) level. In the correlation study, the twotests showed high correlation coefficients. Conclusion ASSTand APST positivity may be related to disease duration andseverity of CSU. The two tests showed a generally consistentresult. Autoreactivity may be gradually lost as disease continues.We suggest the autoreactivity in CSU could arise independentlyfrom IgE mediated immune process.

BACKGROUND: Systemic immunomodulatory treatment is actively recommended in the treatment for moderate to severe atopic dermatitis (AD) patients. However, consensus criteria for the classification of AD severity or treatment refractoriness have not been established yet. OBJECTIVE: To establish consensus criteria on the definition of severity classification and treatment refractoriness of AD to provide a basis for proper treatment strategy. METHODS: The Korean Atopic Dermatitis Association (KADA) comprised a task force team to establish a definition of moderate to severe AD. A draft of definition of moderate to severe AD was made on the basis of evidence. The recommendation was confirmed by KADA members through a web-based survey. RESULTS: KADA approved that AD with 16≤eczema area and severity index (EASI)<23 should be basically defined as moderate AD whereas AD with EASI score ≥23 should be considered as severe AD. They agreed that it would be reasonable to raise the severity level if patient's daytime or nighttime pruritus numerical rating scale is equal to or higher than 7 (≥7) or dermatology life quality index score exceeds 10. AD patients who do not reach EASI 50 after appropriate treatment for three months should be considered as a non-responder. Patients with recurrence (EASI ≥16) within three months after cessation of treatment should be considered as a recurrent AD. CONCLUSION: KADA built a consensus of definition of moderate and severe AD and treatment-refractoriness. These guidelines are expected to help physicians determine proper treatment options in need.
Advisory Committees ; Classification ; Consensus ; Dermatitis, Atopic ; Dermatology ; Diagnosis ; Humans ; Pruritus ; Quality of Life ; Recurrence ; Treatment Failure ; Withholding Treatment

BACKGROUND: AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a pivotal role in the balance of cellular energy metabolism. Recent studies have reported that AMPK has numerous roles in physiological conditions, and dysregulation of AMPK induces pathological processes and diseases. However, the role of AMPK and its activators have not yet been studied in the context of hair growth regulation. OBJECTIVE: To investigate the effects of metformin on dermal papilla (DP) and outer root sheath (ORS) cells, as well as the role of the AMPK pathway in hair growth. METHODS: We evaluated whether metformin, a well-known AMPK activator, had any beneficial effects on hair growth. In addition, to evaluate the molecular and cellular mechanisms that were involved, protein levels of AMPK and β-catenin were analyzed. RESULTS: Metformin increased the cellular proliferation of human DP and ORS cells. Ki-67 expression was also significantly increased after metformin treatment in the ex vivo hair follicle organ culture. Furthermore, DP and ORS cells treated with metformin had a significant increase in AMPK phosphorylation, which in turn suppressed β-catenin degradation and enhanced its nuclear accumulation. CONCLUSION: We demonstrated that metformin promoted hair growth via the AMPK/β-catenin signaling pathway in vitro with DP and ORS cells. The hair-promoting effects of AMPK activators may potentially be used for the treatment of alopecia, and further investigation will be needed in the future.
Alopecia ; AMP-Activated Protein Kinases ; beta Catenin ; Cell Proliferation ; Energy Metabolism ; Hair Follicle ; Hair ; Humans ; In Vitro Techniques ; Metformin ; Organ Culture Techniques ; Pathologic Processes ; Phosphorylation ; Protein Kinases

Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death receptor ligand 1 antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.
Drug Therapy ; Humans ; Immunotherapy ; Radiotherapy ; Sarcoma

BACKGROUND: Topical tacrolimus is an effective anti-inflammatory therapy for acute and chronic states of atopic dermatitis (AD) in both adults and children. Topical tacrolimus has particular use at sensitive areas such as the face, anogenitals, and skin folds of neck and extremities. However, many AD patients also experience aggravated symptoms on trunk. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of topical tacrolimus for AD patients with truncal lesions. METHODS: AD patients with truncal lesions who were aged ≥2 years were recruited from 20 centres in Korea. They received treatment with topical tacrolimus ointment twice daily during 4 weeks. The primary end point was change of the local eczema area and severity index (EASI) of the trunk from baseline to day 28. The secondary end points were changes in the patient global assessment (PGA) score and itch visual analogue scale (VAS) score of the trunk between baseline and day 28. RESULTS: Two hundred and ninety-one patients were recruited, and 176 patients completed the full 4-week treatment course. By the end of the treatment, the mean local EASI of the trunk (2.2±4.71) was significantly decreased from that at baseline (4.71±4.03, p < 0.001). PGA (1.71±1.15) and itch VAS score of the trunk (2.61±2.19) on day 28 were also profoundly decreased compared with the baseline (2.96±1.07 and 5.15±2.47, respectively). No serious adverse events were observed during the study period. CONCLUSION: Topical tacrolimus is an effective and safe therapy for truncal lesions in AD patients.
Administration, Topical ; Adult ; Child ; Dermatitis, Atopic* ; Eczema ; Extremities ; Humans ; Korea ; Neck ; Skin ; Tacrolimus*