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Abstract In the tumor microenvironment, macrophages play crucial roles resulting in tumor suppression and progression, depending on M1 and M2 macrophages, respectively. In particular, macrophage-derived exosomes modulate the gene expression of cancer cells by delivering miRNAs which downregulate specific genes. The communication between macrophages and cancer cells is especially important in immunogenic tumors such as melanoma, where the cancer pogression is significantly influenced by the surrounding immune cells. In this study, we identified that M1 macrophages secrete exosomal miR-29c-3p in the co-culture system with melanoma cells. Simultaneously, ENPP2, the target of miR-29c-3p, decreased in the melanoma cells which are co-cultured with M1 macrophages. Additionally, we observed that the reduction of ENPP2 alleviates melanoma cell migration and invasion, due to the changes of cholesterol metabolism and ECM remodeling. Based on these findings, we demonstrated that M1 macrophages suppress aggressiveness of melanoma cells via exosomal miR-29c-3p-mediated knock-down of ENPP2 in cancer cells. Graphical Abstract

Abstract Background The Global Initiative for Chronic Obstructive Lung Disease 2023 revision proposed that chronic obstructive pulmonary disease (COPD) has various etiologies including infections (COPD-I), such as tuberculosis and human immunodeficiency virus. While nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis share similar clinical manifestations, research on COPD development during longitudinal follow-up in patients with NTM-PD is limited. In this study, we aimed to evaluate the incidence and risk of COPD development in patients with NTM-PD. Methods We retrospectively enrolled patients with NTM-PD with normal lung function and 1:4 age-, sex-, body mass index-, and smoking status-matched controls between November 1994 and January 2022. We compared the risks of spirometry-defined COPD between the NTM-PD and control groups (study 1). A nationwide cohort study using the health insurance claims database was conducted to validate the findings (study 2). Results In study 1, during a mean follow-up of 3.3 years, COPD occurred in 14.0% (241/1,715) and 4.3% (293/6,860) of individuals in the NTM-PD and matched control cohorts, respectively. The NTM-PD cohort exhibited a higher risk of incident COPD (adjusted hazard ratio [aHR], 2.57; 95% CI, 2.15–3.09) compared to matched controls. In study 2, COPD occurred in 6.2% (24/386) and 2.5% (28/1,133) of individuals with and without NTM-PD, respectively. The NTM-PD cohort had a higher risk of incident COPD (aHR, 2.04; 95% CI, 1.21–3.42) compared to matched controls. Conclusion These findings suggest that NTM-PD could be considered a new etiotype of COPD-I and emphasize the importance of monitoring lung function in individuals with NTM-PD.

BackgroundThe interaction between COVID-19 and tuberculosis (TB) is not yet fully understood, and large-scale research on the mortality outcome of such dual infection has been limited. This study aimed to investigate the impact of PTB on mortality among patients with COVID-19 within a Korean population by conducting an extensive analysis of a nationwide large dataset.MethodWe investigated the mortality and disease severity among COVID-19 patients who had PTB in South Korea. This study analyzed 462,444 out of 566,494 COVID-19 patients identified between January 2020 and December 2021.ResultA total of 203 COVID-19 with PTB patients and 812 matched COVID-19 without PTB were analyzed using 1:4 propensity score matching. COVID-19 patients with PTB exhibited higher in-hospital mortality (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.45–6.27, p-value = 0.003) and were at increased risk of requiring conventional oxygen therapy (OR 1.57, 95% CI 1.10–2.25, p-value = 0.013) as well as high flow nasal cannula (HFNC) or noninvasive ventilation (NIV) oxygen therapy (OR 1.91, 95 CI 1.10–3.32, p-value = 0.022) compared to those without PTB. Compared to matched COVID-19 without PTB, co-infected patients showed increased mortality rates across various timeframes, including during hospitalization, and at 30 day and 90 day intervals. In-hospital mortality rates were particularly elevated among women, individuals with malignancy, and those with lower incomes. Furthermore, the increased in-hospital mortality among PTB patients persisted irrespective of the timing of TB diagnosis or vaccination status against COVID-19.ConclusionWe suggest that physicians be aware of the risk of mortality and severity among COVID-19 patients with PTB; coinfection with COVID-19 is a critical situation that remains to be further explored and needs more attention in countries with an intermediate to high PTB burden.

Abstract The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil–lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI

Critical limb ischemia (CLI) is a devastating disease characterized by the progressive blockage of blood vessels. Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI, poor cell survival in the harsh ischemic microenvironment limited its efficacy. Thus, an imperative need exists for a stem-cell delivery method that enhances cell survival. Here, a collagen microgel (CMG) cell-delivery scaffold (40 × 20 μm) was fabricated via micro-fragmentation from collagen–hyaluronic acid polyionic complex to improve transplantation efficiency. Culturing human adipose-derived stem cells (hASCs) with CMG enabled integrin receptors to interact with CMG to form injectable 3-dimensional constructs (CMG-hASCs) with a microporous microarchitecture and enhanced mass transfer. CMG-hASCs exhibited higher cell survival (p

Abstract Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5–13.2], P = 7.2 × 10−6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5–1423], P = 7.5 × 10−6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis.

ABSTRACTCurcumin is a natural polyphenolic compound exerting antioxidative and anti-inflammatory effects on various tissues, including muscles. Nevertheless, its clinical usage has been limited because of its poor bioavailability. Thus, highly bioavailable curcumin, such as Theracurmin (CR-033P) composed of 36% crystalline curcumin, has been developed. This study investigated the antioxidant activity and muscle-protective effect of Theracurmin Super (TS-P1), a new formulation with 36% amorphous curcumin. TS-P1 and CR-033P demonstrated antioxidant activity in vitro. Compared with pure curcumin, orally administered TS-P1 or CR-033P (16.7 or 50 mg per kg of body weight) at one-third dose inhibited the elevation of plasma lactate dehydrogenase and creatine kinase levels in a mouse downhill running model, indicating superior muscle-protective effect. Particularly, TS-P1 showed better or equivalent effectiveness in restoring the activity of antioxidant enzymes including glutathione peroxidase and catalase, and in suppressing inflammatory responses. Therefore, formulation with amorphous curcumin is a promising strategy for curcumin-based supplements.

BackgroundThe impact of long-term chronic periodontal conditions on the risk of lung cancer could not be accurately evaluated. Our aim was to provide more evidence on the connection between chronic periodontitis (CP) and lung cancer using a nationwide dataset.MethodsThis study used data from the Korean National Health Insurance Service National Sample Cohort. We enrolled 72,658 individuals with CP (CP cohort) between 2005 and 2019 and 1:1 age- and sex-matched controls without CP (non-CP cohort).ResultsDuring the median follow-up period of 5.1 (interquartile range, 2.8–8.0) years, 0.56% (n = 405/72,658) of the CP cohort and 0.29% (n = 212/72,658) of the matched non-CP cohort developed lung cancer, with incidence rates of 8.3 and 4.5 per 10,000 person-years. The risk of incident lung cancer was significantly higher in the CP cohort than in the matched non-CP cohort (adjusted hazard ratio = 2.27, 95% confidence interval = 1.94–2.65). The risk of incident lung cancer was 2.45-fold and 2.10-fold higher in mild and moderate-to-severe CP cohorts than in the matched non-CP control. The risk of incident lung cancer was especially higher in the 40–59 age group, females, and never-smokers than their counterparts.ConclusionWe demonstrate that the risk of incident lung cancer is higher in individuals with CP than in those without. The risk of lung cancer was especially high in individuals with more severe CP, females, never-smokers, and obese populations.

Background/Aims Despite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study. Methods This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms. Results Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation. Conclusions SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.

Abstract Background Urine-derived stem cells (UDSCs) can be easily isolated from urine and possess excellent stem cell characteristics, making them a promising source for cell therapeutics. Due to their kidney origin specificity, UDSCs are considered a superior therapeutic alternative for kidney diseases compared to other stem cells. To enhance the therapeutic potential of UDSCs, we developed a culture method that effectively boosts the expression of Klotho, a kidney-protective therapeutic factor. We also optimized the Good Manufacturing Practice (GMP) system to ensure stable and large-scale production of clinical-grade UDSCs from patient urine. In this study, we evaluated the in vivo safety and distribution of Klotho-enhanced UDSCs after intravenous administration in accordance with Good Laboratory Practice (GLP) regulations. Methods Mortality and general symptoms were continuously monitored throughout the entire examination period. We evaluated the potential toxicity of UDSCs according to the administration dosage and frequency using clinical pathological and histopathological analyses. We quantitatively assessed the in vivo distribution and retention period of UDSCs in major organs after single and repeated administration using human Alu-based qPCR analysis. We also conducted long-term monitoring for 26 weeks to assess the potential tumorigenicity. Results Klotho-enhanced UDSCs exhibited excellent homing potential, and recovered Klotho expression in injured renal tissue. Toxicologically harmful effects were not observed in all mice after a single administration of UDSCs. It was also verified that repeated administration of UDSCs did not induce significant toxicological or immunological adverse effects in all mice. Single and repeated administrated UDSCs persisted in the blood and major organs for approximately 3 days and cleared in most organs, except the lungs, within 2 weeks. UDSCs that remained in the lungs were cleared out in approximately 4–5 weeks. There were no significant differences according to the variation of sex and administration frequency. The tumors were found in the intravenous administration group but they were confirmed to be non-human origin. Based on these results, it was clarified that UDSCs have no tumorigenic potential. Conclusions Our results demonstrate that Klotho-enhanced UDSCs can be manufactured as cell therapeutics through an optimized GMP procedure, and they can be safely administered without causing toxicity and tumorigenicity.

Abstract Retinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration. The injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitors, was loaded into the hydrogel to attenuate inflammatory factors. On-demand anti-inflammatory effects of microglia cells via the drug-loaded IRH were verified in vitro and in vivo retinal degeneration 10 (rd10) mice model. Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest the IRH reported here can be used to considerably delay vision loss caused by RP.

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P

Abstract Background The association between systemic sclerosis and the development of bronchiectasis is unclear. This study aimed to compare the risk of bronchiectasis between individuals with systemic sclerosis and those without using a nationwide longitudinal dataset. Methods Using the Korean National Health Insurance Service dataset between 2010 and 2017, we identified 4845 individuals aged ≥ 20 years with systemic sclerosis and 24,225 without systemic sclerosis who were matched 1:5 by age and sex. They were followed up until the date of a bronchiectasis diagnosis, death, or December 31, 2019, whichever came first. Results During a median follow-up period of 6.0 (interquartile range, 3.2–8.7) years, 5.3% of the systemic sclerosis cohort and 1.9% of the matched cohort developed bronchiectasis, with incidence rates of 9.99 and 3.23 per 1000 person-years, respectively. Even after adjusting for potential confounders, the risk of incident bronchiectasis was significantly higher in the systemic sclerosis cohort than in the matched cohort (adjusted hazard ratio 2.63, 95% confidence interval 2.22–3.12). A subgroup analysis of individuals with systemic sclerosis revealed that the risk of incident bronchiectasis was notably higher in younger individuals aged 20–39 years (P for interaction = 0.048) and in those without other coexisting connective tissue diseases (P for interaction = 0.006) than in their counterparts. Conclusions The risk of incident bronchiectasis is higher in individuals with systemic sclerosis than those without. Bronchiectasis should be considered one of the pulmonary manifestations related to systemic sclerosis.

Abstract Background Human omentum-derived mesenchymal stem cells (hO-MSCs) possess great potential to differentiate into multiple lineages and have self-renewal capacity, allowing them to be utilized as patient-specific cell-based therapeutics. Although the use of various stem cell-derived β-cells has been proposed as a novel approach for treating diabetes mellitus, developing an efficient method to establish highly functional β-cells remains challenging. Methods We aimed to develop a novel cell culture platform that utilizes a fibroblast growth factor 2 (FGF2)-immobilized matrix to regulate the adhesion and differentiation of hO-MSCs into insulin-producing β-cells via cell–matrix/cell–cell interactions. In our study, we evaluated the in vitro differentiation potential of hO-MSCs cultured on an FGF2-immobilized matrix and a round-bottom plate (RBP). Further, the in vivo therapeutic efficacy of the β-cells transplanted into kidney capsules was evaluated using animal models with streptozotocin (STZ)-induced diabetes. Results Our findings demonstrated that cells cultured on an FGF2-immobilized matrix could self-organize into insulin-producing β-cell progenitors, as evident from the upregulation of pancreatic β-cell-specific markers (PDX-1, Insulin, and Glut-2). Moreover, we observed significant upregulation of heparan sulfate proteoglycan, gap junction proteins (Cx36 and Cx43), and cell adhesion molecules (E-cadherin and Ncam1) in cells cultured on the FGF2-immobilized matrix. In addition, in vivo transplantation of differentiated β-cells into animal models of STZ-induced diabetes revealed their survival and engraftment as well as glucose-sensitive production of insulin within the host microenvironment, at over 4 weeks after transplantation. Conclusions Our findings suggest that the FGF2-immobilized matrix can support initial cell adhesion, maturation, and glucose-stimulated insulin secretion within the host microenvironment. Such a cell culture platform can offer novel strategies to obtain functional pancreatic β-cells from patient-specific cell sources, ultimately enabling better treatment for diabetes mellitus. Graphical Abstract

ObjectivesPrevious studies suggested that coronavirus disease 2019 (COVID-19) could lead to pulmonary fibrosis, but the incidence of newly diagnosed interstitial lung disease (ILD) after COVID-19 is unclear. We aimed to determine whether COVID-19 increases the risk of newly diagnosed ILD and whether vaccination against COVID-19 can reduce this risk.MethodsThis retrospective cohort study used data from the Korean National Health Insurance claim-based database. Two study groups and propensity score (PS)-matched control groups were constructed: Study 1: participants diagnosed with COVID-19 (COVID-19 cohort) and their PS-matched controls; Study 2: COVID-19 vaccinated participants (vaccination cohort) and their PS-matched controls.ResultsIn Study 1, during a median 6 months of follow-up, 0.50% of the COVID-19 cohort (300/60,518) and 0.04% of controls (27/60,518) developed newly diagnosed ILD, with an incidence of 9.76 and 0.88 per 1,000 person-years, respectively. The COVID-19 cohort had a higher risk of ILD [adjusted hazard ratio (aHR), 11.01; 95% confidence interval (CI), 7.42–16.32] than controls. In Study 2, the vaccination cohort had a lower risk of newly diagnosed ILD than controls (aHR, 0.44; 95% CI, 0.34–0.57).ConclusionUsing nationwide data, we demonstrated that COVID-19 was associated with a higher incidence rate of newly diagnosed ILD, but that this risk could be mitigated by COVID-19 vaccination.

IntroductionAir pollutants are increasingly recognized to affect long-term outcomes in patients with bronchiectasis. We aimed to figure out the association between air pollutants and the risk of healthcare utilization in patients with bronchiectasis.MethodsData for 1,029 subjects with bronchiectasis in Seoul were extracted. The air pollutants included particulate matter of 10 μm or less in diameter (PM10), particulate matter of 2.5 μm or less in diameter (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), and nitrogen dioxide (NO2). The outcome was all-cause healthcare uses, defined as outpatient visit, emergency department visit, or hospitalization. The concentration–response curves between each air pollutant and relative risks for healthcare utilization were obtained.ResultsThere were significant correlations between air pollutant concentrations and the risk of healthcare utilization, particularly for PM10, NO2, SO2, and CO. This risk was observed even at concentrations below the recommended safe thresholds for the general population. The slopes for the association between PM10 and NO2 and the risk of healthcare use showed a logarithmic growth pattern, with the steepest increase up to 30 μg/m3 and 0.030 parts per million (ppm), respectively. The curves for SO2 and CO showed an inverted U-shaped pattern, with a peak at 0.0045 ppm and a slow upward curve, respectively. No specific trends were observed for PM2.5 and O3 and the risk of healthcare use.DiscussionIncreased concentrations of PM10, NO2, SO2, and CO were associated with increased healthcare utilization in patients with bronchiectasis. For patients with bronchiectasis, there were no safety thresholds for those air pollutants, and even low levels of air pollutant exposure can negatively impact bronchiectasis outcomes.

Abstract Background: Although cardiovascular comorbidities negatively impact survival in patients with bronchiectasis, there is limited evidence to recommend exercise in this population. We aimed to evaluate whether exercise habit changes are related to reduced cardiovascular disease risk and explore an optimal exercise amount. Methods: This study identified 165,842 patients with newly diagnosed bronchiectasis during 2010–2016 who underwent two health examinations and were followed up until December 2020. The exposure was the change in weekly habits of moderate- or vigorous-intensity physical activity between the two examinations, classified into non-exercisers and exercisers (further classified into new exercisers, exercise dropouts, and exercise maintainers). The amount of exercise was measured using metabolic equivalents of task (MET). The outcome was the incidence of myocardial infarction (MI) or stroke. Results: During a mean of 6.2 ± 2.1 follow-up years, 4,233 (2.6%) and 3,745 (2.3%) of patients with bronchiectasis had MI or stroke, respectively. Compared to non-exercisers, exercisers had a significantly lower risk of MI or stroke by 9–28% (p

Recent advances in asthma research have led to the development of novel biologicals that hinder the pathological actions of key molecules in severe asthma. Traditional randomised controlled studies (RCTs), the gold standard for evaluating the efficacy and safety of medical interventions with excellent internal validity, have proven the clinical benefits and favourable safety profiles of type 2 biologicals in severe asthma. However, RCTs are not always ideal because of shortcomings such as limited external validity and practical issues in the management of severe asthma that cannot be solved through strictly designed clinical trials. Thus, the applicability of their findings may be questioned because treatment adherence is frequently poor in the real world. Real-world evidence includes a wide range of real-world data (RWD) collected from multiple sources in clinical practice, such as electronic medical records, healthcare insurance claims and retrospective or prospective patient registries. RWD may help clinicians decide how to manage patients with severe asthma. Real-world evidence is also gaining attention in addressing clinical questions not answered by traditional RCTs. Because there are various types of RWD with different possibilities and limitations, it is important to decide which type of RWD could be “fit for purpose” to address a specific question. This narrative review discusses the challenges and opportunities of RWD for evaluating the effectiveness and clinical outcomes of biological treatments for severe asthma.

Abstract Asthmatic patients are generally considered to have an increased risk of mortality compared with subjects without asthma. However, this issue has been less evaluated using nationally representative data. Moreover, it is unclear whether respiratory comorbidities other than chronic obstructive pulmonary disease (COPD) are associated with increased mortality in asthmatic patients compared with subjects without. Using a nationally representative sample database, we performed a retrospective cohort study of patients with asthma and age-sex-matched control cohort. We estimated the hazard ratio (HR) and stratified the asthma cohort based on respiratory comorbidities. During a median 8.9-year follow-up, the overall mortality rate was higher in the asthma cohort than in the control cohort (p

Background The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. Methods Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. Results A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-age-physiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. Conclusion In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

Severe asthma constitutes a serious health burden with significant morbidity and socioeconomic costs. The development and introduction of new biologics targeting type 2 inflammation changed the paradigm for management of severe asthma and initiated a biological era. These changes impose a challenge to clinicians in managing difficult-to-treat and severe asthma. To understand the characteristics and heterogeneity of severe asthma and to develop a better strategy to manage it, the Korean Academy of Asthma, Allergy and Clinical Immunology, Working Group on Severe Asthma, has organized the Korean Severe Asthma Registry (KoSAR). In this review, we describe the challenges of severe asthma management regarding diagnosis, disease burden, heterogeneity, guidelines, and organization of severe asthma clinics. This review also examines the current global activities of national and regional registries and study groups. In addition, we present the KoSAR vision and organization and describe the findings of KoSAR in comparison with those of other countries.

Abstract The aim of this study is to examine the impact of tumor necrosis factor inhibitors (TNFI) on nontuberculous mycobacterium (NTM) infection in rheumatoid arthritis (RA) patients in a mycobacterium tuberculosis (MTB) endemic area. We selected 1089 TNFI-treated RA patients and 4356 untreated RA patients using propensity-matching analysis according to age, gender, and Charlson comorbidity index using the Korean National Health Insurance Service database from July 2009 to December 2010. Both groups were followed-up until the end of 2016 to measure the incidence of mycobacterial diseases. The incidence rate of NTM in TNFI-treated RA group was similar to those of MTB (328.1 and 340.9 per 100,000 person-years, respectively). The adjusted hazard ratio (aHR) of NTM for TNFI-treated RA compared to untreated RA was 1.751(95% CI 1.105–2.774). The risk of TNFI-associated NTM in RA was 2.108-fold higher among women than men. The age-stratified effects of TNFI on NTM development were significantly high in RA patients aged 50–65 years (aHR 2.018). RA patients without comorbidities had a higher incidence of NTM following TNFI treatment (aHR 1.742). This real-world, observational study highlights the need to increase awareness of NTM in TNFI-treated RA patients in an MTB endemic area.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry.Materials and methodsThis is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model.ResultsAmong 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38–3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60–4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p

Background: Despite the importance of influenza vaccination, its rates in subjects with asthma are suboptimal, especially in the young population. Methods: Among 72,843 adults aged ⩾18 years from the Korea National Health and Nutrition Examination Survey conducted between 2010 and 2019, 1643 with asthma were included. The yearly trends and factors associated with influenza vaccination were analyzed in subjects with asthma. In addition, stratified analyses were performed by age group (

Abstract Peripheral artery disease is a progressive, devastating disease that leads to critical limb ischemia (CLI). Therapeutic angiogenesis using stem cell therapy has emerged as a promising approach for its treatment; however, adapting cell-based therapy has been limited by poor cell survival and low treatment efficiency. To overcome unmet clinical needs, we developed a fibroblast growth factor 2 (FGF2)-immobilized matrix that enabled control of cell adhesion to the surface and exerted a priming effect on the cell. Human adipose-derived stem cells (hASCs) grown in this matrix formed a functionally enhanced cells spheroid (FECS-Ad) that secreted various angiogenic factors including interleukin-8 (IL-8). We demonstrated that IL-8 was upregulated by the FGF2-mediated priming effect during FECS-Ad formation. Immobilized FGF2 substrate induced stronger IL-8 expression than soluble FGF2 ligands, presumably through the FGFR1/JNK/NF-κB signaling cascade. In IL-8-silenced FECS-Ad, vascular endothelial growth factor (VEGF) expression was decreased and angiogenic potential was reduced. Intramuscular injection of FECS-Ad promoted angiogenesis and muscle regeneration in mouse ischemic tissue, while IL-8 silencing in FECS-Ad inhibited these effects. Taken together, our data demonstrate that IL-8 contributes to therapeutic angiogenesis and suggest that FECS-Ad generated using the MBP-FGF2 matrix might provide a reliable platform for developing therapeutic agents to treat CLI.

Abstract The bending angle at the peak load is regarded as the most important parameter for evaluating bending properties of hot-press-forming (HPF) steels. However, it is not a mechanics-based parameter for the bending criterion, and the data interpretation is difficult because bending criteria in relation with microstructures and associated bending mechanisms have not been verified yet. In this study, effects of coating and baking treatments on bending angles at the peak load of three kinds of 1470 MPa-grade HPF steels were investigated by interrupted three-point bending tests coupled with direct microstructural observation. According to direct observations of sequential cracking processes of V-shaped crack (V-crack), bending procedures were classified into four stages: (1) formation of small V-crack, (2) increase in number and size of V-cracks, (3) initiation of shear-crack propagation from the V-crack tip, and (4) further propagation and opening of the shear crack. The minimum bending angle required for initiating the shear-crack propagation from the V-crack tip was defined as a critical angle, which meant the boundary between the 2nd and 3rd stages. The present bending behavior related with critical bending angle and V-cracking could be interpreted similarly by the fracture-mechanics concept, i.e., the initiation of shear-crack propagation.

Abstract There are limited data regarding whether mortality is higher in patients with non cystic fibrosis bronchiectasis (bronchiectasis) than in those without bronchiectasis. Using 2005–2015 data from the Korean National Health Insurance Service, we evaluated hazard ratio (HR) for all-cause mortality in the bronchiectasis cohort relative to the matched cohort. The effect of comorbidities over the study period on the relative mortality was also assessed. All-cause mortality was significantly higher in the bronchiectasis cohort than in the matched cohort (2505/100,000 vs 2142/100,000 person-years, respectively; P

Objectives. Sensitization to specific inhalant allergens is a major risk factor for the development of atopic diseases, which impose a major socioeconomic burden and significantly diminish quality of life. However, patterns of inhalant allergic sensitization have yet to be precisely described. Therefore, to enhance the understanding of aeroallergens, we performed a cluster analysis of inhalant allergic sensitization using a computational model. Methods. Skin prick data were collected from 7,504 individuals. A positive skin prick response was defined as an allergen-to-histamine wheal ratio ≥1. To identify the clustering of inhalant allergic sensitization, we performed computational analysis using the four-parameter unified-Richards model. Results. Hierarchical cluster analysis grouped inhalant allergens into three clusters based on the Davies-Bouldin index (0.528): cluster 1 (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cluster 2 (mugwort, cockroach, oak, birch, cat, and dog), and cluster 3 (Alternaria tenus, ragweed, Candida albicans, Kentucky grass, and meadow grass). Computational modeling revealed that each allergen cluster had a different trajectory over the lifespan. Cluster 1 showed a high level (>50%) of sensitization at an early age (before 19 years), followed by a sharp decrease in sensitization. Cluster 2 showed a moderate level (10%–20%) of sensitization before 29 years of age, followed by a steady decrease in sensitization. However, cluster 3 revealed a low level (

Abstract Abundance of stromal cells and extracellular matrix (ECM) is observed in breast cancer, acting as a barrier for drug penetration and presenting a key issue for developing efficient therapeutics. In this study, we aimed to develop a three‐dimensional (3D) multicellular tumor model comprising cancer and stromal cells that could effectively mimic the drug resistance properties of breast cancer. Three different types of spheroid models were designed by co‐culturing breast cancer cells (MDA‐MB‐231) with three different types of stromal cells: human adipose‐derived stromal cells (hASCs), human bone marrow stromal cells, or human dermal fibroblasts. Compared with other models, in the hASC co‐culture model, tissue inhibitor of metalloproteinases‐1 (TIMP‐1) was highly expressed and the activity of matrix metalloproteinases was decreased, resulting in a higher ECM deposition on the spheroid surfaces. This spheroid model showed less drug penetration and treatment efficacy than the other models. TIMP‐1 silencing in hASCs reduced ECM protein expression and increased drug penetration and vulnerability. A quantitative structure–activity relationship study using multiple linear regression drew linear relationships between the chemical properties of drugs and experimentally determined permeability values. Drugs that did not match the drug‐likeness rules exhibited lower permeability in the 3D tumor model. Taken together, our findings indicate that this 3D multicellular tumor model may be used as a reliable platform for efficiently screening therapeutics agents for solid tumors.

IntroductionAlthough respiratory infections are common causes of acute respiratory failure (ARF) in patients with myositis-interstitial lung disease (ILD), limited data are available regarding the treatment outcomes by the etiologies of acute exacerbation (AE) of myositis-related ILD (infectious vs. non-infectious). Our study aimed to investigate the treatment outcomes of AE in patients with myositis-related ILD focused on the infectious etiology.MethodsA single center-based retrospective cohort was performed at Hanyang University Hospital between January 2000 and December 2018. A total of 36 patients with AE of myositis-related ILD were consecutively included. The exposure was the etiologies of AE in myositis-related ILD, and the outcome was in-hospital mortality. The infectious etiology was defined as confirmation of bacteria, virus, or fungus in samples obtained from the respiratory tract.ResultsAmong the 36 patients, 17 were diagnosed with infectious AE. The overall in-hospital mortality rate of AE was 47.2%. Although the mortality rate in patients with infectious AE was lower (41.2%) than in those with non-infectious AE (52.6%), this difference was not statistically significant (p = 0.724). A survival analysis showed no significant difference in mortality between patients with infectious AE versus those with non-infectious AE [risk ratio = 0.78, 95% CI = 0.38–1.59].ConclusionOur study showed that infectious AE is an important cause of mortality in patients with myositis-related ILD, showing a similar risk of mortality as non-infectious AE.

Meteorology and emissions play very important roles in the concentrations of air pollutants during severe haze/smog periods. This study compares the impacts of synoptic meteorology and nationwide/local emissions during high PM10 multi-event and non-event days in the Seoul Metropolitan Area (SMA). The multi-event and non-event cases were selected based on daily mean PM10 concentrations in Seoul from January 2014 to March 2019. The multi-event cases in spring and winter were closely associated with weak synoptic winds, while that in autumn was due to the strong winds at the rear side of a strong cold front, which induced the Asian dust event in northeastern China and Korea. The multi-event case in spring was found to be mainly due to series of migratory anticyclones, while winter case was due to the stagnant system after northerly winds. The surrounding low pressure systems as well as high pressure systems could be important to determine whether the synoptic systems would be stagnant or not. The fractional contributions of SMA emissions to the mean PM10 and PM2.5 concentrations were 24%-35% and 22%-35% for the multi-event cases, respectively. The contributions to the maximum PM10 and PM2.5 concentrations were larger than those to the mean concentrations by 16%-23% and 19%-26% for the multi-event cases, respectively.

Background The Bronchiectasis Health Questionnaire (BHQ) is a simple and repeatable, self-reporting health status questionnaire for bronchiectasis. We have translated the original version of the BHQ into Korean using a standardized methodology. The purpose of this study was to assess the validity of the Korean version of the BHQ (K-BHQ) with Korean patients. Methods Stable state patients with bronchiectasis from two academic hospitals were enrolled in this study. The validity was assessed by investigating the relationship between the K-BHQ scores and the Korean version of the Chronic Obstructive Pulmonary Disease Assessment Test (K-CAT) scores. We also investigated the relationship between the K-BHQ scores and other variables of the modified Medical Research Council’s (mMRC) dyspnea scale, lung function, and exacerbations. Results A total of 126 patients with bronchiectasis were enrolled. The mean age was 64.3 (standard deviation [SD], 9.7). Women comprised 53.2% of the patients. The mean forced expiratory volume in one second (FEV1) was 60% of the predicted value (SD, 18.9%); the mean K-CAT score was 17.6 (SD, 9.1). The K-BHQ scores correlated strongly with the K-CAT scores (r=–0.656, p1 (r=0.406, p

Respiratory disease: Effects of airborne ultrafine particles The ultrafine particles (UFPs) in air pollution aggravate respiratory illnesses via oxidative stress and inflammation, according to a review by South Korean and US researchers. Defined as particles less than 100 nm in diameter, UFPs are about 1/1000th the thickness of a human hair. Inhaling UFPs is known to aggravate respiratory illnesses such as asthma, but the mechanisms remain poorly understood. An-Soo Jang at Soonchunhyang University Bucheon Hospital, Korea and co-workers have reviewed the evidence on how UFPs harm the airways. They report that UFPs are readily deposited in the lungs, where they trigger production of reactive oxygen species, highly reactive molecules that cause cellular and DNA damage. UFPs also provoke airway inflammation, and long-term exposure can scar the lungs. These results will aid in protecting at-risk individuals from the harmful effects of air pollution.

Abstract Background There are few data available about hardcore smokers and their behavioral characteristics among the lung cancer screening (LCS) population. The study investigated the burden of hardcore smokers within the LCS population, and determine the characteristics of hardcore smokers using nationally representative data in South Korea. Methods We used data from 2007 to 2012 from the Korean National Health and Nutrition Examination Survey. This study enrolled current male smokers aged 55–74 years. Among them, subjects eligible for LCS were defined as these populations with smoking histories of at least 30 PY. Hardcore smoking was defined as smoking >15 cigarettes per day, with no plan to quit, and having made no attempt to quit. Multivariate logistic regression analyses were used to estimate associations between hardcore smokers and various sociodemographic and other variables. Results The proportion of hardcore smokers among those who met LCS eligibility criteria decreased from 2007 to 2012 (from 39.07 to 29.47% of the population) but did not change significantly thereafter (P = 0.2770), and that proportion was consistently 10–15% higher than that of hardcore smokers among all male current smokers. The proportion without any plan to quit smoking decreased significantly from 54.35% in 2007 to 38.31% in 2012. However, the smokers who had made no intentional quit attempt in the prior year accounted for more than half of those eligible for LCS, and the proportion of such smokers did not change significantly during the study period (50.83% in 2007 and 51.03% in 2012). Multivariate logistic regression analyses showed that hardcore smokers were older (OR = 1.05, 95% confidence interval [CI] 1.01–1.09) than non-hardcore smokers. Hardcore smokers exhibited higher proportion of depression (OR = 6.55, 95% CI 1.75–24.61) and experienced extreme stress more frequently (OR = 1.93, 95% CI 1.13–3.29). Smokers who did not receive smoking cessation education within the past year were significantly more likely to be hardcore smokers (OR = 4.15, 95% CI 1.30–13.22). Conclusions It is important to identify a subset of smokers unwilling or minimally motivated to quit within the context of lung cancer screening. Anti-smoking education should be enhanced to influence hardcore smokers’ behavior.

Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents [

Response to vaccines generally varies according to individual factors of the vaccinated subjects such as demographics and immune status. While there are various reports of factors associated with immunogenicity of mRNA COVID-19 vaccines, little is known about those of adenovirus vector vaccines. We conducted a prospective observational study to assess the relationships of antibody level with age, sex, body mass index (BMI), and adverse reactions (ARs) to an adenovirus vector vaccine, ChAdOx1 nCoV-19. Healthcare workers who planned to receive both the first and second injections of the ChAdOx1 nCoV-19 vaccine at Hanyang University Hospital, Seoul, Korea, were enrolled in the study. Seven days after each injection, participants were asked to complete an online adverse reaction survey. In addition, anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody concentration was measured 4 weeks after the second injection. All participants (n = 447, 100%) showed serologic positivity (≥ 0.8 U/mL) 4 weeks after the second injection of ChAdOx1 nCoV-19 vaccine. Furthermore, the anti-SARS-CoV-2 S protein RBD concentration was similar among groups when stratified by age, sex, BMI, or presence and severity of AR; multivariable linear regression found no associations between antibody response to the ChAdOx1 nCoV-19 vaccine and age, BMI, sex, and vaccine-induced ARs. In conclusion, age, sex, obesity, and ARs were not associated with antibody responses after two doses of ChAdOx1 nCoV-19 vaccination.

Objective: Limited data are available regarding the rates and risk factors of severe to serious adverse reactions (ARs) to the ChAdOx1 nCoV-19 vaccine.Methods: Eligible participants were healthcare workers who received their first dose of the ChAdOx1 nCoV-19 vaccine in either of two university hospitals in Seoul, Korea. We evaluated the type and severity of ARs 7 days after the first dose of the ChAdOx1 nCoV-19 vaccine using a questionnaire survey delivered via a smartphone application link.Results: Among the 1,603 participants who completed the survey, 684 (42.7%) participants experienced any kind of grade 3 to grade 4 AR. Being young (adjusted odds ratio [OR] for age 21–30 years = 2.49, 95% confidence interval [CI] = 1.75–3.56; adjusted OR for 31–40 years = 1.78, 95% CI = 1.22–2.62; adjusted OR for 41–50 years = 1.47, 95% CI = 1.03–2.11), being female (adjusted OR = 2.16. 95% CI = 1.62–2.89), and being underweight (adjusted OR = 1.61, 95% CI = 1.02–2.55) were identified as risk factors for grade 3 to grade 4 ARs. Among comorbidities, only diabetes mellitus (adjusted OR = 2.36, 95% CI = 1.03–5.53) was identified as a risk factor. When stratified by the type of AR, being young and being female were risk factors for both local and systemic grade 3 to grade 4 ARs.Conclusions: Being young, female, or underweight and having diabetes mellitus were associated with an increased risk of developing grade 3 to grade 4 ARs after receiving the first dose of the ChAdOx1 nCoV-19 vaccine.

Abstract Background Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM. Here, an in vitro three-dimensional (3D) respiratory mucosa-on-a-chip, composed of human nasal epithelial cells, fibroblasts, and endothelial cells, is used to recapitulate and better understand the effects of urban particulate matter (UPM) on human respiratory mucosa. Results We hypothesized that the first cells to contact with UPM, the nasal epithelial cells, would respond similar to the tissue microenvironment, and the 3D respiratory mucosa model would be a suitable platform to capture these events. First, whole transcriptome analysis revealed that UPM induced gene expression alterations in inflammatory and adhesion-related genes in human nasal epithelial cells. Next, we developed an in vitro 3D respiratory mucosa model composed of human nasal epithelial cells, fibroblasts, and endothelial cells and demonstrated that the model is structurally and functionally compatible with the respiratory mucosa. Finally, we used our model to expose human nasal epithelial cells to UPM, which led to a disruption in the integrity of the respiratory mucosa by decreasing the expression of zonula occludens-1 in both the epithelium and endothelium, while also reducing vascular endothelial cadherin expression in the endothelium. Conclusions We demonstrate the potential of the 3D respiratory mucosa model as a valuable tool for the simultaneous evaluation of multicellular responses caused by external stimuli in the human respiratory mucosa. We believe that the evaluation strategy proposed in the study will move us toward a better understanding of the detailed molecular mechanisms associated with pathological changes in the human respiratory system.

In this study, we investigate the meteorological characteristics and the effect of local emissions during high PM10 concentrations in the Seoul Metropolitan Area (SMA) by utilizing data from a high-resolution urban meteorological observation system network (UMS-Seoul) and The Air Pollution Model (TAPM). For a detailed analysis, days with PM10 concentrations higher than 80 μg m-3 for daily average PM10 concentration (classified as unhealthy by the Korean Ministry of Environment) in the Seoul Metropolitan Area (SMA) were classified into 3 Cases. Case I was defined as when the prevailing effect was from outside the SMA. Case II was defined as when the prevailing effect was a local effect with outside. Case III was defined as when the prevailing effect was local. Overall, high PM10 concentrations in the SMA mostly occurred under weak migratory anticyclone systems over the Korean Peninsula during warm temperatures. Prior to the PM10 concentration reaching the peak concentration, the pattern in each case was distinctive. After peak concentrations, however, the pattern for the 3 cases became less distinct. This study showed that nearly 50% of the high PM10 concentrations in the SMA occurred in spring and were governed by the conditions for Case II more than these for Cases I and III. In spring, the main sources of the high PM10 concentrations in the SMA were local emissions due to the predominance of weak winds and local circulation. The simulation showed that the non-SMA emissions were about 63 to 73% contribution to the spring high PM10 concentrations in the SMA. Specifically, local point sources including industrial combustion, electric utility, incineration and cement production facilities scattered around the SMA and could account for PM10 concentrations more than 10 μg m-3 in the SMA.

Abstract Background Cardiac fibrosis is the most common pathway of many cardiac diseases. To date, there has been no suitable in vitro cardiac fibrosis model that could sufficiently mimic the complex environment of the human heart. Here, a three-dimensional (3D) cardiac sphere platform of contractile cardiac microtissue, composed of human embryonic stem cell (hESC)-derived cardiomyocytes (CMs) and mesenchymal stem cells (MSCs), is presented to better recapitulate the human heart. Results We hypothesized that MSCs would develop an in vitro fibrotic reaction in response to treatment with transforming growth factor-β1 (TGF-β1), a primary inducer of cardiac fibrosis. The addition of MSCs improved sarcomeric organization, electrophysiological properties, and the expression of cardiac-specific genes, suggesting their physiological relevance in the generation of human cardiac microtissue model in vitro. MSCs could also generate fibroblasts within 3D cardiac microtissues and, subsequently, these fibroblasts were transdifferentiated into myofibroblasts by the exogenous addition of TGF-β1. Cardiac microtissues displayed fibrotic features such as the deposition of collagen, the presence of numerous apoptotic CMs and the dissolution of mitochondrial networks. Furthermore, treatment with pro-fibrotic substances demonstrated that this model could reproduce key molecular and cellular fibrotic events. Conclusions This highlights the potential of our 3D cardiac microtissues as a valuable tool for manifesting and evaluating the pro-fibrotic effects of various agents, thereby representing an important step forward towards an in vitro system for the prediction of drug-induced cardiac fibrosis and the study of the pathological changes in human cardiac fibrosis.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-β in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Background: Long-term corticosteroid (CS) use is associated with increased mortality in patients with asthma, and comorbid bronchiectasis is also associated with frequent asthma exacerbation and increased healthcare use. However, there is limited information on whether bronchiectasis further increases mortality in patients with CS-dependent asthma. This study examined the impact of bronchiectasis on mortality in patients with CS-dependent asthma. Methods: A retrospective cohort of patients with CS-dependent asthma ⩾18 years old was established using records from the Korean National Health Insurance Service database from 2005 to 2015. Patients with CS-dependent asthma with and without bronchiectasis were matched by age, sex, type of insurance, and Charlson comorbidity index. We evaluated the hazard ratio (HR) for all-cause mortality in patients with bronchiectasis compared with those without bronchiectasis. Results: The study cohort included 754 patients with CS-dependent asthma with bronchiectasis and 3016 patients with CS-dependent asthma without bronchiectasis. Patients with CS-dependent asthma with bronchiectasis had a higher all-cause mortality than those without bronchiectasis (8429/100,000 versus 6962/100,000 person-years, p

Alzheimer’s disease (AD) is a degenerative brain disease that is the most common cause of dementia. The incidence of AD is rapidly rising because of the aging of the world population. Because AD is presently incurable, early diagnosis is very important. The disease is characterized by pathological changes such as deposition of senile plaques and decreased concentration of the amyloid-beta 42 (Aβ42) peptide in the cerebrospinal fluid (CSF). The concentration of Aβ42 in the CSF is a well-studied AD biomarker. The specific peptide probe was screened through four rounds of biopanning, which included the phage display process. The screened peptide showed strong binding affinity in the micromolar range, and the enzyme-linked peptide assay was optimized using the peptide we developed. This diagnostic method showed specificity toward Aβ42 in the presence of other proteins. The peptide-binding site was also estimated using molecular docking analysis. Finally, the diagnostic method we developed could significantly distinguish patients who were classified based on amyloid PET images.

Pneumonia is a serious disease often accompanied by complications, sometimes leading to death. Unfortunately, diagnosis of pneumonia is frequently delayed until physical and radiologic examinations are performed. Diagnosing pneumonia with cough sounds would be advantageous as a non-invasive test that could be performed outside a hospital. We aimed to develop an artificial intelligence (AI)-based pneumonia diagnostic algorithm. We collected cough sounds from thirty adult patients with pneumonia or the other causative diseases of cough. To quantify the cough sounds, loudness and energy ratio were used to represent the level and its spectral variations. These two features were used for constructing the diagnostic algorithm. To estimate the performance of developed algorithm, we assessed the diagnostic accuracy by comparing with the diagnosis by pulmonologists based on cough sound alone. The algorithm showed 90.0% sensitivity, 78.6% specificity and 84.9% overall accuracy for the 70 cases of cough sound in pneumonia group and 56 cases in non-pneumonia group. For same cases, pulmonologists correctly diagnosed the cough sounds with 56.4% accuracy. These findings showed that the proposed AI algorithm has value as an effective assistant technology to diagnose adult pneumonia patients with significant reliability.

Pnuemocystis jirovecii pneumonia (PJP) is one of leading causes of acute respiratory failure in patients infected with human immunodeficiency virus (HIV), and the mortality rate remains high in mechanically ventilated HIV patients with PJP. There are several reported cases who received extracorporeal membrane oxygenation (ECMO) treatment for respiratory failure associated with severe PJP in HIV-infected patients. We report a patient who was newly diagnosed with HIV and PJP whose condition worsened after highly active antiretroviral therapy (HAART) initiation and progressed to acute respiratory distress syndrome requiring veno-venous ECMO. The patient recovered from PJP and is undergoing treatment with HAART. ECMO support can be an effective life-saving salvage therapy for acute respiratory failure refractory to mechanical ventilation following HAART in HIV-infected patients with severe PJP.