Novel Organoid Culture System for Improved Safety Assessment of Nanomaterials.

Over the past few decades, the increased application of nanomaterials has raised questions regarding their safety and possible toxic effects. Organoids have been suggested as promising tools, offering efficient assays for nanomaterial-induced toxicity evaluation. However, organoid systems have some limitations, such as size heterogeneity and poor penetration of nanoparticles because of the extracellular matrix, which is necessary for organoid culture. Here, we developed a novel system for the improved safety assessment of nanomaterials by establishing a 3D floating organoid paradigm. In addition to overcoming the limitations of two-dimensional systems including the lack of in vitro-in vivo cross-talk, our method provides multiple benefits as compared with conventional organoid systems that rely on an extracellular matrix for culture. Organoids cultured using our method exhibited relatively uniform sizing and structural integrity and were more conducive to the internalization of nanoparticles. Our floating culture system will accelerate the research and development of safe nanomaterials.

Understanding patient and physician responses to various cost-sharing programs for prescription drugs in South Korea: A multilevel analysis.

Introduction: Patient and/or physician responses are a pivotal issue in designing rational cost-sharing programs under health insurance systems. Objectives: This study aims to understand patient and/or physician responses to cost-sharing programs designed for prescription drugs in South Korea. Methods: As a framework, we took advantage of a tiered cost-sharing program, including from copayment to coinsurance (threshold 1) and reduced coinsurance (threshold 2). Given the hierarchical structure of prescriptions nested within patients, we utilized a multilevel analysis to assess effects of various cost-sharing programs on patient and/or physician responses using National Health Insurance claims data from 2018. Results: We found that a tiered cost-sharing program was effective in changing the behaviors of patients and/or physicians. Threshold 1 was found to be more effective than threshold 2 in changing their behaviors. At the prescription level, sensitivity to cost-sharing programs was associated with prescribed days of treatment and locations of prescription. In a similar vein, sensitivity to cost-sharing programs was associated with gender and age group of patients. Conclusion: A simplified cost-sharing program with extended intervals should be considered to rationalize cost-sharing programs. Specifically, a cost-sharing program designed for long-term prescriptions for chronic diseases together with an emphasis on cost transparency is required to better guide price-conscious decisions by patients and/or physicians.

Secular Trends of Incidence, Prevalence, and Healthcare Economic Burden in ANCA-Associated Vasculitis: An Analysis of the 2002-2018 South Korea National Health Insurance Database.

Objectives: The incidence and prevalence of AAV in Asia remain poorly understood, especially in a nationwide setting. This study investigated the incidence, prevalence, and healthcare burden of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in South Korea by analyzing a national database. Methods: This study included patients with AAV identified from the National Health Insurance Service Database of South Korea from 2002 to 2018. Patients were diagnosed with AAV in a general or tertiary hospital and were registered in the individual payment beneficiaries program or were prescribed glucocorticoids. A calendar-based meteorological definitions were adopted to assess the differences in the incidence of AAV according to season. The average healthcare expenditure and patient outcomes of mortality and end-stage renal disease (ESRD) in patients with AAV were compared to 1:10 age, sex and residential area matched controls. Results: A total of 2,113 patients [708, 638, and 767 with microscopic polyangiitis (MPA), granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, respectively] were identified. The annual incidence and prevalence of AAV increased continuously, and MPA being the most common disease subtype after 2015. The highest incidence and prevalence of AAV was 0.48/100,000 person-years (PY) and 2.40/100,000 PY in 2017 and 2018, respectively. There were no significant differences in monthly and seasonal incidence of AAV. The average expense of medical care, overall mortality, and ESRD rates of patients with AAV were higher in patients with AAV than in controls, especially in the case of MPA. Conclusion: An increasing trend of AAV diagnosis observed is consistent with the evidence that AAV is more common in recent years; however, a relatively lower incidence and prevalence was observed compared to that in Western countries. The higher medical cost and rates of mortality and ESRD in AAV emphasize the early recognition and implementation of optimal treatment for these patients.

Real-time heart rate monitoring system for cardiotoxicity assessment of Daphnia magna using high-speed digital holographic microscopy.

Machine vision techniques for monitoring heart rates in aquatic bioassays have been applied to cardiotoxicity assessment. However, the requisite large data sizes and long calculation times make long-term observations of heart rates difficult. In this study, we developed a real-time heart rate monitoring system for individual Daphnia magna in a water chamber mounter that immobilizes their movement in 100 mL media. Heart rates are calculated from real-time, time-resolved relative phase information from digital holograms acquired with a 200 fps camera and parallel computation using a graphics processing unit. With this system, we monitored the real-time changes in the heart rates of individual D. magna specimens exposed to H2O2 as a positive control for reactive oxygen species (ROS) levels in an aquatic environment for 10 h, a period long enough to observe dynamic heart rate responses to the mounting process and exposure and to establish heart rate trends. An additional group analysis was conducted to compare to conventional cardiotoxicity assessment, with results of both assessments showing that the heart rates reduced according to ROS level by H2O2 exposure concentration. Notably, the results of our real-time dynamic heart rate monitoring in aquatic conditions indicated that establishing a relaxation heart rate before measurements could improve the accuracy of toxicity assessment. It is believed that the system developed in this study, achieving the simultaneous measurement, analysis, and display of reconstructed results, will find wide application in other aquatic bioassays.

Nationwide External Quality Assessment of SARS-CoV-2 Molecular Testing, South Korea.

External quality assessment (EQA) is essential for ensuring reliable test results, especially when laboratories are using assays authorized for emergency use for newly emerging pathogens. We developed an EQA panel to assess the quality of real-time reverse transcription PCR assays being used in South Korea to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the participation of 23 public health organization laboratories and 95 nongovernmental laboratories involved in SARS-CoV-2 testing, we conducted qualitative and semiquantitative performance assessments by using pooled respiratory samples containing different viral loads of SARS-CoV-2 or human coronavirus OC43. A total of 110 (93.2%) laboratories reported correct results for all qualitative tests; 29 (24.6%) laboratories had >1 outliers according to cycle threshold values. Our EQA panel identified the potential weaknesses of currently available commercial reagent kits. The methodology we used can provide practical experience for those planning to conduct evaluations for testing of SARS-CoV-2 and other emerging pathogens in the future.

Clustering Insomnia Patterns by Data From Wearable Devices: Algorithm Development and Validation Study.

BACKGROUND: As societies become more complex, larger populations suffer from insomnia. In 2014, the US Centers for Disease Control and Prevention declared that sleep disorders should be dealt with as a public health epidemic. However, it is hard to provide adequate treatment for each insomnia sufferer, since various behavioral characteristics influence symptoms of insomnia collectively. OBJECTIVE: We aim to develop a neural-net based unsupervised user clustering method towards insomnia sufferers in order to clarify the unique traits for each derived groups. Unlike the current diagnosis of insomnia that requires qualitative analysis from interview results, the classification of individuals with insomnia by using various information modalities from smart bands and neural-nets can provide better insight into insomnia treatments. METHODS: This study, as part of the precision psychiatry initiative, is based on a smart band experiment conducted over 6 weeks on individuals with insomnia. During the experiment period, a total of 42 participants (19 male; average age 22.00 [SD 2.79]) from a large university wore smart bands 24/7, and 3 modalities were collected and examined: sleep patterns, daily activities, and personal demographics. We considered the consecutive daily information as a form of images, learned the latent variables of the images via a convolutional autoencoder (CAE), and clustered and labeled the input images based on the derived features. We then converted consecutive daily information into a sequence of the labels for each subject and finally clustered the people with insomnia based on their predominant labels. RESULTS: Our method identified 5 new insomnia-activity clusters of participants that conventional methods have not recognized, and significant differences in sleep and behavioral characteristics were shown among groups (analysis of variance on rank: F4,37=2.36, P=.07 for the sleep_min feature; F4,37=9.05, P<.001 for sleep_efficiency; F4,37=8.16, P<.001 for active_calorie; F4,37=6.53, P<.001 for walks; and F4,37=3.51, P=.02 for stairs). Analyzing the consecutive data through a CAE and clustering could reveal intricate connections between insomnia and various everyday activity markers. CONCLUSIONS: Our research suggests that unsupervised learning allows health practitioners to devise precise and tailored interventions at the level of data-guided user clusters (ie, precision psychiatry), which could be a novel solution to treating insomnia and other mental disorders.

Estimation of cost savings between 2011 and 2014 attributed to infliximab biosimilar in the South Korean healthcare market: real-world evidence using a nationwide database.

AIM: The introduction of biosimilars is expected to reduce the cost of biologic drugs, but the actual cost savings have not yet been quantified in Korea. The aim of this study was to estimate the annual cost savings attributed to the introduction of infliximab biosimilar. METHODS: We conducted a retrospective analysis using data from the Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) between 2011 and 2014. The study subjects were patients who were treated with infliximab, adalimumab or etanercept. We compared the drug costs before and after the introduction of infliximab biosimilar in December 2012 (2011-2012 and 2013-2014) to estimate the annual drug cost savings attributed to this and the number of patients who could additionally benefit from the biosimilar in 2013 and 2014. RESULTS: A total of 10 986 prescriptions were identified: 2620 for infliximab. The cost savings were estimated at $262 270 for 133 patients in 2013 and $395 220 for 174 patients in 2014. Among the patients who underwent a 1-year maintenance course of infliximab therapy, the annual expenditure on infliximab was lower in 2014 than in 2011. If the cost savings were used to treat additional patients, 13.3%-38.6% more patients per year could be treated by indication. CONCLUSION: The introduction of infliximab biosimilar reduced direct medical costs for both patients and the payer, which could then be used to increase patient access to biologic medicines. The entry of infliximab biosimilar could result in further reductions in healthcare costs.

Simultaneous analysis of 210 prohibited substances in human urine by ultrafast liquid chromatography/tandem mass spectrometry in doping control.

RATIONALE: Doping analysis is a two-step process consisting of a screening step for prohibited substances and a confirmation step to verify the presence of specific substances found during the screening. The entire process must be performed within a limited time period, but traditional screening procedures commonly employ separate analytical methods for each class of prohibited substances being screened and thus require a great deal of human resources and instrumentation. A single simple and rapid multiresidue analytical method that could accommodate multiple classes of prohibited substances would be extraordinarily useful in doping analyses. METHODS: Urine samples were extracted via two consecutive liquid-liquid extractions at different pH values following enzymatic hydrolysis. Analyses were performed by ultrafast liquid chromatography/triple-quadrupole mass spectrometry with polarity switching and time-dependent selected reaction monitoring. RESULTS: We developed a rapid multiresidue screening and confirmation method for efficient high-throughput doping analyses. The present method was validated with regard to the limits of detection (0.01-100.0 ng/mL for screening analyses and 0.2-500.0 ng/mL for confirmation assays), matrix effects (48.9-118.9%), recovery (20.6-119.7%) and intra- (0.6-17.6%) and inter-day (4.0-20.0%) precision. CONCLUSIONS: A multiresidue analytical method was developed and validated for screening and confirming the presence of performance-enhancing drugs. A total of 210 substances from diverse classes of prohibited substances were successfully identified with an analytical run time of 10 min.

Disease duration and Medsger's severity score are associated with significant liver fibrosis in patients with systemic sclerosis.

OBJECTIVES: We investigated the prevalence and predictors of significant liver fibrosis in patients with systemic sclerosis (SSc) who had no evidences of liver diseases due to viral infection, drug, and heavy alcohol consumption. METHODS: A total of 44 SSc patients were recruited. In addition to the clinical and laboratory data, the 2013 College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria score, modified Rodnan skin score (mRSS), and Medsger's severity score (MSS) were analysed. Liver stiffness (LS) was measured using transient elastography to assess the degree of liver fibrosis and 7.4 kPa was adopted as the cut-off value for significant liver fibrosis. RESULTS: The median age of patients (38 women) was 54 years and the median disease duration was 41.0 months. The median LS value was 4.6 kPa. The median mRSS and MSS were 7.0 and 5.0, respectively. Six (13.6%) patients had significant liver fibrosis. Disease duration (standardised ß=0.375, p=0.018) and MSS (standardised ß=0.398, p=0.047) significantly correlated with LS values. In multivariate analysis, disease duration≥63 months (odds ratio (OR) 19.166, 95% confidence interval 1.090, 336.962, p=0.043) and MSS≥7 (OR 19.796, 95% confidence interval 1.439, 272.252, p=0.026) independently predicted the presence of significant liver fibrosis. CONCLUSIONS: The prevalence of significant liver fibrosis was relatively high (13.6%) and its independent predictors were disease duration and MSS.

Variation in the numbers of red blood cell units transfused at different medical institution types from 2006 to 2010 in Korea.

BACKGROUND: This study aimed at assessing the number of red blood cell (RBC) units transfused at different types of medical institution and examining the characteristics of transfusion recipients. METHODS: We calculated and compared the number of transfusion recipients, total RBC units transfused, and RBC units transfused per recipient. Study data were extracted from insurance benefits reimbursement claims for RBC units at the Health Insurance Review & Assessment Service from 2006 to 2010. RESULTS: Between 2006 and 2010, the number of recipients of RBC units increased from 298,049 to 376,445, the number of RBC units transfused increased from 1,460,799 to 1,841,695, and the number of RBC units transfused per recipient changed from 4.90 to 4.89. The number of recipients aged ≥65 yr increased from 133,833 (44.9%) in 2006 to 196,127 (52.1%) in 2010. The highest number of RBC units was transfused to patients with neoplastic diseases (31.9%) and diseases of the musculoskeletal system and connective tissue (14.4%). More than 80% of the total number of RBC units were transfused at tertiary and general hospitals. However, this composition rate was slightly decreasing, with the composition rate for hospitals increasing from 12.6% to 16.3%. CONCLUSIONS: This study revealed an increase in the number of RBC units transfused over a 5-yr period due to an increase in the number of transfused recipients, especially recipients aged ≥65 yr; moreover, the number of RBC units transfused differed based on medical institution type. These results provide fundamental data on RBC transfusions required for future research.

Pain assessment in brain tumor patients after elective craniotomy.

OBJECTIVE: This study was performed to assess the postoperative pain of brain tumor patients who underwent elective craniotomy and to evaluate the factors associated with pain intensity. METHODS: From January 2010 to December 2011, 47 patients with newly diagnosed brain tumors who underwent craniotomy were enrolled. The postoperative pain status was assessed daily until discharge using the visual analogue scale (VAS). RESULTS: The study participants comprised of 22 males and 25 females with ages ranging from 18-76 years (median age, 50 years). Patients were divided into two groups: the painful group included patients who had a VAS score of more than 3 during their hospital stay after the craniotomy, and the tolerable group included patients who had a VAS score of 1 to 3 during their hospital stay. There were no differences between the two groups in terms of age, sex, location of surgery, history of diabetes, hypertension and smoking, body mass index, and hospital stay. Univariate analysis revealed that operating time, length of wound, head fixation, and perioperative administration of opioid were not associated with the intensity of postoperative pain. Daily assessment of VAS revealed the two peaks of pain on the operation day and the 4th postoperative day. The intensity of pain during the ambulation period was higher than that during intensive care unit (ICU) stay. CONCLUSION: Pain following elective craniotomy for brain tumor removal is insufficiently managed, especially after discharge from the ICU. More attention needs to be paid to patients' pain throughout the hospital stay.

O6-methylguanine-DNA-methyltransferase promoter methylation assessment by microdissection-assisted methylation-specific PCR and high resolution melting analysis in patients with glioblastomas.

We have determined O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status by methylation-specific polymerase chain reaction (MSP) in 22 paraffin-embedded specimens of glioblastoma multiforme. A MGMT methylation-specific high resolution melting (HRM) assay was performed to compare the methylation levels of the tumorous and non-tumorous portions of each sample, which were selectively collected using a microdissection technique. MGMT methylation was detected in 10 patients using MSP, while 8 patients had both methylated and unmethylated MGMT promoters. HRM assays showed that there was no difference in the level of methylation between tumorous and non-tumorous portions of each sample. In patients with MSP-positive tumors, the overall survival (median, 22 months) was longer as compared to those with MSP-negative tumors (median, 14 months). A correlation between the methylation status of the MGMT promoter and MGMT protein expression was observed in 12 samples. This study demonstrates that MGMT methylation is not restricted to glioblastoma cells. Additionally, methylation-specific HRM is a feasible approach that can be readily applied to the methylation analysis of MGMT. A further study will be needed to determine the dynamic change of MGMT methylation in the tumor environment.

The role of (18) F-fluorodeoxyglucose-positron emission tomography in the assessment of disease activity in patients with takayasu arteritis.

OBJECTIVE: The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS: We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS: At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION: (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.

Rapid and efficient protein digestion using trypsin-coated magnetic nanoparticles under pressure cycles.

Trypsin-coated magnetic nanoparticles (EC-TR/NPs), prepared via a simple multilayer random crosslinking of the trypsin molecules onto magnetic nanoparticles, were highly stable and could be easily captured using a magnet after the digestion was complete. EC-TR/NPs showed a negligible loss of trypsin activity after multiple uses and continuous shaking, whereas the conventional immobilization of covalently attached trypsin on NPs resulted in a rapid inactivation under the same conditions due to the denaturation and autolysis of trypsin. A single model protein, a five-protein mixture, and a whole mouse brain proteome were digested at atmospheric pressure and 37°C for 12 h or in combination with pressure cycling technology at room temperature for 1 min. In all cases, EC-TR/NPs performed equally to or better than free trypsin in terms of both the identified peptide/protein number and the digestion reproducibility. In addition, the concomitant use of EC-TR/NPs and pressure cycling technology resulted in very rapid (∼1 min) and efficient digestions with more reproducible digestion results.

Assessment of cetuximab efficacy by bioluminescence monitoring of intracranial glioblastoma xenograft in mouse.

A glioblastoma multiforme xenograft was established in athymic nude mice via inoculation of glioblastoma cells that stably express luciferase (U87MG-LucNeo), and was monitored weekly using bioluminescence imaging (BLI). In the control groups, a steep rise in the signal was associated with the death of mice. As an adjuvant therapy, cetuximab (0.5 mg, two times) was intraperitoneally administered 4 weeks after nitrosourea treatment. For a salvage therapy, cetuximab (0.5 mg, two times) was intraperitoneally administered when recovery of the bioluminescence signal was detected after nitrosourea monotherapy. The antitumor effects of cetuximab adjuvant therapy were superior to those of nitrosourea monotherapy and cetuximab salvage therapy. This finding was consistent with the results from a survival comparison among nitrosourea monotherapy, adjuvant and salvage therapy with cetuximab. These results suggest that BLI could be used as a simple tool for predicting the efficacy of various anticancer treatments in mouse models of brain tumors. The administration of cetuximab as an adjuvant to the conventional chemotherapeutic agent is more efficient than salvage therapy.

Unenhanced CT for assessment of macrovesicular hepatic steatosis in living liver donors: comparison of visual grading with liver attenuation index.

PURPOSE: To retrospectively compare the accuracy of visual grading and the liver attenuation index in the computed tomographic (CT) diagnosis of 30% or higher macrovesicular steatosis in living hepatic donors, by using histologic analysis as the reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained with waiver of informed consent. Of 703 consecutive hepatic donor candidates, 24 patients (22 men and two women; mean age +/- standard deviation, 36.3 years +/- 9.7) who had 30% or higher macrovesicular steatosis at histologic analysis and same-day CT with subsequent needle biopsy in the right hepatic lobe (at least two samples per patient) were evaluated. An age- and sex-matched control group of 24 subjects included those who had less than 30% macrovesicular steatosis but otherwise met the same criteria as the patient group. A diagnostically difficult setting was made by selecting those with the highest degree of macrovesicular steatosis when there were multiple control subjects matched for a particular subject in the patient group. Two independent radiologists assessed steatosis of the right hepatic lobe by using two methods: a five-point visual grading system that used attenuation comparison between the liver and hepatic vessels and the liver attenuation index (CT(L-S)), defined as hepatic attenuation minus splenic attenuation and calculated with region of interest measurements of hepatic attenuation. Interobserver agreement was assessed. Accuracy in the diagnosis of 30% or higher macrovesicular steatosis was compared by using a multireader, multicase receiver operating characteristic (ROC) analysis. RESULTS: For visual grading, kappa = 0.905 (95% confidence interval [CI]: 0.834, 0.976). Intraclass correlation coefficient for CT(L-S) was 0.962 (95% CI: 0.893, 0.983). The area under the ROC curve of visual grading and CT(L-S) were 0.927 (95% CI: 0.822, 1) and 0.929 (95% CI: 0.874, 0.983), respectively, indicating no statistically significant difference (P = .975). CONCLUSION: Both visual grading and CT(L-S) are highly reliable and similarly accurate in the diagnosis of 30% or higher macrovesicular steatosis in living hepatic donor candidates.

[Factors associated with perceived peer smoking prevalence among adolescents].

OBJECTIVES: This study was conducted to examine the factors related to the perceived peer smoking prevalence for adolescents. METHODS: A self-administrated questionnaire was administered to 352 students in a technical high school in Kangwon Province in May, 2002. The questions included in the questionnaire were concerned with the estimated number of smokers among ten students of the same grade in their school, the sociodemographic characteristics, the smoking-related behaviors and attitudes, and the smoking-related environments. All the students had their expiratory carbon monoxide level measured with EC50 Micro-Smokerlyzer? to verify their smoking status. Multiple regression analysis was applied for data analysis using Windows SPSS 11.5. RESULTS: The former and current smokers overestimated the peer smoking prevalence. Multiple regression analysis for estimating the peer smoking prevalence for the male showed that the perceived smoking prevalence was higher in the female students than in the male students, higher in those students whose mothers had a higher educational level, who had smoked more frequently, who had more best friends smoking, and who had a higher actual smoking rate of the class. For estimating the peer smoking prevalence for the female, the perceived smoking prevalence was higher in the female students than in the male students, higher in those who smoked more frequently, whose five best friends smoked, who had higher actual smoking rate of the class, and who had smoking siblings. CONCLUSIONS: This study showed that a higher perceived peer smoking rate is related with their own smoking history and smoking frequency, the smoking related environment, and gender. Smoking prevention and smoking cessation programs need to focus on correcting the falsely perceived smoking prevalence.

Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment.

PURPOSE: To determine prospectively the diagnostic performance of unenhanced computed tomography (CT) in the assessment of macrovesicular steatosis in potential donors for living donor liver transplantation by using same-day biopsy as a reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. A total of 154 candidates, including 104 men (mean age, 30.2 years +/- 10.3 [standard deviation]) and 50 women (mean age, 31.8 years +/- 11.2), underwent same-day unenhanced CT and ultrasonography-guided liver biopsy. Histologic degree of macrovesicular steatosis was determined. Three liver attenuation indices were derived: liver-to-spleen attenuation ratio (CT(L)(/S)), difference between hepatic and splenic attenuation (CT(L)(-S)), and blood-free hepatic parenchymal attenuation (CT(LP)). Regression equations were used to quantitatively estimate the degree of macrovesicular steatosis. Limits of agreement between estimated macrovesicular steatosis and the reference standard were calculated. Receiver operating characteristic analyses were used to determine the performance of each index for qualitative diagnosis of macrovesicular steatosis of 30% or greater. The cutoff value that provided a balance between sensitivity and specificity and the highest cutoff value that yielded 100% specificity were determined. RESULTS: Limits of agreement were -14% to 14% for CT(L)(/S) and CT(L)(-S) and -13% to 13% for CT(LP). Performance in diagnosing macrovesicular steatosis of 30% or greater was not significantly different among indices (P > .05). Cutoff values of 0.9, -7, and 58 were determined for CT(L)(/S), CT(L)(-S), and CT(LP), respectively, and provided a balance between sensitivity and specificity. Cutoff values of 0.8, -9, and 42 were determined for CT(L)(/S), CT(L)(-S), and CT(LP), respectively, and yielded 100% specificity for all indices, with corresponding sensitivities of 82%, 82%, and 73% for CT(L)(/S), CT(L)(-S), and CT(LP), respectively. CONCLUSION: Diagnostic performance of unenhanced CT for quantitative assessment of macrovesicular steatosis is not clinically acceptable. Unenhanced CT, however, provides high performance in qualitative diagnosis of macrovesicular steatosis of 30% or greater.