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PURPOSE We sought to investigate the ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with nonexudative age-related macular degeneration. METHODS We classified eyes into four categories-pachydrusen, soft drusen, subretinal drusenoid deposit (SDD), and soft drusen with SDD-and compared the baseline mean macular GCIPL thickness according to the Early Treatment Diabetic Retinopathy Study grid and its change between groups. RESULTS We classified 53, 29, 36, and 34 eyes into the four categories, respectively. The mean GCIPL thickness values in the 3-mm area were 82.61 ± 9.54 µm for the pachydrusen group, 79.11 ± 10.26 µm for the soft drusen group, 77.72 ± 6.04 µm for the SDD group, and 71.63 ± 8.69 µm for the soft drusen with SDD group (P < 0.001). The soft drusen with the SDD group showed a greater change in GCIPL thickness (-2.50 ± 0.29 µm/year) in the 3-mm area as compared with the pachydrusen group (-0.18 ± 0.35 µm/year), soft drusen group (-0.55 ± 0.36 µm/year), and SDD group (-0.55 ± 0.37) (all P < 0.001). CONCLUSION The GCIPL thickness varied according to the type of nonexudative age-related macular degeneration. The thinner baseline GCIPL and its greater change in eyes with soft drusen with SDD may suggest that these eyes are experiencing more prominent neuroretinal degeneration in the central 3-mm area than those in the other groups.

Background: There is insufficient data on the longevity of immunity acquired following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate the duration of SARS-CoV-2-specific humoral and cellular immunity according to the clinical severity of coronavirus disease 2019 (COVID-19). Methods: Convalescent blood was collected prospectively from 97 patients who had recovered from COVID-19. The level of humoral immunity to SARS-CoV-2 was measured using the anti-SARS-CoV-2 nucleocapsid immunoglobulin G (IgG) assay and the plaque reduction neutralization test with sera collected at three periods: within 8 weeks, at 9-20 weeks, and at 22-27 weeks after diagnosis. IFN-γ ELISpot assays were conducted using overlapping peptides covering spike, nucleocapsid, and membrane proteins of SARS-CoV-2. Findings: The study population comprised asymptomatic (n=14), symptomatic/non-pneumonic (n=42), and pneumonic (n=41) patients. The anti-SARS-CoV-2 IgG and neutralizing antibody (NAb) titers lasted until six months after diagnosis, with positivity rates of 66·7% and 86·9%, respectively. The level of humoral immunity at six months after diagnosis were significantly higher in the pneumonic group than in the symptomatic/non-pneumonic group. Older age, prolonged viral shedding and accompanying pneumonia were more frequently found in patients with sustained humoral immunity. SARS-CoV-2 specific T-cell response was strongly observed in pneumonic patients and prominent in individuals with sustained humoral immunity. Interpretation: Most (> 85%) patients carries NAb until six months after diagnosis of SARS-CoV-2 infection, providing insights for establishing vaccination strategies against COVID-19. Funding Statement: This study was supported by a grant of the Korea National Institute of Health, Korea Disease Control and Prevention Agency (project number: 2020-ER5314-00), Korea University Guro Hospital (Korea research-driven hospital) (No. O2001061), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI20C0452). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of the Korea University Guro Hospital (approval number: 2020GR0130). All participants provided written informed consent.

Background and purpose Lower urinary tract symptoms (LUTS) are the most common nonmotor symptoms usually occurring mid-stage of Parkinson's disease (PD); however, its underlying mechanisms are unknown. We aimed to assess whether corticometry or volumetry can identify a pattern of cerebral cortical changes in PD patients with LUTS. Methods We recruited 85 idiopathic PD patients and performed corticometry and volumetry on various cortical regions using each patient's magnetic resonance imaging. To identify a correlation between the cortical thickness/volume and nonmotor symptoms scale domain 7 scores, which represent the severity of LUTS, we performed general linear model and region of interest analyses. Results Significant regional thinning of the left precuneus, left temporal pole, left precentral, right precuneus, and right pars opercularis was correlated with nonmotor symptoms scale domain 7 scores. We also found that cortical volumes of left precuneus and left frontal pole were inversely correlated with the severity of urinary symptoms. Conclusions This study showed that the thicknesses and volumes of several cortical regions were significantly correlated with the severity of LUTS in PD patients. The findings of regional atrophy and thinning of specific cortical regions in this study provide additional evidence that multiple cortical regions, especially the precuneus cortex, not only may be involved in urinary dysfunctions of PD patients but also may help to elucidate the exact underlying mechanisms for LUTS in PD patients.

INTRODUCTION: Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM. METHODS: We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements. RESULTS: In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18–1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates reactive oxygen/nitrogen species (ROS/RNS)-dependent apoptosis in cancer cells. We investigate the capability of PAM and TRAIL (PAM/TRAIL) combination therapy to overcome TRAIL resistance and improve the anticancer efficacy of TRAIL. The combinatorial treatment of PAM and TRAIL shows synergistic effects on growth inhibition in TRAIL-resistant cancer cells via augmented apoptosis by two attributes. DR5 (TRAIL-R2) transcription by CHOP is upregulated in a PAM-generated ROS/RNS-dependent manner, and PAM itself upregulates PTEN expression mediated by suppression of miR-425 which is involved in Akt inactivation, leading to increased apoptosis induction. Treatment of cancer cell lines with the antioxidant N-acetylcysteine reduces the extent of membrane dysfunction and the expression of both CHOP-DR5 and miR-425-PTEN axes, attenuating PAM/TRAIL-induced cancer cell apoptosis. These data suggest that PAM/TRAIL treatment is a novel approach to sensitizing cancer cells to TRAIL-induced apoptosis and overcoming TRAIL resistance. PAM is a promising candidate for further investigations as a chemotherapeutic sensitizer in the treatment of cancer.

Background: Recent growing evidences suggest that body weight (Bwt) variability, a repeated loss and regain of weight within a specific period, causes metabolic disturbances and can be a marker for poor homeostasis. Although there have been many studies about the association between Bwt variability and various health status, its association with the incidence of dementia among elderly people has not been examined.Methods: We performed a retrospective elderly cohort study from 19,987 participants with mean age 73 years old in the Korean National Health Insurance Service. We examined the risk of incident dementia, including Alzheimer's dementia and vascular dementia, according to the quartile of Bwt variability, represented as coefficient of variation (Bwt-CV), SD (Bwt-SD), and variability independent of the mean (Bwt-VIM).Results: In fully adjusted model, the group with the highest Bwt variability (Bwt-VIM Q4) showed an increased risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.206–1.603) and Alzheimer's dementia (HR 1.46, CI 1.240–1.724) compared to the lowest quartile (Bwt-VIM Q1). We also found that subjects with the highest Bwt variability (Q4) and underweight BMI had a significantly increased risk of developing dementia (HR 1.994, 95% CI 1.302–3.054), while subjects with low Bwt variability (Q1 and Q2) and obese BMI had decreased risk of dementia (HR 0.664, 95% CI 0.505–0.872 and HR 0.648, 95% CI 0.493–0.852, respectively) compared to reference group (lowest Bwt variability (Q1) with normal baseline BMI). The effect of Bwt variability on the incidence of dementia was more prominent in subjects

Aims Pre-pregnancy insulin resistance is one of the main pathophysiologies of gestational diabetes mellitus (GDM). Triglyceride-glucose (TyG) index is a marker of insulin resistance. We aimed to evaluate the association between pre-pregnancy TyG index and GDM in primipara women. Methods A total of 380,208 women who underwent a Korean national health screening exam within 2 years before their first delivery, between January 1, 2012 and December 31, 2015, were included. The TyG index was calculated as ln [triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results Among the 380,208 primipara women, 17,239 women were diagnosed with GDM (4.53%). Multivariate logistic regression analysis adjusted for risk factors showed a higher odds ratio of 1.73 for GDM (95% CI 1.65-1.81) in the highest quartile than that in the lowest quartile. A 1-SD increase in the TyG index increased the risk of GDM (31%) and GDM requiring insulin therapy (82%) in the fully adjusted model. A 1-unit increase in the TyG index significantly increased the risk of GDM and GDM requiring insulin treatment by 1.81 and 3.69 times, respectively.The impact of a high TyG index on the risk of GDM was more profound in the subjects aged ≥ 35 years, with obesity, with impaired fasting glucose, who are current smokers, and with a family history of diabetes mellitus. Conclusions Increased pre-pregnancy TyG index is associated with a risk of GDM. Elevation of the TyG index may be an early marker of GDM.

Background Although neuromyelitis optica spectrum disorder (NMOSD) is known to be a rare disease, its prevalence and incidence have not yet been studied in Korea. We performed a population-based study to examine the prevalence and incidence of NMOSD in Korea using data from the Korean National Health Insurance (NHI) claims database. Methods Data from 2013 to 2017 were obtained, with a washout period set as 2013 and 2014. The prevalence and incidence of NMOSD in 2016 and 2017 were calculated using population census data. Subjects were divided into 5 groups at 15-year intervals, depending on the age at which the diagnostic code was entered. The relative risk (RR) for each age group was compared with the oldest (≥ 60 years) age group. Results The overall prevalence was estimated to be 3.36 and 3.56 per 100,000 individuals, with an incidence of 0.41 and 0.65 per 100,000 individuals-year in 2016 and 2017, respectively. The mean age was 43.08 (standard deviation, 14.56) years, and the ratio of male to females was 1:4.7. The incidence was higher in female individuals aged between 30 and 59 years (RR, 2.8–3.05; P < 0.05). Conclusion Nationwide prevalence of NMOSD in Korea was 3.36 and 3.56/100,000 and its incidence was 0.41 and 0.65/100,000-year in 2016 and 2017 respectively., Graphical Abstract

Aims Previous in-vitro and in-vivo experimental studies have shown that Sestrin2 attenuates oxidative stress and the pro-inflammatory pathway, resulting in improving metabolic homeostasis. However, the relationship between circulating Sestrin2 concentration and cardiometabolic risks in humans has not been explored. Methods Sestrin2 concentration was measured in 240 subjects (46 without diabetes and 194 with diabetes), and the associations between Sestrin2 level and various cardiometabolic risk factors including body composition, insulin resistance, and atherosclerosis was assessed. Results Sestrin2 concentration showed a trend of increasing in subjects with metabolic syndrome. After adjustment for age and gender, Sestrin2 level had a positive relationship with serum triglyceride, alanine aminotransferase (ALT), and creatinine levels, but no association with carotid atherosclerosis. Especially, in subjects with type 2 diabetes Sestrin2 concentration exhibited a significant positive correlation with body mass index (P = 0.015), waist circumference (P = 0.020), high-sensitivity C-reactive protein (P = 0.008), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (P = 0.041), percentage body fat (P = 0.001), and truncal fat mass (P = 0.005) after adjusting age and gender. Multiple stepwise regression analysis identified age, serum ALT and creatinine levels, and percentage body fat as independent determining factors for Sestrin2 concentration in patients with type 2 diabetes (R2 = 0.173). Conclusions This study is the first to demonstrate a trend for increased Sestrin2 level in subjects with metabolic syndrome. In particular, in subjects with type 2 diabetes, Sestrin2 was significantly related to insulin resistance and percentage body fat, suggesting its potential as a novel modulatory factor for metabolic disorders in humans.

BACKGROUND Sarcopenic obesity (SO) is a serious public health concern, few studies have examined the clinical implications of SO in newly-diagnosed type 2 diabetes mellitus (T2DM) patients. We evaluated the prevalence of the newly diagnosed, drug-naive T2DM patients with low muscle mass with abdominal obesity and its association with insulin resistance and other diabetic complications. METHODS We classified 233 drug-naive T2DM subjects into four groups according to abdominal obesity (waist circumference ≥90 cm in men and ≥85 cm in women) and low muscle mass status (appendicular skeletal muscle

Although statin use in patients with acute myocardial infarction (AMI) is mandatory, it has been suggested to be associated with new-onset diabetes mellitus (NODM). In real world practice, moderate-intensity statin therapy is more commonly used than high-intensity statin therapy. In this study, we investigated the impact of moderate-intensity pitavastatin (2 to 4 mg) compared with moderate-intensity atorvastatin (10 to 20 mg) and rosuvastatin (5 to 10 mg) on the development of NODM during a follow-up period of up to 3years. Between November 2011 and May 2015, 2001 patients with AMI who did not have diabetes mellitus were investigated. The cumulative incidence of NODM was evaluated in all groups. To adjust for potential confounders, multinomial propensity scores were used. Cox proportional hazard models were used to assess the hazard ratio of NODM in the atorvastatin and rosuvastatin groups compared with pitavastatin group. The cumulative incidence of NODM was significantly lower in pitavastatin group compared with the atorvastatin and rosuvastatin groups (3.0% vs 8.4% vs 10.4%, respectively; Log-rank p value = 0.001). After weighting the baseline characteristics of the 3 statin groups by multinomial propensity scores, atorvastatin (hazard ratio: 2.615, 95% confidence interval: 1.163 to 5.879) and rosuvastatin (hazard ratio: 3.906, 95% confidence interval: 1.756 to 8.688) were found to be associated with a higher incidence of NODM compared with pitavastatin therapy on multivariable analysis. Moderate-intensity pitavastatin therapy is associated with a lower incidence of NODM in patients with AMI andhas similar clinical outcomes to moderate-intensity atorvastatin and rosuvastatin therapy.

Background: The incidence of thyroid cancer is increasing worldwide due to an increased detection of small well-differentiated papillary thyroid carcinomas. This study aimed to evaluate the effect of screening with ultrasonography on deaths from thyroid cancer. Materials and Methods: We conducted a matched case-control study using data from two sources representative of the adult Korean population. Cases were selected from the National Epidemiologic Survey of Thyroid Cancer database, and controls were selected from the Korean National Cancer Screening Survey database. Controls were individually matched to case patients with respect to age, sex, and area with a ratio of 10:1. The primary outcome was death from thyroid cancer. Controls were required to have been alive on the date of thyroid cancer diagnosis in the corresponding case. Results: The analysis included 120 patients who died from thyroid cancer and 1184 controls. Compared with those who had never been screened, the odds ratios for death from thyroid cancer among those who had been screened were 1.44 (95% confidence interval [CI] 0.68-3.05) if cases with missing information on screening were excluded and 1.13 [CI 0.49-2.63] if all cases were included, and missing information was imputed. Stratification by sex, year of diagnosis, and histological type did not show any statistically significant relationships between screening with ultrasonography and death from thyroid cancer, regardless of the statistical model used. Conclusions: Screening for thyroid cancer with ultrasonography does not prevent death from thyroid cancer; therefore, screening asymptomatic adults for thyroid cancer is unwarranted.

Background A recent concept is that obesity, assessed by body mass index (BMI), is not always a sign of poor health. Thus, in order to use obesity metrics in clinical decision making, it is important to clarify the relationship between waist circumference (WC), a proxy for abdominal obesity, and mortality. Methods Data were used from 8,796,759 subjects aged between 30 and 90 years, who had participated in the Korea National Health Screening Examination between January 1, 2009 and December 31, 2009 and survived at least 1 year post screening. Data from a mean follow-up time of an additional 5.3 years (time at risk) were analyzed for the relationship between WC and mortality according to age, sex, and BMI category. Results An increased WC of more than 90 cm in men and 85 cm in women showed a definite negative influence on mortality. However, the detailed relationship between WC and mortality was J-shaped or U-shaped according to age, sex, and BMI category. In the normal BMI group, the optimal WC range with the lowest mortality was

Objectives Aseptic bone flap resorption (ABFR) is a known complication of cranioplasty (CP) with an autologous bone flap. The incidence of ABFR has been reported to be as high as 34.2% in the literature; however, it is underestimated in clinical fields. We retrospectively reviewed 13 years of clinical cases of patients who underwent CP after decompressive craniectomy (DC) to investigate the incidence and risk factors of ABFR. Methods Ninety-one patients who underwent DC and CP in Guro Hospital, Korea University Medical Center, were enrolled. ABFR was defined using serial brain computed tomography. To identify possible risk factors for ABFR, univariate and multivariate Cox regression and receiver operating characteristic curve analyses were performed. Results Of the 91 patients enrolled, ABFR was diagnosed in 32 patients (35.1%). Bone flap size, existence of a shunting system, and the DC-CP interval were significant in the univariate analysis. Bone flap size was statistically significant in the multivariate analysis (P = 0.0189). The cutoff points of the DC-CP interval and bone flap size were 44 days and 110 cm2, respectively. Conclusions The incidence of ABFR was remarkably high. Bone flap size, the existence of a shunting system, and the DC-CP interval were shown to be potential risk factors of ABFR after CP.

Background: Dizziness is one of the most common complaints in medicine and a frequent symptom among older people. Dizziness has a considerable impact on life quality and is associated with high economic costs. The purpose of this study was to evaluate the prevalence of dizziness in the general population and to describe its clinical characteristics and associated factors. Methods: The Korea National Health and Nutrition Examination Survey (KNHANES) is a cross-sectional survey of the civilian, non-institutionalized population of South Korea. We evaluated data for 12,653 participants (5,450 men and 7,203 women), aged 40 years and above, whom participated in the KNHANES between 2010 and 2012. Results: In the age group over 40 years old, the 1-year prevalence of dizziness was 20.10%. Dizziness was more prevalent among women (25.18%) than among men (14.57%; P < 0.001) and the prevalence rate increased with age (P < 0.001). In multivariable analysis, female sex, older age, serum triglyceride level, experience of depression, limited functional status owing to visual acuity impairment, limited physical performance, smoking, alcohol consumption, and perception of stress were independently associated with dizziness. Conclusions: In our study, the prevalence of dizziness in the general population was 20.10%. There was a stronger relationship between dizziness and physical performance, chronic diseases, and health behaviors compared to that with otologic diseases. Interventions for dizziness should be approached in a multifactorial manner and an understanding of various factors is necessary for the prevention and management of this condition.

The purpose of our study was to investigate characteristics of retinal vessels in eyes with surgically closed macular holes (MH). We included patients who underwent surgery for idiopathic MH and a follow-up examination using optical coherence tomography angiography (OCTA). The area of the foveal avascular zone (FAZ) and retinal vascular densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were calculated on the postoperative OCTA images and compared with those of age-matched normal controls. Twenty-eight patients with MH and 28 controls were included. Mean postoperative FAZ areas of SCP and DCP (0.317 ± 0.129 mm2 and 0.500 ± 0.174 mm2) were smaller than those of normal controls (0.406 ± 0.131 mm2 and 0.687 ± 0.147 mm2) (P = 0.013 and P

Background Previous studies have shown that chronic kidney disease (CKD) is associated with accelerated loss of skeletal muscle in patients on dialysis. However, the relationships of sarcopenia with albuminuria and early-stage CKD in patients with type 2 diabetes have not been examined. Methods We analyzed diabetic subgroup data from 409 patients with type 2 diabetes from the Korean Sarcopenic Obesity Study (KSOS). Sarcopenia was defined as a skeletal muscle mass index (SMI; SMI [%] = total skeletal muscle mass [kg]/weight [kg] × 100) less than 2 SD below the sex-specific mean for a younger reference group. The estimated glomerular filtration rates and urinary albumin-to-creatinine ratios were used to assess renal function and albuminuria. Results The prevalence of sarcopenia was significantly increased in the albuminuria group compared with the normo-albuminuria group (26.7% vs 12.6%, p = .001), as well as in CKD 3 group compared with the CKD 1–2 group (46.7% vs 15.1%, p = .005). After adjusting for age, SMI was negatively correlated with urinary albumin-to-creatinine ratios and positively correlated with aspartate aminotransferase, alanine aminotransferase, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. Multiple logistic regression analysis revealed that the odds ratio for albuminuria association was 3.02 (95% CI 1.37–6.67) in the lowest tertile of SMI compared with the highest tertile after adjusting for various confounding factors. Conclusions Sarcopenia is more prevalent in individuals with albuminuria than in those without albuminuria. Furthermore, increased albuminuria is independently associated with low muscle mass in patients with type 2 diabetes.

PURPOSE OF INVESTIGATION The authors aimed to determine the relationship between meteorological variables and hypertension in pregnancy by using data from a national weather database. MATERIALS AND METHODS For this population-based observational study, the database of the Korea National Health Insurance (KNHI) Claims of the Health Insurance Review and Assessment Service (HIRA) and Korea Meteorological Administration was used. The 48,275 women with preeclampsia among 2,495,383 women who gave birth were included. Monthly meteorological factors and preeclampsia prevalence for five years were statistically analyzed. RESULTS Among temperature, relative humidity, sunlight duration, and rainfall, only relative humidity had a significant inverse correlation with the preeclampsia prevalence (p < 0.001). The other meteorological factors were not associated with preeclampsia. CONCLUSION Relative humidity may be a significant factor for of the development of preeclampsia. Further monitoring of weather parameters during the entire pregnancy period may be the best method for verifying the present results in the development of preeclampsia.

Background Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease as well as metabolic syndrome. FDG-PET is a novel imaging technique that detects vascular inflammation, which may reflect rupture-prone vulnerable atherosclerotic plaques. Methods Vascular inflammation was measured as the maximum target-to-background ratio (maxTBR), along with various cardiometabolic risk factors in 51 subjects with NAFLD, and compared with 100 age- and gender-matched subjects without NAFLD. The liver attenuation index (LAI), which was measured using computed tomography, was used as a parameter for the diagnosis of NAFLD. Results After adjusting for age and sex, both maxTBR and LAI values were associated with several cardiometabolic risk parameters. Furthermore, there was a significant inter-relationship between LAI and maxTBR values ( r = − 0.227, P = 0.005). Individuals with NAFLD had higher maxTBR values than those without NAFLD ( P = 0.026), although their carotid intima–media thickness (CIMT) values did not differ. The proportion of subjects with NAFLD showed a step-wise increment following the tertiles of maxTBR values ( P for trend = 0.015). In multiple logistic regression analysis, maxTBR tertiles were independently associated with NAFLD after adjusting for age, gender, systolic blood pressure, triglycerides, HDL-cholesterol, glucose, BUN, creatinine and homeostasis model assessment of insulin resistance (HOMA-IR) ( P = 0.030). However, their relationship was attenuated after further adjustment for waist circumference or high sensitive C-reactive protein. Conclusion Patients with NAFLD have an increased risk for vascular inflammation as measured via FDG-PET/CT even without difference in CIMT. (Clinical trials No. NCT01958411 , http://www.clinicaltrials.gov /)

Background The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain. Methods The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex. Results In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups. Conclusion Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.

Objectives: A recent experimental study revealed that family with sequence similarity 19 [chemokine (C-C motif)-like] member A5 (FAM19A5), a novel secreted adipokine, has inhibitory effects on vascular smooth muscle cell proliferation and migration, and on neointima formation in injured arteries. We investigated the associations between serum FAM19A5 concentration and cardio-metabolic risk factors for the first time in human subjects. Methods: Circulating FAM19A5 concentrations and their associations with cardio-metabolic risk factors were explored in 223 individuals (45 without diabetes and 178 with type 2 diabetes). Results: Serum FAM19A5 concentrations (pg/mL) were greater in patients with type 2 diabetes [median (interquartile range), 172.70 (116.19, 286.42)] compared with non-diabetic subjects [92.09 (70.32, 147.24)] ( p 2 = 0.0689). Conclusion: A novel adipokine FAM19A5 was related to various metabolic and vascular risk factors in humans, suggesting its potential as a biomarker of cardio-metabolic disease.

PURPOSE To investigate the features of the retinal pigment epithelium (RPE) on optical coherence tomography in eyes with early age-related macular degeneration with subretinal drusenoid deposit. METHODS We classified the eyes into three types: nonundulating RPE, undulating RPE, and wedge-shaped RPE. We compared the retinal vessel densities, retinal thickness, and choroidal thickness of a 3-mm-diameter zone. RESULTS We classified 33, 27, and 20 as nonundulating RPE, undulating RPE, and wedge-shaped RPE eyes, respectively. The vascular densities of the superficial and deep capillary plexus showed differences; nonundulating RPE group (23.93 ± 2.26% and 23.54 ± 1.78%), undulating RPE group (22.29 ± 2.80% and 21.94 ± 2.42%), and wedge-shaped RPE group (21.93 ± 2.70% and 20.63 ± 2.42%, P = 0.010 and P < 0.001). The mean retinal thickness and choroidal thickness were also different, nonundulating RPE group (298.26 ± 13.81 µm and 180.08 ± 55.49 µm), undulating RPE group (285.29 ± 21.88 µm and 148.45 ± 55.08 µm), and wedge-shaped RPE group (274.86 ± 20.62 µm and 135.75 ± 39.77 µm) (P = 0.001 and P = 0.007). CONCLUSION Altered features of the RPE on optical coherence tomography may indicate advancement in disease and be part of an overall degeneration process in these eyes.

OBJECTIVES We evaluated the value of carbohydrate antigen 19-9 (CA 19-9) as a pancreatic cancer (PC) screening tool in an asymptomatic new-onset diabetic patients. METHODS Medical records of asymptomatic patients newly diagnosed with diabetes mellitus (DM) were reviewed retrospectively at our hospital from January 2004 to January 2013. RESULTS In total, 2363 asymptomatic diabetic patients with CA 19-9 measurements were enrolled. Of them, 68 (2.9%) were diagnosed with PC. In the 1719 patients who had CA 19-9 measured within 1 year after the DM diagnosis, a total of 51 (3.0 %) patients developed PC and the odds ratio (OR) of PC according to higher CA 19-9 than normal upper limit, 37 IU/mL was 5.57 (P < 0.001). In 248 patients checked CA 19-9 between 1 and 2 years after DM diagnosis, PC was detected in 9 (3.6%) cases and OR of high CA 19-9 was 4.51 (P = 0.019). However, beyond 2 years, the OR for PC showed no statistical significance. The patients with high CA 19-9 levels tended to have more advanced-stage disease. CONCLUSIONS Early check-up of CA 19-9 could be a useful marker for screening for PC in asymptomatic patients with new-onset DM in the first 2 years.

A new pooled cohort risk equation to estimate atherosclerotic cardiovascular disease (CVD) risk was recently published, but the equation is based primarily on data from Caucasian populations. The relationship of this new risk scoring system with vascular inflammation and calcification has yet to be examined.A total of 74 participants were retrospectively selected based on inclusion and exclusion criteria. All participants underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and multi-detector computed tomography (MDCT) examination in the Korea University Guro Hospital between June 2009 and May 2013. Vascular inflammation of the carotid artery was measured as target-to-background ratio (TBR) using (18)F-FDG-PET/CT and coronary artery calcification was quantified as Agatston score by MDCT.Agatston scores were not significantly associated with any metabolic risk factors, but maximum TBR values exhibited a significant positive correlation with body mass index (r=0.31, P=0.01), waist circumference (r=0.42, P0.01), waist-to-hip ratio (r=0.49, P0.01), and systolic (r=0.35, P0.01) and diastolic blood pressure (r=0.39, P0.01). Furthermore, maximum TBR values were significantly correlated with serum high-sensitivity C-reactive protein (hsCRP) levels (r=0.26, P=0.03), whereas Agatston scores had no correlation. When pooled cohort risk equation scores were divided into incremental tertiles, age, waist circumference, waist-to-hip ratio and systolic blood pressure showed significant incremental trends. In particular, pooled cohort risk scores exhibited a significant positive correlation with maximum TBR values (r=0.35, P0.01), but not with Agatston scores (r=0.11, P=0.34).The pooled cohort risk equation exhibited significant positive correlations with vascular inflammation but not with calcification in Asian subjects without CVD, suggesting that this novel risk equation may detect early inflammatory changes preceding the structural modification of vessel walls.

We aimed to compare changes in subfoveal and peripapillary choroidal thickness (CT) after intravitreal aflibercept or ranibizumab injections for neovascular age-related macular degeneration (AMD). Medical records of 54 treatment-naive, consecutive patients (54 eyes) who were diagnosed with neovascular AMD and received three monthly injections of aflibercept (21 eyes) or ranibizumab (33 eyes) were reviewed. Subfoveal and peripapillary CT were measured with images obtained using spectral domain optical coherence tomography at baseline and at three months. Subfoveal CT decreased from 232.2 ± 94.4 μm at baseline to 207.1 ± 89.3 μm at three months in the aflibercept group (p

Although cranioplasty (CP) is a frequently performed and simple procedure, complications are common, particularly bone flap resorption and infection. The timing of surgery is as an important contributory factor, but the optimal timing has not been clearly determined. We retrospectively investigated bone flap resorption and surgical site infection after CP to determine the optimal timing of surgery for reduction of complications. The study enrolled 126 patients who underwent decompressive craniectomy (DC) and subsequent CP. Patients with bone flap resorption or surgical site infection were analyzed as the “complication” group. Receiver operating characteristic curve analysis was performed and the Youden index was used to dichotomize “early CP” and “late CP” groups. Univariate and multivariate survival analyses were performed. The complication group included 42 patients. The Youden index was used to identify a cutoff value for the DC-CP interval of > 44 days, and this was used to define early (

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive CD133+/CD24− cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

The purpose of the study is to investigate the characteristics of choriocapillaris flow based on the underlying choroidal vasculature in fellow eyes with central serous chorioretinopathy (CSC). We included 57 patients with CSC and normal controls. Characteristics of choriocapillaris flow were evaluated using swept-source optical coherence tomography (OCT) angiography. We divided the choroidal layer into the vascular and stromal beds according to the choroid vessels on en-face OCT images. We compared the flow void area and mean vascular density of the choriocapillaris according to the underlying choroidal beds in the CSC and control group. The mean vascular density of the choriocapillaris in the CSC group was not different from that of the control group (P = 0.289). The flow void area was more frequently found in the CSC group (59.6%) than in the control group (29.8%, P = 0.002). The presence of the flow void area in the CSC group was associated with greater macular choroidal thickness (P = 0.004). In the CSC group, the mean flow void area and ratio of the choriocapillaris over the vascular bed were larger than those over the stromal bed (all P

Background To investigate the characteristics of retinal vessels and retinal thickness in eyes with early age-related macular degeneration (AMD) with or without reticular pseudodrusen. Methods We retrospectively evaluated the clinical history and optical coherence tomography (OCT) and OCT angiography images of consecutive patients with early AMD. We calculated the retinal vessel densities of the superficial and deep capillary plexus with the ImageJ software (National Institutes of Health, Bethesda, MD, USA) and investigated the relationship with mean retinal thickness and subfoveal choroidal thickness. Results We included 135 early AMD eyes and classified 60 of them into a reticular pseudodrusen group and 75 into a non-reticular pseudodrusen group. The vascular densities of the superficial and deep capillary plexus in the reticular pseudodrusen group (32.35% ± 3.67 and 26.71% ± 2.88%) were not different from those of the non-reticular pseudodrusen group (33.18% ± 2.2% and % 27.43 ± 1.79%; P = 0.546 and P = 0.318, respectively). The retinal thickness of the reticular pseudodrusen group (287.31 μm ± 24.36 μm) did not differ from that of the non-reticular pseudodrusen group (294.27 μm ± 20.71 μm; P = 0.493), while subfoveal choroidal thickness in the reticular pseudodrusen group (158.13 μm ± 42.53 μm) was lower than that in the non-reticular pseudodrusen group (237.89 μm ± 60.94 μm; P

Background. Limited information exists about the impact of nonalcoholic fatty liver disease (NAFLD) on mild renal insufficiency. We compared the relative influence of NAFLD, metabolic syndrome (MetS), and subclinical inflammation, alone or in combination, on mild renal insufficiency. Methods. This study included 1174 Korean adults. NAFLD was diagnosed using ultrasonography. Mild renal insufficiency was defined as an estimated glomerular filtration rate (eGFR) ≥ 60 and 2. Results. In partial correlation analysis, several components of MetS and liver aminotransferase levels, but not high-sensitivity C-reactive protein (hsCRP), were associated with eGFR. Multivariate logistic regression analysis demonstrated the independent association of NAFLD (P=0.034) and MetS (P=0.018) with mild renal insufficiency, but not elevated hsCRP (P=0.885). Furthermore, NAFLD without the MetS group (odds ratio (95% confidence interval) = 1.56 (1.05–2.34)) or MetS without the NAFLD group (1.82 (1.11–3.00)) was associated with mild renal insufficiency after adjusting for confounding variables. However, individuals with high hsCRP showed no relationship with mild renal insufficiency, irrespective of the existence of NAFLD. Conclusions. This study demonstrated that NAFLD and MetS are independently associated with mild renal insufficiency, whereas subclinical inflammation did not affect the risk for mild renal insufficiency in Korean adults.

Background/Aims: To prevent hypocalcemia after parathyroidectomy (PTX), parenteral calcium is required in addition to oral calcitriol and calcium. After switching to oral calcium, patients can be discharged from the hospital. The aim of this study was to analyze the clinical characteristics and outcomes of PTX performed at a single Korean center and to investigate the associated laboratory factors used to analyze the total amount of postoperative calcium required. Methods: We enrolled 91 hemodialysis patients undergoing PTX from November 2003 to December 2011. We collected clinical and laboratory data preoperatively, 12 and 48 hours postoperatively, at discharge, and 3 and 6 months postoperatively. Results: In total, 59 patients underwent PTX with autotransplantation (AT), 6 underwent total PTX without AT, 11 underwent subtotal PTX, and 15 underwent limited PTX. Total PTX without AT showed the lowest recurrence rate. At all postoperative time points, the mean levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) decreased significantly, compared with preoperative levels; however, alkaline phosphatase (ALP) increased significantly from 48 hours postoperatively to discharge (p < 0.001). On multiple linear regression analysis, the total amount of injected calcium during hospitalization showed a significant correlation with preoperative ALP (p < 0.001), preoperative iPTH (p = 0.037), and Δphosphorus at 48 hours (p < 0.001). We developed an equation for estimating the total calcium requirement after PTX. Conclusions: Preoperative ALP, preoperative iPTH, and Δphosphorus at 48 hours may be significant factors in estimating the postoperative calcium requirement. The formula for postoperative calcium requirement after PTX may help to predict the duration of postoperative hospitalization.

SummaryObjective Nonalcoholic fatty liver disease (NAFLD) is a well-known contributor for the development of cardiovascular disease (CVD). We examined the influence of NAFLD and metabolic syndrome (MetS) on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), brachial–ankle pulse wave velocity (baPWV) and ankle–brachial pressure index (ABI), after adjusting for cardiometabolic risk factors. Design A cross-sectional study. Patients and measurements The association between NAFLD, MetS and markers of subclinical atherosclerosis was assessed in 955 participants without CVD using multiple logistic regression analysis after adjusting for multiple cardiometabolic risk variables. Results After adjusting for age and sex, CIMT and baPWV were found to be significantly correlated with multiple cardiometabolic risk variables, whereas ABI was only associated with obesity parameters. The prevalence of NAFLD differed significantly according to the presence of subclinical atherosclerosis as defined by both CIMT and baPWV (P = 0·004 and P = 0·007, respectively). After adjusting for potential confounding factors, NAFLD or MetS was not associated with subclinical atherosclerosis as defined by CIMT and baPWV. However, individuals with both NAFLD and MetS had a significantly higher risk of subclinical atherosclerosis as defined by CIMT (OR = 2·06, 95% CI = 1·13–3·74) or baPWV (OR = 2·64, 95% CI = 1·46–4·76) compared to normal subjects, even after adjusting for potential confounders. Conclusions The results show that NAFLD and MetS have a synergistic impact on the subclinical atherosclerosis, which suggests that individuals with both NAFLD and MetS should be strongly advised to engage in CVD prevention strategies.

Background: Anemia is a major risk factor that contributes to mortality in patients with chronic kidney disease. There is controversy over the optimal hemoglobin (Hb) target in these patients. This study investigated the association between Hb level and mortality in a cohort of hemodialysis (HD) patients in Korea. Methods: This study was a multicenter prospective observational study of maintenance HD patients that was performed for 5 years in western Seoul, Korea. Three hundred and sixty-two participants were enrolled. Laboratory values and mortality were accessed every 6 months. Repeated measures of laboratory values in each interval were averaged to obtain one semiannual mean value. The Hb values were divided into six groups: (1) Hb

Recent studies have suggested that body size phenotype may contribute to atherosclerosis and cardiovascular disease. 18 F-fluorodeoxyglucose (FDG) positron emission tomography is a useful imaging technique for detecting vascular inflammation that may reflect plaque vulnerability. Therefore, we analyzed which body size phenotypes cause the increased vascular inflammation using FDG positron emission tomography. We compared 18 F-FDG uptake, measured using the blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), along with various cardiometabolic risk parameters in 250 participants without a history of cardiovascular disease. Body size phenotypes were classified according to body mass index and the presence/absence of metabolic syndrome. Cardiometabolic risk factors were significantly different among the body size phenotype groups. In particular, the maximum TBR (maxTBR) values in the metabolically abnormal but normal-weight, metabolically healthy obese (MHO), and metabolically abnormal obese groups were significantly greater than those of the metabolically healthy normal-weight (MHNW) group. Components of metabolic syndrome, insulin resistance, high-sensitivity C-reactive protein, and Framingham Risk Score were associated with maxTBR value. Interestingly, although the Framingham Risk Score of the MHO group was almost similar to that of the MHNW group, maxTBR value of MHO subjects was significantly higher than that of MHNW subjects (1.38 [1.20, 1.50] vs 1.22 [1.12, 1.37], p = 0.006). In conclusion, the present study suggests that unique subsets of body size phenotype, such as MHO or metabolically abnormal but normal weight, may have distinct effects on vascular inflammation.

PURPOSE To investigate ocular perfusion pressure (OPP) in patients with central serous chorioretinopathy (CSC) and pigment epitheliopathy (PE). METHODS In this retrospective study, we included patients with acute idiopathic unilateral CSC and age- and sex-matched normal controls. The patients with CSC were classified into two groups according to the PE presence on their fellow eyes. We compared OPP among CSC patients with or without PE and normal controls. RESULTS Among a total of 47 patients with CSC, 21 were classified into the PE group and 26 into the non-PE group. The mean OPP (±SD) of CSC and fellow eyes in the PE group (50.02 ± 4.98 and 50.83 ± 4.12 mmHg, respectively) was greater than that in the non-PE group (43.69 ± 6.88 and 44.0 ± 6.57 mmHg, respectively) and normal controls (45.64 ± 8.73 mmHg) (all, P < 0.05). The mean macular choroidal thickness of CSC and fellow eyes in the PE group (344.4 ± 31.8 and 310.1 ± 37.0 μm, respectively) was thicker than that in the non-PE group (318.5 ± 43.8 and 282.8 ± 36.1 μm, respectively) (all, P < 0.05). Greater macular choroidal thickness and higher OPP were associated with PE (P = 0.002 and P = 0.003). CONCLUSION Forty-five percent of the patients with acute unilateral CSC had PE in their fellow eyes. Increased OPP may influence the development of bilateral CSC characteristics.

Background Inpatient suicide is one of the major issues related with hospital patient safety. Although there are many studies addressing suicide in the psychiatric unit, little is known about suicide in a medical setting. This study included the development and validation of a screening tool for the assessment of suicide risk, specialized for medical inpatients. Methods The preliminary questionnaire was based on review of previous suicide ideation scales, mood scales, and clinical experiences of psychiatrists and clinical psychologists in Korea. Initially, the questionnaire consisted of 12 questions. One hundred adult medical inpatients were asked to perform the questionnaire. Explorative factor analysis was used to examine construct validity. Concurrent validity was evaluated by comparison with the Korean versions of the Beck Scale for Suicide Ideation (BSI), the Beck Hopelessness Scale (BHS), and the Hospital Anxiety and Depression Scale (HADS). Results Five questions were removed from the preliminary questionnaire by explorative factor analysis and seven questions remained to comprise the Suicide Risk Scale for Medical inpatients (SRSM). Explorative factor analysis showed that the SRSM is composed of a single factor. SRSM was highly reliable in terms of internal consistency (Cronbach's alpha 0.91). Concurrent validity with the BSI, BHS, and HADS was statistically significant. The proposed cut-off score of the SRSM was five. Conclusion In conclusion, the SRSM is a valid and reliable measure for screening suicide risks in medical inpatients., Graphical Abstract

Meteorin-like (Metrnl) was recently identified as a novel adipomyokine induced by exercise and cold exposure. Metrnl improves glucose tolerance, increases systemic energy expenditure, induces white adipose browning, and promotes anti-inflammatory gene programs in obese/diabetic mice. However, the relationship of Metrnl with diabetes and cardiometabolic risk variables in humans has not been explored.In 800 subjects (400 patients with type 2 diabetes and 400 non-diabetes), Metrnl concentration was measured with an enzyme-linked immunosorbent assay, and the correlations of Metrnl level with anthropometric parameters, lifestyle factors, body composition values, and laboratory measurements were assessed.Metrnl concentration was significantly higher in patients with diabetes than in those without diabetes [median (inter-quartile range); diabetes: 1219.9 (1020.6, 1535.6), non-diabetes: 1131.2 (993.1, 1313.6) pg/ml, P .001]. After adjustment for age and sex, Metrnl level was significantly associated with fasting plasma glucose, blood pressure, lipid profile, and eGFR, but not with BMI or percent body fat. Multiple stepwise regression analysis exhibited that Metrnl level was independently associated with diabetes status (P .001), eGFR (P .001), and total cholesterol (P = .026) (RThis study is the first to demonstrate that Metrnl level is elevated in human subjects with type 2 diabetes and is inversely related to various cardiometabolic risk factors, including renal function.

Objective Previous studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2), a recently discovered hepatokine, is associated with the inflammatory response and insulin resistance. We examined circulating plasma LECT2 levels in the subjects with non-alcoholic fatty liver disease (NAFLD) or metabolic syndrome. Methods We analyzed plasma LECT2 levels from the subjects of age- and sex-matched 320 adults with or without NAFLD who completed a health check-up at the Health Promotion Center of Korea University Guro Hospital. Results Individuals with NAFLD showed significantly higher LECT2 levels (31.2 [20.9, 41.5] vs. 24.5[16.3, 32.7] ng/ml, P

Although the prevalence of interracial marriages in Korea is increasing, little is known regarding the pregnancy outcomes of interracial couples. The aim of this study was to investigate the differences in pregnancy outcomes between Korean and interracial Korean-foreign couples. Data for infants born in 2011 and 2012 were obtained from the national birth registry of the Korean Statistical Office. The couples were subdivided into Korean father-Korean mother, Korean father-foreign mother, and foreign father-Korean mother groups. Pregnancy outcomes included neonates with low birth weight (< 2,500 g) and those with high birth weight (> 4,000 g). In 2010 and 2011, 888,447 Korean father-Korean mother, 36,024 Korean father-foreign mother, and 4,955 foreign father-Korean mother neonates were delivered in Korea. After adjustment for parental age, educational level, parity, gestational age at delivery, and neonatal sex, the birth weights were found to be different between groups, with the highest number of foreign father-Korean mother and lowest number of Korean father-foreign mother pregnancies. Based on multivariate logistic regression analysis, the risk of low and large birth weights was higher in the Korean father-foreign mother and foreign father-Korean mother groups, respectively, compared with that in the Korean father-Korean mother group. There are significant differences in pregnancy outcomes including birth weights between Korean and interracial Korean-foreign couples.

Objectives/Hypothesis In the present study, we aimed to determine the prevalence of hearing loss in the South Korean population and to understand the correlation between aging, sex, and hearing loss prevalence through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES). Study Design Cross-sectional epidemiological study. Methods The KNHANES is an ongoing population study that started in 1998. Examinations to detect diseases of the ear, nose, and throat, including audiological testing and otologic examinations, have been conducted since 2010. We included a total of 18,650 participants in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric testing was conducted in participants aged ≥ 12 years. The frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. Results The prevalence of hearing loss in speech-relevant frequencies in the South Korean population was 9.31% for unilateral hearing loss and 13.42% for bilateral hearing loss. The overall hearing loss (unilateral or bilateral) was 22.73%. Male and older participants were more often affected by hearing loss than female and younger participants. High-frequency hearing loss appeared earlier than hearing loss at speech-relevant frequencies, and unilateral hearing loss showed a weaker correlation with aging than bilateral hearing loss. Conclusion The prevalence of hearing loss in South Korea was higher in men and older participants according to the data collected from the KNHANES. The patterns of hearing loss differed between hearing loss at speech-relevant frequencies and at high frequencies. Level of Evidence 2b. Laryngoscope, 125:690–694, 2015