Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). Conclusion Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Background/Aims: Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. Methods: Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. Results: Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. Conclusions The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.

Purpose: Chronic kidney disease (CKD) is a well-known risk factor for cardiovascular outcomes; however, its association with abdominal aortic aneurysm (AAA) remains unknown. To investigate this association, a national wide population study has been undertaken. Methods: This cohort study extracted data from the Korean National Health Insurance System database for individuals who had health checkups in 2009. The incidence of AAA was ascertained through the end of 2019. The study population was classified into 4 groups based on the CKD stage: stages 1, 2, 3, and ≥4. The primary endpoint was newly diagnosed AAA. Results: During the mean follow-up of 9.3 years, a total of 20,760 patients (0.2%) were diagnosed with AAA. The incidence rates of AAA were 0.10, 0.23, 0.67, and 1.19 per 1,000 person-years in stages 1, 2, 3, and ≥4, respectively. In Cox proportional hazard model, advanced stage of CKD was associate with an increased risk of AAA development after adjusting full covariates (hazard ratio [95% confidence interval]: 1.12 [1.07–1.67], 1.16 [1.10–1.23], and 1.3 [1.15–1.46]; CKD stage 2 to ≥4, respectively; P < 0.001). There was a positive correlation between the degree of dipstick proteinuria and the risk of AAA, which was consistent regardless of age group, sex, smoking, dyslipidemia, diabetes mellitus, and hypertension. Conclusion CKD demonstrated positively associated with the development of AAA, its association showed graded risk as stage of CKD advanced.

Purpose: Abdominal aortic aneurysm (AAA) is a critical disease. Most studies of AAA consider reoperation rate, complications, or mortality, but do not consider a patient’s mental state. However, there is a possibility of interaction between AAA and depression in disease development and prognosis. We investigated the incidence and risk ratio of depression in patients with AAA using nationwide data. Methods: We selected subjects from National Health Insurance System database who were diagnosed with AAA between 2009 and 2015 and survived at least 1 year after diagnosis or AAA surgery (n = 10,373). We determined the control group using propensity score matching by age and sex. The control group had about 3 times the number of subjects as the AAA cohort (n = 31,119). Results: The incidence of depression was 1.4 times higher in the AAA group than the control group. We further analyzed the incidence of depression in the AAA group according to treatment modalities (nonsurgical vs. surgical or nonsurgical vs. open surgical aneurysm repair vs. endovascular aneurysm repair) but found no significant difference among them. The incidence of depression was significantly higher in patients aged <65 years than in patients aged ≥65 years (hazard ratio, 1.539 vs. 1.270; P < 0.001). Conclusion The incidence of depression was higher in the AAA group, with an especially high risk for depression in patients aged <65 years. The psychiatric status of patients with AAA should be carefully monitored for clinicians to intervene when appropriate.

Background: Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. Methods: We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. Results: In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. Conclusion ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD.

Background: Smartphone usage is indispensably beneficial to people’s everyday lives. However, excessive smartphone usage has been associated with physical and mental health problems. This study aimed to evaluate the association of smartphone usage with depressive symptoms, suicidal thoughts, and suicide attempts in Korean adolescents. Methods: This cross-sectional study was conducted in 54,603 Korean adolescent participants (26,930 male and 27,673 female) in the Korea Youth Risk Behavior Survey in 2017 who reported their smartphone use. We performed multiple logistic regression analysis to evaluate the association of smartphone use with mental health after adjusting for relevant covariates. Results: Among the participants, 25.6% of male students and 38.4% of female students reported using their smartphone for at least 30 hours per week. As time duration of smartphone usage increased, the risk of experiencing depressive symptoms, suicidal thoughts, and suicide attempt tended to increase, with odds ratios (95% confidence interval) of 1.18 (1.10–1.26), 1.18 (1.08–1.29), and 1.34 (1.11–1.60), respectively, for high smartphone usage compared with low smartphone usage. These associations remained significant with only slight change in odds ratios after consideration of problems that may be caused by smartphone usage, such as conflicts with family members or peers, or disturbance in school work. Conclusion Smartphone overuse was independently associated with an increased risk of mental health problems, which did not seem to be mediated by the problems caused by smartphone usage.

OBJECTIVE: We aimed to develop the clinical guideline for headache by the systematic review and synthesis of existing evidence-based guidelines. The purpose of developing the guideline was to improve the appropriateness of diagnosis and treatment of headache disorder, and consequently, to improve patients’ pain control and quality of life. The guideline broadly covers the differential diagnosis and treatment of tension-type headache, migraine, cluster headache, and medication-overuse headache. METHODS: This is a methodological study based on the ADAPTE methodology, including a systematic review of the literature, quality assessment of the guidelines using the Appraisal of Clinical Guidelines for REsearch & Evaluation II (AGREE II) Instrument, as well as an external review using a Delphi technique. The inclusion criteria for systematic search were as follows: topic-relevant, up-to-date guidelines including evidence from within 5 years, evidence-based guidelines, guidelines written in English or Korean, and guidelines issued by academic institutions or government agencies. RESULTS: We selected five guidelines and conducted their quality assessment using the AGREE II Instrument. As a result, one guideline was found to be eligible for adaptation. For 13 key questions, a total of 39 recommendations were proposed with the grading system and revised using the nominal group technique. CONCLUSION: Recommendations should be applied to actual clinical sites to achieve the ultimate goal of this guideline; therefore, follow-up activities, such as monitoring of guideline usage and assessment of applicability of the recommendations, should be performed in the future. Further assessment of the effectiveness of the guideline in Korea is needed.
Cluster Headache ; Delphi Technique ; Diagnosis ; Diagnosis, Differential ; Follow-Up Studies ; Government Agencies ; Headache Disorders ; Headache ; Korea ; Methods ; Migraine Disorders ; Quality of Life ; Tension-Type Headache

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.

PURPOSE: This study analyzed iodine intake by establishing an iodine database of general Korean foods eaten by Korean adults based on the data from the 1998 ~ 2014 KNHANES (Korea National Health and Nutrition Examination Survey). METHODS: Data on 56,818 subjects aged 19 years and older were obtained from health behavior interviews and a 24-hour dietary recall survey. Iodine intake of subjects was analyzed according to general characteristics, dietary lifestyle, food groups, and cooking method. RESULTS: An iodine database was established for 312 food items. The mean iodine intake of Korean adults decreased from 641.6 μg in 1998 to 236.2 μg in 2014 per day. Iodine intake of women was higher than that of men. For age distribution, those aged 30 ~ 49 years constituted more than 39 ~ 46% of subjects by survey year. Regarding iodine intake according to dietary lifestyle, the highest iodine intake was 29.4 ~ 34.4% for lunch while that of breakfast decreased. The highest iodine contribution by food group was seaweed such as kelp, sea mustard, and laver. CONCLUSION: The results of this study indicate that iodine intake of Korean adults has been decreasing, and iodine intake is associated with the prevalence of thyroid disease. This study provides basic data for the estimation of iodine intake in Korean adults.
Adult* ; Age Distribution ; Breakfast ; Cooking ; Female ; Functional Food ; Health Behavior ; Humans ; Iodine* ; Kelp ; Korea* ; Life Style ; Lunch ; Male ; Methods ; Mustard Plant ; Nutrition Surveys* ; Prevalence ; Seaweed ; Thyroid Diseases

OBJECTIVE: To compare sexual function before and 12 months after between sacrocolpopexy and sacrocervicopexy. METHODS: This retrospective study examined a cohort of 55 sexually active women who underwent either supracervical hysterectomy with sacrocervicopexy (n=28) or total abdominal hysterectomy with sacrocolpopexy (n=27) for stage II to IV pelvic organ prolapse. Pelvic floor support was measured with Pelvic Organ Prolapse-Quantification examination. Pelvic floor function was measured with the Pelvic Floor Distress Inventory-Short Form 20 and sexual function was measured with Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire-Short Form 12 (PISQ-12). RESULTS: Baseline pelvic floor symptoms, demographics and PISQ-12 questionnaire scores were similar between the two groups. Overall improvements in sexual function were seen based on PISQ-12 scores in both groups, but were not statistically significant. No differences were seen in PISQ-12 scores regardless of sparing the cervix or surgical route. Responses to the PISQ-12 question of avoiding sexual intercourse because of vaginal bulging showed significant improvement in both group. No recurrences of prolapse occurred. CONCLUSION: In women with pelvic organ prolapse, sexual function after either sacrocolpopexy or sacrocervicopexy was not different. Sexual dysfunction in terms of avoidance of sexual activity because of vaginal bulging was greatly improved in both groups with statistical significance.
Cervix Uteri ; Cohort Studies ; Coitus ; Demography ; Female ; Humans ; Hysterectomy ; Pelvic Floor ; Pelvic Organ Prolapse ; Prolapse ; Recurrence ; Retrospective Studies ; Sexual Behavior