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Background: In understanding the pathophysiology of pulmonary fibrosis (PF), macrophage plasticity has been implicated with a crucial role in the fibrogenic process. Growing evidence indicates that accumulation of M2 macrophages correlates with the progression of PF, suggesting that targeted modulation of molecules that influence M2 macrophage polarization could be a promising therapeutic approach for PF. Here, we demonstrated a decisive role of C-X-C motif chemokine ligand 11 (CXCL11) in driving M1 macrophage polarization to alleviate PF in the bleomycin-induced murine model., Results: We intravenously administered secretome derived from naïve (M0) and polarized macrophages (M1 and M2) into PF mice and found that lung fibrosis was effectively reversed in only the M1-treated group, with modulation of the M1/M2 ratio toward the ratio of the control group. These findings suggest that the factors secreted from M1 macrophages contribute to alleviating PF by targeting macrophages and reshaping the immunofibrotic environment in a paracrine manner. Secretome analysis of macrophages identified CXCL11 as an M1-specific chemokine, and administration of recombinant CXCL11 effectively improved fibrosis with the reduction of M2 macrophages in vivo. Furthermore, a mechanistic in vitro study revealed that CXCL11 reprogrammed macrophages from M2 to M1 through the activation of pERK, pAKT, and p65 signaling., Conclusions: Collectively, we demonstrate an unprecedented role for M1 macrophage-derived CXCL11 as an inducer of M1 macrophage polarization to revert the fibrogenic process in mice with PF, which may provide a clinically meaningful benefit., Competing Interests: Declarations Ethics approval and consent to participate The experiment was approved by the Institutional Animal Care and Use Committee (IACUC), Kangwon National University (IACUC No. KW-220509-1). Consent for publication Not applicable. Competing interests The authors have declared that no competing interest exists., (© 2024. The Author(s).)

Background: Effective interventions for overall healthy subjects with mild cognitive impairment are currently limited. Choline alphoscerate (alpha glyceryl phosphorylcholine, αGPC) is a choline-containing phospholipid used to treat cognitive function impairments in specific neurological conditions. This study aimed to investigate the efficacy and safety of αGPC in individuals diagnosed with mild cognitive impairment., Methods: In this multicenter, randomized, placebo-controlled trial, 100 study subjects with mild cognitive impairment underwent a double-blind SHCog™ soft capsule (600 mg αGPC) or placebo treatment for 12 weeks. The primary efficacy outcome included changes from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety assessments included regular monitoring of adverse events, and clinical laboratory tests were conducted at baseline and the end of the trial., Results: After 12 weeks of αGPC treatment, the ADAS-cog score decreased by 2.34 points, which was significantly greater than the change observed in the placebo group. No serious AEs were reported, and no study subjects discontinued the intervention because of AEs. There was no significant difference in incidence rate of AEs between the αGPC group and the placebo group., Conclusion: This study suggests that αGPC is a safe and effective intervention for improving cognitive function in study subjects with mild cognitive impairment., Trial Registration: Clinical Research Information Service; Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SH_CAPK08 on cognitive function improvement in mild cognitive decline., (© 2024. The Author(s).)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored., Methods: A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay., Results: Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis., Conclusions: The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy., (© 2024. The Author(s).)

Background: This study aimed to evaluate the femoral tunnel position and fiber length of the anterolateral ligament (ALL) reconstruction compared with the natural anatomy of the ALL. We also evaluated whether the femoral tunnel position would affect residual pivot shift., Methods: This study was a retrospective review of 55 knees that underwent ALL reconstruction considering the anatomical and functional aspects, during primary anterior cruciate ligament (ACL) reconstruction in the presence of a high-grade pivot shift or revisional ACL reconstruction. We determined the position of the femoral tunnel and the length of graft using a three-dimensional (3D)-computed tomography (CT) model after ALL reconstruction. We also measured graft excursion during surgery and examined pivot shift 2 years after surgery. We conducted a subgroup analysis of femoral tunnel position, fiber length, isometricity, and residual pivot shift depending on whether the tunnel was anterior or posterior to the lateral epicondyle (LE). We also performed a subgroup analysis depending on whether the ACL reconstruction was primary or revisional., Results: The mean femoral tunnel position was 2.04 mm posterior and 14.5 mm proximal from the center of the LE. The mean lengths of the anterior and posterior fibers were 66.6 and 63.4 mm, respectively. The femoral tunnel was positioned more proximally than the anatomical position, and both anterior and posterior ALL fibers were longer than the natural anatomy. The anteroposterior femoral tunnel position was significantly correlated with anterior (p = 0.045) and posterior (p = 0.037) fiber excursion. In the subgroup analysis, there was no significant difference in the residual pivot shift between the posterior and anterior tunnel positions. However, there were significant differences for proximal position (p < 0.001) and fiber length (p = 0.006). There was no significant difference between primary and revisional ACL regarding femoral tunnel position and fiber lengths., Conclusion: It is challenging to reproduce both anatomical and functional aspects of ALL reconstruction in both primary and revision ACL reconstruction. Especially for functional reconstruction, the femoral tunnel tended to be positioned more proximally than the anatomical position. However, the femoral tunnel position did not affect functional clinical outcomes at the 2-year follow-up., Level of Evidence: Level IV Case series., (© 2024. The Author(s).)

Background: Although pregnancy-associated heart failure with preserved ejection fraction (HFpEF) is increasing and contributing to maternal morbidity, little is known about its impact on pregnancy. We examined the risk factors for and adverse pregnancy outcomes of HFpEF in pregnant women., Methods: We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2009 to 2020 using the perinatal database of seven multicenters. Cases of HFpEF were identified using the International Classification of Diseases and echocardiography findings. The patients were categorized into the HFpEF and control groups. Risk factors were evaluated using multivariate logistic regression analysis to generate odds ratios (OR) and 95% confidence intervals (CI). Furthermore, adjusted associations between HFpEF and adverse pregnancy outcomes were determined. Risk scores for the stratification of women at a high risk of HFpEF were calculated using a statistical scoring model., Results: Of the 34,392 women identified, 258 (0.76%) were included in the HFpEF group. In multivariate analysis, HFpEF was significantly associated with old maternal age (OR, 1.04; 95% CI 1.02-1.07), multiple pregnancy (OR, 2.22; 95% CI 1.53-3.23), rheumatic disease (OR, 2.56; 95% CI 1.54-4.26), pregnancy induce hypertension (OR 6.02; 95% CI 3.61-10.05), preeclampsia (OR 24.66; 95% CI 18.61-32.66), eclampsia or superimposed preeclampsia (OR 32.74; 95% CI 21.60-49.64) and transfusion in previous pregnancy (OR 3.89; 95% CI 1.89-8.01). A scoring model to predict HFpEF with those factors achieved an area under the curve of 0.78 at cutoff value of 3. Women with HFpEF also had increased odds ratios of intensive care unit admission during the perinatal period (odds ratio, 5.98; 95% confidence interval, 4.36-8.21) and of postpartum hemorrhage (odds ratio, 5.98; 95% confidence interval, 2.02-3.64)., Conclusions: Pregnancy-associated HFpEF is associated with adverse pregnancy outcomes. A scoring model may contribute to screening HFpEF using echocardiography and preparing adverse pregnancy outcomes., (© 2024. The Author(s).)

Background: Chronic obstructive pulmonary disease (COPD) is associated with a high readmission rate and poses a significant disease burden. South Korea initiated pilot projects on transitional care services (TCS) to reduce readmissions. However, evidence from cost-effectiveness analyses remains undiscovered. This study aimed to evaluate the cost-effectiveness of TCS in patients with COPD from the healthcare system' perspective., Method: A cost-utility analysis was conducted using a Markov model containing six components of possible medical use after discharge. Transition probabilities and medical costs were extracted from the National Health Insurance Service Senior Cohort (NHIS-SC), and utility data were obtained from published literature. Sensitivity analyses were performed to test the robustness of the results., Results: Conducting TCS produced an incremental quality-adjusted life years gain of 0.231, 0.275, 0.296 for those in their 60s, 70s, and 80s, respectively, and cost savings of $225.16, $1668, and $2251.64 for those in their 60s, 70s, and 80s, respectively, per patient over a 10-year time horizon. The deterministic sensitivity analysis indicated that the TCS cost and the cost of readmission by other diseases immensely impact the results. The probabilistic sensitivity analyses showed that the probability that the incremental cost-effectiveness ratio is below $23,050 was over 85%, 93%, and 97% for those in the 60s, 70s, and 80s, respectively., Conclusions: TCS was the dominant option compared to usual care. However, it is advantageous to the healthcare budget preferentially consider patients aged over 70 years with severe TCS symptoms. In addition, it is essential to include the management of underlying comorbidities in TCS intervention., Trial Registration: Clinical Research Information Service (CRIS), KCT0007937. Registered on 24 November 2022., (© 2024. The Author(s).)

Background: Although preserved ratio impaired spirometry (PRISm) has been determined to have poor prognosis, it is a heterogeneous state, and studies regarding its prognosis in Asians are limited. This study investigated the long-term all-cause and cardiovascular mortality of patients with PRISm compared with those of patients with chronic obstructive pulmonary disease (COPD) and normal individuals in the Korean middle-aged general population., Methods: Participants were recruited between 2001 and 2002 from a community-based prospective cohort in South Korea. Mortality data were collected over a 16.5-year mean follow-up period. The all-cause and cardiovascular mortality risks of PRISm were compared between patients with COPD and healthy controls., Results: The PRISm group had a mean age of 53.4 years and mean body mass index of 24.9 kg/m 2 ; furthermore, 55.2% of the PRISm patients had never smoked, and the prevalence of comorbidities was not higher than that in the other groups. Compared with normal individuals, PRISm patients did not show increased all-cause mortality, whereas COPD patients showed increased all-cause mortality (PRISm: adjusted hazard ratio [aHR], 1.19; 95% confidence interval [CI], 0.85-1.65; COPD: aHR, 1.34, 95% CI, 1.07-1.69). Furthermore, the PRISm patients did not show increased cardiovascular mortality compared with normal individuals (PRISm: aHR, 1.65; 95% CI, 0.92-2.95; COPD: aHR, 1.83; 95% CI, 1.09-3.07)., Conclusion: In our population-based cohort, all-cause and cardiovascular mortality risk did not increase in individuals with PRISm compared with normal individuals. Further studies are needed to distinguish a lower-risk subgroup of PRISm with certain characteristics, such as middle-aged, light-smoking Asians without additional cardiovascular risk., (© 2023. The Author(s).)

Background/aims: We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability., Methods: We reviewed the medical records of patients aged 6-18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient's subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near., Results: Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p < 0.001). The mean control scores of patients with controllability (distance: 1.9, near: 1.5) were lower compared with patients without controllability (distance: 3.0, near: 2.2), reflecting a better level of control. Patients with controllability had a better surgical outcome than those without controllability, as analyzed by log-rank test (p < 0.001). Larger preoperative ocular exodeviation at distance (hazard ratio [HR] = 1.083, confidence interval [CI] = 1.018-1.151, p = 0.012) and near (HR = 1.102, CI = 1.037-1.172, p = 0.002) were significantly related to recurrence in patients with controllability., Conclusions: Patients with controllability showed better surgical outcomes, later exotropia onset, and better level of control than patients without controllability. Preoperative ocular exodeviation was a significant factor influencing favorable outcomes in patients with controllable exotropia., (© 2023. The Author(s).)

Background: Codonopsis pilosula (Franch.) Nannf. is a medicinal plant traditionally used in China, Korea, and Japan to treat many diseases including poor gastrointestinal function, low immunity, gastric ulcers, and chronic gastritis. The increasing therapeutic and preventive use of C. pilosula has subsequently led to depletion of the natural populations of this species thus necessitating propagation of this important medicinal plant. Here, we developed an efficient and effective in vitro propagation protocol for C. pilosula using apical shoot segments. We tested various plant tissue culture media for the growth of C. pilosula and evaluated the effects of plant growth regulators on the shoot proliferation and rooting of regenerated C. pilosula plants. Furthermore, the tissues (roots and shoots) of maternal and in vitro-regenerated C. pilosula plants were subjected to Fourier-transform near-infrared (FT-NIR) spectrometry, Gas chromatography-mass spectrometry (GC-MS), and their total flavonoids, phenolics, and antioxidant capacity were determined and compared., Results: Full-strength Murashige and Skoog (MS) medium augmented with vitamins and benzylaminopurine (1.5 mg·L -1 ) regenerated the highest shoot number (12 ± 0.46) per explant. MS medium augmented with indole-3-acetic acid (1.0 mg·L -1 ) produced the highest root number (9 ± 0.89) and maximum root length (20.88 ± 1.48 mm) from regenerated C. pilosula shoots. The survival rate of in vitro-regenerated C. pilosula plants was 94.00% after acclimatization. The maternal and in vitro-regenerated C. pilosula plant tissues showed similar FT-NIR spectra, total phenolics, total flavonoids, phytochemical composition, and antioxidant activity. Randomly amplified polymorphic DNA (RAPD) test confirmed the genetic fidelity of regenerated C. pilosula plants., Conclusions: The proposed in vitro propagation protocol may be useful for the rapid mass multiplication and production of high quality C. pilosula as well as for germplasm preservation to ensure sustainable supply amidst the ever-increasing demand., (© 2023. The Author(s).)

In an aging society, quality of life improvement is emerging as an important issue, and as implants are accepted as the core of oral rehabilitation treatment, competition for leadership in developing related technologies is intensifying. In this trend, unlike what is evident in the literature, the patent landscape shows the status of industrial-based technology development. A database analysis of a total of 32,237 dental implant patents shows improvements in technology, diverse geographical characteristics, and new advances toward technological convergence in this field. Technologically, dental implant technology has shown a tendency to develop from conventional implant materials and surface treatment technologies to new material technologies making use of substances such as pure zirconium and tantalum or software technologies related to diagnosis and prognosis. Regionally, dental implant technology, which was developed mainly in Europe and the Unites States in the past, is growing explosively in East Asian countries accompanied by the recent growth of the Asian market. In summary, dental implant technology seems to be developing while trying to converge with various technological areas based on the local market environment. Therefore, it is necessary to develop a new dental implant material technology that is highly applicable to the development of hybrid information/communication technology and is suitable for a new manufacturing method. Our study may provide important information to help basic and translational researchers and their financial supporters set their research directions in advancing the development of dental implants., (© 2022. The Author(s).)

Background: The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses., Methods: The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems., Results: At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period., Conclusion: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information., (© 2022. The Author(s).)

Background/aims: To investigate the sequential change in intraocular pressure (IOP) during strabismus surgery in patients with thyroid eye disease (TED)., Methods: This prospective study included patients with TED who underwent strabismus surgery (medial rectus [MR], inferior rectus [IR], and superior rectus [SR] recession) between March 2018 and December 2020. The IOP was measured six times during surgery (5 min after intubation, after isolation of the muscle using a hook and dissection of the surrounding tissue, immediately before muscle detachment, immediately after muscle detachment, after reattachment of the muscle, and after closure of the conjunctiva)., Results: Thirty-five eyes of 18 patients were included. The mean IOP at first was 21.1 mmHg, which significantly increased to 28.6 mmHg after muscle isolation. The IOP significantly decreased to 15.5 mmHg after muscle detachment. This increased to 19.1 mmHg after muscle reattachment. The last IOP was 18.9 mmHg. There were similar patterns of sequential change in the IOP among the three muscles. The MR showed the highest increase in IOP. The IR showed the lowest mean IOP compared with the other two muscles., Conclusions: The IOP was elevated during the isolation and dissection of the surrounding muscle tissue, especially in the MR. The IOP significantly decreased after muscle detachment and was maintained until the last measurement, even after muscle reattachment. IR showed the lowest IOP among the three muscles during surgery., (© 2022. The Author(s).)

Background: Data on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV 1 ) and effects of inhaled corticosteroid (ICS) in Korean COPD patients., Methods: Stable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/μL). FEV 1 changes were analyzed over a 3-year follow-up period., Results: Of 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10-2.03). An accelerated FEV 1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV 1 change: - 12.2 mL/y and - 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV 1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (- 19.2 mL/y and - 4.5 mL/y, with and without ICS therapy, respectively)., Conclusions: The annual rate of decline in FEV 1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV 1 ., (© 2022. The Author(s).)

Background: The purpose of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) other than bisphenol A (BPA) and BPA substitutes on placental cells., Methods: HTR-8/SVneo cells were treated with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, which is used as a substitute for BPA-free products. After confirming the dose response for each reagent using the prepared cells, the cells were incubated for 24, 48, and 72 h. Cell viability was confirmed using the XTT assay. Each experiment was performed with the minimum number of samples (n = 3) required for statistical analysis. The results were analyzed using t-tests; p < 0.05 was considered statistically significant., Results: After treatment with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, the absorbance measured using the XTT assay decreased significantly with increasing concentration. The absorbance decreased significantly over time following treatment with each endocrine disruptor at the concentration confirmed by the dose-response analysis., Conclusions: This study showed that anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol-a BPA substitute-affect cell viability and necrosis in the placental cell line. The study indicates the serious effects of PAHs that negatively affect pregnancy but were previously unknown. Further, this study would serve as a reference for the identification of harmful PAHs during pregnancy prognosis in women who are more susceptible to PAH exposure., (© 2022. The Author(s).)

Background: Chronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores., Methods: This study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV 1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB., Results: Among the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV 1 , FEV 1 /FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV 1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB., Conclusions: CB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB., (© 2022. The Author(s).)

Background: Higher soluble receptor for advanced glycation end product (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship remains uncertain when the advanced glycation end-product specific receptor (AGER) gene is involved. We aimed to analyse the association between sRAGE levels and emphysema according to the genotypes of rs2070600 in the AGER gene., Methods: We genotyped rs2070600 and measured the plasma concentration of sRAGE in each participant. Emphysema was quantified based on the chest computed tomography findings. We compared sRAGE levels based on the presence or absence and severity of emphysema in each genotype. Multiple logistic and linear regression models were used for the analyses., Results: A total of 436 participants were included in the study. Among them, 64.2% had chronic obstructive pulmonary disease and 34.2% had emphysema. Among the CC-genotyped participants, the sRAGE level was significantly higher in participants without emphysema than in those with emphysema (P < 0.001). In addition, sRAGE levels were negatively correlated with emphysema severity in CC-genotyped patients (r = - 0.268 P < 0.001). Multiple regression analysis revealed that sRAGE was an independent protective factor for the presence of emphysema (adjusted odds ratio, 0.24; 95% confidence interval (CI) 0.11-0.51) and severity of emphysema (β = - 3.28, 95% CI - 4.86 to - 1.70) in CC-genotyped participants., Conclusion: Plasma sRAGE might be a biomarker with a protective effect on emphysema among CC-genotyped patients of rs2070600 on the AGER gene. This is important in determining the target group for the future prediction and treatment of emphysema., (© 2022. The Author(s).)

Background: Hair cortisol concentration (HCC) has received attention as a useful marker of stress, but evidence on associations between psychological factors and cortisol concentration is inconsistent. The purpose of this study was to investigate the sex differences in the relationship between cortisol concentration and psychological factors in healthy young adults., Methods: A total of 205 (103 females, 102 males) healthy young adults participated. HCC and various stress-related psychological measures were compared between sexes. Multiple linear regression analyses were performed to assess associations between HCC and stress-related psychological measures for all participants and for each sex., Results: The difference in HCC according to sex was not significant. The reported number of stressful life events in the past year, stress perception, depressive and anxiety-related symptoms, and emotion dysregulation were not different between sexes, either. The association between HCC and emotion dysregulation was significant in females but not males., Conclusion: We observed a sex-specific association between HCC and psychological factors. Our findings may imply that HCC could be a useful biomarker of stress and stress-related emotion dysregulation in healthy young women., (© 2021. The Author(s).)

Background: With the emergence of bronchiectasis as a common respiratory disease, epidemiological data have accumulated. However, the prevalence and impact of psychological comorbidities were not sufficiently evaluated. The present study examined the prevalence of depression and its associated factors in patients with bronchiectasis., Methods: This study involved a multicenter cohort of bronchiectasis patients recruited from 33 pulmonary specialist hospitals. The baseline characteristics and bronchiectasis-related factors at enrollment were analyzed. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9)., Results: Of the 810 patients enrolled in the study, 168 (20.7%) patients had relevant depression (PHQ-9 score ≥ 10), and only 20 (11.9%) patients had a diagnosis of depression. Significant differences were noted in the depressive symptoms with disease severity, which was assessed using the Bronchiectasis Severity Index and E-FACED (all p < 0.001). Depressive symptoms inversely correlated with quality-of-life (r = - 0.704, p < 0.001) and positively correlated with fatigue severity score (r = 0.712, p < 0.001). Multivariate analysis showed that depression was significantly associated with the modified Medical Research Council dyspnea scale ≥ 2 (OR 2.960, 95% CI 1.907-4.588, p =  < 0.001) and high number of exacerbations (≥ 3) in the previous year (OR 1.596, 95% CI 1.012-2.482, p = 0.041)., Conclusions: Depression is common, but its association with bronchiectasis was underrecognized. It negatively affected quality-of-life and presented with fatigue symptoms. Among the bronchiectasis-related factors, dyspnea and exacerbation were closely associated with depression. Therefore, active screening for depression is necessary to optimize the treatment of bronchiectasis., Trial Registration: The study was registered at Clinical Research Information Service (CRiS), Republic of Korea (KCT0003088). The date of registration was June 19th, 2018., (© 2021. The Author(s).)

Background: Although the World Health Organization and health authorities in most countries recommend that pregnant women receive inactivated influenza virus vaccines, coverage remains low. This study aimed to investigate (1) the proportion of pregnant women who received an influenza vaccination and influencing factors and (2) the proportion of obstetrics and gynecology (OBGYN) doctors who routinely recommend influenza vaccination to pregnant women and influencing factors., Methods: Two separate, anonymized questionnaires were developed for physicians and pregnant and postpartum women and were distributed to multicenters and clinics in South Korea. The proportions of women who received influenza vaccination during pregnancy and OBGYN doctors who routinely recommend the influenza vaccine to pregnant women were analyzed. Independent influencing factors for both maternal influenza vaccination and OBGYN doctors' routine recommendations to pregnant women were analyzed using log-binomial regression analysis., Results: The proportion of self-reported influenza vaccination during pregnancy among 522 women was 63.2%. Pregnancy-related independent factors influencing maternal influenza vaccination were "(ever) received information about influenza vaccination during pregnancy" (OR 8.9, 95% CI 4.17-19.01), "received vaccine information about from OBGYN doctors" (OR 11.44, 95% CI 5.46-24.00), "information obtained from other sources" (OR 4.38, 95% CI 2.01-9.55), and "second/third trimester" (OR 2.41, 95% CI 1.21-4.82).. Among 372 OBGYN doctors, 76.9% routinely recommended vaccination for pregnant women. Independent factors effecting routine recommendation were "working at a private clinic or hospital" (OR 5.33, 95% CI 2.44-11.65), "awareness of KCDC guidelines" (OR 3.11, 95% CI 1.11-8.73), and "awareness of the 2019 national free influenza vaccination program for pregnant women" (OR 4.88, 95% CI 2.34-10.17). OBGYN doctors most commonly chose 'guidelines proposed by the government or public health (108, 46%) and academic committees (59, 25%), as a factor which expect to affect the future recommendation CONCLUSION: This study showed that providing information about maternal influenza vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Closer cooperation between the government and OBGYN academic societies to educate OBGYN doctors might enhance routine recommendations., (© 2021. The Author(s).)

Background: Renal medullary carcinomas (RMCs) are rare kidney cancers that occur in adolescents and young adults of African ancestry. Although RMC is associated with the sickle cell trait and somatic loss of the tumor suppressor, SMARCB1, the ancestral origins of RMC remain unknown. Further, characterization of structural variants (SVs) involving SMARCB1 in RMC remains limited., Methods: We used linked-read genome sequencing to reconstruct germline and somatic haplotypes in 15 unrelated patients with RMC registered on the Children's Oncology Group (COG) AREN03B2 study between 2006 and 2017 or from our prior study. We performed fine-mapping of the HBB locus and assessed the germline for cancer predisposition genes. Subsequently, we assessed the tumor samples for mutations outside of SMARCB1 and integrated RNA sequencing to interrogate the structural variants at the SMARCB1 locus., Results: We find that the haplotype of the sickle cell mutation in patients with RMC originated from three geographical regions in Africa. In addition, fine-mapping of the HBB locus identified the sickle cell mutation as the sole candidate variant. We further identify that the SMARCB1 structural variants are characterized by blunt or 1-bp homology events., Conclusions: Our findings suggest that RMC does not arise from a single founder population and that the HbS allele is a strong candidate germline allele which confers risk for RMC. Furthermore, we find that the SVs that disrupt SMARCB1 function are likely repaired by non-homologous end-joining. These findings highlight how haplotype-based analyses using linked-read genome sequencing can be applied to identify potential risk variants in small and rare disease cohorts and provide nucleotide resolution to structural variants., (© 2021. The Author(s).)

Background: Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy., Methods: In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI., Results: The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p < 0.001, p = 0.001, p = 0.004, respectively). BMI, prostate volume, Gleason score, resection margin, N-stage, M-stage and IOM mass index was not associated with BCR (p > 0.05)., Conclusions: Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.

Background: Failed treatment of subtrochanteric fractures commonly leads to pain, limping, and poor limb function. Cementless total hip arthroplasty (THA) could serve as an efficient salvage procedure in such cases. This study aimed to evaluate the outcomes and complications of salvage THA in failed subtrochanteric fracture fixation cases., Methods: From January 2001 to December 2017, cementless THA for failed treatment of subtrochanteric fractures was performed in 18 hips of 11 men and 7 women (average age, 74 years; age range, 57.0-89.0 years). Patients were followed up for clinical and radiological assessments in terms of implant survival and complications after a minimum follow-up of 2 years. The Wagner femoral stems (Zimmer, Warsaw, USA) were used in all 18 patients (100%), with the long-length stem (Wagner SL stem) and standard-length stem (Wagner cone stem) used in 11 and 7 patients, respectively., Results: The mean follow-up period was 5.2 years (range: 2.2-10.8 years). The mean Harris hip score (HHS) was 38.2 (range: 24-56) preoperatively and 85.4 (range: 79-92) at the last follow-up. The mean postoperative limb length discrepancy was 6.4 mm (range: 4-9 mm). Only one patient underwent revision due to bone in-growth failure of the femoral stem. One patient had an episode of postoperative dislocation and was treated with closed reduction without reoccurrence. Delayed union of the fracture site occurred in one patient. Patients who were previously treated with an intramedullary nail had a significantly shorter surgical duration, lesser intraoperative blood loss, and fewer blood transfusions than those who were previously treated with plate and screws. Kaplan-Meier survival rate with an endpoint of revision was 94.4% (95% confidence interval 72.7-99.9) at 5 years., Conclusion: Our results indicate that cementless THA is a beneficial and effective procedure for salvaging the failed treatment of subtrochanteric fractures. The Wagner conical prosthesis has shown satisfactory function outcomes, stable fixation, and survival rate for these complex situations. However, attention should be paid to increased operation time, blood loss, and complications when performing THA for subtrochanteric fractures with failed fixation devices especially, plates and screws.

Backgrounds: This study aimed to investigate the characteristic deformities of the hip in multiple hereditary exostoses patients (MHE) and its association with the hip impingement syndrome., Materials and Methods: Between 2001 and 2019, total 51 patients (102 hips) were evaluated in this study. Patients with MHE were classified to femoro-acetabular impingement (FAI) symptom group, ischio-femoral impingement (IFI) symptom group and non-impingement symptom group by comparing the symptoms, clinical signs and imaging studies. To assess the morphometry of the hip in patients with MHE, the femoral neck-shaft angle, Sharp's acetabular angle and center-edge (CE) angle were evaluated. Alpha angle was further evaluated to investigate the FAI using radiographs, and the minimum ischio-femoral distance was further measured to investigate the IFI using computed-tomographic (CT) study., Results: On hip impingement symptom analysis, FAI symptom and IFI symptom were confirmed in 14 hip joints and 18 hip joints, respectively. Unlike general population, the number of the hip with IFI-symptom was higher than those with FAI symptom in this study. In morphometric evaluation of MHE hips, coxa valga was most prominent deformity with occasional tendency of mild acetabular dysplasia. In a comparison of morphometric study between the impingement symptom group and non-symptom group, the FAI symptom showed significant differences of morphometric measure values than those of the non-symptom group (FAI symptom group vs. Non-FAI symptom group; Femoral neck-shaft angle (153.9 vs 142.6), Sharp's angle (45.0 vs 41.5), CE angle (21.1 vs 28.8) and alpha angle (76.7 vs 57.9)). Similarly, the IFI symptom group also showed significant differences of morphometric measure values than those of the non-symptom group (IFI-symptom vs. Non-IFI symptom; Femoral neck-shaft angle (150.9 vs 142.7), Sharp's angle (44.7 vs 41.4), CE angle (21.1 vs 29.3) and alpha angle (73.3 vs 56.8)). In addition, the minimum ischio-femoral distance measured using CT was significantly decreased in the IFI symptom group (IFI symptom group: 6.6, Non-IFI symptom group: 16.4)., Conclusion: The results suggest that the characteristic deformities represented by coxa valga in the MHE hip act as an offset for FAI symptoms, on the contrary, act as a trigger for IFI symptoms., Level of Evidence: Level III.

Background: With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. However, with mortality risks associated with this concomitant use yet to be examined, it remains unclear as to whether this concomitant therapy offers any benefits in treating depression., Methods: We conducted a population-based cohort study using South Korea's nationwide healthcare database from 2002 to 2017. Of 2.6 million patients with depression, we identified 612,729 patients with incident depression and newly prescribed ADs or BZDs, by excluding those with a record of diagnosis or prescription within the 2 years prior to their incident diagnosis. We classified our study cohort into two discrete groups depending on the type of AD treatment received within 6 months of incident diagnosis-AD monotherapy and AD plus BZD (AD+BZD) therapy. We matched our study cohort in a 1:1 ratio using propensity scores to balance baseline characteristics and obtain comparability among groups. The primary outcome was all-cause mortality, and patients were followed until the earliest of outcome occurrence or end of the study period. We conducted multivariable Cox proportional hazards regression analysis to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) for the risk of mortality associated with AD+BZD therapy versus AD monotherapy., Results: The propensity score-matched cohort had 519,780 patients with 259,890 patients in each group, where all baseline characteristics were well-balanced between the two groups. Compared to AD monotherapy, AD+BZD therapy was associated with an increased risk of all-cause mortality (adjusted HR, 1.04; 95% CI, 1.02 to 1.06)., Conclusions: Concomitantly initiating BZDs with ADs was associated with a moderately increased risk of mortality. Clinicians should therefore exercise caution when deciding to co-prescribe BZDs with ADs in treating depression, as associated risks were observed.

Background: Pregnant women are at high risk of influenza-related morbidity and mortality. In addition, maternal influenza infection may lead to adverse birth outcomes. However, there is insufficient data on long-term impact of maternal influenza infection., Methods: This study was conducted to assess the impact of maternal influenza infection on birth outcomes and long-term influence on infants by merging the Korea National Health Insurance (KNHI) claims database and National Health Screening Program for Infants and Children (NHSP-IC). Mother-offspring pairs were categorized by maternal influenza infection based on the ICD-10 code., Results: Multivariate analysis revealed that maternal influenza infection significantly increased the risk of preterm birth (OR 1.408) and low birth weight (OR 1.198) irrespective of gestational age. The proportion of low birth weight neonates was significantly higher in influenza-infected women compared to those without influenza. However, since the fourth health screening (30-80 months after birth), the fraction of underweight was no longer different between children from influenza-infected and non-infected mothers, whereas the rates of overweight increased paradoxically in those born to mothers with influenza infection., Conclusions: Maternal influenza infection might have long-term effects on the health of children and adolescents even after infancy.

Background: Soluble urate has been shown to serve as an antioxidant, especially in the central nervous system. Although there are intriguing data suggesting that low levels of serum urate are associated with worse outcomes in neurodegenerative diseases, its impact on mental health has not been adequately assessed. Thus, we aimed to investigate the association between serum urate and depression using a large, nationally representative sample., Methods: Information on participants' socio-demographic characteristics as well as physical and mental health conditions were retrieved from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016 dataset. The Patient Health Questionnaire (PHQ)-9 was applied to identify depressive symptoms. Analyses were stratified by age: young adults (aged 19-39 years), middle-aged adults (aged 40-59 years), and older adults (aged 60 years and older)., Results: A total of 5332 participants were included. Serum urate concentrations were divided into sex-specific quartiles based on their distribution: ≤ 4.9 (Q1), 5.0-5.7 (Q2), 5.8-6.6 (Q3), and ≥ 6.7 (Q4) mg/dL in men and ≤ 3.7 (Q1), 3.8-4.3 (Q2), 4.4-4.9 (Q3), and ≥ 5.0 (Q4) mg/dL in women. There was a significant negative linear relationship between serum urate quartiles and PHQ-9 scores in older adults (p for trend = 0.020 in men and p for trend = 0.048 in women). Compared to high levels (Q3 and Q4) of serum urate, low levels (Q1 and Q2) were significantly associated with the overall burden of depression in older women (OR 1.78, 95% CI 1.21, 2.61) and clinically relevant depression in older men (OR 3.35, 95% CI 1.16, 9.70), even after adjustment., Conclusions: Based on the KNHANES data, low levels of serum urate are associated with a higher prevalence of depression in older adults. This may have clinical implications for mental health.

Background: Vascular calcification (VC) is a risk factor for cardiovascular disease in end-stage renal disease (ESRD) patients undergoing maintenance haemodialysis (MHD). However, evidence is still insufficient about the association between dialysis parameters and VC. Thus, this study was to evaluate association of dialysis parameters with VC., Methods: We enrolled 297 ESRD patients undergoing MHD at six distinct centers in Korea. Study participants were categorized into 3 groups by the scoring system of abdominal aortic calcification based on lateral lumbar radiography (no VC group: 0, mild VC group: 1-7 and advanced VC group: 8-24). We compared the features of dialysis parameters according to the severity of VC. Multivariate logistic regression analysis was used to calculate adjusted odd ratios (ORs) and 95% confidence interval (CI) for mild and advanced VC in each haemodialysis parameter (adjusted OR [95% CI])., Results: Pooled Kt/V (spKt/V), equilibrated Kt/V (eKt/V), standard Kt/V (stdKt/V) and the proportion of haemodiafiltration were increased along with the severity of VC. Multivariate regression analysis indicated that advanced VC was positively associated with spKt/V (5.27 [1.51-18.41]), eKt/V (6.16 [1.45-26.10]), stdKt/V (10.67 [1.74-65.52]) and haemodiafiltration (3.27 [1.74 to 6.16])., Conclusion: High dose dialysis and haemodiafiltration were significantly associated with advanced VC.

Background: A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service., Methods: Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated., Results: From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter., Conclusions: Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Background: In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study., Methods: TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis., Results: DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA > 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291)., Conclusions: Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.

Background: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea., Results: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficient clinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinically diagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex, atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 in group II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (< 18 years old) and 59 (60.8%) were male. The primary symptoms for 80 patients (82.5%) were neurologic. During the one-year pilot study, 72 patients completed a diagnostic assessment including clinical and molecular genetic analyses; some patients also underwent pathological or biochemical analysis. Twenty-eight of these patients (28/72, 38.9%) achieved molecular genetic diagnosis. Thirteen patients were diagnosed based on traditional tests, including biochemical assay, single or targeted genetic analysis, and chromosomal microarray. We performed whole exome sequencing on 52 patients, among whom 15 (28.8%, 15/52) reached a final diagnosis. One new disorder was identified via international collaboration., Conclusions: Using an efficient clinical diagnostic workflow, this KUDP pilot study resulted in a fair diagnostic success rate, improving the potential for additional diagnoses and new scientific discovery of complex and rare diseases. KUDP also satisfied unmet needs for rare diseases with multisystem involvement, highlighting the value of emerging genomic technologies for further research into rare and still-undiagnosed conditions.

Background: Incilaria (= Meghimatium) fruhstorferi is an air-breathing land slug found in restricted habitats of Japan, Taiwan and selected provinces of South Korea (Jeju, Chuncheon, Busan, and Deokjeokdo). The species is on a decline due to depletion of forest cover, predation by natural enemies, and collection. To facilitate the conservation of the species, it is important to decide on a number of traits related to growth, immunity and reproduction addressing fitness advantage of the species., Results: The visceral mass transcriptome of I. fruhstorferi was enabled using the Illumina HiSeq 4000 sequencing platform. According to BUSCO (Benchmarking Universal Single-Copy Orthologs) method, the transcriptome was considered complete with 91.8% of ortholog genes present (Single: 70.7%; Duplicated: 21.1%). A total of 96.79% of the raw read sequences were processed as clean reads. TransDecoder identified 197,271 contigs that contained candidate-coding regions. Of a total of 50,230 unigenes, 34,470 (68.62% of the total unigenes) annotated to homologous proteins in the Protostome database (PANM-DB). The GO term and KEGG pathway analysis indicated genes involved in metabolism, phosphatidylinositol signalling system, aminobenzoate degradation, and T-cell receptor signalling pathway. Many genes associated with molluscan innate immunity were categorized under pathogen recognition receptor, TLR signalling pathway, MyD88 dependent pathway, endogenous ligands, immune effectors, antimicrobial peptides, apoptosis, and adaptation-related. The reproduction-associated unigenes showed homology to protein fem-1, spermatogenesis-associated protein, sperm associated antigen, and testis expressed sequences, among others. In addition, we identified key growth-related genes categorized under somatotrophic axis, muscle growth, chitinases and collagens. A total of 4822 Simple Sequence Repeats (SSRs) were also identified from the unigene sequences of I. fruhstorferi., Conclusions: This is the first available genomic information for non-model land slug, I. fruhstorferi focusing on genes related to growth, immunity, and reproduction, with additional focus on microsatellites and repeating elements. The transcriptome provides access to greater number of traits of unknown relevance in the species that could be exploited for in-depth analyses of evolutionary plasticity and making informed choices during conservation planning. This would be appropriate for understanding the dynamics of the species on a priority basis considering the ecological, health, and social benefits.

Background: Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI)., Methods: In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay., Results: Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1β in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15 nil ) and negatively with that of TB antigen-stimulated IL-32 (IL-32 TB ) in QFT-GIT supernatants. Although the IL-15 nil and IL-15 TB levels were higher in LTBI subjects than patients with active TB, the IL-32 nil and IL-32 TB levels were higher in the latter patients. A combination of the IL-15 nil and IL-32 TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964., Conclusions: Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.

Background: To improve prognosis after esophageal surgery, intraoperative fluid optimization is important. Herein, we hypothesized that hydroxyethyl starch administration during esophagectomy reduce the total amount of fluid infused and it could have a positive effect on postoperative complication occurrence and mortality., Methods: All consecutive adult patients who underwent elective esophageal surgery for cancer were studied. The primary outcome was the development of composite complications including death, cardio-cerebrovascular complications, respiratory complications, renal complications, gastrointestinal complications, sepsis, empyema or abscess, and multi-organ failure. The relationship between perioperative variables and composite complication was evaluated using multivariable logistic regression., Results: Of 892 patients analyzed, composite complications developed in 271 (30.4%). The higher hydroxyethyl starch ratio in total fluid had a negative relationship with the total fluid infusion amount (r = - 0.256, P <  0.001). In multivariable analysis, intraoperatively administered total fluid per weight per hour (odds ratio, 1.248; 95% CI, 1.153-1.351; P <  0.001) and HES-to-crystalloid ratio (odds ratio, 2.125; 95% CI, 1.521-2.969; P <  0.001) were associated with increased risks of postoperative composite outcomes., Conclusions: Although hydroxyethyl starch administration reduces the total fluid infusion amount during esophageal surgery for cancer, intravenous hydroxyethyl starch infusion is associated with an increasing risk of postoperative composite complications.

Background: We hypothesized that calcaneal reconstruction can relieve chronic pain due to calcaneal malunion. We report the mid-term follow-up results of calcaneal reconstruction for calcaneal malunion., Methods: We reviewed the records of 10 male patients (10 ft) who underwent calcaneal reconstruction for calcaneal malunion between January 2009 and July 2014 at the mid-term follow-up. Talocalcaneal height and angle, calcaneal pitch, calcaneal width, Böhler angle, Stephens classification, and Zwipp classification were evaluated by three orthopedic doctors at each visit (pre-reconstruction, post-reconstruction, and at the last follow-up)., Results: The mean follow-up period was 67.1 months (range, 48-101 months). The sites of pain before reconstruction were lateral aspect (4 patients), plantar aspect (3 patients), diffuse pain (2 patients), and anterior aspect (1 patient). There was a significant difference in talocalcaneal height, talocalcaneal angle, calcaneal pitch, calcaneal width, and Böhler angle before and after reconstruction (p < 0.05). There was no significant difference between reconstruction and the last follow-up. Radiological measurement agreement was calculated to be moderate to strong (intraclass correlation coefficient: 0.659-0.988). Mean American Orthopedic Foot & Ankle Society Ankle and Hindfoot score improved from 66.50 ± 9.37 pre-reconstruction to 80.30 ± 8.52 at the last follow-up (p < 0.05). The mean visual analog scale score improved from 8.60 ± 1.43 before reconstruction to 3.40 ± 0.84 at the last follow-up (p < 0.05). Most patients were satisfied with the outcome postoperatively., Conclusions: Our results showed substantial improvement in the clinical and radiological outcomes after calcaneal reconstruction of calcaneal malunion. This outcome was maintained until the mid-term follow-up. Therefore, calcaneal reconstruction may be a good option for the treatment of chronic pain caused by the malunion of a calcaneal fracture without severe subtalar arthritis. Further prospective studies are needed to test this theory., Level of Evidence: Level IV, Retrospective Case Series.

Background: New biological prognostic predictors have been studied; however, some factors have limited clinical application due to tissue-specific expression and high cost. There is the need for a promising predictive factor that is simple to detect and that is closely linked to oncological outcomes in patients with urothelial bladder cancer (BC) who have undergone radical cystectomy (RC). Therefore, we investigated the clinical prognostic value of the preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) on oncological outcomes in patients with urothelial BC after RC., Methods: We retrospectively evaluated clinicopathological data of 118 patients with non-metastatic urothelial BC after RC between 2008 and 2013 at a single center. The association between the De Ritis ratio and clinicopathological findings was assessed. The potential prognostic value of the De Ritis ratio was analyzed using the Kaplan-Meier method, and multivariate Cox analyses were performed to identify the independent predictors of metastasis-free survival, cancer-specific survival, and overall survival., Results: According to the receiver operating curve of the De Ritis ratio for metastasis, we stratified the patients into 2 groups using a threshold of 1.3. A high De Ritis ratio was more likely to be associated with old age and the female sex. Kaplan-Meier estimates revealed that patients with a high De Ritis ratio had inferior metastasis-free survival, cancer-specific survival, and overall survival outcomes (P = 0.012, 0.024, and 0.022, respectively). Multivariate analysis revealed that a high De Ritis ratio was an independent prognostic factor for metastasis (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.161-4.914; P = 0.018), cancer-related death (HR, 2.755; 95% CI, 1.214-6.249; P = 0.015), and overall death (HR, 2.761; 95% CI, 1.257-6.067; P = 0.011)., Conclusions: An elevated De Ritis ratio was significantly associated with worse prognosis in patients who underwent RC for urothelial BC. This ratio might further improve the predictive accuracy for prognosis in BC.

Background: Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT., Methods: Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b-3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3-6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age., Results: Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12 h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ≤5, 34.6% in 6-10, 58.9% in 11-20, and 63.8% in > 20 (p < 0.001). Nonetheless, the therapeutic benefit of EVT also increased with increasing stroke severity (p for interaction < 0.001): 0.1% in NIHSS ≤5, 18.6% in 6-10, 28.7% in 11-20, and 34.3% in > 20., Conclusions: EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.

Background: When two or more vaccines are administered concurrently, there is concern about safety and immunogenicity from vaccine interaction., Methods: Subjects aged ≥50 years were randomized 1:1:1 to receive tetanus-diphtheria (Td) + 13-valent pneumococcal conjugate vaccine (PCV13; Group 1), PCV13 alone (Group 2), or Td alone (Group 3). After single or concomitant vaccination, enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA) were performed to compare immunogenicity for Td and PCV13, respectively., Results: A total of 448 subjects were available for the assessment. After concomitant administration, the non-inferiority criteria of geometric mean titer (GMT) ratios were met for tetanus, diphtheria, and all four pneumococcal serotypes (1, 5, 18C, and 19A). However, subjects in Group 3 (Td alone) were more likely to have a high IgG anti-tetanus antibody titer (≥ 0.5 U/mL) than those in Group 1 (Td + PCV13) (p <  0.01). As for the pneumococcal serotype 1, the OPA GMT was significantly higher in Group 1 (PCV13 + Td) compared to Group 2 (PCV13 alone) (p = 0.02). No serious adverse event occurred., Conclusions: Concomitant Td and PCV13 administration induced sufficient immunity without significant interference and showed good safety profiles., Trials Registration: NCT03552445 registered at http://www.clinicaltrials.gov on June 11, 2018 (retrospectively registered).

Background: The analgesic effects of dexamethasone have been reported previously, and the present study determined the effects of preoperative dexamethasone on postoperative pain in patients who received thoracotomy., Methods: Forty patients participated in this randomized, double-blind study. All patients received either dexamethasone via a 0.1 mg/kg intravenous bolus before anesthetic induction or an equal volume of saline. Postoperative analgesia was provided to both groups via epidural patient-controlled analgesia (PCA), which consisted of 250 μg of sufentanil in 250 mL of ropivacaine (0.18%) for 72 h. The primary outcome was the cumulative consumption of epidural PCA at postoperative 24 and 72 h. The secondary outcomes were the pain intensity scores during resting and coughing at postoperative 24 and 72 h, quality of recovery, total amount of rescue analgesics required, and length of hospital stay., Results: No significant differences was observed in the consumption of epidural PCA between the control and dexamethasone infusion groups at 24 h (63.6 [55.9-72.7] vs. 68.5 [60.2-89.0] ml, P = 0.281) and 72 h (199.4 [172.4-225.1] vs. 194.7 [169.1-252.2] ml, P = 0.890). Moreover, there was no significant difference in the pain intensity scores during resting and coughing at postoperative 24 and 72 h, quality of recovery, total amount of rescue analgesics required, and length of hospital stay., Conclusion: A single intravenous administration of dexamethasone during the preoperative period does not reduce opioid consumption and post-thoracotomy pain., Trial Registration: The study was registered at http://cris.nih.go.kr ( KCT0000359 ) and was conducted from December 2011 to October 2012.

Background: Insomnia and migraine are closely related; insomnia aggravates migraine symptoms. This study was conducted to investigate the impact of migraine on the clinical presentation of insomnia symptoms., Methods: The data of the Korean Headache-Sleep Study (KHSS) were used in the present study. The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep in Korean adults aged 19 to 69 years. If a participant's Insomnia Severity Index (ISI) score ≥ 10, she/he was classified as having insomnia. The clinical presentation of insomnia symptoms was assessed using total and subcomponent scores of the ISI., Results: Of 2695 participants, 290 (10.8%) and 143 (5.3%) individuals were assigned as having insomnia and migraine, respectively. The proportions of migraine (12.8% vs. 4.4%, p <  0.001) and non-migraine headache (59.0% vs. 39.9%, p <  0.001) were higher among individuals with insomnia compared to those without insomnia. Among participants with insomnia, total ISI scores were not significantly different among participants with migraine, non-migraine, and non-headache [median and interquartile range: 13.0 (11.0-17.5) vs. 13.0 (11.0-17.5) vs. 12.0 (11.0-16.0), p = 0.245]. ISI scores for noticeability of sleep problems to others were significantly higher among participants with migraine [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.011] and non-migraine headache [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.001] compared to those without headache history. Other ISI subcomponent scores did not significantly differ between headache status groups., Conclusions: Participants with insomnia had an increased risk of migraine and non-migraine headache compared to those without insomnia. Among participants with insomnia, overall insomnia severity was not significantly influenced by the headache status.

Background: Exposure to low levels of volatile organic compounds (VOCs) in ordinary life is suspected to be related to oxidative stress and decreased lung function. This study evaluated whether exposure to ambient VOCs in indoor air affects airway inflammation., Methods: Thirty-four subjects from the hospital that had moved to a new building were enrolled. Symptoms of sick building syndrome, pulmonary function tests, and fractional exhaled nitric oxide (FeNO) were evaluated, and random urine samples were collected 1 week before and after the move. Urine samples were analyzed for VOC metabolites, oxidative stress biomarkers, and urinary leukotriene E4 (uLTE4) levels., Results: The level of indoor VOCs in the new building was higher than that in the old building. Symptoms of eye dryness and eye irritation, as well as the level of a xylene metabolite (o-methylhippuric acid) increased after moving into the new building (p = 0.012, p = 0.008, and p < 0.0001, respectively). For the inflammatory markers, FeNO decreased (p = 0.012 and p = 0.04, respectively) and the uLTE4 level increased (p = 0.005) after the move., Conclusion: Exposure to a higher level of VOCs in everyday life could affect airway inflammation.

Background: Probable migraine (PM) is a subtype of migraine that is prevalent in the general population. Previous studies have shown that poor sleep quality is common among migraineurs and is associated with an exacerbation of migraine symptoms. However, information on the prevalence and clinical implication of poor sleep quality among individuals with PM is scarce. Thus, the aim of this study was to assess the prevalence and clinical impact of poor sleep quality in individuals with PM in comparison with those with migraine., Methods: Two-stage cluster random sampling was used to perform the survey for sleep and headache in Korean general population. Participants with Pittsburgh Sleep Quality Index > 5 were considered as having poor sleep quality., Results: Of 2695 participants, 379 (14.1%) had PM and 715 (26.5%) had poor sleep quality. Prevalence of poor sleep quality was 35.4% in the PM group, which was lower than that in the migraine group (47.6%, p = 0.011), but higher than that in the non-headache group (21.4%, p < 0.001). The PM participants with poor sleep quality showed increased headache frequency (median [interquartile range]: 2.0 [0.3-4.0] vs. 1.0 [0.2-2.0]; p = 0.001) and headache intensity (visual analogue scale, 6.0 [4.0-7.0] vs. 5.0 [3.5-6.0]; p = 0.003) compared to PM participants who had no poor sleep quality., Conclusions: Poor sleep quality was prevalent among participants with PM. It was associated with an exacerbation of PM symptoms. Our findings suggest that proper evaluation and treatment for poor sleep quality are needed in the management of PM.

Background: Penile length (PL) shortening is an underreported phenomenon following radical prostatectomy (RP) and risk factors are not fully explored. We aimed to describe longitudinal patterns of PL recovery and evaluate factors predicting complete return to baseline PL., Methods: PL measurement was performed during a preoperative and postoperative follow-up visits at 7 days and 3, 6, 9, and 12 months. Patients who completely recovered (CR: N = 397) their preoperative stretched PL measured during at least one of their follow-up visits were compared to those with incomplete recovery (IR: N = 131). Recovery patterns were analyzed for both groups and were also compared in regards to demographics, nerve-sparing techniques, prostate size, cardiovascular risk profiles, and phosphodiesterase-5 inhibitor (PDE5i) uses. Logistic regression analyses were performed using age and other relevant clinicopathologic variables to predict PL recovery., Results: 60.2% of the total study population regained their preoperative PL at 12 months. Average percent (length) differences from baseline were - 1.70% (- 0.25 cm) and - 16.42% (- 2.35 cm) in the CR and the IR groups, respectively (p < 0.001). Multivariate logistic regression demonstrated that younger age (OR 0.962; 95%CI 0.931-0.994; p = 0.019), high preoperative erectile function (EF) (OR 1.028; 95%CI 1.001-1.056; p = 0.046), and consistent PDE5i use (OR 1.998; 95%CI 1.166-3.425; p = 0.012) were independent predictors of CR. At 12-month follow up, PL difference for consistent PDE5iusers was statistically different from those who did not use PDE5i consistently (- 3.25%vs. -6.64%; P = 0.001)., Conclusion: Age, preoperative EF, and consistent use of PDE5i were associated with complete recovery of baseline PL after RP. The therapeutic effect of PDE5i was most pronounced at 12-month visit, suggesting an added benefit with long-term use.

Background: To compare the rate of exodrift after a second surgery for recurrent exotropia, in patients grouped to fast versus slow exodrift after their first surgery. To determine whether there is a correlation with surgical outcome, and to evaluate the factors associated with fast exodrift., Methods: Patients with recurrent intermittent exotropia, who underwent contralateral lateral rectus recession and medial rectus resection as the second surgery and were followed up for 24 months postoperatively between January 1991 and January 2013, were reviewed retrospectively. The patients were divided into two groups according to the rate of exodrift after the first surgery: Group F, patients exhibiting fast exodrift after the first surgery (> 10 prism diopters [PD] before postoperative month 6); and Group S, patients exhibiting slow exodrift after the first surgery (≤10 PD before postoperative month 6). The difference in the clinical course over the 24 months after the second surgery between the two groups and factors associated with fast exodrift were analyzed., Results: In total, 106 patients with recurrent exotropia were enrolled in this study. Of these, 68 (64.2%) and 38 (35.8%) patients were included in group F and S, respectively. Group F showed more exodrift compared with groups S over the 24-month postoperative period; however, there was no significant difference in the clinical course between the two groups during that time (p = 0.54, repeated-measure ANOVA). In logistic analysis, immediate postoperative deviation after the first surgery was associated with fast exodrift (p <  0.001)., Conclusion: Although patients with recurrent exotropia had shown fast exodrift after the first surgery, no significant difference in the surgical outcome was observed after the second surgery according to the rate of exodrift after the first surgery.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses. In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up., Methods: We analyzed dusty areas cohort comprising 272 patients with COPD. The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline. The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data. The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups., Results: PCA revealed that six independent components accounted for 77.3% of variance. Three distinct subgroups were identified through the cluster analysis. Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up. Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up. Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization., Conclusions: Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes. These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.

Background: Recent studies have shown a significant association between restless legs syndrome (RLS) and primary headache disorders. Nevertheless, information regarding the association between tension-type headache (TTH) and RLS is limited. This study aimed to investigate the association between RLS and TTH in a population-based sample., Methods: We selected a stratified random population sample of Koreans aged 19-69 years and assessed them using a semi-structured interview designed to identify RLS, headache type, and clinical characteristics of TTH. We determined the prevalence and clinical impact of RLS in participants with TTH., Results: Of the 2695 participants, 570 (21.2%) and 142 (5.3%) were classified as having TTH and RLS, respectively. Among the 570 individuals with TTH, 113 (19.8%) also met the criteria for probable migraine (PM). The prevalence of RLS was significantly higher among individuals with TTH than among those with non-headache (6.0% vs 3.6%, p = 0.018). The prevalence of RLS was significantly higher in subjects with TTH who fulfilled PM criteria than in those with non-headache participants (8.0% vs. 3.6%, p = 0.018). However, RLS prevalence in individuals with TTH who did not fulfil PM criteria did not differ from that of participants with non-headache (5.5% vs. 3.6%, p = 0.063). TTH participants with RLS had higher visual analogue scale scores for headache intensity (5.1 ± 2.0 vs. 4.3 ± 1.8, p = 0.038), and higher prevalence of anxiety (20.6% vs. 8.8%, p = 0.022) and depression (14.7% vs. 3.5%, p = 0.002) than TTH participants without RLS. Multivariable analyses revealed that headache aggravation by movement (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.1-5.2) and depression (OR = 3.5, 95% CI = 1.1-11.4) were significant indicators of RLS among individuals with TTH., Conclusions: The prevalence of RLS was higher among individuals with TTH than among those with non-headache. Some clinical presentations varied in accordance with the presence of RLS among participants with TTH.

Background: Sleep disorder and sleep complaints are common in subjects with migraine. Although the association between sleep disorders and migraine has been reported, the association between perceived insufficient sleep and migraine has rarely reported. The aim of this study is to evaluate the association between insufficient sleep and migraine using the data of the Korean Headache-Sleep Study (KHSS)., Methods: The KHSS is a nation-wide cross-sectional population-based survey regarding headache and sleep for Korean adults aged 19 to 69 years. A difference of one hour or more between sleep need and average sleep time indicated insufficient sleep., Results: Of 2,695 participants, 727 (27.0%) individuals were classified as having insufficient sleep. The prevalence of insufficient sleep among individuals with migraine (45.5%) was significantly higher compared to that among individuals with non-migraine headache (32.9%, p = 0.004) or among non-headache (20.4%, p < 0.001). Average sleep time did not differ among migraine, non-migraine headache, and non-headache groups (7.3 ± 1.2 vs. 7.2 ± 1.2 vs. 7.3 ± 1.4, p = 0.207). Multivariable logistic regression analyses demonstrated that migraine had an increased odds ratio (OR) for insufficient sleep after adjusting for sociodemographic variables, short sleep time, insomnia, poor sleep quality, anxiety, and depression (OR = 1.8, 95% confidence interval [CI] = 1. 2 - 2.7, p = 0.002)., Conclusions: The prevalence of insufficient sleep was significantly higher among migraineurs compared to that in non-migraine headache or non-headache group.

Background: Tension-type headache (TTH) represents the most common type of headache among the general population. Although such headaches are usually mild in severity, some individuals with TTH experience severe symptoms and psychiatric comorbidities. Such patients may also experience sleep disturbances, which have been associated with headache exacerbation. Nevertheless, information regarding the prevalence and impact of insomnia among individuals with TTH in a population-based setting is limited. Therefore, the aim of the present study was to evaluate the prevalence and impact of insomnia among individuals with TTH using data from the Korean Headache-Sleep Study (KHSS)., Methods: We analysed data from the KHSS-a nation-wide, cross-sectional, population-based survey on headache and sleep involving Korean adults aged 19 to 69 years. Insomnia was defined as an Insomnia Severity Index score ≥ 10., Results: Among 2695 participants, 570 (21.2%) and 290 (10.8%) were classified as having TTH and insomnia, respectively. Among individuals with TTH, 113 (19.8%) met the criteria for probable migraine (PM). The prevalence of insomnia among individuals with TTH was significantly higher than that among individuals without headache (13.2% vs. 5.8%, p < 0.001). However, among the TTH group, the prevalence of insomnia did not significantly differ between participants fulfilling PM criteria and those not fulfilling PM criteria (14.2% vs. 12.9%, p = 0.725). Among individuals with TTH, headache frequency [median and interquartile range (IQR): 1.0 (0.3-3.0) vs. 0.4 (0.2-1.0), p = 0.002], visual analogue scale scores for headache intensity [median and IQR: 5.0 (4.0-7.0) vs. 4.0 (3.0-6.0), p < 0.001], Headache Impact Test-6 scores [median and IQR: 46.0 (40.0-52.0) vs. 42.0 (38.0-46.0), p < 0.001], anxiety prevalence (28.0% vs. 6.7%, p < 0.001), and depression prevalence (21.3% vs. 1.6%, p < 0.001) were significantly higher in those with insomnia than in those without insomnia., Conclusions: Our findings indicate that insomnia is prevalent among individuals with TTH. Moreover, insomnia was associated with exacerbation of headache symptoms and psychiatric comorbidities. Therefore, identification of insomnia among individuals with TTH is required to improve the management of headache symptoms in such patients.

Background: Previous studies have shown that migraine and sleep disturbances are closely associated. Excessive daytime sleepiness (EDS) is a common symptom of various types of sleep disturbance. Findings from clinic-based studies suggest that a high percentage of migraineurs experience EDS. However, the prevalence and clinical impact of EDS among migraineurs at the population level have rarely been reported. The objective of this study was to investigate the prevalence and impact of EDS among migraineurs using a population-based sample in Korea., Methods: We selected a stratified random sample of Koreans aged 19 to 69 years and evaluated them using a semi-structured interview designed to identify EDS, headache type, and the clinical characteristics of migraine. If the score on the Epworth Sleepiness Scale (ESS) was more than or equal to 11, the participant was classified as having EDS., Results: Of the 2,695 participants that completed the interview, 143 (5.3 %) and 313 (11.6 %) were classified as having migraine and EDS, respectively. The prevalence of EDS was significantly higher in participants with migraine (19.6 %) and non-migraine headache (13.4 %) compared to non-headache controls (9.4 %). Migraineurs with EDS had higher scores on the Visual Analogue Scale (VAS) for headache intensity (6.9 ± 1.8 vs. 6.0 ± 1.9, p = 0.014) and Headache Impact Test-6 (59.8 ± 10.2 vs. 52.5 ± 8.2, p < 0.001) compared to migraineurs without EDS., Conclusions: Approximately 20 % of migraineurs had EDS in this population-based sample. Excessive daytime sleepiness was associated with an exacerbation of some migraine symptoms.

Background: Insomnia is a common complaint among individuals with migraine. The close association between insomnia and migraine has been reported in clinic-based and population-based studies. Probable migraine (PM) is a migrainous headache which fulfills all but one criterion in the migraine diagnostic criteria. However, an association between insomnia and PM has rarely been reported. This study is to investigate the association between insomnia and PM in comparison with migraine using data from the Korean Headache-Sleep Study., Methods: The Korean Headache-Sleep Study is a nation-wide cross-sectional survey for all Korean adults aged 19-69 years. The survey was performed via face-to-face interview using a questionnaire on sleep and headache. If an individual's Insomnia Severity Index score was ≥15.5, she/he was diagnosed as having insomnia., Results: Of 2695 participants, the prevalence of migraine, PM and insomnia was 5.3, 14.1 and 3.6 %, respectively. The prevalence of insomnia among subjects with PM was not significantly different compared to those with migraine (8.2 % vs. 9.1 %, p = 0.860). However, insomnia prevalence in subjects with PM was significantly higher than in non-headache controls (8.2 % vs. 1.8 %, p < 0.001). Insomnia Severity Index score was significantly higher in subjects with migraine compared to those with PM (6.8 ± 5.8 vs. 5.5 ± 5.8, p = 0.012). Headache frequency and Headache Impact Test-6 score were significantly higher in subjects with migraine and PM with insomnia compared to those without insomnia. Multivariable linear analyses showed that anxiety, depression, headache frequency and headache intensity were independent variables for contributing the ISI score among subjects with PM., Conclusions: The prevalence of insomnia among subjects with PM was not significantly different compared to those with migraine. Anxiety, depression, headache frequency and headache intensity were related with ISI score in subjects with PM.

Background: The present study aimed to compare the intravenous bolus effect of oxycodone and fentanyl on hemodynamic response after endotracheal intubation and postoperative pain in patients undergoing closed reduction of nasal bone fracture., Methods: In this prospective randomized double-blinded study, 64 patients undergoing closed reduction of nasal bone fracture were randomized into one of two groups: the fentanyl group (Group F) or the oxycodone group (Group O). Each drug (fentanyl 2 mcg/kg in Group F and oxycodone 0.2 mg/kg in Group O) was administered prior to the induction of general anesthesia. Hemodynamic changes after endotracheal intubation and postoperative pain were then measured in both groups., Results: There was no significant difference in the change in mean arterial pressure and heart rate between pre-induction and post-intubation in both Groups F and O (P > 0.05). Postoperative pain in Group O was milder than that in Group F (P < 0.001); however, time to awakening from the end of operation was shorter in Group F (P = 0.012)., Conclusion: In patients undergoing closed reduction of nasal bone fracture, oxycodone attenuates hemodynamic response to endotracheal intubation similar to fentanyl. However, oxycodone is more effective than fentanyl in improving postoperative pain., Trial Registration: Clinical Research Information Service (Trial registry number: KCT0001153 ) on 3 July, 2014.