Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings.

BACKGROUND AND AIM: In relation to the new umbrella terminology for steatotic liver disease (SLD), we aimed to elucidate the prevalence, distribution, and clinical characteristics of the SLD subgroups in the primary care setting. APPROACH AND RESULTS: We retrospectively collected data from 2535 individuals who underwent magnetic resonance elastography and MRI proton density fat fraction during health checkups in 5 primary care health promotion clinics. We evaluated the presence of cardiometabolic risk factors according to predefined criteria and divided all the participants according to the new SLD classification. The prevalence of SLD was 39.13% in the total cohort, and 95.77% of the SLD cases had metabolic dysfunction (one or more cardiometabolic risk factors). The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) was 29.51%, with those of metabolic dysfunction and alcohol associated steatotic liver disease (MetALD) and alcohol-associated liver disease (ALD) at 7.89% and 0.39%, respectively. According to the old criteria, the prevalence of NAFLD was 29.11%, and 95.80% of the NAFLD cases fulfilled the new criteria for MASLD. The distribution of SLD subtypes was highest for MASLD, at 75.40%, followed by MetALD at 20.06%, cryptogenic SLD at 3.33%, and ALD at 1.01%. The MetALD group had a significantly higher mean magnetic resonance elastography than the MASLD or ALD group. CONCLUSION: Almost all the patients with NAFLD met the new criteria for MASLD. The fibrosis burden of the MetALD group was higher than those of the MASLD and ALD groups.

Diagnostic performance of non-invasive tests in patients with MetALD in a health check-up cohort.

BACKGROUND & AIMS: Non-invasive tests (NITs) for liver fibrosis have been recognized for their clinical utility in metabolic dysfunction-associated steatotic liver disease (MASLD). However, their diagnostic efficacy in detecting liver fibrosis is notably reduced in patients with alcohol-related liver disease. Therefore, ascertaining the reliability of NITs in patients with MASLD with moderate alcohol intake (MetALD) is essential. METHODS: In this cross-sectional study, we reviewed data from 7,918 health check-up participants who underwent both magnetic resonance elastography (MRE) and ultrasound for the diagnosis of hepatic steatosis. The participants were categorized into MASLD and MetALD groups, and the performance of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were assessed. Advanced hepatic fibrosis (F3) was defined as MRE ≥3.6 kPa. RESULTS: The prevalence of MetALD was 5.8% in this health check-up cohort, and 1.5% of these patients exhibited advanced hepatic fibrosis. Both MetALD and MASLD displayed similar metabolic profiles and hepatic fibrosis burdens. The diagnostic performance of FIB-4 and NFS for MRE ≥3.6 kPa showed no noticeable differences in the area under the receiver-operating characteristic values between the two groups (0.85 vs. 0.80 in FIB-4). Moreover, the sensitivity (71.4%), specificity (77.3%), and both positive (4.6%) and negative (99.4%) predictive values of NITs for MetALD closely mirrored those observed for MASLD. CONCLUSION: FIB-4 performed well for the initial screening of advanced hepatic fibrosis in MetALD, demonstrating reasonable sensitivity and negative predictive values. IMPACT AND IMPLICATIONS: In this cross-sectional study, data from 7,918 participants who underwent MRE were analyzed to assess the performance of fibrosis-4 (FIB-4) and non-alcoholic fatty liver disease fibrosis scores in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with moderate alcohol intake (MetALD). We found that FIB-4 had high diagnostic accuracy in the newly identified MetALD group, similar to that in the MASLD population. These results highlight the potential of FIB-4 as a reliable screening tool for MetALD, even when specific subgroups are considered. Therefore, FIB-4 is a valuable screening tool for identifying advanced fibrosis in the MetALD population.

Diagnostic performances of Fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction-associated steatotic liver disease in Asian primary care clinics.

AIMS: We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB-4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort. METHODS: This retrospective cross-sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n = 6740). RESULTS: The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n = 80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB-4 (0.824 in NAFLD vs. 0.818 in MASLD, p = 0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p = 0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB-4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD. CONCLUSIONS: Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB-4 in the MASLD cohort demonstrated satisfactory results.

Leveraging the Fragment Molecular Orbital and MM-GBSA Methods in Virtual Screening for the Discovery of Novel Non-Covalent Inhibitors Targeting the TEAD Lipid Binding Pocket.

The Hippo pathway controls organ size and homeostasis and is linked to numerous diseases, including cancer. The transcriptional enhanced associate domain (TEAD) family of transcription factors acts as a receptor for downstream effectors, namely yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which binds to various transcription factors and is essential for stimulated gene transcription. YAP/TAZ-TEAD facilitates the upregulation of multiple genes involved in evolutionary cell proliferation and survival. TEAD1-4 overexpression has been observed in different cancers in various tissues, making TEAD an attractive target for drug development. The central drug-accessible pocket of TEAD is crucial because it undergoes a post-translational modification called auto-palmitoylation. Crystal structures of the C-terminal TEAD complex with small molecules are available in the Protein Data Bank, aiding structure-based drug design. In this study, we utilized the fragment molecular orbital (FMO) method, molecular dynamics (MD) simulations, shape-based screening, and molecular mechanics-generalized Born surface area (MM-GBSA) calculations for virtual screening, and we identified a novel non-covalent inhibitor-BC-001-with IC50 = 3.7 µM in a reporter assay. Subsequently, we optimized several analogs of BC-001 and found that the optimized compound BC-011 exhibited an IC50 of 72.43 nM. These findings can be used to design effective TEAD modulators with anticancer therapeutic implications.

Nomenclature Dilemma of Metabolic Associated Fatty Liver Disease (MAFLD): Considerable Proportions of MAFLD Are Metabolic Healthy.

BACKGROUND & AIMS: The purpose of this study was to investigate the proportion of subjects with metabolic dysfunction-associated fatty liver disease (MAFLD) and to assess the degree of hepatic fibrosis and cardiovascular risk in metabolically healthy MAFLD subjects. METHODS: A total of 6740 subjects who underwent both magnetic resonance elastography and abdominal ultrasound were included in this study. Significant (≥3.0 kPa) and advanced (≥3.6 kPa) hepatic fibrosis were evaluated by magnetic resonance elastography. The metabolic unhealthy status among subjects with MAFLD was defined as the presence of diabetes or 2 or more metabolic risk abnormalities. RESULTS: The prevalence of MAFLD among the health examination cohort was 44.5% (3002 of 6740). A total of 26.6% (800 of 3002) of MAFLD subjects were metabolically healthy (≤1 risk factors and no diabetes), and 56.3% of MAFLD subjects (1691 of 3002) did not have metabolic syndrome. Hepatic fibrosis burden and cardiovascular risk were significantly higher in the metabolic unhealthy MAFLD group than in the healthy control group. However, the prevalence of significant (5.8% vs 4.3%; P = .099) and advanced hepatic fibrosis (0.8% vs 0.7%; P = .934) did not differ between the metabolically healthy MAFLD and healthy control groups. The prevalence of carotid artery plaque in the metabolically healthy MAFLD (32.7% vs 30.7%; P = .453) group was not different from that in the healthy control group. CONCLUSIONS: Contrary to the definition of MAFLD, a non-negligible number of metabolically healthy individuals are included in the MAFLD group. The metabolic healthy MAFLD group showed a comparable fibrosis burden and prevalence of carotid artery plaque compared with the healthy control group.

Diagnostic Performance of Noninvasive Tests for Advanced Hepatic Fibrosis in Young Age Population.

BACKGROUND & AIMS: Most noninvasive tests (NITs) for hepatic fibrosis are designed for middle-aged patients with chronic liver disease. We compared the diagnostic performance of major NITs (aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score) for a community-based cohort. METHODS: This cross-sectional study analyzed 8775 participants who underwent magnetic resonance elastography at community health check-up centers. Advanced hepatic fibrosis (≥F3) was defined by magnetic resonance elastography thresholds of 3.6 kPa. The diagnostic performance of 3 NITs was evaluated according to the etiology of liver disease, sex, metabolic syndrome, obesity, and increased aminotransferase levels in 4 age groups. RESULTS: The APRI generally showed the best area under the receiver operating characteristic curve in patients aged 45 years or younger, and it was statistically significant in patients with chronic viral hepatitis and alcoholic fatty liver disease (P < .043). The best APRI cut-off value for detecting advanced hepatic fibrosis was 0.4, with a sensitivity and specificity of 75.8% and 73.5%, respectively, in the community-based cohort. The APRI showed balanced sensitivity and specificity across all age groups, whereas the other metrics showed low sensitivity in those aged <45 and low specificity in those >65 years. CONCLUSIONS: The APRI showed better sensitivity and negative predictive value than the Fibrosis-4 index and the nonalcoholic fatty liver disease fibrosis score in community-based populations with mixed etiology, and, thus, can be performed as the primary test in young adults (age, ≤45 y).

Antibody response after two doses of homologous or heterologous SARS-CoV-2 vaccines in healthcare workers at health promotion centers: A prospective observational study.

Assaying of anti-spike-protein receptor-binding domain (S-RBD) antibodies are used to aid evaluations of the immune statuses of individuals. The aim of this study was to determine the antibody response after two doses of homologous or heterologous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and to identify the factors affecting this response among healthcare workers (HCWs) at health promotion centers. In this prospective observational study, 1095 consenting HCWs were recruited from 16 health checkup centers and were tested at T0 (day of first dose), T1-1 (1 month after first dose), T2-0 (day of second dose), T2-1 (1 month after second dose), and T2-3 (3 months after second dose). SARS-CoV-2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS-CoV-2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). At T1-1, anti-SARS-CoV-2 S-RBD IgG levels were significantly higher in participants who received messenger RNA (mRNA) vaccines than in those who received viral vector vaccines (p < 0.001). At T2-1, anti-SARS-CoV-2 S-RBD IgG levels were about 10 times higher than at T1-1 in participants who received homologous mRNA vaccines, which decreased to a third of those at T2-3. Anti-SARS-CoV-2 S-RBD IgG levels were highest among those who received homologous mRNA vaccines, followed by heterologous mRNA viral vector vaccines and homologous viral vector vaccines at T2-3 (p < 0.001). In a multivariable linear regression analysis, being female, taking at least one mRNA vaccine, and having a history of recovery from coronavirus disease 2019 (COVID-19) were significantly associated with anti-S-RBD levels. Anti-SARS-CoV-2 S-RBD IgG levels were decreased at 3 months after two-dose vaccinations and were associated with sex, vaccine type, and COVID-19 history.

Prevalence of advanced hepatic fibrosis and comorbidity in metabolic dysfunction-associated fatty liver disease in Korea.

BACKGROUND & AIMS: There are several reports on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the prevalence of advanced hepatic fibrosis in MAFLD is largely unknown. We aimed to evaluate the prevalence of advanced fibrosis in MAFLD. METHODS: A total of 6775 subjects from nationwide 13 health check-up centres were included in this cross-sectional study. Fatty liver was evaluated using ultrasonography. Significant (≥F2) and advanced (≥F3) hepatic fibrosis were defined by MRE thresholds of 3.0 kPa (range: 2.99-3.65 kPa) and 3.6 kPa (range: 3.4-3.9 kPa) respectively. The sex- and age-standardized prevalence of MAFLD and hepatic fibrosis was estimated. RESULTS: The sex- and age-standardized prevalence of MAFLD was 33.9%. The prevalence of obesity (BMI ≥25 kg/m2 ) in MAFLD was 71.1%, and 79.0% of obese subjects had MAFLD. The prevalence of diabetes in MAFLD was 13.3%, and 73.6% of subjects with diabetes had MAFLD. The sex- and age-standardized prevalence of significant (≥F2) and advanced hepatic fibrosis (≥F3) amongst MAFLD was 9.7% (range: 3.0-9.8%) and 3.0% (range: 2.6-4.6%) respectively. The prevalence of advanced hepatic fibrosis in overweight/obese (group I), lean (group II) and diabetic (group III) MAFLD was 2.3%, 3.1% and 9.5% respectively. CONCLUSION: The sex- and age-standardized prevalence of advanced fibrosis was 3.0% (range: 2.6-4.6%) in subjects with MAFLD.

Comparison of diagnostic performance between FIB-4 and NFS in metabolic-associated fatty liver disease era.

AIMS: Fibrosis-4 index (FIB-4) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are the two most widely used non-invasive tools for screening of advanced fibrosis in subjects with NAFLD. Since metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as a new category of fatty liver disease, we aimed to compare the diagnostic performance of FIB-4 and NFS in subjects with MAFLD and in various subgroups. METHODS: This study was designed as cross-sectional study. Data from 6775 subjects who underwent magnetic resonance elastography (MRE) and abdominal ultrasonography at the same time during a health check-up at 13 various health check-up centers were retrospectively reviewed. Advanced fibrosis was defined as an MRE value of ≥3.6 kPa. RESULTS: The area under the receiver operating characteristic curves (AUROCs) of FIB-4 and NFS for diagnosing advanced fibrosis were similar in subjects with MAFLD. However, the AUROC of NFS was lower than that of FIB-4 in the diabetic subgroup of MAFLD (0.809 in FIB-4 vs. 0.717 in NFS, p = 0.002). The performances of both FIB-4 and NFS were poor in the subgroup of MAFLD with significant alcohol intake. CONCLUSIONS: The overall diagnostic performance of FIB-4 and NFS for diagnosing advanced fibrosis did not differ among subjects with MAFLD. However, the performance of NFS was lower in the diabetes subgroup of MAFLD. The diagnostic performance of FIB-4 was better for fibrosis in various subgroups of MAFLD.

Associations of complete blood count parameters with pancreatic beta-cell function and insulin resistance in prediabetes and type 2 diabetes mellitus.

INTRODUCTION: Previous studies found controversial associations of CBC parameters with pancreatic beta-cell function (BCF) and insulin resistance (IR). The aim of this was to determine the independent associations of CBC parameters with BCF and IR in prediabetes and type 2 diabetes mellitus (T2DM). METHODS: This study selected subjects who underwent health checkups at 16 health-promotion centers in 13 Korean cities during 2021. The subjects comprised 1470 patients with normoglycemia, 1124 with prediabetes, and 396 with T2DM. BCF and IR were assessed using the homeostasis model assessment (HOMA)-ß and HOMA-IR, respectively. Correlation and multiple linear regression analyses were used to determine the correlation between CBC parameters and HOMA. RESULTS: While HOMA-IR gradually increased according to red blood cell count quartiles (1.22, 1.40, 1.47, and 1.91, in the first, second, third, and fourth quartiles, respectively; p < 0.001), there was no correlation after adjusting for waist circumference (WC) and HbA1c. The red blood cell distribution width (RDW) was associated with HOMA-ß [coefficient (ß) = 15.527, p = 0.002], but not with HOMA-IR. White blood cells (WBCs) were associated with HOMA-IR and HOMA-ß, which was stronger in HOMA-ß (ß = 0.505 vs 15.171, p = 0.002) after adjusting for WC and HbA1c. The platelet count was correlated with HOMA-IR and HOMA-ß, which only remained in HOMA-ß (ß = 15.581, p = 0.002) after adjusting for WC and HbA1c. CONCLUSION: RDW, WBC, and platelet counts were independently associated with only HOMA-ß in prediabetes and T2DM. This suggests that these CBC parameters could represent BCF in prediabetes and T2DM.

The usefulness of the estimated average glucose/fasting blood glucose ratio for pancreatic ß-cell function assessment in hyperglycemia during health checkups.

BACKGROUND: Type 2 diabetes (T2DM) is a disease marked by inadequate insulin secretion by pancreatic beta-cell function (BCF) failure and insulin resistance (IR). Assessing and managing the BCF and IR should be started early to prevent or delay the progression of the disease. The aim of this study was to determine the usefulness of the estimated average glucose (eAG)/fasting blood glucose (FBG) ratio for pancreatic BCF in hyperglycemia. METHODS: This cross-sectional study consecutively selected 10,594 subjects who underwent a health checkup at 16 health checkup centers in 13 Korean cities between 2019 and 2021. The subjects consisted of 3003 patients with normoglycemia, 3413 with impaired fasting glucose and 4178 with T2DM. The eAG was calculated using Nathan's regression equation. BCF and IR were estimated by the homeostasis model assessment (HOMA)-ß and HOMA-IR, respectively. Multivariate (adjusted) regression analysis was performed to evaluate the association between the eAG/FBG ratio and HOMA. RESULTS: The median values among FBG groups for the eAG/FBG ratio, HOMA-ß, -IR and insulin differed significantly (p < 0.001). The second-, third- and fourth-quartile groups of the eAG/FBG ratio had positive higher correlation coefficients [9.533, 10.080 and 12.021, respectively (all p < 0.001)] for HOMA-ß than the first quartile group, and higher negative coefficients for HOMA-IR [-0.696, -0.727 and -0.598, respectively (all p = 0.001)]. CONCLUSION: The eAG/FBG ratio was significantly correlated with both HOMA-ß and -IR, which suggests that eAG/FBG ratio reveals BCF and IR in hyperglycemia. Measurement of this ratio could be useful for monitoring BCF and IR in prediabetes and T2DM.

Farnesol induces mitochondrial/peroxisomal biogenesis and thermogenesis by enhancing the AMPK signaling pathway in vivo and in vitro.

Thermogenic activation of brown adipose tissue has been considered as an obesity treatment strategy that consumes energy. In this study, we investigated whether farnesol in vivoandin vitro models induces thermogenesis and affect the activation of the mitochondria and peroxisomes, which are key organelles in activated brown adipocytes. Farnesol induced the expression of thermogenic factors such as uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1α), and PR domain zinc-finger protein 16 (PRDM16) together with the phosphorylation of AMP-activated protein kinase alpha (AMPKα) in brown adipose tissue and primary cultured brown adipocytes. Farnesol promoted lipolytic enzymes: hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). We confirmed that these inductions of lipolysis by farnesol were the underlying causes of ß-oxidation activation. Farnesol also increased the expression of oxidative phosphorylation (OXPHOS) complexes and the oxygen consumption rate (OCR) and the expansion of peroxisomes. Moreover, we proved that the thermogenic activity of farnesol was dependent on AMPKα activation using Compound C inhibitor or siRNA-AMPKα knockdown. These results suggest that farnesol may be a potential agent for the treatment of obesity by inducing energy consumption through heat generation.

Reference interval and the role of plasma oligomeric beta amyloid in screening of risk groups for cognitive dysfunction at health checkups.

BACKGROUND: Alzheimer's disease (AD) has a prolonged preclinical stage characterized by cognitive dysfunction. Simple, reliable, and noninvasive biomarkers reflecting the pathogenesis of AD are needed for screening cognitive dysfunction in primary health care. The aims of this study were to determine (1) the potential utility of the Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) value in cognitive assessments and (2) the reference interval (RI) of plasma MDS-OAß values in the general population. METHODS: This prospective study consecutively recruited 1,594 participants who underwent health checkups including cognitive function examination at 16 health-promotion centers in Korea between December 2020 and January 2021. The inBloodTM OAß test (PeopleBio, Gyeonggi-do, Republic of Korea) was utilized to quantify MDS-OAß values in plasma. The reference subjects were obtained among those with normal general cognition on cognitive screening tools. RIs were established according to the CLSI C28-A3 guidelines. RESULTS: The median MDS-OAß value was higher in subjects with Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) scores ≥8 than in those with KDSQ-C scores of 6-7 (P = 0.013). The median MDS-OAß value was higher in subjects with Mini-Mental State Examination for Dementia Screening (MMSE-DS) scores of 21-26 than in those with MMSE-DS scores ≥27 (P = 0.011). The RI (one-side upper 95th percentile) of the MDS-OAß value was 0.80 ng/mL (95% confidence interval = 0.78-0.82) in those aged ≥50 years. CONCLUSIONS: The plasma MDS-OAß value reflects cognitive function as assessed using the KDSQ-C and MMSE-DS. RIs obtained from a large and cognitively healthy community-based sample are presented.

A phytoestrogen secoisolariciresinol diglucoside induces browning of white adipose tissue and activates non-shivering thermogenesis through AMPK pathway.

Secoisolariciresinol diglucoside (SDG) is the main phytoestrogen component of flaxseed known as an antioxidant. Current study focused on the effect of SDG in white adipose tissue (WAT) browning. Browning of WAT is considered as a promising treatment strategy for metabolic diseases. To demonstrate the effect of SDG as an inducer of browning, brown adipocyte markers were investigated in inguinal WAT (iWAT) of high fat diet-fed obese mice and genetically obese db/db mice after SDG administration. SDG increased thermogenic factors such as uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha and PR domain containing 16 in iWAT and brown adipose tissue (BAT) of mice. Similar results were shown in beige-induced 3T3-L1 adipocytes and primary cultured brown adipocytes. Furthermore, SDG increased factors of mitochondrial biogenesis and activation. We also observed SDG-induced alteration of AMP-activated protein kinase α (AMPKα). As AMPKα is closely related in the regulation of adipogenesis and thermogenesis, we then evaluated the effect of SDG in AMPKα-inhibited conditions. Genetic or chemical inhibition of AMPKα demonstrated that the role of SDG on browning and thermogenesis was dependent on AMPKα signaling. In conclusion, our data suggest SDG as a potential candidate for improvement of obesity and other metabolic disorders.

Subclinical Iron Deficiency in Non-Anemic Individuals: A Retrospective Analysis of Korean Health Examinees.

OBJECTIVES: Non-anemic individuals may have undetected subclinical iron deficiency (SID). The aims of this study were to determine the prevalence of SID and identify the associated factors for SID. In addition, the screening performance of red blood cell (RBC) indices for SID in health check-ups was assessed. METHODS: This study was conducted with 16,485 non-anemic health examinees (3,567 males and 12,918 females) who underwent tests for iron variables (serum iron, total iron-binding capacity, ferritin, and iron saturation) at 16 health-promotion centers in 13 cities in Korea between January 2017 and June 2018. SID was defined as a decreased ferritin level (<24 µg/L in males and <15 µg/L in females) and either a decreased serum iron level (<44 µg/dL in males and <29 µg/dL in females) or a transferrin saturation of <20%. RESULTS: The prevalence rates of SID were 0.6 and 3.3% in males and females, respectively. In terms of age and sex, SID was most prevalent in males aged ≥70 years (7.8%) and females aged 15-49 years (7.6%). There were significant differences in the hemoglobin (Hb) level, white blood cell count, platelet count, mean corpuscular volume, mean corpuscular Hb (MCH), and RBC distribution width (RDW) between the SID and non-SID groups (p < 0.001). The factors associated with SID in males were older age (odds ratio, OR, 1.069, 95% confidence interval, CI, 1.03-1.109, p = 0.004), lower Hb (OR 0.58, 95% CI 0.345-0.976, p = 0.04), lower MCH (OR 0.433, 95% CI 0.298-0.629, p < 0.001), and higher RDW (OR 1.374, 95% CI 1.001-1.887, p = 0.049), while in females they were lower body mass index (BMI; OR 0.929, 95% CI 0.895-0.963, p < 0.001) and younger age (OR 0.954, 95% CI 0.945-0.963, p < 0.001), as well as lower Hb, lower MCH, and higher RDW. The AUC for the MCH (0.877, 95% CI 0.793-0.960 in males; 0.872, 95% CI 0.853-0.890 in females) indicates that the MCH at cut-offs of 29.2 and 29.3 pg are the best discriminators of SID in males and females, respectively (p < 0.001). CONCLUSIONS: Reproductive-age females with a lower BMI and elderly males are high-risk groups for SID. MCH is a reliable RBC index for the screening of SID. For the population with defined risk factors, including females with lower BMI and elderly males, screening for SID is needed to prevent the development of anemia.

Reference interval and the role of soluble suppression of tumorigenicity 2 (sST2) in subclinical cardiac dysfunction at health checkups.

BACKGROUND: Soluble ST2 (sST2) is known to predict adverse outcomes and death in individuals with established heart failure. However, the role of sST2 testing in the general population has not been established. The aims of this study were to determine the reference interval (RI) and the clinical utility of sST2 in subclinical cardiac dysfunction in general population. METHODS: This cross-sectional study consecutively selected 41,806 general subjects at health checkups who underwent echocardiography and sST2 testing at 16 health promotion centers in 13 Korean cities. The reference subjects were obtained among those with normal findings in echocardiography. Sex-specific RIs were established according to the CLSI C28-A3 guidelines. sST2 was measured using immunoassay with the Presage ST2 assay (Critical Diagnostics). RESULTS: In the general subjects, age, sex, BMI, systolic blood pressure, blood glucose, creatinine, liver function, and triglycerides were associated with the sST2 levels. The RI for sST2 was higher in males (≤49.6 ng/mL, 95% CI = 48.5-51.5) than in females (≤44.5 ng/mL, 95% CI = 43.5-45.6) and higher in subjects aged < 40 years than ≥ 40 years in both sexes. The sST2 levels were 29.1 ± 10.7 (mean ± SD) and 29.1 ± 14.4 ng/mL in the groups with normal cardiac function and subclinical cardiac dysfunction, respectively. The sST2 level was not associated with subclinical cardiac dysfunction (odd ratio = 1.002, P = .13). CONCLUSIONS: RIs obtained from a large and echocardiography-proven healthy community-based sample are presented. Subclinical cardiac dysfunction was associated with older age, male sex, and metabolic factors but not with the sST2 level.

Diagnostic performance of Mac-2 binding protein glycosylation isomer (M2BPGi) in screening liver fibrosis in health checkups.

BACKGROUND: Mild-to-moderate fibrosis is rarely diagnosed because the disease is asymptomatic in the early stage. The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis. The aim of this study was to determine the diagnostic performance of M2BPGi in screening liver fibrosis using magnetic resonance elastography (MRE) as a reference standard and to compare it with using the aspartate aminotransferase-to-platelet ratio (APRI) and the Fibrosis-4 index (FIB-4) in health checkups. METHODS: This cross-sectional study consecutively selected subjects at health examinations who underwent MRE and M2BPGi testing at eight health promotion centers in Korea between January and September 2019. The serum M2BPGi level was measured using the chemiluminescence enzyme immunoassay method. The measured levels were indexed using the cutoff index (COI). COI values of M2BPGi were compared with the MRE results. RESULTS: The median (interquartile) values of COI for fibrosis stages F0 (normal liver stiffness), F1 (mild fibrosis), F2 (significant fibrosis), and ≥F3 (advanced fibrosis) were 0.49 (0.34-0.61), 0.48 (0.38-0.68), 0.64 (0.43-1.03), and 1.01 (0.75-1.77), respectively (P < .0001). The AUCs of the COI for the screening of fibrosis stage ≥F1, ≥F2, and ≥F3 were 0.591, 0.698, and 0.853, respectively. Using a threshold of 0.75 for COI to exclude advanced fibrosis had a sensitivity, specificity, and negative predictive value of 80.0%, 77.9%, and 98.9%, respectively. The AUC for excluding advanced fibrosis was better for M2BPGi than for FIB-4 and APRI. CONCLUSION: Serum M2BPGi was useful for screening significant and advanced fibrosis in health checkups.

Effect of Mass Drug Administration with a Single Dose of Albendazole on Ascaris lumbricoides and Trichuris trichiura Infection among Schoolchildren in Yangon Region, Myanmar.

Soil-transmitted helminths, including Ascaris lumbricoides and Trichuris trichiura, are important intestinal parasites mostly affecting younger people in developing countries. In 2014-2015, we performed mass fecal examinations targeting a total of 2,227 schoolchildren in 3 districts (South Dagon, North Dagon, and Hlaing-thar-yar) of Yangon Region, Myanmar, using the Kato-Katz thick smear technique. The egg positive children were subjected to a mass drug administration (MDA) using a single oral dose of 400 mg albendazole. The pre-treatment egg positive rate (EPG/person) of A. lumbricoides averaged 17.2% (15,532); it was 25.2% (21,796), 14.2% (11,816), and 12.8% (12,983) in 3 districts, respectively, and that of T. trichiura averaged 19.4% (1,074), and was 24.1% (1,040), 12.3% (852), and 21.2% (1,330) in 3 districts, respectively. Follow-up fecal examinations performed 4 months post-MDA revealed considerable decreases of A. lumbricoides prevalence (EPG/person) to av. 8.3% (12,429), and 13.7% (17,640), 8.0% (7,797), and 4.5% (11,849) in 3 districts, respectively. However, T. trichiura did not show any recognizable decrease in the prevalence (EPG/person) remaining at av. 18.2% (862), and 18.5% (888), 11.5% (812), and 23.3% (887) in 3 districts, respectively. The results demonstrated difficulty in short-term control of T. trichiura by MDA using albendazole and suggested necessity of either a long-term MDA (>10 years) or changing the albendazole regimen into 2~3-day course (total 800 or 1,200 mg), or using an alternative drug/drug combination.

Low-Grade Endemicity of Opisthorchiasis, Yangon, Myanmar.

We performed an epidemiologic survey of opisthorchiasis in Yangon, Myanmar. The fecal egg-positive rate of residents was 0.7%, and we recovered an adult fluke after chemotherapy and purging of an egg-positive resident. We detected Opisthorchis viverrini metacercariae in freshwater fish. We found the Yangon area to have low-grade endemicity of opisthorchiasis.

Patient Safety Culture Associated With Patient Safety Competencies Among Registered Nurses.

PURPOSE: To investigate the relationships between registered nurses' (RNs') perceptions of the culture of patient safety in their workplace and their patient safety competency-attitudes, skills, and knowledge. DESIGN: A cross-sectional study design was used. Data were collected by using a self-reported survey from 343 RNs working in a university hospital in Seoul, South Korea. METHODS: Patient safety culture was measured using the Korean version of the Agency for Healthcare Research and Quality's Hospital Survey on Patient Safety Culture (Hospital SOPSTM). Patient safety competency was measured using the Patient Safety Competency Self-Evaluation tool. Multiple regression analysis was performed using Stata version 14 to examine the relationships between patient safety culture and RNs' patient safety competency, while adjusting for the RNs nested in their units. FINDINGS: Of the 10 specific aspects of patient safety culture, only teamwork within units was significantly related to overall safety competency. In relation to each of the three patient safety competencies, teamwork within and across units and supervisor or manager expectations were significantly related to attitudes, while teamwork within units and learning were significantly related to skills. Only organizational learning was significantly related to knowledge. CONCLUSIONS: Although teamwork, leadership, and continuous learning in the nursing unit were major factors influencing RNs' safety competency, the relationships of these factors to patient safety attitudes, skills, and knowledge among RNs were varied. CLINICAL RELEVANCE: Creating a unit-specific patient safety culture that is tailored to the competencies of the unit's RNs in patient safety practice would be essential to enhance and maintain high levels of patient safety attitudes, skills, and knowledge among the unit's RNs, which would ultimately affect patient safety.